FN Thomson Reuters Web of Science™ VR 1.0 PT J AU de Courcy, B Pedersen, LG Parisel, O Gresh, N Silvi, B Pilme, J Piquemal, JP AF de Courcy, B. Pedersen, L. G. Parisel, O. Gresh, N. Silvi, B. Pilme, J. Piquemal, J. -P. TI Understanding Selectivity of Hard and Soft Metal Cations within Biological Systems Using the Subvalence Concept. 1. Application to Blood Coagulation: Direct Cation-Protein Electronic Effects versus Indirect Interactions through Water Networks SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; HYDRATED MAGNESIUM-ION; SOLUBLE TISSUE FACTOR; K-DEPENDENT PROTEINS; HUMAN-FACTOR-IX; GLA DOMAIN; LOCALIZATION FUNCTION; MEMBRANE-BINDING; CRYSTAL-STRUCTURE; TOPOLOGICAL ANALYSIS AB Following a previous study by de Courcy et al. (Interdiscip. Sci. Comput. Life Sci. 2009, 1, 55-60), we demonstrate in this contribution, using quantum chemistry, that metal cations exhibit a specific topological signature in the electron localization of their density interacting with ligands according to their "soft" or "hard" character. Introducing the concept of metal cation subvalence, we show that a metal cation can split its outer-shell density (the so-called subvalent domains or basins) according to it capability to form a partly covalent bond involving charge transfer. Such behavior is investigated by means of several quantum chemical interpretative methods encompasing the topological analysis of the Electron Localization Function (ELF) and Bader's Quantum Theory of Atoms in Molecules (QTAIM) and two energy decomposition analyses (EDA), namely, the Reduced Variational Space (RVS) and Constrained Space Orbital Variations (CSOV) approaches. Further rationalization is performed by computing ELF and QTAIM local properties such as electrostatic distributed moments and local chemical descriptors such as condensed Fukui functions and dual descriptors. These reactivity indexes are computed within the ELF topological analysis in addition to QTAIM offering access to a nonatomic reactivity local index, for example, on lone pairs. We apply this "subvalence" concept to study the cation selectivity in enzymes involved in blood coagulation (GLA domains of three coagulation factors). We show that the calcium ions are clearly able to form partially covalent charge transfer networks between the subdomain of the metal ion and the carboxylate oxygen lone pairs, whereas magnesium does not have such ability. Our analysis also explains the different role of two groups (high affinity and low affinity cation binding sites) present in GLA domains. If the presence of Ca(II) is mandatory in the central "high affinity" region to conserve a proper folding and a charge transfer network, external sites are better stabilized by Mg(II), rather than Ca(II), in agreement with the experiment. The central role of discrete water molecules is also discussed in order to understand the stabilities of the observed X-ray structures of the GLA domain. Indeed, the presence of explicit water molecules generating indirect cation protein interactions through water networks is shown to be able to reverse the observed electronic selectivity occurring when cations directly interact with the Gla domain without the need of water. C1 [de Courcy, B.; Parisel, O.; Silvi, B.; Pilme, J.; Piquemal, J. -P.] Univ Paris 06, Chim Theor Lab, UPMC, UMR 7616, F-75005 Paris, France. [de Courcy, B.; Parisel, O.; Silvi, B.; Pilme, J.; Piquemal, J. -P.] CNRS, Chim Theor Lab, UMR 7616, F-75005 Paris, France. [Pedersen, L. G.] Natl Inst Environm Hlth, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Gresh, N.] Univ Paris 05, UFR Biomed, Lab Pharmacochim Mol & Cellulaire, U648,INSERM, F-75006 Paris, France. [Pilme, J.] Univ Lyon 1, Fac Pharm, F-69373 Lyon 08, France. RP Piquemal, JP (reprint author), Univ Paris 06, Chim Theor Lab, UPMC, UMR 7616, Case Courrier 137,4 Pl Jussieu, F-75005 Paris, France. EM jpp@lct.jussieu.fr RI pedersen, lee/A-8567-2009; Piquemal, Jean-Philip/B-9901-2009; Pilme, Julien/G-4858-2012; Pedersen, Lee/E-3405-2013; OI Piquemal, Jean-Philip/0000-0001-6615-9426; Pedersen, Lee/0000-0003-1262-9861; Silvi, Bernard/0000-0002-3872-0121 FU French National Research Agency (ANR) [BLAN08-3_312754]; NIH; NIEHS FX The computations have been performed at the national IDRIS (F. 91403 Orsay, France), CRIHAN (F.76800 Saint-Etienne-du-Rouvray, France), and CINES (F. 34097 Montpellier, France) supercomputing centers. Sonic ELF computations have been run at the local CCRE centre at Universite Pierre et Marie Curie, Univ Paris 6 (F. 75252 Paris CEDEX 05, France). Support from the French National Research Agency (ANR) on project LASIHMODo (BLAN08-3_312754) is acknowledged. This research was supported in part by the Intramural Research program of the NIH and NIEHS. NR 76 TC 36 Z9 36 U1 1 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD APR PY 2010 VL 6 IS 4 BP 1048 EP 1063 DI 10.1021/ct100089s PG 16 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 581XE UT WOS:000276558100007 PM 20419068 ER PT J AU Arnold, LE Farmer, C Kraemer, HC Davies, M Witwer, A Chuang, S DiSilvestro, R McDougle, CJ McCracken, J Vitiello, B Aman, MG Scahill, L Posey, DJ Swiezy, NB AF Arnold, L. Eugene Farmer, Cristan Kraemer, Helena Chmura Davies, Mark Witwer, Andrea Chuang, Shirley DiSilvestro, Robert McDougle, Christopher J. McCracken, James Vitiello, Benedetto Aman, Michael G. Scahill, Lawrence Posey, David J. Swiezy, Naomi B. TI Moderators, Mediators, and Other Predictors of Risperidone Response in Children with Autistic Disorder and Irritability SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; INDUCED WEIGHT-GAIN; CERULOPLASMIN; ADOLESCENTS; METFORMIN; PROTEINS; NETWORK; SCALE AB Objective/Background: The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure in an 8-week double-blind, placebo-controlled trial for irritability in autistic disorder. This paper explores moderators and mediators of this effect. Method: Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the evaluation of the results. Results: Only baseline severity moderated treatment response: Higher severity showed greater improvement for risperidone but not for placebo. Weight gain mediated treatment response negatively: Those who gained more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity negatively predicted outcome. Risperidone moderated the effect of change in 50-nucleotidase, a marker of zinc status, for which decrease was associated with improvement only with risperidone, not with placebo. Conclusion: The benefit-risk ratio of risperidone is better with greater symptom severity. Risperidone can be individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and absence of co-morbid problems non-specifically predict better outcome. Mineral interactions with risperidone deserve further study. C1 [Arnold, L. Eugene] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. [Arnold, L. Eugene; Farmer, Cristan; Witwer, Andrea; Aman, Michael G.] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Kraemer, Helena Chmura] Stanford Univ, Dept Psychiat & Behav Sci Emerita, Pittsburgh, PA USA. [McDougle, Christopher J.; Posey, David J.; Swiezy, Naomi B.] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA. [DiSilvestro, Robert] Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA. [McCracken, James] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Semel Inst, Semel Inst, Los Angeles, CA 90024 USA. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Rockville, MD 20857 USA. [Scahill, Lawrence] Yale Univ, Yale Child Study Ctr, New Haven, CT USA. RP Arnold, LE (reprint author), 1581 Dodd Dr Rm 207, Columbus, OH 43210 USA. EM Arnold.4@osu.edu OI Witwer, Andrea/0000-0002-1268-4222; Scahill, Lawrence/0000-0001-5073-1707 FU National Institute of Mental Health [N01MH70009, N01MH70010, N01MH70001, N01MG80011]; National Institutes of Health [M01 RR00750, M01 RR00052, M01 RR0034, M01 RR06022]; Korczak Foundation; Celgene; Shire; Noven; Lilly; Targacept; Sigma Tau; Neuropharm; Novartis; Bristol-Myers Squibb Co.; Eli Lilly; McNeil; Pfizer; Johnson Johnson; Aspect; Forest FX This research was supported by contracts from the National Institute of Mental Health (N01MH70009, to Dr. Scahill; N01MH70010, to Dr. McCracken; N01MH70001, to Dr. McDougle; and N01MG80011, to Dr. Aman), General Clinical Research Center grants from the National Institutes of Health (M01 RR00750, to Indiana University; M01 RR00052, to Johns Hopkins University; M01 RR0034, to Ohio State University; and M01 RR06022, to Yale University), and a grant from the Korczak Foundation (to Dr. Scahill). Study medications were donated by Janssen Pharmaceutica.; Dr. Arnold has received research funding from Celgene, Shire, Noven, Lilly, Targacept, Sigma Tau, Neuropharm, and Novartis; has consulted for Abbott, Neuropharm, Novartis, Noven, Shire, Sigma Tau, and Organon; and has been on speaker's bureau for Abbott, Shire, McNeil, and Novartis. Dr. Disilvestro consults for Albion Laboratories. Dr. McDougle has received research funding from Bristol-Myers Squibb Co., has consulted to Bristol-Myers Squibb Co., F. Hoffman-LaRoche Ltd., and Forest Research Institute, and has been on speaker's bureau for Bristol-Myers Squibb Co. Dr. McCracken has received research funding from Bristol-Myers Squibb, Eli Lilly, McNeil, Pfizer, Shire, Johnson & Johnson, and Aspect; consulted for Abbott, Eli Lilly, Janssen, Johnson & Johnson, McNeil, Novartis, Wyeth, Shire, and Sanofi-Aventis; and has been on speaker's bureau for UCB and Eli Lilly. Dr. Aman has received research funding from Bristol-Myers Squibb Co. and Johnson and Johnson and has consulted for Bristol-Myers Squibb Co. Dr. Scahill has served as an advisor or consultant for Janssen, Pfizer, and Bristol-Myers Squibb. Dr. Posey has lectured for Janssen and has had financial affiliations with Bristol-Myers Squibb Co., Eli Lilly, Forest, and Shire. The other authors have no financial ties or conflicts of interest to disclose. NR 25 TC 24 Z9 24 U1 5 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD APR PY 2010 VL 20 IS 2 BP 83 EP 93 DI 10.1089/cap.2009.0022 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 587JK UT WOS:000276987500001 PM 20415603 ER PT J AU Maslowsky, J Mogg, K Bradley, BP McClure-Tone, E Ernst, M Pine, DS Monk, CS AF Maslowsky, Julie Mogg, Karin Bradley, Brendan P. McClure-Tone, Erin Ernst, Monique Pine, Daniel S. Monk, Christopher S. TI A Preliminary Investigation of Neural Correlates of Treatment in Adolescents with Generalized Anxiety Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PREFRONTAL CORTEX ACTIVATION; COGNITIVE-BEHAVIORAL THERAPY; CHILDHOOD ANXIETY; FUNCTIONAL NEUROANATOMY; DEPRESSIVE-DISORDERS; MAJOR DEPRESSION; SOCIAL PHOBIA; ANGRY FACES; CHILDREN; PSYCHOTHERAPY AB Objective: Generalized anxiety disorder (GAD) is a prevalent and debilitating psychiatric condition of adolescence. Two effective forms of treatment are cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). This pilot study examined changes in brain function following each type of treatment in GAD. Method: Subjects were 14 youths with GAD (7 had CBT, 7 received fluoxetine) and 10 age- and gender-matched healthy peers. Functional magnetic resonance imaging (fMRI) scans were acquired before and after treatment for patients and over two comparable time points for controls. During fMRI acquisition, a probe detection task with emotional (angry, happy) and neutral faces allowed for assessment of neural response to threat. Following previous research, region of interest analyses were performed in the right ventrolateral prefrontal cortex (VLPFC). Results: fMRI results showed increased right VLPFC activation, relative to controls, in the medication (t(15) = 3.01, p < 0.01) and CBT (t(15) = 3.22, p < 0.01) groups following treatment. Conclusions: This study shows significant increase in right VLPFC activation in response to angry faces following treatment with CBT or fluoxetine for GAD. This is consistent with previous research indicating that the VLPFC may facilitate effective responding to underlying neural correlates of anxiety in other brain regions, such as the amygdala. C1 [Maslowsky, Julie; Monk, Christopher S.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Monk, Christopher S.] Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. [Monk, Christopher S.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Sch Psychol, Southampton, Hants, England. [McClure-Tone, Erin] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. RP Maslowsky, J (reprint author), Univ Michigan, Dept Psychol, 530 Church St,2044 E Hall, Ann Arbor, MI 48109 USA. EM jmaslow@umich.edu RI Bradley, Brendan/B-9724-2008; Mogg, Karin/C-1181-2008; Monk, Christopher/J-1805-2014; OI Mogg, Karin/0000-0002-2738-7378; Bradley, Brendan/0000-0003-2801-4271 FU National Institute of Mental Health (NIMH); [K22MH068017] FX This research was supported in part by K22MH068017 (C.S.M.) and the National Institute of Mental Health (NIMH) Intramural Research Program (D.S.P.). NR 38 TC 43 Z9 43 U1 4 U2 18 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD APR PY 2010 VL 20 IS 2 BP 105 EP 111 DI 10.1089/cap.2009.0049 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 587JK UT WOS:000276987500003 PM 20415605 ER PT J AU Brown, RJ Kelly, MH Collins, MT AF Brown, Rebecca J. Kelly, Marilyn H. Collins, Michael T. TI Cushing Syndrome in the McCune-Albright Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATORY G-PROTEIN; CONGENITAL ADRENAL-HYPERPLASIA; QUALITY-OF-LIFE; ACTIVATING MUTATIONS; FIBROUS DYSPLASIA; CHILDREN; INFANCY; DEXAMETHASONE; ENDOCRINE; SUBUNIT AB Context: Cushing syndrome (CS) is a rare but potentially fatal feature of McCune-Albright syndrome ( MAS). Optimal management, prognostic features, and long-term follow-up of this disorder have not been described. Setting: The study was conducted at an academic tertiary care center. Patients: A total of 112 patients participating in a natural history study at the National Institutes of Health (NIH) were evaluated, and 21 published cases were reviewed. Interventions: Subjects received observation, medical management, or bilateral adrenalectomy. Main Outcome Measures: We measured prevalence, prognostic factors, and natural history. Results: The prevalence of CS among NIH patients was 7.1%. The median age at diagnosis was 3 months. Clinical features included "Cushingoid facies" (66.7%), failure to thrive (60.0%), low birth weight (50.0%), liver disease (36.7%), and heart disease (26.7%). Six patients (20.0%) died, four after adrenalectomy. Death was more likely in patients with comorbid heart disease (odds ratio, 13.3; P < 0.05). Of 23 survivors, 13 underwent adrenalectomy, and 10 exhibited spontaneous resolution. Two patients with spontaneous resolution who were tested later in life (3 and 15 yr after resolution) continued to have low-level, autonomous adrenal function with biochemical adrenal insufficiency. Compared to MAS patients without CS, patients with CS were more likely to have a cognitive/developmental disorder (44.4 vs. 4.8%; P < 0.001; odds ratio, 8.8). Conclusions: Comorbid heart and liver disease were poor prognostic markers and may indicate the need for prompt adrenalectomy. The high incidence of cognitive disorders indicates a need for close developmental follow-up and parental counseling. Patients with spontaneous resolution of CS may develop adrenal insufficiency, and they require long-term monitoring. (J Clin Endocrinol Metab 95: 1508-1515, 2010) C1 [Kelly, Marilyn H.; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Brown, Rebecca J.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20814 USA. RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov FU National Institute of Dental and Craniofacial Research; National Institute of Child Health and Development; National Institute of Diabetes, Digestive and Kidney Diseases FX This work was supported by the intramural research programs of the National Institute of Dental and Craniofacial Research, the National Institute of Child Health and Development, and the National Institute of Diabetes, Digestive and Kidney Diseases. NR 37 TC 24 Z9 26 U1 2 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1508 EP 1515 DI 10.1210/jc.2009-2321 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300005 PM 20157193 ER PT J AU Kiehna, EN Keil, M Lodish, M Stratakis, C Oldfield, EH AF Kiehna, Erin N. Keil, Meg Lodish, Maya Stratakis, Constantine Oldfield, Edward H. TI Pseudotumor Cerebri after Surgical Remission of Cushing's Disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC INTRACRANIAL HYPERTENSION; CEREBROSPINAL-FLUID; ABSORPTION AB Context: Pseudotumor cerebri has only been described after successful surgery for Cushing's disease (CD) in case reports. We sought to establish the incidence and timing of its occurrence, identify predisposing factors, characterize the clinical presentations and their severity, and examine the effects of treatment in patients who underwent surgery for CD. Setting: This study was conducted at two tertiary care centers: The University of Virginia and the National Institutes of Health. Patients: We conducted a retrospective review of 941 surgeries for CD (723 adults, 218 children) to identify patients who developed pseudotumor cerebri after surgery for CD and examine the associated clinical features. Results: Seven children (four males, three females; 3%), but no adults, developed pseudotumor cerebri postoperatively. All underwent resection of an ACTH-secreting adenoma, and postoperative serum cortisol reached a nadir of less than 2 mu g/dl. After surgery, all were placed on tapering hydrocortisone replacement therapy. Within 3-52 wk, all seven patients experienced symptoms of pseudotumor cerebri and had ophthalmological examination demonstrating papilledema. One patient had diplopia from a unilateral VIth nerve palsy. Six patients were still on steroid replacement at onset of symptoms. In three patients, a lumbar puncture demonstrated elevated opening pressure. Four patients were treated successfully with a lumbar puncture, steroids, and/or Diamox. Three patients did not receive treatment, and their symptoms resolved over several months. There was no correlation between the degree of hypercortisolism (24-h urinary free cortisol) before surgery and the likelihood of developing pseudotumor cerebri after surgery (P < 0.23). Conclusions: This series demonstrates a 3% occurrence of pseudotumor cerebri in children after successful surgery for CD, but the absence of the syndrome in adults. Pseudotumor cerebri manifests itself within 1 yr of surgery, often while patients are still undergoing replacement steroid therapy. A patient exhibiting signs of intracranial hypertension after surgery for CD should undergo an evaluation for pseudotumor cerebri. Recognition of the symptoms and treatment should correct and/or prevent ophthalmological sequelae. (J Clin Endocrinol Metab 95: 1528-1532, 2010) C1 [Kiehna, Erin N.; Oldfield, Edward H.] Univ Virginia, Dept Neurosurg, Charlottesville, VA 22908 USA. [Keil, Meg; Lodish, Maya; Stratakis, Constantine] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Keil, Meg; Lodish, Maya; Stratakis, Constantine] NICHHD, Sect Endocrinol & Genet, Pediat Endocrinol Program, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), Univ Virginia, Dept Neurol Surg, POB 800212, Charlottesville, VA 22908 USA. OI Kiehna, Erin/0000-0002-2289-3917 FU Eunice Kennedy Shriver; National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH) [Z01-HD-000642-04]; Louise Eisenhardt Resident Award FX This work was supported by the Eunice Kennedy Shriver, National Institute of Child Health and Human Development (NICHD), intramural National Institutes of Health (NIH) project Z01-HD-000642-04.; E.N.K. will be awarded the Louise Eisenhardt Resident Award for Women in Neurosurgery for this abstract at the American Association of Neurological Surgeons meeting to be held in May 2010 in Philadelphia. NR 16 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1528 EP 1532 DI 10.1210/jc.2009-2449 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300007 PM 20164289 ER PT J AU Kalkwarf, HJ Gilsanz, V Lappe, JM Oberfield, S Shepherd, JA Hangartner, TN Huang, XK Frederick, MM Winer, KK Zemel, BS AF Kalkwarf, Heidi J. Gilsanz, Vicente Lappe, Joan M. Oberfield, Sharon Shepherd, John A. Hangartner, Thomas N. Huang, Xangke Frederick, Margaret M. Winer, Karen K. Zemel, Babette S. TI Tracking of Bone Mass and Density during Childhood and Adolescence SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PHYSICAL-ACTIVITY; MINERAL DENSITY; FOLLOW-UP; GROWTH; CHILDREN; DETERMINANTS; ADULTHOOD; MENARCHE; PUBERTY; CURVES AB Context: Whether a child with low bone mineral density (BMD) at one point in time will continue to have low BMD, despite continued growth and maturation, is important clinically. The stability of a characteristic during growth is referred to as "tracking." Objective: We examined the degree of tracking in bone mineral content (BMC) and BMD during childhood and adolescence and investigated whether tracking varied according to age, sexual maturation, and changes in growth status. Design: We conducted a longitudinal study with measurements at baseline and annually for 3 yr. Setting: The Bone Mineral Density in Childhood Study was conducted at five clinical centers in the United States. Study Participants: A total of 1554 girls and boys, ages 6-16 yr at baseline, participated in the study. Main Outcome Measures: Whole body, spine, hip, and forearm BMC and BMD were measured by dual-energy x-ray absorptiometry, and age-, sex-, and race-specific Z-scores were calculated. Deviation from tracking was calculated as the Z-score at yr 3 minus baseline. Results: Correlations between Z-scores at baseline and yr 3 ranged from 0.76-0.88. Among children with a Z-score below -1.5 at baseline, 72-87% still had a Z-score below -1 after 3 yr. Age, sexual maturation, and deviations in growth status (P < 0.01) were associated with deviation from tracking; however, tracking was strongly evident even after adjusting for the effects of age, maturation, and growth. Conclusions: Bone density showed a high degree of tracking over 3 yr in children and adolescents. Healthy children with low bone density will likely continue to have low bone density unless effective interventions are instituted. (J Clin Endocrinol Metab 95: 1690-1698, 2010) C1 [Kalkwarf, Heidi J.] Cincinnati Childrens Med Ctr, Cincinnati, OH 45229 USA. [Gilsanz, Vicente] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Lappe, Joan M.] Creighton Univ, Omaha, NE 68131 USA. [Oberfield, Sharon] Columbia Univ, New York, NY 10032 USA. [Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hangartner, Thomas N.] Wright State Univ, Dayton, OH 45435 USA. [Huang, Xangke; Frederick, Margaret M.] Clinical Trials & Survey Corp, Baltimore, MD 21210 USA. [Winer, Karen K.] NICHHD, Bethesda, MD 20892 USA. [Zemel, Babette S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Kalkwarf, HJ (reprint author), Cincinnati Childrens Hosp, Med Ctr, Div Gen & Community Pediat, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM heidi.kalkwarf@cchmc.org FU National Institute of Child Health and Human Development [NO1-HD-1-3228, -3329, -3330, -3331, -3332, -3333]; National Center for Research Resources [M01-RR-08084, -000240] FX This work was supported by the National Institute of Child Health and Human Development contracts NO1-HD-1-3228, -3329, -3330, -3331, -3332, and -3333 and the National Center for Research Resources Grants M01-RR-08084 and -000240. Disclosure Summary: J.A.S. has received a research grant from Hologic, Inc. H. J. K., V. G., J. M. L., S. O., T. N. H., X. H., M. M. F., K. K. W., and B. S. Z. have nothing to disclose. NR 30 TC 31 Z9 31 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1690 EP 1698 DI 10.1210/jc.2009-2319 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300026 PM 20194709 ER PT J AU Koller, DL Ichikawa, S Lai, DB Padgett, LR Doheny, KF Pugh, E Paschall, J Hui, SL Edenberg, HJ Xuei, XL Peacock, M Econs, MJ Foroud, T AF Koller, Daniel L. Ichikawa, Shoji Lai, Dongbing Padgett, Leah R. Doheny, Kimberly F. Pugh, Elizabeth Paschall, Justin Hui, Siu L. Edenberg, Howard J. Xuei, Xiaoling Peacock, Munro Econs, Michael J. Foroud, Tatiana TI Genome-Wide Association Study of Bone Mineral Density in Premenopausal European-American Women and Replication in African-American Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID QUANTITATIVE TRAIT LOCI; MULTIPLE GENETIC-LOCI; TRANSMEMBRANE PROTEIN; GENDER SPECIFICITY; LINKAGE; MASS; OSTEOPOROSIS; DETERMINANTS; FRACTURES; VARIANTS AB Context: Several genome-wide association studies (GWAS) have been performed to identify genes contributing to bone mineral density (BMD), typically in samples of elderly women and men. Objective: The objective of the study was to identify genes contributing to BMD in premenopausal women. Design: GWAS using the Illumina 610Quad array in premenopausal European-American (EA) women and replication of the top 50 single-nucleotide polymorphisms (SNPs) for two BMD measures in African-American (AA) women. Subjects: Subjects included 1524 premenopausal EA women aged 20-45 yr from 762 sibships and 669 AA premenopausal women aged 20-44 yr from 383 sibships. Interventions: There were no interventions. Main Outcome Measures: BMD was measured at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Age- and weight-adjusted BMD values were tested for association with each SNP, with P values determined by permutation. Results: SNPs in CATSPERB on chromosome 14 provided evidence of association with femoral neck BMD(rs1298989, P = 2.7 x 10(-5); rs1285635, P = 3.0 x 10(-5)) in the EA women, and some supporting evidence was also observed with these SNPs in the AA women (rs1285635, P = 0.003). Genes identified in other BMD GWAS studies, including IBSP and ADAMTS18, were also among the most significant findings in our GWAS. Conclusions: Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women. (J Clin Endocrinol Metab 95: 1802-1809, 2010) C1 [Koller, Daniel L.; Lai, Dongbing; Edenberg, Howard J.; Econs, Michael J.; Foroud, Tatiana] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Ichikawa, Shoji; Padgett, Leah R.; Hui, Siu L.; Peacock, Munro; Econs, Michael J.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Edenberg, Howard J.; Xuei, Xiaoling] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Doheny, Kimberly F.; Pugh, Elizabeth] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD 21224 USA. [Paschall, Justin] Natl Inst Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA. RP Koller, DL (reprint author), Indiana Univ, Sch Med, Dept Med & Mol Genet, Hlth Informat & Translat Sci Bldg HS 4000,410 W 1, Indianapolis, IN 46202 USA. EM dkoller@iupui.edu OI Econs, Michael/0000-0003-0940-1911; Edenberg, Howard/0000-0003-0344-9690 FU National Institutes of Health (NIH) [P01 AG-18397, M01 RR-00750, HHSN268200782096C]; National Library of Medicine FX This work was supported by National Institutes of Health (NIH) Grants P01 AG-18397 and M01 RR-00750. Genotyping services were provided by Center for Inherited Disease Research, which is fully funded through a federal contract from the NIH to the Johns Hopkins University (Contract HHSN268200782096C). This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. NR 30 TC 42 Z9 45 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2010 VL 95 IS 4 BP 1802 EP 1809 DI 10.1210/jc.2009-1903 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579UT UT WOS:000276402300039 PM 20164292 ER PT J AU Berger, VW Do, AC AF Berger, Vance W. Do, Anh-Chi TI Allocation concealment continues to be misunderstood SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter C1 [Berger, Vance W.; Do, Anh-Chi] NCI, Biometry Res Grp, Bethesda, MD 20892 USA. [Do, Anh-Chi] Coll New Jersey, Ewing, NJ USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 5 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2010 VL 63 IS 4 BP 468 EP 469 DI 10.1016/j.jclinepi.2009.09.004 PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 569ID UT WOS:000275588900017 PM 20004551 ER PT J AU Corpe, CP Tu, HB Eck, P Wang, J Faulhaber-Walter, R Schnermann, J Margolis, S Padayatty, S Sun, H Wang, Y Nussbaum, RL Espey, MG Levine, M AF Corpe, Christopher P. Tu, Hongbin Eck, Peter Wang, Jin Faulhaber-Walter, Robert Schnermann, Jurgen Margolis, Sam Padayatty, Sebastian Sun, He Wang, Yaohui Nussbaum, Robert L. Espey, Michael Graham Levine, Mark TI Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID L-ASCORBIC-ACID; RECOMMENDED DIETARY ALLOWANCE; DEHYDROASCORBIC ACID; PRETERM DELIVERY; GENE-EXPRESSION; GLUCURONIC ACID; KNOCKOUT MICE; PREECLAMPSIA; RISK; WOMEN AB Levels of the necessary nutrient vitamin C (ascorbate) are tightly regulated by intestinal absorption, tissue accumulation, and renal reabsorption and excretion. Ascorbate levels are controlled in part by regulation of transport through at least 2 sodium-dependent transporters: Slc23a1 and Slc23a2 (also known as Svct1 and Svct2, respectively). Previous work indicates that Slc23a2 is essential for viability in mice, but the roles of Slc23a1 for viability and in adult physiology have not been determined. To investigate the contributions of Slc23a1 to plasma and tissue ascorbate concentrations in vivo, we generated Slc23a1(-/-) mice. Compared with wild-type mice, Slc23a1(-/-) mice increased ascorbate fractional excretion up to 18-fold. Hepatic portal ascorbate accumulation was nearly abolished, whereas intestinal absorption was marginally affected. Both heterozygous and knockout pups born to Slc23a1(-/-) dams exhibited approximately 45% perinatal mortality, and this was associated with lower plasma ascorbate concentrations in dams and pups. Perinatal mortality of Slc23a1(-/-) pups born to Slc23a1(-/-) dams was prevented by ascorbate supplementation during pregnancy. Taken together, these data indicate that ascorbate provided by the dam influenced perinatal survival. Although Slc23a1-/- mice lost as much as 70% of their ascorbate body stores in urine daily, we observed an unanticipated compensatory increase in ascorbate synthesis. These findings indicate a key role for Slc23a1 in renal ascorbate absorption and perinatal survival and reveal regulation of vitamin C biosynthesis in mice. C1 [Corpe, Christopher P.; Tu, Hongbin; Eck, Peter; Wang, Jin; Margolis, Sam; Padayatty, Sebastian; Wang, Yaohui; Espey, Michael Graham; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Faulhaber-Walter, Robert; Schnermann, Jurgen] NIDDK, Kidney Dis Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, Div Med Genet, San Francisco, CA USA. [Sun, He] SunTech Res Inst, Rockville, MD USA. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, 10-4D52,MSC 1372,9000 Rockville Pike, Bethesda, MD 20892 USA. EM markL@mail.nih.gov RI WANG, Jin/A-8327-2012; Padayatty, Sebastian/A-8581-2012; OI WANG, Jin/0000-0002-0062-2489; Padayatty, Sebastian/0000-0001-8758-3170; Faulhaber-Walter, Robert/0000-0002-7769-9652; Eck, Peter/0000-0003-2371-9774 FU Intramural NIH HHS NR 56 TC 50 Z9 54 U1 0 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2010 VL 120 IS 4 BP 1069 EP 1083 DI 10.1172/JCI39191 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 577XU UT WOS:000276258100020 PM 20200446 ER PT J AU Park, SH Zhu, PP Parker, RL Blackstone, C AF Park, Seong H. Zhu, Peng-Peng Parker, Rell L. Blackstone, Craig TI Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CORTICAL ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; GTPASE ATLASTIN; MUTATIONS; SPG3A; LOCALIZATION; MECHANISMS; EXPRESSION; GROWTH; MORPHOGENESIS AB Hereditary spastic paraplegias (HSPs; SPG1-45) are inherited neurological disorders characterized by lower extremity spastic weakness. More than half of HSP cases result from autosomal dominant mutations in atlastin-1 (also known as SPG3A), receptor expression enhancing protein 1 (REEP1; SPG31), or spastin (SPG4). The atlastin-1 GTPase interacts with spastin, a microtubule-severing ATPase, as well as with the DP1/Yop1p and reticulon families of ER-shaping proteins, and SPG3A caused by atlastin-1 mutations has been linked pathogenically to abnormal ER morphology. Here we investigated SPG31 by analyzing the distribution, interactions, and functions of REEP1. We determined that REEP1 is structurally related to the DP1/Yop1p family of ER-shaping proteins and localizes to the ER in cultured rat cerebral cortical neurons, where it colocalizes with spastin and adastin-1. Upon overexpression in COS7 cells, REEP1 formed protein complexes with atlastin-1 and spastin within the tubular ER, and these interactions required hydrophobic hairpin domains in each of these proteins. REEP proteins were required for ER network formation in vitro, and REEP1 also bound microtubules and promoted ER alignment along the microtubule cytoskeleton in COS7 cells. A SPG31 mutant REEP1 lacking the C-terminal cytoplasmic region did not interact with microtubules and disrupted the ER network. These data indicate that the HSP proteins adastin-1, spastin, and REEP1 interact within the tubular ER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics. Thus, defects in tubular ER shaping and network interactions with the microtubule cytoskeleton seem to be the predominant pathogenic mechanism of HSP. C1 [Park, Seong H.; Zhu, Peng-Peng; Parker, Rell L.; Blackstone, Craig] NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Parker, Rell L.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bldg 35,Room 2C-913,9000 Rockville Pike, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU Howard Hughes Medical Institute-NIH; NINDS, NIH FX We thank J. Nagle and D. Kauffman (NINDS DNA Sequencing Facility) for DNA sequencing, J. Stadler for technical assistance, and T.A. Rapoport and Y. Shibata for valuable discussions and critical review of the manuscript. R.L. Parker was supported by the Howard Hughes Medical Institute-NIH Research Scholars Program. This research was supported by the Intramural Research Program of the NINDS, NIH. NR 55 TC 142 Z9 148 U1 4 U2 18 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2010 VL 120 IS 4 BP 1097 EP 1110 DI 10.1172/JCI40979 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 577XU UT WOS:000276258100022 PM 20200447 ER PT J AU Hsieh, MM Tisdale, JF Rodgers, GP Young, NS Trimble, EL Little, RF AF Hsieh, Matthew M. Tisdale, John F. Rodgers, Griffin P. Young, Neal S. Trimble, Edward L. Little, Richard F. TI Neutrophil Count in African Americans: Lowering the Target Cutoff to Initiate or Resume Chemotherapy? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BENIGN IDIOPATHIC NEUTROPENIA; STAGE BREAST-CANCER; COLONY-FORMING CELLS; WHITE BLOOD-CELL; ETHNIC NEUTROPENIA; CLINICAL-TRIALS; BONE-MARROW; RACIAL DISPARITIES; HEMOGLOBIN LEVELS; ACUTE-LEUKEMIA C1 [Hsieh, Matthew M.; Tisdale, John F.; Rodgers, Griffin P.] Natl Inst Diabet Digest & Kidney Dis, Mol & Clin Hematol Branch, NHLBI, Bethesda, MD USA. [Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Trimble, Edward L.; Little, Richard F.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Hsieh, MM (reprint author), Natl Inst Diabet Digest & Kidney Dis, Mol & Clin Hematol Branch, NHLBI, Bethesda, MD USA. NR 51 TC 18 Z9 19 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2010 VL 28 IS 10 BP 1633 EP 1637 DI 10.1200/JCO.2009.24.3881 PG 5 WC Oncology SC Oncology GA 576NS UT WOS:000276152200005 PM 20194862 ER PT J AU Mamounas, EP Tang, G Fisher, B Paik, S Shak, S Costantino, JP Watson, D Geyer, CE Wickerham, DL Wolmark, N AF Mamounas, Eleftherios P. Tang, Gong Fisher, Bernard Paik, Soonmyung Shak, Steven Costantino, Joseph P. Watson, Drew Geyer, Charles E., Jr. Wickerham, D. Lawrence Wolmark, Norman TI Association Between the 21-Gene Recurrence Score Assay and Risk of Locoregional Recurrence in Node-Negative, Estrogen Receptor-Positive Breast Cancer: Results From NSABP B-14 and NSABP B-20 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL ADJUVANT BREAST; RANDOMIZED CLINICAL-TRIALS; GENE-EXPRESSION; TAMOXIFEN; CHEMOTHERAPY; BENEFIT; MASTECTOMY; PREDICTION; SIGNATURE; PATTERNS AB Purpose The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). Patients and Methods RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. Results In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.3% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen-treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Conclusion Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer. J Clin Oncol 28: 1677-1683. (C) 2010 by American Society of Clinical Oncology C1 Operat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Mamounas, Eleftherios P.] Aultman Hlth Fdn, Canton, OH 44710 USA. Genom Hlth Inc, Redwood City, CA USA. RP Mamounas, EP (reprint author), Aultman Hlth Fdn, 2600 6th St SW, Canton, OH 44710 USA. EM tmamounas@aultman.com FU National Cancer Institute, Department of Health and Human Services [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651] FX Supported in part by Public Health Service Grants No. U10CA-12027, U10CA-69974, U10CA-37377, and U10CA-69651 from the National Cancer Institute, Department of Health and Human Services. NR 23 TC 202 Z9 212 U1 1 U2 10 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 APR 1 PY 2010 VL 28 IS 10 BP 1677 EP 1683 DI 10.1200/JCO.2009.23.7610 PG 7 WC Oncology SC Oncology GA 576NS UT WOS:000276152200012 PM 20065188 ER PT J AU Hawke, RL Schrieber, SJ Soule, TA Wen, ZM Smith, PC Reddy, KR Wahed, AS Belle, SH Afdhal, NH Navarro, VJ Berman, J Liu, QY Doo, E Fried, MW AF Hawke, Roy L. Schrieber, Sarah J. Soule, Tedi A. Wen, Zhiming Smith, Philip C. Reddy, K. Rajender Wahed, Abdus S. Belle, Steven H. Afdhal, Nezam H. Navarro, Victor J. Berman, Josh Liu, Qi-Ying Doo, Edward Fried, Michael W. CA SyNCH Trial Grp TI Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Silymarin; pharmacokinetics; flavonolignans; hepatitis C virus (HCV); milk thistle; botanical drug; herbal ID THISTLE SILYBUM-MARIANUM; NF-KAPPA-B; DOUBLE-BLIND; LIVER-DISEASE; COMPARATIVE BIOAVAILABILITY; ALTERNATIVE MEDICINE; PLUS RIBAVIRIN; TRIAL; PHARMACOKINETICS; CIRRHOSIS AB Silymarin, derived from the milk thistle plant Silybum marianum, is widely used for self-treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose-exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well-compensated, chronic noncirrhotic HCV who failed interferon-based therapy were randomized 3: 1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg silymarin were administered every 8 hours for 7 days. Steady-state exposures for silybin A and silybin B increased 11-fold and 38-fold, respectively, with a 5-fold increase in dose, suggesting nonlinear pharmacokinetics. No drug-related adverse events were reported, and no clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg. C1 [Hawke, Roy L.; Schrieber, Sarah J.; Soule, Tedi A.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27599 USA. [Wen, Zhiming; Smith, Philip C.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA. [Fried, Michael W.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. [Reddy, K. Rajender] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Wahed, Abdus S.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Belle, Steven H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Afdhal, Nezam H.] Beth Israel Deaconess Med Ctr, Ctr Liver, Boston, MA 02215 USA. [Navarro, Victor J.] Thomas Jefferson Univ, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. [Berman, Josh; Liu, Qi-Ying] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Doo, Edward] NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hawke, RL (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, CB 7360,Kerr Hall Rm 3310, Chapel Hill, NC 27599 USA. EM rhawke@email.unc.edu OI Wahed, Abdus/0000-0001-6911-7221 FU NCCAM and NIDDK [UO1 AT003571-01, UO1 AT003560-01, UO1 AT003573-01, UO1 AT003566-01, UO1 AT003574-01]; Division of Research Resources [RR00046]; Rottapharm | Madaus, Italy FX This research was supported from the following sources: National Institutes of Health Grants jointly funded by NCCAM and NIDDK; UO1 AT003571-01 (Beth Israel Deaconess Medical Center), UO1 AT003560-01 (University of North Carolina at Chapel Hill), UO1 AT003573-01 (University of Pennsylvania), UO1 AT003566-01 (University of Pittsburgh), and UO1 AT003574-01 (Thomas Jefferson University); and RR00046 from the General Clinical Research Centers program of the Division of Research Resources. In addition, Rottapharm | Madaus, Italy, provided silymarin and placebo and partly funded the trial. NR 41 TC 52 Z9 53 U1 4 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2010 VL 50 IS 4 BP 434 EP 449 DI 10.1177/0091270009347475 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 570OI UT WOS:000275687200008 PM 19841158 ER PT J AU Vogelzangs, N Kritchevsky, SB Beekman, ATF Brenes, GA Newman, AB Satterfield, S Yaffe, K Harris, TB Penninx, BWJH AF Vogelzangs, Nicole Kritchevsky, Stephen B. Beekman, Aartjan T. F. Brenes, Gretchen A. Newman, Anne B. Satterfield, Suzanne Yaffe, Kristine Harris, Tamara B. Penninx, Brenda W. J. H. CA Hlth ABC Study TI Obesity and Onset of Significant Depressive Symptoms: Results From a Prospective Community-Based Cohort Study of Older Men and Women SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; BODY-COMPOSITION; HYPERCORTISOLEMIC DEPRESSION; SEX-DIFFERENCES; CES-D; HEALTH; RISK; POPULATION; WEIGHT; ADULTS AB Objective: Although several cross-sectional studies have linked obesity and depression, less is known about their longitudinal association and about the relative influence of obesity subtypes. We prospectively examined whether obesity (specifically, abdominal) increased the risk of onset of depression in a population-based sample of older persons. Method: Participants were 2,547 nondepressed, well-functioning white and black persons, aged 70-79 years, enrolled in the Health, Aging, and Body Composition Study, an ongoing prospective community-based cohort study. Baseline measurements were conducted between April 1997 and June 1998. Overall obesity was assessed by body mass index (BMI) and percent body fat (measured by dual energy x-ray absorptiometry), whereas abdominal obesity measures included waist circumference, sagittal diameter, and visceral fat (measured by computer tomography). Onset of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression 10-item score >= 10 at any annual follow-up over 5 years and/or new antidepressant medication use. Persistent depression was defined as depression at 2 consecutive follow-up visits. Results: Over 5 years, significant depressive symptoms emerged in 23.7% of initially nondepressed persons. In men, both overall (BMI: hazard ratio [HR] per SD increase = 1.20; 95% CI, 1.03-1.40) and abdominal obesity (visceral fat: HR per SD increase = 1.19; 95% CI, 1.07-1.33) predicted onset of depressive symptoms after adjustment for sociodemographics. When BMI and visceral fat were adjusted for each other, only visceral fat was significantly associated with depression onset (HR = 1.18; 95% CI, 1.04-1.34). Stronger associations were found for persistent depressive symptoms. No associations were found in women. Conclusion: This study shows that obesity, in particular visceral fat, increases the risk of onset of significant depressive symptoms in men. These results suggest that specific mechanisms might relate visceral fat to the onset of depression. J Clin Psychiatry 2010;71(4):391-399 (C) Copyright 2009 Physicians Postgraduate Press, Inc. C1 [Vogelzangs, Nicole; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands. [Vogelzangs, Nicole; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 HL Amsterdam, Netherlands. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Brenes, Gretchen A.] Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27109 USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Satterfield, Suzanne] Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Vogelzangs, N (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Psychiat, AJ Ernststr 887, NL-1081 HL Amsterdam, Netherlands. EM n.vogelzangs@ggzingeest.nl RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health, NIA; National Heart, Lung, and Blood Institute (NHLBI) [R01-HL72972-01]; Young Academy of the Royal Netherlands Academy of Arts and Science FX This work was supported by National Institute on Aging (NIA) contract numbers N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and in part by the Intramural Research Program of the National Institutes of Health, NIA. Data analyses were supported by grant R01-HL72972-01 from the National Heart, Lung, and Blood Institute (NHLBI). The work of Ms Vogelzangs was supported by a travel grant from the Young Academy of the Royal Netherlands Academy of Arts and Science. NR 37 TC 75 Z9 75 U1 2 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2010 VL 71 IS 4 BP 391 EP 399 DI 10.4088/JCP.08m04743blu PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 588HI UT WOS:000277059300003 PM 20021992 ER PT J AU Owen, JE Boxley, L Goldstein, MS Lee, JH Breen, N Rowland, JH AF Owen, Jason E. Boxley, Laura Goldstein, Michael S. Lee, Jennifer H. Breen, Nancy Rowland, Julia H. TI Use of Health-Related Online Support Groups: Population Data from the California Health Interview Survey Complementary and Alternative Medicine Study SO JOURNAL OF COMPUTER-MEDIATED COMMUNICATION LA English DT Article DE internet; online; support; adult; survivorship ID RANDOMIZED CONTROLLED-TRIAL; SOCIAL SUPPORT; BREAST-CANCER; SELF-MANAGEMENT; EMOTIONAL EXPRESSION; UNITED-STATES; INTERNET; INFORMATION; COMMUNICATION; WOMEN AB OBJECTIVE: The purpose of this study was to evaluate the prevalence of online support group (OSG) use by those with chronic health problems and to identify characteristics associated with use of OSGs and face-to-face groups. METHODS: 6, 795 Californians living with chronic health problems were asked to describe OSG use, face-to-face support group use, and frequency/perceived benefit of support group use. RESULTS: 16% had used a face-to-face group for health, and 1.8% reported having used an OSG. OSG use was associated with depression/anxiety (OR = 3.51), stroke (OR = 3.03), diabetes (OR = 2.96), cancer (OR = 2.86), and arthritis (OR = 2.52). Use of OSGs was also associated with greater education (OR = 12.2), higher income (OR = 3.1), use of complementary/alternative therapies (OR = 5.2), and worse health status (OR = 3.1). Those with asthma (OR = 0.4), over age 65 (OR = 0.2), and Latinos (OR = 0.2) were less likely to use OSGs. CONCLUSION: Prevalence of use of OSGs for those with chronic health conditions is low, but internet-based health-related services have potential to increase the reach of support services for those living with chronic conditions. C1 [Owen, Jason E.; Boxley, Laura] Loma Linda Univ, Dept Psychol, Loma Linda, CA 92350 USA. [Goldstein, Michael S.] Univ Calif Los Angeles, Ctr Hlth Policy Res, Los Angeles, CA 90024 USA. [Breen, Nancy] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Rowland, Julia H.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. RP Owen, JE (reprint author), Loma Linda Univ, Dept Psychol, 11130 Anderson St, Loma Linda, CA 92350 USA. EM jowen@llu.edu NR 55 TC 16 Z9 16 U1 0 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-6101 J9 J COMPUT-MEDIAT COMM JI J. Comput.-Mediat. Commun. PD APR PY 2010 VL 15 IS 3 BP 427 EP 446 DI 10.1111/j.1083-6101.2010.01501.x PG 20 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 595PJ UT WOS:000277623800005 ER PT J AU Magro, A Swarz, J Ousley, A AF Magro, Adriane Swarz, Jeffrey Ousley, Anita TI CancerSPACE: An Interactive E-learning Tool Aimed to Improve Cancer Screening Rates SO JOURNAL OF COMPUTER-MEDIATED COMMUNICATION LA English DT Article ID HEALTH-CARE; EDUCATION; SIMULATION AB Cancer is the second leading cause of death in the United States today. Due to advances in new medical technology, screening devices for many cancers including breast, cervical, and colon cancers, are drastically reducing mortality rates. These technologies are able to detect cancer early, allowing for earlier treatment and a better survival rate. Unfortunately, many people, especially those in low socioeconomic groups, those without health insurance, and minority groups have very low cancer screening rates. As a result of not being screened, these populations face higher rates of cancer. One way to improve cancer screening rates in low income and minority populations is to target the healthcare staff which works with them. CancerSPACE (Simulated Practice and Collaborative Education) is aimed to improve cancer screening education among healthcare professionals in a virtual, interactive, easy to use online simulation presented in a game format. Simulated education, such as this, can be used on an individual basis at times and locations which are convenient for staff members. It also helps the user to retain information, stay engaged with the task at hand, and learn how to apply the information presented into a real clinical environment. C1 [Magro, Adriane; Swarz, Jeffrey; Ousley, Anita] NCI, Bethesda, MD 20892 USA. RP Magro, A (reprint author), NCI, Bethesda, MD 20892 USA. EM magroa@mail.nih.gov NR 25 TC 2 Z9 2 U1 2 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-6101 J9 J COMPUT-MEDIAT COMM JI J. Comput.-Mediat. Commun. PD APR PY 2010 VL 15 IS 3 BP 482 EP 499 DI 10.1111/j.1083-6101.2010.01512.x PG 18 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 595PJ UT WOS:000277623800008 ER PT J AU Park, E Levis, WK Greig, N Jung, ES Schuller-Levis, G AF Park, Eunkyue Levis, William K. Greig, Nigel Jung, Euisun Schuller-Levis, Georgia TI Effect of Thalidomide on Nitric Oxide Production in Lipopolysaccharide-activated RAW 264.7 Cells SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TNF-ALPHA; EXACERBATION; INFLAMMATION; ENDOTOXEMIA; INHIBITION; EXPRESSION; PSORIASIS; SYNTHASE; RATS AB Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 (T helper 1) immunity measured by increased IL-2 (Interleukin-2) and gamma interferon. The authors have assessed the effect of thalidomide and analogues, di- and tri-thiothalidomide, on a lipopolysaccharide (LPS) activated macrophage cell line (RAW 246.7 cells). The authors' findings showed that nitric oxide (NO) was significantly inhibited by thalidomide (15%) and its analogues (di-thiothalidomide; 15%, tri-thiothalidomide; 32%). The proinflammatory molecules TNF-alpha (tumor necrosis factor-alpha) and IL-6 were not significantly inhibited. Pretreatment with thalidomide and analogues before activation was not different from simultaneous treatment. Inhibition of inducible nitric oxide synthase (iNOS) may prove to be an important target for the anti-inflammatory and anti-cancer effects of thalidomide and related immunomodulatory drugs (IMiDs). C1 [Park, Eunkyue; Jung, Euisun; Schuller-Levis, Georgia] New York State Inst Basic Res Dev Disabil, Dept Dev Neurobiol, Staten Isl, NY 10314 USA. [Levis, William K.] NYU, Dept Dermatol, New York, NY 10016 USA. [Greig, Nigel] NIA, Intramural Res Program, Neurosci Lab, Drug Design & Dev Sect, Baltimore, MD 21224 USA. RP Park, E (reprint author), New York State Inst Basic Res Dev Disabil, Dept Dev Neurobiol, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. EM parkek@omr.state.ny.us FU New York State Institute for Basic Research in Developmental Disabilities; National Institute on Aging, NIH FX The described research was supported in part by the New York State Institute for Basic Research in Developmental Disabilities and the Intramural Research Program, National Institute on Aging, NIH. NR 27 TC 5 Z9 5 U1 1 U2 2 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD APR PY 2010 VL 9 IS 4 BP 330 EP 333 PG 4 WC Dermatology SC Dermatology GA 595MX UT WOS:000277615900004 PM 20514789 ER PT J AU El-Serag, H McGlynn, KA Graham, GN So, S Howell, CD Fang, T Anderson, JT Thiel, TK AF El-Serag, Hashem McGlynn, Katherine A. Graham, Garth N. So, Samuel Howell, Charles D. Fang, Ted Anderson, Janelle Tangonan Thiel, Thelma King TI Achieving health equity to eliminate racial, ethnic, and socioeconomic disparities in HBV- and HCV-associated liver disease SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID HEPATITIS-C-VIRUS; UNITED-STATES; HEPATOCELLULAR-CARCINOMA; AFRICAN-AMERICAN; ASIAN-AMERICANS; B-VIRUS; INFECTION; TRANSPLANTATION; SURVIVAL; PROGRAM C1 [El-Serag, Hashem] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Graham, Garth N.] Dept Hlth & Human Serv, Minor Hlth Off Minor Hlth, Rockville, MD USA. [So, Samuel] Asian Liver Ctr, Stanford, CA USA. [So, Samuel] Liver Canc Program, Stanford, CA USA. [So, Samuel] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Howell, Charles D.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Fang, Ted] Asian Week Fdn, San Francisco, CA USA. [Fang, Ted] San Francisco Hep B Free, San Francisco, CA USA. [Anderson, Janelle Tangonan] Focus Asian Americans & Pacific Islanders, Natl Task Force Hepatitis B, St Paul, MN USA. [Thiel, Thelma King] Hepatitis Fdn Int, Silver Spring, MD USA. RP El-Serag, H (reprint author), Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. FU Intramural NIH HHS [ZIA CP010158-13] NR 33 TC 5 Z9 5 U1 1 U2 4 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2010 VL 59 IS 4 SU S BP S37 EP S42 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 796XH UT WOS:000293086300006 PM 20398589 ER PT J AU Peters, MG Perrillo, RP Jacobson, IM Ross, DB Doo, EC Murray, JS Wong, JB AF Peters, Marion G. Perrillo, Robert P. Jacobson, Ira M. Ross, David B. Doo, Edward C. Murray, Jeffrey S. Wong, John B. TI Entering the new era of therapy for HBV and HCV infections SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; PLUS RIBAVIRIN; PEGYLATED INTERFERON; ANTIVIRAL TREATMENT; GENOTYPE 1; PEGINTERFERON; MANAGEMENT; MORTALITY C1 [Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Perrillo, Robert P.] Baylor Reg Transplant Inst, Dallas, TX USA. [Jacobson, Ira M.] Weill Cornell Med Coll, New York, NY USA. [Ross, David B.] Dept Vet Affairs, Washington, DC USA. [Doo, Edward C.] NIH, Bethesda, MD 20892 USA. [Murray, Jeffrey S.] US FDA, Silver Spring, MD USA. [Wong, John B.] Tufts Med Ctr, Boston, MA USA. RP Peters, MG (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. FU Genentech; Anadys; Boehringer Ingelheim; Gilead Sciences Inc.; GlobeImmune, Inc; Human Genome Sciences; Idenix; Intarcia; Merck; Novartis; Pharmasset; Roche Pharmaceuticals; Romark; Schering-Plough; Tibotec; Valeant; Vertex Pharmaceuticals FX Dr Peters reports the following: Consultant: Clinical Care Options, Genentech, Pharmasset. Salary: Dr Peters' spouse receives a salary from Genentech; Dr Jacobson reports the following: Consultant: Abbott, Anadys, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences Inc., GlobeImmune, Inc, Human Genome Sciences, Idenix, Intermune, Merck, Novartis, Pfizer, Pharmasset, Progenics, Roche Pharmaceuticals, Sanofi-Aventis, Schering-Plough, Tibotec, Vertex Pharmaceuticals, Virochem, Zymogenetics. Grant/Research Support: Anadys, Boehringer Ingelheim, Gilead Sciences Inc., GlobeImmune, Inc, Human Genome Sciences, Idenix, Intarcia, Merck, Novartis, Pharmasset, Roche Pharmaceuticals, Romark, Schering-Plough, Tibotec, Valeant, Vertex Pharmaceuticals. Speakers Bureau: Bristol-Myers Squibb, Gilead Sciences Inc., Novartis, Schering-Plough NR 57 TC 1 Z9 1 U1 0 U2 1 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2010 VL 59 IS 4 SU S BP S51 EP S57 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 796XH UT WOS:000293086300008 PM 20398591 ER PT J AU Thomas, DL Di Bisceglie, AM Alter, HJ Terrault, NA AF Thomas, David L. Di Bisceglie, Adrian M. Alter, Harvey J. Terrault, Norah A. TI Understanding the natural history of chronic HBV and HCV infections SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID HEPATITIS-B-VIRUS; C-VIRUS; HEPATOCELLULAR-CARCINOMA; FIBROSIS PROGRESSION; MANAGEMENT; CIRRHOSIS; RISK; PERSISTENCE; UPDATE; LEVEL C1 [Thomas, David L.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO USA. [Alter, Harvey J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Terrault, Norah A.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Thomas, DL (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. FU Bristol-Myers Squibb; Gilead Sciences Inc.; GlobeImmune, Inc; Idenix; Pharmasset; Roche Pharmaceuticals; Vertex Pharmaceuticals; Eisai; Human Genome Sciences FX Dr Di Bisceglie reports the following: Consultant: Abbott, Anadys, Bristol-Myers Squibb, GlobeImmune, Inc, Idenix, Novartis, Pharmasset, Roche Pharmaceuticals, Schering Plough, Vertex Pharmaceuticals. Grant/Research Support: Bristol-Myers Squibb, Gilead Sciences Inc., GlobeImmune, Inc, Idenix, Pharmasset, Roche Pharmaceuticals, Vertex Pharmaceuticals. Speakers Bureau: Novartis; Dr Terrault reports the following: Consultant: Bristol-Myers Squibb, Roche Pharmaceuticals, Schering-Plough, Siemens Diagnostics. Grant/Research Support: Eisai, Human Genome Sciences, Roche Pharmaceuticals, Vertex Pharmaceuticals NR 26 TC 1 Z9 1 U1 0 U2 0 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2010 VL 59 IS 4 SU S BP S17 EP S22 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 796XH UT WOS:000293086300003 PM 20398586 ER PT J AU Horwitz, BN Neiderhiser, JM Ganiban, JM Spotts, EL Lichtenstein, P Reiss, D AF Horwitz, Briana N. Neiderhiser, Jenae M. Ganiban, Jody M. Spotts, Erica L. Lichtenstein, Paul Reiss, David TI Genetic and Environmental Influences on Global Family Conflict SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE family conflict; heritable characteristics; TOSS; FES; multi-rater assessment ID BEHAVIOR; SPILLOVER AB This study examined genetic and environmental influences on global family conflict. The sample comprised 872 same-sex pairs of twin parents, their spouses/partners, and one adolescent child per twin from the Twin and Offspring Study in Sweden. The twins, spouses, and child each reported on the degree of family conflict, and there was significant agreement among the family members' ratings. These shared perspectives were explained by one common factor, indexing global family conflict. Genetic influences explained 36% of the variance in this common factor, suggesting that twins' heritable characteristics contribute to family conflict, via genotype-environment correlation. Nonshared environmental effects explained the remaining 64% of this variance, indicating that twins' unique childhood and/or current family experiences also play an important role. C1 [Horwitz, Briana N.; Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Ganiban, Jody M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Spotts, Erica L.] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. [Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. RP Neiderhiser, JM (reprint author), Penn State Univ, Dept Psychol, 111 Moore, University Pk, PA 16802 USA. EM jenaemn@psu.edu OI lichtenstein, paul/0000-0003-3037-5287 FU NIMH NIH HHS [R01 MH054610, R01 MH054610-05A1, R01MH54610] NR 20 TC 2 Z9 2 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD APR PY 2010 VL 24 IS 2 BP 217 EP 220 DI 10.1037/a0019064 PG 4 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 587CM UT WOS:000276965000014 PM 20438198 ER PT J AU Locatis, C Williamson, D Gould-Kabler, C Zone-Smith, L Detzler, I Roberson, J Maisiak, R Ackerman, M AF Locatis, Craig Williamson, Deborah Gould-Kabler, Carrie Zone-Smith, Laurie Detzler, Isabel Roberson, Jason Maisiak, Richard Ackerman, Michael TI Comparing In-Person, Video, and Telephonic Medical Interpretation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE telephonic; in-person; video; medical interpretation ID PATIENT SATISFACTION; SPANISH INTERPRETATION; SPEAKING PATIENTS; CONTROLLED-TRIAL; CARE; IMPACT; ENCOUNTERS; SERVICES; QUALITY AB Using trained interpreters to provide medical interpretation services is superior to services provided on an ad hoc basis, but little is known about the effectiveness of providing their services remotely, especially using video. To compare remote medical interpretation services by trained interpreters via telephone and videoconference to those provided in-person. Quasi-randomized control study. Two hundred and forty-one Spanish speaking patient volunteers, twenty-four health providers, and seven interpreters. Patients, providers and interpreters each independently completed scales evaluating the quality of clinical encounters and, optionally, made free text comments. Interviews were conducted with 23 of the providers, the seven interpreters, and a subset of 30 patients. Time data were collected. Encounters with in-person interpretation were rated significantly higher by providers and interpreters, while patients rated all methods the same. There were no significant differences in provider and interpreter ratings of remote methods. Provider and interpreter comments on scales and interview data support the higher in-person ratings, but they also showed a distinct preference for video over the phone. Phone interviews were significantly shorter than in-person. Patients rated interpretation services highly no matter how they were provided but experienced only the method employed at the time of the encounter. Providers and interpreters were exposed to all three methods, were more critical of remote methods, and preferred videoconferencing to the telephone as a remote method. The significantly shorter phone interviews raise questions about the prospects of miscommunication in telephonic interpretation, given the absence of a visual channel, but other factors might have affected time results. Since the patient population studied was Hispanic and predominantly female care must be taken in generalizing these results to other populations. C1 [Locatis, Craig; Ackerman, Michael] Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. [Williamson, Deborah; Zone-Smith, Laurie; Detzler, Isabel] Med Univ S Carolina, Charleston, SC 29425 USA. [Gould-Kabler, Carrie] Ctr Publ Serv Commun, Arlington, VA USA. [Roberson, Jason] Pacific Interpreters, Portland, OR USA. [Maisiak, Richard] Maisiak Associates, Scottsdale, AZ USA. RP Locatis, C (reprint author), Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. EM locatis@nlm.nih.gov FU National Institutes of Health [HHSN276200700281P, HHSN276200700292P] FX This work was supported by the National Institutes of Health intramural research program and by NIH contracts, HHSN276200700281P and HHSN276200700292P. NR 23 TC 23 Z9 23 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2010 VL 25 IS 4 BP 345 EP 350 DI 10.1007/s11606-009-1236-x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 571TS UT WOS:000275779300013 PM 20107916 ER PT J AU Hobday, JV Savik, K Smith, S Gaugler, JE AF Hobday, John V. Savik, Kay Smith, Stan Gaugler, Joseph E. TI Feasibility of Internet Training for Care Staff of Residents with Dementia The CARES Program SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID NURSING-HOME AB This study evaluated an Internet-based training module, CARES* (Connect with the resident; Assess behavior; Respond appropriately; Evaluate what works; Share with the team), to determine its feasibility for certified nursing assistants (CNAs) in three nursing homes and one assisted living facility. Pre- and posttest questionnaires were administered to 40 CNAs to determine improvements in dementia care knowledge and perceptions of competence in dementia care. Dementia care knowledge improved significantly after CARES training. More than 85% of the sample agreed or strongly agreed that the CARES protocol improved mastery, improved care competency, and reduced stress related to care of residents with dementia. Open-ended feedback indicated that CARES provided CNAs with new information and skills pertaining to dementia care. The results suggest that Internet-based programs such as CARES represent time- and cost-efficient methods to deliver dementia care training in long-term care settings. C1 [Gaugler, Joseph E.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Gaugler, Joseph E.] Hlth Care Interact Inc, CARES Training Protocol, Edina, MN USA. [Savik, Kay] NIA, Bethesda, MD 20892 USA. RP Gaugler, JE (reprint author), Univ Minnesota, Sch Nursing, 308 Harvard St SE, Minneapolis, MN 55455 USA. EM gaug0015@umn.edu FU NIA NIH HHS [1R43AG023451-01, R43 AG023451, R43 AG023451-01] NR 9 TC 14 Z9 14 U1 0 U2 14 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD APR PY 2010 VL 36 IS 4 BP 13 EP 21 DI 10.3928/00989134-20100302-01 PG 9 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 583WV UT WOS:000276711900008 PM 20349855 ER PT J AU Montasser, ME Shimmin, LC Gu, DF Chen, J Gu, C Kelly, TN Jaquish, CE Rice, T Rao, DC Cao, J Chen, JC Liu, DP Whelton, P He, J Hixson, JE AF Montasser, May E. Shimmin, Lawrence C. Gu, Donfeng Chen, Jing Gu, Charles Kelly, Tanika N. Jaquish, Cashell E. Rice, Treva Rao, D. C. Cao, Jie Chen, Jichun Liu, De-Pei Whelton, Paul He, Jiang Hixson, James E. TI Blood pressure response to potassium supplementation is associated with genetic variation in endothelin 1 and interactions with E selectin in rural Chinese SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure response; dietary intervention; gene-by-gene interaction; genetic association; hypertension; potassium ID ESSENTIAL-HYPERTENSION; POLYMORPHISMS; POPULATION; DISEASE; SODIUM; METAANALYSIS; VOLUNTEERS; PREVENTION; CHLORIDE; PROGRAM AB Objective Although beneficial effects of potassium intake on blood pressure (BP) are well established, little is known about genetic factors that underlie interindividual variability in BP response to dietary potassium. In a previous study, we reported the first evidence for significant heritabilities for BP response in a dietary intervention study in rural Chinese. In this report, we extend our genetic studies to examine associations with polymorphisms in genes in vascular endothelial pathways. Methods We genotyped study participants for 23 single nucleotide polymorphisms (SNPs) in endothelin 1 (EDN1), nitric oxide synthase 3, and E selectin (SELE). We tested 17 of these SNPs for associations with BP response to potassium supplementation in 1843 participants. Association tests used population-based [generalized estimation equation (GEE)] and family-based (quantitative transmission disequilibrium test) methods, as well as tests for gene-by-gene (GxG) interaction (generalized multifactor dimensionalilty reduction and GEE). Results Single SNP analysis identified significant associations for several SNPs in EDN1 with multiple measures of BP response to potassium supplementation. The cumulative effects of the minor EDN1 alleles that showed significant associations were to reduce measures of BP response by 0.5-0.9 mmHg. We found significant evidence for effects of GxG interactions between EDN1 and SELE, even in the absence of individual associations with SELE variants. Conclusion Our results implicate variability in EDN1 and SELE as genetic factors that influence BP response to potassium intake. Although such epidemiological studies do not allow direct determination of physiologic mechanisms, our findings of joint effects identify EDN1 and SELE as targets for functional studies to determine their interactions in BP response to potassium intake. J Hypertens 28:748-755 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Montasser, May E.; Shimmin, Lawrence C.; Hixson, James E.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. [Gu, Donfeng; Cao, Jie; Chen, Jichun] Chinese Acad Med Sci, Fu Wai Hosp, Beijing 100037, Peoples R China. [Gu, Donfeng; Cao, Jie; Chen, Jichun] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China. [Chen, Jing] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Gu, Charles; Rice, Treva; Rao, D. C.] Washington Univ, Sch Med, St Louis, MO USA. [Kelly, Tanika N.; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Jaquish, Cashell E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Liu, De-Pei] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China. [Whelton, Paul] Loyola Univ Hlth Syst, Chicago, IL USA. RP Hixson, JE (reprint author), UT Houston Sch Publ Hlth, 1200 Hermann Pressler, Houston, TX 77030 USA. EM James.E.Hixson@uth.tmc.edu RI Gu, Charles/A-7934-2010 OI Gu, Charles/0000-0002-8527-8145 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [U01HL072507] FX The study was supported by the NIH grant U01HL072507. Upsher-Smith Laboratories, Inc. provided potassium tablets.; This report is from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study that is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (U01HL072507). Upsher-Smith Laboratories Inc. has provided Klor-Con M20 potassium tablets for the GenSalt study. NR 43 TC 9 Z9 9 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD APR PY 2010 VL 28 IS 4 BP 748 EP 755 DI 10.1097/HJH.0b013e3283355672 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 571CQ UT WOS:000275729300020 PM 19996987 ER PT J AU Zhao, Q Hixson, JE Rao, DC Gu, DF Jaquish, CE Rice, T Shimmin, LC Chen, JC Cao, J Kelly, TN Hamm, LL He, J AF Zhao, Qi Hixson, James E. Rao, Dabeeru C. Gu, Dongfeng Jaquish, Cashell E. Rice, Treva Shimmin, Lawrence C. Chen, Jichun Cao, Jie Kelly, Tanika N. Hamm, Lotuce Lee He, Jiang TI Genetic variants in the apelin system and blood pressure responses to dietary sodium interventions: a family-based association study SO JOURNAL OF HYPERTENSION LA English DT Article DE ACE2; apelin; apelin receptor; blood pressure; dietary sodium; polymorphism; salt sensitivity ID GENOME-WIDE ASSOCIATION; SALT-SENSITIVITY; BLACK-AMERICANS; CONSCIOUS RATS; IN-VIVO; RECEPTOR; HYPERTENSION; LINKAGE; APJ; CHINESE AB Objective We examined the association between genetic variants in the apelin system and blood pressure (BP) responses to low-sodium and high-sodium interventions in the GenSalt Study. Methods A 7-day low-sodium intervention (51.3 mmol sodium per day) followed by a 7-day high-sodium intervention (307.8 mmol sodium per day) was conducted among 1906 participants from 637 Han Chinese families. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer. Twenty-three single nucleotide polymorphisms (SNPs), including both tag and functional SNPs, were selected from three candidate genes (APLN, APLNR, and ACE2). Single marker and haplotype analyses were conducted using the Family Based Association Test program. The false discovery rate method was used to correct for multiple testing. Results SNPs rs2282623 and rs746886 of the APLNR gene were significantly associated with DBP (both P=0.002) and mean arterial pressure (MAP) (P=0.001 and 0.005, respectively) responses to low-sodium intervention. Six SNPs of the ACE2 gene were significantly associated with SBP, DBP, or MAP responses to low-sodium intervention. Three of them, rs1514283, rs1514282, and rs4646176, were also significantly associated with MAP response to high-sodium intervention (all P <= 0.006). Haplotype analysis indicated the A-T-T haplotype of APLNR SNPs rs721608-rs2282623-rs746886 was associated with decreased DBP and MAP responses to low-sodium intervention (P=0.001 and 0.003, respectively), whereas G-C-C was associated with increased SBP and MAP responses to high-sodium intervention (P=0.004 and 0.01, respectively). Conclusion This large family-based study indicates that genetic variants in the APLNR and ACE2 genes are significantly associated with BP responses to dietary sodium intervention. J Hypertens 28:756-763 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Zhao, Qi; Kelly, Tanika N.; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. [Hixson, James E.; Shimmin, Lawrence C.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol, Houston, TX USA. [Rao, Dabeeru C.; Rice, Treva] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Gu, Dongfeng; Chen, Jichun; Cao, Jie] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China. [Gu, Dongfeng; Chen, Jichun; Cao, Jie] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China. [Gu, Dongfeng; Chen, Jichun; Cao, Jie] Peking Union Med Coll, Beijing 100021, Peoples R China. [Gu, Dongfeng; Chen, Jichun; Cao, Jie] Chinese Natl Ctr Cardiovasc Dis, Beijing, Peoples R China. [Jaquish, Cashell E.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Hamm, Lotuce Lee] Tulane Univ, Sch Med, Dept Internal Med, New Orleans, LA 70112 USA. RP Zhao, Q (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,SL18, New Orleans, LA 70112 USA. EM qizhao@tulane.edu FU NHLBI NIH HHS [R01 HL090682, R01 HL087263, R01 HL087263-04, R01 HL090682-03, R01HL087263, R01HL090682, U01 HL072507, U01 HL072507-06, U01HL072507] NR 35 TC 24 Z9 25 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD APR PY 2010 VL 28 IS 4 BP 756 EP 763 DI 10.1097/HJH.0b013e3283370d32 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 571CQ UT WOS:000275729300021 PM 20125035 ER PT J AU Mayer-Barber, KD Barber, DL Shenderov, K White, SD Wilson, MS Cheever, A Kugler, D Hieny, S Caspar, P Nunez, G Schlueter, D Flavell, RA Sutterwala, FS Sher, A AF Mayer-Barber, Katrin D. Barber, Daniel L. Shenderov, Kevin White, Sandra D. Wilson, Mark S. Cheever, Allen Kugler, David Hieny, Sara Caspar, Patricia Nunez, Gabriel Schlueter, Dirk Flavell, Richard A. Sutterwala, Fayyaz S. Sher, Alan TI Cutting Edge: Caspase-1 Independent IL-1 beta Production Is Critical for Host Resistance to Mycobacterium tuberculosis and Does Not Require TLR Signaling In Vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ADAPTIVE IMMUNITY; INNATE IMMUNITY; INFECTION; INFLAMMASOME; MICE; INTERLEUKIN-1-BETA; RECOGNITION; RESPONSES; CYTOKINE; RECEPTOR AB To investigate the respective contributions of TLR versus lL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIP MyD88, IL-1R1, and IL-1 beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1 beta signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1 beta expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1 beta maturation, showed unimpaired IL-1 beta production and importantly, were considerably less susceptible to infection than IL-1 beta deficierit mice. Together our findings reveal a major role for IL-1 beta in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1. The Journal of Immunology, 2010, 184: 3326-3330. C1 [Mayer-Barber, Katrin D.; Barber, Daniel L.; Shenderov, Kevin; White, Sandra D.; Cheever, Allen; Kugler, David; Hieny, Sara; Caspar, Patricia; Sher, Alan] NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. [Wilson, Mark S.] NIAID, Parasit Dis Lab, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA. [Nunez, Gabriel] Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA. [Schlueter, Dirk] Otto von Guericke Univ, Inst Med Mikrobiol, Magdeburg, Germany. [Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. [Sutterwala, Fayyaz S.] Univ Iowa, Div Infect Dis, Dept Internal Med, Iowa City, IA 52242 USA. RP Mayer-Barber, KD (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bldg 50-6146,50 South Dr, Bethesda, MD 20892 USA. EM rnayerk@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. R.A.F. is an Investigator of the Howard Hughes Medical Institute. NR 26 TC 205 Z9 206 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 3326 EP 3330 DI 10.4049/jimmunol.0904189 PG 5 WC Immunology SC Immunology GA 573PV UT WOS:000275927600005 PM 20200276 ER PT J AU Chen, KQ Le, YY Liu, Y Gong, WH Ying, GG Huang, J Yoshimura, T Tessarollo, L Wang, JM AF Chen, Keqiang Le, Yingying Liu, Ying Gong, Wanghua Ying, Guoguang Huang, Jian Yoshimura, Teizo Tessarollo, Lino Wang, Ji Ming TI Cutting Edge: A Critical Role for the G Protein-Coupled Receptor mFPR2 in Airway Inflammation and Immune Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID N-FORMYLPEPTIDE RECEPTOR; DENDRITIC CELLS; LIPOXIN A(4); PEPTIDE; ACTIVATION; INDUCTION; ANTIGEN; ASTHMA; FPRL2 AB The formylpeptide receptor-like 1, now officially termed FPR2, in human and its mouse homolog mFPR2 mediate leukocyte migration in response to agonists associated with inflammation and immune responses. To clarify the in vivo role of the receptor, we generated mice deficient in mFPR2. mFPR2(-/-) mice showed markedly reduced severity in OVA/alum-induced allergic airway inflammation. This was associated with diminished recruitment of CD11c(+) dendritic cells into the airway mucosa and secondary lymphoid organs, as well as reduced production of Type 2 cytokines and Igs. We also found that the bronchoalveolar lavage fluid from wild type mice with airway inflammation contained mFPR2 agonist activity. This study reveals a critical role for mFPR2 in the progression of allergic airway inflammation and immune responses. The Journal of Immunology, 2010, 184: 3331-3335. C1 [Chen, Keqiang; Liu, Ying; Huang, Jian; Yoshimura, Teizo; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Gong, Wanghua] Sci Applicat Int Corp, Frederick, MD 21702 USA. [Chen, Keqiang] Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai, Peoples R China. [Le, Yingying] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. [Ying, Guoguang] Tianjin Med Univ, Canc Res Inst & Hosp, Tianjin, Peoples R China. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Bldg 560,Room 31-76, Frederick, MD 21702 USA. EM wangji@mail.nih.gov FU National Cancer Institute and National Institutes of Health [HHSN261200800001E]; National Cancer Institute; National Institutes of Health; National Basic Research Program of China [2010CB529701] FX This work was supported in part by federal funds from the National Cancer Institute and National Institutes of Health under Contract No. HHSN261200800001E and by the Intramural Research Program of the National Cancer Institute and National Institutes of Health. Y.L. was supported by Grant 2010CB529701 from the National Basic Research Program of China. NR 22 TC 54 Z9 55 U1 1 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 3331 EP 3335 DI 10.4049/jimmunol.0903022 PG 5 WC Immunology SC Immunology GA 573PV UT WOS:000275927600006 PM 20200280 ER PT J AU Thornton, AM Korty, PE Tran, DQ Wohlfert, EA Murray, PE Belkaid, Y Shevach, EM AF Thornton, Angela M. Korty, Patricia E. Tran, Dat Q. Wohlfert, Elizabeth A. Murray, Patrick E. Belkaid, Yasmine Shevach, Ethan M. TI Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3(+) T Regulatory Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TGF-BETA; IN-VIVO; GENE; ACTIVATION; GENERATION; INDUCTION; ABSENCE; SELF; LYMPHOCYTES; ENTEROPATHY AB Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4(+)CD8(-)Foxp3(+) thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation (similar to 70%) of Foxp3(+) T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-beta expressed Helios. Ag-specific Foxp3(+) T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3(+) Treg cells are generated extrathymically. The Journal of Immunology, 2010, 184: 3433-3441. C1 [Thornton, Angela M.; Korty, Patricia E.; Tran, Dat Q.; Murray, Patrick E.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wohlfert, Elizabeth A.; Belkaid, Yasmine] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Room 11N315,Bldg 10, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by funds from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 46 TC 579 Z9 594 U1 1 U2 30 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 3433 EP 3441 DI 10.4049/jimmunol.0904028 PG 9 WC Immunology SC Immunology GA 573PV UT WOS:000275927600020 PM 20181882 ER PT J AU Rosenblum, JM Shimoda, N Schenk, AD Zhang, H Kish, DD Keslar, K Farber, JM Fairchild, RL AF Rosenblum, Joshua M. Shimoda, Naohiko Schenk, Austin D. Zhang, Howard Kish, Danielle D. Keslar, Karen Farber, Joshua M. Fairchild, Robert L. TI CXC Chemokine Ligand (CXCL) 9 and CXCL10 Are Antagonistic Costimulation Molecules during the Priming of Alloreactive T Cell Effectors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CARDIAC ALLOGRAFT-REJECTION; RECEPTOR-GENE-EXPRESSION; IFN-GAMMA; IN-VIVO; MICE; INFLAMMATION; RESPONSES; IP-10; VASCULOPATHY; LYMPHOCYTES AB Donor Ag-reactive CD4 and CD8 T cell production of IFN-gamma is a principal effector mechanism promoting tissue injury during allograft rejection. The CXCR3-binding chemokines CXCL9 and CXCL10 recruit donor-reactive T cells to the allograft, but their role during the priming of donor-reactive T cells to effector function is unknown. Using a murine model of MHC-mismatched cardiac transplantation, we investigated the influence of CXCL9 and CXCL10 during donor-reactive T cell priming. In allograft recipient spleens, CXCL9 and CXCL10 were expressed as early as 24 h posttransplant and increased with similar kinetics, concurrently with CXCR3 expression on T cells. CXCL9, but not CXCL10, expression required NK cell production of IFN-gamma. The absence of CXCL9 in donor allografts, recipients, or both significantly decreased the frequency of donor-reactive CD8 T cells producing IFN-gamma and increased the frequency of donor-reactive CD8 T cells producing IL-17A. In contrast, the absence of CXCL10 increased the frequency of IFN-gamma-producing CD8 T cells in a CXCL9-dependent manner. These data provide novel evidence that donor-reactive CD8 T cells use the CXCR3 chemokine axis as a costimulation pathway during priming to allografts where CXCL9 promotes the development of IFN-gamma-producing CD8 T cells, and CXCL10 antagonizes this skewing. The Journal of Immunology, 2010, 184: 3450-3460. C1 [Rosenblum, Joshua M.; Schenk, Austin D.; Kish, Danielle D.; Keslar, Karen; Fairchild, Robert L.] Cleveland Clin Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. [Rosenblum, Joshua M.; Schenk, Austin D.; Fairchild, Robert L.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Shimoda, Naohiko] Hokkaido Univ, Sch Med, Dept Urol, Sapporo, Hokkaido 060, Japan. [Zhang, Howard; Farber, Joshua M.] NIAID, Inflammat Biol Sect, NIH, Bethesda, MD 20892 USA. RP Rosenblum, JM (reprint author), Cleveland Clin Lerner Res Inst, Dept Immunol, Mail Code NB30,9500 Euclid Ave, Cleveland, OH 44195 USA. EM jmr55@case.edu FU National Institutes of Health [RO1 AI51620, AI40459, T32 GM07250, F30 HL940052] FX This work was supported by National Institutes of Health Grants RO1 AI51620 and AI40459 (to R.L.F.). J.M.R. was supported in part by the Case Western Reserve University Medical Scientist Training Program (National Institutes of Health T32 GM07250) and an individual National Research Service Award (National Institutes of Health F30 HL940052). NR 54 TC 31 Z9 31 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 3450 EP 3460 DI 10.4049/jimmunol.0903831 PG 11 WC Immunology SC Immunology GA 573PV UT WOS:000275927600022 PM 20194716 ER PT J AU Madala, SK Pesce, JT Ramalingam, TR Wilson, MS Minnicozzi, S Cheever, AW Thompson, RW Mentink-Kane, MM Wynn, TA AF Madala, Satish K. Pesce, John T. Ramalingam, Thirumalai R. Wilson, Mark S. Minnicozzi, Samantha Cheever, Allen W. Thompson, Robert W. Mentink-Kane, Margaret M. Wynn, Thomas A. TI Matrix Metalloproteinase 12-Deficiency Augments Extracellular Matrix Degrading Metalloproteinases and Attenuates IL-13-Dependent Fibrosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; HEPATIC-FIBROSIS; SCHISTOSOMA-MANSONI; LIVER FIBROSIS; INFLAMMATION; IL-13; REVEAL; MICE; ACTIVATION; RESPONSES AB Infection with the parasitic helminth Schistosoma mansoni causes significant liver fibrosis and extracellular matrix (ECM) remodeling. Matrix metalloproteinases (MMP) are important regulators of the ECM by regulating cellular inflammation, extracellular matrix deposition, and tissue reorganization. MMP12 is a macrophage-secreted elastase that is highly induced in the liver and lung in response to S. mansoni eggs, confirmed by both DNA microarray and real-time PCR analysis. However, the function of MMP12 in chronic helminth-induced inflammation and fibrosis is unclear. In this study, we reveal that MMP12 acts as a potent inducer of inflammation and fibrosis after infection with the helminth parasite S. mansoni. Surprisingly, the reduction in liver and lung fibrosis in MMP12-deficient mice was not associated with significant changes in cytokine, chemokine, TGF-beta 1, or tissue inhibitors of matrix metalloproteinase expression. Instead, we observed marked increases in MMP2 and MMP13 expression, suggesting that Mmp12 was promoting fibrosis by limiting the expression of specific ECM-degrading MMPs. Interestingly, like MMP12, MMP13 expression was highly dependent on IL-13 and type II-IL-4 receptor signaling. However, in contrast to MMP12, expression of MMP13 was significantly suppressed by the endogenous IL-13 decoy receptor, IL-13R alpha 2. In the absence of MMP12, expression of IL-13R alpha 2 was significantly reduced, providing a possible explanation for the increased IL-13-driven MMP13 activity and reduced fibrosis. As such, these data suggest important counter-regulatory roles between MMP12 and ECM-degrading enzymes like MMP2, MMP9, and MMP13 in Th2 cytokine-driven fibrosis. The Journal of Immunology, 2010, 184: 3955-3963. C1 [Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Pesce, John T.] USN, Med Res Ctr, Rockville, MD 20852 USA. [Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH,Dept Hlth & Human Serv, 50 South Dr,Room 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 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 40 TC 56 Z9 59 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 3955 EP 3963 DI 10.4049/jimmunol.0903008 PG 9 WC Immunology SC Immunology GA 573PV UT WOS:000275927600074 PM 20181883 ER PT J AU Niland, B Miklossy, G Banki, K Biddison, WE Casciola-Rosen, L Rosen, A Martinvalet, D Lieberman, J Perl, A AF Niland, Brian Miklossy, Gabriella Banki, Katalin Biddison, William E. Casciola-Rosen, Livia Rosen, Antony Martinvalet, Denis Lieberman, Judy Perl, Andras TI Cleavage of Transaldolase by Granzyme B Causes the Loss of Enzymatic Activity with Retention of Antigenicity for Multiple Sclerosis Patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; CD8(+) T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; CLONAL EXPANSIONS; INDUCED APOPTOSIS; MOUSE MODELS; BRAIN; OLIGODENDROCYTE; AUTOANTIBODIES AB Multiple sclerosis (MS) is an autoimmune demyelinating disease of the CNS resulting from a progressive loss of oligodendrocytes. Transaldolase (TAL) is expressed at selectively high levels in oligodendrocytes of the brain, and postmortem sections show concurrent loss of myelin basic protein and TAL from sites of demyelination. Infiltrating CD8(+) CTLs are thought to play a key role in oligodendrocyte cell death. Cleavage by granzyme B (GrB) is predictive for autoantigenicity of self-proteins, thereby further implicating CTL-induced death in the initiation and propagation of autoimmunity. The precursor frequency and CTL activity of HLA-A2-restricted TAL 168-176-specific CD8(+) T cells is increased in MS patients. In this paper, we show that TAL, but not myelin basic protein, is specifically cleaved by human GrB. The recognition site of GrB that resulted in the cleavage of a dominant TAL fragment was mapped to a VVAD motif at aa residue 27 by N-terminal sequencing and confirmed by site-directed mutagenesis. The major C-terminal GrB cleavage product, residues 28-337, had no enzymatic activity but retained the antigenicity of full-length TAL, effectively stimulating the proliferation and CTL, activity of PBMCs and of CD8(+) T cell lines from patients with MS. Sera of MS patients exhibited similar binding affinity to wild-type and GrB-cleaved TAL. Because GrB mediates the killing of target cells and cleavage by GrB is predictive of autoantigen status of self proteins, GrB-cleaved TAL-specific T cell-mediated cytotoxicity may contribute to the progressive destruction of oligodendrocytes in patients with MS. The journal of Immunology,2010, 184: 4025-4032. C1 [Niland, Brian; Miklossy, Gabriella; Perl, Andras] SUNY Syracuse, Dept Med, Coll Med, Syracuse, NY 13210 USA. [Banki, Katalin] SUNY Syracuse, Dept Pathol, Coll Med, Syracuse, NY 13210 USA. [Perl, Andras] SUNY Syracuse, Dept Microbiol, Coll Med, Syracuse, NY 13210 USA. [Biddison, William E.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Casciola-Rosen, Livia; Rosen, Antony] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. [Martinvalet, Denis; Lieberman, Judy] Harvard Univ, Ctr Blood Res, Boston, MA 02115 USA. RP Perl, A (reprint author), SUNY Syracuse, Dept Med, Coll Med, 750 E Adams St, Syracuse, NY 13210 USA. EM perla@upstate.edu RI Lieberman, Judy/A-2717-2015; OI Perl, Andras/0000-0002-5017-1348 FU National Institutes of Health [RO1 DK 49221]; National Multiple Sclerosis Society [RG 2466] FX This work was supported in part by Grant RO1 DK 49221 from the National Institutes of Health and Grant RG 2466 from the National Multiple Sclerosis Society. NR 66 TC 7 Z9 7 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 IS 7 BP 4025 EP 4032 DI 10.4049/jimmunol.0804174 PG 8 WC Immunology SC Immunology GA 573PV UT WOS:000275927600081 PM 20194725 ER PT J AU Adriani, M Jones, K Kirby, M Anderson, S Silvin, C Wincowitch, S Candotti, F AF Adriani, Marsilio Jones, Krystin Kirby, Martha Anderson, Stacie Silvin, Christopher Wincowitch, Stephen Candotti, Fabio TI Defects of Regulatory T Cell function In The Wiskott-Aldrich Syndrome. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Adriani, Marsilio; Jones, Krystin; Silvin, Christopher; Candotti, Fabio] NHGRI, Disorder Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Kirby, Martha; Anderson, Stacie] NHGRI, Flow Cytometry Core, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Wincowitch, Stephen] NHGRI, Cytogenet & Microscopy Core, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 49.25 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301098 ER PT J AU Akpinarli, A Matzinger, P AF Akpinarli, Akgul Matzinger, Polly TI Do Maternal Antibodies Inhibit Newborn Immunization? SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Akpinarli, Akgul; Matzinger, Polly] NIAID, LCMI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 84.15 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301219 ER PT J AU An, J Golech, S Klaewsongkram, J Huston, G Wood, W Zhang, YQ Wersto, R Becker, K Swain, S Weng, NP AF An, Jie Golech, Susanne Klaewsongkram, Jettanong Huston, Gail Wood, William Zhang, Yongqing Wersto, Robert Becker, Kevin Swain, Susan Weng, Nan-ping TI Role of Kruppel-like factor 4 (K1f4) in regulation of T cell number and TH-17 differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [An, Jie; Golech, Susanne; Klaewsongkram, Jettanong; Wood, William; Zhang, Yongqing; Wersto, Robert; Becker, Kevin; Weng, Nan-ping] NIA, Baltimore, MD 21224 USA. [Huston, Gail; Swain, Susan] Trudeau Inst, Saranac Lake, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 139.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304102 ER PT J AU Antony, P Xie, Y Akpinarli, A Maris, C Hipkiss, E Lane, M Kwon, EK Muranski, P Restifo, N AF Antony (PI), Paul Xie, Ying Akpinarli, Akgul Maris, Charles Hipkiss, Edward Lane, Malcolm Kwon, Eun-Kyung Muranski, Pawel Restifo, Nicholas TI Naive tumor-specific CD4+T cells differentiated in vivo eradicate established melanoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Antony (PI), Paul; Xie, Ying; Lane, Malcolm; Kwon, Eun-Kyung] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Muranski, Pawel; Restifo, Nicholas] NCI, Surg Branch, Bethesda, MD 20892 USA. [Antony (PI), Paul; Akpinarli, Akgul] NIAID, NIH, Bethesda, MD 20892 USA. [Maris, Charles; Hipkiss, Edward] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303141 ER PT J AU Anzinger, J Chang, J Xu, Q Buono, C Li, YF Leyva, F Park, BC Greene, L Kruth, H AF Anzinger, Joshua Chang, Janet Xu, Qing Buono, Chiara Li, Yifu Leyva, Francisco Park, Bum-Chan Greene, Lois Kruth, Howard TI Native low-density lipoprotein uptake by Macrophage Colony-Stimulating Factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Anzinger, Joshua; Chang, Janet; Xu, Qing; Buono, Chiara; Li, Yifu; Leyva, Francisco; Park, Bum-Chan; Greene, Lois; Kruth, Howard] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 134.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303246 ER PT J AU Baatar, D Lee, JH Brill, M Lustig, A Carter, A Taub, D AF Baatar, Dolgor Lee, Jun Ho Brill, Margaret Lustig, Ana Carter, Arneil Taub, Dennis TI An orexigenic hormone ghrelin enhances LPS-induced IL-10 production in human peripheral blood-derived macrophages. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Baatar, Dolgor; Lee, Jun Ho; Brill, Margaret; Lustig, Ana; Carter, Arneil; Taub, Dennis] NIA, Immunol, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 138.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304069 ER PT J AU Bai, Y Simakova, O Fu, WM Woelfel, J Maric, D Maric, I Metcalfe, D Wilson, T AF Bai, Yun Simakova, Olga Fu, Weiming Woelfel, Jessica Maric, Dragan Maric, Irina Metcalfe, Dean Wilson, Todd TI Cell lineage analysis of KIT D816V and NRAS G12D activating mutations in aggressive systemic mastocytosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bai, Yun; Metcalfe, Dean; Wilson, Todd] NIAID, Lab Allerg Dis, NIH, Bethesda, MD USA. [Simakova, Olga; Fu, Weiming; Woelfel, Jessica; Maric, Irina] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD USA. [Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.25 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300070 ER PT J AU Barber, D Mayer-Barber, K Antonelli, L Sher, A AF Barber, Daniel Mayer-Barber, Katrin Antonelli, Lis Sher, Alan TI Role of host lymphopenia in the immune reconstitution disease triggered by CD4 T cell transfer into mycobacterial infected T cell deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Barber, Daniel; Mayer-Barber, Katrin; Antonelli, Lis; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 40.20 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300204 ER PT J AU Barda-Saad, M Shirasu, N Pauker, M Hasan, N Perl, O Balbo, A Yamaguchi, H Houtman, J Appella, E Schuck, P Samelson, L AF Barda-Saad, Mira Shirasu, Naoto Pauker, Maor Hasan, Nirit Perl, Orly Balbo, Andrea Yamaguchi, Hiroshi Houtman, Jon Appella, Ettore Schuck, Peter Samelson, Lawrence TI Studying the cooperativity at the SLP-76 signaling complex critical for the immune response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Barda-Saad, Mira; Pauker, Maor; Hasan, Nirit; Perl, Orly] Bar Ilan Univ, Ramat Gan, Israel. [Shirasu, Naoto; Samelson, Lawrence] NCI, Cellular & Mol Biol Lab, CCI, NIH, Bethesda, MD 20892 USA. [Yamaguchi, Hiroshi; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Balbo, Andrea; Schuck, Peter] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. [Houtman, Jon] Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 50.7 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301135 ER PT J AU Bergamaschi, C Ganneru, B Rosati, M Usami, O Valentin, A Beach, R Alicea, C Felber, B Pavlakis, G AF Bergamaschi, Cristina Ganneru, Brunda Rosati, Margherita Usami, Osamu Valentin, Antonio Beach, Rachel Alicea, Candido Felber, Barbara Pavlakis, George TI Supraphysiological levels of IL-15 accelerate immune reconstitution in lymphopenic mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bergamaschi, Cristina; Ganneru, Brunda; Rosati, Margherita; Usami, Osamu; Valentin, Antonio; Beach, Rachel; Alicea, Candido; Felber, Barbara; Pavlakis, George] NCI Frederick, Ctr Canc Res, Frederidk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 134.16 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303247 ER PT J AU Bradfute, S Tailor, P Anthony, S Ozato, K Bavari, S AF Bradfute, Steven Tailor, Prafullakumar Anthony, Scott Ozato, Keiko Bavari, Sina TI Mechanisms of post-exposure protection mediated by virus-like particles against Ebola virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bradfute, Steven; Anthony, Scott; Bavari, Sina] USAMRIID, TOX, Ft Detrick, MD USA. [Tailor, Prafullakumar; Ozato, Keiko] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 52.18 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301160 ER PT J AU Cannons, J Qi, H Lu, K Ghai, M Gomez-Rodriguez, J Germain, R Schwartzberg, P AF Cannons, Jennifer Qi, Hai Lu, Kristina Ghai, Mala Gomez-Rodriguez, Julio Germain, Ronald Schwartzberg, Pamela TI Humoral responses require a multi-stage T:B lymphocyte interaction process SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Cannons, Jennifer; Lu, Kristina; Ghai, Mala; Gomez-Rodriguez, Julio; Schwartzberg, Pamela] NHGRI, NIH, Bethesda, MD 20892 USA. [Qi, Hai; Germain, Ronald] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 99.5 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303014 ER PT J AU Capitini, C Larabee, S Qin, HY Song, Y Khan, J Mackall, C Fry, T AF Capitini, Christian Larabee, Shannon Qin, Haiying Song, Young Khan, Javed Mackall, Crystal Fry, Terry TI STAT1-deficient bone marrow prevents GVHD by modulating plasmacytoid DCs while preserving vaccine-mediated responses to tumor SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Capitini, Christian; Larabee, Shannon; Qin, Haiying; Song, Young; Khan, Javed; Mackall, Crystal; Fry, Terry] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fry, Terry] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 145.40 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304232 ER PT J AU Castro, R Zhang, J Jamur, M Oliver, C Siraganian, R AF Castro, Rodrigo Zhang, Juan Jamur, Maria Oliver, Constance Siraganian, Reuben TI Tyrosines in the carboxy-terminal region regulate Syk function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Castro, Rodrigo; Zhang, Juan; Siraganian, Reuben] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Castro, Rodrigo; Jamur, Maria; Oliver, Constance] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 86.18 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301271 ER PT J AU Chan, T Back, T Subleski, J Weiss, J Ortaldo, J Wiltrout, R AF Chan, Tim Back, Timothy Subleski, Jeffrey Weiss, Jonathan Ortaldo, John Wiltrout, Robert TI Systemic IL-12 administration modulates dendritic cells to overcome the immunosuppressive microenvironment of the liver SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chan, Tim; Back, Timothy; Subleski, Jeffrey; Weiss, Jonathan; Ortaldo, John; Wiltrout, Robert] NCI, NIH, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 134.14 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303244 ER PT J AU Chen, X Hamano, R Subleski, J Hurwitz, A Howard, OMZ Oppenheim, J AF Chen, Xin Hamano, Ryoko Subleski, Jeffrey Hurwitz, Arthur Howard, O. M. Zack Oppenheim, Joost TI Expression of co-stimulatory TNFR2 enhances resistance of CD4+FoxP3-conventional T cells to suppression by CD4+FoxP3+regulatory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chen, Xin] SAIC Frederick Inc, Frederick, MD USA. [Hamano, Ryoko; Subleski, Jeffrey; Hurwitz, Arthur; Howard, O. M. Zack; Oppenheim, Joost] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 49.13 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758301094 ER PT J AU Chiang, J Hodes, R AF Chiang, Jeffrey Hodes, Richard TI CbI Inhibits Vav-1-Independent T Cell Differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chiang, Jeffrey; Hodes, Richard] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.56 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300092 ER PT J AU Choi, SC Narayanan, S Krzewski, K Borrego, F Coligan, J AF Choi, Seung-Chul Narayanan, Sriram Krzewski, Konrad Borrego, Francisco Coligan, John TI Expression and regulation of Toso, a new Fc receptor for IgM, during B cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Choi, Seung-Chul; Narayanan, Sriram; Krzewski, Konrad; Coligan, John] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. [Borrego, Francisco] US FDA, Lab Mol & Dev Biol, DMA, CDER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 132.15 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303194 ER PT J AU Crampton, S Deane, J Hasty, K Otubusin, O Bolland, S AF Crampton, Steve Deane, Jonathan Hasty, Karen Otubusin, Owokunile Bolland, Silvia TI Transgenic Expression of the RNA-sensing Molecule MDA-5 Accelerates Autoimmunity in the Lupus-prone FcgammaR2-Deficient Mouse SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Crampton, Steve; Hasty, Karen; Otubusin, Owokunile; Bolland, Silvia] NIAID, NIH, Autoimmun & Funct Genom Sect, Rockville, MD USA. [Deane, Jonathan] Novartis Res Fdn, Genom Inst, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 93.20 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302210 ER PT J AU Cruz, A Ramaswamy, M Siegei, R AF Cruz, Anthony Ramaswamy, Madhu Siegei, Richard TI Localization of Fas/CD95 to lipid raft microdomains sensitizes human CD4+effector memory T cells to Fas-induced apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Cruz, Anthony; Ramaswamy, Madhu; Siegei, Richard] NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 85.13 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301242 ER PT J AU Cui, YZ Garber, H Zhang, H Mackall, C AF Cui, Yongzhi Garber, Haven Zhang, Hua Mackall, Crystal TI Survivin: A Potential Target of Adoptive Immunotherapy for Pediatric Sarcomas SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Cui, Yongzhi; Garber, Haven; Zhang, Hua; Mackall, Crystal] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 101.19 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303077 ER PT J AU Damdinsuren, B Grumont, R Zhang, YQ Wood, W Becker, K Gerondakis, S Sen, R AF Damdinsuren, Bazarragchaa Grumont, Raelene Zhang, Yongqing Wood, William Becker, Kevin Gerondakis, Steve Sen, Ranjan TI Kinetic and function of c-Rel in naive B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Damdinsuren, Bazarragchaa; Sen, Ranjan] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Grumont, Raelene; Gerondakis, Steve] Burnet Inst, Ctr Immunol, Melbourne, Vic, Australia. [Zhang, Yongqing; Wood, William; Becker, Kevin] NIA, RRB, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 84.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301223 ER PT J AU Damsker, J Luger, D Silver, P Chan, CC Iwakura, Y Caspi, R AF Damsker, Jesse Luger, Dror Silver, Phyllis Chan, Chi-Chao Iwakura, Yoichiro Caspi, Rachel TI Experimental autoimmune uveitis in mice with defective Th1 and Th17 effector responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Damsker, Jesse; Luger, Dror; Silver, Phyllis; Chan, Chi-Chao; Caspi, Rachel] NEI, Bethesda, MD 20892 USA. [Iwakura, Yoichiro] Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 93.17 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302197 ER PT J AU de Kluyver, R Stauffer, J Brooks, A Shanker, A Sayers, T AF de Kluyver, Rachel Stauffer, Jim Brooks, Alan Shanker, Anil Sayers, Tom TI Murine Hepatocellular Carcinoma Stem Cells Express Pluripotency-associated Transcription Factors and are Sensitive to Immune Mediated Apoptosis. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [de Kluyver, Rachel; Stauffer, Jim] NCI, Canc Inflammat Program, Frederick, MD 21701 USA. [Brooks, Alan; Shanker, Anil; Sayers, Tom] SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 101.16 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303075 ER PT J AU de la Rosa, G Tewary, P Yang, D Gattis, J Lubkowski, J Oppenheim, J McVicar, D Washington, V AF de la Rosa, Gonzalo Tewary, Poonam Yang, De Gattis, James Lubkowski, Jacek Oppenheim, Joost McVicar, Daniel Washington, Valance TI Platelet-derived soluble TREM-Like Transcrip-1 (TLT-1) induces human and mouse Dendritic Cell activation through a TLR-4-dependent mechanism. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [de la Rosa, Gonzalo; Tewary, Poonam; Oppenheim, Joost] NCI, Lab Mol Immunoregulat, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Yang, De] NCI, BRP SAIC Frederick, Ctr Canc Res, Frederick, MD 21701 USA. [McVicar, Daniel] NCI, Lab Expt Immunoregulat, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Gattis, James; Lubkowski, Jacek] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Washington, Valance] Univ Cent Caribe, Dept Anat & Cell Biol, Bayamon, PR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.32 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304020 ER PT J AU Deng, M Arias, M Ramaswamy, M Siege, R AF Deng, Min Arias, Marco Ramaswamy, Madhu Siege, Richard TI Deciphering the function of the microRNA-181a in effector CD4+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Deng, Min; Arias, Marco; Ramaswamy, Madhu; Siege, Richard] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 85.19 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301237 ER PT J AU Do, J Fink, P Li, L Spolski, R Robinson, J Leonard, W Letterio, J Min, B AF Do, Jeongsu Fink, Pamela Li, Lily Spolski, Rosanne Robinson, Janet Leonard, Warren Letterio, John Min, Booki TI Spontaneous development of IL-17-producing gamma delta T cells in the thymus occurs via a TGF beta 1-dependent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Do, Jeongsu; Li, Lily; Min, Booki] Cleveland Clin Fdn, Immunol, Cleveland, OH USA. [Fink, Pamela] Univ Washington, Dept Immunol, Seattle, WA 98195 USA. [Li, Lily] Cleveland Clin Fdn, Cleveland Clin Lerner Coll Med, Cleveland, OH USA. [Spolski, Rosanne; Leonard, Warren] NHLBI, Lab Mol Immunol & Immunol Ctr, NIH, Bethesda, MD USA. [Robinson, Janet; Letterio, John] Case Western Reserve Univ, Dept Pediat, Div Pediat Hematol Oncol, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.37 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300055 ER PT J AU Dolan, B Bennink, J Yewdell, J AF Dolan, Brian Bennink, Jack Yewdell, Jonathan TI Drug Controlled Antigen Degradation Defines Sources of MHC Class I Peptides and Enables Pathway Discovery SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Dolan, Brian; Bennink, Jack; Yewdell, Jonathan] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 130.29 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303123 ER PT J AU Druey, K Lu, YB Kuehn, H Gilfillan, A Xie, ZH AF Druey, Kirk Lu, Yunbiao Kuehn, Hyesun Gilfillan, Alasdair Xie, Zhihui TI Regulation of RGS13 expression by the tumor suppressor p53 in mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Druey, Kirk; Lu, Yunbiao; Kuehn, Hyesun; Gilfillan, Alasdair; Xie, Zhihui] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 86.22 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301270 ER PT J AU Ford, J Howard, OMZ Subleski, J Yang, YF Rayman, P Weiss, J Linehan, W Sayers, T Finke, J McVicar, D AF Ford, Jill Howard, O. M. Zack Subleski, Jeff Yang, Youfeng Rayman, Pat Weiss, Jon Linehan, W. Sayers, Tom Finke, James McVicar, Daniel TI Enhanced Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) and Soluble TREM-1 Levels in the Myeloid Cells of Tumor-Bearing Mice and Patients with Renal Cell Carcinoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ford, Jill; Howard, O. M. Zack; Subleski, Jeff; Weiss, Jon; Sayers, Tom; McVicar, Daniel] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Yang, Youfeng; Linehan, W.] NCI, Bethesda, MD 20892 USA. [Rayman, Pat; Finke, James] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. [Sayers, Tom] SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 100.8 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303042 ER PT J AU Ghai, M Cannons, J Schwartzberg, P AF Ghai, Mala Cannons, Jennifer Schwartzberg, Pamela TI Investigating signaling downstream of SLAM family members CD84 and Ly108 in thymocytes and activated T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ghai, Mala; Cannons, Jennifer; Schwartzberg, Pamela] NIH, Bethesda, MD 20892 USA. [Ghai, Mala] George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 99.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303021 ER PT J AU Gibbs, J Bian, T Menendez, D Resnick, M Imani, F AF Gibbs, John Bian, Tao Menendez, Daniel Resnick, Michael Imani, Farhad TI Respiratory syncytial virus hijacks the tumor suppressor p53 to enhance its replication in lung epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Gibbs, John; Bian, Tao; Menendez, Daniel; Resnick, Michael; Imani, Farhad] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 137.3 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304040 ER PT J AU Gomez-Rodriguez, J Sahu, N Handon, R Sacta, M Anderson, S Kirby, M August, A Schwartzberg, P AF Gomez-Rodriguez, Julio Sahu, Nisebita Handon, Robin Sacta, Maria Anderson, Stacie Kirby, Martha August, Avery Schwartzberg, Pamela TI Differential expression of IL-17A and IL-17F is coupled to TCR signaling via Itk-mediated regulation of NFATc1 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Gomez-Rodriguez, Julio; Handon, Robin; Sacta, Maria; Anderson, Stacie; Kirby, Martha; Schwartzberg, Pamela] NIH, Bethseda, MD USA. [Sahu, Nisebita; August, Avery] Penn State Univ, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 139.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304105 ER PT J AU Greenwell-Wild, T Moutsopoulos, N Gliozzi, M Kapsogeorgou, E Rangel, Z Munson, P Moutsopoulos, H Wahl, S AF Greenwell-Wild, Teresa Moutsopoulos, N. Gliozzi, M. Kapsogeorgou, E. Rangel, Z. Munson, P. Moutsopoulos, H. Wahl, S. TI Expression of chitinase-like proteins in inflamed tissues of Sjogren's Syndrome (SS) patients SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Greenwell-Wild, Teresa; Moutsopoulos, N.; Gliozzi, M.; Wahl, S.] NIDCR, NIH, Bethesda, MD USA. [Rangel, Z.; Munson, P.] NIH, CIT, Bethesda, MD 20892 USA. [Kapsogeorgou, E.; Moutsopoulos, H.] Natl Univ Athens, Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 135.6 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303275 ER PT J AU Handon, R Mueller, K Schwatzberg, P Hoogstraten-Miller, S AF Handon, Robin Mueller, Kristen Schwatzberg, Pamela Hoogstraten-Miller, Shelley TI An Alternative Method for Intrathymic Injection in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Handon, Robin] Prior One Serv Inc, Alexandria, VA USA. [Mueller, Kristen; Schwatzberg, Pamela; Hoogstraten-Miller, Shelley] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 144.8 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304195 ER PT J AU Hedrick, M Zhang, HW Farber, J AF Hedrick, Michael Zhang, Hongwei Farber, Joshua TI Exaggerated IL-23-induced psoriasis-like inflammation in mice lacking CCR4 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hedrick, Michael; Zhang, Hongwei; Farber, Joshua] NIAID, Inflammat Biol Sect, LMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 135.32 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303291 ER PT J AU Hillyer, P Chen, A Schramm, L Mane, V Navarro, M Luongo, C Raviv, N Collins, P Rabin, R AF Hillyer, Philippa Chen, Aaron Schramm, Lynnsie Mane, Viraj Navarro, Maria Luongo, Cindy Raviv, Nataly Collins, Peter Rabin, Ronald TI An attenuated innate immune response to a clinical strain of respiratory syncytial virus (RSV) in human monocyte derived dendritic cells (MDDC) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hillyer, Philippa; Chen, Aaron; Schramm, Lynnsie; Mane, Viraj; Navarro, Maria; Raviv, Nataly; Rabin, Ronald] USFDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Bethesda, MD USA. [Luongo, Cindy; Collins, Peter] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 37.43 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300103 ER PT J AU Hwang, SJ Song, KD Chu, H Lee, J Lesourne, R Li, LQ Pinkhasov, J Jenkins, M Love, P AF Hwang, SuJin Song, Ki-Duk Chu, Hamlet Lee, Jan Lesourne, Renaud Li, LiQi Pinkhasov, Julia Jenkins, Marc Love, Paul TI Importance of TCR ITAM multiplicity in the establishment of central tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hwang, SuJin; Lee, Jan; Lesourne, Renaud; Li, LiQi; Pinkhasov, Julia; Love, Paul] NICHD, NIH, Bethesda, MD USA. [Chu, Hamlet; Jenkins, Marc] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Song, Ki-Duk] Univ Texas MD Anderson, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.48 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300085 ER PT J AU Jin, WW Wen, J Starost, M McGrady, G Shapiro, S Wahl, S AF Jin, Wenwen Wen, Jie Starost, Matthew McGrady, George Shapiro, Steven Wahl, Sharon TI Secretory Leukocyte Protease Inhibitor (SLPI) delays development of murine squamous cell carcinoma and inhibits metastasis. W Jin, J Wen, MF Starost, G McGrady, SD Shapiro and SM Wahl, OIIB, NIDCR, NIH, and DVR, NIH, Bethesda, MD and Univ Pittsburg, Pittsburg, PA. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Jin, Wenwen; Wen, Jie; Starost, Matthew; McGrady, George; Wahl, Sharon] NIH, Bethesda, MD 20892 USA. [Shapiro, Steven] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 101.33 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303083 ER PT J AU Joyce, MG Colonna, M Sun, P AF Joyce, M. Gordon Colonna, Marco Sun, Peter TI Crystal structure of NKp30 and identification of ligand binding site through peptide mapping and blocking antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Joyce, M. Gordon; Sun, Peter] NIAID, Immunogenet, NIH, Rockville, MD USA. [Colonna, Marco] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 94.12 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302226 ER PT J AU Kim, HS Das, A Gross, C Bryceson, Y Long, E AF Kim, Hun Sik Das, Asmita Gross, Catharina Bryceson, Yenan Long, Eric TI Synergistic Signals for Natural Cytotoxicity Are Required to Overcome Inhibition by c-CbI SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kim, Hun Sik; Das, Asmita; Gross, Catharina; Long, Eric] NIAID, Immunogenet, Rockville, MD USA. [Bryceson, Yenan] Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 89.16 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302042 ER PT J AU Kothapalli, NR Norton, D Fugmann, S AF Kothapalli, Naga Rama Norton, Darrell Fugmann, Sebastian TI IDENTIFICATION OF CIS-REGULATORY ELEMENTS TARGETING AID-MEDIATED SEQUENCE DIVERSIFICATION TO THE CHICKEN IMMUNOGLOBULIN LIGHT CHAIN GENE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kothapalli, Naga Rama; Norton, Darrell; Fugmann, Sebastian] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 88.2 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302021 ER PT J AU Kraus, Z Horai, R Schwartzberg, P AF Kraus, Zachary Horai, Reiko Schwartzberg, Pamela TI Transcriptional regulation of innate alpha beta CD8+T cell development in ltk deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kraus, Zachary; Horai, Reiko; Schwartzberg, Pamela] Natl Human Res Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.35 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300076 ER PT J AU Krzewski, K Gil-Krzewska, A Watts, J Coligan, J Strominger, J AF Krzewski, Konrad Gil-Krzewska, Aleksandra Watts, James Coligan, John Strominger, Jack TI Both VAMP4 and VAMP7 are indispensable for NK cell cytotoxicity: the requirement for two R-SNARE proteins in granule exocytosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Krzewski, Konrad; Coligan, John] NIAID, NIH, Rockville, MD USA. [Krzewski, Konrad; Gil-Krzewska, Aleksandra; Watts, James; Strominger, Jack] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 89.24 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302050 ER PT J AU Lau-Kilby, A Kretz, C O'Shea, J Trinchieri, G Tarbell, K AF Lau-Kilby, Annie Kretz, Cosima O'Shea, John Trinchieri, Giorgio Tarbell, Kristin TI Interleukin-2 Controls flt3L-dependent Development and Phenotype of Conventional and Plasmacytoid Dendritic Cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lau-Kilby, Annie; Kretz, Cosima; Tarbell, Kristin] NIDDK, Immune Tolerance Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. [O'Shea, John] NIAMS, NIH, Bethesda, MD USA. [Trinchieri, Giorgio] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.19 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304273 ER PT J AU Li, HM Weng, NP AF Li, Hoi Ming Weng, Nan-ping TI Identification and characterization of highly expressed microRNAs (miRNAs) in memory CD8 T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Li, Hoi Ming; Weng, Nan-ping] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 132.21 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303207 ER PT J AU Liao, JY Prater, C Thakur, S Zalinger, Z Imani, F AF Liao, Jie-Ying Prater, Chrissy Thakur, Sheetal Zalinger, Zachary Imani, Farhad TI Conversion of Adenines to Inosines in RNA During Virus Infections Is an Innate Immune Stimulus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Liao, Jie-Ying; Prater, Chrissy; Thakur, Sheetal; Zalinger, Zachary; Imani, Farhad] NIEHS, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 89.10 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302037 ER PT J AU Liu, DF Meckel, T Long, E AF Liu, Dongfang Meckel, Tobias Long, Eric TI Distinct Roles of Rab27a in Lytic Granule Movement at the Plasma Membrane and in the Cytosol SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Liu, Dongfang; Meckel, Tobias; Long, Eric] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 89.47 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302052 ER PT J AU Livak, F Hathcock, K Hodes, R Bowen, S AF Livak, Ferenc Hathcock, Karen Hodes, Richard Bowen, Steven TI Normal and Pathological Regulation of DNA Damage Response to T-cell Receptor Gene Rearrangement SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Livak, Ferenc; Bowen, Steven] Univ Maryland, Microbiol & Immunol, Baltimore, MD 21201 USA. [Hathcock, Karen; Hodes, Richard] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.61 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300080 ER PT J AU Lu, JH Marjon, K Marnell, L Mold, C Du Clos, T Sun, P AF Lu, Jinghua Marjon, Kristopher Marnell, Lorraine Mold, Carolyn Du Clos, Terry Sun, Peter TI Cross-talk between innate and adaptive immunity through pentraxins and Fc receptors SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lu, Jinghua; Sun, Peter] NIAID, Struct Immunol Sect, Lab Immunogenet, Rockville, MD USA. [Marjon, Kristopher; Marnell, Lorraine; Mold, Carolyn; Du Clos, Terry] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Marjon, Kristopher; Marnell, Lorraine; Mold, Carolyn; Du Clos, Terry] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Du Clos, Terry] VA Med Ctr, Albuquerque, NM USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.42 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303300 ER PT J AU Lu, JH Du Clos, T Mold, C Sun, P AF Lu, Jinghua Du Clos, Terry Mold, Carolyn Sun, Peter TI The structural mechanism of Serum Amyloid A -mediated Secondary amyloid formation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lu, Jinghua; Sun, Peter] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA. [Du Clos, Terry; Mold, Carolyn] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Du Clos, Terry; Mold, Carolyn] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 135.34 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303259 ER PT J AU Lu, K Cannons, J Kanno, Y O'Shea, J Schwartzberg, P AF Lu, Kristina Cannons, Jennifer Kanno, Yuka O'Shea, John Schwartzberg, Pamela TI SLAM-associated protein (SAP)-deficiency impedes the function of T follicular helper cells in germinal center formation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lu, Kristina; Cannons, Jennifer; Schwartzberg, Pamela] NHGRI, NIH, Bethesda, MD 20892 USA. [Kanno, Yuka; O'Shea, John] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 99.3 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303023 ER PT J AU Mattapallil, M Silver, P Mattapalli, J Horai, R Karabekian, Z McDowell, H Chan, CC James, E Kwok, W David, C Caspi, R AF Mattapallil, Mary Silver, Phyllis Mattapalli, Joseph Horai, Reiko Karabekian, Zaruhi McDowell, Hugh Chan, Chi-Chao James, Eddie Kwok, William David, Chella Caspi, Rachel TI Uveitis-associated epitopes of retinal antigens are pathogenic in the humanized mouse model of EAU and identify autoaggressive T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mattapallil, Mary; Silver, Phyllis; Horai, Reiko; Karabekian, Zaruhi; Chan, Chi-Chao; Caspi, Rachel] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Mattapalli, Joseph] USUHS, Bethesda, MD USA. [McDowell, Hugh] Univ Florida, Gainesville, FL USA. [James, Eddie; Kwok, William] BRI Virginia Mason, Seattle, WA USA. [David, Chella] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 93.1 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302170 ER PT J AU Mayer-Barber, K Barber, D Shenderov, K White, S Wilson, M Cheever, A Kugler, D Sutterwala, F Sher, A AF Mayer-Barber, Katrin Barber, Daniel Shenderov, Kevin White, Sandra Wilson, Mark Cheever, Allen Kugler, David Sutterwala, Fayyaz Sher, Alan TI Caspase-1 independent IL-1 beta Production is critical for MyD88-mediated host resistance to Mycobacterium tuberculosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mayer-Barber, Katrin; Barber, Daniel; Shenderov, Kevin; White, Sandra; Wilson, Mark; Cheever, Allen; Kugler, David; Sher, Alan] NIAID, Immunobiol & Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD USA. [Sutterwala, Fayyaz] Univ Iowa, Dept Internal Med, Div Infect Dis, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 42.13 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300235 ER PT J AU McFarland, A Savan, R Wagage, S Addison, A Young, H AF McFarland, Adelle Savan, Ram Wagage, Sagie Addison, Augustina Young, Howard TI Exacerbation of DSS induced colitis by localized delivery of IFN-beta secreted by Lactobacillus acidpohilus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [McFarland, Adelle; Savan, Ram; Wagage, Sagie; Addison, Augustina; Young, Howard] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 47.6 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301054 ER PT J AU McGavern, D Kang, S Kim, J Dustin, M AF McGavern, Dorian Kang, Silvia Kim, Jiyun Dustin, Michael TI Intravital 2P-imaging reveals anti-viral CTL mediate fatal pathology by recruiting myelomonocytic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [McGavern, Dorian; Kang, Silvia] NIH, Bethesda, MD 20892 USA. [Kim, Jiyun; Dustin, Michael] NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 137.17 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304051 ER PT J AU McGavern, D Kang, S Herz, J Kim, J Dustin, M AF McGavern, Dorian Kang, Silvia Herz, Jasmin Kim, Jiyun Dustin, Michael TI Continual cell cycle progression during migration permits rapid CTL division at sites of viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [McGavern, Dorian; Kang, Silvia; Herz, Jasmin] NIH, Bethesda, MD 20892 USA. [Kim, Jiyun; Dustin, Michael] NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 39.24 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300193 ER PT J AU McPhee, C Bubier, J Sproule, T Wettstein, P Morse, H Roopenian, D AF McPhee, Caroline Bubier, Jason Sproule, Thomas Wettstein, Peter Morse, Herbert Roopenian, Derry TI CD8+T suppressor cells protect from Lupus-like autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [McPhee, Caroline; Bubier, Jason; Sproule, Thomas; Roopenian, Derry] Jackson Lab, Bar Harbor, ME 04609 USA. [Wettstein, Peter] Mayo Clin, Rochester, MN USA. [Morse, Herbert] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 143.31 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304138 ER PT J AU Miura, K Diakite, M Moretz, S Zhou, H Diouf, A Tullo, G Lopera-Mesal, T Anderson, J Fairhurst, R Long, C AF Miura, Kazutoyo Diakite, Mahamadou Moretz, Samuel Zhou, Hong Diouf, Ababacar Tullo, Gregory Lopera-Mesal, Tatiana Anderson, Jennifer Fairhurst, Rick Long, Carole TI Impact of sickle-cell trait on humoral immunity against Plasmodium falciparum in children living in malaria endemic areas of Mali SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Miura, Kazutoyo; Moretz, Samuel; Zhou, Hong; Diouf, Ababacar; Tullo, Gregory; Lopera-Mesal, Tatiana; Anderson, Jennifer; Fairhurst, Rick; Long, Carole] NIAID, Rockville, MD USA. [Diakite, Mahamadou] Univ Bamako, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 45.10 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301013 ER PT J AU Modiano, J Highfill, S Matise, I Morse, H Jubala, C Coffey, D O'Sullivan, G Bellgrau, D AF Modiano, Jaime Highfill, Sarah Matise, Ilse Morse, Herbert Jubala, Cristan Coffey, David O'Sullivan, Gerard Bellgrau, Donald TI Anaplastic plasmacytomas associated with NFATc2 deficiency in aged B6 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Modiano, Jaime; Highfill, Sarah; Matise, Ilse; O'Sullivan, Gerard] Univ Minnesota, Vet Clin Sci, Minneapolis, MN USA. [Modiano, Jaime; Jubala, Cristan; Coffey, David; Bellgrau, Donald] Univ Colorado, Aurora, CO USA. [Morse, Herbert] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 100.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303035 ER PT J AU Mohammed, J Ryscavage, A Perez-Lorenzo, R Gunderson, A Blazanin, N Glick, A AF Mohammed, Javed Ryscavage, Andrew Perez-Lorenzo, Rolando Gunderson, Andrew Blazanin, Nicholas Glick, Adam TI TGF beta 1 Modulation of Inflammation in Premalignant Squamous Lesions is IL-17-dependent and Independent SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mohammed, Javed; Perez-Lorenzo, Rolando; Gunderson, Andrew; Blazanin, Nicholas; Glick, Adam] Penn State Univ, University Pk, PA 16802 USA. [Ryscavage, Andrew] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 95.5 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302232 ER PT J AU Moore, C Liu, Y Shao, CS Bishop, G Covey, L Morse, H Xie, P AF Moore, Carissa Liu, Yan Shao, Changshun Bishop, Gail Covey, Lori Morse, Herbert Xie, Ping TI Specific deletion of TRAF3 in B lymphocytes leads to B lymphoma development in mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Moore, Carissa; Liu, Yan; Shao, Changshun; Covey, Lori; Xie, Ping] Rutgers State Univ, Piscataway, NJ USA. [Bishop, Gail] Univ Iowa, Iowa City, IA USA. [Morse, Herbert] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 138.6 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304089 ER PT J AU Ng, S Li, A Ozato, K Kino, T AF Ng, Sinnie Li, Andrew Ozato, Keiko Kino, Tomoshige TI Dexamethasone synergistically increases secretion of the anti-inflammatory cytokine interleukin(IL)-10 in murine dendritic cells (DCs) upon viral infection: Potential implication to stress-mediated modification of susceptibility to viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ng, Sinnie; Li, Andrew; Kino, Tomoshige] NICHD, PRAE, NIH, Bethesda, MD USA. [Ozato, Keiko] NICHD, LMGR, NIH, Bethesda, MD USA. [Ng, Sinnie] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 94.4 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302225 ER PT J AU Novikov, A Thompson, R Sher, A Feng, C AF Novikov, Aleksey Thompson, Robert Sher, Alan Feng, Carl TI Proinflammatory cytokines and type I interferon are differentially induced by virulent and avirulent mycobacteria in human macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Novikov, Aleksey; Thompson, Robert; Sher, Alan; Feng, Carl] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 37.36 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300099 ER PT J AU O'Connor, G Yamada, E Rampersaud, A McVicar, D AF O'Connor, Geraldine Yamada, Eriko Rampersaud, Andy McVicar, Daniel TI Identification of Critical Residues in the Natural Killer (NK) Cell Receptor KIR3DS1 that Control HLA (Human Leukocyte Antigen) Binding SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [O'Connor, Geraldine; Yamada, Eriko; Rampersaud, Andy; McVicar, Daniel] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 89.55 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302093 ER PT J AU O'Konek, J Illarionov, P Khursigara, DS Ambrosino, E Castillo, B Raju, R Khalili, M Kim, HY Howell, A Besra, G Porcelli, S Berzofsky, J Terabe, M AF O'Konek, Jessica Illarionov, Petr Khursigara, Deborah Stewart Ambrosino, Elena Castillo, Bernard, II Raju, Ravinder Khalili, Maryam Kim, Hee-Yong Howell, Amy Besra, Gurdyal Porcelli, Steven Berzofsky, Jay Terabe, Masaki TI Beta-mannosylceramide represents a new class of NKT agonists that induces tumor immunity by a novel IFN-gamma-independent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [O'Konek, Jessica; Khursigara, Deborah Stewart; Ambrosino, Elena; Berzofsky, Jay; Terabe, Masaki] NCI, NIH, Bethesda, MD 20892 USA. [Illarionov, Petr; Besra, Gurdyal] Univ Birmingham, Birmingham, W Midlands, England. [Castillo, Bernard, II; Raju, Ravinder; Khalili, Maryam; Howell, Amy] Univ Connecticut, Storrs, CT USA. [Kim, Hee-Yong] NIAAA, NIH, Bethesda, MD USA. [Porcelli, Steven] Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 89.7 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302088 ER PT J AU Oliveira, F Rowton, E Gomes, R Lawyer, P Teixeira, C Aslan, H Valenzuela, J Kamhawi, S AF Oliveira, Fabiano Rowton, Edgar Gomes, Regis Lawyer, Phillip Teixeira, Clarissa Aslan, Hamide Valenzuela, Jesus Kamhawi, Shaden TI Pre-exposure to uninfected sand fly bites protects rhesus monkeys against cutaneous leishmaniasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Oliveira, Fabiano; Gomes, Regis; Lawyer, Phillip; Teixeira, Clarissa; Aslan, Hamide; Valenzuela, Jesus; Kamhawi, Shaden] NIAID, NIH, LMVR, Rockville, MD USA. [Rowton, Edgar; Lawyer, Phillip] WRAIR, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 94.14 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302222 ER PT J AU Olkhanud, P Damdinsuren, B Sen, RJ Gress, R Biragyn, A AF Olkhanud, Purevdorj Damdinsuren, Bazarragchaa Sen, Ranjan Gress, Ronald Biragyn, Arya TI Cancer cells utilize a novel regulatory subset of B cells to promote escape and metastasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Olkhanud, Purevdorj; Biragyn, Arya] NIA, Lab Immunol, NIH, Baltimore, MD 21224 USA. [Damdinsuren, Bazarragchaa; Sen, Ranjan] NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA. [Gress, Ronald] NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 100.26 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303052 ER PT J AU Orr, S Quigley, L Roessler, S Hodge, D Razzook, C Cardone, M Zhang, WG Trinchieri, G Lyakh, L McVicar, D AF Orr, Selinda Quigley, Laura Roessler, Stephen Hodge, Deborah Razzook, Catherine Cardone, Marco Zhang, Weiguo Trinchieri, Giorgio Lyakh, Lyudmila McVicar, Daniel TI LAB/NTAL regulates zymosan-mediated inflammatory responses in Bone Marrow Derived Dendritic Cells (BMDC) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Orr, Selinda; Quigley, Laura; Roessler, Stephen; Hodge, Deborah; Razzook, Catherine; Cardone, Marco; Trinchieri, Giorgio; Lyakh, Lyudmila; McVicar, Daniel] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Zhang, Weiguo] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 98.14 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303002 ER PT J AU Pandiyan, P Conti, H Gaffen, S Lenardo, M AF Pandiyan, Pushpa Conti, Heather Gaffen, Sarah Lenardo, Michael TI Dual roles of CD4+CD25+Foxp3+Tregs in regulating Th17 cells and promoting host resistance to Candida albicans SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pandiyan, Pushpa; Lenardo, Michael] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Gaffen, Sarah] Univ Pittsburgh, Pittsburgh, PA USA. [Conti, Heather; Gaffen, Sarah] SUNY Buffalo, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 137.7 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304048 ER PT J AU Pelletier, M Bulua, A Kastner, D Siege, R AF Pelletier, Martin Bulua, Ariel Kastner, Daniel Siege, Richard TI Evaluation of the effects of disease-causing mutations in type I TNF receptor (TNFR1) on neutrophil responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pelletier, Martin; Bulua, Ariel; Siege, Richard] NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. [Kastner, Daniel] NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 140.8 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304121 ER PT J AU Pinkhasov, J Lee, J Li, LQ El-khoury, D Lesourne, R Hwang, SJ Zhang, YG Weng, NP Love, P AF Pinkhasov, Julia Lee, Jan Li, LiQi El-khoury, Dalai Lesourne, Renaud Hwang, SuJin Zhang, Yongging Weng, Nan Ping Love, Paul TI Identifying molecules that "fine-tune" T cell antigen receptor signaling during thymocyte selection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pinkhasov, Julia; Lee, Jan; Li, LiQi; El-khoury, Dalai; Lesourne, Renaud; Hwang, SuJin; Love, Paul] NIH, Bldg 10, Bethesda, MD 20892 USA. [Zhang, Yongging; Weng, Nan Ping] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.40 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300064 ER PT J AU Pisitkun, P Claudio, E Ren, N Wang, HS Bolland, S Siebenlist, U AF Pisitkun, Prapaporn Claudio, Estefania Ren, Nina Wang, Hongshan Bolland, Silvia Siebenlist, Ulrich TI CIKS/Act1 is required for collagen-induced arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pisitkun, Prapaporn; Claudio, Estefania; Ren, Nina; Wang, Hongshan; Siebenlist, Ulrich] NIAID, IAS, LIR, NIH, Bethesda, MD 20892 USA. [Bolland, Silvia] NIAID, AFGS, LIG, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 93.3 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302208 ER PT J AU Qi, Q Bai, YT Schwartzberg, P August, A AF Qi, Qian Bai, Yuting Schwartzberg, Pamela August, Avery TI Partial rescue of Itk-/- iNKT cell development by Txk/Rlk reveals a unique role for Itk in the survival of iNKT cells. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Qi, Qian; Bai, Yuting; August, Avery] Penn State Univ, Immunol & Infect Dis, University Pk, PA 16802 USA. [Schwartzberg, Pamela] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 50.40 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301132 ER PT J AU Ramaswamy, M Cruz, A Price, S Rao, VK Siegel, R AF Ramaswamy, Madhu Cruz, Anthony Price, Susan Rao, V. Koneti Siegel, Richard TI TCR and Fas-mediated apoptosis targets Effector Memory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ramaswamy, Madhu; Cruz, Anthony; Siegel, Richard] NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD USA. [Price, Susan; Rao, V. Koneti] NIAID, ALPS Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 85.14 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301233 ER PT J AU Ranatunga, D Hedrich, C Wang, FY McVicar, D Norwak, N Joshi, T Feigenbaum, L Grant, L Stager, S Bream, J AF Ranatunga, Dilini Hedrich, Christian Wang, Fengying McVicar, Daniel Norwak, Nathan Joshi, Trupti Feigenbaum, Lionel Grant, Lindsay Stager, Simona Bream, Jay TI Effects of cell-type specific hIL-10 expression on disease susceptibility SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ranatunga, Dilini; Hedrich, Christian; Wang, Fengying; Grant, Lindsay; Bream, Jay] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. [McVicar, Daniel] NCI, Frederick, MD 21701 USA. [Norwak, Nathan] Transnetyx Inc, Cordova, TN USA. [Joshi, Trupti; Stager, Simona] Johns Hopkins Sch Med, Baltimore, MD USA. [Feigenbaum, Lionel] SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 51.5 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301146 ER PT J AU Rittenhouse-Olson, K Abdulla, J Heimburg-Molinaro, J Sahoo, P Almogren, A Roy, R Chang, R Morey, S Barchi, J AF Rittenhouse-Olson, Kate Abdulla, Julia Heimburg-Molinaro, Jamie Sahoo, Padmini Almogren, Adel Roy, Rene Chang, Richard Morey, Susan Barchi, Joseph TI Carbohydrate Tumor Antigen Vaccines using Unique Strategies SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Rittenhouse-Olson, Kate; Abdulla, Julia; Heimburg-Molinaro, Jamie; Sahoo, Padmini; Morey, Susan] Univ Buffalo, Buffalo, NY USA. [Almogren, Adel] King Saud Univ, Riyadh, Saudi Arabia. [Roy, Rene] Univ Quebec, Montreal, PQ, Canada. [Chang, Richard] Natl Taiwan Univ, Taipei, Taiwan. [Barchi, Joseph] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.27 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303151 ER PT J AU Salcedo, R Worschech, A Cardone, M Jones, Y Gyulai, Z Dai, RM Marincola, F Trinchieri, G AF Salcedo, Rosalba Worschech, Andrea Cardone, Marco Jones, Yava Gyulai, Zsofia Dai, Ren-Ming Marincola, Francesco Trinchieri, Giorgio TI Role of Myd88-mediated signaling in the prevention of colon adenocarcinomas SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Salcedo, Rosalba; Dai, Ren-Ming] SAIC Frederick Inc, Frederick, MD USA. [Cardone, Marco; Jones, Yava; Gyulai, Zsofia; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, CCR, Frederick, MD 21701 USA. [Worschech, Andrea; Marincola, Francesco] NCI, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 95.10 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302239 ER PT J AU Sato, T Shimosato, T Yamamoto, M Kobayashi, N Miyazawa, N Ishigatsubo, Y Klinman, D AF Sato, Takashi Shimosato, Takeshi Yamamoto, Masaki Kobayashi, Nobuaki Miyazawa, Naoki Ishigatsubo, Yoshiaki Klinman, Dennis TI Accelerated wound healing in mice by local administration of sustained-release CpG oligodeoxynucleotide SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sato, Takashi; Kobayashi, Nobuaki; Miyazawa, Naoki; Ishigatsubo, Yoshiaki] Yokohama City Univ, Internal Med & Clin Immunol, Yokohama, Kanagawa, Japan. [Shimosato, Takeshi] Shinshu Univ, Nagano, Japan. [Sato, Takashi; Yamamoto, Masaki; Klinman, Dennis] NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304022 ER PT J AU Savan, R Reynolds, D McFarland, A Feigenbaum, L Ramakrishnan, K Shirota, H Klinman, D Donnelly, R Young, H AF Savan, Ram Reynolds, Della McFarland, AdeIle Feigenbaum, Lionel Ramakrishnan, Karthika Shirota, Hidekazu Klinman, Dennis Donnelly, Raymond Young, Howard TI Ectopic expression of Interleukin-22 receptors (IL-22R1) on lymphocytes induces multi-organ inflammation and premature death SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Savan, Ram; Reynolds, Della; McFarland, AdeIle; Feigenbaum, Lionel; Ramakrishnan, Karthika; Shirota, Hidekazu; Klinman, Dennis; Young, Howard] Natl Canc Inst, Frederick, MD USA. [Donnelly, Raymond] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 35.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300034 ER PT J AU Scarzello, A Stauffer, J Back, T Subleski, J Weiss, J Ortaldo, J Wiltrout, R AF Scarzello, Anthony Stauffer, Jim Back, Tim Subleski, Jeff Weiss, Jonathan Ortaldo, John Wiltrout, Robert TI Immunological characterization of oncogene-driven models of hepatocellular carcinoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Scarzello, Anthony; Stauffer, Jim; Back, Tim; Subleski, Jeff; Weiss, Jonathan; Ortaldo, John; Wiltrout, Robert] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 100.19 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303029 ER PT J AU Sckisel, G Nzigira, N Hurwitz, A Blazar, B Murphy, W AF Sckisel, Gail Nzigira, Ngabo Hurwitz, Andrew Blazar, Bruce Murphy, William TI Combination of CTLA-4 blockade with anti-CD40/IL-2 immunotherapy augments the CD8+T cell response in resting and tumor-bearing mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sckisel, Gail; Nzigira, Ngabo; Murphy, William] Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA. [Hurwitz, Andrew] NCI, Tumor Immun & Tolerance Grp, Frederick, MD 21701 USA. [Blazar, Bruce] Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN USA. [Blazar, Bruce] Univ Minnesota, Ctr Canc, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.17 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303165 ER PT J AU Shankar, S Divietro, J Xie, ZH Wilson, M Wynn, T Druey, K AF Shankar, Sucharita Divietro, Jeffrey Xie, Zhihui Wilson, Mark Wynn, Thomas Druey, Kirk TI RGS16 regulation of Th2-mediated inflammatory responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shankar, Sucharita; Divietro, Jeffrey; Xie, Zhihui; Druey, Kirk] NIAID, Mol & Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Wilson, Mark; Wynn, Thomas] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 141.9 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302143 ER PT J AU Shanker, A De Kluyver, R Sayers, T AF Shanker, Anil De Kluyver, Rachel Sayers, Thomas TI Impact of bortezomib-induced proteasome inhibition in vivo on anti-tumor T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shanker, Anil; De Kluyver, Rachel; Sayers, Thomas] NCI Frederick, Canc & Inflammat Program, Frederick, MD USA. [Shanker, Anil; Sayers, Thomas] SAIC Frederick, Basic Sci Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 101.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303084 ER PT J AU Sharma, A Yu, Q Sen, JM AF Sharma, Archna Yu, Qing Sen, Jyoti Misra TI What goes up must come down: The consequences of not turning down pre-TCR induced beta-catenin SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sharma, Archna; Yu, Qing; Sen, Jyoti Misra] NIA, NIH, Baltimore, MD 21224 USA. RI Sharma, Archna/R-9377-2016 OI Sharma, Archna/0000-0003-4745-0220 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.29 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300083 ER PT J AU Shen, W Li, WQ Feigenbaum, L Hixon, J Durum, S AF Shen, Wei Li, Wenqing Feigenbaum, Lionel Hixon, Julie Durum, Scott TI Establishment of IL-17A/F BAC construct for transgenic reporter mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shen, Wei; Li, Wenqing; Feigenbaum, Lionel; Hixon, Julie; Durum, Scott] NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 34.10 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300013 ER PT J AU Shenderov, K Barber, D Mayer, K Jankovic, D White, S Caspar, P Hieny, S Trinchieri, G Besra, G Cerundolo, V Sher, A AF Shenderov, Kevin Barber, Daniel Mayer, Katrin Jankovic, Dragana White, Sandy Caspar, Pat Hieny, Sara Trinchieri, Giorgio Besra, Gurdyal Cerundolo, Vincenzo Sher, Alan TI Inflammasome-dependent IL-1 beta production is critical for complete Freund's adjuvant-induced helper T cell polarization SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shenderov, Kevin; Barber, Daniel; Mayer, Katrin; Jankovic, Dragana; White, Sandy; Caspar, Pat; Hieny, Sara; Sher, Alan] NIAID, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA. [Shenderov, Kevin; Cerundolo, Vincenzo] Univ Oxford, Weatherall Inst Mol Med, Oxford, England. [Trinchieri, Giorgio] NCI, Lab Expt Immunol, NIH, Frederick, MD 21701 USA. [Besra, Gurdyal] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.44 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304009 ER PT J AU Shi, GP Vistica, B Lovaas, J Tang, CY Aziz, M Gery, I AF Shi, Guangpu Vistica, Barbara Lovaas, Jenna Tang, Cuiyan Aziz, Mehak Gery, Igal TI Pathogenic or non-pathogenic subpopulations of Th17 cells are generated by stimulation of naive CD4 cells via antigen/APC or anti-CD3/CD28 antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shi, Guangpu; Vistica, Barbara; Lovaas, Jenna; Tang, Cuiyan; Aziz, Mehak; Gery, Igal] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 135.10 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303262 ER PT J AU Shirota, H Klinman, D AF Shirota, Hidekazu Klinman, Dennis TI CpG-conjugated apoptotic tumor cells elicit potent tumor immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shirota, Hidekazu; Klinman, Dennis] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.41 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303154 ER PT J AU Shulzhenko, N Morgun, A Dzutsev, A Matzinger, P AF Shulzhenko, Natalia Morgun, Andrey Dzutsev, Amiran Matzinger, Polly TI Dissecting the effects of microflora and antibiotics on immune and metabolic compartments in the gut SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shulzhenko, Natalia; Morgun, Andrey; Matzinger, Polly] NIAID, NIH, Bethesda, MD 20892 USA. [Dzutsev, Amiran] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 90.7 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302102 ER PT J AU Shulzhenko, N Morgun, A Gavrilova, O Battle, M Matzinger, P AF Shulzhenko, Natalia Morgun, Andrey Gavrilova, Oksana Battle, Michele Matzinger, Polly TI Shaping of the gut microbiota by B lymphocytes influences GATA4-dependent lipid absorption and body fat accumulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shulzhenko, Natalia; Morgun, Andrey; Matzinger, Polly] NIAID, NIH, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDK, NIH, Bethesda, MD 20892 USA. [Battle, Michele] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 90.8 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302096 ER PT J AU Singh, S Foley, J Zhang, HW Farber, J AF Singh, Satya Foley, John Zhang, Hongwei Farber, Joshua TI The DRF motif in CXCR6 is important for selectivity among G-proteins in receptor signaling, which is cell-type specific SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Singh, Satya; Foley, John; Zhang, Hongwei; Farber, Joshua] NIAID, LMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 133.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303231 ER PT J AU Smrz, D Iwaki, S Metcalfe, D Gilfillan, A AF Smrz, Daniel Iwaki, Shoko Metcalfe, Dean Gilfillan, Alasdair TI Contrasting requirements for DAP12 in receptor-mediated mast cell activation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Smrz, Daniel; Iwaki, Shoko; Metcalfe, Dean; Gilfillan, Alasdair] NIAID, LAD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 86.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301257 ER PT J AU Snyder, G Jiang, JS Chen, K Fresguez, T Smith, P Snyder, N Luchetti, T Cirl, C Miethke, T Tjandra, N Xiao, T AF Snyder, Greg Jiang, Jiansheng Chen, Kang Fresguez, Theresa Smith, Patrick Snyder, Nathaniel Luchetti, Timothy Cirl, Christine Miethke, Thomas Tjandra, Nico Xiao, Tsan TI Structural studies of Toll like receptor signaling adaptors. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Snyder, Greg; Jiang, Jiansheng; Fresguez, Theresa; Smith, Patrick; Snyder, Nathaniel; Luchetti, Timothy; Xiao, Tsan] NIAID, Lab Immunol, NIH, Bethesda, MD 20892 USA. [Cirl, Christine; Miethke, Thomas] Tech Univ Munich, Ilnst Med Mikrobiol, D-80290 Munich, Germany. [Chen, Kang; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.45 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304021 ER PT J AU Strbo, N Vaccari, M Pahwa, S Kolber, M Fisher, E Gonzalez, L Franchini, G Podack, E AF Strbo, Natasa Vaccari, Monica Pahwa, Savita Kolber, Michael Fisher, Eva Gonzalez, Louis Franchini, Genoveffa Podack, Eckhard TI Heat shock protein Gp96-Ig-peptide complexes based vaccine induce predominant immune responses at mucosal sites SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Strbo, Natasa; Pahwa, Savita; Kolber, Michael; Fisher, Eva; Gonzalez, Louis; Podack, Eckhard] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Vaccari, Monica; Franchini, Genoveffa] NCI, NIH, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 46.13 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301039 ER PT J AU Subleski, J Hall, V Wolfe, T Scarzello, A Weiss, J Chan, T Hodge, D Back, T Ortaldo, J Wiltrout, R AF Subleski, Jeff Hall, Veronica Wolfe, Thomas Scarzello, Anthony Weiss, Jonathan Chan, Tim Hodge, Deborah Back, Timothy Ortaldo, John Wiltrout, Robert TI Activated NKT cells are depleted specifically in the liver and utilize different mechanisms for expansion that depend on TCR dependent vs independent mechanisms of activation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Subleski, Jeff; Hall, Veronica; Wolfe, Thomas; Scarzello, Anthony; Weiss, Jonathan; Chan, Tim; Hodge, Deborah; Back, Timothy; Ortaldo, John; Wiltrout, Robert] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 50.41 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301114 ER PT J AU Tan, CY Vistica, B Shi, GP Aziz, M Gery, I AF Tan, Cuiyan Vistica, Barbara Shi, Guangpu Aziz, Mehak Gery, Igal TI Antigen-specific Th9 cell lines exhibit unique features SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tan, Cuiyan; Vistica, Barbara; Shi, Guangpu; Aziz, Mehak; Gery, Igal] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 99.2 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303022 ER PT J AU Tarasenko, T Bolland, S AF Tarasenko, Tatiana Bolland, Silvia TI A BALB/c locus on chromosome 12 confers resistance to lupus in Fc gamma R2-/- mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tarasenko, Tatiana; Bolland, Silvia] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 93.23 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302171 ER PT J AU Teixeira, C Oliveira, L Gomes, R Meneses, C Elnaiem, DE Kamhawi, S Valenzuela, J AF Teixeira, Clarissa Oliveira, Luiz Gomes, Regis Meneses, Claudio Elnaiem, Dia-Eldim Kamhawi, Shaden Valenzuela, Jesus TI The early inflammatory response to bites of Leishmania major infected Phlebotomus duboscqi sand flies in naive and pre-exposed mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Teixeira, Clarissa; Oliveira, Luiz; Gomes, Regis; Meneses, Claudio; Elnaiem, Dia-Eldim; Kamhawi, Shaden; Valenzuela, Jesus] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 94.15 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302227 ER PT J AU Tewary, P Redmond, C Clifton, M Yang, D Oppenheim, J AF Tewary, Poonam Redmond, Chris Clifton, Mathew Yang, De Oppenheim, Joost TI Neutrophil gelatinase-associated lipocalin (NGAL): Endogenous activators of the immune system SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tewary, Poonam; Oppenheim, Joost] NCI, CCR, CIP, LMI,NIH, Frederick, MD 21701 USA. [Redmond, Chris] Rutgers, Piscataway, NJ USA. [Clifton, Mathew] Fred Hutchinson Canc Res, Seattle, WA USA. [Yang, De] SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 89.15 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302047 ER PT J AU Thakur, S Zallinger, Z Corn-Minor, R Johnson, T Graham, B AF Thakur, Sheetal Zallinger, Zachary Corn-Minor, Radiah Johnson, Teresa Graham, Barney TI lmmunoglobulin Class Switching During RSV Infection Is PKR-Dependent SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Thakur, Sheetal; Zallinger, Zachary] NIEHS, NIH, RTP, Res Triangle Pk, NC USA. [Johnson, Teresa; Graham, Barney] NIAID, Vaccine Res Inst, NIH, Bethesda, MD USA. [Corn-Minor, Radiah] North Carolina Agr & Technol State Univ, Greensboro, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 38.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300160 ER PT J AU Tran, D Thornton, A Shevach, E AF Tran, Dat Thornton, Angela Shevach, Ethan TI Helios is a Marker for Human Thymic-derived FOXP3+Regulatory T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tran, Dat] Univ Texas Med Sch Houston, Pediat, Houston, TX USA. [Thornton, Angela; Shevach, Ethan] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 143.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304153 ER PT J AU Tran, D Bebris, L Shevach, E Illei, G AF Tran, Dat Bebris, Lolita Shevach, Ethan Illei, Gabor TI Efalizumab down-regulates CD25 expression on FOXP3+regulatory T cells and exacerbates the autoimmunity in primary Sjogren's syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tran, Dat] Univ Texas Med Sch Houston, Pediat, Houston, TX USA. [Bebris, Lolita; Illei, Gabor] NIDCR, NIH, Bethesda, MD USA. [Shevach, Ethan] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 96.4 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302267 ER PT J AU Vazquez, N Schmeisser, H Bekisz, J Zoon, K Wahl, S AF Vazquez, Nancy Schmeisser, Hana Bekisz, Joseph Zoon, Kathryn Wahl, Sharon TI Structural Determinants of IFN alpha Distinguish Antiviral and Potentially Toxic Functions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Vazquez, Nancy; Wahl, Sharon] NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. [Schmeisser, Hana; Bekisz, Joseph; Zoon, Kathryn] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 39.7 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300191 ER PT J AU Voynova, E Bolland, S AF Voynova, Elisaveta Bolland, Silvia TI Role of NK cells in TLR7-induced systemic autoimmune disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Voynova, Elisaveta; Bolland, Silvia] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 93.30 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302184 ER PT J AU Wang, HS Shin, DM Gonzalez-Garcia, I Abbasi, S Feng, JX Morse, H AF Wang, Hongsheng Shin, Dong-Mi Gonzalez-Garcia, Ines Abbasi, Sadia Feng, Jianxun Morse, Herbert TI ENPP1 is a novel cell surface marker of germinal center and memory B cells and is highly expressed in plasma cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wang, Hongsheng; Shin, Dong-Mi; Gonzalez-Garcia, Ines; Abbasi, Sadia; Feng, Jianxun; Morse, Herbert] NIAID, Immunopathol Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.3 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300062 ER PT J AU Wang, H Park, O Lafdil, F Yin, S Horiguchi, N Gao, B AF Wang, Hua Park, Ogyi Lafdil, Fouad Yin, Shi Horiguchi, Norio Gao, Bin TI Coordination of hepatic and myeloid signal transducer and activator of transcription 3 in governing liver carcinogenesis and regeneration SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wang, Hua; Park, Ogyi; Lafdil, Fouad; Yin, Shi; Horiguchi, Norio; Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 100.36 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303039 ER PT J AU Watanabe, M Hathcock, K Vacchio, M Moon, K Hodes, R AF Watanabe, Masashi Hathcock, Karen Vacchio, Melanie Moon, Kyungduk Hodes, Richard TI The role of p53 in antigen-specific and bystander T cell proliferative responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Watanabe, Masashi; Hathcock, Karen; Vacchio, Melanie; Moon, Kyungduk; Hodes, Richard] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 50.15 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301133 ER PT J AU Wilkins, D Tietze, J Alderson, K Weiss, J Bouchlaka, M Priest, S Taub, D Wiltrout, R Longo, D Baumgarth, N Blazar, B Redelman, D Murphy, W AF Wilkins, Danice Tietze, Julia Alderson, Kory Weiss, Jon Bouchlaka, Myriam Priest, Stephen Taub, Dennis Wiltrout, Robert Longo, Dan Baumgarth, Nicole Blazar, Bruce Redelman, Doug Murphy, William TI Antigen nonspecific memory CD8 T cells expand and gain effector function in response to immunotherapy or to viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wilkins, Danice; Alderson, Kory; Bouchlaka, Myriam] Univ Nevada, Microbiol & Immunol, Reno, NV 89557 USA. [Weiss, Jon; Wiltrout, Robert] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. [Blazar, Bruce] Univ Minnesota, Div Hematol Oncol & Blood & Marrow Transplantat, Minneapolis, MN USA. [Taub, Dennis; Longo, Dan] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Tietze, Julia; Murphy, William] Univ Calif Davis, Dept Dermatol & Internal Med, Sacramento, CA 95817 USA. [Redelman, Doug] Univ Nevada, Dept Physiol, Reno, NV 89557 USA. [Priest, Stephen; Baumgarth, Nicole] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.28 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303176 ER PT J AU Williams, J Zhang, JJ Klug, D Nitta, T Kruhlak, M Sharrow, S Granger, L Adams, A Gress, R Takahama, Y Hodes, R AF Williams, Joy Zhang, Jingjing Klug, David Nitta, Takeshi Kruhlak, Michael Sharrow, Susan Granger, Larry Adams, Anthony Gress, Ronald Takahama, Yousuke Hodes, Richard TI Thymocyte autoreactivity and altered thymic epithelial development in the absence of CD28-CD80/86 and CD40-CD40L interactions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Williams, Joy; Zhang, Jingjing; Klug, David; Kruhlak, Michael; Sharrow, Susan; Granger, Larry; Adams, Anthony; Gress, Ronald] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Nitta, Takeshi; Takahama, Yousuke] Univ Tokushima, Div Expt Immunol, Tokushima, Japan. [Hodes, Richard] NIA, NIH, Bethesda, MD 20892 USA. RI Takahama, Yousuke/A-5863-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.69 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304285 ER PT J AU Wright, J Castro, I Damdinsuren, B Hoek, K Carlesso, G Shinners, N Gerstein, R Woodland, R Sen, R Khan, W AF Wright, Jacqueline Castro, Iris Damdinsuren, Bazarragchaa Hoek, Kristen Carlesso, Gianluca Shinners, Nicholas Gerstein, Rachel Woodland, Robert Sen, Ranjan Khan, Wasif TI BCR mediated c-Rel induction facilitates NF-kappa B2 and ReIB expression SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wright, Jacqueline; Castro, Iris; Khan, Wasif] Univ Miami, Microbiol & Immunol, Miami, FL USA. [Damdinsuren, Bazarragchaa; Sen, Ranjan] NIA, Baltimore, MD 21224 USA. [Gerstein, Rachel; Woodland, Robert] Univ Massachusetts, Sch Med, Worcester, MA USA. [Wright, Jacqueline; Castro, Iris; Hoek, Kristen; Carlesso, Gianluca; Shinners, Nicholas; Khan, Wasif] Vanderbilt Univ, Nashville, TN 37235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 84.22 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301213 ER PT J AU Wurster, A De, S Precht, P Wood, W Becker, K Pazin, M AF Wurster, Andrea De, Supriyo Precht, Patricia Wood, William Becker, Kevin Pazin, Michael TI The chromatin remodeling landscape of T helper cell differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wurster, Andrea; De, Supriyo; Precht, Patricia; Wood, William; Becker, Kevin; Pazin, Michael] NIA, LCMB, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 88.6 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302015 ER PT J AU Wynn, T Ramalingam, T Madala, S Thompson, R Mentink, M Barron, L Cheever, A Wilson, M AF Wynn, Thomas Ramalingam, Thirumalai Madala, Satish Thompson, Robert Mentink, Margaret Barron, Luke Cheever, Allen Wilson, Mark TI Distinct roles for IL-13 and IL-17 in chronic inflammation and fibrosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wynn, Thomas; Ramalingam, Thirumalai; Madala, Satish; Thompson, Robert; Mentink, Margaret; Barron, Luke; Cheever, Allen; Wilson, Mark] NIH, LPD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 134.8 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303253 ER PT J AU Xiao, WH Fang, F Wang, Y Li, R Zhao, Y Yang, G Jiang, M Sun, J Ma, Y Ren, ZJ Tian, ZG Feng, W Yang, D AF Xiao, Weihua Fang, Fang Wang, Yan Li, Rui Zhao, Ying Yang, Guo Jiang, Ming Sun, Jie Ma, Yang Ren, Zijia Tian, Zhigang Feng, Wei Yang, De TI E2F1 Suppreses DC Maturation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Xiao, Weihua; Fang, Fang; Wang, Yan; Li, Rui; Zhao, Ying; Yang, Guo; Jiang, Ming; Sun, Jie; Ma, Yang; Ren, Zijia; Tian, Zhigang] Univ Sci & Technol China, Sch Life Sci, Hefei, Peoples R China. [Feng, Wei; Yang, De] NCI, Frederick, MD 21701 USA. [Yang, De] SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 88.22 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302011 ER PT J AU Xiong, YB Qiu, F Piao, WJ Song, C Wahl, LM Medvedev, AE AF Xiong, Yanbao Qiu, Fu Piao, Wenji Song, Chang Wahl, Larry M. Medvedev, Andrei E. TI Reprogramming of TLR4 signaling in endotoxin tolerance: altered IRAK4 and TAK1 activation, K63-linked polyubiquitination and signalosome assembly of IRAM, TRAF6, IKK gamma and increased A20 expression SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Xiong, Yanbao; Qiu, Fu; Piao, Wenji; Song, Chang; Medvedev, Andrei E.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Wahl, Larry M.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.23 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304034 ER PT J AU Xu, X Ido, W Wilson, M Farber, J AF Xu, Xin Weiss, Ido Wilson, Mark Farber, Joshua TI NK cells are required for defense against pulmonary K. pneumoniae infection in mice and mediate optimal production of protective cytokines, including IL-22 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Xu, Xin; Weiss, Ido; Wilson, Mark; Farber, Joshua] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 37.41 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300147 ER PT J AU Yang, D Zhao, YL Guo, H Li, Y Tewary, P Zhang, N Oppenheim, J AF Yang, De Zhao, Yuliang Guo, Hua Li, Yana Tewary, Poonam Zhang, Ning Oppenheim, Joost TI Nanoparticle [Gd@C82(OH)22]n induces dendritic cell maturation and promotes Th1 immune responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yang, De; Li, Yana; Tewary, Poonam; Oppenheim, Joost] NCI, Lab Mol Immunoregulat, Frederick, MD 21701 USA. [Zhao, Yuliang] Inst High Energy Phys, Beijing, Peoples R China. [Guo, Hua; Zhang, Ning] Tianjin Med Univ, Tianjin, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.2 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303172 ER PT J AU Yang, XX Angkasekwinai, P Zhu, JF Peng, J Liu, ZD Nurieva, R Liu, XK Chung, Y Chang, SH Sun, B Dong, C AF Yang, Xuexian Angkasekwinai, Pornpimon Zhu, Jinfang Peng, Juan Liu, Zhiduo Nurieva, Roza Liu, Xikui Chung, Yeonseok Chang, Seon Hee Sun, Bing Dong, Chen TI Dec2 regulates initial TH2 lineage commitment SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yang, Xuexian; Angkasekwinai, Pornpimon; Peng, Juan; Nurieva, Roza; Liu, Xikui; Chung, Yeonseok; Chang, Seon Hee; Dong, Chen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Angkasekwinai, Pornpimon] Thammasat Univ, Pathum Thani, Thailand. [Zhu, Jinfang] NIAID, NIH, Bethesda, MD 20892 USA. [Peng, Juan] Wuhan Univ, Wuhan, Peoples R China. [Liu, Zhiduo; Sun, Bing] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China. RI Zhu, Jinfang/B-7574-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 99.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303018 ER PT J AU Yao, X Ahmadzadeh, M Rosenberg, S Robbins, P AF Yao, Xin Ahmadzadeh, Mojgan Rosenberg, Steven Robbins, Paul TI Reconstitution of peripheral CD4+FOXP3+regulatory T cells in cancer patients receiving adoptive immunotherapy is related to the clinical response to therapy. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yao, Xin; Ahmadzadeh, Mojgan; Rosenberg, Steven; Robbins, Paul] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.18 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303169 ER PT J AU Yin, S Wang, H Park, O Wei, W Shen, JL Gao, B AF Yin, Shi Wang, Hua Park, Ogyi Wei, Wei Shen, Jilong Gao, Bin TI Enhanced liver regeneration in MO deficient mice after partial hepatectomy via activating hepatocyte STAT3 and stimulating inflammatory response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yin, Shi; Wei, Wei; Shen, Jilong] Anhui Med Univ, Inst Clin Pharmacol, Hefei, Peoples R China. [Yin, Shi; Wang, Hua; Park, Ogyi; Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD USA. [Shen, Jilong] Anhui Med Univ, Prov Lab Microbiol & Parasitol Anhui, Minist Educ, Hefei, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 134.6 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303249 ER PT J AU Yin, YY Li, YL Martin, R Mariuzza, R AF Yin, Yiyuan Li, Yili Martin, Roland Mariuzza, Roy TI Crystal structure of an autoimmune TCR with optimal binding to its self-antigen - an alternative strategy for escaping negative selection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yin, Yiyuan; Li, Yili; Mariuzza, Roy] Univ Maryland, Ctr Adv Res Biotechnol, Inst Biotechnol, Rockville, MD USA. [Yin, Yiyuan] Univ Maryland, Program Mol & Cell Biol, College Pk, MD 20742 USA. [Martin, Roland] NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Martin, Roland] Univ Med Ctr Hamburg Eppendorf, Inst Neuroimmunol & Clin MS Res, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 93.32 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302195 ER PT J AU Young, H Hodge, D Berthel, C Subleski, J Coppola, V Schaughency, P Razzook, C Buschman, M AF Young, Howard Hodge, Deborah Berthel, Cyril Subleski, Jeff Coppola, Vincenzo Schaughency, Paul Razzook, Catherine Buschman, Matthew TI Novel Gene Expression Patterns in IFN-gamma 3 ' Untranslated Region AU-Rich Element-Deleted Mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Young, Howard; Hodge, Deborah; Berthel, Cyril; Subleski, Jeff; Coppola, Vincenzo; Schaughency, Paul; Razzook, Catherine; Buschman, Matthew] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 51.7 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301139 ER PT J AU Yu, Q Sharma, A Sen, J AF Yu, Qing Sharma, Archna Sen, Jyoti TI T Cell Factor-1 Initiates T Helper 2 Fate by Inducing GATA-3 and Repressing IFNgamma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yu, Qing; Sharma, Archna; Sen, Jyoti] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Yu, Qing] ORAU ORISE, Oak Ridge, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 99.8 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303024 ER PT J AU Yu, SY Zhao, DM Jothi, R Xue, HH AF Yu, Shuyang Zhao, Dongmei Jothi, Raja Xue, Hai-hui TI GABPalpha is required for normal T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yu, Shuyang; Zhao, Dongmei; Xue, Hai-hui] Univ Iowa, Microbiol, Iowa City, IA USA. [Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 36.67 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300074 ER PT J AU Zamisch, M Wang, L Yockey, L Vinson, C Bosselut, R AF Zamisch, Monica Wang, Lie Yockey, Laura Vinson, Charles Bosselut, Remy TI Two distinct functions for the BTB domain of the CD4-differentiating factor Thpok SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zamisch, Monica; Wang, Lie; Yockey, Laura; Bosselut, Remy] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. [Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 85.20 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301235 ER PT J AU Zeng, M Wietgrefe, S Schacker, T Southern, P Reilly, C Feldman, D Carlis, J Silvestri, G Lifson, J Haase, A AF Zeng, Ming Wietgrefe, Stephen Schacker, Timothy Southern, Peter Reilly, Cavan Feldman, Daniel Carlis, John Silvestri, Guido Lifson, Jeffery Haase, Ashley TI SIVmac251 infection of Rhesus Macaques destroys secondary lymphoid tissue architecture and depletes naive T cell populations SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zeng, Ming; Wietgrefe, Stephen; Schacker, Timothy; Southern, Peter; Reilly, Cavan; Feldman, Daniel; Carlis, John; Haase, Ashley] Univ Minnesota, Minneapolis, MN USA. [Silvestri, Guido] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Lifson, Jeffery] NCI, AIDS Vaccine Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 45.9 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301028 ER PT J AU Zhou, R Horai, R Mattapallil, M Rigden, R Villasmil, R Caspi, R AF Zhou, Ru Horai, Reiko Mattapallil, Mary Rigden, Rachael Villasmil, Rafael Caspi, Rachel TI Conversion of conventional T cells to Tregs within the eye and the dual role of the vision related molecule, retinoic acid, in ocular immune privilege SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zhou, Ru; Horai, Reiko; Mattapallil, Mary; Rigden, Rachael; Villasmil, Rafael; Caspi, Rachel] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 48.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301075 ER PT J AU Zhu, ZG Singh, V Bronte, V Feigenbaum, L Hurwitz, A AF Zhu, Zigiang Singh, Vinod Bronte, Vincenzo Feigenbaum, Lionel Hurwitz, Arthur TI Provision of CD4+T cell help preferentially enhances anti-tumor immunity of high avidity T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zhu, Zigiang; Singh, Vinod; Hurwitz, Arthur] NCI, CCR, CIP, LMI,NIH, Frederick, MD 21701 USA. [Bronte, Vincenzo] Univ Padua, Padua, Italy. [Feigenbaum, Lionel] SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 131.19 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303143 ER PT J AU Hansen, JK Weldon, JE Xiang, L Beers, R Onda, M Pastan, I AF Hansen, Johanna K. Weldon, John E. Xiang, Laiman Beers, Richard Onda, Masanori Pastan, Ira TI A Recombinant Immunotoxin Targeting CD22 With Low Immunogenicity, Low Nonspecific Toxicity, and High Antitumor Activity in Mice SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE HA22; BL22; deimmunization; protein engineering; B-cell epitopes ID B-CELL EPITOPES; PSEUDOMONAS-EXOTOXIN; ANIMAL TOXICITY; PHASE-I; CANCER; TRANSPORT; CLEAVAGE; THERAPY; TUMORS; TOXIN AB Recombinant immunotoxins (RITs) are genetically engineered proteins designed to kill cancer cells. The RIT HA22 contains the Fv portion of an anti-CD22 antibody fused to a 38 kDa fragment of Pseudomonas exotoxin A (PE38). As PE38 is a bacterial protein, patients frequently produce antibodies that neutralize its activity, preventing retreatment. We have earlier shown in mice that PE38 contains 7 major B-cell epitopes located in domains II and III of the protein. Here we present a new mutant RIT, HA22-LR-6X, in which we removed most B-cell epitopes by deleting domain II and mutating 6 residues in domain III. HA22-LR-6X is cytotoxic to several lymphoma cell lines, has very low nonspecific toxicity, and retains potent antitumor activity in mice with CA46 lymphomas. To assess its immunogenicity, we immunized 3 MHC-divergent strains of mice with 5 mu g doses of HA22-LR-6X, and found that HA22-LR-6X elicited significantly lower antibody responses than HA22 or other mutant RITs with fewer epitopes removed. Furthermore, large (50 mu g) doses of HA22-LR-6X induced markedly lower antibody responses than 5 mu g of HA22, indicating that high doses can be administered with low immunogenicity. Our experiments show that we have correctly identified and removed B-cell epitopes from PE38, producing a highly active immunotoxin with low immunogenicity and low animal toxicity. Future studies will determine if these properties carry over to humans with cancer. C1 [Hansen, Johanna K.; Weldon, John E.; Xiang, Laiman; Beers, Richard; Onda, Masanori; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Hansen, Johanna K.; Weldon, John E.] Natl Inst Gen Med Sci, NIH, Bethesda, MD USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Rm 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov OI Weldon, John/0000-0002-6516-9064 FU NIH; National Cancer Institute FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and with a Cooperative Research and Development Agreement with MedImmune, LLC. NR 20 TC 22 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD APR PY 2010 VL 33 IS 3 BP 297 EP 304 DI 10.1097/CJI.0b013e3181cd1164 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 575BF UT WOS:000276037500008 PM 20445350 ER PT J AU Doria-Rose, NA AF Doria-Rose, Nicole A. TI HIV Neutralizing Antibodies: Clinical Correlates and Implications for Vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTED INDIVIDUALS; EFFICACY TRIALS; RESPONSES; BREADTH; BROAD; IMMUNIZATION; PROTECTION; SELECTION; THAILAND C1 NIAID, HIV Specif Immun Sect, NIH, Bethesda, MD 20892 USA. RP Doria-Rose, NA (reprint author), NIAID, HIV Specif Immun Sect, NIH, Bldg 10,Rm 11B07,10 Ctr Dr, Bethesda, MD 20892 USA. EM doriarosen@mail.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 36 TC 6 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2010 VL 201 IS 7 BP 981 EP 983 DI 10.1086/651143 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 563KG UT WOS:000275129900004 PM 20170372 ER PT J AU Minor, RAC Limmon, GV Miller-DeGraff, L Dixon, D Andrews, DMK Kaufman, RJ Imani, F AF Minor, Radiah A. Corn Limmon, Gino V. Miller-DeGraff, Laura Dixon, Darlene Andrews, Danica M. K. Kaufman, Randal J. Imani, Farhad TI Double-Stranded RNA-Activated Protein Kinase Regulates Early Innate Immune Responses During Respiratory Syncytial Virus Infection SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID NF-KAPPA-B; INDUCED LUNG INFLAMMATION; AIRWAY EPITHELIAL-CELLS; FACTOR (NF)-KAPPA B; TNF-ALPHA; IN-VITRO; NASOPHARYNGEAL SECRETIONS; ALVEOLAR MACROPHAGES; GENE-EXPRESSION; TRANSGENIC MICE AB Respiratory syncytial virus (RSV) is the most common cause of childhood viral bronchiolitis and lung injury. Inflammatory responses significantly contribute to lung pathologies during RSV infections and bronchiolitis but the exact mechanisms have not been completely defined. The double-stranded RNA-activated protein kinase (PKR) functions to inhibit viral replication and participates in several signaling pathways associated with innate inflammatory immune responses. Using a functionally defective PKR (PKR(-/-)) mouse model, we investigated the role of this kinase in early events of RSV-induced inflammation. Our data showed that bronchoalveolar lavage (BAL) fluid from infected PKR(-/-) mice had significantly lower levels of several innate inflammatory cytokines and chemokines. Histological examinations revealed that there was less lung injury in infected PKR(-/-) mice as compared to the wild type. A genome-wide analysis showed that several early antiviral and immune regulatory genes were affected by PKR activation. These data suggest that PKR is a signaling molecule for immune responses during RSV infections. C1 [Miller-DeGraff, Laura; Dixon, Darlene; Andrews, Danica M. K.; Imani, Farhad] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Kaufman, Randal J.] Univ Michigan, Dept Biochem, Ann Arbor, MI 48109 USA. [Minor, Radiah A. Corn] N Carolina A&T Univ, Greensboro, NC USA. [Limmon, Gino V.] Ctr Life Sci, Singapore MIT Alliance Res & Technol, Singapore, Singapore. RP Imani, F (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM imani@niehs.nih.gov RI minor, radiah/B-6412-2012 FU National Institute of Environmental Health Sciences/NIH FX We would like to thank Ms. Kimwa Walker and the NIEHS Histology and Micro array core facilities for their assistance. This research was supported entirely by the Intramural Research Program at National Institute of Environmental Health Sciences/NIH. NR 64 TC 6 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR PY 2010 VL 30 IS 4 BP 263 EP 272 DI 10.1089/jir.2009.0051 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 580NM UT WOS:000276456100008 PM 20038207 ER PT J AU Wang, Y Tan, XH DiGiovanna, JJ Lee, CCR Stern, JB Raffeld, M Jaffe, ES Kraemer, KH AF Wang, Yun Tan, Xiao Hui DiGiovanna, John J. Lee, Chyi-Chia Richard Stern, Jere B. Raffeld, Mark Jaffe, Elaine S. Kraemer, Kenneth H. TI Genetic Diversity in Melanoma Metastases from a Patient with Xeroderma Pigmentosum SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID DNA-POLYMERASE-ETA; RECURRENT MELANOMA; CUTANEOUS MELANOMA; HIGH-FREQUENCY; VARIANT CELLS; MUTATIONS; PTEN; SPECTRUM; DISEASE; REPAIR C1 [Wang, Yun; Tan, Xiao Hui; DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Wang, Yun] Peking Univ, Dept Dermatol, Hosp 1, Beijing 100871, Peoples R China. [Tan, Xiao Hui] Peking Univ, Mol Oncol Lab, Sch Oncol, Beijing Canc Hosp & Inst, Beijing 100871, Peoples R China. [DiGiovanna, John J.] Brown Univ, Div Dermatopharmacol, Dept Dermatol, Warren Alpert Med Sch, Providence, RI 02912 USA. [Lee, Chyi-Chia Richard; Stern, Jere B.; Raffeld, Mark; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kraemer, KH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. EM kraemerk@nih.gov RI Lee, Chyi-Chia/I-1938-2013; OI Lee, Chyi-Chia/0000-0002-5306-7781; Jaffe, Elaine/0000-0003-4632-0301 FU Intramural NIH HHS [ZIA BC004517-35] NR 24 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 IS 4 BP 1188 EP 1191 DI 10.1038/jid.2009.377 PG 5 WC Dermatology SC Dermatology GA 577VB UT WOS:000276251000038 PM 19956187 ER PT J AU Adamson, AS Laurence, A Ghoreschi, K Rittler, M Kanno, Y Wei, L Stetler-Stevenson, W O'Shea, J AF Adamson, A. S. Laurence, A. Ghoreschi, K. Rittler, M. Kanno, Y. Wei, L. Stetler-Stevenson, W. O'Shea, J. 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PD APR PY 2010 VL 130 SU 1 MA 595 BP S100 EP S100 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100595 ER PT J AU Bartels, AK Gentile, NB Duverger, O Morasso, MI AF Bartels, A. K. Gentile, N. B. Duverger, O. Morasso, M. I. TI Effect of inducible misexpression of Dlx3 in basal keratinocytes on epidermal differentiation and hair development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Bartels, A. K.; Gentile, N. B.; Duverger, O.; Morasso, M. I.] NIAMS, NIH, Dev Skin Biol Sect, Bethesda, MD 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. 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PD APR PY 2010 VL 130 SU 1 MA 751 BP S126 EP S126 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100749 ER PT J AU Bradford, PT Goldstein, AM DiGiovanna, JJ Tamura, D Khan, SC Tucker, MA Kraemer, KH AF Bradford, P. T. Goldstein, A. M. DiGiovanna, J. J. Tamura, D. Khan, S. C. Tucker, M. A. Kraemer, K. H. TI 39-year follow-up of xeroderma pigmentosum: Skin cancer, neurologic degeneration and mortality SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Bradford, P. T.; Goldstein, A. M.; DiGiovanna, J. J.; Tamura, D.; Khan, S. C.; Tucker, M. A.; Kraemer, K. H.] NCI, Bethesda, MD 20892 USA. [DiGiovanna, J. J.] Brown Univ, Sch Med, Providence, RI 02912 USA. RI Tucker, Margaret/B-4297-2015 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 364 BP S61 EP S61 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100365 ER PT J AU Chaudhary, SC Singh, T Kapur, P Kurundkar, D Weng, Z Elmets, CA Kopelovich, L Athar, M AF Chaudhary, S. C. Singh, T. Kapur, P. Kurundkar, D. Weng, Z. Elmets, C. A. Kopelovich, L. Athar, M. TI Nitric oxide (NO)-releasing exisulind suppresses UVB-induced cutaneous photocarcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Chaudhary, S. C.; Singh, T.; Kapur, P.; Kurundkar, D.; Weng, Z.; Elmets, C. A.; Athar, M.] Univ Alabama, Birmingham, AL USA. [Kopelovich, L.] Natl Canc Inst, Canc Prevent Div, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 821 BP S137 EP S137 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100817 ER PT J AU Choi, W Miyamura, Y Wolber, R Smuda, C Reinhold, W Liu, H Kolbe, L Hearing, VJ AF Choi, W. Miyamura, Y. Wolber, R. Smuda, C. Reinhold, W. Liu, H. Kolbe, L. Hearing, V. J. TI Regulation of human skin pigmentation in situ by repetitive UV exposure - molecular characterization of responses to UVA and/or UVB SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Choi, W.; Miyamura, Y.; Reinhold, W.] NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. 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TI Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Cui, C.; Piao, Y.; Childress, V.; Ko, M.; Schlessinger, D.] NIA, NIH, Baltimore, MD 21224 USA. [Cui, C.] Medstar Res Inst, Baltimore, MD USA. [Kunisada, M.] Kobe Univ, Sch Med, Div Dermatol, Kobe, Hyogo 650, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 612 BP S102 EP S102 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100611 ER PT J AU Duverger, O Gentile, NB Bartels, AK Maddox, KM Lee, AD Okano, J Morasso, MI AF Duverger, O. Gentile, N. B. Bartels, A. K. Maddox, K. M. Lee, A. D. Okano, J. Morasso, M. I. TI Dlx3 expression in neural crest-derived cells is required for normal hair and tooth development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Duverger, O.; Gentile, N. B.; Bartels, A. K.; Maddox, K. M.; Lee, A. D.; Okano, J.; Morasso, M. I.] NIAMS, NIH, Dev Skin Biol Sect, Bethesda, MD 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 644 BP S108 EP S108 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100644 ER PT J AU Gerstenblith, MR Shi, J Landi, MT AF Gerstenblith, M. R. Shi, J. Landi, M. T. TI Pigmentation and skin cancer genome-wide association studies: A review and meta-analysis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Gerstenblith, M. R.; Shi, J.; Landi, M. T.] NCI, NIH, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 841 BP S141 EP S141 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100839 ER PT J AU Hoashi, T Kanda, N Watanabe, S Sato, S Hearing, VJ AF Hoashi, T. Kanda, N. Watanabe, S. Sato, S. Hearing, V. J. TI The melanocyte-specific glycoprotein, Pmel17/gp100, is released by ectodomain shedding SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Hoashi, T.] Sanraku Hosp, Dept Dermatol, Tokyo, Japan. [Hoashi, T.; Sato, S.] Univ Tokyo, Dept Dermatol, Tokyo 113, Japan. [Hoashi, T.; Kanda, N.] Teikyo Univ, Sch Med, Dept Dermatol, Tokyo 173, Japan. [Watanabe, S.; Hearing, V. J.] NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 830 BP S139 EP S139 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100830 ER PT J AU Huter, E Glass, D Shevach, E AF Huter, E. N. Glass, D. D. Shevach, E. M. TI In vivo conversion of CD4+FoxP3-to FoxP3+T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Huter, E. N.; Glass, D. D.; Shevach, E. M.] NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. [Huter, E. N.] Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 046 BP S8 EP S8 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100048 ER PT J AU Hwang, H Diwakar, G Zaidi, MR Merlino, GT Hornyak, TJ AF Hwang, H. Diwakar, G. Zaidi, M. R. Merlino, G. T. Hornyak, T. J. 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TI IRF8 as a potentially key determinant in the activation or death of CD8T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Miyagawa, F.; Nelson, E. A.; Katz, S. I.] NIH, Dermatol Branch, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 707 BP S118 EP S118 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100703 ER PT J AU Motegi, S Lu, M Heneghan, M Wu, C Chavakis, T Udey, MC AF Motegi, S. Lu, M. Heneghan, M. Wu, C. Chavakis, T. Udey, M. C. 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TI Defective metabolic degradation of retinoic acid in mice lacking Cyp26b1 alters skin development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Okano, J.; Aronova, M.; Morasso, M. I.] NIH, NIAMS, Dev Skin Biol Sect, Bethesda, MD USA. [Lichti, U.; Yuspa, S. H.] NCI, NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Zhang, G.] NIH, NIBIB, Lab Bioengn & Phys Sci, Bethesda, MD USA. [Sakai, Y.] Osaka Univ, Grad Sch Med, Dept Plast & Reconstruct Surg, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 610 BP S102 EP S102 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100610 ER PT J AU Paek, S Miyagawa, F Katz, SI AF Paek, S. Miyagawa, F. Katz, S. I. TI Peptide protection of the pinna: a model for studying the role of CD8+T cells in mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Paek, S.; Miyagawa, F.; Katz, S. I.] NIH, Dermatol Branch, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 100 BP S17 EP S17 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100102 ER PT J AU Patel, GK Yee, CL Montemorano, A Maggio, K Vogel, IC AF Patel, G. K. Yee, C. L. Montemorano, A. Maggio, K. Vogel, I. C. TI The role of cancer stem cells in the initiation and propagation of human cutaneous squamous cell carcinoma in an in vivo model SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Patel, G. K.] Cardiff Univ, Dept Dermatol & Wound Healing, Cardiff, Wales. [Patel, G. K.; Yee, C. L.; Vogel, I. C.] Natl Canc Inst, Dermatol Branch, Bethesda, MD USA. [Montemorano, A.] Rockledge Skin Canc Clin, Bethesda, MD USA. [Maggio, K.] Walter Reed Army Med Ctr, Dermatol Serv, Washington, DC 20307 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 167 BP S28 EP S28 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100165 ER PT J AU Purwar, R Jetten, AM Kupper, TS AF Purwar, R. Jetten, A. M. Kupper, T. S. TI Retionoid Orphan Receptor-gamma (ROR-gamma) deficient mice generate potent Th9 responses, but not Th17 responses, under Th17 polarizing conditions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Purwar, R.; Kupper, T. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Jetten, A. M.] NIEHS, NIH, Res Triangle Pk, NC 27709 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 710 BP S119 EP S119 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100710 ER PT J AU Purwar, R Jetten, AM Kupper, T AF Purwar, R. Jetten, A. M. Kupper, T. TI Deficiency of retinoid related orphan receptor-gamma (ROR-gamma) results in impaired contact hypersensitivity (CHS) responses, but enhanced melanoma tumor immunity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Purwar, R.; Kupper, T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jetten, A. M.] NIEHS, NIH, Res Triangle Pk, NC 27709 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 711 BP S119 EP S119 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100708 ER PT J AU Qian, Y Valenzuela, JG Flores, G Rivitti, EA Aoki, V Hans-Filhio, G Diaz, LA AF Qian, Y. Valenzuela, J. G. Flores, G. Rivitti, E. A. Aoki, V. Hans-Filhio, G. Diaz, L. A. TI IgG4 and IgE anti-Dsg1 auto-antibodies recognize Lutzomyia longipalpis salivary gland antigens SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Qian, Y.; Flores, G.; Rivitti, E. A.; Diaz, L. A.] Univ N Carolina, Chapel Hill, NC USA. [Valenzuela, J. G.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA. [Aoki, V.] Univ Sao Paulo, Dept Dermatol, Sao Paulo, Brazil. [Hans-Filhio, G.] Univ Fed Mato Grosso do Sul, Dept Dermatol, Campo Grande, RJ, Brazil. NR 0 TC 1 Z9 1 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 117 BP S20 EP S20 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100117 ER PT J AU Qureshi, A Vleugels, R Puett, R Fears, TR Laden, F Han, J AF Qureshi, A. Vleugels, R. Puett, R. Fears, T. R. Laden, F. Han, J. TI Cumulative ultraviolet radiation flux and risk for incident skin cancer in the United States SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Qureshi, A.; Vleugels, R.; Han, J.] Brigham & Womens Hosp, Dept Dermatol, Clin Res Program, Boston, MA 02115 USA. [Qureshi, A.; Puett, R.; Laden, F.; Han, J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Fears, T. R.] NCI, NIH, Bethesda, MD 20892 USA. RI Puett, Robin/A-4449-2012 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 401 BP S67 EP S67 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100399 ER PT J AU Rajesh, S Li, S Wang, J Thangapazham, R Moss, J Darling, TN AF Rajesh, S. Li, S. Wang, J. Thangapazham, R. Moss, J. Darling, T. N. TI Rapamycin blocks lymphangiogenesis induced by TSC2-null hamartoma cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Rajesh, S.; Li, S.; Wang, J.; Thangapazham, R.; Darling, T. N.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Moss, J.] NHLBI, NIH, Translat Med Branch, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 016 BP S3 EP S3 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100018 ER PT J AU Shukla, A Yang, Y Chellamal, PV Madanikia, S Yuspa, SH AF Shukla, A. Yang, Y. Chellamal, P. V. Madanikia, S. Yuspa, S. H. TI TGF beta dependent differentiation of dermal fibroblasts to myofibroblasts is regulated by CLIC4 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Shukla, A.; Yang, Y.; Chellamal, P. V.; Madanikia, S.; Yuspa, S. H.] NCI, NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RI Shukla, Anjali/G-4046-2014 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 023 BP S4 EP S4 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100022 ER PT J AU Singh, T Kapur, P Chaudhary, SC Elemts, CA Kopelovich, L Athar, M AF Singh, T. Kapur, P. Chaudhary, S. C. Elemts, C. A. Kopelovich, L. Athar, M. TI ERB-041, an estrogen receptor beta agonist inhibits skin photocarcinogesis in SKH-1 hair-less mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Singh, T.; Kapur, P.; Chaudhary, S. C.; Elemts, C. A.; Athar, M.] Univ Alabama, Birmingham, AL USA. [Kopelovich, L.] 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 134 BP S23 EP S23 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100136 ER PT J AU Strong, CD Conlan, S Deming, CB Cheng, J Sears, K Segre, JA AF Strong, C. de Guzman Conlan, S. Deming, C. B. Cheng, J. Sears, K. Segre, J. A. TI A milieu of regulatory elements in the epidermal differentiation complex (EDC) syntenic block: Implications for atopic dermatitis and psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Strong, C. de Guzman; Conlan, S.; Deming, C. B.; Cheng, J.; Segre, J. A.] NHGRI, Bethesda, MD 20892 USA. [Sears, K.] Univ Illinois, Urbana, IL 61801 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 543 BP S91 EP S91 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100542 ER PT J AU Tan, X Anzick, S Khan, SG Ueda, T Stone, G DiGiovanna, JJ Tamura, D Wattendorf, D Brewer, C Zalewski, C Walker, R Butman, J Griffith, A Meltzer, P Bergstresser, P Kraemer, KH AF Tan, X. Anzick, S. Khan, S. G. Ueda, T. Stone, G. DiGiovanna, J. J. Tamura, D. Wattendorf, D. Brewer, C. Zalewski, C. Walker, R. Butman, J. A. Griffith, A. Meltzer, P. Bergstresser, P. Kraemer, K. H. TI Balanced 9p22q translocation in a patient with melanoma, deafness and DNA repair deficiency disrupts p14arf and down-regulates TBX1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Tan, X.; Anzick, S.; Khan, S. G.; Ueda, T.; Stone, G.; DiGiovanna, J. J.; Tamura, D.; Walker, R.; Meltzer, P.; Kraemer, K. H.] NCI, Bethesda, MD 20892 USA. [Ueda, T.] Pharm Med Device Agcy, Tokyo, Japan. [DiGiovanna, J. J.] Brown Med Sch, Providence, RI USA. [Wattendorf, D.] Off Air Force Surg Gen, Washington, DC USA. [Brewer, C.; Zalewski, C.; Griffith, A.] NIDCD, Bethesda, MD USA. [Butman, J. A.] NIH, CC, Bethesda, MD USA. [Bergstresser, P.] Univ Texas Dallas, Dallas, TX 75230 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 143 BP S24 EP S24 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100141 ER PT J AU Tock, CL Altiner, A Turner, LR Batra, P Warner, JA Therrien, J Turner, ML Miller, SA Beer, JZ Kraemer, KH Udey, MC Vogel, JC Terunuma, A AF Tock, C. L. Altiner, A. Turner, L. R. Batra, P. Warner, J. A. Therrien, J. Turner, M. L. Miller, S. A. Beer, J. Z. Kraemer, K. H. Udey, M. C. Vogel, J. C. Terunuma, A. TI A typical daily close of ultraviolet radiation on human skin treated with an FDA-standardized sunscreen leaves a unique "UVA signature" on the transcriptome SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Tock, C. L.; Altiner, A.; Turner, L. R.; Batra, P.; Warner, J. A.; Therrien, J.; Turner, M. L.; Kraemer, K. H.; Udey, M. C.; Vogel, J. C.; Terunuma, A.] NCI, NIH, Bethesda, MD 20892 USA. [Miller, S. A.; Beer, J. Z.] US FDA, Rockville, MD 20857 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 318 BP S53 EP S53 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100318 ER PT J AU Valencia, JC Coelho, S Zhang, G Hearing, VJ AF Valencia, J. C. Coelho, S. Zhang, G. Hearing, V. J. TI MDM2 antagonists increase pigmentation and induce epidermal thinning in human reconstructed skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Valencia, J. C.; Coelho, S.; Hearing, V. J.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Zhang, G.] NIBIB, Lab Bioengn & Phys Sci, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 881 BP S147 EP S147 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100877 ER PT J AU Xiao, Y Vogel, JC AF Xiao, Y. Vogel, J. C. TI Structural relationships between dermal blood vessels and the epithelium in mouse skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Xiao, Y.; Vogel, J. C.] NIH, Natl Canc Inst, Dermatol Branch, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 026 BP S5 EP S5 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100029 ER PT J AU Xu, J Weng, Z Kim, H Li, C Kopelovich, L Christiano, AM Bickers, DR Athar, M AF Xu, J. Weng, Z. Kim, H. Li, C. Kopelovich, L. Christiano, A. M. Bickers, D. R. Athar, M. TI Hairless gene confers resistance to nonmelanoma skin cancer development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Xu, J.; Weng, Z.; Li, C.; Athar, M.] Univ Alabama, Birmingham, AL USA. [Kim, H.; Christiano, A. M.; Bickers, D. R.] Columbia Univ, Dept Dermatol, New York, NY 10027 USA. [Kopelovich, L.] Natl Canc Inst, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 177 BP S30 EP S30 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100176 ER PT J AU Zhuang, A Cataisson, C Zaidi, R Hakim, S Merlino, G Yuspa, SH AF Zhuang, A. Cataisson, C. Zaidi, R. Hakim, S. Merlino, G. Yuspa, S. H. TI Exploring the role of keratinocyte-derived inflammation in melanomagenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 05-08, 2010 CL Atlanta, GA SP Soc Investtigat Dermatol C1 [Zhuang, A.; Cataisson, C.; Zaidi, R.; Hakim, S.; Merlino, G.; Yuspa, S. H.] NCI, CCR, Lab Canc Biol & Genet, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2010 VL 130 SU 1 MA 845 BP S141 EP S141 PG 1 WC Dermatology SC Dermatology GA 580ND UT WOS:000276455100841 ER PT J AU Quinn, MT Deleo, FR Nauseef, WM AF Quinn, Mark T. DeLeo, Frank R. Nauseef, William M. TI Memorial: Gary Michael Bokoch, 1954-2010 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Biographical-Item C1 [Quinn, Mark T.] Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59715 USA. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Nauseef, William M.] Univ Iowa, Inflammat Program, Iowa City, IA USA. [Nauseef, William M.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Nauseef, William M.] Vet Adm Med Ctr, Iowa City, IA USA. RP Quinn, MT (reprint author), Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59715 USA. EM mquinn@montana.edu OI DeLeo, Frank/0000-0003-3150-2516 FU BLRD VA [I01 BX000513] NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 2010 VL 87 IS 4 BP 535 EP 536 DI 10.1189/jlb.0210081 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 618GL UT WOS:000279339500001 PM 20356902 ER PT J AU Kim, WK Sun, Y Do, H Autissier, P Halpern, EF Piatak, M Lifson, JD Burdo, TH McGrath, MS Williams, K AF Kim, Woong-Ki Sun, Yue Do, Hien Autissier, Patrick Halpern, Elkan F. Piatak, Michael, Jr. Lifson, Jeffrey D. Burdo, Tricia H. McGrath, Michael S. Williams, Kenneth TI Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE subsets; macrophage; CD16; HIV; AIDS ID PERIPHERAL-BLOOD MONOCYTES; IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; TRANSFORMING GROWTH-FACTOR; HIV-POSITIVE PATIENTS; FC-GAMMA RECEPTORS; ADHESION MOLECULES; HIV-1-INFECTED PATIENTS; MONONUCLEAR PHAGOCYTES; CD16(+) MONOCYTES AB Infection by HIV is associated with the expansion of monocytes expressing CD16 antigens, but the significance of this in HIV pathogenesis is largely unknown. In rhesus macaques, at least three subpopulations of blood monocytes were identified based on their expression of CD14 and CD16: CD14(high)CD16(-), CD14(high)CD16(low), and CD14(low)CD16(high). The phenotypes and functions of these subpopulations, including CD16(+) monocytes, were investigated in normal, uninfected rhesus macaques and macaques that were infected with SIV or chimeric SHIV. To assess whether these different monocyte subpopulations expand or contract in AIDS pathogenesis, we conducted a cross-sectional study of 54 SIV-or SHIV-infected macaques and 48 uninfected controls. The absolute numbers of monocyte populations were examined in acutely infected animals, chronically infected animals with no detectable plasma virus RNA, chronically infected animals with detectable plasma virus RNA, and animals that died with AIDS. The absolute numbers of CD14(high)CD16(low) and CD14(low)CD16(high) monocytes were elevated significantly in acutely infected animals and chronically infected animals with detectable plasma virus RNA compared with uninfected controls. Moreover, a significant, positive correlation was evident between the number of CD14(high)CD16(low) or CD14(low)CD16(high) monocytes and plasma viral load in the infected cohort. These data show the dynamic changes of blood monocytes, most notably, CD14(high)CD16(low) monocytes during lentiviral infection, which are specific to disease stage. J. Leukoc. Biol. 87: 557-567; 2010. C1 [Burdo, Tricia H.; Williams, Kenneth] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Kim, Woong-Ki; Sun, Yue; Autissier, Patrick; Williams, Kenneth] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Do, Hien; McGrath, Michael S.] Pathologica LLC, San Francisco, CA USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [McGrath, Michael S.] Univ Calif San Francisco, Dept Lab Med, Posit Hlth Program, San Francisco, CA 94143 USA. RP Williams, K (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. EM williauy@bc.edu FU Public Health Service [NS040237, NS037654, NS0500041, MH81835] FX This work was supported by Public Health Service grants NS040237 (K. W.), NS037654 (K. W.), NS0500041 (K. W.), and MH81835 (K. W. and M. S. M.). NR 70 TC 42 Z9 42 U1 1 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 2010 VL 87 IS 4 BP 557 EP 567 DI 10.1189/jlb.0209082 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 618GL UT WOS:000279339500005 PM 19843579 ER PT J AU Moore, G Fetterman, B Cox, JT Poitras, N Lorey, T Kinney, W Castle, PE AF Moore, Gaea Fetterman, Barbara Cox, J. Thomas Poitras, Nancy Lorey, Thomas Kinney, Walter Castle, Philip E. TI Lessons From Practice: Risk of CIN 3 or Cancer Associated With an LSIL or HPV-Positive ASC-US Screening Result in Women Aged 21 to 24 SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE Pap; ASC-US; LSIL ID CERVICAL INTRAEPITHELIAL NEOPLASIA; HUMAN-PAPILLOMAVIRUS; CONSENSUS GUIDELINES; YOUNG-WOMEN; METAANALYSIS; MANAGEMENT; REGRESSION; OUTCOMES; LESIONS AB Objective. To characterize the risks of cervical intraepithelial neoplasia 3 (CIN 3) and cancer in women aged 21 to 24 with human papillomavirus (HPV)-positive atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) screening results in routine clinical practice. Materials and Methods. Quality assurance databases containing records of screening test and histologic findings from the Regional Laboratory of the Northern California Kaiser Permanente Medical Care Program were reviewed. Numbers of LSIL and HPV-positive ASCUS results and associated cancers and CIN 3 in women aged 21 to 24 during 2003 to 2007 were tabulated, and the corresponding risks were calculated overall and by year of age. Results. During the 5-year period from 2003 to 2007, 1,620 HPV-positive ASC-US and 2,175 LSIL were diagnosed in women aged 21 to 24, for which corresponding histologic finding is available. No invasive cancers were detected in association with LSIL and HPV-positive ASC-US screening results in this age group during this period. The risk of cancer was therefore 0% (95% CI = 0.00%-0.10%). The risk of CIN 3 associated with an HPV-positive ASC-US was 2.90% (95% CI = 2.14%-3.84%), with LSIL was 2.44% (95% CI = 1.83%-3.18%), and, for the 2 combined, the risk was 2.64% (95% CI = 2.15%-3.20%). Conclusions. The risk of CIN 3 and cancer is low enough that management of women aged 21 to 24 with ASC-US and LSIL smears without immediate colposcopy should be considered, as is currently recommended for women aged 20 and younger. C1 [Kinney, Walter] Permanente Med Grp Inc, Div Gynecol Oncol, Sacramento, CA 95815 USA. [Moore, Gaea] Univ Calif Davis, Sacramento, CA 95817 USA. [Fetterman, Barbara; Poitras, Nancy; Lorey, Thomas] Permanente Med Grp Inc, Reg Lab, Oakland, CA USA. [Cox, J. Thomas] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Kinney, W (reprint author), Permanente Med Grp Inc, Div Gynecol Oncol, 1650 Response Rd, Sacramento, CA 95815 USA. EM walter.kinney@kp.org FU National Institutes of Health; National Cancer Institute FX Dr Castle was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The authors thank the support of the Women's Health Research Institute at Kaiser Permanente Northern California. NR 19 TC 15 Z9 16 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD APR PY 2010 VL 14 IS 2 BP 97 EP 102 DI 10.1097/LGT.0b013e3181b8b024 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 575XX UT WOS:000276106600003 PM 20354416 ER PT J AU Chen, K Delaglio, F Tjandra, N AF Chen, Kang Delaglio, Frank Tjandra, Nico TI A practical implementation of cross-spectrum in protein backbone resonance assignment SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Backbone assignment; Cross-spectrum; Heteronuclear experiments; Automation ID HYPERDIMENSIONAL NMR-SPECTROSCOPY; HIGH-SENSITIVITY; RECONSTRUCTION; AMIDE; N-15; C-13 AB The concept of cross-spectrum is applied in protein NMR spectroscopy to assist in the backbone sequential resonance assignment. Cross-spectrum analysis is used routinely to reveal correlations in frequency domains as a means to reveal common features contained in multiple time series. Here the cross-spectrum between related NMR spectra, for example HNCO and HN(CA)CO, can be calculated with point-by-point multiplications along their common C' carbon axis. In the resulting higher order cross-spectrum, an enhanced correlation signal occurs at every common i-1 carbon frequency allowing the amide proton H(N) (and nitrogen N) resonances from residues i and i-1 to be identified. The cross-spectrum approach is demonstrated using 2D spectra H(N)CO, H(NCA)CO, H(NCO)CACB, and H(N)CACB measured on a (15)N/(13)C double-labeled Ubiquitin sample. These 2D spectra are used to calculate two pseudo-3D cross-spectra, H(i)-H(i-1)-C'(i-1) and H(i)-H(i-1)-CA(i-1)CB(i-1). We show using this approach, backbone resonances of H, C', CA, and CB can be fully assigned without ambiguity. The cross-spectrum principle is expected to offer an easy, practical, and more quantitative approach for heteronuclear backbone resonance assignment. Published by Elsevier Inc. C1 [Chen, Kang; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Delaglio, Frank] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 50,Room 3503, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov FU NIH; National Heart, Lung, and Blood Institute FX We thank Xiongwu Wu, Melvin J. Hinich, Robert Gahl and Yang Shell for helpful discussions. This work was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute. NR 23 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 2010 VL 203 IS 2 BP 208 EP 212 DI 10.1016/j.jmr.2009.12.018 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 578XI UT WOS:000276329700002 PM 20053573 ER PT J AU Wang, RL Wang, GJ Goldstein, RZ Caparelli, EC Volkow, ND Fowler, JS Tomasi, D AF Wang, Ruiliang Wang, Gene-Jack Goldstein, Rita Z. Caparelli, Elisabeth C. Volkow, Nora D. Fowler, Joanna S. Tomasi, Dardo TI Induced Magnetic Force in Human Heads Exposed to 4 T MRI SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; magnetic gradient field; induced magnetic force; MRI safety; phase mapping; ROI analysis; susceptibility-weighted MR pulse sequence ID PHASE REFERENCE; FIELD; VERTIGO; BRAIN; TASTE; TESLA AB Purpose: To map the distribution of the magnetic force induced in the human head during magnetic resonance imaging (MRI) at 4 T for a large group of healthy volunteers. Materials and Methods: The magnetic field distribution in the head of 100 men and 18 women was mapped using phase mapping techniques. Statistical parametric mapping methods using a family-wise error (EWE) corrected threshold P < 0.05 and region-of-interest analyses were used to assess the significance of the results. Results: Eyeballs, orbitofrontal and temporal cortices, subcallosal gyrus, anterior cingulate, midbrain, and brain-stem (pons) are the brain regions most susceptible to magnetic force. The strength of the magnetic force density in the head was lower than 11.5 +/- 5.3 N/m(3) (right eyeball). The strength of the magnetic force density induced in occipital cortex varied linearly with the x-rotation (pitch) angle. Conclusion: We found that the induced magnetic force is highly significant in the eyeballs, orbitofrontal and temporal cortices. subcallosal gyrus, anterior cingulate as well as midbrain and brainstem (pons), regardless of subjects' age or gender. The maximum induced magnetic force was 6 x 10(5) times weaker than the gravitational force: thus. biological effects of the magnetic force during imaging are not expected to be significant. C1 [Wang, Ruiliang; Wang, Gene-Jack; Goldstein, Rita Z.; Caparelli, Elisabeth C.; Fowler, Joanna S.; Tomasi, Dardo] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Caparelli, Elisabeth C.] SUNY Stony Brook, SCAN Ctr, Stony Brook, NY 11794 USA. [Volkow, Nora D.; Tomasi, Dardo] NIAAA, Bethesda, MD USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. RP Wang, RL (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 555A, Upton, NY 11973 USA. EM rlwang@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU Intramural NIH HHS [ZIA AA000550-06] NR 23 TC 2 Z9 2 U1 0 U2 3 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 APR PY 2010 VL 31 IS 4 BP 815 EP 820 DI 10.1002/jmri.22125 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 578WU UT WOS:000276328200005 PM 20373424 ER PT J AU Saybasili, H Faranesh, AZ Saikus, CE Ozturk, C Lederman, RJ Guttman, MA AF Saybasili, Hans Faranesh, Anthony Z. Saikus, Christina E. Ozturk, Cengizhan Lederman, Robert J. Guttman, Michael A. TI Interventional MRI Using Multiple 3D Angiography Roadmaps With Real-Time Imaging SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE image-guided interventions; real-time MRI; 3D roadmaps; MRA; MRCP; maximum intensity projection (MIP) ID MAGNETIC-RESONANCE; CARDIOVASCULAR PROCEDURES; TGRAPPA; TSENSE AB Purpose: To enhance real-time magnetic resonance (MR)-guided catheter navigation by overlaying colorized multi-phase MR angiography (MRA) and cholangiopancreatography (MRCP) roadmaps in an anatomic context. Materials and Methods: Time-resolved MRA and respiratory-gated MRCP were acquired prior to real-lime imaging in a pig model. MRA and MRCP data were loaded into a custom real-time MRI reconstruction and visualization workstation where they were displayed as maximum intensity projections (MIPs) in distinct colors. The MIPs were rendered in 3D together with real-time multislice imaging data using alpha blending. Interactive rotation allowed different views of the combined data. Results: Fused display of the previously acquired MIP angiography data with real-time imaging added anatomical context during endovascular interventions in swine. The use of multiple MIPs rendered in different colors facilitated differentiation of vascular structures, improving visual feedback during device navigation. Conclusion: Interventional real-time MRI may be enhanced by combining with previously acquired multi-phase angiograms. Rendered as 3D MIPs together with 2D slice data, this technique provided useful anatomical context that enhanced M RI -guided interventional applications. C1 [Saybasili, Hans; Faranesh, Anthony Z.; Saikus, Christina E.; Lederman, Robert J.; Guttman, Michael A.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Saybasili, Hans; Ozturk, Cengizhan] Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey. RP Saybasili, H (reprint author), NHLBI, Translat Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA. EM saybasilih@nhlbi.nih.gov RI Ozturk, Cengizhan/A-6177-2016; OI Ozturk, Cengizhan/0000-0002-6966-0774; lederman, robert/0000-0003-1202-6673 FU Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health, USA [Z01-HL005062-07] FX Contract grant sponsor: Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health, USA; Contract grant number: Z01-HL005062-07 (to R.J.L.). NR 20 TC 10 Z9 10 U1 0 U2 5 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 APR PY 2010 VL 31 IS 4 BP 1015 EP 1019 DI 10.1002/jmri.22097 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 578WU UT WOS:000276328200029 PM 20373448 ER PT J AU Romero, R Kusanovic, JP Gotsch, F Erez, O Vaisbuch, E Mazaki-Tovi, S Moser, A Tam, S Leszyk, J Master, SR Juhasz, P Pacora, P Ogge, G Gomez, R Yoon, BH Yeo, L Hassan, SS Rogers, WT AF Romero, Roberto Kusanovic, Juan Pedro Gotsch, Francesca Erez, Offer Vaisbuch, Edi Mazaki-Tovi, Shali Moser, Allan Tam, Sunny Leszyk, John Master, Stephen R. Juhasz, Peter Pacora, Percy Ogge, Giovanna Gomez, Ricardo Yoon, Bo H. Yeo, Lami Hassan, Sonia S. Rogers, Wade T. TI Isobaric labeling and tandem mass spectrometry: A novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra-amniotic infection/inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Proteomic; preterm birth; prematurity; MIAC; microbial invasion of the amniotic cavity; chorioamnionitis; isotopic; multiplex; label; high-dimensional biology; 'bottom-up'; 'top-down'; computational biology; high-dimensional biology; systems biology; endoplasmic reticulum stress; misfolded protein; unfolded protein ID BLOOD-CELL COUNT; C-REACTIVE PROTEIN; MULTIDIMENSIONAL LIQUID-CHROMATOGRAPHY; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; HIGH-DIMENSIONAL BIOLOGY; TOLL-LIKE RECEPTORS; MICROBIAL INVASION; GENE-EXPRESSION; PREMATURE RUPTURE; PROTEOMIC ANALYSIS AB Methods. A cross-sectional study was designed and included AF samples from patients with spontaneous PTL and intact membranes in the following groups: (1) patients without IAI who delivered at term (n = 26); (2) patients who delivered preterm without IAI (n = 25); and (3) patients with IAI (n = 24). Proteomic profiling of AF samples was performed using a workflow involving tryptic digestion, iTRAQ labeling and multiplexing, strong cation exchange fractionation, and liquid chromatography tandem mass spectrometry. Twenty-five separate 4-plex samples were prepared and analyzed. Results. Collectively, 123,011 MS 20 cells/mm 20% of eosinophils. Controls were selected among women with an amniotic fluid eosinophil count < 20% and matched for gestational age at amniocentesis. The analysis was conducted with non-parametric statistics. Results. The study population consisted of 10 cases and 50 controls. Gestational age and cervical dilatation at admission were similar in both groups. Cases had a lower gestational age at delivery than controls [34.6 weeks, inter-quartile range (IQR) 32-37.3 weeks vs. 38.0 weeks, IQR 35-40 weeks, respectively; p = 0.018]. The prevalence of preterm delivery < 35 weeks was higher among patients who had > 20% eosinophils than in the control group [50% (5/10) vs. 18% (9/50), respectively; p = 0.029]. Similar results were observed for delivery at < 37 weeks [cases: 70% (7/10) vs. controls: 36% (18/50); p = 0.046]. Conclusions. Women with preterm labor and intact membranes who have a large proportion of eosinophils in the amniotic fluid are at an increased risk for spontaneous preterm delivery. These patients may have had an episode of preterm labor related to a type I hypersensitivity reaction. C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Romero, Roberto; Kusanovic, Juan Pedro; Lamont, Ronald; Mittal, Pooja; Hassan, Sonia S.; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto; Kusanovic, Juan Pedro; Lamont, Ronald; Mittal, Pooja; Hassan, Sonia S.; Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Sotero del Rio Hosp, Dept Obstet & Gynecol, CEDIP Ctr Perinatal Diag & Res, Santiago, Chile. [Bytautiene, Egle] Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77550 USA. [Garfield, Robert E.] St Josephs Hosp, Dept Obstet & Gynecol, Phoenix, AZ USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu 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 112 TC 16 Z9 16 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR PY 2010 VL 23 IS 4 BP 320 EP 329 DI 10.3109/14767050903168465 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 567TX UT WOS:000275470600010 PM 19900034 ER PT J AU Romero, R Kusanovic, JP Munoz, H Gomez, R Lamont, RF Yeo, L AF Romero, Roberto Kusanovic, Juan Pedro Munoz, Hernan Gomez, Ricardo Lamont, Ronald F. Yeo, Lami TI Allergy-induced preterm labor after the ingestion of shellfish SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Allergy; preterm delivery; preterm birth; eosinophils; uterine allergy; pregnancy; preterm parturition; seafood; hypersensitivity; atopy; gestation; parturition; labor; allergic reaction ID AMNIOTIC-FLUID SLUDGE; IGE-BINDING EPITOPES; HOUSE-DUST-MITE; MAST-CELLS; FOOD ALLERGY; CLINICAL-SIGNIFICANCE; INTACT MEMBRANES; IMMUNOGLOBULIN-E; MAJOR ALLERGEN; GUINEA-PIG AB Preterm parturition is a syndrome caused by several mechanisms of disease, including intrauterine infection/inflammation, uteroplacental ischemia, uterine overdistension, cervical disease, maternal/fetal stress, abnormal allogeneic responses, allergic reactions, and unknown insults. An allergic-like mechanism was proposed as a potential etiology for the preterm parturition syndrome, based on the observation that eosinophils were present in the amniotic fluid in a fraction of women with preterm labor and a history of allergy, coupled with the observation that conditioned media from degranulated mast cells (the effector cells of type 1 hypersensitivity) induced contractility of human myometrial strips. This communication describes a case of a pregnant woman who had an allergic reaction and regular uterine contractions after the ingestion of lobster meat, to which she was known to be allergic. Preterm labor subsided after the treatment of antihistamines and steroids. The patient subsequently delivered at term. At follow-up, the child was diagnosed with atopy and asthma, and required frequent use of inhaled corticosteroids and beta-2 adrenergic agents. The immunological basis for preterm labor induced by an allergic-like reaction (hypersensitivity) is reviewed.= 1 y using NHANES 2003-2006 data and the Dietary Reference Intake panel age groupings. Similar estimates were calculated for vitamin D intake from food and dietary supplements using NHANES 2005-2006. Diet was assessed with 2 24-h recalls; dietary supplement and antacid use were determined by questionnaire. The National Cancer Institute method was used to estimate usual nutrient intake from dietary sources. The mean daily nutrient intake from supplemental sources was added to the adjusted dietary intake estimates to produce total usual nutrient intakes for calcium and vitamin D. A total of 53% of the U.S. population reported using any dietary supplement (2003-2006), 43% used calcium (2003-2006), and 37% used vitamin D (2005-2006). For users, dietary supplements provided the adequate intake (AI) recommendation for calcium intake for similar to 12% of those 71 y. Males and females aged 1-3 y had the highest prevalence of meeting the AI from dietary and total calcium intakes. For total vitamin D intake, males and females >= 71, and females 14-18 y had the lowest prevalence of meeting the AI. Dietary supplement use is associated with higher prevalence of groups meeting the AI for calcium and vitamin D. Monitoring usual total nutrient intake is necessary to adequately characterize and evaluate the population's nutritional status and adherence to recommendations for nutrient intake. J. Nutr. 140: 817-822, 2010. C1 [Bailey, Regan L.; Dwyer, Johanna T.; Sempos, Christopher T.; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Dodd, Kevin W.] NCI, NIH, Bethesda, MD 20892 USA. [Goldman, Joseph A.; Moshfegh, Alanna J.] ARS, USDA, Beltsville, MD USA. [Gahche, Jaime J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. EM baileyr@mail.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769 NR 37 TC 214 Z9 214 U1 2 U2 25 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 2010 VL 140 IS 4 BP 817 EP 822 DI 10.3945/jn.109.118539 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 571FI UT WOS:000275736700015 PM 20181782 ER PT J AU Chiba, Y Goto, K Matsusue, K Kimura, S Misawa, M AF Chiba, Yoshihiko Goto, Kumiko Matsusue, Kimihiko Kimura, Shioko Misawa, Miwa TI Identification and Characterization of Rat RhoA Gene Promoter SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Article DE RhoA; transcriptional regulation; bronchial smooth muscle ID BRONCHIAL SMOOTH-MUSCLE; MEDIATED CA2+ SENSITIZATION; INHIBITOR; ASTHMA; INTERLEUKIN-13; KINASE; CELLS; JAK2 AB RhoA upregulation has been suggested in bronchial smooth muscles (BSMs) of asthmatic rats. Here, we cloned/characterized the 5'-promoter region of the rat rhoA. A transcription-initiation site was identified at 66-bp upstream of the reference sequence, GenBank-BC061732. Luciferase assay using interleukin-13 (IL-13) stimulated cells revealed a significant promoter activity at 238- to 166-bp upstream of the transcription-initiation site, which contains a signal transducer and activation of transcription (STAT) 6 binding region. The IL-13 induced increase in luciferase activity was inhibited by a STAT6 inhibitor, AS 1517499, or a Janus kinases (JAKs) inhibitor, JAK Inhibitor-1, but not by tyrphostin-AG490, WHI-P131, or tyrphostin-AG9 (selective JAK2, JAK3, and Tyk2 inhibitors, respectively). Thus, rat BSM rhoA expression may have causal relation to the IL-13-JAK1-STAT6 signaling. C1 [Chiba, Yoshihiko; Goto, Kumiko; Misawa, Miwa] Hoshi Univ, Sch Pharm, Dept Pharmacol, Tokyo 1428501, Japan. [Matsusue, Kimihiko] Fukuoka Univ, Fac Pharmaceut Sci, Fukuoka 8140180, Japan. [Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20814 USA. RP Chiba, Y (reprint author), Hoshi Univ, Sch Pharm, Dept Pharmacol, Tokyo 1428501, Japan. EM chiba@hoshi.ac.jp FU Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This work was partly supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan. NR 17 TC 4 Z9 4 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD APR PY 2010 VL 112 IS 4 BP 467 EP 472 DI 10.1254/jphs.09346SC PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 588JW UT WOS:000277066900012 PM 20308800 ER PT J AU Li, JX Koek, W Rice, KC France, CP AF Li, Jun-Xu Koek, Wouter Rice, Kenner C. France, Charles P. TI Differential Effects of Serotonin 5-HT1A Receptor Agonists on the Discriminative Stimulus Effects of the 5-HT2A Receptor Agonist 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane in Rats and Rhesus Monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MONOAMINE REUPTAKE INHIBITORS; ISOBOLOGRAPHIC ANALYSIS; GAMMA-HYDROXYBUTYRATE; SQUIRREL-MONKEYS; HIGH-EFFICACY; TIME-COURSE; COCAINE; ANTAGONISM; 8-OH-DPAT; BRAIN AB Although many drugs act by indirectly stimulating multiple receptors (e. g., reuptake inhibitors), relatively little is known about interactions between agonism at different receptors. This study compared the effect of serotonin (5-HT)(1A) receptor agonists with the discriminative stimulus effects of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats and rhesus monkeys. Eight rats discriminated 0.56 mg/kg i.p. DOM and responded under a fixed ratio (FR) 10 schedule of food presentation, whereas three rhesus monkeys discriminated 0.32 mg/kg s.c. DOM and responded under an FR 5 schedule of stimulus shock termination. DOM and the 5-HT2A receptor agonists 2,5-dimethoxy-4-n-propylthiophenethylamine (2C-T-7) and dipropyltryptamine (DPT), but not the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride (8-OH-DPAT) and 3-chloro-4-fluorophenyl(4-fluoro-4-([(5-methyl-6-methylaminopyridin-2-ylmethyl) amino) methyl] piperidin-1-yl) methanone (F13714), occasioned responding on the DOM-associated lever in rats and monkeys. Both 8-OH-DPAT and F13714 attenuated the discriminative stimulus effects of DOM in monkeys but not in rats; these effects of 8-OH-DPAT and F13714 were prevented by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridyl) cyclohexanecarboxamide (WAY 100635). DPT and 2C-T-7 enhanced the discriminative stimulus effects of DOM in rats and monkeys in an additive manner. Taken together, the results suggest that the DOM discriminative stimulus is pharmacologically similar and mediated by 5-HT2A receptors in rats and monkeys; however, the ability of 5-HT1A receptor agonists to modify the effects of DOM is markedly different between these species. These results indicate possible differences in the neurobiology of 5-HT systems that could be important for studying drugs that have multiple mechanisms of action (e.g., reuptake inhibitors that indirectly stimulate multiple receptors). C1 [Li, Jun-Xu; 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.] Natl Inst Drug Abuse, Chem Biol Res Branch, Rockville, MD USA. [Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, 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 Institutes of Health National Institute on Drug Abuse and the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; National Institutes of Health National Institute on Drug Abuse [K05-DA17918] FX This work was supported in part by the Intramural Research Programs of the National Institutes of Health National Institute on Drug Abuse and the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism. C.P.F. is supported by a Senior Scientist Award from the National Institutes of Health National Institute on Drug Abuse [Grant K05-DA17918]. NR 41 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2010 VL 333 IS 1 BP 244 EP 252 DI 10.1124/jpet.109.163451 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 571YT UT WOS:000275793200026 PM 20053932 ER PT J AU Albarran-Juarez, J Gilsbach, R Piekorz, R Pexa, K Beetz, N Schneider, J Nuernberg, B Birnbaumer, L Hein, L AF Albarran-Juarez, J. Gilsbach, R. Piekorz, R. Pexa, K. Beetz, N. Schneider, J. Nuernberg, B. Birnbaumer, L. Hein, L. TI Modulation of alpha(2)-Adrenoceptor Functions by Heterotrimeric G alpha(i) Protein Isoforms (vol 331, pg 35, 2009) SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Correction C1 [Birnbaumer, L.] Natl Inst Environm Hlth Sci, Neurobiol Lab, NIH, Res Triangle Pk, NC USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2010 VL 333 IS 1 BP 351 EP 351 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 571YT UT WOS:000275793200037 ER PT J AU Lati, C Guthrie, LC Ward, MM AF Lati, Chili Guthrie, Lori C. Ward, Michael M. TI Comparison of the Construct Validity and Sensitivity to Change of the Visual Analog Scale and a Modified Rating Scale as Measures of Patient Global Assessment in Rheumatoid Arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE PATIENT GLOBAL ASSESSMENT; RHEUMATOID ARTHRITIS; RATING SCALE; MARKER STATES; CONSTRUCT VALIDITY ID QUALITY-OF-LIFE; DISEASE-ACTIVITY; STANDARD GAMBLE; MARKER STATES; EVALUATE; TRIAL AB Objective. Patient global assessment (PGA) is commonly measured using a visual analog scale (VAS). The VAS asks patients to integrate many dimensions of rheumatoid arthritis (RA) activity, yet its scope is poorly defined and its endpoints are vague. We investigated whether a modified Rating Scale that used marker states and more defined endpoints would provide a more valid measure of PGA. Methods. In our prospective longitudinal study, 164 patients with active RA rated their global arthritis activity using the VAS and Rating Scale before and after treatment. To compare construct validity, we correlated each score with 2 reference measures of RA activity, the 28-joint count Disease Activity Score (DAS28) and the physician global assessment, and examined how each measure was associated with different aspects of RA activity, including pain, functioning, and depressive symptoms, in multivariate regression analyses. We also examined sensitivity to change. Results. Both measures were correlated with the DAS28 (r = 0.39 for VAS; r = 0.35 for Rating Scale) and physician global assessment (r = 0.41 for VAS; r = 0.26 for Rating Scale) at the baseline visit. Pain and depressive symptoms had the strongest association with the VAS, while functional limitations and depressive symptoms had the strongest association with the Rating Scale. Residual analysis showed no differences in heterogeneity of patients' ratings. VAS was more sensitive to change than the Rating Scale (standardized response means of 0.55 and 0.45). Conclusion. As measures of PGA, the VAS and Rating Scale had comparable construct validity, but differed in which aspects of arthritis activity influenced scores. VAS was more sensitive to change. (First Release March 1 2010; J Rheumatol 2010;37:717-22; doi:10.3899/jrheum.090764) C1 [Lati, Chili; Guthrie, Lori C.; Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS, NIH, 10 CRC,4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural Research Program of the NIAMS/NIH FX Supported by the Intramural Research Program of the NIAMS/NIH. NR 22 TC 18 Z9 18 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2010 VL 37 IS 4 BP 717 EP 722 DI 10.3899/jrheum.090764 PG 6 WC Rheumatology SC Rheumatology GA 584WI UT WOS:000276783900007 PM 20194445 ER PT J AU Brionez, TF Assassi, S Reveille, JD Green, C Learch, T Diekman, L Ward, MM Davis, JC Weisman, MH Nicassio, P AF Brionez, Tamar F. Assassi, Shervin Reveille, John D. Green, Charles Learch, Thomas Diekman, Laura Ward, Michael M. Davis, John C., Jr. Weisman, Michael H. Nicassio, Perry TI Psychological Correlates of Self-reported Disease Activity in Ankylosing Spondylitis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ANKYLOSING SPONDYLITIS; DISEASE ACTIVITY; PSYCHOSOCIAL FACTORS ID PATIENT HEALTH QUESTIONNAIRE; QUALITY-OF-LIFE; ERYTHROCYTE SEDIMENTATION-RATE; ARTHRITIS HELPLESSNESS INDEX; RHEUMATOID-ARTHRITIS; DEPRESSIVE SYMPTOMS; ASSESSED HEALTH; PAIN; PERSPECTIVE; OUTCOMES AB Objective. To investigate the role of psychological variables in self-reported disease activity in patients with ankylosing spondylitis (AS), while controlling for demographic and medical variables. Methods. Patients with AS (n = 294) meeting modified New York criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality, and helplessness. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of the correlation of psychological variables with disease activity, as measured by the Bath AS Disease Activity Index (BASDAI). Results. In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASDAI scores, adding an additional 33% to the overall R-square beyond that accounted for by demographic and medical variables (combined R-square 18%). Specifically, arthritis helplessness and depression accounted for the most significant portion of the variance in BASDAI scores in the final model. Conclusion. Arthritis helplessness and depression accounted for significant variability in self-reported disease activity beyond clinical and demographic variables in patients with AS. These findings have important clinical implications in the treatment and monitoring of disease activity in AS, and suggest potential avenues of intervention. (First Release Feb 15 2010; J Rheumatol 2010;37:829-34; doi:10.3899/jrheum.090476) C1 [Brionez, Tamar F.; Assassi, Shervin; Reveille, John D.; Diekman, Laura] Univ Texas Hlth Sci Ctr Houston, Dept Med, Div Rheumatol, Houston, TX USA. [Green, Charles] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Houston, TX USA. [Learch, Thomas; Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Nicassio, Perry] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90048 USA. [Davis, John C., Jr.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Assassi, S (reprint author), Univ Texas Houston, Dept Med, Div Rheumatol, 6431 Fannin St,MSB 5-270, Houston, TX 77030 USA. EM shervin.assassi@uth.tmc.edu FU Australo-Anglo-American Spondylitis Consortium (TASC); US Department of Health and Human Services; NIH; NIAMS [P01-AR-052915-01]; NIAMS/NIH FX Supported by grants from the Australo-Anglo-American Spondylitis Consortium (TASC), US Department of Health and Human Services, NIH, and the NIAMS P01-AR-052915-01 and the Intramural Research Program, NIAMS/NIH. NR 36 TC 11 Z9 13 U1 1 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2010 VL 37 IS 4 BP 829 EP 834 DI 10.3899/jrheum.090476 PG 6 WC Rheumatology SC Rheumatology GA 584WI UT WOS:000276783900023 PM 20156952 ER PT J AU Stringaris, A Baroni, A Haimm, C Brotman, M Lowe, CH Myers, F Rustgi, E Wheeler, W Kayser, R Towbin, K Leibenluft, E AF Stringaris, Argyris Baroni, Argelinda Haimm, Caroline Brotman, Melissa Lowe, Catherine H. Myers, Frances Rustgi, Eileen Wheeler, Wanda Kayser, Reilly Towbin, Kenneth Leibenluft, Ellen TI Pediatric Bipolar Disorder Versus Severe Mood Dysregulation: Risk for Manic Episodes on Follow-Up SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; pediatric; severe mood dysregulation; irritability; ADHD ID LONGITUDINAL COURSE; LABELING DEFICITS; NATIONAL TRENDS; CHILDREN; YOUTH; IRRITABILITY; ADOLESCENTS; PHENOTYPE; DIAGNOSIS; OPPOSITIONALITY AB Objective: An important question in pediatric bipolar research is whether marked nonepisodic irritability is a manifestation of bipolar disorder in youth. This study tests the hypothesis that youth with severe mood dysregulation (SMD), a category created for the purpose of studying children presenting with severe nonepisodic irritability, will be significantly less likely to develop (hypo-)manic or mixed episodes over time than will youth with bipolar disorder (BD). Method: Patients with SMID (N = 84) and narrowly defined BD (N = 93) at baseline were followed up in 6-monthly intervals using the relevant K-SADS modules to ascertain (hypo-)manic or mixed episodes. Results: Only one of 84 SMD subjects (1/84 [1.2%]; 95% confidence interval CI = 0.0003 to 0.064) experienced a (hypo-)manic or mixed episode during the study (median follow-up = 28.7 months). The frequency of such episodes was more than 50 times higher in those with narrowly defined BD (58/93 [62.48%]; 95% CI 0.52 to 0.72). Conclusions: These data suggest that, over an approximately 2-year follow-up period, youth with SMD are unlikely to develop (hypo-)manic or mixed episodes. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(4):397-405. C1 [Stringaris, Argyris; Baroni, Argelinda; Haimm, Caroline; Brotman, Melissa; Lowe, Catherine H.; Myers, Frances; Rustgi, Eileen; Wheeler, Wanda; Kayser, Reilly; Towbin, Kenneth; Leibenluft, Ellen] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Stringaris, A (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, Denmark Hill, London SE5 8AF, England. EM argyris.stringaris@kcl.ac.uk RI Brotman, Melissa/H-7409-2013 FU National Institute of Mental Health FX This work was supported by the National Institute of Mental Health, Intramural Program. NR 33 TC 64 Z9 65 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2010 VL 49 IS 4 BP 397 EP 405 DI 10.1016/j.jaac.2010.01.013 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 576OF UT WOS:000276153500013 PM 20410732 ER PT J AU Aman, MG Arnold, LE Lecavalier, L Hollway, JA Mulick, JA McDougle, CJ Swiezy, NB Stigler, KA Handen, BL Johnson, C Vitiello, B Bearss, K Dziura, J Scahill, L AF Aman, Michael G. Arnold, L. Eugene Lecavalier, Luc Hollway, Jill A. Mulick, James A. McDougle, Christopher J. Swiezy, Naomi B. Stigler, Kimberly A. Handen, Benjamin L. Johnson, Cynthia Vitiello, Benedetto Bearss, Karen Dziura, James Scahill, Lawrence TI Risperidone and Parent Training in Pervasive Developmental Disorders reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter ID CHILDREN; MEDICATION; TRIAL C1 [Aman, Michael G.; Arnold, L. Eugene; Lecavalier, Luc; Hollway, Jill A.; Mulick, James A.] Ohio State Univ, Columbus, OH 43210 USA. [McDougle, Christopher J.; Swiezy, Naomi B.; Stigler, Kimberly A.] Indiana Univ, Indianapolis, IN 46204 USA. [Handen, Benjamin L.; Johnson, Cynthia] Univ Pittsburgh, Pittsburgh, PA USA. [Vitiello, Benedetto] NIMH, Rockville, MD 20857 USA. [Bearss, Karen; Dziura, James; Scahill, Lawrence] Yale Univ, New Haven, CT USA. RP Aman, MG (reprint author), Ohio State Univ, Columbus, OH 43210 USA. EM aman1@osu.edu NR 4 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 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2010 VL 49 IS 4 BP 407 EP 408 DI 10.1016/j.jaac.2010.01.017 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 576OF UT WOS:000276153500015 ER PT J AU Breslow, RA Guenther, PM Juan, WY Graubard, BI AF Breslow, Rosalind A. Guenther, Patricia M. Juan, Wenyen Graubard, Barry I. TI Alcoholic Beverage Consumption, Nutrient Intakes, and Diet Quality in the US Adult Population, 1999-2006 SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NUTRITION EXAMINATION SURVEY; HEALTHY EATING INDEX-2005; NATIONAL-HEALTH; ITALIAN WOMEN; SMOKING; HABITS; FOOD; MEN; EDUCATION; CANCER AB Background Little is known about associations between alcoholic beverage consumption, nutrient intakes, and diet quality, although each has been independently associated with chronic disease outcomes. Objective This study examines cross-sectional relationships between alcoholic beverage consumption, nutrient intakes, and diet quality (Healthy Eating Index-2005 [HEI-2005] scores) in the US adult population. Methods Data were from four cycles of the National Health and Nutrition Examination Survey (1999-2006). Weighted multiple regression analyses, adjusted for age, race/ethnicity, education, smoking status, and body mass index included 8,155 men and 7,715 women aged >= 20 years who reported their past-year alcoholic beverage consumption and 24-hour dietary intake. Alcoholic beverage consumption was defined by drinking status (never, former, current drinker) and, among current drinkers, by drinking level (number of drinks per day, on average: men <1 to >= 5; women <1 to >= 3). Results Among men, there was no association between drinking status and intakes of energy, most nutrients, or total HEI-2005 score. Among women, former and current (compared to never) drinkers had significantly higher intakes of energy and several nutrients, and current drinkers had significantly lower total HEI-2005 scores (current drinkers 58.9; never drinkers 63.2). Among current drinkers of both sexes, as drinking level increased, intakes of energy and several nutrients significantly increased, whereas total HEI-2005 scores significantly decreased (from 55.9 to 41.5 in men, and from 59.5 to 51.8 in women). Conclusions Among men and women, increasing alcoholic beverage consumption was associated with a decline in total diet quality as measured by the HEI-2005, apparently due to higher energy intake from alcohol as well as other differences in food choices. Educational messages should focus on nutrition and chronic disease risk associated with high consumption of alcoholic beverages and poor food choices, including excessive energy intake. J Am Diet Assoc. 2010;110:551-562. C1 [Breslow, Rosalind A.] NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD USA. [Guenther, Patricia M.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. [Juan, Wenyen] Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Nutr Labeling & Dietary Supplements, College Pk, MD USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Breslow, RA (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Ln,Rm 2071, Rockville, MD 20892 USA. EM rbreslow@mail.nih.gov FU Intramural NIH HHS [Z99 AA999999] NR 38 TC 50 Z9 50 U1 0 U2 7 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 APR PY 2010 VL 110 IS 4 BP 551 EP 562 DI 10.1016/j.jada.2009.12.026 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 581LS UT WOS:000276525200013 PM 20338281 ER PT J AU Young, K Abbott, R Petrovitch, H Chen, R White, L Ross, G Launer, L Bell, C Masaki, K AF Young, K. Abbott, R. Petrovitch, H. Chen, R. White, L. Ross, G. Launer, L. Bell, C. Masaki, K. TI Resting Heart Rate and Cognitive Function: The Honolulu-Asia Aging Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Young, K.; Abbott, R.; Petrovitch, H.; White, L.; Ross, G.; Bell, C.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [Abbott, R.; Petrovitch, H.; Chen, R.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [White, L.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, G.] Dept Vet Affairs, Honolulu, HI USA. [Launer, L.] NIA, Bethesda, MD 20892 USA. NR 0 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 65 EP 65 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100186 ER PT J AU Saito, LY White, L Bell, C Chen, R Petrovitch, H Ross, G Abbott, R Launer, L Masaki, K AF Saito, L. Y. White, L. Bell, C. Chen, R. Petrovitch, H. Ross, G. Abbott, R. Launer, L. Masaki, K. TI Dietary Vitamin D in Mid-Life and Cognitive Function in Late-Life: The Honolulu-Asia Aging Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Saito, L. Y.; Bell, C.; Petrovitch, H.; Ross, G.; Abbott, R.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [White, L.; Chen, R.; Petrovitch, H.; Abbott, R.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [White, L.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, G.] Dept Vet Affairs, Honolulu, HI USA. [Launer, L.] Natl Inst Aging, Bethesda, MD 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 122 EP 122 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100351 ER PT J AU Lee, DS Jeffery, S Gill, T Hanlon, J Meibohm, B Bauer, D Van Ness, PH Harris, T de Rekeneire, N AF Lee, D. S. Jeffery, S. Gill, T. Hanlon, J. Meibohm, B. Bauer, D. Van Ness, P. H. Harris, T. de Rekeneire, N. TI Medication Complexity in a Population of Community-Living Older Persons: The Health, Aging and Body Composition Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Lee, D. S.; Jeffery, S.; Gill, T.; Van Ness, P. H.; de Rekeneire, N.] Yale Univ, Sect Geriatr, New Haven, CT USA. [Jeffery, S.] Univ Connecticut, Sch Pharm, Storrs, CT USA. [Hanlon, J.] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. [Meibohm, B.] Univ Tennessee, Dept Pharmaceut Sci, Memphis, TN USA. [Bauer, D.] Univ Calif San Francisco, Div Gen & Internal Med, San Francisco, CA 94143 USA. [Harris, T.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NR 0 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 147 EP 147 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100423 ER PT J AU Pham, C Launer, L Bell, C Chen, R Petrovitch, H White, L He, Q Abbott, R Ross, GW Masaki, K AF Pham, C. Launer, L. Bell, C. Chen, R. Petrovitch, H. White, L. He, Q. Abbott, R. Ross, G. W. Masaki, K. TI Midlife Dietary Fat and Cholesterol Intake and Late-Life Cognitive Function: The Honolulu-Asia Aging Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Pham, C.; Bell, C.; Petrovitch, H.; Abbott, R.; Ross, G. W.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [Chen, R.; Petrovitch, H.; White, L.; He, Q.; Abbott, R.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [White, L.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, G. W.] Dept Vet Affairs, Honolulu, HI USA. [Launer, L.] NIA, Bethesda, MD 20892 USA. NR 0 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 177 EP 178 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100513 ER PT J AU Kim, I Bell, C Launer, L White, L Chen, R Petrovitch, H Abbott, R Ross, G Masaki, K AF Kim, I. Bell, C. Launer, L. White, L. Chen, R. Petrovitch, H. Abbott, R. Ross, G. Masaki, K. TI Poor Olfaction is Associated with Low Hippocampal Volume in Cognitively Intact Elderly Men: The Honolulu-Asia Aging Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Kim, I.; Bell, C.; Petrovitch, H.; Abbott, R.; Ross, G.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [White, L.; Chen, R.; Petrovitch, H.; Abbott, R.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [White, L.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, G.] Dept Vet Affairs, Honolulu, HI USA. [Launer, L.] NIA, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 179 EP 179 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100518 ER PT J AU Inaba, M White, L Bell, C Chen, R Petrovitch, H Launer, L Abbott, R Ross, G Masaki, K AF Inaba, M. White, L. Bell, C. Chen, R. Petrovitch, H. Launer, L. Abbott, R. Ross, G. Masaki, K. TI White Matter Lesions on Brain MRI Scan and Five-Year Cognitive Decline: The Honolulu-Asia Aging Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Inaba, M.; Bell, C.; Petrovitch, H.; Abbott, R.; Ross, G.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [White, L.; Chen, R.; Petrovitch, H.; Abbott, R.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [White, L.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, G.] Dept Vet Affairs, Honolulu, HI USA. [Launer, L.] NIA, Bethesda, MD 20892 USA. NR 0 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 182 EP 182 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100525 ER PT J AU Chang, DS Simonsick, EM AF Chang, D. S. Simonsick, E. M. TI Association of BMI, adiposity, and weight change on the 1 year incidence of mobility loss and declining endurance capacity. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc C1 [Simonsick, E. M.] NIA, Baltimore, MD 21224 USA. [Simonsick, E. M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Chang, D. S.] UMDNJ SOM, Stratford, NJ USA. NR 0 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 SU 1 BP 189 EP 189 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TO UT WOS:000276247100547 ER PT J AU Strotmeyer, ES Arnold, AM Boudreau, RM Ives, DG Cushman, M Robbins, JA Harris, TB Newman, AB AF Strotmeyer, Elsa S. Arnold, Alice M. Boudreau, Robert M. Ives, Diane G. Cushman, Mary Robbins, John A. Harris, Tamara B. Newman, Anne B. TI Long-Term Retention of Older Adults in the Cardiovascular Health Study: Implications for Studies of the Oldest Old SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE epidemiology; retention; aging; longitudinal cohort ID SKELETAL-MUSCLE STRENGTH; BONE LOSS; COGNITIVE DECLINE; BODY-COMPOSITION; HIP; RISK; PERFORMANCE; PREDICTORS; FRACTURES; TELEPHONE AB OBJECTIVES To describe retention according to age and visit type (clinic, home, telephone) and to determine characteristics associated with visit types for a longitudinal epidemiological study in older adults. DESIGN Longitudinal cohort study. SETTING Four U.S. clinical sites. PARTICIPANTS Five thousand eight hundred eighty-eight Cardiovascular Health Study (CHS) participants aged 65 to 100 at 1989/90 or 1992/93 enrollment (58.6% female; 15.7% black). CHS participants were contacted every 6 months, with annual assessments through 1999 and in 2005/06 for the All Stars Study visit of the CHS cohort (aged 77-102; 66.5% female; 16.6% black). MEASUREMENTS All annual contacts through 1999 (n=43,772) and for the 2005/06 visit (n=1,942). RESULTS CHS had 43,772 total participant contacts from 1989 to 1999: 34,582 clinic visits (79.0%), 2,238 refusals (5.1%), 4,401 telephone visits (10.1%), 1,811 home visits (4.1%), and 740 other types (1.7%). In 2005/06, the All Stars participants of the CHS cohort had 36.6% clinic, 22.3% home, and 41.1% telephone visits. Compared with participants aged 65 to 69, odds ratios of not attending a CHS clinic visit were 1.82 (95% confidence interval (CI)=1.54-2.13), 2.94 (95% CI=2.45-3.57), 4.55 (95% CI=3.70-5.56), and 9.09 (95% CI=7.69-11.11) for those aged 70 to 74, 75 to 79, 80 to 84, and 85 and older, respectively, in sex-adjusted regression. In multivariable regression, participants with a 2005/06 clinic visit were younger, more likely to be male and in good health, and had had better cognitive and physical function 7 years earlier than participants with other visit types. Participants with home, telephone, and missing visits were similar on characteristics measured 7 years earlier. CONCLUSION Offering home, telephone, and proxy visits are essential to optimizing follow-up of aging cohorts. Home visits increased in-person retention from 36.5% to 58.8% and diversified the cohort with respect to age, health, and physical functioning. C1 [Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15213 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Robbins, John A.] Univ Calif Davis, Dept Med, Davis, CA 95616 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, 130 N Bellefield Ave,Room 515, Pittsburgh, PA 15213 USA. EM strotmeyere@edc.pitt.edu RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187; Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institute on Aging (NIA) [R01-AG-023629]; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-35129, N01-HC-45133, N01-HC-75150, N01-HC-85079, N01-HC-85086, N01 HC-15103, N01 HC-55222, U01 HL080295]; National Institute of Neurological Disorders and Stroke; Intramural Research Program of the National Institutes of Health, NIA; NHLBI [R01-AG-15928, R01-AG-20098, R01-AG-027058]; NIA [HL-075366]; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG-024827] FX This work was supported by National Institute on Aging (NIA) Grant R01-AG-023629. The CHS was supported from contracts N01-HC-35129, N01-HC-45133, N01-HC-75150, N01-HC-85079 through N01-HC-85086, N01 HC-15103, N01 HC-55222, and U01 HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke and the Intramural Research Program of the National Institutes of Health, NIA. Additional support was provided through R01-AG-15928, R01-AG-20098, and R01-AG-027058 from NIA, HL-075366 from the NHLBI, and the University of Pittsburgh Claude D. Pepper Older Americans Independence Center P30-AG-024827. NR 22 TC 17 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 IS 4 BP 696 EP 701 DI 10.1111/j.1532-5415.2010.02770.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TN UT WOS:000276247000010 PM 20398149 ER PT J AU Vazzana, R Bandinelli, S Lauretani, F Volpato, S Lauretani, F Di Iorio, A Abate, M Corsi, AM Milaneschi, Y Guralnik, JM Ferrucci, L AF Vazzana, Rosamaria Bandinelli, Stefania Lauretani, Fabrizio Volpato, Stefano Lauretani, Fulvio Di Iorio, Angelo Abate, Michele Corsi, Anna Maria Milaneschi, Yuri Guralnik, Jack M. Ferrucci, Luigi TI Trail Making Test Predicts Physical Impairment and Mortality in Older Persons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE trail making test; neuropsychological tests; physical impairment; mortality ID LOWER-EXTREMITY FUNCTION; FUNCTIONAL STATUS; SUBSEQUENT DISABILITY; PERFORMANCE BATTERY; EXECUTIVE FUNCTION; ASSOCIATION; COMMUNITY; ADULTS; INCHIANTI; DEMENTIA AB OBJECTIVES To examine whether performance in the Trail Making Test (TMT) predicts mobility impairment and mortality in older persons. DESIGN Prospective cohort study. SETTING Community-dwelling older persons enrolled in the Invecchiare in Chianti (InCHIANTI) Study. PARTICIPANTS Five hundred eighty-three participants aged 65 and older and free of major cognitive impairment (Mini-Mental State Examination score > 21) with baseline data on TMT performance. Of these, 427 performed the Short Physical Performance Battery (SPPB) for the assessment of lower extremity function at baseline and after 6 years. Of the initial 583 participants, 106 died during a 9-year follow-up. MEASUREMENTS The TMT Parts A and B (TMT-A and TMT-B) and SPPB were administered at baseline and 6-year follow-up. Impaired mobility was defined as an SPPB score less than 10. Vital status was ascertained over a 9-year follow-up. RESULTS InCHIANTI participants in the fourth quartile of the time to complete TMT-B minus time to complete TMT-A (TMT (B-A)) were significantly more likely to develop an SPPB score less than 10 during the 6-year follow-up than those in the first quartile (relative risk (RR)=2.4, 95% confidence interval (CI)=1.4-3.9, P=.001). After adjusting for potential confounders, these findings were substantially unchanged (RR=2.2, 95% CI=1.4-3.6, P=.001). Worse performance on the TMT was associated with significantly greater decline in SPPB score over the 6-year follow-up, after adjusting for age, sex, and baseline SPPB scores (beta=-0.01, standard error=0.003, P=.004). During the 9-year follow-up, 18.2% of the participants died. After adjustment for age and sex, the proportion of participants who died was higher in participants in the worst than the best performance quartile of TMT (B-A) scores (hazard ratio (HR)=1.7, 95% CI=1.0-2.9, P=.048). Results were similar in a parsimonious adjusted model (HR=1.8, 95% CI=1.0-3.2, P=.04). CONCLUSION Performance on the TMT is a strong, independent predictor of mobility impairment, accelerated decline in lower extremity function, and death in older adults living in the community. The TMT could be a useful addition to geriatric assessment. C1 [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Gerontol Res Ctr, NIH,Clin Res Branch, Baltimore, MD 21224 USA. [Vazzana, Rosamaria; Di Iorio, Angelo] Univ G DAnnunzio, Lab Clin Epidemiol, Dept Med & Sci Aging, Chieti, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Lauretani, Fabrizio; Corsi, Anna Maria; Milaneschi, Yuri] Tuscany Hlth Reg Agcy, Florence, Italy. [Volpato, Stefano] Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. [Lauretani, Fulvio] Univ Hosp Parma, Geriatr Rehabil Dept, Geriatr Unit & Clin Geriatr, Parma, Italy. [Abate, Michele] Univ G DAnnunzio, Dept Clin Sci & Bioimaging, Chieti, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Clin Res Branch, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Gerontol Res Ctr, NIH,Clin Res Branch, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ferruccilu@grc.nia.nih.gov RI VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016 OI VOLPATO, STEFANO/0000-0003-4335-6034; Lauretani, Fulvio/0000-0002-5287-9972 FU Italian Ministry of Health [ICS110.1/RF97.71]; U. S. National Institute on Aging (NIA) [263 MD 9164, 263 MD 821336, N. 1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institutes of Health, Baltimore, Maryland FX The InCHIANTI Study baseline (1998-2000) was supported as a "targeted project'' (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U. S. National Institute on Aging (NIA; Contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the NIA (Contracts: N. 1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by the NIA (Contract: N01-AG-5-0002); supported in part by the Intramural Research Program of the NIA, National Institutes of Health, Baltimore, Maryland. NR 27 TC 28 Z9 28 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 IS 4 BP 719 EP 723 DI 10.1111/j.1532-5415.2010.02780.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TN UT WOS:000276247000014 PM 20398153 ER PT J AU High, KP D'Aquila, RT Fuldner, RA Gerding, DN Halter, JB Haynes, L Hazzard, WR Jackson, LA Janoff, E Levin, MJ Nayfield, SG Nichol, KL Prabhudas, M Talbot, HK Clayton, CP Henderson, R Scott, CM Tarver, ED Woolard, NF Schmader, KE AF High, Kevin P. D'Aquila, Richard T. Fuldner, Rebecca A. Gerding, Dale N. Halter, Jeffrey B. Haynes, Laura Hazzard, William R. Jackson, Lisa A. Janoff, Edward Levin, Myron J. Nayfield, Susan G. Nichol, Kristin L. Prabhudas, Mercy Talbot, Helen K. Clayton, Charles P. Henderson, Randi Scott, Catherine M. Tarver, Erika D. Woolard, Nancy F. Schmader, Kenneth E. TI Workshop on Immunizations in Older Adults: Identifying Future Research Agendas SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE immunization; vaccination ID PNEUMOCOCCAL POLYSACCHARIDE VACCINE; T-CELL RESPONSES; RESPIRATORY SYNCYTIAL VIRUS; AGE-RELATED DEFECTS; IMMUNE-RESPONSES; INFLUENZA VACCINE; STAPHYLOCOCCUS-AUREUS; CLOSTRIDIUM-DIFFICILE; ELDERLY ADULTS; UNITED-STATES AB Goals for immunization in older adults may differ from those in young adults and children, in whom complete prevention of disease is the objective. Often, reduced hospitalization and death but also averting exacerbation of underlying chronic illness, functional decline, and frailty are important goals in the older age group. Because of the effect of age on dendritic cell function, T cell-mediated immune suppression, reduced proliferative capacity of T cells, and other immune responses, the efficacy of vaccines often wanes with advanced age. This article summarizes the discussion and proceedings of a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. Leading researchers and clinicians in the fields of immunology, epidemiology, infectious diseases, geriatrics, and gerontology reviewed the current status of vaccines in older adults, identified knowledge gaps, and suggest priority areas for future research. The goal of the workshop was to identify what is known about immunizations (efficacy, effect, and current schedule) in older adults and to recommend priorities for future research. Investigation in the areas identified has the potential to enhance understanding of the immune process in aging individuals, inform vaccine development, and lead to more-effective strategies to reduce the risk of vaccine-preventable illness in older adults. C1 [High, Kevin P.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med,Div Infect Dis, Infect Dis Sect, Winston Salem, NC 27157 USA. [D'Aquila, Richard T.; Talbot, Helen K.] Vanderbilt Univ, Sch Med, Dept Internal Med, Div Infect Dis, Nashville, TN 37212 USA. [Fuldner, Rebecca A.; Nayfield, Susan G.] NIA, Bethesda, MD 20892 USA. [Gerding, Dale N.] Hines Vet Affairs Hosp, Hines, IL USA. [Halter, Jeffrey B.] Univ Michigan, Sch Med, Dept Internal Med, Div Geriatr Med, Ann Arbor, MI USA. [Haynes, Laura] Trudeau Inst Inc, Sarnac Lake, NY USA. [Hazzard, William R.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Hazzard, William R.] Veteras Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Jackson, Lisa A.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Janoff, Edward; Levin, Myron J.] Univ Colorado, Sch Med, Dept Internal Med, Div Infect Dis, Denver, CO USA. [Nichol, Kristin L.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. [Prabhudas, Mercy] NIAID, Bethesda, MD 20892 USA. [Clayton, Charles P.; Henderson, Randi; Scott, Catherine M.; Tarver, Erika D.] Assoc Specialty Professors, Washington, DC USA. [Schmader, Kenneth E.] Duke Univ, Sch Med, Dept Med, Div Geriatr, Durham, NC 27706 USA. RP High, KP (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med,Div Infect Dis, Infect Dis Sect, 100 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM khigh@wfubmc.edu FU John A. Hartford Foundation; National Institute on Aging; Atlantic Philanthropies, Optimer, Pfizer, Covance, and Viropharma; GSK and Virco; U. S. Department of Veterans Affairs; Sanofi-Aventis; Protein Sciences, Wyeth, Vaxlnnate; Merck and Co.; Wyeth Vaccines and VaxIndex Inc.; Merck and Wyeth; U. S. Preventative Services Task Force FX This workshop was supported by a generous grant from the John A. Hartford Foundation to ASP. For a list of the planning committee and attendees of the conference, please visit http://www.im.org/CareerDevelopment/Grantsand Scholarships/IGP/ExpandingResearchEfforts/Pages/ASP-ID SAWorkshoponImmunizationsinOlderAdults.aspx.; KPH: Grants/Funds: National Institute on Aging, the John A. Hartford Foundation, the Atlantic Philanthropies, Optimer, Pfizer, Covance, and Viropharma. Consultant: Optimer (advisory board). Personal Relationship: Textbook Editor: Hazzard's Geriatric Medicine and Gerontology; Board of Directors (American Board of Internal Medicine).; RTD: Grants/Funds: GSK and Virco. Consultant: Boehringer Ingelheim, Gilead Sciences, Tibotec, Merck.; DNG: Employment: U. S. Department of Veterans Affairs, Loyola University Chicago Stritch School of Medicine. Grants/Funding: U. S. Department of Veterans Affairs, ViroPharma, Optimer, MassBiologics, Merck, Cepheid, GOJO, CDC. Honoraria: Robert Michael. Consultant: Optimer, ViroPharma, Cepheid, Merck, GOJO, Salix, TheraDoc, Schering-Plough, BD GeneOhm. Expert Testimony: Phillip Taxman, MD, JD. Board Member: TheraDoc, Optimer, ViroPharma, Cepheid. Patents: Prevention and treatment of Clostridium difficile disease. Licensed to ViroPharma.; JBH: Grants/Funds: Sanofi-Aventis. Honoraria: Takeda, Eli Lilly Inc, Novartis. Speaker Forum: Eli Lilly Inc. Consultant: Takeda. Royalties: McGraw-Hill.; LJ: Grants/Funds: Research funding received from Wyeth, Sanofi Pasteur, and Novartis Vaccines. Honoraria: Received from Wyeth, Sanofi Pasteur, GSK, Merck, and Novartis Vaccines. Consultant: Wyeth, Merck, GSK, Novartis Vaccines.; HKT: Grants/Funds: Protein Sciences, Wyeth, Vaxlnnate.; ML: Grants/Funds: Merck and Co.; EJ: Grant: Wyeth Vaccines and VaxIndex Inc.; KES: Grants/Funds: Merck and Wyeth. Consultant: Merck, GSK.; KN: Grants/Funds: Sanofi Pasteur, GSK. Consultant: Sanofi Pasteur, GSK, MedImmune, CSL, Novartis, and Merck.; RH: Consultant: National Institute on Aging and the U. S. Preventative Services Task Force. NR 94 TC 8 Z9 8 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2010 VL 58 IS 4 BP 765 EP 776 DI 10.1111/j.1532-5415.2010.02772.x PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 577TN UT WOS:000276247000023 PM 20398161 ER PT J AU Grefsheim, SF Whitmore, SC Rapp, BA Rankin, JA Robison, RR Canto, CC AF Grefsheim, Suzanne F. Whitmore, Susan C. Rapp, Barbara A. Rankin, Jocelyn A. Robison, Rex R. Canto, Candace C. TI The informationist: building evidence for an emerging health profession SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID CLINICAL QUESTIONS; BIOMEDICAL-RESEARCH; CARE; PROGRAM; SERVICE; NEEDS; IMPLEMENTATION; ANSWERS AB Background: To encourage evidence-based practice, an Annals of Internal Medicine editorial called for a new professional on clinical teams: an informationist trained in science or medicine as well as information science. Objectives: The study explored the effects of informationists on information behaviors of clinical research teams, specifically, frequency of seeking information for clinical or research decisions, range of resources consulted, perceptions about access to information, confidence in adequacy of literature searches, and effects on decision making and practice. It also explored perceptions about training and experience needed for successful informationists. Methods: Exploratory focus groups and key interviews were followed by baseline and follow-up surveys conducted with researchers and clinicians receiving the service. Survey data were analyzed with Pearson's chi-square or Fisher's exact test. Results: Comparing 2006 to 2004 survey responses, the researchers found that study participants reported: seeking answers to questions more frequently, spending more time seeking or using information, believing time was less of an obstacle to finding or using information, using more information resources, and feeling greater satisfaction with their ability to find answers. Participants' opinions on informationists' qualifications evolved to include both subject knowledge and information searching expertise. Conclusion: Over time, clinical research teams with informationists demonstrated changes in their information behaviors, and they valued an informationist's subject matter expertise more. C1 [Grefsheim, Suzanne F.; Whitmore, Susan C.] NIH Lib, Informat & Educ Serv Branch, Div Lib Serv, NIH, Bethesda, MD 20892 USA. [Rapp, Barbara A.] Natl Lib Med, Off Hlth Informat Programs Dev, Nihon Univ, Bethesda, MD 20894 USA. [Rankin, Jocelyn A.] Ctr Dis Control & Prevent, CDC Informat Ctr, Atlanta, GA 30333 USA. RP Grefsheim, SF (reprint author), NIH Lib, Informat & Educ Serv Branch, Div Lib Serv, NIH, 10 Ctr Dr,MSC 1150, Bethesda, MD 20892 USA. EM grefshes@nih.gov; whitmors@mail.nih.gov; rappb@nlm.nih.gov; jrankin@cdc.gov; robisonr@mail.nih.gov; cantoc@gmail.com RI Robison, Rex/B-4174-2008 OI Robison, Rex/0000-0002-6885-5051 NR 26 TC 8 Z9 9 U1 3 U2 18 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD APR PY 2010 VL 98 IS 2 BP 147 EP 156 DI 10.3163/1536-5050.98.2.007 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA 593IN UT WOS:000277447300007 PM 20428280 ER PT J AU Coberly, E Boren, SA Davis, JW McConnell, AL Chitima-Matsiga, R Ge, B Logan, RA Steinmann, WC Hodge, RH AF Coberly, Emily Boren, Suzanne Austin Davis, J. Wade McConnell, Amanda L. Chitima-Matsiga, Rebecca Ge, Bin Logan, Robert A. Steinmann, William C. Hodge, Robert H. TI Linking clinic patients to Internet-based, condition-specific information prescriptions SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID HEALTH INFORMATION C1 [Coberly, Emily; Boren, Suzanne Austin; Davis, J. Wade] Univ Missouri, Sch Med, Dept Hlth Management & Informat, Columbia, MO 65212 USA. [Boren, Suzanne Austin] Harry S Truman Mem Vet Hosp, Columbia, MO 65212 USA. [Davis, J. Wade] Univ Missouri, Dept Stat, Columbia, MO 65212 USA. [Davis, J. Wade; Ge, Bin] Univ Missouri, Sch Med, Biostat Grp, Columbia, MO 65212 USA. [McConnell, Amanda L.; Chitima-Matsiga, Rebecca; Steinmann, William C.; Hodge, Robert H.] Univ Missouri, Sch Med, Dept Internal Med, Columbia, MO 65212 USA. [Logan, Robert A.] Natl Lib Med, Bethesda, MD USA. RP Coberly, E (reprint author), Univ Missouri, Sch Med, Dept Hlth Management & Informat, MA432 Med Sci Bldg, Columbia, MO 65212 USA. EM coberlye@health.missouri.edu; borens@health.missouri.edu; davisjwa@health.missouri.edu; amcconnell@lawrence.lib.ks.us; chitima-matsigar@health.missouri.edu; geb@health.missouri.edu; logan@nlm.nih.gov; steinmannw@health.missouri.edu; hodger@health.missouri.edu RI Boren, Suzanne/M-6589-2014 OI Boren, Suzanne/0000-0003-4727-399X FU PHS HHS [HHSN276200700263P] NR 7 TC 12 Z9 12 U1 0 U2 2 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD APR PY 2010 VL 98 IS 2 BP 160 EP 164 DI 10.3163/1536-5050.98.2.009 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA 593IN UT WOS:000277447300009 PM 20428282 ER PT J AU Basu, S Tiwari, RC AF Basu, Sanjib Tiwari, Ram C. TI Breast cancer survival, competing risks and mixture cure model: a Bayesian analysis SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE Bayes factor; Breast cancer; Competing risks; Cumulative probability of death; Cure rate; Mixture cure model; Model comparison; Surveillance; epidemiology; end results programme ID CUMULATIVE INCIDENCE FUNCTIONS; SYSTEM LIFETIME DATA; NONPARAMETRIC-ESTIMATION; MARGINAL LIKELIHOOD; DEATH CERTIFICATES; FAILURE TYPES; MISSING CAUSE; MASKED CAUSES; MORTALITY; ACCURACY AB Cancer is a major public health burden and is the second leading cause of death in the USA. The US National Cancer Institute estimated overall costs of cancer in 2007 at $ 219.2 billion. Breast cancer has the highest cancer incidence rates among women and is the second leading cause of cancer death among women. The 'Surveillance, epidemiology, and end results' programme of the National Cancer Institute collects and publishes cancer survival data from 17 population-based cancer registries. The CANSURV software of the National Cancer Institute analyses cancer survival data from the programme by using parametric and semiparametric mixture cure models. Another popular approach in cancer survival is the competing risks approach which considers the simultaneous risks from cancer and various other causes. The paper develops a model that unifies the mixture cure and competing risks approaches and that can handle the masked causes of death in a natural way. Markov chain sampling is used for Bayesian analysis of this model, and modelling and computational issues of general and restricted structures are discussed. The various model structures are compared by using Bayes factors. This Bayesian model is used to analyse survival data for the approximately 620000 breast cancer cases from the programme. The estimated cumulative probabilities of death from breast cancer from the proposed mixture cure competing risks model is found to be lower than the estimates that are obtained from the CANSURV software. Whereas the estimate of the cure fraction is found to be dependent on the modelling assumptions, the survival and cumulative probability estimates are not sensitive to these assumptions. Breast cancer survival in different ethnic subgroups, in different age subgroups and in patients with localized, regional and distant stages of the disease are compared. The risk of mortality from breast cancer is found to be the dominant cause of death in the beginning part of the follow-up whereas the risk from other competing causes often became the dominant cause in the latter part. This interrelation between breast cancer and other competing risks varies among the different ethnic groups, the different stages and the different age groups. C1 [Basu, Sanjib] No Illinois Univ, Div Stat, De Kalb, IL 60115 USA. [Tiwari, Ram C.] NCI, Bethesda, MD 20892 USA. RP Basu, S (reprint author), No Illinois Univ, Div Stat, De Kalb, IL 60115 USA. EM basu@niu.edu FU National Science Foundation [DMS-0306416]; National Cancer Institute, USA FX Sanjib Basu's research was partially supported by National Science Foundation grant DMS-0306416 and the National Cancer Institute, USA. NR 57 TC 6 Z9 6 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-1998 EI 1467-985X J9 J R STAT SOC A STAT JI J. R. Stat. Soc. Ser. A-Stat. Soc. PD APR PY 2010 VL 173 BP 307 EP 329 PN 2 PG 23 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 563DU UT WOS:000275108800003 ER PT J AU Recio, L Hobbs, C Caspary, W Witt, KL AF Recio, Leslie Hobbs, Cheryl Caspary, William Witt, Kristine L. TI Dose-response assessment of four genotoxic chemicals in a combined mouse and rat micronucleus (MN) and Comet assay protocol SO JOURNAL OF TOXICOLOGICAL SCIENCES LA English DT Article DE DNA damage; Comet assay; Acrylamide; Ethyl methanesulfonate; Cyclophosphamide; Vincristine sulfate ID IN-VIVO; DNA-DAMAGE; RISK-ASSESSMENT; ACRYLAMIDE; MICE; IDENTIFICATION; ADDUCTS; VITRO; MUTAGENICITY; LYMPHOCYTES AB The in vivo micronucleus (MN) assay has proven to be an effective measure of genotoxicity potential. However, sampling a single tissue (bone marrow) for a single indicator of genetic damage using the MN assay provides a limited genotoxicity profile. The in vivo alkaline (pH >13) Comet assay, which detects a broad spectrum of DNA damage, can be applied to a variety of rodent tissues following administration of test agents. To determine if the Comet assay is a useful supplement to the in vivo MN assay, a combined test protocol (MN/Comet assay) was conducted in male B6C3F1 mice and F344/N rats using four model genotoxicants: ethyl methanesulfonate (EMS), acrylamide (ACM), cyclophosphamide (CP), and vincristine sulfate (VS). Test compounds were administered on 4 consecutive days at 24-hr intervals (VS was administered to rats for 3 days); animals were euthanized 4 hr after the last administration. All compounds induced significant increases in micronucleated reticulocytes (MN-RET) in the peripheral blood of mice, and all but ACM induced MN-RET in rats. EMS and ACM induced significant increases in DNA damage, measured by the Comet assay, in multiple tissues of mice and rats. CP-induced DNA damage was detected in leukocytes and duodenum cells. VS, a spindle fiber disrupting agent, was negative in the Comet assay. Based on these results, the MN/Comet assay holds promise for providing more comprehensive assessments of potential genotoxicants, and the National Toxicology Program (NTP) is presently using this combined protocol in its overall evaluation of the genotoxicity of substances of public health concern. C1 [Caspary, William; Witt, Kristine L.] NIEHS, Natl Toxicol Program, RTP, Res Triangle Pk, NC 27709 USA. [Recio, Leslie; Hobbs, Cheryl] ILS Inc, Div Genet Toxicol, RTP, Res Triangle Pk, NC 27709 USA. RP Witt, KL (reprint author), NIEHS, Natl Toxicol Program, RTP, POB 12233, Res Triangle Pk, NC 27709 USA. EM witt@niehs.nih.gov FU National Institute of Environmental Health Sciences/National Toxicology Program [NO1-ES-35514] FX This work was supported by the National Institute of Environmental Health Sciences/National Toxicology Program [contract number NO1-ES-35514]. NR 35 TC 38 Z9 38 U1 0 U2 7 PU JAPANESE SOC TOXICOLOGICAL SCIENCES PI TOKYO PA INTERNATIONAL MEDICAL INFORMATION CENTER, SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI, SHINJUKU-KU, TOKYO, 160-0016, JAPAN SN 0388-1350 EI 1880-3989 J9 J TOXICOL SCI JI J. Toxicol. Sci. PD APR PY 2010 VL 35 IS 2 BP 149 EP 162 PG 14 WC Toxicology SC Toxicology GA 581NK UT WOS:000276530200002 PM 20371966 ER PT J AU Lubet, RA Steele, VE Juliana, MM Grubbs, CJ AF Lubet, Ronald A. Steele, Vernon E. Juliana, M. Margaret Grubbs, Clinton J. TI Screening Agents for Preventive Efficacy in a Bladder Cancer Model: Study Design, End Points, and Gefitinib and Naproxen Efficacy SO JOURNAL OF UROLOGY LA English DT Article DE urinary bladder; urinary bladder neoplasms; chemoprevention; gefitinib; anti-inflammatory agents; non-steroidal ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SPORADIC COLORECTAL ADENOMAS; URINARY-BLADDER; BREAST-CANCER; COLON-CANCER; CARCINOGENESIS; EXPRESSION; TUMORS; TRIAL; RISK AB Purpose: We optimized agent testing in an in vivo bladder cancer model and determined the most sensitive, relevant protocol to test efficacy in clinical prevention trials. Materials and Methods: Female Fischer-344 rats (Harlan (TM)) were treated with the bladder carcinogen OH-BBN (TCI America, Portland, Oregon) for 8 weeks. Rats were treated with naproxen (400 mg/kg diet), aspirin (Sigma()) (300 or 3,000 mg/kg diet), Iressa (10 mg/kg gefitinib body weight daily) or resveratrol (1,000 mg/kg diet) using 1 of 3 protocols, including treatment beginning 1) 1 week after OH-BBN and continuing for 7 months, 2) 3 months after OH-BBN after microscopic lesions already existed and continuing for 3 months, and 3) 1 week after OH-BBN and continuing for 4 months. In protocols 1 and 2 bladder lesion weight and large tumors were primary end points, and in protocol 3 microscopic cancer was the end point. Results: Using protocol 1 naproxen, Iressa, resveratrol, and low and high dose aspirin altered the formation of large bladder tumors by 87% (decreased), 90% (decreased), 3% (increased), 6% (decreased) and 60% (decreased), respectively. Using protocol 2 Iressa and naproxen were also highly effective. Protocol 3 evaluation revealed that only Iressa caused a significant decrease in microscopic bladder cancers (63%). Conclusions: Initiating treatment after OH-BBN or when bladder lesions already existed showed naproxen and Iressa to be effective in preventing formation of large cancers. Low dose aspirin and resveratrol were ineffective. In protocol 3, in which microscopic lesions were the end point, only Iressa was effective. Thus, an established cancer end point appears preferable. Naproxen, which has an excellent cardiovascular profile, or epidermal growth factor receptor inhibitors may be effective in an adjuvant setting. C1 [Lubet, Ronald A.] NCI, Canc Prevent Div, Bethesda, MD 20852 USA. [Juliana, M. Margaret; Grubbs, Clinton J.] Univ Alabama, Dept Genet, Birmingham, AL USA. [Juliana, M. Margaret; Grubbs, Clinton J.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Lubet, RA (reprint author), NCI, Canc Prevent Div, Execut Plaza N,Suite 2110,6130 Execut Blvd, Bethesda, MD 20852 USA. EM lubetr@mail.nih.gov FU PHS HHS [HHSN261200433001C] NR 30 TC 15 Z9 17 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2010 VL 183 IS 4 BP 1598 EP 1603 DI 10.1016/j.juro.2009.12.001 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 574DG UT WOS:000275968200133 PM 20172542 ER PT J AU Xiang, SH Finzi, A Pacheco, B Alexander, K Yuan, W Rizzuto, C Huang, CC Kwong, PD Sodroski, J AF Xiang, Shi-Hua Finzi, Andres Pacheco, Beatriz Alexander, Kevin Yuan, Wen Rizzuto, Carlo Huang, Chih-Chin Kwong, Peter D. Sodroski, Joseph TI A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 GP120; TYPE-1 GP120; CELL-LINE; MONOCLONAL-ANTIBODIES; CHEMOKINE RECEPTORS; SOLUBLE CD4; N-TERMINUS; NEUTRALIZATION SENSITIVITY; MOLECULAR CHARACTERIZATION; DISTINCT CONFORMATIONS AB Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding of gp120 to receptors on the target cell alters the gp120-gp41 relationship and activates the membrane-fusing capacity of gp41. Interaction of gp120 with the primary receptor, CD4, results in the exposure of the gp120 third variable (V3) loop, which contributes to binding the CCR5 or CXCR4 chemokine receptors. We show here that insertions in the V3 stem or polar substitutions in a conserved hydrophobic patch near the V3 tip result in decreased gp120-gp41 association (in the unliganded state) and decreased chemokine receptor binding (in the CD4-bound state). Subunit association and syncytium-forming ability of the envelope glycoproteins from primary HIV-1 isolates were disrupted more by V3 changes than those of laboratory-adapted HIV-1 envelope glycoproteins. Changes in the gp120 beta 2, beta 19, beta 20, and beta 21 strands, which evidence suggests are proximal to the V3 loop in unliganded gp120, also resulted in decreased gp120-gp41 association. Thus, a gp120 element composed of the V3 loop and adjacent beta strands contributes to quaternary interactions that stabilize the unliganded trimer. CD4 binding dismantles this element, altering the gp120-gp41 relationship and rendering the hydrophobic patch in the V3 tip available for chemokine receptor binding. C1 [Xiang, Shi-Hua; Finzi, Andres; Pacheco, Beatriz; Alexander, Kevin; Yuan, Wen; Rizzuto, Carlo; Sodroski, Joseph] Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med,Dept Pathol,Div AIDS, Boston, MA 02115 USA. [Huang, Chih-Chin; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med,Dept Pathol,Div AIDS, 44 Binney St,CLS 1010, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIH [AI24755, AI39420, AI40895]; Center for HIV/AIDS Vaccine Immunology [AI67854]; Center for AIDS Research [AI24848]; Bristol-Myers Squibb Foundation; International AIDS Vaccine Initiative FX We thank Yvette McLaughlin and Elizabeth Carpelan for manuscript preparation. We thank Michael Fung (Tanox) for the G3-299 antibody.; This study was supported by NIH grants AI24755, AI39420, and AI40895; by a Center for HIV/AIDS Vaccine Immunology grant (AI67854); by a Center for AIDS Research grant (AI24848); by an unrestricted research grant from the Bristol-Myers Squibb Foundation; by a gift from the late William F. McCarty-Cooper; and by funds from the International AIDS Vaccine Initiative. NR 88 TC 49 Z9 49 U1 0 U2 13 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 APR PY 2010 VL 84 IS 7 BP 3147 EP 3161 DI 10.1128/JVI.02587-09 PG 15 WC Virology SC Virology GA 565PV UT WOS:000275307400002 PM 20089638 ER PT J AU Fusaro, A Nelson, MI Joannis, T Bertolotti, L Monne, I Salviato, A Olaleye, O Shittu, I Sulaiman, L Lombin, LH Capua, I Holmes, EC Cattoli, G AF Fusaro, Alice Nelson, Martha I. Joannis, Tony Bertolotti, Luigi Monne, Isabella Salviato, Annalisa Olaleye, Olufemi Shittu, Ismaila Sulaiman, Lanre Lombin, Lami H. Capua, Ilaria Holmes, Edward C. Cattoli, Giovanni TI Evolutionary Dynamics of Multiple Sublineages of H5N1 Influenza Viruses in Nigeria from 2006 to 2008 SO JOURNAL OF VIROLOGY LA English DT Article ID AVIAN INFLUENZA; PHYLOGENETIC ANALYSIS; AFRICA; SPREAD; INTRODUCTIONS; INFECTION; SEQUENCES; INFERENCE; BIRDS AB Highly pathogenic A/H5N1 avian influenza (HPAI H5N1) viruses have seriously affected the Nigerian poultry industry since early 2006. Previous studies have identified multiple introductions of the virus into Nigeria and several reassortment events between cocirculating lineages. To determine the spatial, evolutionary, and population dynamics of the multiple H5N1 lineages cocirculating in Nigeria, we conducted a phylogenetic analysis of whole-genome sequences from 106 HPAI H5N1 viruses isolated between 2006 and 2008 and representing all 25 Nigerian states and the Federal Capital Territory (FCT) reporting outbreaks. We identified a major new subclade in Nigeria that is phylogenetically distinguishable from all previously identified sublineages, as well as two novel reassortment events. A detailed analysis of viral phylogeography identified two major source populations for the HPAI H5N1 virus in Nigeria, one in a major commercial poultry area (southwest region) and one in northern Nigeria, where contact between wild birds and backyard poultry is frequent. These findings suggested that migratory birds from Eastern Europe or Russia may serve an important role in the introduction of HPAI H5N1 viruses into Nigeria, although virus spread through the movement of poultry and poultry products cannot be excluded. Our study provides new insight into the genesis and evolution of H5N1 influenza viruses in Nigeria and has important implications for targeting surveillance efforts to rapidly identify the spread of the virus into and within Nigeria. C1 [Fusaro, Alice; Monne, Isabella; Salviato, Annalisa; Capua, Ilaria; Cattoli, Giovanni] Ist Zooprofilatt Sperimentale Venezie, Dept Res & Dev, OIE FAO, I-35020 Padua, Italy. [Fusaro, Alice; Monne, Isabella; Salviato, Annalisa; Capua, Ilaria; Cattoli, Giovanni] OIE Collaborating Ctr Epidemiol Training & Contro, Natl Reference Lab Newcastle Dis & Avian Influenz, I-35020 Padua, Italy. [Nelson, Martha I.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Bertolotti, Luigi] Univ Turin, Dept Anim Prod Epidemiol & Ecol, Fac Vet Med, Gugliasco, TO, Italy. [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Olaleye, Olufemi] Univ Ibadan, Dept Virol, Univ Coll Hosp, Ibadan, Nigeria. RP Fusaro, A (reprint author), Ist Zooprofilatt Sperimentale Venezie, Dept Res & Dev, OIE FAO, Viale Univ 10, I-35020 Padua, Italy. EM afusaro@izsvenezie.it RI Bertolotti, Luigi/F-9236-2013; Shittu, Ismaila/C-3092-2016; OI Bertolotti, Luigi/0000-0001-7931-4528; Shittu, Ismaila/0000-0002-2977-9578; Fusaro, Alice/0000-0002-8213-5472; Holmes, Edward/0000-0001-9596-3552 FU EU FX We acknowledge the Ministry of Agriculture of Nigeria for its continuous support for and assistance with the avian influenza control program in the country. We thank the staff of the Food and Agriculture Organization of the United Nations (UN-FAO) headquarters in Rome, Italy, and Tesfai Tseggai and the UN-FAO/ECTAD unit, Abuja, Nigeria, for their assistance in facilitating exchange of information, data sharing, and sample submissions.; Part of this study was conducted in the framework of the EU projects EPIZONE (Network of Excellence for Epizootic Disease Diagnosis and Control) and FLUTRAIN (Training and Technology Transfer of Avian Influenza Diagnostics and Disease Management Skills). NR 35 TC 18 Z9 18 U1 1 U2 9 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 APR PY 2010 VL 84 IS 7 BP 3239 EP 3247 DI 10.1128/JVI.02385-09 PG 9 WC Virology SC Virology GA 565PV UT WOS:000275307400010 PM 20071565 ER PT J AU Zhang, YY Zhang, BH Ishii, K Liang, TJ AF Zhang, Yong-Yuan Zhang, Bai-Hua Ishii, Koji Liang, T. Jake TI Novel Function of CD81 in Controlling Hepatitis C Virus Replication SO JOURNAL OF VIROLOGY LA English DT Article ID CLOSED CIRCULAR DNA; RNA REPLICATION; TETRASPANIN PROTEINS; SIGNALING COMPLEXES; CELLULAR COFACTORS; HUMAN HEPATOCYTES; HEPATOMA-CELLS; IN-VITRO; INFECTION; ENTRY AB The mechanisms of hepatitis C virus (HCV) replication remain poorly understood, and the cellular factors required for HCV replication are yet to be completely defined. CD81 is known to mediate HCV entry. Our study uncovered an unexpected novel function of CD81 in the HCV life cycle that is important for HCV RNA replication. HCV replication occurred efficiently in infected cells with high levels of CD81 expression. In HCV-infected or RNA-transfected cells with low levels of CD81 expression, initial viral protein synthesis occurred normally, but efficient replication failed to proceed. The aborted replication could be restored by the transient transfection of a CD81 expression plasmid. CD81-dependent replication was demonstrated with both an HCV infectious cell culture and HCV replicon cells of genotypes 1b and 2a. We also showed that CD81 expression is positively correlated with the kinetics of HCV RNA synthesis but inversely related to the kinetics of viral protein production, suggesting that CD81 may control viral replication by directing viral RNA template function to RNA replication. Thus, CD81 may be necessary for the efficient replication of the HCV genome in addition to its role in viral entry. C1 [Zhang, Yong-Yuan; Zhang, Bai-Hua; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Ishii, Koji] Natl Inst Infect Dis, Dept Virol 2, Tokyo 1628640, Japan. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. EM jakel@bdg10.niddk.nih.gov FU NIDDK, National Institutes of Health FX We thank Matthew Evans and Charlie Rice for providing the J6/JFH1p7Rluc2A plasmid and H77 HCVpp and Huh 7.5 cells, Shoshana Levy for the human CD81 plasmid, Michael Niepmann for the pHCV-FLuc-3'-UTR plasmid, Takanobu Kato and Takaji Wakita for the Huh7-25 and SGR-JFH1-C4/1 cell lines, and Naoya Sakamoto for the Huh7/Rep-Feo cell line.; This study was supported by the Intramural Research Program of NIDDK, National Institutes of Health. NR 52 TC 16 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2010 VL 84 IS 7 BP 3396 EP 3407 DI 10.1128/JVI.02391-09 PG 12 WC Virology SC Virology GA 565PV UT WOS:000275307400025 PM 20089661 ER PT J AU Laurent-Rolle, M Boer, EF Lubick, KJ Wolfinbarger, JB Carmody, AB Rockx, B Liu, WJ Ashour, J Shupert, WL Holbrook, MR Barrett, AD Mason, PW Bloom, ME Garcia-Sastre, A Khromykh, AA Best, SM AF Laurent-Rolle, Maudry Boer, Elena F. Lubick, Kirk J. Wolfinbarger, James B. Carmody, Aaron B. Rockx, Barry Liu, Wenjun Ashour, Joseph Shupert, W. Lesley Holbrook, Michael R. Barrett, Alan D. Mason, Peter W. Bloom, Marshall E. Garcia-Sastre, Adolfo Khromykh, Alexander A. Best, Sonja M. TI The NS5 Protein of the Virulent West Nile Virus NY99 Strain Is a Potent Antagonist of Type I Interferon-Mediated JAK-STAT Signaling SO JOURNAL OF VIROLOGY LA English DT Article ID JAPANESE ENCEPHALITIS-VIRUS; TICK-BORNE FLAVIVIRUS; DENGUE VIRUS; V-PROTEIN; ALPHA-INTERFERON; SUBCELLULAR-LOCALIZATION; NONSTRUCTURAL PROTEINS; GENETIC-DETERMINANTS; W-PROTEINS; REPLICATION AB Flaviviruses transmitted by arthropods represent a tremendous disease burden for humans, causing millions of infections annually. All vector-borne flaviviruses studied to date suppress host innate responses to infection by inhibiting alpha/beta interferon (IFN-alpha/beta)-mediated JAK-STAT signal transduction. The viral nonstructural protein NS5 of some flaviviruses functions as the major IFN antagonist, associated with inhibition of IFN-dependent STAT1 phosphorylation (pY-STAT1) or with STAT2 degradation. West Nile virus (WNV) infection prevents pY-STAT1 although a role for WNV NS5 in IFN antagonism has not been fully explored. Here, we report that NS5 from the virulent NY99 strain of WNV prevented pY-STAT1 accumulation, suppressed IFN-dependent gene expression, and rescued the growth of a highly IFN-sensitive virus (Newcastle disease virus) in the presence of IFN, suggesting that this protein can function as an efficient IFN antagonist. In contrast, NS5 from Kunjin virus (KUN), a naturally attenuated subtype of WNV, was a poor suppressor of pY-STAT1. Mutation of a single residue in KUN NS5 to the analogous residue in WNV-NY99 NS5 (S653F) rendered KUN NS5 an efficient inhibitor of pY-STAT1. Incorporation of this mutation into recombinant KUN resulted in 30-fold greater inhibition of JAK-STAT signaling than with the wild-type virus and enhanced KUN replication in the presence of IFN. Thus, a naturally occurring mutation is associated with the function of NS5 in IFN antagonism and may influence virulence of WNV field isolates. C1 [Boer, Elena F.; Lubick, Kirk J.; Wolfinbarger, James B.; Rockx, Barry; Shupert, W. Lesley; Bloom, Marshall E.; Best, Sonja M.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Carmody, Aaron B.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Laurent-Rolle, Maudry; Ashour, Joseph; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY USA. [Liu, Wenjun; Khromykh, Alexander A.] Univ Queensland, Sch Chem & Mol Biosci, Ctr Infect Dis Res, Brisbane, Qld, Australia. [Holbrook, Michael R.; Barrett, Alan D.; Mason, Peter W.] Univ Texas Med Branch, Dept Pathol, Galveston, TX USA. [Mason, Peter W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA. RP Best, SM (reprint author), NIAID, Virol Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM sbest@niaid.nih.gov OI Khromykh, Alexander/0000-0001-6206-6935; Garcia-Sastre, Adolfo/0000-0002-6551-1827 FU National Institutes of Health (NIH) [U54 AI057158, FAI077333A]; National Institute of Allergy and Infectious Diseases (NIAID) [5UO1AI66321] FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and by grants 5UO1AI66321 and U54 AI057158 from NIAID, NIH, to A. A. K. and A.G.-S., respectively. M.L.-R. is the recipient of an NIH fellowship (FAI077333A). NR 59 TC 95 Z9 100 U1 1 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 APR PY 2010 VL 84 IS 7 BP 3503 EP 3515 DI 10.1128/JVI.01161-09 PG 13 WC Virology SC Virology GA 565PV UT WOS:000275307400035 PM 20106931 ER PT J AU Schell, AM Granger, EL Koczot, F Fischer, MA Norbury, CC AF Schell, Amanda M. Granger, Erica L. Koczot, Frank Fischer, Matthew A. Norbury, Christopher C. TI Dendritic Cell Migration Limits the Duration of CD8(+) T-Cell Priming to Peripheral Viral Antigen SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; LANGERHANS CELLS; LYMPH-NODES; SELF-ANTIGENS; IN-VIVO; CUTTING EDGE; STEADY-STATE; INFECTION; ACTIVATION; IMMUNITY AB CD8(+) T cells (TCD8+) play a crucial role in immunity to viruses. Antiviral TCD8+ are initially activated by recognition of major histocompatibility complex (MHC) class I-peptide complexes on the surface of professional antigen-presenting cells (pAPC). Migration of pAPC from the site of infection to secondary lymphoid organs is likely required during a natural infection. Migrating pAPC can be directly infected with virus or may internalize antigen derived from virus-infected cells. The use of experimental virus infections to assess the requirement for pAPC migration in initiation of TCD8+ responses has proven difficult to interpret because injected virus can readily drain to secondary lymphoid organs without the need for cell-mediated transport. To overcome this ambiguity, we examined the generation of antigen-specific TCD8+ after immunization with recombinant adenoviruses that express antigen driven by skin-specific or ubiquitous promoters. We show that the induction of TCD8+ in response to tissue-targeted antigen is less efficient than the response to ubiquitously expressed antigen and that the resulting TCD8+ fail to clear all target cells pulsed with the antigenic peptide. This failure to prime a fully functional TCD8+ response results from a reduced period of priming to peripherally expressed antigen versus ubiquitously expressed antigen and correlated with a brief burst of pAPC migration from the skin, a requirement for induction of the response to peripheral antigen. These results indicate that a reduced duration of pAPC migration after virus infection likely reduces the amplitude of the TCD8+ response, allowing persistence of the peripheral virus. C1 [Schell, Amanda M.; Granger, Erica L.; Fischer, Matthew A.; Norbury, Christopher C.] Penn State MS Hershey Coll Med, Dept Microbiol & Immunol, MC H107, Hershey, PA 17033 USA. [Koczot, Frank] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Norbury, CC (reprint author), Penn State MS Hershey Coll Med, Dept Microbiol & Immunol H107, Room C6764E, Hershey, PA 17033 USA. EM ccn1@psu.edu FU National Institutes of Health [AI056094, AI076537, AI0830008, C06 RR-15428, T32 CA60395] FX This study was supported by National Institutes of Health grants AI056094, AI076537, and AI0830008 to C.C.N.; by grant C06 RR-15428 to the Penn State College of Medicine Department of Comparative Medicine; and T32 CA60395 training grant to E. L. G. (P. I. R. Courtney). NR 38 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2010 VL 84 IS 7 BP 3586 EP 3594 DI 10.1128/JVI.01975-09 PG 9 WC Virology SC Virology GA 565PV UT WOS:000275307400042 PM 20089641 ER PT J AU Saenz, RA Quinlivan, M Elton, D MacRae, S Blunden, AS Mumford, JA Daly, JM Digard, P Cullinane, A Grenfell, BT McCauley, JW Wood, JLN Gog, JR AF Saenz, Roberto A. Quinlivan, Michelle Elton, Debra MacRae, Shona Blunden, Anthony S. Mumford, Jennifer A. Daly, Janet M. Digard, Paul Cullinane, Ann Grenfell, Bryan T. McCauley, John W. Wood, James L. N. Gog, Julia R. TI Dynamics of Influenza Virus Infection and Pathology SO JOURNAL OF VIROLOGY LA English DT Article ID 1918 PANDEMIC VIRUS; A VIRUS; NS1 PROTEIN; IMMUNE-RESPONSE; H5N1; INTERFERON; DISEASE; INDUCTION; MODEL; IFN AB A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore how differences in the influence of viral proteins on interferon kinetics can account for the observed spectrum of virus shedding, immune response, and influenza pathology. In particular, induction of high levels of interferon ("cytokine storms"), coupled with evasion of its effects, could lead to severe pathology, as hypothesized for some fatal cases of influenza. C1 [Saenz, Roberto A.; Gog, Julia R.] Univ Cambridge, Dept Appl Math & Theoret Phys, Cambridge CB3 0WA, England. [Quinlivan, Michelle; Cullinane, Ann] Irish Equine Ctr, Virol Unit, Naas, Kildare, Ireland. [Elton, Debra; MacRae, Shona; Blunden, Anthony S.; Daly, Janet M.] Anim Hlth Trust, Newmarket CB8 7UU, Suffolk, England. [Mumford, Jennifer A.; Wood, James L. N.] Univ Cambridge, Cambridge Infect Dis Consortium, Dept Vet Med, Cambridge CB3 0ES, England. [Digard, Paul] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England. [Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. [Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08540 USA. [Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [McCauley, John W.] Natl Inst Med Res, MRC, Div Virol, London NW7 1AA, England. RP Saenz, RA (reprint author), Univ Cambridge, Dept Appl Math & Theoret Phys, Wilberforce Rd, Cambridge CB3 0WA, England. EM ras93@cam.ac.uk RI Digard, Paul/B-7717-2008; Wood, James/A-1626-2008; Daly, Janet/G-9797-2011; OI Digard, Paul/0000-0002-0872-9440; Wood, James/0000-0002-0258-3188; Daly, Janet/0000-0002-1912-4500 FU Biotechnology and Biological Sciences Research Council [BBS/B/00522]; NICHD NIH HHS [R24 HD047879]; NIGMS NIH HHS [R01 GM083983, R01 GM083983-01] NR 49 TC 72 Z9 72 U1 2 U2 23 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 APR PY 2010 VL 84 IS 8 BP 3974 EP 3983 DI 10.1128/JVI.02078-09 PG 10 WC Virology SC Virology GA 571UO UT WOS:000275781500023 PM 20130053 ER PT J AU Harker, JA Godlee, A Wahlsten, JL Lee, DCP Thorne, LG Sawant, D Tregoning, JS Caspi, RR Bukreyev, A Collins, PL Openshaw, PJM AF Harker, James A. Godlee, Alexandra Wahlsten, Jennifer L. Lee, Debbie C. P. Thorne, Lucy G. Sawant, Devika Tregoning, John S. Caspi, Rachel R. Bukreyev, Alexander Collins, Peter L. Openshaw, Peter J. M. TI Interleukin 18 Coexpression during Respiratory Syncytial Virus Infection Results in Enhanced Disease Mediated by Natural Killer Cells SO JOURNAL OF VIROLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; T-CELLS; IMMUNE-RESPONSE; TH2 CELLS; NK-CELLS; MICE; IL-18; REPLICATION; PATHOGENESIS; EXPRESSION AB Respiratory syncytial virus (RSV) causes bronchiolitis, the main cause of infantile hospitalization. Immunity against reinfection is poor, and there is great interest in boosting vaccine responses using live vectors expressing host cytokines. We therefore constructed a recombinant RSV expressing murine interleukin 18 (RSV/IL-18), a cytokine capable of inducing strong antiviral immune responses. In vitro RSV/IL-18 replicated at wild-type levels and produced soluble IL-18. In naive BALB/c mice, RSV/IL-18 infection significantly increased both IL-18 mRNA and protein and attenuated the peak viral load 3-fold. Despite a reduced viral load, RSV/IL-18 infection caused a biphasic weight loss at days 2 and 6 postinfection that was not seen in wild-type infection. Day 2 disease was associated with enhanced pulmonary natural killer (NK) cell numbers and activity and was prevented by NK cell depletion during infection; day 6 disease was correlated with CD8 T-cell recruitment and was enhanced by NK cell depletion. IL-18 expression during priming also enhanced RSV-specific antibody responses and T-cell responses on secondary RSV infection. Therefore, while IL-18 boosted antiviral immunity and reduced the viral load, its coexpression worsened disease. This is the first recombinant RSV with this property, and these are the first studies to demonstrate that NK cells can induce pathology during pulmonary viral infections. C1 [Harker, James A.; Godlee, Alexandra; Lee, Debbie C. P.; Thorne, Lucy G.; Sawant, Devika; Tregoning, John S.; Openshaw, Peter J. M.] Univ London Imperial Coll Sci Technol & Med, Dept Resp Med, Ctr Resp Infect, Natl Heart & Lung Inst, London W2 1PG, England. [Wahlsten, Jennifer L.; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Bukreyev, Alexander; Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Openshaw, PJM (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Resp Med, Ctr Resp Infect, Natl Heart & Lung Inst, St Marys Campus, London W2 1PG, England. EM p.openshaw@imperial.ac.uk OI Caspi, Rachel/0000-0002-7140-7671; Tregoning, John/0000-0001-8093-8741 FU Wellcome Trust, (United Kingdom) [071381/Z/03/Z]; National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Eye Institute, National Institutes of Health FX Members of the Department of Respiratory Medicine, Imperial College London, were funded by Wellcome Trust Programme Grant 071381/Z/03/Z (United Kingdom). A. B. and P. L. C. were supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. J.L.W. and R. R. C. were supported by the Intramural Research Programs of the National Eye Institute, National Institutes of Health. NR 35 TC 24 Z9 26 U1 1 U2 7 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 APR PY 2010 VL 84 IS 8 BP 4073 EP 4082 DI 10.1128/JVI.02014-09 PG 10 WC Virology SC Virology GA 571UO UT WOS:000275781500032 PM 20130064 ER PT J AU Ballard, E Bosk, A Pao, M AF Ballard, Elizabeth Bosk, Abigail Pao, Maryland TI Invited Commentary: Understanding Brain Mechanisms of Pain Processing in Adolescents' Non-Suicidal Self-Injury SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Editorial Material DE Pain; Non-suicidal self-injury; Adolescence ID BORDERLINE PERSONALITY-DISORDER; CHILDHOOD SEXUAL-ABUSE; COMMUNITY SAMPLE; MODULATES PAIN; FRONTAL-LOBE; EARLY STRESS; SOCIAL PAIN; PERCEPTION; ATTENTION; BEHAVIOR AB Whereas non-suicidal self injury (NSSI) is reported in 13-23% of adolescents and is an increasingly studied topic, there has been little investigation into the pathophysiology behind self-injury. This commentary examines recent research into pain and emotional distress to discuss implications for the manner we should understand, research, and treat NSSI in the future. Research indicates that adolescents may be particularly vulnerable to NSSI behaviors due to neurodevelopmental changes in the processing of distress and pain. Additionally, emotional distress and physical pain neural pathways may have been altered in these individuals, leading to the development of NSSI behaviors during adolescence when changes in ongoing brain development may lead to further emotional dysregulation and poor impulse control. Further studies that directly characterize the relationship between emotional distress and physical pain in adolescence, as well as the neural differences between self-injurers and non-self-injurers, are needed. C1 [Ballard, Elizabeth; Bosk, Abigail; Pao, Maryland] NIMH, Clin Res Ctr, Bethesda, MD 20892 USA. RP Pao, M (reprint author), NIMH, Clin Res Ctr, Bldg 10,6-5340, Bethesda, MD 20892 USA. EM ballarde@mail.nih.gov; boska@mail.nih.gov; paom@mail.nih.gov FU Intramural NIH HHS NR 77 TC 8 Z9 8 U1 1 U2 5 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 APR PY 2010 VL 39 IS 4 BP 327 EP 334 DI 10.1007/s10964-009-9457-1 PG 8 WC Psychology, Developmental SC Psychology GA 568RY UT WOS:000275541500001 PM 19830534 ER PT J AU Fernandez-Llama, P Khositseth, S Gonzales, PA Star, RA Pisitkun, T Knepper, MA AF Fernandez-Llama, Patricia Khositseth, Sookkasem Gonzales, Patricia A. Star, Robert A. Pisitkun, Trairak Knepper, Mark A. TI Tamm-Horsfall protein and urinary exosome isolation SO KIDNEY INTERNATIONAL LA English DT Article DE urine biomarkers; uromodulin; ZP domain ID BIOMARKERS; UROMODULIN; DISCOVERY AB Urinary exosomes have been proposed as starting material for discovery of protein biomarkers of kidney disease. Current protocols for their isolation use a two-step differential centrifugation process. Due to their low density, exosomes are expected to remain in the low-speed (17,000 x g) supernatant and to sediment only when the sample is spun at high speed (200,000 x g). Analysis using western blot and electron microscopy found that urinary exosomes are also present in the low-speed pellet entrapped by polymeric Tamm-Horsfall protein, thus diminishing the procedure's reproducibility. Here we show that addition of dithiothreitol to the low-speed pellet disrupted the polymeric network, presumably by reduction of disulfide bonds linking the monomers. This modification shifted the exosomal proteins from the low-to the high-speed pellet. Also, by shifting the Tamm-Horsfall protein to the high-speed pellet, the use of dithiothreitol makes it feasible to use Tamm-Horsfall protein to normalize excretion rates of exosomal proteins in spot urines. We tested this by western blot, and found that there was a high degree of correlation between exosomal proteins and Tamm-Horsfall protein in the highspeed pellet. Since the yield of exosomes by differential centrifugation can be increased by chemical reduction, Tamm-Horsfall protein may be a suitable normalizing variable for urinary exosome studies when quantitative urine collections are not practical. Kidney International (2010) 77, 736-742; doi:10.1038/ki.2009.550; published online 3 February 2010 C1 [Fernandez-Llama, Patricia; Khositseth, Sookkasem; Gonzales, Patricia A.; Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Star, Robert A.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU NHLBI [Z01-HL001285]; Spanish Society of Nephrology; Catalan Society of Nephrology FX This study was supported by the Intramural Budget of the NHLBI (Project Z01-HL001285). PF-L was supported by the Spanish Society of Nephrology and the Catalan Society of Nephrology. We thank the NHLBI Electron Microscopy Core Facility (M Daniels, Director) for outstanding support. NR 16 TC 74 Z9 76 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2010 VL 77 IS 8 BP 736 EP 742 DI 10.1038/ki.2009.550 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 576MX UT WOS:000276149700012 PM 20130532 ER PT J AU Hall, BE Zheng, CY Swaim, WD Cho, A Nagineni, CN Eckhaus, MA Flanders, KC Ambudkar, IS Baum, BJ Kulkarni, AB AF Hall, Bradford E. Zheng, Changyu Swaim, William D. Cho, Andrew Nagineni, Chandrasekharam N. Eckhaus, Michael A. Flanders, Kathleen C. Ambudkar, Indu S. Baum, Bruce J. Kulkarni, Ashok B. TI Conditional overexpression of TGF-beta 1 disrupts mouse salivary gland development and function SO LABORATORY INVESTIGATION LA English DT Article DE transforming growth factor-beta; fibrosis; salivary glands; saliva ID GROWTH-FACTOR-BETA; TGF-BETA; SJOGRENS-SYNDROME; TRANSGENIC MICE; SUBMANDIBULAR-GLAND; TRANSFORMING GROWTH-FACTOR-BETA-1; BRANCHING MORPHOGENESIS; ABNORMAL DISTRIBUTION; EXTRACELLULAR-MATRIX; IMMUNE-RESPONSES AB Transforming growth factor-beta (TGF-beta) signaling is known to affect salivary gland physiology by influencing branching morphogenesis, regulating ECM deposition, and controlling immune homeostasis. To study the role of TGF-beta 1 in the salivary gland, we created a transgenic mouse (beta 1(glo)) that conditionally overexpresses active TGF-beta 1 upon genomic recombination by Cre recombinase. beta 1(glo) mice were bred with an MMTV (mouse mammary tumor virus)-Cre (MC) transgenic line that expresses the Cre recombinase predominantly in the secretory cells of both the mammary and salivary glands. Although most of the double positive (beta 1(glo)/MC) pups die either in utero or just after birth, clear defects in salivary gland morphogenesis such as reduced branching and increased mesenchyme could be seen. Those beta 1(glo)/MC mice that survived into adulthood, however, had hyposalivation due to salivary gland fibrosis and acinar atrophy. Increased TGF-beta signaling was observed in the salivary gland with elevated phosphorylation of Smad2 and concomitant increase in ECM deposition. In particular, aberrant TGF-beta 1 overexpression caused salivary gland hypofunction in this mouse model because of the replacement of normal glandular parenchyma with interstitial fibrous tissue. These results further implicate TGF-beta in pathological cases of salivary gland inflammation and fibrosis that occur with chronic infections in the glands or with the autoimmune disease, Sjogren's syndrome, or with radiation therapy given to head-and-neck cancer patients. Laboratory Investigation (2010) 90, 543-555; doi: 10.1038/labinvest.2010.5; published online 8 February 2010 C1 [Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Zheng, Changyu; Swaim, William D.; Ambudkar, Indu S.; Baum, Bruce J.] Mol Physiol & Therapeut Branch, Bethesda, MD USA. [Cho, Andrew] Natl Inst Dent & Craniofacial Res, Gene Targeting Facil, Bethesda, MD 20892 USA. [Nagineni, Chandrasekharam N.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Eckhaus, Michael A.] Off Res Serv, Diagnost & Res Serv Branch, Div Vet Resources, Bethesda, MD USA. [Flanders, Kathleen C.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,MSC 4395, Bethesda, MD 20892 USA. EM ak40m@nih.gov FU Division of Intramural Research; National Institute of Dental and Craniofacial Research; National Eye Institute; National Cancer Institute; Division of Veterinary Resources; The National Institutes of Health FX We thank Drs Matthew Hoffman, Wan-Jun Chen, and Nancy Francis for critically reading the paper, and Drs Ana Cotrim, Thomas Bugge, Alfredo Molinolo and Robert Redman for helpful discussions. We also thank Drs John Letterio and Andrzej Dlugosz for the gift of active hemagglutinin epitope-tagged TGF-beta 1 cDNA and pCLE vector, respectively. These studies were supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Eye Institute, National Cancer Institute, Division of Veterinary Resources, The National Institutes of Health. NR 60 TC 25 Z9 25 U1 0 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 APR PY 2010 VL 90 IS 4 BP 543 EP 555 DI 10.1038/labinvest.2010.5 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 582AQ UT WOS:000276567800004 PM 20142803 ER PT J AU Yiu, WH Mead, PA Jun, HS Mansfield, BC Chou, JY AF Yiu, Wai Han Mead, Paul A. Jun, Hyun Sik Mansfield, Brian C. Chou, Janice Y. TI Oxidative stress mediates nephropathy in type Ia glycogen storage disease SO LABORATORY INVESTIGATION LA English DT Article DE Akt/protein kinase B; Forkhead box O; glycogen storage disease type Ia; NADPH oxidase; renal oxidative stress; catalase ID FOXO TRANSCRIPTION FACTORS; DIABETIC KIDNEY-DISEASE; REACTIVE OXYGEN; ANGIOTENSIN-II; RENAL-DISEASE; NADPH OXIDASES; PATHWAY; DYSFUNCTION; ACTIVATION; PATHOPHYSIOLOGY AB Glycogen storage disease type Ia (GSD-Ia) patients, deficient in glucose-6-phosphatase-alpha, manifest disturbed glucose homeostasis with long-term renal disease. We have previously shown that renal fibrosis in GSD-Ia is mediated by the angiotensin/transforming growth factor-beta 1 (TGF-beta 1) pathway, which also elicits renal damage through oxidative stress. In this study, we further elucidate the mechanism of renal disease by showing that renal expression of Nox-2, p22(phox), and p47(phox), components of NADPH oxidase, are upregulated in GSD-Ia mice compared with controls. Akt/protein kinase B, a downstream mediator of angiotensin II and TGF-beta 1, is also activated, leading to phosphorylation and inactivation of the Forkhead box O family of transcription factors. This in turn triggers downregulation of superoxide dismutase and catalase (CAT) activities that have essential roles in oxidative detoxification in mammals. Renal oxidative stress in GSD-Ia mice is shown by increased oxidation of dihydroethidium and by oxidative damage of DNA. Importantly, renal dysfunction, reflected by elevated serum levels of blood urea nitrogen, reduced renal CAT activity, and increased renal fibrosis, is improved in GSD-Ia mice treated with the antioxidant drug tempol. These data provide the first evidence that oxidative stress is one mechanism that underlies GSD-Ia nephropathy. Laboratory Investigation (2010) 90, 620-629; doi: 10.1038/labinvest.2010.38; published online 1 March 2010 C1 [Yiu, Wai Han; Mead, Paul A.; Jun, Hyun Sik; Mansfield, Brian C.; Chou, Janice Y.] NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov RI Jun, Hyun Sik/C-6799-2013; OI Mansfield, Brian/0000-0002-8533-2789 FU NICHD, NIH FX This research was supported by the Intramural Research Program of the NICHD, NIH. NR 48 TC 13 Z9 13 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 APR PY 2010 VL 90 IS 4 BP 620 EP 629 DI 10.1038/labinvest.2010.38 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 582AQ UT WOS:000276567800011 PM 20195241 ER PT J AU Li, YF Sheu, CC Ye, YQ de Andrade, M Wang, L Chang, SC Aubry, MC Aakre, JA Allen, MS Chen, F Cunningham, JM Deschamps, C Jiang, RX Lin, JE Marks, RS Pankratz, VS Su, L Li, Y Sun, ZF Tang, H Vasmatzis, G Harris, CC Spitz, MR Jen, J Wang, RY Zhang, ZF Christian, DC Wu, XF Yang, P AF Li, Yafei Sheu, Chau-Chyun Ye, Yuanqing de Andrade, Mariza Wang, Liang Chang, Shen-Chih Aubry, Marie C. Aakre, Jeremiah A. Allen, Mark S. Chen, Feng Cunningham, Julie M. Deschamps, Claude Jiang, Ruoxiang Lin, Jie Marks, Randolph S. Pankratz, V. Shane Su, Li Li, Yan Sun, Zhifu Tang, Hui Vasmatzis, George Harris, Curtis C. Spitz, Margaret R. Jen, Jin Wang, Renyi Zhang, Zuo-Feng Christian, David C. Wu, Xifeng Yang, Ping TI Genetic variants and risk of lung cancer in never smokers: a genome-wide association study SO LANCET ONCOLOGY LA English DT Article ID SUSCEPTIBILITY LOCUS; MULTIPLE-SCLEROSIS; SMOKING-CESSATION; CIGARETTE-SMOKING; TOBACCO-SMOKE; EXPRESSION; GLYPICANS; 5P15.33; ADENOCARCINOMA; AMPLIFICATION AB Background Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers. Methods We did a four-stage investigation. First, a genome-wide association study of single nucleotide polymorphisms (SNPs) was done with 754 never smokers (377 matched case-control pairs at Mayo Clinic, Rochester, MN, USA). Second, the top candidate SNPs from the first study were validated in two independent studies among 735 (MD Anderson Cancer Center, Houston, TX, USA) and 253 (Harvard University, Boston, MA, USA) never smokers. Third, further replication of the top SNP was done in 530 never smokers (UCLA, Los Angeles, CA, USA). Fourth, expression quantitative trait loci (eQTL) and gene-expression differences were analysed to further elucidate the causal relation between the validated SNPs and the risk of lung cancer in never smokers. Findings 44 top candidate SNPs were identified that might alter the risk of lung cancer in never smokers. rs2352028 at chromosome 13q31.3 was subsequently replicated with an additive genetic model in the four independent studies, with a combined odds ratio of 1.46 (95% CI 1.26-1.70, p=5.94x10(-6)). A cis eQTL analysis showed there was a strong correlation between genotypes of the replicated SNPs and the transcription level of the gene GPC5 in normal lung tissues (p=1.96x10(-4)), with the high-risk allele linked with lower expression. Additionally, the transcription level of GPC5 in normal lung tissue was twice that detected in matched lung adenocarcinoma tissue (p=6.75x10(-11)). Interpretation Genetic variants at 13q31.3 alter the expression of GPC5, and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute to the development of lung cancer in never smokers. C1 [Li, Yafei; de Andrade, Mariza; Aakre, Jeremiah A.; Jiang, Ruoxiang; Pankratz, V. Shane; Li, Yan; Sun, Zhifu; Tang, Hui; Yang, Ping] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Wang, Liang; Aubry, Marie C.; Cunningham, Julie M.; Vasmatzis, George] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Allen, Mark S.; Deschamps, Claude] Mayo Clin, Coll Med, Dept Surg, Rochester, MN 55905 USA. [Marks, Randolph S.] Mayo Clin, Coll Med, Div Med Oncol, Rochester, MN 55905 USA. [Jen, Jin] Mayo Clin, Coll Med, Dept Pulm & Crit Care Med, Rochester, MN 55905 USA. [Sheu, Chau-Chyun; Chen, Feng; Su, Li; Christian, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Ye, Yuanqing; Lin, Jie; Spitz, Margaret R.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Chang, Shen-Chih; Wang, Renyi; Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Chang, Shen-Chih; Wang, Renyi; Zhang, Zuo-Feng] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Christian, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christian, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Yang, P (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM yang.ping@mayo.edu RI Tang, Hui/B-3643-2010; OI Sun, Zhifu/0000-0001-8461-7523 FU US National Institutes of Health [R01-CA80127, R01-CA84354, CA111646, CA127615, CA055769, CA092824, CA074386, CA090578, P50 CA90833, T32 CA09142]; Mayo Foundation FX Funding US National Institutes of Health; Mayo Foundation.; We thank Susan Ernst for her technical assistance with the manuscript. The Microarray Shared Resource and the Genotyping Shared Resource of the Mayo Clinic Advanced Genomic Technology Center, respectively, did all the genome-wide association and gene-expression analyses described in this study. This study was supported by US National Institutes of Health research grants R01-CA80127 (to PY), R01-CA84354 (to PY), CA111646 (to XW), CA127615 (to XW), CA055769 (to MRS), CA092824 (to DCC), CA074386 (to DCC), CA090578 (to DCC), P50 CA90833 (to ZFZ), T32 CA09142 (to ZFZ). and Mayo Foundation funds (to PY and JJ). NR 47 TC 114 Z9 120 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2010 VL 11 IS 4 BP 321 EP 330 DI 10.1016/S1470-2045(10)70042-5 PG 10 WC Oncology SC Oncology GA 584PQ UT WOS:000276765100018 PM 20304703 ER PT J AU Cheng, KL Brody, J Warshall, CE Sloand, EM Allen, SL AF Cheng, Kit L. Brody, Judith Warshall, Craig E. Sloand, Elaine M. Allen, Steven L. TI Paroxysmal nocturnal hemoglobinuria following alemtuzumab immunosuppressive therapy for myelodysplastic syndrome and complicated by recurrent life-threatening thrombosis despite anticoagulation: Successful intervention with eculizumab and fondaparinux SO LEUKEMIA RESEARCH LA English DT Letter ID PNH C1 [Allen, Steven L.] N Shore Univ Hosp, Monter Canc Ctr, Albert Einstein Coll Med, Lake Success, NY 11042 USA. [Sloand, Elaine M.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Warshall, Craig E.] Long Isl Jewish Med Ctr, Albert Einstein Coll Med, Dept Radiol, New Hyde Pk, NY 11042 USA. [Cheng, Kit L.] NYU, Sch Med, N Shore Univ Hosp, Monter Canc Ctr, Lake Success, NY USA. [Brody, Judith] NYU, N Shore Univ Hosp, Sch Med, Dept Pathol, Manhasset, NY USA. RP Allen, SL (reprint author), N Shore Univ Hosp, Monter Canc Ctr, Albert Einstein Coll Med, 450 Lakeville Rd, Lake Success, NY 11042 USA. EM SAllen@nshs.edu FU Intramural NIH HHS [Z99 HL999999] NR 8 TC 4 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2010 VL 34 IS 4 BP E85 EP E87 DI 10.1016/j.leukres.2009.09.024 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 559YP UT WOS:000274868900030 PM 19836075 ER PT J AU Leyva, FJ Roberts, K AF Leyva, Francisco J. Roberts, Kevan TI Crocidolite Induces Prostaglandin I-2 Release Mediated by Vitronectin Receptor and Cyclooxygenase-2 in Lung Cells SO LUNG LA English DT Article DE Crocidolite; Pulmonary fibrosis; Cyclooxygenase 2; Prostaglandin I2; Vitronectin receptor ID INDUCED PULMONARY-FIBROSIS; MESOTHELIAL CELLS; FIBER PHAGOCYTOSIS; ASBESTOS; ACTIVATION; INJURY; INFLAMMATION; INDUCTION; APOPTOSIS; TOXICITY AB Interstitial lung disease (ILD) produces disruption of alveolar walls with loss of functionality and scar tissue accumulation. Asbestosis is the ILD produced by the inhalation of asbestos fibers. This study attempts to elucidate the role of lung epithelial cells in the generation of asbestos-induced ILD. When exposed to crocidolite LA-4 cells had a decrease in viability and an increase in the release of lactate dehydrogenase (LDH) and 6-keto PGF(1 alpha), a PGI(2) metabolite. PGI(2) release was mediated by cyclooxygenase-2 (COX-2) and vitronectin receptor (VNR). When LA-4 cells were treated with VNR inhibitors, either RGD (Arg-Gly-Asp) peptide or VNR blocking antibody, a statistically significant decrease in PGI(2) metabolite production was observed, but crocidolite-induced cytotoxicity was not prevented. These findings propose that crocidolite is coated by an RGD protein and binds VNR-inducing COX-2 expression and PGI(2) release. Moreover, when LA-4 cells were exposed to crocidolite in the presence of reduced serum culture media, PGI(2) production was prevented, and when bronchoalveolar lavage fluid (BALF) was added, PGI(2) production was rescued. Cytotoxicity did not occur, either in reduced serum culture media or when BALF was added. In conclusion, crocidolite requires the presence of an RGD protein coating the fibers to induce inflammation (PGI(2) production) and crocidolite alone cannot induce cytotoxicity in lung cells. C1 [Leyva, Francisco J.] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Baltimore, MD 21287 USA. [Leyva, Francisco J.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20824 USA. [Roberts, Kevan] Univ Montana, Ctr Environm Hlth Sci Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. RP Leyva, FJ (reprint author), Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, 600 N Wolfe St,Osler 527, Baltimore, MD 21287 USA. EM fleyva1@jhmi.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) [R01-HL079189-01A1]; Centers of Biomedical Research Excellence [P20RR017670] FX This work was supported by grants from National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) (R01-HL079189-01A1) and from the Centers of Biomedical Research Excellence (P20RR017670). We thank Rex Robinson from the NIH library for editorial assistance. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 34 TC 1 Z9 1 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD APR PY 2010 VL 188 IS 2 BP 133 EP 141 DI 10.1007/s00408-010-9229-4 PG 9 WC Respiratory System SC Respiratory System GA 568NP UT WOS:000275529600006 PM 20155273 ER PT J AU Liu, CY Redheuil, A Ouwerkerk, R Lima, JAC Bluemke, DA AF Liu, Chia-Ying Redheuil, Alban Ouwerkerk, Ronald Lima, Joao A. C. Bluemke, David A. TI Myocardial Fat Quantification in Humans: Evaluation by Two-Point Water-Fat Imaging and Localized Proton Spectroscopy SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cardiac steatosis; Dixon; spectroscopy; magnetic resonance imaging; water-fat separation ID IN-VIVO; MAGNETIC-RESONANCE; INDEPENDENT PREDICTOR; LIPID-ACCUMULATION; DIASTOLIC FUNCTION; DIABETES-MELLITUS; HEPATIC STEATOSIS; HEALTHY-SUBJECTS; HUMAN HEART; IDEAL AB Proton MR spectroscopy ((1)H-MRS) has been used for in vivo quantification of intracellular triglycerides within the sarcolemma. The purpose of this study was to assess whether breath-hold dual-echo in- and out-of-phase MRI at 3.0 T can quantify the fat content of the myocardium. Biases, including T(1), T(2)*, and noise, that confound the calculation of the fat fraction were carefully corrected. Thirty-four of 46 participants had both MRI and MRS data. The fat fractions from MRI showed a strong correlation with fat fractions from MRS (r = 0.78; P < 0.05). The mean myocardial fat fraction for all 34 subjects was 0.7 +/- 0.5% (range: 0.11-3%) assessed with MRS and 1.04 +/- 0.4% (range: 0.32-2.44%) assessed with in- and out-of-phase MRI (P < 0.05). Scanning times were less than 15 sec for Dixon imaging, plus an additional minute for the acquisition used for T(2)* calculation, and 15-20 min for MRS. The average postprocessing time for MRS was 3 min and 5 min for MRI including T(2)* measurement. We conclude that the dual echo method provides a rapid means to detect and quantifying myocardial fat content in vivo. Correction/adjustment for field inhomogeneity using three or more echoes seems crucial for the dual echo approach. Magn Reson Med 63:892-901, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Liu, Chia-Ying; Redheuil, Alban; Ouwerkerk, Ronald; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Ouwerkerk, Ronald] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Liu, CY (reprint author), Johns Hopkins Univ Hosp, Dept Radiol, MRI Room 110,600 N Wolfe St, Baltimore, MD 21287 USA. EM cliu51@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [ZIA CL090019-01, ZIA EB000072-01] NR 44 TC 14 Z9 14 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2010 VL 63 IS 4 BP 892 EP 901 DI 10.1002/mrm.22289 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 575JW UT WOS:000276064300006 PM 20373390 ER PT J AU George, AK Derbyshire, JA Saybasili, H Saikus, CE Kocaturk, O Guttman, MA McVeigh, ER Lederman, RJ Faranesh, AZ AF George, Ashvin K. Derbyshire, J. Andrew Saybasili, Haris Saikus, Christina E. Kocaturk, Ozgur Guttman, Michael A. McVeigh, Elliot R. Lederman, Robert J. Faranesh, Anthony Z. TI Visualization of Active Devices and Automatic Slice Repositioning ("Snap To") for MRI-Guided Interventions SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE real-time MRI; interventional MRI; visualization; active devices; parallel MRI; projection imaging ID MAGNETIC-RESONANCE; RECONSTRUCTION AB The accurate visualization of interventional devices is crucial for the safety and effectiveness of MRI-guided interventional procedures. In this paper, we introduce an improvement to the visualization of active devices. The key component is a fast, robust method ("Curve Find") that reconstructs the three-dimensional trajectory of the device from projection images in a fraction of a second. Curve Find is an iterative prediction-correction algorithm that acts on a product of orthogonal projection images. By varying step size and search direction, it is robust to signal inhomogeneities. At the touch of a key, the imaged slice is repositioned to contain the relevant section of the device ("SnapTo"), the curve of the device is plotted in a three-dimensional display, and the point on a target slice, which the device will intersect, is displayed. These features have been incorporated into a real-time MRI system. Experiments in vitro and in vivo (in a pig) have produced successful results using a variety of single- and multichannel devices designed to produce both spatially continuous and discrete signals. Curve Find is typically able to reconstruct the device curve, with an average error of approximately 2 mm, even in the case of complex geometries. Magn Reson Med 63:1070-1079, 2010. (C) 2010 Wiley-Liss, Inc. C1 [George, Ashvin K.; Derbyshire, J. Andrew; Saybasili, Haris; Saikus, Christina E.; Kocaturk, Ozgur; Guttman, Michael A.; McVeigh, Elliot R.; Lederman, Robert J.; Faranesh, Anthony Z.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Saybasili, Haris] Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey. RP George, AK (reprint author), 10 Ctr Dr,Bldg 10 B1D416, Bethesda, MD 20892 USA. EM georgeak@nhlbi.nih.gov RI Kocaturk, Ozgur/A-1419-2016; OI lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [NIH0013614081]; PHS HHS [NIH0013614081] NR 17 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2010 VL 63 IS 4 BP 1070 EP 1079 DI 10.1002/mrm.22307 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 575JW UT WOS:000276064300025 PM 20373408 ER PT J AU Bernard, DJ Nussbaum, RL AF Bernard, David J. Nussbaum, Robert L. TI X-inactivation analysis of embryonic lethality in Ocrl (wt/-);Inpp5b (-/-) mice SO MAMMALIAN GENOME LA English DT Article ID INOSITOL POLYPHOSPHATE 5-PHOSPHATASE; LINKED PHOSPHOGLYCERATE KINASE; CONTROLLING ELEMENTS; LOWE-SYNDROME; CHROMOSOME; MOUSE; DEFICIENT; POLYPHOSPHATE-5-PHOSPHATASE; EXPRESSION; REGIONS AB Mutations in the human OCRL gene, which encodes a phosphatidylinositol(4,5)bisphosphate 5-phosphatase, result in the X-linked oculocerebrorenal syndrome of Lowe. Mice with a targeted disruption of Ocrl have no phenotypic abnormalities. Targeted disruption of its closest paralog, Inpp5b, causes male infertility in the 129S6 background. Mice with disruptions of both genes are lost in utero prior to 9.5-10.5 dpc, indicating that there is a functional overlap between the two paralogs early in development. We analyzed the pattern of X-inactivation in four tissues of distinct embryonic origin from Ocrl (wt/-);Inpp5b (-/-) females to explore the timing and tissue distribution of the functional overlap. X-inactivation was strongly skewed against the disrupted Ocrl (-) allele being on the active X chromosome in all four tissues tested, indicating that there is early selection against cell lineages lacking both Ocrl and Inpp5b. Extraembryonic tissue was also involved in the lethality because there were never any live-born Ocrl (wt/-);Inpp5b (-/-) females when the functional Ocrl (wt) allele was on the paternal X chromosome, which is preferentially inactivated in trophoblast-derived extraembryonic tissues. Live-born Ocrl (wt/-);Inpp5b (-/-) females were found when the functional Ocrl (wt) allele was maternal, although in fewer numbers than expected. The importance of the extraembryonic tissues in the early embryonic lethality of embryos lacking both Ocrl and Inpp5b is reinforced by the successful isolation of a viable 40,XX Ocrl (-/-);Inpp5b (-/-) embryonic stem cell from the inner cell mass of a 3.5-dpc blastocyst prior to implantation. These results indicate a functional overlap of Ocrl and Inpp5b in most cell lineages, especially in extraembryonic tissues. C1 [Nussbaum, Robert L.] Univ Calif San Francisco, Div Med Genet, Dept Med, San Francisco, CA 94143 USA. [Bernard, David J.; Nussbaum, Robert L.] Natl Human Genome Res Inst, Inborn Errors & Cell Biol Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP Nussbaum, RL (reprint author), Univ Calif San Francisco, Div Med Genet, Dept Med, 513 Parnassus Ave,HSE 901E,Box 0794, San Francisco, CA 94143 USA. EM robert.nussbaum@ucsf.edu FU National Human Genome Research Institute/NIH; Department of Medicine, University of California School of Medicine FX This work was supported by the Division of Intramural Research of the National Human Genome Research Institute/NIH and by the Department of Medicine, University of California School of Medicine. NR 24 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 2010 VL 21 IS 3-4 BP 186 EP 194 DI 10.1007/s00335-010-9255-9 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 574LN UT WOS:000275990800007 PM 20195868 ER PT J AU Clark, DB Gordon, AJ Ettaro, LR Owens, JM Moss, HB AF Clark, Duncan B. Gordon, Adam J. Ettaro, Lorraine R. Owens, Jill M. Moss, Howard B. TI Screening and Brief Intervention for Underage Drinkers SO MAYO CLINIC PROCEEDINGS LA English DT Review ID ALCOHOL-USE DISORDERS; SUBSTANCE USE DISORDERS; RANDOMIZED CONTROLLED-TRIAL; BEHAVIORAL-COUNSELING INTERVENTIONS; PRIMARY-CARE INTERVENTION; UNITED-STATES; EMERGENCY-DEPARTMENT; OLDER ADOLESCENTS; COLLEGE-STUDENTS; PROBLEM DRINKING AB In a 2007 report, the US Surgeon General called for health care professionals to renew efforts to reduce underage drinking. Focusing on the adolescent patient, this review provides health care professionals with recommendations for alcohol-related screening, brief intervention, and referral to treatment. MEDLINE and published reviews were used to identify relevant literature. Several brief screening methods have been shown to effectively identify underage drinkers likely to have alcohol use disorders. After diagnostic assessment when germane, the initial intervention typically focuses on education, motivation for change, and consideration of treatment options. Internet-accessible resources providing effective brief interventions are available, along with supplemental suggestions for parents. Recent changes in federal and commercial insurance reimbursement policies provide some fiscal support for these services, although rate increases and expanded applicability may be required to prompt the participation of many practitioners. Nevertheless, advances in clinical methods and progress on reimbursement policies have made screening and brief intervention for underage drinking more feasible In general health care practice. C1 [Clark, Duncan B.] Univ Pittsburgh, Sch Med, Div Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Ettaro, Lorraine R.] Univ Pittsburgh, Ctr Rural Hlth Practice, Bradford, PA USA. [Moss, Howard B.] NIAAA, Bethesda, MD USA. RP Clark, DB (reprint author), WPIC, 3811 OHara St, Pittsburgh, PA 15213 USA. FU National Institutes of Health [U01AA016482, K02AA00291, P50DA05605] FX This work was supported by National Institutes of Health grants U01AA016482. K02AA00291. and P50DA05605 to Dr Clark NR 59 TC 13 Z9 13 U1 5 U2 8 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2010 VL 85 IS 4 BP 380 EP 391 DI 10.4065/mcp.2008.0638 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 578ZZ UT WOS:000276337100009 PM 20360296 ER PT J AU Jagger, BW Memoli, MJ Sheng, ZM Qi, L Hrabal, RJ Allen, GL Dugan, VG Wang, RX Digard, P Kash, JC Taubenberger, JK AF Jagger, Brett W. Memoli, Matthew J. Sheng, Zong-Mei Qi, Li Hrabal, Rachel J. Allen, Genevieve L. Dugan, Vivien G. Wang, Ruixue Digard, Paul Kash, John C. Taubenberger, Jeffery K. TI The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase SO MBIO LA English DT Article ID H5N1 INFLUENZA; A VIRUSES; HIGH VIRULENCE; ENHANCED VIRULENCE; MOLECULAR-BASIS; AMINO-ACID; HOST-RANGE; TRANSMISSION; PATHOGENESIS; FERRETS AB The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus's recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice. IMPORTANCE Influenza A virus (IAV) evolution is characterized by host-specific lineages, and IAVs derived in whole or in part from animal reservoirs have caused pandemics in humans. Because IAVs are known to acquire host-adaptive genome mutations, and since the PB2 gene of the 2009 H1N1 virus is of recent avian derivation, there exists concern that the pathogenicity of the 2009 H1N1 influenza A pandemic virus could be potentiated by acquisition of the host-adaptive PB2-E627K or -D701N mutations, which have been shown to enhance the virulence of other influenza viruses. We present data from a mouse model of influenza infection showing that such mutations do not increase the virulence of viruses containing the 2009 H1N1 viral polymerase. C1 [Jagger, Brett W.; Memoli, Matthew J.; Sheng, Zong-Mei; Qi, Li; Hrabal, Rachel J.; Allen, Genevieve L.; Dugan, Vivien G.; Wang, Ruixue; Kash, John C.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Digard, Paul] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov RI Digard, Paul/B-7717-2008 OI Digard, Paul/0000-0002-0872-9440 FU NIH; NIAID FX This work was supported by the Intramural Research Program of the NIH and the NIAID. Authors B.W.J., P.D., and J.K.T. further acknowledge the support of the NIH-Oxford/Cambridge Research Scholars program. NR 40 TC 30 Z9 31 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD APR PY 2010 VL 1 IS 1 AR e00067-10 DI 10.1128/mBio.00067-10 PG 9 WC Microbiology SC Microbiology GA 686SS UT WOS:000284716600010 ER PT J AU Cheng, WH Bohr, VA de Cabo, R AF Cheng, Wen-Hsing Bohr, Vilhelm A. de Cabo, Rafael TI Nutrition and aging Preface SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material ID CALORIC RESTRICTION; GENOMIC STABILITY; VITAMIN-B12; SELENIUM C1 [Cheng, Wen-Hsing] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 21029 USA. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, IRP, Baltimore, MD 21224 USA. [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, IRP, Baltimore, MD 21224 USA. RP Cheng, WH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 3107B Skinner Bldg, College Pk, MD 21029 USA. EM whcheng@umd.edu; deCaboRa@grc.nia.nih.gov FU Intramural NIH HHS [ZIA AG000368-05, ZIA AG000733-15] NR 11 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR PY 2010 VL 131 IS 4 SI SI BP 223 EP 224 DI 10.1016/j.mad.2010.03.011 PG 2 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 604VQ UT WOS:000278307000001 PM 20362608 ER PT J AU Tilburt, JC Miller, FG Jenkins, S Kaptchuk, TJ Clarridge, B Bolcic-Jankovic, D Emanuel, EJ Curlin, FA AF Tilburt, Jon C. Miller, Franklin G. Jenkins, Sarah Kaptchuk, Ted J. Clarridge, Brian Bolcic-Jankovic, Dragana Emanuel, Ezekiel J. Curlin, Farr A. TI Factors That Influence Practitioners' Interpretations of Evidence From Alternative Medicine Trials A Factorial Vignette Experiment Embedded in a National Survey SO MEDICAL CARE LA English DT Article DE complementary therapies; evidence based medicine; clinical decision making; bias ID ACUPUNCTURE TREATMENT; COMPLEMENTARY; BIAS; KNEE; PAIN AB Background: Clinical trial evidence in controversial areas such as complementary and alternative medicine (CAM) must be approached with an open mind. Objective: To determine what factors may influence practitioners' interpretation of evidence from CAM trials. Research Design: In a mailed survey of 2400 US CAM and conventional medicine practitioners we included 2 hypothetical factorial vignettes of positive and negative research results for CAM clinical trials. Vignettes contained randomly varied journal (Annals of Internal Medicine vs. Journal of Complementary and Alternative Medicine) and CAM treatment type (acupuncture, massage, glucosamine, meditation, and reiki). Response items also included randomly varied patient circumstances-chronic refractory symptoms and the patient requesting CAM. Measures: All practitioners rated the effectiveness and their willingness to recommend the therapy for a described patient. We used logistic regression to determine the independent influence of the 4 factors on respondents' effectiveness and legitimacy judgments. Results: A total of 1561 practitioners responded (65%). Relative to Reiki, conventional medicine practitioners were most willing to recommend glucosamine (OR = 3.0; 95% CI [1.6-5.4]), than massage (1.9 [1.1-3.3]), acupuncture (1.3 [0.8-2.2]), and meditation (1.2 [0.7-2.0]). CAM practitioners rated acupuncture as effective more than other CAM therapies (OR = 5.8 [2.6-12.8] compared with Reiki), and were more willing to recommend acupuncture (OR = 12.3 [4.8 31.8]). When presented evidence of inefficacy, CAM practitioners were most willing to recommend acupuncture relative to other CAM therapies (OR = 15.5 [9.0-26.9]). Conclusions: Practitioners' judgments about CAM trial evidence depend on the type of treatments reported. Confirmation bias may play a role in the clinical translation of new evidence from clinical trials. C1 [Tilburt, Jon C.; Miller, Franklin G.; Emanuel, Ezekiel J.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Tilburt, Jon C.] Mayo Clin, Div Gen Internal Med, Rochester, MN USA. [Tilburt, Jon C.] Mayo Clin, Program Professionalism & Bioeth, Rochester, MN USA. [Jenkins, Sarah] Mayo Clin, Div Biomed Stat & Informat, Survey Res Ctr, Rochester, MN USA. [Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA. [Clarridge, Brian; Bolcic-Jankovic, Dragana] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Curlin, Farr A.] Univ Chicago, Sect Internal Med, Chicago, IL 60637 USA. [Curlin, Farr A.] Univ Chicago, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. RP Tilburt, JC (reprint author), 200 1st St SW, Rochester, MN 55905 USA. EM tilburt.jon@mayo.edu FU National Center for Complementary and Alternative Medicine; Department of Bioethics, National Institutes of Health; National Center for Complementary and Alternative Medicine [1 K23 AT002749, K24 AT004095] FX Supported by the National Center for Complementary and Alternative Medicine and the Department of Bioethics, National Institutes of Health; National Center for Complementary and Alternative Medicine (1 K23 AT002749, K24 AT004095, respectively, to F. A. C. and T.J.K.). The funder was not involved in data collection, analysis, or writing of the manuscript. NR 18 TC 4 Z9 4 U1 0 U2 3 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 APR PY 2010 VL 48 IS 4 BP 341 EP 348 DI 10.1097/MLR.0b013e3181ca3ee2 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 582ZE UT WOS:000276639300009 PM 20355265 ER PT J AU Linguraru, MG Pura, JA Uitert, RL Mukherjee, N Summers, RM Minniti, C Gladwin, MT Kato, G Machado, RF Wood, BJ AF Linguraru, Marius George Pura, John A. Van Uitert, Robert L. Mukherjee, Nisha Summers, Ronald M. Minniti, Caterina Gladwin, Mark T. Kato, Gregory Machado, Roberto F. Wood, Bradford J. TI Segmentation and quantification of pulmonary artery for noninvasive CT assessment of sickle cell secondary pulmonary hypertension SO MEDICAL PHYSICS LA English DT Article DE angiocardiography; blood vessels; computerised tomography; diseases; lung ID COMPUTED-TOMOGRAPHY; RISK-FACTOR; 3D IMAGES; DISEASE; ANGIOGRAPHY; TREE; EXTRACTION; DIAMETER; VESSELS; DEATH AB Purpose: Pulmonary arterial hypertension (PAH) is a progressive vascular disease that results in high mortality and morbidity in sickle cell disease (SCD) patients. PAH diagnosis is invasive via right heart catheterization, but manual measurements of the main pulmonary artery (PA) diameters from computed tomography (CT) have shown promise as noninvasive surrogate marker of PAH. The authors propose a semiautomated computer-assisted diagnostic (CAD) tool to quantify the main PA size from pulmonary CT angiography (CTA). Methods: A follow-up retrospective study investigated the potential of CT and image analysis to quantify the presence of PAH secondary to SCD based on PA size. The authors segmented the main pulmonary arteries using a combination of fast marching level sets and geodesic active contours from smoothed pulmonary CTA images of 20 SCD patients with proven PAH by right heart catheterization and 20 matched negative controls. From the PA segmentation, a Euclidean distance map was calculated and an algorithm based on fast marching methods was used to compute subvoxel precise centerlines of the PA trunk (PT) and main left/right PA (PM). Maximum distentions of PT and PM were automatically quantified using the centerline and validated with manual measurements from two observers. Results: The pulmonary trunk and main were significantly larger (p < 0.001) in PAH/SCD patients (33.73 +/- 3.92 mm for PT and 25.17 +/- 2.90 for PM) than controls (27.03 +/- 2.94 mm for PT and 20.62 +/- 3.06 for PM). The discrepancy was qualitatively improved when vessels' diameters were normalized by body surface area (p < 0.001). The validation of the method showed high correlation (mean R=0.9 for PT and R=0.91 for PM) and Bland-Altman agreement (0.4 +/- 3.6 mm for PT and 0.5 +/- 2.9 mm for PM) between CAD and manual measurements. Quantification errors were comparable to intraobserver and interobserver variability. CAD measurements between two different users were robust and reproducible with correlations of R=0.99 for both PT and PM and Bland-Altman agreements of -0.13 +/- 1.33 mm for PT and -0.08 +/- 0.84 mm for PM. Conclusion: Results suggest that the semiautomated quantification of pulmonary artery has sufficient accuracy and reproducibility for clinical use. CT with image processing and extraction of PA biomarkers show great potential as a surrogate indicator for diagnosis or quantification of PAH, and could be an important tool for drug discovery and noninvasive clinical surveillance. C1 [Linguraru, Marius George; Minniti, Caterina; Kato, Gregory] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Minniti, Caterina; Kato, Gregory] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gladwin, Mark T.] Univ Pittsburgh, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA 15213 USA. [Machado, Roberto F.] Univ Chicago, Dept Med, Sect Pulm Crit Care, Chicago, IL 60637 USA. RP Linguraru, MG (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov OI Kato, Gregory/0000-0003-4465-3217 FU National Institutes of Health, Clinical Center and National Heart, Lung and Blood Institute FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, Clinical Center and National Heart, Lung and Blood Institute. The authors would like to thank Babak J. Orandi for helping to collect data. NR 53 TC 10 Z9 10 U1 3 U2 9 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD APR PY 2010 VL 37 IS 4 BP 1522 EP 1532 DI 10.1118/1.3355892 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 577GT UT WOS:000276211200016 PM 20443473 ER PT J AU Kashaw, SK Gupta, V Kashaw, V Mishra, P Stables, JP Jain, NK AF Kashaw, Sushil K. Gupta, Vivek Kashaw, Varsha Mishra, P. Stables, J. P. Jain, N. K. TI Anticonvulsant and sedative-hypnotic activity of some novel 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2-styrylquinazoline-4(3H)-ones SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article DE 4(3H)-quinazolinones; MES; Subcutaneous pentylenetetrazole-induced seizure; CNS depressant activity ID CNS-DEPRESSANT ACTIVITY; QUINAZOLINE-4(3H)-ONES; SEMICARBAZONES AB A few novel 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones were synthesized and evaluated for anticonvulsant, neurotoxicity, sedative-hypnotic, and phenobarbitone-induced hypnosis potentiation test. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight derivatives were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models in mice. Spectroscopic data were consistence with the newly synthesized compounds. The neurotoxicity was assessed using the Rotorod method. Out of 15 compounds only 7e and 7o showed anticonvulsant activity at various doses in one or more test models. All except 7d, 7m, and 7n exhibited significant sedative-hypnotic activity via actophotometer screen. Central nervous system (CNS)-depressant activity screened with the help of the forced swim method resulted into some potent compounds. No percentage increase in the sleeping time was observed in any of the synthesized compounds evaluated by the phenobarbitone-induced hypnosis potentiation test. On the basis of experimental data, it can be concluded that synthesized compounds possessed relatively better sedative-hypnotic and CNS-depressant activities. C1 [Kashaw, Sushil K.; Gupta, Vivek; Kashaw, Varsha; Mishra, P.; Jain, N. K.] Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar, India. [Stables, J. P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Kashaw, SK (reprint author), Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar, India. EM sushilkashaw@gmail.com FU NIH, USA FX The authors acknowledge the assistance of the Antiepileptic Drug Development Program, Epilepsy Branch, Preclinical Pharmacology Section, NIH, USA. NR 20 TC 17 Z9 18 U1 0 U2 0 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PD APR PY 2010 VL 19 IS 3 BP 250 EP 261 DI 10.1007/s00044-009-9188-6 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 570FQ UT WOS:000275658100004 ER PT J AU Zeno, SA Deuster, PA Davis, JL Kim-Dorner, SJ Remaley, AT Poth, M AF Zeno, Stacey A. Deuster, Patricia A. Davis, Jennifer L. Kim-Dorner, Su-Jong Remaley, Alan T. Poth, Merrily TI Diagnostic Criteria for Metabolic Syndrome: Caucasians Versus African-Americans SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID C-REACTIVE PROTEIN; CARDIORESPIRATORY FITNESS; SYNDROME COMPONENTS; INSULIN-RESISTANCE; ETHNIC-DIFFERENCES; WOMEN; RISK; ASSOCIATION; SAMPLE; MEN AB Background: Metabolic syndrome is a constellation of risk factors used to identify individuals at greatest risk for developing cardiovascular disease (CVD). Early diagnosis of CVD would benefit African-Americans (AA), who have a higher prevalence of and mortality rate from CVD compared to Caucasians (CA). Two definitions for metabolic syndrome were used to classify healthy CA and AA, and evaluate how other CVD risk factors [C-reactive protein (CRP), percent body fat, fitness level, insulin resistance, and non-high-density lipoprotein cholesterol (HDL-C)] changed metabolic syndrome classification. Methods: Healthy AA (n = 97) and CA (n = 51) ranging from normal weight to obese, 18-45 years of age, with neither hypertension nor diabetes, were evaluated for cardiorespiratory fitness, height, weight, percent body fat, hip and waist circumference, blood pressure (BP), and fasting blood glucose, insulin, triglycerides, HDL, non-HDL-C, and CRP. Participants were classified as meeting the criteria for metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III 2004 (NCEP ATP III) and the International Diabetes Federation (IDF) definitions. Results: Significant ethnic differences (P < 0.01) in classification were noted for both metabolic syndrome definitions (NCEP ATP III, CA = 16.7% vs. AA = 5.7%; IDF, CA = 23.5% vs. AA = 8.2%). Ethnic differences were eliminated when fitness level or percent body fat was included as a criterion. Conclusions: If diagnosis of metabolic syndrome is intended for early recognition of CVD risk and slowing CVD development, current definitions for metabolic syndrome will not capture healthy AA. Health-care providers may consider assessing percent body fat and participation in regular exercise, because these criteria would help identify AA at risk. C1 [Zeno, Stacey A.; Deuster, Patricia A.; Davis, Jennifer L.; Kim-Dorner, Su-Jong] Uniformed Serv Univ Hlth Sci, Dept Mil, Bethesda, MD 20814 USA. [Zeno, Stacey A.; Deuster, Patricia A.; Davis, Jennifer L.; Kim-Dorner, Su-Jong] Uniformed Serv Univ Hlth Sci, Dept Emergency Med, Bethesda, MD 20814 USA. [Poth, Merrily] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Deuster, PA (reprint author), 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM pdeuster@usuhs.mil RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 FU Human Performance Laboratory; U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland [DAMD17-03-2-0024] FX The authors would like gratefully acknowledge the contributions of Dr. Remaley and his team at the National Institutes of Health (NIH). We would also like to sincerely thank the entire Human Performance Laboratory for their hard work and support. This project was made possible by U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland, Peer Reviewed Medical Research Program Award Number DAMD17-03-2-0024. The opinions and assertions expressed herein are those of the authors and should not be construed as reflecting those of the Uniformed Services University of the Health Sciences (USUHS) or the Department of Defense. NR 30 TC 9 Z9 9 U1 2 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD APR PY 2010 VL 8 IS 2 BP 149 EP 155 DI 10.1089/met.2009.0053 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 579FT UT WOS:000276354500008 PM 20156068 ER PT J AU Hivert, MF Sullivan, LM Shrader, P Fox, CS Nathan, DM D'Agostino, RB Wilson, PWF Benjamin, EJ Meigs, JB AF Hivert, Marie-France Sullivan, Lisa M. Shrader, Peter Fox, Caroline S. Nathan, David M. D'Agostino, Ralph B., Sr. Wilson, Peter W. F. Benjamin, Emelia J. Meigs, James B. TI The association of tumor necrosis factor alpha receptor 2 and tumor necrosis factor alpha with insulin resistance and the influence of adipose tissue biomarkers in humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID C-REACTIVE PROTEIN; TNF-ALPHA; METABOLIC SYNDROME; IN-VITRO; 3T3-L1 ADIPOCYTES; HEART-DISEASE; ADIPONECTIN; PLASMA; EXPRESSION; CYTOKINES AB Tumor necrosis factor alpha (TNF alpha) is a proinflammatory adipokine hypothesized to link obesity with insulin resistance. Functional studies suggest that TNF alpha acts through pathways involving adipokines and fatty acids to induce insulin resistance. We tested the hypothesis that the association of measures of TNF alpha activity with insulin resistance is independent of obesity and adipose tissue biomarkers. We analyzed data from 2131 participants (without diabetes) of the Framingham Offspring Study examination 7. The outcome of interest was insulin resistance, measured using the homeostasis model assessment (HOMA-IR). Tumor necrosis factor alpha activity was measured by plasma tumor necrosis factor alpha receptor 2 (TNFr2) or TNF alpha; possible confounders included adipose tissue biomarkers (plasma adiponectin, resistin, and triglycerides). We used multivariable age- and sex-adjusted linear regression analyses to adjust for waist circumference and for biomarkers individually and simultaneously, and in biomarker-stratified (above and below median) models. We found that TNFr2 was positively associated with HOMA-IR (r = 0.21, P < .0001). In age- and sex-adjusted model, for each increase of 1 standard deviation of TNFr2 (SD = 746 pg/mL), the log (HOMA-IR) value was increased by 0.11 units (P < .0001). Adjustment for waist circumference reduced the TNFr2 beta-coefficient (by about 45%), but the association between TNFr2 and HOMA-IR remained significant (P < .0001). Tumor necrosis factor a receptor 2 was still associated to HOMA-IR after adding adiponectin, resistin, and triglycerides (individually and simultaneously). We found similar associations with plasma levels of TNF alpha. We conclude that, in a representative community sample, measures of TNF alpha activity are associated with insulin resistance, even after accounting for central adiposity and other adipose tissue biomarkers. (C) 2010 Elsevier Inc. All rights reserved. C1 [Hivert, Marie-France; Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Hivert, Marie-France; Nathan, David M.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol & Metab, Boston, MA 02115 USA. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Dept Med, Boston, MA 02114 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Consulting Unit, Boston, MA 02115 USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [RO1 HL064753, RO1 HL076784, R01 AG028321]; National Center for Research Resources; General Clinical Research Centers Program [M01-RR-01066]; American Diabetes Association and National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; Earle Charlton Fund; Centre de Recherche Medicale de l'Universite de Sherbrooke; Canadian Institute of Health Research; GlaxoSmithKline FX The study was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195); the National Institutes of Health; National Center for Research Resources, National Institutes of Health grants RO1 HL064753, RO1 HL076784, and R01 AG028321 (EJB); General Clinical Research Centers Program (Grant No. M01-RR-01066); and a Career Development Award from the American Diabetes Association and National Institute of Diabetes and Digestive and Kidney Diseases K24 DK080140 (JBM). DMN is supported in part by the Earle Charlton Fund for Innovative Diabetes Research. MFH was supported by the Centre de Recherche Medicale de l'Universite de Sherbrooke and a Canadian Institute of Health Research Fellowships Health Professional Award. JBM currently has research grants from GlaxoSmithKline and sanofi-aventis, and has consulting agreements with Eli Lilly, Interleukin Genetics, Kalypsis, and Outcomes Science. NR 38 TC 12 Z9 15 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2010 VL 59 IS 4 BP 540 EP 546 DI 10.1016/j.metabol.2009.08.017 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 576ZO UT WOS:000276189200013 PM 19846171 ER PT J AU Ibarra, JA Knodler, LA Sturdevant, DE Virtaneva, K Carmody, AB Fischer, ER Porcella, SF Steele-Mortimer, O AF Ibarra, J. Antonio Knodler, Leigh A. Sturdevant, Daniel E. Virtaneva, Kimmo Carmody, Aaron B. Fischer, Elizabeth R. Porcella, Stephen F. Steele-Mortimer, Olivia TI Induction of Salmonella pathogenicity island 1 under different growth conditions can affect Salmonella-host cell interactions in vitro SO MICROBIOLOGY-SGM LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; GREEN FLUORESCENT PROTEIN; III SECRETION SYSTEM; VIRULENCE GENE-EXPRESSION; SET ENRICHMENT ANALYSIS; EPITHELIAL-CELLS; STATIONARY-PHASE; SEROTYPE TYPHIMURIUM; BACTERIAL MOTILITY; MAMMALIAN-CELLS AB Salmonella invade non-phagocytic cells by inducing massive actin rearrangements, resulting in membrane ruffle formation and phagocytosis of the bacteria. This process is mediated by a cohort of effector proteins translocated into the host cell by type III secretion system 1, which is encoded by genes in the Salmonella pathogenicity island (SPI) 1 regulon. This network is precisely regulated and must be induced outside of host cells. In vitro invasive Salmonella are prepared by growth in synthetic media although the details vary. Here, we show that culture conditions affect the frequency, and therefore invasion efficiency, of SPI1-induced bacteria and also can affect the ability of Salmonella to adapt to its intracellular niche following invasion. Aerobically grown late-exponential-phase bacteria were more invasive and this was associated with a greater frequency of SPI1-induced, motile bacteria, as revealed by single-cell analysis of gene expression. Culture conditions also affected the ability of Salmonella to adapt to the intracellular environment, since they caused marked differences in intracellular replication. These findings show that induction of SPI1 under different pre-invasion growth conditions can affect the ability of Salmonella to interact with eukaryotic host cells. C1 [Ibarra, J. Antonio; Knodler, Leigh A.; Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Sturdevant, Daniel E.; Virtaneva, Kimmo; Porcella, Stephen F.] NIAID, Genom Unit, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Carmody, Aaron B.] NIAID, Flow Cytometry Unit, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Fischer, Elizabeth R.] NIAID, Microscopy Unit, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Steele-Mortimer, O (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM omortimer@niaid.nih.gov FU National Institutes of Health (NIH), National Institute for Allergy and Infectious Diseases (NIAID) FX We thank Seth Winfree, Patricia Fuentes, Ron Messer, Alissa Curda, Craig Martens, Greg Farneth, Damon Ellison and Luke Wicke for expert experimental and technical assistance. We are grateful to Ed Miao for kindly providing phages, to Andreas Baumler for providing phage stock and the anti-FimA antibody, to the Rocky Mountain Laboratories Genomics Unit for DNA sequencing analysis, to members of our lab for their helpful discussions and criticism and to the reviewers for constructive suggestions. This research was supported by the Intramural Research Program (DIR) of the National Institutes of Health (NIH), National Institute for Allergy and Infectious Diseases (NIAID). NR 60 TC 40 Z9 40 U1 0 U2 9 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD APR PY 2010 VL 156 BP 1120 EP 1133 DI 10.1099/mic.0.032896-0 PN 4 PG 14 WC Microbiology SC Microbiology GA 596QG UT WOS:000277699500016 PM 20035008 ER PT J AU Kang, HS Kim, YS ZeRuth, G Beak, JY Gerrish, K Kilic, G Sosa-Pineda, B Jensen, J Pierreux, CE Lemaigre, FP Foley, J Jetten, AM AF Kang, Hong Soon Kim, Yong-Sik ZeRuth, Gary Beak, Ju Youn Gerrish, Kevin Kilic, Gamze Sosa-Pineda, Beatriz Jensen, Jan Pierreux, Christophe E. Lemaigre, Frederic P. Foley, Julie Jetten, Anton M. TI Transcription Factor Glis3, a Novel Critical Player in the Regulation of Pancreatic beta-Cell Development and Insulin Gene Expression (vol 29, pg 6366, 2009) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 [Kang, Hong Soon; Kim, Yong-Sik; ZeRuth, Gary; Beak, Ju Youn; Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Gerrish, Kevin] NIEHS, Microarray Lab Core, NIH, Res Triangle Pk, NC 27709 USA. [Kim, Yong-Sik; Jensen, Jan] Cleveland Clin, Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44195 USA. [Kilic, Gamze; Sosa-Pineda, Beatriz] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. [Foley, Julie] NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. [Pierreux, Christophe E.; Lemaigre, Frederic P.] Univ Catholique Louvain, de Duve Inst, B-1200 Brussels, Belgium. RP Kang, HS (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR 1 PY 2010 VL 30 IS 7 BP 1864 EP 1864 DI 10.1128/MCB.00108-10 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 565NY UT WOS:000275302000023 ER PT J AU Aschrafi, A Natera-Naranjo, O Gioio, AE Kaplan, BB AF Aschrafi, Armaz Natera-Naranjo, Orlangie Gioio, Anthony E. Kaplan, Barry B. TI Regulation of axonal trafficking of cytochrome c oxidase IV mRNA SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Sympathetic neurons; Superior cervical ganglion; Intra-axonal translation; mRNA localization; 3 ' UTR; Axonal growth; Mitochondria; ATP synthesis ID LOCAL PROTEIN-SYNTHESIS; 3'-UNTRANSLATED REGION; SYMPATHETIC NEURONS; IN-VIVO; MITOCHONDRIA; LOCALIZATION; TRANSPORT; YEAST; VICINITY; GROWTH AB Trafficking and local translation of axonal mRNAs play a critical role in the development and function of this neuronal subcellular structural domain. In this report, we studied cytochrome c oxidase subunit IV (COXIV) mRNA trafficking into distal axons of primary superior cervical ganglia (SCG) neurons, and provided evidence that axonal trafficking and mitochondrial association of the mRNA are mediated by an element located in a 38 bp-long, hairpin-loop forming region within the 3'UTR of the transcript. Our results also suggest that suppression of local translation of COXIV mRNA results in significant attenuation of axonal elongation. Taken together, the results provide the first evidence for the existence of a cis-acting axonal transport element within a nuclear-encoding mitochondrial gene, and demonstrate the importance of the axonal trafficking and local translation of nuclear-encoded mitochondrial mRNAs in axonal growth. Published by Elsevier Inc. C1 [Aschrafi, Armaz; Natera-Naranjo, Orlangie; Gioio, Anthony E.; Kaplan, Barry B.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, Bldg 10,Room 4A15,10 Ctr Dr, Bethesda, MD 20892 USA. EM kaplanb@mail.nih.gov RI Aschrafi, Armaz/E-2202-2012 FU National Institute of Mental Health FX This work was supported by the Division of Intramural Research Programs of the National Institute of Mental Health. NR 36 TC 26 Z9 26 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 EI 1095-9327 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD APR PY 2010 VL 43 IS 4 BP 422 EP 430 DI 10.1016/j.mcn.2010.01.009 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 574ME UT WOS:000275992700009 PM 20144716 ER PT J AU Luther, N Cheung, NK Souliopoulos, EP Karempelas, I Bassiri, D Edgar, MA Guo, HF Pastan, I Gutin, PH Souweidane, MM AF Luther, Neal Cheung, Nai-Kong Souliopoulos, Eleni P. Karempelas, Ioannis Bassiri, Daniel Edgar, Mark A. Guo, Hong-fen Pastan, Ira Gutin, Philip H. Souweidane, Mark M. TI Interstitial Infusion of Glioma-Targeted Recombinant Immunotoxin 8H9scFv-PE38 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; RAT-BRAIN-STEM; MONOCLONAL-ANTIBODY 81C6; INTERLEUKIN-13 RECEPTOR; PRIMATE BRAIN; IN-VITRO; THERAPY; CANCER; TUMOR AB Monoclonal antibodies have the potential to target therapy for high-grade gliomas. Monoclonal antibody 8H9 is specific for membrane protein B7H3 and is reactive with most human high-grade gliomas. We tested the 8H9scFv-PE38 recombinant Pseudomonas immunotoxin in a preclinical model of high-grade glioma. The half maximal inhibitory concentration (IC(50)) of 8H9scFv-PE38 in vitro was determined using glioblastoma cell lines U87 and U251. Maximum tolerated infusion dose of 8H9scFv-PE38 following interstitial infusion to the striatum and pons was defined using athymic rats. Maximum tolerated infusion dose of 8H9scFv-PE38 or PBS control were interstitially delivered to athymic rats xenografted with U87 in the striatum or brain stem. Radiographic response and survivals were measured and compared between treatment groups. The in vitro IC50 of 8H9scFv-PE38 for U87 was 1,265 ng/mL and, for U251, 91 ng/mL. The maximum tolerated infusion doses of interstitially infused 8H9scFv-PE38 to the striatum and brain stem were 0.75 and 1.8 mu g, respectively. For rats harboring intracranial U87 xenografts, infusion of 8H9scFv-PE38 increased mean survival (striatum, 43.4 versus 24.6 days; brain stem, 80.6 versus 45.5 days; n = 28 total) and produced three long-term survivors past 120 days. None of the 14 placebo-treated animals survived >54 days. Tumors also showed volumetric response to infusion of 8H9scFv-PE38 by magnetic resonance imaging. Interstitial infusion of 8H9scFv-PE38 shows potential for the treatment of hemispherical and brain stem glioma. Mol Cancer Ther; 9(4); 1039-46. (C) 2010 AACR. C1 [Luther, Neal] Cornell Univ, Weill Med Coll, Dept Neurol Surg, New York, NY 10021 USA. [Cheung, Nai-Kong; Guo, Hong-fen] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Edgar, Mark A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Gutin, Philip H.; Souweidane, Mark M.] Mem Sloan Kettering Canc Ctr, Dept Neurol Surg, New York, NY 10021 USA. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Luther, N (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol Surg, Room A-969,1300 York Ave, New York, NY 10021 USA. EM nel2003@nyp.org FU Pediatric Brain Tumor Foundation; Ian's Friends Foundation; NIH [CA106450]; Robert Steel Foundation; Hope Street Kids; Center for Cancer Research, National Cancer Institute, NIH FX Grant Support; Pediatric Brain Tumor Foundation, Ian's Friends Foundation, NIH CA106450, Robert Steel Foundation, Hope Street Kids, and the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 49 TC 16 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2010 VL 9 IS 4 BP 1039 EP 1046 DI 10.1158/1535-7163.MCT-09-0996 PG 8 WC Oncology SC Oncology GA 607GP UT WOS:000278487400024 PM 20371725 ER PT J AU Stepp, MA Pal-Ghosh, S Tadvalkar, G Rajjoub, L Jurjus, RA Gerdes, M Ryscavage, A Cataisson, C Shukla, A Yuspa, SH AF Stepp, Mary Ann Pal-Ghosh, Sonali Tadvalkar, Gauri Rajjoub, Lamise Jurjus, Rosalyn A. Gerdes, Michael Ryscavage, Andrew Cataisson, Christophe Shukla, Anjali Yuspa, Stuart H. TI Loss of Syndecan-1 Is Associated With Malignant Conversion in Skin Carcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Article DE skin carcinogenesis; keratinocytes; syndecan-1; integrin; laminin 332; TGF beta 1; ras oncogene ID TRANSFORMING-GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; ALPHA-6-BETA-4 INTEGRIN; TGF-BETA; EPITHELIAL HOMEOSTASIS; EXPRESSION; MOUSE; TGF-BETA-1; MICE; PROGRESSION AB Syndecan-1 (sdc-1) is a cell surface proteoglycan that mediates the interaction of cells with their matrix, influencing attachment, migration, and response to growth factors. In keratinocytes, loss of sdc-1 delays wound healing, reduces migration, and increases Transforming growth factor beta (TGF beta) 1 expression. In this study we show that sdc-1 expression is significantly reduced in basal cell, squamous cell, and metastatic human skin cancers compared to normal human skin. In experimental mouse skin tumor induction, compared to wildtype (wt) BALB/c mice, papilloma formation in sdc-1 null mice was reduced by 50% and the percent of papillomas converting to squamous cell carcinoma (SCC) was enhanced. sdc-1 expression on wt mouse papillomas decreased as they converted to SCC. Furthermore, papillomas forming on sdc-1 null mice expressed suprabasal alpha 3 and beta 4 integrins; suprabasal beta 4 integrin is a marker of a high risk for progression. While the proliferative response to phorbol-12-myristate-13-acetate (TPA) did not differ among the genotypes, sdc-1 null mice had an enhanced inflammatory response and retained higher levels of total TGF beta 1 within their skin after TPA treatment. sdc-1 null keratinocytes, transduced in vitro by oncogenic ras(Ha), expressed higher levels of beta 4 integrin and had enhanced pSmad2 signaling and reduced senescence when compared to wt ras(Ha)-transduced keratinocytes. When ras(Ha)-transduced cells of both genotypes were grafted onto nude mice, null tumors converted to SCC with higher frequency confirming the skin painting experiments. These data indicate that sdc-1 is important both early in the development of skin tumors and in progression of skin cancers suggesting that reduced expression of sdc-1 could be a useful marker for progression in neoplastic skin lesions. (C) 2010 Wiley-Liss, Inc. C1 [Stepp, Mary Ann; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Rajjoub, Lamise; Jurjus, Rosalyn A.] George Washington Univ, Med Ctr, Dept Anat & Regenerat Biol, Washington, DC 20037 USA. [Stepp, Mary Ann] George Washington Univ, Med Ctr, Dept Ophthalmol, Washington, DC 20037 USA. [Gerdes, Michael] GE Global Res, Niskayuna, NY USA. [Ryscavage, Andrew; Cataisson, Christophe; Shukla, Anjali; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Stepp, MA (reprint author), Ross Hall Rm 226C,2300 1 St NW, Washington, DC 20037 USA. RI Shukla, Anjali/G-4046-2014; OI Stepp, Mary Ann/0000-0001-5623-2538 FU NIH, National Cancer Institute, Center for Cancer Research; NIH [RO1-EY08512, EY13559] FX We thank Adam Glick, Mariam Malik, Jonathan Jones, and Luowei Li for advice and assistance at various stages of this project as well as to Aleksandra Michalowski for help with statistics. This work was initiated during a sabbatical from GWU Medical School for M.A.S. and was supported in part by the intramural research program of the NIH, National Cancer Institute, Center for Cancer Research. In addition, this work was funded by NIH RO1-EY08512 and EY13559 (M.A.S.). NR 35 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 2010 VL 49 IS 4 BP 363 EP 373 DI 10.1002/mc.20609 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 584CY UT WOS:000276728900006 PM 20082322 ER PT J AU Young, MR Santhanam, AN Yoshikawa, N Colburn, NH AF Young, Matthew R. Santhanam, Arti N. Yoshikawa, Noriko Colburn, Nancy H. TI Have Tumor Suppressor PDCD4 and its Counteragent Oncogenic miR-21 Gone Rogue? SO MOLECULAR INTERVENTIONS LA English DT Editorial Material ID INITIATION-FACTOR 4A; PROGRAMMED CELL-DEATH-4; TRANSFORMATION SUPPRESSOR; EUKARYOTIC TRANSLATION; COLORECTAL-CANCER; KAPPA-B; PROTEIN; MICRORNA-21; EXPRESSION; CELLS C1 [Young, Matthew R.; Santhanam, Arti N.; Yoshikawa, Noriko; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. RP Young, MR (reprint author), NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. EM young-ma@mail.nih.gov; santhana@mail.nih.gov; yoshikawan@mail.nih.gov; colburna@mail.nih.gov NR 27 TC 28 Z9 30 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD APR PY 2010 VL 10 IS 2 BP 76 EP 79 DI 10.1124/mi.10.2.5 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578QO UT WOS:000276309200004 PM 20368367 ER PT J AU Coornaert, A Lu, A Mandin, P Springer, M Gottesman, S Guillier, M AF Coornaert, Audrey Lu, Alisa Mandin, Pierre Springer, Mathias Gottesman, Susan Guillier, Maude TI MicA sRNA links the PhoP regulon to cell envelope stress SO MOLECULAR MICROBIOLOGY LA English DT Article ID 2-COMPONENT REGULATORY SYSTEM; OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; DOWN-REGULATION; NONCODING RNAS; ANTISENSE RNA; HFQ; BINDING; RPOS; SALMONELLA AB P>Numerous small RNAs regulators of gene expression exist in bacteria. A large class of them binds to the RNA chaperone Hfq and act by base pairing interactions with their target mRNA, thereby affecting their translation and/or stability. They often have multiple direct targets, some of which may be regulators themselves, and production of a single sRNA can therefore affect the expression of dozens of genes. We show in this study that the synthesis of the Escherichia coli pleiotropic PhoPQ two-component system is repressed by MicA, a sigma E-dependent sRNA regulator of porin biogenesis. MicA directly pairs with phoPQ mRNA in the translation initiation region of phoP and presumably inhibits translation by competing with ribosome binding. Consequently, MicA downregulates several members of the PhoPQ regulon. By linking PhoPQ to sigma E, our findings suggest that major cellular processes such as Mg2+ transport, virulence, LPS modification or resistance to antimicrobial peptides are modulated in response to envelope stress. In addition, we found that Hfq strongly affects the expression of phoP independently of MicA, raising the possibility that even more sRNAs, which remain to be identified, could regulate PhoPQ synthesis. C1 [Coornaert, Audrey; Springer, Mathias; Guillier, Maude] Univ Paris 07, Inst Biol Physicochim, CNRS, UPR9073, Paris, France. [Lu, Alisa; Mandin, Pierre; Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Guillier, M (reprint author), Univ Paris 07, Inst Biol Physicochim, CNRS, UPR9073, Paris, France. EM maude.guillier@ibpc.fr FU CNRS [UPR 9073]; University of Paris 7- Denis Diderot; NIH; National Cancer Institute; Center for Cancer Research FX We thank E. Gogol and C. Gross for sharing unpublished results. We are grateful to K. Moon for providing strains and communicating unpublished results and to A. Bougdour, K. Thompson and N. Majdalani for sending strains and plasmids. We also thank C. Condon for insightful comments on the manuscript. This work was supported by the CNRS (UPR 9073) and the University of Paris 7- Denis Diderot and, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 48 TC 51 Z9 51 U1 2 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2010 VL 76 IS 2 BP 467 EP 479 DI 10.1111/j.1365-2958.2010.07115.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 583SJ UT WOS:000276699600015 PM 20345657 ER PT J AU Hayashi, T Fujimoto, M AF Hayashi, Teruo Fujimoto, Michiko TI Detergent-Resistant Microdomains Determine the Localization of sigma-1 Receptors to the Endoplasmic Reticulum-Mitochondria Junction SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT-LIVER MEMBRANES; LIPID RAFTS; BINDING-SITES; CA2+; CHOLESTEROL; CELLS; COMPARTMENTALIZATION; METABOLISM; MODULATION; PROTEINS AB sigma-1 receptors (Sig-1Rs) that bind diverse synthetic and endogenous compounds have been implicated in the pathophysiology of several human diseases such as drug addiction, depression, neurodegenerative disorders, pain-related disorders, and cancer. Sig-1Rs were identified recently as novel ligand-operated molecular chaperones. Although Sig-1Rs are predominantly expressed at endoplasmic reticulum (ER) subdomains apposing mitochondria [i.e., the mitochondria-associated ER membrane (MAM)], they dynamically change the cellular distribution, thus regulating both MAM-specific and plasma membrane proteins. However, what determines the location of Sig-1R at the MAM and how the receptor translocation is initiated is unknown. Here we report that the detergent-resistant membranes (DRMs) play an important role in anchoring Sig-1Rs to the MAM. The MAM, which is highly capable of accumulating ceramides, is enriched with both cholesterol and simple sphingolipids, thus forming Triton X-114-resistant DRMs. Sig-1Rs associate with MAM-derived DRMs but not with those from microsomes. A lipid overlay assay found that solubilized Sig-1Rs preferentially associate with simple sphingolipids such as ceramides. Disrupting DRMs by lowering cholesterol or inhibiting de novo synthesis of ceramides at the ER largely decreases Sig-1R at DRMs and causes translocation of Sig-1R from the MAM to ER cisternae. These findings suggest that the MAM, bearing cholesterol and ceramide-enriched microdomains at the ER, may use the microdomains to anchor Sig-1Rs to the location; thus, it serves to stage Sig-1R at ER-mitochondria junctions. C1 [Hayashi, Teruo; Fujimoto, Michiko] NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, IRP,NIH,DHHS, Baltimore, MD 21224 USA. RP Hayashi, T (reprint author), NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, IRP,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM thayashi@mail.nih.gov FU Intramural Research Program; National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services FX This study was supported by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services. NR 40 TC 73 Z9 73 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2010 VL 77 IS 4 BP 517 EP 528 DI 10.1124/mol.109.062539 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 571BZ UT WOS:000275725600003 PM 20053954 ER PT J AU Groth, C Alvord, WG Quinones, OA Fortini, ME AF Groth, Casper Alvord, W. Gregory Quinones, Octavio A. Fortini, Mark E. TI Pharmacological Analysis of Drosophila melanogaster gamma-Secretase with Respect to Differential Proteolysis of Notch and APP SO MOLECULAR PHARMACOLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; C-TERMINAL FRAGMENT; ALZHEIMERS-DISEASE; PRESENILIN; INHIBITOR; CLEAVAGE; GENERATION; EXPRESSION; DISTINCT; COMPLEX AB The gamma-secretase aspartyl protease is responsible for the cleavage of numerous type I integral membrane proteins, including amyloid precursor protein (APP) and Notch. APP cleavage contributes to the generation of toxic amyloid beta peptides in Alzheimer's disease, whereas cleavage of the Notch receptor is required for normal physiological signaling between differentiating cells. Mutagenesis studies as well as in vivo analyses of Notch and APP activity in the presence of pharmacological inhibitors indicate that these substrates can be differentially modulated by inhibition of mammalian gamma-secretase, although some biochemical studies instead show nearly identical dose-response inhibitor effects on Notch and APP cleavages. Here, we examine the dose-response effects of several inhibitors on Notch and APP in Drosophila melanogaster cells, which possess a homogeneous form of gamma-secretase. Four different inhibitors that target different domains of gamma-secretase exhibit similar dose-response effects for both substrates, including rank order of inhibitor potencies and effective concentration ranges. For two inhibitors, modest differences in inhibitor dose responses toward Notch and APP were detected, suggesting that inhibitors might be identified that possess some discrimination in their ability to target alternative gamma-secretase substrates. These findings also indicate that despite an overall conservation in inhibitor potencies toward different gamma-secretase substrates, quantitative differences might exist that could be relevant for the development of therapeutically valuable substrate-specific inhibitors. C1 [Groth, Casper; Fortini, Mark E.] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA. [Alvord, W. Gregory; Quinones, Octavio A.] Data Management Serv Inc, Natl Canc Inst, Frederick, MD USA. RP Fortini, ME (reprint author), Thomas Jefferson Univ, Dept Biochem & Mol Biol, Bluemle Life Sci Bldg 830A,233 S 10th St, Philadelphia, PA 19107 USA. EM mark.fortini@jefferson.edu FU National Institutes of Health National Institute of General Medical Sciences [GM087650]; Data Management Services [HHSN2612008000016C]; Department of Biochemistry and Molecular Biology, Thomas Jefferson University; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by National Institutes of Health National Institute of General Medical Sciences [Grant GM087650]; Data Management Services contract HHSN2612008000016C; the Department of Biochemistry and Molecular Biology, Thomas Jefferson University; and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 47 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2010 VL 77 IS 4 BP 567 EP 574 DI 10.1124/mol.109.062471 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 571BZ UT WOS:000275725600008 PM 20064975 ER PT J AU Rao, JS Harry, GJ Rapoport, SI Kim, HW AF Rao, J. S. Harry, G. J. Rapoport, S. I. Kim, H. W. TI Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar disorder; IL-1beta; NMDA receptors; excitotoxicity; inflammation; postmortem brain ID MESSENGER-RNA LEVELS; CYTOSOLIC PHOSPHOLIPASE A(2); TUMOR-NECROSIS-FACTOR; D-ASPARTATE RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; FIBRILLARY ACIDIC PROTEIN; NITRIC-OXIDE SYNTHASE; ARACHIDONIC-ACID; GENE-EXPRESSION; INTERLEUKIN-1 RECEPTOR AB Reports of cognitive decline, symptom worsening and brain atrophy in bipolar disorder (BD) suggest that the disease progresses over time. The worsening neuropathology may involve excitotoxicity and neuroinflammation. We determined protein and mRNA levels of excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from 10 BD patients and 10 age-matched controls. The brain tissue was matched for age, postmortem interval and pH. The results indicated statistically significant lower protein and mRNA levels of the N-methyl-D-aspartate receptors, NR-1 and NR-3A, but significantly higher protein and mRNA levels of interleukin (IL)-1 beta, the IL-1 receptor (IL-1R), myeloid differentiation factor 88, nuclear factor-kappa B subunits, and astroglial and microglial markers (glial fibrillary acidic protein, inducible nitric oxide synthase, c-fos and CD11b) in postmortem frontal cortex from BD compared with control subjects. There was no significant difference in mRNA levels of tumor necrosis factor alpha or neuronal nitric oxide synthase in the same region. These data show the presence of excitotoxicity and neuroinflammation in BD frontal cortex, with particular activation of the IL-R cascade. The changes may account for reported evidence of disease progression in BD and be a target for future therapy. Molecular Psychiatry (2010) 15, 384-392; doi: 10.1038/mp.2009.47; published online 2 June 2009 C1 [Rao, J. S.; Rapoport, S. I.; Kim, H. W.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Harry, G. J.] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, NIH, Res Triangle Pk, NC USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Buld 9,Room 1S-126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov FU Intramural Research Programs of the National Institute on Aging; National Institute of Environmental Health Sciences, National Institutes of Health Bethesda [MD 20892] FX We thank the Harvard Brain Bank, Boston, MA for providing the postmortem brain samples under PHS grant number R24MH068855. This research was entirely supported by the Intramural Research Programs of the National Institute on Aging and the National Institute of Environmental Health Sciences, National Institutes of Health Bethesda, MD 20892. We thank the National Cancer Institute (NCI) and the Center for Cancer Research (CCR) Fellows Editorial Board for proofreading the manuscript. NR 55 TC 174 Z9 177 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD APR PY 2010 VL 15 IS 4 BP 384 EP 392 DI 10.1038/mp.2009.47 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 573QH UT WOS:000275929100007 PM 19488045 ER PT J AU Morgan, RA Yang, JC Kitano, M Dudley, ME Laurencot, CM Rosenberg, SA AF Morgan, Richard A. Yang, James C. Kitano, Mio Dudley, Mark E. Laurencot, Carolyn M. Rosenberg, Steven A. TI Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2 SO MOLECULAR THERAPY LA English DT Article ID MONOCLONAL-ANTIBODY TGN1412; METASTATIC BREAST-CANCER; PHASE-I TRIAL; CYTOKINE STORM; ADOPTIVE IMMUNOTHERAPY; ORGAN-TRANSPLANTATION; OVEREXPRESSING HER2; GENE AMPLIFICATION; ANTITUMOR-ACTIVITY; ENHANCED SURVIVAL AB In an attempt to treat cancer patients with ERBB2 overexpressing tumors, we developed a chimeric antigen receptor (CAR) based on the widely used humanized monoclonal antibody (mAb) Trastuzumab (Herceptin). An optimized CAR vector containing CD28, 41BB, and CD3 zeta signaling moieties was assembled in a gamma-retroviral vector and used to transduce autologous peripheral blood lymphocytes (PBLs) from a patient with colon cancer metastatic to the lungs and liver, refractory to multiple standard treatments. The gene transfer efficiency into autologous T cells was 79% CAR(+) in CD3(+) cells and these cells demonstrated high-specific reactivity in in vitro coculture assays. Following completion of nonmyeloablative conditioning, the patient received 10(10) cells intravenously. Within 15 minutes after cell infusion the patient experienced respiratory distress, and displayed a dramatic pulmonary infiltrate on chest Xray. She was intubated and despite intensive medical intervention the patient died 5 days after treatment. Serum samples after cell infusion showed marked increases in interferon-gamma (IFN-gamma), granulocyte macrophagecolony stimulating factor (GMCSF), tumor necrosis factora (TNF-alpha), interleukin-6 (IL-6), and IL-10, consistent with a cytokine storm. We speculate that the large number of administered cells localized to the lung immediately following infusion and were triggered to release cytokine by the recognition of low levels of ERBB2 on lung epithelial cells. C1 [Morgan, Richard A.; Yang, James C.; Kitano, Mio; Dudley, Mark E.; Laurencot, Carolyn M.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr,CRC 3W5940, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Center for Cancer Research; National Cancer Institute; National Institutes of Health FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 61 TC 575 Z9 606 U1 17 U2 89 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2010 VL 18 IS 4 BP 843 EP 851 DI 10.1038/mt.2010.24 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 582YH UT WOS:000276636800024 PM 20179677 ER PT J AU Sedelnikova, OA Redon, CE Dickey, JS Nakamura, AJ Georgakilas, AG Bonner, WM AF Sedelnikova, Olga A. Redon, Christophe E. Dickey, Jennifer S. Nakamura, Asako J. Georgakilas, Alexandros G. Bonner, William M. TI Role of oxidatively induced DNA lesions in human pathogenesis SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article; Proceedings Paper CT ESF-EMBO Symposium on Spatio-Temporal Radiation Biology CY MAY 16-21, 2009 CL St Feliu de Guixols, SPAIN SP European Sci Fdn, European Mol Biol Org, Catalunya Reg, CNRS, CEA, European Synchrotron Radiat Facil, Fdn Fourmentin Guilberg, Inst Natl Canc, INSERM, Soc Int Radiobiol Langue Francaise, Synchrotron Soleil, Radiat Biol Melusyn Network DE Reactive oxygen species; DNA damage; DNA double-strand breaks; Aging; Cancer; Bystander effect ID DOUBLE-STRAND BREAKS; BASE EXCISION-REPAIR; IONIZING-RADIATION; GENOMIC INSTABILITY; BYSTANDER CELLS; FREE-RADICALS; SHORTENS TELOMERES; DAMAGE CHECKPOINT; MAMMALIAN-CELLS; TOPOISOMERASE-I AB Genome stability is essential for maintaining cellular and organismal homeostasis, but it is subject to many threats. One ubiquitous threat is from a class of compounds known as reactive oxygen species (ROS), which can indiscriminately react with many cellular biomolecules including proteins, lipids, and DNA to produce a variety of oxidative lesions. These DNA oxidation products are a direct risk to genome stability, and of particular importance are oxidative clustered DNA lesions (OCDLs), defined as two or more oxidative lesions present within 10 bp of each other. ROS can be produced by exposure of cells to exogenous environmental agents including ionizing radiation, light, chemicals, and metals. In addition, they are produced by cellular metabolism including mitochondrial ATP generation. However, ROS also serve a variety of critical cellular functions and optimal ROS levels are maintained by multiple cellular antioxidant defenses. Oxidative DNA lesions can be efficiently repaired by base excision repair or nucleotide excision repair. If ROS levels increase beyond the capacity of its antioxidant defenses, the cell's DNA repair capacity can become overwhelmed, leading to the accumulation of oxidative DNA damage products including OCDLs, which are more difficult to repair than individual isolated DNA damage products. Here we focus on the induction and repair of OCDLs and other oxidatively induced DNA lesions. If unrepaired, these lesions can lead to the formation of mutations, DNA DSBs, and chromosome abnormalities. We discuss the roles of these lesions in human pathologies including aging and cancer, and in bystander effects. Published by Elsevier B.V. C1 [Sedelnikova, Olga A.; Redon, Christophe E.; Dickey, Jennifer S.; Nakamura, Asako J.; Bonner, William M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Georgakilas, Alexandros G.] E Carolina Univ, Thomas Harriot Coll Arts & Sci, Dept Biol, Greenville, NC 27858 USA. RP Sedelnikova, OA (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5050,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sedelnio@mail.nih.gov FU Intramural NIH HHS [ZIA BC006140-34] NR 129 TC 145 Z9 148 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 EI 1388-2139 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD APR-JUN PY 2010 VL 704 IS 1-3 SI SI BP 152 EP 159 DI 10.1016/j.mrrev.2009.12.005 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 609CS UT WOS:000278633300019 PM 20060490 ER PT J AU Chanda, N Kan, P Watkinson, LD Shukla, R Zambre, A Carmack, TL Engelbrecht, H Lever, JR Katti, K Fent, GM Casteel, SW Smith, CJ Miller, WH Jurisson, S Boote, E Robertson, JD Cutler, C Dobrovolskaia, M Kannan, R Katti, KV AF Chanda, Nripen Kan, Para Watkinson, Lisa D. Shukla, Ravi Zambre, Ajit Carmack, Terry L. Engelbrecht, Hendrik Lever, John R. Katti, Kavita Fent, Genevieve M. Casteel, Stan W. Smith, C. Jeffrey Miller, William H. Jurisson, Silvia Boote, Evan Robertson, J. David Cutler, Cathy Dobrovolskaia, Marina Kannan, Raghuraman Katti, Kattesh V. TI Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy studies of GA-(AuNP)-Au-198 nanoconstruct in prostate tumor-bearing mice SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Radioactive gold nanoparticles; Prostate tumor; Therapeutics; Tumor vasculature; Intratumoral ID PLGA-PEG NANOPARTICLES; DRUG-DELIVERY; RADIATION-THERAPY; IN-VITRO; NANOTECHNOLOGY; BRACHYTHERAPY; STABILIZATION; RADIOTHERAPY; FABRICATION; MORTALITY AB Biocompatibility studies and cancer therapeutic applications of nanoparticulate beta-emitting gold-198 (Au-198; beta(max) = 0.96 MeV; half-life of 2.7 days) are described. Gum arabic glycoprotein (GA)-functionalized gold nanoparticles (AuNPs) possess optimum sizes (12-18 nm core diameter and 85 nm hydrodynamic diameter) to target individual tumor cells and penetrate through tumor vasculature and pores. We report the results of detailed in vivo therapeutic investigations demonstrating the high tumor affinity of GA-(198)AuNPs in severely compromised immunodeficient (SCID) mice bearing human prostate tumor xenografts. Intratumoral administration of a single dose of beta-emitting GA-(198)AuNPs (70 Gy) resulted in clinically significant tumor regression and effective control in the growth of prostate tumors over 30 days. Three weeks after administration of GA-(198)AuNPs, tumor volumes for the treated animals were 82% smaller as compared with tumor volume of control group. The treatment group showed only transitory weight loss in sharp contrast to the tumor-bearing control group, which underwent substantial weight loss. Pharmacokinetic studies have provided unequivocal evidence for the optimum retention of therapeutic payload of GA-(198)AuNPs within the tumor site throughout the treatment regimen with minimal or no leakage of radioactivity to various nontarget organs. The measurements of white and red blood cells, platelets, and lymphocytes within the treatment group resembled those of the normal SCID mice, thus providing further evidence on the therapeutic efficacy and concomitant in vivo tolerance and nontoxic features of GA-(198)AuNPs. From the Clinical Editor: In this study, the biocompatibility and cancer therapeutic applications of glycoprotein (GA) functionalized gold nanoparticles containing b-emitting Au-198 are described in SCID mice bearing human prostate tumor xenografts. The findings of significant therapeutic efficacy, good in vivo tolerance and non-toxic features make these particles ideal candidates for future human applications. (C) 2010 Published by Elsevier Inc. C1 [Chanda, Nripen; Shukla, Ravi; Zambre, Ajit; Katti, Kavita; Smith, C. Jeffrey; Boote, Evan; Kannan, Raghuraman; Katti, Kattesh V.] Univ Missouri, Dept Radiol, Columbia, MO 65211 USA. [Kan, Para; Jurisson, Silvia; Robertson, J. David; Cutler, Cathy] Univ Missouri, Dept Chem, Columbia, MO 65211 USA. [Watkinson, Lisa D.; Carmack, Terry L.; Lever, John R.; Fent, Genevieve M.; Casteel, Stan W.; Smith, C. Jeffrey] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA. [Watkinson, Lisa D.; Carmack, Terry L.; Lever, John R.; Fent, Genevieve M.; Casteel, Stan W.; Smith, C. Jeffrey] Univ Missouri, Dept Vet Med, Columbia, MO 65211 USA. [Watkinson, Lisa D.; Carmack, Terry L.; Lever, John R.; Fent, Genevieve M.; Casteel, Stan W.; Smith, C. Jeffrey] Univ Missouri, Harry S Truman Vet Adm Med Ctr, Columbia, MO 65211 USA. [Engelbrecht, Hendrik; Smith, C. Jeffrey; Miller, William H.; Robertson, J. David; Cutler, Cathy; Katti, Kattesh V.] Univ Missouri, Missouri Univ Res Reactor, Columbia, MO 65211 USA. [Jurisson, Silvia; Robertson, J. David; Cutler, Cathy] Univ Missouri, Nucl Sci & Engn Inst, Columbia, MO 65211 USA. [Jurisson, Silvia; Robertson, J. David; Cutler, Cathy] Univ Missouri, Dept Nucl Engn, Columbia, MO 65211 USA. [Dobrovolskaia, Marina] NCI, Nanotechnol Characterizat Lab, SAIC Frederick, Frederick, MD 21701 USA. [Kannan, Raghuraman; Katti, Kattesh V.] Nanoparticle Biochem Inc, Columbia, MO USA. RP Kannan, R (reprint author), Univ Missouri, Dept Radiol, Columbia, MO 65211 USA. EM kannanr@health.missouri.edu; kattik@health.missouri.edu RI Nanotechnology Characterization Lab, NCL/K-8454-2012; OI Shukla, Ravi/0000-0002-1537-9637 FU National Institutes of Health-National Cancer Institute [5R01CA119412-01, NIH-1R21CA128460-01]; NIH-SBIR [241]; University of Missouri [C8761 RB 06-030] FX This research was supported by grants from the National Institutes of Health-National Cancer Institute under the Cancer Nanotechnology Platform Program: 5R01CA119412-01, NIH-1R21CA128460-01, NIH-SBIR-Contract No. 241, and University of Missouri Research Board Program: C8761 RB 06-030. NR 51 TC 77 Z9 77 U1 7 U2 41 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD APR PY 2010 VL 6 IS 2 BP 201 EP 209 DI 10.1016/j.nano.2009.11.001 PG 9 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 575TG UT WOS:000276090600001 PM 19914401 ER PT J AU Collins, F AF Collins, Francis TI Has the revolution arrived? SO NATURE LA English DT Editorial Material C1 [Collins, Francis] NIH, Bethesda, MD 20892 USA. [Collins, Francis] NHGRI, Bethesda, MD USA. RP Collins, F (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM francis.collins@nih.gov NR 0 TC 145 Z9 150 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 1 PY 2010 VL 464 IS 7289 BP 674 EP 675 DI 10.1038/464674a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 577EO UT WOS:000276205000018 PM 20360716 ER PT J AU Bhattaram, P Penzo-Mendez, A Sock, E Colmenares, C Kaneko, KJ Vassilev, A DePamphilis, ML Wegner, M Lefebvre, V AF Bhattaram, Pallavi Penzo-Mendez, Alfredo Sock, Elisabeth Colmenares, Clemencia Kaneko, Kotaro J. Vassilev, Alex DePamphilis, Melvin L. Wegner, Michael Lefebvre, Veronique TI Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors SO NATURE COMMUNICATIONS LA English DT Article ID EMBRYONIC STEM-CELLS; CRE RECOMBINASE; DIFFERENTIAL EXPRESSION; BONE-FORMATION; GENE; MICE; CANCER; INDUCTION; ENHANCER; ROLES AB During organogenesis, neural and mesenchymal progenitor cells give rise to many cell lineages, but their molecular requirements for self-renewal and lineage decisions are incompletely understood. In this study, we show that their survival critically relies on the redundantly acting SoxC transcription factors Sox4, Sox11 and Sox12. The more SoxC alleles that are deleted in mouse embryos, the more severe and widespread organ hypoplasia is. SoxC triple-null embryos die at midgestation unturned and tiny, with normal patterning and lineage specification, but with massively dying neural and mesenchymal progenitor cells. Specific inactivation of SoxC genes in neural and mesenchymal cells leads to selective apoptosis of these cells, suggesting SoxC cell-autonomous roles. Tead2 functionally interacts with SoxC genes in embryonic development, and is a direct target of SoxC proteins. SoxC genes therefore ensure neural and mesenchymal progenitor cell survival, and function in part by activating this transcriptional mediator of the Hippo signalling pathway. C1 [Sock, Elisabeth; Wegner, Michael] Univ Erlangen Nurnberg, Emil Fischer Zentrum, Inst Biochem, D-91054 Erlangen, Germany. [Bhattaram, Pallavi; Penzo-Mendez, Alfredo; Lefebvre, Veronique] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. [Bhattaram, Pallavi; Penzo-Mendez, Alfredo; Lefebvre, Veronique] Cleveland Clin, Lerner Res Inst, Orthopaed & Rheumatol Res Ctr, Cleveland, OH 44195 USA. [Colmenares, Clemencia] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. [Kaneko, Kotaro J.; Vassilev, Alex; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Wegner, M (reprint author), Univ Erlangen Nurnberg, Emil Fischer Zentrum, Inst Biochem, D-91054 Erlangen, Germany. EM m.wegner@biochem.uni-erlangen.de; lefebvv@ccf.org OI Wegner, Michael/0000-0002-4586-3294 FU NIH [AR54153]; DFG [SO251/3-1]; Arthritis Foundation FX We thank H. Wang, P. Dy and A. Silvester for expert technical assistance; J. Jensen, T. Sakai, J.A. Drazba, P.W. Faber and C. Shemo for scientific and technical advice; R. Conlon, J. Martin Y. Mishina and H. Sasaki for in situ probes; and D. Driscoll, Y. Mishina, O. Reizes and A. Zhu for advice on the paper. This work was funded by NIH Grant AR54153 to V.L., DFG Grant SO251/3-1 to E.S. and an Arthritis Foundation postdoctoral fellowship to A.P.-M. NR 58 TC 72 Z9 72 U1 0 U2 3 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 APR PY 2010 VL 1 AR 9 DI 10.1038/ncomms1008 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649OJ UT WOS:000281781400009 PM 20596238 ER PT J AU Sung, HJ Ma, WZ Wang, PY Hynes, J O'Riordan, TC Combs, CA Mccoy, JP Bunz, F Kang, JG Hwang, PM AF Sung, Ho Joong Ma, Wenzhe Wang, Ping-yuan Hynes, James O'Riordan, Tomas C. Combs, Christian A. McCoy, J. Philip, Jr. Bunz, Fred Kang, Ju-Gyeong Hwang, Paul M. TI Mitochondrial respiration protects against oxygen-associated DNA damage SO NATURE COMMUNICATIONS LA English DT Article ID P53 TUMOR-SUPPRESSOR; RIBONUCLEOTIDE REDUCTASE; SPECIES GENERATION; COLORECTAL-CANCER; CELLS; PATHWAY; TENSION; MAINTENANCE; PGC-1-ALPHA; SENSITIVITY AB Oxygen is not only required for oxidative phosphorylation but also serves as the essential substrate for the formation of reactive oxygen species (ROS), which is implicated in ageing and tumorigenesis. Although the mitochondrion is known for its bioenergetic function, the symbiotic theory originally proposed that it provided protection against the toxicity of increasing oxygen in the primordial atmosphere. Using human cells lacking Synthesis of Cytochrome c Oxidase 2 (SCO2-/-), we have tested the oxygen toxicity hypothesis. These cells are oxidative phosphorylation defective and glycolysis dependent; they exhibit increased viability under hypoxia and feature an inverted growth response to oxygen compared with wild-type cells. SCO2-/- cells have increased intracellular oxygen and nicotinamide adenine dinucleotide (NADH) levels, which result in increased ROS and oxidative DNA damage. Using this isogenic cell line, we have revealed the genotoxicity of ambient oxygen. Our study highlights the importance of mitochondrial respiration both for bioenergetic benefits and for maintaining genomic stability in an oxygen-rich environment. C1 [Sung, Ho Joong; Ma, Wenzhe; Wang, Ping-yuan; Combs, Christian A.; McCoy, J. Philip, Jr.; Kang, Ju-Gyeong; Hwang, Paul M.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Hynes, James; O'Riordan, Tomas C.] Univ Coll Cork, Luxcel Biosci Ltd, Cork, Ireland. [Bunz, Fred] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21231 USA. RP Hwang, PM (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH FX We thank C. Lago, T. Matsumoto, J.Y. Park, S. Matoba, L. Samsel and A. Williams of the NHLBI FACS core facility, and I. Rovira, L. Cao, H. Liu and Z. Lu for advice and technical support. We thank Eric A. Schon for the rho degrees cells. We are grateful to Toren Finkel for helpful suggestions and critical reading of this paper. This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH. NR 48 TC 44 Z9 46 U1 1 U2 17 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 APR PY 2010 VL 1 AR 5 DI 10.1038/ncomms1003 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649OJ UT WOS:000281781400005 PM 20975668 ER PT J AU Cullinane, AR Straatman-Iwanowska, A Zaucker, A Wakabayashi, Y Bruce, CK Luo, GM Rahman, F Gurakan, F Utine, E Ozkan, TB Denecke, J Vukovic, J Di Rocco, M Mandel, H Cangul, H Matthews, RP Thomas, SG Rappoport, JZ Arias, IM Wolburg, H Knisely, AS Kelly, DA Muller, F Maher, ER Gissen, P AF Cullinane, Andrew R. Straatman-Iwanowska, Anna Zaucker, Andreas Wakabayashi, Yoshiyuki Bruce, Christopher K. Luo, Guanmei Rahman, Fatimah Gurakan, Figen Utine, Eda Ozkan, Tanju B. Denecke, Jonas Vukovic, Jurica Di Rocco, Maja Mandel, Hanna Cangul, Hakan Matthews, Randolph P. Thomas, Steve G. Rappoport, Joshua Z. Arias, Irwin M. Wolburg, Hartwig Knisely, A. S. Kelly, Deirdre A. Mueller, Ferenc Maher, Eamonn R. Gissen, Paul TI Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization SO NATURE GENETICS LA English DT Article ID ARC SYNDROME; RECYCLING ENDOSOMES; CARCINOEMBRYONIC ANTIGEN; PLASMA-MEMBRANE; TIGHT JUNCTIONS; E-CADHERIN; INTRACELLULAR TRAFFICKING; VACUOLE FUSION; MYOSIN VB; CELLS AB Arthrogryposis, renal dysfunction and cholestasis syndrome (ARC) is a multisystem disorder associated with abnormalities in polarized liver and kidney cells. Mutations in VPS33B account for most cases of ARC. We identified mutations in VIPAR (also called C14ORF133) in individuals with ARC without VPS33B defects. We show that VIPAR forms a functional complex with VPS33B that interacts with RAB11A. Knockdown of vipar in zebrafish resulted in biliary excretion and E-cadherin defects similar to those in individuals with ARC. Vipar-and Vps33b-deficient mouse inner medullary collecting duct (mIMDC-3) cells expressed membrane proteins abnormally and had structural and functional tight junction defects. Abnormal Ceacam5 expression was due to mis-sorting toward lysosomal degradation, but reduced E-cadherin levels were associated with transcriptional downregulation. The VPS33B-VIPAR complex thus has diverse functions in the pathways regulating apical-basolateral polarity in the liver and kidney. C1 [Cullinane, Andrew R.; Straatman-Iwanowska, Anna; Zaucker, Andreas; Bruce, Christopher K.; Luo, Guanmei; Rahman, Fatimah; Cangul, Hakan; Mueller, Ferenc; Maher, Eamonn R.; Gissen, Paul] Univ Birmingham, Sch Clin & Expt Med, Birmingham, W Midlands, England. [Wakabayashi, Yoshiyuki; Arias, Irwin M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, US Natl Inst Hlth, Bethesda, MD USA. [Gurakan, Figen] Hacettepe Univ, Dept Pediat Gastroenterol Hepatol & Nutr, Ankara, Turkey. [Utine, Eda] Hacettepe Univ, Dept Pediat, Clin Genet Unit, Ankara, Turkey. [Ozkan, Tanju B.] Uludag Univ, Sch Med, Dept Pediat Gastroenterol Hepatol & Nutr, Bursa, Turkey. [Denecke, Jonas] Univ Hosp Rostock, Dept Pediat, Rostock, Germany. [Vukovic, Jurica] Univ Zagreb, Univ Hosp Rebro, Dept Pediat, Zagreb, Croatia. [Di Rocco, Maja] Gaslini Inst, Pediat Unit 2, Genoa, Italy. [Mandel, Hanna] Technion Israel Inst Technol, Rambam Med Ctr, Metabol Unit, Meyer Childrens Hosp,Fac Med, Haifa, Israel. [Cangul, Hakan] Uludag Univ, Dept Med Genet, Sch Med, Bursa, Turkey. [Matthews, Randolph P.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Gastroenterol Hepatol & Nutr,Dept Pediat, Philadelphia, PA 19104 USA. [Thomas, Steve G.] Univ Birmingham, Birmingham Platelet Grp, Sch Clin & Expt Med, Birmingham, W Midlands, England. [Rappoport, Joshua Z.] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. [Wolburg, Hartwig] Univ Tubingen, Inst Pathol, D-7400 Tubingen, Germany. [Knisely, A. S.] Kings Coll Hosp London, Inst Liver Studies, London SE5 8RX, England. [Kelly, Deirdre A.] Birmingham Childrens Hosp, Liver Unit, Birmingham, W Midlands, England. [Maher, Eamonn R.] Birmingham Womens Hosp, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Gissen, Paul] Birmingham Childrens Hosp, Inherited Metab Dis Unit, Birmingham, W Midlands, England. RP Gissen, P (reprint author), Univ Birmingham, Sch Clin & Expt Med, Birmingham, W Midlands, England. EM p.gissen@bham.ac.uk RI Gissen, Paul/A-4352-2010; Vukovic, Jurica/B-3717-2013; MAHER, EAMONN/A-9507-2008; Muller, Ferenc/C-6426-2009 OI Gissen, Paul/0000-0002-9712-6122; Vukovic, Jurica/0000-0001-8675-9170; MAHER, EAMONN/0000-0002-6226-6918; FU Children Liver Disease Foundation; Framework 6 IP EUTRACC [LSGH CT 2006037445]; European Molecular Biology Organization [ASTF 121:2007]; European Science Foundation [2008]; Biotechnology and Biosciences Research Council [BB/H002308/1]; ARC syndrome association; Children Living with Inherited Metabolic Diseases (CLIMB); Birmingham Children's Hospital Research Foundation (BCHRF); WellChild; Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health FX A. R. C. holds the Children Liver Disease Foundation PhD Studentship and P. G. is a GlaxoSmithKline Clinician Scientist. A.Z. and F. M. are supported by Framework 6 IP EUTRACC, LSGH CT 2006037445. H. C. is supported by grants from the European Molecular Biology Organization (ASTF 121:2007) and European Science Foundation (Exchange Grant 2008). J.Z.R. is supported by the Biotechnology and Biosciences Research Council (BB/H002308/1). Thanks to F. Lock for her help with the E-cadherin luciferase assay, G. Reynolds for help with E-cadherin immunostaining and R. Knittel for her help with freeze fracture experiments. The authors also wish to thank all the families and clinicians who contributed to this research and thank the ARC syndrome association; Children Living with Inherited Metabolic Diseases (CLIMB); Birmingham Children's Hospital Research Foundation (BCHRF); WellChild; the Wellcome Trust; and the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health, for their generous financial support. NR 79 TC 62 Z9 73 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2010 VL 42 IS 4 BP 303 EP U55 DI 10.1038/ng.538 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 576NE UT WOS:000276150500009 PM 20190753 ER PT J AU McGovern, DPB Gardet, A Torkvist, L Goyette, P Essers, J Taylor, KD Neale, BM Ong, RTH Lagace, C Li, C Green, T Stevens, CR Beauchamp, C Fleshner, PR Carlson, M D'Amato, M Halfvarson, J Hibberd, ML Lordal, M Padyukov, L Andriulli, A Colombo, E Latiano, A Palmieri, O Bernard, EJ Deslandres, C Hommes, DW de Jong, DJ Stokkers, PC Weersma, RK Sharma, Y Silverberg, MS Cho, JH Wu, J Roeder, K Brant, SR Schumm, LP Duerr, RH Dubinsky, MC Glazer, NL Haritunians, T Ippoliti, A Melmed, GY Siscovick, DS Vasiliauskas, EA Targan, SR Annese, V Wijmenga, C Pettersson, S Rotter, JI Xavier, RJ Daly, MJ Rioux, JD Seielstad, M AF McGovern, Dermot P. B. Gardet, Agnes Torkvist, Leif Goyette, Philippe Essers, Jonah Taylor, Kent D. Neale, Benjamin M. Ong, Rick T. H. Lagace, Caroline Li, Chun Green, Todd Stevens, Christine R. Beauchamp, Claudine Fleshner, Phillip R. Carlson, Marie D'Amato, Mauro Halfvarson, Jonas Hibberd, Martin L. Lordal, Mikael Padyukov, Leonid Andriulli, Angelo Colombo, Elisabetta Latiano, Anna Palmieri, Orazio Bernard, Edmond-Jean Deslandres, Colette Hommes, Daan W. de Jong, Dirk J. Stokkers, Pieter C. Weersma, Rinse K. Sharma, Yashoda Silverberg, Mark S. Cho, Judy H. Wu, Jing Roeder, Kathryn Brant, Steven R. Schumm, L. Phillip Duerr, Richard H. Dubinsky, Marla C. Glazer, Nicole L. Haritunians, Talin Ippoliti, Andy Melmed, Gil Y. Siscovick, David S. Vasiliauskas, Eric A. Targan, Stephan R. Annese, Vito Wijmenga, Cisca Pettersson, Sven Rotter, Jerome I. Xavier, Ramnik J. Daly, Mark J. Rioux, John D. Seielstad, Mark CA NIDDK IBD Genetics Consortium TI Genome-wide association identifies multiple ulcerative colitis susceptibility loci SO NATURE GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; RETICULUM STRESS-RESPONSE; CROHNS-DISEASE; GENETIC-VARIANTS; RISK; POPULATION; CONTRIBUTE; IMMUNITY AB Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan(1), comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5). Seven of these loci exceeded genome-wide significance (P < 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis. C1 [McGovern, Dermot P. B.; Fleshner, Phillip R.; Dubinsky, Marla C.; Ippoliti, Andy; Melmed, Gil Y.; Vasiliauskas, Eric A.; Targan, Stephan R.] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Gardet, Agnes; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Gardet, Agnes; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [Torkvist, Leif] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Torkvist, Leif; Lordal, Mikael] Karolinska Univ Hosp, IBD Clin Res Grp, Stockholm, Sweden. [Goyette, Philippe; Lagace, Caroline; Beauchamp, Claudine; Rioux, John D.] Univ Montreal, Montreal, PQ, Canada. [Goyette, Philippe; Lagace, Caroline; Beauchamp, Claudine; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Essers, Jonah; Neale, Benjamin M.; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Taylor, Kent D.; Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Ong, Rick T. H.; Seielstad, Mark] Genome Inst Singapore, Singapore, Singapore. [Green, Todd; Stevens, Christine R.; Xavier, Ramnik J.; Daly, Mark J.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Carlson, Marie] Univ Uppsala Hosp, Dept Med Sci, Gastroenterol Res Grp, Uppsala, Sweden. [D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden. [Halfvarson, Jonas] Orebro Univ Hosp, Dept Internal Med, Div Gastroenterol, Orebro, Sweden. [Hibberd, Martin L.] Genome Inst Singapore, Singapore, Singapore. [Lordal, Mikael] Karolinska Univ Hosp, Dept Med, Stockholm, Sweden. [Padyukov, Leonid] Karolinska Univ Hosp Solna, Rheumatol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden. [Andriulli, Angelo; Colombo, Elisabetta; Latiano, Anna; Palmieri, Orazio; Annese, Vito] Osped Casa Sollievo Sofferenza, Ist Ricovero & Cura Carattere Sci, San Giovanni Rotondo, Italy. [Bernard, Edmond-Jean] Univ Montreal, Ctr Hosp Univ, Montreal, PQ, Canada. [Deslandres, Colette] Hop St Justine, Dept Gastroenterol, Montreal, PQ H3T 1C5, Canada. [Hommes, Daan W.] Leiden Univ, Dept Gastroenterol & Hepatol, Med Ctr, Leiden, Netherlands. [de Jong, Dirk J.] Radboud Univ Nijmegen, Dept Gastroenterol & Hepatol, NL-6525 ED Nijmegen, Netherlands. [Stokkers, Pieter C.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Weersma, Rinse K.] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands. [NIDDK IBD Genetics Consortium] Yale Univ, NIDDK, New Haven, CT USA. [Sharma, Yashoda; Cho, Judy H.] Yale Univ, Dept Med, Sect Digest Dis, New Haven, CT 06520 USA. [Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada. [Cho, Judy H.] Yale Univ, Dept Genet, New Haven, CT USA. [Wu, Jing] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Roeder, Kathryn; Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Roeder, Kathryn; Brant, Steven R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Schumm, L. Phillip] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Glazer, Nicole L.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Glazer, Nicole L.; Siscovick, David S.] Univ Washington, Dept Gen Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Pettersson, Sven] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Pettersson, Sven] Singapore Gen Hosp, Lab Inflammat Biol, Singapore 0316, Singapore. [Seielstad, Mark] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP McGovern, DPB (reprint author), Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. EM mcgovernd@cshs.org; john.david.rioux@umontreal.ca; mark.seielstad@ucsf.edu RI D'Amato, Mauro/F-2450-2010; Hibberd, Martin/D-5050-2009; Silverberg, Mark/B-4183-2008; Wijmenga, Cisca/D-2173-2009; Rioux, John/A-9599-2015; Jong, D.J./L-4417-2015; Palmieri, Orazio/J-7697-2012; Latiano, Anna/R-1965-2016; Andriulli, Angelo/B-5027-2017; OI Wijmenga, Cisca/0000-0002-5635-1614; D'Amato, Mauro/0000-0003-2743-5197; Rioux, John/0000-0001-7560-8326; Palmieri, Orazio/0000-0002-0019-7929; Latiano, Anna/0000-0003-3719-2061; Andriulli, Angelo/0000-0001-8862-7083; Seielstad, Mark/0000-0001-5783-1401; Duerr, Richard/0000-0001-6586-3905; Hibberd, Martin/0000-0001-8587-1849; Halfvarson, Jonas/0000-0003-0122-7234; Padyukov, Leonid/0000-0003-2950-5670 FU US National Center for Research Resources (NCRR) [M01-RR00425]; US National Institutes of Health/NIDDK [P01-DK046763, DK83756, DK086502, DK043351, DK062431, DK062422, DK062420, DK062432, DK062423, DK062413, DK062429]; Diabetes Endocrinology Research Center [DK063491]; Cedars-Sinai Medical Center; US National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652]; US National Institute of Neurological Disorders and Stroke; Crohn's and Colitis Foundation of America; Bohmfalk Funds for Medical Research; Burroughs Wellcome Medical Foundation; US National Institute of Allergy and Infectious Diseases [AI065687, AI067152]; US National Institute of Diabetes and Digestive and Kidney Diseases [DK064869]; Swedish Society of Medicine; Bengt Ihre Foundation; Karolinska Institutet; Swedish National Program for IBD Genetics; Swedish Organization for IBD; Swedish Medical Research Council; Soderbergh Foundation; Swedish Cancer Foundation; [DK76984]; [DK084554] FX This study was supported in part by US National Center for Research Resources (NCRR) grant M01-RR00425 to the Cedars-Sinai General Research Center Genotyping core; US National Institutes of Health/NIDDK grant P01-DK046763; Diabetes Endocrinology Research Center grant DK063491; Cedars-Sinai Medical Center Inflammatory Bowel Disease Research Funds. Additional funding was provided by grants DK76984 (M. C. D.) and DK084554 (M. C. D. and D. P. B. M.). Cardiovascular Health Study research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150 and N01-HC-45133; grant numbers U01 HL080295 and R01 HL087652 from the US National Heart, Lung, and Blood Institute; and additional contribution from the US National Institute of Neurological Disorders and Stroke. A full list of principal Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. A. G. is supported by the Crohn's and Colitis Foundation of America. R.J.X. and M.J.D. are supported by grants DK83756, DK086502 and DK043351 (NIDDK).; The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (S. R. B.), DK062422 (J.H.C.), DK062420 (R. H. D.), DK062432 (J.D.R.), DK062423 (M. S. S.), DK062413 (D. P. B. M.) and DK062429 (J.H.C.). J.H.C. is also funded by Bohmfalk Funds for Medical Research, Burroughs Wellcome Medical Foundation and the Crohn's and Colitis Foundation of America. J.D.R. is also funded by grants from the US National Institute of Allergy and Infectious Diseases (AI065687; AI067152) and from the US National Institute of Diabetes and Digestive and Kidney Diseases (DK064869).; Activities in Sweden were supported by the Swedish Society of Medicine, the Bengt Ihre Foundation, the Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, the Swedish Medical Research Council, the Soderbergh Foundation and the Swedish Cancer Foundation. Support for genotyping and genetic data analysis was provided by the Singapore National Cancer Centre, Singapore General Hospital and the Singapore Millennium Foundation (to S. P.) and the Agency for Science Technology and Research (A*STAR), Singapore (to M. L. H. and M. S.). Genotyping and DNA handling at the Genome Institute of Singapore were performed by W.Y. Meah, K. K. Heng, H. B. Toh, X. Lin, S. Rajaram, D. Tan and C. H. Wong. We are grateful to the funders and investigators of the Epidemiological Investigation of Rheumatoid Arthritis for providing genotype data from healthy Swedish individuals. NR 27 TC 320 Z9 328 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2010 VL 42 IS 4 BP 332 EP U88 DI 10.1038/ng.549 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 576NE UT WOS:000276150500013 PM 20228799 ER PT J AU He, HSHS Meyer, CA Shin, HJ Bailey, ST Wei, G Wang, QB Zhang, Y Xu, KX Ni, M Lupien, M Mieczkowski, P Lieb, JD Zhao, KJ Brown, M Liu, XS AF He, Housheng Hansen Meyer, Clifford A. Shin, Hyunjin Bailey, Shannon T. Wei, Gang Wang, Qianben Zhang, Yong Xu, Kexin Ni, Min Lupien, Mathieu Mieczkowski, Piotr Lieb, Jason D. Zhao, Keji Brown, Myles Liu, X. Shirley TI Nucleosome dynamics define transcriptional enhancers SO NATURE GENETICS LA English DT Article ID ANDROGEN RECEPTOR; PROSTATE-CANCER; HIGH-RESOLUTION; HUMAN GENOME; CHROMATIN-STRUCTURE; CHIP-SEQ; PROMOTERS; GENE; NKX3.1; MODEL AB Chromatin plays a central role in eukaryotic gene regulation. We performed genome-wide mapping of epigenetically marked nucleosomes to determine their position both near transcription start sites and at distal regulatory elements, including enhancers. In prostate cancer cells, where androgen receptor binds primarily to enhancers, we found that androgen treatment dismisses a central nucleosome present at androgen receptor binding sites that is flanked by a pair of marked nucleosomes. A new quantitative model built on the behavior of such nucleosome pairs correctly identified regions bound by the regulators of the immediate androgen response, including androgen receptor and FOXA1. More importantly, this model also correctly predicted previously unidentified binding sites for other transcription factors present after prolonged androgen stimulation, including OCT1 and NKX3-1. Therefore, quantitative modeling of enhancer structure provides a powerful predictive method to infer the identity of transcription factors involved in cellular responses to specific stimuli. C1 [He, Housheng Hansen; Meyer, Clifford A.; Shin, Hyunjin; Zhang, Yong; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Housheng Hansen; Meyer, Clifford A.; Shin, Hyunjin; Zhang, Yong; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [He, Housheng Hansen; Bailey, Shannon T.; Wang, Qianben; Xu, Kexin; Ni, Min; Lupien, Mathieu; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, Housheng Hansen; Bailey, Shannon T.; Wang, Qianben; Xu, Kexin; Ni, Min; Lupien, Mathieu; Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. [Wei, Gang; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Mieczkowski, Piotr; Lieb, Jason D.] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Mieczkowski, Piotr; Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Wei, Gang/A-3291-2011; Zhang, Yong/B-4838-2011; He, Housheng/G-9614-2011; Wang, Qianben/E-4267-2011; Bailey, Shannon/B-8045-2014; OI Zhang, Yong/0000-0001-6316-2734; Brown, Myles/0000-0002-8213-1658 FU US National Institutes of Health [1R01 HG004069-02, 2P50 CA090381-06]; Department of Defense [W81XWH-07-1-0037]; Prostate Cancer Foundation FX This work was supported by grants from US National Institutes of Health (1R01 HG004069-02 to X. S. L., and 2P50 CA090381-06 to X. S. L. and M. B.), the Department of Defense (W81XWH-07-1-0037 to X. S. L.) and the Prostate Cancer Foundation (to M. B.). NR 32 TC 250 Z9 253 U1 6 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2010 VL 42 IS 4 BP 343 EP U101 DI 10.1038/ng.545 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 576NE UT WOS:000276150500015 PM 20208536 ER PT J AU Said, EA Dupuy, FP Trautmann, L Zhang, YW Shi, Y El-Far, M Hill, BJ Noto, A Ancuta, P Peretz, Y Fonseca, SG Van Grevenynghe, J Boulassel, MR Bruneau, J Shoukry, NH Routy, JP Douek, DC Haddad, EK Sekaly, RP AF Said, Elias A. Dupuy, Franck P. Trautmann, Lydie Zhang, Yuwei Shi, Yu El-Far, Mohamed Hill, Brenna J. Noto, Alessandra Ancuta, Petronela Peretz, Yoav Fonseca, Simone G. Van Grevenynghe, Julien Boulassel, Mohamed R. Bruneau, Julie Shoukry, Naglaa H. Routy, Jean-Pierre Douek, Daniel C. Haddad, Elias K. Sekaly, Rafick-Pierre TI Programmed death-1-induced interleukin-10 production by monocytes impairs CD4(+) T cell activation during HIV infection SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC VIRAL-INFECTION; SERUM IL-10 LEVELS; DISEASE PROGRESSION; PD-1 EXPRESSION; DENDRITIC CELLS; ANTIRETROVIRAL THERAPY; CYTOKINE SIGNALING-3; IMMUNE ACTIVATION; HUMAN MACROPHAGES AB Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4(+) T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4(+) T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1. C1 [Said, Elias A.; Dupuy, Franck P.; Trautmann, Lydie; Zhang, Yuwei; Shi, Yu; El-Far, Mohamed; Noto, Alessandra; Ancuta, Petronela; Peretz, Yoav; Fonseca, Simone G.; Van Grevenynghe, Julien; Bruneau, Julie; Shoukry, Naglaa H.; Haddad, Elias K.; Sekaly, Rafick-Pierre] CRCHUM, Hop St Luc, Montreal, PQ, Canada. [Said, Elias A.; Dupuy, Franck P.; Trautmann, Lydie; Zhang, Yuwei; Shi, Yu; El-Far, Mohamed; Noto, Alessandra; Ancuta, Petronela; Peretz, Yoav; Fonseca, Simone G.; Van Grevenynghe, Julien; Haddad, Elias K.; Sekaly, Rafick-Pierre] Univ Montreal, Dept Microbiol & Immunol, Immunol Lab, Montreal, PQ H3C 3J7, Canada. [Said, Elias A.; Dupuy, Franck P.; Trautmann, Lydie; Zhang, Yuwei; Shi, Yu; El-Far, Mohamed; Noto, Alessandra; Ancuta, Petronela; Peretz, Yoav; Fonseca, Simone G.; Van Grevenynghe, Julien; Routy, Jean-Pierre; Haddad, Elias K.; Sekaly, Rafick-Pierre] Univ Montreal, CRCHUM, Inst Nat Sante & Rech Med, U743, Montreal, PQ H3C 3J7, Canada. [Trautmann, Lydie; Sekaly, Rafick-Pierre] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Boulassel, Mohamed R.; Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Immunodeficiency Serv & Div Hematol, Montreal, PQ, Canada. [Bruneau, Julie] Univ Montreal, Dept Med Familiale, Montreal, PQ, Canada. [Shoukry, Naglaa H.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Haddad, Elias K.; Sekaly, Rafick-Pierre] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. RP Sekaly, RP (reprint author), CRCHUM, Hop St Luc, Montreal, PQ, Canada. EM Rafick-pierre.sekaly@umontreal.ca OI Said, Elias/0000-0003-4224-6351 FU Canadian Institutes of Health Research (CIHR); Canadian Foundation for Infectious Diseases; Fonds de la recherche en sante du Quebec; US National Institutes of Health; Canadian Foundation for AIDS Research; Canadian Network for Vaccines and Immunotherapeutics FX We thank the subjects for their participation in this study. We also thank M. Legault and C. Grignon for their clinical assistance with the recruitment of study subjects. We are grateful to V. A. Evans and J. D. Schatzle for help in manuscript revision. E. A. S., L. T., M. E.-F. and J. V. G. are funded by the Canadian Institutes of Health Research (CIHR). N. H. S. holds a joint New Investigator Award from the Canadian Foundation for Infectious Diseases and CIHR. J. B. and J.-P. R. are clinician-scientists supported by Fonds de la recherche en sante du Quebec. R.-P. S. is the Canada Research Chair in Human Immunology. This study was supported by funds from the US National Institutes of Health, the CIHR, the Canadian Foundation for AIDS Research, the Fonds de la recherche en sante du Quebec AIDS and Infectious Disease Network (SIDA-MI) and the Canadian Network for Vaccines and Immunotherapeutics. This study was funded in part by the Intramural Program of the US National Institutes of Health. Vectors were generously provided by E. Cohen at the Institut de Recherches Cliniques de Montreal. The lentiviral vector pWPI (empty vector), packaging plasmid psPAX2 and envelope plasmid pMD2G were generously provided by D. Trono (University of Geneva). NR 50 TC 186 Z9 197 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2010 VL 16 IS 4 BP 452 EP U136 DI 10.1038/nm.2106 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 580KJ UT WOS:000276446800050 PM 20208540 ER PT J AU Quaranta, V Garbett, SP AF Quaranta, Vito Garbett, Shawn P. TI Not all noise is waste SO NATURE METHODS LA English DT Editorial Material ID MICROSCOPY C1 [Quaranta, Vito] Vanderbilt Univ, Natl Canc Inst, Integrat Canc Biol Program, Ctr Canc Syst Biol, Nashville, TN 37203 USA. Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. RP Quaranta, V (reprint author), Vanderbilt Univ, Natl Canc Inst, Integrat Canc Biol Program, Ctr Canc Syst Biol, Nashville, TN 37203 USA. EM vito.quaranta@vanderbilt.edu RI Quaranta, Vito/G-6512-2016 OI Quaranta, Vito/0000-0001-7491-8672 NR 6 TC 5 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD APR PY 2010 VL 7 IS 4 BP 269 EP 272 DI 10.1038/nmeth0410-269 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 576NF UT WOS:000276150600014 PM 20354516 ER PT J AU Li, W Chen, S DeVries, SH AF Li, Wei Chen, Shan DeVries, Steven H. TI A fast rod photoreceptor signaling pathway in the mammalian retina SO NATURE NEUROSCIENCE LA English DT Article ID BIPOLAR CELLS; RECEPTORS; KINETICS; RELEASE; SYNAPSE; CONES AB Rod photoreceptors were recently shown to contact 'Off' cone bipolar cells, providing an alternative pathway for rod signal flow in the mammalian retina. By recording from pairs of rods and Off cone bipolar cells in the ground squirrel (Spermophilus tridecemlineatus), we measured the synaptic responses of mammalian rods unfiltered by the slow kinetics of the rod bipolar cell response. We show that vesicle fusion and turnover in mammalian rods is fast, and that this new pathway can mediate rapid signaling. C1 [DeVries, Steven H.] Northwestern Univ, Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA. [DeVries, Steven H.] Northwestern Univ, Sch Med, Dept Physiol, Chicago, IL 60611 USA. [Li, Wei; Chen, Shan] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA. RP DeVries, SH (reprint author), Northwestern Univ, Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA. EM liwei2@nei.nih.gov; s-devries@northwestern.edu FU National Institutes of Health [R01EY12141, F32EY017257]; National Eye Institute FX This work was supported by National Institutes of Health grants (R01EY12141) to S. H. D. and (F32EY017257) to W. L., the National Eye Institute Intramural Research Program to W. L. and S. C., and Research to Prevent Blindness. NR 15 TC 26 Z9 26 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2010 VL 13 IS 4 BP 414 EP 416 DI 10.1038/nn.2507 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 575NI UT WOS:000276073500008 PM 20190742 ER PT J AU Chan, AWY Kravitz, DJ Truong, S Arizpe, J Baker, CI AF Chan, Annie W-Y Kravitz, Dwight J. Truong, Sandra Arizpe, Joseph Baker, Chris I. TI Cortical representations of bodies and faces are strongest in commonly experienced configurations SO NATURE NEUROSCIENCE LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; ANTERIOR PARIETAL CORTEX; BODY; EXPERTISE; AREA; PERCEPTION; OBJECTS AB Faces and bodies are perhaps the most salient and evolutionarily important visual stimuli. Using human functional imaging, we found that the strength of face and body representations depends on long-term experience. Representations were strongest for stimuli in their typical combinations of visual field and side (for example, left field, right body), although all conditions were simply reflections and translations of one another. Thus, high-level representations reflect the statistics with which stimuli occur. C1 [Chan, Annie W-Y; Kravitz, Dwight J.; Truong, Sandra; Arizpe, Joseph; Baker, Chris I.] NIMH, Lab Brain & Cognit, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Chan, AWY (reprint author), NIMH, Lab Brain & Cognit, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM chanannie@mail.nih.gov RI Kravitz, Dwight/B-8430-2012; Arizpe, Joseph/N-1399-2014; OI Arizpe, Joseph/0000-0001-8958-7757; Baker, Chris/0000-0001-6861-8964 FU National Institute of Mental Health FX We thank M. Behrmann, P. Downing, S. Gotts, A. Ghuman, A. Martin, H. P. Op de Beeck and W. K. Simmons for comments on an earlier version of this manuscript and N. Kriegeskorte for helpful discussions. We also thank V. Elkis for assistance with fMRI data collection. This work was supported by the US National Institutes of Health Intramural Research Program of the National Institute of Mental Health. NR 15 TC 42 Z9 42 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2010 VL 13 IS 4 BP 417 EP 418 DI 10.1038/nn.2502 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 575NI UT WOS:000276073500009 PM 20208528 ER PT J AU McCurry, CL Shepherd, JD Tropea, D Wang, KH Bear, MF Sur, M AF McCurry, Cortina L. Shepherd, Jason D. Tropea, Daniela Wang, Kuan H. Bear, Mark F. Sur, Mriganka TI Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation SO NATURE NEUROSCIENCE LA English DT Article ID OCULAR DOMINANCE PLASTICITY; AMPA RECEPTOR TRAFFICKING; LONG-TERM POTENTIATION; IMMEDIATE-EARLY GENE; DEPENDENT PLASTICITY; MONOCULAR DEPRIVATION; SYNAPTIC PLASTICITY; IN-VIVO; CORTICAL PLASTICITY; INTRINSIC SIGNAL AB A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arc(-/-) mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arc(-/-) mice lacked stimulus-selective response potentiation. Although Arc(-/-) mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex. C1 [Shepherd, Jason D.; Bear, Mark F.; Sur, Mriganka] MIT, Dept Brain & Cognit Sci, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Wang, Kuan H.] NIMH, Bethesda, MD 20892 USA. RP Sur, M (reprint author), MIT, Dept Brain & Cognit Sci, Howard Hughes Med Inst, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA. EM mbear@mit.edu; msur@mit.edu RI Wang, Kuan Hong/J-1150-2016; OI Wang, Kuan Hong/0000-0002-2249-5417; Tropea, Daniela/0000-0001-9730-6636; Shepherd, Jason/0000-0001-7384-8289 FU US National Institutes of Health; Howard Hughes Medical Institute FX We thank T. Emery for assistance with the preparation of the manuscript. We thank members of the Sur and Bear laboratories for their comments and helpful discussions. This work was supported by grants from the US National Institutes of Health (C. L. M., D. T. and M. S.) and the Howard Hughes Medical Institute (J. D. S. and M. F. B.). NR 50 TC 67 Z9 67 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2010 VL 13 IS 4 BP 450 EP U69 DI 10.1038/nn.2508 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 575NI UT WOS:000276073500014 PM 20228806 ER PT J AU Paul, WE Zhu, JF AF Paul, William E. Zhu, Jinfang TI How are T(H)2-type immune responses initiated and amplified? SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID T-HELPER-CELL; THYMIC STROMAL LYMPHOPOIETIN; TRANSCRIPTION FACTOR GATA-3; EOSINOPHILIC AIRWAY INFLAMMATION; CYTOKINE-DEPENDENT IMMUNITY; ANTIGEN-PRESENTING CELLS; MYELOID DENDRITIC CELLS; HUMAN EPITHELIAL-CELLS; IN-VIVO; TH2 DIFFERENTIATION AB CD4(+) T helper (T-H) cells have crucial roles in orchestrating adaptive immune responses. T(H)2 cells control immunity to extracellular parasites and all forms of allergic inflammatory responses. Although we understand the initiation of the T(H)2-type response in tissue culture in great detail, much less is known about T(H)2 cell induction in vivo. Here we discuss the involvement of allergen-and parasite product-mediated activation of epithelial cells, basophils and dendritic cells and the functions of the cytokines interleukin-4 (IL-4), IL-25, IL-33 and thymic stromal lymphopoietin in the initiation and amplification of T(H)2-type immune responses in vivo. C1 [Paul, William E.; Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov; jfzhu@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012 FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases; US National Institutes of Health FX The work is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and the US National Institutes of Health. NR 116 TC 348 Z9 357 U1 3 U2 50 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2010 VL 10 IS 4 BP 225 EP 235 DI 10.1038/nri2735 PG 11 WC Immunology SC Immunology GA 574AM UT WOS:000275960800009 PM 20336151 ER PT J AU Zou, WP Restifo, NP AF Zou, Weiping Restifo, Nicholas P. TI T(H)17 cells in tumour immunity and immunotherapy SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID REGULATORY T-CELLS; POTENT ANTITUMOR IMMUNITY; GROWTH-FACTOR-BETA; TH17 CELLS; DENDRITIC CELLS; OVARIAN-CANCER; CUTTING EDGE; AUTOIMMUNE ENCEPHALOMYELITIS; INFILTRATING LYMPHOCYTES; IL-17-PRODUCING CELLS AB T helper 17 (T(H)17) cells have well-described roles in autoimmune disease. Recent evidence suggests that this effector T cell subset is also involved in tumour immunology and may be a target for cancer therapy. In this Review, we summarize recent findings regarding the nature and relevance of T(H)17 cells in mouse models of cancer and human disease. We describe the interplay between T(H)17 cells and other immune cells in the tumour microenvironment, and we assess both the potential antitumorigenic and pro-tumorigenic activities of T(H)17 cells and their associated cytokines. Understanding the nature of T(H)17 cell responses in the tumour microenvironment will be important for the design of more efficacious cancer immunotherapies. C1 [Zou, Weiping] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA. [Restifo, Nicholas P.] NCI, Bethesda, MD 20892 USA. RP Zou, WP (reprint author), Univ Michigan, Sch Med, Dept Surg, C560B MSRB 2,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM wzou@med.umich.edu; restifo@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU United States National Cancer Institute FX We thank our former and current trainees and collaborators for their intellectual input and hard work. The work described in this Review was supported by the extramural (W. Z.) and intramural (N. P. R.) funds from the United States National Cancer Institute. NR 106 TC 263 Z9 275 U1 9 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2010 VL 10 IS 4 BP 248 EP 256 DI 10.1038/nri2742 PG 9 WC Immunology SC Immunology GA 574AM UT WOS:000275960800011 PM 20336152 ER PT J AU Cohen, SD Phillips, TM Khetpal, P Kimmel, PL AF Cohen, Scott D. Phillips, Terry M. Khetpal, Prashant Kimmel, Paul L. TI Cytokine patterns and survival in haemodialysis patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE cytokines; ESRD; factor analysis; survival ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; STAGE RENAL-DISEASE; CARDIOVASCULAR MORTALITY; ALL-CAUSE; SERUM-ALBUMIN; INTERLEUKIN-6; INFLAMMATION; DIALYSIS; RISK AB Background. Increased pro-inflammatory cytokine levels are associated with decreased survival. We performed factor analyses to determine if pro-inflammatory and anti-inflammatory cytokines in haemodialysis (HD) patients load onto one or two discrete factors and assessed if patients with a specific pattern of high pro-inflammatory cytokines have decreased survival compared to patients with a high anti-inflammatory cytokine pattern. Methods. We evaluated 231 HD patients and analyzed them based on the three most common cytokine distribution patterns seen: a high pro-inflammatory group, a high anti-inflammatory group and all others. Survival and Cox regression analyses were performed. Results. Factor analyses of individual cytokines showed that they loaded onto a single factor. Sixty-five patients had a pro-inflammatory pattern of high IL-1, IL-6 and TNF-alpha levels and low anti-inflammatory parameters, including IL-2, IL-4, IL-5, IL-12, CH50 and T-cell number. The next most frequent cytokine pattern was found in 20 patients with high levels of anti-inflammatory parameters. The patients with high pro-inflammatory cytokines had decreased survival compared to patients without a characteristic cytokine pattern. Conclusions. Further research is needed to better define the underlying causes of increased inflammation among end-stage renal disease patients and to apply anti-inflammatory therapies that may mitigate adverse effects on patient outcomes. C1 [Cohen, Scott D.; Khetpal, Prashant; Kimmel, Paul L.] George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20052 USA. [Kimmel, Paul L.] NIDDK, Bethesda, MD USA. [Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Kimmel, PL (reprint author), George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20052 USA. EM kimmelp@extra.niddk.nih.gov NR 26 TC 15 Z9 15 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2010 VL 25 IS 4 BP 1239 EP 1243 DI 10.1093/ndt/gfp625 PG 5 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 591DO UT WOS:000277279400035 PM 20007982 ER PT J AU Lee, HJ Bazinet, RP Rapoport, SI Bhattacharjee, AK AF Lee, Ho-Joo Bazinet, Richard P. Rapoport, Stanley I. Bhattacharjee, Abesh Kumar TI Brain Arachidonic Acid Cascade Enzymes are Upregulated in a Rat Model of Unilateral Parkinson Disease SO NEUROCHEMICAL RESEARCH LA English DT Article DE 6-OHDA; Cyclooxygenase-2; Parkinson disease; Cytosolic phospholipase A(2); Rat; Arachidonic acid; Cascade; Signaling; Dopamine; Upregulation; Unilateral; Asymmetry ID POSITRON-EMISSION-TOMOGRAPHY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SECRETORY PHOSPHOLIPASE A(2); GROUP-SPECIFIC ASSAYS; SIGNAL-TRANSDUCTION; UNANESTHETIZED RATS; 6-OHDA LESIONS; D-2 RECEPTORS; TIME-COURSE; 6-HYDROXYDOPAMINE LESION AB Arachidonic acid (AA) signaling is upregulated in the caudate-putamen and frontal cortex of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, a model for asymmetrical Parkinson disease. AA signaling can be coupled to D-2-like receptor initiated AA hydrolysis from phospholipids by cytosolic phospholipase A(2) (cPLA(2)) and subsequent metabolism by cyclooxygenase (COX)-2. In unilaterally 6-OHDA-and sham-lesioned rats, we measured brain expression of cPLA(2), other PLA(2) enzymes, and COX-2. Activity and protein levels of cPLA(2) were significantly higher as was COX-2-protein in caudate-putamen, frontal cortex and remaining brain on the lesioned compared to intact side of the 6-OHDA lesioned rats, and compared to sham brain. Secretory sPLA(2) and Ca2+ independent iPLA(2) expression did not differ between sides or groups. Thus, the tonically increased ipsilateral AA signal in the lesioned rat corresponds to upregulated cPLA(2) and COX-2 expression within the AA metabolic cascade, which may contribute to symptoms and pathology in Parkinson disease. C1 [Lee, Ho-Joo; Bazinet, Richard P.; Rapoport, Stanley I.; Bhattacharjee, Abesh Kumar] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bhattacharjee, AK (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM abeshb@mail.nih.gov FU National Institute on Aging FX This research was supported entirely by the Intramural Program of the National Institute on Aging. NR 72 TC 13 Z9 13 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 2010 VL 35 IS 4 BP 613 EP 619 DI 10.1007/s11064-009-0106-6 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 572HZ UT WOS:000275820500013 PM 19997776 ER PT J AU Smith, JF Alexander, GE Chen, KW Husain, FT Kim, J Pajor, N Horwitz, B AF Smith, Jason F. Alexander, Gene E. Chen, Kewei Husain, Fatima T. Kim, Jieun Pajor, Nathan Horwitz, Barry TI Imaging systems level consolidation of novel associate memories: A longitudinal neuroimaging study SO NEUROIMAGE LA English DT Article DE Consolidation; fMRI; Memory; Long-term memory ID MEDIAL TEMPORAL-LOBE; EVENT-RELATED FMRI; TIME-LIMITED ROLE; RETROGRADE-AMNESIA; AUTOBIOGRAPHICAL MEMORY; RECOGNITION MEMORY; PREFRONTAL CORTEX; ENTORHINAL CORTEX; WORKING-MEMORY; FRONTAL DISCONNECTION AB Previously, a standard theory of systems level memory consolidation was developed to describe how memory recall becomes independent of the medial temporal memory system. More recently, an extended consolidation theory was proposed that predicts seven changes in regional neural activity and inter-regional functional connectivity. Using longitudinal event-related functional magnetic resonance imaging of an associate memory task, we simultaneously tested all predictions and additionally tested for consolidation-related changes in recall of associate memories at a sub-trial temporal resolution, analyzing cue, delay and target periods of each trial separately. Results consistent with the theoretical predictions were observed though two inconsistent results were also obtained. In particular, while medial temporal recall related delay period activity decreased with consolidation as predicted, visual cue activity increased for consolidated memories. Though the extended theory of memory consolidation is largely supported by our study, these results suggest that the extended theory needs further refinement and the medial temporal memory system has multiple, temporally distinct roles in associate memory recall. Neuroimaging analysis at a sub-trial temporal resolution, as used here, may further clarify the role of the hippocampal complex in memory consolidation. Published by Elsevier Inc. C1 [Smith, Jason F.; Husain, Fatima T.; Kim, Jieun; Pajor, Nathan; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. [Smith, Jason F.] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. [Alexander, Gene E.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. [Alexander, Gene E.] Univ Arizona, Evelyn F McKnight Brain Inst, Tucson, AZ 85721 USA. [Alexander, Gene E.; Chen, Kewei] Arizona Alzheimers Dis Consortium, Phoenix, AZ USA. [Chen, Kewei] Arizona State Univ, Dept Math & Stat, Tempe, AZ 85287 USA. [Chen, Kewei] Banner Good Samaritan Med Ctr, Banner Alzheimers Dis Inst, Phoenix, AZ USA. [Chen, Kewei] Positron Emiss Tomog Ctr, Phoenix, AZ USA. RP Smith, JF (reprint author), Rm 8S235B,10 Ctr Dr, Bethesda, MD USA. EM smithjas@nidcd.nih.gov RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU National Institute on Deafness and Other Communication Disorders, National Institutes of Health, National Institutes of Health Intramural Research; National Institute on Aging [AG19610, AG025526]; Evelyn F. McKnight Brain Institute FX This work was supported by the intramural program of the National Institute on Deafness and Other Communication Disorders, the National Institutes of Health, and a National Institutes of Health Intramural Research Training Award to JFS. The authors would also like to acknowledge support from the National Institute on Aging (AG19610, AG025526 [GEA]), the Evelyn F. McKnight Brain Institute [GEA], and the State of Arizona [GEA, KC]. We thank L Talagala, J. Black, and R. Hill for their assistance with data acquisition, A. R. Braun for assistance with medical evaluations, J. Cooper for granting permission to use the fractal images, and A. R. Braun, L. Ungerleider, M. Mishkin, E. Murray, S. Goldinger, P. Killeen, and three anonymous reviewers for comments on earlier versions of the manuscript. NR 71 TC 7 Z9 7 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2010 VL 50 IS 2 BP 826 EP 836 DI 10.1016/j.neuroimage.2009.11.053 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 561AX UT WOS:000274948400052 PM 19948227 ER PT J AU Terracciano, A Tanaka, T Sutin, AR Deiana, B Balaci, L Sanna, S Olla, N Maschio, A Uda, M Ferrucci, L Schlessinger, D Costa, PT AF Terracciano, Antonio Tanaka, Toshiko Sutin, Angelina R. Deiana, Barbara Balaci, Lenuta Sanna, Serena Olla, Nazario Maschio, Andrea Uda, Manuela Ferrucci, Luigi Schlessinger, David Costa, Paul T., Jr. TI BDNF Val66Met is Associated with Introversion and Interacts with 5-HTTLPR to Influence Neuroticism SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE personality; depression; BDNF Val66Met; serotonin transporter; GWA; gene-gene interaction ID NEUROTROPHIC-FACTOR BDNF; FAMILY-BASED ASSOCIATION; NEO-PI-R; PERSONALITY-TRAITS; SEROTONIN TRANSPORTER; BIPOLAR DISORDER; POLYMORPHISM 5-HTTLPR; ANXIETY DISORDERS; GENETIC-VARIATION; HEALTHY-SUBJECTS AB Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurotransmission, and has been linked to neuroticism, a major risk factor for psychiatric disorders. A recent genome-wide association (GWA) scan, however, found the BDNF Val66Met polymorphism (rs6265) associated with extraversion but not with neuroticism. In this study, we examine the links between BDNF and personality traits, assessed using the Revised NEO Personality Inventory (NEO-PI-R), in a sample from SardiNIA (n = 1560) and the Baltimore Longitudinal Study of Aging (BLSA; n = 1131). Consistent with GWA results, we found that BDNF Met carriers were more introverted. By contrast, in both samples and in a meta-analysis inclusive of published data (n = 15251), we found no evidence for a main effect of BDNF Val66Met on neuroticism. Finally, on the basis of recent reports of an epistatic effect between BDNF and the serotonin transporter, we explored a Val66Met x 5-HTTLPR interaction in a larger SardiNIA sample (n = 2333). We found that 5-HTTLPR LL carriers scored lower on neuroticism in the presence of the BDNF Val variant, but scored higher on neuroticism in the presence of the BDNF Met variant. Our findings support the association between the BDNF Met variant and introversion and suggest that BDNF interacts with the serotonin transporter gene to influence neuroticism. Neuropsychopharmacology (2010) 35, 1083-1089; doi: 10.1038/npp.2009.213; published online 30 December 2009 C1 [Terracciano, Antonio] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA. [Deiana, Barbara; Balaci, Lenuta; Sanna, Serena; Olla, Nazario; Maschio, Andrea; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. RP Terracciano, A (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM terraccianoa@mail.nih.gov RI terracciano, antonio/B-1884-2008; OI sanna, serena/0000-0002-3768-1749; Costa, Paul/0000-0003-4375-1712 FU NIH, National Institute on Aging FX We thank the individuals who participated in this study; The SardiNIA team thanks Monsignore Piseddu (Bishop of Ogliastra), the mayors of the four Sardinian towns (Lanusei, Ilbono, Arzana, and Elini), and the head of the Public Health Unit ASL4 for cooperation. We thank Professor Antonio Cao for his leadership of the SardiNIA project. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 69 TC 53 Z9 53 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2010 VL 35 IS 5 BP 1083 EP 1089 DI 10.1038/npp.2009.213 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 570CA UT WOS:000275648000004 PM 20042999 ER PT J AU Srivastava, V Buzas, B Momenan, R Oroszi, G Pulay, AJ Enoch, MA Hommer, DW Goldman, D AF Srivastava, Vibhuti Buzas, Beata Momenan, Reza Oroszi, Gabor Pulay, Attila J. Enoch, Mary-Anne Hommer, Daniel W. Goldman, David TI Association of SOD2, a Mitochondrial Antioxidant Enzyme, with Gray Matter Volume Shrinkage in Alcoholics SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcoholism; oxidative stress; brain volume; gray matter shrinkage; SOD2; Ala16Val ID CHRONIC CIGARETTE-SMOKING; INDUCED BRAIN-DAMAGE; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; PARKINSONS-DISEASE; HAPLOTYPE RECONSTRUCTION; LONGITUDINAL CHANGES; TARGETING SEQUENCE; FAMILY-HISTORY; HEAVY DRINKING AB Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O(2)(-)) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo. Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal sections. Gray matter, white matter, sulcal, and ventricular CSF volumes were estimated using intensity-based K-means clustering. Ala16Val (rs4880) and a second haplotype tagging SNP, rs10370, were genotyped. The q-value package was used to correct for multiple comparisons. In the alcoholics, cerebrospinal fluid and intra-cranial volumes showed significant differences across the six diplotype categories. The homozygous Ala16-containing diplotype rs10370TT-rs4880GG was associated with lowest gray matter ratio (greater shrinkage; p = 0.005). Presence of one or two copies of the low activity Ala16 allele was a risk factor for lower gray matter volume in alcoholics below the median alcohol consumption (p = 0.03) but not in alcoholics above this level. White matter ratio was associated with sex (p = 0.002) and lifetime total alcohol consumption (p = 0.01) but not with diplotypes. In this exploratory analysis, a putative functional missense variant of SOD2 appears to influence gray matter loss in alcoholics. This may be due to impaired clearance of reactive oxygen species formed as a result of alcohol exposure. The risk/protective effect was observed in alcoholics with lower levels of lifetime alcohol consumption. Highest levels of exposure may overwhelm the protective action of the SOD2 enzyme. Neuropsychopharmacology (2010) 35, 1120-1128; doi: 10.1038/npp.2009.217; published online 30 December 2009 C1 [Srivastava, Vibhuti; Oroszi, Gabor; Pulay, Attila J.; Enoch, Mary-Anne; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20851 USA. [Buzas, Beata] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Momenan, Reza; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20851 USA. [Pulay, Attila J.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20851 USA. RP Srivastava, V (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane, Bethesda, MD 20851 USA. EM srivastavav@mail.nih.gov RI Goldman, David/F-9772-2010; Pulay, Attila/B-6155-2011 OI Goldman, David/0000-0002-1724-5405; FU Intramural NIH HHS [ZIA AA000306-05] NR 52 TC 8 Z9 8 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2010 VL 35 IS 5 BP 1120 EP 1128 DI 10.1038/npp.2009.217 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 570CA UT WOS:000275648000008 PM 20043000 ER PT J AU Tost, H Alam, T Meyer-Lindenberg, A AF Tost, Heike Alam, Tajvar Meyer-Lindenberg, Andreas TI Dopamine and psychosis: Theory, pathomechanisms and intermediate phenotypes SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Psychosis; Dopamine; Schizophrenia; Dopamine hypothesis; Prefrontal function; Striatum; Intermediate phenotypes; Imaging genetics; Susceptibility genes ID CATECHOL-O-METHYLTRANSFERASE; POSITRON EMISSION TOMOGRAPHY; FRONTAL-LOBE FUNCTION; D2 RECEPTOR GENE; PREFRONTAL CORTEX; WORKING-MEMORY; SCHIZOPHRENIC-PATIENTS; HUMAN-BRAIN; CEREBRAL-CORTEX; D1 RECEPTORS AB Schizophrenia is a chronic, severe, and disabling brain disorder arising from the adverse interaction of predisposing risk genes and environmental factors. The psychopathology is characterized by a wide array of disturbing cognitive, emotional, and behavioral symptoms that interfere with the individual's capacity to function in society. Contemporary pathophysiological models assume that psychotic symptoms are triggered by a dysregulation of dopaminergic activity in the brain, a theory that is tightly linked to the serendipitous discovery of the first effective antipsychotic agents in the early 1950s. In recent years, the availability of modern neuroimaging techniques has significantly expanded our understanding of the key mediator circuits that bridge the gap between genetic susceptibility and clinical phenotype. This paper discusses the pathophysiological concepts, molecular mechanisms and neuroimaging evidence that link psychosis to disturbances in dopamine neurotransmission. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-68159 Mannheim, Germany. [Tost, Heike; Meyer-Lindenberg, Andreas] NIMH, Unit Syst Neurosci Psychiat, NIH, DHHS, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] NIMH, Neuroimaging Core Facil, NIH, DHHS, Bethesda, MD 20892 USA. [Tost, Heike; Alam, Tajvar; Meyer-Lindenberg, Andreas] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,DHHS, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, J5, D-68159 Mannheim, Germany. EM A.Meyer-Lindenberg@zi-mannheim.de RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU National Institute of Mental Health, NIH FX The authors thank Matthew Geramita for helpful comments on the manuscript. This research was supported by the Intramural Research Program of the National Institute of Mental Health, NIH. NR 132 TC 42 Z9 46 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD APR PY 2010 VL 34 IS 5 BP 689 EP 700 DI 10.1016/j.neubiorev.2009.06.005 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 584AN UT WOS:000276722500007 PM 19559045 ER PT J AU Rico, D Earl, J Diaz-Uriarte, R Rueda, OM Marenne, G Pita, G AF Rico, D. Earl, J. Diaz-Uriarte, R. Rueda, O. M. Marenne, G. Pita, G. TI Genomic copy number alterations in cancer: high-resolution analysis of the NCI-60 panel SO NEW BIOTECHNOLOGY LA English DT Meeting Abstract CT 4th ESF Conference on Functional Genomics & Disease CY APR 14-17, 2010 CL Dresden, GERMANY C1 [Rico, D.; Earl, J.; Diaz-Uriarte, R.; Marenne, G.; Pita, G.] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain. [Rueda, O. M.] Canc Res UK, Cambridge, England. [Rico, D.; Earl, J.; Diaz-Uriarte, R.; Rueda, O. M.; Marenne, G.; Pita, G.] NCI, Bethesda, MD 20892 USA. [Rico, D.; Earl, J.; Diaz-Uriarte, R.; Rueda, O. M.; Marenne, G.; Pita, G.] Univ Pompeu Fabra, Barcelona, Spain. [Marenne, G.] INSERM, UMR S946, F-75654 Paris 13, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1871-6784 EI 1876-4347 J9 NEW BIOTECHNOL JI New Biotech. PD APR PY 2010 VL 27 SU 1 MA ST06 BP S81 EP S81 DI 10.1016/j.nbt.2010.01.228 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA V45OD UT WOS:000209825000193 ER PT J AU Xi, WZ Seidel, J Kakareka, JW Pohida, TJ Milenic, DE Proffitt, J Majewski, S Weisenberger, AG Green, MV Choyke, PL AF Xi, Wenze Seidel, Jurgen Kakareka, John W. Pohida, Thomas J. Milenic, Diane E. Proffitt, James Majewski, Stan Weisenberger, Andrew G. Green, Michael V. Choyke, Peter L. TI MONICA: a compact, portable dual gamma camera system for mouse whole-body imaging SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE MONICA; Small animal imaging; Cancer drug development; Mouse whole-body imaging; Miniature gamma cameras; Single photon imaging AB Introduction: We describe a compact, portable dual-gamma camera system (named "MONICA" for MObile Nuclear Imaging CAmeras) for visualizing and analyzing the whole-body biodistribution of putative diagnostic and therapeutic single photon emitting radiotracers in animals the size of mice. Methods: Two identical, miniature pixelated Na(TI) gamma cameras were fabricated and installed "looking up" through the tabletop of a compact portable cart. Mice are placed directly on the tabletop for imaging. Camera imaging performance was evaluated with phantoms and field performance was evaluated in a weeklong In-111 imaging study performed in a mouse tumor xenograft model. Results: Tc-99m performance measurements, using a photopeak energy window of 140 keV +/- 10%, yielded the following results: spatial resolution (FWHM at 1 cm), 2.2 mm; sensitivity, 149 cps (counts per seconds)/MBq (5.5 cps/mu Ci); energy resolution (FWHM, full width at half maximum). 10.8%; count rate linearity (count rate vs. activity), r(2)=0.99 for 0-185 MBq (0-5 mCi) in the field of view (FOV); spatial uniformity, <3% count rate variation across the FOV. Tumor and whole-body distributions of the In-111 agent were well visualized in all animals in 5-min images acquired throughout the 168-h study period. Conclusion: Performance measurements indicate that MONICA is well suited to whole-body single photon mouse imaging. The field study suggests that inter-device communications and user-oriented interfaces included in the MONICA design facilitate use of the system in practice. We believe that MONICA may be particularly useful early in the (cancer) drug development cycle where basic whole-body biodistribution data can direct future development of the agent under study and where logistical factors, e.g., limited imaging space, portability and, potentially, cost are important. (C) 2010 Elsevier Inc. All rights reserved. C1 [Xi, Wenze; Seidel, Jurgen; Green, Michael V.; Choyke, Peter L.] Natl Canc Inst, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Xi, Wenze; Seidel, Jurgen; Green, Michael V.] Sci Applicat Int Corp, Frederick, MD USA. [Kakareka, John W.; Pohida, Thomas J.] NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Milenic, Diane E.] Natl Canc Inst, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Proffitt, James] Adapt IO Technol, Blacksburg, VA USA. [Majewski, Stan] W Virginia Univ, Dept Radiol, Morgantown, WV 26506 USA. [Weisenberger, Andrew G.] Thomas Jefferson Natl Accelerator Facil, Radiat Detectors & Imaging Grp, Newport News, VA USA. RP Choyke, PL (reprint author), Natl Canc Inst, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov OI Kakareka, John/0000-0003-0072-0035 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Financial support: This project has been funded in whole or 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 9 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 2010 VL 37 IS 3 BP 245 EP 253 DI 10.1016/j.nucmedbio.2009.12.003 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 581VB UT WOS:000276551800002 PM 20346864 ER PT J AU Seneca, N Zoghbi, SS Shetty, HU Tuan, E Kannan, P Taku, A Innis, RB Pike, VW AF Seneca, Nicholas Zoghbi, Sami S. Shetty, H. Umesha Tuan, Edward Kannan, Pavitra Taku, Andrew Innis, Robert B. Pike, Victor W. TI Effects of ketoconazole on the biodistribution and metabolism of [C-11]loperamide and [C-11]N-desmethyl-loperamide in wild-type and P-gp knockout mice SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE [C-11]Loperamide; [C-11]dLop; P-glycoprotein; Ketoconazole; Biodistribution; Metabolism ID HUMAN LIVER-MICROSOMES; N-HYDROXYMETHYL COMPOUNDS; CYTOCHROME-P450 3A4; IN-VIVO; PLASMA-CONCENTRATIONS; DOPAMINE TRANSPORTER; 5-HT1A RECEPTORS; DRUG-METABOLISM; PET RADIOTRACER; HUMAN BRAIN AB Introduction: [C-11]Loperamide and [C-11]N-desmethyl-loperamide ([C-11]dLop) have been proposed as radiotracers for imaging brain P-glycoprotein (P-gp) function. A major route of [C-11]loperamide metabolism is N-demethylation to [C-11]dLop. We aimed to test whether inhibition of CYP3A4 with ketoconazole might reduce the metabolism of [C-11]loperamide and [C-11]dLop in mice, and thereby improve the quality of these radiotracers. Methods: Studies were performed in wild-type and P-gp knockout (mdr-la/b -/-) mice. During each of seven study sessions, one pair of mice, comprising one wild-type and one knockout mouse, was pretreated with ketoconazole (50 mg/kg, ip), while another such pair was left untreated. Mice were sacrificed at 30 min after injection of [C-11]loperamide or [C-11]dLop. Whole brain and plasma samples were measured for radioactivity and analyzed with radio-high-performance liquid chromatography. Results: Ketoconazole increased the plasma concentrations of [C-11]loperamide and its main radioinetabolite, [C-11]dLop, by about twofold in both wild-type and knockout mice, whereas the most polar radiometabolite was decreased threefold. Furthermore, ketoconazole increased the brain concentrations of [C-11]loperamide and the radiometabolite [C-11]dLop by about twofold in knockout mice, and decreased the brain concentrations of the major and most polar radiometabolite in wild-type and knockout mice by 82% and 49%, respectively. In contrast, ketoconazole had no effect on plasma and brain distribution of administered [C-11]dLop and its radiometabolites in either wild-type or knockout mice, except to increase the low plasma [C-11]dLop concentration. The least polar radiometabolite of [C-11]dLop was identified with LC-MSn as the N-hydroxymethyl analog of [C-11]dLop and this also behaved as a P-gp substrate. Conclusion: In this study, ketoconazole (50 mg/kg, ip) proved partially effective for inhibiting the N-demethylation of [C-11]loperamide in mouse in vivo but had relatively smaller or no effect on [C-11]dLop. Published by Elsevier Inc. C1 [Seneca, Nicholas; Zoghbi, Sami S.; Shetty, H. Umesha; Tuan, Edward; Kannan, Pavitra; Taku, Andrew; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov FU National Institute of Mental Health [Z01 MH002793, Z01 MH002796, Z01-MH002795] FX This research was supported by the Intramural Research Program of the National Institute of Mental Health (projects numbers Z01 MH002793, Z01 MH002796, AND Z01-MH002795). We are grateful to Ms. Kimberley Jenko for assistance with experiments and to the NIH Clinical PET Center for the cyclotron production of carbon-II. NR 46 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 2010 VL 37 IS 3 BP 335 EP 345 DI 10.1016/j.nucmedbio.2009.12.010 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 581VB UT WOS:000276551800011 PM 20346873 ER PT J AU Hansen, L Marino-Ramirez, L Landsman, D AF Hansen, Loren Marino-Ramirez, Leonardo Landsman, David TI Many sequence-specific chromatin modifying protein-binding motifs show strong positional preferences for potential regulatory regions in the Saccharomyces cerevisiae genome SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSACTIVATOR POTENTIATION; NUCLEOSOME OCCUPANCY; YEAST; TRANSCRIPTION; PROMOTER; RAP1; ELEMENTS; GENE; LOCATION; REVEALS AB Initiation and regulation of gene expression is critically dependent on the binding of transcriptional regulators, which is often temporal and position specific. Many transcriptional regulators recognize and bind specific DNA motifs. The length and degeneracy of these motifs results in their frequent occurrence within the genome, with only a small subset serving as actual binding sites. By occupying potential binding sites, nucleosome placement can specify which sequence motif is available for DNA-binding regulatory factors. Therefore, the specification of nucleosome placement to allow access to transcriptional regulators whenever and wherever required is critical. We show that many DNA-binding motifs in Saccharomyces cerevisiae show a strong positional preference to occur only in potential regulatory regions. Furthermore, using gene ontology enrichment tools, we demonstrate that proteins with binding motifs that show the strongest positional preference also have a tendency to have chromatin-modifying properties and functions. This suggests that some DNA-binding proteins may depend on the distribution of their binding motifs across the genome to assist in the determination of specificity. Since many of these DNA-binding proteins have chromatin remodeling properties, they can alter the local nucleosome structure to a more permissive and/or restrictive state, thereby assisting in determining DNA-binding protein specificity. C1 [Hansen, Loren; Landsman, David] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Hansen, Loren] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. RP Landsman, D (reprint author), Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, 8900 Rockville Pike, Bethesda, MD 20894 USA. EM landsman@ncbi.nlm.nih.gov RI Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU CORPOICA; National Library of Medicine, National Institutes of Health FX L. M. R. was supported by CORPOICA. Funding for open access charge: Intramural Program of the National Library of Medicine, National Institutes of Health. NR 39 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2010 VL 38 IS 6 BP 1772 EP 1779 DI 10.1093/nar/gkp1195 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578PB UT WOS:000276304600010 PM 20047965 ER PT J AU Wong, CM Tang, HMV Kong, KYE Wong, GWO Qiu, HF Jin, DY Hinnebusch, AG AF Wong, Chi-Ming Tang, Hei-Man Vincent Kong, Ka-Yiu Edwin Wong, Gee-Wan Oscar Qiu, Hongfang Jin, Dong-Yan Hinnebusch, Alan G. TI Yeast arginine methyltransferase Hmt1p regulates transcription elongation and termination by methylating Npl3p SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-POLYMERASE-II; CAP-BINDING COMPLEX; SR-LIKE PROTEIN; MESSENGER-RNA; IN-VIVO; SACCHAROMYCES-CEREVISIAE; NUCLEAR EXPORT; 3'-END FORMATION; BUDDING YEAST; GENE DELETION AB The heterogeneous nuclear ribonucleoprotein Npl3p of budding yeast is a substrate of arginine methyltransferase Hmt1p, but the role of Hmt1p in regulating Npl3p's functions in transcription antitermination and elongation were unknown. We found that mutants lacking Hmt1p methyltransferase activity exhibit reduced recruitment of Npl3p, but elevated recruitment of a component of mRNA cleavage/termination factor CFI, to the activated GAL10-GAL7 locus. Consistent with this, hmt1 mutants displayed increased termination at the defective gal10-delta 56 terminator. Remarkably, hmt1 delta cells also exhibit diminished recruitment of elongation factor Tho2p and a reduced rate of transcription elongation in vivo. Importantly, the defects in Npl3p and Tho2p recruitment, antitermination and elongation in hmt1 delta cells all were mitigated by substitutions in Npl3p RGG repeats that functionally mimic arginine methylation by Hmt1p. Thus, Hmt1p promotes elongation and suppresses termination at cryptic terminators by methylating RGG repeats in Npl3p. As Hmt1p stimulates dissociation of Tho2p from an Npl3p-mRNP complex, it could act to recycle these elongation and antitermination factors back to sites of ongoing transcription. C1 [Wong, Chi-Ming; Tang, Hei-Man Vincent; Kong, Ka-Yiu Edwin; Jin, Dong-Yan] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [Wong, Gee-Wan Oscar] Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Qiu, Hongfang; Hinnebusch, Alan G.] Eunice Kennedy Shriver NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Wong, CM (reprint author), Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. EM wispwong@hkucc.hku.hk RI Wong, Chi-Ming/A-7627-2013 OI Wong, Chi-Ming/0000-0002-0025-7135 FU University Research Committee of the University of Hong Kong; Hong Kong Research Grants Council [HKU 7486/06M]; NIH FX The University Research Committee of the University of Hong Kong; Hong Kong Research Grants Council (project HKU 7486/06M); Intramural Research Program of the NIH. NR 37 TC 14 Z9 15 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2010 VL 38 IS 7 BP 2217 EP 2228 DI 10.1093/nar/gkp1133 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 584IJ UT WOS:000276744600020 PM 20053728 ER PT J AU Dexheimer, TS Stephen, AG Fivash, MJ Fisher, RJ Pommier, Y AF Dexheimer, Thomas S. Stephen, Andrew G. Fivash, Matthew J. Fisher, Robert J. Pommier, Yves TI The DNA binding and 3'-end preferential activity of human tyrosyl-DNA phosphodiesterase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STRAND BREAK REPAIR; TOPOISOMERASE-I; SPINOCEREBELLAR ATAXIA; AXONAL NEUROPATHY; CRYSTAL-STRUCTURE; PHOSPHOLIPASE-D; TDP1; DAMAGE; COMPLEXES; ENZYME AB Human tyrosyl-DNA phosphodiesterase (Tdp1) processes 3'-blocking lesions, predominantly 3'-phosphotyrosyl bonds resulting from the trapping of topoisomerase I (Top1) cleavage complexes. The controversial ability of yeast Tdp1 to hydrolyze 5'-phosphotyrosyl linkage between topoisomerase II (Top2) and DNA raises the question whether human Tdp1 possesses 5'-end processing activity. Here we characterize the end-binding and cleavage preference of human Tdp1 using single-stranded 5'- and 3'-fluorescein-labeled oligonucleotides. We establish 3'-fluorescein as an efficient surrogate substrate for human Tdp1, provided it is attached to the DNA by a phosphodiester (but not a phosphorothioate) linkage. We demonstrate that human Tdp1 lacks the ability to hydrolyze a phosphodiester linked 5'-fluorescein. Using both fluorescence anisotropy and time-resolved fluorescence quenching techniques, we also show the preferential binding of human Tdp1 to the 3'-end. However, DNA binding competition experiments indicate that human Tdp1 binding is dependent on DNA length rather than number of DNA ends. Lastly, using surface plasmon resonance, we show that human Tdp1 selectively binds the 3'-end of DNA. Together, our results suggest human Tdp1 may act using a scanning mechanism, in which Tdp1 bind non-specifically upstream of a 3'-blocking lesion and is preferentially stabilized at 3'-DNA ends corresponding to its site of action. C1 [Dexheimer, Thomas S.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stephen, Andrew G.; Fisher, Robert J.] SAIC Frederick Inc, Prot Chem Lab, Adv Technol Program, Frederick, MD 21702 USA. [Fivash, Matthew J.] Data Management Syst Inc, NCI Frederick, Frederick, MD 21702 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, Maryland [Z01 BC 006150-19LMP]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Our studies are supported by the Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, Maryland (Grant number Z01 BC 006150-19LMP). The wild-type human Tdp1 construct were generous gift from Dr H. Nash (Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. NR 35 TC 23 Z9 24 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2010 VL 38 IS 7 BP 2444 EP 2452 DI 10.1093/nar/gkp1206 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 584IJ UT WOS:000276744600038 PM 20097655 ER PT J AU Godiska, R Mead, D Dhodda, V Wu, CC Hochstein, R Karsi, A Usdin, K Entezam, A Ravin, N AF Godiska, Ronald Mead, David Dhodda, Vinay Wu, Chengcang Hochstein, Rebecca Karsi, Attila Usdin, Karen Entezam, Ali Ravin, Nikolai TI Linear plasmid vector for cloning of repetitive or unstable sequences in Escherichia coli SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COPY-NUMBER PLASMID; HUMAN GENOME; PROPHAGE N-15; PHAGE N-15; DNA; GENE; REPLICATION; TRANSCRIPTION; EXPRESSION; GENERATION AB Despite recent advances in sequencing, complete finishing of large genomes and analysis of novel proteins they encode typically require cloning of specific regions. However, many of these fragments are extremely difficult to clone in current vectors. Superhelical stress in circular plasmids can generate secondary structures that are substrates for deletion, particularly in regions that contain numerous tandem or inverted repeats. Common vectors also induce transcription and translation of inserted fragments, which can select against recombinant clones containing open reading frames or repetitive DNA. Conversely, transcription from cloned promoters can interfere with plasmid stability. We have therefore developed a novel Escherichia coli cloning vector (termed 'pJAZZ' vector) that is maintained as a linear plasmid. Further, it contains transcriptional terminators on both sides of the cloning site to minimize transcriptional interference between vector and insert. We show that this vector stably maintains a variety of inserts that were unclonable in conventional plasmids. These targets include short nucleotide repeats, such as those of the expanded Fragile X locus, and large AT-rich inserts, such as 20-kb segments of genomic DNA from Pneumocystis, Plasmodium, Oxytricha or Tetrahymena. The pJAZZ vector shows decreased size bias in cloning, allowing more uniform representation of larger fragments in libraries. C1 [Godiska, Ronald; Mead, David; Dhodda, Vinay; Wu, Chengcang] Lucigen Corp, Middleton, WI 53562 USA. [Hochstein, Rebecca] Montana State Univ, Bozeman, MT 59717 USA. [Karsi, Attila] Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Mississippi State, MS 39762 USA. [Usdin, Karen; Entezam, Ali] NIDDKD, NIH, Bethesda, MD 20892 USA. [Ravin, Nikolai] Russian Acad Sci, Ctr Bioengn, Moscow, Russia. RP Godiska, R (reprint author), Lucigen Corp, 2120 W Greenview Dr, Middleton, WI 53562 USA. EM rgodiska@lucigen.com RI Ravin, Nikolai/C-5907-2014; OI Karsi, Attila/0000-0001-6845-3346; Godiska, Ronald/0000-0003-0101-6365 FU National Institutes of Health [5R44 HG003076-03]; Lucigen's general budget FX An SBIR grant awarded to Lucigen by the National Institutes of Health (grant no. 5R44 HG003076-03). Funding for open access charge: Page charges will be funded from Lucigen's general budget. The source of funds is from commercial sales of products. NR 42 TC 32 Z9 33 U1 3 U2 13 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 APR PY 2010 VL 38 IS 6 AR e88 DI 10.1093/nar/gkp1181 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578PB UT WOS:000276304600004 PM 20040575 ER PT J CA Womens Hlth Initiative Study Cogni TI Effects of Conjugated Equine Estrogens on Cognition and Affect in Postmenopausal Women With Prior Hysterectomy EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 NIA, Baltimore, MD 21224 USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Medstar Res Inst, Hyattsville, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD APR PY 2010 VL 65 IS 4 BP 242 EP 243 DI 10.1097/01.ogx.0000371720.87500.99 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 591YQ UT WOS:000277341900018 ER PT J AU Zhang, J Troendle, J Mikolajczyk, R Sundaram, R Beaver, J Fraser, W AF Zhang, Jun Troendle, James Mikolajczyk, Rafael Sundaram, Rajeshwari Beaver, Julie Fraser, William TI The Natural History of the Normal First Stage of Labor SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Maternal Fetal Med ID CESAREAN DELIVERY RATES; ACTIVE LABOR; PREGNANCY; INDUCTION; ARREST AB OBJECTIVE: To examine labor patterns in a large population and to explore an alternative approach for diagnosing abnormal labor progression. METHODS: Data from the National Collaborative Perinatal Project were used. A total of 26,838 parturients were selected who had a singleton term gestation, spontaneous onset of labor, vertex presentation, and a normal perinatal outcome. A repeated-measures analysis was used to construct average labor curves by parity. An interval-censored regression was used to estimate duration of labor stratified by cervical dilation at admission and centimeter by centimeter. RESULTS: The median time needed to progress from one centimeter to the next became shorter as labor advanced (eg, from 1.2 hours at 3-4 cm to 0.4 hours at 7-8 cm in nulliparas). Nulliparous women had the longest and most gradual labor curve; multiparous women of different parities had very similar curves. Nulliparas may start the active phase after 5 cm of cervical dilation and may not necessarily have a clear active phase characterized by precipitous dilation. The deceleration phase in the late active phase of labor may be an artifact in many cases. CONCLUSION: The active phase of labor may not start until 5 cm of cervical dilation in multiparas and even later in nulliparas. A 2-hour threshold for diagnosing labor arrest may be too short before 6 cm of dilation, whereas a 4-hour limit may be too long after 6 cm. Given that cervical dilation accelerates as labor advances, a graduated approach based on levels of cervical dilation to diagnose labor protraction and arrest is proposed. (Obstet Gynecol 2010; 115: 705-10) C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Univ Bremen, Bremen Inst Prevent Res & Social Med, Dept Clin Epidemiol, Bremen, Germany. Univ Montreal, Dept Obstet & Gynecol, Montreal, PQ, Canada. RP Zhang, J (reprint author), NICHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM zhangj@mail.nih.gov OI Mikolajczyk, Rafael/0000-0003-1271-7204; Sundaram, Rajeshwari/0000-0002-6918-5002 FU Intramural NIH HHS NR 22 TC 73 Z9 85 U1 3 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 APR PY 2010 VL 115 IS 4 BP 705 EP 710 DI 10.1097/AOG.0b013e3181d55925 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 580QH UT WOS:000276463700005 PM 20308828 ER PT J AU Sangave, A Faia, LJ Yeh, S Chan, CC Nussenblatt, RB Sen, HN AF Sangave, Amit Faia, Lisa J. Yeh, Steven Chan, Chi-Chao Nussenblatt, Robert B. Sen, H. Nida TI A Case of Rapid Progression and Vision Loss in a Patient with Primary Intraocular Lymphoma SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Primary intraocular lymphoma; progression; sudden; rapid AB Methods: A 71-year-old woman with a history of PIOL presented with a sudden decline in vision. MRI, CSF cytology, and ocular examination 2 months prior were unremarkable. Results: Repeat MRI of the brain and orbits at this time revealed a 0.8 x 2.4-cm lesion of the left choroid plexus. LP revealed rare atypical B cells. The patient rapidly deteriorated and died a month later. Conclusion: Recognition of the potential for rapid progression and mortality in patients with PIOL is essential. C1 [Sangave, Amit; Faia, Lisa J.; Yeh, Steven; Chan, Chi-Chao; Nussenblatt, Robert B.; Sen, H. Nida] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sen, HN (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10 N 112, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU NEI FX This study was supported by the NEI intramural research program. NR 5 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2010 VL 18 IS 2 BP 99 EP 100 DI 10.3109/09273940903370748 PG 2 WC Ophthalmology SC Ophthalmology GA 579IR UT WOS:000276363400006 PM 20370335 ER PT J AU Zhu, XG Zhao, L Willingham, MC Cheng, SY AF Zhu, X-G Zhao, L. Willingham, M. C. Cheng, S-Y TI Thyroid hormone receptors are tumor suppressors in a mouse model of metastatic follicular thyroid carcinoma SO ONCOGENE LA English DT Article DE thyroid cancer; mouse model; mutations of thyroid hormone receptors ID DOMINANT-NEGATIVE ACTIVITY; SECRETING PITUITARY-TUMOR; TRANSFORMING GENE PTTG; CLEAR-CELL CARCINOMA; LINKED KINASE ILK; BETA-RECEPTOR; TRANSCRIPTIONAL ACTIVITY; NUCLEAR RECEPTORS; TRANSGENIC MICE; V-ERBA AB Aberrant expression and mutations of thyroid hormone receptor genes (TRs) are closely associated with several types of human cancers. To test the hypothesis that TRs could function as tumor suppressors, we took advantage of mice with deletion of all functional TRs (TR alpha 1(-/-)TR beta(-/-) mice). As these mice aged, they spontaneously developed follicular thyroid carcinoma with pathological progression from hyperplasia to capsular invasion, vascular invasion, anaplasia and metastasis to the lung, similar to human thyroid cancer. Detailed molecular analysis revealed that known tumor promoters such as pituitary tumor-transforming gene were activated and tumor suppressors such as peroxisome proliferator-activated receptor gamma and p53 were suppressed during carcinogenesis. In addition, consistent with the human cancer, AKT-mTOR-p70(S6K) signaling and vascular growth factor and its receptor were activated to facilitate tumor progression. This report presents in vivo evidence that functional loss of both TR alpha 1 and TR beta genes promotes tumor development and metastasis. Thus, TRs could function as tumor suppressors in a mouse model of metastatic follicular thyroid cancer. Oncogene (2010) 29, 1909-1919; doi:10.1038/onc.2009.476; published online 11 January 2010 C1 [Zhu, X-G; Zhao, L.; Cheng, S-Y] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Willingham, M. C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural Research Program of the 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 Drs H Ying and Y Kato for the analyses of survival curves and thyroid growth in the early phase of the present work. NR 63 TC 30 Z9 31 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 13 BP 1909 EP 1919 DI 10.1038/onc.2009.476 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 577CV UT WOS:000276199600004 PM 20062085 ER PT J AU Yamasaki, N Miyazaki, K Nagamachi, A Koller, R Oda, H Miyazaki, M Sasaki, T Honda, Z Wolff, L Inaba, T Honda, H AF Yamasaki, N. Miyazaki, K. Nagamachi, A. Koller, R. Oda, H. Miyazaki, M. Sasaki, T. Honda, Z-i Wolff, L. Inaba, T. Honda, H. TI Identification of Zfp521/ZNF521 as a cooperative gene for E2A-HLF to develop acute B-lineage leukemia SO ONCOGENE LA English DT Article DE E2A-HLF; inducible knock-in mice; retrovirus insertional mutagenesis; Zfp521/ZNF521 ID ZINC-FINGER PROTEIN; RETROVIRAL INSERTIONAL MUTAGENESIS; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSGENIC MICE; TRANSCRIPTION FACTOR; DOWNSTREAM TARGET; MYELOID-LEUKEMIA; CELL DEVELOPMENT; BLAST CRISIS AB E2A-hepatic leukemia factor (HLF) is a chimeric protein found B-lineage acute lymphoblastic leukemia (ALL) with t(17;19). To analyze the leukemogenic process and to create model mice for t(17;19)-positive leukemia, we generated inducible knock-in (iKI) mice for E2A-HLF. Despite the induced expression of E2A-HLF in the hematopoietic tissues, no disease was developed during the long observation period, indicating that additional gene alterations are required to develop leukemia. To elucidate this process, E2A-HLF iKI and control littermates were subjected to retroviral insertional mutagenesis. Virus infection induced acute leukemias in E2A-HLF iKI mice with higher morbidity and mortality than in control mice. Inverse PCR detected three common integration sites specific for E2A-HLF iKI leukemic mice, which induced overexpression of zinc-finger transcription factors: growth factor independent 1 (Gfi1), zinc-finger protein subfamily 1A1 isoform a (Zfp1a1, also known as Ikaros) and zinc-finger protein 521 (Zfp521). Interestingly, tumors with Zfp521 integration exclusively showed B-lineage ALL, which corresponds to the phenotype of human t(17;19)-positive leukemia. In addition, ZNF521 (human counterpart of Zfp521) was found to be over-expressed in human leukemic cell lines harboring t(17;19). Moreover, both iKI for E2A-HLF and transgenic for Zfp521 mice frequently developed B-lineage ALL. These results indicate that a set of transcription factors promote leukemic transformation of E2A-HLF-expressing hematopoietic progenitors and suggest that aberrant expression of Zfp521/ZNF521 may be clinically relevant to t(17;19)positive B-lineage ALL. Oncogene (2010) 29, 1963-1975; doi:10.1038/onc.2009.475; published online 11 January 2010 C1 [Yamasaki, N.; Miyazaki, K.; Sasaki, T.; Honda, H.] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Dev Biol, Minami Ku, Hiroshima 7348553, Japan. [Nagamachi, A.; Inaba, T.] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Mol Oncol, Minami Ku, Hiroshima 7348553, Japan. [Koller, R.; Wolff, L.] NCI, Leukemogenosis Sect, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Oda, H.] Tokyo Womens Med Univ, Dept Pathol, Shinjuku Ku, Tokyo, Japan. [Miyazaki, M.] Hiroshima Univ, Grad Sch Biomed Sci, Dept Immunol, Minami Ku, Hiroshima 7348553, Japan. [Honda, Z-i] Univ Tokyo, Grad Sch Med, Fac Med, Dept Allergy & Rheumatol,Bunkyo Ku, Tokyo, Japan. RP Honda, H (reprint author), Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Dev Biol, Minami Ku, 1-2-3 Kasumi, Hiroshima 7348553, Japan. EM hhonda@hiroshima-u.ac.jp FU Ministry of Education, Science and Culture of Japan; Ministry of Health, Labour and Welfare of Japan [13-2]; Takeda Science Foundation; Astellas Foundation FX We thank Yuki Sakai, Kayoko Hashimoto, Yuko Tsukawaki and Rika Tai, for the care of the mice and technical assistance, Dr Nobuaki Yoshida for E14 ES cells, Dr Soren Warming, Dr Neal G Copeland and Dr Nancy A Jenkins for mouse Zfp521 cDNA, Dr Koichi Ikuta for mouse TCRJb probe, Dr Hirotaka Matsui for statistical analysis and Dr Takuro Nakamura for helpful discussion. This work was in part supported by a grant-in-aid from the Ministry of Education, Science and Culture of Japan, a grant-in-aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (13-2), Takeda Science Foundation, Astellas Foundation for Research on Metabolic Disorders, the Japan Leukaemia Research Fund and Tsuchiya Foundation. NR 43 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 13 BP 1963 EP 1975 DI 10.1038/onc.2009.475 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 577CV UT WOS:000276199600009 PM 20062079 ER PT J AU Mishra, PJ Ha, L Rieker, J Sviderskaya, EV Bennett, DC Oberst, MD Kelly, K Merlino, G AF Mishra, P. J. Ha, L. Rieker, J. Sviderskaya, E. V. Bennett, D. C. Oberst, M. D. Kelly, K. Merlino, G. TI Dissection of RAS downstream pathways in melanomagenesis: a role for Ral in transformation SO ONCOGENE LA English DT Article DE anchorage-independent growth; BRaf; melanoma; NRas; PI3K; RalGEF ID CELLULAR-TRANSFORMATION; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; SIGNALING PATHWAYS; BRAF MUTATIONS; CANCER; GTPASES; CELLS; ACTIVATION; MIGRATION AB Cutaneous malignant melanoma is considered one of the most deadly human cancers, based on both its penchant for metastatic spread and its typical resistance to currently available therapy. Long known to harbor oncogenic NRAS mutations, melanomas were more recently reported to be frequent bearers of activating mutations in BRAF, one of the effectors situated downstream of wild-type NRAS. NRAS and BRAF mutations are rarely found in the same melanoma, suggesting that they may possess important overlapping oncogenic activities. Here, we compare and contrast the oncogenic roles of the three major NRas downstream effectors, Raf, phosphatidylinositol 3-kinase (PI3K) and Ral guanine exchange factor (RalGEF), using genetically engineered Arf-deficient immortalized mouse melanocytes as a model system. Although no single downstream pathway could recapitulate all of the consequences of oncogenic NRas expression, our data indicate a prominent role for BRaf and PI3K in melanocyte senescence and invasiveness, respectively. More surprisingly, we discovered that constitutive RalGEF activation had a major impact on several malignant phenotypes, particularly anchorage-independent growth, indicating that this often overlooked pathway should be more carefully evaluated as a possible therapeutic target. Oncogene (2010) 29, 2449-2456; doi:10.1038/onc.2009.521; published online 1 February 2010 C1 [Mishra, P. J.; Ha, L.; Rieker, J.; Merlino, G.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Ha, L.] US FDA, Div Monoclonal Antibody, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Sviderskaya, E. V.; Bennett, D. C.] Univ London, Div Basic Med Sci, London, England. [Oberst, M. D.; Kelly, K.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. RP Merlino, G (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bldg 37,Room 5002,37 Convent Dr, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov RI Sviderskaya, Elena/D-2419-2009; Bennett, Dorothy/C-2418-2008 OI Bennett, Dorothy/0000-0002-3639-7527 FU NCI [N01-CO-12400]; National Institutes of Health; Wellcome Trust [078327] FX We thank Dr Christopher Counter (Duke University) for useful discussions, and for communicating data before publication. We acknowledge Dr Paul Khavari (Stanford University) for gifting the NRas, PI3K and BRaf retroviral vectors, and Drs Frederique Zindy and Charles Sherr (St Jude Children's Research Hospital) for the Arf-deficient mouse skins from which the immortalized melanocytes were generated. The PEP7 and PEP8H antibodies were a gift from Dr Vince Hearing (NCI). The pEF-CAAX-Raf-1 vector was a gift from Dr Silvio J Gutkind (NIH/NIDCR). This work was supported in part by the Intramural Research Program of the NCI, National Institutes of Health, in part by NCI Contract N01-CO-12400, and in part by Wellcome Trust Program Grant 078327 (to EVS). NR 41 TC 37 Z9 37 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 16 BP 2449 EP 2456 DI 10.1038/onc.2009.521 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 586YK UT WOS:000276951500013 PM 20118982 ER PT J AU Zheng, C Voutetakis, A Metzger, M Afione, S Cotrim, AP Eckhaus, MA Rivera, VM Clackson, T Chiorini, JA Donahue, RE Dunbar, CE Baum, BJ AF Zheng, C. Voutetakis, A. Metzger, M. Afione, S. Cotrim, A. P. Eckhaus, M. A. Rivera, V. M. Clackson, T. Chiorini, J. A. Donahue, R. E. Dunbar, C. E. Baum, B. J. TI Evaluation of a rapamycin-regulated serotype 2 adeno-associated viral vector in macaque parotid glands SO ORAL DISEASES LA English DT Article DE AAV2; rapamycin-regulation; gene transfer; macaque; parotid ID MEDIATED GENE-TRANSFER; RAT SALIVARY-GLANDS; NONHUMAN-PRIMATES; IN-VIVO; ADENOVIRAL VECTOR; AAV VECTOR; VIRUS; EXPRESSION; SECRETION; THERAPEUTICS AB Objectives: Salivary glands are useful target organs for local and systemic gene therapeutics. For such applications, the regulation of transgene expression is important. Previous studies by us in murine submandibular glands showed that a rapamycin transcriptional regulation system in a single serotype 2, adeno-associated viral (AAV2) vector was effective for this purpose. This study evaluated if such a vector was similarly useful in rhesus macaque parotid glands. Methods: A recombinant AAV2 vector (AAV-TF-RhEpo-2.3w), encoding rhesus erythropoietin (RhEpo) and a rapamycin-inducible promoter, was constructed. The vector was administered to macaques at either of two doses [1.5 x 1011 (low dose) or 1.5 x 1012 (high dose) vector genomes] via cannulation of Stensen's duct. Animals were followed up for 12-14 weeks and treated at intervals with rapamycin (0.1 or 0.5 mg kg-1) to induce gene expression. Serum chemistry, hematology, and RhEpo levels were measured at interval. Results: AAV-TF-RhEpo-2.3w administration led to low levels of rapamycin-inducible RhEpo expression in the serum of most macaques. In five animals, no significant changes were seen in serum chemistry and hematology values over the study. One macaque, however, developed pneumonia, became anemic and subsequently required euthanasia. After the onset of anemia, a single administration of rapamycin led to significant RhEpo production in this animal. Conclusion: Administration of AAV-TF-RhEpo-2.3w to macaque parotid glands was generally safe, but led only to low levels of serum RhEpo in healthy animals following rapamycin treatment. C1 [Baum, B. J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. [Metzger, M.; Donahue, R. E.; Dunbar, C. E.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Eckhaus, M. A.] NIH, Div Vet Resources, Dept Human Hlth Serv, Bethesda, MD 20892 USA. [Rivera, V. M.; Clackson, T.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. RP Baum, BJ (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU National Institute of Dental and Craniofacial Research and National Heart, Lung and Blood Institute FX This research was supported by the Intramural Research Programs of the National Institute of Dental and Craniofacial Research and National Heart, Lung and Blood Institute. NR 32 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD APR PY 2010 VL 16 IS 3 BP 269 EP 277 DI 10.1111/j.1601-0825.2009.01631.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 570AS UT WOS:000275644600007 PM 20374510 ER PT J AU Benke, EM Ji, Y Patel, V Wang, HX Miyazaki, H Yeudall, WA AF Benke, Emily M. Ji, Youngmi Patel, Vyomesh Wang, Huixin Miyazaki, Hiroshi Yeudall, W. Andrew TI VEGF-C contributes to head and neck squamous cell carcinoma growth and motility SO ORAL ONCOLOGY LA English DT Article DE Squamous cell carcinoma; Proliferation; Motility; Vascular endothelial cell growth factor; Oral cancer ID LYMPH-NODE METASTASIS; ACTIVATED PROTEIN-KINASE; FACTOR-KAPPA-B; SIGNALING PATHWAYS; FACTOR RECEPTOR; CANCER CELLS; IN-VIVO; ANGIOGENESIS; PROLIFERATION; INTERLEUKIN-8 AB Previous work from our laboratory has demonstrated overexpression of chemokines in head and neck cancer and the utility of targeting these proteins for tumor therapy in a preclinical model. However, the mechanisms involved are unexplored. Through gene expression analysis, we found that expression of vascular endothelial growth factor (VEGF-C) was elevated in HN12 cells expressing high levels of CXCL5. In the present study, we have investigated the contribution of VEGF-C to tumor cell growth and motility. RNAi-mediated knockdown of VEGF-C expression in HN12 cells, which express high levels of CXCL5, resulted in a decrease in proliferation. Conversely, forced expression of VEGF-C in HN4 tumor cells with low endogenous CXCL5 levels increased cell growth. Suppression of VEGF-C inhibited migration of HN12 cells. Similarly, HN4 cells showed reduced migration towards conditioned media collected from HN12 cells with VEGF-C knockdown compared to controls, while HN4/VEGF-C conditioned media stimulated cell migration. Moreover, tumor growth in vivo was markedly reduced when VEGF-C expression was blocked by shRNA. Finally, determination of VEGF-C expression in squamous carcinoma cell lines revealed universal overexpression compared to normal keratinocytes. These findings support a role for VEGF-C in head and neck squamous cell carcinogenesis. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Yeudall, W. Andrew] Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, VCU Sch Dent, Richmond, VA 23298 USA. [Yeudall, W. Andrew] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Yeudall, W. Andrew] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Ji, Youngmi] NIAMSD, Clin & Expt Orthoped Branch, Bethesda, MD 20892 USA. [Patel, Vyomesh] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. RP Yeudall, WA (reprint author), Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, VCU Sch Dent, 521 N 11th St,POB 980566, Richmond, VA 23298 USA. EM wayeudall@vcu.edu NR 38 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD APR PY 2010 VL 46 IS 4 BP E19 EP E24 DI 10.1016/j.oraloncology.2010.02.006 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 575TS UT WOS:000276092200020 PM 20227330 ER PT J AU Lang, T Streeper, T Cawthon, P Baldwin, K Taaffe, DR Harris, TB AF Lang, T. Streeper, T. Cawthon, P. Baldwin, K. Taaffe, D. R. Harris, T. B. TI Sarcopenia: etiology, clinical consequences, intervention, and assessment SO OSTEOPOROSIS INTERNATIONAL LA English DT Review DE Aging; Falls; Imaging; Muscle strength; Sarcopenia; Skeletal muscle ID AGE-RELATED-CHANGES; POSITRON-EMISSION-TOMOGRAPHY; MUSCLE PROTEIN-SYNTHESIS; HUMAN SKELETAL-MUSCLE; MAGNETIC-RESONANCE-SPECTROSCOPY; MITOCHONDRIAL-DNA MUTATIONS; LOWER-EXTREMITY PERFORMANCE; FIBER CONTRACTILE FUNCTION; ELITE SOCCER PLAYERS; BODY-COMPOSITION AB The aging process is associated with loss of muscle mass and strength and decline in physical functioning. The term sarcopenia is primarily defined as low level of muscle mass resulting from age-related muscle loss, but its definition is often broadened to include the underlying cellular processes involved in skeletal muscle loss as well as their clinical manifestations. The underlying cellular changes involve weakening of factors promoting muscle anabolism and increased expression of inflammatory factors and other agents which contribute to skeletal muscle catabolism. At the cellular level, these molecular processes are manifested in a loss of muscle fiber cross-sectional area, loss of innervation, and adaptive changes in the proportions of slow and fast motor units in muscle tissue. Ultimately, these alterations translate to bulk changes in muscle mass, strength, and function which lead to reduced physical performance, disability, increased risk of fall-related injury, and, often, frailty. In this review, we summarize current understanding of the mechanisms underlying sarcopenia and age-related changes in muscle tissue morphology and function. We also discuss the resulting long-term outcomes in terms of loss of function, which causes increased risk of musculoskeletal injuries and other morbidities, leading to frailty and loss of independence. C1 [Lang, T.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, UCB Joint Bioengn Grad Grp, Ctr Mol & Funct Imaging, San Francisco, CA 94143 USA. [Cawthon, P.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Baldwin, K.] Univ Calif Irvine, Irvine, CA USA. [Taaffe, D. R.] Univ Queensland, Sch Human Movement Studies, Brisbane, Qld, Australia. [Harris, T. B.] NIA, Lab Epidemiol & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Lang, T (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, UCB Joint Bioengn Grad Grp, Ctr Mol & Funct Imaging, 185 Berry St,Suite 350, San Francisco, CA 94143 USA. EM thomas.lang@radiology.ucsf.edu RI Lang, Thomas/B-2685-2012 OI Lang, Thomas/0000-0002-3720-8038 NR 155 TC 203 Z9 217 U1 5 U2 60 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2010 VL 21 IS 4 BP 543 EP 559 DI 10.1007/s00198-009-1059-y PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 567BD UT WOS:000275416400002 PM 19779761 ER PT J AU El Feghaly, RE McGann, L Bonville, CA Branigan, PJ Suryadevera, M Rosenberg, HF Domachowske, JB AF El Feghaly, Rana E. McGann, Lindsay Bonville, Cynthia A. Branigan, Patrick J. Suryadevera, Manika Rosenberg, Helene F. Domachowske, Joseph B. TI Local Production of Inflammatory Mediators During Childhood Parainfluenza Virus Infection SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE parainfluenza virus; innate immunity; respiratory viral infection ID RESPIRATORY SYNCYTIAL VIRUS; HELPER TYPE-2 CYTOKINES; YOUNG-CHILDREN; NEBULIZED BUDESONIDE; ORAL DEXAMETHASONE; INFLUENZA-VIRUS; UNITED-STATES; BRONCHIOLITIS; INFANTS; DISEASE AB Objective: To describe the clinical manifestations of parainfluenza virus (PIV) infection and to characterize biochemical markers of PIV disease severity. Patients and Methods: We reviewed the medical records of 165 children who had a nasal wash culture positive for PIV at our institution between 1998 and 2008. Nasal wash samples were assayed for 26 inflammatory mediators using Luminex bead proteomics. Results: A total of 153 patients, ages 2 weeks to 12 years, with single virus infection were included in our final analysis. Fifty-two patients were infected with PIV1, 19 with PIV2, 74 with PIV3, and 8 with PIV4. Lower respiratory tract infection (LRTI) was diagnosed in 67 (44%) patients, 21 (14%) had laryngotracheobronchitis, and 49 (32%) had an upper respiratory infection other than laryngotracheobronchitis. LRTI was diagnosed in 54% of patients infected with PIV3, 35% of those infected with PIV1, 26% of those with PIV2, and 50% of those with PIV4. Compared with uninfected control patients, PIV-infected patients had higher nasal wash concentrations of interleukin-6, CX-chemokine ligand 8 (CXCL8 or interleukin-8), CCL3 (macrophage inflammatory protein-1 beta), CCL4 (macrophage inflammatory protein-1 beta), CXCL9 (monokine induced by interferon gamma), and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES). Patients with LRTI, moderate or severe illness, and PIV 1 or 3 (respirovirus) infection had higher nasal wash concentrations of CXCL8 when compared with patients with upper respiratory infection, mild illness, or PIV 2 and 4 (rubulavirus) infection (P < 0.05). Conclusions: PIV infection causes a spectrum of illnesses associated with the expression and release of several proinflammatory mediators. Of note, elevated concentrations of CXCL8 in nasal wash samples are associated with more severe forms of PIV disease. C1 [El Feghaly, Rana E.; McGann, Lindsay; Bonville, Cynthia A.; Suryadevera, Manika; Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. [Branigan, Patrick J.] Centocor Inc, Dept Infect Dis Res, Radnor, PA USA. [Rosenberg, Helene F.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. EM domachoj@upstate.edu OI Branigan, Patrick/0000-0001-9741-9067 FU NIAID Division of Intramural Research and the Children's Miracle Network of Central New York FX NIAID Division of Intramural Research and the Children's Miracle Network of Central New York. NR 40 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2010 VL 29 IS 4 BP E26 EP E31 DI 10.1097/INF.0b013e3181d5da2a PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 581ZW UT WOS:000276565600031 PM 20182399 ER PT J AU Andrade, AC Lui, JC Nilsson, O AF Andrade, Anenisia C. Lui, Julian C. Nilsson, Ola TI Temporal and spatial expression of a growth-regulated network of imprinted genes in growth plate SO PEDIATRIC NEPHROLOGY LA English DT Article; Proceedings Paper CT 8th International Symposium on Growth and Nutrition in Children with Chronic Renal Disease CY MAY 28-30, 2009 CL Asturias, SPAIN DE Growth plate; Chondrocyte; Growth; Gene expression; Imprinted genes; Network ID DEPENDENT KINASE INHIBITOR; LONGITUDINAL BONE-GROWTH; MESSENGER-RNA; RESTING ZONE; H19 GENE; DISRUPTION; SENESCENCE; P57(KIP2); CARTILAGE; NECDIN AB In mammals, the somatic growth rate is rapid during fetal and early postnatal life and then gradually declines and eventually stops. In search of the fundamental biological mechanism causing coordinated growth deceleration in multiple tissues, a network of imprinted genes was recently identified based on a coordinated decline in expression in several organs during postnatal growth. To explore a possible role in longitudinal bone growth, we characterized expression of the network during postnatal growth in microdissected metaphyseal bone and growth plate zones of 1-, 3-, and 9-week-old rats using real-time PCR. The expression pattern of the network is modified in growth plate. Similar to the coordinated decline previously observed in kidney, lung, liver, and heart, expression of all genes, except Gtl2, decreased with age in metaphyseal bone. On the contrary, Mest, Dlk1, H19, and Gtl2 decreased, and Cdkn1c, Grb10, and Slc38a4 increased with age in growth plate. During differentiation from resting to hypertrophic zone, Mest, Dlk1, Grb10, and Gtl2 expression decreased, whereas Slc38a4 expression increased. In particular, developmental changes in the expression of growth-promoting genes, Mest, Dlk1, Gtl2, and growth-inhibitory genes, Cdkn1c and Grb10, may contribute to the decline in longitudinal bone growth that occurs with age. C1 [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Pediat Endocrinol Unit, S-17176 Stockholm, Sweden. [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Ctr Mol Med, Dept Woman & Child Hlth, S-17176 Stockholm, Sweden. [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Univ Hosp, S-17176 Stockholm, Sweden. [Andrade, Anenisia C.] Santa Casa Sao Paulo, Dept Pediat, Pediat Endocrinol Unit, Sao Paulo, Brazil. [Lui, Julian C.] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Nilsson, O (reprint author), Karolinska Inst, Pediat Endocrinol Unit, Q2-08, S-17176 Stockholm, Sweden. EM Ola.Nilsson@ki.se RI Lui, Chun Kin Julian/E-2253-2012; OI Nilsson, Ola/0000-0002-9986-8138 NR 28 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD APR PY 2010 VL 25 IS 4 BP 617 EP 623 DI 10.1007/s00467-009-1339-y PG 7 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 560LQ UT WOS:000274904600006 PM 19902269 ER PT J AU El-Mohandes, AAE Kiely, M Blake, SM Gantz, MG El-Khorazaty, MN AF El-Mohandes, Ayman A. E. Kiely, Michele Blake, Susan M. Gantz, Marie G. El-Khorazaty, M. Nabil TI An Intervention to Reduce Environmental Tobacco Smoke Exposure Improves Pregnancy Outcomes SO PEDIATRICS LA English DT Article DE behavioral intervention; environmental tobacco smoke; pregnant women; black; birth weight; preterm birth ID AFRICAN-AMERICAN WOMEN; LOW-BIRTH-WEIGHT; METAANALYSIS; DISPARITIES; NONSMOKERS; CHILDREN; HEALTH; TRIAL AB OBJECTIVE: We tested the efficacy of a cognitive-behavioral intervention in reducing environmental tobacco smoke exposure (ETSE) and improving pregnancy outcomes among black women. METHODS: We recruited 1044 women to a randomized, controlled trial during 2001-2004 in Washington, DC. Data on 691 women with self-reported ETSE were analyzed. A subset of 520 women with ETSE and salivary cotinine levels (SCLs) of <20 ng/mL were also analyzed. Individually tailored counseling sessions, adapted from evidence-based interventions for ETSE and other risks, were delivered to the intervention group. The usual-care group received routine prenatal care as determined by their provider. Logistic regression models were used to predict ETSE before delivery and adverse pregnancy outcomes. RESULTS: Women in the intervention were less likely to self-report ETSE before delivery when controlling for other covariates (odds ratio [OR]: 0.50 [95% confidence interval (CI): 0.35-0.71]). Medicaid recipients were more likely to have ETSE (OR: 1.97 [95% CI: 1.31-2.96]). With advancing maternal age, the likelihood of ETSE was less (OR: 0.96 [95% CI: 0.93-0.99]). For women in the intervention, the rates of very low birth weight (VLBW) and very preterm birth (VPTB) were significantly improved (OR: 0.11 [95% CI: 0.01-0.86] and OR: 0.22 [95% CI: 0.07-0.68], respectively). For women with an SCL of <20 ng/mL, maternal age was not significant. Intimate partner violence at baseline significantly increased the chances of VLBW and VPTB (OR: 3.75 [95% CI: 1.02-13.81] and 2.71 [95% CI: 1.11-6.62], respectively). These results were true for mothers who reported ETSE overall and for those with an SCL of <20 ng/mL. CONCLUSIONS: This is the first randomized clinical trial demonstrating efficacy of a cognitive-behavioral intervention targeting ETSE in pregnancy. We significantly reduced ETSE as well as VPTB and VLBW, leading causes of neonatal mortality and morbidity in minority populations. This intervention may reduce health disparities in reproductive outcomes. Pediatrics 2010;125:721-728 C1 [El-Mohandes, Ayman A. E.] Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE 68198 USA. [Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Blake, Susan M.] George Washington Univ, Dept Prevent & Community Hlth, Washington, DC USA. [Gantz, Marie G.; El-Khorazaty, M. Nabil] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. RP El-Mohandes, AAE (reprint author), Univ Nebraska Med Ctr, Coll Publ Hlth, 984355 Nebraska Med Ctr, Omaha, NE 68198 USA. EM aelmohandes@unmc.edu FU National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development [3U18HD030445, 3U18HD030447, 5U18HD31206, 3U18HD03919, 5U18HD036104]; National Center on Minority Health and Health Disparities FX Funded by the National Institutes of Health (NIH).; This study was supported by grants 3U18HD030445, 3U18HD030447, 5U18HD31206, 3U18HD03919, and 5U18HD036104 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center on Minority Health and Health Disparities. NR 29 TC 30 Z9 31 U1 0 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2010 VL 125 IS 4 BP 721 EP 728 DI 10.1542/peds.2009-1809 PG 8 WC Pediatrics SC Pediatrics GA 577QR UT WOS:000276239600016 PM 20211945 ER PT J AU Kim, NH Pavkov, ME Knowler, WC Hanson, RL Weil, EJ Curtis, JM Bennett, PH Nelson, RG AF Kim, Nan Hee Pavkov, Meda E. Knowler, William C. Hanson, Robert L. Weil, E. Jennifer Curtis, Jeffrey M. Bennett, Peter H. Nelson, Robert G. TI Predictive Value of Albuminuria in American Indian Youth With or Without Type 2 Diabetes SO PEDIATRICS LA English DT Article DE diabetic nephropathy; epidemiology; incidence; longitudinal; prevalence; risk factors ID GLOMERULAR-FILTRATION-RATE; PIMA-INDIANS; GLUCOSE-TOLERANCE; RENAL-DISEASE; MELLITUS; MICROALBUMINURIA; PREVALENCE; CHILDREN; COMPLICATIONS; NEPHROPATHY AB OBJECTIVE: To examine the prognostic significance of elevated albuminuria in youth with type 2 diabetes. PATIENTS AND METHODS: Cross-sectional and prospective studies were conducted on Pima Indian youth aged 5 to 19 years at baseline who were examined between July 1, 1982, and December 31, 2007. Prevalence and sequential changes in the level of microalbuminuria (30 <= albumin-to-creatinine ratio [ACR] < 300 mg/g) and macroalbuminuria (ACR >= 300 mg/g) and incidence of macroalbuminuria were computed according to the presence or absence of type 2 diabetes. RESULTS: The prevalence of microalbuminuria and macroalbuminuria was 6.5% and 0.6% in the 3856 nondiabetic youth and 18.5% and 2.9% in the 103 youth with diabetes, respectively. One hundred forty-one of 187 (75.4%) nondiabetic youth, but only 1 of 14 (7.1%) diabetic youth with an elevated ACR (>= 30 mg/g) regressed to an undetectable or normal ACR (<30 mg/g) on subsequent examination. In a subset of 2666 youth with a median follow-up of 8.1 years, 36 nondiabetic and 30 diabetic youth with baseline ACRs of <300 mg/g developed macroalbuminuria. For a given ACR, the incidence of macroalbuminuria was 15.9-fold (95% confidence interval: 11.1-22.6) higher in the diabetic than in the nondiabetic youth. CONCLUSIONS: Elevated albuminuria is infrequent and largely transient in nondiabetic youth, but it is relatively frequent and largely persistent in those with diabetes. Microalbuminuria in youth with type 2 diabetes strongly predicts progression to macroalbuminuria, which supports annual screening for albuminuria. Pediatrics 2010; 125: e844-e851 C1 [Kim, Nan Hee; Pavkov, Meda E.; Knowler, William C.; Hanson, Robert L.; Weil, E. Jennifer; Curtis, Jeffrey M.; Bennett, Peter H.; Nelson, Robert G.] NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. [Kim, Nan Hee] Korea Univ, Sch Med, Dept Endocrinol & Metab, Seoul, South Korea. [Pavkov, Meda E.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Nelson, RG (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rnelson@nih.gov RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 43 TC 11 Z9 11 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2010 VL 125 IS 4 BP E844 EP E851 DI 10.1542/peds.2009-1230 PG 8 WC Pediatrics SC Pediatrics GA 577QR UT WOS:000276239600053 PM 20194283 ER PT J AU Cui, YX Paules, RS AF Cui, Yuxia Paules, Richard S. TI Use of transcriptomics in understanding mechanisms of drug-induced toxicity SO PHARMACOGENOMICS LA English DT Review DE adverse drug reaction; hepatotoxicity; idiosyncratic toxicity; mechanism; nephrotoxicity; toxicogenomics ID GENE-EXPRESSION ANALYSIS; INDUCED LIVER-INJURY; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; METHAPYRILENE-INDUCED HEPATOTOXICITY; PERIPHERAL-BLOOD TRANSCRIPTOME; PRIMARY HUMAN HEPATOCYTES; RENAL TUBULAR TOXICITY; IN-VITRO; PPAR-ALPHA; MICROARRAY ANALYSIS AB Adverse drug reactions (ADRs) are an important clinical issue and a serious public health risk. Understanding the underlying mechanisms is critical for clinical diagnosis and management of different ADRs. Toxicogenomics can reveal impacts on biological pathways and processes that had not previously been considered to be involved in a drug response. Mechanistic hypotheses can be generated that can then be experimentally tested using the full arsenal of pharmacology, toxicology, molecular biology and genetics. Recent transcriptomic studies on drug-induced toxicity, which have provided valuable mechanistic insights into various ADRs, have been reviewed with a focus on nephrotoxicity and hepatotoxicity. Related issues have been discussed, including extrapolation of mechanistic findings from experimental model systems to humans using blood as a surrogate tissue for organ damage and comparative systems biology approaches. C1 [Cui, Yuxia; Paules, Richard S.] NIEHS, Environm Stress & Canc Grp, Res Triangle Pk, NC 27709 USA. RP Paules, RS (reprint author), NIEHS, Environm Stress & Canc Grp, Mail Drop D2-03,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX This research was supported (in part) by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. 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 99 TC 46 Z9 48 U1 0 U2 12 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2010 VL 11 IS 4 SI SI BP 573 EP 585 DI 10.2217/PGS.10.37 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584RD UT WOS:000276769300019 PM 20350139 ER PT J AU Reutov, VP Schechter, AN AF Reutov, V. P. Schechter, A. N. TI How in the 20th century physicists, chemists and biologists answered the question: what is life? SO PHYSICS-USPEKHI LA English DT Review ID NITRIC-OXIDE CYCLE; ACID CYCLE; ORIGIN; TETRAHYMENA; TELOMERES; SYNTHASE; MATTER; YEAST; HELIX AB The most essential achievements in 20th century biology are analyzed and the question of how throughout the last century physicists, chemists and biologists answered the question "What is life?" is considered. The most considerable scientific achievement of 20th century biology, and perhaps of all science, is considered by many to be the discovery by biologist J Watson and physicists F Crick and M Wilkins that resulted in establishing the DNA structure. The related work of well-known scientists of the USA and Europe, E Schrodinger, L Pauling, M Perutz, J Kendrew, and of the Russian scientists N K Koltsov, N W Timofeeff-Ressovsky, G A Gamow, A M Olovnikov, is analyzed. Presently, when the structure of DNA, the process of gene expression and even the genomes of human beings are already known, scientists realize that we still do not know many of the most important things. In our opinion, the 20th century studies of nucleic acids largely ignored the principle of the cyclic organization of DNA. In this connection, we analyze the principle of cyclicity, which in its generality may well complement the concept of the atomic structure of matter. C1 [Reutov, V. P.] Russian Acad Sci, Inst Higher Nervous Act & Neurophysiol, Moscow 117485, Russia. [Schechter, A. N.] NIH, Bethesda, MD 20892 USA. RP Reutov, VP (reprint author), Russian Acad Sci, Inst Higher Nervous Act & Neurophysiol, Ul Butlerova 5-A, Moscow 117485, Russia. EM valentinreutov@mail.ru; alans@intra.niddk.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 138 TC 8 Z9 9 U1 1 U2 8 PU TURPION LTD PI BRISTOL PA C/O TURPION LTD, IOP PUBLISHING, DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1063-7869 J9 PHYS-USP+ JI Phys. Usp. PD APR PY 2010 VL 53 IS 4 BP 377 EP 396 DI 10.3367/UFNe.0180.201004d.0393 PG 20 WC Physics, Multidisciplinary SC Physics GA 633YI UT WOS:000280543000004 ER PT J AU Bassett, DS Greenfield, DL Meyer-Lindenberg, A Weinberger, DR Moore, SW Bullmore, ET AF Bassett, Danielle S. Greenfield, Daniel L. Meyer-Lindenberg, Andreas Weinberger, Daniel R. Moore, Simon W. Bullmore, Edward T. TI Efficient Physical Embedding of Topologically Complex Information Processing Networks in Brains and Computer Circuits SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID CEREBRAL-CORTEX; WHITE-MATTER; HIERARCHICAL ORGANIZATION; CORTICAL THICKNESS; FRACTAL DIMENSION; GRAY-MATTER; RENTS RULE; SCHIZOPHRENIA; CONNECTIVITY; NEOCORTEX AB Nervous systems are information processing networks that evolved by natural selection, whereas very large scale integrated (VLSI) computer circuits have evolved by commercially driven technology development. Here we follow historic intuition that all physical information processing systems will share key organizational properties, such as modularity, that generally confer adaptivity of function. It has long been observed that modular VLSI circuits demonstrate an isometric scaling relationship between the number of processing elements and the number of connections, known as Rent's rule, which is related to the dimensionality of the circuit's interconnect topology and its logical capacity. We show that human brain structural networks, and the nervous system of the nematode C. elegans, also obey Rent's rule, and exhibit some degree of hierarchical modularity. We further show that the estimated Rent exponent of human brain networks, derived from MRI data, can explain the allometric scaling relations between gray and white matter volumes across a wide range of mammalian species, again suggesting that these principles of nervous system design are highly conserved. For each of these fractal modular networks, the dimensionality of the interconnect topology was greater than the 2 or 3 Euclidean dimensions of the space in which it was embedded. This relatively high complexity entailed extra cost in physical wiring: although all networks were economically or cost-efficiently wired they did not strictly minimize wiring costs. Artificial and biological information processing systems both may evolve to optimize a trade-off between physical cost and topological complexity, resulting in the emergence of homologous principles of economical, fractal and modular design across many different kinds of nervous and computational networks. C1 [Bassett, Danielle S.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA. [Bassett, Danielle S.] Univ Calif Santa Barbara, Inst Collaborat Biotechnol, Santa Barbara, CA 93106 USA. [Bassett, Danielle S.; Bullmore, Edward T.] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge, England. [Greenfield, Daniel L.; Moore, Simon W.] Univ Cambridge, Comp Lab, Cambridge CB2 3QG, England. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. [Bassett, Danielle S.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Bassett, DS (reprint author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA. EM dbassett@physics.ucsb.edu; etb23@cam.ac.uk RI Bullmore, Edward/C-1706-2012; Meyer-Lindenberg, Andreas/H-1076-2011; OI Bullmore, Edward/0000-0002-8955-8283; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Moore, Simon William/0000-0002-2806-495X FU National Institute of Biomedical Imaging & Bioengineering and the National Institute of Mental Health; National Institutes of Health, NIMH; National Institutes of Health; Gates Cambridge Trust FX This research was supported by a Human Brain Project grant from the National Institute of Biomedical Imaging & Bioengineering and the National Institute of Mental Health, and by the Intramural Research Program of the National Institutes of Health, NIMH. DSB was supported by the National Institutes of Health Graduate Partnerships Program. DLG was supported by the Gates Cambridge Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 76 TC 127 Z9 127 U1 0 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2010 VL 6 IS 4 AR e1000748 DI 10.1371/journal.pcbi.1000748 PG 14 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 602GA UT WOS:000278125300024 PM 20421990 ER PT J AU Galli, A Robay, D Osterwalder, M Bao, XZ Benazet, JD Tariq, M Paro, R Mackem, S Zeller, R AF Galli, Antonella Robay, Dimitri Osterwalder, Marco Bao, Xiaozhong Benazet, Jean-Denis Tariq, Muhammad Paro, Renato Mackem, Susan Zeller, Rolf TI Distinct Roles of Hand2 in Initiating Polarity and Posterior Shh Expression during the Onset of Mouse Limb Bud Development SO PLOS GENETICS LA English DT Article ID BHLH TRANSCRIPTION FACTOR; APICAL ECTODERMAL RIDGE; SONIC-HEDGEHOG; VERTEBRATE LIMB; FEEDBACK LOOP; RETINOIC ACID; DIGIT NUMBER; DNA-BINDING; GLI3; GENE AB The polarization of nascent embryonic fields and the endowment of cells with organizer properties are key to initiation of vertebrate organogenesis. One such event is antero-posterior (AP) polarization of early limb buds and activation of morphogenetic Sonic Hedgehog (SHH) signaling in the posterior mesenchyme, which in turn promotes outgrowth and specifies the pentadactylous autopod. Inactivation of the Hand2 transcriptional regulator from the onset of mouse forelimb bud development disrupts establishment of posterior identity and Shh expression, which results in a skeletal phenotype identical to Shh deficient limb buds. In wild-type limb buds, Hand2 is part of the protein complexes containing Hoxd13, another essential regulator of Shh activation in limb buds. Chromatin immunoprecipitation shows that Hand2-containing chromatin complexes are bound to the far upstream cis-regulatory region (ZRS), which is specifically required for Shh expression in the limb bud. Cell-biochemical studies indicate that Hand2 and Hoxd13 can efficiently transactivate gene expression via the ZRS, while the Gli3 repressor isoform interferes with this positive transcriptional regulation. Indeed, analysis of mouse forelimb buds lacking both Hand2 and Gli3 reveals the complete absence of antero-posterior (AP) polarity along the entire proximo-distal axis and extreme digit polydactyly without AP identities. Our study uncovers essential components of the transcriptional machinery and key interactions that set-up limb bud asymmetry upstream of establishing the SHH signaling limb bud organizer. C1 [Galli, Antonella; Robay, Dimitri; Osterwalder, Marco; Benazet, Jean-Denis; Zeller, Rolf] Univ Basel, Dept Biomed, Basel, Switzerland. [Bao, Xiaozhong; Mackem, Susan] Natl Canc Inst, Canc & Dev Biol Lab, Bethesda, MD USA. [Tariq, Muhammad; Paro, Renato] ETH, Dept Biosyst Sci & Engn, Basel, Switzerland. [Paro, Renato] Univ Basel, Fac Sci, Basel, Switzerland. RP Galli, A (reprint author), Columbia Univ, Med Ctr, Dept Med, New York, NY 10027 USA. EM ag2994@columbia.edu; rolf.zeller@unibas.ch RI Zeller, Rolf /C-2610-2013; Benazet, Jean-Denis/I-8495-2016; OI Zeller, Rolf/0000-0002-3186-7403 FU Swiss National Science Foundation [3100A0-100240, -113866]; University of Basel; Center for Cancer Research, NCI; NIH; EU Epigenome Network of Excellence; ETH Zurich FX This research was supported by the Swiss National Science Foundation (grants 3100A0-100240 and -113866) and the University of Basel (to RZ); the Center for Cancer Research, NCI and NIH (to SM); the EU Epigenome Network of Excellence; and the ETH Zurich (to RP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 60 Z9 60 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD APR PY 2010 VL 6 IS 4 AR e1000901 DI 10.1371/journal.pgen.1000901 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 592CY UT WOS:000277354200018 PM 20386744 ER PT J AU Scuteri, A Sanna, S Chen, WM Uda, M Albai, G Strait, J Najjar, S Nagaraja, R Orru, M Usala, G Dei, M Lai, S Maschio, A Busonero, F Mulas, A Ehret, GB Fink, AA Weder, AB Cooper, RS Galan, P Chakravarti, A Schlessinger, D Cao, A Lakatta, E Abecasis, GR AF Scuteri, Angelo Sanna, Serena Chen, Wei-Min Uda, Manuela Albai, Giuseppe Strait, James Najjar, Samer Nagaraja, Ramaiah Orru, Marco Usala, Gianluca Dei, Mariano Lai, Sandra Maschio, Andrea Busonero, Fabio Mulas, Antonella Ehret, Georg B. Fink, Ashley A. Weder, Alan B. Cooper, Richard S. Galan, Pilar Chakravarti, Aravinda Schlessinger, David Cao, Antonio Lakatta, Edward Abecasis, Goncalo R. TI Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related Traits SO PLOS GENETICS LA English DT Article ID BODY-MASS INDEX; UNITED-STATES; ANTIOXIDANT VITAMINS; QUANTITATIVE TRAITS; PROSPECTIVE COHORT; BLOOD-PRESSURE; ADULT OBESITY; US ADULTS; LINKAGE; DISEASE AB The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x 10(-7)), hip circumference (p = 3.4 x 10(-8)), and weight (p = 9.1 x 10(-7)). In Sardinia, homozygotes for the rare "G'' allele of this SNP (minor allele frequency - 0.46) were 1.3 BMI units heavier than homozygotes for the common "A'' allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6)). Homozygotes for the rare "A" allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common "G" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A'' allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G'' allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population. C1 [Scuteri, Angelo; Strait, James; Najjar, Samer; Nagaraja, Ramaiah; Schlessinger, David; Lakatta, Edward] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Scuteri, Angelo] Ist Patol Endocrina & Metab, Unita Operat Geriatria, Rome, Italy. [Sanna, Serena; Chen, Wei-Min; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Sanna, Serena; Uda, Manuela; Albai, Giuseppe; Orru, Marco; Usala, Gianluca; Dei, Mariano; Lai, Sandra; Maschio, Andrea; Busonero, Fabio; Mulas, Antonella; Cao, Antonio] Cittadella Univ Monserrato, CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. [Orru, Marco] Presidio Osped Santa Barbara, Div Med, Unita Operat Semplice Cardiol, Iglesias, Italy. [Ehret, Georg B.; Fink, Ashley A.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. [Weder, Alan B.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Cooper, Richard S.] Loyola Stritch Sch Med, Dept Prevent Med & Epidemiol, Chicago, IL USA. [Galan, Pilar] Conservatoire Natl Arts & Metiers, Inst Sci & Tech Nutr & Alimentat, F-75003 Paris, France. [Galan, Pilar] UMR INSERM INRA CNAM, U557, Paris, France. RP Schlessinger, D (reprint author), NIA, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov; goncalo@umich.edu RI Abecasis, Goncalo/B-7840-2010 FU National Institute on Aging, NIH; National Institute on Aging [NO1-AG-1-2109, 263-MA-410953]; National Institutes of Health [HG02651, HL084729] FX This work was supported by the Intramural Research Program of the National Institute on Aging, NIH. The SardiNIA ("Progenia'') team was supported by Contract NO1-AG-1-2109 from the National Institute on Aging. The efforts of SS, WC, and GRA, were supported in part by contract 263-MA-410953 from the National Institute on Aging to the University of Michigan and by research grants HG02651 and HL084729 from the National Institutes of Health (to GRA). NR 55 TC 0 Z9 0 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD APR PY 2010 VL 6 IS 4 AR e115 DI 10.1371/journal.pgen.0030115 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 592CY UT WOS:000277354200002 ER PT J AU Viboud, C Simonsen, L AF Viboud, Cecile Simonsen, Lone TI Does Seasonal Influenza Vaccination Increase the Risk of Illness with the 2009 A/H1N1 Pandemic Virus? SO PLOS MEDICINE LA English DT Editorial Material ID H1N1 INFLUENZA; A H1N1; INFECTION; MEXICO; CITY C1 [Viboud, Cecile; Simonsen, Lone] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Simonsen, Lone] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Viboud, C (reprint author), NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 17 TC 18 Z9 18 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2010 VL 7 IS 4 AR e1000259 DI 10.1371/journal.pmed.1000259 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 590PO UT WOS:000277239500002 PM 20386730 ER PT J AU Tran, NBC Anders, KL Le, BL Nguyen, TH Lu, TMH Nguyen, MT Tran, TT Le, TP Nguyen, THT Mai, NL Farrar, JJ Whitehead, SS Simmons, CP AF Tran Nguyen Bich Chau Anders, Katherine L. Le Bich Lien Nguyen Thanh Hung Lu Thi Minh Hieu Nguyen Minh Tuan Tran Thi Thuy Le Thi Phuong Nguyen Thi Hong Tham Mai Ngoc Lanh Farrar, Jeremy J. Whitehead, Stephen S. Simmons, Cameron P. TI Clinical and Virological Features of Dengue in Vietnamese Infants SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID NS1 ANTIGEN-DETECTION; HEMORRHAGIC-FEVER; VIRUS-INFECTION; CHILDREN; ANTIBODIES; DIAGNOSIS; ADULTS; PATTERNS; DISEASE; TESTS AB Background: Infants account for a small proportion of the overall dengue case burden in endemic countries but can be clinically more difficult to manage. The clinical and laboratory features in infants with dengue have not been extensively characterised. Methodology/Principal Findings: This prospective, cross-sectional descriptive study of infants hospitalized with dengue was conducted in Vietnam from November 2004 to December 2007. More than two-thirds of 303 infants enrolled on clinical suspicion of dengue had a serologically confirmed dengue virus (DENV) infection. Almost all were primary dengue infections and 80% of the infants developed DHF/DSS. At the time of presentation and during hospitalization, the clinical signs and symptoms in infants with dengue were difficult to distinguish from those with other febrile illnesses, suggesting that in infants early laboratory confirmation could assist appropriate management. Detection of plasma NS1 antigen was found to be a sensitive marker of acute dengue in infants with primary infection, especially in the first few days of illness. Conclusions/Significance: Collectively, these results provide a systematic description of the clinical features of dengue in infants and highlight the value of NS1 detection for diagnosis. C1 [Tran Nguyen Bich Chau; Anders, Katherine L.; Farrar, Jeremy J.; Simmons, Cameron P.] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Le Bich Lien; Nguyen Thanh Hung; Lu Thi Minh Hieu; Nguyen Minh Tuan] Childrens Hosp 1, Dept Dengue Haemorrhag Fever, Ho Chi Minh City, Vietnam. [Tran Thi Thuy] Childrens Hosp 2, Dept Infect Dis, Ho Chi Minh City, Vietnam. [Le Thi Phuong; Nguyen Thi Hong Tham; Mai Ngoc Lanh] Dong Thap Hosp, Cao Lanh, Vietnam. [Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tran, NBC (reprint author), Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam. EM csimmons@oucru.org OI Simmons, Cameron P./0000-0002-9039-7392; Farrar, Jeremy/0000-0002-2700-623X FU Wellcome Trust FX This work was supported by the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 24 TC 0 Z9 0 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2010 VL 4 IS 4 AR e657 DI 10.1371/journal.pntd.0000657 PG 7 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 590PX UT WOS:000277240400015 ER PT J AU Aumakhan, B Gaydos, CA Quinn, TC Beyrer, C Benning, L Minkoff, H Merenstein, DJ Cohen, M Greenblatt, R Nowicki, M Anastos, K Gange, SJ AF Aumakhan, Bulbulgul Gaydos, Charlotte A. Quinn, Thomas C. Beyrer, Chris Benning, Lorie Minkoff, Howard Merenstein, Daniel J. Cohen, Mardge Greenblatt, Ruth Nowicki, Marek Anastos, Kathryn Gange, Stephen J. TI Clinical Reactivations of Herpes Simplex Virus Type 2 Infection and Human Immunodeficiency Virus Disease Progression Markers SO PLOS ONE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; WOMENS INTERAGENCY HIV; GENITAL HERPES; T-LYMPHOCYTES; VIRAL SYNERGY; RNA LEVELS; THERAPY; HSV-2; ACYCLOVIR; RISK AB Background: The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear. Methods: Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS) into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit. Results: A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p=0.004), an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001) and 51 to 101 reduced CD4+ T cells/mm(3) over time compared to asymptomatic HSV-2 infection (trend p<0.001). Conclusions: HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression. C1 [Aumakhan, Bulbulgul; Beyrer, Chris; Benning, Lorie; Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. [Gaydos, Charlotte A.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA. [Minkoff, Howard] SUNY Downstate, Brooklyn, NY USA. [Merenstein, Daniel J.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Cohen, Mardge] Cook Cty Med Ctr, Chicago, IL USA. [Greenblatt, Ruth] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. [Greenblatt, Ruth] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Nowicki, Marek] Univ So Calif, Los Angeles, CA USA. [Anastos, Kathryn] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Aumakhan, B (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. EM baumakhan@hivresearch.org RI Gaydos, Charlotte/E-9937-2010; OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131] FX Data in this manuscript was collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/ Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington, DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 4 Z9 4 U1 0 U2 1 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 APR 1 PY 2010 VL 5 IS 3 AR e9973 DI 10.1371/journal.pone.0009973 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580AG UT WOS:000276418200046 PM 20376310 ER PT J AU Cui, CY Kunisada, M Piao, Y Childress, V Ko, MSH Schlessinger, D AF Cui, Chang-Yi Kunisada, Makoto Piao, Yulan Childress, Victoria Ko, Minoru S. H. Schlessinger, David TI Dkk4 and Eda Regulate Distinctive Developmental Mechanisms for Subtypes of Mouse Hair SO PLOS ONE LA English DT Article ID SWEAT GLAND DEVELOPMENT; FOLLICLE MORPHOGENESIS; ECTODERMAL DYSPLASIA; SONIC-HEDGEHOG; BETA-CATENIN; GENE-EXPRESSION; WNT; SKIN; DIFFERENTIATION; ECTODYSPLASIN AB The mouse hair coat comprises protective "primary'' and thermo-regulatory "secondary'' hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda(-/y)) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda. C1 [Cui, Chang-Yi; Kunisada, Makoto; Piao, Yulan; Childress, Victoria; Ko, Minoru S. H.; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Cui, CY (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM SchlessingerD@grc.nia.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU NIH/National Institute on Aging FX This work was supported by the IRP of the NIH/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 47 TC 16 Z9 17 U1 0 U2 0 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 APR 1 PY 2010 VL 5 IS 3 AR e10009 DI 10.1371/journal.pone.0010009 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580AG UT WOS:000276418200064 PM 20386733 ER PT J AU Banki, Z Posch, W Ejaz, A Oberhauser, V Willey, S Gassner, C Stoiber, H Dittmer, U Dierich, MP Hasenkrug, KJ Wilflingseder, D AF Banki, Zoltan Posch, Wilfried Ejaz, Asim Oberhauser, Verena Willey, Suzanne Gassner, Christoph Stoiber, Heribert Dittmer, Ulf Dierich, Manfred P. Hasenkrug, Kim J. Wilflingseder, Doris TI Complement as an Endogenous Adjuvant for Dendritic Cell-Mediated Induction of Retrovirus-Specific CTLs SO PLOS PATHOGENS LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; ADENYLATE-CYCLASE TOXIN; REGULATORY T-CELLS; WEST-NILE-VIRUS; BORDETELLA-PERTUSSIS; IMMUNE-RESPONSES; VIRAL-INFECTION; HUMORAL RESPONSE; FRIEND; HIV AB Previous studies have demonstrated the involvement of complement (C) in induction of efficient CTL responses against different viral infections, but the exact role of complement in this process has not been determined. We now show that C opsonization of retroviral particles enhances the ability of dendritic cells (DCs) to induce CTL responses both in vitro and in vivo. DCs exposed to C-opsonized HIV in vitro were able to stimulate CTLs to elicit antiviral activity significantly better than non-opsonized HIV. Furthermore, experiments using the Friend virus (FV) mouse model illustrated that the enhancing role of complement on DC-mediated CTL induction also occurred in vivo. Our results indicate that complement serves as natural adjuvant for DC-induced expansion and differentiation of specific CTLs against retroviruses. C1 [Banki, Zoltan; Posch, Wilfried; Ejaz, Asim; Oberhauser, Verena; Stoiber, Heribert; Dierich, Manfred P.; Wilflingseder, Doris] Innsbruck Med Univ, Div Virol, Dept Hyg Microbiol & Social Med, Innsbruck, Tirol, Austria. [Willey, Suzanne] UCL, Div Infect & Immun, MRC UCL Ctr Med Mol Virol, London, England. [Gassner, Christoph] Cent Inst Blood Transfus & Immunol Dept, Innsbruck, Tirol, Austria. [Dittmer, Ulf] Univ Duisburg Essen, Inst Virol, Essen, Germany. [Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Banki, Z (reprint author), Innsbruck Med Univ, Div Virol, Dept Hyg Microbiol & Social Med, Innsbruck, Tirol, Austria. EM doris.wilflingseder@i-med.ac.at RI Gassner, Christoph/B-2171-2012; OI Posch, Wilfried/0000-0001-8955-7654; Wilflingseder, Doris/0000-0002-5888-5118 FU Austrian Science Funds [P18960, 22165, P21508, P14917]; Innsbruck Medical University [6400]; Deutsche Forschungsgemeinschaft [TRR60]; National Institute of Allergy and Infectious Diseases; NIH FX The work was supported by the Austrian Science Funds (FWF, P18960 and 22165 to DW, P21508 to ZB and P14917 to HS), the Innsbruck Medical University (MFI, 6400 to ZB) and the European Union (DEC-VAC # 018685). Part of this work was supported by a grant to UD from the Deutsche Forschungsgemeinschaft (TRR60 project B4). This research was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 12 Z9 12 U1 1 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 APR PY 2010 VL 6 IS 4 AR e1000891 DI 10.1371/journal.ppat.1000891 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400051 PM 20442876 ER PT J AU Bessen, RA Shearin, H Martinka, S Boharski, R Lowe, D Wilham, JM Caughey, B Wiley, JA AF Bessen, Richard A. Shearin, Harold Martinka, Scott Boharski, Ryan Lowe, Diana Wilham, Jason M. Caughey, Byron Wiley, James A. TI Prion Shedding from Olfactory Neurons into Nasal Secretions SO PLOS PATHOGENS LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CHRONIC WASTING DISEASE; TRANSMISSIBLE MINK ENCEPHALOPATHY; NATURAL SCRAPIE; MULE DEER; PROTEIN; SHEEP; INFECTION; HAMSTERS; NEUROINVASION AB This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium including the olfactory receptor neurons (ORNs) and vomeronasal receptor neurons (VRNs), whose axons comprise the two olfactory cranial nerves. A distinct glycoform of the disease-specific isoform of the prion protein, PrP Sc, was found in the olfactory mucosa compared to the olfactory bulb, but the total amount of HY TME infectivity in the nasal turbinates was within 100-fold of the titer in the olfactory bulb. PrP Sc colocalized with olfactory marker protein in the soma and dendrites of ORNs and VRNs and also with adenylyl cyclase III, which is present in the sensory cilia of ORNs that project into the lumen of the nasal airway. Nasal lavages from HY TME-infected hamsters contained prion titers as high as 10(3.9) median lethal doses per ml, which would be up to 500-fold more infectious in undiluted nasal fluids. These findings were confirmed using the rapid PrP Sc amplification QuIC assay, indicating that nasal swabs have the potential to be used for prion diagnostics. These studies demonstrate that prion infection in the olfactory epithelium is likely due to retrograde spread from the olfactory bulb along the olfactory and vomeronasal axons to the soma, dendrites, and cilia of these peripheral neurons. Since prions can replicate to high levels in neurons, we propose that ORNs can release prion infectivity into nasal fluids. The continual turnover and replacement of mature ORNs throughout the adult lifespan may also contribute to prion shedding from the nasal passage and could play a role in transmission of natural prion diseases in domestic and free-ranging ruminants. C1 [Bessen, Richard A.; Shearin, Harold; Martinka, Scott; Boharski, Ryan; Lowe, Diana; Wiley, James A.] Montana State Univ, Bozeman, MT 59717 USA. [Wilham, Jason M.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Hamilton, MT USA. RP Bessen, RA (reprint author), Montana State Univ, Bozeman, MT 59717 USA. EM rbessen@montana.edu FU National Institutes of Health [R01 AI055043, R21 AI084094, P20 RR020185]; USDA CSREES [2006-35201-16626]; The Murphy Foundation FX This work was supported by Public Health Service grants R01 AI055043, R21 AI084094, and P20 RR020185 from the National Institutes of Health, by the National Research Initiative of the USDA CSREES grant 2006-35201-16626, and The Murphy Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 31 Z9 31 U1 0 U2 6 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 APR PY 2010 VL 6 IS 4 AR e1000837 DI 10.1371/journal.ppat.1000837 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400009 PM 20419120 ER PT J AU Chong, YL Padhi, A Hudson, PJ Poss, M AF Chong, Yee Ling Padhi, Abinash Hudson, Peter J. Poss, Mary TI The Effect of Vaccination on the Evolution and Population Dynamics of Avian Paramyxovirus-1 SO PLOS PATHOGENS LA English DT Article ID NEWCASTLE-DISEASE VIRUS; INFECTIOUS BURSAL DISEASE; LIVE-BIRD MARKETS; AMINO-ACID SITES; PHYLOGENETIC ANALYSIS; FUSION PROTEIN; HONG-KONG; GENOTYPIC CHARACTERIZATION; MOLECULAR EPIDEMIOLOGY; NUCLEOTIDE-SEQUENCE AB Newcastle Disease Virus (NDV) is a pathogenic strain of avian paramyxovirus (aPMV-1) that is among the most serious of disease threats to the poultry industry worldwide. Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences. Modified live vaccines have been developed to decrease the economic losses caused by this virus. Vaccines derived from avirulent genotype II strains were developed in the 1950s and are in use globally, whereas Australian strains belonging to genotype I were developed as vaccines in the 1970s and are used mainly in Asia. In this study, we evaluated the consequences of attenuated live virus vaccination on the evolution of aPMV-1 genotypes. There was phylogenetic incongruence among trees based on individual genes and complete coding region of 54 full length aPMV-1 genomes, suggesting that recombinant sequences were present in the data set. Subsequently, five recombinant genomes were identified, four of which contained sequences from either genotype I or II. The population history of vaccine-related genotype II strains was distinct from other aPMV-1 genotypes; genotype II emerged in the late 19(th) century and is evolving more slowly than other genotypes, which emerged in the 1960s. Despite vaccination efforts, genotype II viruses have experienced constant population growth to the present. In contrast, other contemporary genotypes showed population declines in the late 1990s. Additionally, genotype I and II viruses, which are circulating in the presence of homotypic vaccine pressure, have unique selection profiles compared to nonvaccine-related strains. Collectively, these data show that vaccination with live attenuated viruses has changed the evolution of aPMV-1 by maintaining a large effective population size of a vaccine-related genotype, allowing for coinfection and recombination of vaccine and wild type strains, and by applying unique selective pressures on viral glycoproteins. C1 [Chong, Yee Ling; Padhi, Abinash; Hudson, Peter J.; Poss, Mary] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Hudson, Peter J.; Poss, Mary] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Chong, YL (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM mposs@bx.psu.edu FU Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX Funding: MP and PJH were supported, in part, by the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 81 TC 35 Z9 37 U1 1 U2 11 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 APR PY 2010 VL 6 IS 4 AR e1000872 DI 10.1371/journal.ppat.1000872 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400044 PM 20421950 ER PT J AU Frieman, MB Chen, J Morrison, TE Whitmore, A Funkhouser, W Ward, JM Lamirande, EW Roberts, A Heise, M Subbarao, K Baric, RS AF Frieman, Matthew B. Chen, Jun Morrison, Thomas E. Whitmore, Alan Funkhouser, William Ward, Jerrold M. Lamirande, Elaine W. Roberts, Anjeanette Heise, Mark Subbarao, Kanta Baric, Ralph S. TI SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism SO PLOS PATHOGENS LA English DT Article ID ACUTE RESPIRATORY SYNDROME; CORONAVIRUS CAUSES DISEASE; INFLUENZA-A VIRUS; SYNCYTIAL VIRUS; INNATE IMMUNITY; NUCLEAR ACCUMULATION; HOST-DEFENSE; BALB/C MICE; JAK-STAT; INFECTION AB Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1(-/-) mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS CoV infection in STAT1(-/-) mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation. C1 [Frieman, Matthew B.; Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Chen, Jun; Lamirande, Elaine W.; Roberts, Anjeanette; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Morrison, Thomas E.; Whitmore, Alan; Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Funkhouser, William] Univ N Carolina, Dept Anat Pathol & Surg Pathol, Chapel Hill, NC USA. [Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Ward, Jerrold M.] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Frieman, MB (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. EM ralph_baric@unc.edu FU NIAID, NIH [AI66542, AI075297, AI059443] FX This work was supported by grants AI66542 to Matthew Frieman, AI075297 and AI059443 to Ralph Baric and by the Intramural Research Program of NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 40 Z9 40 U1 0 U2 4 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 APR PY 2010 VL 6 IS 4 AR e1000849 DI 10.1371/journal.ppat.1000849 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400021 PM 20386712 ER PT J AU Lamb, EW Walls, CD Pesce, JT Riner, DK Maynard, SK Crow, ET Wynn, TA Schaefer, BC Davies, SJ AF Lamb, Erika W. Walls, Colleen D. Pesce, John T. Riner, Diana K. Maynard, Sean K. Crow, Emily T. Wynn, Thomas A. Schaefer, Brian C. Davies, Stephen J. TI Blood Fluke Exploitation of Non-Cognate CD4(+) T Cell Help to Facilitate Parasite Development SO PLOS PATHOGENS LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; HUMAN SCHISTOSOMIASIS MANSONI; TOLL-LIKE RECEPTORS; NF-KAPPA-B; DENDRITIC CELLS; MYELOID DIFFERENTIATION; TRANSCRIPTION FACTOR; INFECTIOUS-DISEASE; IMMUNE-RESPONSES AB Schistosoma blood flukes, which infect over 200 million people globally, co-opt CD4(+) T cell-dependent mechanisms to facilitate parasite development and egg excretion. The latter requires Th2 responses, while the mechanism underpinning the former has remained obscure. Using mice that are either defective in T cell receptor (TCR) signaling or that lack TCRs that can respond to schistosomes, we show that naive CD4(+) T cells facilitate schistosome development in the absence of T cell receptor signaling. Concurrently, the presence of naive CD4(+) T cells correlates with both steady-state changes in the expression of genes that are critical for the development of monocytes and macrophages and with significant changes in the composition of peripheral mononuclear phagocyte populations. Finally, we show that direct stimulation of the mononuclear phagocyte system restores blood fluke development in the absence of CD4(+) T cells. Thus we conclude that schistosomes co-opt innate immune signals to facilitate their development and that the role of CD4(+) T cells in this process may be limited to the provision of non-cognate help for mononuclear phagocyte function. Our findings have significance for understanding interactions between schistosomiasis and other co-infections, such as bacterial infections and human immunodeficiency virus infection, which potently stimulate innate responses or interfere with T cell help, respectively. An understanding of immunological factors that either promote or inhibit schistosome development may be valuable in guiding the development of efficacious new therapies and vaccines for schistosomiasis. C1 [Lamb, Erika W.; Walls, Colleen D.; Riner, Diana K.; Maynard, Sean K.; Crow, Emily T.; Schaefer, Brian C.; Davies, Stephen J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Pesce, John T.; Wynn, Thomas A.] NIAID, Parasit Dis Lab, NIH, Rockville, MD USA. RP Lamb, EW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. EM sdavies@usuhs.mil RI Wynn, Thomas/C-2797-2011; OI Schaefer, Brian C/0000-0001-8877-3507; Maynard, Sean/0000-0002-0953-4362 FU NIH/NIAID [AI053054, AI066227, AI057481]; Val G. Hemming Fellowship FX Supported by grants from the NIH/NIAID [AI053054 and AI066227 (to SJD) and AI057481 (to BCS)] and a Val G. Hemming Fellowship (to EWL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 78 TC 19 Z9 21 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2010 VL 6 IS 4 AR e1000892 DI 10.1371/journal.ppat.1000892 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400052 PM 20442785 ER PT J AU Magadan, JG Perez-Victoria, FJ Sougrat, R Ye, YH Strebel, K Bonifacino, JS AF Magadan, Javier G. Perez-Victoria, F. Javier Sougrat, Rachid Ye, Yihong Strebel, Klaus Bonifacino, Juan S. TI Multilayered Mechanism of CD4 Downregulation by HIV-1 Vpu Involving Distinct ER Retention and ERAD Targeting Steps SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RETICULUM-ASSOCIATED DEGRADATION; ENDOPLASMIC-RETICULUM; AAA-ATPASE; PROTEIN-DEGRADATION; UBIQUITIN LIGASE; T-CELLS; POLYUBIQUITIN CHAINS; MISFOLDED PROTEINS; CYTOPLASMIC DOMAIN AB A key function of the Vpu protein of HIV-1 is the targeting of newly-synthesized CD4 for proteasomal degradation. This function has been proposed to occur by a mechanism that is fundamentally distinct from the cellular ER-associated degradation (ERAD) pathway. However, using a combination of genetic, biochemical and morphological methodologies, we find that CD4 degradation induced by Vpu is dependent on a key component of the ERAD machinery, the VCP-UFD1L-NPL4 complex, as well as on SCF(beta-TrCP)-dependent ubiquitination of the CD4 cytosolic tail on lysine and serine/threonine residues. When degradation of CD4 is blocked by either inactivation of the VCP- UFD1L-NPL4 complex or prevention of CD4 ubiquitination, Vpu still retains the bulk of CD4 in the ER mainly through transmembrane domain interactions. Addition of a strong ER export signal from the VSV-G protein overrides this retention. Thus, Vpu exerts two distinct activities in the process of downregulating CD4: ER retention followed by targeting to late stages of ERAD. The multiple levels at which Vpu engages these cellular quality control mechanisms underscore the importance of ensuring profound suppression of CD4 to the life cycle of HIV-1. C1 [Magadan, Javier G.; Perez-Victoria, F. Javier; Sougrat, Rachid; Bonifacino, Juan S.] NIH, Cell Biol & Metab Program, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Ye, Yihong] NIH, Mol Biol Lab, Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA. [Strebel, Klaus] NIH, Mol Microbiol Lab, Natl Inst Allergy & Infect Dis, Bethesda, MD 20892 USA. RP Magadan, JG (reprint author), NIH, Cell Biol & Metab Program, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bldg 10, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Sougrat, Rachid/0000-0001-6476-1886 FU NIH; NICHD; NIDDK; NIAID; Pew Charitable Trusts FX Funding: This work was funded by the NIH Intramural AIDS Targeted Antiviral Program (IATAP) and the Intramural Programs of NICHD, NIDDK and NIAID. J. G. M. is the recipient of a fellowship from The Pew Charitable Trusts. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 79 Z9 80 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 APR PY 2010 VL 6 IS 4 AR e1000869 DI 10.1371/journal.ppat.1000869 PG 18 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400041 PM 20442859 ER PT J AU Sionov, E Lee, H Chang, YC Kwon-Chung, KJ AF Sionov, Edward Lee, Hyeseung Chang, Yun C. Kwon-Chung, Kyung J. TI Cryptococcus neoformans Overcomes Stress of Azole Drugs by Formation of Disomy in Specific Multiple Chromosomes SO PLOS PATHOGENS LA English DT Article ID INCREASED FLUCONAZOLE RESISTANCE; TRANSPORTER-ENCODING GENE; CANDIDA-ALBICANS; PETITE MUTANTS; MECHANISMS; EVOLUTION; GLABRATA; YEAST; AIDS; MENINGITIS AB Cryptococcus neoformans is a haploid environmental organism and the major cause of fungal meningoencephalitis in AIDS patients. Fluconazole (FLC), a triazole, is widely used for the maintenance therapy of cryptococcosis. Heteroresistance to FLC, an adaptive mode of azole resistance, was associated with FLC therapy failure cases but the mechanism underlying the resistance was unknown. We used comparative genome hybridization and quantitative real-time PCR in order to show that C. neoformans adapts to high concentrations of FLC by duplication of multiple chromosomes. Formation of disomic chromosomes in response to FLC stress was observed in both serotype A and D strains. Strains that adapted to FLC concentrations higher than their minimal inhibitory concentration (MIC) contained disomies of chromosome 1 and stepwise exposure to even higher drug concentrations induced additional duplications of several other specific chromosomes. The number of disomic chromosomes in each resistant strain directly correlated with the concentration of FLC tolerated by each strain. Upon removal of the drug pressure, strains that had adapted to high concentrations of FLC returned to their original level of susceptibility by initially losing the extra copy of chromosome 1 followed by loss of the extra copies of the remaining disomic chromosomes. The duplication of chromosome 1 was closely associated with two of its resident genes: ERG11, the target of FLC and AFR1, the major transporter of azoles in C. neoformans. This adaptive mechanism in C. neoformans may play an important role in FLC therapy failure of cryptococcosis leading to relapse during azole maintenance therapy. C1 [Sionov, Edward; Lee, Hyeseung; Chang, Yun C.; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Lab, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Sionov, E (reprint author), NIAID, Mol Microbiol Lab, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU National Institute of Allergy and Infectious Diseases, NIH FX This study was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 112 Z9 114 U1 4 U2 10 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 APR PY 2010 VL 6 IS 4 AR e1000848 DI 10.1371/journal.ppat.1000848 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 596YS UT WOS:000277722400020 PM 20368972 ER PT J AU Kim, HY Akbar, M Kim, YS AF Kim, Hee-Yong Akbar, Mohammed Kim, Yang-Suk TI Phosphatidylserine-dependent neuroprotective signaling promoted by docosahexaenoic acid SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 9th Fatty Acids and Cell Signalling Meeting (FACS-09) CY JUL 13-16, 2009 CL Keble Coll, Oxford, ENGLAND SP Amarin Corporat, Vifor Pharma, Abbott Nutr, Croda Hlth Care, Danone Res Ctr Specialised Nutr, Fresenius Kabi, Solvay Hlth Care, B Braun, Efamol, Ocean Nutr, Unilever HO Keble Coll ID PROTEIN-KINASE-C; POLYUNSATURATED FATTY-ACIDS; PEROXISOMAL DISORDERS; NEURONAL APOPTOSIS; ALZHEIMERS-DISEASE; PLASMA-MEMBRANE; RAF; ACTIVATION; CELLS; AKT AB Enrichment of polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA, 22:6n-3), in the brain is known to be critical for optimal brain development and function. Mechanisms for DHA's beneficial effects in the nervous system are not clearly understood at present. DHA is incorporated into the phospholipids in neuronal membranes, which in turn can influence not only the membrane chemical and physical properties but also the cell signaling involved in neuronal survival, proliferation and differentiation. Our studies have indicated that DHA supplementation promotes phosphatidylserine (PS) accumulation and inhibits neuronal cell death under challenged conditions, supporting a notion that DHA is an important neuroprotective agent. This article summarizes our findings on the DHA-mediated membrane-related signaling mechanisms that might explain some of the beneficial effects of DHA, particularly on neuronal survival. Published by Elsevier Ltd. C1 [Kim, Hee-Yong; Akbar, Mohammed; Kim, Yang-Suk] NIAAA, Mol Signalling Lab, NIH, Bethesda, MD 20892 USA. RP Kim, HY (reprint author), NIAAA, Mol Signalling Lab, NIH, 5625 Fishers Lane,Room 3N-07, Bethesda, MD 20892 USA. EM hykim@nih.gov FU Intramural NIH HHS [Z99 AA999999] NR 66 TC 35 Z9 36 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD APR-JUN PY 2010 VL 82 IS 4-6 SI SI BP 165 EP 172 DI 10.1016/j.plefa.2010.02.025 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 600EQ UT WOS:000277967800005 PM 20207120 ER PT J AU Rapoport, SI Igarashi, M Gao, F AF Rapoport, Stanley I. Igarashi, Miki Gao, Fei TI Quantitative contributions of diet and liver synthesis to docosahexaenoic acid homeostasis SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 9th Fatty Acids and Cell Signalling Meeting (FACS-09) CY JUL 13-16, 2009 CL Keble Coll, Oxford, ENGLAND SP Amarin Corporat, Vifor Pharma, Abbott Nutr, Croda Hlth Care, Danone Res Ctr Specialised Nutr, Fresenius Kabi, Solvay Hlth Care, B Braun, Efamol, Ocean Nutr, Unilever HO Keble Coll ID ALPHA-LINOLENIC ACID; POLYUNSATURATED FATTY-ACIDS; N-3 PUFA DEPRIVATION; RAT-BRAIN; PHOSPHOLIPASE A(2); ADULT-RATS; NUTRITIONAL DEPRIVATION; FRONTAL-CORTEX; METABOLISM; TRANSCRIPTION AB Dietary requirements for maintaining brain and heart docosahexaenoic acid (DHA, 22:6n-3) homeostasis are not agreed on, in part because rates of liver DHA synthesis from circulating alpha-linolenic acid (alpha-LNA, 18:3n-3) have not been quantified. These rates can be estimated using intravenous radiotracer- or heavy isotope-labeled alpha-LNA infusion. In adult unanesthetized male rats, such infusion shows that liver synthesis-secretion rates of DHA from alpha-LNA markedly exceed brain and heart DHA synthesis rates and the brain DHA consumption rate, and that liver but not heart or brain synthesis is upregulated when dietary n-3 PUFA content is reduced. These rate differences reflect much higher expression of DHA-synthesizing enzymes in liver, and upregulation of liver but not heart or brain enzyme expression by reduced dietary n-3 PUFA content. A noninvasive intravenous [U-(13)C]alpha-LNA infusion method that produces steady-state liver tracer metabolism gives exact liver DHA synthesis-secretion rates and could be extended for human studies. Published by Elsevier Ltd. C1 [Rapoport, Stanley I.; Igarashi, Miki; Gao, Fei] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Room 1S128, Bethesda, MD 20892 USA. EM sir@helix.nih.gov FU Intramural NIH HHS [Z01 AG000399-03] NR 42 TC 37 Z9 38 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD APR-JUN PY 2010 VL 82 IS 4-6 SI SI BP 273 EP 276 DI 10.1016/j.plefa.2010.02.015 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 600EQ UT WOS:000277967800020 PM 20226642 ER PT J AU Arana, ME Powell, GK Edwards, LL Kunkel, TA Petrovich, RM AF Arana, Mercedes E. Powell, Gary K. Edwards, Lori L. Kunkel, Thomas A. Petrovich, Robert M. TI Refolding active human DNA polymerase v from inclusion bodies SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE DNA polymerase; High pressure refolding; Aggregation; Insoluble inclusion bodies ID HIGH-PRESSURE; IN-VITRO; PROTEINS; FIDELITY; POLN AB Human DNA polymerase v (Pol v) is a conserved family A DNA polymerase of uncertain biological function. Physical and biochemical characterization aimed at understanding Pol v function is hindered by the fact that, when over-expressed in Escherichia coli, Pol v is largely insoluble. and the small amount of soluble protein is difficult to purify. Here we describe the use of high hydrostatic pressure to refold Pol v from inclusion bodies, in soluble and active form. The refolded Pol v has properties comparable to those of the small amount of Pol v that was purified from the soluble fraction. The approach described here may be applicable to other DNA polymerases that are expressed as insoluble inclusion bodies in E coli. (C) 2009 Published by Elsevier Inc. C1 [Arana, Mercedes E.; Kunkel, Thomas A.; Petrovich, Robert M.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Arana, Mercedes E.; Powell, Gary K.; Edwards, Lori L.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Petrovich, RM (reprint author), NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM petrovi1@niehs.nih.gov FU Division of Intramural Research of the National Institutes of Health [Z01 ES065070]; National Institute of Environmental Health Sciences; NIH/NIEHS [HHS27300700046U] FX The authors thank Dr. Lars C. Pedersen and Andrea F. Moon for critical review of this manuscript. We thank the NIEHS DNA sequencing and Protein Microcharacterization core facilities for expert technical assistance. This work was supported in part by Project Z01 ES065070 to TAK from the Division of Intramural Research of the National Institutes of Health, National Institute of Environmental Health Sciences. Dr. Powell's contribution was funded in whole with federal funds from NIH/NIEHS, under delivery order HHS27300700046U to SRA International, Inc. NR 22 TC 7 Z9 8 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2010 VL 70 IS 2 BP 163 EP 171 DI 10.1016/j.pep.2009.10.010 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 565PE UT WOS:000275305500006 PM 19853037 ER PT J AU Berger, C Ho, JTC Kimura, T Hess, S Gawrisch, K Yeliseev, A AF Berger, Christian Ho, Jenny T. C. Kimura, Tomohiro Hess, Sonja Gawrisch, Klaus Yeliseev, Alexei TI Preparation of stable isotope-labeled peripheral cannabinoid receptor CB2 by bacterial fermentation SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Cannabinoid CB2 receptor; Stable isotope-labeling; Bacterial fermentation; G protein-coupled receptor ID PROTEIN-COUPLED RECEPTORS; IONIZATION-MASS SPECTROMETRY; ESCHERICHIA-COLI; MEMBRANE-PROTEINS; AMINO-ACIDS; EXPRESSION; PURIFICATION; NEUROTENSIN; PROTEOMICS; ASPARTATE AB We developed a bacterial fermentation protocol for production of a stable isotope-labeled cannabinoid receptor CB2 for subsequent structural studies of this protein by nuclear magnetic resonance spectroscopy. The human peripheral cannabinoid receptor was expressed in Escherichia coli as a fusion with maltose binding protein and two affinity tags. The fermentation was performed in defined media comprised of mineral salts, glucose and (15)N(2)-L-tryptophan to afford incorporation of the labeled amino acid into the protein. Medium, growth and expression conditions were optimized so that the fermentation process produced about 2 mg of purified, labeled CB2/L of culture medium. By performing a mass spectroscopic characterization of the purified CB2, we determined that one of the two (15)N atoms in tryptophan was incorporated into the recombinant protein. NMR analysis of (15)N chemical shifts strongly suggests that the (15)N atoms are located in Trp-indole rings. Importantly, analysis of the peptides derived from the CNBr cleavage of the purified protein confirmed a minimum of 95% incorporation of the labeled tryptophan into the CB2 sequence. The labeled CB2, purified and reconstituted into liposomes at a protein-to-lipid molar ratio of 1:500, was functional as confirmed by activation of cognate G proteins in an in vitro coupled assay. To our knowledge, this is the first reported production of a biologically active, stable isotope-labeled G protein-coupled receptor by bacterial fermentation. Published by Elsevier Inc. C1 [Kimura, Tomohiro; Gawrisch, Klaus; Yeliseev, Alexei] NIAAA, NIH, Rockville, MD 20852 USA. [Berger, Christian] Univ Halle Wittenberg, Inst Biochem & Biotechnol, D-06120 Halle, Germany. [Berger, Christian] Univ Leipzig, Inst Med Phys & Biophys, D-04107 Leipzig, Germany. [Ho, Jenny T. C.; Hess, Sonja] CALTECH, Proteome Explorat Lab, Beckman Inst, Pasadena, CA 91125 USA. RP Yeliseev, A (reprint author), NIAAA, NIH, 5625 Fishers Lane,Room 3N17, Rockville, MD 20852 USA. EM yeliseeva@mail.nih.gov RI Yeliseev, Alexei/B-3143-2009; Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU NIAAA; NIH; Beckman Institute; Betty and Gordon Moore Foundation; Federal State Sachsen-Anhalt, Germany FX This study was supported by the intramural research program of the NIAAA, NIH. J.T.C.H. and S.H. were supported by the Beckman Institute and the Betty and Gordon Moore Foundation. C.B. acknowledges support from the "Exzellenznetzwerk Biowissenschaften" funded by the Federal State Sachsen-Anhalt, Germany. We thank Mrs. Lioudmila Zoubak for technical assistance. NR 35 TC 20 Z9 20 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2010 VL 70 IS 2 BP 236 EP 247 DI 10.1016/j.pep.2009.12.011 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 565PE UT WOS:000275305500017 PM 20044006 ER PT J AU Chen, B Tycko, R AF Chen, Bo Tycko, Robert TI Structural and dynamical characterization of tubular HIV-1 capsid protein assemblies by solid state nuclear magnetic resonance and electron microscopy SO PROTEIN SCIENCE LA English DT Article DE solid state NMR; virus structure; protein self-assembly; electron microscopy ID HUMAN-IMMUNODEFICIENCY-VIRUS; C-TERMINAL DOMAIN; ANGLE-SPINNING NMR; BETA-SHEET STRUCTURE; HUMAN CYCLOPHILIN-A; IN-VITRO; DIMERIZATION DOMAIN; AMYLOID FIBRILS; CONFORMATIONAL DISTRIBUTIONS; POLARIZATION TRANSFER AB The wild-type HIV-1 capsid protein (CA) self-assembles in vitro into tubular structures at high ionic strength. We report solid state nuclear magnetic resonance (NMR) and electron microscopy measurements on these tubular CA assemblies, which are believed to contain a triangular lattice of hexameric CA proteins that is similar or identical to the lattice of capsids in intact HIV-1. Mass-per-length values of CA assemblies determined by dark-field transmission electron microscopy indicate a variety of structures, ranging from single-wall tubes to multiwall tubes that approximate solid rods. Two-dimensional (2D) solid state (13)C-(13)C and (15)N-(13C) NMR spectra of uniformly (15)N,(13)C-labeled CA assemblies are highly congested, as expected for a 25.6 kDa protein in which nearly the entire amino acid sequence is immobilized. Solid state NMR spectra of partially labeled CA assemblies, expressed in 1,3-(13)C(2)-glycerol medium, are better resolved, allowing the identification of individual signals with line widths below 1 ppm. Comparison of crosspeak patterns in the experimental 2D spectra with simulated patterns based on solution NMR chemical shifts of the individual N-terminal (NTD) and C-terminal (CTD) domains indicates that NTD and CTD retain their individual structures upon self-assembly of full-length CA into tubes. 2D (1)H-(13)C NMR spectra of CA assemblies recorded under solution NMR conditions show relatively few signals, primarily from segments that link the a-helices of NTD and CTD and from the N- and C-terminal ends. Taken together, the data support the idea that CA assemblies contain a highly ordered 2D protein lattice in which the NTD and CTD structures are retained and largely immobilized. C1 [Chen, Bo; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov RI Chen, Bo/F-3573-2015 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health FX Grant sponsors: Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; Intramural AIDS Targeted Antiviral Program. NR 83 TC 31 Z9 31 U1 1 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD APR PY 2010 VL 19 IS 4 BP 716 EP 730 DI 10.1002/pro.348 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578DY UT WOS:000276274900009 PM 20095046 ER PT J AU Vitiello, B Waslick, B AF Vitiello, Benedetto Waslick, Bruce TI Pharmacotherapy for Children and Adolescents with Anxiety Disorders SO PSYCHIATRIC ANNALS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; CHILDHOOD ANXIETY; ATTENTION-DEFICIT/HYPERACTIVITY; MULTICENTER TRIAL; DOUBLE-BLIND; SERTRALINE; FLUOXETINE; PSYCHOPHARMACOLOGY C1 [Vitiello, Benedetto] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Waslick, Bruce] Baystate Med Ctr, Dept Psychiat, Springfield, MA USA. [Waslick, Bruce] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Vitiello, B (reprint author), NIMH Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 31 TC 2 Z9 2 U1 1 U2 9 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD APR PY 2010 VL 40 IS 4 BP 185 EP 191 DI 10.3928/00485713-20100330-09 PG 7 WC Psychiatry SC Psychiatry GA 586RH UT WOS:000276929000004 ER PT J AU Suliman, H Schumacher, J Becker, T Cichon, S Schulze, TG Propping, P Rietschel, M Nothen, MM Abou Jamra, R AF Suliman, Husam Schumacher, Johannes Becker, Tim Cichon, Sven Schulze, Thomas G. Propping, Peter Rietschel, Marcella Noethen, Markus M. Abou Jamra, Rami TI Association study of 20 genetic variants at the D-amino acid oxidase gene in schizophrenia SO PSYCHIATRIC GENETICS LA English DT Editorial Material ID DAOA; G72 C1 [Suliman, Husam; Schumacher, Johannes; Cichon, Sven; Propping, Peter; Noethen, Markus M.; Abou Jamra, Rami] Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany. [Becker, Tim] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53111 Bonn, Germany. [Cichon, Sven; Noethen, Markus M.; Abou Jamra, Rami] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53111 Bonn, Germany. [Schulze, Thomas G.; Rietschel, Marcella] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. [Suliman, Husam] Univ Zurich, Dept Psychiat, Zurich, Switzerland. [Schumacher, Johannes; Schulze, Thomas G.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. RP Abou Jamra, R (reprint author), Univ Bonn, Inst Human Genet, Wilhelmstr 31, D-53111 Bonn, Germany. EM rami.aboujamra@uni-bonn.de RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schumacher, Johannes/F-4970-2015; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399; Schumacher, Johannes/0000-0001-9217-6457; Nothen, Markus/0000-0002-8770-2464 NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD APR PY 2010 VL 20 IS 2 BP 82 EP 83 DI 10.1097/YPG.0b013e3283351244 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 572WX UT WOS:000275867300005 PM 20145586 ER PT J AU Vythilingam, M Gill, JM Luckenbaugh, DA Gold, PW Collin, C Bonne, O Plumb, K Polignano, E West, K Charney, D AF Vythilingam, M. Gill, J. M. Luckenbaugh, D. A. Gold, P. W. Collin, C. Bonne, O. Plumb, K. Polignano, E. West, K. Charney, D. TI Low early morning plasma cortisol in posttraumatic stress disorder is associated with co-morbid depression but not with enhanced glucocorticoid feedback inhibition SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; Depression; Cortisol; DHEA-S; ACTH ID PITUITARY-ADRENAL AXIS; HPA-AXIS; HORMONE CONCENTRATIONS; ATYPICAL DEPRESSION; MAJOR DEPRESSION; PTSD; TRAUMA; VETERANS; DEHYDROEPIANDROSTERONE; WOMEN AB Background: Co-morbid major depressive disorder (MDD) in individuals with posttraumatic stress disorder (PTSD) confers a more severe clinical course and is associated with distinct biologic abnormalities. Although dysregulation in the hypothalamic pituitary adrenal (HPA) axis has been well established in PTSD, the impact of commonly co-occuring MDD has received scant attention. Methods: Overnight (7 p.m. to 7 a.m.) plasma cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulphate (DHEA-S) were measured at 30 min intervals in 9 participants with PTSD with MDD (PTSD + MDD), 9 with PTSD without MDD (PTSD - MDD) and 16 non-traumatized healthy controls. A low-dose dexamethasone suppression test was administered to evaluate feedback sensitivity to glucocorticoids. Linear mixed models with body mass index (BMI) and age as covariates and Bonferroni corrected post hoc tests assessed group differences. Results: Compared to healthy controls, subjects with PTSD + MDD, but not those subjects with PTSD - MDD, exhibited lower basal plasma cortisol levels between 1:30 a.m. and 3:30 a.m. and at 4:30 a.m. and 6:30 a.m. (effect size d = 0.75). Despite similar plasma ACTH levels between the three groups, the ACTH/cortisol ratio was higher in PTSD + MDD patients compared to controls. We obtained similar results when the patient and control groups were re-studied 1 week later, and when men and current smokers were excluded. Basal plasma DHEA-S levels, and cortisol and ACTH response to a low-dose dexamethasone suppression test were similar in all three groups. Conclusions: Lower early morning plasma cortisol levels and a high ACTH/cortisol ratio in subjects with PTSD and co-morbid MDD may not be due to enhanced peripheral sensitivity to glucocorticoids. A central abnormality in glucocorticoid regulation could explain HPA axis dysfunction in this subgroup. Published by Elsevier Ltd. C1 [Vythilingam, M.; Luckenbaugh, D. A.; Gold, P. W.; Collin, C.; Plumb, K.; West, K.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Gill, J. M.] NINR, Bethesda, MD 20892 USA. [Bonne, O.] Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, Jerusalem, Israel. [Polignano, E.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Charney, D.] Mt Sinai Sch Med, New York, NY USA. RP Vythilingam, M (reprint author), Off Assistant Secretary Def Hlth Affairs, Skyline 4,Suite 403,5113 Leesburg Pike, Falls Church, VA 22041 USA. EM meena.vythilingam@ha.osd.mil FU National Institute of Mental Health Intramural Research Program FX The research reported in this manuscript was undertaken at the National Institute of Mental Health and funded by the National Institute of Mental Health Intramural Research Program. NR 42 TC 22 Z9 22 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 2010 VL 35 IS 3 BP 442 EP 450 DI 10.1016/j.psyneuen.2009.08.006 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 570TD UT WOS:000275700000012 PM 19766403 ER PT J AU Solinas, M Tanda, G Wertheim, CE Goldberg, SR AF Solinas, Marcello Tanda, Gianluigi Wertheim, Carrie E. Goldberg, Steven R. TI Dopaminergic augmentation of delta-9-tetrahydrocannabinol (THC) discrimination: possible involvement of D-2-induced formation of anandamide SO PSYCHOPHARMACOLOGY LA English DT Article DE Cannabis; THC; Endocannabinoid; Dopamine; Behavior; Psychostimulants; Rats ID ACID AMIDE HYDROLASE; BRAIN REWARD PROCESSES; ENDOCANNABINOID SYSTEM; RECEPTOR SUBTYPES; NUCLEUS-ACCUMBENS; CANNABINOID CB1; RATS; INHIBITION; COCAINE; TRANSMISSION AB Although delta-9-tetreahydrocannabinol (THC)-induced elevations in accumbal dopamine levels are believed to play an important role in the abuse-related effects of cannabis, little direct evidence has been provided that the dopaminergic system is involved in the psychotropic effects of THC. The objective of this study is to investigate whether drugs activating or blocking the dopaminergic system modulate the discriminative effects of THC. In rats that had learned to discriminate 3 mg/kg of THC from vehicle injections, the indirect dopaminergic agonists cocaine and amphetamine, the D-1-receptor agonist SKF-38393, and the D-2-receptor agonists quinpirole and apomorphine did not produce significant THC-like discriminative effects. However, both cocaine and amphetamine and D-2-, but not the D-1-, receptor agonists, augmented THC discrimination. Neither the D-1-receptor antagonist SCH-23390 nor the D-2-receptor antagonist raclopride reduced the discriminative effects of THC, even at doses that significantly depressed baseline operant responding. However, the D-2-, but not the D-1-, antagonist counteracted the augmentation of THC's discriminative effects produced by cocaine and amphetamine. We hypothesized that release of anandamide by activation of D-2 receptors was responsible for the observed augmentation of THC discrimination. This hypothesis was supported by two findings. First, the cannabinoid CB1-receptor antagonist rimonabant blocked quinpirole-induced augmentation of THC discrimination. Second, inhibition of anandamide degradation by blockade of fatty acid amide hydrolase augmented the THC-like effects of quinpirole. Dopamine does not play a major role in THC discrimination. However, activation of the dopaminergic system positively modulates the discriminative effects of THC, possibly through D-2-induced elevations in brain levels of anandamide. C1 [Solinas, Marcello] Univ Poitiers, CNRS 6187, Lab Biol & Physiol Cellulaires, F-86022 Poitiers, France. [Tanda, Gianluigi] NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD USA. [Wertheim, Carrie E.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD USA. RP Solinas, M (reprint author), Univ Poitiers, CNRS 6187, Lab Biol & Physiol Cellulaires, 40 Ave Recteur Pineau, F-86022 Poitiers, France. EM marcello.solinas@univ-poitiers.fr RI Tanda, Gianluigi/B-3318-2009; Solinas, Marcello/M-3500-2016 OI Tanda, Gianluigi/0000-0001-9526-9878; Solinas, Marcello/0000-0002-0664-5964 FU Centre National de la Recherche Scientifique (CNRS); University of Poitiers, France; National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA FX This research was supported by the Centre National de la Recherche Scientifique (CNRS) and the University of Poitiers, France, and the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA. NR 43 TC 11 Z9 11 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 APR PY 2010 VL 209 IS 2 BP 191 EP 202 DI 10.1007/s00213-010-1789-8 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 567BL UT WOS:000275417200006 PM 20179908 ER PT J AU Marsh, AA Yu, HH Pine, DS Blair, RJR AF Marsh, Abigail A. Yu, Henry H. Pine, Daniel S. Blair, R. J. R. TI Oxytocin improves specific recognition of positive facial expressions SO PSYCHOPHARMACOLOGY LA English DT Article DE Oxytocin; Neuropeptide; Emotion; Facial; Affinity ID BILATERAL AMYGDALA DAMAGE; SOCIAL PHOBIA; MATERNAL-BEHAVIOR; NEURAL CIRCUITRY; HUMANS; FACES; FEAR; TRUSTWORTHINESS; EMOTION; IDENTIFICATION AB Oxytocin is a neuropeptide that is associated with increased trust. Perceptions of trustworthiness are associated with detection of positive facial affect, which suggests that oxytocin may enhance the recognition of positive facial affect. The present study tests this hypothesis. A double-blind, between-groups design was used, with 50 volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Thirty-five minutes following the administration of oxytocin or placebo, participants identified anger, disgust, fear, happiness, sadness, and surprise expressions that were morphed with neutral faces such that they varied from 10% to 100% intensity. Oxytocin significantly and specifically improved the recognition of happy facial expressions; no significant differences in recognition of other expression were found. The improvement was not associated with gender, response biases, or changes in mood, and it was most pronounced for subtle expressions. Acute oxytocin administration enhances healthy adults' ability to accurately identify positive emotional facial expressions. These findings reinforce oxytocin's role in facilitating affiliative interactions and have implications for the treatment of conditions that are marked by social affiliation deficits. C1 [Marsh, Abigail A.; Yu, Henry H.; Pine, Daniel S.; Blair, R. J. R.] NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. [Marsh, Abigail A.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. RP Marsh, AA (reprint author), NIMH, Mood & Anxiety Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM aam72@georgetown.edu FU National Institutes of Health: National Institute of Mental Health FX This research was supported by the Intramural Research Program of the National Institutes of Health: National Institute of Mental Health. We wish to thank Samantha Crowe, Elizabeth Finger, David Fink, Adriana Pavletic, Nanette Schell, Andy Speer, and Judith Starling for their assistance in conducting this research. NR 47 TC 112 Z9 116 U1 4 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2010 VL 209 IS 3 BP 225 EP 232 DI 10.1007/s00213-010-1780-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 572AM UT WOS:000275798400002 PM 20186397 ER PT J AU Taubenberger, JK Morens, DM AF Taubenberger, Jeffery K. Morens, David M. TI Influenza: The Once and Future Pandemic SO PUBLIC HEALTH REPORTS LA English DT Article ID H5N1 INFLUENZA; A VIRUSES; H1N1 INFLUENZA; UNITED-STATES; CONTINUING EVOLUTION; ORIGIN; TRANSMISSION; MORTALITY; ASIA; EPIDEMIOLOGY AB Influenza A viruses infect large numbers of warm-blooded animals, including wild birds, domestic birds, pigs, horses, and humans. Influenza viruses can switch hosts to form new lineages in novel hosts. The most significant of these events is the emergence of antigenically novel influenza A viruses in humans, leading to pandemics. Influenza pandemics have been reported for at least 500 years, with inter-pandemic intervals averaging approximately 40 years. C1 [Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Morens, David M.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,Rm 3E19A-2,MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov 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 and the National Institute of Allergy and Infectious Diseases. NR 90 TC 74 Z9 77 U1 1 U2 9 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD APR PY 2010 VL 125 SU 3 BP 16 EP 26 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 601BV UT WOS:000278033900004 PM 20568566 ER PT J AU Turkbey, B Pinto, PA Mani, H Bernardo, M Pang, YX McKinney, YL Khurana, K Ravizzini, GC Albert, PS Merino, MJ Choyke, PL AF Turkbey, Baris Pinto, Peter A. Mani, Haresh Bernardo, Marcelino Pang, Yuxi McKinney, Yolanda L. Khurana, Kiranpreet Ravizzini, Gregory C. Albert, Paul S. Merino, Maria J. Choyke, Peter L. TI Prostate Cancer: Value of Multiparametric MR Imaging at 3 T for Detection-Histopathologic Correlation SO RADIOLOGY LA English DT Article ID PHASED-ARRAY COIL; RADICAL PROSTATECTOMY; ENDORECTAL COIL; PERIPHERAL ZONE; TUMOR VOLUME; LOCALIZATION; SPECTROSCOPY; PREDICTION; ACCURACY; OUTCOMES AB Purpose: To determine utility of multiparametric imaging performed at 3 T for detection of prostate cancer by using T2-weighted magnetic resonance (MR) imaging, MR spectroscopy, and dynamic contrast material-enhanced MR imaging, with whole-mount pathologic findings as reference standard. Materials and Methods: This prospectively designed, HIPAA-compliant, single-institution study was approved by the local institutional review board. Seventy consecutive patients (mean age, 60.4 years; mean prostate-specific antigen level, 5.47 ng/mL [5.47 m g/L]; range, 1-19.9 ng/mL [1-19.9 m g/L]) were included; informed consent was obtained from each patient. All patients had biopsy-proved prostate cancer, with a median Gleason score of 7 (range, 6-9). Images were obtained by using a combination of six-channel cardiac and endorectal coils. MR imaging and pathologic findings were evaluated independently and blinded and then correlated with histopathologic findings by using side-by-side comparison. Analyses were conducted with a raw stringent approach and an alternative neighboring method, which accounted for surgical deformation, shrinkage, and nonuniform slicing factors in pathologic specimens. Generalized estimating equations (GEEs) were used to estimate the predictive value of region-specific, pathologically determined cancer for all three modalities. This approach accounts for the correlation among multiple regions in the same individual. Results: For T2-weighted MR imaging, sensitivity and specificity values obtained with stringent approach were 0.42 (95% confidence interval [CI]: 0.36, 0.47) and 0.83 (95% CI: 0.81, 0.86), and for the alternative neighboring approach, sensitivity and specificity values were 0.73 (95% CI: 0.67, 0.78) and 0.89 (95% CI: 0.85, 0.93), respectively. The combined diagnostic accuracy of T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy for peripheral zone tumors was examined by calculating their predictive value with different combinations of techniques; T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy provided significant independent and additive predictive value when GEEs were used (P < .001, P = .02, P = .002, respectively). Conclusion: Multiparametric MR imaging (T2-weighted MR imaging, MR spectroscopy, dynamic contrast-enhanced MR imaging) of the prostate at 3 T enables tumor detection, with reasonable sensitivity and specificity values. (C) RSNA, 2010 C1 [Turkbey, Baris; Bernardo, Marcelino; Pang, Yuxi; McKinney, Yolanda L.; Ravizzini, Gregory C.; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Pinto, Peter A.; Khurana, Kiranpreet] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Mani, Haresh; Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Pang, Yuxi] Philips Healthcare, Cleveland, OH USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM pchoyke@nih.gov OI Khurana, Kiranpreet/0000-0002-2750-4909 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research [ZIA BC 010655] FX This research was supported by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research (grant number ZIA BC 010655). NR 26 TC 228 Z9 233 U1 3 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2010 VL 255 IS 1 BP 89 EP 99 DI 10.1148/radiol.09090475 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572VU UT WOS:000275863000013 PM 20308447 ER PT J AU Marotta, F Harada, M Minelli, E Yadav, H Polimeni, A Lorenzetti, A Locorotondo, N AF Marotta, Francesco Harada, Masatoshi Minelli, Emilio Yadav, Hariom Polimeni, Ascanio Lorenzetti, Alao Locorotondo, Nicola TI Progression of Atherosclerotic Lesions in the Arteries and Related Gene Expression: Protective Effect of Phytonutrients SO REJUVENATION RESEARCH LA English DT Article; Proceedings Paper CT 4th Conference on Strategies Engineered Negligible Senescence CY SEP 03-07, 2009 CL Queen Coll, Cambridge, ENGLAND HO Queen Coll ID E-DEFICIENT MICE; TNF; DISEASE; AGGREGATION; RISK AB We investigated the effect of the phytocompound Denshici-to-Chiusei (DTS) on the atherogenesis in apolipoprotein E(-/-)/low-density lipoprotein receptor(-/-) (apoE(-/-)/LDL receptor(-/-)) mice (E0). E0 mice were fed for 16 weeks with: (1) placebo or (2) 25 mg or (3) 50 mg of DTS/day. Aortic lesions were reduced by 38% (p < 0.01) in mice fed 50 mg/day, whereas peritoneal macrophages after both dosages had a 45%-60% lower (p < 0.01) capacity to oxidize LDL and to degrade it. This was associated with reduced LDL-associated lipoperoxides and a 22% inhibition (p < 0.05) in LDL aggregation. Tumor necrosis factor-alpha (TNF-alpha) expression and immunoreactivity in the aortic media increased five-fold, but this was significantly mitigated by DTS (50 mg > 25 mg) (p < 0.05). DTS significantly attenuated inflammatory mechanisms preceding atherogenesis with reduced LDL susceptibility to oxidation-aggregation. C1 [Marotta, Francesco; Polimeni, Ascanio; Lorenzetti, Alao] ReGenera Res Grp, Milan, Italy. [Marotta, Francesco; Harada, Masatoshi] HMC Hosp, Tokyo, Japan. [Marotta, Francesco; Minelli, Emilio] Univ Milan, WHO, Ctr Biotech & Tradit Med, Milan, Italy. [Yadav, Hariom] NIDDKD, NIH, Bethesda, MD 20892 USA. [Locorotondo, Nicola] Grp Locorotondo Labs, Palermo, Italy. RP Marotta, F (reprint author), Piazza Firenze 12, I-20154 Milan, Italy. EM fmarchimede@libero.it OI Yadav, Hariom/0000-0003-4504-1597 NR 21 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD APR-JUN PY 2010 VL 13 IS 2-3 BP 242 EP 245 DI 10.1089/rej.2009.0949 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 595HV UT WOS:000277602200026 PM 20370493 ER PT J AU Lima, LH Shakin, E Sen, HN Nussenblatt, RB Yannuzzi, LA Jampol, LM Cunningham, ET AF Lima, Luiz H. Shakin, Eric Sen, Hatice N. Nussenblatt, Robert B. Yannuzzi, Lawrence A. Jampol, Lee M. Cunningham, Emmett T. TI Diagnostic and Therapeutic Challenges SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Editorial Material ID OCCULT OUTER RETINOPATHY; EVANESCENT WHITE DOT; IDIOPATHIC RETINAL VASCULITIS; MULTIFOCAL CHOROIDITIS; ARTERIAL MACROANEURYSMS; CHOROIDOPATHY; UVEITIS; SARCOIDOSIS; ANEURYSMS; RETINITIS C1 [Lima, Luiz H.; Yannuzzi, Lawrence A.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA. [Shakin, Eric] NYU, Dept Ophthalmol, New York, NY 10016 USA. [Sen, Hatice N.; Nussenblatt, Robert B.] NEI, Dept Uveitis & Ocular Immunol, NIH, Bethesda, MD 20892 USA. RP Lima, LH (reprint author), Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA. FU Intramural NIH HHS [Z99 EY999999] NR 22 TC 1 Z9 1 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 APR PY 2010 VL 30 IS 4 BP 700 EP 704 DI 10.1097/IAE.0b013e3181cbd9fc PG 5 WC Ophthalmology SC Ophthalmology GA 608AE UT WOS:000278548900023 PM 20234333 ER PT J AU Brindle, TJ Lebiedowska, MK Miller, JL Stanhope, SJ AF Brindle, T. J. Lebiedowska, M. K. Miller, J. L. Stanhope, S. J. TI The influence of ankle joint movement on knee joint kinesthesia at various movement velocities SO SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS LA English DT Article DE proprioception; muscle; lower extremity; somatosensory ID ANTERIOR CRUCIATE LIGAMENT; DEFICIENT KNEE; PROPRIOCEPTION; AGE; RECONSTRUCTION; CONCUSSION; STABILITY; POSITION; FINGER; ADULTS AB The purpose of this study was to determine if gastrocnemius elongation or shortening and direction and velocity of knee movement influenced knee kinesthesia. Healthy volunteers sat with their knee flexed (20 degrees) and was then passively rotated (flexion or extension) at three velocities (0.5, 2, or 10 degrees/s) while the ankle was either fixed or rotated (dorsiflexed or plantar flexed at 0.17, 0.65, or 3.3 degrees/s) creating gastrocnemius elongation or shortening. Subjects activated a thumb switch, stopping motion once they detected onset and direction of the motion. Detection of passive movement sense (DPMS) was the angular movement before activation of a thumb-switch. Significant differences (P=0.003) in the rate of change in DPMS across a variety of movement velocities was observed but shortening or elongation of the gastrocnemius did not affect DPMS. Gastrocnemius elongation/shortening did not affect knee DPMS, simple reaction time plays an important role in testing kinesthesia especially at faster movements. While feedback from the gastrocnemius muscle plays a limited role in healthy subjects, differences in testing velocities may incorporate higher levels of central nervous system processing. Clinical measures of kinesthesia can be affected by both movement direction and movement velocity that are speed dependent. C1 [Brindle, T. J.] NIH, Biomech Lab, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA. RP Brindle, TJ (reprint author), NIH, Biomech Lab, Funct & Appl Biomech Sect, Room 1-1469,Bldg 10 CRC,10 Ctr Dr,MCS 1604, Bethesda, MD 20892 USA. EM tbrindle@cc.nih.gov NR 27 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0905-7188 J9 SCAND J MED SCI SPOR JI Scand. J. Med. Sci. Sports PD APR PY 2010 VL 20 IS 2 BP 262 EP 267 DI 10.1111/j.1600-0838.2009.00887.x PG 6 WC Sport Sciences SC Sport Sciences GA 566TF UT WOS:000275395400013 PM 19486484 ER PT J AU Law, A AF Law, Amanda TI ERBB4 AND PI3KCD AND ARE INTERACTING BIOLOGICAL AND GENETIC FACTORS THAT REGULATE NRG1-MEDIATED PI3K SIGNALING AND RISK FOR SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Law, Amanda] NIMH, Bethesda, MD 20892 USA. RI Law, Amanda/G-6372-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 105 EP 106 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800007 ER PT J AU Owen, M Gejman, P Kennedy, J King, MC Lehner, T Murray, R Rujescu, D Visscher, P AF Owen, Michael Gejman, Pablo Kennedy, James King, Mary Claire Lehner, Thomas Murray, Robin Rujescu, Dan Visscher, Peter TI PLENARY SESSION - CLINICAL IMPLICATIONS OF RECENT GENETIC FINDINGS: GWAS, ENDOPHENOTYPES AND COMMERCIAL TESTING SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Owen, Michael] Cardiff Univ, MRC Ctr Neuropsychiatr Genet & Gen, Cardiff, S Glam, Wales. [Gejman, Pablo] Northwestern Univ, Evanston, IL USA. [Kennedy, James] Univ Toronto, Toronto, ON, Canada. [King, Mary Claire] Univ Washington, Washington, DC USA. [Lehner, Thomas] NIMH, Bethesda, MD 20892 USA. [Murray, Robin] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Rujescu, Dan] Univ Munich, Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 109 EP 109 DI 10.1016/j.schres.2010.02.022 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800020 ER PT J AU Weinberger, D Bertolino, A McGuire, P Meisenzahl, E Lindenberg, AM Potkin, S Tianmei, S AF Weinberger, Daniel Bertolino, Alessandro McGuire, Philip Meisenzahl, Eva Lindenberg, Andreas Meyer Potkin, Steven Tianmei, Si TI PLENARY SESSION - ON THE MATTER OF NEUROIMAGING IN THE CONTEXT OF SCHIZOPHRENIA GENETICS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Weinberger, Daniel] NIMH, Bethesda, MD 20892 USA. [Bertolino, Alessandro] Univ Bari, I-70121 Bari, Italy. [McGuire, Philip] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Meisenzahl, Eva] Univ Munich, Munich, Germany. [Potkin, Steven] Univ Calif Irvine, Brain Imaging Ctr, Irvine, CA 92717 USA. [Tianmei, Si] Peking Univ, Inst Mental Hlth, Beijing, Peoples R China. NR 0 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 109 EP 110 DI 10.1016/j.schres.2010.02.023 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800021 ER PT J AU Gogtay, N AF Gogtay, Nitin TI ADVANCES IN NEUROIMAGING ALLOW PROSPECTIVE STUDY OF HUMAN BRAIN DEVELOPMENT SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 147 EP 147 DI 10.1016/j.schres.2010.02.133 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800135 ER PT J AU Gogtay, N AF Gogtay, Nitin TI BRAIN DEVELOPMENT IN CHILDHOOD ONSET SCHIZOPHRENIA: GENETIC AND ENVIRONMENTAL INFLUENCES SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Gogtay, Nitin] NIMH, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 152 EP 152 DI 10.1016/j.schres.2010.02.146 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800148 ER PT J AU Weinberger, DR Savostyanova, AA Geramita, M Stern, A Callicott, JH Shen, J Straub, RE Genes, SM AF Weinberger, Daniel R. Savostyanova, Antonina A. Geramita, Matthew Stern, Alexa Callicott, Joseph H. Shen, Jun Straub, Richard E. Genes, Stefano Marenco TI GENETIC REGULATION OF GABA ACTIVITY AND RISK FOR SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Weinberger, Daniel R.; Savostyanova, Antonina A.; Geramita, Matthew; Stern, Alexa; Callicott, Joseph H.; Shen, Jun; Straub, Richard E.; Genes, Stefano Marenco] NIMH, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 157 EP 157 DI 10.1016/j.schres.2010.02.161 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800163 ER PT J AU Toulopoulou, T Goldberg, T Weinberger, D Seidman, L Picchioni, M Murray, R AF Toulopoulou, Timothea Goldberg, Terry Weinberger, Danny Seidman, Larry Picchioni, Marco Murray, Robin TI ORAL PRESENTATION 2-PREDICTING THE DEVELOPMENT OF PSYCHOSIS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Toulopoulou, Timothea; Picchioni, Marco; Murray, Robin] Kings Coll London, Inst Psychiat, Psychosis Clin Acad Grp, London WC2R 2LS, England. [Goldberg, Terry] Zucker Hillside Hosp, New York, NY USA. [Weinberger, Danny] NIMH, Genes Cognit & Psychosis Program, IRP, NIH, Bethesda, MD 20892 USA. [Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 173 EP 173 DI 10.1016/j.schres.2010.02.203 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800205 ER PT J AU Seidman, LJ Giuliano, AJ Meyer, EC Addington, J Cadenhead, KS Cannon, TD McGlashan, TH Perkins, DO Tsuang, MT Walkers, EF Woods, SW Heinssen, R Cornblatt, BA AF Seidman, Larry J. Giuliano, Anthony J. Meyer, Eric C. Addington, Jean Cadenhead, Kristen S. Cannon, Tyrone D. McGlashan, Thomas H. Perkins, Diana O. Tsuang, Ming T. Walkers, Elaine F. Woods, Scott W. Heinssen, Robert Cornblatt, Barbara A. TI NEUROPSYCHOLOGY OF THE PRODROME TO PSYCHOSIS IN THE NAPLS CONSORTIUM: RELATIONSHIP TO FAMILY HISTORY AND CONVERSION TO PSYCHOSIS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Seidman, Larry J.; Giuliano, Anthony J.; Tsuang, Ming T.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02115 USA. [Meyer, Eric C.] Texas A&M Univ, Hlth Sci Ctr, Coll Med, Dept Psychiat & Behav Sci, Waco, TX USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cadenhead, Kristen S.; Tsuang, Ming T.] UCSD, Dept Psychiat, San Diego, CA USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Walkers, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Adult Translat Res, Schizophrenia Spectrum Res Program, Bethesda, MD 20892 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Walkers, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Seidman, Larry J.; Giuliano, Anthony J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 176 EP 176 DI 10.1016/j.schres.2010.02.210 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800212 ER PT J AU Jones, EM Trotman, H Esterberg, ML Brasfield, J Walker, EF Addington, J Cadenhead, KS Cannon, TD Cornblatt, B McGlashan, TH Perkins, DD Seidman, LJ Tsuang, M Woods, SW Heinssen, R AF Jones, Erin M. Trotman, Hanan Esterberg, Michelle L. Brasfield, Joy Walker, Elaine F. Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara McGlashan, Thomas H. Perkins, Diana D. Seidman, Larry J. Tsuang, Ming Woods, Scott W. Heinssen, Robert TI PRODROMAL SYMPTOMS: DIFFERENTIAL EFFECTS OF SEX AND FAMILY HISTORY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Jones, Erin M.; Trotman, Hanan; Esterberg, Michelle L.; Brasfield, Joy; Walker, Elaine F.] Emory Univ, Atlanta, GA 30322 USA. [Addington, Jean] Univ Toronto, Toronto, ON, Canada. [Cadenhead, Kristin S.; Tsuang, Ming] Univ Calif San Diego, San Diego, CA 92103 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Cornblatt, Barbara] Zucker Hillside Hosp, Glen Oaks, NY USA. [Cornblatt, Barbara] Albert Einstein Coll Med, Bronx, NY 10467 USA. [McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, New Haven, CT USA. [Perkins, Diana D.] Univ N Carolina, Chapel Hill, NC USA. [Seidman, Larry J.; Tsuang, Ming] Harvard Univ, Boston, MA 02115 USA. [Heinssen, Robert] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 197 EP 197 DI 10.1016/j.schres.2010.02.262 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800261 ER PT J AU Derks, EM Gladwin, T Rietschel, M Mattheisen, M Breuer, R Schulze, TG Nothen, MM Levinson, D Shi, JX Cichon, S Freimer, NB Cantor, R Ophoff, RA AF Derks, Eske M. Gladwin, Thomas Rietschel, Marcella Mattheisen, Manuel Breuer, Rene Schulze, Thomas G. Nothen, Markus M. Levinson, Douglas Shi, Jianxin Cichon, Sven Freimer, Nelson B. Cantor, Rita Ophoff, Roel A. CA Group XXX TI SEGMENT-WISE GENOME-WIDE ASSOCIATION ANALYSIS IDENTIFIES A LIMITED NUMBER OF REPLICABLE CANDIDATE REGIONS ASSOCIATED WITH SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Derks, Eske M.; Gladwin, Thomas; Group XXX] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Rietschel, Marcella; Breuer, Rene; Schulze, Thomas G.] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Mattheisen, Manuel; Nothen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Mattheisen, Manuel] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany. [Mattheisen, Manuel; Cichon, Sven] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. Unit Genet Basis Mood & Anxiety, Bethesda, MD USA. [Levinson, Douglas] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. [Shi, Jianxin] Natl Canc Inst, Bethesda, MD USA. [Freimer, Nelson B.; Cantor, Rita; Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehavioral Genet, Semel Inst Neuroscience & Human Behav, Los Angeles, CA USA. RI Gladwin, Thomas/F-6685-2010; Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Mattheisen, Manuel/B-4949-2012; Derks, Eske/A-1652-2017 OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Mattheisen, Manuel/0000-0002-8442-493X; Derks, Eske/0000-0002-6292-6883 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 219 EP 219 DI 10.1016/j.schres.2010.02.312 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800311 ER PT J AU Apud, LA Mattay, VS Rasetti, R Stankevich, B Magalona, C Decot, H Skjei, K Blasi, G Sambataro, F Callicott, JH Weinberger, DR AF Apud, Lose A. Mattay, V. S. Rasetti, Roberta Stankevich, Beth Magalona, Carmela Decot, Heather Skjei, Kelsey Blasi, Giuseppe Sambataro, Favio Callicott, Joseph H. Weinberger, Daniel R. TI EFFECT OF TOLCAPONE ON BRAIN REGIONS UNDERLYING RESPONSE INHIBITION IN A SAMPLE OF PATIENTS WITH SCHIZOPHRENIA COMPARED TO NORMAL CONTROLS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Apud, Lose A.; Mattay, V. S.; Rasetti, Roberta; Stankevich, Beth; Magalona, Carmela; Decot, Heather; Skjei, Kelsey; Blasi, Giuseppe; Sambataro, Favio; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, NIH, GCAP, CBDB, Bethesda, MD 20892 USA. RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 232 EP 232 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800341 ER PT J AU Geramita, MA Savostyanova, AA van der Veen, J Rebsch, C Barnett, AS Shen, J Weinberger, DR Marenco, S AF Geramita, Matthew A. Savostyanova, Antonina A. van der Veen, Johan Rebsch, Christine Barnett, Alan S. Shen, Jun Weinberger, Daniel R. Marenco, Stefano TI GABA LEVELS IN THE MEDIAL PREFRONAL CORTEX OF PATIENTS WITH SCHIZOPHRENIA: A PROTON MAGNETIC RESONANCE SPECTROSCOPY (H-1-MRS) STUDY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Geramita, Matthew A.; Savostyanova, Antonina A.; Rebsch, Christine; Barnett, Alan S.; Weinberger, Daniel R.; Marenco, Stefano] NIMH, Natl Inst Hlth, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [van der Veen, Johan; Shen, Jun] NIMH, Natl Inst Hlth, Magnet Resonance Spect Unit, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 242 EP 242 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800363 ER PT J AU Addington, J Cornblatt, B Cadenhead, K Cannon, T Heinssen, R McGlashan, T Perkins, D Tsuang, M Walker, E Woods, S Seidman, L AF Addington, Jean Cornblatt, Barbara Cadenhead, Kristin Cannon, Ty Heinssen, Robert McGlashan, Thomas Perkins, Diana Tsuang, Ming Walker, Elaine Woods, Scott Seidman, Larry TI CLINICAL HIGH RISK FOR PSYCHOSIS: THE RISK OF FALSE POSITIVE SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Addington, Jean] Univ Calgary, Calgary, AB, Canada. [Cornblatt, Barbara] Zucker Hillside Hosp, Glen Oaks, NY USA. [Cadenhead, Kristin; Tsuang, Ming] UCSD, San Diego, CA USA. [Cannon, Ty] Univ Calif Los Angeles, Los Angeles, CA USA. [Heinssen, Robert] NIMH, Washington, DC USA. [McGlashan, Thomas; Woods, Scott] Yale Univ, New Haven, CT USA. [Perkins, Diana] UNC, Raleigh, NC USA. [Walker, Elaine] Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 279 EP 279 DI 10.1016/j.schres.2010.02.452 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800447 ER PT J AU Holtzman, CW Larson, MK Addington, J Cadenhead, K Cannon, TD Cornblatt, B Heinssen, R McGlashan, T Perkins, D Seidman, LJ Tsuang, M Woods, SW Walker, EF AF Holtzman, Carrie W. Larson, Molly K. Addington, Jean Cadenhead, Kristin Cannon, Tyrone D. Cornblatt, Barbara Heinssen, Robert McGlashan, Thomas Perkins, Diana Seidman, Larry J. Tsuang, Ming Woods, Scott W. Walker, Elaine F. TI SEX DIFFERENCES IN SYMPTOM PRESENTATION IN INDIVIDUALS AT RISK FOR PSYCHOSIS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Holtzman, Carrie W.; Larson, Molly K.; Walker, Elaine F.] Emory Univ, Atlanta, GA 30322 USA. [Addington, Jean] Univ Toronto, Toronto, ON, Canada. [Cadenhead, Kristin; Tsuang, Ming] Univ Calif San Diego, San Diego, CA 92103 USA. [Cannon, Tyrone D.] Calif State Univ Los Angeles, Los Angeles, CA 90032 USA. [Cornblatt, Barbara] RAP Program New York, New York, NY USA. [Heinssen, Robert] NIMH, Washington, DC USA. [McGlashan, Thomas] Yale Univ, Sch Med, New Haven, CT USA. [Perkins, Diana] Univ N Carolina, Chapel Hill, NC USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 304 EP 305 DI 10.1016/j.schres.2010.02.508 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800510 ER PT J AU Kelly, DL Gallagher, H Lo, S Wright, K Moolchan, E Feldman, S Liu, F McMahon, R Richardson, C Wehring, H Boggs, D Heishman, S AF Kelly, Deanna L. Gallagher, Heather Lo, Suzanne Wright, Katherine Moolchan, Eric Feldman, Stephanie Liu, Fang McMahon, Robert Richardson, Charles Wehring, Heidi Boggs, Douglas Heishman, Stephen TI MOTIVATORS FOR SMOKING CESSATION AND KNOWLEDGE AND PERCEPTION OF SMOKING RISKS/CONSEQUENCES AMONG PEOPLE WITH SCHIZOPHRENIA COMPARED TO NORMAL CONTROLS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Kelly, Deanna L.; Gallagher, Heather; Wright, Katherine; Feldman, Stephanie; Liu, Fang; McMahon, Robert; Richardson, Charles; Wehring, Heidi; Boggs, Douglas] Univ Maryland, Baltimore, MD 21201 USA. [Lo, Suzanne; Heishman, Stephen] Natl Inst Drug Abuse, Baltimore, MD USA. [Moolchan, Eric] Alkermes Inc, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 309 EP 310 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800522 ER PT J AU Hosanagar, A Mattai, A Lalonde, F Greenstein, D Clasen, L Weisinger, B Rappaort, JL Gogtay, N AF Hosanagar, Avinash Mattai, Anand Lalonde, Francois Greenstein, Deanna Clasen, Liv Weisinger, Brian Rappaort, Judith L. Gogtay, Nitin TI THALAMIC DEVELOPMENT IN CHILDHOOD ONSET SCHIZOPHRENIA; A VOLUMETRIC ANALYSIS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Mattai, Anand; Lalonde, Francois; Greenstein, Deanna; Clasen, Liv; Weisinger, Brian; Rappaort, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Hosanagar, Avinash] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 323 EP 323 DI 10.1016/j.schres.2010.02.549 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936800551 ER PT J AU Pietersen, CY Lim, MP Chen, J Stephens, R McCarley, RM Wool, TUW AF Pietersen, Charmaine Y. Lim, Maribel P. Chen, Jack Stephens, Robert McCarley, Robert M. Wool, Tsung-Ung W. TI MICROARRAY ANALYSIS OF PARVALBUMIN-CONTAINING INHIBITORY NEURONS IN THE SUPERIOR TEMPORAL GYRUS IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Pietersen, Charmaine Y.; Lim, Maribel P.; Wool, Tsung-Ung W.] McLean Hosp, Belmont, MA 02178 USA. [Chen, Jack; Stephens, Robert] SAIC Frederik, NCI, NIH, ABCC, Bethesda, MD USA. [Pietersen, Charmaine Y.; McCarley, Robert M.; Wool, Tsung-Ung W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pietersen, Charmaine Y.; McCarley, Robert M.; Wool, Tsung-Ung W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [McCarley, Robert M.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 371 EP 372 PG 2 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801032 ER PT J AU Keefe, R Vinogradov, S Medalia, A Buckley, P Caroff, S D'Souza, D Harvey, P Graham, K Marder, S Miller, D Olson, S Patel, J Velligan, D Walker, T Haim, A Stroup, S AF Keefe, Richard Vinogradov, Sophia Medalia, Alice Buckley, Peter Caroff, Stanley D'Souza, Deepak Harvey, Phillip Graham, Karen Marder, Steve Miller, Del Olson, Steve Patel, Jayendra Velligan, Dawn Walker, Trina Haim, Adam Stroup, Scott TI FEASIBILITY STUDY OF MULTI-SITE COGNITIVE REMEDIATION IN THE SCHIZOPHRENIA TRIALS NETWORK (CRSTN) SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Keefe, Richard; Walker, Trina] Duke Univ, Med Ctr, Durham, NC USA. [Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Medalia, Alice; Stroup, Scott] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Buckley, Peter] Med Coll Georgia, Augusta, GA 30912 USA. [Caroff, Stanley] Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [D'Souza, Deepak] Yale Univ, Sch Med, New Haven, CT USA. [Harvey, Phillip] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Graham, Karen] Univ N Carolina, Chapel Hill, NC USA. [Marder, Steve] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Marder, Steve] VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. [Miller, Del] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Olson, Steve] Univ Minnesota, Minneapolis, MN USA. [Patel, Jayendra] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Velligan, Dawn] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Haim, Adam] NIMH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 394 EP 394 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801081 ER PT J AU Wisner, KM Kleinman, JE Weinberger, DR Elvevag, B AF Wisner, Krista M. Kleinman, Joel E. Weinberger, Daniel R. Elvevag, Brita TI ARE COGNITIVE IMPAIRMENTS IN PATIENTS WHO ONLY SUFFER FROM DELUSIONS THE SAME AS SCHIZOPHRENIA PATIENTS? AN EXPLORATORY STUDY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Wisner, Krista M.; Kleinman, Joel E.; Weinberger, Daniel R.; Elvevag, Brita] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 447 EP 447 DI 10.1016/j.schres.2010.02.830 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801201 ER PT J AU Rosa, EC Apud, J Weinberger, D Elvevag, B AF Rosa, Elise C. Apud, Jose Weinberger, Daniel Elvevag, Brita TI THE EFFECT OF THE COMT VAL158MET POLYMORPHISM ON COGNITIVE STABILITY AND COGNITIVE FLEXIBILITY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Rosa, Elise C.; Apud, Jose; Weinberger, Daniel; Elvevag, Brita] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 451 EP 451 DI 10.1016/j.schres.2010.02.839 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801210 ER PT J AU Testa, LR Callicott, JH Morita, Y Kolachana, B Struab, RE Weinberger, DR Hyde, TM AF Testa, Lauren R. Callicott, Joseph H. Morita, Yukitaka Kolachana, Bhaskar Struab, Richard E. Weinberger, Daniel R. Hyde, Thomas M. TI ALLELIC VARIATION IN NKCC1 IS ASSOCIATED WITH HIPPOCAMPAL AND DORSOLATERAL PREFRONTAL CORTEX ACTIVATION DURING WORKING MEMORY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 2nd Conference of the Schizophrenia-International-Research-Society (SIRS) CY APR 10-14, 2010 CL Florence, ITALY SP Schizophrenia Int Res Soc C1 [Testa, Lauren R.; Callicott, Joseph H.; Morita, Yukitaka; Kolachana, Bhaskar; Struab, Richard E.; Weinberger, Daniel R.; Hyde, Thomas M.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2010 VL 117 IS 2-3 SI SI BP 473 EP 473 DI 10.1016/j.schres.2010.02.890 PG 1 WC Psychiatry SC Psychiatry GA 586TR UT WOS:000276936801261 ER PT J AU Padilla, CD Krotoski, D Therrell, BL AF Padilla, Carmencita D. Krotoski, Danuta Therrell, Bradford L., Jr. TI Newborn Screening Progress in Developing Countries-Overcoming Internal Barriers SO SEMINARS IN PERINATOLOGY LA English DT Review DE newborn screening; Asia Pacific; Middle East and North Africa; newborn bloodspot screening ID STRATEGIES; POLICY C1 [Padilla, Carmencita D.] Univ Philippines, Dept Pediat, Coll Med, Manila 1000, Philippines. [Padilla, Carmencita D.] Natl Inst Hlth Philippines, Newborn Screening Reference Ctr, Manila, Philippines. [Krotoski, Danuta] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Therrell, Bradford L., Jr.] Natl Newborn Screening & Genet Resource Ctr, Austin, TX USA. [Therrell, Bradford L., Jr.] Univ Texas Hlth Ctr San Antonio, Dept Pediat, San Antonio, TX USA. RP Padilla, CD (reprint author), Univ Philippines, Dept Pediat, Coll Med, Pedro Gil St, Manila 1000, Philippines. EM carmencita.padilla@gmail.com FU HRSA [U32MC00148] FX Supported in part by HRSA grant U32MC00148. NR 30 TC 17 Z9 17 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 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD APR PY 2010 VL 34 IS 2 BP 145 EP 155 DI 10.1053/j.semperi.2009.12.007 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 572RR UT WOS:000275851000006 PM 20207264 ER PT J AU Yu, BB Gastwirth, JL AF Yu, Binbing Gastwirth, Joseph L. TI HOW WELL DO SELECTION MODELS PERFORM? ASSESSING THE ACURACY OF ART AUCTION PRE-SALE ESTIMATES SO STATISTICA SINICA LA English DT Article DE Art auction; forecast error; nonignorable missing data; selection model ID SAMPLE SELECTION; T-DISTRIBUTION; ALGORITHM; DISTRIBUTIONS; BIAS; EM AB Art auction catalogs provide a pre-sale prediction interval for the price each item is expected to fetch. When the owner consigns art work to the auction house, a reserve price is agreed upon, which is not announced to the bidders. If the highest bid does not reach it, the item is brought in. Since only the prices of the sold items are published, analysts only have a biased sample to examine due to the selective sale process. Relying on the published data leads to underestimating the forecast error of the pre-sale estimates. However, we were able to obtain several art auction catalogs with the highest bids for the unsold items as well as those of the sold items. With these data we were able to evaluate the accuracy of the predictions of the sale prices or highest bids for all item obtained from the original Heckman selection model that assumed normal error distributions as well as those derived from an alternative model using the t(2) distribution, which yielded a noticeably better fit to several sets of auction data. The measures of prediction accuracy are of more than academic interest as they are used by auction participants to guide their bidding or selling strategy, and similar appraisals are accepted by the US Internal Revenue Services to justify the deductions for charitable contributions donors make on their tax returns. C1 [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Gastwirth, Joseph L.] George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov; jlgast@gwu.edu FU NSF [SES-0317956] FX This research was supported in part by NSF grant SES-0317956 awarded to the George Washington University. The authors wish to thank Mr. John Cavaliero of Cavalier Fine Arts, an art dealer in New York, for his interest in this project and for introducing us to the experts in Christie's, and Mr. Chris Eykyn and Ms. Loren Rubin of Christie's for kindly providing us the three print catalogs with the complete data. NR 28 TC 1 Z9 1 U1 4 U2 8 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 EI 1996-8507 J9 STAT SINICA JI Stat. Sin. PD APR PY 2010 VL 20 IS 2 BP 837 EP 852 PG 16 WC Statistics & Probability SC Mathematics GA 593HC UT WOS:000277442600020 PM 22190840 ER PT J AU Luo, XH Wang, MC Huang, CY AF Luo, Xianghua Wang, Mei-Cheng Huang, Chiung-Yu TI A comparison of various rate functions of a recurrent event process in the presence of a terminal event SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID FAILURE TIME DATA; SEMIPARAMETRIC ANALYSIS; REGRESSION; MODELS AB Several different rate functions of the recurrent event process have been proposed for analysing recurrent event data when the observation of a study subject can be terminated by a failure event, such as death. When the terminal event is correlated with the underlying recurrent event process, these rate functions have different interpretations; however, recognition of the differences has been lacking theoretically and practically. In this article, we study the relationship between these rate functions and demonstrate that models based on an inappropriate rate function may lead to misleading scientific conclusions in various scenarios. An analysis of data from an AIDS clinical trial is presented to emphasise the importance of cautious model selection. C1 [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Wang, Mei-Cheng] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Luo, XH (reprint author), Univ Minnesota, Sch Publ Hlth, Div Biostat, 420 Delaware St SE,MMC 303, Minneapolis, MN 55455 USA. EM xianghua@biostat.umn.edu RI Luo, Xianghua/D-6934-2011 NR 19 TC 7 Z9 7 U1 0 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD APR PY 2010 VL 19 IS 2 BP 167 EP 182 DI 10.1177/0962280208090220 PG 16 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 587RU UT WOS:000277010900004 PM 18445699 ER PT J AU Stuelten, CH Mertins, SD Busch, JI Gowens, M Scudiero, DA Burkett, MW Hite, KM Alley, M Hollingshead, M Shoemaker, RH Niederhuber, JE AF Stuelten, Christina H. Mertins, Susan D. Busch, Johanna I. Gowens, Meghan Scudiero, Dominic A. Burkett, Mark W. Hite, Karen M. Alley, Mike Hollingshead, Melinda Shoemaker, Robert H. Niederhuber, John E. TI Complex Display of Putative Tumor Stem Cell Markers in the NCI60 Tumor Cell Line Panel SO STEM CELLS LA English DT Article DE Cancer stem cell; Cell surface marker; Fluorescence-activated cell sorting; Cell culture; NCI60 panel ID CANCER STEM/PROGENITOR CELLS; BREAST-CANCER; PROSPECTIVE IDENTIFICATION; DRUG-SENSITIVITY; GENE-EXPRESSION; MAMMARY-GLAND; BETA-1-INTEGRINS; SUBPOPULATION; PROGENITORS; RESISTANCE AB Tumor stem cells or cancer initiating cells (CICs) are single tumor cells that can regenerate a tumor or a metastasis. The identification and isolation of CICs remain challenging, and a variety of putative CIC markers have been described. We hypothesized that cell lines of the NCI60 panel contain CICs and express putative CIC markers. We investigated expression of putative CIC surface markers (CD15, CD24, CD44, CD133, CD166, CD326, PgP) and the activity of aldehyde dehydrogenase in the NCI60 panel singly and in combination by six-color fluorescence-activated cell sorting analysis. All investigated markers were expressed in cell lines of the NCI60 panel. Expression levels of individual markers varied widely across the 60 cell lines, and neither single marker expression nor simple combinations nor coexpression patterns correlated with the colony-formation capacity of cell lines. Rather, marker expression patterns correlated with tumor types in multidimensional analysis. Whereas some expression patterns correlated with tumor entities such as basal breast cancer, other expression patterns occurred across different tumor types and largely related to expression of a more mesenchymal phenotype in individual breast, lung, renal, and melanoma cell lines. Our data for the first time demonstrate that tumor cell lines display CIC markers in a complex pattern that relates to the tumor type. The complexity and tumor type specificity of marker display creates challenges for the application of cell sorting and other approaches to isolation of putative tumor stem cell populations and suggests that therapeutic targeting strategies will need to take this into account. STEM CELLS 2010;28:649-660 C1 [Stuelten, Christina H.] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. [Mertins, Susan D.; Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. [Scudiero, Dominic A.; Burkett, Mark W.; Hite, Karen M.; Alley, Mike] NCI, SAIC Frederick, Frederick, MD 21702 USA. [Hollingshead, Melinda] NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Stuelten, CH (reprint author), NCI, Cell & Canc Biol Branch, NIH, 37 Convent Dr,Room 1042, Bethesda, MD 20892 USA. EM chrisstu@mail.nih.gov FU NIH, NCI [HHSN261200800001E]; Division of Cancer Treatment and Diagnosis of the National Cancer Institute FX We thank Dr. Anne Monks and Curtis Hose for useful discussions and assistance with creation of the heat map shown in Figure 5, Tom Silvers for assistance with data processing, Dr. Larry Rubinstein for advice regarding statistical treatment of the data, and Dr. Bill Matsui for introducing us to the use of Aldefluor. This research was supported in part by the Intramural Research Program of the NIH, NCI, and 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. This research was supported [in part] by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NCI-Frederick is accredited by AAALACi and follows the Public Health Service Policy on the Care and Use of Laboratory Animals. All animals used in this research project were cared for and used humanely according to the following policies: The U. S. Public Health Service Policy on Humane Care and Use of Animals (1996); the Guide for the Care and Use of Laboratory Animals (NIH publication No. 86-23, 1985); and the U. S. Government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (1985). NR 41 TC 57 Z9 59 U1 0 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD APR PY 2010 VL 28 IS 4 BP 649 EP 660 DI 10.1002/stem.324 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 588SY UT WOS:000277095400004 PM 20178109 ER PT J AU Winkler, T Cantilena, A Metais, JY Xu, XL Nguyen, AD Borate, B Antosiewicz-Bourget, JE Wolfsberg, TG Thomson, JA Dunbar, CE AF Winkler, Thomas Cantilena, Amy Metais, Jean-Yves Xu, Xiuli Nguyen, Anh-Dao Borate, Bhavesh Antosiewicz-Bourget, Jessica E. Wolfsberg, Tyra G. Thomson, James A. Dunbar, Cynthia E. TI No Evidence for Clonal Selection Due to Lentiviral Integration Sites in Human Induced Pluripotent Stem Cells SO STEM CELLS LA English DT Article DE Induced pluripotent stem cells; Gene delivery systems in vivo or in vitro; Cellular reprogramming; Lentiviral vector; Insertional mutagenesis; Pluripotent stem cells; Transcription factor; Cellular therapy ID HUMAN SOMATIC-CELLS; RETROVIRAL DNA INTEGRATION; VECTOR INTEGRATION; HEMATOPOIETIC-CELLS; GENE-THERAPY; TRANSGENE EXPRESSION; DEFINED FACTORS; MOUSE MODEL; HOT-SPOTS; GENERATION AB Derivation of induced pluripotent stem (iPS) cells requires the expression of defined transcription factors (among Oct3/4, Sox2, Klf4, c-Myc, Nanog, and Lin28) in the targeted cells. Lentiviral or standard retroviral gene transfer remains the most robust and commonly used approach. Low reprogramming frequency overall, and the higher efficiency of derivation utilizing integrating vectors compared to more recent nonviral approaches, suggests that gene activation or disruption via proviral integration sites (IS) may play a role in obtaining the pluripotent phenotype. We provide for the first time an extensive analysis of the lentiviral integration profile in human iPS cells. We identified a total of 78 independent IS in eight recently established iPS cell lines derived from either human fetal fibroblasts or newborn foreskin fibroblasts after lentiviral gene transfer of Oct4, Sox2, Nanog, and Lin28. The number of IS ranged from 5 to 15 IS per individual iPS clone, and 75 IS could be assigned to a unique chromosomal location. The different iPS clones had no IS in common. Expression analysis as well as extensive bioinformatic analysis did not reveal functional concordance of the lentiviral targeted genes between the different clones. Interestingly, in six of the eight iPS clones, some of the IS were found in pairs, integrated into the same chromosomal location within six base pairs of each other or in very close proximity. Our study supports recent reports that efficient reprogramming of human somatic cells is not dependent on insertional activation or deactivation of specific genes or gene classes. STEM CELLS 2010;28:687-694 C1 [Winkler, Thomas; Cantilena, Amy; Metais, Jean-Yves; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Xu, Xiuli] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Nguyen, Anh-Dao; Borate, Bhavesh; Wolfsberg, Tyra G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Antosiewicz-Bourget, Jessica E.; Thomson, James A.] Genome Ctr Wisconsin, Madison, WI USA. Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA. Univ Wisconsin, Dept Anat, Madison, WI 53706 USA. Morgidge Inst Res, Madison, WI USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Room 4E-5132,Bldg 10-CRC,10 Ctr Dr, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute; National Human Genome Research Institute, National Institutes of Health FX This research was supported in part by the Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute, National Institutes of Health. NR 47 TC 23 Z9 24 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD APR PY 2010 VL 28 IS 4 BP 687 EP 694 DI 10.1002/stem.322 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 588SY UT WOS:000277095400007 PM 20166152 ER PT J AU Yan, X Qin, HY Qu, CY Tuan, RS Shi, ST Huang, GTJ AF Yan, Xing Qin, Haiyan Qu, Cunye Tuan, Rocky S. Shi, Songtao Huang, George T. -J. TI iPS Cells Reprogrammed From Human Mesenchymal-Like Stem/Progenitor Cells of Dental Tissue Origin SO STEM CELLS AND DEVELOPMENT LA English DT Article ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; IN-VITRO; HUMAN FIBROBLASTS; DEFINED FACTORS; PULP CELLS; GENERATION; MOUSE; TOOTH; INDUCTION AB Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. Many types of cells have been successfully reprogrammed into iPS cells in the mouse system; however, reprogramming human cells have been more difficult. To date, human dermal fibroblasts are the most accessible and feasible cell source for iPS generation. Dental tissues derived from ectomesenchyme harbor mesenchymal-like stem/progenitor cells and some of the tissues have been treated as biomedical wastes, for example, exfoliated primary teeth and extracted third molars. We asked whether stem/progenitor cells from discarded dental tissues can be reprogrammed into iPS cells. The 4 factors Lin28/Nanog/Oct4/Sox2 or c-Myc/Klf4/Oct4/Sox2 carried by viral vectors were used to reprogram 3 different dental stem/progenitor cells: stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), and dental pulp stem cells (DPSCs). We showed that all 3 can be reprogrammed into iPS cells and appeared to be at a higher rate than fibroblasts. They exhibited a morphology indistinguishable from human embryonic stem (hES) cells in cultures and expressed hES cell markers SSEA-4, TRA-1-60, TRA-1-80, TRA-2-49, Nanog, Oct4, and Sox2. They formed embryoid bodies in vitro and teratomas in vivo containing tissues of all 3 germ layers. We conclude that cells of ectomesenchymal origin serve as an excellent alternative source for generating iPS cells. C1 [Yan, Xing; Huang, George T. -J.] Columbia Univ, Coll Dent Med, Div Endodont, Sect Oral & Diagnost Sci, New York, NY USA. [Qin, Haiyan; Shi, Songtao] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90089 USA. [Qu, Cunye] Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90089 USA. [Tuan, Rocky S.; Huang, George T. -J.] NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Huang, George T. -J.] Univ Maryland, Sch Dent, Coll Dent Surg, Dept Endodont Prosthodont & Operat Dent, Baltimore, MD 21201 USA. RP Huang, GTJ (reprint author), Boston Univ, Dept Endodont, Henry M Goldman Sch Dent Med, 100 E Newton St, Boston, MA 02118 USA. EM gtjhuang@bu.edu FU National Institutes of Health [R01 DE019156-01, RO1 DE17449]; NIAMS/NIH [Z01 AR41131] FX This work was supported in part by grants from the National Institutes of Health R01 DE019156-01 (G.T.-J.H.), RO1 DE17449 (S.S.), and by the NIAMS/NIH Intramural Research Program Z01 AR41131 (R.S.T). We wish to thank Dr. Barbara Mallon (NIH, Stem Cell Unit, Bethesda, MD), Dr. Qi-Long Ying (Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA), Dr. Shinya Yamanaka (Center for iPS cell research and application, Kyoto University, Japan), and Dr. Junying Yu (University of Wisconsin, Madison, WI) for providing assistance and advice in human ES cell or iPS cell cultures. NR 41 TC 119 Z9 129 U1 3 U2 29 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD APR PY 2010 VL 19 IS 4 BP 469 EP 480 DI 10.1089/scd.2009.0314 PG 12 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 579HI UT WOS:000276359200005 PM 19795982 ER PT J AU An, L Dani, KA Shen, J Warach, S AF An, Li Dani, Krishna A. Shen, Jun Warach, Steven CA NINDS Nat Hist Stroke Investigator TI Pilot Results of in vivo Brain Glutathione Measurements in Stroke Patients Using Magnetic Resonance Spectroscopy SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [An, Li; Dani, Krishna A.; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. [Shen, Jun] NIMH, NIH, Bethesda, MD 20892 USA. RI Dani, Krishna/B-4516-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E386 EP E386 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100762 ER PT J AU Barr, TL Conley, Y Dillman, A Ding, JH Warach, S Singleton, A Matarin, M AF Barr, Taura L. Conley, Yvette Dillman, Allissa Ding, Jinhui Warach, Steven Singleton, Andrew Matarin, Mar TI Inflammatory Regulation as a Biomarker of Ischemic Stroke Diagnosis: Evidence From Gene Expression Profiling SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Barr, Taura L.] NINR, NIH, Bethesda, MD 20892 USA. [Conley, Yvette] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Dillman, Allissa; Ding, Jinhui; Singleton, Andrew] NIA, NIH, Bethesda, MD 20892 USA. [Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. [Matarin, Mar] UCL, London, England. RI Singleton, Andrew/C-3010-2009; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E371 EP E371 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100706 ER PT J AU Batra, A Latour, LL Ruetzler, CA Hallenbeck, JM Spatz, M Warach, S Henning, EC AF Batra, Ayush Latour, Lawrence L. Ruetzler, Christl A. Hallenbeck, John M. Spatz, Maria Warach, Steven Henning, Erica C. TI Increased Plasma but Not Brain Matrix Metalloproteinase Levels Are Associated With Early Blood-Brain Barrier Disruption Following Experimental Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Batra, Ayush; Latour, Lawrence L.; Ruetzler, Christl A.; Hallenbeck, John M.; Spatz, Maria; Warach, Steven; Henning, Erica C.] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E225 EP E225 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100153 ER PT J AU Bogoslovsky, T Chaudhry, A Luby, M Maric, D Latour, L Spatz, M Frank, J Warach, S AF Bogoslovsky, Tanya Chaudhry, Aneeka Luby, Marie Maric, Dragan Latour, Lawrence Spatz, Maria Frank, Joseph Warach, Steven CA NINDS Nat Hist Stroke Investigator TI Endothelial Progenitor Cells Correlate With Acute Lesion Volume, Lesion Growth Volume and Final Infarct Volume SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Bogoslovsky, Tanya; Luby, Marie; Maric, Dragan; Latour, Lawrence; Spatz, Maria; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. [Chaudhry, Aneeka] NIH, CC, ORIS, LDRR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E385 EP E385 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100760 ER PT J AU Bokkers, RP Warach, S van Osch, MJ Duyn, J Latour, LL AF Bokkers, Reinoud P. Warach, Steven van Osch, Matthias J. Duyn, Jeff Latour, Lawrence L. TI Whole-brain Arterial Spin Labeling Perfusion MR Imaging in Patients With Acute Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Bokkers, Reinoud P.] UMC Utrecht, Utrecht, Netherlands. [Warach, Steven; Duyn, Jeff; Latour, Lawrence L.] NINDS, NIH, Bethesda, MD 20892 USA. [van Osch, Matthias J.] LUMC, Leiden, Netherlands. RI Duyn, Jozef/F-2483-2010 NR 0 TC 1 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E273 EP E273 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100328 ER PT J AU Campen, CJ Kranick, SM Kessler, SK Kasner, SE Ichord, RN Beslow, LA Smith, SE Licht, DJ Fisher, MJ AF Campen, Cynthia J. Kranick, Sarah M. Kessler, Sudah K. Kasner, Scott E. Ichord, Rebecca N. Beslow, Lauren A. Smith, Sabrina E. Licht, Daniel J. Fisher, Michael J. TI Late Neurovascular Events in Pediatric Brain Tumor Patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Campen, Cynthia J.] Stanford Univ, Packard Hosp, Stanford, CA 94305 USA. [Kranick, Sarah M.] NIH, Washington, DC USA. [Kessler, Sudah K.; Ichord, Rebecca N.; Beslow, Lauren A.; Smith, Sabrina E.; Licht, Daniel J.; Fisher, Michael J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kasner, Scott E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. RI Kasner, Scott/C-6109-2011; Licht, Daniel/I-3370-2013 OI Licht, Daniel/0000-0002-4080-843X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E217 EP E217 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100125 ER PT J AU Conforto, AB Melo, E Nagaya, E Reis, F Tomasi, C Scaff, M Cohen, LG AF Conforto, Adriana B. Melo, Eduardo Nagaya, Erina Reis, Felipe Tomasi, Camilla Scaff, Milberto Cohen, Leonardo G. TI Safety of Repetitive Transcranial Magnetic Stimulation of the Unaffected Hemisphere in Subacute Stroke Patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. [Conforto, Adriana B.; Melo, Eduardo; Nagaya, Erina; Reis, Felipe; Tomasi, Camilla; Scaff, Milberto] Hosp Clin Paulo Univ, Sao Paulo, Brazil. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E387 EP E387 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100767 ER PT J AU Dani, KA Latour, L Warach, S AF Dani, Krishna A. Latour, Lawrence Warach, Steven CA NINDS Nat Hist Stroke Investigator TI Hyperintense Vessel Sign on Fluid Attenuated Inversion Recovery Magnetic Resonance Imaging is Reduced by Gadolinium SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Dani, Krishna A.; Latour, Lawrence; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. RI Dani, Krishna/B-4516-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E369 EP E369 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100698 ER PT J AU Davis, LA Luby, M Butman, J Warach, S AF Davis, Lisa A. Luby, Marie Butman, John Warach, Steven CA CATALIST Investigators TI Early Antiplatelet and Anticoagulation After Standard Alteplase Therapy for Acute Ischemic Stroke Does Not Increase Risk of Intracranial Hemorrhage SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Davis, Lisa A.; Luby, Marie; Butman, John; Warach, Steven] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E330 EP E330 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100545 ER PT J AU Ginsberg, MD Martin, RH Hill, MD Palesch, YY Yeatts, S Moy, CS Tamariz, D Ryckborst, K Waldman, BD AF Ginsberg, Myron D. Martin, Renee H. Hill, Michael D. Palesch, Yuko Y. Yeatts, Sharon Moy, Claudia S. Tamariz, Diego Ryckborst, Karla Waldman, Bonnie D. TI The Albumin in Acute Stroke (ALIAS) Trial: Part 1 Safety Analysis SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Ginsberg, Myron D.; Tamariz, Diego] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Martin, Renee H.; Palesch, Yuko Y.; Yeatts, Sharon; Waldman, Bonnie D.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hill, Michael D.; Ryckborst, Karla] Univ Calgary, Calgary, AB, Canada. [Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E228 EP E228 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100163 ER PT J AU Henning, EC Warach, S Latour, LL AF Henning, Erica C. Warach, Steven Latour, Lawrence L. TI Quantifying the Impact of Pre-treatment MRI Inclusion Criteria on Type-I/Type-II Error in Experimental Stroke Modeling SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Henning, Erica C.; Warach, Steven; Latour, Lawrence L.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E279 EP E279 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100350 ER PT J AU Henning, EC Paiva, FF Silva, AC Latour, LL AF Henning, Erica C. Paiva, Fernando F. Silva, Afonso C. Latour, Lawrence L. TI Assessing Stroke Evolution in SHR Rats: Arterial Spin Labeling is Superior to Dynamic Susceptibility Contrast SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Henning, Erica C.; Paiva, Fernando F.; Silva, Afonso C.; Latour, Lawrence L.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RI Silva, Afonso/A-7129-2009; Paiva, Fernando/C-1429-2012 OI Paiva, Fernando/0000-0002-8989-9707 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E277 EP E277 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100342 ER PT J AU Howard, G Kissela, BM Kleindorfer, DO McClure, LA Safford, MM Rhodes, D Cushman, M Soliman, EZ Moy, CS Howard, VJ AF Howard, George Kissela, Brett M. Kleindorfer, Dawn O. McClure, Leslie A. Safford, Monika M. Rhodes, David Cushman, Mary Soliman, Elsayed Z. Moy, Claudia S. Howard, Virginia J. TI Traditional Risk Factors Play a Minor Role in the Excess Stroke Incidence of African Americans: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Howard, George; McClure, Leslie A.; Safford, Monika M.; Rhodes, David; Howard, Virginia J.] Univ Alabama, Birmingham, AL USA. [Kissela, Brett M.; Kleindorfer, Dawn O.] Univ Cincinnati, Cincinnati, OH USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Moy, Claudia S.] NINDS, NIH, Bethesda, MD 20892 USA. RI Soliman, Elsayed/D-8124-2011 OI Soliman, Elsayed/0000-0001-5632-8150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E225 EP E225 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100150 ER PT J AU Howard, VJ Kleindorfer, D McClure, LA Kissela, BM Safford, MM Rhodes, JD Cushman, M Moy, CS Soliman, EZ Howard, G AF Howard, Virginia J. Kleindorfer, Dawn McClure, Leslie A. Kissela, Brett M. Safford, Monika M. Rhodes, James D. Cushman, Mary Moy, Claudia S. Soliman, Elsayed Z. Howard, George CA REGARDS Investigators TI Stroke Incidence as the Major Contributor to Racial and Regional Disparities in Stroke Mortality: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Howard, Virginia J.; McClure, Leslie A.; Safford, Monika M.; Rhodes, James D.; Howard, George] Univ Alabama, Birmingham, AL USA. [Kleindorfer, Dawn; Kissela, Brett M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. [Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. RI Soliman, Elsayed/D-8124-2011 OI Soliman, Elsayed/0000-0001-5632-8150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E244 EP E245 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100224 ER PT J AU Ku, KD Luby, M Latour, LL Warach, S AF Ku, Katherine D. Luby, Marie Latour, Lawrence L. Warach, Steven CA NINDS Nat Hist Stroke Investigator TI Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION Project): MRI Defined Pathology in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Ku, Katherine D.; Luby, Marie; Latour, Lawrence L.; Warach, Steven] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E334 EP E334 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100561 ER PT J AU Ku, KD Latour, LL Merino, JG Hsia, AW Lynch, JK Warach, S Luby, M AF Ku, Katherine D. Latour, Lawrence L. Merino, Jose G. Hsia, Amie W. Lynch, John K. Warach, Steven Luby, Marie TI Diffusion-perfusion Mismatch Selection for Clinical Trials: Visual Determination Reliably Estimates Quantitative Mismatch Criteria SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Ku, Katherine D.; Latour, Lawrence L.; Merino, Jose G.; Hsia, Amie W.; Lynch, John K.; Warach, Steven; Luby, Marie] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E296 EP E296 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100413 ER PT J AU Lees, KR Bluhmki, E Toni, D von Kummer, R Marler, J Brott, TG Kaste, M Grotta, JC Albers, GW Hamilton, S Tilley, BC Hacke, W AF Lees, Kennedy R. Bluhmki, Erich Toni, Danilo von Kummer, Ruediger Marler, John Brott, Thomas G. Kaste, Markku Grotta, James C. Albers, Gregory W. Hamilton, Scott Tilley, Barbara C. Hacke, Werner CA ECASS I-III ATLANTIS Investigator NINDS Investigator TI Time Dependent Response to Treatment With Intravenous rtPA for Stroke: An Updated Pooled Analysis of ECASS, ATLANTIS and NINDS Stroke Trials SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Lees, Kennedy R.] Univ Glasgow, Fac Med, Glasgow, Lanark, Scotland. [Bluhmki, Erich] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Toni, Danilo] Univ Roma La Sapienza, Dept Neurol Sci, Rome, Italy. [von Kummer, Ruediger] Tech Univ Dresden, Dresden, Germany. [Marler, John] NINDS, Bethesda, MD 20892 USA. [Brott, Thomas G.] Mayo Clin, Jacksonville, FL 32224 USA. [Kaste, Markku] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. [Grotta, James C.] Univ Texas Houston, Sch Med, Houston, TX USA. [Albers, Gregory W.] Stanford Univ, Stanford, CA 94305 USA. [Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA. [Tilley, Barbara C.] Univ Texas Hlth Sci Cntr, Sch Publ Hlth, Houston, TX USA. [Hacke, Werner] Univ Heidelberg, Dept Neurol, Heidelberg, Germany. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E247 EP E248 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100234 ER PT J AU Lima, FO Silva, GS Batista, LM Camargo, EC Singhal, AB Ay, H Greer, DM Yoo, AJ Lev, MH Harris, GJ Koroshetz, WJ Smith, WS Furie, KL Nogueira, RG AF Lima, Fabricio O. Silva, Gisele S. Batista, Leonardo M. Camargo, Erica C. Singhal, Aneesh B. Ay, Hakan Greer, David M. Yoo, Albert J. Lev, Michael H. Harris, Gordon J. Koroshetz, Walter J. Smith, Wade S. Furie, Karen L. Nogueira, Raul G. TI Natural History of Untreated Strokes Due to Proximal Anterior Circulation Occlusions Detected on CT Angiography SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Lima, Fabricio O.; Silva, Gisele S.; Batista, Leonardo M.; Camargo, Erica C.; Singhal, Aneesh B.; Ay, Hakan; Greer, David M.; Yoo, Albert J.; Lev, Michael H.; Harris, Gordon J.; Furie, Karen L.; Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD 20892 USA. [Smith, Wade S.] UCSF Med Ctr, San Francisco, CA USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E333 EP E333 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100559 ER PT J AU Lima, FO Silva, GS Levy, MH Harris, G Smith, WS Halpern, EF Koroshetz, W Furie, KL AF Lima, Fabricio O. Silva, Gisele S. Levy, Michael H. Harris, Gordon Smith, Wade S. Halpern, Elkan F. Koroshetz, Walter Furie, Karen L. TI Differences in Risk Factors Between Intracranial and Extracranial Atherosclerosis in a Predominantly White American Population SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Lima, Fabricio O.; Silva, Gisele S.; Levy, Michael H.; Harris, Gordon; Halpern, Elkan F.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Wade S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Koroshetz, Walter] NINDS, Bethesda, MD 20892 USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E271 EP E271 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100320 ER PT J AU Magadan, A Luby, M Warach, S AF Magadan, Alejandro Luby, Marie Warach, Steven CA NINDS Nat Hist Stroke Investigator TI Clinical Diffusion Mismatch and MRA Diffusion Mismatch Are Specific but Not Sensitive to Identify Perfusion Diffusion Mismatch SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Magadan, Alejandro] Georgetown Univ, Washington, DC USA. [Luby, Marie; Warach, Steven] NIH, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E295 EP E295 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100411 ER PT J AU Sanossian, N Starkman, S Hamilton, S Liebeskind, DS Ali, LK Restrepo, L Sung, G Conwit, R Eckstein, M Pratt, F Stratton, S Saver, JL AF Sanossian, Nerses Starkman, Sidney Hamilton, Scott Liebeskind, David S. Ali, Latisha K. Restrepo, Lucas Sung, Gene Conwit, Robin Eckstein, Mark Pratt, Frank Stratton, Samuel Saver, Jeffrey L. CA FAST-MAG Investigators Nurses TI Development and Validation of a Clinical Scale Distinguishing Hemorrhagic and Ischemic Stroke in the First Two Hours After Onset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Sanossian, Nerses; Sung, Gene; Eckstein, Mark] Univ So Calif, Los Angeles, CA USA. [Starkman, Sidney; Liebeskind, David S.; Ali, Latisha K.; Restrepo, Lucas; Stratton, Samuel; Saver, Jeffrey L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA. [Conwit, Robin] NIH, Bethesda, MD 20892 USA. [Pratt, Frank] Torrance Mem Med Cntr, Torrance, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E309 EP E309 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100463 ER PT J AU Sheng, X Thomas, A Warach, S Latour, L AF Sheng, Xi Thomas, Adam Warach, Steven Latour, Lawrence CA NINDS Nat Hist Stroke Investigator TI Acute Cortical Lesions "Disappear" on MRI but Are Associated With Cortical Atrophy in Stroke Patients: Implications for Brain Aging and Vascular Cognitive Impairment SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Sheng, Xi; Warach, Steven; Latour, Lawrence] NINDS, Washington, DC USA. [Thomas, Adam] NIMH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E213 EP E213 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100111 ER PT J AU Song, SS Ritter, CH Ku, KD Latour, LL Warach, S AF Song, Shlee S. Ritter, Carsten H. Ku, Katherine D. Latour, Lawrence L. Warach, Steven CA NINDS Nat Hist Stroke TI The Upper Time Limit of DWI Positive - FLAIR Negative MRI in Witnessed-onset Acute Ischemic Strokes is Less Than 6 hours: Implications for the Design of Wake-up Stroke Treatment Trials SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Song, Shlee S.; Ritter, Carsten H.; Ku, Katherine D.; Latour, Lawrence L.; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E247 EP E247 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100232 ER PT J AU Trollinger, S McDowell, K Miller, K Stout, A Kunitz, S Saver, J Janis, S Odenkirchen, J Warach, S AF Trollinger, Stacie McDowell, Katherine Miller, Kristy Stout, Alexandra Kunitz, Selma Saver, Jeffrey Janis, Scott Odenkirchen, Joanne Warach, Steven TI National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Common Data Element (CDE) Project: Stroke CDE Update SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Trollinger, Stacie; McDowell, Katherine; Miller, Kristy; Stout, Alexandra; Kunitz, Selma] KAI Rsch Inc, Rockville, MD USA. [Saver, Jeffrey] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. [Janis, Scott; Odenkirchen, Joanne; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E390 EP E390 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100779 ER PT J AU Warach, S Latour, L AF Warach, Steven Latour, Lawrence CA NINDS Nat Hist Stroke Investigator TI Blood Brain Barrier Disruption Remote From the Infarct in Alteplase-Treated Stroke Patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 23-26, 2010 CL San Antonio, TX SP Amer Heart Assoc, Amer Stroke Assoc C1 [Warach, Steven; Latour, Lawrence; NINDS Nat Hist Stroke Investigator] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2010 VL 41 IS 4 BP E385 EP E386 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 575XU UT WOS:000276106100761 ER PT J AU Lacouture, ME Maitland, ML Segaert, S Setser, A Baran, R Fox, LP Epstein, JB Barasch, A Einhorn, L Wagner, L West, DP Rapoport, BL Kris, MG Basch, E Eaby, B Kurtin, S Olsen, EA Chen, A Dancey, JE Trotti, A AF Lacouture, Mario E. Maitland, Michael L. Segaert, Siegfried Setser, Ann Baran, Robert Fox, Lindy P. Epstein, Joel B. Barasch, Andrei Einhorn, Lawrence Wagner, Lynne West, Dennis P. Rapoport, Bernardo L. Kris, Mark G. Basch, Ethan Eaby, Beth Kurtin, Sandra Olsen, Elise A. Chen, Alice Dancey, Janet E. Trotti, Andy TI A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Adverse events; Dermatologic; Skin; Mucosa; Quality of life; EGFR inhibitors; Grading ID FACTOR RECEPTOR INHIBITORS; PATIENT-REPORTED OUTCOMES; METASTATIC COLORECTAL-CANCER; CLINICAL-TRIALS NETWORKS; MANAGEMENT; THERAPY; PLUS; INSTITUTE; ERLOTINIB; CETUXIMAB AB Accurate grading of dermatologic adverse events (AE) due to epidermal growth factor receptor (EGFR) inhibitors (EGFRIs) is necessary for drug toxicity determinations, interagent comparisons, and supportive care trials. The most widely used severity grading scale, the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0), was not designed specifically for this class of agents and may result in underreporting and poor grading of distinctive adverse events. We believe a class-specific grading scale is needed to help standardize assessment and improve reporting of EGFRI-associated dermatologic AEs. The Multinational Association of Supportive Care in Cancer (MASCC) Skin Toxicity Study Group conducted an international multidisciplinary meeting that included 20 clinicians and researchers from academic centers and government agencies. Experts from different disciplines presented current information specific to EGFRI-induced dermatologic toxicities: grading scale development, pharmacovigilance safety reporting, health-related quality of life, patient reporting, and pharmacology. Group discussions, literature reviews, and professional expertise established the theoretical foundation for the proposed grading scale. A new grading system is proposed for the most common events associated with EGFRI-induced dermatologic AEs: papulopustular reaction or acneiform rash, nail changes, erythema, pruritus, xerosis, hair changes, telangiectasias, hyperpigmentation, mucositis, flushing, radiation dermatitis, hyposalivation, and taste changes. The proposed scale maintains consistency with the grading principles and language of the existing CTCAE version 4.0 and MedDRA terminology and includes relevant patient-reported health-related quality of life factors. A grading scale specific to EGFR inhibitor dermatologic AEs is presented for formal integration into future versions of CTCAE and for validation in clinical trial settings. The study group designed this scale to detect and report EGFRI-related toxicities with greater sensitivity, specificity, and range than the scales currently used. This scale should serve as a foundation for efforts to perform objective interdrug comparisons and assessments of supportive care treatment strategies more effectively than with current methods. C1 [Lacouture, Mario E.; Wagner, Lynne; West, Dennis P.] Dermatol Serv, New York, NY 10022 USA. [Maitland, Michael L.] Univ Chicago, Chicago, IL 60637 USA. [Segaert, Siegfried] Univ Hosp, Louvain, Belgium. [Setser, Ann; Chen, Alice] NCI, Rockville, MD USA. [Baran, Robert] Nail Dis Ctr, Cannes, France. [Fox, Lindy P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Epstein, Joel B.] Univ Illinois, Chicago, IL USA. [Barasch, Andrei] Univ Alabama, Birmingham, AL USA. [Einhorn, Lawrence] Indiana Univ, Indianapolis, IN 46204 USA. [Rapoport, Bernardo L.] Rosebank, Med Oncol Ctr, Johannesburg, South Africa. [Kris, Mark G.; Basch, Ethan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Eaby, Beth] Univ Penn, Philadelphia, PA 19104 USA. [Kurtin, Sandra] Univ Arizona, Tucson, AZ USA. [Olsen, Elise A.] Duke Univ, Durham, NC USA. [Dancey, Janet E.] Ontario Inst Canc Res, Toronto, ON, Canada. [Trotti, Andy] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Wagner, Lynne; West, Dennis P.] Northwestern Univ, Chicago, IL 60611 USA. RP Lacouture, ME (reprint author), Dermatol Serv, Rockefeller Outpatient Pavil,Mem Sloan Kettering, New York, NY 10022 USA. EM LacoutuM@mskcc.org OI Kris, Mark/0000-0002-7317-5341; West, Dennis/0000-0002-9107-6697; Rapoport, Bernardo/0000-0001-7610-3653 FU OSI Pharmaceuticals; Amgen, Inc; Robert H Lurie Comprehensive Cancer Center; Dermatology Foundation Career Development Award FX This project was supported by OSI Pharmaceuticals and Amgen, Inc. M.E.L. is supported by a Zell Scholarship from the Robert H Lurie Comprehensive Cancer Center and a Dermatology Foundation Career Development Award. NR 31 TC 69 Z9 71 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD APR PY 2010 VL 18 IS 4 BP 509 EP 522 DI 10.1007/s00520-009-0744-x PG 14 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 563JV UT WOS:000275126000013 PM 20145956 ER PT J AU Tsai, SY Lee, CT Hayashi, T Freed, WJ Su, TP AF Tsai, Shang-Yi Lee, Chung-Ting Hayashi, Teruo Freed, William J. Su, Tsung-Ping TI Delta Opioid Peptide DADLE and Naltrexone Cause Cell Cycle Arrest and Differentiation in a CNS Neural Progenitor Cell Line SO SYNAPSE LA English DT Article DE delta opioid; DADLE; naltrexone; dopamine (DA); AF5; differentiation ID ADULT HIPPOCAMPAL PROGENITORS; GROWTH-FACTOR; DOPAMINERGIC-NEURONS; IN-VITRO; PROLIFERATION; NEUROGENESIS; NALOXONE; INHIBITION; CULTURES; PATHWAY AB Opioids have been demonstrated to play an important role in CNS development by affecting proliferation and differentiation in various types of neural cells. This study examined the effect of a stable delta opioid peptide [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) on proliferation and differentiation in an AF5 CNS neural progenitor cell line derived from rat mesencephalic cells. DADLE (1 pM, 0.1 nM, or 10 nM) caused a significant growth inhibition on AF5 cells. The opioid antagonist naltrexone at 0.1 nM also caused growth inhibition in the same cells. When DADLE and naltrexone were both added to the AF5 cells, the resultant growth inhibition was apparently additive. DADLE alone or DADLE in combination with naltrexone did not cause apoptosis as evidenced by negative TUNEL staining. The cell-cycle progression analysis indicated that both DADLE (0.1 nM) and naltrexone (0.1 nM) caused an arrest of AF5 cell cycle progression at the G1 checkpoint. Neuronal marker indicated that DADLE- or naltrexone-treated AF5 cells tend to differentiate more when compared to controls. Results demonstrate the nonopioid action of both DADLE and naltrexone on cell cycle arrest and differentiation in a CNS neural progenitor cell line. Results also suggest some potential utilization of DADLE and/or naltrexone in stem cell research. Synapse 64:267-273, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Tsai, Shang-Yi; Hayashi, Teruo; Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch,IRP, NIH,DHHS, Baltimore, MD 21224 USA. [Lee, Chung-Ting; Freed, William J.] NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch,IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch,IRP, NIH,DHHS, Triad Bldg,Room 3304,333 Cassell Dr, Baltimore, MD 21224 USA. EM TSU@intra.nida.nih.gov FU National Institute on Drug abuse; NIH; DHHS FX Contract grant sponsors: Intramural Research Program of the National Institute on Drug abuse, NIH, and DHHS NR 19 TC 12 Z9 12 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2010 VL 64 IS 4 BP 267 EP 273 DI 10.1002/syn.20727 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 561AV UT WOS:000274948200001 PM 19953654 ER PT J AU Sally, EJ Xu, H Dersch, CM Hsin, LW Chang, LT Prisinzano, TE Simpson, DS Giuvelis, D Rice, KC Jacobson, AE Cheng, KJ Bilsky, EJ Rothman, RB AF Sally, Elliott J. Xu, Heng Dersch, Christina M. Hsin, Ling-Wei Chang, Li-Te Prisinzano, Thomas E. Simpson, Denise S. Giuvelis, Denise Rice, Kenner C. Jacobson, Arthur E. Cheng, Kejun Bilsky, Edward J. Rothman, Richard B. TI Identification of a Novel "Almost Neutral" mu-Opioid Receptor Antagonist in CHO Cells Expressing the Cloned Human mu-Opioid Receptor SO SYNAPSE LA English DT Article DE opioid receptor; G proteins; herkinorin; inverse agonist; neutral antagonist ID IN-VIVO; ANTINOCICEPTIVE TOLERANCE; PEPTIDE RECEPTOR; SALVINORIN-A; AGONIST; DEPENDENCE; NALOXONE; EFFICACY; PROTEIN; PROBES AB The basal (constitutive) activity of G protein-coupled receptors allows for the measurement of inverse agonist activity. Some competitive antagonists turn into inverse agonists under conditions where receptors are constitutively active. In contrast, neutral antagonists have no inverse agonist activity, and they block both agonist and inverse agonist activity. The mu-opioid receptor (MOR) demonstrates detectable constitutive activity only after a state of dependence is produced by chronic treatment with a MOR agonist. We therefore sought to identify novel MOR inverse agonists and novel neutral MOR antagonists in both untreated and agonist-treated MOR cells. CHO cells expressing the cloned human mu receptor (hMOR-CHO cells) were incubated for 20 h with medium (control) or 10 mu M (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(benzoyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester (herkinorin, HERK). HERK treatment generates a high degree of basal signaling and enhances the ability to detect inverse agonists. [(35)S]-GTP-gamma-S assays were conducted using established methods. We screened 21 MOR "antagonists" using membranes prepared from HERK-treated hMOR-CHO cells. All antagonists, including CTAP and 6 beta-naltrexol, were inverse agonists. However, LTC-274 ((-)-3-cyclopropylmethyl-2,3,4,4a alpha,5,6,7,7a alpha-octahydro-1H-benzofuro[3,2-e]isoquinolin-9-ol)) showed the lowest efficacy as an inverse agonist, and, at concentrations less than 5 nM, had minimal effects on basal [(35)S]-GTP-gamma-S binding. Other efforts in this study identified KC-2-009 ((+)-3-((1R,5S)-2-((Z)-3-phenylallyl)-2-azabicyclo[3.3.1]-nonan-5-yl)phenol hydrochloride) as an inverse agonist at untreated MOR cells. In HERK-treated cells, KC-2-009 had the highest efficacy as an inverse agonist. In summary, we identified a novel and selective MOR inverse agonist (KC-2-009) and a novel MOR antagonist (LTC-274) that shows the least inverse agonist activity among 21 MOR antagonists. LTC-274 is a promising lead compound for developing a true MOR neutral antagonist. Synapse 64:280-288, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Sally, Elliott J.; Xu, Heng; Dersch, Christina M.; Rothman, Richard B.] NIDA, NIH, Clin Psychopharmacol Sect, IRP,DHHS, Baltimore, MD 21224 USA. [Hsin, Ling-Wei; Chang, Li-Te] Natl Taiwan Univ, Inst Pharmaceut Sci, Coll Med, Taipei 10018, Taiwan. [Prisinzano, Thomas E.; Simpson, Denise S.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Giuvelis, Denise; Bilsky, Edward J.] Univ New England, Dept Pharmacol, Biddeford, ME 04005 USA. [Rice, Kenner C.; Jacobson, Arthur E.; Cheng, Kejun] NIDA, Drug Design & Synth Sect, IRP, NIH,DHHS, Bethesda, MD 20892 USA. RP Rothman, RB (reprint author), NIDA, NIH, Clin Psychopharmacol Sect, IRP,DHHS, Suite 4500,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov RI Prisinzano, Thomas/B-7877-2010 FU National Institute on Drug Abuse; DHHS [DA018151] FX Contract grant sponsors: Intramural Research Program, National Institute on Drug Abuse, DHHS; Contract grant number: DA018151. NR 21 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2010 VL 64 IS 4 BP 280 EP 288 DI 10.1002/syn.20723 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 561AV UT WOS:000274948200003 PM 19953652 ER PT J AU Concheiro, M Jones, HE Johnson, RE Choo, R Shakleya, DM Huestis, MA AF Concheiro, Marta Jones, Hendree E. Johnson, Rolley E. Choo, Robin Shakleya, Diaa M. Huestis, Marilyn A. TI Maternal Buprenorphine Dose, Placenta Buprenorphine, and Metabolite Concentrations and Neonatal Outcomes SO THERAPEUTIC DRUG MONITORING LA English DT Article DE buprenorphine; placenta; Neonatal Abstinence Syndrome; in utero drug exposure; opioid-dependence ID BIOLOGICAL MATRICES; PREGNANT-WOMEN; AMNIOTIC-FLUID; HUMAN LIVER; EXPRESSION; EXPOSURE; METHADONE; MOTHERS; AROMATASE; MECONIUM AB Buprenorphine is approved as pharmacotherapy for opioid dependence in nonpregnant patients in multiple countries and is currently under investigation for pregnant women in the United States and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in five term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships among maternal buprenorphine dose, placenta concentrations, and neonatal outcomes after controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (coefficient of variation less than 27.5%, four locations), except for buprenorphine in three placentas. In two of these, buprenorphine was not detected in some locations and in the third placenta was totally absent. Median (range) concentrations were 1.6 ng/g buprenorphine (not detected to 3.2), 14.9 ng/g norbuprenorphine (6.2-24.2), 3 ng/g buprenorphine-glucuronide (1.3-5.0), and 14.7 ng/g norbuprenorphine-glucuronide (11.4-25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15- to 70-fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome onset and duration, for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum neonatal abstinence syndrome score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. C1 [Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. [Jones, Hendree E.; Johnson, Rolley E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Johnson, Rolley E.] Reckitt Benckiser Pharmaceut Inc, Richmond, VA USA. [Choo, Robin] Univ Pittsburgh, Dept Biol, Titusville, PA USA. RP Huestis, MA (reprint author), Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural Research Program of the National Institute on Drug Abuse (NIDA) [RO1 DA12220]; National Institutes of Health (NIH) FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), and NIDA grant RO1 DA12220. NR 37 TC 15 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD APR PY 2010 VL 32 IS 2 BP 206 EP 215 DI 10.1097/FTD.0b013e3181d0bd68 PG 10 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 576RK UT WOS:000276165300014 PM 20216119 ER PT J AU de Oliveira, AD Lima, LG Machado, DE Nasciutti, LE Petersen, LC Francischetti, IMB Monteiro, RQ AF de Oliveira, A. Da Silva Lima, L. G. Machado, D. E. Nasciutti, L. E. Petersen, L. C. Francischetti, I. M. B. Monteiro, R. Q. TI Inhibition of tissue factor by Ixolaris reduces primary tumor growth and metastasis in a murine model of melanoma SO THROMBOSIS RESEARCH LA English DT Meeting Abstract CT 5th International Conference on Thrombosis and Hemostasis Issues in Cancer CY APR 23-25, 2010 CL Stresa, ITALY C1 [de Oliveira, A. Da Silva; Lima, L. G.; Monteiro, R. Q.] UFRJ, Inst Bioquim Med, Rio De Janeiro, Brazil. [Machado, D. E.; Nasciutti, L. E.] UFRJ, Inst Ciencias Biomed, Rio De Janeiro, Brazil. [Petersen, L. C.] Biopharmaceut Res Unit, Novo Nordisk, Maalov, Denmark. [Francischetti, I. M. B.] NIH, Vector Biol Sect, Bethesda, MD 20892 USA. RI PCM, PG/D-1034-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD APR PY 2010 VL 125 SU 2 BP S162 EP S162 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 590FX UT WOS:000277211400040 ER PT J AU Horvath, A Faucz, F Finkielstain, GP Nikita, ME Rothenbuhler, A Almeida, M Mericq, V Stratakis, CA AF Horvath, Anelia Faucz, Fabio Finkielstain, Gabriela P. Nikita, Maria Eleni Rothenbuhler, Anya Almeida, Madson Mericq, Veronica Stratakis, Constantine A. TI Haplotype Analysis of the Promoter Region of Phosphodiesterase Type 8B (PDE8B) in Correlation with Inactivating PDE8B Mutation and the Serum Thyroid-Stimulating Hormone Levels SO THYROID LA English DT Article ID THYROTROPIN RECEPTOR; ADRENAL-HYPERPLASIA; GENE; GENOME; TUMORS AB Background: Human phosphodiesterase (PDE) type 8B (PDE8B) is located at 5q14.1 and is known as the PDE with the highest affinity to cAMP. We recently described a family with bilateral micronodular adrenocortical disease that was apparently caused by an inactivating PDE8B mutation (H305P). As a result of a genome-wide study, a strong association between six polymorphic variants in the PDE8B promoter and serum levels of the thyroid-stimulating hormone (TSH) has been recently reported. Despite an extended analysis of the regions surrounding 5q14.1, no other potential genetic variants that could be responsible for the associated TSH levels were found. Methods: In this study, we genotyped by polymerase chain reaction the described six polymorphic variants in the PDE8B promoter in the family with micronodular adrenocortical disease and inactivating PDE8B mutation and analyzed their correlation with individual TSH values in the family members. Results: We observed complete segregation between the reported association and individual TSH values in the family we studied. Haplotype analysis showed that the haplotype associated with the high TSH levels is different from the one that segregated with H305P, suggesting that the mutation most probably has arisen on an allele independent of the high TSH-associated allele. Conclusions: The proposed mechanism by which PDE8B may influence TSH levels is through control of cAMP signaling. Our analysis revealed separate segregation of an inactivating PDE8B allele from the high-TSH-allele and showed low TSH levels in persons who carry an inactivating PDE8B allele. These data suggest that, indeed, PDE8B may be involved in regulation of TSH levels. C1 [Horvath, Anelia; Faucz, Fabio; Finkielstain, Gabriela P.; Nikita, Maria Eleni; Rothenbuhler, Anya; Almeida, Madson; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. [Faucz, Fabio] Pontificia Univ Catolica Parana, Ctr Healthy & Biol Sci, Mol Genet Lab, Curitiba, Parana, Brazil. [Mericq, Veronica] Univ Chile, Fac Med, Inst Maternal & Child Res, Santiago 7, Chile. RP Stratakis, CA (reprint author), NICHHD, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH, Bldg 10,CRC Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Mericq, Veronica/F-3927-2010; Faucz, Fabio/C-1607-2009; OI Mericq, Veronica/0000-0003-2287-0181 FU NIH [Z01-HD-000642-04] FX This work was supported by NIH intramural project Z01-HD-000642-04 to Dr. C.A. Stratakis (PDEGEN, NICHD, NIH). We are grateful to our patient and her family. NR 19 TC 12 Z9 14 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2010 VL 20 IS 4 BP 363 EP 367 DI 10.1089/thy.2009.0260 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579YL UT WOS:000276413300006 PM 20373981 ER PT J AU Pearce, EN Yang, Q Benjamin, EJ Aragam, J Vasan, RS AF Pearce, Elizabeth N. Yang, Qiong Benjamin, Emelia J. Aragam, Jayashri Vasan, Ramachandran S. TI Thyroid Function and Left Ventricular Structure and Function in the Framingham Heart Study SO THYROID LA English DT Article ID ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM; THYROTROPIN-SUPPRESSIVE THERAPY; QUALITY-OF-LIFE; CARDIAC-FUNCTION; DIASTOLIC FUNCTION; L-THYROXINE; LOADING CONDITIONS; HYPOTHYROIDISM; LEVOTHYROXINE; PERFORMANCE AB Background: Thyroid hormone acts on the heart and peripheral vasculature in multiple ways. Even in patients with subclinical hypo- or hyperthyroidism, subclinical alterations in left ventricular (LV) structure and function may be associated with important clinical effects. Our objective was to determine whether thyroid function is related to echocardiographic indices of LV structure and function. Methods: Cross-sectional association of serum thyroid-stimulating hormone (TSH) with two-dimensional-guided M-mode echo LV dimensions and function. Participants were 1376 Framingham Heart Study participants (61% women, mean age 69 years) who attended a routine examination 1979-1981. We excluded participants with myocardial infarction or heart failure, renal insufficiency, and missing data, and those using thyroid hormone or antithyroid medications. Serum TSH was measured 1977-1979. The following echocardiographic measurements were analyzed both as continuous variables and dichotomized at the top quintile: LV end-diastolic dimensions, LV wall thickness, LV mass, LV fractional shortening (an indicator of systolic function), and left atrial diameter. Sex-specific multiple regression models were adjusted for age, height, weight, blood pressure, heart rate, total to high-density lipoprotein cholesterol ratio, and the presence of diabetes, hypertension treatment, and valve disease. Results: In multivariable linear models, log-TSH was not related to LV mass, LV wall thickness, or left atrial size in either sex, or to LV systolic function in men. Log-TSH had a borderline inverse association with fractional shortening (p = 0.06) in women. In multivariable logistic models, women with TSH <0.5mU/L (n=81) had a greater odds of being in the highest quintile of fractional shortening compared to euthyroid subjects (odds ratio 2.2, 95% confidence interval 1.3-3.8, p = 0.01). Conclusions: In our moderate-sized community-based sample, TSH concentration was not associated with LV structure in either sex, but was inversely related to LV contractility, consistent with the known inotropic effects of thyroid hormone. C1 [Pearce, Elizabeth N.] Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Pearce, Elizabeth N.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.; Aragam, Jayashri; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA. RP Pearce, EN (reprint author), Boston Med Ctr, Sect Endocrinol Diabet & Nutr, 88 E Newton St,Evans 201, Boston, MA 02118 USA. EM elizabeth.pearce@bmc.org RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NIH [N01-HC 25195]; [5K23DK4611]; [2K24HL04334] FX This work was supported by grants from NIH: N01-HC 25195; 5K23DK4611 to Dr. Pearce; and 2K24HL04334 to Dr. Vasan. The authors are indebted to the late Clark T. Sawin, M. D., for the collection of the thyroid function data from the Framingham study participants. NR 38 TC 31 Z9 34 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD APR PY 2010 VL 20 IS 4 BP 369 EP 373 DI 10.1089/thy.2009.0272 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579YL UT WOS:000276413300007 PM 20210671 ER PT J AU Terunuma, A Limgala, RP Park, CJ Choudhary, I Vogel, JC AF Terunuma, Atsushi Limgala, Renuka Pudi Park, Christine J. Choudhary, Isha Vogel, Jonathan C. TI Efficient Procurement of Epithelial Stem Cells from Human Tissue Specimens Using a Rho-Associated Protein Kinase Inhibitor Y-27632 SO TISSUE ENGINEERING PART A LA English DT Article ID IN-VIVO; SIDE POPULATION; KERATINOCYTES; APOPTOSIS; PATHWAY; EXPRESSION; INJURY; ASSAY; SKIN AB The efficient culture of stem cells from epithelial tissues such as skin and corneas is important for both experimental studies and clinical applications of tissue engineering. We now demonstrate that treatment of human-skin-derived keratinocytes with a Rho-associated protein kinase inhibitor Y-27632 for the initial 6 days of primary culture can increase the number of keratinocytes that possess stem cell properties to form colonies during in vitro culture of freshly isolated cells and subsequent passage (50-fold). Further, we show that Y-27632 treatment can increase the total number of prostate epithelial cells derived from human prostate specimens. Therefore, the use of Y-27632 during primary cultures offers a simple and effective way to prepare a large number of epithelial stem cells from various human epithelial tissues. C1 [Terunuma, Atsushi; Limgala, Renuka Pudi; Park, Christine J.; Choudhary, Isha; Vogel, Jonathan C.] Natl Canc Inst, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Terunuma, A (reprint author), 10 Ctr Dr MSC 1908,Bldg 10 Room 12N260, Bethesda, MD 20892 USA. EM atsushi@mail.nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX The authors thank Mark Udey for valuable suggestions. This study was supported by Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research. NR 24 TC 23 Z9 25 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD APR PY 2010 VL 16 IS 4 BP 1363 EP 1368 DI 10.1089/ten.tea.2009.0339 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 579GJ UT WOS:000276356700023 PM 19912046 ER PT J AU Singh, BP Nyska, A Kissling, GE Lieuallen, W Johansson, SL Malarkey, DE Hooth, MJ AF Singh, B. P. Nyska, A. Kissling, G. E. Lieuallen, W. Johansson, S. L. Malarkey, D. E. Hooth, M. J. TI Urethral Carcinoma and Hyperplasia in Male and Female B6C3F1 Mice Treated With 3,3 ',4,4 '-Tetrachloroazobenzene (TCAB) SO TOXICOLOGIC PATHOLOGY LA English DT Article DE 3, 3 ', 4, 4 '-tetrachloroazobenzene (TCAB); urethra; carcinoma; mice; transitional cell carcinoma ID INCREASED CARCINOGENICITY; FISCHER-344 RATS; PROPANIL; TESTS; 3,4-DICHLOROANILINE; EXPRESSION; HERBICIDE; MORTALITY; RECEPTOR; BLADDER AB B6C3F1 mice chronically exposed to 3,3',4,4'-tetrachloroazobenzene (TCAB), a contaminant of dichloroaniline-derived herbicides, developed a number of neoplastic and nonneoplastic lesions, including carcinoma of the urinary tract. Groups of fifty male and fifty female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10, and 30 mg/kg five days a week for two years. Control animals received corn oil: acetone (99: 1) vehicle. Decreased survival of male mice in the mid-dose group and of male and female mice in the high-dose groups was related mainly to the occurrence of urethral transitional cell (urothelial) carcinoma and resulting urinary obstruction. Increased urethral transitional cell carcinomas were seen in all treated male groups in a dose-related manner as well as in the females treated with 30 mg/kg TCAB. Administration of TCAB was also associated with increased transitional cell hyperplasia of the urethra. Most nonneoplastic lesions of the urogenital tract were considered secondary to local invasion and urinary obstruction by the urethral transitional cell carcinomas. The mechanism of tumor induction is uncertain, but the high frequency of tumors in the proximal urethra of male mice suggests that the neoplasms result from the exposure of a susceptible population of urothelial cells to a carcinogenic metabolite of TCAB. C1 [Singh, B. P.; Kissling, G. E.; Malarkey, D. E.; Hooth, M. J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Nyska, A.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Lieuallen, W.] Charles River Labs Pathol Associates, Durham, NC USA. [Johansson, S. L.] Nebraska Med Ctr, Eppley Canc Ctr, Dept Pathol & Microbiol, Omaha, NE USA. RP Hooth, MJ (reprint author), NIEHS, Natl Toxicol Program, POB 12233,MD K2-13,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hooth@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [1 Z01 ESO45004-11 BB] FX This research was supported (in part) by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences under Research Project Number 1 Z01 ESO45004-11 BB. The authors wish to thank Drs. Flake and Masten for critical review of this manuscript. NR 55 TC 6 Z9 6 U1 0 U2 5 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 APR PY 2010 VL 38 IS 3 BP 372 EP 381 DI 10.1177/0192623310362708 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 592EA UT WOS:000277357200005 PM 20233943 ER PT J AU Cho, HY Kleeberger, SR AF Cho, Hye-Youn Kleeberger, Steven R. TI Nrf2 protects against airway disorders SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE ARE; Keap1; Lung; Knockout mice; Oxidant; Polymorphism; Mutation ID RESPIRATORY SYNCYTIAL VIRUS; ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; INDUCED LUNG INJURY; GLUTATHIONE-S-TRANSFERASE; EXTRACELLULAR-SUPEROXIDE DISMUTASE; IDIOPATHIC PULMONARY-FIBROSIS; TRANSPEPTIDASE-DEFICIENT MICE; INDUCED INFLAMMATORY RESPONSE; ADENOVIRUS-MEDIATED TRANSFER AB Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, air-way, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome Or lung cancer, which further supports the role for NRF2 in these lung diseases. In the Current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies. Published by Elsevier Inc. C1 [Cho, Hye-Youn; Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Cho, HY (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Bldg 101,MD D-201,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov NR 183 TC 94 Z9 100 U1 3 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 1 PY 2010 VL 244 IS 1 SI SI BP 43 EP 56 DI 10.1016/j.taap.2009.07.024 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 573DU UT WOS:000275889400007 PM 19646463 ER PT J AU Gall, L Stan, RC Kress, A Hertel, B Thiel, G Meckel, T AF Gall, Lars Stan, Razvan C. Kress, Alice Hertel, Brigitte Thiel, Gerhard Meckel, Tobias TI Fluorescent Detection of Fluid Phase Endocytosis Allows for In Vivo Estimation of Endocytic Vesicle Sizes in Plant Cells with Sub-Diffraction Accuracy SO TRAFFIC LA English DT Article DE AFM; Alexa 488 hydrazide; CLSM; dynamic light scattering; fluid phase endocytosis; guard cells; liposomes; molecular brightness ID LARGE UNILAMELLAR VESICLES; PHOTON-CORRELATION SPECTROSCOPY; RAPID EXTRUSION PROCEDURE; DYNAMIC LIGHT-SCATTERING; ATOMIC-FORCE MICROSCOPY; INDUCED VOLUME CHANGES; INTACT GUARD-CELLS; PLASMA-MEMBRANE; SURFACE-AREA; K+-CHANNEL AB Using the bright, photostable, charged and hydrophilic fluorescent dye Alexa 488 hydrazide to label the fluid phase around intact guard cells, we show that these cells incorporate the fluid phase during constitutive endocytosis against the high turgor. Mobile, cortical and diffraction-limited signals were not observed if a concentration < 4 mm was used to stain the fluid phase, suggesting that endocytic vesicles had to be loaded with a minimal number of dye molecules to produce a signal above the background. To quantify the number of molecules taken up by the vesicles, we prepared liposomes, filled with various concentrations of Alexa 488 hydrazide, fractionated them according to their size and imaged them under identical conditions as the guard cells. From the size/intensity relations of these liposomes, we extrapolated the molecular brightness of Alexa 488 hydrazide. Using this calibration, the mean fluorescent intensity of single endocytic vesicles translates into a mean number of 573 Alexa 488 molecules. If a vesicle needs to take up 573 molecules from a 4 mm solution, it requires a diameter of at least 87 nm. This number provides the first in vivo estimate for the size of endocytic vesicles in intact, turgid plant cells. C1 [Gall, Lars; Kress, Alice; Hertel, Brigitte; Thiel, Gerhard] Tech Univ Darmstadt, Dept Biol, D-64287 Darmstadt, Germany. [Stan, Razvan C.] Leiden Univ, Leiden Inst Phys, NL-2333 CA Leiden, Netherlands. [Meckel, Tobias] NIAID, Immunogenet Lab, NIH, Rockville, MD 20897 USA. RP Meckel, T (reprint author), Tech Univ Darmstadt, Dept Biol, Petersenstr 30, D-64287 Darmstadt, Germany. EM tobias.meckel@web.de RI Meckel, Tobias/F-4372-2010 OI Meckel, Tobias/0000-0003-0759-2072 FU German Research Council (DFG) [TH 558/6-1]; German Academy of Sciences Leopoldina [BMBF-LPD 9901/8-124] FX The authors would like to thank Professor Dr N. A. Dencher, Professor Dr T. Schmidt, Dr D. Kramer and the Graduate College GRK1114 for valuable input and helpful comments. This work was supported by Grants from the German Research Council (DFG) to G. T. (TH 558/6-1) and the German Academy of Sciences Leopoldina to T. M. (BMBF-LPD 9901/8-124). NR 48 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD APR PY 2010 VL 11 IS 4 BP 548 EP 559 DI 10.1111/j.1600-0854.2010.01037.x PG 12 WC Cell Biology SC Cell Biology GA 568NZ UT WOS:000275530700011 PM 20136778 ER PT J AU Wohr, M AF Woehr, Markus TI Ultrasonic vocalizations in rodents-relevance for rodent models of neuropsychiatric disorders SO TRANSGENIC RESEARCH LA English DT Meeting Abstract C1 [Woehr, Markus] NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD APR PY 2010 VL 19 IS 2 MA 17 BP 316 EP 316 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 555XO UT WOS:000274550300033 ER PT J AU Garrett, L Elliott, G Cheng, J AF Garrett, Lisa Elliott, Gene Cheng, Jun TI Overview and initial results of embryonic stem cells received through the international mouse knockout consortium and related repositories SO TRANSGENIC RESEARCH LA English DT Meeting Abstract C1 [Garrett, Lisa; Elliott, Gene; Cheng, Jun] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD APR PY 2010 VL 19 IS 2 MA 51 BP 328 EP 329 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 555XO UT WOS:000274550300066 ER PT J AU Deschamps, AM Murphy, E Sun, JH AF Deschamps, Anne M. Murphy, Elizabeth Sun, Junhui TI Estrogen Receptor Activation and Cardioprotection in Ischemia Reperfusion Injury SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID ACUTE MYOCARDIAL PROTECTION; S-NITROSYLATION; POSTMENOPAUSAL WOMEN; CARDIAC MYOCYTES; BLOOD-PRESSURE; FEMALE RATS; IN-VIVO; BETA; ALPHA; HEART AB Premenopausal females have a comparably lower incidence of cardiovascular disease than their male counterparts. Although estrogen and activation of estrogen receptors (ERs) have been found to contribute to female protection, the complex mechanisms involved are unclear. Besides altering gene transcription, estrogen could elicit its cardio protective effect via ER-mediated nongenomic signaling pathways. In addition to the two classic nuclear ER isoforms, ER alpha and ER beta, a G-protein coupled ER (GPR30 or GPER) has been found to be expressed in cardiomyocytes and plays an acute cardioprotective role in ischemia reperfusion injury. By using isoform-specific ER knockout mouse models and/or their specific modulators, the mechanisms of the different ERs involved in cardioprotection have been explored. In this review, we will focus on the signaling pathways leading to cardioprotection in ischemia reperfusion injury after ER activation and discuss the possibility and promise of specific ER modulators to treat ischemic heart diseases. (Trends Cardiovasc Med 2010;20:73-78) (C) 2010, Elsevier Inc. C1 [Deschamps, Anne M.; Murphy, Elizabeth; Sun, Junhui] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Sun, JH (reprint author), NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. EM sun1@mail.nih.gov RI Sun, Junhui/C-3499-2011; OI Deschamps, Anne/0000-0001-7415-1408 FU Intramural NIH HHS [Z99 HL999999] NR 40 TC 45 Z9 50 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD APR PY 2010 VL 20 IS 3 BP 73 EP 78 AR PII S1050-1738(10)00085-X DI 10.1016/j.tcm.2010.05.001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 737OV UT WOS:000288579000001 PM 21130949 ER PT J AU Fox, CS AF Fox, Caroline S. TI Cardiovascular Disease Risk Factors, Type 2 Diabetes Mellitus, and the Framingham Heart Study SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID IMPAIRED FASTING GLUCOSE; INSULIN-RESISTANCE; TRENDS; ADULTS; COMPLICATIONS; PREDICTION; OBESITY; BURDEN; IMPACT AB Type 2 diabetes is a common disorder and an important risk factor for cardiovascular disease. The Framingham Heart Study is a population-based epidemiologic study that has contributed to our knowledge of cardiovascular disease and its risk factors. This review will focus on the contemporary contributions of the Framingham Heart Study to the field of diabetes epidemiology, including data on diabetes trends, genetics, and future advances in population-based studies. (Trends Cardiovasc Med 2010;20:90-95) (C) 2010, Elsevier Inc. C1 [Fox, Caroline S.] NHLBI, Framingham Heart Study, Div Endocrinol Diabet & Metab, Framingham, MA 01702 USA. [Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Div Endocrinol Diabet & Metab, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute [N01-HC-25195] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195). Caroline S. Fox are at the NHLBI's Framingham Heart Study and the Center for Population Studies, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA; and Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. NR 37 TC 39 Z9 43 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD APR PY 2010 VL 20 IS 3 BP 90 EP 95 AR PII S1050-1738(10)00120-9 DI 10.1016/j.tcm.2010.08.001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 737OV UT WOS:000288579000004 PM 21130952 ER PT J AU Hikosaka, O Isoda, M AF Hikosaka, Okihide Isoda, Masaki TI Switching from automatic to controlled behavior: cortico-basal ganglia mechanisms SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID MEDIAL FRONTAL-CORTEX; ANTERIOR CINGULATE CORTEX; SUPPLEMENTARY MOTOR AREA; ERROR-RELATED NEGATIVITY; HUMAN PREFRONTAL CORTEX; STOP-SIGNAL INHIBITION; COGNITIVE CONTROL; RESPONSE-INHIBITION; PARKINSONS-DISEASE; DISSOCIABLE COMPONENTS AB Most daily tasks are performed almost automatically, but occasionally it is necessary to alter a routine if something changes in the environment and the routine behavior becomes inappropriate. Such behavioral switching can occur either retroactively based on error feedback or proactively by detecting a contextual cue. Recent imaging and electrophysiological data in humans and monkeys support the view that the frontal cortical areas play executive roles in behavioral switching. The anterior cingulate cortex acts retroactively and the pre-supplementary motor area acts proactively to enable behavioral switching. The lateral prefrontal cortex reconfigures cognitive processes constituting the switched behavior. The subthalamic nucleus and the striatum in the basal ganglia mediate these cortical signals to achieve behavioral switching. We discuss how breaking a routine to allow more adaptive behavior requires a fine-tuned recruitment of the frontal cortical-basal ganglia neural network. C1 [Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Isoda, Masaki] RIKEN, Brain Sci Inst, Lab Symbol Cognit Dev, Wako, Saitama 3510198, Japan. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 EY000415-05, Z01 EY000415-06, ZIA EY000415-07] NR 88 TC 134 Z9 134 U1 3 U2 33 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD APR PY 2010 VL 14 IS 4 BP 154 EP 161 DI 10.1016/j.tics.2010.01.006 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 589YD UT WOS:000277189200002 PM 20181509 ER PT J AU Bosmans, F Swartz, KJ AF Bosmans, Frank Swartz, Kenton J. TI Targeting voltage sensors in sodium channels with spider toxins SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID DEPENDENT K+ CHANNEL; GATING MODIFIER TOXINS; ALPHA-SCORPION TOXIN; GATED ION CHANNELS; POTASSIUM CHANNELS; TARANTULA TOXINS; LIPID-MEMBRANE; DOMAIN-II; MOLECULAR DETERMINANTS; SKELETAL-MUSCLE AB Voltage-activated sodium (Nav) channels are essential in generating and propagating nerve impulses, placing them amongst the most widely targeted ion channels by toxins from venomous organisms. An increasing number of spider toxins have been shown to interfere with the voltage-driven activation process of mammalian Nav channels, possibly by interacting with one or more of their voltage sensors. This review focuses on our existing knowledge of the mechanism by which spider toxins affect Nav channel gating and the possible applications of these toxins in the drug discovery process. C1 [Bosmans, Frank; Swartz, Kenton J.] Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Bosmans, Frank] Univ Louvain, Toxicol Lab, B-3000 Louvain, Belgium. RP Bosmans, F (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM bosmansf@ninds.nih.gov RI Bosmans, Frank/A-9660-2013 OI Bosmans, Frank/0000-0002-6476-235X FU NINDS; NIH; NIH-FWO FX We thank the members of the Swartz Research Team for helpful discussions and B. Billen, J. Tytgat, and G. Corzo for making the Magi5 data available. This work was supported by the Intramural Research Program of the NINDS, NIH, and by a NIH-FWO postdoctoral fellowship to F.B. NR 86 TC 59 Z9 60 U1 1 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD APR PY 2010 VL 31 IS 4 BP 175 EP 182 DI 10.1016/j.tips.2009.12.007 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586CB UT WOS:000276877600006 PM 20097434 ER PT J AU Chang, JH Kim, HH Lee, J Shung, KK AF Chang, Jin Ho Kim, Hyung Ham Lee, Jungwoo Shung, K. Kirk TI Frequency compounded imaging with a high-frequency dual element transducer SO ULTRASONICS LA English DT Article DE Frequency compounding; High frequency ultrasound imaging; Dual element transducer; High resolution ID SPECKLE REDUCTION; ULTRASOUND; IMAGES; MHZ AB This paper proposes a frequency compounding method to reduce speckle interferences, where a concentric annular type high-frequency dual element transducer is used to broaden the bandwidth of an imaging system. In frequency compounding methods, frequency division is carried out to obtain sub-band images containing uncorrelated speckles, which sacrifices axial resolution. Therefore, frequency compounding often deteriorates the target-detecting capability, quantified by the total signal-to-noise ratio (SNR), when the speckle's SNR (SSNR) is not improved as much as the degraded axial resolution. However, this could be avoided if the effective bandwidth required for frequency compounding is increased. The primary goal of the proposed approach, hence, is to improve SSNR by a factor of two under the condition where axial resolution is degraded by a factor of less than two, which indicates the total SNR improvement to higher than 40% compared to that of an original image. Since the method here employs a dual element transducer operating at 20 and 40 MHz, the effective bandwidth necessary for frequency compounding becomes broadened. By dividing each spectrum of RF samples from both elements into two sub-bands, this method eventually enables four sets of the sub-band samples to contain uncorrelated speckles. This causes the axial resolution to be reduced by a factor of as low as 1.85, which means that this method would improve total SNR by at least 47%. An in vitro experiment on an excised pig eye was performed to validate the proposed approach, and the results showed that the SSNR was improved from 2.081 +/- 0.365 in the original image to 4.206 +/- 0.635 in the final compounding image. (C) 2009 Elsevier B. V. All rights reserved. C1 [Chang, Jin Ho; Kim, Hyung Ham; Lee, Jungwoo; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Resource Ctr Med Ultrason Transducer Technol, NIH, Los Angeles, CA 90089 USA. RP Chang, JH (reprint author), Univ So Calif, Dept Biomed Engn, Resource Ctr Med Ultrason Transducer Technol, NIH, 1042 Downey Way,Denny Res Bldg 132, Los Angeles, CA 90089 USA. EM jhchang@ieee.org FU NIH [P41-EB002182] FX This work was supported by NIH Grants P41-EB002182. NR 9 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0041-624X J9 ULTRASONICS JI Ultrasonics PD APR PY 2010 VL 50 IS 4-5 BP 453 EP 457 DI 10.1016/j.ultras.2009.10.003 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 554PI UT WOS:000274446500003 PM 19914674 ER PT J AU Klinman, DM Klaschik, S Tross, D Shirota, H Steinhagen, F AF Klinman, Dennis M. Klaschik, Sven Tross, Debra Shirota, Hidekazu Steinhagen, Folkert TI FDA guidance on prophylactic DNA vaccines: Analysis and recommendations SO VACCINE LA English DT Editorial Material DE DNA vaccines; Guidance; Clinical trials ID CYTOTOXIC T-LYMPHOCYTES; HEPATITIS-B-VIRUS; PLASMID DNA; INTRAMUSCULAR INJECTION; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; MALARIA VACCINE; ANTIGEN PRESENTATION; TISSUE DISTRIBUTION; AUTOIMMUNE-DISEASE AB The FDA has been regulating the conduct of prophylactic DNA vaccine trials in the US for nearly 15 years. This work describes the evolution of FDA policy over that period, the status of current regulatory guidance, and provides recommendations for further changes to facilitate development in this field. Published by Elsevier Ltd. C1 [Klinman, Dennis M.; Tross, Debra; Shirota, Hidekazu; Steinhagen, Folkert] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Klaschik, Sven] Univ Hosp Bonn, Dept Anesthesiol & Intens Care Med, D-53105 Bonn, Germany. RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Bldg 567 Rm 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov FU Intramural NIH HHS [ZIA BC010852-03] NR 52 TC 26 Z9 28 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 1 PY 2010 VL 28 IS 16 BP 2801 EP 2805 DI 10.1016/j.vaccine.2009.11.025 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 587EJ UT WOS:000276972100002 PM 19941989 ER PT J AU Kumar, S Nayak, B Samuel, AS Xiao, S Collins, PL Samal, SK AF Kumar, Sachin Nayak, Baibaswata Samuel, Arthur S. Xiao, Sa Collins, Peter L. Samal, Siba K. TI Complete genome sequence of avian paramyxovirus-3 strain Wisconsin: Evidence for the existence of subgroups within the serotype SO VIRUS RESEARCH LA English DT Article DE APMV; Avian paramyxovirus; Paramyxoviridae; Paramyxovirinae; Genome sequence; Serotype ID NEWCASTLE-DISEASE VIRUS; RNA REPLICATION; G-GLYCOPROTEIN; GREAT-BRITAIN; V-PROTEIN; RULE; GENE; PATHOGENICITY; AMPLIFICATION; INFLUENZA AB The complete consensus genome sequence was determined for avian paramyxovirus (APMV) serotype 3 strain Wisconsin. The genome is 16,182 nucleotides (nt) in length, consisting of six non-overlapping genes in the order of 3'-N-P/V/W-M-F-HN-L-5', with a 55-nt leader at its 3' end and a 681-nt trailer at its 5' end. Comparison of the APMV-3 strain Wisconsin nt and the aggregate predicted amino acid (aa) sequences with those of APMV-3 strain Netherlands revealed 67% and 78%, identity, respectively. The nt and aa sequence identities between the two APMV-3 strains were lower than between the two antigenic subgroups of human respiratory syncytial virus (81% and 88% identity, respectively) and the two subgroups of human metapeumovirus (80% and 90% identity, respectively). Reciprocal cross-hemagglutination inhibition and cross-neutralization assays using post-infection sera from chickens indicated that strains Wisconsin and Netherlands are highly related antigenically, with only a 2- to 4-fold difference in antibody reactivity between the homologous and heterologous strains. Taken together, our results indicate that the two APMV-3 strains represent a single serotype with two subgroups that differ substantially based on nt and aa sequences, but with only a modest antigenic difference. (C) 2010 Elsevier B.V. All rights reserved. C1 [Kumar, Sachin; Nayak, Baibaswata; Samuel, Arthur S.; Xiao, Sa; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. [Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. EM ssamal@umd.edu RI Nayak, Baibaswata/L-6156-2016 FU NIAID [N01A060009]; NIH FX We thank Daniel Rockemann and all our laboratory members for their excellent technical assistance and help. "This research was supported by NIAID contract no. N01A060009 (85% support) and NIAID, NIH Intramural Research Program (15% support). The views expressed herein do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government." NR 45 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD APR PY 2010 VL 149 IS 1 BP 78 EP 85 DI 10.1016/j.virusres.2009.12.015 PG 8 WC Virology SC Virology GA 579BQ UT WOS:000276341900011 PM 20079781 ER PT J AU Laliberte, JP Moss, B AF Laliberte, Jason P. Moss, Bernard TI Lipid Membranes in Poxvirus Replication SO VIRUSES-BASEL LA English DT Review DE phospholipids; transmembrane proteins; virus entry; endocytosis; virus assembly; exocytosis ID VACCINIA VIRUS MORPHOGENESIS; INTRACELLULAR MATURE VIRIONS; CELL-CELL FUSION; GOLGI INTERMEDIATE COMPARTMENT; SURFACE HEPARAN-SULFATE; ENDOPLASMIC-RETICULUM; EXTRACELLULAR VIRUS; ENVELOPE PROTEIN; A27L PROTEIN; INITIATE MORPHOGENESIS AB Poxviruses replicate in the cytoplasm, where they acquire multiple lipoprotein membranes. Although a proposal that the initial membrane arises de novo has not been substantiated, there is no accepted explanation for its formation from cellular membranes. A subsequent membrane-wrapping step involving modified trans-Golgi or endosomal cisternae results in a particle with three membranes. These wrapped virions traverse the cytoplasm on microtubules; the outermost membrane is lost during exocytosis, the middle one is lost just prior to cell entry, and the remaining membrane fuses with the cell to allow the virus core to enter the cytoplasm and initiate a new infection. C1 [Laliberte, Jason P.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM lalibertej@niaid.nih.gov; bmoss@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The preparation of this review was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 103 TC 12 Z9 12 U1 0 U2 5 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD APR PY 2010 VL 2 IS 4 BP 972 EP 986 DI 10.3390/v2040972 PG 15 WC Virology SC Virology GA 632HP UT WOS:000280413600010 PM 21994664 ER PT J AU Artieri, CG Singh, RS AF Artieri, Carlo G. Singh, Rama S. TI Molecular evidence for increased regulatory conservation during metamorphosis, and against deleterious cascading effects of hybrid breakdown in Drosophila SO BMC BIOLOGY LA English DT Article ID GENE-EXPRESSION; INTERSPECIFIC HYBRIDS; POPULATION-GENETICS; SEQUENCE DIVERGENCE; PROTEIN-SEQUENCE; EVO-DEVO; EVOLUTION; MELANOGASTER; SIMULANS; STAGE AB Background: Speculation regarding the importance of changes in gene regulation in determining major phylogenetic patterns continues to accrue, despite a lack of broad-scale comparative studies examining how patterns of gene expression vary during development. Comparative transcriptional profiling of adult interspecific hybrids and their parental species has uncovered widespread divergence of the mechanisms controlling gene regulation, revealing incompatibilities that are masked in comparisons between the pure species. However, this has prompted the suggestion that misexpression in adult hybrids results from the downstream cascading effects of a subset of genes improperly regulated in early development. Results: We sought to determine how gene expression diverges over development, as well as test the cascade hypothesis, by profiling expression in males of Drosophila melanogaster, D. sechellia, and D. simulans, as well as the D. simulans (female) x D. sechellia (male) male F1 hybrids, at four different developmental time points (3rd instar larval, early pupal, late pupal, and newly-emerged adult). Contrary to the cascade model of misexpression, we find that there is considerable stage-specific autonomy of regulatory breakdown in hybrids, with the larval and adult stages showing significantly more hybrid misexpression as compared to the pupal stage. However, comparisons between pure species indicate that genes expressed during earlier stages of development tend to be more conserved in terms of their level of expression than those expressed during later stages, suggesting that while Von Baer's famous law applies at both the level of nucleotide sequence and expression, it may not apply necessarily to the underlying overall regulatory network, which appears to diverge over the course of ontogeny and which can only be ascertained by combining divergent genomes in species hybrids. Conclusion: Our results suggest that complex integration of regulatory circuits during morphogenesis may lead to it being more refractory to divergence of underlying gene regulatory mechanisms - more than that suggested by the conservation of gene expression levels between species during earlier stages. This provides support for a 'developmental hourglass' model of divergence of gene expression in Drosophila resulting in a highly conserved pupal stage. C1 [Artieri, Carlo G.; Singh, Rama S.] McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. [Artieri, Carlo G.] NIDDKD, Cellular & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Singh, RS (reprint author), McMaster Univ, Dept Biol, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM singh@mcmaster.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN235-07] FX The authors are grateful to Marisa Melas who helped with collection and sexing of flies, as well as Wilfried Haerty, Mohamed Noor, and three anonymous reviewers for comments raised on an earlier version of the manuscript. We also thank the Canadian Drosophila Microarray Center for performing the microarray hybridizations. This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Post-Graduate Doctoral Scholarship to CGA and an NSERC grant to RSS (grant No. RGPIN235-07). NR 53 TC 9 Z9 9 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD MAR 31 PY 2010 VL 8 AR 26 DI 10.1186/1741-7007-8-26 PG 15 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 601IR UT WOS:000278052300001 PM 20356354 ER PT J AU Redd, AD Ciccone, EJ Nakigozi, G Keruly, JC Ndyanabo, A Iga, B Gray, RH Serwadda, D Quinn, TC AF Redd, Andrew D. Ciccone, Emily J. Nakigozi, Gertrude Keruly, Jeanne C. Ndyanabo, Anthony Iga, Boaz Gray, Ronald H. Serwadda, David Quinn, Thomas C. TI T-cell enumeration from dried blood spots by quantifying rearranged T-cell receptor-beta genes SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Dried blood spots; HIV; Africa; T-cell receptor ID ANTIRETROVIRAL THERAPY; HIV DISEASE; DEPLETION; SURVIVAL; COUNTS; UGANDA; RAKAI AB Significant hurdles remain to large-scale implementation of medical interventions in the developing world due to the lack of a modern diagnostic infrastructure. This is especially pertinent to the international roll-out of antiretroviral drugs to treat HIV, which ideally includes a CD4 T-cell count to determine eligibility. We designed a novel technique to estimate mature T-cell numbers by calculating the amount of rearranged T-cell receptor beta genes from dried blood spots of HIV-infected individuals in the United States and Uganda. It was observed that the rearranged T-cell receptor beta count correlated well with total lymphocyte counts from both study populations (Baltimore R=0.602, Uganda R = 0.497; p < 0.001) and the ability for this measurement to determine antiretroviral initiation was similar to total lymphocyte counts, which can be used to determine eligibility in HIV + children. This technique as well as other dried blood spot based technologies could increase the diagnostic and monitoring capabilities in resource-limited settings. Published by Elsevier B.V. C1 [Redd, Andrew D.; Ciccone, Emily J.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Nakigozi, Gertrude; Ndyanabo, Anthony; Iga, Boaz] Rakai Hlth Sci Program, Rakai, Uganda. [Keruly, Jeanne C.; Quinn, Thomas C.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Serwadda, David] Makarere Univ, Sch Publ Hlth, Kampala, Uganda. RP Redd, AD (reprint author), 855 N Wolfe St,Rangos Bldg,Room 527, Baltimore, MD 21205 USA. EM aredd2@jhmi.edu RI Redd, Andrew/D-1802-2010 FU Johns Hopkins Center for Global Health and the Division of Intramural Research; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The authors would like to thank all the participants of the study in Rakai Uganda and at Johns Hopkins Hospital, as well as the staff of the RHSP and the Moore clinic. The following reagent was obtained through the AIDS Research and Reference Program, Division of AIDS, NIAID, NIH: Een 217 from Dr Robert F. Siliciano. AD Redd designed and performed the research, analyzed the data and wrote the paper; EJ Ciccone performed the research and analyzed the data; G Nakigozi designed the research; J.C Keruly performed the research; A Ndyanabo and B Iga analyzed the data; RH Gray, D Serwadda, and TC Quinn designed the research. Funding for this study was provided by Johns Hopkins Center for Global Health and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 31 PY 2010 VL 354 IS 1-2 BP 40 EP 44 DI 10.1016/j.jim.2010.01.008 PG 5 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 594LO UT WOS:000277539400005 PM 20109463 ER PT J AU Brigman, JL Wright, T Talani, G Prasad-Mulcare, S Jinde, S Seabold, GK Mathur, P Davis, MI Bock, R Gustin, RM Colbran, RJ Alvarez, VA Nakazawa, K Delpire, E Lovinger, DM Holmes, A AF Brigman, Jonathan L. Wright, Tara Talani, Giuseppe Prasad-Mulcare, Shweta Jinde, Seiichiro Seabold, Gail K. Mathur, Poonam Davis, Margaret I. Bock, Roland Gustin, Richard M. Colbran, Roger J. Alvarez, Veronica A. Nakazawa, Kazu Delpire, Eric Lovinger, David M. Holmes, Andrew TI Loss of GluN2B-Containing NMDA Receptors in CA1 Hippocampus and Cortex Impairs Long-Term Depression, Reduces Dendritic Spine Density, and Disrupts Learning SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SYNAPTIC PLASTICITY; SUBTYPE SELECTIVITY; SUBUNIT COMPOSITION; DIFFERENTIAL ROLES; DORSAL HIPPOCAMPUS; REFERENCE MEMORY; SPATIAL MEMORY; MICE LACKING; POTENTIATION; TRACE AB NMDA receptors (NMDARs) are key mediators of certain forms of synaptic plasticity and learning. NMDAR complexes are heteromers composed of an obligatory GluN1 subunit and one or more GluN2 (GluN2A-GluN2D) subunits. Different subunits confer distinct physiological and molecular properties to NMDARs, but their contribution to synaptic plasticity and learning in the adult brain remains uncertain. Here, we generated mice lacking GluN2B in pyramidal neurons of cortex and CA1 subregion of hippocampus. We found that hippocampal principal neurons of adult GluN2B mutants had faster decaying NMDAR-mediated EPSCs than nonmutant controls and were insensitive to GluN2B but not NMDAR antagonism. A subsaturating form of hippocampal long-term potentiation (LTP) was impaired in the mutants, whereas a saturating form of LTP was intact. An NMDAR-dependent form of long-term depression (LTD) produced by low-frequency stimulation combined with glutamate transporter inhibition was abolished in the mutants. Additionally, mutants exhibited decreased dendritic spine density in CA1 hippocampal neurons compared with controls. On multiple assays for corticohippocampal-mediated learning and memory (hidden platform Morris water maze, T-maze spontaneous alternation, and pavlovian trace fear conditioning), mutants were impaired. These data further demonstrate the importance of GluN2B for synaptic plasticity in the adult hippocampus and suggest a particularly critical role in LTD, at least the form studied here. The finding that loss of GluN2B was sufficient to cause learning deficits illustrates the contribution of GluN2B-mediated forms of plasticity to memory formation, with implications for elucidating NMDAR-related dysfunction in disease-related cognitive impairment. C1 [Brigman, Jonathan L.; Wright, Tara; Mathur, Poonam; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Talani, Giuseppe; Prasad-Mulcare, Shweta; Davis, Margaret I.; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Seabold, Gail K.; Bock, Roland; Alvarez, Veronica A.] NIAAA, Sect Neuronal Struct, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Jinde, Seiichiro; Nakazawa, Kazu] NIMH, Unit Genet Cognit & Behav, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. [Gustin, Richard M.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Colbran, Roger J.; Delpire, Eric] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Delpire, Eric] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37232 USA. RP Brigman, JL (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM brigmanj@mail.nih.gov RI Davis, Margaret/F-4165-2010; yu, yan/C-2322-2012; Nakazawa, Kazutoshi/J-6195-2015; Alvarez, Veronica /E-9745-2015; Bock, Roland/G-2982-2016; Brigman, Jonathan/O-4978-2016; OI Nakazawa, Kazutoshi/0000-0001-5699-9093; Alvarez, Veronica /0000-0003-2611-8675; Bock, Roland/0000-0002-8654-1080; Davis, Margaret/0000-0002-0489-8351 FU National Institute on Alcohol Abuse and Alcoholism; National Institute of Mental Health Intramural Research Programs; National Institute of Mental Health [RO1-MH063232]; National Institute of Neurological Disorders and Stroke [F31-NS061537]; Integrative Neuroscience Initiative on Alcoholism Stress Consortium [U01 AA013514] FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism and National Institute of Mental Health Intramural Research Programs, National Institute of Mental Health Grant RO1-MH063232 (R.J. C.), National Institute of Neurological Disorders and Stroke Grant F31-NS061537 (R.M.G.), and Integrative Neuroscience Initiative on Alcoholism Stress Consortium Grant U01 AA013514 (E.D.). We are grateful to Bai Lu and Yuan Lu for advice on the LTD protocol, Guoxiang Luo for genotyping, and Yoshihiro Kashiwaya for use of the confocal microscope. NR 61 TC 134 Z9 137 U1 1 U2 17 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 31 PY 2010 VL 30 IS 13 BP 4590 EP 4600 DI 10.1523/JNEUROSCI.0640-10.2010 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 576VP UT WOS:000276178000010 PM 20357110 ER PT J AU Zheng, CY Petralia, RS Wang, YX Kachar, B Wenthold, RJ AF Zheng, Chan-Ying Petralia, Ronald S. Wang, Ya-Xian Kachar, Bechara Wenthold, Robert J. TI SAP102 Is a Highly Mobile MAGUK in Spines SO JOURNAL OF NEUROSCIENCE LA English DT Article ID NMDA RECEPTOR TRAFFICKING; DENSITY PROTEIN PSD-95; N-TERMINAL DOMAINS; POSTSYNAPTIC DENSITY; GUANYLATE KINASES; AMPA RECEPTORS; GLUTAMATERGIC SYNAPSES; SCAFFOLDING PROTEINS; HIPPOCAMPAL-NEURONS; SYNAPTIC STRENGTH AB Membrane-associated guanylate kinases (MAGUKs), which are essential proteins in the postsynaptic density (PSD), cluster and anchor glutamate receptors and other proteins at synapses. The MAGUK family includes PSD-95, PSD-93, SAP102, and SAP97. Individual family members can compensate for one another in their ability to recruit and retain receptors at the postsynaptic membrane as shown through deletion and knock-down studies. SAP102 is highly expressed in both young and mature neurons; however, little is known about its localization and mobility at synapses. Here, we compared the distribution, mobility, and turnover times of SAP102 to the well studied MAGUK PSD-95. Using light and electron microscopy, we found that SAP102 shows a broader distribution as well as peak localization further away from the postsynaptic membrane than PSD-95. Using fluorescence recovery after photobleaching (FRAP), we found that 80% of SAP102 and 36% of PSD-95 are mobile in spines. Previous studies showed that PSD-95 was stabilized at the PSD by N-terminal palmitoylation. We found that stabilization of SAP102 at the PSD was dependent on its SH3/GK domains but not its PDZ interactions. Furthermore, we showed that stabilizing actin or blocking NMDA/AMPA receptors reduced the mobile pool of SAP102 but did not affect the mobile pool of PSD-95. Our results show significant differences in the localization, binding mechanism, and mobility of SAP102 and PSD-95. These differences and the compensatory properties of the MAGUKs point out an unrecognized versatility of the MAGUKs in their function in synaptic organization and plasticity. C1 [Zheng, Chan-Ying; Petralia, Ronald S.; Wang, Ya-Xian; Wenthold, Robert J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA. RP Zheng, CY (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. EM zhengchan@nidcd.nih.gov; petralia@nidcd.nih.gov FU National Institute on Deafness; Other Communication Disorders Intramural Program FX This work was supported by the National Institute on Deafness and Other Communication Disorders Intramural Program. NR 55 TC 29 Z9 29 U1 2 U2 7 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 MAR 31 PY 2010 VL 30 IS 13 BP 4757 EP 4766 DI 10.1523/JNEUROSCI.6108-09.2010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 576VP UT WOS:000276178000026 PM 20357126 ER PT J AU Yao, LS Grishaev, A Cornilescu, G Bax, A AF Yao, Lishan Grishaev, Alexander Cornilescu, Gabriel Bax, Ad TI Site-Specific Backbone Amide N-15 Chemical Shift Anisotropy Tensors in a Small Protein from Liquid Crystal and Cross-Correlated Relaxation Measurements SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; SOLID-STATE NMR; NUCLEAR-SPIN RELAXATION; HYDROGEN-BOND LENGTH; MODEL PEPTIDES; BIOLOGICAL MACROMOLECULES; MICROCRYSTALLINE PROTEIN; CONSERVATIVE MUTAGENESIS; PRINCIPAL COMPONENTS; SHIELDING TENSORS AB Site-specific N-15 chemical shift anisotropy (CSA) tensors have been derived for the well-ordered backbone amide N-15 nuclei in the B3 domain of protein G (GB3) from residual chemical shift anisotropy (RCSA) measured in six different mutants that retain the native structure but align differently relative to the static magnetic field when dissolved in a liquid crystalline Pf1 suspension. This information is complemented by measurement of cross-correlated relaxation rates between the N-15 CSA tensor and either the N-15-H-1 or N-15-C-13' dipolar interaction. In agreement with recent solid state NMR measurements, the N-15 CSA tensors exhibit only a moderate degree of variation from averaged values, but have larger magnitudes in a-helical (-173 +/- 7 ppm) than in beta-sheet (-162 +/- 6 ppm) residues, a finding also confirmed by quantum computations. The orientations of the least shielded tensor component cluster tightly around an in-peptide-plane vector that makes an angle of 19.6 +/- 2.5 degrees with the N-H bond, with the asymmetry of the N-15 CSA tensor being slightly smaller in alpha-helix (eta = 0.23 +/- 0.17) than in beta-sheet (eta = 0.31 +/- 0.11). The residue-specific N-15 CSA values are validated by improved agreement between computed and experimental N-15 R-1p relaxation rates measured for N-15-{H-2} sites in GB3, which are dominated by the CSA mechanism. Use of residue-specific N-15 CSA values also results in more uniform generalized order parameters, S-2, and predicts considerable residue-by-residue variations in the magnetic field strengths where TROSY line narrowing is most effective. C1 [Yao, Lishan; Grishaev, Alexander; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Cornilescu, Gabriel] Natl Magnet Resonance Facil, Madison, WI 53706 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI yao, lishan/H-3662-2012; Cornilescu, Gabriel/H-3113-2011 OI yao, lishan/0000-0003-1797-922X; Cornilescu, Gabriel/0000-0002-1204-8904 FU NIDDK, NIH; Office of the Director, NIH; NIH [P41RR02301, P41GM66326] FX We thank Dennis A. Torchia and Jinfa Ying for helpful discussions and Werner Maas and Jochem Struppe (Bruker Instruments) for help with the MAS measurements. This work was supported in part by the Intramural Research Program of the NIDDK, NIH, by the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH, and by NIH grants P41RR02301 (BRTP/NCRR) and P41GM66326 (NIGMS) to G.C. NR 97 TC 51 Z9 51 U1 6 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 31 PY 2010 VL 132 IS 12 BP 4295 EP 4309 DI 10.1021/ja910186u PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA 574RE UT WOS:000276009500055 PM 20199098 ER PT J AU Gu, HZ Yang, W Seeman, NC AF Gu, Hongzhou Yang, Wei Seeman, Nadrian C. TI DNA Scissors Device Used to Measure MutS Binding to DNA Mis-pairs SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESONANCE ENERGY-TRANSFER; MISMATCH REPAIR; HOLLIDAY JUNCTION AB MutS is a DNA repair protein that recognizes unpaired and bulged bases. When it binds to DNA, it bends the double helix. We have developed a novel DNA-based nanomechanical device that measures the amount of work that a DNA-bending protein can do when it binds to the double helix. The device we report here is a scissors-like device consisting of two double-crossover (DX) molecules connected to each other by a flexible Holliday junction. The two DX components are connected by a double helix that contains the binding site for MutS; when the binding site duplex is bent, the scissors contracts. The two DX molecules are also joined by sticky ends on an edge adjacent to the binding site; the sticky ends can be disrupted if the protein binds with sufficient free energy. Those sticky ends are flanked by a pair of dyes; when the sticky ends are disrupted, the dyes separate, and the fluorescence resonance energy transfer signal can monitor the disruption. The strength of the sticky ends is readily varied, so that the ability of the protein to disrupt them can be quantitated. We use this device to measure work in conjunction with a second device that measures the bending angle resulting from protein binding, so as to calibrate the system. Our data are in good agreement with previous measurements of MutS binding, indicating that this device is able to measure the strength of binding correctly. C1 [Gu, Hongzhou; Seeman, Nadrian C.] NYU, Dept Chem, New York, NY 10003 USA. [Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Seeman, NC (reprint author), NYU, Dept Chem, New York, NY 10003 USA. EM ned.seeman@nyu.edu RI Yang, Wei/D-4926-2011; Gu, Hongzhou/H-5308-2011 OI Yang, Wei/0000-0002-3591-2195; FU National Institute of General Medical Sciences [GM-29544]; National Science Foundation [CTS-0608889, CCF-0726378]; Army Research Office [48681-EL, W911NF-07-1-0439]; Office of Naval Research [N000140910181, N000140911118]; W.M. Keck Foundation FX This research has been supported by grants GM-29544 from the National Institute of General Medical Sciences, CTS-0608889 and CCF-0726378 from the National Science Foundation, 48681-EL and W911NF-07-1-0439 from the Army Research Office, and N000140910181 and N000140911118 from the Office of Naval Research and a grant from the W.M. Keck Foundation. NR 17 TC 30 Z9 30 U1 1 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 31 PY 2010 VL 132 IS 12 BP 4352 EP 4357 DI 10.1021/ja910188p PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 574RE UT WOS:000276009500061 PM 20205420 ER PT J AU Frohmader, KS Wiskerke, J Wise, RA Lehman, MN Coolen, LM AF Frohmader, K. S. Wiskerke, J. Wise, R. A. Lehman, M. N. Coolen, L. M. TI METHAMPHETAMINE ACTS ON SUBPOPULATIONS OF NEURONS REGULATING SEXUAL BEHAVIOR IN MALE RATS SO NEUROSCIENCE LA English DT Article DE nucleus accumbens; basolateral amygdala; prefrontal cortex; substance abuse; reproduction; addiction ID COCAINE-SEEKING BEHAVIOR; CONDITIONED PLACE PREFERENCES; NUCLEUS-ACCUMBENS DOPAMINE; MEDIAL PREOPTIC AREA; FREELY MOVING RATS; BASOLATERAL AMYGDALA; PREFRONTAL CORTEX; VENTRAL STRIATUM; C-FOS; TEMPORAL CHARACTERISTICS AB Methamphetamine (Meth) is a highly addictive stimulant. Meth abuse is commonly associated with the practice of sexual risk behavior and increased prevalence of Human Immunodeficiency Virus and Meth users report heightened sexual desire, arousal, and sexual pleasure. The biological basis for this drug sex nexus is unknown. The current study demonstrates that Meth administration in male rats activates neurons in brain regions of the mesolimbic system that are involved in the regulation of sexual behavior. Specifically, Meth and mating co-activate cells in the nucleus accumbens core and shell, basolateral amygdala, and anterior cingulate cortex. These findings illustrate that in contrast to current belief drugs of abuse can activate the same cells as a natural reinforcer, that is sexual behavior, and in turn may influence compulsive seeking of this natural reward. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Frohmader, K. S.; Lehman, M. N.; Coolen, L. M.] Univ Western Ontario, Dept Anat & Cell Biol, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada. [Wiskerke, J.; Coolen, L. M.] Univ Western Ontario, Dept Physiol & Pharmacol, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada. [Wise, R. A.] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Coolen, LM (reprint author), Univ Western Ontario, Dept Anat & Cell Biol, Schulich Sch Med & Dent, Med Sci Bldg,Room 460, London, ON N6A 5C1, Canada. EM lique.coolen@schulich.uwo.ca RI Wise, Roy/A-6465-2012; OI Wiskerke, Joost/0000-0001-5029-341X FU National Institutes of Health [R01 DA014591]; Canadian Institutes of Health Research [RN 014705] FX This research was supported by grants from the National Institutes of Health R01 DA014591 and Canadian Institutes of Health Research RN 014705 to LMC. NR 93 TC 19 Z9 19 U1 0 U2 7 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 MAR 31 PY 2010 VL 166 IS 3 BP 771 EP 784 DI 10.1016/j.neuroscience.2009.12.070 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 582LD UT WOS:000276597900004 PM 20045448 ER PT J AU Nakamura, NH Fukunaga, M Akama, KT Soga, T Ogawa, S Pavlides, C AF Nakamura, N. H. Fukunaga, M. Akama, K. T. Soga, T. Ogawa, S. Pavlides, C. TI HIPPOCAMPAL CELLS ENCODE PLACES BY FORMING SMALL ANATOMICAL CLUSTERS SO NEUROSCIENCE LA English DT Article DE place cells; functional organization; cell assemblies; nearest neighbor distance; zif268; Homer 1a ID IMMEDIATE-EARLY GENE; IN-SITU HYBRIDIZATION; METABOTROPIC GLUTAMATE RECEPTORS; TO-SAMPLE PERFORMANCE; PYRAMIDAL CELLS; RAT HIPPOCAMPUS; SYNAPTIC ACTIVITY; ENSEMBLE ACTIVITY; MESSENGER-RNA; GROWTH-FACTOR AB The hippocampus has been hypothesized to function as a "spatial" or "cognitive" map, however, the functional cellular organization of the spatial map remains a mystery. The majority of electrophysiological studies, thus far, have supported the view of a random-type organization in the hippocampus. However, using immediate early genes (IEGs) as an indicator of neuronal activity, we recently observed a cluster-type organization of hippocampal principal cells, whereby a small number (similar to 4) of nearby cells were activated in rats exposed to a restricted part of an environment. To determine the fine structure of these clusters and to provide a 3D image of active hippocampal cells that encode for different parts of an environment, we established a functional mapping of IEGs zif268 and Homerla, using in situ hybridization and 3D-reconstruction imaging methods. We found that, in rats exposed to the same location twice, there were significantly more double IEG-expressing cells, and the clusters of nearby cells were more "tightly" formed, in comparison to rats exposed to two different locations. We propose that spatial encoding recruits specific cell ensembles in the hippocampus and that with repeated exposure to the same place the ensembles become better organized to more accurately represent the "spatial map." Published by Elsevier Ltd on behalf of IBRO. C1 [Nakamura, N. H.; Akama, K. T.; Soga, T.; Ogawa, S.; Pavlides, C.] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10065 USA. [Nakamura, N. H.] Okinawa Inst Sci & Technol, Okinawa 9042234, Japan. [Fukunaga, M.] NINDS, Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA. [Soga, T.] Monash Univ, Bandar Sunway 46150, Malaysia. [Ogawa, S.] Univ Tsukuba, Tsukuba, Ibaraki 3058577, Japan. RP Nakamura, NH (reprint author), Okinawa Inst Sci & Technol OITC 3FL, Mol Neurosci Unit, 12-2 Suzaki, Okinawa 9042234, Japan. EM nakamun@oist.jp RI Nakamura, Nozomu/F-3698-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 FU National Institutes of Mental Health [MH067283] FX Acknowledgments We like to thank Jilda A. Caccavo and Christine R. McPherson (Rockefeller University) for technical support, and Yuji Ikegaya (University of Tokyo), Stephan Haupt, and Robert Sinclair (Okinawa Institute of Science and Technology) for theoretical comments. This work was supported by National Institutes of Mental Health grant MH067283 to CP. NR 52 TC 9 Z9 9 U1 0 U2 0 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 MAR 31 PY 2010 VL 166 IS 3 BP 994 EP 1007 DI 10.1016/j.neuroscience.2009.12.069 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 582LD UT WOS:000276597900023 PM 20060034 ER PT J AU Hurt, EM Chan, K Serrat, MAD Thomas, SB Veenstra, TD Farrar, WL AF Hurt, Elaine M. Chan, King Duhagon Serrat, Maria Ana Thomas, Suneetha B. Veenstra, Timothy D. Farrar, William L. TI Identification of Vitronectin as an Extrinsic Inducer of Cancer Stem Cell Differentiation and Tumor Formation SO STEM CELLS LA English DT Article DE Prostate cancer; Breast cancer; Tumor-initiating; Vitronectin; Arginine-glycine-aspartic acid peptide; Integrin alphaVbeta3 ID ACUTE MYELOID-LEUKEMIA; FOCAL-ADHESION KINASE; BREAST-CANCER; SELF-RENEWAL; IN-VITRO; STEM/PROGENITOR CELLS; INITIATING CELLS; INTEGRINS; MAINTENANCE; EXPRESSION AB There is mounting evidence that tumors are initiated by a rare subset of cells called cancer stem cells (CSCs). CSCs are generally quiescent, self-renew, form tumors at low numbers, and give rise to the heterogeneous cell types found within a tumor. CSCs isolated from multiple tumor types differentiate both in vivo and in vitro when cultured in serum, yet the factors responsible for their differentiation have not yet been identified. Here we show that vitronectin is the component of human serum driving stem cell differentiation through an integrin alpha V beta 3-dependent mechanism. CSCs cultured on vitronectin result in downregulation of stem cell genes, modulation of differentiation markers, and loss of beta-catenin nuclear localization. Blocking integrin alpha V beta 3 inhibits differentiation and subsequently tumor formation. Thus, CSCs must be engaged by one or more extracellular signals to differentiate and initiate tumor formation, defining a new axis for future novel therapies aimed at both the extrinsic and intracellular pathways. STEM CELLS 2010; 28: 390-398 C1 [Hurt, Elaine M.; Duhagon Serrat, Maria Ana; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA. [Chan, King; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Frederick, MD 21701 USA. [Thomas, Suneetha B.] NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Ctr Canc Res, Frederick, MD 21701 USA. [Duhagon Serrat, Maria Ana] Univ Republica, LIM F Ciencias, Montevideo, Uruguay. RP Hurt, EM (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, 1050 Boyles St,Bldg 560,Room 21-81, Frederick, MD 21701 USA. EM hurte@ncifcrf.gov FU National Cancer Institute, NIH [N01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research FX This research has been funded in part with federal funds from the National Cancer Institute, NIH, under contract No. N01-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. 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 54 TC 26 Z9 27 U1 0 U2 10 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAR 31 PY 2010 VL 28 IS 3 BP 390 EP 398 DI 10.1002/stem.271 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 588SJ UT WOS:000277093700002 PM 19998373 ER PT J AU Sherman, KJ Cherkin, DC Cook, AJ Hawkes, RJ Deyo, RA Wellman, R Khalsa, PS AF Sherman, Karen J. Cherkin, Daniel C. Cook, Andrea J. Hawkes, Rene J. Deyo, Richard A. Wellman, Robert Khalsa, Partap S. TI Comparison of yoga versus stretching for chronic low back pain: protocol for the Yoga Exercise Self-care (YES) trial SO TRIALS LA English DT Article ID MARGINAL STRUCTURAL MODELS; PHYSICAL-THERAPY; RANDOMIZED-TRIAL; NATURAL-HISTORY; NATIONAL-SURVEY; BODY AWARENESS; DISABILITY; MANAGEMENT; OUTCOMES; ADULTS AB Background: Back pain, one of the most prevalent conditions afflicting American adults, is the leading reason for using complementary and alternative medicine (CAM) therapies. Yoga is an increasingly popular "mind-body" CAM therapy often used for relieving back pain and several small studies have found yoga effective for this condition. This study will assess whether yoga is effective for treating chronic low back pain compared with self care and exercise and will explore the mechanisms responsible for any observed benefits. Methods/Design: A total of 210 participants with low back pain lasting at least 3 months will be recruited from primary care clinics of a large healthcare system based in Seattle. They will be randomized in a 2: 2: 1 ratio to receive 12 weekly yoga classes, 12 weekly conventional therapeutic exercise classes of comparable physical exertion, or a self-care book. Interviewers masked to participants' treatment group will assess outcomes at baseline and 6, 12 and 26 weeks after randomization. Primary outcomes will be back-related dysfunction and symptom bothersomeness. In addition, data will be collected on physical measurements (e.g., flexion) at baseline and 12 weeks and saliva samples will be obtained at baseline, 6 and 12 weeks. Information will be collected on specific physical, psychological, and physiological factors to allow exploration of possible mechanisms of action through which yoga could relieve back pain and dysfunction. The effectiveness of yoga will be assessed using analysis of covariance (using general estimating equations - GEE) within an intention-to-treat context. If yoga is found effective, further analyses will explore whether yoga's benefits are attributable to physical, psychological and/or physiological factors. Conclusions: This study will provide the clearest evidence to date about the value of yoga as a therapeutic option for treating chronic back pain, and if the results are positive, will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study. C1 [Sherman, Karen J.; Cherkin, Daniel C.; Cook, Andrea J.; Hawkes, Rene J.; Wellman, Robert] Grp Hlth Res Inst, Seattle, WA USA. [Sherman, Karen J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Cherkin, Daniel C.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Cherkin, Daniel C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Cook, Andrea J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Khalsa, Partap S.] NIH, Div Extramural Res & Training, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Sherman, KJ (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA USA. EM sherman.k@ghc.org FU National Center for Complementary and Alternative Medicine (NCCAM) [U01 AT003208] FX We used the yoga intervention developed for an earlier trial we conducted [19], which was developed by Gary Kraftsow and Robin Rothenberg. We thank John Maisano for developing the exercise intervention. We thank Elissa Epel, PhD and Brad Jacobs, MD, MPH for sharing their saliva collection protocol with us. The National Center for Complementary and Alternative Medicine (NCCAM) funded this trial (U01 AT003208). The design of this trial was reviewed and approved by NCCAM's Office of Clinical and Regulatory Affairs before being funded. NR 60 TC 12 Z9 12 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD MAR 31 PY 2010 VL 11 AR 36 DI 10.1186/1745-6215-11-36 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 605FL UT WOS:000278333000001 PM 20356395 ER PT J AU Wang, C Xuan, JH Li, H Wang, Y Zhan, M Hoffman, EP Clarke, R AF Wang, Chen Xuan, Jianhua Li, Huai Wang, Yue Zhan, Ming Hoffman, Eric P. Clarke, Robert TI Knowledge-guided gene ranking by coordinative component analysis SO BMC BIOINFORMATICS LA English DT Article ID EMBRYONIC STEM-CELLS; SET ENRICHMENT ANALYSIS; MICROARRAY DATA; EXPRESSION; MOUSE; DIFFERENTIATION; CLASSIFICATION; SIGNATURE; PROFILES; GENOME AB Background: In cancer, gene networks and pathways often exhibit dynamic behavior, particularly during the process of carcinogenesis. Thus, it is important to prioritize those genes that are strongly associated with the functionality of a network. Traditional statistical methods are often inept to identify biologically relevant member genes, motivating researchers to incorporate biological knowledge into gene ranking methods. However, current integration strategies are often heuristic and fail to incorporate fully the true interplay between biological knowledge and gene expression data. Results: To improve knowledge-guided gene ranking, we propose a novel method called coordinative component analysis (COCA) in this paper. COCA explicitly captures those genes within a specific biological context that are likely to be expressed in a coordinative manner. Formulated as an optimization problem to maximize the coordinative effort, COCA is designed to first extract the coordinative components based on a partial guidance from knowledge genes and then rank the genes according to their participation strengths. An embedded bootstrapping procedure is implemented to improve statistical robustness of the solutions. COCA was initially tested on simulation data and then on published gene expression microarray data to demonstrate its improved performance as compared to traditional statistical methods. Finally, the COCA approach has been applied to stem cell data to identify biologically relevant genes in signaling pathways. As a result, the COCA approach uncovers novel pathway members that may shed light into the pathway deregulation in cancers. Conclusion: We have developed a new integrative strategy to combine biological knowledge and microarray data for gene ranking. The method utilizes knowledge genes for a guidance to first extract coordinative components, and then rank the genes according to their contribution related to a network or pathway. The experimental results show that such a knowledge-guided strategy can provide context-specific gene ranking with an improved performance in pathway member identification. C1 [Wang, Chen; Xuan, Jianhua; Wang, Yue] Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Arlington, VA USA. [Li, Huai; Zhan, Ming] NIA, Bioinformat Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. [Hoffman, Eric P.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Clarke, Robert] Georgetown Univ, Sch Med, Dept Oncol, Washington, DC USA. [Clarke, Robert] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Xuan, JH (reprint author), Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Arlington, VA USA. EM xuan@vt.edu RI Clarke, Robert/A-6485-2008; Wang, Chen/B-3244-2011 OI Clarke, Robert/0000-0002-9278-0854; Wang, Chen/0000-0003-2638-3081 FU NIH [NS29525-13A, EB000830, CA109872, CA096483, CA129080, CA139246]; DoD/CDMRP [BC030280]; IRP/NIA/NIH FX This research was supported in part by NIH Grants (NS29525-13A, EB000830, CA109872, CA096483, CA129080 and CA139246) and DoD/CDMRP Grant (BC030280). HL and MZ were supported by IRP/NIA/NIH. NR 44 TC 6 Z9 6 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAR 30 PY 2010 VL 11 AR 162 DI 10.1186/1471-2105-11-162 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 593FB UT WOS:000277437000002 PM 20353603 ER PT J AU Alves-Silva, J Ribeiro, JMC Van Den Abbeele, J Attardo, G Hao, ZR Haines, LR Soares, MB Berriman, M Aksoy, S Lehane, MJ AF Alves-Silva, Juliana Ribeiro, Jose M. C. Van Den Abbeele, Jan Attardo, Geoffrey Hao, Zhengrong Haines, Lee R. Soares, Marcelo B. Berriman, Matthew Aksoy, Serap Lehane, Michael J. TI An insight into the sialome of Glossina morsitans morsitans SO BMC GENOMICS LA English DT Article ID ADULT FEMALE MOSQUITO; SALIVARY-GLAND HYPERTROPHY; FLY LUTZOMYIA-LONGIPALPIS; BLOWFLY CALLIPHORA-VICINA; RICH SECRETORY PROTEINS; PATHWAY INHIBITOR TFPI; AEDES-AEGYPTI; TSETSE-FLY; ANOPHELES-GAMBIAE; IMMUNE-RESPONSE AB Background: Blood feeding evolved independently in worms, arthropods and mammals. Among the adaptations to this peculiar diet, these animals developed an armament of salivary molecules that disarm their host's antibleeding defenses (hemostasis), inflammatory and immune reactions. Recent sialotranscriptome analyses (from the Greek sialo = saliva) of blood feeding insects and ticks have revealed that the saliva contains hundreds of polypeptides, many unique to their genus or family. Adult tsetse flies feed exclusively on vertebrate blood and are important vectors of human and animal diseases. Thus far, only limited information exists regarding the Glossina sialome, or any other fly belonging to the Hippoboscidae. Results: As part of the effort to sequence the genome of Glossina morsitans morsitans, several organ specific, high quality normalized cDNA libraries have been constructed, from which over 20,000 ESTs from an adult salivary gland library were sequenced. These ESTs have been assembled using previously described ESTs from the fat body and midgut libraries of the same fly, thus totaling 62,251 ESTs, which have been assembled into 16,743 clusters (8,506 of which had one or more EST from the salivary gland library). Coding sequences were obtained for 2,509 novel proteins, 1,792 of which had at least one EST expressed in the salivary glands. Despite library normalization, 59 transcripts were overrepresented in the salivary library indicating high levels of expression. This work presents a detailed analysis of the salivary protein families identified. Protein expression was confirmed by 2D gel electrophoresis, enzymatic digestion and mass spectrometry. Concurrently, an initial attempt to determine the immunogenic properties of selected salivary proteins was undertaken. Conclusions: The sialome of G. m. morsitans contains over 250 proteins that are possibly associated with blood feeding. This set includes alleles of previously described gene products, reveals new evidence that several salivary proteins are multigenic and identifies at least seven new polypeptide families unique to Glossina. Most of these proteins have no known function and thus, provide a discovery platform for the identification of novel pharmacologically active compounds, innovative vector-based vaccine targets, and immunological markers of vector exposure. C1 [Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Alves-Silva, Juliana; Haines, Lee R.; Lehane, Michael J.] Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England. [Van Den Abbeele, Jan] Inst Trop Med, Dept Parasitol, Unit Entomol, B-2000 Antwerp, Belgium. [Attardo, Geoffrey; Hao, Zhengrong; Aksoy, Serap] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA. [Soares, Marcelo B.] Northwestern Univ, Childrens Mem Res Ctr, Chicago, IL 60614 USA. [Berriman, Matthew] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. RP Ribeiro, JMC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, Rockville, MD 20852 USA. EM jribeiro@niaid.nih.gov RI Berriman, Matthew/A-7618-2011; OI Aksoy, Serap/0000-0001-9941-143X; Ribeiro, Jose/0000-0002-9107-0818 FU National Institute of Allergy and Infectious Diseases; Wellcome Trust; Li FoundationLi Foundation; NIH [F32 GM077964, AI51584]; WHO/TDR FX We are grateful to the NIAID Research Technology Grant under the direction of Dr. Robert Hohmann for performing the 2D Gel MS/MS work. This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. The sequencing and part of the laboratory studies were funded by the Wellcome Trust. Z.H. was supported by the Li Foundation, GMA was the recipient of NIH Ruth Kirschstein Postdoctoral Training Award F32 GM077964. Part of the laboratory studies were funded by NIH AI51584 awarded to SA. This study is part of the International Glossina Genomics Initiative (IGGI), established in 2004 with support from WHO/TDR to promote knowledge on Glossina biology including host-pathogen interactions, genetics of vector competence, olfactory biology and population genetics to support vector control efforts. 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 organization imply endorsement by the government of the United States of America. Because J.M.C.R. is a government employee and this is a government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the NIH reserves the right to provide the work to PubMedCentral for display and use by the public, and PubMedCentral may tag or modify the work consistent with its customary practices. You can establish rights outside of the U. S. subject to a government use license. NR 185 TC 43 Z9 47 U1 1 U2 15 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 MAR 30 PY 2010 VL 11 AR 213 DI 10.1186/1471-2164-11-213 PG 28 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 581ZX UT WOS:000276565700001 PM 20353571 ER PT J AU Andreotti, G Hou, L Gao, YT Brinton, LA Rashid, A Chen, J Shen, MC Wang, BS Han, TQ Zhang, BH Sakoda, LC Fraumeni, JF Hsing, AW AF Andreotti, G. Hou, L. Gao, Y-T Brinton, L. A. Rashid, A. Chen, J. Shen, M-C Wang, B-S Han, T-Q Zhang, B-H Sakoda, L. C. Fraumeni, J. F., Jr. Hsing, A. W. TI Reproductive factors and risks of biliary tract cancers and stones: a population-based study in Shanghai, China SO BRITISH JOURNAL OF CANCER LA English DT Article DE reproductive factors; gallstones; biliary tract cancer ID GALLBLADDER CANCER; GALLSTONE DISEASE; CONTRACEPTIVE STEROIDS; NATURAL-HISTORY; SYMPTOMATIC GALLSTONES; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; ORAL CONTRACEPTION; LIPID-METABOLISM; HUMAN FEMALE AB BACKGROUND: Parity has been linked to gallbladder cancer and gallstones, but the effects of other reproductive factors are less clear. METHODS: We examined 361 incident biliary tract cancer cases, 647 biliary stone cases, and 586 healthy women in a population-based study in Shanghai. RESULTS: The effects of parity (odds ratios, OR(>= 3 vs 1 child) = 2.0, 95% confidence interval (CI) 0.7-5.1), younger age at first birth (OR(per 1-year decrease) = 1.2, 95% CI 0.99-1.6), and older age at menarche (OR(per 1-year increase) = 1.4, 95% CI 1.1-1.8) on gallbladder cancer risk were more pronounced among women with stones, but the interactions were not significant. CONCLUSION: Our results provide support for high parity, younger age at first birth, and late age at menarche in the development of gallbladder cancer, particularly among women with biliary stones. British Journal of Cancer (2010) 102, 1185-1189. doi:10.1038/sj.bjc.6605597 www.bjcancer.com Published online 9 March 2010 (C) 2010 Cancer Research UK C1 [Andreotti, G.; Brinton, L. A.; Fraumeni, J. F., Jr.; Hsing, A. W.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Hou, L.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Gao, Y-T] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Rashid, A.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Shen, M-C] Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China. [Chen, J.] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Han, T-Q] Second Med Univ, Ruijin Hosp, Dept Surg, Shanghai, Peoples R China. [Wang, B-S] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Zhang, B-H] Second Mil Univ, Inst Oriental Hepatobiliary Surg, Shanghai, Peoples R China. [Sakoda, L. C.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Andreotti, G (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 8011,MSC 7240, Bethesda, MD 20892 USA. EM andreotg@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU National Institutes of Health, National Cancer Institute FX We thank Jiarong Cheng, Lu Sun, Kai Wu, Enju Liu, and Xuehong Zhang, as well as the staff at the Shanghai Cancer Institute, for data collection, specimen collection, and processing; the surgeons at the collaborating hospitals for data collection; the local pathologists for pathology review; and Hope Webb-Cohen and Shelley Niwa of Westat for data preparation and management. This research was supported by the Intramural Research Programme of the National Institutes of Health, National Cancer Institute. NR 50 TC 12 Z9 13 U1 1 U2 3 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 MAR 30 PY 2010 VL 102 IS 7 BP 1185 EP 1189 DI 10.1038/sj.bjc.6605597 PG 5 WC Oncology SC Oncology GA 576QE UT WOS:000276159900015 PM 20216539 ER PT J AU Scanarotti, C Bassi, AM Catalano, M Guida, C Coradeghini, R Falugi, C Aluigi, M Santi, P Raposio, E AF Scanarotti, Chiara Bassi, Anna Maria Catalano, Mariafrancesca Guida, Chiara Coradeghini, Rosella Falugi, Carla Aluigi, Mariagrazia Santi, Pierluigi Raposio, Edoardo TI Neurogenic-committed human pre-adipocytes express CYP1A isoforms SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE Neurogenic pre-adipocytes; Cytochrome P450 1A1; Cholinergic system; ECOD; EROD; beta-Naphthoflavone ID POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN ADIPOSE-TISSUE; CYTO-TOXICITY ASSAYS; HEPATOMA-CELL LINES; AIR-POLLUTION; BETA-NAPHTHOFLAVONE; NUCLEAR RECEPTOR; RAINBOW-TROUT; STEM-CELLS; BILE-ACIDS AB Stem cell models offer an opportunity both for therapeutic use and for the assessment of alternative in vitro models. Human lipoaspirate is a source of adult stem cells (pre-adipocytes), which are able to differentiate into various phenotypes, such as neurogenic lineage. Here, we analyse the suitability of these in vitro models in screening exogenous compounds, such as environmental pollutants, that may affect adipose cells and neurogenic development. To evaluate neurogenic differentiation, we analysed expression of cholinergic system and acetylcholinesterase immunoreactivity. Heterocyclic derivatives of polycyclic aromatic hydrocarbons (PAHs) are often significant components of environmental contaminants. As they contain inducers of cytochrome P450 1A1 (CYP1A1). we explored the activity of CYP1A1-related enzymes, i.e. 7-ethoxycoumarin- and 7-ethoxyresorufin-O-deethylase (ECOD and EROD) in both cell systems in basal conditions and after exposure to non-cytotoxic doses of beta-naphthoflavone (BNF), a well-known PAH-type inducer. Both cell models showed basal and inducible levels of ECOD. Analysis of CYP1A1 protein expression and EROD-related enzyme activity confirmed the inducibility of the CYP1A1 isoform by BNF. These results demonstrate that mesenchymal adult stem cells can constitute innovative models. We therefore propose the use of pre-adipocytes and their neurogenic derivates to evaluate the cytotoxic/biological effects of unintended exposure to contaminants. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Scanarotti, Chiara; Bassi, Anna Maria; Catalano, Mariafrancesca] Univ Genoa, Cell Culture Lab, DIMES, I-16132 Genoa, Italy. [Guida, Chiara] Univ Genoa, Tissue Engn Lab, Div Plast Surg, DICMI, I-16132 Genoa, Italy. [Coradeghini, Rosella] JRC European Commiss, Inst Hlth & Consumer Protect, Nanobiosci Unit, I-21020 Ispra, VA, Italy. [Falugi, Carla; Aluigi, Mariagrazia] Univ Genoa, Dept Biol, DIBIO, I-16132 Genoa, Italy. [Santi, Pierluigi; Raposio, Edoardo] Univ Genoa, Natl Canc Inst, IST, I-16132 Genoa, Italy. RP Scanarotti, C (reprint author), Univ Genoa, Cell Culture Lab, DIMES, Via LB Alberti 2, I-16132 Genoa, Italy. EM chiara_scanarotti@yahoo.it; ambassi@medicina.unige.it; mfcatalano@unige.it; chiara.guida@unige.it; r_coradeghini@hotmail.it; falugi@unige.it; mariagrazialuigi@libero.it; plsanti@unige.it; raposio@unige.it OI Raposio, Edoardo/0000-0001-7200-0243 NR 70 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 EI 1872-7786 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD MAR 30 PY 2010 VL 184 IS 3 BP 474 EP 483 DI 10.1016/j.cbi.2010.01.009 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 586OQ UT WOS:000276920400020 PM 20080079 ER PT J AU Smith, NL Chen, MH Dehghan, A Strachan, DP Basu, S Soranzo, N Hayward, C Rudan, I Sabater-Lleal, M Bis, JC de Maat, MPM Rumley, A Kong, XX Yang, Q Williams, FMK Vitart, V Campbell, H Malarstig, A Wiggins, KL Van Duijn, CM McArdle, WL Pankow, JS Johnson, AD Silveira, A McKnight, B Uitterlinden, AG Aleksic, N Meigs, JB Peters, A Koenig, W Cushman, M Kathiresan, S Rotter, JI Bovill, EG Hofman, A Boerwinkle, E Tofler, GH Peden, JF Psaty, BM Leebeek, F Folsom, AR Larson, MG Spector, TD Wright, AF Wilson, JF Hamsten, A Lumley, T Witteman, JCM Tang, WH O'Donnell, CJ AF Smith, Nicholas L. Chen, Ming-Huei Dehghan, Abbas Strachan, David P. Basu, Saonli Soranzo, Nicole Hayward, Caroline Rudan, Igor Sabater-Lleal, Maria Bis, Joshua C. de Maat, Moniek P. M. Rumley, Ann Kong, Xiaoxiao Yang, Qiong Williams, Frances M. K. Vitart, Veronique Campbell, Harry Maelarstig, Anders Wiggins, Kerri L. Van Duijn, Cornelia M. McArdle, Wendy L. Pankow, James S. Johnson, Andrew D. Silveira, Angela McKnight, Barbara Uitterlinden, Andre G. Aleksic, Nena Meigs, James B. Peters, Annette Koenig, Wolfgang Cushman, Mary Kathiresan, Sekar Rotter, Jerome I. Bovill, Edwin G. Hofman, Albert Boerwinkle, Eric Tofler, Geoffrey H. Peden, John F. Psaty, Bruce M. Leebeek, Frank Folsom, Aaron R. Larson, Martin G. Spector, Timothy D. Wright, Alan F. Wilson, James F. Hamsten, Anders Lumley, Thomas Witteman, Jacqueline C. M. Tang, Weihong O'Donnell, Christopher J. CA Wellcome Trust Case Control Consor TI Novel Associations of Multiple Genetic Loci With Plasma Levels of Factor VII, Factor VIII, and von Willebrand Factor The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium SO CIRCULATION LA English DT Article DE genetic variation; factor VII; factor VIII; von Willebrand factor; epidemiology; meta-analysis; thrombosis; hemostasis ID CARDIOVASCULAR RISK-FACTORS; CORONARY-ARTERY-DISEASE; COAGULATION-FACTOR-VII; C-REACTIVE PROTEIN; ABO BLOOD-GROUP; WIDE ASSOCIATION; ATHEROSCLEROSIS RISK; MYOCARDIAL-INFARCTION; TRIGLYCERIDE LEVELS; MOLECULAR-GENETICS AB Background-Plasma levels of coagulation factors VII (FVII), VIII (FVIII), and von Willebrand factor (vWF) influence risk of hemorrhage and thrombosis. We conducted genome-wide association studies to identify new loci associated with plasma levels. Methods and Results-The setting of the study included 5 community-based studies for discovery comprising 23 608 European-ancestry participants: Atherosclerosis Risk In Communities Study, Cardiovascular Health Study, British 1958 Birth Cohort, Framingham Heart Study, and Rotterdam Study. All subjects had genome-wide single-nucleotide polymorphism (SNP) scans and at least 1 phenotype measured: FVII activity/antigen, FVIII activity, and vWF antigen. Each study used its genotype data to impute to HapMap SNPs and independently conducted association analyses of hemostasis measures using an additive genetic model. Study findings were combined by meta-analysis. Replication was conducted in 7604 participants not in the discovery cohort. For FVII, 305 SNPs exceeded the genome-wide significance threshold of 5.0X10(-8) and comprised 5 loci on 5 chromosomes: 2p23 (smallest P value 6.2X10(-24)), 4q25 (3.6X10(-12)), 11q12 (2.0X10(-10)), 13q34 (9.0X10(-259)), and 20q11.2 (5.7X10(-37)). Loci were within or near genes, including 4 new candidate genes and F7 (13q34). For vWF, 400 SNPs exceeded the threshold and marked 8 loci on 6 chromosomes: 6q24 (1.2X10(-22)), 8p21 (1.3X10(-16)), 9q34 (<5.0X10(-324)), 12p13 (1.7X10(-32)), 12q23 (7.3X10(-10)), 12q24.3 (3.8X10(-11)), 14q32 (2.3X10(-10)), and 19p13.2 (1.3X10(-9)). All loci were within genes, including 6 new candidate genes, as well as ABO (9q34) and VWF (12p13). For FVIII, 5 loci were identified and overlapped vWF findings. Nine of the 10 new findings were replicated. Conclusions-New genetic associations were discovered outside previously known biological pathways and may point to novel prevention and treatment targets of hemostasis disorders. (Circulation. 2010; 121: 1382-1392.) C1 [Smith, Nicholas L.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA. [Basu, Saonli; Kong, Xiaoxiao] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Pankow, James S.; Folsom, Aaron R.; Tang, Weihong] Univ Minnesota, Div Epidemiol, Minneapolis, MN USA. [Pankow, James S.; Folsom, Aaron R.; Tang, Weihong] Univ Minnesota, Div Community Hlth, Minneapolis, MN USA. [Aleksic, Nena] Univ Texas Hlth Sci Ctr Houston, DNA Lab, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA. [Strachan, David P.] Univ London, Div Community Hlth Sci, London WC1E 7HU, England. [Rumley, Ann] Univ Glasgow, Royal Infirm, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Bristol BS8 1TH, Avon, England. [Bis, Joshua C.; Wiggins, Kerri L.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Cushman, Mary; Bovill, Edwin G.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT 05405 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Chen, Ming-Huei; Yang, Qiong; Johnson, Andrew D.; Kathiresan, Sekar; Larson, Martin G.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Yang, Qiong] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Chen, Ming-Huei] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia. [Dehghan, Abbas; Van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [de Maat, Moniek P. M.; Leebeek, Frank] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England. [Soranzo, Nicole; Williams, Frances M. K.; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Hayward, Caroline; Vitart, Veronique; Wright, Alan F.] Inst Genet & Mol Med, Human Genet Unit, MRC, Edinburgh, Midlothian, Scotland. [Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Soltanska, Croatia. [Rudan, Igor; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Sabater-Lleal, Maria; Maelarstig, Anders; Silveira, Angela; Hofman, Albert] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden. [Peden, John F.] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Peters, Annette] German Res Ctr Environm & Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Koenig, Wolfgang] Univ Ulm, Ulm, Germany. RP Smith, NL (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM nlsmith@u.washington.edu; odonnellc@nhlbi.nih.gov RI Spector, Tim/F-6533-2012; Rudan, Igor/I-1467-2012; Johnson, Andrew/G-6520-2013; Sabater-Lleal, Maria/I-5832-2013; Peters, Annette/A-6117-2011; Yang, Qiong/G-5438-2014; Wilson, James F/A-5704-2009; Hayward, Caroline/M-8818-2016; OI Rudan, Igor/0000-0001-6993-6884; Larson, Martin/0000-0002-9631-1254; Soranzo, Nicole/0000-0003-1095-3852; Williams, Frances/0000-0002-2998-2744; Wilson, James F/0000-0001-5751-9178; Hayward, Caroline/0000-0002-9405-9550; Dehghan, Abbas/0000-0001-6403-016X; Sabater Lleal, Maria/0000-0002-0128-379X FU NHLBI [N01-HC-55015, N01-HC55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01-HL-087641, R01-HL59367]; National Human Genome Research Institute [U01-HG-004402]; National Institutes of Health (NIH) [HHSN268200625226C, UL1-RR-025005]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; National Institute of Neurological Disorders and Stroke; National Center for Research Resources [M01-RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491, K24 DK080140]; NHLBI's FHS [N01-HC-25195, N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO) [175.010.2005.011, 911.03.012]; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; Research Institute for Diseases in the Elderly (RIDE) [94800022]; Netherlands Genomics Initiative (NGI)/NWO [050-060-810]; Wellcome Trust; European Community [FP-6/2005-2008]; FP7/2007-2013 [HEALTH-F4-2007-201413]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; Department of Health via a National Institute for Health Research (NIHR); Biotechnology and Biological Sciences Research Council [G20234]; National Eye Institute via an NIH/Center for Inherited Disease Research; Medical Research Council UK; Ministry of Science, Education and Sport of the Republic of Croatia [108-1080315-0302]; European Union [LSHG-CT-2006-018947]; Chief Scientist Office of the Scottish Government; Royal Society; EC [LSHM-CT-2007-037273]; Swedish Research Council [8691]; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung Foundation; Leducq Foundation, Paris; Stockholm County Council [560283]; AstraZeneca; Sanofi-Aventis; GlaxoSmithKline; NHLBI contracts [R01-HL-086694, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, HL073410, HL095080] FX ARIC is supported by NHLBI contracts N01-HC-55015, N01-HC55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, and N01-HC-55022 and grants R01-HL-087641, R01-HL59367, and R01-HL-086694; National Human Genome Research Institute contract U01-HG-004402; and National Institutes of Health (NIH) contract HHSN268200625226C. The infrastructure was supported in part by grant No. UL1-RR-025005, a component of the NIH and NIH Roadmap for Medical Research. We acknowledge use of phenotype and genotype data from the B58C DNA collection, funded by Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02 (http://www.b58cgene.sgul.ac.uk/). The CHS is supported by contract Nos. N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133 and grant Nos. U01 HL080295 and R01 HL 087652 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. Support was also provided by NHLBI grants HL073410 and HL095080 and the Leducq Foundation, Paris, France, for the development of Transatlantic Networks of Excellence in Cardiovascular Research. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01-RR00425 to the Cedars-Sinai General Clinical Research Center genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. This research was conducted in part with data and resources from the FHS of the NHLBI of the NIH and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the FHS investigators participating in the SNP Health Association Resource (SHARe) project. Partial investigator support was provided by National Institute of Diabetes and Digestive and Kidney Diseases grant K24 DK080140 (Dr Meigs). This work was supported in part by the NHLBI's FHS (contract No. N01-HC-25195) and its contract with Affymetrix Inc for genotyping services (contract No. N02-HL-6-4278). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Support for genotyping was provided by the Netherlands Organization for Scientific Research (NWO; 175.010.2005.011, 911.03.012) and Research Institute for Diseases in the Elderly (RIDE). This study was further supported by the Netherlands Genomics Initiative (NGI)/NWO project No. 050-060-810. Dr Dehghan is supported by NWO, RIDE (94800022).; The Twins UK study was funded by the Wellcome Trust; European Community's Sixth and Seventh Framework Programmes (FP-6/2005-2008) Life Sciences & Health (Ref 005268, genetic regulation of the end-stage clotting process that leads to thrombotic stroke: The EuroClot Consortium) and FP7/2007-2013, ENGAGE project HEALTH-F4-2007-201413, and the FP-5 GenomEUtwin Prject (QLG2-CT-2002-01254). The study also received support from the Department of Health via a National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London. Dr Spector is an NIHR Senior Investigator. The project also received support from a Biotechnology and Biological Sciences Research Council project grant (G20234). The authors acknowledge the funding and support of the National Eye Institute via an NIH/Center for Inherited Disease Research genotyping project (principal investigator: Terri Young). The VIS study in the Croatian island of Vis was supported through grants from the Medical Research Council UK and Ministry of Science, Education and Sport of the Republic of Croatia (No. 108-1080315-0302) and the European Union framework program 6 EUROSPAN project (contract No. LSHG-CT-2006-018947). ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, and the European Union framework program 6 EUROSPAN project (contract No. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. The PROCARDIS program was funded by the EC Sixth Framework Programme (LSHM-CT-2007-037273), the Swedish Research Council (8691), the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Leducq Foundation, Paris, the Stockholm County Council (560283), and AstraZeneca. Genotyping of Swedish PROCARDIS control samples was performed at the SNP Technology Platform (head: Professor Ann-Christine Syvanen), Department of Medical Sciences, Uppsala University, Sweden.; Dr Meigs reports receiving grant support from Sanofi-Aventis and GlaxoSmithKline and serving as a consultant/advisor to Interleukin Genetics and Eli Lilly. The remaining authors report no conflicts. NR 62 TC 144 Z9 147 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 30 PY 2010 VL 121 IS 12 BP 1382 EP U45 DI 10.1161/CIRCULATIONAHA.109.869156 PG 30 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 575RD UT WOS:000276084400003 PM 20231535 ER PT J AU Eagle, KA Ginsburg, GS Musunuru, K Aird, WC Balaban, RS Bennett, SK Blumenthal, RS Coughlin, SR Davidson, KW Frohlich, ED Greenland, P Jarvik, GP Libby, P Pepine, CJ Ruskin, JN Stillman, AE Van Eyk, JE Tolunay, HE McDonald, CL Smith, SC AF Eagle, Kim A. Ginsburg, Geoffrey S. Musunuru, Kiran Aird, William C. Balaban, Robert S. Bennett, Susan K. Blumenthal, Roger S. Coughlin, Shaun R. Davidson, Karina W. Frohlich, Edward D. Greenland, Philip Jarvik, Gail P. Libby, Peter Pepine, Carl J. Ruskin, Jeremy N. Stillman, Arthur E. Van Eyk, Jennifer E. Tolunay, H. Eser McDonald, Cheryl L. Smith, Sidney C., Jr. TI Identifying Patients at High Risk of a Cardiovascular Event in the Near Future Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group SO CIRCULATION LA English DT Article DE cardiovascular diseases; death, sudden; myocardial infarction; risk factors; risk prediction ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; SYNDROME EVALUATION WISE; GENE-EXPRESSION; UNSTABLE ANGINA; POSTDISCHARGE DEATH; PREDICTION MODEL; INFLAMMATION; ATHEROSCLEROSIS C1 [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Ginsburg, Geoffrey S.] Duke Univ, Durham, NC USA. [Musunuru, Kiran; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Aird, William C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Balaban, Robert S.; Tolunay, H. Eser; McDonald, Cheryl L.] NHLBI, Bethesda, MD 20892 USA. [Bennett, Susan K.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Coughlin, Shaun R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Davidson, Karina W.] Columbia Coll Phys & Surg, New York, NY USA. [Frohlich, Edward D.] Ochsner Clin Fdn, New Orleans, LA USA. [Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Jarvik, Gail P.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Libby, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pepine, Carl J.] Univ Florida, Coll Med, Gainesville, FL USA. [Stillman, Arthur E.] Emory Univ, Atlanta, GA 30322 USA. [Smith, Sidney C., Jr.] Univ N Carolina, Chapel Hill, NC USA. RP Eagle, KA (reprint author), Univ Michigan, Ctr Cardiovasc, 1500 E Med Ctr Dr,Suite 2131, Ann Arbor, MI 48109 USA. EM keagle@umich.edu RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 FU National Heart, Lung, and Blood Institute at the National Institutes of Health, Bethesda, Md FX The Working Group meetings were underwritten by the National Heart, Lung, and Blood Institute at the National Institutes of Health, Bethesda, Md. NR 61 TC 35 Z9 35 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 30 PY 2010 VL 121 IS 12 BP 1447 EP 1454 DI 10.1161/CIRCULATIONAHA.109.904029 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 575RD UT WOS:000276084400010 PM 20351302 ER PT J AU Mukamal, KJ Chen, CM Rao, SR Breslow, RA AF Mukamal, Kenneth J. Chen, Chiung M. Rao, Sowmya R. Breslow, Rosalind A. TI Alcohol Consumption and Cardiovascular Mortality Among US Adults, 1987 to 2002 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE alcohol; epidemiology; mortality ID CORONARY-HEART-DISEASE; HEALTH INTERVIEW SURVEY; ALL-CAUSE MORTALITY; MYOCARDIAL-INFARCTION; ISCHEMIC-STROKE; AVERAGE VOLUME; UNITED-STATES; OLDER-ADULTS; RISK-FACTORS; METAANALYSIS AB Objectives The aim of this study was to determine the association of alcohol consumption and cardiovascular mortality in the U. S. population. Background Alcohol consumption has been associated with a lower risk of cardiovascular disease in cohort studies, but this association has not been prospectively examined in large, detailed, representative samples of the U. S. population. Methods We analyzed 9 iterations of the National Health Interview Survey, an annual survey of a nationally representative sample of U. S. adults between 1987 and 2000. Exposures of interest included usual volume, frequency, and quantity of alcohol consumption and binge drinking. Mortality was ascertained through linkage to the National Death Index through 2002. Relative risks were derived from random-effects meta-analyses of weighted, multivariable-adjusted hazard ratios for cardiovascular mortality from individual survey administrations. Results Light and moderate volumes of alcohol consumption were inversely associated with cardiovascular mortality. Compared with lifetime abstainers, summary relative risks were 0.95 (95% confidence interval [CI]: 0.88 to 1.02) among lifetime infrequent drinkers, 1.02 (95% CI: 0.94 to 1.11) among former drinkers, 0.69 (95% CI: 0.59 to 0.82) among light drinkers, 0.62 (95% CI: 0.50 to 0.77) among moderate drinkers, and 0.95 (95% CI: 0.82 to 1.10) among heavy drinkers. The magnitude of lower risk was similar in subgroups of sex, age, or baseline health status. There was no simple relation of drinking pattern with risk, but risk was consistently higher among those who consumed >= 3 compared with 2 drinks/drinking day. Conclusions In 9 nationally representative samples of U. S. adults, light and moderate alcohol consumption were inversely associated with CVD mortality, even when compared with lifetime abstainers, but consumption above recommended limits was not. (J Am Coll Cardiol 2010; 55: 1328-35) (C) 2010 by the American College of Cardiology Foundation C1 [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Chen, Chiung M.] CSR Inc, Arlington, VA USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Breslow, Rosalind A.] NIAAA, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. RP Mukamal, KJ (reprint author), BIDMC, Div Gen Med & Primary Care, Res Program, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA. EM kmukamal@bidmc.harvard.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [N0AA32007, HHSN267200800023C]; GE Corporate Healthcare FX From the *Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts; dagger CSR Incorporated, Arlington, Virginia; Biostatistics Center and Institute for Health Policy, Massachusetts General Hospital, Boston, Massachusetts; and the Division of Epidemiology and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland. Computer programming and statistical support were provided through the Alcohol Epidemiologic Data System funded by contracts N0AA32007 and HHSN267200800023C from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The NIAAA reviewed and approved this report before submission. The findings and conclusions in this report are those of the authors and not necessarily those of the agency. Dr. Rao has received funding from GE Corporate Healthcare. NR 53 TC 80 Z9 81 U1 2 U2 7 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 MAR 30 PY 2010 VL 55 IS 13 BP 1328 EP 1335 DI 10.1016/j.jacc.2009.10.056 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 573CL UT WOS:000275885900006 PM 20338493 ER PT J AU DiMattia, MA Watts, NR Stahl, SJ Rader, C Wingfield, PT Stuart, DI Steven, AC Grimes, JM AF DiMattia, Michael A. Watts, Norman R. Stahl, Stephen J. Rader, Christoph Wingfield, Paul T. Stuart, David I. Steven, Alasdair C. Grimes, Jonathan M. TI Implications of the HIV-1 Rev dimer structure at 3.2 angstrom resolution for multimeric binding to the Rev response element SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nuclear export; ribonucleoprotein structure; Fab cocrystallization; posttranscriptional regulation; crystal structure ID PROTEIN-STRUCTURE; GENE-EXPRESSION; TRANS-ACTIVATOR; RNA; MUTANTS; RRE; OLIGOMERIZATION; MODEL; STATE; ASSEMBLIES AB HIV-1 Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process Rev oligomerizes in association with a highly structured RNA motif, the Rev response element. Crystallographic studies of Rev have been hampered by the protein's tendency to aggregate, but Rev has now been found to form a stable soluble equimolar complex with a specifically engineered monoclonal Fab fragment. We have determined the structure of this complex at 3.2 angstrom resolution. It reveals a molecular dimer of Rev, bound on either side by a Fab, where the ordered portion of each Rev monomer (residues 9-65) contains two coplanar alpha-helices arranged in hairpin fashion. Subunits dimerize through overlapping of the hairpin prongs. Mating of hydrophobic patches on the outer surface of the dimer is likely to promote higher order interactions, suggesting a model for Rev oligomerization onto the viral RNA. C1 [DiMattia, Michael A.; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [DiMattia, Michael A.; Stuart, David I.; Grimes, Jonathan M.] Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Watts, Norman R.; Stahl, Stephen J.; Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. EM stevena@mail.nih.gov FU National Institute for Arthritis and Skin Diseases; National Cancer Institute; National Institutes of Health (NIH); UK Medical Research Council; SPINE2COMPLEXES [LSHGCT-2006-031220]; Wellcome Trust [075491/Z/04] FX We thank Drs. N. Noinaj and S. Buchanan for advice and provision of resources during the initial crystallization experiments; Drs. E. Kandiah and S. Graham for insightful discussions; and the staff at Diamond Light Source beamline I02 for support in data collection. This work was supported in part by the Intramural Research Programs of the National Institute for Arthritis and Skin Diseases and the National Cancer Institute, the National Institutes of Health (NIH) Intramural Targeted Antiviral Program, and the NIH-Oxford Scholars Program. D. I. S. is supported by the UK Medical Research Council and J.M.G. by SPINE2COMPLEXES (LSHGCT-2006-031220). The Wellcome Trust is acknowledged for providing administrative support (Grant 075491/Z/04). NR 32 TC 66 Z9 66 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 30 PY 2010 VL 107 IS 13 BP 5810 EP 5814 DI 10.1073/pnas.0914946107 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 576QA UT WOS:000276159500023 PM 20231488 ER PT J AU Stroncek, DF Puri, RK AF Stroncek, David F. Puri, Raj K. TI Cell and gene therapies: moving from research to clinic SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material C1 [Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAR 29 PY 2010 VL 8 AR 31 DI 10.1186/1479-5876-8-31 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 589HA UT WOS:000277136500001 PM 20350323 ER PT J AU D'Souza, MP Frahm, N AF D'Souza, M. Patricia Frahm, Nicole TI Adenovirus 5 serotype vector-specific immunity and HIV-1 infection: a tale of T cells and antibodies SO AIDS LA English DT Editorial Material DE adenovirus; HIV-1 vaccines; preexisting immunity ID PRIME-BOOST REGIMENS; NONHUMAN-PRIMATES; CROSS-REACTIVITY; VACCINE VECTORS; RHESUS-MONKEYS; HEXON PROTEIN; REPLICATION; RESPONSES; AD5; SEROPREVALENCE C1 [D'Souza, M. Patricia] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Frahm, Nicole] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA. RP D'Souza, MP (reprint author), NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. EM pdsouza@niaid.nih.gov NR 30 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 27 PY 2010 VL 24 IS 6 BP 803 EP 809 DI 10.1097/QAD.0b013e3283379712 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 569XM UT WOS:000275636100002 PM 20168203 ER PT J AU Genovese, S Foreman, JE Borland, MG Epifano, F Gonzalez, FJ Curini, M Peters, JM AF Genovese, Salvatore Foreman, Jennifer E. Borland, Michael G. Epifano, Francesco Gonzalez, Frank J. Curini, Massimo Peters, Jeffrey M. TI A natural propenoic acid derivative activates peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) SO LIFE SCIENCES LA English DT Article DE Peroxisome proliferator-activated receptor; Natural ligand; Cell proliferation; Cancer ID INHIBITS CELL-PROLIFERATION; LIGAND ACTIVATION; COLON CARCINOGENESIS; SKIN; EXPRESSION; AURAPTENE; CANCER; ALPHA; DELTA; KERATINOCYTES AB Aims Previous studies showed that natural prenyloxyphenylpropanoid derivatives have potent biological properties in vivo Given the structural similarities between these compounds and known peroxisome proliferator-activated receptor (PPAR) agonists, the present study examined the hypothesis that propenoic acid derivatives activate PPARs Main methods Chimeric reporter assays were performed to identify propenoic acid denvates that could activate PPARs Quantitative polymerase chain reaction (qPCR) analysis of wild-type and Ppar beta/delta-null mouse primary kerannocytes was performed to determine if a test compound could specifically activate PPAR beta/delta, A human epithelial carcinoma cell line and pi unary mouse kerannocytes were used to determine the effect of the compound on cell proliferation Key findings. Three of the propenoic acid derivatives activated PPARs, with the greatest efficacy being observed with prenyloxycinnamic acid derivatives 4'-geranyloxyferulic acid (compound 1) for PPAR beta/delta, Compound 1 increased expression of a known PPAR beta/delta target gene through a mechanism that requires PPAR beta/delta Inhibition of cell proliferation by compound 1 was found in a human epithelial carcinoma cell line Significance Results from these studies demonstrate that compound 1 can activate PPAR beta/delta and inhibit cell proliferation of a human skin cancer cell line, suggesting that the biological effects of 4'-geranyloxyferulic acid may be mediated in part by activating this PPAR isoform (C) 2010 Elsevier Inc All rights reserved C1 [Foreman, Jennifer E.; Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Foreman, Jennifer E.; Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Genovese, Salvatore; Epifano, Francesco] Univ G dAnnunzio, Dipartimento Sci Farmaco, I-66100 Chieti, Italy. [Curini, Massimo] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, Sez Chim Organ, I-06123 Perugia, Italy. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20814 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. RI Curini, Massimo/A-2950-2011; Peters, Jeffrey/D-8847-2011; OI Curini, Massimo/0000-0003-0376-9686 FU National Institutes of Health [CA124533, CA126826, CA141029] FX This work was supported in part by the National Institutes of Health, CAl24533, CAl26826, and CA141029 (IMP.). NR 32 TC 11 Z9 11 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 27 PY 2010 VL 86 IS 13-14 BP 493 EP 498 DI 10.1016/j.lfs.2010.02.008 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 576KD UT WOS:000276142300005 PM 20153754 ER PT J AU DeFelipe, J Fields, RD Hof, PR Hoistad, M Kostovic, I Meyer, G Rockland, KS AF DeFelipe, Javier Fields, R. Douglas Hof, Patrick R. Hoeistad, Malin Kostovic, Ivica Meyer, Gundela Rockland, Kathleen S. TI Cortical white matter: beyond the pale remarks, main conclusions and discussion SO FRONTIERS IN NEUROANATOMY LA English DT Editorial Material C1 [DeFelipe, Javier] Univ Politecn Madrid, Lab Circuitos Corticales, Ctr Tecnol Biomed, Madrid, Spain. [DeFelipe, Javier] Inst Cajal CSIC, Madrid, Spain. [Fields, R. Douglas] NICHHD, NIH, Bethesda, MD 20892 USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Kostovic, Ivica] Univ Zagreb, Zagreb 41000, Croatia. [Meyer, Gundela] Univ La Laguna, Fac Med, Dept Anat, Tenerife, Spain. [Rockland, Kathleen S.] MIT, RIKEN MIT Ctr Neural Circuit Genet, Cambridge, MA 02139 USA. RP DeFelipe, J (reprint author), Univ Politecn Madrid, Lab Circuitos Corticales, Ctr Tecnol Biomed, Madrid, Spain. EM defelipe@cajal.csic.es; kathrock@mit.edu NR 30 TC 5 Z9 5 U1 0 U2 3 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5129 J9 FRONT NEUROANAT JI Front. Neuroanat. PD MAR 26 PY 2010 VL 4 AR 4 DI 10.3389/neuro.05.004.2010 PG 28 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA V21FB UT WOS:000208192400001 PM 20428509 ER PT J AU Damdinsuren, B Zhang, YQ Khalil, A Wood, WH Becker, KG Shlomchik, MJ Sen, R AF Damdinsuren, Bazarragchaa Zhang, Yongqing Khalil, Ashraf Wood, William H., III Becker, Kevin G. Shlomchik, Mark J. Sen, Ranjan TI Single Round of Antigen Receptor Signaling Programs Naive B Cells to Receive T Cell Help SO IMMUNITY LA English DT Article ID UP-REGULATION; G1 PHASE; LYMPHOCYTES; ACTIVATION; SURVIVAL; IG; PROLIFERATION; EXPRESSION; SUBSTRATE; MIGRATION AB To simulate transient B cell activation that is the likely initiator of T-dependent responses, we examined the molecular and functional consequences of a single round of immunoglobulin M (IgM) signaling. This form of activation triggered early cytosolic signaling and the transcription factor NF-kappa B activation indistinguishably from conventional continuous IgM crosslinking but did not induce G1 progression. However, single round IgM signaling changed the expression of chemokine and chemokine receptor genes implicated in initiating T-dependent responses, as well as accentuated responsiveness to CD40 signaling. Several features of single-round IgM signaling in vitro were recapitulated in B cells after short-term exposure to antigen in vivo. We propose that transient BCR signals prime B cells to receive T cell help by increasing the probability of B-T encounter and creating a cellular environment that is hyper-responsive to CD40 signaling. C1 [Damdinsuren, Bazarragchaa; Sen, Ranjan] NIA, Gene Regulat Sect, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. [Zhang, Yongqing; Wood, William H., III; Becker, Kevin G.] NIA, Res Resources Branch, Baltimore, MD 21224 USA. [Khalil, Ashraf; Shlomchik, Mark J.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Khalil, Ashraf; Shlomchik, Mark J.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA. RP Sen, R (reprint author), NIA, Gene Regulat Sect, Cellular & Mol Biol Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM rs465z@nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU National Institute on Aging; NIH [R01-AI43603] FX We thank G. Kokkonen for sorting of follicular B cells; Drs. T. Kurosaki and Y. Aiba for providing reagents; Drs. J. Cerny, A. Roy, S. Gerondakis, D. Parker, P. Gearhart, S. Fugmann, and R. Wersto for comments on the manuscript; and V. Martin for editorial assistance. This work was supported by the Intramural Research Program of the National Institute on Aging and by NIH grant R01-AI43603 to M.J.S. NR 30 TC 24 Z9 25 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR 26 PY 2010 VL 32 IS 3 BP 355 EP 366 DI 10.1016/j.immuni.2010.02.013 PG 12 WC Immunology SC Immunology GA 576DV UT WOS:000276125400009 PM 20226693 ER PT J AU Li, Q Li, G Lan, XM Zheng, M Chen, KH Cao, CM Xiao, RP AF Li, Qian Li, Geng Lan, Xiaomei Zheng, Ming Chen, Kuang-Hueih Cao, Chun-Mei Xiao, Rui-Ping TI Receptor Interacting Protein 3 Suppresses Vascular Smooth Muscle Cell Growth by Inhibition of the Phosphoinositide 3-Kinase-Akt Axis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; ANGIOTENSIN-CONVERTING ENZYME; RIP-LIKE KINASE; NEOINTIMAL HYPERPLASIA; BALLOON ANGIOPLASTY; DEATH DOMAIN; APOPTOSIS; AKT; PROLIFERATION; RESTENOSIS AB Proliferation of vascular smooth muscle cells (VSMCs) is a primary mechanism underlying cardiovascular proliferative disorders. Phosphoinositide 3-kinase (PI3K)-Akt (or protein kinase B) axis has been assigned at the center of pathways that regulate cell proliferation. Here we demonstrate that enhanced PI3K-Akt signaling by mitogenic stimulation or arterial injury profoundly elevates expression of receptor interacting protein 3 (RIP3) in primary cultured rat VSMCs and in vivo and that the up-regulation of RIP3 leads toVSMCgrowth arrest and apoptosis via inhibiting the PI3K-Akt signaling pathway, thereby alleviating balloon injury-induced neointimal formation. Specifically, mitogenic stimulation with platelet-derived growth factor-BB or angiotensin II leads to a profound increase in RIP3 expression, which is abolished by inhibition of PI3K or Akt, and increased PI3K-Akt signaling by expression of a constitutively active PI3K mutant also elevates RIP3 expression. Importantly, adenoviral overexpression of RIP3 not only triggers apoptosis but also causes cell cycle arrest at G(1)/G(0) phases that is associated with suppressed Akt activation. In sharp contrast, RIP3 gene silencing enhances serum- and platelet-derived growth factor-induced cell proliferation and Akt activation. In vivo adenoviral gene delivery of rat RIP3 (rRIP3) increased apoptosis and reduced VSMC proliferation, thus, effectively alleviating balloon injury-induced neointimal formation. The growth-suppressive and pro-apoptotic effects are independent of rRIP3 Ser/Thr kinase activity, because overexpression of a kinase-in-active mutant of rRIP3, similar to its wild type, is sufficient to induce growth arrest and apoptosis. These findings reveal a novel growth-suppressive action of RIP3, marking RIP3 as an important factor to prevent excessive mitogenic stimulation- or injury-induced vascular smooth muscle cells hyperplasia. C1 [Li, Qian; Lan, Xiaomei; Zheng, Ming; Cao, Chun-Mei; Xiao, Rui-Ping] Peking Univ, Inst Mol Med, Beijing 100083, Peoples R China. [Li, Qian; Li, Geng; Lan, Xiaomei; Xiao, Rui-Ping] Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China. [Chen, Kuang-Hueih; Xiao, Rui-Ping] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Cao, CM (reprint author), Peking Univ, Inst Mol Med, Beijing 100083, Peoples R China. EM Caochunmei@pku.edu.cn; Xiaor@grc.nia.nih.gov FU National Institutes of Health Intramural Research Program, NIA; Peking University; Chinese 973 Program [2007CB512100] FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program, NIA (to K.-H.C. and R.-P.X.). This work was also supported by Peking University 985 Project and Chinese 973 Program (2007CB512100) (to Q.Li, G.Li, X.L., M.Z., C.-M.C, and R.-P.X). NR 53 TC 14 Z9 16 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 26 PY 2010 VL 285 IS 13 BP 9535 EP 9544 DI 10.1074/jbc.M109.071332 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 576RP UT WOS:000276165900027 PM 20042608 ER PT J AU Huang, J Dorsey, J Chuikov, S Zhang, XY Jenuwein, T Reinberg, D Berger, SL AF Huang, Jing Dorsey, Jean Chuikov, Sergei Zhang, Xinyue Jenuwein, Thomas Reinberg, Danny Berger, Shelley L. TI G9a and Glp Methylate Lysine 373 in the Tumor Suppressor p53 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PATHWAY; H3-K9 AB The tumor suppressor p53 is regulated by numerous post-translational modifications. Lysine methylation has recently emerged as a key post-translational modification that alters the activity of p53. Here, we describe a novel lysine methylation site in p53 that is carried out by two homologous histone methyltransferases, G9a and Glp. G9a and Glp specifically methylate p53 at Lys(373), resulting mainly in dimethylation. During DNA damage, the overall level of p53 modified at Lys(373)me2 does not increase, despite the dramatic increase in total p53, indicating that Lys(373)me2 correlates with inactive p53. Further, reduction of G9a and/or Glp levels leads to a larger population of apoptotic cells. Examination of the Oncomine data base shows that G9a and Glp are overexpressed in various cancers compared with corresponding normal tissues, suggesting that they are putative oncogenes. These data reveal a new methylation site within p53 mediated by the methylases G9a and Glp and indicate that G9a is a potential inhibitory target for cancer treatment. C1 [Huang, Jing; Zhang, Xinyue] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Huang, Jing; Dorsey, Jean; Berger, Shelley L.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Jenuwein, Thomas] Res Inst Mol Pathol, A-1030 Vienna, Austria. [Jenuwein, Thomas] Max Planck Inst Immunobiol, D-076151080 Freiburg, Germany. [Chuikov, Sergei; Reinberg, Danny] NYU, Sch Med, Smilow Res Ctr, New York, NY 10016 USA. [Reinberg, Danny] Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. [Berger, Shelley L.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Berger, Shelley L.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Berger, Shelley L.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Huang, J (reprint author), NCI, Lab Canc Biol & Genet, NIH, 37 Convent Dr,MSC 4258,Bldg 37,Rm 3140, Bethesda, MD 20892 USA. EM huangj3@mail.nih.gov RI Huang, Jing/A-2566-2009 OI Huang, Jing/0000-0002-7163-5156 FU NCI, National Institutes of Health Intramural Research Program and Center for Cancer Research [CA 078831] FX This work was supported, in whole or in part, by the NCI, National Institutes of Health Intramural Research Program and Center for Cancer Research (J. H.). This work was also supported by NCI, National Institutes of Health Grant CA 078831 (to S. L. B.). NR 18 TC 143 Z9 150 U1 1 U2 15 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 MAR 26 PY 2010 VL 285 IS 13 BP 9636 EP 9641 DI 10.1074/jbc.M109.062588 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 576RP UT WOS:000276165900036 PM 20118233 ER PT J AU Liu, X Shu, S Hong, MSS Yu, B Korn, ED AF Liu, Xiong Shu, Shi Hong, Myoung-Soon S. Yu, Bin Korn, Edward D. TI Mutation of Actin Tyr-53 Alters the Conformations of the DNase I-binding Loop and the Nucleotide-binding Cleft SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DICTYOSTELIUM MYOSIN-II; TYROSINE PHOSPHORYLATION; MONOMERIC ACTIN; CRYSTAL-STRUCTURES; SUBDOMAIN 2; CELLS; DISCOIDEUM; FILAMENT; DYNAMICS; STATE AB All but 11 of the 323 known actin sequences have Tyr at position 53, and the 11 exceptions have the conservative substitution Phe, which raises the following questions. What is the critical role(s) of Tyr-53, and, if it can be replaced by Phe, why has this happened so infrequently? We compared the properties of purified endogenous Dictyostelium actin and mutant constructs with Tyr-53 replaced by Phe, Ala, Glu, Trp, and Leu. The Y53F mutant did not differ significantly from endogenous actin in any of the properties assayed, but the Y53A and Y53E mutants differed substantially; affinity for DNase I was reduced, the rate of nucleotide exchange was increased, the critical concentration for polymerization was increased, filament elongation was inhibited, and polymerized actin was in the form of small oligomers and imperfect filaments. Growth and/or development of cells expressing these actin mutants were also inhibited. The Trp and Leu mutations had lesser but still significant effects on cell phenotype and the biochemical properties of the purified actins. We conclude that either Tyr or Phe is required to maintain the functional conformations of the DNase I-binding loop (D-loop) in both G- and F-actin, and that the conformation of the D-loop affects not only the properties that directly involve the D-loop (binding to DNase I and polymerization) but also allosterically modifies the conformation of the nucleotide-binding cleft, thus increasing the rate of nucleotide exchange. The apparent evolutionary "preference" for Tyr at position 53 may be the result of Tyr allowing dynamic modification of the D-loop conformation by phosphorylation (Baek, K., Liu, X., Ferron, F., Shu, S., Korn, E. D., and Dominguez, R. (2008) Proc. Natl. Acad. Sci. U. S. A. 105, 11748-11753) with effects similar, but not identical, to those of the Ala and Glu mutations. C1 [Liu, Xiong; Shu, Shi; Hong, Myoung-Soon S.; Yu, Bin; Korn, Edward D.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2517,9000 Rockville Pike, Bethesda, MD 20892 USA. EM edk@nih.gov RI Korn, Edward/F-9929-2012 NR 43 TC 9 Z9 9 U1 1 U2 2 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 MAR 26 PY 2010 VL 285 IS 13 BP 9729 EP 9739 DI 10.1074/jbc.M109.073452 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 576RP UT WOS:000276165900045 PM 20100837 ER PT J AU Zhang, Y Doherty, T Li, J Lu, WY Barinka, C Lubkowski, J Hong, M AF Zhang, Yuan Doherty, Tim Li, Jing Lu, Wuyuan Barinka, Cyril Lubkowski, Jacek Hong, Mei TI Resonance Assignment and Three-Dimensional Structure Determination of a Human alpha-Defensin, HNP-1, by Solid-State NMR SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE human alpha-defensin; solid-state NMR; resonance assignment; structure determination; antimicrobial peptides ID HAIRPIN ANTIMICROBIAL PEPTIDE; ANGLE-SPINNING NMR; NUCLEAR-MAGNETIC-RESONANCE; CHEMICAL-SHIFT; LIPID-BILAYERS; MICROCRYSTALLINE UBIQUITIN; CORRELATION SPECTROSCOPY; SECONDARY STRUCTURE; MEMBRANE PEPTIDE; AMYLOID FIBRILS AB Human alpha-defensins [human neutrophil peptides (HNPs)] are immune defense mini-proteins that act by disrupting microbial cell membranes. Elucidating the three-dimensional (3D) structures of HNPs in lipid membranes is important for understanding their mechanisms of action. Using solid-state NMR (SSNMR), we have determined the 3D structure of HNP-1 in a microcrystalline state outside the lipid membrane, which provides benchmarks for structure determination and comparison with the membrane-bound state. From a suite of two-dimensional and 3D magic-angle spinning experiments, (13)C and (15)N chemical shifts that yielded torsion angle constraints were obtained, while inter-residue distances were obtained to restrain the 3D fold. Together, these constraints led to the first high-resolution SSNMR structure of a human defensin. The SSNMR structure has close similarity to the crystal structures of the HNP family, with the exception of the loop region between the first and second beta-strands. The difference, which is partially validated by direct torsion angle measurements of selected loop residues, suggests possible conformational variation and flexibility of this segment of the protein, which may regulate HNF interaction with the phospholipid membrane of microbial cells. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Zhang, Yuan; Doherty, Tim; Hong, Mei] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Li, Jing; Lu, Wuyuan] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Li, Jing; Lu, Wuyuan] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Barinka, Cyril; Lubkowski, Jacek] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Hong, M (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. EM mhong@iastate.edu RI Lu, Wuyuan/B-2268-2010; Barinka, Cyril/G-9803-2014 FU NIH [GM66976]; [P41-EB-002026] FX The authors thank Chih-Chia Su for assistance with microcrystal visualization; Professor Chad Rienstra for sharing the design of microcrystal transfer tools; Professor Robert Griffin, Dr. Jozef Lewandowski, Dr. Gael De Paepe, and Dr. Tony Bielecki for assistance with the 900-MHz NMR experiments; and Dr. Andrew Severin and Dr. Shenhui Li for help with the Xplor-NTH structure calculations. This work is supported by the NIH grant GM66976 to M.H. and P41-EB-002026 for the 900-MHz NMR time at MIT. NR 59 TC 26 Z9 26 U1 1 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 26 PY 2010 VL 397 IS 2 BP 408 EP 422 DI 10.1016/j.jmb.2010.01.030 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578DI UT WOS:000276273300005 PM 20097206 ER PT J AU Yan, ZJ Delannoy, M Ling, C Daee, D Osman, F Muniandy, PA Shen, X Oostra, AB Du, HS Steltenpool, J Lin, T Schuster, B Decaillet, C Stasiak, A Stasiak, AZ Stone, S Hoatlin, ME Schindler, D Woodcock, CL Joenje, H Sen, R de Winter, JP Li, L Seidman, MM Whitby, MC Myung, K Constantinou, A Wang, W AF Yan, Zhijiang Delannoy, Mathieu Ling, Chen Daee, Danielle Osman, Fekret Muniandy, Parameswary A. Shen, Xi Oostra, Anneke B. Du, Hansen Steltenpool, Jurgen Lin, Ti Schuster, Beatrice Decaillet, Chantal Stasiak, Andrzej Stasiak, Alicja Z. Stone, Stacie Hoatlin, Maureen E. Schindler, Detlev Woodcock, Christopher L. Joenje, Hans Sen, Ranjan de Winter, Johan P. Li, Lei Seidman, Michael M. Whitby, Matthew C. Myung, Kyungjae Constantinou, Angelos Wang, Weidong TI A Histone-Fold Complex and FANCM Form a Conserved DNA-Remodeling Complex to Maintain Genome Stability SO MOLECULAR CELL LA English DT Article ID ANEMIA CORE COMPLEX; OUTER KINETOCHORE; REPLICATION FORKS; MONOUBIQUITINATION; RECOMBINATION; REPAIR; PROTEINS AB FANCM remodels branched DNA structures and plays essential roles in the cellular response to DNA replication stress. Here, we show that FANCM forms a conserved DNA-remodeling complex with a histone-fold heterodimer, MHF. We find that MHF stimulates DNA binding and replication fork remodeling by FANCM. In the cell, FANCM and MHF are rapidly recruited to forks stalled by DNA interstrand crosslinks, and both are required for cellular resistance to such lesions. In vertebrates, FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage, and suppresses sister-chromatid exchanges. Yeast orthologs of these proteins function together to resist MMS-induced DNA damage and promote gene conversion at blocked replication forks. Thus, FANCM-MHF is an essential DNA-remodeling complex that protects replication forks from yeast to human. C1 [Delannoy, Mathieu; Decaillet, Chantal; Constantinou, Angelos] Univ Lausanne, Dept Biochem, Lausanne, Switzerland. [Stasiak, Andrzej; Stasiak, Alicja Z.] Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland. [Yan, Zhijiang; Ling, Chen; Lin, Ti; Wang, Weidong] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Muniandy, Parameswary A.; Seidman, Michael M.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Du, Hansen; Sen, Ranjan] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Daee, Danielle; Myung, Kyungjae] NHGRI, Genome Instabil Sect, NIH, Bethesda, MD 20892 USA. [Osman, Fekret; Whitby, Matthew C.] Univ Oxford, Dept Biochem, Oxford OX 3QU, England. [Shen, Xi; Li, Lei] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Oostra, Anneke B.; Steltenpool, Jurgen; Joenje, Hans; de Winter, Johan P.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, NL-1007 MB Amsterdam, Netherlands. [Schuster, Beatrice; Schindler, Detlev] Univ Wurzburg, Dept Human Genet, D-97070 Wurzburg, Germany. [Stone, Stacie; Hoatlin, Maureen E.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. [Woodcock, Christopher L.] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. RP Constantinou, A (reprint author), Univ Lausanne, Dept Biochem, Lausanne, Switzerland. EM angelos.constantinou@unil.ch; wangw@grc.nia.nih.gov RI Stasiak, Andrzej/E-5551-2010; Constantinou, Angelos/E-5337-2013; OI Whitby, Matthew/0000-0003-0951-3374 FU National Institute on Aging [AG000688-07]; NHGRI [HG0120030-7]; National Institute of Health [HL007781, CA112775]; Fanconi Anemia Research Foundation; Swiss National Science Foundation [3100A0-116275, PP00A-118991]; Wellcome Trust FX We thank Y. Xue for providing recombinant FANCM754 protein, Drs. K.J. Patel for FANCM-/- cells and antibody, M. Takata for chicken FANCD2 antibody, Y. Li for FAAP24 antibody, and D. Schlessinger for critical reading of the manuscript. This work was supported in part by the Intramural Research Program of the National Institute on Aging (grant AG000688-07), NHGRI (grant HG0120030-7), National Institute of Health (grants HL007781 and CA112775), and the Fanconi Anemia Research Foundation and Swiss National Science Foundation (grant 3100A0-116275). A.C. was supported by a Swiss National Science Foundation Professorship (grant PP00A-118991). M.C.W. and F.O. were supported by a Wellcome Trust Senior Research Fellowship to M.C.W. NR 22 TC 107 Z9 115 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 26 PY 2010 VL 37 IS 6 BP 865 EP 878 DI 10.1016/j.molcel.2010.01.039 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 576HM UT WOS:000276135100013 PM 20347428 ER PT J AU Kumar, S Molina-Cruz, A Gupta, L Rodrigues, J Barillas-Mury, C AF Kumar, Sanjeev Molina-Cruz, Alvaro Gupta, Lalita Rodrigues, Janneth Barillas-Mury, Carolina TI A Peroxidase/Dual Oxidase System Modulates Midgut Epithelial Immunity in Anopheles gambiae SO SCIENCE LA English DT Article ID PERITROPHIC MATRIX PROTEIN; DROSOPHILA GUT IMMUNITY; DUAL OXIDASE; PLASMODIUM; INFECTION; PATHWAY; DUOX AB Extracellular matrices in diverse biological systems are cross-linked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. We show that a peroxidase, secreted by the Anopheles gambiae midgut, and dual oxidase form a dityrosine network that decreases gut permeability to immune elicitors. This network protects the microbiota by preventing activation of epithelial immunity. It also provides a suitable environment for malaria parasites to develop within the midgut lumen without inducing nitric oxide synthase expression. Disruption of this barrier results in strong and effective pathogen-specific immune responses. C1 [Kumar, Sanjeev; Molina-Cruz, Alvaro; Gupta, Lalita; Rodrigues, Janneth; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Barillas-Mury, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM cbarillas@niaid.nih.gov FU Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. We thank A. Laughinghouse, K. Lee, T. Lehman, and R. Gwadz for insectary support; J. Kabat for assistance with confocal imaging; J. Ribeiro and J. Valenzuela for their comments and insight; and B. Marshall for editorial assistance. The complete data set for this microarray experiment has been submitted to the National Center for Biotechnology Information Gene Expression Omnibus database with accession number GSE20204. NR 15 TC 110 Z9 113 U1 4 U2 36 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 MAR 26 PY 2010 VL 327 IS 5973 BP 1644 EP 1648 DI 10.1126/science.1184008 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 574ED UT WOS:000275970600044 PM 20223948 ER PT J AU Merchant, MS AF Merchant, Melinda S. TI Chaperoning the lympho-stromal dance SO BLOOD LA English DT Editorial Material ID GP96; INTEGRIN; HSP90B1; GRP94 C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Merchant, MS (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 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 MAR 25 PY 2010 VL 115 IS 12 BP 2334 EP 2335 PG 2 WC Hematology SC Hematology GA 574IF UT WOS:000275981900004 PM 20339105 ER PT J AU Bisaglia, M Greggio, E Maric, D Miller, DW Cookson, MR Bubacco, L AF Bisaglia, Marco Greggio, Elisa Maric, Dragan Miller, David W. Cookson, Mark R. Bubacco, Luigi TI alpha-Synuclein overexpression increases dopamine toxicity in BE(2)-M17 cells SO BMC NEUROSCIENCE LA English DT Article ID CHAPERONE-MEDIATED AUTOPHAGY; PARKINSONS-DISEASE; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; CYTOSOLIC DOPAMINE; SH-SY5Y CELLS; LEWY BODIES; WILD-TYPE; MUTANT; MUTATION AB Background: Oxidative stress has been proposed to be involved in the pathogenesis of Parkinson's disease (PD). A plausible source of oxidative stress in nigral dopaminergic neurons is the redox reactions that specifically involve dopamine and produce various toxic molecules, i.e., free radicals and quinone species. alpha-Synuclein, a protein found in Lewy bodies characteristic of PD, is also thought to be involved in the pathogenesis of PD and point mutations and multiplications in the gene coding for alpha-synuclein have been found in familial forms of PD. Results: We used dopaminergic human neuroblastoma BE(2)-M17 cell lines stably transfected with WT or A30P mutant alpha-synuclein to characterize the effect of alpha-synuclein on dopamine toxicity. Cellular toxicity was analyzed by lactate dehydrogenase assay and by fluorescence-activated cell sorter analysis. Increased expression of either wildtype or mutant alpha-synuclein enhances the cellular toxicity induced by the accumulation of intracellular dopamine or DOPA. Conclusions: Our results suggest that an interplay between dopamine and alpha-synuclein can cause cell death in a neuron-like background. The data presented here are compatible with several models of cytotoxicity, including the formation of alpha-synuclein oligomers and impairment of the lysosomal degradation. C1 [Bisaglia, Marco; Bubacco, Luigi] Univ Padua, Dept Biol, I-35121 Padua, Italy. [Greggio, Elisa; Miller, David W.; Cookson, Mark R.] NIH, Cell Biol & Gene Express Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [Maric, Dragan] NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Bubacco, L (reprint author), Univ Padua, Dept Biol, I-35121 Padua, Italy. EM luigi.bubacco@unipd.it RI Bubacco, Luigi/B-5602-2012; Greggio, Elisa/H-6119-2013; OI Greggio, Elisa/0000-0002-8172-3598; Bubacco, Luigi/0000-0001-7927-9208 FU Italian Ministry of Education, University and Research; NIH, National Institute on Aging [1 Z01 AG000953]; EMBO short term fellowship FX This work was funded by grants from the Italian Ministry of Education, University and Research, MIUR-PRIN and MIUR-FIRB, (L. B.) and in part by the Intramural Research Program of the NIH, National Institute on Aging, project number 1 Z01 AG000953 (M. R. C.). M. B. was supported through an EMBO short term fellowship. NR 45 TC 14 Z9 14 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD MAR 25 PY 2010 VL 11 AR 41 DI 10.1186/1471-2202-11-41 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 580JP UT WOS:000276444600001 PM 20334701 ER PT J AU Kumar, TS Zhou, SY Joshi, BV Balasubramanian, R Yang, TH Liang, BT Jacobson, KA AF Kumar, T. Santhosh Zhou, Si-Yuan Joshi, Bhalchandra V. Balasubramanian, Ramachandran Yang, Tiehong Liang, Bruce T. Jacobson, Kenneth A. TI Structure Activity Relationship of (N)-Methanocarba Phosphonate Analogues of 5 '-AMP as Cardioprotective Agents Acting Through a Cardiac P2X Receptor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID OVEREXPRESSING CALSEQUESTRIN; NUCLEOSIDE PHOSPHONATES; VENTRICULAR MYOCYTES; HEART-FAILURE; INHIBITION; ADENOSINE; MODEL; MICE; CARDIOMYOPATHY; DERIVATIVES AB P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart failure) compared to vehicle-infused mice (all inactive at the vasodilatory P2Y(1) receptor). Two phosphonates, (1'S,2'R,3',5,4'R,5'S)-4'-(6-amino-2-chloropurin-9-y1)-2',3'-(dihydroxy)-1'-(phosphonomethylene)-bicyclo[3.1.0]hexane, 4 (MRS2775), and its homologue 9 (MRS2935), both 5'-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5'-extended phosphonates, all 2-H analogues, and a CH(3)-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure. C1 [Jacobson, Kenneth A.] NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. [Zhou, Si-Yuan; Yang, Tiehong; Liang, Bruce T.] Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06030 USA. RP Jacobson, KA (reprint author), NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bldg 8A,Room B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NI National Institute of Diabetes and Digestive and Kidney Diseases; Ray Neag Distinguished Professorship [RO1-HL48225] FX Mass spectral measurements were carried out by Dr. John Lloyd and Dr. Noel Whittaker (NIDDK). We thank Dr. T. Kendall Harden (University of North Carolina, Chapel Hill, NC) for the gift of tran reeled 1321N1 astrocyoma cells and Dr. William Trenkle (NIDDK) for helpful discussion. This research was supported in part by the Intramural Research Program of the NI National Institute of Diabetes and Digestive and Kidney Diseases. This work was supported in part by RO1-HL48225 and a Ray Neag Distinguished Professorship to Bruce T. Liang. NR 35 TC 41 Z9 41 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 25 PY 2010 VL 53 IS 6 BP 2562 EP 2576 DI 10.1021/jm9018542 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 570XE UT WOS:000275711000023 PM 20192270 ER PT J AU Insel, TR AF Insel, Thomas R. TI The Challenge of Translation in Social Neuroscience: A Review of Oxytocin, Vasopressin, and Affiliative Behavior SO NEURON LA English DT Review ID PAIR-BOND FORMATION; PARTNER-PREFERENCE FORMATION; AUTISM SPECTRUM DISORDERS; MONOGAMOUS PRAIRIE VOLE; CENTRAL-NERVOUS-SYSTEM; RECEPTOR GENE OXTR; MATERNAL-BEHAVIOR; ARGININE-VASOPRESSIN; NUCLEUS-ACCUMBENS; GENOME-WIDE AB Social neuroscience is rapidly exploring the complex territory between perception and action where recognition, value, and meaning are instantiated. This review follows the trail of research on oxytocin and vasopressin as an exemplar of one path for exploring the "dark matter" of social neuroscience. Studies across vertebrate species suggest that these neuropeptides are important for social cognition, with gender- and steroid-dependent effects. Comparative research in voles yields a model based on interspecies and intraspecies variation of the geography of oxytocin receptors and vasopressin Via receptors in the forebrain. Highly affiliative species have receptors in brain circuits related to reward or reinforcement. The neuroanatomical distribution of these receptors may be guided by variations in the regulatory regions of their respective genes. This review describes the promises and problems of extrapolating these findings to human social cognition, with specific reference to the social deficits of autism. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 134 TC 387 Z9 390 U1 18 U2 161 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 25 PY 2010 VL 65 IS 6 BP 768 EP 779 DI 10.1016/j.neuron.2010.03.005 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 576MP UT WOS:000276148900007 PM 20346754 ER PT J AU Grimes, WN Zhang, J Graydon, CW Kachar, B Diamond, JS AF Grimes, William N. Zhang, Jun Graydon, Cole W. Kachar, Bechara Diamond, Jeffrey S. TI Retinal Parallel Processors: More than 100 Independent Microcircuits Operate within a Single Interneuron SO NEURON LA English DT Article ID ROD BIPOLAR CELLS; INNER PLEXIFORM LAYER; RABBIT RETINA; MAMMALIAN RETINA; GANGLION-CELLS; AMACRINE CELLS; OLFACTORY-BULB; PYRAMIDAL NEURONS; RIBBON SYNAPSE; GRANULE CELLS AB Most neurons are highly polarized cells with branched dendrites that receive and integrate synaptic inputs and extensive axons that deliver action potential output to distant targets. By contrast, amacrine cells, a diverse class of inhibitory interneurons in the inner retina, collect input and distribute output within the same neuritic network. The extent to which most amacrine cells integrate synaptic information and distribute their output is poorly understood. Here, we show that single A17 amacrine cells provide reciprocal feedback inhibition to presynaptic bipolar cells via hundreds of independent microcircuits operating in parallel. The A17 uses specialized morphological features, biophysical properties, and synaptic mechanisms to isolate feedback microcircuits and maximize its capacity to handle many independent processes. This example of a neuron employing distributed parallel processing rather than spatial integration provides insights into how unconventional neuronal morphology and physiology can maximize network function while minimizing wiring cost. C1 [Grimes, William N.; Zhang, Jun; Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. [Grimes, William N.] Univ Maryland, Biophys Grad Partnership Program, NIH, Bethesda, MD 20892 USA. [Graydon, Cole W.; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. [Graydon, Cole W.] Brown Univ, Neurosci Grad Partnership Program, NIH, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov RI Zhang, Jun/K-2424-2012; Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU NIDCD Intramural Research Programs FX This work was supported by the NINDS and NIDCD Intramural Research Programs. NR 52 TC 54 Z9 54 U1 3 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 25 PY 2010 VL 65 IS 6 BP 873 EP 885 DI 10.1016/j.neuron.2010.02.028 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 576MP UT WOS:000276148900015 PM 20346762 ER PT J AU Insel, TR AF Insel, Thomas R. TI Psychiatrists' Relationships With Pharmaceutical Companies Part of the Problem or Part of the Solution? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CONFLICT-OF-INTEREST; CLINICAL-PRACTICE GUIDELINES; INDUSTRY C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, 6001 Execut Blvd,Room 8235, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 10 TC 17 Z9 17 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 24 PY 2010 VL 303 IS 12 BP 1192 EP 1193 DI 10.1001/jama.2010.317 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 573AC UT WOS:000275879600026 PM 20332407 ER PT J AU Davis, AA Fritz, JJ Wess, J Lah, JJ Levey, AI AF Davis, Albert A. Fritz, Jason J. Wess, Juergen Lah, James J. Levey, Allan I. TI Deletion of M-1 Muscarinic Acetylcholine Receptors Increases Amyloid Pathology In Vitro and In Vivo SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; A-BETA; TRANSGENIC MICE; AGONIST AF102B; SECRETED FORMS; RAT-BRAIN; EXPRESSION; CELLS AB Alzheimer's disease (AD) is a progressive neurological disorder that causes dementia and poses a major public health crisis as the population ages. Aberrant processing of the amyloid precursor protein (APP) is strongly implicated as a proximal event in AD pathophysiology, but the neurochemical signals that regulate APP processing in the brain are not completely understood. Activation of muscarinic acetylcholine receptors (mAChRs) has been shown to affect APP processing and AD pathology, but less is known about the roles of specific mAChR subtypes. In this study, we used M-1 mAChR knock-out mice (M1KO) to isolate the effects of the M-1 mAChR on APP processing in primary neurons and on the development of amyloid pathology in a transgenic mouse model of AD. We demonstrate that the loss of M-1 mAChRs increases amyloidogenic APP processing in neurons, as evidenced by decreased agonist-regulated shedding of the neuroprotective APP ectodomain APPs alpha and increased production of toxic A beta peptides. Expression of M-1 mAChRs on the M1KO background rescued this phenotype, indicating that M-1 mAChRs are sufficient to modulate nonamyloidogenic APP processing. In APP(Swe/Ind) transgenic mice, the loss of M-1 mAChRs resulted in increased levels of brain A beta and greater accumulation of amyloid plaque pathology. Analysis of APP metabolites in APP(Swe/Ind) brain tissue indicates that the loss of M-1 mAChRs increases amyloidogenic APP processing. These results indicate that the M-1 mAChR is an important regulator of amyloidogenesis in the brain and provide strong support for targeting the M-1 mAChR as a therapeutic candidate in AD. C1 [Davis, Albert A.; Fritz, Jason J.; Lah, James J.; Levey, Allan I.] Emory Univ, Dept Neurol, Sch Med, Atlanta, GA 30322 USA. [Davis, Albert A.; Fritz, Jason J.; Lah, James J.; Levey, Allan I.] Emory Univ, Ctr Neurodegenerat Dis, Sch Med, Atlanta, GA 30322 USA. [Wess, Juergen] NIDDK, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. RP Levey, AI (reprint author), Emory Univ, Dept Neurol, Sch Med, Woodruff Mem Res Bldg,101 Woodruff Circle,Suite 6, Atlanta, GA 30322 USA. EM alevey@emory.edu FU National Institutes of Health [NS030454, F30 AG029731]; PhRMA Foundation FX This work was supported by National Institutes of Health Grants NS030454 (A. I. L.) and F30 AG029731 (A. A. D.) and a predoctoral fellowship from the PhRMA Foundation (A. A. D.). We are grateful to Yinghong Cui, Guofu Fang, Xinping Huang, Howard Rees, and Zoe White for expert technical assistance. NR 34 TC 59 Z9 62 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 MAR 24 PY 2010 VL 30 IS 12 BP 4190 EP 4196 DI 10.1523/JNEUROSCI.6393-09.2010 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 573XQ UT WOS:000275950100003 PM 20335454 ER PT J AU Koizumi, H Smerin, SE Yamanishi, T Moorjani, BR Zhang, RL Smith, JC AF Koizumi, Hidehiko Smerin, Stanley E. Yamanishi, Tadashi Moorjani, Bindiya R. Zhang, Ruli Smith, Jeffrey C. TI TASK Channels Contribute to the K+-Dominated Leak Current Regulating Respiratory Rhythm Generation In Vitro SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PRE-BOTZINGER COMPLEX; 2-PORE-DOMAIN POTASSIUM CHANNELS; PREBOTZINGER COMPLEX; PACEMAKER NEURONS; PH; MODULATION; ACID; NEUROTRANSMITTERS; MOTONEURONS; INHIBITION AB Leak channels regulate neuronal activity and excitability. Determining which leak channels exist in neurons and how they control electrophysiological behavior is fundamental. Here we investigated TASK channels, members of the two-pore domain K+ channel family, as a component of the K+-dominated leak conductance that controls and modulates rhythm generation at cellular and network levels in the mammalian pre-Botzinger complex (pre-BotC), an excitatory network of neurons in the medulla critically involved in respiratory rhythmogenesis. By voltage-clamp analyses of pre-BotC neuronal current-voltage (I-V) relations in neonatal rat medullary slices in vitro, we demonstrated that pre-BotC inspiratory neurons have a weakly outward-rectifying total leak conductance with reversal potential that was depolarized by similar to 4 mV from the K+ equilibrium potential, indicating that background K+ channels are dominant contributors to leak. This K+ channel component had I-V relations described by constant field theory, and the conductance was reduced by acid and was augmented by the volatile anesthetic halothane, which are all hallmarks of TASK. We established by single-cell RT-PCR that pre-BotC inspiratory neurons express TASK-1 and in some cases also TASK-3 mRNA. Furthermore, acid depolarized and augmented bursting frequency of pre-BotC inspiratory neurons with intrinsic bursting properties. Microinfusion of acidified solutions into the rhythmically active pre-BotC network increased network bursting frequency, halothane decreased bursting frequency, and acid reversed the depressant effects of halothane, consistent with modulation of network activity by TASK channels. We conclude that TASK-like channels play a major functional role in chemosensory modulation of respiratory rhythm generation in the pre-Botzinger complex in vitro. C1 [Koizumi, Hidehiko; Smerin, Stanley E.; Yamanishi, Tadashi; Moorjani, Bindiya R.; Zhang, Ruli; Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Koizumi, Hidehiko] Osaka Univ, Grad Sch Dent, Suita, Osaka 5650871, Japan. RP Smith, JC (reprint author), NINDS, Cellular & Syst Neurobiol Sect, NIH, Bldg 49,Room 2A10, Bethesda, MD 20892 USA. EM jsmith@helix.nih.gov FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. We thank Murtaza Mogri for scripting modeling simulations. NR 56 TC 31 Z9 32 U1 0 U2 1 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 MAR 24 PY 2010 VL 30 IS 12 BP 4273 EP 4284 DI 10.1523/JNEUROSCI.4017-09.2010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 573XQ UT WOS:000275950100012 PM 20335463 ER PT J AU Ghosh, D Berg, JM AF Ghosh, Debdip Berg, Jeremy M. TI A Proteome-Wide Perspective on Peroxisome Targeting Signal 1(PTS1)-Pex5p Affinities SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MESSENGER-RNA EXPRESSION; BIOGENESIS DISORDERS; IMPORT RECEPTOR; PEX5P; RECOGNITION; PROTEINS; OXIDASE; IDENTIFICATION; TRIPEPTIDE; ABUNDANCE AB Most proteins are targeted to the peroxisomal matrix by virtue of a peroxisomal targeting signal-1 (PTS1), a short carboxy-terminal sequence specifically recognized by the PTS1 receptor Pex5p. We had previously developed a model that allowed the estimation of the affinities of many PTS1 sequences within the human proteome for Pex5p that revealed a wide range of predicted affinities. We have now experimentally determined the affinities of the PTS1-containing peptides from 42 proteins from the human proteome for Pex5p and show that these range over 4 orders of magnitude. These affinities correlate reasonably well with the predicted values and are substantially more precise. In an attempt to provide a possible explanation for the wide range of PTS1-Pex5p affinities, we compared these affinities with mRNA levels (as a proxy for rates of protein production) of the genes encoding these proteins in 79 human tissues and cell types. We note that high affinity PTS1-Pex5p interactions tend to correspond to proteins encoded by genes expressed at relatively low levels, whereas lower affinity PTS1-Pex5p interactions tend to correspond to proteins encoded by genes exhibiting higher levels and wider ranges of expression. Further analysis revealed that these relationships are consistent with the notion that a relatively uniform pool of protein-Pex5p complexes is maintained for appropriate peroxisome assembly. C1 [Ghosh, Debdip; Berg, Jeremy M.] NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. RP Berg, JM (reprint author), NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. EM bergj@mail.nih.gov OI Berg, Jeremy/0000-0003-3022-0963 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences FX This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of General Medical Sciences. We thank Drs. Barbara Amann, Douglas Barrick, and Gregory J. Gatto, Jr. for useful discussions. NR 31 TC 19 Z9 20 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 24 PY 2010 VL 132 IS 11 BP 3973 EP 3979 DI 10.1021/ja9109049 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 572XC UT WOS:000275868700057 PM 20178365 ER PT J AU Kaul, H Riazuddin, SA Shahid, M Kousar, S Butt, NH Zafar, AU Khan, SN Husnain, T Akram, J Hejtmancik, JF Riazuddin, S AF Kaul, Haiba Riazuddin, S. Amer Shahid, Mariam Kousar, Samra Butt, Nadeem H. Zafar, Ahmad U. Khan, Shaheen N. Husnain, Tayyab Akram, Javed Hejtmancik, J. Fielding Riazuddin, Sheikh TI Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family SO MOLECULAR VISION LA English DT Article ID CHROMOSOME 1P; NONSENSE MUTATION; GENE; LOCUS; BLINDNESS; MAPS AB Purpose: To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous Pakistani family. Methods: All affected individuals underwent a detailed ophthalmological and clinical examination. Blood samples were collected and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic microsatellite markers. Logarithm of odds (LOD) scores were calculated, and Eph-receptor type-A2 (EPHA2), residing in the critical interval, was sequenced bidirectionally. Results: The clinical and ophthalmological examinations suggested that all affected individuals have nuclear cataracts. Genome-wide linkage analyses localized the critical interval to a 20.78 cM (15.08 Mb) interval on chromosome 1p, with a maximum two-point LOD score of 5.21 at theta=0. Sequencing of EPHA2 residing in the critical interval identified a missense mutation: c.2353G>A, which results in an alanine to threonine substitution (p.A785T). Conclusions: Here, we report for the first time a missense mutation in EPHA2 associated with autosomal recessive congenital cataracts. C1 [Kaul, Haiba; Riazuddin, S. Amer; Shahid, Mariam; Kousar, Samra; Zafar, Ahmad U.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Butt, Nadeem H.; Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@aimrc.org RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015 FU Higher Education Commission, Islamabad, Pakistan; Ministry of Science and Technology, Islamabad, Pakistan FX The authors are grateful to all members for their participation in this study. We are also thankful to members of the staff of Layton Rehmatullah Benevolent Trust (LRBT) hospital, for clinical evaluation of affected individuals. This study was supported in part by Higher Education Commission, Islamabad, Pakistan and Ministry of Science and Technology, Islamabad, Pakistan. NR 29 TC 46 Z9 47 U1 0 U2 3 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD MAR 24 PY 2010 VL 16 IS 58-59 BP 511 EP 517 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 614RG UT WOS:000279076800001 PM 20361013 ER PT J AU Wei, CJ Boyington, JC Dai, KF Houser, KV Pearce, MB Kong, WP Yang, ZY Tumpey, TM Nabel, GJ AF Wei, Chih-Jen Boyington, Jeffrey C. Dai, Kaifan Houser, Katherine V. Pearce, Melissa B. Kong, Wing-Pui Yang, Zhi-yong Tumpey, Terrence M. Nabel, Gary J. TI Cross-Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID RECEPTOR-BINDING; ANTIGENIC STRUCTURE; H1N1 INFLUENZA; A VIRUS; HEMAGGLUTININ; RECOGNITION; EPITOPE; CHALLENGE; PANDEMICS; PROTEINS AB New strains of H1N1 influenza virus have emerged episodically over the last century to cause human pandemics, notably in 1918 and recently in 2009. Pandemic viruses typically evolve into seasonal forms that develop resistance to antibody neutralization, and cross-protection between strains separated by more than 3 years is uncommon. Here, we define the structural basis for cross-neutralization between two temporally distant pandemic influenza viruses-from 1918 and 2009. Vaccination of mice with the 1918 strain protected against subsequent lethal infection by 2009 virus. Both were resistant to antibodies directed against a seasonal influenza, A/New Caledonia/20/1999 (1999 NC), which was insensitive to antisera to the pandemic strains. Pandemic strain-neutralizing antibodies were directed against a subregion of the hemagglutinin (HA) receptor binding domain that is highly conserved between the 1918 and the 2009 viruses. In seasonal strains, this region undergoes amino acid diversification but is shielded from antibody neutralization by two highly conserved glycosylation sites absent in the pandemic strains. Pandemic HA trimers modified by glycosylation at these positions were resistant to neutralizing antibodies to wild-type HA. Yet, antisera generated against the glycosylated HA mutant neutralized it, suggesting that the focus of the immune response can be selectively changed with this modification. Collectively, these findings define critical determinants of H1N1 viral evolution and have implications for vaccine design. Immunization directed to conserved receptor binding domain subregions of pandemic viruses could potentially protect against similar future pandemic viruses, and vaccination with glycosylated 2009 pandemic virus may limit its further spread and transformation into a seasonal influenza. C1 [Wei, Chih-Jen; Boyington, Jeffrey C.; Dai, Kaifan; Kong, Wing-Pui; Yang, Zhi-yong; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Houser, Katherine V.; Pearce, Melissa B.; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 30 TC 84 Z9 87 U1 2 U2 11 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 MAR 24 PY 2010 VL 2 IS 24 AR 24ra21 DI 10.1126/scitranslmed.3000799 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 591MG UT WOS:000277304200004 PM 20375007 ER PT J AU Richard, SA Viboud, C Miller, MA AF Richard, Stephanie A. Viboud, Cecile Miller, Mark A. TI Evaluation of Southern Hemisphere influenza vaccine recommendations SO VACCINE LA English DT Article DE Influenza; Vaccine match; WHO recommendations; Antigenic characteristics; Southern Hemisphere; Northern Hemisphere; Seasonality ID ANTIGENIC DRIFT; A VIRUS; SENTINEL SURVEILLANCE; GUINEA-BISSAU; UNITED-STATES; EVOLUTION; SELECTION; SEASONALITY; CHILDHOOD; MORTALITY AB In 1999, the World Health Organization switched from annual to semi-annual recommendations for influenza vaccine composition. We compared the antigenic match between recommendations and circulating viruses before and after 1999, in the Northern and Southern Hemispheres. Vaccine match proportion for A/H3N2 viruses increased from 31% to 59% in the Southern Hemisphere (P < 0.05). and is now comparable to that in the Northern Hemisphere. Vaccine match for influenza B decreased from similar to 100% to 33-54% in both hemispheres (P < 0.05), following the unexpected resurgence of influenza B/Victoria in 1997. No estimate was available for influenza A/H1N1. We conclude that semi-annual vaccine recommendations are useful overall and discuss potential ways forward, including a recommendation for the improvement of vaccination policy and influenza surveillance in tropical areas. Published by Elsevier Ltd. C1 [Richard, Stephanie A.; Viboud, Cecile; Miller, Mark A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Richard, SA (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr,MSC 6705,Bldg 16, Bethesda, MD 20892 USA. EM richardst@mail.nih.gov; viboudc@mail.nih.gov; millemar@mail.nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 76 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 24 PY 2010 VL 28 IS 15 BP 2693 EP 2699 DI 10.1016/j.vaccine.2010.01.053 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 576UK UT WOS:000276174600002 PM 20153352 ER PT J AU Schaap-Nutt, A Scull, MA Schmidt, AC Murphy, BR Pickles, RJ AF Schaap-Nutt, Anne Scull, Margaret A. Schmidt, Alexander C. Murphy, Brian R. Pickles, Raymond J. TI Growth restriction of an experimental live attenuated human parainfluenza virus type 2 vaccine in human ciliated airway epithelium in vitro parallels attenuation in African green monkeys SO VACCINE LA English DT Article DE Human parainfluenza virus; Live attenuated vaccine candidate; Human ciliated airway epithelium ID RESPIRATORY SYNCYTIAL VIRUS; HOST-RANGE RESTRICTION; V-PROTEIN; NONHUMAN-PRIMATES; MEASLES-VIRUS; ALPHA/BETA-INTERFERON; INFLUENZA-VIRUSES; REVERSE GENETICS; RHESUS-MONKEYS; CELLS AB Human parainfluenza viruses (HPIVs) are common causes of severe pediatric respiratory viral disease. We characterized wild-type HPIV2 infection in an in vitro model of human airway epithelium (HAE) and found that the virus replicates to high titer, sheds apically, targets ciliated cells, and induces minimal cytopathology. Replication of an experimental, live attenuated HPIV2 vaccine strain, containing both temperature sensitive (ts) and non-ts attenuating mutations, was restricted >30-fold compared to rHPIV2-WT in HAE at 32 degrees C and exhibited little productive replication at 37 degrees C. This restriction paralleled attenuation in the upper and lower respiratory tract of African green monkeys, supporting the HAE model as an appropriate and convenient system for characterizing HPIV2 vaccine candidates. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Schaap-Nutt, Anne; Schmidt, Alexander C.; Murphy, Brian R.] NIAID, Infect Dis Lab, RNA Viruses Sect, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Scull, Margaret A.; Pickles, Raymond J.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. RP Pickles, RJ (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Sch Med, 7023 Thurston Bowles, Chapel Hill, NC 27599 USA. EM raymond_pickles@med.unc.edu FU NIH [R01 HL77844]; NIAID; Molecular Biology of Viral Diseases Training [5-T32-AI007419] FX We thank the directors and teams of the UNC Cystic Fibrosis Center Tissue Culture Core, the Morphology and Morphometry Core, and the Michael Hooker Microscopy Facility for supplying reagents and technical expertise. We also thank Susan Burkett and Emerito Amaro-Carambot for technical assistance. This research was supported by the Intramural Research Program of the NIH, NIAID, and by NIH grant R01 HL77844 (RJP) and the Molecular Biology of Viral Diseases Training Grant 5-T32-AI007419. NR 57 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAR 24 PY 2010 VL 28 IS 15 BP 2788 EP 2798 DI 10.1016/j.vaccine.2010.01.050 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 576UK UT WOS:000276174600016 PM 20139039 ER PT J AU Zhi, L Mans, J Paskow, MJ Brown, PH Schuck, P Jonjic, S Natarajan, K Margulies, DH AF Zhi, Li Mans, Janet Paskow, Michael J. Brown, Patrick H. Schuck, Peter Jonjic, Stipan Natarajan, Kannan Margulies, David H. TI Direct Interaction of the Mouse Cytomegalovirus m152/gp40 Immunoevasin with RAE-1 Isoforms SO BIOCHEMISTRY LA English DT Article ID MURINE CYTOMEGALOVIRUS; PROTEIN INTERACTIONS; NKG2D RECEPTOR; IMMUNE EVASION; NK CELLS; T-CELLS; CRYSTAL-STRUCTURE; LIGANDS; GLYCOPROTEIN; EXPRESSION AB Cytomegalovirus (CMVs) are ubiquitous species-specific viruses that establish acute, persistent, and latent infections. Both human and mouse CMVs encode proteins that inhibit the activation of natural killer(NK)cells by downregulating cellular ligands for the NK cell activating receptor, NKG2D. The MCMV glycoprotein ml52/gp40 downregulates the surface expression of RAE-1 to prevent NK cell control in vivo. SO far, it is Unclear if there is a direct interaction between m152 and RAF-1 and, if so, if m152 Interacts differentially With the Five identified RAE-1 isoforms, which are expressed as two groups in MCMV-susceptible or-resistant mouse strains. To address these questions, we expressed and purified(I the extracellular domains of RAE-I and m152 and performed size exclusion chromatography binding assays as well as analytical ultracentifugation and isothermal titration calorimetry to characterize these Interactions quantitatively. We further evaluated the role of full-length and naturally glycosylated m152 and RAE-1 In contransfected HEK293T cells. Our results confirmed that m152 binds RAE-1 directly, relatively tightly (K(d) < 5 mu M), and with 1:1 stoichiometry. The binding is quantitatively different depending oil particular RAE-1 beta isoforms, corresponding to the susceptibility to downregulation by in 152. A PLWY motif found in RAE-1 beta, although contributing to its affinity for m152, does not Influence the affinity of RAE-1 gamma or RAE-1 delta, Suggesting that other difference Contribute to the RAE-I-m152 interaction. Molecular modeling of the different RAE-I isoforms Suggests a potential site for the m152 Interaction. C1 [Zhi, Li; Mans, Janet; Paskow, Michael J.; Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Brown, Patrick H.; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, Natl Inst Hlth, Bethesda, MD 20892 USA. [Mans, Janet] Univ Witwatersrand, ZA-2050 Wits, South Africa. [Jonjic, Stipan] Univ Rijeka, Fac Med, Dept Histol & Embryol, Rijeka 51000, Croatia. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr, Bethesda, MD 20892 USA. EM dhm@nih.gov RI Margulies, David/H-7089-2013; Jonjic, Stipan/C-5657-2016; OI Schuck, Peter/0000-0002-8859-6966; Mans, Janet/0000-0001-6721-1177; Margulies, David/0000-0001-8530-7375 FU Intramural NIH HHS [Z01 EB000051-02, ZIA AI001028-02]; NIAID NIH HHS [R01 AI083201] NR 46 TC 19 Z9 19 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 23 PY 2010 VL 49 IS 11 BP 2443 EP 2453 DI 10.1021/bi902130j PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 570XI UT WOS:000275711400016 PM 20166740 ER PT J AU Seshadri, S Beiser, A Pikula, A Himali, JJ Kelly-Hayes, M Debette, S DeStefano, AL Romero, JR Kase, CS Wolf, PA AF Seshadri, Sudha Beiser, Alexa Pikula, Aleksandra Himali, Jayandra J. Kelly-Hayes, Margaret Debette, Stephanie DeStefano, Anita L. Romero, Jose R. Kase, Carlos S. Wolf, Philip A. TI Parental Occurrence of Stroke and Risk of Stroke in Their Children The Framingham Study SO CIRCULATION LA English DT Article DE epidemiology; heredity; ischemia; stroke ID CORONARY-HEART-DISEASE; ISCHEMIC-STROKE; FAMILY-HISTORY; INTERMEDIATE PHENOTYPES; CARDIOVASCULAR-DISEASE; LIFETIME RISK; FOLLOW-UP; GENETICS; HERITABILITY; WOMEN AB Background-Data relating parental history of stroke to stroke risk in offspring remain surprisingly inconsistent, largely because of heterogeneity of study design and the absence of verified, as opposed to historical, data on parental stroke status. Methods and Results-We determined whether prospectively verified parental occurrence of stroke increased incident stroke risk among offspring in a community-based sample by studying 3443 stroke-free Framingham offspring (53% female; mean age, 48 +/- 14 years) with verified parental stroke status (by 65 years of age) who attended the first, third, fifth, and/or seventh offspring examinations and were followed up for up to 8 years after each baseline examination. Over up to 11 029 such person-observation periods (77 534 person-years), we documented 106 parental strokes by 65 years of age and 128 offspring strokes (74 parental and 106 offspring strokes were ischemic). Using multivariable Cox models adjusted for age, sex, sibship, and baseline stroke risk factors, we observed that parental stroke, both all stroke generally and ischemic stroke specifically, was associated with an increased risk of incident stroke of the same type in the offspring (hazard ratio, 2.79; 95% confidence interval, 1.68 to 4.66; P<0.001 for all stroke; and hazard ratio, 3.15; 95% confidence interval, 1.69 to 5.88; P<0.001 for ischemic stroke). This was true for both maternal and paternal stroke. Conclusions-Documented parental stroke by 65 years of age was associated with a 3-fold increase in risk of offspring stroke. This increased risk persisted after adjustment for conventional stroke risk factors. Thus, verified parental stroke may serve as a clinically useful risk marker of an individual's propensity to stroke. (Circulation. 2010; 121: 1304-1312.) C1 [Seshadri, Sudha; Beiser, Alexa; Pikula, Aleksandra; Himali, Jayandra J.; Kelly-Hayes, Margaret; Debette, Stephanie; DeStefano, Anita L.; Romero, Jose R.; Kase, Carlos S.; Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Beiser, Alexa; Himali, Jayandra J.; DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Seshadri, Sudha; Beiser, Alexa; Pikula, Aleksandra; Himali, Jayandra J.; Kelly-Hayes, Margaret; Debette, Stephanie; DeStefano, Anita L.; Romero, Jose R.; Kase, Carlos S.; Wolf, Philip A.] NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 E Concord St,B602, Boston, MA 02118 USA. EM suseshad@bu.edu OI Seshadri, Sudha/0000-0001-6135-2622; Pikula, Aleksandra/0000-0002-8378-5522; Beiser, Alexa/0000-0001-8551-7778; /0000-0003-1391-9481 FU Framingham Heart Study National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institute of Neurological Disorders and Stroke [R01 NS17950]; National Institute on Aging [R01 AG16495, R01 AG08122, R01 AG033193, R01 AG031287]; Fulbright grant; Bettencourt-Scheuller Foundation FX This work was supported by the Framingham Heart Study National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the National Institute of Neurological Disorders and Stroke (R01 NS17950) and National Institute on Aging (R01 AG16495, AG08122, AG033193, and AG031287). Dr Debette is supported by a Fulbright grant and received an award from the Bettencourt-Scheuller Foundation. NR 38 TC 51 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 23 PY 2010 VL 121 IS 11 BP 1304 EP U52 DI 10.1161/CIRCULATIONAHA.109.854240 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 572VW UT WOS:000275863200006 PM 20212282 ER PT J AU Denchev, P Kaltman, JR Schoenbaum, M Vitiello, B AF Denchev, Peter Kaltman, Jonathan R. Schoenbaum, Michael Vitiello, Benedetto TI Modeled Economic Evaluation of Alternative Strategies to Reduce Sudden Cardiac Death Among Children Treated for Attention Deficit/Hyperactivity Disorder SO CIRCULATION LA English DT Article DE death, sudden; drugs; electrocardiography ID DEFICIT HYPERACTIVITY DISORDER; HEART-ASSOCIATION COUNCIL; COST-EFFECTIVENESS; SCIENTIFIC STATEMENT; STIMULANT-DRUGS; FOLLOW-UP; RISK; ADHD; ADOLESCENTS; RECOMMENDATIONS AB Background-Stimulants are widely used to treat children with attention deficit/hyperactivity disorder and may increase the risk for sudden cardiac death (SCD). We examined the cost-effectiveness of pretreatment screening with ECG for reducing SCD risk in children diagnosed with attention deficit/hyperactivity disorder who are candidates for stimulant medication. Method and Results-We constructed a state-transition Markov model with 10 annual cycles spanning 7 to 17 years of age. Taking a societal perspective, we compared the cost-effectiveness of 3 screening strategies: (1) performing a history and physical examination with cardiology referral if abnormal (current standard of care); (2) performing a history and physical examination plus ECG after negative history and physical examination, with cardiology referral if either is abnormal; and (3) performing a history and physical examination plus ECG, with cardiology referral only if ECG is abnormal. Children identified with SCD-associated cardiac abnormalities would be restricted from stimulants and from playing competitive sports. The expected incremental cost-effectiveness over strategy 1 was $39 300 and $27 200 per quality-adjusted life-year for strategies 2 and 3, respectively. Monte Carlo simulation found that the chance of incremental cost-effectiveness was 55% for strategy 2 and 71% for strategy 3 (willingness to pay <=$50 000 per quality-adjusted life-year). Both strategies 2 and 3 would avert 13 SCDs per 400 000 children seeking stimulant treatment for ADHD, for a cost of $1.6 million per life for strategy 2 and $1.2 million per life for strategy 3. Conclusions-Relative to current practice, adding ECG screening to history and physical examination pretreatment screening for children with attention deficit/hyperactivity disorder has borderline cost-effectiveness for preventing SCD. Relative cost-effectiveness may be improved by basing cardiology referral on ECG alone. Benefits of ECG screening arise primarily by restricting children identified with SCD risk from competitive sports. (Circulation. 2010; 121: 1329-1337.) C1 [Denchev, Peter] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Kaltman, Jonathan R.] NHLBI, Bethesda, MD 20892 USA. RP Denchev, P (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM denchevp@mail.nih.gov NR 38 TC 23 Z9 24 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 23 PY 2010 VL 121 IS 11 BP 1329 EP 1337 DI 10.1161/CIRCULATIONAHA.109.901256 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 572VW UT WOS:000275863200009 PM 20212277 ER PT J AU Koh, KK Quon, MJ Han, SH Lee, Y Kim, SJ Shin, EK AF Koh, Kwang Kon Quon, Michael J. Han, Seung Hwan Lee, Yonghee Kim, Soo Jin Shin, Eak Kyun TI Atorvastatin Causes Insulin Resistance and Increases Ambient Glycemia in Hypercholesterolemic Patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc DE adipocytokines; glycated hemoglobin; insulin resistance; metabolic syndrome; statins ID CARDIOVASCULAR EVENTS; CONTROLLED-TRIAL; PRAVASTATIN; SIMVASTATIN; PREVENTION; SENSITIVITY; CORONARY; STATINS; GLUCOSE AB Objectives We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients. Background Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein (LDL) cholesterol and improvement in endothelial dysfunction. Methods A randomized, single-blind, placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42, 44, 43, and 40 patients given daily atorvastatin 10, 20, 40, and 80 mg, respectively, during a 2-month treatment period. Results Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (39%, 47%, 52%, and 56%, respectively) and apolipoprotein B levels (33%, 37%, 42%, and 46%, respectively) after 2 months of therapy when compared with either baseline (all p < 0.001 by paired t test) or placebo (p = 0.001 by analysis of variance [ANOVA]). Atorvastatin 10, 20, 40, and 80 mg significantly increased fasting plasma insulin (mean changes: 25%, 42%, 31%, and 45%, respectively) and glycated hemoglobin levels (2%, 5%, 5%, and 5%, respectively) when compared with either baseline (all p < 0.05 by paired t test) or placebo (p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA). Atorvastatin 10, 20, 40, and 80 mg decreased insulin sensitivity (1%, 3%, 3%, and 4%, respectively) when compared with either baseline (p = 0.312, p = 0.008, p < 0.001, and p = 0.008, respectively, by paired t test) or placebo (p = 0.033 by ANOVA). Conclusions Despite beneficial reductions in LDL cholesterol and apolipoprotein B, atorvastatin treatment resulted in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients. (Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients; NCT00745836) (J Am Coll Cardiol 2010; 55: 1209-16) (C) 2010 by the American College of Cardiology Foundation C1 [Koh, Kwang Kon; Han, Seung Hwan; Kim, Soo Jin; Shin, Eak Kyun] Gachon Univ, Gil Med Ctr, Dept Cardiol, Inchon 405760, South Korea. [Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Lee, Yonghee] Univ Seoul, Dept Stat, Seoul, South Korea. RP Koh, KK (reprint author), Gachon Univ, Gil Hosp, 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 FU Intramural NIH HHS [Z01 AT000001-07] NR 23 TC 111 Z9 118 U1 1 U2 6 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 MAR 23 PY 2010 VL 55 IS 12 BP 1209 EP 1216 DI 10.1016/j.jacc.2009.10.053 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570HK UT WOS:000275663200007 PM 20298928 ER PT J AU Kaltman, JR Schramm, C Pearson, GD AF Kaltman, Jonathan R. Schramm, Charlene Pearson, Gail D. TI The National Heart, Lung, and Blood Institute Bench to Bassinet Program: A New Paradigm for Translational Research SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE congenital heart disease; cardiac development; genomics ID REGULATORY NETWORKS; DISEASE; RATIONALE; DESIGN; TRIAL; ASSOCIATION; VENTRICLE; GENETICS; DEFECTS; THERAPY C1 [Kaltman, Jonathan R.] NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Kaltman, JR (reprint author), NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 8222, Bethesda, MD 20892 USA. EM kaltmanj@nhlbi.nih.gov NR 14 TC 12 Z9 12 U1 0 U2 0 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 MAR 23 PY 2010 VL 55 IS 12 BP 1262 EP 1265 DI 10.1016/j.jacc.2009.11.055 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570HK UT WOS:000275663200013 PM 20298934 ER PT J AU Rao, SS Kong, WP Wei, CJ Van Hoeven, N Gorres, JP Nason, M Andersen, H Tumpey, TM Nabel, GJ AF Rao, Srinivas S. Kong, Wing-Pui Wei, Chih-Jen Van Hoeven, Neal Gorres, J. Patrick Nason, Martha Andersen, Hanne Tumpey, Terrence M. Nabel, Gary J. TI Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret SO PLOS ONE LA English DT Article ID CD8(+) T-CELLS; RECEPTOR SPECIFICITY; VIRUS-REPLICATION; A VACCINE; NEUTRALIZING ANTIBODIES; EXTRACELLULAR DOMAIN; PROTECTIVE IMMUNITY; LETHAL CHALLENGE; PLASMID DNA; M2 PROTEIN AB Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge. C1 [Rao, Srinivas S.; Kong, Wing-Pui; Wei, Chih-Jen; Gorres, J. Patrick; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Van Hoeven, Neal; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. [Nason, Martha] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Andersen, Hanne] BIOQUAL Inc, Rockville, MD USA. RP Rao, SS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU National Institutes of Allergy; National Institutes of Health FX This work was funded by the intramural research program of the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 51 Z9 51 U1 0 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 MAR 23 PY 2010 VL 5 IS 3 AR e9812 DI 10.1371/journal.pone.0009812 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573FS UT WOS:000275894400015 PM 20352112 ER PT J AU Stuelten, CH Busch, JI Tang, BW Flanders, KC Oshima, A Sutton, E Karpova, TS Roberts, AB Wakefield, LM Niederhuber, JE AF Stuelten, Christina H. Busch, Johanna I. Tang, Binwu Flanders, Kathleen C. Oshima, Akira Sutton, Emily Karpova, Tatiana S. Roberts, Anita B. Wakefield, Lalage M. Niederhuber, John E. TI Transient Tumor-Fibroblast Interactions Increase Tumor Cell Malignancy by a TGF-beta Mediated Mechanism in a Mouse Xenograft Model of Breast Cancer SO PLOS ONE LA English DT Article ID GROWTH-FACTOR-BETA; SQUAMOUS CARCINOMA-CELLS; ENHANCES TUMORIGENESIS; MAMMARY ADENOCARCINOMA; SUPPRESSES METASTASIS; STROMAL FIBROBLASTS; MICROENVIRONMENT; PROGRESSION; INVASION; MICE AB Carcinoma are complex societies of mutually interacting cells in which there is a progressive failure of normal homeostatic mechanisms, causing the parenchymal component to expand inappropriately and ultimately to disseminate to distant sites. When a cancer cell metastasizes, it first will be exposed to cancer associated fibroblasts in the immediate tumor microenvironment and then to normal fibroblasts as it traverses the underlying connective tissue towards the bloodstream. The interaction of tumor cells with stromal fibroblasts influences tumor biology by mechanisms that are not yet fully understood. Here, we report a role for normal stroma fibroblasts in the progression of invasive tumors to metastatic tumors. Using a coculture system of human metastatic breast cancer cells (MCF10CA1a) and normal murine dermal fibroblasts, we found that medium conditioned by cocultures of the two cell types (CoCM) increased migration and scattering of MCF10CA1a cells in vitro, whereas medium conditioned by homotypic cultures had little effect. Transient treatment of MCF10CA1a cells with CoCM in vitro accelerated tumor growth at orthotopic sites in vivo, and resulted in an expanded pattern of metastatic engraftment. The effects of CoCM on MCF10CA1a cells were dependent on small amounts of active TGF-beta 1 secreted by fibroblasts under the influence of the tumor cells, and required intact ALK5-, p38-, and JNK signaling in the tumor cells. In conclusion, these results demonstrate that transient interactions between tumor cells and normal fibroblasts can modify the acellular component of the local microenvironment such that it induces long-lasting increases in tumorigenicity and alters the metastatic pattern of the cancer cells in vivo. TGF-beta appears to be a key player in this process, providing further rationale for the development of anti-cancer therapeutics that target the TGF-beta pathway. C1 [Stuelten, Christina H.; Busch, Johanna I.; Sutton, Emily; Niederhuber, John E.] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. [Tang, Binwu; Flanders, Kathleen C.; Oshima, Akira; Roberts, Anita B.; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Karpova, Tatiana S.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Stuelten, CH (reprint author), NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. EM chrisstu@mail.nih.gov FU National Cancer Institute, NIH, Bethesda, USA FX This research was supported by the Intramural Research Program of the National Cancer Institute, NIH, Bethesda, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 45 Z9 48 U1 1 U2 6 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 MAR 23 PY 2010 VL 5 IS 3 AR e9832 DI 10.1371/journal.pone.0009832 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573FS UT WOS:000275894400031 PM 20352126 ER PT J AU Tarazona-Santos, E Fabbri, C Yeager, M Magalhaes, WC Burdett, L Crenshaw, A Pettener, D Chanock, SJ AF Tarazona-Santos, Eduardo Fabbri, Cristina Yeager, Meredith Magalhaes, Wagner C. Burdett, Laurie Crenshaw, Andrew Pettener, Davide Chanock, Stephen J. TI Diversity in the Glucose Transporter-4 Gene (SLC2A4) in Humans Reflects the Action of Natural Selection along the Old-World Primates Evolution SO PLOS ONE LA English DT Article ID LINKAGE DISEQUILIBRIUM; HUMAN GENOME; RECOMBINATION HOTSPOTS; GLUCOSE-TRANSPORTER; POPULATION-GENETICS; HAPLOTYPE STRUCTURE; POSITIVE SELECTION; POLYMORPHISM; MODEL; ASSOCIATION AB Background: Glucose is an important source of energy for living organisms. In vertebrates it is ingested with the diet and transported into the cells by conserved mechanisms and molecules, such as the trans-membrane Glucose Transporters (GLUTs). Members of this family have tissue specific expression, biochemical properties and physiologic functions that together regulate glucose levels and distribution. GLUT4-coded by SLC2A4 (17p13) is an insulin-sensitive transporter with a critical role in glucose homeostasis and diabetes pathogenesis, preferentially expressed in the adipose tissue, heart muscle and skeletal muscle. We tested the hypothesis that natural selection acted on SLC2A4. Methodology/Principal Findings: We re-sequenced SLC2A4 and genotyped 104 SNPs along a similar to 1 Mb region flanking this gene in 102 ethnically diverse individuals. Across the studied populations (African, European, Asian and Latin-American), all the eight common SNPs are concentrated in the N-terminal region upstream of exon 7 (similar to 3700 bp), while the C-terminal region downstream of intron 6 (similar to 2600 bp) harbors only 6 singletons, a pattern that is not compatible with neutrality for this part of the gene. Tests of neutrality based on comparative genomics suggest that: (1) episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity downstream of intron 6 and, (2) the target of natural selection may not be in the SLC2A4 coding sequence. Conclusions: We propose that the contrast in the pattern of genetic variation between the N-terminal and C-terminal regions are signatures of the action of natural selection and thus follow-up studies should investigate the functional importance of differnet regions of the SLC2A4 gene. C1 [Tarazona-Santos, Eduardo; Fabbri, Cristina; Magalhaes, Wagner C.; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Tarazona-Santos, Eduardo; Magalhaes, Wagner C.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Belo Horizonte, MG, Brazil. [Fabbri, Cristina; Pettener, Davide] Univ Bologna, Dipartimento Biol Evoluzionist Sperimentale, Bologna, Italy. [Yeager, Meredith; Burdett, Laurie; Crenshaw, Andrew] NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. [Yeager, Meredith; Burdett, Laurie; Crenshaw, Andrew] NCI, Core Genotype Facil, NIH, Gaithersburg, MD USA. RP Tarazona-Santos, E (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM edutars@icb.ufmg.br RI Magalhaes, Wagner/D-8822-2015; Pettener, Davide/E-1576-2017 FU National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research; University of Bologna; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil); Fundacao de Amparo a Pesquisa de Minas Gerais (Brazil); Brazilian Ministry of Education (Agency for the Development of Graduate Education-CAPES) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. CF and DP were supported by the University of Bologna, ET-S by NIH, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil) and Fundacao de Amparo a Pesquisa de Minas Gerais (Brazil) and WCSM by Brazilian Ministry of Education (Agency for the Development of Graduate Education-CAPES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 2 Z9 3 U1 0 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 MAR 23 PY 2010 VL 5 IS 3 AR e9827 DI 10.1371/journal.pone.0009827 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573FS UT WOS:000275894400027 PM 20352120 ER PT J AU Bouldin, CM Gritli-Linde, A Ahn, S Harfe, BD AF Bouldin, Cortney M. Gritli-Linde, Amel Ahn, Sohyun Harfe, Brian D. TI Shh pathway activation is present and required within the vertebrate limb bud apical ectodermal ridge for normal autopod patterning SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE limb patterning; polydactyly; Shh signaling ID SONIC-HEDGEHOG; POLARIZING ACTIVITY; FEEDBACK LOOP; CHICK LIMB; SIGNALS; EXPRESSION; EXPANSION; OUTGROWTH; GREMLIN; GROWTH AB Expression of Sonic Hedgehog (Shh) in the posterior mesenchyme of the developing limb bud regulates patterning and growth of the developing limb by activation of the Hedgehog (Hh) signaling pathway. Through the analysis of Shh and Hh signaling target genes, it has been shown that activation in the limb bud mesoderm is required for normal limb development to occur. In contrast, it has been stated that Hh signaling in the limb bud ectoderm cannot occur because components of the Hh signaling pathway and Hh target genes have not been found in this tissue. However, recent array-based data identified both the components necessary to activate the Hh signaling pathway and targets of this pathway in the limb bud ectoderm. Using immunohistochemistry and various methods of detection for targets of Hh signaling, we found that SHH protein and targets of Hh signaling are present in the limb bud ectoderm including the apex of the bud. To directly test whether ectodermal Hh signaling was required for normal limb patterning, we removed Smo, an essential component of the Hh signaling pathway, from the apical ectodermal ridge (AER). Loss of functional Hh signaling in the AER resulted in disruption of the normal digit pattern and formation of additional postaxial cartilaginous condensations. These data indicate that contrary to previous accounts, the Hh signaling pathway is present and required in the developing limb AER for normal autopod development. C1 [Bouldin, Cortney M.; Harfe, Brian D.] Univ Florida, Genet Inst, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. [Gritli-Linde, Amel] Univ Gothenburg, Sahlgrenska Acad, Dept Oral Biochem, SE-41390 Gothenburg, Sweden. [Ahn, Sohyun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Harfe, BD (reprint author), Univ Florida, Genet Inst, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. EM bharfe@mgm.ufl.edu FU Swedish Research Council [1581, 20614]; Institute of Odontology, Sahlgrenska Academy; University of Florida, College of Medicine FX We thank W. J. Scott, M. McFarlane, S. A. Vokes, and A. P. McMahon for helpful discussion, sharing unpublished data, and for commenting on an early draft of this work. Some probes used in this report were generous gifts from C. J. Tabin (Harvard Medical School) and M. J. Cohn (University of Florida). A. G.-L. is supported by the Swedish Research Council-Medicine Grants 1581 and 20614 and the Institute of Odontology, Sahlgrenska Academy. This work was supported by start-up funds granted to B. D. H. from the University of Florida, College of Medicine. NR 28 TC 22 Z9 23 U1 1 U2 5 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 MAR 23 PY 2010 VL 107 IS 12 BP 5489 EP 5494 DI 10.1073/pnas.0912818107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573GY UT WOS:000275898300041 PM 20212115 ER PT J AU Diep, BA Chan, L Tattevin, P Kajikawa, O Martin, TR Basuino, L Mai, TT Marbach, H Braughton, KR Whitney, AR Gardner, DJ Fan, XM Tseng, CW Liu, GY Badiou, C Etienne, J Lina, G Matthay, MA Deleo, FR Chambers, HF AF Diep, Binh An Chan, Liana Tattevin, Pierre Kajikawa, Osamu Martin, Thomas R. Basuino, Li Mai, Thuy T. Marbach, Helene Braughton, Kevin R. Whitney, Adeline R. Gardner, Donald J. Fan, Xuemo Tseng, Ching W. Liu, George Y. Badiou, Cedric Etienne, Jerome Lina, Gerard Matthay, Michael A. DeLeo, Frank R. Chambers, Henry F. TI Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton-Valentine leukocidin-induced lung inflammation and injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MRSA; USA300; virulence; pneumonia; rabbit infection model ID COMMUNITY-ONSET PNEUMONIA; HUMAN NEUTROPHILS; VIRULENCE DETERMINANT; NECROTIZING PNEUMONIA; IN-VITRO; GENERATION; BINDING; TOXINS; SKIN; INFECTIONS AB Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is epidemic in the United States, even rivaling HIV/AIDS in its public health impact. The pandemic clone USA300, like other CA-MRSA strains, expresses Panton-Valentine leukocidin (PVL), a pore-forming toxin that targets polymorphonuclear leukocytes (PMNs). PVL is thought to play a key role in the pathogenesis of necrotizing pneumonia, but data from rodent infection models are inconclusive. Rodent PMNs are less susceptible than human PMNs to PVL-induced cytolysis, whereas rabbit PMNs, like those of humans, are highly susceptible to PVL-induced cytolysis. This difference in target cell susceptibility could affect results of experimental models. Therefore, we developed a rabbit model of necrotizing pneumonia to compare the virulence of a USA300 wild-type strain with that of isogenic PVL-deletion mutant and -complemented strains. PVL enhanced the capacity of USA300 to cause severe lung necrosis, pulmonary edema, alveolar hemorrhage, hemoptysis, and death, hallmark clinical features of fatal human necrotizing pneumonia. Purified PVL instilled directly into the lung caused lung inflammation and injury by recruiting and lysing PMNs, which damage the lung by releasing cytotoxic granule contents. These findings provide insights into the mechanism of PVL-induced lung injury and inflammation and demonstrate the utility of the rabbit for studying PVL-mediated pathogenesis. C1 [Diep, Binh An; Chan, Liana; Tattevin, Pierre; Basuino, Li; Mai, Thuy T.; Marbach, Helene; Chambers, Henry F.] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94110 USA. [Tattevin, Pierre] CHU Pontchaillou, F-35033 Rennes, France. [Tattevin, Pierre] Univ Rennes 1, U835, Inst Natl Sante & Rech Med, F-35033 Rennes, France. [Kajikawa, Osamu; Martin, Thomas R.] Univ Washington, Sch Med, Med Res Serv Vet Affairs & Puget Sound Hlth Care, Seattle, WA 98108 USA. [Kajikawa, Osamu; Martin, Thomas R.] Univ Washington, Sch Med, Div Pulm & Crit Care Med, Dept Med, Seattle, WA 98108 USA. [Braughton, Kevin R.; Whitney, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. [Gardner, Donald J.] NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Fan, Xuemo] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Tseng, Ching W.; Liu, George Y.] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. [Tseng, Ching W.; Liu, George Y.] Cedars Sinai Med Ctr, Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Tseng, Ching W.; Liu, George Y.] Univ Calif Los Angeles, Los Angeles, CA 90048 USA. [Badiou, Cedric; Etienne, Jerome; Lina, Gerard] Univ Lyon 1, Fac Med Laennec, F-69008 Lyon, France. [Badiou, Cedric; Etienne, Jerome; Lina, Gerard] Ctr Natl Reference Staphylocoques, U851, Inst Natl Sante & Rech Med, F-69008 Lyon, France. [Etienne, Jerome; Lina, Gerard] Hosp Civils Lyon, Ctr Biol Est, F-69500 Lyon, France. [Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med & Anesthesia, San Francisco, CA 94143 USA. RP Diep, BA (reprint author), Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94110 USA. EM bdiep@medsfgh.ucsf.edu; hchambers@medsfgh.ucsf.edu RI ETIENNE, Jerome/C-5471-2014; Lina, Gerard/L-9352-2014; OI ETIENNE, Jerome/0000-0002-3348-3315; DeLeo, Frank/0000-0003-3150-2516 FU US Public Health Service National Institute of Allergy and Infectious Diseases [AI070289]; Intramural Research Program of the NIAID; National Institutes of Health; University of California San Francisco Research Evaluation and Allocation Committee Pilot; College des Universitaires des Maladies Infectieuses et Tropicales; Pontchaillou University Hospital, Rennes, France; European Community [222718]; Pfizer and LeoPharma.; National Heart, Lung and Blood Institute (NHLBI) [HL081764, HL51854]; NIAID [AI074832, 2P01A1053194] FX We thank Paul M. Sullam and Michael Otto for critical discussion and reading of the manuscript and Florence Couzon for technical assistance. This work was supported by US Public Health Service National Institute of Allergy and Infectious Diseases (NIAID) Grant AI070289 (to H. F. C.), by the Intramural Research Program of the NIAID, National Institutes of Health (to F. R. D.), and by University of California San Francisco Research Evaluation and Allocation Committee Pilot Award for Junior Faculty (to B. A. D.). P. T. was supported by a grant from the College des Universitaires des Maladies Infectieuses et Tropicales and by the Pontchaillou University Hospital, Rennes, France. C. B., J.E., and G. L. were supported by Grant EC 222718 from the European Community and by grants from Pfizer and LeoPharma. T. R. M. was supported by Grant HL081764 from the National Heart, Lung and Blood Institute (NHLBI), G. Y. L. by Grant AI074832 from the NIAID, and M. A. M. by Grants HL51854 from the NHLBI and 2P01A1053194 from the NIAID. NR 36 TC 165 Z9 178 U1 3 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 23 PY 2010 VL 107 IS 12 BP 5587 EP 5592 DI 10.1073/pnas.0912403107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573GY UT WOS:000275898300058 PM 20231457 ER PT J AU Nemeth, K Keane-Myers, A Brown, JM Metcalfe, DD Gorham, JD Bundoc, VG Hodges, MG Jelinek, I Madala, S Karpati, S Mezey, E AF Nemeth, Krisztian Keane-Myers, Andrea Brown, Jared M. Metcalfe, Dean D. Gorham, Jared D. Bundoc, Victor G. Hodges, Marcus G. Jelinek, Ivett Madala, Satish Karpati, Sarolta Mezey, Eva TI Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allergy; cellular therapy; immunomodulation; mesenchymal stem cell ID MESENCHYMAL STEM-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REGULATORY T-CELLS; LUNG INJURY; LYMPHOCYTE PROLIFERATION; INFLAMMATION; SURVIVAL; DISEASE; PROLONG; MANNER AB Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-beta production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions-specifically therapy resistant asthma-might also be a likely target of the recently discovered cellular therapy approach using BMSCs. C1 [Nemeth, Krisztian; Mezey, Eva] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Nemeth, Krisztian; Karpati, Sarolta] Semmelweis Univ, Dept Dermatovenereol & Dermatooncol, H-1085 Budapest, Hungary. [Keane-Myers, Andrea; Brown, Jared M.; Metcalfe, Dean D.; Bundoc, Victor G.; Hodges, Marcus G.; Madala, Satish] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Gorham, Jared D.] Dartmouth Med Sch, Dept Pathol & Microbiol & Immunol, Lebanon, NH 03756 USA. [Jelinek, Ivett] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Nemeth, K (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. EM nemethk@mail.nih.gov; mezeye@mail.nih.gov FU National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases FX We thank Dr. William Paul for his continuing support and suggestions during the preparation of the study. We also thank Dr. Natasha Chairman for her help with the differentiation assays, Dr. Silvio Gutkind for providing the luciferase expressing lentiviral vectors, and Dr. Daniel Martin for his help with the bioluminescence measurements. This research was supported by the Division of Intramural Research Program of the National Institute of Dental and Craniofacial Research and National Institute of Allergy and Infectious Diseases. NR 40 TC 179 Z9 191 U1 4 U2 23 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 MAR 23 PY 2010 VL 107 IS 12 BP 5652 EP 5657 DI 10.1073/pnas.0910720107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 573GY UT WOS:000275898300069 PM 20231466 ER PT J AU Mattson, MP AF Mattson, Mark P. TI ER Calcium and Alzheimer's Disease: In a State of Flux SO SCIENCE SIGNALING LA English DT Article ID AMYLOID BETA-PEPTIDE; KNOCK-IN MICE; SYNAPTIC PLASTICITY; CORTICAL-NEURONS; RELEASE CHANNELS; MUTANT MICE; PC12 CELLS; A-BETA; PRESENILIN-1; HOMEOSTASIS AB The calcium ion (Ca(2+)) plays fundamental roles in orchestrating dynamic changes in the function and structure of nerve cell circuits in the brain. The endoplasmic reticulum (ER), an organelle that actively removes Ca(2+) from the cytoplasm, can release stored Ca(2+) through ER membrane receptor channels responsive either to the lipid messenger inositol trisphosphate (IP(3)) or to cytosolic Ca(2+). Emerging findings suggest that perturbed ER Ca(2+) homeostasis contributes to the dysfunction and degeneration of neurons that occurs in Alzheimer's disease (AD). Presenilin-1 (PS1) is an integral membrane protein in the ER; mutations in PS1 that cause early-onset inherited AD increase the pool of ER Ca(2+) available for release and also enhance Ca(2+) release through ER IP(3)- and ryanodine-sensitive channels. By enhancing Ca(2+) flux across the ER membrane, PS1 mutations may exaggerate Ca(2+) signaling in synaptic terminals and thereby render them vulnerable to dysfunction and degeneration in the settings of aging and amyloid accumulation in AD. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000317-07, Z01 AG000312-07, Z01 AG000313-07, Z01 AG000314-07, Z01 AG000331-01] NR 34 TC 52 Z9 52 U1 2 U2 10 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 MAR 23 PY 2010 VL 3 IS 114 AR pe10 DI 10.1126/scisignal.3114pe10 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 577MT UT WOS:000276228400003 PM 20332425 ER PT J AU Pemov, A Park, C Reilly, KM Stewart, DR AF Pemov, Alexander Park, Caroline Reilly, Karlyne M. Stewart, Douglas R. TI Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION; NEUROFIBROMATOSIS TYPE-1; SIGNALING PATHWAY; NF1 EXPRESSION; BREAST-CANCER; HAPLOINSUFFICIENCY; IDENTIFICATION; BLOOD; PROFILES; GROWTH AB Background: Neurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells, however the intracellular mechanisms for this tumor-promoting effect are less clear. Most primary human NF1(+/-) cells are a challenge to obtain, however lymphoblastoid cell lines (LCLs) have been collected from large NF1 kindreds. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells ( LCLs) from NF1-affected and -unaffected individuals. As a cross-species filter for heterogeneity, we compared the results from two human kindreds to whole-genome transcriptional profiling in spleen-derived B lymphocytes from age- and gender-matched Nf1(+/-) and wild-type mice, and used gene set enrichment analysis (GSEA), Onto-Express, Pathway-Express and MetaCore tools to identify genes perturbed in NF1-haploinsufficiency. Results: We observed moderate expression of NF1 in human LCLs and of Nf1 in CD19+ mouse B lymphocytes. Using the t test to evaluate individual transcripts, we observed modest expression differences in the transcriptome in NF1-haploinsufficient LCLs and Nf1-haploinsuffiicient mouse B lymphocytes. However, GSEA, Onto-Express, Pathway-Express and MetaCore analyses identified genes that control cell cycle, DNA replication and repair, transcription and translation, and immune response as the most perturbed in NF1-haploinsufficient conditions in both human and mouse. Conclusions: Haploinsufficiency arises when loss of one allele of a gene is sufficient to give rise to disease. Haploinsufficiency has traditionally been viewed as a passive state. Our observations of perturbed, up-regulated cell cycle and DNA repair pathways may functionally contribute to NF1-haploinsufficiency as an "active state" that ultimately promotes the loss of the wild-type allele. C1 [Pemov, Alexander; Stewart, Douglas R.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Park, Caroline] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Reilly, Karlyne M.] NCI, Frederick, MD 21702 USA. RP Stewart, DR (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM drstewart@mail.nih.gov FU Division of Intramural Research of the National Human Genome Research Institute (DRS); U.S. National Cancer Institute of the National Institutes of Health (KMR) FX The authors thank Abdel Elkahloun, Jennifer Cannons, Tyra Wolfsberg, Christopher Pan, Bhavesh Borate (all of NHGRI), Sean Davis (NCI), Paul Meltzer (NCI), Mark Bryant (Office of Research Services, NIH) and Ludwine Messiaen (University of Alabama, Birmingham). The work was supported in part by the Division of Intramural Research of the National Human Genome Research Institute (DRS) and the U.S. National Cancer Institute of the National Institutes of Health (KMR). NR 43 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 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 22 PY 2010 VL 11 AR 194 DI 10.1186/1471-2164-11-194 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 588DJ UT WOS:000277047100002 PM 20307317 ER PT J AU Pasapera, AM Schneider, IC Rericha, E Schlaepfer, DD Waterman, CM AF Pasapera, Ana M. Schneider, Ian C. Rericha, Erin Schlaepfer, David D. Waterman, Clare M. TI Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylation SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EARLY MOLECULAR EVENTS; TYROSINE PHOSPHORYLATION; BINDING-SITE; MIGRATING CELLS; IN-VIVO; INTEGRIN ACTIVATION; MATRIX ADHESIONS; TALIN BINDING; ALPHA-ACTININ; LEADING-EDGE AB Focal adhesions (FAs) are mechanosensitive adhesion and signaling complexes that grow and change composition in response to myosin II-mediated cytoskeletal tension in a process known as FA maturation. To understand tension-mediated FA maturation, we sought to identify proteins that are recruited to FAs in a myosin II-dependent manner and to examine the mechanism for their myosin II-sensitive FA association. We find that recruitment of both the cytoskeletal adapter protein vinculin and the tyrosine kinase FA kinase (FAK) are myosin II and extracellular matrix (ECM) stiffness dependent. Myosin II activity promotes FAK/Src-mediated phosphorylation of paxillin on tyrosines 31 and 118 and vinculin association with paxillin. We show that phosphomimic mutations of paxillin can specifically induce the recruitment of vinculin to adhesions independent of myosin II activity. These results reveal an important role for paxillin in adhesion mechanosensing via myosin II-mediated FAK phosphorylation of paxillin that promotes vinculin FA recruitment to reinforce the cytoskeletal ECM linkage and drive FA maturation. C1 [Pasapera, Ana M.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Rericha, Erin] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA. [Schneider, Ian C.] Iowa State Univ, Dept Chem & Biol Engn, Ames, IA 50011 USA. [Schneider, Ian C.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA. [Schlaepfer, David D.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Schlaepfer, David D.] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA. [Schneider, Ian C.; Rericha, Erin; Waterman, Clare M.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. RP Waterman, CM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM watermancm@nhlbi.nih.gov OI Waterman, Clare/0000-0001-6142-6775; Schneider, Ian/0000-0002-4414-3842 FU NHLBI [HL093156]; Burroughs Wellcome Fund FX We thank Joan Brugge, Mike Davidson, and Mary Beckerle for reagents, the NHLBI Flow Cytometry Core Facility, William Shin, Sergei Plotnikov, and members of the Waterman laboratory. Experiments in Fig. 3 were first performed in conjunction with Michelle Knowles in the Physiology Course at the Marine Biological Laboratory (Woods Hole, MA).; This work was supported by NHLBI (C. M. Waterman and A. M. Pasapera; and grant HL093156 to D. D. Schlaepfer) and the Burroughs Wellcome Fund (E. Rericha). NR 62 TC 216 Z9 216 U1 2 U2 40 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD MAR 22 PY 2010 VL 188 IS 6 BP 877 EP 890 DI 10.1083/jcb.200906012 PG 14 WC Cell Biology SC Cell Biology GA 572VT UT WOS:000275862800013 PM 20308429 ER PT J AU Bahde, RJ Jenkins, LMM Appella, E Appella, DH Trenkle, WC AF Bahde, Robert J. Jenkins, Lisa M. Miller Appella, Ettore Appella, Daniel H. Trenkle, William C. TI One-pot multi-component synthesis of 2-mercaptobenzamide thioesters for investigation into the HIV-1 nucleocapsid protein (NCp7) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 335-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303797 ER PT J AU Ballard, BD Jiang, ZW Clifford, T Cutler, CS Brechbiel, M Dadachova, E Francesconi, LC AF Ballard, Beau D. Jiang, Zewei Clifford, Thomas Cutler, Cathy S. Brechbiel, Martin Dadachova, Ekaterina Francesconi, Lynn C. TI Radiolanthanides for treatment of malignant melanoma SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. Yeshiva Univ, Albert Einstein Coll Med, Dept Nucl Med, Bronx, NY USA. NCI, Dept Radioimmune & Inorgan Chem, Bethesda, MD 20892 USA. MURR, Columbia, MO USA. RI Ballard, Beau/E-2925-2017 OI Ballard, Beau/0000-0003-1206-9358 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 185-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303612 ER PT J AU Bedosky, SJ Newcombe, PGAC Heikkinen, CM Dellarco, M Quackenboss, J AF Bedosky, Stephen J. Newcombe, P. G. Andrew C. Heikkinen, CChem Maire Dellarco, Michael Quackenboss, James TI Pesticide occurrence in US homes: Research design for The National Children's Study SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ARCADIS, Tallahassee, FL USA. ARCADIS, Wilmington, DE USA. Westat Corp, Rockville, MD USA. Natl Childrens Study Eunice Kennedy Shriver Natl, Bethesda, MD USA. Exposure Measurement & Anal US Environm Protect A, Las Vegas, NV 89193 USA. RI Quackenboss, James/I-1960-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 159-AGRO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300130 ER PT J AU Brandys, B AF Brandys, Barbara TI Marketing chemical research with custom web databases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Brandys, Barbara] NIH, Dept Lib Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 101-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189301737 ER PT J AU Fitch, RW Spande, TF Garraffo, HM Yeh, HJC Whittaker, NF Daly, JW AF Fitch, Richard W. Spande, Thomas F. Garraffo, H. Martin Yeh, Herman J. C. Whittaker, Noel F. Daly, John W. TI Phantasmidine: A novel nicotinic agonist from Epipedobates anthonyi SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Indiana State Univ, Dept Chem & Phys, Terre Haute, IN 47809 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 338-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303798 ER PT J AU Gildersleeve, JC AF Gildersleeve, Jeffrey C. TI Glycan arrays and cancer vaccines: Partners for life SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gildersleeve, Jeffrey C.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 16-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300377 ER PT J AU Marley, B Wendeler, M Kaczmarczyk, SJ Chatterjee, DK Le Grice, SFJ AF Marley, Bridget Wendeler, Michaela Kaczmarczyk, Stanislaw J. Chatterjee, Deb K. Le Grice, Stuart F. J. TI Incorporation of the unnatural amino acid p-benzoyl-L-phenylalanine to determine interaction partners of XMRV reverse transcriptase SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NCI, Prot Express Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 64-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300462 ER PT J AU Maruoka, H de Castro, S Besada, P Kim, N Barrett, M Fricks, I Ivanov, AA Cosanzi, S Harden, TK Jacobson, KA AF Maruoka, Hiroshi de Castro, Sonia Besada, Pedro Kim, Nathaniel Barrett, Matt Fricks, Ingrid Ivanov, Andrei A. Cosanzi, Stefano Harden, T. Kendall Jacobson, Kenneth A. TI Uracil nucleotides as human P2Y(2) receptor agonists: Probing the distal region of the oligophosphate moiety SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA. Emory Univ, Dept Biochem, Atlanta, GA 30322 USA. RI Besada Pereira, Pedro/E-6051-2012 OI Besada Pereira, Pedro/0000-0002-9985-9063 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 112-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303409 ER PT J AU Nwe, K Bernardo, M Regino, CAS Williams, M Brechbiel, MW AF Nwe, Kido Bernardo, Marcelino Regino, Celeste A. S. Williams, Mark Brechbiel, Martin W. TI Recent advances on the assembly of chelated Gd+3 dendrimer conjugates for MRI contrast agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, Bethesda, MD 20892 USA. SAIC Frederick Inc, Res Technol Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 178-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303609 ER PT J AU O'Shea, JJ AF O'Shea, John J. TI Targeting Janus kinases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [O'Shea, John J.] NIAMSD, Dept Mol Immunol, Bethesda, MD 20892 USA. [O'Shea, John J.] NIAMSD, Inflammat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 338-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303483 ER PT J AU Shi, C Vasan, L Wilson, D Boshoff, H Barry, CE Aldrich, CC AF Shi, Ce Vasan, Lakshmi Wilson, Daniel Boshoff, Helena Barry, Clifton E., III Aldrich, Courtney C. TI Design of mechanism-based inhibitors of biotin biosynthesis in Mycobacterium tuberculosis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Minnesota, Ctr Drug Design, Minneapolis, MN USA. NIAID, TB Res Sect, Bethesda, MD 20892 USA. RI Barry, III, Clifton/H-3839-2012 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 440-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189303514 ER PT J AU Sitzmann, M Ihlenfeldt, WD Nicklaus, MC AF Sitzmann, Markus Ihlenfeldt, Wolf-Dietrich Nicklaus, Marc C. TI NCI/CADD: Open-access chemical structure web platform SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21701 USA. Xemistry GmbH, Lahntal, Germany. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 2010 VL 239 MA 147-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189301761 ER PT J AU Ahmadibeni, Y Dash, C Hanley, MJ Le Grice, SFJ Agarwal, HK Parang, K AF Ahmadibeni, Y. Dash, C. Hanley, M. J. Le Grice, S. F. J. Agarwal, H. K. Parang, K. TI Synthesis of nucleoside 5 '-O-alpha,beta-methylene-beta-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID CELLULAR-DNA-POLYMERASES; RNASE-H ACTIVITY; 5'-TRIPHOSPHATES; PHOSPHORYLATION; TRIPHOSPHATES; NUCLEOTIDES; DERIVATIVES; MECHANISM; SUBSTRATE; REAGENTS AB A polymer-bound alpha,beta-methylene-beta-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5 '-O-alpha,beta-methylene-beta-triphosphates. Among all the compounds, cytidine 5 '-O-alpha,beta-methylene-beta-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a K(i) value of 225 mu M. C1 [Ahmadibeni, Y.; Hanley, M. J.; Agarwal, H. K.; Parang, K.] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. [Dash, C.] Meharry Med Coll, Ctr AIDS Hlth Dispar Res, Nashville, TN 37208 USA. [Ahmadibeni, Y.] Columbus State Univ, Dept Chem, Columbus, GA 31907 USA. [Le Grice, S. F. J.] NCI, Resistance Mech Lab, HIV Drug Resistance Program, Natl Inst Hlth, Frederick, MD 21702 USA. RP Parang, K (reprint author), Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. EM kparang@uri.edu RI Parang, Keykavous/F-9236-2010 FU National Science Foundation [CHE 0748555]; Intramural Research Program of the NIH; NCI; Center for Cancer Research FX We acknowledge the financial support from National Science Foundation, Grant Number CHE 0748555. The work at NCI was supported in part by the Intramural Research Program of the NIH, NCI and Center for Cancer Research. NR 38 TC 5 Z9 5 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PD MAR 21 PY 2010 VL 8 IS 6 BP 1271 EP 1274 DI 10.1039/b922846b PG 4 WC Chemistry, Organic SC Chemistry GA 564BU UT WOS:000275187000003 PM 20204192 ER PT J AU Wang, HJ Zakhari, S Lung, MK AF Wang, H. Joe Zakhari, Samir Lung, M. Katherine TI Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Chronic alcohol use; Chronic inflammation; Lipopolysaccharides; Pro-inflammatory and anti-inflammatory cytokines; Kupffer cells; Monocytes; Tumor necrosis factor alpha; Interleukin-10; Neuroendocrine; Hypothalamopituitary-adrenal axis; Glucocorticoid ID PITUITARY-ADRENAL AXIS; NECROSIS-FACTOR-ALPHA; ACUTE-PHASE RESPONSE; TOLL-LIKE RECEPTORS; NF-KAPPA-B; KUPFFER CELLS; INTESTINAL PERMEABILITY; GASTROINTESTINAL-TRACT; CYTOKINE PRODUCTION; OXIDATIVE STRESS AB Chronic inflammation is often associated with alcohol-related medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs, The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention. (C) 2010 Baishideng. All rights reserved, C1 [Wang, H. Joe; Zakhari, Samir; Lung, M. Katherine] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. RP Zakhari, S (reprint author), NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. EM szakhari@mail.nih.gov NR 128 TC 59 Z9 63 U1 3 U2 16 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAR 21 PY 2010 VL 16 IS 11 BP 1304 EP 1313 DI 10.3748/wjg.v16.i11.1304 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 572SJ UT WOS:000275853000003 PM 20238396 ER PT J AU Friedenreich, CM Woolcott, CG McTiernan, A Ballard-Barbash, R Brant, RF Stanczyk, FZ Terry, T Boyd, NF Yaffe, MJ Irwin, ML Jones, CA Yasui, Y Campbell, KL McNeely, ML Karvinen, KH Wang, QG Courneya, KS AF Friedenreich, Christine M. Woolcott, Christy G. McTiernan, Anne Ballard-Barbash, Rachel Brant, Rollin F. Stanczyk, Frank Z. Terry, Tim Boyd, Norman F. Yaffe, Martin J. Irwin, Melinda L. Jones, Charlotte A. Yasui, Yutaka Campbell, Kristin L. McNeely, Margaret L. Karvinen, Kristina H. Wang, Qinggang Courneya, Kerry S. TI Alberta Physical Activity and Breast Cancer Prevention Trial: Sex Hormone Changes in a Year-Long Exercise Intervention Among Postmenopausal Women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE FACTORS; AROMATASE INHIBITORS; FREE TESTOSTERONE; SERUM ANDROGENS; CLINICAL-TRIAL; BODY-FAT; RISK; POPULATION; ESTROGENS AB Purpose We examined how an aerobic exercise intervention influenced circulating estradiol, estrone, sex hormone-binding globulin (SHBG), androstenedione, and testosterone levels, which may be involved in the association between physical activity and breast cancer risk. Methods A two-center, two-arm randomized controlled trial of exercise was conducted in 320 postmenopausal, sedentary women age 50 to 74 years. Participants were randomly assigned to a 1-year aerobic exercise intervention of 225 min/wk (n = 160) or to a control group who maintained their usual level of activity (n = 160). Baseline, 6-month, and 12-month assessments of estrone, estradiol, androstenedione, and testosterone were quantified by radioimmunoassay after extraction, and SHBG was quantified by an immunometric assay. Intent-to-treat analyses were performed using linear mixed models. Results Blood data were available on 309 women (96.6%) at 12 months. Women in the intervention group exercised an average of 3.6 d/wk for 178 min/wk. At 12 months, statistically significant reductions in estradiol (treatment effect ratio [TER] = 0.93; 95% CI, 0.88 to 0.98) and free estradiol (TER = 0.91; 95% CI, 0.87 to 0.96) and increases in SHBG (TER = 1.04; 95% CI, 1.02 to 1.07) were observed in the exercise group compared with the control group. No significant differences in estrone, androstenedione, and testosterone levels were observed between exercisers and controls at 12 months. Conclusion This trial found that previously sedentary postmenopausal women can adhere to a moderate-to vigorous-intensity exercise program that results in changes in estradiol and SHBG concentrations that are consistent with a lower risk for postmenopausal breast cancer. C1 [Friedenreich, Christine M.] Alberta Hlth Serv, Cross Canc Inst, Calgary, AB T2N 4N2, Canada. Univ Calgary, Dept Med, Calgary, AB, Canada. Univ Alberta, Dept Publ Hlth Sci Phys Therapy & Oncol, Edmonton, AB, Canada. Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB, Canada. Univ British Columbia, Dept Stat, Vancouver, BC V6T 1W5, Canada. Univ British Columbia, Dept Phys Therapy, Vancouver, BC V6T 1W5, Canada. Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M4X 1K9, Canada. Sunnybrook Res Inst, Toronto, ON, Canada. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. E Carolina Univ, Dept Exercise & Sport Sci, Greenville, NC USA. RP Friedenreich, CM (reprint author), Alberta Hlth Serv, Cross Canc Inst, Calgary, AB T2N 4N2, Canada. EM christine.friedenreich@albertahealthservices.ca RI Perez , Claudio Alejandro/F-8310-2010; Yasui, Yutaka/E-2564-2015; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Yasui, Yutaka/0000-0002-7717-8638; Brant, Rollin/0000-0002-8026-2451 FU Canadian Breast Cancer Research Alliance [017468]; Canadian Institutes of Health Research; Alberta Heritage Foundation for Medical Research; Canada Research Chairs Program FX Supported by Research Grant No. 017468 from the Canadian Breast Cancer Research Alliance. C. M. F. is supported by career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research. K. S. C. is supported by the Canada Research Chairs Program. NR 42 TC 84 Z9 84 U1 1 U2 17 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 MAR 20 PY 2010 VL 28 IS 9 BP 1458 EP 1466 DI 10.1200/JCO.2009.24.9557 PG 9 WC Oncology SC Oncology GA 572IR UT WOS:000275824600005 PM 20159820 ER PT J AU Levine, AM Seaberg, EC Hessol, NA Preston-Martin, S Silver, S Cohen, MH Anastos, K Minkoff, H Orenstein, J Dominguez, G Watts, DH AF Levine, Alexandra M. Seaberg, Eric C. Hessol, Nancy A. Preston-Martin, Susan Silver, Sylvia Cohen, Mardge H. Anastos, Kathryn Minkoff, Howard Orenstein, Jan Dominguez, Geraldina Watts, D. Heather TI HIV As a Risk Factor for Lung Cancer in Women: Data From the Women's Interagency HIV Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; GENERAL-POPULATION; INFECTED PATIENTS; AIDS; DIAGNOSIS; ERA; CARCINOMA; MORTALITY; DISEASE AB Purpose Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS). Methods A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III. Results Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III. Conclusion HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified. C1 [Levine, Alexandra M.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. Eunice Kennedy Shriver NICHHD, NIH, Rockville, MD USA. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. Stroger, Dept Med, Chicago, IL USA. Rush Univ, Dept Med, Chicago, IL 60612 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Maimonides Hosp, Brooklyn, NY 11219 USA. NCI, Bethesda, MD 20892 USA. RP Levine, AM (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM alevine@coh.org FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; UCSF-CTSI [UL1 RR024131] FX WIHS is funded by Grants No. UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590 from the National Institute of Allergy and Infectious Diseases and by Grant No. UO1-HD-32632 from the National Institute of Child Health and Human Development; co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders; and by UCSF-CTSI Grant No. UL1 RR024131 from the National Center for Research Resources. NR 28 TC 29 Z9 29 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 MAR 20 PY 2010 VL 28 IS 9 BP 1514 EP 1519 DI 10.1200/JCO.2009.25.6149 PG 6 WC Oncology SC Oncology GA 572IR UT WOS:000275824600013 PM 20177022 ER PT J AU Ramanathan, RK Egorin, MJ Erlichman, C Remick, SC Ramalingam, SS Naret, C Holleran, JL TenEyck, CJ Ivy, SP Belani, CP AF Ramanathan, Ramesh K. Egorin, Merrill J. Erlichman, Charles Remick, Scot C. Ramalingam, Suresh S. Naret, Cynthia Holleran, Julianne L. TenEyck, Cynthia J. Ivy, S. Percy Belani, Chandra P. TI Phase I Pharmacokinetic and Pharmacodynamic Study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an Inhibitor of Heat-Shock Protein 90, in Patients With Advanced Solid Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REFRACTORY ADVANCED CANCERS; FISCHER-344 RATS; ADULT PATIENTS; 17-(ALLYLAMINO)-17-DEMETHOXYGELDANAMYCIN; TRIAL; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; NSC-707545; NSC-330507; CHAPERONE; ONCOLOGY AB Purpose To define the maximum tolerated dose, toxicities, pharmacokinetics, and pharmacodynamics of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG). Methods 17DMAG was given intravenously over 1 hour daily for 5 days (schedule A) or daily for 3 days (schedule B) every 3 weeks. Plasma 17DMAG concentrations were measured by liquid chromatography/ mass spectrometry. Heat-shock proteins (HSPs) and client proteins were evaluated at baseline and after treatment on day 1 in peripheral blood mononuclear cells (PBMCs) and in pre- and post-treatment (24 hours) biopsies done during cycle 1 at the recommended phase II dose (n = 7). Results Fifty-six patients were entered: 26 on schedule A; 30 on schedule B. The recommended phase II doses for schedules A and B were 16 mg/m(2) and 25 mg/m(2), respectively. Grade 3/4 toxicities included liver function test elevation (14%), pneumonitis (9%), diarrhea (4%), nausea (4%), fatigue (4%) and thrombocytopenia (4%). There were no objective responses. Four patients had stable disease. 17DMAG half-life was 24 +/- 15 hours. 17DMAG area under the curve (range, 0.7 to 14.7 mg/mL x h) increased linearly with dose. The median HSP90, HSP70, and integrin-linked kinase levels were 87.5% (n = 14), 124% (n = 20), and 99.5% (n = 20) of baseline. Changes in HSPs and client proteins in tumor biopsies were not consistent between baseline and 24 hours nor did they change in the same direction as those in PBMCs collected at the time of biopsy. Conclusion The recommended phase II doses of 17DMAG (16 mg/m(2) x 5 days or 25 mg/m(2) x 3 days, every 3 weeks) are well tolerated and suitable for further evaluation. C1 Univ Pittsburgh, Sch Med, Dept Med & Pharmacol, Div Hematol Oncol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Biol Chem, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Mol Therapeutics Drug Discovery Program, Pittsburgh, PA USA. Mayo Clin, Dept Oncol, Rochester, MN USA. Univ Hosp Cleveland, Case Med Ctr, Case Comprehens Canc Ctr, Dev Therapeut Program, Cleveland, OH 44106 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Ctr, Bethesda, MD 20892 USA. RP Ramanathan, RK (reprint author), Scottsdale Clin, Res Inst, 13208 E Shea Blvd,Ste 100, Scottsdale, AZ 85259 USA. EM rramanathan@tgen.org OI Belani, Chandra/0000-0001-5049-5329 FU National Institutes of Health [UO1-CA099168, UO1-CA69855, P30CA47904]; NIH/GCRC [5M01 RR 00056, M01-RR00080]; NCI [U01 CA 62502]; [U01CA69912]; [R01CA90390]; [CA15083]; [UL1RR24150] FX Supported in part by National Institutes of Health Grants No. UO1-CA099168, UO1-CA69855, and P30CA47904, and NIH/GCRC #5M01 RR 00056 to the University of Pittsburgh Cancer Institute and Medical Center; NCI U01 CA 62502 and NIH/GCRC M01-RR00080 to University Hospitals Case Medical Center; and U01CA69912, R01CA90390, CA15083, and UL1RR24150 to the Mayo Clinic. NR 29 TC 62 Z9 62 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2010 VL 28 IS 9 BP 1520 EP 1526 DI 10.1200/JCO.2009.25.0415 PG 7 WC Oncology SC Oncology GA 572IR UT WOS:000275824600014 PM 20177028 ER PT J AU Anantharaman, V Zhang, DP Aravind, L AF Anantharaman, Vivek Zhang, Dapeng Aravind, L. TI OST-HTH: a novel predicted RNA-binding domain SO BIOLOGY DIRECT LA English DT Article ID GERM; SPERMATOGENESIS; MAELSTROM; GRANULES; OSKAR; NUAGE; FOLD AB Background: The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. Results: Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid-interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Conclusions: Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. C1 [Anantharaman, Vivek; Zhang, Dapeng; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU National Library of Medicine at the National Institutes of Health, USA FX Work by the authors is supported by the intramural funds of the National Library of Medicine at the National Institutes of Health, USA. NR 25 TC 25 Z9 28 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD MAR 19 PY 2010 VL 5 AR 13 DI 10.1186/1745-6150-5-13 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 578EO UT WOS:000276276500001 PM 20302647 ER PT J AU Biong, M Gram, IT Brill, I Johansen, F Solvang, HK Alnaes, GIG Fagerheim, T Bremnes, Y Chanock, SJ Burdett, L Yeager, M Ursin, G Kristensen, VN AF Biong, Margarethe Gram, Inger T. Brill, Ilene Johansen, Fredrik Solvang, Hiroko K. Alnaes, Grethe I. G. Fagerheim, Toril Bremnes, Yngve Chanock, Stephen J. Burdett, Laurie Yeager, Meredith Ursin, Giske Kristensen, Vessela N. TI Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density SO BMC MEDICAL GENOMICS LA English DT Article ID BREAST-CANCER RISK; POSTMENOPAUSAL NORWEGIAN WOMEN; I IGF-I; CIRCULATING LEVELS; GENETIC POLYMORPHISMS; HORMONE-THERAPY; CHINESE WOMEN; SERUM-LEVELS; IGFBP-3; ASSOCIATION AB Background: Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here. Methods: Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromso Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS (TM) (SAS 9.1.3). Results: The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis. Conclusion: Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women. C1 [Biong, Margarethe; Johansen, Fredrik; Solvang, Hiroko K.; Alnaes, Grethe I. G.; Kristensen, Vessela N.] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. [Gram, Inger T.; Bremnes, Yngve] Univ Tromso, Inst Community Med, Breivika, Norway. [Brill, Ilene] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Solvang, Hiroko K.] Univ Oslo, Inst Basic Med Sci, Dept Biostat, Oslo, Norway. [Fagerheim, Toril] Univ Hosp N Norway, Dept Genet, Tromso, Norway. [Chanock, Stephen J.] NCI, NIH, Pediat Branch, Bethesda, MD 20892 USA. [Chanock, Stephen J.; Burdett, Laurie; Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Ctr, Bethesda, MD 20892 USA. [Ursin, Giske] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway. [Ursin, Giske] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Kristensen, Vessela N.] UiO, Fac Div Ahus, Fac Med, Oslo, Norway. RP Kristensen, VN (reprint author), Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. EM vessela.kristensen@medisin.uio.no FU Norwegian Foundation for Health and Rehabilitation [2003/2/0068]; University of Tromso; Norwegian Cancer Society; Aakre Foundation; Norwegian Women's Public Health Association; National Cancer Institute [R03CA105948]; The Research Council of Norway [175240/S10] FX We specially thank the women who participated in the Tromso Mammography and Breast Cancer Study. The study was conducted in collaboration with the Department of Clinical Research and the Department of Radiology, Center for Breast Imaging, University Hospital of North Norway, the Cancer Registry of Norway and the Norwegian Women and Cancer Study (PI Professor Eiliv Lund). The study was supported by grants from the EXTRA funds from Norwegian Foundation for Health and Rehabilitation 2003/2/0068, the University of Tromso; the Norwegian Cancer Society, the Aakre Foundation, the Norwegian Women's Public Health Association, the National Cancer Institute grant R03CA105948 (PI Professor Gertraud Maskarinec), Northern Norway Regional Health Authority. MB was supported by a PhD fellowship grant from The Research Council of Norway, grant 175240/S10. FJ was supported by the Norwegian Cancer Society. We would also like to thank Tonje Braaten for statistical advice. NR 68 TC 14 Z9 14 U1 0 U2 4 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 MAR 19 PY 2010 VL 3 AR 9 DI 10.1186/1755-8794-3-9 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 582AL UT WOS:000276567300001 PM 20302654 ER PT J AU Kastner, DL Aksentijevich, I Goldbach-Mansky, R AF Kastner, Daniel L. Aksentijevich, Ivona Goldbach-Mansky, Raphaela TI Autoinflammatory Disease Reloaded: A Clinical Perspective SO CELL LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; NALP3 INFLAMMASOME; INTERLEUKIN-1-RECEPTOR ANTAGONIST; CIAS1 MUTATIONS; B30.2 DOMAIN; PYRIN; GENE; PROTEIN; ACTIVATION; INHIBITION AB Our understanding of the etiology of autoinflammatory disease is growing rapidly. Recent advances offer new opportunities for therapeutic intervention and suggest that the definition of what constitutes an autoinflammatory disease should be reassessed. C1 [Kastner, Daniel L.; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela] NIAMSD, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Kastner, DL (reprint author), NIAMSD, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. EM kastnerd@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal FX This work was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 51 TC 165 Z9 171 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 19 PY 2010 VL 140 IS 6 BP 784 EP 790 DI 10.1016/j.cell.2010.03.002 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 571IX UT WOS:000275746600003 PM 20303869 ER PT J AU Zhang, LP McHale, CM Rothman, N Li, GL Ji, ZY Vermeulen, R Hubbard, AE Ren, XF Shen, M Rappaport, SM North, M Skibola, CF Yin, SN Vulpe, C Chanock, SJ Smith, MT Lan, Q AF Zhang, Luoping McHale, Cliona M. Rothman, Nathaniel Li, Guilan Ji, Zhiying Vermeulen, Roel Hubbard, Alan E. Ren, Xuefeng Shen, Min Rappaport, Stephen M. North, Matthew Skibola, Christine F. Yin, Songnian Vulpe, Christopher Chanock, Stephen J. Smith, Martyn T. Lan, Qing TI Systems biology of human benzene exposure SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Review DE Benzene; Toxicogenomics; Epigenetics; Systems biology; Hematotoxicity; Human ID ACUTE MYELOID-LEUKEMIA; ENVIRONMENTAL EPIGENOMICS; INDUCED HEMATOTOXICITY; GENE-EXPRESSION; POTENTIAL ROLE; DNA-DAMAGE; WORKERS; SUSCEPTIBILITY; HYDROQUINONE; METABOLITE AB Toxicogenomic studies, including genome-wide analyses of susceptibility genes (genomics), gene expression (transcriptomics), protein expression (proteomics), and epigenetic modifications (epigenomics), of human populations exposed to benzene are crucial to understanding gene-environment interactions, providing the ability to develop biomarkers of exposure, early effect and susceptibility. Comprehensive analysis of these toxicogenomic and epigenomic profiles by bioinformatics in the context of phenotypic endpoints, comprises systems biology, which has the potential to comprehensively define the mechanisms by which benzene causes leukemia. We have applied this approach to a molecular epidemiology study of workers exposed to benzene. Hematotoxicity, a significant decrease in almost all blood cell counts, was identified as a phenotypic effect of benzene that occurred even below 1 ppm benzene exposure. We found a significant decrease in the formation of progenitor colonies arising from bone marrow stem cells with increasing benzene exposure, showing that progenitor cells are more sensitive to the effects of benzene than mature blood cells, likely leading to the observed hematotoxicity. Analysis of transcriptomics by microarray in the peripheral blood mononuclear cells of exposed workers, identified genes and pathways (apoptosis, immune response, and inflammatory response) altered at high (>10 ppm) and low (<1 ppm) benzene levels. Serum proteomics by SELDI-TOF-MS revealed proteins consistently down-regulated in exposed workers. Preliminary epigenomics data showed effects of benzene on the DNA methylation of specific genes. Genomic screens for candidate genes involved in susceptibility to benzene toxicity are being undertaken in yeast, with subsequent confirmation by RNAi in human cells, to expand upon the findings from candidate gene analyses. Data on these and future biomarkers will be used to populate a large toxicogenomics database, to which we will apply bioinformatic approaches to understand the interactions among benzene toxicity, susceptibility genes, mRNA, and DNA methylation through a systems biology approach (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Zhang, Luoping; McHale, Cliona M.; Ji, Zhiying; Hubbard, Alan E.; Ren, Xuefeng; Rappaport, Stephen M.; Skibola, Christine F.; Smith, Martyn T.] Univ Calif Berkeley, Div Environm Hlth Sci, Sch Publ Hlth, Berkeley, CA 94720 USA. [Rothman, Nathaniel; Shen, Min; Chanock, Stephen J.; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Beijing 100050, Peoples R China. [Vermeulen, Roel] Inst Risk Assessment Sci, NL-3584 CK Utrecht, Netherlands. [North, Matthew; Vulpe, Christopher] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. RP Zhang, LP (reprint author), Univ Calif Berkeley, Div Environm Hlth Sci, Sch Publ Hlth, 237 Hildebrand Hall, Berkeley, CA 94720 USA. EM luoping@berkeley.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU NIH [RO1ES06721, P42ES04705, P42ES05948, P30ES10126] FX We thank the participants for taking part in this study. We are extremely grateful to Heather Lustig and Kshama Mehta at Agilent Technologies, for facilitating the miRNA pilot study. We thank Ms. Suzanne May for her technical assistance with the DNA methylation analysis. We are grateful to Ms. Anh Duong for her tireless contribution and editorial assistance to this manuscript, and to Mr. Patrick Chang for his technical talent to illustrate the Systems Biology figure. This work was supported by NIH grants RO1ES06721 and P42ES04705 (MTS), P42ES05948 and P30ES10126 (SMR). NR 56 TC 36 Z9 49 U1 4 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD MAR 19 PY 2010 VL 184 IS 1-2 SI SI BP 86 EP 93 DI 10.1016/j.cbi.2009.12.011 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 586CD UT WOS:000276877800014 PM 20026094 ER EF