FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Spong, CY Reddy, UM Willinger, M AF Spong, Catherine Y. Reddy, Uma M. Willinger, Marian TI Addressing the complexity of disparities in stillbirths SO LANCET LA English DT Editorial Material ID RISK-FACTORS C1 [Spong, Catherine Y.; Reddy, Uma M.; Willinger, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Rockville, MD 20852 USA. RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Rockville, MD 20852 USA. EM spongc@mail.nih.gov NR 10 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 14 PY 2011 VL 377 IS 9778 BP 1635 EP 1636 DI 10.1016/S0140-6736(11)60025-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 766JF UT WOS:000290777700009 PM 21496913 ER PT J AU Wang, WC Ware, RE Miller, ST Iyer, RV Casella, JF Minniti, CP Rana, S Thornburg, CD Rogers, ZR Kalpatthi, RV Barredo, JC Brown, RC Sarnaik, SA Howard, TH Wynn, LW Kutlar, A Armstrong, FD Files, BA Goldsmith, JC Waclawiw, MA Huang, XK Thompson, BW AF Wang, Winfred C. Ware, Russell E. Miller, Scott T. Iyer, Rathi V. Casella, James F. Minniti, Caterina P. Rana, Sohail Thornburg, Courtney D. Rogers, Zora R. Kalpatthi, Ram V. Barredo, Julio C. Brown, R. Clark Sarnaik, Sharada A. Howard, Thomas H. Wynn, Lynn W. Kutlar, Abdullah Armstrong, F. Daniel Files, Beatrice A. Goldsmith, Jonathan C. Waclawiw, Myron A. Huang, Xiangke Thompson, Bruce W. CA BABY HUG Investigators TI Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG) SO LANCET LA English DT Article ID HYDROXYUREA THERAPY; ADVERSE OUTCOMES; SPLENIC FUNCTION; CLINICAL-TRIAL; RISK-FACTORS; FOLLOW-UP; DISEASE; PREDICTION; MORTALITY; EFFICACY AB Background Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. Methods This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin S beta(0)thalassaemia, were aged 9-18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on (99)Tc spleen scan) and renal function (glomerular filtration rate by (99m)Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2-4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400. Findings 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0.21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 ml/min per 1.73 m(2), p=0.84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0.002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0.0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia. Interpretation On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. C1 [Wang, Winfred C.] St Jude Childrens Hosp, Dept Hematol, Memphis, TN 38105 USA. [Miller, Scott T.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Iyer, Rathi V.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Casella, James F.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Minniti, Caterina P.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Rana, Sohail] Howard Univ, Coll Med, Washington, DC USA. [Thornburg, Courtney D.] Duke Univ, Med Ctr, Raleigh, NC USA. [Rogers, Zora R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kalpatthi, Ram V.] Med Univ S Carolina, Charleston, SC 29425 USA. [Barredo, Julio C.; Armstrong, F. Daniel] Univ Miami, Miami, FL USA. [Brown, R. Clark; Files, Beatrice A.] Emory Univ, Sch Med, Atlanta, GA USA. [Howard, Thomas H.] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Kutlar, Abdullah] Med Coll Georgia, Augusta, GA 30912 USA. [Goldsmith, Jonathan C.; Waclawiw, Myron A.] NHLBI, Bethesda, MD 20892 USA. [Huang, Xiangke; Thompson, Bruce W.] Clinical Trials & Surveys Corp, Owings Mills, MD USA. RP Wang, WC (reprint author), St Jude Childrens Hosp, Dept Hematol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM winfred.wang@stjude.org FU National Heart, Lung and Blood Institute; National Institutes of Health [N01-HB-07150, N01-HB-07160]; Children's National Medical Center; Duke University Medical Center; Howard University College of Medicine; Johns Hopkins University School of Medicine; Sinai Hospital, Baltimore; Medical University of South Carolina; St Jude Children's Research Hospital; SUNY Downstate Medical Center/Kings County Hospital Center; University of Miami; University of Mississippi Medical Center; University of Texas Southwestern Medical Center, Dallas; University of Alabama at Birmingham; Drexel University; Emory University School of Medicine; Children's Hospital of Michigan; Clinical Trials and Surveys Corp; National Institute of Child Health and Human Development FX The National Heart, Lung and Blood Institute and National Institutes of Health (contracts N01-HB-07150 to N01-HB-07160) funded the study, with partial support from the Best Pharmaceuticals for Children Act and the National Institute of Child Health and Human Development. We thank the following people at the participating Clinical Centers, the Medical Coordinating Center, and the sponsoring institutes: Children's National Medical Center (Catherine Driscoll, Lori Luchtman-Jones, Brenda Martin, Barbara Speller-Brown, Romuladus Azuine); Duke University Medical Center (Sherri Zimmerman, William Schultz, Tracy Kelly, Shelly Burgett); Howard University College of Medicine (Caroline K Reed, Erin Yeagley, Patricia Houston-Yu); Johns Hopkins University School of Medicine (Phillip Seaman, Jeffrey Keefer, Sue Dixon, Patrice Sharp); Sinai Hospital, Baltimore (Jason Fixler, Joan Marasciulo); Medical University of South Carolina (Miguel Abboud, Mary Ellen Cavalier, Sherron Jackson, Betsy Rackoff, Lisa Kuisel, Deborah Disco); St Jude Children's Research Hospital (Lane Faughnan); SUNY Downstate Medical Center/Kings County Hospital Center (Kathy Rey, Sreedhar P Rao); University of Miami (Stuart Toledano, Tally Hustace, Noeline Lewis, Ofelia Alvarez); University of Mississippi Medical Center (Glenda Thomas, Tobi Breland, Amy Forsythe, Torn Hogan); University of Texas Southwestern Medical Center, Dallas (Cindy Cochran, Nicole Corrigan, Jennifer Marshall, Roxanna Mars, Leah Adix); University of Alabama at Birmingham (Jennifer McDuffie, Kimberly Whelan, Roy McDonald); Drexel University (Canton Dampier, Lori Luck, Mary Lou MacDermott, Maureen Meier, Michele Cahill); Emory University School of Medicine (Peter Lane, Ifeyinwa Osunkwo, Ellen Debenham, Leann Hassen, Terrell Faircloth); Children's Hospital of Michigan (Wanda Whitten-Shurney, Mary Murphy, Kristin Stone-Kennedy); Clinical Trials and Surveys Corp (Zhibao Mi, Zhaoyu Luo, Billie Fish, Joulia Haziminas, Renee Rees, Franka Barton); the National Heart, Lung and Blood Institute (Charles Peterson); and the National Institute of Child Health and Human Development (Donald Mattison). We thank the following consultants: Robert Adams (Medical University of South Carolina); Steven Pavlakis (Maimonides Medical Center); Michael Jeng (Stanford University Medical Center); Stephen Dertinger (Litron Corporation); Beth McCarville and Barry Shulkin (St Jude Children's Research Hospital); Eglal Rana (Howard University); and Niren Patel (Medical College of Georgia). Additionally, we appreciate the contributions of Charles Pegelow, who led the University of Miami Center until his untimely death. We acknowledge the efforts of the BABY HUG participants and their families, and the contributions of all who participated in BABY HUG. NR 30 TC 208 Z9 210 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 14 PY 2011 VL 377 IS 9778 BP 1663 EP 1672 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 766JF UT WOS:000290777700031 PM 21571150 ER PT J AU Li, L Xiao, XS Li, SQ Jia, XY Wang, PF Guo, XM Jiao, XD Zhang, QJ Hejtmancik, JF AF Li, Lin Xiao, Xueshan Li, Shiqiang Jia, Xiaoyun Wang, Panfeng Guo, Xiangming Jiao, Xiaodong Zhang, Qingjiong Hejtmancik, J. Fielding TI Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis SO PLOS ONE LA English DT Article ID GENOTYPING MICROARRAY; RETINITIS-PIGMENTOSA; RETINAL DYSTROPHIES; MOLECULAR-GENETICS; MISSENSE MUTATIONS; ALLELES; SPECTRUM; PROTEIN; CRX AB Background: Leber congenital amaurosis (LCA) is the earliest onset and most severe form of hereditary retinal dystrophy. So far, full spectrum of variations in the 15 genes known to cause LCA has not been systemically evaluated in East Asians. Therefore, we performed comprehensive detection of variants in these 15 genes in 87 unrelated Han Chinese patients with LCA. Methodology/Principal Findings: The 51 most frequently mutated exons and introns in the 15 genes were selected for an initial scan using cycle sequencing. All the remaining exons in 11 of the 15 genes were subsequently sequenced. Fifty-three different variants were identified in 44 of the 87 patients (50.6%), involving 78 of the 88 alleles (11 homozygous and 56 heterozygous variants). Of the 53 variants, 35 (66%) were novel pathogenic mutations. In these Chinese patients, variants in GUCY2D are the most common cause of LCA (16.1% cases), followed by CRB1 (11.5%), RPGRIP1 (8%), RPE65 (5.7%), SPATA7 (4.6%), CEP290 (4.6%), CRX (3.4%), LCA5 (2.3%), MERTK (2.3%), AIPL1 (1.1%), and RDH12 (1.1%). This differs from the variation spectrum described in other populations. An initial scan of 55 of 215 PCR amplicons, including 214 exons and 1 intron, detected 83.3% (65/78) of the mutant alleles ultimately found in these 87 patients. In addition, sequencing only 9 exons would detect over 50% of the identified variants and require less than 5% of the labor and cost of comprehensive sequencing for all exons. Conclusions/Significance: Our results suggest that specific difference in the variation spectrum found in LCA patients from the Han Chinese and other populations are related by ethnicity. Sequencing exons in order of decreasing risk is a cost-effective way to identify causative mutations responsible for LCA, especially in the context of genetic counseling for individual patients in a clinical setting. C1 [Li, Lin; Xiao, Xueshan; Li, Shiqiang; Jia, Xiaoyun; Wang, Panfeng; Guo, Xiangming; Zhang, Qingjiong] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China. [Li, Lin; Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Li, L (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China. EM qingjiongzhang@yahoo.com FU National Science Fund for Distinguished Young Scholars [30725044]; National 973 Plan of China [2010CB529904] FX This study was supported by National Science Fund for Distinguished Young Scholars (30725044, http://www.nsfc.gov.cn/Portal0/default124.htm) and National 973 Plan of China (2010CB529904, http://program.most.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 45 Z9 56 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2011 VL 6 IS 5 AR e19458 DI 10.1371/journal.pone.0019458 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763LP UT WOS:000290558500010 PM 21602930 ER PT J AU O'Donovan, A Pantell, MS Puterman, E Dhabhar, FS Blackburn, EH Yaffe, K Cawthon, RM Opresko, PL Hsueh, WC Satterfield, S Newman, AB Ayonayon, HN Rubin, SM Harris, TB Epel, ES AF O'Donovan, Aoife Pantell, Matthew S. Puterman, Eli Dhabhar, Firdaus S. Blackburn, Elizabeth H. Yaffe, Kristine Cawthon, Richard M. Opresko, Patricia L. Hsueh, Wen-Chi Satterfield, Suzanne Newman, Anne B. Ayonayon, Hilsa N. Rubin, Susan M. Harris, Tamara B. Epel, Elissa S. CA Hlth Aging Body Composition Study TI Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study SO PLOS ONE LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; CALORIE RESTRICTION; HUMAN HEPATOCYTES; DNA-DAMAGE; MORTALITY; RISK; INTERLEUKIN-6; CANCER; CELLS AB Background: Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. Methodology/Principal Findings: To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70-79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-alpha had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-alpha had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37-0.72), only IL-6 high (OR = 0.57, CI = 0.39-0.83) or only TNF-alpha high (OR = 0.67, CI = 0.46-0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL. Conclusions/Significance: Results suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-alpha, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population. C1 [O'Donovan, Aoife; Puterman, Eli; Yaffe, Kristine; Epel, Elissa S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [O'Donovan, Aoife; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Pantell, Matthew S.] Univ Calif Berkeley, Univ Calif, San Francisco Joint Med Program, Berkeley, CA 94720 USA. [Pantell, Matthew S.] Univ Calif Berkeley, Univ Calif, San Francisco Joint Med Program, San Francisco, CA USA. [Dhabhar, Firdaus S.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Blackburn, Elizabeth H.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine; Hsueh, Wen-Chi; Ayonayon, Hilsa N.; Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cawthon, Richard M.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. [Opresko, Patricia L.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA. [Hsueh, Wen-Chi] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, Tamara B.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP O'Donovan, A (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM aoife.odonovan@ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Opresko, Patricia/0000-0002-6470-2189; Puterman, Eli/0000-0002-5898-2348 FU National Institutes of Health (NIH) National Institute on Aging (NIA) [AG-6-2101, AG-6-2103, AG-6-2106, AG021918]; Society in Science: The Branco Weiss Fellowship FX The study was conducted on behalf of the Health, Aging and Body Composition (Health ABC) Study and was funded by National Institutes of Health (NIH) National Institute on Aging (NIA) grants AG-6-2101, AG-6-2103, AG-6-2106, and AG021918. This work was also supported by the Intramural Research Program of the NIH, NIA as well as by Society in Science: The Branco Weiss Fellowship (AOD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 82 Z9 84 U1 1 U2 12 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 MAY 13 PY 2011 VL 6 IS 5 AR e19687 DI 10.1371/journal.pone.0019687 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763LP UT WOS:000290558500023 PM 21602933 ER PT J AU Valenzuela, MS Chen, YD Davis, S Yang, F Walker, RL Bilke, S Lueders, J Martin, MM Aladjem, MI Massion, PP Meltzer, PS AF Valenzuela, Manuel S. Chen, Yidong Davis, Sean Yang, Fan Walker, Robert L. Bilke, Sven Lueders, John Martin, Melvenia M. Aladjem, Mirit I. Massion, Pierre P. Meltzer, Paul S. TI Preferential Localization of Human Origins of DNA Replication at the 5 '-Ends of Expressed Genes and at Evolutionarily Conserved DNA Sequences SO PLOS ONE LA English DT Article ID HUMAN-CELLS; SACCHAROMYCES-CEREVISIAE; INITIATION; GENOME; SITES; CHROMATIN; ELEMENTS; IDENTIFICATION; ORGANIZATION; METAZOANS AB Background: Replication of mammalian genomes requires the activation of thousands of origins which are both spatially and temporally regulated by as yet unknown mechanisms. At the most fundamental level, our knowledge about the distribution pattern of origins in each of the chromosomes, among different cell types, and whether the physiological state of the cells alters this distribution is at present very limited. Methodology/Principal Findings: We have used standard lambda-exonuclease resistant nascent DNA preparations in the size range of 0.7-1.5 kb obtained from the breast cancer cell line MCF-7 hybridized to a custom tiling array containing 50-60 nt probes evenly distributed among genic and non-genic regions covering about 1% of the human genome. A similar DNA preparation was used for high-throughput DNA sequencing. Array experiments were also performed with DNA obtained from BT-474 and H520 cell lines. By determining the sites showing nascent DNA enrichment, we have localized several thousand origins of DNA replication. Our major findings are: (a) both array and DNA sequencing assay methods produced essentially the same origin distribution profile; (b) origin distribution is largely conserved (> 70%) in all cell lines tested; (c) origins are enriched at the 5' ends of expressed genes and at evolutionarily conserved intergenic sequences; and (d) ChIP on chip experiments in MCF-7 showed an enrichment of H3K4Me3 and RNA Polymerase II chromatin binding sites at origins of DNA replication. Conclusions/Significance: Our results suggest that the program for origin activation is largely conserved among different cell types. Also, our work supports recent studies connecting transcription initiation with replication, and in addition suggests that evolutionarily conserved intergenic sequences have the potential to participate in origin selection. Overall, our observations suggest that replication origin selection is a stochastic process significantly dependent upon local accessibility to replication factors. C1 [Valenzuela, Manuel S.; Chen, Yidong; Davis, Sean; Yang, Fan; Walker, Robert L.; Bilke, Sven; Lueders, John; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Valenzuela, Manuel S.] Meharry Med Coll, Dept Biochem & Canc Biol, Nashville, TN 37208 USA. [Martin, Melvenia M.; Aladjem, Mirit I.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Massion, Pierre P.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. RP Valenzuela, MS (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM mvalenzuela@mmc.edu; pmeltzer@mail.nih.gov RI Aladjem, Mirit/G-2169-2010; OI Aladjem, Mirit/0000-0002-1875-3110; Davis, Sean/0000-0002-8991-6458 FU NIH [CA138180, CA102353] FX This work has been supported by NIH intramural funding and by NIH grants [CA138180 to MSV, and CA102353 to PPM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 25 Z9 25 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2011 VL 6 IS 5 AR e17308 DI 10.1371/journal.pone.0017308 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763LP UT WOS:000290558500001 PM 21602917 ER PT J AU Xu, J Walsh, SB Verney, ZM Kopelovich, L Elmets, CA Athar, M AF Xu, Jianmin Walsh, Stephanie B. Verney, Zoe M. Kopelovich, Levy Elmets, Craig A. Athar, Mohammad TI Procarcinogenic effects of cyclosporine A are mediated through the activation of TAK1/TAB1 signaling pathway SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Cyclosporine A; Nonmelanoma skin cancer; Immune suppression; TAK1 signaling; Nuclear factor kappa B ID ORGAN TRANSPLANT RECIPIENTS; KAPPA-B ACTIVATION; CANCER PROGRESSION; KINASE; TRANSCRIPTION; PATHOGENESIS; AP-1 AB Cyclosporine A (CsA) is an immunosuppressive drug commonly used for maintaining chronic immune suppression in organ transplant recipients. It is known that patients receiving CsA manifest increased growth of aggressive non-melanoma skin cancers. However, the underlying mechanism by which CsA augments tumor growth is not fully understood. Here, we show that CsA augments the growth of A431 epidermoid carcinoma xenograft tumors by activating tumor growth factor beta-activated kinase1 (TAK1). The activation of TAK1 by CsA occurs at multiple levels by kinases ZMP, AMPK and IRAK. TAK1 forms heterodimeric complexes with TAK binding protein 1 and 2 (TAB1/TAB2) which in term activate nuclear factor kappa B (NF kappa B) and p38 MAP kinase. Transcriptional activation of NF kappa B is evidenced by IKK beta-mediated phosphorylation-dependent degradation of I kappa B and consequent nuclear translocation of p65. This also leads to enhancement in the expression of its transcriptional target genes cyclin D1, Bcl2 and COX-2. Similarly, activation of p38 leads to enhanced inflammation-related signaling shown by increased phosphorylation of MAPKAPK2 and which in turn phosphorylates its substrate HSP27. Activation of both NF kappa B and p38 MAP kinase provide mitogenic stimuli to augment the growth of SCCs. (C) 2011 Elsevier Inc. All rights reserved. C1 [Xu, Jianmin; Walsh, Stephanie B.; Verney, Zoe M.; Elmets, Craig A.; Athar, Mohammad] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Elmets, Craig A.; Athar, Mohammad] Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Athar, M (reprint author), Univ Alabama, Dept Dermatol, Volker Hall,Room 509,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mathar@uab.edu FU NCI [HHSN261200433001C-521958]; [R01 ES015323]; [R21 ES017494]; [P30AR050948]; [T32 AR053458] FX Grant Support from the following awards, R01 ES015323, R21 ES017494, NCI HHSN261200433001C-521958, P30AR050948, T32 AR053458. NR 21 TC 13 Z9 13 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 13 PY 2011 VL 408 IS 3 BP 363 EP 368 DI 10.1016/j.bbrc.2011.02.039 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 768IC UT WOS:000290926400001 PM 21333626 ER PT J AU Shewmaker, F McGlinchey, RP Wickner, RB AF Shewmaker, Frank McGlinchey, Ryan P. Wickner, Reed B. TI Structural Insights into Functional and Pathological Amyloid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID SOLID-STATE NMR; PARALLEL BETA-SHEET; NUCLEAR-MAGNETIC-RESONANCE; TRANSMISSION ELECTRON-MICROSCOPY; S PRION PROTEIN; EXPERIMENTAL CONSTRAINTS; FORMING SEQUENCES; FIBRIL FORMATION; MOLECULAR-BASIS; REPEAT DOMAIN AB Amyloid is traditionally viewed as a consequence of protein misfolding and aggregation and is most notorious for its association with debilitating and chronic human diseases. However, a growing list of examples of "functional amyloid" challenges this bad reputation and indicates that many organisms can employ the biophysical properties of amyloid for their benefit. Because of developments in the structural studies of amyloid, a clearer picture is emerging about what defines amyloid structure and the properties that unite functional and pathological amyloids. Here, we review various amyloids and place them within the framework of the latest structural models. C1 [Shewmaker, Frank] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [McGlinchey, Ryan P.; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Shewmaker, F (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM fshewmaker@usuhs.mil NR 100 TC 76 Z9 78 U1 4 U2 45 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 MAY 13 PY 2011 VL 286 IS 19 BP 16533 EP 16540 DI 10.1074/jbc.R111.227108 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 760CZ UT WOS:000290301900001 PM 21454545 ER PT J AU Kasaikina, MV Lobanov, AV Malinouski, MY Lee, BC Seravalli, J Fomenko, DE Turanov, AA Finney, L Vogt, S Park, TJ Miller, RA Hatfield, DL Gladyshev, VN AF Kasaikina, Marina V. Lobanov, Alexei V. Malinouski, Mikalai Y. Lee, Byung Cheon Seravalli, Javier Fomenko, Dmitri E. Turanov, Anton A. Finney, Lydia Vogt, Stefan Park, Thomas J. Miller, Richard A. Hatfield, Dolph L. Gladyshev, Vadim N. TI Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONGEST-LIVING RODENT; GLUTATHIONE-PEROXIDASE; HETEROCEPHALUS-GLABER; OXIDATIVE STRESS; MICE; CELLS; SELENOCYSTEINE; RESISTANCE; CANCER; SELENOPROTEINS AB Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (> 28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with (75)Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression. C1 [Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kasaikina, Marina V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Kasaikina, Marina V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. [Finney, Lydia] Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. [Vogt, Stefan] Argonne Natl Lab, Xray Sci Div, Argonne, IL 60439 USA. [Park, Thomas J.] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. [Miller, Richard A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, New Res Bldg,Rm 435,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu RI Gladyshev, Vadim/A-9894-2013; Vogt, Stefan/B-9547-2009; Vogt, Stefan/J-7937-2013 OI Vogt, Stefan/0000-0002-8034-5513; Vogt, Stefan/0000-0002-8034-5513 FU National Institutes of Health [GM061603, CA080946, AG021518]; Center for Cancer Research, NCI, National Institutes of Health; Department of Energy Office of Science [DE-AC02-06CH11357] FX This work was supported, in whole or in part, by National Institutes of Health Grants GM061603, CA080946, and AG021518 (to V. N. G.) and the Intramural Research Program of the Center for Cancer Research, NCI, National Institutes of Health (to D. L. H.). This work was also supported by the Department of Energy Office of Science under Contract DE-AC02-06CH11357. NR 47 TC 15 Z9 15 U1 2 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 2011 VL 286 IS 19 BP 17005 EP 17014 DI 10.1074/jbc.M110.216267 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 760CZ UT WOS:000290301900051 PM 21372135 ER PT J AU Melchior-Becker, A Dai, G Ding, ZP Schafer, L Schrader, J Young, MF Fischer, JW AF Melchior-Becker, Ariane Dai, Guang Ding, Zhaoping Schaefer, Liliana Schrader, Juergen Young, Marian F. Fischer, Jens W. TI Deficiency of Biglycan Causes Cardiac Fibroblasts to Differentiate into a Myofibroblast Phenotype SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-BETA; SMOOTH-MUSCLE-CELLS; EXTRACELLULAR-MATRIX TURNOVER; COLLAGEN GEL CONTRACTION; TGF-BETA; MYOCARDIAL-INFARCTION; TARGETED DISRUPTION; TISSUE-REPAIR; DECORIN; APOPTOSIS AB Myocardial infarction (MI) is followed by extracellular matrix (ECM) remodeling, which is on the one hand required for the healing response and the formation of stable scar tissue. However, on the other hand, ECM remodeling can lead to fibrosis and decreased ventricular compliance. The small leucine-rich proteoglycan (SLRP), biglycan (bgn), has been shown to be critically involved in these processes. During post-infarct remodeling cardiac fibroblasts differentiate into myofibroblasts which are the main cell type mediating ECM remodeling. The aim of the present study was to characterize the role of bgn in modulating the phenotype of cardiac fibroblasts. Cardiac fibroblasts were isolated from hearts of wild-type (WT) versus bgn(-/0) mice. Phenotypic characterization of the bgn(-/0) fibroblasts revealed increased proliferation. Importantly, this phenotype of bgn(-/0) fibroblasts was abolished to the WT level by reconstitution of biglycan in the ECM. TGF-beta receptor II expression and phosphorylation of SMAD2 were increased. Furthermore, indicative of a myofibroblast phenotype bgn(-/0) fibroblasts were characterized by increased alpha-smooth muscle actin (alpha-SMA) incorporated into stress fibers, increased formation of focal adhesions, and increased contraction of collagen gels. Administration of neutralizing antibodies to TGF-beta reversed the pro-proliferative, myofibroblastic phenotype. In vivo post-MI alpha-SMA, TGF-beta receptor II expression, and SMAD2 phosphorylation were markedly increased in bgn(-/0) mice. Collectively, the data suggest that bgn deficiency promotes myofibroblast differentiation and proliferation in vitro and in vivo likely due to increased responses to TGF-beta and SMAD2 signaling. C1 [Melchior-Becker, Ariane; Dai, Guang; Fischer, Jens W.] Univ Dusseldorf, Inst Pharmakol & Klin Pharmakol, Univ Klinikum Dusseldorf, D-40225 Dusseldorf, Germany. [Ding, Zhaoping; Schrader, Juergen] Univ Dusseldorf, Inst Herz & Kreislaufphysiol, D-40225 Dusseldorf, Germany. [Schaefer, Liliana] Klinikum JW Goethe Univ, Pharmazentrum Frankfurt, Inst Allgemeine Pharmakol & Toxikol ZAFES, D-60590 Frankfurt, Germany. [Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Fischer, JW (reprint author), Univ Dusseldorf, Inst Pharmakol & Klin Pharmakol, Univ Klinikum Dusseldorf, Moorenstr 5, D-40225 Dusseldorf, Germany. EM jens.fischer@uni-duesseldorf.de FU Deutsche Forschungsgemeinschaft [GRK 1089] FX This work was supported by Deutsche Forschungsgemeinschaft Grant GRK 1089. NR 67 TC 36 Z9 38 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 2011 VL 286 IS 19 BP 17365 EP 17375 DI 10.1074/jbc.M110.192682 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 760CZ UT WOS:000290301900084 PM 21454527 ER PT J AU Balwit, JM Kalinski, P Sondak, VK Coulie, PG Jaffee, EM Gajewski, TF Marincola, FM AF Balwit, James M. Kalinski, Pawel Sondak, Vernon K. Coulie, Pierre G. Jaffee, Elizabeth M. Gajewski, Thomas F. Marincola, Francesco M. TI Review of the 25(th) annual scientific meeting of the International Society for Biological Therapy of Cancer SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID BIOMARKERS AB Led by key opinion leaders in the field, the 25(th) Annual Meeting of the International Society for Biological Therapy of Cancer (iSBTc, recently renamed the Society for Immunotherapy of Cancer, SITC) provided a scientific platform for similar to 500 attendees to exchange cutting-edge information on basic, clinical, and translational research in cancer immunology and immunotherapy. The meeting included keynote addresses on checkpoint blockade in cancer therapy and recent advances in therapeutic vaccination against cancer induced by Human Papilloma Virus 16. Participants from 29 countries interacted through oral presentations, panel discussions, and posters on topics that included dendritic cells and cancer, targeted therapeutics and immunotherapy, innate/adaptive immune interplay in cancer, clinical trial endpoints, vaccine combinations, countering negative regulation, immune cell trafficking to tumor microenvironment, and adoptive T cell transfer. In addition to the 50 oral presentations and > 180 posters on these topics, a new SITC/iSBTc initiative to create evidence-based Cancer Immunotherapy Guidelines was announced. The SITC/iSBTc Biomarkers Taskforce announced the release of recommendations on immunotherapy biomarkers and a highly successful symposium on Immuno-Oncology Biomarkers that took place on the campus of the National Institutes of Health (NIH) immediately prior to the Annual Meeting. At the Annual Meeting, the NIH took the opportunity to publicly announce the award of the U01 grant that will fund the Cancer Immunotherapy Trials Network (CITN). In summary, the Annual Meeting gathered clinicians and scientists from academia, industry, and regulatory agencies from around the globe to interact and exchange important scientific advances related to tumor immunobiology and cancer immunotherapy. C1 [Balwit, James M.; Gajewski, Thomas F.; Marincola, Francesco M.] Soc Immunotherapy Canc, Milwaukee, WI USA. [Kalinski, Pawel] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Sondak, Vernon K.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Cutaneous Oncol, Tampa, FL 33682 USA. [Sondak, Vernon K.] Univ S Florida, Dept Oncol Sci, Tampa, FL USA. [Sondak, Vernon K.] Univ S Florida, Dept Surg, Tampa, FL 33620 USA. [Coulie, Pierre G.] de Duve Inst, Brussels, Belgium. [Coulie, Pierre G.] Catholic Univ Louvain, B-1200 Brussels, Belgium. [Jaffee, Elizabeth M.] Johns Hopkins Univ, Dept Oncol, Skip Viragh Pancreat Canc Ctr, Baltimore, MD USA. [Gajewski, Thomas F.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Gajewski, Thomas F.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Translat Med, Ctr Clin, Bethesda, MD 20892 USA. [Marincola, Francesco M.] NIH, CHI, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), Soc Immunotherapy Canc, Milwaukee, WI USA. EM FMarincola@mail.cc.nih.gov FU Bayer/Onyx; BMS/Medarex; Eli Lilly; Glaxo SmithKline/Synta; Merck(Schering); Merck (Schering); Pfizer FX JB and FM declare that they have no competing interests. PK discussed aDC1s, which are the subject of a pending patent application. There are no active commercialization efforts and PK does not receive any royalties or other forms of remuneration related to this intellectual property. This situation is considered a minimal conflict of interest by the University of Pittsburgh. VS discloses the following relationships: Abbott, Consultant/Advisory Board receiving Consulting Fees/Honoraria; Bayer/Onyx, Consultant/Advisory Board receiving Consulting Fees/Honoraria; BMS/Medarex, Consultant/Advisory Board receiving Consulting Fees/Honoraria; Eli Lilly, Consultant/Advisory Board receiving Consulting Fees/Honoraria; Glaxo SmithKline/Synta, Consultant/Advisory Board receiving Consulting Fees/Honoraria; Merck(Schering), Speaker's Bureau receiving Honoraria; Merck (Schering), Consultant/Advisory Board receiving Consulting Fees/Honoraria; Pfizer, Consultant/Advisory Board receiving Consulting Fees/Honoraria. PC discloses the following relationship: Transgene, Advisory Committee receiving Honorarium. EJ discloses that The Johns Hopkins University, through a licensing agreement with BioSante, has the rights to future royalties on the GVAX approach discussed in this meeting. TG discloses the following relationships: GSK-Bio, Consultant and Protocol PI, receiving Honoraria and Clinical Trial Support; Eisai, Consultant and Protocol PI, receiving Honoraria and Clinical Trial Support; BMS, Consultant and Protocol PI, receiving Honoraria and Clinical Trial Support; Novartis, Protocol PI, receiving Clinical Trial Support; Roche, Protocol PI, receiving Clinical Trial Support. NR 5 TC 1 Z9 1 U1 1 U2 2 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 MAY 12 PY 2011 VL 9 AR 60 DI 10.1186/1479-5876-9-60 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 779ZP UT WOS:000291821000001 PM 21569425 ER PT J AU Graham, BS Crowe, JE AF Graham, Barney S. Crowe, James E., Jr. TI Tribute to David T. Karzon, MD and Robert M. Chanock, MD SO VACCINE LA English DT Biographical-Item C1 [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Crowe, James E., Jr.] Vanderbilt Univ, Sch Med, Vanderbilt Vaccine Ctr, Nashville, TN 37212 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Ctr Dr,MSC 3017 Bldg 40,Room 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 12 PY 2011 VL 29 IS 21 BP 3725 EP 3727 DI 10.1016/j.vaccine.2010.12.091 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 770FN UT WOS:000291072500001 ER PT J AU Ashby, MC Isaac, JTR AF Ashby, Michael C. Isaac, John T. R. TI Maturation of a Recurrent Excitatory Neocortical Circuit by Experience-Dependent Unsilencing of Newly Formed Dendritic Spines SO NEURON LA English DT Article ID RAT BARREL CORTEX; POSTSYNAPTICALLY SILENT SYNAPSES; MOUSE SOMATOSENSORY CORTEX; CORTICAL MAP PLASTICITY; SYNAPTIC CONNECTIONS; PYRAMIDAL NEURONS; THALAMOCORTICAL SYNAPSES; SENSORY DEPRIVATION; LAYER-IV; IN-VIVO AB Local recurrent excitatory circuits are ubiquitous in neocortex, yet little is known about their development or architecture. Here we introduce a quantitative technique for efficient single-cell resolution circuit mapping using 2-photon (2P) glutamate un-caging and analyze experience-dependent neonatal development of the layer 4 barrel cortex local excitatory circuit. We show that sensory experience specifically drives a 3-fold increase in connectivity at postnatal day (P) 9, producing a highly recurrent network. A profound dendritic spinogenesis occurs concurrent with the connectivity increase, but this is not experience dependent. However, in experience-deprived cortex, a much greater proportion of spines lack postsynaptic AMPA receptors (AMPARs) and synaptic connectivity via NMDA receptors (NMDARs) is the same as in normally developing cortex. Thus we describe a approach for quantitative circuit mapping and show that sensory experience sculpts an intrinsically developing template network, which is based on NMDAR-only synapses, by driving AMPARs into newly formed silent spines. C1 [Ashby, Michael C.; Isaac, John T. R.] Natl Inst Neurol Disorders & Stroke, NIH, Dev Synapt Plast Sect, Bethesda, MD 20892 USA. RP Ashby, MC (reprint author), Univ Walk, Univ Bristol, Sch Physiol & Pharmacol, Med Sci Bldg, Bristol BS8 1TD, Avon, England. EM m.c.ashby@bristol.ac.uk; isaac_john@lilly.com FU NINDS FX We thank members of the Isaac, Diamond, and McBain labs for helpful discussions during this study and to Dietmar Plenz for advice on network topology and graph theoretical analysis. We thank Dr. Ramesh Chittajallu and Dr. Sarah Caddick for contributing to the paired recording connectivity data set. This work was supported by the NINDS Intramural program. NR 53 TC 33 Z9 33 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 12 PY 2011 VL 70 IS 3 BP 510 EP 521 DI 10.1016/j.neuron.2011.02.057 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 768HZ UT WOS:000290926100012 PM 21555076 ER PT J AU Campo, E Swerdlow, SH Harris, NL Pileri, S Stein, H Jaffe, ES AF Campo, Elias Swerdlow, Steven H. Harris, Nancy L. Pileri, Stefano Stein, Harald Jaffe, Elaine S. TI The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications SO BLOOD LA English DT Article ID B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; PERIPHERAL T-CELL; GENE-EXPRESSION ANALYSIS; COMPARATIVE GENOMIC HYBRIDIZATION; PYOTHORAX-ASSOCIATED LYMPHOMA; NON-HODGKINS-LYMPHOMAS; GRAY ZONE LYMPHOMA; FOLLICULAR LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS AB The World Health Organization classification of lymphoid neoplasms updated in 2008 represents a worldwide consensus on the diagnosis of these tumors and is based on the recognition of distinct diseases, using a multidisciplinary approach. The updated classification refined the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. However, some questions were unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors, and the status of provisional entities, categories for which the World Health Organization working groups felt there was insufficient evidence to recognize as distinct diseases at this time. In addition, since its publication, new findings and ideas have been generated. This review summarizes the scientific rationale for the classification, emphasizing changes that have had an effect on practice guidelines. The authors address the criteria and significance of early or precursor lesions and the identification of certain lymphoid neoplasms largely associated with particular age groups, such as children and the elderly. The issue of borderline categories having overlapping features with large B-cell lymphomas, as well as several provisional entities, is reviewed. These new observations chart a course for future research in the field. (Blood. 2011; 117(19): 5019-5032) C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. [Campo, Elias] Univ Barcelona, Hematopathol Sect, Dept Anat Pathol, Hosp Clin,Inst Biomed Res August Pi i Sunyer IDIB, Barcelona, Spain. [Swerdlow, Steven H.] Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopathol, Pittsburgh, PA USA. [Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pileri, Stefano] Univ Bologna, Dept Haematol & Oncol Sci, Seragnoli St Orsola Malpighi Hosp, Bologna, Italy. [Stein, Harald] Reference Ctr Lymphoma & Hematopathol, Berlin, Germany. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov OI Jaffe, Elaine/0000-0003-4632-0301; Campo, elias/0000-0001-9850-9793 FU Associazione S.P.E.S. Onlus, Bologna; Friends of Jose Carreras International Leukemia Foundation; National Cancer Institute; Office of Rare Diseases, National Institutes of Health; Hoffman-La Roche; Genentech FX The preparatory works and the meeting of the Clinical Advisory Committee for the World Health Organization classification were supported in part by the Associazione S.P.E.S. Onlus, Bologna; Friends of Jose Carreras International Leukemia Foundation; National Cancer Institute; and the Office of Rare Diseases, National Institutes of Health; and unrestricted educational grants from Hoffman-La Roche and Genentech. NR 127 TC 498 Z9 538 U1 4 U2 41 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 MAY 12 PY 2011 VL 117 IS 19 BP 5019 EP 5032 DI 10.1182/blood-2011-01-293050 PG 14 WC Hematology SC Hematology GA 763BU UT WOS:000290528900008 PM 21300984 ER PT J AU Le, RQ Melenhorst, JJ Battiwalla, M Hill, B Memon, S Savani, BN Shenoy, A Hensel, NF Koklanaris, EK Keyvanfar, K Hakim, FT Douek, DC Barrett, AJ AF Le, Robert Quan Melenhorst, J. Joseph Battiwalla, Minoo Hill, Brenna Memon, Sarfraz Savani, Bipin N. Shenoy, Aarthi Hensel, Nancy F. Koklanaris, Eleftheria K. Keyvanfar, Keyvan Hakim, Frances T. Douek, Daniel C. Barrett, A. John TI Evolution of the donor T-cell repertoire in recipients in the second decade after allogeneic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; THYMIC FUNCTION; IMMUNE RECONSTITUTION; CLONAL COMPOSITION; CHIMERISM; DIVERSITY; MEMORY; ADULTS; AGE AB After allogeneic stem cell transplantation (SCT), T lymphocyte function is reestablished from the donor's postthymic T cells and through thymic T-cell neogenesis. The immune repertoire and its relation to that of the donor have not been characterized in detail in long-term adult SCT survivors. We studied 21 healthy patients in their second decade after a myeloablative SCT for hematologic malignancy (median follow-up, 12 years). Immune profiles were compared with donor samples cryopreserved at transplant and beyond 10 years from SCT. Only one recipient was on continuing immunosuppression. Compared with the donor at transplant, there was no significant difference in CD4, CD8, natural killer, and B-cell blood counts. However, compared with donors, recipients had significantly fewer naive T cells, lower T-cell receptor excision circle levels, fewer CD4 central memory cells, more effector CD8(+) cells, and more regulatory T cells. TCR repertoire analysis showed no significant difference in complexity of TCRV beta spectratype between recipients and donors, although spectratype profiles had diverged with both gain and loss of donor repertoire peaks in the recipient. In conclusion, long-term allogeneic SCT survivors have subtle defects in their immune profile consistent with defective thymic function but compatible with normal health. This study is registered at http://www.clinicaltrials.gov as NCT00106925. (Blood. 2011; 117(19): 5250-5256) C1 [Barrett, A. John] NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH,Hatfield CRC, Bethesda, MD 20892 USA. [Hill, Brenna; Douek, Daniel C.] NHLBI, Human Immunol Sect, VRC, NIH, Bethesda, MD 20892 USA. [Memon, Sarfraz; Hakim, Frances T.] NCI, Expt Transplantat Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol,Hematol & Stem Cell Transplanta, Nashville, TN USA. [Savani, Bipin N.] VAMC, Nashville, TN USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH,Hatfield CRC, Hlth Bldg 10,Rm 3-5330,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov FU National Institutes of Health, NHLBI FX This work was supported by the National Institutes of Health intramural research programs of the NHLBI. NR 25 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 12 PY 2011 VL 117 IS 19 BP 5250 EP 5256 DI 10.1182/blood-2011-01-329706 PG 7 WC Hematology SC Hematology GA 763BU UT WOS:000290528900033 PM 21421838 ER PT J AU Caracciolo, L Barbon, A Palumbo, S Mora, C Toscano, CD Bosetti, F Barlati, S AF Caracciolo, Luca Barbon, Alessandro Palumbo, Sara Mora, Cristina Toscano, Christopher D. Bosetti, Francesca Barlati, Sergio TI Altered mRNA Editing and Expression of Ionotropic Glutamate Receptors after Kainic Acid Exposure in Cyclooxygenase-2 Deficient Mice SO PLOS ONE LA English DT Article ID D-ASPARTATE RECEPTOR; GLUR6 KAINATE RECEPTORS; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; CEREBRAL-ISCHEMIA; NEURONAL DEATH; MEDIATED EXCITOTOXICITY; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; KINETIC-PROPERTIES AB Kainic acid (KA) binds to the AMPA/KA receptors and induces seizures that result in inflammation, oxidative damage and neuronal death. We previously showed that cyclooxygenase-2 deficient (COX-2(-/-)) mice are more vulnerable to KA-induced excitotoxicity. Here, we investigated whether the increased susceptibility of COX-2(-/-) mice to KA is associated with altered mRNA expression and editing of glutamate receptors. The expression of AMPA GluR2, GluR3 and KA GluR6 was increased in vehicle-injected COX-2(-/-) mice compared to wild type (WT) mice in hippocampus and cortex, whereas gene expression of NMDA receptors was decreased. KA treatment decreased the expression of AMPA, KA and NMDA receptors in the hippocampus, with a significant effect in COX-2(-/-) mice. Furthermore, we analyzed RNA editing levels and found that the level of GluR3 R/G editing site was selectively increased in the hippocampus and decreased in the cortex in COX-2(-/-) compared with WT mice. After KA, GluR4 R/G editing site, flip form, was increased in the hippocampus of COX-2(-/-) mice. Treatment of WT mice with the COX-2 inhibitor celecoxib for two weeks decreased the expression of AMPA/KA and NMDAR subunits after KA, as observed in COX-2(-/-) mice. After KA exposure, COX-2(-/-) mice showed increased mRNA expression of markers of inflammation and oxidative stress, such as cytokines (TNF-alpha, IL-1 beta and IL-6), inducible nitric oxide synthase (iNOS), microglia (CD11b) and astrocyte (GFAP). Thus, COX-2 gene deletion can exacerbate the inflammatory response to KA. We suggest that COX-2 plays a role in attenuating glutamate excitotoxicity by modulating RNA editing of AMPA/KA and mRNA expression of all ionotropic glutamate receptor subunits and, in turn, neuronal excitability. These changes may contribute to the increased vulnerability of COX-2(-/-) mice to KA. The overstimulation of glutamate receptors as a consequence of COX-2 gene deletion suggests a functional coupling between COX-2 and the glutamatergic system. C1 [Caracciolo, Luca; Palumbo, Sara; Toscano, Christopher D.; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Caracciolo, Luca; Barbon, Alessandro; Mora, Cristina; Barlati, Sergio] Univ Brescia, Div Biol & Genet, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Caracciolo, Luca; Barbon, Alessandro; Mora, Cristina; Barlati, Sergio] Univ Brescia, Natl Inst Neurosci, Brescia, Italy. RP Caracciolo, L (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM frances@mail.nih.gov RI Barbon, Alessandro/E-7037-2010; palumbo, sara/B-1603-2013 OI palumbo, sara/0000-0002-3809-6058 FU National Institute on Aging, National Institutes of Health FX This work was entirely supported by the Intramural Research Program of the National Institute on Aging, 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 66 TC 7 Z9 7 U1 1 U2 5 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 MAY 12 PY 2011 VL 6 IS 5 AR e19398 DI 10.1371/journal.pone.0019398 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763CL UT WOS:000290531100007 PM 21589914 ER PT J AU Roescher, N Vosters, JL Yin, HE Illei, GG Tak, PP Chiorini, JA AF Roescher, Nienke Vosters, Jelle L. Yin, Hongen Illei, Gabor G. Tak, Paul P. Chiorini, John A. TI Effect of Soluble ICAM-1 on a Sjogren's Syndrome-like Phenotype in NOD Mice Is Disease Stage Dependent SO PLOS ONE LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; SALIVARY-GLANDS; GENE-TRANSFER; CELLS; EXPRESSION; ACTIVATION; PATHWAYS; SELECTIN AB Introduction: Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjogren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility of ICAM-1 as a therapeutic target, we used local gene therapy in Non Obese Diabetic (NOD) mice to express soluble (s) ICAM-1 to compete with membrane bound ICAM-1 for binding with its receptor. Therapy was given prior to and just after the influx of immune cells into the SG. Methods: A recombinant serotype 2 adeno associated virus (rAAV2) encoding ICAM-1/Fc was constructed and its efficacy tested in the female NOD mice after retrograde instillation in SG at eight (early treatment) and ten (late treatment) weeks of age. SG inflammation was evaluated by focus score and immunohistochemical quantification of infiltrating cell types. Serum and SG tissue were analyzed for immunoglobulins (Ig). Results: Early treatment with ICAM-1/Fc resulted in decreased average number of inflammatory foci without changes in T and B cell composition. In contrast, late treated mice did not show any change in focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average higher IgG and IgA. Conclusions: Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since most patients are diagnosed when inflammation is clearly present within the SG. C1 [Roescher, Nienke; Vosters, Jelle L.; Tak, Paul P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. [Roescher, Nienke; Vosters, Jelle L.; Yin, Hongen; Illei, Gabor G.; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. RP Roescher, N (reprint author), Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM jchiorini@dir.nidcr.nih.gov FU Dutch Arthritis Association [NR 07-1-406]; NIH, NIDCR FX This work is supported by a Dutch Arthritis Association grant [NR 07-1-406] to JLV and an NIH, NIDCR intramural research grant to JAC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 6 Z9 8 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 MAY 12 PY 2011 VL 6 IS 5 AR e19962 DI 10.1371/journal.pone.0019962 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763CL UT WOS:000290531100035 PM 21589878 ER PT J AU Sung, HJ Ma, WZ Starost, MF Lago, CU Lim, PK Sack, MN Kang, JG Wang, PY Hwang, PM AF Sung, Ho Joong Ma, Wenzhe Starost, Matthew F. Lago, Cory U. Lim, Philip K. Sack, Michael N. Kang, Ju-Gyeong Wang, Ping-yuan Hwang, Paul M. TI Ambient Oxygen Promotes Tumorigenesis SO PLOS ONE LA English DT Article ID P53 TUMOR-SUPPRESSOR; DNA-DAMAGE; MITOCHONDRIAL-FUNCTION; ANTIOXIDANT DEFENSE; LIFE-SPAN; CANCER; HYPEROXIA; MICE; REQUIREMENT; HYPOXIA AB Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also cause genomic instability in cultured mammalian cells, its effect on de novo tumorigenesis at the organismal level is unclear. Herein, by decreasing ambient oxygen exposure, we report a similar to 50% increase in the median tumor-free survival time of p53-/- mice. In the thymus, reducing oxygen exposure decreased the levels of oxidative DNA damage and RAG recombinase, both of which are known to promote lymphomagenesis in p53-/- mice. Oxygen is further shown to be associated with genomic instability in two additional cancer models involving the APC tumor suppressor gene and chemical carcinogenesis. Together, these observations represent the first report directly testing the effect of ambient oxygen on de novo tumorigenesis and provide important physiologic evidence demonstrating its critical role in increasing genomic instability in vivo. C1 [Sung, Ho Joong; Ma, Wenzhe; Starost, Matthew F.; Lago, Cory U.; Lim, Philip K.; Sack, Michael N.; Kang, Ju-Gyeong; Wang, Ping-yuan; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Sung, Ho Joong] Eulji Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Gyeonggi Do, South Korea. RP Sung, HJ (reprint author), NHLBI, Ctr Mol Med, 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 This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 15 Z9 15 U1 2 U2 7 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 MAY 12 PY 2011 VL 6 IS 5 AR e19785 DI 10.1371/journal.pone.0019785 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763CL UT WOS:000290531100026 PM 21589870 ER PT J AU Serrano, MC Vavra, AK Jen, M Hogg, ME Murar, J Martinez, J Keefer, LK Ameer, GA Kibbe, MR AF Serrano, M. Concepcion Vavra, Ashley K. Jen, Michele Hogg, Melissa E. Murar, Jozef Martinez, Janet Keefer, Larry K. Ameer, Guillermo A. Kibbe, Melina R. TI Poly(diol-co-citrate)s as Novel Elastomeric Perivascular Wraps for the Reduction of Neointimal Hyperplasia SO MACROMOLECULAR BIOSCIENCE LA English DT Article DE biological application of polymers; elastomers; neointimal hyperplasia; nitric oxide; vascular ID NITRIC-OXIDE; INTIMAL HYPERPLASIA; ARTERIAL INJURY; VASCULAR GRAFTS; RELAXING FACTOR; VEIN GRAFTS; POLYMERS; DELIVERY; POLYURETHANES; ENDOTHELIUM AB The synthesis of poly(diol-co-citrate) elastomers that are biocompatible with vascular cells and can modulate the kinetics of the NO release based on the diol of selection is reported. NO-mediated cytostatic or cytotoxic effects can be controlled depending on the NO dose and the exposure time. When implanted in vivo in a rat carotid artery injury model, these materials demonstrate a significant reduction of neointimal hyperplasia. This is the first report of a NO-releasing polymer fabricated in the form of an elastomeric perivascular wrap for the treatment of neointimal hyperplasia. These elastomers also show promise for other cardiovascular pathologies where NO-based therapies could be beneficial. C1 [Serrano, M. Concepcion; Jen, Michele; Ameer, Guillermo A.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Vavra, Ashley K.; Hogg, Melissa E.; Murar, Jozef; Martinez, Janet; Ameer, Guillermo A.; Kibbe, Melina R.] Northwestern Univ, Inst BioNanotechnol Med, Div Vasc Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Ameer, GA (reprint author), Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. EM g-ameer@northwestern.edu; mkibbe@nmh.org RI Ameer, Guillermo/B-6765-2009; Serrano, Maria Concepcion/D-7442-2014; Keefer, Larry/N-3247-2014 OI Serrano, Maria Concepcion/0000-0002-5010-644X; Keefer, Larry/0000-0001-7489-9555 FU NSF-NSEC; NSF-MRSEC; Keck Foundation; State of Illinois; Northwestern University; National Institutes of Health (NIH) [1 K08HL084203, N01-CO-2008-00001, HHSN261200800001E]; American Vascular Association; Alpha Omega Alpha Honor Medical Society; National Cancer Institute (NCI); NIH, NCI, Center for Cancer Research; Ministerio de Ciencia e Innovacion of Spain FX FT-IR and XPS work was performed in the Keck-II facility of NUANCE Center at Northwestern University. NUANCE Center is supported by NSF-NSEC, NSF-MRSEC, Keck Foundation, the State of Illinois, and Northwestern University. In addition, this project has been funded in part with Federal funds from the National Institutes of Health (NIH, under contracts 1 K08HL084203 - MRK-, N01-CO-2008-00001 with SAIC-Frederick, Inc., and HHSN261200800001E - LKK), the American Vascular Association (MRK), the Alpha Omega Alpha Honor Medical Society (JM), the National Cancer Institute (NCI), and by the Intramural Research Program of the NIH, NCI, Center for Cancer Research (LKK). It was also supported in part by the generosity of Mrs. Hilda Rosenbloom. The authors would like to thank Dr. Messersmith's laboratory for the assistance with the contact angle measurements. M.C.S. is greatly indebted to the Ministerio de Ciencia e Innovacion of Spain for a postdoctoral fellowship. NR 46 TC 11 Z9 12 U1 1 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1616-5187 J9 MACROMOL BIOSCI JI Macromol. Biosci. PD MAY 12 PY 2011 VL 11 IS 5 BP 700 EP 709 DI 10.1002/mabi.201000509 PG 10 WC Biochemistry & Molecular Biology; Materials Science, Biomaterials; Polymer Science SC Biochemistry & Molecular Biology; Materials Science; Polymer Science GA 761ZY UT WOS:000290443200014 PM 21341372 ER PT J AU Alter, H AF Alter, Harvey TI Baruch Blumberg (1925-2011) OBITUARY SO NATURE LA English DT Biographical-Item RP Alter, H (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM halter@dtm.cc.nih.gov NR 0 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 12 PY 2011 VL 473 IS 7346 BP 155 EP 155 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 762NT UT WOS:000290487200022 PM 21562549 ER PT J AU DeFusco, A Ivanic, J Schmidt, MW Gordon, MS AF DeFusco, Albert Ivanic, Joseph Schmidt, Michael W. Gordon, Mark S. TI Solvent-Induced Shifts in Electronic Spectra of Uracil SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID FRAGMENT POTENTIAL METHOD; ASTERISK EXCITED-STATE; REACTION FIELD-THEORY; NUCLEIC-ACID BASES; CONFIGURATION-INTERACTION; CONICAL INTERSECTIONS; PERTURBATION-THEORY; MOLECULAR-DYNAMICS; AQUEOUS-SOLUTION; PI-ASTERISK AB Highly accurate excitation spectra are predicted for the low-lying n-pi* and pi-pi* states of uracil for both the gas phase and in water employing the complete active space self-consistent field (CASSCF) and multiconfigurational quaside-generate perturbation theory (MCQDPT) methods. Implementation of the effective fragment potential (EFP) solvent method with CASSCF and MCQDPT enables the prediction of highly accurate solvated spectra, along with a direct interpretation of solvent shifts in terms of intermolecular interactions between solvent and solute. Solvent shifts of the n-pi* and pi-pi* ye excited states arise mainly from a change in the electrostatic interaction between solvent and solute upon photoexcitation. Polarization (induction) interactions contribute about 0.1 eV to the solvent-shifted excitation. The blue shift of the n-pi* state is found to be 0.43 eV and the red shift of the pi-pi* state is found to be -0.26 eV. Furthermore, the spectra show that in solution the pi-pi* state is 0.4 eV lower in energy than the n-pi* state. C1 [DeFusco, Albert; Schmidt, Michael W.; Gordon, Mark S.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [DeFusco, Albert; Schmidt, Michael W.; Gordon, Mark S.] Iowa State Univ, Ames Lab, Ames, IA 50011 USA. [Ivanic, Joseph] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Gordon, MS (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. EM mark@si.msg.chem.iastate.edu FU National Science Foundation; Department of Energy FX This work was supported in part by a National Science Foundation Petascale Applications grant and in part by a Department of Energy Computational and Theoretical Chemistry grant. NR 57 TC 37 Z9 37 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD MAY 12 PY 2011 VL 115 IS 18 BP 4574 EP 4582 DI 10.1021/jp112230f PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 757YZ UT WOS:000290126900002 PM 21491886 ER PT J AU Wang, EN Bussom, S Chen, JG Quinn, C Bedognetti, D Lam, W Guan, FL Jiang, ZL Mark, Y Zhao, YD Stroncek, DF White, J Marincola, FM Cheng, YC AF Wang, Ena Bussom, Scott Chen, Jinguo Quinn, Courtney Bedognetti, Davide Lam, Wing Guan, Fulan Jiang, Zaoli Mark, Yichao Zhao, Yingdong Stroncek, David F. White, Jeffrey Marincola, Francesco M. Cheng, Yung-Chi TI Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment SO BMC MEDICAL GENOMICS LA English DT Article ID INTERFERON REGULATORY FACTOR; TOLL-LIKE RECEPTORS; NF-KAPPA-B; INDUCED APOPTOSIS; CELL-DEATH; CANCER; ACTIVATION; CHEMOTHERAPY; INDUCTION; REJECTION AB Background -: Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906. Methods -: Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of CPT-11 (CPT-11) by PHY906 in a well-characterized pre-clinical model; the administration of PHY906 and CPT-11 to female BDF-1 mice bearing subcutaneous Colon 38 tumors. Results -: We observed that 1) individually PHY906 and CPT-11 induce distinct alterations in tumor, liver and spleen; 2) PHY906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of CPT-11, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection. Conclusions -: PHY906 together with CPT-11 triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response. C1 [Wang, Ena; Chen, Jinguo; Quinn, Courtney; Bedognetti, Davide; Mark, Yichao; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Chen, Jinguo; Quinn, Courtney; Bedognetti, Davide; Mark, Yichao; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA. [Bussom, Scott; Lam, Wing; Guan, Fulan; Jiang, Zaoli; Cheng, Yung-Chi] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Bedognetti, Davide] Univ Genoa, Dept Oncol Biol & Genet, I-16132 Genoa, Italy. [Bedognetti, Davide] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy. [Bedognetti, Davide] Natl Canc Res Inst Genoa, I-16132 Genoa, Italy. [Zhao, Yingdong] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Stroncek, David F.] NIH, Cell Therapy Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [White, Jeffrey] NCI, Off Canc Complementary & Alternat Med, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM FMarincola@mail.cc.nih.gov; yccheng@yale.edu RI Bedognetti, Davide/A-9090-2012; Guan, Fulan/I-2235-2013; GUAN, FULAN/I-5971-2013; OI Bedognetti, Davide/0000-0002-5857-773X FU National Cancer Institute (NCI) [UO-63477]; National Institutes of Health (NIH), USA FX This study was in part supported by Grant UO-63477 from the National Cancer Institute (NCI) and National Institutes of Health (NIH), USA; Dr. Yung-Chi Cheng is a Fellow of the National Foundation for Cancer Research. NR 36 TC 31 Z9 35 U1 3 U2 37 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 MAY 11 PY 2011 VL 4 AR 38 DI 10.1186/1755-8794-4-38 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 778KN UT WOS:000291702700001 PM 21569348 ER PT J AU Sakai, K Barnitz, RA Chaigne-Delalande, B Bidere, N Lenardo, MJ AF Sakai, Keiko Barnitz, R. Anthony Chaigne-Delalande, Benjamin Bidere, Nicolas Lenardo, Michael J. TI Human Immunodeficiency Virus Type 1 Vif causes dysfunction of Cdk1 and CyclinB1: implications for cell cycle arrest SO VIROLOGY JOURNAL LA English DT Article ID MATURATION-PROMOTING FACTOR; UBIQUITIN LIGASE COMPLEX; PROTEIN-KINASE; HIV-1 VPR; PHOSPHORYLATION SITES; T-CELLS; M-PHASE; P34CDC2 PHOSPHORYLATION; NUCLEAR IMPORT; G(2) ARREST AB The two major cytopathic factors in human immunodeficiency virus type 1 (HIV-1), the accessory proteins viral infectivity factor (Vif) and viral protein R (Vpr), inhibit cell-cycle progression at the G2 phase of the cell cycle. Although Vpr-induced blockade and the associated T-cell death have been well studied, the molecular mechanism of G2 arrest by Vif remains undefined. To elucidate how Vif induces arrest, we infected synchronized Jurkat T-cells and examined the effect of Vif on the activation of Cdk1 and CyclinB1, the chief cell-cycle factors for the G2 to M phase transition. We found that the characteristic dephosphorylation of an inhibitory phosphate on Cdk1 did not occur in infected cells expressing Vif. In addition, the nuclear translocation of Cdk1 and CyclinB1 was disregulated. Finally, Vif-induced cell cycle arrest was correlated with proviral expression of Vif. Taken together, our results suggest that Vif impairs mitotic entry by interfering with Cdk1-CyclinB1 activation. C1 [Sakai, Keiko; Barnitz, R. Anthony; Chaigne-Delalande, Benjamin; Bidere, Nicolas; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Sakai, Keiko] Kumamoto Univ, Ctr AIDS Res, Div Viral Immunol, Kumamoto, Japan. [Barnitz, R. Anthony] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bidere, Nicolas] Univ Paris 11, Hop Paul Brousse, INSERM, U542, Villejuif, France. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI sakai, Keiko/F-5807-2013; Kumamoto University, CAIDS/G-8446-2013; bidere, nicolas/K-8887-2015; OI bidere, nicolas/0000-0001-9177-0008; Barnitz, Tony/0000-0002-9634-4558 FU National Institutes of Allergy and Infectious Diseases, National Institutes of Health, USA; Japan Society for the Promotion of Science (JSPS) FX The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 Vif Monoclonal Antibody (# 319) from Dr. Michael H. Malim and HIV-1HXB2 Vif Antiserum from Dr. Dana Gabuzda. We thank Owen Schwartz for microscopy assistance; Anthony Fauci for generous availability of his BL-3 facility; Diane Bolton and the members of the Lenardo laboratory for helpful discussions. This research was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, USA. KS was partially supported as a Research Fellow by Japan Society for the Promotion of Science (JSPS). NR 57 TC 6 Z9 8 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAY 11 PY 2011 VL 8 AR 219 DI 10.1186/1743-422X-8-219 PG 8 WC Virology SC Virology GA 777RJ UT WOS:000291641900003 PM 21569376 ER PT J AU Hill, LD Hilliard, DD York, TP Srinivas, S Kusanovic, JP Gomez, R Elovitz, MA Romero, R Strauss, JF AF Hill, Lori D. Hilliard, DaShaunda D. York, Timothy P. Srinivas, Sindhu Kusanovic, Juan P. Gomez, Ricardo Elovitz, Michal A. Romero, Roberto Strauss, Jerome F., III TI Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study SO BMC MEDICAL GENETICS LA English DT Article ID SEX-RATIO; ENDOPLASMIC-RETICULUM; OXYTOCINASE SUBFAMILY; NORMAL-PREGNANCY; MATERNAL ANEMIA; SPIRAL ARTERIES; PLACENTAL BED; RISK; AMINOPEPTIDASES; GENE AB Background: Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia. Methods: A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal). Results: We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population. Conclusions: We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia. C1 [Hill, Lori D.; Hilliard, DaShaunda D.; Strauss, Jerome F., III] Virginia Commonwealth Univ Sch Med, Dept Obstet & Gynecol, Richmond, VA 23298 USA. [Hill, Lori D.; Hilliard, DaShaunda D.; Strauss, Jerome F., III] Virginia Commonwealth Univ Sch Med, Ctr Hlth Dispar, Richmond, VA 23298 USA. [York, Timothy P.] Virginia Commonwealth Univ Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Srinivas, Sindhu; Elovitz, Michal A.] Univ Penn Sch Med, Maternal & Child Hlth Res Program, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Kusanovic, Juan P.; Romero, Roberto] NICHD NIH DHHS, Perinatol Res Branch, Bethesda, MD USA. [Kusanovic, Juan P.; Romero, Roberto] NICHD NIH DHHS, Perinatol Res Branch, Detroit, MI 48201 USA. [Gomez, Ricardo] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Santiago, Chile. [Kusanovic, Juan P.; Gomez, Ricardo] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile. RP Strauss, JF (reprint author), Virginia Commonwealth Univ Sch Med, Dept Obstet & Gynecol, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS [P60MD002256, R01HD034612]; National Center for Research Resources [UL1RR031990]; NIH Roadmap for Medical Research, NIH; University of Pennsylvania Research foundation from Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS [K12HD001265]; National Heart, Lung, and Blood Institute, NIH, DHHS [1T32HLO942900-1A1] FX This study was supported, in part, by P60MD002256 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS; R01HD034612 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS; UL1RR031990 from the National Center for Research Resources and the NIH Roadmap for Medical Research, NIH; University of Pennsylvania Research foundation grant, K12HD001265 (PI Driscoll; Scholar Srinivas) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS; the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS; and 1T32HLO942900-1A1 from the National Heart, Lung, and Blood Institute, NIH, DHHS. NR 73 TC 15 Z9 17 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD MAY 11 PY 2011 VL 12 AR 64 DI 10.1186/1471-2350-12-64 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 771IG UT WOS:000291149800001 PM 21569342 ER PT J AU Silva, APG Chechik, M Byrne, RT Waterman, DG Ng, CL Dodson, EJ Koonin, EV Antson, AA Smits, C AF Silva, Ana P. G. Chechik, Maria Byrne, Robert T. Waterman, David G. Ng, C. Leong Dodson, Eleanor J. Koonin, Eugene V. Antson, Alfred A. Smits, Callum TI Structure and Activity of a Novel Archaeal beta-CASP Protein with N-Terminal KH Domains SO STRUCTURE LA English DT Article ID POLYADENYLATION SPECIFICITY FACTOR; CRYSTAL-STRUCTURE; RNA-BINDING; MESSENGER-RNA; SEQUENCE ALIGNMENT; NUCLEIC-ACIDS; EXOSOME; DEGRADATION; CLEAVAGE; MOTIF AB MTH1203, a beta-CASP metallo-beta-lactamase family nuclease from the archaeon Methanothermobacter thermautotrophicus, was identified as a putative nuclease that might contribute to RNA processing. The crystal structure of MTH1203 reveals that, in addition to the metallo-beta-lactamase nuclease and the beta-CASP domains, it contains two contiguous KH domains that are unique to MTH1203 and its orthologs. RNA-binding experiments indicate that MTH1203 preferentially binds U-rich sequences with a dissociation constant in the micromolar range. In vitro nuclease activity assays demonstrated that MTH1203 is a zinc-dependent nuclease. MTH1203 is also shown to be a dimer and, significantly, this dimerization enhances the nuclease activity. Transcription termination in archaea produces mRNA transcripts with U-rich 3' ends that could be degraded by MTH1203 considering its RNA-binding specificity. We hypothesize that this nuclease degrades mRNAs of proteins targeted for degradation and so regulates archaeal RNA turnover, possibly in concert with the exosome. C1 [Ng, C. Leong] MRC Lab Mol Biol, Struct Studies Div, Cambridge CB2 0QH, England. [Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Silva, Ana P. G.; Chechik, Maria; Byrne, Robert T.; Waterman, David G.; Dodson, Eleanor J.; Antson, Alfred A.; Smits, Callum] Univ York, York Struct Biol Lab, Dept Chem, York YO10 5YW, N Yorkshire, England. RP Smits, C (reprint author), Univ Manchester, Fac Life Sci, Michael Smith Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. EM callum@ysbl.york.ac.uk RI Ng, Chyan Leong/E-9689-2014; Antson, Alfred/N-2551-2016; OI Ng, Chyan Leong/0000-0001-8590-7418; Antson, Alfred/0000-0002-4533-3816; Byrne, Robert/0000-0002-2351-6937 FU Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BD/17372/2004]; BBSRC; Wellcome Trust [081916] FX We thank Johan Turkenburg and Sam Hart for collecting the X-ray data and ESRF (Grenoble) for provision of data collection facilities. We also thank James Chong for the M. thermautotrophicus cells. This work was supported by Fundacao para a Ciencia e a Tecnologia, Portugal (studentship SFRH/BD/17372/2004 to A.P.G.S.), by the BBSRC (PhD studentship to R.T.B.) and by the Wellcome Trust (fellowship 081916 to A.A.A.). NR 47 TC 10 Z9 10 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD MAY 11 PY 2011 VL 19 IS 5 BP 622 EP 632 DI 10.1016/j.str.2011.03.002 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 766VU UT WOS:000290815500005 PM 21565697 ER PT J AU Justinova, Z Yasar, S Redhi, GH Goldberg, SR AF Justinova, Zuzana Yasar, Sevil Redhi, Godfrey H. Goldberg, Steven R. TI The Endogenous Cannabinoid 2-Arachidonoylglycerol Is Intravenously Self-Administered by Squirrel Monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ENDOCANNABINOID CONTENTS; RECEPTOR-LIGAND; ANANDAMIDE; BRAIN; AGONIST; RATS; INHIBITION; HYDROLYSIS; ANTAGONISM; BLOCKADE AB Two endogenous ligands for cannabinoid CB(1) receptors, anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol (2-AG), have been identified and characterized. 2-AG is the most prevalent endogenous cannabinoid ligand in the brain, and electrophysiological studies suggest 2-AG, rather than anandamide, is the true natural ligand for cannabinoid receptors and the key endocannabinoid involved in retrograde signaling in the brain. Here, we evaluated intravenously administered 2-AG for reinforcing effects in nonhuman primates. Squirrel monkeys that previously self-administered anandamide or nicotine under a fixed-ratio schedule with a 60 s timeout after each injection had their self-administration behavior extinguished by vehicle substitution and were then given the opportunity to self-administer 2-AG. Intravenous 2-AG was a very effective reinforcer of drug-taking behavior, maintaining higher numbers of self-administered injections per session and higher rates of responding than vehicle across a wide range of doses. To assess involvement of CB(1) receptors in the reinforcing effects of 2-AG, we pretreated monkeys with the cannabinoid CB(1) receptor inverse agonist/antagonist rimonabant [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide]. Rimonabant produced persistent blockade of 2-AG self-administration without affecting responding maintained by food under similar conditions. Thus, 2-AG was actively self-administered by monkeys with or without a history of cannabinoid self-administration, and the reinforcing effects of 2-AG were mediated by CB(1) receptors. Self-administration of 2-AG by squirrel monkeys provides a valuable procedure for studying abuse liability of medications that interfere with 2-AG signaling within the brain and for investigating mechanisms involved in the reinforcing effects of endocannabinoids. C1 [Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, IRP, NIH,Behav Neurosci Res Branch,Dept Hlth & Human S, Baltimore, MD 21224 USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Catonsville, MD 21228 USA. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, IRP, NIH,Behav Neurosci Res Branch,Dept Hlth & Human S, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sgoldber@mail.nih.gov RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 FU National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services. NR 29 TC 29 Z9 29 U1 0 U2 0 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 MAY 11 PY 2011 VL 31 IS 19 BP 7043 EP 7048 DI 10.1523/JNEUROSCI.6058-10.2011 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 762XB UT WOS:000290514400013 PM 21562266 ER PT J AU Raznahan, A Shaw, P Lalonde, F Stockman, M Wallace, GL Greenstein, D Clasen, L Gogtay, N Giedd, JN AF Raznahan, Armin Shaw, Phillip Lalonde, Francois Stockman, Mike Wallace, Gregory L. Greenstein, Dede Clasen, Liv Gogtay, Nitin Giedd, Jay N. TI How Does Your Cortex Grow? SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CORTICAL SURFACE-AREA; HUMAN CEREBRAL-CORTEX; BRAIN-DEVELOPMENT; TRAJECTORIES; ADOLESCENCE; CHILDHOOD; ANATOMY; VOLUME; SIZE; TWIN AB Understanding human cortical maturation is a central goal for developmental neuroscience. Significant advances toward this goal have come from two recent strands of in vivo structural magnetic resonance imaging research: (1) longitudinal study designs have revealed that factors such as sex, cognitive ability, and disease are often better related to variations in the tempo of anatomical change than to variations in anatomy at any one time point; (2) largely cross-sectional applications of new surface-based morphometry (SBM) methods have shown how the traditional focus on cortical volume (CV) can obscure information about the two evolutionarily and genetically distinct determinants of CV: cortical thickness (CT) and surface area (SA). Here, by combining these two strategies for the first time and applying SBM in > 1250 longitudinally acquired brain scans from 647 healthy individuals aged 3-30 years, we deconstruct cortical development to reveal that distinct trajectories of anatomical change are hidden within, and give rise to, a curvilinear pattern of CV maturation. Developmental changes in CV emerge through the sexually dimorphic and age-dependent interaction of changes in CT and SA. Moreover, SA change itself actually reflects complex interactions between brain size-related changes in exposed cortical convex hull area, and changes in the degree of cortical gyrification, which again vary by age and sex. Knowing of these developmental dissociations, and further specifying their timing and sex-biases, provides potent new research targets for basic and clinical neuroscience. C1 [Raznahan, Armin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Raznahan, A (reprint author), NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. EM raznahana@mail.nih.gov RI Giedd, Jay/A-3080-2008; Gogtay, Nitin/A-3035-2008; Raznahan, Armin/F-4534-2012; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace, Gregory/0000-0003-0329-5054 FU National Institutes of Health, National Institute of Health Intramural Research; UK Medical Research Council [G0701370] FX This study was supported by the National Institutes of Health, National Institute of Health Intramural Research, and a UK Medical Research Council Clinical Research Training Fellowship (G0701370 to A.R.). We thank the participants who took part in this study. NR 24 TC 202 Z9 203 U1 1 U2 23 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 MAY 11 PY 2011 VL 31 IS 19 BP 7174 EP 7177 DI 10.1523/JNEUROSCI.0054-11.2011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 762XB UT WOS:000290514400028 PM 21562281 ER PT J AU Lantos, J Matlock, AM Wendler, D AF Lantos, John Matlock, Ann Marie Wendler, David TI Patient Autonomy and Clinician Integrity in Treatment Decisions Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Lantos, John] Childrens Mercy Hosp, Childrens Mercy Bioeth Ctr, Kansas City, MO 64108 USA. [Matlock, Ann Marie; Wendler, David] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Lantos, J (reprint author), Childrens Mercy Hosp, Childrens Mercy Bioeth Ctr, Kansas City, MO 64108 USA. EM jlantos@cmh.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 11 PY 2011 VL 305 IS 18 BP 1861 EP 1862 DI 10.1001/jama.2011.586 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 761YH UT WOS:000290438800020 ER PT J AU Najjar, SS Rao, SV Melloni, C Raman, SV Povsic, TJ Melton, L Barsness, GW Prather, K Heitner, JF Kilaru, R Gruberg, L Hasselblad, V Greenbaum, AB Patel, M Kim, RJ Talan, M Ferrucci, L Longo, DL Lakatta, EG Harrington, RA AF Najjar, Samer S. Rao, Sunil V. Melloni, Chiara Raman, Subha V. Povsic, Thomas J. Melton, Laura Barsness, Gregory W. Prather, Kristi Heitner, John F. Kilaru, Rakhi Gruberg, Luis Hasselblad, Vic Greenbaum, Adam B. Patel, Manesh Kim, Raymond J. Talan, Mark Ferrucci, Luigi Longo, Dan L. Lakatta, Edward G. Harrington, Robert A. CA REVEAL Investigators TI Intravenous Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction REVEAL: A Randomized Controlled Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; ISCHEMIA-REPERFUSION INJURY; MORTALITY; DISEASE; AGE; THROMBOLYSIS; ENHANCEMENT; EXPRESSION; EXPANSION; PROTECTS AB Context Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. Objective To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. Design, Setting, and Patients A prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60 000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October 2006 and February 2010, and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. Intervention Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. Main Outcome Measure Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2 to 6 days after study medication administration (first CMR) and again 12 +/- 2 weeks later (second CMR). Results In the efficacy cohort, the infarct size did not differ between groups on either the first CMR scan (n=136; 15.8% LV mass [95% confidence interval {CI}, 13.3-18.2% LV mass] for the epoetin alfa group vs 15.0% LV mass [95% CI, 12.6-17.3% LV mass] for the placebo group; P=.67) or on the second CMR scan (n=124; 10.6% LV mass [95% CI, 8.4-12.8% LV mass] vs 10.4% LV mass [95% CI, 8.5-12.3% LV mass], respectively; P=.89). In a prespecified analysis of patients aged 70 years or older (n=21), the mean infarct size within the first week (first CMR) was larger in the epoetin alfa group (19.9% LV mass; 95% CI, 14.0-25.7% LV mass) than in the placebo group (11.7% LV mass; 95% CI, 7.2-16.1% LV mass) (P=.03). In the safety cohort, of the 125 patients who received epoetin alfa, the composite outcome of death, MI, stroke, or stent thrombosis occurred in 5 (4.0%; 95% CI, 1.31%-9.09%) but in none of the 97 who received placebo (P=.04). Conclusions In patients with STEMI who had successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Subgroup analyses raised concerns about an increase in infarct size among older patients. C1 [Najjar, Samer S.] Washington Hosp Ctr, MedStar Hlth Res Inst, Washington, DC 20010 USA. [Najjar, Samer S.; Talan, Mark; Ferrucci, Luigi; Longo, Dan L.; Lakatta, Edward G.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Rao, Sunil V.; Melloni, Chiara; Povsic, Thomas J.; Patel, Manesh; Kim, Raymond J.; Harrington, Robert A.] Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA. [Rao, Sunil V.; Melloni, Chiara; Povsic, Thomas J.; Melton, Laura; Prather, Kristi; Kilaru, Rakhi; Hasselblad, Vic; Patel, Manesh; Harrington, Robert A.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Raman, Subha V.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA. [Barsness, Gregory W.] Mayo Clin, Rochester, MN USA. [Heitner, John F.] New York Methodist Hosp, Brooklyn, NY USA. [Gruberg, Luis] SUNY Stony Brook, Med Ctr, Div Cardiol, Stony Brook, NY 11794 USA. [Greenbaum, Adam B.] Henry Ford Hlth Syst, Div Cardiol, W Bloomfield, MI USA. RP Najjar, SS (reprint author), Washington Hosp Ctr, MedStar Hlth Res Inst, 110 Irving St NW, Washington, DC 20010 USA. EM Samer.S.Najjar@medstar.net RI Kim, Raymond/B-1426-2008 FU Novartis; Cordis Corporation; Ikaria; National Institutes of Health; Siemens Corporation; Baxter International; Regado Biosciences; Theragen; Empire Clinical Research Investigator Program; Eli Lilly; Medicure Inc; National Institute on Aging [HHS-N-260-2005-00010-C]; Centocor Ortho Biotech nor Florida Biologix FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Najjar reported receiving research funding from HeartWare. Dr Rao reported receiving research funding from Novartis, Cordis Corporation, and Ikaria; and being a consultant for sanofi-aventis, Bristol-Meyers Squibb, Astra-Zeneca, Daiichi Sankyo-Lilly, and Terumo USA. Dr Raman reported receiving grant support from the National Institutes of Health and from Siemens Corporation. Dr Povsic reported receiving grants from Baxter International, Regado Biosciences, and Theragen. Dr Barsness reported being a consultant for Gilead Sciences Inc and receiving travel compensation from Novartis Pharmaceuticals Corporation. Dr Heitner reported that New York Methodist Hospital received compensation for his work as a principal investigator for a study; receiving compensation for his expert testimony in an individual malpractice case; receiving grant support from the Empire Clinical Research Investigator Program; and receiving compensation for serving on a steering committee for a trial. Dr Hasselblad reported receiving salary support via grants from Eli Lilly and Medicure Inc administered through Duke University. Dr Greenbaum reported receiving compensation from various law firms for expert testimony; compensation for serving on speakers bureaus for various companies; and owning stock or stock options in various other device and health care companies. Dr Patel reported being a board member for Genzyme's advisory board and Bayer Healthcare; and serving as a consultant for Ikaria. Dr Kim reported being an inventor on a US patent for Delayed Enhancement MRI, which is owned by Northwestern University. Dr Harrington reported that a complete listing of disclosure information is available at https://dcri.org/about-us/conflict-of-interest/Harrington-COI_2010.pdf. None of the other authors reported disclosures.; This study was supported by Intramural Research Program contract HHS-N-260-2005-00010-C from the National Institute on Aging.; The Duke Clinical Research Institute served as the coordinating center under contract from the National Institute on Aging. Investigators from the National Institute on Aging and the Duke Clinical Research Institute collaborated in designing and supervising the conduct of the study. Neither Centocor Ortho Biotech nor Florida Biologix provided funding or had input into the design or conduct of the study nor any input into data collection, data analysis, or the writing of the manuscript. NR 40 TC 133 Z9 140 U1 0 U2 3 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 MAY 11 PY 2011 VL 305 IS 18 BP 1863 EP 1872 DI 10.1001/jama.2011.592 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 761YH UT WOS:000290438800023 PM 21558517 ER PT J AU Gahl, WA Tifft, CJ AF Gahl, William A. Tifft, Cynthia J. TI The NIH Undiagnosed Diseases Program Lessons Learned SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MUTATIONS C1 [Tifft, Cynthia J.] NHGRI, NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Tifft, CJ (reprint author), NHGRI, NIH, Undiagnosed Dis Program, 10 Ctr Dr,MSC 1205,Bldg 10,Room CRC3-2551, Bethesda, MD 20892 USA. EM ctifft@nih.gov NR 6 TC 41 Z9 41 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 MAY 11 PY 2011 VL 305 IS 18 BP 1904 EP 1905 DI 10.1001/jama.2011.613 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 761YH UT WOS:000290438800030 PM 21558523 ER PT J AU Blackstone, C Chang, CR AF Blackstone, Craig Chang, Chuang-Rung TI Mitochondria unite to survive SO NATURE CELL BIOLOGY LA English DT Editorial Material ID DEPENDENT PROTEIN-KINASE; DRP1; PHOSPHORYLATION; MITOPHAGY; FISSION; DEGRADATION; STARVATION; DEATH AB Starvation of animals or cells triggers autophagic degradation of cell contents to retrieve nutrients, but, paradoxically, mitochondria enlarge. This is now shown to result from inhibition of mitochondrial fission through PKA-mediated phosphorylation of the GTPase DRP1. Elongation of mitochondria optimizes ATP production and spares them from autophagy-mediated destruction. C1 [Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Chang, Chuang-Rung] Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu 30013, Taiwan. [Chang, Chuang-Rung] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu 30013, Taiwan. RP Blackstone, C (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov RI Chang, Chuang-Rung /C-1815-2012 NR 15 TC 23 Z9 24 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY 11 PY 2011 VL 13 IS 5 BP 521 EP 522 DI 10.1038/ncb0511-521 PG 2 WC Cell Biology SC Cell Biology GA 758FY UT WOS:000290148700009 PM 21540850 ER PT J AU Bai, M Gad, H Turacchio, G Cocucci, E Yang, JS Li, J Beznoussenko, GV Nie, ZZ Luo, RB Fu, LW Collawn, JF Kirchhausen, T Luini, A Hsu, VW AF Bai, Ming Gad, Helge Turacchio, Gabriele Cocucci, Emanuele Yang, Jia-Shu Li, Jian Beznoussenko, Galina V. Nie, Zhongzhen Luo, Ruibai Fu, Lianwu Collawn, James F. Kirchhausen, Tomas Luini, Alberto Hsu, Victor W. TI ARFGAP1 promotes AP-2-dependent endocytosis SO NATURE CELL BIOLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CLATHRIN-MEDIATED ENDOCYTOSIS; COPI VESICLE FORMATION; TRANSFERRIN RECEPTOR; SORTING SIGNALS; GOLGI TRANSPORT; ENDOPLASMIC-RETICULUM; ADAPTER COMPLEX; ALPHA-APPENDAGE; COATED VESICLES AB COPI (coat protein I) and the clathrin-AP-2 (adaptor protein 2) complex are well-characterized coat proteins, but a component that is common to these two coats has not been identified. The GTPase-activating protein (GAP) for ADP-ribosylation factor 1 (ARF1), ARFGAP1, is a known component of the COPI complex. Here, we show that distinct regions of ARFGAP1 interact with AP-2 and coatomer (components of the COPI complex). Selectively disrupting the interaction of ARFGAP1 with either of these two coat proteins leads to selective inhibition in the corresponding transport pathway. The role of ARFGAP1 in AP-2-regulated endocytosis has mechanistic parallels with its roles in COPI transport, as both its GAP activity and coat function contribute to promoting AP-2 transport. C1 [Bai, Ming; Yang, Jia-Shu; Li, Jian; Hsu, Victor W.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA. [Bai, Ming; Yang, Jia-Shu; Li, Jian; Hsu, Victor W.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Gad, Helge; Turacchio, Gabriele; Beznoussenko, Galina V.; Luini, Alberto] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Chieti, Italy. [Gad, Helge] Stockholm Univ, Dept Genet Microbiol & Toxicol, S-10691 Stockholm, Sweden. [Turacchio, Gabriele] CNR, Inst Prot Biochem, I-80131 Naples, Italy. [Cocucci, Emanuele; Kirchhausen, Tomas] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. [Cocucci, Emanuele; Kirchhausen, Tomas] Immune Dis Inst, Boston, MA 02115 USA. [Nie, Zhongzhen] Univ Florida Coll Med, Dept Urol, Gainesville, FL 32610 USA. [Luo, Ruibai] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Fu, Lianwu; Collawn, James F.] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. [Luini, Alberto] Telethon Inst Genet & Med, I-80131 Naples, Italy. RP Hsu, VW (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA. EM vhsu@rics.bwh.harvard.edu RI Gad, Helge/J-2238-2014; Luini, Alberto/L-1372-2013 OI Luini, Alberto/0000-0002-8729-2549 FU National Institutes of Health [GM058615, GM073016, GM075252, U54 AI057159, DK060065]; Telethon (Italy); AIRC (Italy); Marie Curie Fellowship; GlaxoSmithKline FX We thank B. Wendland for critical comments. This work was financially supported by grants from the National Institutes of Health to V.W.H. (GM058615 and GM073016), T.K. (GM075252 and U54 AI057159-NERCE Imaging Resource) and J.F.C. (DK060065). A.L. was financially supported by the Telethon (Italy) and AIRC (Italy). H.G. was supported by a Marie Curie Fellowship. E.C. was supported by a GlaxoSmithKline fellowship. NR 58 TC 14 Z9 14 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY 11 PY 2011 VL 13 IS 5 BP 559 EP U144 DI 10.1038/ncb2221 PG 20 WC Cell Biology SC Cell Biology GA 758FY UT WOS:000290148700015 PM 21499258 ER PT J AU Bonnet, C Grati, M Marlin, S Levilliers, J Hardelin, JP Parodi, M Niasme-Grare, M Zelenika, D DelePine, M Feldmann, D Jonard, L El-Amraoui, A Weil, D Delobel, B Vincent, C Dollfus, H Eliot, MM David, A Calais, C Vigneron, J Montaut-Verient, B Bonneau, D Dubin, J Thauvin, C Duvillard, A Francannet, C Mom, T Lacombe, D Duriez, F Drouin-Garraud, V Thuillier-Obstoy, MF Sigaudy, S Frances, AM Collignon, P Challe, G Couderc, R Lathrop, M Sahel, JA Weissenbach, J Petit, C Denoyelle, F AF Bonnet, Crystel Grati, M'hamed Marlin, Sandrine Levilliers, Jacqueline Hardelin, Jean-Pierre Parodi, Marine Niasme-Grare, Magali Zelenika, Diana DelePine, Marc Feldmann, Delphine Jonard, Laurence El-Amraoui, Aziz Weil, Dominique Delobel, Bruno Vincent, Christophe Dollfus, Helene Eliot, Marie-Madeleine David, Albert Calais, Catherine Vigneron, Jacqueline Montaut-Verient, Bettina Bonneau, Dominique Dubin, Jacques Thauvin, Christel Duvillard, Alain Francannet, Christine Mom, Thierry Lacombe, Didier Duriez, Francoise Drouin-Garraud, Valerie Thuillier-Obstoy, Marie-Francoise Sigaudy, Sabine Frances, Anne-Marie Collignon, Patrick Challe, Georges Couderc, Remy Lathrop, Mark Sahel, Jose-Alain Weissenbach, Jean Petit, Christine Denoyelle, Francoise TI Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article ID SYNDROME-TYPE-II; MYOSIN-VIIA GENE; SENSORY HAIR-CELLS; SYNDROME TYPE 1D; SYNDROME TYPE 1F; RECESSIVE DEAFNESS; HEARING-LOSS; TIP-LINK; SYNDROME TYPE-2; LONG ISOFORM AB Background: Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods: We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Results: Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Conclusions: Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy. C1 [Bonnet, Crystel; Grati, M'hamed; Levilliers, Jacqueline; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Weil, Dominique; Petit, Christine; Denoyelle, Francoise] UPMC, Inst Pasteur, INSERM UMRS 587, Unite Genet & Physiol Audit, Paris, France. [Bonnet, Crystel; Grati, M'hamed; Marlin, Sandrine; Feldmann, Delphine; Jonard, Laurence; Couderc, Remy] Hop Enfants Armand Trousseau, AP HP, INSERM UMRS 587, Unite Genet Med, Paris, France. [Parodi, Marine; Niasme-Grare, Magali; Feldmann, Delphine; Jonard, Laurence; Couderc, Remy] Hop Enfants Armand Trousseau, AP HP, INSERM UMR 587, Serv Biochim & Biol Mol, Paris, France. [Zelenika, Diana; DelePine, Marc; Lathrop, Mark] CEA, Ctr Natl Genotypage, Evry, France. [Delobel, Bruno] Hop St Antoine, Ctr Genet, Lille, France. [Vincent, Christophe] Hop St Antoine, Serv ORL, Lille, France. [Dollfus, Helene] Hop Hautepierre, Serv Genet Med, Strasbourg, France. [David, Albert] Hop Hotel Dieu, Serv Genet, Nantes, France. [Calais, Catherine] CHU Hotel Dieu, Serv ORL, Nantes, France. [Montaut-Verient, Bettina] Maternite Regionale Adolphe Pinard, Serv ORL, Nancy, France. [Bonneau, Dominique] CHU Angers, Ctr Reference Malad Neurogenet, Angers, France. [Dubin, Jacques] CHU Angers, Serv ORL, Angers, France. [Thauvin, Christel] Hop Dijon, Unite Gen Med, Dijon, France. [Duvillard, Alain] Hop Dijon, Serv ORL, Dijon, France. [Francannet, Christine] Hop Hotel Dieu, Genet Med, Clermont Ferrand, France. [Mom, Thierry] Hop Hotel Dieu, Serv ORL, Clermont Ferrand, France. [Lacombe, Didier] Hop Pellegrin, Ctr Genet, Bordeaux, France. [Duriez, Francoise] Hop Pellegrin, Serv ORL, Bordeaux, France. [Drouin-Garraud, Valerie] Hop Charles Nicolle, Unite Genet Clin, Rouen, France. [Thuillier-Obstoy, Marie-Francoise] Hop Charles Nicolle, Serv ORL Pediat, Rouen, France. [Sigaudy, Sabine] Hop Enfants La Timone, Serv Genet Med, Marseille, France. [Collignon, Patrick] Hop Intercommunal Font Pre, Serv Genet Med, Toulon La Seyne Sur Mer, France. [Challe, Georges] Hop La Pitie Salpetriere, AP HP, Dept Ophtalmol & Med Interne, Paris, France. [Sahel, Jose-Alain] UPMC, INSERM UMRS 968, Inst Vis, Paris, France. [Weissenbach, Jean] Univ Evry, UEVE, CNRS UMR 8030, CEA,DSV,IG, Evry, France. [Petit, Christine] Coll France, F-75231 Paris, France. [Denoyelle, Francoise] UPMC, Hop Enfants Armand Trousseau, AP HP, INSERM UMRS 587,Serv ORL & Chirurg Cervicofaciale, Paris, France. [Grati, M'hamed] NIDCD, NIH, Bethesda, MD 20894 USA. [Eliot, Marie-Madeleine] Hop Hautepierre, Serv ORL, Strasbourg, France. RP Petit, C (reprint author), UPMC, Inst Pasteur, INSERM UMRS 587, Unite Genet & Physiol Audit, Paris, France. EM christine.petit@pasteur.fr; f.denoyelle@trs.aphp.fr RI lacombe, didier/K-7967-2014; Bonneau, Dominique/K-6110-2015; MOM, Thierry/L-5809-2015; Vincent, Christophe/F-6261-2016; Sahel, Jose-Alain/F-3172-2017 OI Vincent, Christophe/0000-0003-3201-7213; FU European Commission [LSHG-CT-2004-512063, HEALTH-F2-2010-242013]; French Foundation "Voir et Entendre"; Fondation R & G Strittmatter (under the aegis of Fondation de France); FAUN Stiftung (Suchert Foundation); Foundation Fighting Blindness; LHW-Stiftung; Fondation Orange; Conny-Maeva Charitable Foundation; Genoscope-CNRG [AP2005]; Sentendre Foundation FX We thank the patients and their families for participation in the study. We are very grateful to Laurent Abel, Jamila El Baghdadi and Cecile Julier for providing us with control DNA samples from Moroccan and Algerian individuals. We thank Corinne Chauve, Catherine Meunier, France Michel, and Isabelle Sargis for expert technical assistance. We also thank Sophie Bahaban, Anne-Flore Grange, Elizabeth Alden Landis and Patrick Joynt for collaboration. We thank Jean-Louis Mandel for helpful discussions. M.G. was supported by European Commission FP6 Integrated project, EuroHear (LSHG-CT-2004-512063) and C.B. by the French Foundation "Voir et Entendre". This work was supported by Fondation R & G Strittmatter (under the aegis of Fondation de France), FAUN Stiftung (Suchert Foundation), EC-FP7 TREATRUSH (HEALTH-F2-2010-242013), Foundation Fighting Blindness, LHW-Stiftung, Fondation Orange, The Conny-Maeva Charitable Foundation, Genoscope-CNRG project AP2005, and Sentendre Foundation. NR 98 TC 41 Z9 42 U1 3 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD MAY 11 PY 2011 VL 6 AR 21 DI 10.1186/1750-1172-6-21 PG 19 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 785BS UT WOS:000292203000001 PM 21569298 ER PT J AU Littman, BH Marincola, FM AF Littman, Bruce H. Marincola, Francesco M. TI Create a translational medicine knowledge repository - Research downsizing, mergers and increased outsourcing have reduced the depth of in-house translational medicine expertise and institutional memory at many pharmaceutical and biotech companies: how will they avoid relearning old lessons? SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material AB Pharmaceutical industry consolidation and overall research downsizing threatens the ability of companies to benefit from their previous investments in translational research as key leaders with the most knowledge of the successful use of biomarkers and translational pharmacology models are laid off or accept their severance packages. Two recently published books may help to preserve this type of knowledge but much of this type of information is not in the public domain. Here we propose the creation of a translational medicine knowledge repository where companies can submit their translational research data and access similar data from other companies in a precompetitive environment. This searchable repository would become an invaluable resource for translational scientists and drug developers that could speed and reduce the cost of new drug development. C1 [Littman, Bruce H.] Translat Med Associates LLC, Stonington, CT 06378 USA. [Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Littman, BH (reprint author), Translat Med Associates LLC, Stonington, CT 06378 USA. EM bruce.littman@transmedassociates.com NR 7 TC 4 Z9 4 U1 0 U2 13 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 MAY 10 PY 2011 VL 9 AR 56 DI 10.1186/1479-5876-9-56 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 779ZN UT WOS:000291820800001 PM 21569250 ER PT J AU Xue, Y Cai, T Shi, ST Wang, WG Zhang, YL Mao, TQ Duan, XH AF Xue, Yang Cai, Tao Shi, Songtao Wang, Weiguang Zhang, Yanli Mao, Tianqiu Duan, Xiaohong TI Clinical and animal research findings in pycnodysostosis and gene mutations of cathepsin K from 1996 to 2011 SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Review DE cathepsin K pycnodysostosis; osteoclast; bone; oral deformities ID LYSOSOMAL CYSTEINE PROTEASES; HUMAN PROCATHEPSIN K; GROWTH-HORMONE; MANDIBULAR RECONSTRUCTION; CLEIDOCRANIAL DYSOSTOSIS; BONE-RESORPTION; CTSK GENE; MATRIX DEGRADATION; MOLECULAR ANALYSIS; CRYSTAL-STRUCTURE AB Cathepsin K (CTSK) is a member of the papain-like cysteine protease family. Mutations in the CTSK gene cause a rare autosomal recessive bone disorder called pycnodysostosis (OMIM 265800). In order to follow the advances in the research about CTSK and pycnodysostosis, we performed a literature retrospective study of 159 pycnodysostosis patients reported since 1996 and focused on the genetic characteristics of CTSK mutations and/or the clinical phenotypes of pycnodysostosis. Thirty three different CTSK mutations have been found in 59 unrelated pycnodysostosis families. Of the 59 families, 37.29% are from Europe and 30.51% are from Asia. A total of 69.70% of the mutations were identified in the mature domain of CTSK, 24.24% in the proregion, and 6.06% in the preregion. The hot mutation spots are found in exons 6 and 7. CTSK mutations result in total loss or inactivity of the CTSK protein, which causes abnormal degradation of bone matrix proteins such as type I collagen. Skeletal abnormalities, including short stature, an increase in bone density with pathologic fractures, and open fontanels and sutures, are the typical phenotypes of pycnodysostosis. Research on Ctsk(-/-) mouse models was also reviewed here to elucidate the biological function of Ctsk and the mechanism of pycnodysostosis. New evidence suggests that Ctsk plays an important role in the immune system and may serve as a valid therapeutic target in the future treatment of pycnodysostosis. C1 [Xue, Yang; Mao, Tianqiu] Fourth Mil Med Univ, Sch Stomatol, Dept Oral & Maxillofacial Surg, Xian 710032, Peoples R China. [Xue, Yang; Zhang, Yanli; Duan, Xiaohong] Fourth Mil Med Univ, Sch Stomatol, Dept Oral Biol, Xian 710032, Peoples R China. [Cai, Tao] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Shi, Songtao] Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA. [Wang, Weiguang] Fourth Mil Med Univ, Xijing Hosp, Ctr Cardiovasc Surg, Xian 710032, Peoples R China. RP Mao, TQ (reprint author), Fourth Mil Med Univ, Sch Stomatol, Dept Oral & Maxillofacial Surg, 145 W Changle Rd, Xian 710032, Peoples R China. EM tqmao@fmmu.edu.cn; xhduan@fmmu.edu.cn FU Key Projects of Science and Technology of Xi'an City of China [SF09027(4)]; Key Projects of Science and Technology of Shaanxi Province of China [2009K17-06]; National Scientific Foundation of China [81070819] FX This work was supported in part by grants of Key Projects of Science and Technology of Xi'an City of China [SF09027(4)], Key Projects of Science and Technology of Shaanxi Province of China (2009K17-06), and National Scientific Foundation of China (81070819). As a disclaimer, T. C. represented his own perspective in the paper, not the NIDCR/NIH. NR 99 TC 24 Z9 25 U1 3 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD MAY 10 PY 2011 VL 6 AR 20 DI 10.1186/1750-1172-6-20 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 777IV UT WOS:000291610000001 PM 21569238 ER PT J AU Dostalova, A Votypka, J Favreau, AJ Barbian, KD Volf, P Valenzuela, JG Jochim, RC AF Dostalova, Anna Votypka, Jan Favreau, Amanda J. Barbian, Kent D. Volf, Petr Valenzuela, Jesus G. Jochim, Ryan C. TI The midgut transcriptome of Phlebotomus (Larroussius) perniciosus, a vector of Leishmania infantum: comparison of sugar fed and blood fed sand flies SO BMC GENOMICS LA English DT Article ID PERITROPHIC-MATRIX-PROTEIN; ANOPHELES-GAMBIAE; LUTZOMYIA-LONGIPALPIS; AEDES-AEGYPTI; DROSOPHILA-MELANOGASTER; VISCERAL LEISHMANIASIS; BINDING-PROTEIN; FLY VECTORS; PLASMODIUM; PAPATASI AB Background: Parasite-vector interactions are fundamental in the transmission of vector-borne diseases such as leishmaniasis. Leishmania development in the vector sand fly is confined to the digestive tract, where sand fly midgut molecules interact with the parasites. In this work we sequenced and analyzed two midgut-specific cDNA libraries from sugar fed and blood fed female Phlebotomus perniciosus and compared the transcript expression profiles. Results: A total of 4111 high quality sequences were obtained from the two libraries and assembled into 370 contigs and 1085 singletons. Molecules with putative roles in blood meal digestion, peritrophic matrix formation, immunity and response to oxidative stress were identified, including proteins that were not previously reported in sand flies. These molecules were evaluated relative to other published sand fly transcripts. Comparative analysis of the two libraries revealed transcripts differentially expressed in response to blood feeding. Molecules up regulated by blood feeding include a putative peritrophin (PperPer1), two chymotrypsin-like proteins (PperChym1 and PperChym2), a putative trypsin (PperTryp3) and four putative microvillar proteins (PperMVP1, 2, 4 and 5). Additionally, several transcripts were more abundant in the sugar fed midgut, such as two putative trypsins (PperTryp1 and PperTryp2), a chymotrypsin (PperChym3) and a microvillar protein (PperMVP3). We performed a detailed temporal expression profile analysis of the putative trypsin transcripts using qPCR and confirmed the expression of blood-induced and blood-repressed trypsins. Trypsin expression was measured in Leishmania infantum-infected and uninfected sand flies, which identified the L. infantum-induced down regulation of PperTryp3 at 24 hours post-blood meal. Conclusion: This midgut tissue-specific transcriptome provides insight into the molecules expressed in the midgut of P. perniciosus, an important vector of visceral leishmaniasis in the Old World. Through the comparative analysis of the libraries we identified molecules differentially expressed during blood meal digestion. Additionally, this study provides a detailed comparison to transcripts of other sand flies. Moreover, our analysis of putative trypsins demonstrated that L. infantum infection can reduce the transcript abundance of trypsin PperTryp3 in the midgut of P. perniciosus. C1 [Valenzuela, Jesus G.; Jochim, Ryan C.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Dostalova, Anna; Votypka, Jan; Volf, Petr] Charles Univ Prague, Fac Sci, Dept Parasitol, CR-12844 Prague 2, Czech Republic. [Favreau, Amanda J.; Barbian, Kent D.] NIAID, Rocky Mt Labs, Res Technol Sect, Genom Unit, Hamilton, MT 59840 USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM jvalenzuela@niaid.nih.gov; rjochim@niaid.nih.gov RI Dostalova, Anna/F-3203-2011; Volf, Petr/C-4300-2012; Votypka, Jan/C-5313-2012; Jochim, Ryan/C-6756-2013 OI Volf, Petr/0000-0003-1790-1123; Votypka, Jan/0000-0002-0552-9363; FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Wellcome trust [078937]; Czech Science Foundation [206/09/0777, 206/09/H026]; Czech Ministry of Education [MSM0021620828, LC06009]; Boehringer Ingelheim Fonds FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, the Wellcome trust project 078937, Czech Science Foundation (projects 206/09/0777 and 206/09/H026), Czech Ministry of Education (projects MSM0021620828 and LC06009) and the Boehringer Ingelheim Fonds. 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. NR 68 TC 11 Z9 12 U1 0 U2 10 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 MAY 10 PY 2011 VL 12 AR 223 DI 10.1186/1471-2164-12-223 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 772VJ UT WOS:000291265300001 PM 21569254 ER PT J AU Sokolov, MV Panyutin, IV Panyutin, IG Neumann, RD AF Sokolov, Mykyta V. Panyutin, Irina V. Panyutin, Igor G. Neumann, Ronald D. TI Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Human embryonic stem cell; Ionizing radiation; Gene expression; DNA microarray ID NORMAL HUMAN FIBROBLASTS; CYCLE CHECKPOINT CONTROL; DNA-DAMAGE RESPONSE; GENE-EXPRESSION; SELF-RENEWAL; MICROARRAY EXPERIMENTS; GENOTOXIC STRESS; MESSENGER-RNA; CANCER-CELLS; P53 AB One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data fora subset of genes. In parallel, the cell growth. DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells. Published by Elsevier B.V. C1 [Sokolov, Mykyta V.; Panyutin, Irina V.; Panyutin, Igor G.; Neumann, Ronald D.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), 9000 Rockville Pike,Bldg 10,Room 1C492, Bethesda, MD 20892 USA. EM sokolovm@mail.nih.gov; ipanyutinv@mail.nih.gov; igorp@helix.nih.gov; rneumann@mail.nih.gov FU NIH, Clinical Center FX We thank W. DeGraff for his invaluable help with cell culture irradiation. This research was supported by the Intramural Research Program of the NIH, Clinical Center. NR 62 TC 18 Z9 18 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 10 PY 2011 VL 709-10 BP 40 EP 48 DI 10.1016/j.mrfmmm.2011.02.008 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 766AB UT WOS:000290749400006 PM 21376742 ER PT J AU Ly, M Haynes, MR Barter, JW Weinberger, DR Zink, CF AF Ly, Martina Haynes, M. Ryan Barter, Joseph W. Weinberger, Daniel R. Zink, Caroline F. TI Subjective Socioeconomic Status Predicts Human Ventral Striatal Responses to Social Status Information SO CURRENT BIOLOGY LA English DT Article ID MONKEYS AB The enormous influence of hierarchical rank on social interactions [1] suggests that neural mechanisms exist to process status-related information [2] and ascribe value to it. The ventral striatum is prominently implicated in processing value and salience, independent of hedonic properties [3, 4], and a functional magnetic resonance imaging (fMRI) study of social status perception in humans demonstrated that viewing higher-ranked compared to lower-ranked individuals evokes a ventral striatal response [5], indicative of a greater assignment of value/salience to higher status. Consistent with this interpretation, nonhuman primates value information associated with higher-ranked conspecifics more than lower-ranked, as illustrated using a choice paradigm in which monkeys preferentially take the opportunity to view high-status monkeys [6]. Interestingly, this status-related value assignment in nonhuman primates is influenced by one's own hierarchical rank: high-status monkeys preferentially attend to conspecifics of high status, whereas low-status monkeys will also attend to other low-status monkeys [7]. Complementary to these findings, using fMRI and a social status judgment task in humans, we suggest a neurobiological mechanism by which one's own relative hierarchical rank influences the value attributed to particular social status information by demonstrating that one's subjective socioeconomic status differentially influences ventral striatal activity during processing of statusrelated information. C1 [Ly, Martina; Haynes, M. Ryan; Barter, Joseph W.; Weinberger, Daniel R.; Zink, Caroline F.] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RP Zink, CF (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. EM zinkc@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health FX We thank Andreas Meyer-Lindenberg for thoughtful discussion inspiring this work and Sam A. Colallilo and David N. Blitzer for assisting with questionnaire data collection. This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 10 TC 24 Z9 25 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 10 PY 2011 VL 21 IS 9 SI SI BP 794 EP 797 DI 10.1016/j.cub.2011.03.050 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 763JY UT WOS:000290553800032 PM 21530264 ER PT J AU Khadra, A Pietropaolo, M Nepom, GT Sherman, A AF Khadra, Anmar Pietropaolo, Massimo Nepom, Gerald T. Sherman, Arthur TI Investigating the Role of T-Cell Avidity and Killing Efficacy in Relation to Type 1 Diabetes Prediction SO PLOS ONE LA English DT Article ID PANCREATIC BETA-CELLS; COMPUTATIONAL APPROACH; AUTOIMMUNE RESPONSES; MINIMAL MODEL; INSULIN; AUTOANTIBODIES; PROGRESSION; RISK; CHILDREN; IDDM AB During the progression of the clinical onset of Type 1 Diabetes (T1D), high-risk individuals exhibit multiple islet autoantibodies and high-avidity T cells which progressively destroy beta cells causing overt T1D. In particular, novel autoantibodies, such as those against IA-2 epitopes (aa1-577), had a predictive rate of 100% in a 10-year follow up (rapid progressors), unlike conventional autoantibodies that required 15 years of follow up for a 74% predictive rate (slow progressors). The discrepancy between these two groups is thought to be associated with T-cell avidity, including CD8(+) and/or CD4(+) T cells. For this purpose, we build a series of mathematical models incorporating first one clone then multiple clones of islet-specific and pathogenic CD8(+) and/or CD4(+) T cells, together with B lymphocytes, to investigate the interaction of T-cell avidity with autoantibodies in predicting disease onset. These models are instrumental in examining several experimental observations associated with T-cell avidity, including the phenomenon of avidity maturation (increased average T-cell avidity over time), based on intra-and cross-clonal competition between T cells in high-risk human subjects. The model shows that the level and persistence of autoantibodies depends not only on the avidity of T cells, but also on the killing efficacy of these cells. Quantification and modeling of autoreactive T-cell avidities can thus determine the level of risk associated with each type of autoantibodies and the timing of T1D disease onset in individuals that have been tested positive for these autoantibodies. Such studies may lead to early diagnosis of the disease in high-risk individuals and thus potentially serve as a means of staging patients for clinical trials of preventive or interventional therapies far before disease onset. C1 [Khadra, Anmar; Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. [Pietropaolo, Massimo] Univ Michigan, Immunogenet Lab, Ann Arbor, MI 48109 USA. [Nepom, Gerald T.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. RP Khadra, A (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. EM khadraa@niddk.nih.gov OI Nepom, Gerald/0000-0002-8063-1464 FU National Institutes of Health [R01 DK53456, DK56200, NIDDK PA-04-081]; NIDDK; Brehm Coalition; University of Michigan Center for Computational Medicine and Biology (CCMB); Pilot Research Program FX National Institutes of Health: grants R01 DK53456, DK56200, NIDDK PA-04-081 (M. Pietropaolo); Intramural Research Program of the NIDDK (A. Khadra and A. Sherman). Brehm Coalition (M. Pietropaolo). University of Michigan Center for Computational Medicine and Biology (CCMB). Pilot Research Program (M. Pietropaolo). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 6 Z9 6 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 10 PY 2011 VL 6 IS 5 AR e14796 DI 10.1371/journal.pone.0014796 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761YU UT WOS:000290440200001 PM 21573001 ER PT J AU Munk, RB Sugiyama, K Ghosh, P Sasaki, CY Rezanka, L Banerjee, K Takahashi, H Sen, R Longo, DL AF Munk, Rachel B. Sugiyama, Katsuki Ghosh, Paritosh Sasaki, Carl Y. Rezanka, Louis Banerjee, Kasturi Takahashi, Hidenori Sen, Ranjan Longo, Dan L. TI Antigen-Independent IFN-gamma Production by Human Naive CD4(+) T Cells Activated by IL-12 Plus IL-18 SO PLOS ONE LA English DT Article ID NF-KAPPA-B; GENE-EXPRESSION; PROMOTER ACTIVATION; CYTOKINE RECEPTORS; PERIPHERAL-BLOOD; LYMPHOCYTES; INTERLEUKIN-12; TRANSCRIPTION; SYNERGIZES; INDUCTION AB The role of T cells in innate immunity is not well defined. In this report, we show that a subset of human peripheral blood CD4(+) T cells responds to IL-12 plus IL-18, but not to IL-12 or IL-18 alone, by producing IFN-gamma in the absence of any antigenic stimulation or cell proliferation. Intracellular staining reveals a small percentage of resting CD4(+) T cells (0.5 to 1.5%) capable of producing IFN-gamma in response to IL-12 plus IL-18. Interestingly, both naive (CD45RA(+)) and memory (CD45RO(+)) CD4(+) populations were responsive to IL-12 plus IL-18 stimulation in producing IFN-gamma. The expression of IFN-gamma induced by IL-12 and IL-18 is sensitive to rapamycin and SB203580, indicating the possible involvement of mTOR and p38 MAP kinase, respectively, in this synergistic pathway. While p38MAP kinase is involved in transcription, mTOR is involved in message stabilization. We have also shown that NF kappa B family member, cRel, but not GADD45 beta and GADD45 gamma, plays an important role in IL-12 plus IL-18-induced IFN-gamma transcription. Thus, the present study suggests that naive CD4(+) T cells may participate in innate immunity or amplify adaptive immune responses through cytokine-induced antigen-independent cytokine production. C1 [Munk, Rachel B.; Sugiyama, Katsuki; Ghosh, Paritosh; Sasaki, Carl Y.; Rezanka, Louis; Takahashi, Hidenori; Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Banerjee, Kasturi; Sen, Ranjan] NIA, Gene Regulat Sect, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Munk, RB (reprint author), NIA, Lymphocyte Cell Biol Unit, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. EM ghoshp@grc.nia.nih.gov FU National Institute on Aging, National Institutes of Health FX This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 10 Z9 12 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 MAY 10 PY 2011 VL 6 IS 5 AR e18553 DI 10.1371/journal.pone.0018553 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761YU UT WOS:000290440200002 PM 21572994 ER PT J AU Prescott, J Kraft, P Chasman, DI Savage, SA Mirabello, L Berndt, SI Weissfeld, JL Han, JL Hayes, RB Chanock, SJ Hunter, DJ De Vivo, I AF Prescott, Jennifer Kraft, Peter Chasman, Daniel I. Savage, Sharon A. Mirabello, Lisa Berndt, Sonja I. Weissfeld, Joel L. Han, Jiali Hayes, Richard B. Chanock, Stephen J. Hunter, David J. De Vivo, Immaculata TI Genome-Wide Association Study of Relative Telomere Length SO PLOS ONE LA English DT Article ID POSTMENOPAUSAL BREAST-CANCER; RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE ASPIRIN; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; CIGARETTE-SMOKING; PATERNAL AGE; MYOCARDIAL-INFARCTION; SEQUENCE VARIANTS; GENETIC-VARIATION AB Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele beta = -0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had > 80% power to detect beta estimates as small as +/- 0.10 for SNPs with minor allele frequencies of >= 0.15 at genome-wide significance. However, power is greatly reduced for beta estimates smaller than +/- 0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed. C1 [Prescott, Jennifer; Han, Jiali; Hunter, David J.; De Vivo, Immaculata] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Prescott, Jennifer; Kraft, Peter; Han, Jiali; Hunter, David J.; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Chasman, Daniel I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Ctr Cardiovasc Res, Boston, MA 02115 USA. [Savage, Sharon A.; Mirabello, Lisa; Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Weissfeld, Joel L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Han, Jiali] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hayes, Richard B.] NYU Med Ctr, Div Epidemiol, New York, NY 10016 USA. [Hunter, David J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Prescott, J (reprint author), Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. EM devivo@channing.harvard.edu RI Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Hayes, Richard/0000-0002-0918-661X FU National Institutes of Health (NIH) [CA49449, CA87969, CA065725, CA133914, U01-CA98233, T32 CA 09001]; National Cancer Institute [CA047988]; Amgen; National Heart, Lung, and Blood Institute [HL043851, HL69757]; Donald W. Reynolds Foundation; Leducq Foundation FX The NHS was supported by National Institutes of Health (NIH) grants CA49449, CA87969, CA065725, CA133914, and U01-CA98233. Dr. Prescott was supported by NIH training grant T32 CA 09001. The PLCO and work of Drs. Mirabello, Berndt, Hayes, Chanock, and Savage was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. Primary financial support for the WGHS genome-wide scans was provided by Amgen, with additional financial support provided by the National Heart, Lung, and Blood Institute (HL043851 and HL69757), National Cancer Institute (CA047988), the Donald W. Reynolds Foundation, and the Leducq Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 108 TC 41 Z9 41 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 MAY 10 PY 2011 VL 6 IS 5 AR e19635 DI 10.1371/journal.pone.0019635 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761YU UT WOS:000290440200017 PM 21573004 ER PT J AU Rong, YG McPhee, C Deng, SS Huang, L Chen, LL Liu, M Tracy, K Baehreck, EH Yu, L Lenardo, MJ AF Rong, Yueguang McPhee, Christina Deng, Shuangshen Huang, Lei Chen, Lilian Liu, Mei Tracy, Kirsten Baehreck, Eric H. Yu, Li Lenardo, Michael J. TI Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lysosomal storage disease ID CELL-DEATH; MUTATIONS; DISEASE AB Autophagy is a conserved cellular process to degrade and recycle cytoplasmic components. During autophagy, lysosomes fuse with an autophagosome to form an autolysosome. Sequestered components are degraded by lysosomal hydrolases and presumably released into the cytosol by lysosomal efflux permeases. Following starvation-induced autophagy, lysosome homeostasis is restored by autophagic lysosome reformation (ALR) requiring activation of the "target of rapamycin" (TOR) kinase. Spinster (Spin) encodes a putative lysosomal efflux permease with the hallmarks of a sugar transporter. Drosophila spin mutants accumulate lysosomal carbohydrates and enlarged lysosomes. Here we show that defects in spin lead to the accumulation of enlarged autolysosomes. We find that spin is essential for mTOR reactivation and lysosome reformation following prolonged starvation. Further, we demonstrate that the sugar transporter activity of Spin is essential for ALR. C1 [Rong, Yueguang; Deng, Shuangshen; Huang, Lei; Liu, Mei; Yu, Li] Tsinghua Univ, Sch Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. [McPhee, Christina] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. [McPhee, Christina; Tracy, Kirsten; Baehreck, Eric H.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Chen, Lilian] China Agr Univ, Coll Biol Sci, Beijing 100193, Peoples R China. [Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Yu, L (reprint author), Tsinghua Univ, Sch Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. EM liyulab@mail.tsinghua.edu.cn OI Kary, Christina/0000-0002-2586-4185 FU National Science Foundation [31030043, 30971484]; 973 Program [2010CB833704, 2011CB910100]; Tsinghua University [2010THZ0, 2009THZ03071]; NIH [GM079431]; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services FX We are grateful to Olympus China and the Tsinghua cell biology core facility for providing technical support and O. Schwartz, Juraj Kabat, Lily Koo, Meggan Czapiga (Biological Imaging Facility, National Institute for Allergy and Infectious Diseases, National Institutes of Health (NIH), Qi Dong, and Ying Li for assistance with confocal microscopy, TEM, and imaging processing. We thank J. Lippincott-Schwartz and J. Bonifacino for helpful discussions and D. Yamamoto, G. Davis, and H. Kramer for constructs and fly strains. This research was supported by National Science Foundation Grants 31030043 and 30971484, 973 Program 2010CB833704, 2011CB910100, and Tsinghua University Grants 2010THZ0 and 2009THZ03071 (to L.Y.), NIH Grant GM079431 (to E. H. B.), and the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services. NR 15 TC 74 Z9 77 U1 4 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 10 PY 2011 VL 108 IS 19 BP 7826 EP 7831 DI 10.1073/pnas.1013800108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761YN UT WOS:000290439500040 PM 21518918 ER PT J AU Ohnuma, S Chufan, E Nandigama, K Jenkins, LMM Durell, SR Appella, E Sauna, ZE Ambudkar, SV AF Ohnuma, Shinobu Chufan, Eduardo Nandigama, Krishnamachary Jenkins, Lisa M. Miller Durell, Stewart R. Appella, Ettore Sauna, Zuben E. Ambudkar, Suresh V. TI Inhibition of Multidrug Resistance-Linked P-Glycoprotein (ABCB1) Function by 5 '-Fluorosulfonylbenzoyl 5 '-Adenosine: Evidence for an ATP Analogue That Interacts with Both Drug-Substrate-and Nucleotide-Binding Sites SO BIOCHEMISTRY LA English DT Article ID CATALYTIC CYCLE; CASSETTE TRANSPORTERS; INVARIANT LYSINE; TRANSITION-STATE; PROTEIN-KINASE; A-LOOP; HYDROLYSIS; AFFINITY; DOMAIN; IDENTIFICATION AB 5'-Fluorosulfonylbenzonyl 5'-adenosine (FSBA) is an ATP analogue that covalently modifies several residues in the nudeotide-binding domains (NBDs) of several ATPases, kinases, and other proteins. P-glycoprotein (P-gp, ABCB1) is a member of the ATP-binding cassette (ABC) transporter superfamily that anticancer agents from cancer cells. We investigated the interactions of FSBA with P-gp to study the catalytic cycle of ATP hydrolysis. Incubation of P-gp with FSBA inhibited ATP hydrolysis (IC(50) = 0.21 mM) and the binding of 8-azido[alpha-(32)P]ATP (IC(50) = 0.68 mM). In addition, (14)C-FSBA cross-links to P-gp, suggesting that FSBA-mediated inhibition of ATP hydrolysis is irreversible due to covalent modification of P-gp. However, when the NBDs were occupied with a saturating concentration of ATP prior to treatment, FSBA stimulated ATP hydrolysis by P-gp. Furthermore, FSBA inhibited the photo-cross-linking of P-gp with [(125)I]iodoarylazidoprazosin (IAAP; IC(50) = 0.17 mM). As IAAP is a transport substrate for P-gp, this suggests that FSBA affects not only the NBDs but also the transport-substrate site in the transmembrane domains. Consistent with these results, FSBA blocked efflux of rhodamine 123 from P-gp-expressing cells. Additionally, mass spectrometric analysis identified FSBA cross-links to residues within or nearby the NBDs but not in the transmembrane domains, and docking of FSBA in a homology model of human P-gp NBDs supports the biochemical studies. Thus, FSBA is an ATP analogue that interacts with both the drug-binding and ATP-binding sites of P-gp, but fluorosulfonyl-mediated cross-linking is observed only at the NBDs. C1 [Ohnuma, Shinobu; Chufan, Eduardo; Nandigama, Krishnamachary; Jenkins, Lisa M. Miller; Durell, Stewart R.; Appella, Ettore; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 52 TC 9 Z9 9 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 10 PY 2011 VL 50 IS 18 BP 3724 EP 3735 DI 10.1021/bi200073f PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757AK UT WOS:000290056000015 PM 21452853 ER PT J AU Gail, MH AF Gail, Mitchell H. TI Personalized estimates of breast cancer risk in clinical practice and public health SO STATISTICS IN MEDICINE LA English DT Article DE absolute risk; allocation of prevention resources; breast cancer; calibration; crude risk; cumulative incidence; discriminatory accuracy; disease prevention; designing disease prevention trials; high-risk prevention strategy; risk versus benefit ID RANDOMIZED CONTROLLED-TRIAL; PROPHYLACTIC MASTECTOMY; POSTMENOPAUSAL WOMEN; ASSESSMENT MODELS; CERVICAL-CANCER; AMERICAN WOMEN; ROC CURVE; PREDICTION; VALIDATION; PREVENTION AB This paper defines absolute risk and some of its properties, and presents applications in breast cancer counseling and prevention. For counseling, estimates of absolute risk give useful perspective and can be used in management decisions that require weighing risks and benefits, such as whether or not to take tamoxifen to prevent breast cancer. Absolute risk models are also useful in designing intervention trials to prevent breast cancer and in assessing the potential reductions in absolute risk of disease that might result from reducing exposures that are associated with breast cancer. In these applications, it is important that the risk model be well calibrated, namely that it accurately predicts the numbers of women who will develop breast cancer in various subsets of the population. Absolute risk models are also needed to implement a 'high risk' prevention strategy that identifies a high-risk subset of the population and focuses intervention efforts on that subset. The limitations of the high-risk strategy are discussed, including the need for risk models with high discriminatory accuracy, and the need for less toxic interventions that can reduce the threshold of risk above which the intervention provides a net benefit. I also discuss the potential use of risk models in allocating prevention resources under cost constraints. High discriminatory accuracy of the risk model, in addition to good calibration, is desirable in this application, and the risk assessment should not be expensive in comparison with the intervention. Published in 2011 by John Wiley & Sons, Ltd. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, EPS 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. I would like to thank Dr Ruth Pfeiffer and the reviewers and editor for helpful suggestions. I would also like to thank Professor Peter Armitage, whose writings and leadership are an inspiration. NR 64 TC 33 Z9 33 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAY 10 PY 2011 VL 30 IS 10 BP 1090 EP 1104 DI 10.1002/sim.4187 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 756GT UT WOS:000290000400004 PM 21337591 ER PT J AU Bolton, EE Kim, S Bryant, SH AF Bolton, Evan E. Kim, Sunghwan Bryant, Stephen H. TI PubChem3D: Similar conformers SO JOURNAL OF CHEMINFORMATICS LA English DT Article ID GAUSSIAN DESCRIPTION; MOLECULAR SHAPE; COEFFICIENTS; INFORMATION; INHIBITION; FENBUFEN; DATABASE AB Background: PubChem is a free and open public resource for the biological activities of small molecules. With many tens of millions of both chemical structures and biological test results, PubChem is a sizeable system with an uneven degree of available information. Some chemical structures in PubChem include a great deal of biological annotation, while others have little to none. To help users, PubChem pre-computes "neighboring" relationships to relate similar chemical structures, which may have similar biological function. In this work, we introduce a "Similar Conformers" neighboring relationship to identify compounds with similar 3-D shape and similar 3-D orientation of functional groups typically used to define pharmacophore features. Results: The first two diverse 3-D conformers of 26.1 million PubChem Compound records were compared to each other, using a shape Tanimoto (ST) of 0.8 or greater and a color Tanimoto (CT) of 0.5 or greater, yielding 8.16 billion conformer neighbor pairs and 6.62 billion compound neighbor pairs, with an average of 253 "Similar Conformers" compound neighbors per compound. Comparing the 3-D neighboring relationship to the corresponding 2-D neighboring relationship ("Similar Compounds") for molecules such as caffeine, aspirin, and morphine, one finds unique sets of related chemical structures, providing additional significant biological annotation. The PubChem 3-D neighboring relationship is also shown to be able to group a set of non-steroidal anti-inflammatory drugs (NSAIDs), despite limited PubChem 2-D similarity. In a study of 4,218 chemical structures of biomedical interest, consisting of many known drugs, using more diverse conformers per compound results in more 3-D compound neighbors per compound; however, the overlap of the compound neighbor lists per conformer also increasingly resemble each other, being 38% identical at three conformers and 68% at ten conformers. Perhaps surprising is that the average count of conformer neighbors per conformer increases rather slowly as a function of diverse conformers considered, with only a 70% increase for a ten times growth in conformers per compound (a 68-fold increase in the conformer pairs considered). Neighboring 3-D conformers on the scale performed, if implemented naively, is an intractable problem using a modest sized compute cluster. Methodology developed in this work relies on a series of filters to prevent performing 3-D superposition optimization, when it can be determined that two conformers cannot possibly be a neighbor. Most filters are based on Tanimoto equation volume constraints, avoiding incompatible conformers; however, others consider preliminary superposition between conformers using reference shapes. Conclusion: The "Similar Conformers" 3-D neighboring relationship locates similar small molecules of biological interest that may go unnoticed when using traditional 2-D chemical structure graph-based methods, making it complementary to such methodologies. The computational cost of 3-D similarity methodology on a wide scale, such as PubChem contents, is a considerable issue to overcome. Using a series of efficient filters, an effective throughput rate of more than 150,000 conformers per second per processor core was achieved, more than two orders of magnitude faster than without filtering. C1 [Bolton, Evan E.; Kim, Sunghwan; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM bolton@ncbi.nlm.nih.gov RI Kim, Sunghwan/A-6738-2008 OI Kim, Sunghwan/0000-0001-9828-2074 FU National Library of Medicine, National Institutes of Health, U.S. Department of Health and Human Services FX Many thanks to Roger Sayle for providing key insights on ways to improve the rotational/translational matrix pack/unpack scheme. We are grateful to the NCBI Systems staff, especially Ron Patterson, Charlie Cook, and Don Preuss, whose efforts helped make the PubChem3D project possible. This research was supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health, U.S. Department of Health and Human Services. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Md. (http://biowulf.nih.gov). NR 29 TC 12 Z9 12 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PD MAY 9 PY 2011 VL 3 AR 13 DI 10.1186/1758-2946-3-13 PG 22 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 891OF UT WOS:000300225800001 PM 21554721 ER PT J AU Argraves, KM Sethi, AA Gazzolo, PJ Wilkerson, BA Remaley, AT Tybjaerg-Hansen, A Nordestgaard, BG Yeatts, SD Nicholas, KS Barth, JL Argraves, WS AF Argraves, Kelley M. Sethi, Amar A. Gazzolo, Patrick J. Wilkerson, Brent A. Remaley, Alan T. Tybjaerg-Hansen, Anne Nordestgaard, Borge G. Yeatts, Sharon D. Nicholas, Katherine S. Barth, Jeremy L. Argraves, W. Scott TI S1P, dihydro-S1P and C24:1-ceramide levels in the HDL-containing fraction of serum inversely correlate with occurrence of ischemic heart disease SO LIPIDS IN HEALTH AND DISEASE LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; SPHINGOSINE 1-PHOSPHATE; CARDIOVASCULAR-DISEASE; MATRIX METALLOPROTEINASE-1; CHOLESTEROL LEVELS; POTENTIAL ROLE; HUMAN PLASMA; RISK-FACTORS; SPHINGOSINE-1-PHOSPHATE AB Background: The lysosphingolipid sphingosine 1-phosphate (S1P) is carried in the blood in association with lipoproteins, predominantly high density lipoproteins (HDL). Emerging evidence suggests that many of the effects of HDL on cardiovascular function may be attributable to its S1P cargo. Methods: Here we have evaluated how levels of S1P and related sphingolipids in an HDL-containing fraction of human serum correlate with occurrence of ischemic heart disease (IHD). To accomplish this we used liquid chromatography-mass spectrometry to measure S1P levels in the HDL-containing fraction of serum (depleted of LDL and VLDL) from 204 subjects in the Copenhagen City Heart Study (CCHS). The study group consisted of individuals having high serum HDL cholesterol (HDL-C) (females:>= 73.5 mg/dL; males:>= 61.9 mg/dL) and verified IHD; subjects with high HDL-C and no IHD; individuals with low HDL-C (females:<= 38.7 mg/dL; males:<= 34.1 mg/dL) and IHD, and subjects with low HDL-C and no IHD. Results: The results show a highly significant inverse relationship between the level of S1P in the HDL-containing fraction of serum and the occurrence of IHD. Furthermore, an inverse relationship with IHD was also observed for two other sphingolipids, dihydro-S1P and C24:1-ceramide, in the HDL-containing fraction of serum. Additionally, we demonstrated that the amount of S1P on HDL correlates with the magnitude of HDL-induced endothelial cell barrier signaling. Conclusions: These findings indicate that compositional differences of sphingolipids in the HDL-containing fraction of human serum are related to the occurrence of IHD, and may contribute to the putative protective role of HDL in IHD. C1 [Argraves, Kelley M.; Gazzolo, Patrick J.; Wilkerson, Brent A.; Barth, Jeremy L.; Argraves, W. Scott] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Sethi, Amar A.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Tybjaerg-Hansen, Anne] Univ Copenhagen, Dept Clin Biochem, Rigshosp, Copenhagen Univ Hosp,Fac Hlth Sci, DK-1168 Copenhagen, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Dept Clin Biochem, Herlev Hosp, Copenhagen Univ Hosp,Fac Hlth Sci, DK-1168 Copenhagen, Denmark. [Tybjaerg-Hansen, Anne; Nordestgaard, Borge G.] Univ Copenhagen, Bispebjerg Hosp, Copenhagen City Heart Study, Copenhagen Univ Hosp,Fac Hlth Sci, DK-1168 Copenhagen, Denmark. [Yeatts, Sharon D.; Nicholas, Katherine S.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. RP Argraves, KM (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. EM argravek@musc.edu FU NIH [HL80404, RR107677, HL52813, HL007260, AHA 10PRE3910006, RR018823]; NHLBI, National Institutes of Health (Bethesda, MD); NIH/NCRR [RR16434, RR16461]; Danish Heart Foundation FX This work was supported by NIH grants HL80404, RR107677 (to K. M. A.) and HL52813 (to W. S. A.), by intramural research funds from NHLBI, National Institutes of Health (Bethesda, MD) (to A. T. R.) and by NIH Training Grant to Improve Cardiovascular Therapies HL007260 and AHA 10PRE3910006 (to B. A. W.). Biostatistical efforts were supported in part through NIH/NCRR grants RR16434 and RR16461. We thank members of the Lipidomics Core Facility (Drs. J. Bielawski and A. Bielawska) at the Medical University of South Carolina which is supported by NIH grant RR018823. The Copenhagen City Heart Study was supported by the Danish Heart Foundation. NR 38 TC 43 Z9 43 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-511X J9 LIPIDS HEALTH DIS JI Lipids Health Dis. PD MAY 9 PY 2011 VL 10 AR 70 DI 10.1186/1476-511X-10-70 PG 12 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 780KN UT WOS:000291854900001 PM 21554699 ER PT J AU Hasnain, SZ Evans, CM Roy, M Gallagher, AL Kindrachuk, KN Barron, L Dickey, BF Wilson, MS Wynn, TA Grencis, RK Thornton, DJ AF Hasnain, Sumaira Z. Evans, Christopher M. Roy, Michelle Gallagher, Amanda L. Kindrachuk, Kristen N. Barron, Luke Dickey, Burton F. Wilson, Mark S. Wynn, Thomas A. Grencis, Richard K. Thornton, David J. TI Muc5ac: a critical component mediating the rejection of enteric nematodes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRICHURIS-MURIS INFECTION; MUCIN GENE-EXPRESSION; ABNORMAL EXPRESSION; ULCERATIVE-COLITIS; AIRWAYS MUCUS; RESPONSES; IMMUNITY; BARRIER; ALPHA; MODEL AB De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced in the cecum of mice resistant to Trichuris muris infection. In this study, we investigated the role of Muc5ac, which is detected shortly before worm expulsion and is associated with the production of interleukin-13 (IL-13), in resistance to this nematode. Muc5ac-deficient mice were incapable of expelling T. muris from the intestine and harbored long-term chronic infections, despite developing strong T(H)2 responses. Muc5ac-deficient mice had elevated levels of IL-13 and, surprisingly, an increase in the T(H)1 cytokine IFN-gamma. Because T(H)1 inflammation is thought to favor chronic nematode infection, IFN-gamma was neutralized in vivo, resulting in an even stronger T(H)2-type immune response. Nevertheless, despite a more robust T(H)2 effector response, the Muc5ac-deficient mice remained highly susceptible to chronic T. muris infection. Importantly, human MUC5AC had a direct detrimental effect on nematode vitality. Moreover, the absence of Muc5ac caused a significant delay in the expulsion of two other gut-dwelling nematodes (Trichinella spiralis and Nippostrongylus brasiliensis). Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection. C1 [Hasnain, Sumaira Z.; Thornton, David J.] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. [Hasnain, Sumaira Z.; Gallagher, Amanda L.; Grencis, Richard K.] Univ Manchester, Manchester Immunol Grp, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Evans, Christopher M.; Roy, Michelle; Dickey, Burton F.] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. [Kindrachuk, Kristen N.; Barron, Luke; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA. [Wilson, Mark S.] Natl Inst Med Res, Div Mol Immunol, Med Res Council, London NW7 1AA, England. RP Thornton, DJ (reprint author), Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. EM richard.k.grencis@manchester.ac.uk; dave.thornton@manchester.ac.uk RI Wynn, Thomas/C-2797-2011; Hasnain, Sumaira /C-5047-2013; Hasnain, Sumaira/N-3412-2014; OI Hasnain, Sumaira/0000-0001-8577-8628; Dickey, Burton/0000-0002-4780-1847 FU Wellcome Trust; National Institutes of Health [R01-HL080396, P30-CA016672]; National Institute of Allergy and Infectious Diseases/National Institutes of Health; Biotechnology and Biological Sciences Research Council FX This work is supported by grants from the Wellcome Trust (to R. K. Grencis), National Institutes of Health grants R01-HL080396 (to C. M. Evans) and P30-CA016672 (The University of Texas MD Anderson Cancer Center support grant), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases/National Institutes of Health (grant to T. A. Wynn), and by a PhD studentship for S.Z. Hasnain from the Biotechnology and Biological Sciences Research Council (grant to D.J. Thornton and R. K. Grencis). NR 31 TC 106 Z9 107 U1 1 U2 44 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 9 PY 2011 VL 208 IS 5 BP 893 EP 900 DI 10.1084/jem.20102057 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 774ZL UT WOS:000291425400003 PM 21502330 ER PT J AU Fahey, LM Wilson, EB Elsaesser, H Fistonich, CD McGavern, DB Brooks, DG AF Fahey, Laura M. Wilson, Elizabeth B. Elsaesser, Heidi Fistonich, Chris D. McGavern, Dorian B. Brooks, David G. TI Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DEFICIENT MICE; C-MAF; INFECTION; RESPONSES; IL-21; RECEPTOR; ANTIGEN; MEMORY; INTERLEUKIN-21; REPERTOIRE AB CD4 T cell responses are crucial to prevent and control viral infection; however, virus-specific CD4 T cell activity is considered to be rapidly lost during many persistent viral infections. This is largely caused by the fact that during viral persistence CD4 T cells do not produce the classical Th1 cytokines associated with control of acute viral infections. Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control of persistent viral replication. We now demonstrate that CD4 T cell function is not extinguished as a result of viral persistence. Instead, viral persistence and prolonged T cell receptor stimulation progressively redirects CD4 T cell development away from the Th1 response induced during an acute infection toward T follicular helper cells. Importantly, this sustained CD4 T cell functionality is critical to maintain immunity and ultimately aid in the control of persistent viral infection. C1 [Fahey, Laura M.; Wilson, Elizabeth B.; Elsaesser, Heidi; Fistonich, Chris D.; Brooks, David G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Fahey, Laura M.; Wilson, Elizabeth B.; Elsaesser, Heidi; Fistonich, Chris D.; Brooks, David G.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA. [McGavern, Dorian B.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. RP Brooks, DG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. EM dbrooks@microbio.ucla.edu OI McGavern, Dorian/0000-0001-9568-545X FU UCLA Center for AIDS Research; National Institutes of Health [AI 082975, AI 007323] FX Our work was supported by the UCLA Center for AIDS Research and by National Institutes of Health Grants (AI 082975 to D. G. Brooks and AI 007323 to L. M. Fahey). NR 48 TC 120 Z9 123 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD MAY 9 PY 2011 VL 208 IS 5 BP 987 EP 999 DI 10.1084/jem.20101773 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 774ZL UT WOS:000291425400011 PM 21536743 ER PT J AU Lai, DZ Zhu, JF Wang, TH Hu-Li, J Terabe, M Berzofsky, JA Clayberger, C Krensky, AM AF Lai, Dazhi Zhu, Jinfang Wang, Tianhong Hu-Li, Jane Terabe, Masaki Berzofsky, Jay A. Clayberger, Carol Krensky, Alan M. TI KLF13 sustains thymic memory-like CD8(+) T cells in BALB/c mice by regulating IL-4-generating invariant natural killer T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION-FACTOR; IMMUNE-RESPONSE; AIRWAY HYPERRESPONSIVENESS; CHEMOKINE RANTES; LEISHMANIA-MAJOR; CUTTING EDGE; IN-VIVO; EXPRESSION; EFFECTOR; GAMMA AB "Memory-like T cells" are a subset of thymic cells that acquire effector function through the maturation process rather than interaction with specific antigen. Disruption of genes encoding T cell signaling proteins or transcription factors have provided insights into the differentiation of such cells. In this study, we show that in BALB/c, but not C57BL/6, mice, a large portion of thymic CD4(-)CD8(+) T cells exhibit a memory-like phenotype. In BALB/c mice, IL-4 secreted by invariant natural killer T (iNKT) cells is both essential and sufficient for the generation of memory-like T cells. In C57BL/6 mice, iNKT cells are less abundant, producing IL-4 that is insufficient to induce thymic memory-like CD8(+) T cells. BALB/c mice deficient in the transcription factor Kruppel-like factor (KLF) 13 have comparable numbers of iNKT cells to C57BL/6 mice and extremely low levels of thymic memory-like CD8(+) T cells. This work documents the impact of a small number of KLF13-dependent iNKT cells on the generation of memory-like CD8(+) T cells. C1 [Lai, Dazhi; Wang, Tianhong; Clayberger, Carol; Krensky, Alan M.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. [Terabe, Masaki; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Zhu, Jinfang; Hu-Li, Jane] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Krensky, AM (reprint author), NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. EM krenskya@mail.nih.gov RI Zhu, Jinfang/B-7574-2012 FU National Institutes of Health; National Cancer Institute; National Institute of Allergy and Infectious Diseases FX The Intramural Research Programs of the National Institutes of Health, the National Cancer Institute, and the National Institute of Allergy and Infectious Diseases supported this research. NR 65 TC 34 Z9 34 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 9 PY 2011 VL 208 IS 5 BP 1093 EP 1103 DI 10.1084/jem.20101527 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 774ZL UT WOS:000291425400019 PM 21482696 ER PT J AU Zhu, DM McClellan, H Dai, WL Gebregeorgis, E Kidwell, MA Aebig, J Rausch, KM Martin, LB Ellis, RD Miller, L Wu, YM AF Zhu, Daming McClellan, Holly Dai, Weili Gebregeorgis, Elizabeth Kidwell, Mary Anne Aebig, Joan Rausch, Kelly M. Martin, Laura B. Ellis, Ruth D. Miller, Louis Wu, Yimin TI Long term stability of a recombinant Plasmodium falciparum AMA1 malaria vaccine adjuvanted with Montanide (R) ISA 720 and stabilized with glycine SO VACCINE LA English DT Article DE Montanide (R) ISA 720; AMA1; Malaria; Vaccine ID APICAL MEMBRANE ANTIGEN-1; PHASE-I TRIAL; BLOOD-STAGE VACCINE; CLINICAL-TRIAL; POLYPEPTIDE TAB9; IMMUNOGENICITY; CANDIDATE; SAFETY; ISA-720; PROTEINS AB Plasmodium falciparum apical membrane antigen 1 (AMA1) is an asexual blood-stage vaccine candidate against the malaria parasite. AMA1-C1/ISA720 refers to a mixture of recombinant AMA1 proteins representing the FVO and 3D7 alleles in 1:1 mass ratio, formulated with Montanide (R) ISA 720 as a water-in oil emulsion. In order to develop the AMA1-C1/ISA720 vaccine for human use, it was important to determine the shelf life of this formulation. Previously it was found 267 mM glycine stabilized the proteins in Montanide (R) ISA 720 formulations for a short period of time at 2-8 degrees C [25]. We now test the long term stability of AMA1-Cl at 10 and 40 mu g/mL formulated with Montanide ISA 720 with 50 mM glycine as a stabilizer. Stability of AMA1-C1/ISA720 at different time points following formulation (0.5. 12 or 18 months) was evaluated by determining the mean particle size (diameter of the mean droplet volume), total protein content by a Modified Lowry assay, identity and integrity using western blot and SDS-PAGE. Our results showed that the mean particle size of these emulsions increased over time, whereas protein content, as determined by an ELISA method using a monoclonal antibody against penta-his, decreased over time. For the 10 mu g/mL AMA1-C1/ISA720 vaccine, the protein content was 6.5 +/- 2.2 mu g/mL, and for the 40 mu g/mL AMA1-C1/ISA720 vaccine, the protein content was only 8.2 +/- 2.3 mu g/mL after 18 months of storage at 2-8 degrees C. These results suggest that the integrity of the protein was affected by long-term storage. The results of the present study indicate that the AMA1-C1/ISA720 emulsion was unstable after 12 months of storage, after which AMA1-C1 proteins were partially degraded. Published by Elsevier Ltd. C1 [Zhu, Daming; McClellan, Holly; Dai, Weili; Gebregeorgis, Elizabeth; Kidwell, Mary Anne; Aebig, Joan; Rausch, Kelly M.; Martin, Laura B.; Ellis, Ruth D.; Miller, Louis; Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. RP Zhu, DM (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, 5640 Fishers Lane,Room 1118, Rockville, MD 20852 USA. EM dzhu@niaid.nih.gov RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 FU Intramural NIH HHS [ZIA AI001005-03, ZIA AI001005-04] NR 31 TC 3 Z9 3 U1 0 U2 10 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 MAY 9 PY 2011 VL 29 IS 20 BP 3640 EP 3645 DI 10.1016/j.vaccine.2011.03.015 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 768ZB UT WOS:000290977700004 PM 21440641 ER PT J AU Morris, CA Onyamboko, MA Capparelli, E Koch, MA Atibu, J Lokomba, V Douoguih, M Hemingway-Foday, J Wesche, D Ryder, RW Bose, C Wright, L Tshefu, AK Meshnick, S Fleckenstein, L AF Morris, Carrie A. Onyamboko, Marie A. Capparelli, Edmund Koch, Matthew A. Atibu, Joseph Lokomba, Vicky Douoguih, Macaya Hemingway-Foday, Jennifer Wesche, David Ryder, Robert W. Bose, Carl Wright, Linda Tshefu, Antoinette K. Meshnick, Steven Fleckenstein, Lawrence TI Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria SO MALARIA JOURNAL LA English DT Article ID UNCOMPLICATED FALCIPARUM-MALARIA; ORAL ARTESUNATE; DISPOSITION; PHARMACODYNAMICS; GLUCURONIDATION; BIOAVAILABILITY; LAMOTRIGINE; METABOLITES; VOLUNTEERS; NONMEM AB Background: The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC. Methods: Data were obtained from 26 pregnant women in the second (22 - 26 weeks) or the third (32 - 36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling. Results: A simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7 - 72.3%). Conclusions: In this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls. C1 [Morris, Carrie A.; Fleckenstein, Lawrence] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. [Onyamboko, Marie A.; Atibu, Joseph; Lokomba, Vicky; Tshefu, Antoinette K.] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Capparelli, Edmund; Ryder, Robert W.] Univ Calif San Diego, San Diego, CA 92103 USA. [Koch, Matthew A.; Hemingway-Foday, Jennifer] RTI Int, Res Triangle Pk, NC USA. [Douoguih, Macaya] Aeras Global TB Vaccine Fdn, Rockville, MD USA. [Wesche, David] David Wesche Consulting LLC, Ann Arbor, MI USA. [Bose, Carl] Univ N Carolina, Chapel Hill, NC USA. [Wright, Linda] NICHHD, NIH, Rockville, MD USA. [Meshnick, Steven] UNC Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Fleckenstein, L (reprint author), Univ Iowa, Coll Pharm, 115 S Grand Ave, Iowa City, IA 52242 USA. EM l-fleckenstein@uiowa.edu OI Fleckenstein, Lawrence/0000-0001-5320-4531 FU National Institute of Child Health and Human Development FX This study was a Global Network Study supported by grants from the National Institute of Child Health and Human Development. We thank the staff of Maternite des Soeurs de Saint Marc de Kingasani, the community health workers of the Kingasani Health Zone and their MCZ, and the dedicated research staff from the Kinshasa School of Public Health for all their support and commitment in this research project. We thank Mark Schmidt for artesunate/DHA analysis and RJ Nemeyer for the PCR analyses. We have a special thanks addressed to all the participants (pregnant and non-pregnant women) for their volunteered participation in our study. NR 31 TC 26 Z9 27 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAY 8 PY 2011 VL 10 AR 114 DI 10.1186/1475-2875-10-114 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 767NT UT WOS:000290864000001 PM 21548983 ER PT J AU Dodd, LE Wilkinson, RJ AF Dodd, Lori Elizabeth Wilkinson, Robert John TI Isoniazid preventive therapy in HIV infection SO LANCET LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY; TUBERCULOSIS C1 [Wilkinson, Robert John] Univ Cape Town, Inst Infect Dis & Mol Med, Clin Infect Dis Res Initiat, ZA-7925 Cape Town, South Africa. [Dodd, Lori Elizabeth] NIAID, Biostat Res Branch, Div Clin Res, Bethesda, MD 20892 USA. [Wilkinson, Robert John] Natl Inst Med Res, MRC, Div Mycobacterial Res, London NW7 1AA, England. [Wilkinson, Robert John] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. RP Wilkinson, RJ (reprint author), Univ Cape Town, Inst Infect Dis & Mol Med, Clin Infect Dis Res Initiat, ZA-7925 Cape Town, South Africa. EM r.j.wilkinson@imperial.ac.uk OI Wilkinson, Robert/0000-0002-2753-1800 FU Medical Research Council [MC_U117588499, U117588499(88499)]; Wellcome Trust [088316] NR 12 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 7 PY 2011 VL 377 IS 9777 BP 1548 EP 1550 DI 10.1016/S0140-6736(11)60434-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 763IJ UT WOS:000290549700006 PM 21492928 ER PT J AU Collin-Osdoby, P Rothe, L Kwong, M Frigerio, B Morinishi, L Cabral, WA Osdoby, P Marini, JC AF Collin-Osdoby, P. Rothe, L. Kwong, M. Frigerio, B. Morinishi, L. Cabral, W. A. Osdoby, P. Marini, J. C. TI Osteoclast increases in the Brtl mouse model for osteogenesis imperfecta occur through marrow mesenchymal stromal cell dependent and independent mechanisms SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Collin-Osdoby, P.; Rothe, L.; Kwong, M.; Frigerio, B.; Morinishi, L.; Osdoby, P.] Washington Univ, Dept Biol Bone & Mineral Metab, St Louis, MO USA. [Cabral, W. A.; Marini, J. C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S238 EP S238 DI 10.1016/j.bone.2011.03.571 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800573 ER PT J AU Trichet, V Forlino, A Gioia, R Domene, A Heymann, D Marini, J Rousseau, J AF Trichet, V. Forlino, A. Gioia, R. Domene, A. Heymann, D. Marini, J. Rousseau, J. TI Specific suppression of the mutant COL1A1 allele by siRNA/shRNA in fibroblasts of the osteogenesis imperfecta murine model BrtlIV SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Trichet, V.; Domene, A.; Heymann, D.; Rousseau, J.] Univ Nantes, INSERM, U957, Nantes, France. [Forlino, A.; Gioia, R.] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. [Marini, J.] NIH, Bone & Extracellular Matrix Branch, Bethesda, MD 20892 USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S159 EP S160 DI 10.1016/j.bone.2011.03.352 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800328 ER PT J AU Valli, M Barnes, A Cabral, WA Gallanti, A Viglio, S Weis, M Eyre, D Antoniazzi, F Mottes, M Marini, JC AF Valli, M. Barnes, A. Cabral, W. A. Gallanti, A. Viglio, S. Weis, M. Eyre, D. Antoniazzi, F. Mottes, M. Marini, J. C. TI Null CRTAP mutation associated with non-lethal OI and minimal collagen deposition in culture SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Valli, M.; Gallanti, A.; Viglio, S.] Univ Pavia, I-27100 Pavia, Italy. [Barnes, A.; Cabral, W. A.; Marini, J. C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Weis, M.; Eyre, D.] Univ Washington, Orthopaed Res Labs, Seattle, WA 98195 USA. [Antoniazzi, F.; Mottes, M.] Univ Verona, I-37100 Verona, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S84 EP S84 DI 10.1016/j.bone.2011.03.111 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800095 ER PT J AU Cabral, WA Fratzl-Zelman, N Roschger, P Marini, JC AF Cabral, W. A. Fratzl-Zelman, N. Roschger, P. Marini, J. C. TI Cellular dysregulation of gene expression in response to abnormal extracellular matrix may contribute to matrix hypermineralization in Osteogenesis Imperfecta SO BONE LA English DT Meeting Abstract CT 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY MAY 07-11, 2011 CL Athens, GREECE SP European Calcified Tissue Soc, Int Bone & Mineral Soc C1 [Cabral, W. A.; Marini, J. C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Fratzl-Zelman, N.; Roschger, P.] Hanusch Hosp WGKK, Ludwig Boltzmann Inst Osteol, Vienna, Austria. [Fratzl-Zelman, N.; Roschger, P.] Hanusch Hosp, Dept Med 4, AUVA Trauma Ctr Meidling, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY 7 PY 2011 VL 48 SU 2 BP S71 EP S71 DI 10.1016/j.bone.2011.03.077 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754TJ UT WOS:000289879800066 ER PT J AU Watts, M Tabak, J Zimliki, C Sherman, A Bertram, R AF Watts, Margaret Tabak, Joel Zimliki, Charles Sherman, Arthur Bertram, Richard TI Slow variable dominance and phase resetting in phantom bursting SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE Bursting; Multi-scale; Islet; Oscillations ID PANCREATIC BETA-CELLS; MODEL; OSCILLATIONS; DEPENDENCE; NOISE AB Bursting oscillations are common in neurons and endocrine cells. One type of bursting model with two slow variables has been called 'phantom bursting' since the burst period is a blend of the time constants of the slow variables. A phantom bursting model can produce bursting with a wide range of periods: fast (short period), medium, and slow (long period). We describe a measure, which we call the 'dominance factor', of the relative contributions of the two slow variables to the bursting produced by a simple phantom bursting model. Using this tool, we demonstrate how the control of different phases of the burst can be shifted from one slow variable to another by changing a model parameter. We then show that the dominance curves obtained as a parameter is varied can be useful in making predictions about the resetting properties of the model cells. Finally, we demonstrate two mechanisms by which phase-independent resetting of a burst can be achieved, as has been shown to occur in the electrical activity of pancreatic islets. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Watts, Margaret; Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA. [Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. [Zimliki, Charles] US FDA, Artificial Pancreas Working Grp, Gen Hosp Devices Branch, Silver Spring, MD USA. [Tabak, Joel] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu OI Tabak, Joel/0000-0002-0588-957X FU NSF [DMS0917664]; NIH [DA19356]; NIH (NIDDK) FX This work was partially supported by NSF Grant DMS0917664 and NIH Grant DA19356 to Richard Bertram. Arthur Sherman is supported by the Intramural Research Program of the NIH (NIDDK). NR 15 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD MAY 7 PY 2011 VL 276 IS 1 BP 218 EP 228 DI 10.1016/j.jtbi.2011.01.042 PG 11 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 750JW UT WOS:000289543400025 PM 21315733 ER PT J AU Wang, SM de Zwart, JA Duyn, JH AF Wang, Shumin de Zwart, Jacco A. Duyn, Jeff H. TI A fast integral equation method for simulating high-field radio frequency coil arrays in magnetic resonance imaging SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MRI; APPROXIMATION; SENSE AB A fast full-wave numerical approach was developed for simulating high-field multi-channel radio-frequency (RF) receive coil arrays in magnetic resonance imaging. To improve the efficiency, the impedance matrix was compressed by a multilevel adaptive cross approximation method. Furthermore, careful organization of multiple coil simulations was applied so that the impedance matrix associated with biological subjects is constructed and pre-conditioned only once. Numerical examples demonstrate the efficacy of the proposed approach for RF coil simulations. C1 [Wang, Shumin] Auburn Univ, Dept Elect & Comp Engn, Auburn, AL 36849 USA. [Wang, Shumin; de Zwart, Jacco A.; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Wang, SM (reprint author), Auburn Univ, Dept Elect & Comp Engn, 200 Broun Hall, Auburn, AL 36849 USA. EM james.wang@ieee.org FU NINDS FX This work was supported in part by the NINDS intramural research program. The authors gratefully acknowledge Dr Alan P Koretsky for insightful discussions. NR 26 TC 1 Z9 1 U1 1 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2011 VL 56 IS 9 BP 2779 EP 2789 DI 10.1088/0031-9155/56/9/010 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 747UR UT WOS:000289346000010 PM 21464529 ER PT J AU Bothmer, A Robbiani, DF Di Virgilio, M Bunting, SF Klein, IA Feldhahn, N Barlow, J Chen, HT Bosque, D Callen, E Nussenzweig, A Nussenzweig, MC AF Bothmer, Anne Robbiani, Davide F. Di Virgilio, Michela Bunting, Samuel F. Klein, Isaac A. Feldhahn, Niklas Barlow, Jacqueline Chen, Hua-Tang Bosque, David Callen, Elsa Nussenzweig, Andre Nussenzweig, Michel C. TI Regulation of DNA End Joining, Resection, and Immunoglobulin Class Switch Recombination by 53BP1 SO MOLECULAR CELL LA English DT Article ID STRAND BREAK REPAIR; HISTONE H2AX; DAMAGE-RESPONSE; CHROMOSOMAL TRANSLOCATIONS; REGION RECOMBINATION; GENOMIC INSTABILITY; PROTEIN 53BP1; HUMAN CANCER; LIGASE 4; C-MYC AB 53BP1 is a DNA damage protein that forms phosphorylated H2AX (gamma-H2AX) dependent foci in a 1 Mb region surrounding DNA double-strand breaks (DSBs). In addition, 53BP1 promotes genomic stability by regulating the metabolism of DNA ends. We have compared the joining rates of paired DSBs separated by 1.2 kb to 27 Mb on chromosome 12 in the presence or absence of 53BP1. 53BP1 facilitates joining of intrachromosomal DSBs but only at distances corresponding to gamma-H2AX spreading. In contrast, DNA end protection by 53BP1 is distance independent. Furthermore, analysis of 53BP1 mutants shows that chromatin association, oligomerization, and N-terminal ATM phosphorylation are all required for DNA end protection and joining as measured by immunoglobulin class switch recombination. These data elucidate the molecular events that are required for 53BP1 to maintain genomic stability and point to a model wherein 53BP1 and H2AX cooperate to repress resection of DSBs. C1 [Bunting, Samuel F.; Barlow, Jacqueline; Chen, Hua-Tang; Nussenzweig, Andre; Nussenzweig, Michel C.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Bothmer, Anne; Robbiani, Davide F.; Di Virgilio, Michela; Klein, Isaac A.; Feldhahn, Niklas; Bosque, David; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM nussenza@exchange.nih.gov; nussen@mail.rockefeller.edu FU Fondazione Ettore e Valeria Rossi; NIH [AI037526, GM07739]; Department of Defense [BC102335]; National Cancer Institute; Center for Cancer Research FX All members of the Nussenzweig labs for discussions. Thanos Halazonetis for wild type human 53BP1 plasmid and Philip Carpenter for plasmid with 53BP1 alanine substitutions. The Rockefeller University Gene Targeting Facility for the generation of mutant mice. The work was supported in part by a Fondazione Ettore e Valeria Rossi grant to D.F.R., by a NIH grant to M.C.N (AI037526), and a Department of Defense grant to A.N. (BC102335). A.N. and S.B. were supported by the Intramural Research Program of the NIH, the National Cancer Institute, and the Center for Cancer Research and I.A.K by NIH Medical Scientist Training Program grant GM07739. A.B. is a Predoctoral Fellow of the Cancer Research Institute, N.F. is and D.F.R. was a Fellow of the Leukemia and Lymphoma Society, M.D.V. is a Fellow of the American-Italian Cancer Foundation, and M.C.N. is a Howard Hughes Medical Institute Investigator. NR 53 TC 117 Z9 120 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 6 PY 2011 VL 42 IS 3 BP 319 EP 329 DI 10.1016/j.molcel.2011.03.019 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762HN UT WOS:000290465900008 PM 21549309 ER PT J AU Ng, SSM Chang, TH Tailor, P Ozato, K Kino, T AF Ng, Sinnie Sin Man Chang, Tsung-Hsien Tailor, Prafullakumar Ozato, Keiko Kino, Tomoshige TI Virus-induced differential expression of nuclear receptors and coregulators in dendritic cells: Implication to interferon production SO FEBS LETTERS LA English DT Article DE Coregulator; Dendritic cell; Histone deacetylase; Neuron-derived orphan receptor-1; Nuclear receptor; Viral infection ID LIVER-X-RECEPTORS; PATHOGEN RECOGNITION; GENE-EXPRESSION; INNATE; IMMUNITY; LXR; ACTIVATION; INDUCTION; GAMMA; INFLAMMATION AB We investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in mouse bone marrow-derived dendritic cells (DCs) upon infection with Newcastle Disease virus (NDV) or murine cytomegalovirus (MCMV). These viruses regulated mRNA expression of some NRs among which NOR1 and LXR alpha were highly induced at mRNA and protein levels. Exogenous expression of the latter NRs repressed IRF3- or IRF7-induced transactivation of the interferon beta promoter and NDV infection further potentiated their repressive effect. The viral infection also significantly regulated mRNA expression of some coregulators, including HDAC1. Toll-like receptor ligands regulated NR and coregulator mRNA expression similar to the viruses. Thus, NRs and coregulators are integral components of DC-organizing anti-viral response wherein NOR1 and LXR alpha participate in regulating interferon production. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Ng, Sinnie Sin Man; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Ng, Sinnie Sin Man] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Chang, Tsung-Hsien; Tailor, Prafullakumar; Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Kino, T (reprint author), Clin Res Ctr, Bldg 10,Rm 1E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health FX This study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 34 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 6 PY 2011 VL 585 IS 9 BP 1331 EP 1337 DI 10.1016/j.febslet.2011.04.001 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 759LZ UT WOS:000290248300013 PM 21492741 ER PT J AU Miller, EH Harrison, JS Radoshitzky, SR Higgins, CD Chi, XL Dong, L Kuhn, JH Bavari, S Lai, JR Chandran, K AF Miller, Emily Happy Harrison, Joseph S. Radoshitzky, Sheli R. Higgins, Chelsea D. Chi, Xiaoli Dong, Lian Kuhn, Jens H. Bavari, Sina Lai, Jonathan R. Chandran, Kartik TI Inhibition of Ebola Virus Entry by a C-peptide Targeted to Endosomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRAL MEMBRANE-FUSION; HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; AVIAN-SARCOMA; COILED-COIL; TYPE-1 GP41; INFECTION; MECHANISMS; PROTEINS AB Ebola virus (EboV) and Marburg virus (MarV) (filoviruses) are the causative agents of severe hemorrhagic fever. Infection begins with uptake of particles into cellular endosomes, where the viral envelope glycoprotein (GP) catalyzes fusion between the viral and host cell membranes. This fusion event is thought to involve conformational rearrangements of the transmembrane subunit (GP2) of the envelope spike that ultimately result in formation of a six-helix bundle by the N- and C-terminal heptad repeat (NHR and CHR, respectively) regions of GP2. Infection by other viruses employing similar viral entry mechanisms (such as HIV-1 and severe acute respiratory syndrome coronavirus) can be inhibited with synthetic peptides corresponding to the native CHR sequence ("C-peptides"). However, previously reported EboV C-peptides have shown weak or insignificant antiviral activity. To determine whether the activity of a C-peptide could be improved by increasing its intracellular concentration, we prepared an EboV C-peptide conjugated to the arginine-rich sequence from HIV-1 Tat, which is known to accumulate in endosomes. We found that this peptide specifically inhibited viral entry mediated by filovirus GP proteins and infection by authentic filoviruses. We determined that antiviral activity was dependent on both the Tat sequence and the native EboV CHR sequence. Mechanistic studies suggested that the peptide acts by blocking a membrane fusion intermediate. C1 [Harrison, Joseph S.; Higgins, Chelsea D.; Lai, Jonathan R.] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. [Miller, Emily Happy; Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Radoshitzky, Sheli R.; Chi, Xiaoli; Dong, Lian; Bavari, Sina] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA. [Kuhn, Jens H.] Tunnell Consulting Inc, King Of Prussia, PA 19406 USA. RP Lai, JR (reprint author), Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jon.lai@einstein.yu.edu; kartik.chandran@einstein.yu.edu RI Kuhn, Jens H./B-7615-2011 OI Kuhn, Jens H./0000-0002-7800-6045 FU National Institutes of Health [R01 AI088027, R01 AI090249]; Albert Einstein College of Medicine; Arnold and Mabel Beckman Foundation; Joint Science and Technology Office Transformational Medical Technologies [TMTI0048_09_RD_T]; Defense Threat Reduction Agency [4.10022_08_RD_B]; NIAID [HHSN272200200016I] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 AI088027 (to K. C.) and R01 AI090249 (to J. R. L.). This work was also supported by the Albert Einstein College of Medicine, the Arnold and Mabel Beckman Foundation Young Investigators Program (to J. R. L.), and Joint Science and Technology Office Transformational Medical Technologies Proposal TMTI0048_09_RD_T and Defense Threat Reduction Agency Proposal 4.10022_08_RD_B (to S. B.). J. H. K. performed this work as an employee of Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under Contract No. HHSN272200200016I. NR 48 TC 28 Z9 31 U1 1 U2 23 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 MAY 6 PY 2011 VL 286 IS 18 DI 10.1074/jbc.M110.207084 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756ON UT WOS:000290022800026 PM 21454542 ER PT J AU Wang, H Bell, M Sreenevasan, U Hu, H Liu, J Dalen, K Londos, C Yamaguchi, T Rizzo, MA Coleman, R Gong, DW Brasaemle, D Sztalryd, C AF Wang, Hong Bell, Ming Sreenevasan, Urmilla Hu, Hong Liu, Jun Dalen, Knut Londos, Constantine Yamaguchi, Tomohiro Rizzo, Mark A. Coleman, Rosalind Gong, Dawei Brasaemle, Dawn Sztalryd, Carole TI Unique Regulation of Adipose Triglyceride Lipase (ATGL) by Perilipin 5, a Lipid Droplet-associated Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-SENSITIVE LIPASE; DIFFERENTIATION-RELATED PROTEIN; CHANARIN-DORFMAN-SYNDROME; MEDIATED LIPOLYSIS; INSULIN-RESISTANCE; ADIPOCYTES; CGI-58; MICE; OBESITY; TISSUE AB Lipolysis is a critical metabolic pathway contributing to energy homeostasis through degradation of triacylglycerides stored in lipid droplets (LDs), releasing fatty acids. Neutral lipid lipases act at the oil/water interface. In mammalian cells, LD surfaces are coated with one or more members of the perilipin protein family, which serve important functions in regulating lipolysis. We investigated mechanisms by which three perilipin proteins control lipolysis by adipocyte triglyceride lipase (ATGL), a key lipase in adipocytes and non-adipose cells. Using a cell culture model, we examined interactions of ATGL and its co-lipase CGI-58 with perilipin 1 (perilipin A), perilipin 2 (adipose differentiation-related protein), and perilipin 5 (LSDP5) using multiple techniques as follows: anisotropy Forster resonance energy transfer, co-immunoprecipitation, [P-32] orthophosphate radiolabeling, and measurement of lipolysis. The results show that ATGL interacts with CGI-58 and perilipin 5; the latter is selectively expressed in oxidative tissues. Both proteins independently recruited ATGL to the LD surface, but with opposite effects; interaction of ATGL with CGI-58 increased lipolysis, whereas interaction of ATGL with perilipin 5 decreased lipolysis. In contrast, neither perilipin 1 nor 2 interacted directly with ATGL. Activation of protein kinase A (PKA) increased [P-32] orthophosphate incorporation into perilipin 5 by 2-fold, whereas neither ATGL nor CGI-58 was labeled under the incubation conditions. Cells expressing both ectopic perilipin 5 and ATGL showed a 3-fold increase in lipolysis following activation of PKA. Our studies establish perilipin 5 as a novel ATGL partner and provide evidence that the protein composition of perilipins at the LD surface regulates lipolytic activity of ATGL. C1 [Wang, Hong; Bell, Ming; Sreenevasan, Urmilla; Gong, Dawei; Sztalryd, Carole] Univ Maryland, Sch Med, Dept Med,Div Endocrinol, Geriatr Res Educ & Clin Ctr,Baltimore Vet Affairs, Baltimore, MD 21201 USA. [Liu, Jun] Univ Kentucky, Dept Pediat, Lexington, KY 40506 USA. [Dalen, Knut; Londos, Constantine] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Yamaguchi, Tomohiro] Univ Hyogo, Grad Sch Life Sci, Kamigori, Hyogo 6781297, Japan. [Rizzo, Mark A.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Coleman, Rosalind] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Brasaemle, Dawn] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08901 USA. RP Sztalryd, C (reprint author), Univ Maryland, Sch Med, Dept Med,Div Endocrinol, Geriatr Res Educ & Clin Ctr,Baltimore Vet Affairs, Rm 445,Howard Hall,660 W Redwood St, Baltimore, MD 21201 USA. EM csztalry@grecc.umaryland.edu RI Dalen, Knut Tomas/C-4719-2016 OI Dalen, Knut Tomas/0000-0002-0270-5982 FU National Institutes of Health [1RO1 DK 075017, R01 DK54797]; NIDDK; American Diabetes Association [1-05-CD-17]; Geriatric Research, Education and Clinical Center; Baltimore Veterans Affairs Health Care Center; Clinical Nutrition Research Unit of Maryland [DK072488] FX This work was supported, in whole or in part, by National Institutes of Health Grants 1RO1 DK 075017 (to C. S.) and R01 DK54797 (to D. B.) and by Intramural Research Programs of NIDDK. This work was also supported by Career Development Award 1-05-CD-17 from the American Diabetes Association (to C. S.), the Geriatric Research, Education and Clinical Center, Baltimore Veterans Affairs Health Care Center, and Clinical Nutrition Research Unit of Maryland Grant DK072488. NR 38 TC 92 Z9 97 U1 2 U2 24 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 MAY 6 PY 2011 VL 286 IS 18 DI 10.1074/jbc.M110.207779 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756ON UT WOS:000290022800010 PM 21393244 ER PT J AU Berezhkovskii, AM Sample, C Shvartsman, SY AF Berezhkovskii, Alexander M. Sample, Christine Shvartsman, Stanislav Y. TI Formation of morphogen gradients: Local accumulation time SO PHYSICAL REVIEW E LA English DT Article ID POSITIONAL INFORMATION; DROSOPHILA-EMBRYO; DPP GRADIENT; DIFFUSION; KINETICS; PATTERN; MODEL AB Spatial regulation of cell differentiation in embryos can be provided by morphogen gradients, which are defined as the concentration fields of molecules that control gene expression. For example, a cell can use its surface receptors to measure the local concentration of an extracellular ligand and convert this information into a corresponding change in its transcriptional state. We characterize the time needed to establish a steady-state gradient in problems with diffusion and degradation of locally produced chemical signals. A relaxation function is introduced to describe how the morphogen concentration profile approaches its steady state. This function is used to obtain a local accumulation time that provides a time scale that characterizes relaxation to steady state at an arbitrary position within the patterned field. To illustrate the approach we derive local accumulation times for a number of commonly used models of morphogen gradient formation. C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Sample, Christine; Shvartsman, Stanislav Y.] Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08544 USA. [Sample, Christine; Shvartsman, Stanislav Y.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. FU National Institutes of Health, Center for Information Technology; National Institutes of Health [HHSN266200500021C]; ADB [N01-AI-50021] FX We are grateful to Ruth Baker for helpful discussion and suggesting the term "local accumulation time." S.Y.S. thanks Marcos Gonzalez-Gaitan and Ortrud Wattlick for helpful discussion and advice on the application of our results to the Dpp gradient. The authors were partially supported by the Intramural Research program of the National Institutes of Health, Center for Information Technology (A.M.B.) and the National Institutes of Health Contract No. HHSN266200500021C, ADB No. N01-AI-50021 (S.Y.S. and C.S.). NR 34 TC 18 Z9 18 U1 0 U2 4 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD MAY 6 PY 2011 VL 83 IS 5 AR 051906 DI 10.1103/PhysRevE.83.051906 PN 1 PG 7 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 760FT UT WOS:000290310800001 PM 21728570 ER PT J AU Pepe, A Pamment, M Georg, GI Malhotra, SV AF Pepe, Antonella Pamment, Michael Georg, Gunda I. Malhotra, Sanjay V. TI Synthesis of Fused Bicyclic Systems with Nitrogen Atom at the Bridgehead, Including Indolizidines and Quinolizidines SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID BETA-LACTAMS; ENANTIOSELECTIVE SYNTHESIS; ASYMMETRIC-SYNTHESIS; FORMAL SYNTHESIS; BUILDING-BLOCKS; (-)-SWAINSONINE; ENAMINONES; STRATEGY; ACYL AB Monocyclic as well as fused bicyclic systems with a nitrogen 10 atom at the bridgehead, including indolizidines and quinolizidines, can be prepared in four steps from N-Boc beta-lactams. These easily prepared, highly robust, and flexible building blocks allow the incorporation of chirality and structural diversity, rendering the method feasible for diversity- as well as target-oriented synthesis. C1 [Pepe, Antonella; Georg, Gunda I.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55414 USA. [Pepe, Antonella; Georg, Gunda I.] Univ Minnesota, Inst Therapeut Discovery & Dev, Minneapolis, MN 55414 USA. [Pepe, Antonella; Pamment, Michael; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Georg, GI (reprint author), Univ Minnesota, Dept Med Chem, 717 Delaware St SE, Minneapolis, MN 55414 USA. EM georg@umn.edu; malhotrasa@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH [GM081267] FX This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and from NIH grant GM081267. 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 26 TC 12 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 6 PY 2011 VL 76 IS 9 BP 3527 EP 3530 DI 10.1021/jo102558u PG 4 WC Chemistry, Organic SC Chemistry GA 755SO UT WOS:000289956900063 PM 21452823 ER PT J AU Geng, SA Yu, Y Kang, YM Pavlakis, G Jin, HL Li, JY Hu, YX Hu, WB Wang, SA Wang, B AF Geng, Shuang Yu, Yang Kang, Youmin Pavlakis, George Jin, Huali Li, Jinyao Hu, Yanxin Hu, Weibin Wang, Shuang Wang, Bin TI Efficient induction of CD25(-) iTreg by co-immunization requires strongly antigenic epitopes for T cells SO BMC IMMUNOLOGY LA English DT Article ID IMMUNE SUPPRESSION; REGULATORY CELLS; TGF-BETA; RECOGNITION; TOLERANCE; VACCINES; FLEA; SELF; DNA AB Background: We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40(low) IL-10(high) tolerogenic DCs, which in turn stimulates the expansion of antigen-specific CD4(+) CD25-Foxp3(+) regulatory T cells (CD25(-) iTreg). However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25(-) iTreg induction. Results: In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25(-) iTreg induction. Firstly, we showed that the induction of CD25(-) iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25(-) iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25(-) iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes. Conclusions: Our data thus indicate that efficient induction of CD25(-) iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25(-) iTreg for clinical applications such as flea allergic dermatitis. C1 [Geng, Shuang; Yu, Yang; Kang, Youmin; Jin, Huali; Li, Jinyao; Hu, Weibin; Wang, Shuang; Wang, Bin] China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China. [Pavlakis, George] NCI, Ctr Canc Res, Frederick, MD 21702 USA. [Hu, Yanxin] China Agr Univ, Coll Vet Med, Beijing 100193, Peoples R China. [Jin, Huali] Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA. RP Wang, B (reprint author), China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China. EM bwang03@gmail.com RI Jin, Huali/F-3650-2011 FU National Nature Science Foundation of China [20771602, 30930068]; State Key Lab Innovative Research initiation [2008SKLAB05-02] FX This work was supported in part by the National Nature Science Foundation of China (20771602 and 30930068) and State Key Lab Innovative Research initiation (2008SKLAB05-02) to BW. We would like to thank Dr. Jane QL Yu and Zhonghuai He for their assistances in this work. NR 27 TC 8 Z9 8 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD MAY 5 PY 2011 VL 12 AR 27 DI 10.1186/1471-2172-12-27 PG 9 WC Immunology SC Immunology GA 772VZ UT WOS:000291267200001 PM 21542943 ER PT J AU Schorzman, AN Perera, L Cutalo-Patterson, JM Pedersen, LC Pedersen, LG Kunkel, TA Tomer, KB AF Schorzman, Allison N. Perera, Lalith Cutalo-Patterson, Jenny M. Pedersen, Lars C. Pedersen, Lee G. Kunkel, Thomas A. Tomer, Kenneth B. TI Modeling of the DNA-binding site of yeast Pms1 by mass spectrometry SO DNA REPAIR LA English DT Article DE Mismatch repair; MutL alpha; Pms1; DNA binding; Mass spectrometry ID CATALYZED OXIDATION REACTIONS; INDUCED CONFORMATIONAL-CHANGES; AMINO-ACID-RESIDUES; C-TERMINAL DOMAIN; MISMATCH REPAIR; HYDROGEN-PEROXIDE; PHOTOCHEMICAL OXIDATION; RADIOLYTIC MODIFICATION; MLH1-PMS1 HETERODIMER; PROTEIN INTERACTIONS AB Mismatch repair (MMR) corrects replication errors that would otherwise lead to mutations and, potentially, various forms of cancer. Among several proteins required for eukaryotic MMR, MutL alpha is a heterodimer comprised of Mlh1 and Pms1. The two proteins dimerize along their C-terminal domains (CTDs), and the CTD of Pms1 houses a latent endonuclease that is required for MMR. The highly conserved N-terminal domains (NTDs) independently bind DNA and possess ATPase active sites. Here we use two protein footprinting techniques, limited proteolysis and oxidative surface mapping, coupled with mass spectrometry to identify amino acids involved along the DNA-binding surface of the Pms1-NTD. Limited proteolysis experiments elucidated several basic residues that were protected in the presence of DNA, while oxidative surface mapping revealed one residue that is uniquely protected from oxidation. Furthermore, additional amino acids distributed throughout the Pms1-NTD were protected from oxidation either in the presence of a non-hydrolyzable analog of ATP or DNA, indicating that each ligand stabilizes the protein in a similar conformation. Based on the recently published X-ray crystal structure of yeast Pms1-NTD, a model of the Pms1-NTD/DNA complex was generated using the mass spectrometric data as constraints. The proposed model defines the DNA-binding interface along a positively charged groove of the Pms1-NTD and complements prior mutagenesis studies of Escherichia coli and eukaryotic MutL. Published by Elsevier B.V. C1 [Schorzman, Allison N.; Perera, Lalith; Cutalo-Patterson, Jenny M.; Pedersen, Lars C.; Pedersen, Lee G.; Kunkel, Thomas A.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Schorzman, AN (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233,MD F0-04, Res Triangle Pk, NC 27709 USA. EM schorzmana@niehs.nih.gov; tomer@niehs.nih.gov RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013; Tomer, Kenneth/E-8018-2013 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861; FU Division of Intramural Research of the National Institute for Environmental Health Sciences/National Institutes of Health [Z01 ES0050127, Z01 ES065089, Z01 ES43010-24, Z01 ES102645-01] FX The authors gratefully acknowledge Dr. Leesa Deterding and Dr. Mercedes Arana for thoughtful review of this manuscript. We thank the Protein Microcharacterization Core Facility for use of their instrumentation. This research was supported by Project Z01 ES0050127 CANS, JMC-P, KBT), Project Z01 ES065089 (TAK), Project Z01 ES43010-24 (LP, LGP) and Project Z01 ES102645-01 (LCP), all from the Division of Intramural Research of the National Institute for Environmental Health Sciences/National Institutes of Health. NR 66 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAY 5 PY 2011 VL 10 IS 5 BP 454 EP 465 DI 10.1016/j.dnarep.2011.01.010 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 772NA UT WOS:000291239400001 PM 21354867 ER PT J AU Clark, AB Lujan, SA Kissling, GE Kunkel, TA AF Clark, Alan B. Lujan, Scott A. Kissling, Grace E. Kunkel, Thomas A. TI Mismatch repair-independent tandem repeat sequence instability resulting from ribonucleotide incorporation by DNA polymerase epsilon SO DNA REPAIR LA English DT Article DE Ribonucleotide incorporation; RNase H2; DNA mismatch repair; Deletions; Genome instability ID SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; REPLICATION FORK; LYNCH-SYNDROME; MUTATIONS; CANCER; DISCRIMINATION; MECHANISMS; BIOLOGY AB During DNA synthesis in vitro using dNTP and rNTP concentrations present in vivo, yeast replicative DNA polymerases alpha, delta and epsilon (Pols alpha, delta and epsilon) stably incorporate rNTPs into DNA. rNTPs are also incorporated during replication in vivo, and they are repaired in an RNase H2-dependent manner. In strains encoding a mutator allele of Pol epsilon (pol2-M644G), failure to remove rNMPs from DNA due to deletion of the RNH201 gene encoding the catalytic subunit of RNase H2, results in deletion of 2-5 base pairs in short repetitive sequences. Deletion rates depend on the orientation of the reporter gene relative to a nearby replication origin, suggesting that mutations result from rNMPs incorporated during replication. Here we demonstrate that 2-5 base pair deletion mutagenesis also strongly increases in rnh201 Delta strains encoding wild type DNA polymerases. As in the pol2-M644G strains, the deletions occur at repetitive sequences and are orientation-dependent, suggesting that mismatches involving misaligned strands arise that could be subject to mismatch repair. Unexpectedly however, 2-5 base pair deletion rates resulting from loss of RNH201 in the pol2-M644G strain are unaffected by concomitant loss of MSH3, MSH6, or both. It could be that the mismatch repair machinery is unable to repair mismatches resulting from unrepaired rNMPs incorporated into DNA by M644G Pol epsilon, but this possibility is belied by the observation that Msh2-Msh6 can bind to a ribonucleotide-containing mismatch. Alternatively, following incorporation of rNMPs by M644G Pol epsilon during replication, the conversion of unrepaired rNMPs into mutations may occur outside the context of replication, e.g., during the repair of nicks resulting from rNMPs in DNA. The results make interesting predictions that can be tested. Published by Elsevier B.V. C1 [Clark, Alan B.; Lujan, Scott A.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Clark, Alan B.; Lujan, Scott A.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Division of Intramural Research of the NIH, NIEHS [Z01 ES065089] FX We thank Shay Covo and Jessica Williams for thoughtful comments on the manuscript, and the NIEHS Molecular Genetics Core for technical support in DNA sequence analysis of ura3 mutants. This work was funded by the Division of Intramural Research of the NIH, NIEHS, Project Z01 ES065089. NR 32 TC 36 Z9 36 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAY 5 PY 2011 VL 10 IS 5 BP 476 EP 482 DI 10.1016/j.dnarep.2011.02.001 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 772NA UT WOS:000291239400003 PM 21414850 ER PT J AU Abdulovic, AL Hile, SE Kunkel, TA Eckert, KA AF Abdulovic, Amy L. Hile, Suzanne E. Kunkel, Thomas A. Eckert, Kristin A. TI The in vitro fidelity of yeast DNA polymerase delta and polymerase epsilon holoenzymes during dinucleotide microsatellite DNA synthesis SO DNA REPAIR LA English DT Article DE Microsatellite instability; Indel mutation; DNA replication fidelity; Polymerase proofreading; HSV-tk gene ID SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; FRAMESHIFT MUTATIONS; STRAND MISALIGNMENT; MONONUCLEOTIDE RUNS; GENOME INSTABILITY; REPETITIVE DNA; REPLICATION; SEQUENCES; ERRORS AB Elucidating the sources of genetic variation within microsatellite alleles has important implications for understanding the etiology of human diseases. Mismatch repair is a well described pathway for the suppression of microsatellite instability. However, the cellular polymerases responsible for generating microsatellite errors have not been fully described. We address this gap in knowledge by measuring the fidelity of recombinant yeast polymerase delta (Pol delta) and epsilon (Pol epsilon) holoenzymes during synthesis of a [GT/CA] microsatellite. The in vitro HSV-tk forward assay was used to measure DNA polymerase errors generated during gap-filling of complementary GT(10) and CA(10)-containing substrates and similar to 90 nucleotides of HSV-tk coding sequence surrounding the microsatellites. The observed mutant frequencies within the microsatellites were 4 to 30-fold higher than the observed mutant frequencies within the coding sequence. More specifically, the rate of Pol delta and Pol epsilon misalignment-based insertion/deletion errors within the microsatellites was similar to 1000-fold higher than the rate of insertion/deletion errors within the HSV-tk gene. Although the most common microsatellite error was the deletion of a single repeat unit, similar to 20% of errors were deletions of two or more units for both polymerases. The differences in fidelity for wild type enzymes and their exonuclease-deficient derivatives were similar to 2-fold for unit-based microsatellite insertion/deletion errors. Interestingly, the exonucleases preferentially removed potentially stabilizing interruption errors within the microsatellites. Since Pol delta and Pol epsilon perform not only the bulk of DNA replication in eukaryotic cells but also are implicated in performing DNA synthesis associated with repair and recombination, these results indicate that microsatellite errors may be introduced into the genome during multiple DNA metabolic pathways. (C) 2011 Elsevier B.V. All rights reserved. C1 [Hile, Suzanne E.; Eckert, Kristin A.] Penn State Univ, Coll Med, Gittlen Canc Res Fdn, Dept Pathol, Hershey, PA 17033 USA. [Abdulovic, Amy L.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Abdulovic, Amy L.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Hile, Suzanne E.; Eckert, Kristin A.] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. RP Eckert, KA (reprint author), Penn State Univ, Coll Med, Gittlen Canc Res Fdn, Dept Pathol, 500 Univ Dr, Hershey, PA 17033 USA. EM kae4@psu.edu FU National Institutes of Health [R01 CA100060]; Department of Intramural Research of the National Institutes of Health [Z01 ES065070] FX The DNA sequencing Research Support group at the NIEHS completed the sequencing reactions. We thank Ms. Noelle Strubczweski for determining the unfilled gapped substrate background mutant frequency. We also thank E. Johansson and E.B. Lundstrom for providing purified Pol epsilon exonuclease deficient enzyme for in vitro reactions. This work was supported by Grant R01 CA100060 from the National Institutes of Health to K.A.E and by Project Z01 ES065070 to T.A.K from the Department of Intramural Research of the National Institutes of Health. The funding sources had no role of any type in the study. NR 48 TC 15 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAY 5 PY 2011 VL 10 IS 5 BP 497 EP 505 DI 10.1016/j.dnarep.2011.02.003 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 772NA UT WOS:000291239400005 PM 21429821 ER PT J AU Dojcinov, SD Venkataraman, G Pittaluga, S Wlodarska, I Schrager, JA Raffeld, M Hills, RK Jaffe, ES AF Dojcinov, Stefan D. Venkataraman, Girish Pittaluga, Stefania Wlodarska, Iwona Schrager, Jeffrey A. Raffeld, Mark Hills, Robert K. Jaffe, Elaine S. TI Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; B-CELL LYMPHOMA; HODGKINS-DISEASE; AGGRESSIVE LYMPHOMA; ELDERLY-PATIENTS; VIRAL-INFECTION; T-LYMPHOCYTES; TISSUE; REARRANGEMENT; PHENOTYPE AB We investigated age-related EBV(+) B-cell lymphoproliferations in the Western population. The clinical features, histology, immunophenotype, EBV-encoded RNA in situ hybridization, and clonality by PCR of T-cell receptor gamma and immunoglobulin genes were categorized in 122 EBV(+) lesions as follows: (1) reactive lymphoid hyperplasia; (2) polymorphic extranodal or (3) polymorphic nodal lymphoproliferative disease (LPD); and (4) diffuse large B-cell lymphoma (DLBCL). Interphase FISH for IG and PAX5 gene rearrangements was performed on 17 cases of DLBCL. The overall median age was 75 years (range, 45-101 years; 67 men, 55 women), and 67, 79, 73, and 77 years, respectively, for groups 1 through 4. Sixteen of 21 cases of polymorphic extranodal LPD were classified as EBV(+) mucocutaneous ulcer. PCR for immunoglobulin genes was polyclonal in reactive lymphoid hyperplasia (84%) and monoclonal in 33%, 63%, and 56% of polymorphic extranodal and nodal LPD cases and DLBCL, respectively. All groups showed restricted/clonal T-cell receptor responses (27%-70%). By FISH, 19% of DLBCLs showed IGH@ rearrangements, but PAX5 was unaffected. Disease-specific 5-year survival was 100%, 93%, 57%, and 25% for groups 1-4, respectively, and 100% for patients with EBV(+) mucocutaneous ulcer. Disease volume was predictive of therapy response (P = .0002), and pathologic subtype was predictive of overall outcome (P = .001). Age-related EBV(+) B-cell LPD encompasses a wider disease spectrum than previously recognized and includes both reactive and neoplastic conditions. Reduction in the T-cell repertoire may contribute to decreased immune surveillance. (Blood. 2011; 117(18): 4726-4735) C1 [Venkataraman, Girish; Pittaluga, Stefania; Schrager, Jeffrey A.; Raffeld, Mark; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Dojcinov, Stefan D.] Univ Wales Hosp, Dept Pathol, All Wales Lymphoma Panel, Cardiff CF4 4XW, S Glam, Wales. [Hills, Robert K.] Cardiff Univ, Sch Med, Dept Haematol, Cardiff, S Glam, Wales. [Wlodarska, Iwona] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Rm 2B 42,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov OI Venkataraman, Girish/0000-0002-8674-2608; Hills, Robert/0000-0003-0166-0062; Jaffe, Elaine/0000-0003-4632-0301 FU Center for Cancer Research, National Cancer Institute; British Division of the International Academy of Pathology; British Society for Hematology FX This work was supported by the intramural program of the Center for Cancer Research, National Cancer Institute. S. D. D. received financial support from the British Division of the International Academy of Pathology and British Society for Hematology. NR 39 TC 93 Z9 96 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4726 EP 4735 DI 10.1182/blood-2010-12-323238 PG 10 WC Hematology SC Hematology GA 759VD UT WOS:000290275700013 PM 21385849 ER PT J AU Waldmann, TA Lugli, E Roederer, M Perera, LP Smedley, JV Macallister, RP Goldman, CK Bryant, BR Decker, JM Fleisher, TA Lane, HC Sneller, MC Kurlander, RJ Kleiner, DE Pletcher, JM Figg, WD Yovandich, JL Creekmore, SP AF Waldmann, Thomas A. Lugli, Enrico Roederer, Mario Perera, Liyanage P. Smedley, Jeremy V. Macallister, Rhonda P. Goldman, Carolyn K. Bryant, Bonita R. Decker, Jean M. Fleisher, Thomas A. Lane, H. Clifford Sneller, Michael C. Kurlander, Roger J. Kleiner, David E. Pletcher, John M. Figg, William D. Yovandich, Jason L. Creekmore, Stephen P. TI Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques SO BLOOD LA English DT Article ID CD8(+) T-CELLS; ANTITUMOR-ACTIVITY; NONHUMAN-PRIMATES; IN-VIVO; INTERLEUKIN-15; PROLIFERATION; CANCER; NK; HOMEOSTASIS; MICE AB IL-15 uses the heterotrimeric receptor IL-2/IL-15R beta and the gamma chain shared with IL-2 and the cytokine-specific IL-15R alpha. Although IL-15 shares actions with IL-2 that include activation of natural killer (NK) and CD8 T cells, IL-15 is not associated with capillary leak syndrome, activation-induced cell death, or with a major effect on the number of functional regulatory T cells. To prepare for human trials to determine whether IL-15 is superior to IL-2 in cancer therapy, recombinant human IL-15 (rhIL-15) was produced under current good manufacturing practices. A safety study in rhesus macaques was performed in 4 groups of 6 animals each that received vehicle diluent control or rhIL-15 at 10, 20, or 50 mu g/kg/d IV for 12 days. The major toxicity was grade 3/4 transient neutropenia. Bone marrow examinations demonstrated increased marrow cellularity, including cells of the neutrophil series. Furthermore, neutrophils were observed in sinusoids of enlarged livers and spleens, suggesting that IL-15 mediated neutrophil redistribution from the circulation to tissues. The observation that IL-15 administration was associated with increased numbers of circulating NK and CD8 central and effector-memory T cells, in conjunction with efficacy studies in murine tumor models, supports the use of multiple daily infusions of rhIL-15 in patients with metastatic malignancies. (Blood. 2011; 117(18): 4787-4795) C1 [Waldmann, Thomas A.; Lugli, Enrico; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Waldmann, Thomas A.; Perera, Liyanage P.; Goldman, Carolyn K.; Bryant, Bonita R.; Decker, Jean M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Smedley, Jeremy V.; Macallister, Rhonda P.] SAIC Frederick Inc, Lab Anim Sci Program, Bethesda, MD USA. [Fleisher, Thomas A.] Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD USA. [Lane, H. Clifford; Sneller, Michael C.] NIAID, Clin Res Ctr, Bethesda, MD 20892 USA. [Kurlander, Roger J.] Warren G Magnuson Clin Ctr, Hematol Serv Clin Pathol Dept, Bethesda, MD USA. [Kleiner, David E.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Pletcher, John M.] Pathol Associates Inc, Charles River Labs, Frederick, MD USA. [Figg, William D.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Yovandich, Jason L.; Creekmore, Stephen P.] NCI, Biol Resources Branch, Dev Therapeut Program, Frederick, MD 21701 USA. RP Waldmann, TA (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov RI Figg Sr, William/M-2411-2016; OI Smedley, Jeremy/0000-0003-3369-4662; Kleiner, David/0000-0003-3442-4453 FU National Cancer Institute (Frederick, MD); National Institute of Allergy and Infectious Diseases, National Institutes of Health (Bethesda, MD) FX This research was supported by the intramural programs of the National Cancer Institute (Frederick, MD) and the National Institute of Allergy and Infectious Diseases, National Institutes of Health (Bethesda, MD). NR 42 TC 57 Z9 57 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4787 EP 4795 DI 10.1182/blood-2010-10-311456 PG 9 WC Hematology SC Hematology GA 759VD UT WOS:000290275700020 PM 21385847 ER PT J AU Yamamoto, T Price, DA Casazza, JP Ferrari, G Nason, M Chattopadhyay, PK Roederer, M Gostick, E Katsikis, PD Douek, DC Haubrich, R Petrovas, C Koup, RA AF Yamamoto, Takuya Price, David A. Casazza, Joseph P. Ferrari, Guido Nason, Martha Chattopadhyay, Pratip K. Roederer, Mario Gostick, Emma Katsikis, Peter D. Douek, Daniel C. Haubrich, Richard Petrovas, Constantinos Koup, Richard A. TI Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8(+) T-cell exhaustion in HIV infection SO BLOOD LA English DT Article ID CHRONIC VIRAL-INFECTION; PROGRAMMED DEATH-1; SPARING REGIMENS; 2B4 CD244; MEMORY; DIFFERENTIATION; ANTIGEN; PERSISTENCE; ACTIVATION; RESPONSES AB A highly complex network of coinhibitory and costimulatory receptors regulates the outcome of virus-specific CD8(+) T-cell responses. Here, we report on the expression patterns of multiple inhibitory receptors on HIV-specific, cytomegalovirusspecific, and bulk CD8(+) T-cell memory populations. In contrast to cytomegalovirus-specific CD8(+) T cells, the majority of HIV-specific CD8(+) T cells exhibited an immature phenotype and expressed Programmed Death-1, CD160 and 2B4 but not lymphocyte activation gene-3. Notably, before antiretroviral therapy, simultaneous expression of these negative regulators correlated strongly with both HIV load and impaired cytokine production. Suppression of HIV replication by antiretroviral therapy was associated with reduced surface expression of inhibitory molecules on HIV-specific CD8(+) T cells. Furthermore, in vitro manipulation of Programmed Death-1 and 2B4 inhibitory pathways increased the proliferative capacity of HIV-specific CD8(+) T cells. Thus, multiple coinhibitory receptors can affect the development of HIV-specific CD8(+) T-cell responses and, by extension, represent potential targets for new immune-based interventions in HIV-infected persons. (Blood. 2011; 117(18): 4805-4815) C1 [Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Price, David A.; Douek, Daniel C.] NIH, Human Immunol Sect, Bethesda, MD 20892 USA. [Price, David A.; Gostick, Emma] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales. [Ferrari, Guido] Duke Univ, Med Ctr, Dept Surg Sci, Durham, NC USA. [Nason, Martha] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Chattopadhyay, Pratip K.; Roederer, Mario] NIH, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Katsikis, Peter D.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Haubrich, Richard] Univ Calif San Diego, Div Infect Dis, Antiviral Res Ctr, San Diego, CA 92103 USA. RP Koup, RA (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3022,Bldg 40,Rm 3502, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov RI Yamamoto, Takuya/L-2642-2013; Price, David/C-7876-2013; Ferrari, Guido/A-6088-2015; OI Yamamoto, Takuya/0000-0003-3753-1211; Price, David/0000-0001-9416-2737; Katsikis, Peter/0000-0001-7690-5218; Chattopadhyay, Pratip/0000-0002-5457-9666 FU Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health [K24 AI64086]; University of California San Diego Center for AIDS Research [AI36214]; San Diego AIDS Clinical Trial Group (CTU) [AI69432] FX This work was supported by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (K24 AI64086; R. H.), the University of California San Diego Center for AIDS Research (AI36214; R. H.), and the San Diego AIDS Clinical Trial Group (CTU AI69432; R. H.). D. A. P. is a Medical Research Council (United Kingdom) Senior Clinical Fellow. NR 39 TC 78 Z9 81 U1 0 U2 4 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 MAY 5 PY 2011 VL 117 IS 18 BP 4805 EP 4815 DI 10.1182/blood-2010-11-317297 PG 11 WC Hematology SC Hematology GA 759VD UT WOS:000290275700022 PM 21398582 ER PT J AU Hanada, KI Wang, QJ Inozume, T Yang, JC AF Hanada, Ken-ichi Wang, Qiong J. Inozume, Takashi Yang, James C. TI Molecular identification of an MHC-independent ligand recognized by a human alpha/beta T-cell receptor SO BLOOD LA English DT Article ID APOPTOSIS-INDUCING LIGAND; MEDIATED CYTOTOXICITY; FAS LIGAND; DEATH DOMAIN; NK CELLS; TRAIL; EXPRESSION; COMPLEX; SPECIFICITY; INVOLVEMENT AB During an analysis of T-cell responses against human renal cell carcinoma (RCC), we identified a CD4(+) T-cell line that showed TCR-mediated recognition and lysis of nearly all RCC lines regardless of MHC type. We have now elucidated the nature of the ligand for this alpha/beta TCR, and it contains no MHC-related moiety and does not involve classic peptide processing. First, matrix metalloproteinase 14 (MMP14) expressed on RCC cells releases membrane-bound TRAIL expressed by the T cell; then, soluble TRAIL binds to its receptor DR4 (TRAIL-R1), which is expressed on tumor cells, and this TRAIL-DR4 complex is recognized by the TCR through a complementarity-determining region 3 alpha (CDR3 alpha)-mediated interaction. Direct and specific antigen-TCR interaction was demonstrated when the immobilized recombinant TRAIL/DR4 complex stimulated the TCR. In addition, amino acid substitutions in the CDR3 alpha of the TCR either obliterated or enhanced target-specific recognition. This description of the molecular nature of a non-MHC target structure recognized by a naturally occurring alpha/beta TCR not only broadens our concept of what the TCR can recognize, but also raises the question of whether such a T cell could be of clinical utility against RCC. (Blood. 2011; 117(18): 4816-4825) C1 [Hanada, Ken-ichi; Wang, Qiong J.; Inozume, Takashi; Yang, James C.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Hanada, KI (reprint author), 10 Ctr Dr,Bldg 10 CRC,Rm 3W-3840, Bethesda, MD 20892 USA. EM hanadak@mail.nih.gov RI Hanada, Ken-ichi/L-2481-2013 OI Hanada, Ken-ichi/0000-0003-2959-1257 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD. NR 31 TC 13 Z9 15 U1 0 U2 4 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 MAY 5 PY 2011 VL 117 IS 18 BP 4816 EP 4825 DI 10.1182/blood-2010-11-317743 PG 10 WC Hematology SC Hematology GA 759VD UT WOS:000290275700023 PM 21300979 ER PT J AU Arons, E Roth, L Sapolsky, J Suntum, T Stetler-Stevenson, M Kreitman, RJ AF Arons, Evgeny Roth, Laura Sapolsky, Jeffrey Suntum, Tara Stetler-Stevenson, Maryalice Kreitman, Robert J. TI Evidence of canonical somatic hypermutation in hairy cell leukemia SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; V-H GENES; IMMUNOGLOBULIN HEAVY; ANTIGEN SELECTION; B-CELLS; MUTATION STATUS; TUMOR-CELLS; REARRANGEMENTS; REPERTOIRE; PATTERNS AB To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition. (Blood. 2011; 117(18):4844-4851) C1 [Arons, Evgeny; Roth, Laura; Sapolsky, Jeffrey; Suntum, Tara; Kreitman, Robert J.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, NIH, 37-5124B,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU National Cancer Institute, National Institutes of Health FX This work was supported by the intramural program of the National Cancer Institute, National Institutes of Health. NR 45 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 5 PY 2011 VL 117 IS 18 BP 4844 EP 4851 DI 10.1182/blood-2010-11-316737 PG 8 WC Hematology SC Hematology GA 759VD UT WOS:000290275700026 PM 21368287 ER PT J AU Rende, F Cavallari, I Corradin, A Silic-Benussi, M Toulza, F Toffolo, GM Tanaka, Y Jacobson, S Taylor, GP D'Agostino, DM Bangham, CRM Ciminale, V AF Rende, Francesca Cavallari, Ilaria Corradin, Alberto Silic-Benussi, Micol Toulza, Frederic Toffolo, Gianna M. Tanaka, Yuetsu Jacobson, Steven Taylor, Graham P. D'Agostino, Donna M. Bangham, Charles R. M. Ciminale, Vincenzo TI Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNAs SO BLOOD LA English DT Article ID VIRUS TYPE-I; CELL LEUKEMIA-LYMPHOMA; REX PROTEIN; T-CELLS; TYPE-1; ROLES; LINES AB Human T-cell leukemia virus type 1 (HTLV-1) codes for 9 alternatively spliced transcripts and 2 major regulatory proteins named Tax and Rex that function at the transcriptional and posttranscriptional levels, respectively. We investigated the temporal sequence of HTLV-1 gene expression in primary cells from infected patients using splice site-specific quantitative RT-PCR. The results indicated a two-phase kinetics with the tax/rex mRNA preceding expression of other viral transcripts. Analysis of mRNA compartmentalization in cells transfected with HTLV-1 molecular clones demonstrated the strict Rex-dependency of the two-phase kinetics and revealed strong nuclear retention of HBZ mRNAs, supporting their function as noncoding transcripts. Mathematical modeling under-scored the importance of a delay between the functions of Tax and Rex, which was supported by experimental evidence of the longer half-life of Rex. These data provide evidence for a temporal pattern of HTLV-1 expression and reveal major differences in the intracellular compartmentalization of HTLV-1 transcripts. (Blood. 2011;117(18):4855-4859) C1 [Rende, Francesca; Cavallari, Ilaria; Silic-Benussi, Micol; D'Agostino, Donna M.; Ciminale, Vincenzo] Univ Padua, Dipartimento Sci Oncol & Chirurg, I-35128 Padua, Italy. [Rende, Francesca; D'Agostino, Donna M.; Ciminale, Vincenzo] Ist Ricoveroe Cura Carattere Sci, Ist Oncol Veneto, Padua, Italy. [Corradin, Alberto; Toffolo, Gianna M.] Univ Padua, Dept Informat Engn, I-35128 Padua, Italy. [Toulza, Frederic; Taylor, Graham P.; Bangham, Charles R. M.] Univ London Imperial Coll Sci Technol & Med, Dept Immunol, London, England. [Tanaka, Yuetsu] Univ Ryukyus, Grad Sch Med, Dept Immunol, Okinawa, Japan. [Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Ciminale, V (reprint author), Univ Padua, Dipartimento Sci Oncol & Chirurg, Via Gattamelata 64, I-35128 Padua, Italy. EM v.ciminale@unipd.it OI Cavallari, Ilaria/0000-0002-7430-9137; Bangham, Charles/0000-0003-2624-3599 FU European Union [2005-018704]; Associazione Italiana per la Ricerca sul Cancro (AIRC); Fondazione Cariverona; Ministero per l'Universita e la Ricerca Scientifica, e Tecnologica Progetti di Ricerca di Interesse Nazionale (PRIN); Ministero della Salute [RFPS-2006-2-342-010]; University of Padova FX This work was supported by grants from the European Union ("The role of chronic infections in the development of cancer," contract no. 2005-018704), the Associazione Italiana per la Ricerca sul Cancro (AIRC), the Fondazione Cariverona, the Ministero per l'Universita e la Ricerca Scientifica, e Tecnologica Progetti di Ricerca di Interesse Nazionale (PRIN), the Ministero della Salute (project RFPS-2006-2-342-010), and the University of Padova. NR 24 TC 36 Z9 38 U1 0 U2 3 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 MAY 5 PY 2011 VL 117 IS 18 BP 4855 EP 4859 DI 10.1182/blood-2010-11-316463 PG 5 WC Hematology SC Hematology GA 759VD UT WOS:000290275700028 PM 21398577 ER PT J AU Letvin, NL Rao, SS Montefiori, DC Seaman, MS Sun, Y Lim, SY Yeh, WW Asmal, M Gelman, RS Shen, L Whitney, JB Seoighe, C Lacerda, M Keating, S Norris, PJ Hudgens, MG Gilbert, PB Buzby, AP Mach, LV Zhang, JR Balachandran, H Shaw, GM Schmidt, SD Todd, JP Dodson, A Mascola, JR Nabel, GJ AF Letvin, Norman L. Rao, Srinivas S. Montefiori, David C. Seaman, Michael S. Sun, Yue Lim, So-Yon Yeh, Wendy W. Asmal, Mohammed Gelman, Rebecca S. Shen, Ling Whitney, James B. Seoighe, Cathal Lacerda, Miguel Keating, Sheila Norris, Philip J. Hudgens, Michael G. Gilbert, Peter B. Buzby, Adam P. Mach, Linh V. Zhang, Jinrong Balachandran, Harikrishnan Shaw, George M. Schmidt, Stephen D. Todd, John-Paul Dodson, Alan Mascola, John R. Nabel, Gary J. TI Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PREVENT HIV-1 INFECTION; RHESUS-MONKEYS; DOUBLE-BLIND; TRIAL; ANTIBODIES; CHALLENGE; THAILAND; STEP AB The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01-negative monkeys challenged with SIVsmE660, no CD8(+) T cell response or innate immune response was associated with protection against virus acquisition. However, low levels of neutralizing antibodies and an envelope-specific CD4(+) T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at least one permissive TRIM5 allele. This study begins to elucidate the mechanisms of vaccine protection against immunodeficiency viruses and highlights the need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies. C1 [Letvin, Norman L.; Seaman, Michael S.; Sun, Yue; Lim, So-Yon; Yeh, Wendy W.; Asmal, Mohammed; Shen, Ling; Whitney, James B.; Buzby, Adam P.; Mach, Linh V.; Zhang, Jinrong; Balachandran, Harikrishnan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rao, Srinivas S.; Schmidt, Stephen D.; Todd, John-Paul; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Gelman, Rebecca S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gelman, Rebecca S.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Seoighe, Cathal; Lacerda, Miguel] Natl Univ Ireland, Sch Math Stat & Appl Math, Galway, Ireland. [Lacerda, Miguel] Univ Cape Town, Dept Stat Sci, ZA-7925 Cape Town, South Africa. [Keating, Sheila; Norris, Philip J.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94118 USA. [Hudgens, Michael G.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. [Gilbert, Peter B.] Univ Washington, Fred Hutchinson Canc Res Ctr, Vaccine Infect Dis Inst, Seattle, WA 98109 USA. [Gilbert, Peter B.] Univ Washington, Dept Biostat, Seattle, WA 98109 USA. [Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35233 USA. [Dodson, Alan] BioQual Inc, Rockville, MD 20850 USA. RP Letvin, NL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. EM nletvin@caregroup.harvard.edu RI Schmidt, Stephen/B-5398-2012; Keating, Sheila/B-1652-2013 FU Vaccine Research Center, NIAID, NIH; Harvard Medical School Center for AIDS Research [AI060354]; NIAID [K08 AI069995]; NIH [N01-AI30033]; NIAID Center for HIV/AIDS Vaccine Immunology [AI067854] FX This work was supported by funds from the intramural research program of the Vaccine Research Center, NIAID, NIH; the Harvard Medical School Center for AIDS Research grant AI060354; NIAID K08 AI069995 (W.W.Y.); NIH grant N01-AI30033; and the NIAID Center for HIV/AIDS Vaccine Immunology grant AI067854. NR 18 TC 101 Z9 103 U1 0 U2 9 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 MAY 4 PY 2011 VL 3 IS 81 AR 81ra36 DI 10.1126/scitranslmed.3002351 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 795MG UT WOS:000292977700003 PM 21543722 ER PT J AU Greenblum, SI Efroni, S Schaefer, CF Buetow, KH AF Greenblum, Sharon I. Efroni, Sol Schaefer, Carl F. Buetow, Ken H. TI The PathOlogist: an automated tool for pathway-centric analysis SO BMC BIOINFORMATICS LA English DT Article ID NETWORKS AB Background: The PathOlogist is a new tool designed to transform large sets of gene expression data into quantitative descriptors of pathway-level behavior. The tool aims to provide a robust alternative to the search for single-gene-to-phenotype associations by accounting for the complexity of molecular interactions. Results: Molecular abundance data is used to calculate two metrics - 'activity' and 'consistency' - for each pathway in a set of more than 500 canonical molecular pathways (source: Pathway Interaction Database, http://pid.nci.nih.gov). The tool then allows a detailed exploration of these metrics through integrated visualization of pathway components and structure, hierarchical clustering of pathways and samples, and statistical analyses designed to detect associations between pathway behavior and clinical features. Conclusions: The PathOlogist provides a straightforward means to identify the functional processes, rather than individual molecules, that are altered in disease. The statistical power and biologic significance of this approach are made easily accessible to laboratory researchers and informatics analysts alike. Here we show as an example, how the PathOlogist can be used to establish pathway signatures that robustly differentiate breast cancer cell lines based on response to treatment. C1 [Greenblum, Sharon I.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Efroni, Sol] Bar Ilan Univ, Ramat Gan, Israel. [Greenblum, Sharon I.; Schaefer, Carl F.; Buetow, Ken H.] NCI, Lab Populat Genet, NIH, Rockville, MD USA. RP Greenblum, SI (reprint author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. EM sharongreenblum@gmail.com RI Efroni, Sol/I-6752-2012 OI Efroni, Sol/0000-0001-7927-6349 FU NIH; National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH and the National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 17 TC 11 Z9 11 U1 0 U2 1 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 MAY 4 PY 2011 VL 12 AR 133 DI 10.1186/1471-2105-12-133 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 766LW UT WOS:000290784800002 PM 21542931 ER PT J AU Famakin, BM Mou, YS Ruetzler, CA Bembry, J Maric, D Hallenbeck, JM AF Famakin, Bolanle M. Mou, Yongshan Ruetzler, Christ A. Bembry, Joliet Maric, Dragan Hallenbeck, John M. TI Disruption of downstream MyD88 or TRIF Toll-like receptor signaling does not protect against cerebral ischemia SO BRAIN RESEARCH LA English DT Article DE Toll-like receptor (TLR); Focal ischemia; MCAO; Global ischemia; MyD88; TRIF ID INNATE IMMUNITY; BRAIN-INJURY; STROKE; TOLL-LIKE-RECEPTOR-4; DAMAGE; ISCHEMIA/REPERFUSION; EXPRESSION; PATHWAYS; DANGER; MODEL AB Toll-like receptor (TLR) signaling plays an important role in cerebral ischemia, but downstream signaling events, which can be organ-specific, are incompletely understood. We thereby investigated involvement of the MyD88-dependent (MyD88) and MyD88-independent (TRIF) TLR signaling pathways in 2 in vitro and 2 in vivo models of cerebral ischemia. For in vitro studies, we used a model of oxygen-glucose deprivation (OGD) followed by flow cytometric analysis to determine:1) viability of PC12 cells following knock-down with MyD88 siRNA compared to negative control siRNA and 2) viability, apoptosis and necrosis of cortical neurons from MyD88 null (-/-), TRIF mutant, and wild type (WT) mice. In addition, in vivo, 1) We examined CA1 neuronal survival 7 days after global forebrain ischemia and 2) infarct volumes 24 h after Middle Cerebral Artery Occlusion (MCAO) in all 3 types of mice. OGD: 1) There were no differences in either percent viability of PC12 cells transfected with MyD88 compared to negative control siRNA or 2) in percent viability, apoptosis and necrosis of cortical neurons from MyD88-/-,TRIF mutant and WT mice. Global ischemia: neuronal survival was similar in all 3 groups of mice. Finally, MCAO: infarct volumes were not statistically different among all 3 groups of mice: MyD88-/-, 23.9 +/- 9.9 mm(3), TRIF mutant, 26.7 +/- 5.8 mm(3) and WT, 17.9 +/- 8.4 mm(3). These findings show that disruption of MyD88 or TRIF signaling does not confer protection in brain ischemia and suggests the possibility of additional or alternate downstream adaptors during TLR signaling in cerebral ischemia. Published by Elsevier B.V. C1 [Famakin, Bolanle M.; Mou, Yongshan; Ruetzler, Christ A.; Bembry, Joliet] Natl Inst Neurol Disorders & Stroke, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Maric, Dragan; Hallenbeck, John M.] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Famakin, BM (reprint author), Natl Inst Neurol Disorders & Stroke, Stroke Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 5806,MSC 1401, Bethesda, MD 20892 USA. EM famakinb@ninds.nih.gov FU National Institutes of Health, National institute of Neurological Disorders and Stroke FX Dr. Maria Spatz for editorial and scientific suggestions and Dr. Sungyoung Auh for help with the statistical analysis. This research was supported by the Intramural Research Program of the National Institutes of Health, National institute of Neurological Disorders and Stroke. NR 24 TC 24 Z9 28 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 4 PY 2011 VL 1388 BP 148 EP 156 DI 10.1016/j.brainres.2011.02.074 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 764BW UT WOS:000290604400016 PM 21376021 ER PT J AU Zhao, HY Brown, PH Schuckt, P AF Zhao, Huaying Brown, Patrick H. Schuckt, Peter TI On the Distribution of Protein Refractive Index Increments SO BIOPHYSICAL JOURNAL LA English DT Article ID PARTIAL SPECIFIC VOLUMES; SIZE-EXCLUSION CHROMATOGRAPHY; LASER-LIGHT-SCATTERING; AMINO-ACID; ANALYTICAL ULTRACENTRIFUGATION; MEMBRANE-PROTEINS; MOLECULAR-WEIGHT; LENS CRYSTALLINS; POLARIZABILITIES; STABILITY AB The protein refractive index increment, dn/dc, is an important parameter underlying the concentration determination and the biophysical characterization of proteins and protein complexes in many techniques. In this study, we examine the widely used assumption that most proteins have dn/dc values in a very narrow range, and reappraise the prediction of dn/dc of unmodified proteins based on their amino acid composition. Applying this approach in large scale to the entire set of known and predicted human proteins, we obtain, for the first time, to our knowledge, an estimate of the full distribution of protein dn/dc values. The distribution is close to Gaussian with a mean of 0.190 ml/g (for unmodified proteins at 589 nm) and a standard deviation of 0.003 ml/g. However, small proteins <10 kDa exhibit a larger spread, and almost 3000 proteins have values deviating by more than two standard deviations from the mean. Due to the widespread availability of protein sequences and the potential for outliers, the compositional prediction should be convenient and provide greater accuracy than an average consensus value for all proteins. We discuss how this approach should be particularly valuable for certain protein classes where a high dn/dc is coincidental to structural features, or may be functionally relevant such as in proteins of the eye. C1 [Zhao, Huaying; Schuckt, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. RP Schuckt, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. EM schuckp@mail.nih.gov RI Zhao, Huaying/F-5716-2012; OI Schuck, Peter/0000-0002-8859-6966 FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX We thank Dr. Medha Bhagwat and Dr. Elliott Margulies for their help with the NCBI databases, Dr. David Dong for help with computer programming, and Dr. Nathan Coussens for discussions. This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 60 TC 96 Z9 96 U1 12 U2 49 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY 4 PY 2011 VL 100 IS 9 BP 2309 EP 2317 DI 10.1016/j.bpj.2011.03.004 PG 9 WC Biophysics SC Biophysics GA 760YE UT WOS:000290360000030 PM 21539801 ER PT J AU Kim, JY Muallem, S AF Kim, Joo Young Muallem, Shmuel TI Unlocking SOAR releases STIM SO EMBO JOURNAL LA English DT Editorial Material ID CHANNELS; ACTIVATION; DOMAIN; ORAI1; CRAC AB A crucial component of the receptor-evoked Ca(2+) signal is Ca(2+) influx mediated by the store-operated Ca(2+) channels (SOCs). The molecular makeup of one SOC is the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and the pore-forming Orai1. Ca(2+) release from the ER leads to co-clustering of STIM1 and Orai1 to activate Orai1. The short STIM1 SOAR/CAD domain (STIM1 Orai1-activating region/CRAC-activating domain), which has two coiled-coil (C-C) domains, interacts with the Orai1 C terminus C-C domain to activate the channel. How the function of SOAR is regulated is not known. Korzeniowski et al (2010) and Muik et al (2011; this issue) now identified an autoinhibitory domain in STIM1 that occludes SOAR. Release of SOAR involves a conformational transition that is aided by the Orai1 C-C domain. C1 [Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, NIH, Bethesda, MD USA. [Kim, Joo Young] Yonsei Univ, Dept Pharmacol, Seoul 120749, South Korea. RP Muallem, S (reprint author), NIDCR, Epithelial Signaling & Transport Sect, NIH, Bethesda, MD USA. EM shmuel.muallem@nih.gov NR 11 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 4 PY 2011 VL 30 IS 9 BP 1673 EP 1675 DI 10.1038/emboj.2011.107 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 760ER UT WOS:000290307500001 PM 21540881 ER PT J AU Khursigara, CM Lan, GH Neumann, S Wu, XW Ravindran, S Borgnia, MJ Sourjik, V Milne, J Tu, Y Subramaniam, S AF Khursigara, Cezar M. Lan, Ganhui Neumann, Silke Wu, Xiongwu Ravindran, Suchie Borgnia, Mario J. Sourjik, Victor Milne, Jacqueline Tu, Yuhai Subramaniam, Sriram TI Lateral density of receptor arrays in the membrane plane influences sensitivity of the E. coli chemotaxis response SO EMBO JOURNAL LA English DT Article DE chemotaxis; cryo-electron tomography; receptors; signal transduction ID BACTERIAL CHEMOTAXIS; ESCHERICHIA-COLI; CRYOELECTRON TOMOGRAPHY; CAULOBACTER-CRESCENTUS; SPATIAL-ORGANIZATION; SIGNALING COMPLEX; IN-VIVO; MODEL; CHEMORECEPTORS; ARCHITECTURE AB In chemotactic bacteria, transmembrane chemoreceptors, CheA and CheW form the core signalling complex of the chemotaxis sensory apparatus. These complexes are organized in extended arrays in the cytoplasmic membrane that allow bacteria to respond to changes in concentration of extracellular ligands via a cooperative, allosteric response that leads to substantial amplification of the signal induced by ligand binding. Here, we have combined cryo-electron tomographic studies of the 3D spatial architecture of chemoreceptor arrays in intact E. coli cells with computational modelling to develop a predictive model for the cooperativity and sensitivity of the chemotaxis response. The predictions were tested experimentally using fluorescence resonance energy transfer (FRET) microscopy. Our results demonstrate that changes in lateral packing densities of the partially ordered, spatially extended chemoreceptor arrays can modulate the bacterial chemotaxis response, and that information about the molecular organization of the arrays derived by cryo-electron tomography of intact cells can be translated into testable, predictive computational models of the chemotaxis response. The EMBO Journal (2011) 30, 1719-1729. doi:10.1038/emboj.2011.77; Published online 25 March 2011 C1 [Khursigara, Cezar M.; Ravindran, Suchie; Borgnia, Mario J.; Milne, Jacqueline; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lan, Ganhui; Tu, Yuhai] IBM TJ Watson Res Ctr, Yorktown Hts, NY USA. [Neumann, Silke; Sourjik, Victor] Univ Heidelberg, Zentrum Mol Biol, DKFZ ZMBH Alliance, D-6900 Heidelberg, Germany. [Wu, Xiongwu] NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 50,Rm 4306, Bethesda, MD 20892 USA. EM yuhai@us.ibm.com; ss1@nih.gov FU Center for Cancer Research, National Cancer Institute, NIH; Deutsche Forschungsgemeinschaft [SO 421/7-1] FX This work was supported by funds from the Center for Cancer Research, National Cancer Institute, NIH (to SS) and from the Deutsche Forschungsgemeinschaft (grant SO 421/7-1 to SN and VS). We thank Dr Martin Kessel for useful discussions during the course of this work. NR 36 TC 24 Z9 25 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 4 PY 2011 VL 30 IS 9 BP 1719 EP 1729 DI 10.1038/emboj.2011.77 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 760ER UT WOS:000290307500006 PM 21441899 ER PT J AU Fontana, JR Iannuzzi, MC AF Fontana, Joseph R. Iannuzzi, Michael C. TI Thrombocytopenia and Sarcoidosis Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID THERAPY C1 [Fontana, Joseph R.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. [Iannuzzi, Michael C.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. RP Fontana, JR (reprint author), NHLBI, Cardiovasc & Pulm Branch, Bldg 10, Bethesda, MD 20892 USA. EM fontanaj@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 1 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 MAY 4 PY 2011 VL 305 IS 17 BP 1765 EP 1766 DI 10.1001/jama.2011.561 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 758HZ UT WOS:000290156200013 ER PT J AU Forni, PE Taylor-Burds, C Melvin, VS Williams, T Wray, S AF Forni, Paolo Emanuele Taylor-Burds, Carol Melvin, Vida Senkus Williams, Taylor Wray, Susan TI Neural Crest and Ectodermal Cells Intermix in the Nasal Placode to Give Rise to GnRH-1 Neurons, Sensory Neurons, and Olfactory Ensheathing Cells SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HORMONE-RELEASING HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; SKIN-DERIVED PRECURSORS; STEM-CELLS; KALLMANN-SYNDROME; GENE-EXPRESSION; SCHWANN-CELLS; BRAIN-DEVELOPMENT; PROGENITOR CELLS; EARLY COMMITMENT AB The origin of GnRH-1 cells and olfactory ensheathing cells has been controversial. Genetic Cre-lox lineage tracing of the neural crest (NC) versus ectodermal contribution to the developing nasal placode was performed using two complementary mouse models, the NC-specific Wnt1Cre mouse line and an ectodermal-specific Crect mouse line. Using these lines we prove that the NC give rise to the olfactory ensheathing cells and subpopulations of GnRH-1 neurons, olfactory and vomeronasal cells. These data demonstrate that Schwann cells and olfactory ensheathing cells share a common developmental origin. Furthermore, the results indicate that certain conditions that impact olfaction and sexual development, such as Kallmann syndrome, may be in part neurocristopathies. C1 [Forni, Paolo Emanuele; Taylor-Burds, Carol; Wray, Susan] Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Melvin, Vida Senkus; Williams, Taylor] Univ Colorado Denver, Dept Craniofacial Biol, Aurora, CO USA. [Melvin, Vida Senkus; Williams, Taylor] Univ Colorado Denver, Dept Cell & Dev Biol, Aurora, CO USA. RP Wray, S (reprint author), Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, NIH, Bldg 35,Room 3A-1012, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 FU National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke; NIH [DE12728] FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke and NIH Grant DE12728 to T. W. We thank Dr. Hui Yang for generation of the Crect mice. Several monoclonal antibodies used in these studies were obtained from the Developmental Studies Hybridoma Bank developed under the National Institute of Child Health and Human Development and maintained by Department of Biology of the University of Iowa. NR 105 TC 71 Z9 71 U1 0 U2 9 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 MAY 4 PY 2011 VL 31 IS 18 BP 6915 EP 6927 DI 10.1523/JNEUROSCI.6087-10.2011 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 759AO UT WOS:000290212100033 PM 21543621 ER PT J AU Zhang, HT Curreli, F Zhang, XH Bhattacharya, S Waheed, AA Cooper, A Cowburn, D Freed, EO Debnath, AK AF Zhang, Hongtao Curreli, Francesca Zhang, Xihui Bhattacharya, Shibani Waheed, Abdul A. Cooper, Alan Cowburn, David Freed, Eric O. Debnath, Asim K. TI Antiviral activity of alpha-helical stapled peptides designed from the HIV-1 capsid dimerization domain SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HOMOLOGY REGION; PROTEIN-PROTEIN INTERACTIONS; C-TERMINAL DOMAIN; AMINO-ACID SUBSTITUTIONS; INFECTIOUS-ANEMIA VIRUS; IN-VITRO; FUSION INHIBITOR; CYCLOPHILIN-A; ENVELOPE GLYCOPROTEINS AB Background: The C-terminal domain (CTD) of HIV-1 capsid (CA), like full-length CA, forms dimers in solution and CTD dimerization is a major driving force in Gag assembly and maturation. Mutations of the residues at the CTD dimer interface impair virus assembly and render the virus non-infectious. Therefore, the CTD represents a potential target for designing anti-HIV-1 drugs. Results: Due to the pivotal role of the dimer interface, we reasoned that peptides from the alpha-helical region of the dimer interface might be effective as decoys to prevent CTD dimer formation. However, these small peptides do not have any structure in solution and they do not penetrate cells. Therefore, we used the hydrocarbon stapling technique to stabilize the alpha-helical structure and confirmed by confocal microscopy that this modification also made these peptides cell-penetrating. We also confirmed by using isothermal titration calorimetry (ITC), sedimentation equilibrium and NMR that these peptides indeed disrupt dimer formation. In in vitro assembly assays, the peptides inhibited mature-like virus particle formation and specifically inhibited HIV-1 production in cell-based assays. These peptides also showed potent antiviral activity against a large panel of laboratory-adapted and primary isolates, including viral strains resistant to inhibitors of reverse transcriptase and protease. Conclusions: These preliminary data serve as the foundation for designing small, stable, alpha-helical peptides and small-molecule inhibitors targeted against the CTD dimer interface. The observation that relatively weak CA binders, such as NYAD-201 and NYAD-202, showed specificity and are able to disrupt the CTD dimer is encouraging for further exploration of a much broader class of antiviral compounds targeting CA. We cannot exclude the possibility that the CA-based peptides described here could elicit additional effects on virus replication not directly linked to their ability to bind CA-CTD. C1 [Zhang, Hongtao; Curreli, Francesca; Zhang, Xihui; Debnath, Asim K.] New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Mol Modeling & Drug Design, New York, NY 10065 USA. [Bhattacharya, Shibani] New York Struct Biol Ctr, New York, NY 10027 USA. [Waheed, Abdul A.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Cooper, Alan] Univ Glasgow, Sch Chem, Glasgow G12 8QQ, Lanark, Scotland. [Cowburn, David] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Debnath, AK (reprint author), New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Mol Modeling & Drug Design, 310 E 67th St, New York, NY 10065 USA. EM adebnath@nybloodcenter.org RI Cooper, Alan/F-7813-2011; Cowburn, David/A-8448-2008; OI Cooper, Alan/0000-0001-6709-7343; Cowburn, David/0000-0001-6770-7172 FU NIH [RO1 AI081604, GM-47021, GM-66356]; New York Blood Center; Keck Foundation; NYSBC; Center for Cancer Research, National Cancer Institute, NIH FX This study was supported by NIH Grant RO1 AI081604 (AKD) and the intramural fund from the New York Blood Center (AKD). NMR studies were supported by NIH GM-47021 and GM-66356 (DC), the Keck Foundation, and the member institutions of NYSBC. This work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. We thank Lyudmil Angelov (confocal microscopy), Yelena Oksov (electron microscopy) and Dr. Wu He (flow cytometry) for their technical help. We thank K. Waki for constructing the pCMVdeltaR8.2/PR-clone and. J. Burns for providing the VSV-G expression vector and R. Montelaro for anti-EIAV serum. HIV-Ig was obtained from the NIH AIDS Research and Reference Reagent Program. NR 99 TC 32 Z9 32 U1 0 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAY 3 PY 2011 VL 8 AR 28 DI 10.1186/1742-4690-8-28 PG 18 WC Virology SC Virology GA 765SX UT WOS:000290730000001 PM 21539734 ER PT J AU Shiels, MS Pfeiffer, RM Engels, EA AF Shiels, Meredith S. Pfeiffer, Ruth M. Engels, Eric A. TI Age at Cancer Diagnosis Among Persons With AIDS RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Shiels, Meredith S.; Pfeiffer, Ruth M.; Engels, Eric A.] NCI, Rockville, MD 20892 USA. RP Shiels, MS (reprint author), NCI, Rockville, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 3 PY 2011 VL 154 IS 9 BP 643 EP 643 DI 10.7326/0003-4819-154-9-201105030-00014 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 757UD UT WOS:000290112300011 ER PT J AU Smith, NL Huffman, JE Strachan, DP Huang, J Dehghan, A Trompet, S Lopez, LM Shin, SY Baumert, J Vitart, V Bis, JC Wild, SH Rumley, A Yang, Q Uitterlinden, AG Stott, DJ Davies, G Carter, AM Thorand, B Polasek, O McKnight, B Campbell, H Rudnicka, AR Chen, MH Buckley, BM Harris, SE Peters, A Pulanic, D Lumley, T de Craen, AJM Liewald, DC Gieger, C Campbell, S Ford, I Gow, AJ Luciano, M Porteous, DJ Guo, XQ Sattar, N Tenesa, A Cushman, M Slagboom, PE Visscher, PM Spector, TD Illig, T Rudan, I Bovill, EG Wright, AF McArdle, WL Tofler, G Hofman, A Westendorp, RGJ Starr, JM Grant, PJ Karakas, M Hastie, ND Psaty, BM Wilson, JF Lowe, GDO O'Donnell, CJ Witteman, JCM Jukema, JW Deary, IJ Soranzo, N Koenig, W Hayward, C AF Smith, Nicholas L. Huffman, Jennifer E. Strachan, David P. Huang, Jie Dehghan, Abbas Trompet, Stella Lopez, Lorna M. Shin, So-Youn Baumert, Jens Vitart, Veronique Bis, Joshua C. Wild, Sarah H. Rumley, Ann Yang, Qiong Uitterlinden, Andre G. Stott, David. J. Davies, Gail Carter, Angela M. Thorand, Barbara Polasek, Ozren McKnight, Barbara Campbell, Harry Rudnicka, Alicja R. Chen, Ming-Huei Buckley, Brendan M. Harris, Sarah E. Peters, Annette Pulanic, Drazen Lumley, Thomas de Craen, Anton J. M. Liewald, David C. Gieger, Christian Campbell, Susan Ford, Ian Gow, Alan J. Luciano, Michelle Porteous, David J. Guo, Xiuqing Sattar, Naveed Tenesa, Albert Cushman, Mary Slagboom, P. Eline Visscher, Peter M. Spector, Tim D. Illig, Thomas Rudan, Igor Bovill, Edwin G. Wright, Alan F. McArdle, Wendy L. Tofler, Geoffrey Hofman, Albert Westendorp, Rudi G. J. Starr, John M. Grant, Peter J. Karakas, Mahir Hastie, Nicholas D. Psaty, Bruce M. Wilson, James F. Lowe, Gordon D. O. O'Donnell, Christopher J. Witteman, Jacqueline C. M. Jukema, J. Wouter Deary, Ian J. Soranzo, Nicole Koenig, Wolfgang Hayward, Caroline TI Genetic Predictors of Fibrin D-Dimer Levels in Healthy Adults SO CIRCULATION LA English DT Article DE epidemiology; fibrin fragment D; genome-wide association study; hemostasis; meta-analysis; thrombosis ID GENOME-WIDE ASSOCIATION; TISSUE-PLASMINOGEN ACTIVATOR; CORONARY HEART-DISEASE; VON-WILLEBRAND-FACTOR; VENOUS THROMBOEMBOLISM; THR312ALA POLYMORPHISM; CARDIOVASCULAR HEALTH; MYOCARDIAL-INFARCTION; AGING RESEARCH; RISK AB Background-Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. Methods and Results-A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between approximate to 2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log-transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4 x 10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4x10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9x10(-18)) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log-transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. Conclusions-Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported. (Circulation. 2011;123:1864-1872.) C1 [Smith, Nicholas L.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [McKnight, Barbara; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Strachan, David P.; Rudnicka, Alicja R.] Univ London, Div Community Hlth Sci, London, England. [Rumley, Ann; Lowe, Gordon D. O.] Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Bristol, Avon, England. [Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas L.] Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, 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. [Guo, Xiuqing] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Huffman, Jennifer E.; Vitart, Veronique; Campbell, Susan; Tenesa, Albert; Wright, Alan F.; Hastie, Nicholas D.; Hayward, Caroline] Western Gen Hosp, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Wild, Sarah H.; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Polasek, Ozren; Rudan, Igor] Gen Info Ltd, Zagreb, Croatia. [Polasek, Ozren] Univ Zagreb, Sch Med, Zagreb 41001, Croatia. [Pulanic, Drazen] Clin Hosp Ctr Zagreb, Div Haematol, Dept Internal Med, Zagreb, Croatia. [Pulanic, Drazen] Univ Osijek, Sch Med, Osijek, Croatia. [Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia. [Huang, Jie; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Yang, Qiong] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Chen, Ming-Huei] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Gieger, Christian] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Illig, Thomas] Unit Mol Epidemiol, Neuherberg, Germany. [Baumert, Jens; Thorand, Barbara; Peters, Annette] Inst Epidemiol II, Neuherberg, Germany. [Karakas, Mahir; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany. [Lopez, Lorna M.; Harris, Sarah E.; Liewald, David C.; Gow, Alan J.; Luciano, Michelle; Porteous, David J.; Visscher, Peter M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Lopez, Lorna M.; Davies, Gail; Liewald, David C.; Gow, Alan J.; Luciano, Michelle; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Geriatr Med Unit, Edinburgh, Midlothian, Scotland. [Harris, Sarah E.; Porteous, David J.] Univ Edinburgh, Med Genet Sect, Edinburgh, Midlothian, Scotland. [Tenesa, Albert] Univ Edinburgh, Roslin Inst, Royal Dick Sch Vet Studies, Roslin, Midlothian, Scotland. [Visscher, Peter M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Dehghan, Abbas; Uitterlinden, Andre G.; Slagboom, P. Eline; Hofman, Albert; Westendorp, Rudi G. J.; Witteman, Jacqueline C. M.] Netherlands Consortium Healthy Ageing, Rotterdam, Netherlands. [Rumley, Ann; Stott, David. J.; Lowe, Gordon D. O.] Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Soranzo, Nicole] Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Buckley, Brendan M.] Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Dehghan, Abbas; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Shin, So-Youn; Soranzo, Nicole] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. [Spector, Tim D.; Soranzo, Nicole] Kings Coll London, Dept Twin Res, London WC2R 2LS, England. [Spector, Tim D.; Soranzo, Nicole] Kings Coll London, Genet Epidemiol Unit, London WC2R 2LS, England. [Carter, Angela M.; Grant, Peter J.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England. RP Smith, NL (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, 1730 Minor Ave,Ste 1360, Seattle, WA 98101 USA. EM nlsmith@u.washington.edu; C.Hayward@hgu.mrc.ac.uk RI Luciano, Michelle/F-7277-2010; Peters, Annette/A-6117-2011; Gow, Alan/A-6070-2009; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Hayward, Caroline/M-8818-2016; Slagboom, P. Eline/R-4790-2016; Lopez, Lorna/F-7265-2010; Deary, Ian/C-6297-2009; Rudan, Igor/I-1467-2012; Porteous, David/C-7289-2013; Yang, Qiong/G-5438-2014; Thorand, Barbara/B-5349-2014 OI Luciano, Michelle/0000-0003-0935-7682; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Visscher, Peter/0000-0002-2143-8760; Dehghan, Abbas/0000-0001-6403-016X; Gow, Alan/0000-0002-3320-4531; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Hayward, Caroline/0000-0002-9405-9550; Slagboom, P. Eline/0000-0002-2875-4723; Rudan, Igor/0000-0001-6993-6884; Porteous, David/0000-0003-1249-6106; Thorand, Barbara/0000-0002-8416-6440 FU Medical Research Council (MRC) [G0000934]; Wellcome Trust [068545/Z/02, 076113/B/04/Z]; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute; National Institute of Child Health and Human Development; Juvenile Diabetes Research Foundation International; National Institute for Health Research Cambridge Biomedical Research Centre; Wellcome Trust Strategic Award [079895]; European Commission [018996]; French Ministry of Research; NHLBI [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]; Leducq Foundation, Paris, France; National Center for Research Resources [M01-RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491, K24 DK080140]; Medical Research Council UK; Ministry of Science, Education and Sport of the Republic of Croatia [108-1080315-0302]; European Union [LSHG-CT-2006-018947]; NHLBI's FHS [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Department of Medicine at Boston University School of Medicine; Boston Medical Center; Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research; German National Genome Research Network [01GS0834]; University of Ulm; Munich Center of Health Sciences as part of the Ludwig Maximilians University innovative; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F019394/1]; Chief Scientists Office of the Scottish Executive [CZB/4/505]; BBSRC; Engineering and Physical Sciences Research Council; Economic and Social Research Council; MRC, as part of the cross-council Lifelong Health and Wellbeing Initiative [G0700704/84698]; Australian National Health; Chief Scientist Office of the Scottish Government; Royal Society; Bristol-Myers Squibb; Netherlands Heart Foundation [2001 D 032]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; Netherlands Organization for Scientific Research (NWO) [918-76-619]; Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [050-060-810]; European Community; EuroClot Consortium [HEALTH-F4-2007-201413]; GenomEUtwin Project [QLG2-CT-2002-01254]; Department of Health via the National Institute for Health Research (NIHR); Biotechnology and Biological Sciences Research Council [G20234]; National Eye Institute via an NIH/CIDR; [U01 DK062418] FX We acknowledge the use of phenotype and genotype data from the B58C DNA collection, funded by Medical Research Council (MRC) grant G0000934 and Wellcome Trust grant 068545/Z/02 (http://www.b58cgene.sgul.ac.uk/). Genotyping for the B58C-WTCCC subset was funded by Wellcome Trust grant 076113/B/04/Z. The B58C-T1DGC genotyping used resources provided by the T1DGC, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development, and Juvenile Diabetes Research Foundation International and supported by U01 DK062418. B58C-T1DGC genome-wide association study data were deposited by the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, which is funded by Juvenile Diabetes Research Foundation International, the Wellcome Trust, and the National Institute for Health Research Cambridge Biomedical Research Centre; the Cambridge Institute for Medical Research has received a Wellcome Trust Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a contract from the European Commission Framework Programme 6 (018996) and grants from the French Ministry of Research. The CHS is supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133 and grants 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 were 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. The CROATIA-Vis study in the Croatian island of Vis was supported by 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 European Special Populations Research Network project (contract LSHG-CT-2006-018947). This research was conducted in part using 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 project. Partial investigator support was provided by National Institute of Diabetes and Digestive and Kidney Diseases K24 DK080140 (J.B. Meigs). This work was partially supported by the NHLBI's FHS (contract N01-HC-25195) and its contract with Affymetrix, Inc, for genotyping services (contract 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 MONICA/KORA Augsburg studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants fromthe German Federal Ministry of Education and Research. Part of this work was financed by the German National Genome Research Network (project 01GS0834) and through additional funds from the University of Ulm. The research was supported within the Munich Center of Health Sciences as part of the Ludwig Maximilians University innovative. The LBC whole-genome association study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC; Reference BB/F019394/1). The LBC1936 research was supported by a program grant from Research Into Ageing (Reference 251) and continues with program grants from Help the Aged/Research Into Ageing (Disconnected Mind). The LBC1921 data collection was funded by the Chief Scientists Office of the Scottish Executive (CZB/4/505). The study was conducted within the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, supported by the BBSRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council, and MRC, as part of the cross-council Lifelong Health and Wellbeing Initiative (G0700704/84698). Dr Luciano is a Royal Society of Edinburgh/Lloyds TSB Foundation for Scotland Personal Research Fellow. Dr Visscher acknowledges support from the Australian National Health and MRC. ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, and the European Union framework program 6 European Special Populations Research Network project (contract LSHG-CT-2006-018947). The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. Dr Jukema is an established clinical investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). The RS is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly (RIDE); 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. Dr Dehghan is supported by the Netherlands Organization for Scientific Research (NWO, VICI No. 918-76-619). Support for genotyping was provided by the Netherlands Organization of Scientific Research NWO Investments (No. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging project No. 050-060-810. Dr Nicole Soranzo is supported by the Wellcome Trust (Core Grant Number 091746/Z/10/Z). The TwinsUK study was funded by the Wellcome Trust; European Community's Sixth and Seventh Framework Programmes (FP-6/2005-2008) Life Sciences and Health (Reference 005268, genetic regulation of the end-stage clotting process that leads to thrombotic stroke: The EuroClot Consortium and (FP7/2007 to 2013), ENGAGE project HEALTH-F4-2007-201413, and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254).; The study also receives support from the Department of Health via the National Institute for Health Research (NHR) 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/CIDR genotyping project (principal investigator, Terri Young). NR 46 TC 19 Z9 22 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 3 PY 2011 VL 123 IS 17 BP 1864 EP + DI 10.1161/CIRCULATIONAHA.110.009480 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758GB UT WOS:000290149300010 PM 21502573 ER PT J AU Kaltman, JR Thompson, PD Lantos, J Berul, CI Botkin, J Cohen, JT Cook, NR Corrado, D Drezner, J Frick, KD Goldman, S Hlatky, M Kannankeril, PJ Leslie, L Priori, S Saul, JP Shapiro-Mendoza, CK Siscovick, D Vetter, VL Boineau, R Burns, KM Friedman, RA AF Kaltman, Jonathan R. Thompson, Paul D. Lantos, John Berul, Charles I. Botkin, Jeffrey Cohen, Joshua T. Cook, Nancy R. Corrado, Domenico Drezner, Jonathan Frick, Kevin D. Goldman, Stuart Hlatky, Mark Kannankeril, Prince J. Leslie, Laurel Priori, Silvia Saul, J. Philip Shapiro-Mendoza, Carrie K. Siscovick, David Vetter, Victoria L. Boineau, Robin Burns, Kristin M. Friedman, Richard A. TI Screening for Sudden Cardiac Death in the Young Report From a National Heart, Lung, and Blood Institute Working Group SO CIRCULATION LA English DT Article DE death, sudden; pediatrics; screening ID HYPERTROPHIC CARDIOMYOPATHY; SCIENTIFIC STATEMENT; ASSOCIATION COUNCIL; CHILDREN; PREVENTION; ADOLESCENTS; STRATEGIES; GUIDELINES; AUTOPSY; DISEASE C1 [Kaltman, Jonathan R.; Boineau, Robin; Burns, Kristin M.] NHLBI, NIH, Bethesda, MD 20817 USA. [Thompson, Paul D.] Univ Connecticut, Hartford, CT 06112 USA. [Lantos, John] Univ Missouri, Kansas City, MO 64110 USA. [Berul, Charles I.; Burns, Kristin M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Botkin, Jeffrey] Univ Utah, Salt Lake City, UT USA. [Cohen, Joshua T.; Leslie, Laurel] Tufts Univ, Boston, MA 02111 USA. [Corrado, Domenico] Univ Padua, Sch Med, Padua, Italy. [Drezner, Jonathan; Siscovick, David] Univ Washington, Seattle, WA 98195 USA. [Frick, Kevin D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Cook, Nancy R.; Goldman, Stuart] Harvard Univ, Sch Med, Boston, MA USA. [Hlatky, Mark] Stanford Univ, Stanford, CA 94305 USA. [Kannankeril, Prince J.] Vanderbilt Univ, Nashville, TN USA. [Priori, Silvia] NYU, Med Ctr, New York, NY 10016 USA. [Saul, J. Philip] Med Univ S Carolina, Charleston, SC 29425 USA. [Shapiro-Mendoza, Carrie K.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Vetter, Victoria L.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Friedman, Richard A.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Kaltman, JR (reprint author), NHLBI, NIH, 6701 Rockledge Dr,Room 8222, Bethesda, MD 20817 USA. EM kaltmanj@nhlbi.nih.gov OI Friedman, Richard/0000-0003-3046-1505; Cohen, Joshua/0000-0003-1737-0991 FU National Institutes of Health research [HL100546] FX Drs Leslie and Cohen are the recipients of a National Institutes of Health research grant (No. HL100546). NR 38 TC 77 Z9 80 U1 1 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 MAY 3 PY 2011 VL 123 IS 17 BP 1911 EP 1918 DI 10.1161/CIRCULATIONAHA.110.017228 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758GB UT WOS:000290149300015 PM 21537007 ER PT J AU Cleveland, SB Davies, J McClure, MA AF Cleveland, Sean B. Davies, John McClure, Marcella A. TI A Bioinformatics Approach to the Structure, Function, and Evolution of the Nucleoprotein of the Order Mononegavirales SO PLOS ONE LA English DT Article ID VESICULAR STOMATITIS-VIRUS; RESPIRATORY SYNCYTIAL VIRUS; INTRINSICALLY UNSTRUCTURED PROTEINS; PHOSPHOPROTEIN BINDING-SITE; NUCLEOCAPSID PROTEIN; RNA COMPLEX; CORRELATED MUTATIONS; IMPORTANT RESIDUES; CRYSTAL-STRUCTURE; GENOME SEQUENCE AB The goal of this Bioinformatic study is to investigate sequence conservation in relation to evolutionary function/structure of the nucleoprotein of the order Mononegavirales. In the combined analysis of 63 representative nucleoprotein (N) sequences from four viral families (Bomaviridae, Filoviridae, Rhabdoviridae, and Paramyxoviridae) we predict the regions of protein disorder, intra-residue contact and co-evolving residues. Correlations between location and conservation of predicted regions illustrate a strong division between families while high-lighting conservation within individual families. These results suggest the conserved regions among the nucleoproteins, specifically within Rhabdoviridae and Paramyxoviradae, but also generally among all members of the order, reflect an evolutionary advantage in maintaining these sites for the viral nucleoprotein as part of the transcription/replication machinery. Results indicate conservation for disorder in the C-terminus region of the representative proteins that is important for interacting with the phosphoprotein and the large subunit polymerase during transcription and replication. Additionally, the C-terminus region of the protein preceding the disordered region, is predicted to be important for interacting with the encapsidated genome. Portions of the N-terminus are responsible for N:N stability and interactions identified by the presence or lack of co-evolving intra-protein contact predictions. The validation of these prediction results by current structural information illustrates the benefits of the Disorder, Intra-residue contact and Compensatory mutation Correlator (DisICC) pipeline as a method for quickly characterizing proteins and providing the most likely residues and regions necessary to target for disruption in viruses that have little structural information available. C1 [Cleveland, Sean B.; McClure, Marcella A.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. [Cleveland, Sean B.; McClure, Marcella A.] Montana State Univ, Ctr Computat Biol, Bozeman, MT 59717 USA. [Davies, John] NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Cleveland, SB (reprint author), Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. EM sean.b.cleveland@gmail.com OI Cleveland, Sean/0000-0002-7130-3434; Davies, John/0000-0002-9482-1066 FU National Institutes of Health [1R21AI063510] FX This project was supported by a National Institutes of Health grant (1R21AI063510). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 4 Z9 4 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 3 PY 2011 VL 6 IS 5 AR e19275 DI 10.1371/journal.pone.0019275 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 759EM UT WOS:000290223500015 PM 21559282 ER PT J AU Patton, TG Dietrich, G Dolan, MC Piesman, J Carroll, JA Gilmore, RD AF Patton, Toni G. Dietrich, Gabrielle Dolan, Marc C. Piesman, Joseph Carroll, James A. Gilmore, Robert D., Jr. TI Functional Analysis of the Borrelia burgdorferi bba64 Gene Product in Murine Infection via Tick Infestation SO PLOS ONE LA English DT Article ID LYME-DISEASE SPIROCHETE; OUTER SURFACE-PROTEINS; TOLL-LIKE RECEPTORS; BORRELIA-BURGDORFERI; MAMMALIAN HOST; LINEAR PLASMID; IXODES TICKS; LIFE-CYCLE; EXPRESSION; TRANSMISSION AB Borrelia burgdorferi, the causative agent of Lyme borreliosis, transmitted to humans to from the bite of Ixodes spp. ticks. During the borrelial tick-to-mammal life cycle, B. burgdorferi must adapt to many environmental changes by regulating several genes, including bba64. Our laboratory recently demonstrated that the bba64 gene product is necessary for mouse infectivity when B. burgdorferi is transmitted by an infected tick bite, but not via needle inoculation. In this study we investigated the phenotypic properties of a bba64 mutant strain, including 1) replication during tick engorgement, 2) migration into the nymphal salivary glands, 3) host transmission, and 4) susceptibility to the MyD88-dependent innate immune response. Results revealed that the bba64 mutant's attenuated infectivity by tick bite was not due to a growth defect inside an actively feeding nymphal tick, or failure to invade the salivary glands. These findings suggested there was either a lack of spirochete transmission to the host dermis or increased susceptibility to the host's innate immune response. Further experiments showed the bba64 mutant was not culturable from mouse skin taken at the nymphal bite site and was unable to establish infection in MyD88-deficient mice via tick infestation. Collectively, the results of this study indicate that BBA64 functions at the salivary gland-to-host delivery interface of vector transmission and is not involved in resistance to MyD88-mediated innate immunity. C1 [Patton, Toni G.; Dietrich, Gabrielle; Dolan, Marc C.; Piesman, Joseph; Gilmore, Robert D., Jr.] Ctr Dis Control & Prevent, Div Vector Borne Dis, Natl Ctr Emerging & Zoonot Infect Dis, Ft Collins, CO 80521 USA. [Carroll, James A.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Patton, TG (reprint author), Ctr Dis Control & Prevent, Div Vector Borne Dis, Natl Ctr Emerging & Zoonot Infect Dis, Ft Collins, CO 80521 USA. EM rbg9@cdc.gov FU Centers for Disease Control and Prevention, a branch of the Department of Health and Human Services within the federal government FX This work was supported by the Centers for Disease Control and Prevention, a branch of the Department of Health and Human Services within the federal government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 19 Z9 19 U1 0 U2 5 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 MAY 3 PY 2011 VL 6 IS 5 AR e19536 DI 10.1371/journal.pone.0019536 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 759EM UT WOS:000290223500028 PM 21559293 ER PT J AU Sykora, P Croteau, DL Bohr, VA Wilson, DM AF Sykora, Peter Croteau, Deborah L. Bohr, Vilhelm A. Wilson, David M., III TI Aprataxin localizes to mitochondria and preserves mitochondrial function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STRAND BREAK REPAIR; OCULOMOTOR APRAXIA TYPE-1; OCULAR MOTOR APRAXIA; BASE EXCISION-REPAIR; EARLY-ONSET ATAXIA; HISTIDINE TRIAD SUPERFAMILY; DISEASE PROTEIN APRATAXIN; OXIDATIVE DNA-DAMAGE; SYNDROME GROUP-B; SPINOCEREBELLAR ATAXIA AB Ataxia with oculomotor apraxia 1 is caused by mutation in the APTX gene, which encodes the DNA strand-break repair protein aprataxin. Aprataxin exhibits homology to the histidine triad superfamily of nucleotide hydrolases and transferases and removes 5'-adenylate groups from DNA that arise from aborted ligation reactions. We report herein that aprataxin localizes to mitochondria in human cells and we identify an N-terminal amino acid sequence that targets certain isoforms of the protein to this intracellular compartment. We also show that transcripts encoding this unique N-terminal stretch are expressed in the human brain, with highest production in the cerebellum. Depletion of aprataxin in human SH-SY5Y neuroblastoma cells and primary skeletal muscle myoblasts results in mitochondrial dysfunction, which is revealed by reduced citrate synthase activity and mtDNA copy number. Moreover, mtDNA, not nuclear DNA, was found to have higher levels of background DNA damage on aprataxin knockdown, suggesting a direct role for the enzyme in mtDNA processing. C1 [Sykora, Peter; Croteau, Deborah L.; Bohr, Vilhelm A.; Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM wilsonda@mail.nih.gov FU National Institutes of Health, National Institute on Aging FX We thank Dr. Marie Rossi and Ms. Jingyan (Jane) Tian for assistance with some of the experimentation. This research was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 53 TC 43 Z9 44 U1 0 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 MAY 3 PY 2011 VL 108 IS 18 BP 7437 EP 7442 DI 10.1073/pnas.1100084108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 758YF UT WOS:000290203100036 PM 21502511 ER PT J AU Lambrechts, L Paaijmans, KP Fansiri, T Carrington, LB Kramer, LD Thomas, MB Scott, TW AF Lambrechts, Louis Paaijmans, Krijn P. Fansiri, Thanyalak Carrington, Lauren B. Kramer, Laura D. Thomas, Matthew B. Scott, Thomas W. TI Impact of daily temperature fluctuations on dengue virus transmission by Aedes aegypti SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE arbovirus; climate; vectorial capacity ID WESTERN EQUINE ENCEPHALOMYELITIS; CULEX-TARSALIS DIPTERA; VECTOR-BORNE DISEASES; CLIMATE-CHANGE; ENVIRONMENTAL-TEMPERATURE; MALARIA TRANSMISSION; EXTRINSIC INCUBATION; INFECTIOUS-DISEASES; ENCEPHALITIS-VIRUS; KAMPHAENG PHET AB Most studies on the ability of insect populations to transmit pathogens consider only constant temperatures and do not account for realistic daily temperature fluctuations that can impact vector-pathogen interactions. Here, we show that diurnal temperature range (DTR) affects two important parameters underlying dengue virus (DENV) transmission by Aedes aegypti. In two independent experiments using different DENV serotypes, mosquitoes were less susceptible to virus infection and died faster under larger DTR around the same mean temperature. Large DTR (20 degrees C) decreased the probability of midgut infection, but not duration of the virus extrinsic incubation period (EIP), compared with moderate DTR (10 degrees C) or constant temperature. A thermodynamic model predicted that at mean temperatures < 18 degrees C, DENV transmission increases as DTR increases, whereas at mean temperatures > 18 degrees C, larger DTR reduces DENV transmission. The negative impact of DTR on Ae. aegypti survival indicates that large temperature fluctuations will reduce the probability of vector survival through EIP and expectation of infectious life. Seasonal variation in the amplitude of daily temperature fluctuations helps to explain seasonal forcing of DENV transmission at locations where average temperature does not vary seasonally and mosquito abundance is not associated with dengue incidence. Mosquitoes lived longer and were more likely to become infected under moderate temperature fluctuations, which is typical of the high DENV transmission season than under large temperature fluctuations, which is typical of the low DENV transmission season. Our findings reveal the importance of considering short-term temperature variations when studying DENV transmission dynamics. C1 [Lambrechts, Louis; Fansiri, Thanyalak] Inst Pasteur, Dept Virol, F-75724 Paris 15, France. [Paaijmans, Krijn P.; Thomas, Matthew B.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Fansiri, Thanyalak] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand. [Carrington, Lauren B.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Kramer, Laura D.] New York State Dept Hlth, Wadsworth Ctr, Slingerlands, NY 12159 USA. [Kramer, Laura D.] SUNY Albany, Sch Publ Hlth, Albany, NY 12237 USA. [Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Lambrechts, L (reprint author), Inst Pasteur, Dept Virol, F-75724 Paris 15, France. EM louis.lambrechts@pasteur.fr RI Lambrechts, Louis/A-2057-2010; Carrington, Lauren/B-8269-2013; OI Lambrechts, Louis/0000-0001-5958-2138; Carrington, Lauren Bree/0000-0001-9273-7912 FU European Commission [MOIF-CT-2006-039855]; French Agence Nationale de la Recherche [ANR-09-RPDOC-007-01]; Science and Technology Directorate, Department of Homeland Security, and Fogarty International Center; National Institutes of Health (NIH), Bethesda, MD; National Science Foundation Ecology of Infectious Disease [EF-0914384]; National Institutes of Health [R01 GM-083224] FX The authors are grateful to Laura C. Harrington and Alongkot Ponlawat for providing mosquito eggs and field temperature data from Thailand. We thank Richard G. Jarman and Alan L. Rothman for providing the DENV isolates, Pam Chin for expert technical support, and Linda M. Styer and Caroline Lego for their help during vector competence assays in the first experiment. Anna-Bella Failloux, Marie Vazeille, Laurence Mousson, Estelle Martin, and Camilo Arias-Goeta provided support during the second experiment. Christopher M. Barker and Romain Gallet helped with fruitful discussions. Two anonymous reviewers provided helpful comments on a previous version of the manuscript. L. L. was supported by Marie Curie Fellowship MOIF-CT-2006-039855 from the European Commission and French Agence Nationale de la Recherche Grant ANR-09-RPDOC-007-01. T.W.S. received support from the Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security, and Fogarty International Center, National Institutes of Health (NIH), Bethesda, MD. This study was supported by National Science Foundation Ecology of Infectious Disease Program Grant EF-0914384 and National Institutes of Health Grant R01 GM-083224. NR 42 TC 172 Z9 177 U1 5 U2 89 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 MAY 3 PY 2011 VL 108 IS 18 BP 7460 EP 7465 DI 10.1073/pnas.1101377108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 758YF UT WOS:000290203100040 PM 21502510 ER PT J AU Adams, WC Gujer, C McInerney, G Gall, JGD Petrovas, C Hedestam, GBK Koup, RA Lore, K AF Adams, William C. Gujer, Cornelia McInerney, Gerald Gall, Jason G. D. Petrovas, Constantinos Hedestam, Gunilla B. Karlsson Koup, Richard A. Lore, Karin TI Adenovirus type-35 vectors block human CD4(+) T-cell activation via CD46 ligation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COFACTOR PROTEIN CD46; PLASMACYTOID DENDRITIC CELLS; DOWN-REGULATION; MEASLES-VIRUS; RECEPTOR CD46; IMMUNITY; FIBER; SEROTYPE-35; INFECTION; BINDING AB Recombinant adenoviruses (rAds) based on types 5 (rAd5) and 35 (rAd35) have emerged as important vaccine delivery vectors in clinical testing for a variety of pathogens. A major difference between these vectors is their binding to cellular receptors used for infection. Whereas rAd5 binds coxsackie-adenovirus receptor (CAR), rAd35 binds the complement regulatory protein CD46. Although rAd35 infected and phenotypically matured human blood dendritic cells (DCs) more efficiently than rAd5, we show here that rAd35 markedly suppressed DC-induced activation of naive CD4(+) T cells. rAd35 specifically blocked both DCs and anti-CD3/CD28 mAb-induced naive T-cell proliferation and IL-2 production. This effect was also observed in CD4(+) memory T cells but to a lesser extent. The suppression occurred by rAd35 binding to CD46 on T cells and was independent of infection. CD46 engagement with mAb mimicked the effects of rAd35 and also led to deficient NF-kappa B nuclear translocation. In contrast, rAd5 and rAd35 vectors with ablated CD46 binding did not inhibit T-cell activation. Our findings provide insights into the basic biology of adenoviruses and indicate that CD46 binding may have an impact on the generation of primary CD4(+) T-cell responses by Ad35. C1 [Adams, William C.; Gujer, Cornelia; Lore, Karin] Karolinska Inst, Ctr Infect Med, Dept Med, S-17177 Stockholm, Sweden. [McInerney, Gerald; Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden. [Adams, William C.; Petrovas, Constantinos; Koup, Richard A.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA. RP Lore, K (reprint author), Karolinska Inst, Ctr Infect Med, Dept Med, S-17177 Stockholm, Sweden. EM karin.lore@ki.se RI McInerney, Gerald/G-5344-2012; OI McInerney, Gerald/0000-0003-2257-7241 FU Ake Wiberg's foundation; Swedish Society for Medical Research, Vetenskapsradet; Jeansson's Foundation; Swedish Society for Medicine FX The authors are grateful to Kai Eng, Kerrie Sandgren, Peter Sahlstrom, Matthew Johnson, and the Department of Transfusion Medicine (Karolinska Hospital) for technical assistance. This study was supported by the Ake Wiberg's foundation, the Swedish Society for Medical Research, Vetenskapsradet, Jeansson's Foundation, and the Swedish Society for Medicine. NR 41 TC 21 Z9 22 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 3 PY 2011 VL 108 IS 18 BP 7499 EP 7504 DI 10.1073/pnas.1017146108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 758YF UT WOS:000290203100047 PM 21502499 ER PT J AU Jiang, LB Gaur, D Mu, JB Zhou, H Long, CA Miller, LH AF Jiang, Lubin Gaur, Deepak Mu, Jianbing Zhou, Hong Long, Carole A. Miller, Louis H. TI Evidence for erythrocyte-binding antigen 175 as a component of a ligand-blocking blood-stage malaria vaccine SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Plasmodium falciparum; receptor ID APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM EBA-175; INVASION PATHWAYS; HUMAN-ANTIBODIES; GLYCOPHORIN-C; RECEPTOR; PARASITES; DOMAIN; POLYMORPHISMS; EXPRESSION AB The ligands that pathogens use to invade their target cells have often proven to be good targets for vaccine development. However, Plasmodium falciparum has redundant ligands that mediate invasion of erythrocytes. The first requirement for the development of a successful ligand-blocking malaria vaccine is the demonstration that antibodies induced to each ligand can block the erythrocyte invasion of parasites with polymorphic sequences. Because of P. falciparum's redundancy in erythrocyte invasion, each ligand needs to be studied under artificial conditions in which parasite invasion is restricted in its use of alternative pathways. Here we investigate the role of erythrocyte-binding antigen 175 (EBA-175), a parasite ligand that binds to sialic acid on glycophorin A, in the invasion of erythrocytes by 10 P. falciparum clones under conditions in which invasion is partially limited to the EBA-175-glycophorin A pathway, using chymotrypsin-treated erythrocytes. We show that the ability to invade erythrocytes for both sialic acid-independent and sialic acid-dependent pathways requires the EBA-175-glycophorin A pathway for erythrocyte invasion. Importantly, antibodies against region II of EBA-175 from the 3D7 clone blocked invasion of chymotrypsin-treated erythrocytes by > 50% by all parasite clones studied, including those with multiple different mutations described in the literature. The one exception was FCR3, which had a similar sequence to 3D7 but only 30% inhibition of invasion of chymotrypsin-treated erythrocytes, indicating alternative pathways for invasion of chymotrypsin-treated erythrocytes. Our findings suggest that antibodies to region II of EBA-175, as one component of a ligand-blocking malaria vaccine, are largely unaffected by polymorphism in EBA-175. C1 [Jiang, Lubin; Gaur, Deepak; Mu, Jianbing; Zhou, Hong; Long, Carole A.; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Gaur, Deepak] Int Ctr Genet Engn & Biotechnol, Malaria Grp, New Delhi 110067, India. RP Jiang, LB (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM ljiang@niaid.nih.gov; dgaur@icgeb.res.in; lmiller@niaid.nih.gov FU Division of Microbiology and Infectious Diseases/National Institute of Allergy and Infectious Diseases [AI-N01-054210]; PATH/Malaria Vaccine Initiative; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Drs. Lee Hall and Annie Mo at the Malaria Vaccine Development Section, Parasitology and International Programs Branch, Division of Microbiology and Infectious Diseases, National Institutes of Health for kindly providing the EBA-175 region II recombinant protein and the rabbit antibodies to EBA-175 created under Division of Microbiology and Infectious Diseases/National Institute of Allergy and Infectious Diseases Contract AI-N01-054210. We thank Dr. Susan K. Pierce, National Institute of Allergy and Infectious Diseases, for suggestions on the manuscript, and Ababacar Diouf and Kazutoyo Miura for their excellent technical assistance with total IgG purification and GIA. The GIA Reference Center is supported in part by the PATH/Malaria Vaccine Initiative. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 39 TC 35 Z9 35 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 3 PY 2011 VL 108 IS 18 BP 7553 EP 7558 DI 10.1073/pnas.1104050108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 758YF UT WOS:000290203100056 PM 21502513 ER PT J AU Forman, DE Rich, MW Alexander, KP Zieman, S Maurer, MS Najjar, SS Cleveland, JC Krumholz, HM Wenger, NK AF Forman, Daniel E. Rich, Michael W. Alexander, Karen P. Zieman, Susan Maurer, Mathew S. Najjar, Samer S. Cleveland, Joseph C., Jr. Krumholz, Harlan M. Wenger, Nanette K. TI Cardiac Care for Older Adults Time for a New Paradigm SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiac care; cardiovascular aging; CVD; older adults ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; ACUTE CORONARY SYNDROMES; LAST 6 MONTHS; HEART-FAILURE; ELDERLY-PATIENTS; CARDIOVASCULAR-DISEASE; RISK-FACTOR; MYOCARDIAL-INFARCTION; MEDICARE BENEFICIARIES; TRANSITIONAL CARE C1 [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Forman, Daniel E.] Boston VA Healthcare Ctr, New England GRECC, Boston, MA USA. [Rich, Michael W.] Washington Univ, Sch Med, St Louis, MO USA. [Alexander, Karen P.] Duke Univ, Med Ctr, Durham, NC USA. [Zieman, Susan] NIA, NIH, Bethesda, MD 20892 USA. [Maurer, Mathew S.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Najjar, Samer S.] Washington Hosp Ctr, MedStar Hlth Res Inst, Washington, DC 20010 USA. [Cleveland, Joseph C., Jr.] Univ Colorado, Div Cardiothorac Surg, Denver, CO 80202 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, New Haven, CT USA. [Wenger, Nanette K.] Emory Univ, Sch Med, Atlanta, GA USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM DEForman@partners.org FU NIA NIH HHS [K24 AG036778] NR 76 TC 64 Z9 66 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 3 PY 2011 VL 57 IS 18 BP 1801 EP 1810 DI 10.1016/j.jacc.2011.02.014 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 755YM UT WOS:000289977500002 PM 21527153 ER PT J AU Okwuosa, TM Greenland, P Ning, HY Liu, K Bild, DE Burke, GL Eng, J Lloyd-Jones, DM AF Okwuosa, Tochi M. Greenland, Philip Ning, Hongyan Liu, Kiang Bild, Diane E. Burke, Gregory L. Eng, John Lloyd-Jones, Donald M. TI Distribution of Coronary Artery Calcium Scores by Framingham 10-Year Risk Strata in the MESA (Multi-Ethnic Study of Atherosclerosis) Potential Implications for Coronary Risk Assessment SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atherosclerosis; coronary calcium; coronary heart disease; Framingham risk score; low risk; number needed to screen; population; risk factors ID CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; RACIAL-DIFFERENCES; HEART-DISEASE; ASYMPTOMATIC INDIVIDUALS; PRIMARY PREVENTION; WHITE SUBJECTS; EVENTS; ADULTS; CALCIFICATION AB Objectives By examining the distribution of coronary artery calcium (CAC) levels across Framingham risk score (FRS) strata in a large, multiethnic, community-based sample of men and women, we sought to determine if lower-risk persons could benefit from CAC screening. Background The 10-year FRS and CAC levels are predictors of coronary heart disease. A CAC level of 300 or more is associated with the highest risk for coronary heart disease even in low-risk persons (FRS, <10%); however, expert groups have suggested CAC screening only in intermediate-risk groups (FRS, 10% to 20%). Methods We included 5,660 Multi-Ethnic Study of Atherosclerosis participants. The number needed to screen (number of people that need to be screened to detect 1 person with CAC level above the specified cutoff point) was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using chi-square tests. Results CAC levels of more than 0, of 100 or more, and of 300 or more were present in 46.4%, 20.6%, and 10.1% of participants, respectively. The prevalence and amount of CAC increased with higher FRS. A CAC level of 300 or more was observed in 1.7% and 4.4% of those with FRS of 0% to 2.5% and of 2.6% to 5%, respectively (number needed to screen, 59.7 and 22.7, respectively). Likewise, a CAC level of 300 or more was observed in 24% and 30% of those with FRS of 15.1% to 20% and more than 20%, respectively (number needed to screen, 4.2 and 3.3, respectively). Trends were similar when stratified by age, sex, and race or ethnicity. Conclusions Our study suggests that in very low-risk individuals (FRS <= 5%), the yield of screening and probability of identifying persons with clinically significant levels of CAC is low, but becomes greater in low-and intermediate-risk persons (FRS 5.1% to 20%). (J Am Coll Cardiol 2011; 57: 1838-45) (C) 2011 by the American College of Cardiology Foundation C1 [Greenland, Philip; Ning, Hongyan; Liu, Kiang; Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Greenland, Philip; Ning, Hongyan; Liu, Kiang; Lloyd-Jones, Donald M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Okwuosa, Tochi M.] Wayne State Univ, Sch Med, Div Cardiol, Detroit, MI USA. [Bild, Diane E.] NHLBI, Prevent & Populat Sci Program, NIH, Bethesda, MD 20892 USA. [Burke, Gregory L.] Wake Forest Univ, Div Publ Hlth Sci, Sch Med, Wake Forest, NC USA. [Eng, John] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009 FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-95159, N01-HC-95169] FX Supported by contracts N01-HC-95159 through N01-HC-95169 from the ~. Dr. Greenland received an honorarium from GE/Toshiba in 2008. All other authors have reported that they have no relationships to disclose. NR 30 TC 42 Z9 42 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 MAY 3 PY 2011 VL 57 IS 18 BP 1838 EP 1845 DI 10.1016/j.jacc.2010.11.053 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 755YM UT WOS:000289977500008 PM 21527159 ER PT J AU Kim, A Benning, MM OkLee, S Quinn, J Martin, BM Holden, HM Dunaway-Mariano, D AF Kim, Alexander Benning, Matthew M. OkLee, Sang Quinn, John Martin, Brian M. Holden, Hazel M. Dunaway-Mariano, Debra TI Divergence of Chemical Function in the Alkaline Phosphatase Superfamily: Structure and Mechanism of the P-C Bond Cleaving Enzyme Phosphonoacetate Hydrolase SO BIOCHEMISTRY LA English DT Article ID PSEUDOMONAS-FLUORESCENS 23F; INDEPENDENT PHOSPHOGLYCERATE MUTASE; CRYSTAL-STRUCTURES; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; EVOLUTION; CATALYSIS; GENE; PHOSPHODIESTERASE; INTERMEDIATE AB Phosphonates constitute a class of natural products that mimic the properties of the more common organophosphate ester metabolite yet are not readily degraded owing to the direct linkage of the phosphorus atom to the carbon atom. Phosphonate hydrolases have evolved to allow bacteria to utilize environmental phosphonates as a source of carbon and phosphorus. The work reported in this paper examines one such enzyme, phosphonoacetate hydrolase. By using a bioinformatic approach, we circumscribed the biological range of phosphonoacetate hydrolase to a select group of bacterial species from different classes of Proteobacteria. In addition, using gene context, we identified a novel 2-aminoethylphosphonate degradation pathway in which phosphonoacetate hydrolase is a participant. The X-ray structure of phosphonoformate-bound phosphonoacetate hydrolase was determined to reveal that this enzyme is most closely related to nucleotide pyrophosphatase/diesterase, a promiscuous two-zinc ion metalloenzyme of the alkaline phosphatase enzyme superfamily. The X-ray structure and metal ion specificity tests showed that phosphonoacetate hydrolase is also a two-zinc ion metalloenzyme. By using site-directed mutagenesis and (32)P-labeling strategies, the catalytic nucleophile was shown to be Thr64. A structure-guided, site-directed mutation-based inquiry of the catalytic contributions of active site residues identified Lys126 and Lys128 as the most likely candidates for stabilization of the aci-carboxylate dianion leaving group. A catalytic mechanism is proposed which combines Lys12/Lys128 leaving group stabilization with zinc ion activation of the Thr64 nucleophile and the substrate phosphoryl group. C1 [Kim, Alexander; OkLee, Sang; Dunaway-Mariano, Debra] Univ New Mexico, Dept Chem & Chem Biol, Albuquerque, NM 87131 USA. [Benning, Matthew M.; Holden, Hazel M.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Quinn, John] Queens Univ Belfast, Ctr Med Biol, Questor Ctr, Belfast BT9 7BL, Antrim, North Ireland. [Quinn, John] Queens Univ Belfast, Ctr Med Biol, Sch Biol & Biochem, Belfast BT9 7BL, Antrim, North Ireland. [Martin, Brian M.] NIMH, Mol Struct Unit, Lab Neurotoxicol, Bethesda, MD 20892 USA. EM hazel_holden@biochem.wisc.edu; dd39@unm.edu FU NIH [GM 28688, DK47814]; BBSRC (UK) [81/P11488]; IRP, NIMH FX This work was supported by NIH Grant GM 28688 (D.D.-M.), NIH Grant DK47814 (H.M.H..) and BBSRC (UK) Grant 81/P11488 (J.P.Q) and intramural funding from the IRP, NIMH (B.M.M.). NR 58 TC 17 Z9 18 U1 4 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 3 PY 2011 VL 50 IS 17 BP 3481 EP 3494 DI 10.1021/bi200165h PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753CM UT WOS:000289742400010 PM 21366328 ER PT J AU Terrazas, M Ocampo, SM Perales, JC Marquez, VE Eritja, R AF Terrazas, Montserrat Ocampo, Sandra M. Carlos Perales, Jose Marquez, Victor E. Eritja, Ramon TI Effect of North Bicyclo[3.1.0]hexane 2 '-Deoxy-pseudosugars on RNA Interference: A Novel Class of siRNA Modification SO CHEMBIOCHEM LA English DT Article DE deoxymethanocarba nucleoside; immunochemistry; Renilla luciferase; RNA; TNF-alpha ID CULTURED-MAMMALIAN-CELLS; BASE-PAIRING PROPERTIES; ACID DUPLEX STABILITY; BIOLOGICAL-ACTIVITY; TRICYCLO-DNA; CONFORMATIONAL-ANALYSIS; CARBOCYCLIC THYMIDINE; NUCLEOSIDE ANALOGS; NEPLANOCIN-C; SUGAR RING AB North bicyclo methanocarba thymidine (T(N)) nucleosides were substituted into siRNAs to investigate the effect of bicyclo-[3.1.0]hexane 2'-deoxy-pseudosugars on RNA interference activity. Here we provide evidence that these modified siRNAs are compatible with the intracellular RNAi machinery. We studied the effect of the T(N) modification in a screen involving residue- specific changes in an siRNA targeting Renilla luciferase and we applied the most effective pattern of modification to the knockdown of murine tumor necrosis factor (TNF-alpha). We also showed that incorporation of T(N) units into siRNA duplexes increased their thermal stabilities, substantially enhanced serum stabilities, and decreased innate immunostimulation. Comparative RNAi studies involving the T(N) substitution and locked nucleic acids (LNAs) showed that the gene-silencing activities of T(N)-modified siRNAs were comparable to those obtained with the LNA modification. An advantage of the North 2'-deoxy-methanocarba modification is that it may be explored further in the future by changing the 2'-position. The results from these studies suggest that this modification might be valuable for the development of siRNAs for therapeutic applications. C1 [Terrazas, Montserrat; Ocampo, Sandra M.; Eritja, Ramon] Spanish Res Council CSIC, Inst Adv Chem Catalonia IQAC, Inst Res Biomed IRB Barcelona, CIBER BBN, Barcelona 08028, Spain. [Carlos Perales, Jose] Univ Barcelona, Sch Med, Dept Ciencies Fisiol, Barcelona 08907, Spain. [Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Eritja, R (reprint author), Spanish Res Council CSIC, Inst Adv Chem Catalonia IQAC, Inst Res Biomed IRB Barcelona, CIBER BBN, Cluster Bldg,Baldiri & Reixac 10, Barcelona 08028, Spain. EM recgma@cid.csic.es RI PERALES, JOSE C./D-5586-2012; eritja, ramon/B-5613-2008 OI PERALES, JOSE C./0000-0001-7363-2226; eritja, ramon/0000-0001-5383-9334 FU European Union; Spanish Ministry of Education [BFU2007-63287, CTQ2010-20541]; Generalitat the Catalunya [2009/SGR/208]; Center for Cancer Research, National Cancer Institute, NIH; CSIC, Spain; Juan de la Cierva (MICINN, Spain) FX This research was supported by the European Union (MULTIFUN consortium), the Spanish Ministry of Education (BFU2007-63287, CTQ2010-20541), and the Generalitat the Catalunya (2009/SGR/208). This work was funded in part by the Center for Cancer Research, National Cancer Institute, NIH. M.T. acknowledges the JAE-Doc 2008 contract (CSIC, Spain) and the Juan de la Cierva contract (MICINN, Spain) for financial support. NR 64 TC 12 Z9 12 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD MAY 2 PY 2011 VL 12 IS 7 BP 1056 EP 1065 DI 10.1002/cbic.201000791 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 754MH UT WOS:000289858200013 PM 21452187 ER PT J AU Maraia, RJ Lamichhane, TN AF Maraia, Richard J. Lamichhane, Tek N. TI 3 ' processing of eukaryotic precursor tRNAs SO WILEY INTERDISCIPLINARY REVIEWS-RNA LA English DT Review ID POLYMERASE-III TRANSCRIPTION; YEAST LA PROTEIN; 5S RIBOSOMAL-RNA; TERMINATION SIGNAL RECOGNITION; METHIONYL-TRANSFER-RNA; LUPUS ANTIGEN-LA; SACCHAROMYCES-CEREVISIAE; U6 SNRNA; LSM PROTEINS; QUALITY-CONTROL AB Biogenesis of eukaryotic tRNAs requires transcription by RNA polymerase III and subsequent processing. 5' processing of precursor tRNA occurs by a single mechanism, cleavage by RNase P, and usually occurs before 3' processing although some conditions allow observation of the 3'-first pathway. 3' processing is relatively complex and is the focus of this review. Precursor RNA 3' end formation begins with pol III termination generating a variable length 3' oligo(U) tract that represents an underappreciated and previously unreviewed determinant of processing. Evidence that the pol III-intrinsic 3' exonuclease activity mediated by Rpc11p affects 3' oligo(U) length is reviewed. In addition to multiple 3' nucleases, precursor tRNA (pre-tRNA) processing involves La and Lsm, distinct oligo(U)-binding proteins with proposed chaperone activities. 3' processing is performed by the endonuclease RNase Z or the exonuclease Rex1p (possibly others) along alternate pathways conditional on La. We review a Schizosaccharomyces pombe tRNA reporter system that has been used to distinguish two chaperone activities of La protein to its two conserved RNA binding motifs. Pre-tRNAs with structural impairments are degraded by a nuclear surveillance system that mediates polyadenylation by the TRAMP complex followed by 3' digestion by the nuclear exosome which appears to compete with 3' processing. We also try to reconcile limited data on pre-tRNA processing and Lsm proteins which largely affect precursors but not mature tRNAs. A pathway is proposed in which 3' oligo(U) length is a primary determinant of La binding with subsequent steps distinguished by 3' endo versus exo nucleases, chaperone activities, and nuclear surveillance. (C) 2010 John Wiley & Sons, Ltd. WIREs RNA 2011 2 362-375 DOI: 10.1002/wrna.64 C1 [Maraia, Richard J.; Lamichhane, Tek N.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD USA. [Maraia, Richard J.] Commissioned Corps, US Publ Hlth Serv, Bethesda, MD USA. RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD USA. EM maraiar@mail.nih.gov FU NICHD, NIH FX We thank the members of the Maraia laboratory for comments and discussion as well as J. Iben, A. Russo, and V. Cherkasova for editing. This work was supported by the Intramural Research Program of the NICHD, NIH. R.J.M. is a Commissioned Officer in the U.S. Public Health Service. NR 97 TC 34 Z9 36 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1757-7004 J9 WIRES RNA JI Wiley Interdiscip. Rev.-RNA PD MAY-JUN PY 2011 VL 2 IS 3 BP 362 EP 375 DI 10.1002/wrna.64 PG 14 WC Cell Biology SC Cell Biology GA 913GB UT WOS:000301863400004 PM 21572561 ER PT J AU Kainerstorfer, JM Riley, JD Ehler, M Najafizadeh, L Amyot, F Hassan, M Pursley, R Demos, SG Chernomordik, V Pircher, M Smith, PD Hitzenberger, CK Gandjbakhche, AH AF Kainerstorfer, Jana M. Riley, Jason D. Ehler, Martin Najafizadeh, Laleh Amyot, Franck Hassan, Moinuddin Pursley, Randall Demos, Stavros G. Chernomordik, Victor Pircher, Michael Smith, Paul D. Hitzenberger, Christoph K. Gandjbakhche, Amir H. TI Quantitative principal component model for skin chromophore mapping using multi-spectral images and spatial priors SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; HEMOGLOBIN OXYGENATION; LESION CLASSIFICATION; EPIDERMAL THICKNESS; COLOR IMAGE; SEGMENTATION; ABSORPTION; SIMULATION; FEATURES AB We describe a novel reconstruction algorithm based on Principal Component Analysis (PCA) applied to multi-spectral imaging data. Using numerical phantoms, based on a two layered skin model developed previously, we found analytical expressions, which convert qualitative PCA results into quantitative blood volume and oxygenation values, assuming the epidermal thickness to be known. We also evaluate the limits of accuracy of this method when the value of the epidermal thickness is not known. We show that blood volume can reliably be extracted (less than 6% error) even if the assumed thickness deviates 0.04mm from the actual value, whereas the error in blood oxygenation can be as large as 25% for the same deviation in thickness. This PCA based reconstruction was found to extract blood volume and blood oxygenation with less than 8% error, if the underlying structure is known. We then apply the method to in vivo multi-spectral images from a healthy volunteer's lower forearm, complemented by images of the same area using Optical Coherence Tomography (OCT) for measuring the epidermal thickness. Reconstruction of the imaging results using a two layered analytical skin model was compared to PCA based reconstruction results. A point wise correlation was found, showing the proof of principle of using PCA based reconstruction for blood volume and oxygenation extraction. (C) 2011 Optical Society of America C1 [Kainerstorfer, Jana M.; Riley, Jason D.; Najafizadeh, Laleh; Hassan, Moinuddin; Chernomordik, Victor; Gandjbakhche, Amir H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Pediat Imaging & Tissue Sci, Sect Analyt & Funct Biophoton, Bethesda, MD 20892 USA. [Kainerstorfer, Jana M.; Pircher, Michael; Hitzenberger, Christoph K.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, A-1090 Vienna, Austria. [Ehler, Martin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Phys Biol, Lab Integrat & Med Biophys,Sect Med Biophys, Bethesda, MD 20892 USA. [Najafizadeh, Laleh] Henry M Jackson Fdn, Rockville, MD 20852 USA. [Amyot, Franck] NINDS, NIH, Clin Neurosci Program, Bethesda, MD 20892 USA. [Pursley, Randall] NIH, Ctr Informat Technol, Div Computat Biosci, Signal Proc & Instrumentat Sect, Bethesda, MD 20892 USA. [Demos, Stavros G.] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA. [Smith, Paul D.] Natl Inst Biomed Imaging & Bioengn, NIH, Lab Cellular Imaging & Macromol Biophys, Biomed Instrumentat & Multiscale Imaging Sect, Bethesda, MD 20892 USA. RP Kainerstorfer, JM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Pediat Imaging & Tissue Sci, Sect Analyt & Funct Biophoton, Bethesda, MD 20892 USA. EM kainersj@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The research was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Graduate Partnership Program at the National Institutes of Health and the Faculty of Physics at the University of Vienna / Austria are also acknowledged. NR 46 TC 10 Z9 10 U1 0 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAY 1 PY 2011 VL 2 IS 5 BP 1040 EP 1058 PG 19 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 886TY UT WOS:000299878000002 PM 21559118 ER PT J AU Janicak, PG AF Janicak, Philip G. TI IN THIS ISSUE: Treatment Challenges of Schizophrenia SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Janicak, Philip G.] Rush Univ, Chicago, IL 60612 USA. [Janicak, Philip G.] Amer Psychiat Assoc, Washington, DC 20005 USA. [Janicak, Philip G.] Univ Illinois, NIH, Gen Clin Res Ctr, Med Ctr, Chicago, IL 60680 USA. RP Janicak, PG (reprint author), Rush Univ, Chicago, IL 60612 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAY PY 2011 VL 41 IS 5 BP 246 EP 247 PG 2 WC Psychiatry SC Psychiatry GA 884ZO UT WOS:000299747600002 ER PT J AU Orru, CD Wilham, JM Raymond, LD Kuhn, F Schroeder, B Raeber, AJ Caughey, B AF Orru, Christina D. Wilham, Jason M. Raymond, Lynne D. Kuhn, Franziska Schroeder, Bjoern Raeber, Alex J. Caughey, Byron TI Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion SO MBIO LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; MISFOLDING CYCLIC AMPLIFICATION; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; IN-VITRO AMPLIFICATION; ULTRASENSITIVE DETECTION; SEEDED CONVERSION; INFECTIOUS PRIONS; PROTEIN; SCRAPIE; PRPSC AB A key challenge in managing transmissible spongiform encephalopathies (TSEs) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. Of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. One of the latter tests is quaking-induced conversion (QuIC), which can be as sensitive as in vivo bioassays, but much more rapid, higher throughput, and less expensive. Now we have integrated antibody 15B3-based immunoprecipitation with QuIC reactions to increase sensitivity and isolate prions from inhibitors such as those in plasma samples. Coupling of immunoprecipitation and an improved real-time QuIC reaction dramatically enhanced detection of variant Creutzfeldt-Jakob disease (vCJD) brain tissue diluted into human plasma. Dilutions of 10(14)-fold, containing similar to 2 attogram (ag) per ml of proteinase K-resistant prion protein, were readily detected, indicating similar to 10,000-fold greater sensitivity for vCJD brain than has previously been reported. We also discriminated between plasma and serum samples from scrapie-infected and uninfected hamsters, even in early preclinical stages. This combined assay, which we call "enhanced QuIC" (eQuIC), markedly improves prospects for routine detection of low levels of prions in tissues, fluids, or environmental samples. IMPORTANCE Transmissible spongiform encephalopathies (TSEs) are largely untreatable and are difficult to diagnose definitively prior to irreversible clinical decline or death. The transmissibility of TSEs within and between species highlights the need for practical tests for even the smallest amounts of infectivity. A few sufficiently sensitive in vitro methods have been reported, but most have major limitations that would preclude their use in routine diagnostic or screening applications. Our new assay improves the outlook for such critical applications. We focused initially on blood plasma because a practical blood test for prions would be especially valuable for TSE diagnostics and risk reduction. Variant Creutzfeldt-Jakob disease (vCJD) in particular has been transmitted between humans via blood transfusions. Enhanced real-time quaking-induced conversion (eQuIC) provides by far the most sensitive detection of vCJD to date. The 15B3 antibody binds prions of multiple species, suggesting that our assay may be useful for clinical and fundamental studies of a variety of TSEs of humans and animals. C1 [Orru, Christina D.; Wilham, Jason M.; Raymond, Lynne D.; Caughey, Byron] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. [Kuhn, Franziska; Schroeder, Bjoern; Raeber, Alex J.] Prion AG, Zurich, Switzerland. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM bcaughey@nih.gov FU NIAID, NIH; Prionics AG; EU FX This research was funded by the Intramural Research Program of the NIAID, NIH; Prionics AG; and the EU grant PRIORITY. NR 45 TC 43 Z9 45 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2011 VL 2 IS 3 AR e00078-11 DI 10.1128/mBio.00078-11 PG 9 WC Microbiology SC Microbiology GA 845SW UT WOS:000296843900017 PM 21558432 ER PT J AU Curlin, G Landry, S Bernstein, J Gorman, RL Mulach, B Hackett, CJ Foster, S Miers, SE Strickler-Dinglasan, P AF Curlin, George Landry, Sarah Bernstein, Jessica Gorman, Richard L. Mulach, Barbara Hackett, Charles J. Foster, Stephanie Miers, Sarah E. Strickler-Dinglasan, Patricia TI Integrating Safety and Efficacy Evaluation Throughout Vaccine Research and Development SO PEDIATRICS LA English DT Article C1 [Gorman, Richard L.] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Gorman, RL (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 6610 Rockledge Dr,MSC 6604, Bethesda, MD 20892 USA. EM gormanr@niaid.nih.gov OI Hackett, Charles/0000-0003-4586-9669 NR 4 TC 5 Z9 5 U1 0 U2 0 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 MAY PY 2011 VL 127 SU 1 BP S9 EP S15 DI 10.1542/peds.2010-1722C PG 7 WC Pediatrics SC Pediatrics GA 846QK UT WOS:000296918100003 PM 21502246 ER PT J AU Qin, LX Ma, W Li, DW Li, Y Chen, XY Kraatz, HB James, TD Long, YT AF Qin, Li-Xia Ma, Wei Li, Da-Wei Li, Yang Chen, Xiaoyuan Kraatz, Heinz-Bernhard James, Tony D. Long, Yi-Tao TI Coenzyme Q Functionalized CdTe/ZnS Quantum Dots for Reactive Oxygen Species (ROS) Imaging SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE coenzyme Q; electrochemistry; fluorescence; quantum dots; reactive oxygen species ID SEMICONDUCTOR NANOCRYSTALS; CDSE NANOPARTICLES; ELECTRON-TRANSFER; ANTIOXIDANT; UBIQUINONE; INTERFACE; SYSTEMS; PROTEIN; CELLS; PROBE AB Quantum dots (QDs) have been widely used for fluorescent imaging in cells. In particular, surface functionalized QDs are of interest, since they possess the ability to recognize and detect the analytes in the surrounding nanoscale environment based on electron and hole transfer between the analytes and the QDs. Here we demonstrate that fluorescence enhancement/quenching in QDs can be switched by electrochemically modulating electron transfer between attached molecules and QDs. For this purpose, a number of redox-active coenzyme Q (CoQ) disulfide derivatives [CoQCnS](2) were synthesized with different alkyl chain lengths (n = 1, 5, and 10). The system supremely sensitive to NADH ( nicotinamide adenine dinucleotide) and superoxide radical (O2C center dot-), and represents a biomimetic electron-transfer system, modeling part of the mitochondrial respiratory chain. The results of our in situ fluorescence spectroelectro-chemical study demonstrate that the reduced state of [ CoQCnS] 2 significantly enhanced the fluorescence intensity of CdTe/ZnS QDs, while the oxidized state of the CoQ conjugates quench the fluorescence to varying degrees. Fluorescence imaging of cells loaded with the conjugate QD-[CoQCnS](2) displayed strikingly differences in the fluorescence depending on the redox state of the capping layer, thus introducing a handle for evaluating the status of the cellular redox potential status. Moreover, an MTT assay (MTT=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proved that the cytotoxicity of QDs was significantly reduced after immobilization by CoQ derivatives. Those unique features make CoQ derivatived QDs as a promising probe to image redox coenzyme function in vitro and in vivo. C1 [Qin, Li-Xia; Ma, Wei; Li, Da-Wei; Li, Yang; Long, Yi-Tao] E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China. [Qin, Li-Xia; Ma, Wei; Li, Da-Wei; Long, Yi-Tao] E China Univ Sci & Technol, Dept Chem, Shanghai 200237, Peoples R China. [Chen, Xiaoyuan] NIH, Lab Mol Imaging & Nanomed LOMIN, Bethesda, MD 20892 USA. [Kraatz, Heinz-Bernhard] Univ Western Ontario, Dept Chem, London, ON N5A 5B9, Canada. [James, Tony D.] Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England. RP Long, YT (reprint author), E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, 130 Meilong Rd, Shanghai 200237, Peoples R China. EM ytlong@ecust.edu.cn RI James, Tony/B-5125-2009; Kraatz, Heinz-Bernhard/D-2246-2014; Long, Yitao/P-4089-2014; OI James, Tony/0000-0002-4095-2191; Kraatz, Heinz-Bernhard/0000-0002-7149-0110; Long, Yitao/0000-0002-4466-3119; Long, Yitao/0000-0003-2571-7457 FU National Natural Science Foundation of China [91027035]; Shanghai Pujiang Program Grant of China [09 J1403300]; Ministry of Health of China [2009ZX10004-301]; National Science and Engineering Research Council of Canada FX This work was support by the Major Research Plan of the National Natural Science Foundation of China (Grant No. 91027035), Shanghai Pujiang Program Grant of China (Grant No. 09 J1403300) and the Ministry of Health of China (Grant No. 2009ZX10004-301). This research was also partly funded by the National Science and Engineering Research Council of Canada. We also thank the Catalysis and Sensing for our Environment (CASE) consortium for networking opportunities. NR 45 TC 28 Z9 28 U1 4 U2 63 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 0947-6539 EI 1521-3765 J9 CHEM-EUR J JI Chem.-Eur. J. PD MAY PY 2011 VL 17 IS 19 BP 5262 EP 5271 DI 10.1002/chem.201003749 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 759BF UT WOS:000290214200009 PM 21503990 ER PT J AU Gautam, P Zhao, LP Patel, P AF Gautam, Pawan Zhao, Linping Patel, Pravin TI Biomechanical response of the maxillofacial skeleton to transpalatal orthopedic force in a unilateral palatal cleft SO ANGLE ORTHODONTIST LA English DT Article DE Rapid maxillary expansion; Cleft palate; FEM ID RAPID MAXILLARY EXPANSION; CRANIOFACIAL SKELETON; STABILITY AB Objectives: To assess the skeletal and dental effects of rapid maxillary expansion in a patient with unilateral cleft deformity of secondary palate and alveolus using the finite element method. Materials and Methods: A patient-specific composite skull model was developed from a patient computed tomographic scan and a surface scan of the patient's maxillary cast using MIMICS imaging analysis software. For volumetric meshing and the finite element analysis, Abaqus (6.7) was used. Results: The typical wedge-shaped opening that occurs after RME, seen in non-cleft patients, is not seen in cleft patients. A clockwise rotation of the maxilla as a result of maxillary expansion was evident. The areas of maximum stress were the intact primary palate region, inferior orbital foramen of the non-cleft and the cleft sides, and the zygomatic buttress of the cleft side. During expansion, the intact primary palate showed high stress and acted as a region of major resistance, followed by the zygomatic buttress on the cleft side. Conclusions: Clinicians should consider a need for customization of expansion therapy for cleft patients depending on 1:he patient's age, the type of cleft present (primary or secondary palate), and the desired area of expansion (anterior or posterior). (Angle Orthod. 201181:503-509.) C1 [Gautam, Pawan; Zhao, Linping; Patel, Pravin] Univ Illinois, Craniofacial Ctr, Chicago, IL 60612 USA. [Gautam, Pawan] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Gautam, P (reprint author), Univ Illinois, Craniofacial Ctr, MC 588,811 S Paulina St, Chicago, IL 60612 USA. NR 25 TC 5 Z9 5 U1 1 U2 11 PU E H ANGLE EDUCATION RESEARCH FOUNDATION, INC PI NEWTON N PA 1615 BEACON ST, NEWTON N, MA 02468-1507 USA SN 0003-3219 J9 ANGLE ORTHOD JI Angle Orthod. PD MAY PY 2011 VL 81 IS 3 BP 503 EP 509 DI 10.2319/070110-367.1 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 753HB UT WOS:000289761800021 PM 21299384 ER PT J AU Li, Y Sun, JF Cui, XZ Mani, H Danner, RL Li, XM Su, JW Fitz, Y Eichacker, PQ AF Li, Yan Sun, Jun-Feng Cui, Xizhong Mani, Haresh Danner, Robert L. Li, Xuemei Su, Jun-Wu Fitz, Yvonne Eichacker, Peter Q. TI The effect of heparin administration in animal models of sepsis: A prospective study in Escherichia coli-challenged mice and a systematic review and metaregression analysis of published studies SO CRITICAL CARE MEDICINE LA English DT Article DE sepsis; infection; pneumonia; heparin; treatment; metaregression analysis; animal models ID MOLECULAR-WEIGHT HEPARIN; LOW-DOSE HEPARIN; ENDOTOXIN-SHOCK; SEPTIC SHOCK; FIBRINOPURULENT PERITONITIS; UNFRACTIONATED HEPARIN; RECOMBINANT HIRUDIN; METAANALYSIS; SURVIVAL; RAT AB Introduction: If thrombosis contributes to sepsis, heparin titrated using activated partial thromboplastin times may be efficacious. We investigated heparin in preclinical models. Methods and Main Results: In unchallenged mice (n = 107), heparin at 100, 500, or 2500 units/kg produced activated partial thromboplastin time levels less than, within, or greater than a prespecified therapeutic range (1.5-2.5 times control), respectively. In animals (n = 142) administered intratracheal Escherichia coli challenge, compared to placebo treatment, heparin at 100, 500, or 2500 units/kg were associated with dose dependent increases in the hazard ratios of death (hazard ratio [ 95% confidence interval]: 1.08 [0.66, 1.76]; 1.34 [0.80, 2.24]; 3.02 [1.49, 6.10], respectively) (p = .001 for the dose effect). Compared to normal saline challenge, E. coli without heparin (i.e., with placebo) increased the activated partial thromboplastin time (p = .002) close to the therapeutic range. While heparin at 100 and 500 units/kg with E. coli further increased activated partial thromboplastin time (p < .0001 vs. placebo) within or above the therapeutic range, respectively, these did not decrease inflammatory cytokines or lung injury. In metaregression analysis of published preclinical studies, heparin improved survival with lipopolysaccharide (n = 23, p < .0001) or surgically induced infection (n = 14, p < .0001) but not monobacterial (n = 7, p = .29) challenges. Conclusion: Coagulopathy with sepsis or other variables, such as type of infectious source, may influence the efficacy of heparin therapy for sepsis. (Crit Care Med 2011; 39:1104-1112) C1 [Li, Yan; Sun, Jun-Feng; Cui, Xizhong; Danner, Robert L.; Li, Xuemei; Su, Jun-Wu; Fitz, Yvonne; Eichacker, Peter Q.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. [Mani, Haresh] Penn State Hershey Med Ctr, Dept Pathol, Hershey, PA USA. [Li, Xuemei] Peking Union Med Coll, Dept Nephrol, Beijing 100021, Peoples R China. [Su, Jun-Wu] Capital Med Univ, Anzhen Hosp, Surg Dept Pediat Cardiol, Beijing, Peoples R China. RP Eichacker, PQ (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov FU National Institutes of Health, Clinical Center FX Supported, in part, by the Intramural Program of the National Institutes of Health, Clinical Center. NR 54 TC 7 Z9 8 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2011 VL 39 IS 5 BP 1104 EP 1112 DI 10.1097/CCM.0b013e31820eb718 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 752CX UT WOS:000289667000025 PM 21317646 ER PT J AU Wind, JJ Bakhtian, KD Sweet, JA Mehta, GU Thawani, JP Asthagiri, AR Oldfield, EH Lonser, RR AF Wind, Joshua J. Bakhtian, Kamran D. Sweet, Jennifer A. Mehta, Gautam U. Thawani, Jayesh P. Asthagiri, Ashok R. Oldfield, Edward H. Lonser, Russell R. TI Long-term outcome after resection of brainstem hemangioblastomas in von Hippel-Lindau disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE brainstem; hemangioblastoma; outcome; surgical treatment; von Hippel-Lindau disease ID CENTRAL-NERVOUS-SYSTEM; STEREOTACTIC RADIOSURGERY; SURGICAL-MANAGEMENT; MEDULLA-OBLONGATA; NATURAL-HISTORY; SPINAL-CORD AB Object. Brainstem hemangioblastomas are frequently encountered in patients with von Hippel-Lindau (VHL) disease. These tumors can cause significant morbidity, and their optimal management has not been defined. To better define the outcome and management of these tumors, the authors analyzed the long-term results in patients who underwent resection of brainstem hemangioblastomas. Methods. Consecutive patients with VHL disease who underwent resection of brainstem hemangioblastomas with a follow-up of 12 months or more were included in this study. Serial functional assessments, radiographic examinations, and operative records were analyzed. Results. Forty-four patients (17 male and 27 female) underwent 51 operations for resection of 71 brainstem hemangioblastomas. The most common presenting symptoms were headache, swallowing difficulties, singultus, gait difficulties, and sensory abnormalities. The mean follow-up was 5.9 +/- 5.0 years (range 1.0-20.8 years). Immediately after 34 operations (66.7%), the patients remained at their preoperative functional status; they improved after 8 operations (15.7%) and worsened after 9 operations (17.6%) as measured by the McCormick scale. Eight (88.9%) of the 9 patients who were worse immediately after resection returned to their preoperative status within 6 months. Two patients experienced functional decline during long-term follow-up (beginning at 2.5 and 5 years postoperatively) caused by extensive VHL disease associated CNS disease. Conclusions. Generally, resection of symptomatic brainstem hemangioblastomas is a safe and effective management strategy in patients with VHL disease. Most patients maintain their preoperative functional status, although long-term decline in functional status may occur due to VHL disease associated progression. (DOI: 10.3171/2010.9.JNS10839) C1 [Wind, Joshua J.; Bakhtian, Kamran D.; Sweet, Jennifer A.; Mehta, Gautam U.; Thawani, Jayesh P.; Asthagiri, Ashok R.; Oldfield, Edward H.; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Wind, Joshua J.; Sweet, Jennifer A.] George Washington Univ, Med Ctr, Dept Neurol Surg, Washington, DC 20037 USA. [Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 3D20, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Wind, Joshua/D-5480-2013; OI Wind, Joshua/0000-0003-3443-8476; Mehta, Gautam/0000-0002-8009-6430 FU National Institute of Neurological Disorders and Stroke at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. NR 30 TC 15 Z9 16 U1 0 U2 7 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2011 VL 114 IS 5 BP 1312 EP 1318 DI 10.3171/2010.9.JNS10839 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 755FW UT WOS:000289913900018 PM 20932100 ER PT J AU Niu, LL Xie, ZS Cai, TX Wu, P Xue, P Chen, XL Wu, ZY Ito, Y Li, FM Yang, FQ AF Niu, Lili Xie, Zhensheng Cai, Tanxi Wu, Peng Xue, Peng Chen, Xiulan Wu, Zhiyong Ito, Yoichiro Li, Famei Yang, Fuquan TI Preparative isolation of alkaloids from Corydalis bungeana Turcz. by high-speed counter-current chromatography using stepwise elution SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Alkaloids; Corydalis bungeana Turcz.; ESI-MS; High-speed countercurrent chromatography ID ISOQUINOLINE ALKALOIDS; MASS-SPECTROMETRY; INCISA PERS; PURIFICATION; SEPARATION; BASES AB High-speed counter-current chromatography (HSCCC) was successfully applied for the preparative separation and purification of alkaloids from Corydalis bungeana Turcz. (Kudiding in Chinese) for the first time. After the measurement of partition coefficient of seven target alkaloids in the nine two-phase solvent systems composed of CHCl(3)-MeOH-(0.1 M; 0.2 M; 0.3 M) HCl (4: 1.5: 2; 4: 2: 2; 4: 3: 2, v/v), CHCl(3)-MeOH- 0.2M HCl (4: 2: 2, v/v) and CHCl(3)-MeOH-0.3M HCl (4: 3: 2, v/v) were finally selected for the HSCCC separation using the first upper phase as the stationary phase and the stepwise elution of the two lower mobile phases. Consequently, sanguinarine (10 mg), corynoline (25 mg), protopine (20 mg), corynoloxine (18 mg), and 12-hydroxycorynoline (8 mg) were obtained from 200 mg of crude alkaloid extracts with purities of 94-99% as determined by HPLC. Their chemical structures were characterized on the basis of (1)H-NMR, (13)C-NMR, and LC-ESI-Q-TOF-MS/MS analyses. C1 [Niu, Lili; Xie, Zhensheng; Cai, Tanxi; Wu, Peng; Xue, Peng; Chen, Xiulan; Yang, Fuquan] Chinese Acad Sci, Inst Biophys, Lab Prote, Beijing 100101, Peoples R China. [Niu, Lili; Li, Famei] Shenyang Pharmaceut Univ, Sch Pharm, Shenyang, Peoples R China. [Wu, Zhiyong] Northeastern Univ, Res Ctr Analyt Sci, Shenyang, Peoples R China. [Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD USA. RP Yang, FQ (reprint author), Chinese Acad Sci, Inst Biophys, Lab Prote, 15 Datun Rd, Beijing 100101, Peoples R China. EM lifamei@syphu.edu.cn; fqyang@sun5.ibp.ac.cn FU National Basic Research Program of China [2010CB833703]; National Natural Science Foundation of China [90919047] FX This research was supported by the National Basic Research Program of China (973) (grant no. 2010CB833703) and the National Natural Science Foundation of China (grant no. 90919047). NR 26 TC 20 Z9 21 U1 6 U2 34 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD MAY PY 2011 VL 34 IS 9 BP 987 EP 994 DI 10.1002/jssc.201000785 PG 8 WC Chemistry, Analytical SC Chemistry GA 764MV UT WOS:000290634600003 PM 21387560 ER PT J AU Liu, W Turkbey, B Senegas, J Remmele, S Xu, S Kruecker, J Bernardo, M Wood, BJ Pinto, PA Choyke, PL AF Liu, Wei Turkbey, Baris Senegas, Julien Remmele, Stefanie Xu, Sheng Kruecker, Jochen Bernardo, Marcelino Wood, Bradford J. Pinto, Peter A. Choyke, Peter L. TI Accelerated T-2 Mapping for Characterization of Prostate Cancer SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE prostate cancer; k-space undersampling; T-2 mapping ID SPIN-ECHO SEQUENCE; PATHOLOGICAL PROSTATE; CITRATE CONCENTRATION; QUANTITATIVE T2; IN-VIVO; FUSION; TIME; MRI; DIFFUSION; BIOPSIES AB Prostate T-2 mapping was performed in 34 consecutive patients using an accelerated multiecho spin-echo sequence with 4-fold k-space undersampling leading to a net acceleration factor of 3.3 on a 3T scanner. The mean T-2 values from the accelerated and conventional, unaccelerated sequences demonstrated a very high correlation (r = 0.99). Different prostate segments demonstrated similarly good interscan reproducibility (p = not significant) with slightly larger difference at base: 2.0% +/- 1.6% for left base and 2.1% +/- 1.1% for right base. In patients with subsequent targeted biopsy, T-2 values of histologically proven malignant tumor areas were significantly lower than the suspicious looking but nonmalignant lesions (p < 0.05) and normal areas (p < 0.001): 100 +/- 10 ms for malignant tumors, 114 +/- 23 ms for suspicious lesions and 149 +/- 32 ms for normal tissues. The proposed method can provide an effective approach for accelerated T-2 quantification for prostate patients. Magn Reson Med 65:1400-1406, 2011. (c) 2011 Wiley-Liss, Inc. C1 [Liu, Wei; Xu, Sheng; Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY USA. [Senegas, Julien; Remmele, Stefanie] Philips Res Europe, Hamburg, Germany. [Bernardo, Marcelino] SAIC Frederick Inc, Mol Imaging Program, NCI, Bethesda, MD USA. [Wood, Bradford J.; Pinto, Peter A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Liu, W (reprint author), Natl Intrepid Ctr Excellence, Natl Capital Neuroimaging Consortium, 8901 Wisconsin Ave,Bldg 51, Bethesda, MD 20889 USA. EM wei.liu2.ctr@us.army.mil FU Intramural NIH HHS [Z01 BC010655-03, ZIA BC010655-06, Z01 BC010655-04, ZIA BC010655-05] NR 20 TC 21 Z9 21 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAY PY 2011 VL 65 IS 5 BP 1400 EP 1406 DI 10.1002/mrm.22874 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753GR UT WOS:000289760800025 PM 21394778 ER PT J AU Yeo, L Romero, R Jodicke, C Kim, SK Gonzalez, JM Ogge, G Lee, W Kusanovic, JP Vaisbuch, E Hassan, S AF Yeo, L. Romero, R. Jodicke, C. Kim, S. K. Gonzalez, J. M. Ogge, G. Lee, W. Kusanovic, J. P. Vaisbuch, E. Hassan, S. TI Simple targeted arterial rendering (STAR) technique: a novel and simple method to visualize the fetal cardiac outflow tracts SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE aorta; congenital heart disease; fetal echocardiography; OmniView; prenatal diagnosis; pulmonary artery; STIC; ultrasound; ventricular septum ID CONGENITAL HEART-DISEASE; SPATIOTEMPORAL IMAGE CORRELATION; 4-CHAMBER VIEW; 4-DIMENSIONAL ULTRASONOGRAPHY; 3-DIMENSIONAL ULTRASOUND; INTERVENTRICULAR SEPTUM; AORTIC ROOT; LOW-RISK; ANOMALIES; ECHOCARDIOGRAPHY AB Objective To describe a novel and simple technique-simple targeted arterial rendering (STAR) - to visualize the fetal cardiac outflow tracts from dataset volumes obtained with spatiotemporal image correlation (STIC) and applying a new display technology (OmniView). Methods We developed a technique to image the outflow tracts by drawing three dissecting lines through the four-chamber view of the heart contained in a STIC volume dataset. Each line generated the following plane: (a) Line 1: ventricular septum en face with both great vessels (pulmonary artery anterior to the aorta); (b) Line 2: pulmonary artery with continuation into the longitudinal view of the ductal arch; and (c) Line 3: long-axis view of the aorta arising from the left ventricle. The pattern formed by all three lines intersecting approximately through the crux of the heart resembles a star. The technique was then tested in 50 normal fetal hearts at 15.3-40.4 weeks' gestation. To determine whether the technique could identify planes that departed from the normal images, we tested the technique in four cases with proven congenital heart defects (ventricular septal defect (VSD), transposition of great vessels, tetralogy of Fallot and pulmonary atresia with intact ventricular septum). Results The STAR technique was able to generate the intended planes in all 50 normal cases. In the abnormal cases, the STAR technique allowed identification of the VSD, demonstrated great vessel anomalies and displayed views that deviated from what was expected from the examination of normal hearts. Conclusions This novel and simple technique can be used to visualize the outflow tracts and ventricular septum en face in normal fetal hearts. Inability to obtain expected views or the appearance of abnormal views in the generated planes should raise the index of suspicion for congenital heart disease involving the great vessels and/or the ventricular septum. The STAR technique may simplify examination of the fetal heart and could reduce operator dependency. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd. C1 [Yeo, L.] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Yeo, L.; Romero, R.; Jodicke, C.; Kim, S. K.; Gonzalez, J. M.; Ogge, G.; Lee, W.; Kusanovic, J. P.; Vaisbuch, E.; Hassan, S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Yeo, L.; Romero, R.; Jodicke, C.; Gonzalez, J. M.; Lee, W.; Kusanovic, J. P.; Vaisbuch, E.; Hassan, S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Lee, W.] William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48072 USA. RP Yeo, L (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM lyeo@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 47 TC 12 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD MAY PY 2011 VL 37 IS 5 BP 549 EP 556 DI 10.1002/uog.8841 PG 8 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 762MO UT WOS:000290483300008 PM 20878672 ER PT J AU Butte, NF Ellis, KJ Shypailo, RJ Wong, WW Brandt, ML Sherman, V Hall, KD Chow, CC Zakeri, IF AF Butte, N. F. Ellis, K. J. Shypailo, R. J. Wong, W. W. Brandt, M. L. Sherman, V. Hall, K. D. Chow, C. C. Zakeri, I. F. TI Modeling Energetic Adaptations in Extremely Obese Adolescents in Response to Roux-en-Y Gastric Bypass Surgery SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Meeting Abstract CT 9th International Symposium on In Vivo Body Composition Studies CY MAY, 2011 CL Hangzhou, PEOPLES R CHINA C1 [Butte, N. F.; Ellis, K. J.; Shypailo, R. J.; Wong, W. W.] Baylor Coll Med, USDA ARS Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA. [Brandt, M. L.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Sherman, V.] Methodist Hosp, Houston, TX 77030 USA. [Hall, K. D.; Chow, C. C.] NIH NIDDK, Bethesda, MD USA. [Zakeri, I. F.] Drexel Univ, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. RI Chow, Carson/A-7970-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2011 VL 35 SU 2 BP S5 EP S5 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 836UZ UT WOS:000296141100005 ER PT J AU Ayriss, J Reisfeld, R Kuan, CT Keir, S Pastan, I Bigner, D AF Ayriss, Joanne Reisfeld, Ralph Kuan, Chien-Tsun Keir, Steve Pastan, Ira Bigner, Darell TI MEL-14 AND 9.2.27 IMMUNOTOXINS: PROMISING THERAPEUTICS FOR PEDIATRIC GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 19-20, 2011 CL New Orleans, LA C1 [Ayriss, Joanne; Kuan, Chien-Tsun; Keir, Steve; Bigner, Darell] Duke Univ, Durham, NC USA. [Reisfeld, Ralph] Scripps Res Inst, La Jolla, CA 92037 USA. [Pastan, Ira] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 SU 1 MA 0029 BP I6 EP I7 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 836VE UT WOS:000296141800024 ER PT J AU Chandramohan, V Kaneko, MK Kato, Y Pegram, CN Keir, ST Pastan, IH Kuan, CT Bigner, DD AF Chandramohan, Vidyalakshmi Kaneko, Mika Kato Kato, Yukinari Pegram, Charles N. Keir, Stephen T. Pastan, Ira H. Kuan, Chien-Tsun Bigner, Darell D. TI CONSTRUCTION OF A NOVEL ANTIPODOPLANIN (NZ-1) IMMUNOTOXIN FOR BRAIN TUMOR THERAPY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT Pediatric Neuro-Oncology Basic and Translational Research Conference CY MAY 19-20, 2011 CL New Orleans, LA C1 [Chandramohan, Vidyalakshmi; Kaneko, Mika Kato; Kato, Yukinari; Pegram, Charles N.; Keir, Stephen T.; Kuan, Chien-Tsun; Bigner, Darell D.] Duke Univ, Med Ctr, Pediat Brain Tumor Fdn Inst, Durham, NC USA. [Pastan, Ira H.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 SU 1 MA 0098 BP I26 EP I26 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 836VE UT WOS:000296141800091 ER PT J AU Rosenblum, LT Kosaka, N Mitsunaga, M Choyke, PL Kobayashi, H AF Rosenblum, Lauren T. Kosaka, Nobuyuki Mitsunaga, Makoto Choyke, Peter L. Kobayashi, Hisataka TI Optimizing quantitative in vivo fluorescence imaging with near-infrared quantum dots SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE fluorescence imaging; in vivo imaging; quantum dot; quantitative imaging; nanotechnology ID MULTICOLOR; CANCER AB Quantum dots (QDs) are fluorescent nanoparticles with broad excitation and narrow, wavelength-tunable emission spectra. They are used extensively for in vitro fluorescence imaging studies and more recently for in vivo small animal and pre-clinical studies. To date there has been little concern about the selection of QD size (and thus emission wavelength peak) and excitation wavelengths, as they have little relevance to the results of in vitro studies. In vivo imaging, however, poses additional constraints, such as the scattering and absorption by tissue, which may influence the signal intensity at the body surface. Here, we demonstrate that longer-wavelength excitation and emission yield less quantization error in measured relative fluorescence intensity, using three near-infrared QDs (QD655, QD705 and QD800) applied to in vivo lymphatic imaging, and a range of excitation wavelengths from the blue to the red. Statistically significant differences in quantization error were observed between nearly all pairs of excitation wavelengths (445-490, 503-555, 575-605, 615-665 and 671-705 nm). Similarly, quantization error decreased with longer emission wavelengths (655, 705 and 800 nm). Light absorbance and scattering were demonstrated to be more potent factors than absorbance efficiency of QDs in producing quantization error in the measured fluorescence intensity. As a result, while wavelengths can be adjusted for qualitative experiments, the longest possible wavelengths should be used if quantification is desired during QD imaging experiments. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Rosenblum, Lauren T.; Kosaka, Nobuyuki; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 15 TC 8 Z9 8 U1 3 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD MAY-JUN PY 2011 VL 6 IS 3 BP 148 EP 152 DI 10.1002/cmmi.409 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 825PW UT WOS:000295294500005 PM 20936710 ER PT J AU Hersperger, AR Migueles, SA Betts, MR Connors, M AF Hersperger, Adam R. Migueles, Stephen A. Betts, Michael R. Connors, Mark TI Qualitative features of the HIV-specific CD8(+) T-cell response associated with immunologic control SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE CD8(+) T cells; cytotoxicity; elite controllers; long-term nonprogressors; perforin ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL REPLICATION CAPACITY; LONG-TERM NONPROGRESSORS; PERFORIN EXPRESSION; CYTOTOXIC GRANULES; ELITE SUPPRESSORS; IMMUNE CONTROL; UP-REGULATION; INFECTION; MEMORY AB Purpose of review Over the past 2 years, a clearer picture has emerged regarding the properties of HIV-specific CD8(+) T cells associated with immunologic control of HIV replication. These properties represent a potential mechanism by which rare patients might control HIV replication in the absence of antiretroviral therapy. This review addresses the background and recent findings that have lead to our current understanding of these mechanism(s). Recent findings Patients with immunologic control of HIV are not distinguished by targeted specificities, or greater numbers or breadth of their HIV-specific CD8(+) T-cell response. For this reason, recent work has focused greater attention on qualitative features of this response. The qualitative features most closely associated with immunologic control of HIV are related to the granule-exocytosis-mediated elimination of HIV-infected CD4(+) T cells. The ability of HIV-specific CD8(+) T cells to increase their contents of proteins known to mediate cytotoxicity, such as granzyme B and perforin, appears to be a critical means by which HIV-specific cytotoxic capacity is regulated. Summary Investigation from multiple groups has now focused upon HIV-specific CD8(+) T-cell granule-exocytosis-mediated cytotoxicity as a correlate of immunologic control of HIV. In the near future, a more detailed understanding of the qualities associated with immunologic control may provide critical insights regarding the necessary features of a response that should be stimulated by immunotherapies or T-cell-based vaccines. C1 [Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Hersperger, Adam R.; Betts, Michael R.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-09,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM mconnors@nih.gov FU NIH, National Institute of Allergy and Infectious Diseases; NIH [R01 AI076066] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. The work of A.R.H. and M.R.B. is funded through NIH R01 AI076066. NR 58 TC 52 Z9 53 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2011 VL 6 IS 3 BP 169 EP 173 DI 10.1097/COH.0b013e3283454c39 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828OZ UT WOS:000295513000005 PM 21399496 ER PT J AU Liu, YN Norton, JT Witschi, MA Xu, Q Lou, GH Wang, C Appella, DH Chen, Z Huang, S AF Liu, Yanning Norton, John T. Witschi, Mark A. Xu, Qun Lou, Guohua Wang, Chen Appella, Daniel H. Chen, Zhi Huang, Sui TI Methoxyethylamino-numonafide Is an Efficacious and Minimally Toxic Amonafide Derivative in Murine Models of Human Cancer SO NEOPLASIA LA English DT Article ID ILLUMINA MICROARRAY; METALLOTHIONEIN 1G; ANTICANCER AGENTS; NAPHTHALIMIDE; TRANSFORMATION; COMBINATION; CARCINOMA; LEUKEMIA AB Amonafide is a DNA intercalator in clinical development for the treatment of cancer. The drug has a 5-position amine that is variably acetylated to form a toxic metabolite in humans, increasing adverse effects and complicating the dosing of amonafide. Numonafides, 6-amino derivatives of amonafide that avoid the toxic acetylation, also show in vitro anticancer activity, as we have previously described. Here, we report the in vitro and in vivo activities of two numonafides, 6-methoxyethylamino-numonafide (MEAN) and 6-amino-numonafide (AN) with comparisons to amonafide. The in vitro potencies and cellular anticancer mechanisms are similar for the two numonafides and amonafide. Results from several mouse models of human cancer demonstrate that AN and MEAN require slightly higher doses than amonafide for equal efficacy in short-term dosing models, but the same dose of all three compounds in long-term dosing models are equally efficacious. MEAN is tolerated much better than amonafide and AN at equally efficacious doses based on weight change, activity, stool consistency, and dose tolerance with survival as the end point. The studies presented here demonstrate that MEAN is much less toxic than amonafide or AN in mouse models of human liver and gastric cancers while being equally efficacious in vivo and inhibiting cancer cells through similar mechanisms. These findings demonstrate that numonafides can be less toxic than amonafide and support further preclinical development and novel anticancer agents or as replacements or amonafide. C1 [Norton, John T.; Wang, Chen; Huang, Sui] Northwestern Univ, Sch Med, Chicago, IL 60611 USA. [Liu, Yanning; Lou, Guohua; Chen, Zhi] Zhejiang Univ, State Key Lab Infect Dis Diag & Treatment, Affiliated Hosp 1, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China. [Witschi, Mark A.; Xu, Qun; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Huang, S (reprint author), Northwestern Univ, Sch Med, 303E Chicago Ave,Ward 11-240, Chicago, IL 60611 USA. EM chenzhi@zju.edu.cn; s-huang2@northwestern.edu FU Robert H. Lurie Comprehensive Cancer Center; National Institutes of Health [R01 GM078555] FX The authors thank the partial funding from the Robert H. Lurie Comprehensive Cancer Center and grant to S.H. from the National Institutes of Health (R01 GM078555). NR 15 TC 9 Z9 10 U1 0 U2 6 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY PY 2011 VL 13 IS 5 BP 453 EP 460 DI 10.1593/neo.101738 PG 8 WC Oncology SC Oncology GA 827SO UT WOS:000295448600007 PM 21532886 ER PT J AU Ouyang, XS Zhang, RH Yang, JJ Li, QS Qin, LH Zhu, C Liu, JG Ning, H Shin, MS Gupta, M Qi, CF He, JC Lira, SA Morse, HC Ozato, K Mayer, L Xiong, HB AF Ouyang, Xinshou Zhang, Ruihua Yang, Jianjun Li, Qingshan Qin, Lihui Zhu, Chen Liu, Jianguo Ning, Huan Shin, Min Sun Gupta, Monica Qi, Chen-Feng He, John Cijiang Lira, Sergio A. Morse, Herbert C., III Ozato, Keiko Mayer, Lloyd Xiong, Huabao TI Transcription factor IRF8 directs a silencing programme for T(H)17 cell differentiation SO NATURE COMMUNICATIONS LA English DT Article ID SEQUENCE-BINDING-PROTEIN; ROR-GAMMA-T; CHRONIC INTESTINAL INFLAMMATION; TH17 CELLS; HELPER-CELLS; TGF-BETA; GENE-EXPRESSION; CUTTING EDGE; MACROPHAGES; CYTOKINE AB T(H)17 cells are recognized as a unique subset of T helper cells that have critical roles in the pathogenesis of autoimmunity and tissue inflammation. Although ROR gamma t is necessary for the generation of T(H)17 cells, the molecular mechanisms underlying the functional diversity of T(H)17 cells are not fully understood. Here we show that a member of interferon regulatory factor (IRF) family of transcription factors, IRF8, has a critical role in silencing T(H)17-cell differentiation. Mice with a conventional knockout, as well as a T cell-specific deletion, of the Irf8 gene exhibited more efficient T(H)17 cells. Indeed, studies of an experimental model of colitis showed that IRF8 deficiency resulted in more severe inflammation with an enhanced T(H)17 phenotype. IRF8 was induced steadily and inhibited T(H)17-cell differentiation during T(H)17 lineage commitment at least in part through its physical interaction with ROR gamma t. These findings define IRF8 as a novel intrinsic transcriptional inhibitor of T(H)17-cell differentiation. C1 [Ouyang, Xinshou; Zhang, Ruihua; Yang, Jianjun; Li, Qingshan; He, John Cijiang; Lira, Sergio A.; Mayer, Lloyd; Xiong, Huabao] Mt Sinai Sch Med, Dept Med, Inst Immunol, New York, NY 10029 USA. [Qin, Lihui] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. [Zhu, Chen] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Liu, Jianguo; Ning, Huan] St Louis Univ, Sch Med, Div Immunobiol, St Louis, MO 63104 USA. [Shin, Min Sun; Qi, Chen-Feng; Morse, Herbert C., III] NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. [Gupta, Monica; Ozato, Keiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Xiong, HB (reprint author), Mt Sinai Sch Med, Dept Med, Inst Immunol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM huabao.xiong@mssm.edu OI Morse, Herbert/0000-0002-9331-3705 FU NIH [P01 DK072201]; Crohn's and Colitis Foundation of America; Eli and Edythe L. Broad Foundation; NIH, National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank C. Dong, A. Yoshimura, T. Taniguchi, O. Sakaguchi, M. Ono, H. Wang, J. Yang and G. Lu for providing reagents, technical supports and helpful suggestions. We are grateful to J. Unkeless, K. Honda and J. Blander for critical reading of the manuscript. This work was supported by the NIH P01 DK072201, a Crohn's and Colitis Foundation of America grant, a grant from the Eli and Edythe L. Broad Foundation, and by the intramural research programme of the NIH, National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 50 TC 45 Z9 48 U1 0 U2 2 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 MAY PY 2011 VL 2 AR 314 DI 10.1038/ncomms1311 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 819CI UT WOS:000294802600019 PM 21587231 ER PT J AU Weinstein, AM Gorelick, DA AF Weinstein, A. M. Gorelick, David A. TI Pharmacological Treatment of Cannabis Dependence SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Cannabis; withdrawal; dependence; pharmacotherapy; treatment ID DEFICIT HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED TRIAL; PLACEBO-CONTROLLED TRIAL; HEAVY MARIJUANA SMOKERS; FREELY-MOVING RATS; DOUBLE-BLIND; WITHDRAWAL SYNDROME; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; OPEN-LABEL AB Cannabis is the most frequently used illegal psychoactive substance in the world. There is a significant increase in the number of treatment admissions for cannabis use disorders in the past few years, and the majority of cannabis-dependent individuals who enter treatment have difficulty in achieving and maintaining abstinence. Thus, there is increased need for medications that can be used to treat this population. So far, no medication has been shown broadly and consistently effective; none has been approved by any national regulatory authority. Medications studied have included those that alleviate symptoms of cannabis withdrawal (e.g., dysphoric mood, irritability), those that directly affect endogenous cannabinoid receptor function, and those that have shown efficacy in treatment of other drugs of abuse or psychiatric conditions. Buspirone is the only medication to date that has shown efficacy for cannabis dependence in a controlled clinical trial. Results from controlled human laboratory studies and small open-label clinical trials suggest that dronabinol, the COMT inhibitor entacapone, and lithium may warrant further study. Recent pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes, and nicotinic alpha7 receptor antagonists such as methyllycaconitine (MLA). Controlled clinical trials are needed to evaluate the clinical efficacy of these medications and to validate the laboratory models being used to study candidate medications. C1 [Weinstein, A. M.] Hadassah Med Org, Dept Med Biophys & Nucl Med, IL-91120 Jerusalem, Israel. [Gorelick, David A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Weinstein, AM (reprint author), Hadassah Med Org, Dept Med Biophys & Nucl Med, IL-91120 Jerusalem, Israel. EM avivweinstein@yahoo.com FU Charles E. Smith Foundation; US National Institute on Drug Abuse, National Institutes of Health FX Dr. Weinstein is supported by the National Institute for Psychobiology in Israel that is funded by the Charles E. Smith Foundation. Dr. Gorelick is supported by the US National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health. NR 86 TC 32 Z9 32 U1 3 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 14 BP 1351 EP 1358 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814AU UT WOS:000294415500006 PM 21524266 ER PT J AU Jacques, SM Qureshi, F Kim, CJ Lee, JH Giorgadze, T Mittal, P Hassan, SS Romero, R AF Jacques, Suzanne M. Qureshi, Faisal Kim, Chong Jai Lee, Joon Ho Giorgadze, Tamar Mittal, Pooja Hassan, Sonia S. Romero, Roberto TI Eosinophilic/T-cell Chorionic Vasculitis: A Clinicopathologic and Immunohistochemical Study of 51 Cases SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE chorionic vasculitis; eosinophils; fetal membranes; placenta; T lymphocytes; villitis of unknown etiology ID CORNEAL ALLOGRAFT-REJECTION; UNKNOWN ETIOLOGY; CHRONIC CHORIOAMNIONITIS; CLINICAL-SIGNIFICANCE; MICROBIAL INVASION; CHRONIC DECIDUITIS; AMNIOTIC CAVITY; CEREBRAL-PALSY; PRETERM LABOR; TERM INFANTS AB We report 51 placentas diagnosed with eosinophilic/T-cell chorionic vasculitis (E/TCV), an unusual form of chorionic vasculitis characterized by an infiltrate composed predominantly of CD3+ T cells and eosinophils. The placentas were all 3rd trimester, with 48 (94.1%) being term. Forty-seven (92.2%) were singleton placentas, and the remaining 4 were twins. The E/TCV was limited to 1 chorionic surface vessel in 40 (78.4%) and involved 50% or less of the vessel circumference in 30 (58.8%) placentas. The inflammation faced the intervillous space in 12 (23.5%) and the amniotic cavity in 8 (15.7%) and had no distinct predominant direction in the remaining 31 (60.8%) placentas. Twelve (25.5%) placentas showed mural thrombi or intramural fibrin in association with the E/TCV. One hundred six term singleton placentas were selected as the control group, and the 47 singleton placentas with E/TCV made up the study group for comparison of demographic and histopathologic features. Villitis of unknown etiology was identified more frequently in study group placentas (20 [42.6%]) compared with control group placentas (14 [13.2%]) (P < 0.001). Vascular changes of fetal vascular thrombo-occlusive disease were identified away from the E/TCV more frequently in study group placentas (8 [17.0%]) compared with control group placentas (4 [3.8%]) (P = 0.008). There were no significant differences in the frequencies of other placental lesions studied, including acute inflammatory lesions and lesions related to maternal underperfusion. There were no significant differences in maternal age, race, parity, birth weight, allergy history, blood type, or medication use. C1 [Jacques, Suzanne M.; Qureshi, Faisal; Kim, Chong Jai; Giorgadze, Tamar] Detroit Med Ctr, Dept Pathol, Detroit, MI 48201 USA. [Jacques, Suzanne M.; Qureshi, Faisal; Kim, Chong Jai; Giorgadze, Tamar] Wayne State Univ, Sch Med, Hutzel Womens Hosp, Detroit, MI 48201 USA. [Kim, Chong Jai; Lee, Joon Ho; Mittal, Pooja; Hassan, Sonia S.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. [Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Jacques, SM (reprint author), Detroit Med Ctr, Dept Pathol, 3990 John R St, Detroit, MI 48201 USA. EM sjacques@dmc.org NR 35 TC 11 Z9 11 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 EI 1615-5742 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD MAY PY 2011 VL 14 IS 3 BP 198 EP 205 DI 10.2350/10-07-0867-OA.1 PG 8 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 814LE UT WOS:000294453700005 PM 21050080 ER PT J AU Thomas, AC Nouls, JC Driehuys, B Voltz, JW Fubara, B Foley, J Bradbury, JA Zeldin, DC AF Thomas, Abe C. Nouls, John C. Driehuys, Bastiaan Voltz, James W. Fubara, Boma Foley, Julie Bradbury, J. Alyce Zeldin, Darryl C. TI Ventilation Defects Observed with Hyperpolarized He-3 Magnetic Resonance Imaging in a Mouse Model of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE ventilation defect; lipopolysaccharide; lung inflammation; magnetic resonance imaging; cytokines ID REGIONAL VENTILATION; INDUCED INFLAMMATION; ANIMAL-MODELS; XE-129 MRI; GAS; CHALLENGE; ASTHMA; MICE AB Regions of diminished ventilation are often evident during functional pulmonary imaging studies, including hyperpolarized gas magnetic resonance imaging (MRI), positron emission tomography, and computed tomography (CT). The objective of this study was to characterize the hypointense regions observed via He-3 MRI in a murine model of acute lung injury. LPS at doses ranging from 1550 mu g was intratracheally administered to C57BL/6 mice under anesthesia. Four hours after exposure to either LPS or saline vehicle, mice were imaged via hyperpolarized He-3 MRI. All images were evaluated to identify regions of hypointense signals. Lungs were then characterized by conventional histology, or used to obtain tissue samples from regions of normal and hypointense He-3 signals and analyzed for cytokine content. The characterization of He-3 MRI images identified three distinct types of hypointense patterns: persistent defects, atelectatic defects, and dorsal lucencies. Persistent defects were associated with the administration of LPS. The number of persistent defects depended on the dose of LPS, with a significant increase in mean number of defects in 30-50-mu g LPS-dosed mice versus saline-treated control mice. Atelectatic defects predominated in LPS-dosed mice under conditions of low-volume ventilation, and could be reversed with deep inspiration. Dorsal lucencies were present in nearly all mice studied, regardless of the experimental conditions, including control animals that did not receive LPS. A comparison of He-3 MRI with histopathology did not identify tissue abnormalities in regions of low He-3 signal, with the exception of a single region of atelectasis in one mouse. Furthermore, no statistically significant differences were evident in concentrations of IL-1 beta, IL-6, macrophage inflammatory protein (MIP)-1 alpha MIP-2, chemokine (C-X-C motif) ligand 1 (KC), TNF alpha, and monocyte chemotactic protein (MCP)-1 between hypointense and normally ventilated lung regions in LPS-dosed mice. Thus, this study defines the anatomic, functional, and biochemical characteristics of ventilation defects associated with the administration of LPS in a murine model of acute lung injury. C1 [Thomas, Abe C.; Voltz, James W.; Foley, Julie; Bradbury, J. Alyce; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Thomas, Abe C.; Nouls, John C.; Driehuys, Bastiaan; Fubara, Boma] Duke Univ, Dept Radiol, Ctr Vivo Microscopy, Durham, NC 27710 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, 111 Alexander Dr,Bldg 101,Room A222, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU National Institutes of Health [RO1 ES11961, RO1 ES16347, P41 RR005959, R21 HL87094]; National Institute of Environmental Health Sciences, National Institutes of Health [ZO1 ES101885] FX This work was supported by National Institutes of Health grants RO1 ES11961, RO1 ES16347, P41 RR005959, and R21 HL87094, and by grant ZO1 ES101885 from the Intramural Research Program, National Institute of Environmental Health Sciences, National Institutes of Health (D.C.Z.). NR 24 TC 6 Z9 7 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2011 VL 44 IS 5 BP 648 EP 654 DI 10.1165/rcmb.2009-0287OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 808AO UT WOS:000293945500009 PM 20595465 ER PT J AU Agochukwu, NB Pineda-Alvarez, DE Keaton, AA Warren-Mora, N Raam, MS Kamat, A Chandrasekharappa, SC Solomon, BD AF Agochukwu, Nneamaka B. Pineda-Alvarez, Daniel E. Keaton, Amelia A. Warren-Mora, Nicole Raam, Manu S. Kamat, Aparna Chandrasekharappa, Settara C. Solomon, Benjamin D. TI Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE VACTERL; VACTERL association; FOXF1; FOX gene cluster; VATER; VATER association ID TRACHEOESOPHAGEAL FISTULA; ESOPHAGEAL ATRESIA; VATER ASSOCIATION; MUTATION; ANOMALIES AB VACTERL association, a relatively common condition with an incidence of approximately 1 in 20,000-35,000 births, is a non-randomassociation of birth defects that includes vertebral defects (V), anal atresia (A), cardiac defects (C), tracheo-esophageal fistula (TE), renal anomalies (R) and limb malformations (L). Although the etiology is unknown in the majority of patients, there is evidence that it is causally heterogeneous. Several studies have shown evidence for inheritance in VACTERL, implying a role for genetic loci. Recently, patients with component features of VACTERL and a lethal developmental pulmonary disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), were found to harbor deletions or mutations affecting FOXF1 and the FOX gene cluster on chromosome 16q24. We investigated this gene through direct sequencing and high-density SNP microarray in 12 patients with VACTERL association but without ACD/MPV. Our mutational analysis of FOXF1 showed normal sequences and no genomic imbalances affecting the FOX gene cluster on chromosome 16q24 in the studied patients. Possible explanations for these results include the etiologic and clinical heterogeneity of VACTERL association, the possibility that mutations affecting this gene may occur only in more severely affected individuals, and insufficient study sample size. Published by Elsevier Masson SAS. C1 [Agochukwu, Nneamaka B.; Pineda-Alvarez, Daniel E.; Keaton, Amelia A.; Warren-Mora, Nicole; Raam, Manu S.; Solomon, Benjamin D.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Keaton, Amelia A.; Raam, Manu S.] NIH, HHMI, Res Scholars Program, Chevy Chase, MD 20815 USA. [Kamat, Aparna; Chandrasekharappa, Settara C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35,Room 1B207,35 Convent Dr,MSC 3717, Bethesda, MD 20892 USA. EM nneamaka.agochukwu@nih.gov; pinedaad@mail.nih.gov; Amelia.keaton@nih.gov; nicolewarrenm@gmail.com; raamm@ccf.org; anantraykamata@mail.nih.gov; chandra@mail.nih.gov; solomonb@mail.nih.gov FU Howard Hughes Medical Institute; Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health, Department of Health and Human Services, United States of America) FX We would like to express our gratitude to the patients described in this article for their willingness to take part in this study, and to Dr. Max Muenke for his support and mentorship. This research was supported in part by the Howard Hughes Medical Institute and by the Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health, Department of Health and Human Services, United States of America). NR 21 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD MAY-JUN PY 2011 VL 54 IS 3 BP 323 EP 328 DI 10.1016/j.ejmg.2011.01.007 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 805QR UT WOS:000293744600025 PM 21315191 ER PT J AU Croswell, JM Kramer, BS Crawford, ED AF Croswell, Jennifer M. Kramer, Barnett S. Crawford, E. David TI Screening for Prostate Cancer With PSA Testing: Current Status and Future Directions SO ONCOLOGY-NEW YORK LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; RADICAL PROSTATECTOMY; MORTALITY; ANTIGEN; OUTCOMES; MEN; POPULATION; CARCINOMA; TRENDS AB The ultimate utility of the serum prostate specific antigen (PSA) assay as a screening test for reducing prostate cancer mortality has been an area of intense controversy since its introduction. PSA testing was not initially envisioned as a screening tool, but as a way to evaluate treatment responses in men with prostate cancer. Far in advance of evidence from randomized trials, the rapid and widespread uptake of PSA screening into US practice was initially driven by the intuitively logical assumption that the earlier one detects a malignancy, the more likely treatment is to be curative while minimizing associated harms. However, a growing body of observational evidence began to point to a substantial burden of associated overdiagnosis and overtreatment triggered by PSA testing. The interim results of several randomized clinical trials specifically designed to evaluate the impact of PSA testing on prostate cancer mortality have recently become available, but their incongruent results seem to have added fuel to the debate. This article presents a review of the literature on screening for prostate cancer with PSA testing; we include a detailed discussion of potential explanations for the contradictory results of the two largest randomized trials as well as reflections on the future of prostate cancer screening. C1 [Croswell, Jennifer M.] Agcy Healthcare Res & Qual, Rockville, MD 20850 USA. [Kramer, Barnett S.] NCI, Rockville, MD USA. [Crawford, E. David] Univ Colorado, Ctr Canc, Hlth Sci Ctr, Denver, CO 80262 USA. RP Croswell, JM (reprint author), Agcy Healthcare Res & Qual, 540 Gaither Rd, Rockville, MD 20850 USA. EM jennifer.croswell@ahrq.hhs.gov NR 57 TC 17 Z9 19 U1 0 U2 5 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2011 VL 25 IS 6 BP 452 EP 463 PG 10 WC Oncology SC Oncology GA 800EW UT WOS:000293343600002 PM 21717898 ER PT J AU Mollapour, M Tsutsumi, S Kim, YS Trepel, J Neckers, L AF Mollapour, Mehdi Tsutsumi, Shinji Kim, Yeong Sang Trepel, Jane Neckers, Len TI Casein kinase 2 phosphorylation of Hsp90 threonine 22 modulates chaperone function and drug sensitivity SO ONCOTARGET LA English DT Article DE Heat Shock Protein 90; phosphorylation; casein kinase 2; Hsp90 inhibitors; heat shock response ID HEAT-SHOCK-PROTEIN; MOLECULAR CHAPERONE; SIGNALING NETWORKS; IN-VIVO; PHOSPHOPROTEOMIC ANALYSIS; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; ATPASE ACTIVITY AB The molecular chaperone Heat Shock Protein 90 (Hsp90) is essential for the function of various oncoproteins that are vital components of multiple signaling networks regulating cancer cell proliferation, survival, and metastasis. Hsp90 chaperone function is coupled to its ATPase activity, which can be inhibited by natural products such as the ansamycin geldanamycin (GA) and the resorcinol radicicol (RD). These compounds have served as templates for development of numerous natural product Hsp90 inhibitors. More recently, second generation, fully synthetic Hsp90 inhibitors, based on a variety of chemical scaffolds, have also been synthesized. Together, 18 natural product and synthetic Hsp90 inhibitors have entered clinical trial in cancer patients. To successfully develop Hsp90 inhibitors for oncology indications it is important to understand the factors that influence the susceptibility of Hsp90 to these drugs in vivo. We recently reported that Casein Kinase 2 phosphorylates a conserved threonine residue (T22) in helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. Phosphorylation of this residue reduces ATPase activity and affects Hsp90 chaperone function. Here, we present additional data demonstrating that ATP binding but not N-domain dimerization is a prerequisite for T22 phosphorylation. We also provide evidence that T22 is an important determinant of Hsp90 inhibitor sensitivity in yeast and we show that T22 phosphorylation status contributes to drug sensitivity in vivo. C1 [Mollapour, Mehdi; Tsutsumi, Shinji; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kim, Yeong Sang; Trepel, Jane] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Mollapour, M (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM mollapourm@mail.nih.gov; neckers@nih.gov FU National Cancer Institute FX We gratefully acknowledge our colleagues and collaborators, Laurence H. Pearl, Peter W. Piper, Chris Prodromou, Barry Panaretou, Wanping Xu, Kristin Beebe, Cara Vaughan and Andrew Truman, for their scientific contributions and stimulating discussions. We thank Weiwen Ying of Synta Pharmaceuticals, Inc. for supplying ganetespib and Timothy Haystead (Duke University) for supplying SNX-2112. This work was supported by the Intramural Research Program of the National Cancer Institute. NR 72 TC 24 Z9 25 U1 0 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY PY 2011 VL 2 IS 5 BP 407 EP 417 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802KN UT WOS:000293509800009 PM 21576760 ER PT J AU Hu, DN Chen, M Zhang, DY Ye, F McCormick, SA Chan, CC AF Hu, Dan-Ning Chen, Min Zhang, David Y. Ye, Fei McCormick, Steven A. Chan, Chi-Chao TI Interleukin-1 beta Increases Baseline Expression and Secretion of Interleukin-6 by Human Uveal Melanocytes In Vitro via the p38 MAPK/NF-kappa B Pathway SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PIGMENT EPITHELIAL-CELLS; KOYANAGI-HARADA-DISEASE; AQUEOUS-HUMOR; INFLAMMATORY MEDIATORS; CHOROIDAL MELANOCYTES; OCULAR INFLAMMATION; INDUCED UVEITIS; STROMAL CELLS; MACULAR EDEMA; CYTOKINES AB PURPOSE. Melanocyte is the major cell component in the uvea. Interleukin (IL)-6 is a proinflammatory cytokine. The authors studied the expression of IL-6 in cultured human uveal melanocytes (UMs) and their modulation by IL-1 beta and explored the relevant signal pathways. METHODS. Conditioned media and cells were collected from UMs cultured in medium with and without serum and were stimulated by IL-1 beta. IL-6 protein and transcript were measured using an ELISA kit and RT-PCR, respectively. NF-kappa B in nuclear extracts and phosphorylated p38 MAPK, ERK, and JNK in cells cultured with and without IL-1 beta were measured by ELISA kits. Inhibitors of p38 (SB203580), ERK (UO1026), JNK (SP600125), and NF-kappa B (BAY11-7082) were added to the cultures to evaluate their effects. RESULTS. Low levels of IL-6 protein were detected in the conditioned medium in UMs cultured without serum. The addition of serum increased the secretion of IL-6. IL-1 beta (0.1-10 ng/mL) increased IL-6 transcript and protein levels in a dose-and time-dependent manner up to sixfold, accompanied by a significant increase of NF-kappa B in nuclear extracts and phosphorylated p38 MAPK in cell lysates. NF-kappa B and p38 inhibitors alone decreased, whereas a combination of these two inhibitors completely abolished the IL-1 beta-induced expression of IL-6. CONCLUSIONS. This is the first report on the expression and secretion of IL-6 by UMs. IL-1 beta augments IL-6 production from the melanocytes. The data suggest that UMs may play a role in the pathogenesis of ocular inflammatory and autoimmune diseases. (Invest Ophthalmol Vis Sci. 2011;52:3767-3774) DOI: 10.1167/iovs.10-6908 C1 [Hu, Dan-Ning; Chen, Min; McCormick, Steven A.] New York Eye & Ear Infirm, Dept Pathol, Tissue Culture Ctr, New York Med Coll, New York, NY 10003 USA. [Hu, Dan-Ning; Chen, Min; McCormick, Steven A.] New York Eye & Ear Infirm, Dept Ophthalmol, Tissue Culture Ctr, New York Med Coll, New York, NY 10003 USA. [Zhang, David Y.; Ye, Fei] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Chan, Chi-Chao] NEI, Immunol Lab, Immunopathol Sect, Bethesda, MD 20892 USA. RP Hu, DN (reprint author), New York Eye & Ear Infirm, Dept Pathol, Tissue Culture Ctr, New York Med Coll, 310 E 14th St, New York, NY 10003 USA. EM hu2095@yahoo.com FU Pathology Research Fund of New York Eye and Ear Infirmary; Bendheim-Lowenstein Family Foundation, New York FX Supported by the Pathology Research Fund of New York Eye and Ear Infirmary and the Bendheim-Lowenstein Family Foundation, New York. NR 52 TC 11 Z9 12 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 3767 EP 3774 DI 10.1167/iovs.10-6908 PG 8 WC Ophthalmology SC Ophthalmology GA 800CF UT WOS:000293335400047 PM 21398280 ER PT J AU McGlynn, KA London, WT AF McGlynn, Katherine A. London, W. Thomas TI The Global Epidemiology of Hepatocellular Carcinoma: Present and Future SO CLINICS IN LIVER DISEASE LA English DT Article DE Incidence; Hepatitis B virus; Hepatitis C virus; Aflatoxin; Alcohol; Diabetes ID HEPATITIS-C-VIRUS; CHRONIC LIVER-DISEASE; POPULATION-BASED COHORT; B-VIRUS; DIABETES-MELLITUS; NONALCOHOLIC STEATOHEPATITIS; FOLLOW-UP; RISK-FACTORS; CIGARETTE-SMOKING; ALCOHOL-CONSUMPTION AB The global risk of hepatocellular carcinoma (HOC) has been largely driven by hepatitis B virus (HBV) infection for the past century, along with hepatitis C virus (HCV), aflatoxin, excessive alcohol consumption, and obesity/diabetes. The dominant effect of HBV on global HCC risk should decline as the population vaccinated against HBV grows older. Infection with HCV is also expected to decline. Projections of HCV-related HCC rates remaining high for another 30 years may be overly pessimistic. Alcohol may be less of a factor in HOC in coming years. However, obesity and diabetes may become even more important risk factors for HOC. C1 [McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [London, W. Thomas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, EPS-5020,6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov FU NCI FX This work was supported by funding of the NCI Intramural Research Program. NR 144 TC 135 Z9 146 U1 1 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1089-3261 J9 CLIN LIVER DIS JI Clin. Liver Dis. PD MAY PY 2011 VL 15 IS 2 BP 223 EP + DI 10.1016/j.cld.2011.03.006 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 798IB UT WOS:000293195200003 PM 21689610 ER PT J AU Rouse, DJ Weiner, SJ Bloom, SL Varner, MW Spong, CY Ramin, SM Caritis, SN Grobman, WA Sorokin, Y Sciscione, A Carpenter, MW Mercer, BM Thorp, JM Malone, FD Harper, M Iams, JD Anderson, GD AF Rouse, Dwight J. Weiner, Steven J. Bloom, Steven L. Varner, Michael W. Spong, Catherine Y. Ramin, Susan M. Caritis, Steve N. Grobman, William A. Sorokin, Yorom Sciscione, Anthony Carpenter, Marshall W. Mercer, Brian M. Thorp, John M., Jr. Malone, Fergal D. Harper, Margaret Iams, Jay D. Anderson, Garland D. CA Eunice Kennedy Shriver Natl Inst C Maternal Fetal Med Units Network TI Failed Labor Induction Toward an Objective Diagnosis EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Rouse, Dwight J.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Utah, Salt Lake City, UT USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Univ Pittsburgh, Pittsburgh, PA USA. Northwestern Univ, Chicago, IL 60611 USA. Wayne State Univ, Detroit, MI USA. Drexel Univ, Philadelphia, PA 19104 USA. Brown Univ, Providence, RI 02912 USA. Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. Univ N Carolina, Chapel Hill, NC USA. Columbia Univ, New York, NY USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Texas Med Branch, Galveston, TX USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Rouse, DJ (reprint author), Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. RI Malone, Fergal/D-6233-2012 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 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2011 VL 66 IS 5 BP 265 EP 266 DI 10.1097/OGX.0b013e3182294291 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 797KT UT WOS:000293127200003 ER PT J AU Hintz, SR Kendrick, DE Wilson-Costello, DE Das, A Bell, EF Vohr, BR Higgins, RD AF Hintz, Susan R. Kendrick, Douglas E. Wilson-Costello, Deanne E. Das, Abhik Bell, Edward F. Vohr, Betty R. Higgins, Rosemary D. CA NICHD Neonatal Res Network TI Early-Childhood Neurodevelopmental Outcomes Are Not Improving for Infants Born at < 25 Weeks' Gestational Age EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Hintz, Susan R.] Stanford Univ, Sch Med, Div Neonatol, Dept Pediat, Palo Alto, CA 94304 USA. RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Hintz, SR (reprint author), Stanford Univ, Sch Med, Div Neonatol, Dept Pediat, Palo Alto, CA 94304 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 MAY PY 2011 VL 66 IS 5 BP 273 EP 275 DI 10.1097/OGX.0b013e31822942fd PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 797KT UT WOS:000293127200007 ER PT J AU Harper, M Zheng, SL Thom, E Klebanoff, MA Thorp, J Sorokin, Y Varner, MW Iams, JD Dinsmoor, M Mercer, BM Rouse, DJ Ramin, SM Anderson, GD AF Harper, Margaret Zheng, S. Lilly Thom, Elizabeth Klebanoff, Mark A. Thorp, John, Jr. Sorokin, Yoram Varner, Michael W. Iams, Jay D. Dinsmoor, Mara Mercer, Brian M. Rouse, Dwight J. Ramin, Susan M. Anderson, Garland D. CA Eunice Kennedy Shriver Natl Inst C Maternal Fetal Med Units Network M TI Cytokine Gene Polymorphisms and Length of Gestation EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Harper, Margaret] Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA. Wake Forest Univ Hlth Sci, Ctr Human Genom, Winston Salem, NC USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Wayne State Univ, Detroit, MI USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. Ohio State Univ, Columbus, OH 43210 USA. Northwestern Univ, Chicago, IL 60611 USA. Case Western Reserve Univ, MetroHth Med Ctr, Cleveland, OH 44106 USA. Univ Alabama, Birmingham, AL USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Univ Texas Med Branch, Galveston, TX USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Harper, M (reprint author), Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2011 VL 66 IS 5 BP 279 EP 281 DI 10.1097/OGX.0b013e3182294359 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 797KT UT WOS:000293127200010 ER PT J AU Cook, NL Lauer, MS AF Cook, Nakela L. Lauer, Michael S. TI The Socio-Geography of Heart Failure Why it Matters SO CIRCULATION-HEART FAILURE LA English DT Editorial Material DE Editorials; comorbidities; heart failure; outcomes; socioeconomic position; geography ID CARE C1 [Cook, Nakela L.; Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Cook, NL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Rockledge 2,Suite 10018, Bethesda, MD 20892 USA. EM cookn2@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 9 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2011 VL 4 IS 3 BP 244 EP 245 DI 10.1161/CIRCHEARTFAILURE.111.962191 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794BN UT WOS:000292869800007 PM 21586735 ER PT J AU Sharma, S Lee, J Gao, P Steele, VE AF Sharma, Sheela Lee, Jin Gao, Pu Steele, Vernon E. TI Toxicity Profile of Solvents by Aspiration Approach for Topical Agent Delivery to Respiratory Tract Epithelium SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE pulmonary toxicity; aspiration; solvents; mouse lung; inflammatory cytokines; A/J mice ID INTESTINAL-ABSORPTION; IN-VIVO; GASTROINTESTINAL ABSORPTION; AEROSOL INHALATION; LAVAGE FLUID; MOUSE LUNG; MICE; RATS; LABRASOL; EXCIPIENTS AB Agent solubility is a problem for aspiration of agents into lungs for chemopreventive efficacy evaluation, since many agents have to be dissolved in solvents. These solvents may be toxic to the lung epithelium. A study was conducted in female A/J mice to determine toxicity of different solvent concentrations by using saline, dimethyl sulfoxide (DMSO), ethanol, polyethylene glycol 400 (PEG-400), and labrasol for 1, 5, and 28 days via aspiration route. Toxicity was determined by measuring changes in body weight and bronchoalveolar lavage fluid (BALF). No significant difference was observed in body weight, differential cell counts, lactate dehydrogenase (LDH) and total protein in all solvent groups compared to saline by 28 days except 50% ethanol. However, myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) showed significant increase in 2% and 10% DMSO, 10% ethanol, 0.1% and 2% PEG-400, and 1% labrasol by longer dosing. All solvents except for 10% ethanol and 2% PEG-400 are suitable for agent aspiration. C1 [Sharma, Sheela; Lee, Jin; Gao, Pu] Hamner Inst Hlth Sci, Div Toxicol & Preclin Studies, Res Triangle Pk, NC 27709 USA. [Steele, Vernon E.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Sharma, S (reprint author), Hamner Inst Hlth Sci, Div Toxicol & Preclin Studies, POB 12137, Res Triangle Pk, NC 27709 USA. EM ssharma@thehamner.org FU National Cancer Institute, Bethesda, Maryland, USA [N01-CN-53301] FX The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: (Contract/grant no.: N01-CN-53301) from the National Cancer Institute, Bethesda, Maryland 20892, USA. NR 42 TC 1 Z9 1 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY PY 2011 VL 30 IS 3 BP 358 EP 366 DI 10.1177/1091581810396729 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 795OB UT WOS:000292982400009 PM 21633126 ER PT J AU Creson, TK Austin, DR Shaltiel, G McCammon, J Wess, J Manji, HK Chen, G AF Creson, Thomas K. Austin, Daniel R. Shaltiel, Galit McCammon, Joseph Wess, Juergen Manji, Husseini K. Chen, Guang TI Lithium treatment attenuates muscarinic M-1 receptor dysfunction SO BIPOLAR DISORDERS LA English DT Article DE ERK; GSK-3; lithium; M-1; mania; miRNA ID FORCED SWIMMING TEST; ACETYLCHOLINE-RECEPTOR; MOOD STABILIZERS; SIGNALING PATHWAY; PROTEIN-SYNTHESIS; BIPOLAR DISORDER; MUTANT MICE; KINASE; HYPERACTIVITY; ACTIVATION AB Objective: Altered muscarinic acetylcholine receptor levels and receptor-coupled signaling processes have been reported in mood disorders. M-1, one of five muscarinic receptor subtypes, couples to the phospholipase C/protein kinase C and extracellular signal-regulated kinase (ERK) pathways. Mood stabilizers regulate these pathways. MicroRNAs (miRNAs) are small noncoding RNAs that suppress translation in a sequence-selective manner. Lithium downregulates several miRNAs, including let-7b and let-7c. One predicted target of let-7b and let-7c is the M-1 receptor. We hypothesized that miRNAs regulate M-1 receptor translation, and that disrupted M-1 expression leads to aberrant behaviors and disrupted downstream signaling pathways that are rescued by lithium treatment. Methods: The effects of miRNAs and chronic treatment with mood stabilizers on M-1 levels were tested in primary cultures and in rat frontal cortex. Effects of M-1 ablation and chronic treatment with mood stabilizers on several signaling cascades and M-1-modulated behaviors were examined in wild-type and M-1 knockout mice. Results: Let-7b, but not let-7c, negatively regulated M-1 levels. Chronic treatment with lithium, but not valproate, increased M-1 levels in the rat cortex. M-1 knockout mice exhibit ERK pathway deficits and behavioral hyperactivity; chronic treatment with lithium attenuated these deficits and hyperactivity. Conclusions: Lithium treatment can affect M-1 receptor function through intracellular signaling enhancement and, in situations without M-1 ablation, concomitant receptor upregulation via mechanisms involving miRNAs. Muscarinic dysfunction may contribute to mood disorders, while M-1 receptors and the downstream ERK pathway may serve as potential therapeutic targets for alleviating manic symptoms such as psychomotor hyperactivity. C1 [Creson, Thomas K.; Austin, Daniel R.; Shaltiel, Galit; McCammon, Joseph; Manji, Husseini K.; Chen, Guang] NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Wess, Juergen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Chen, G (reprint author), NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. EM gchen13@its.jnj.com RI Chen, Guang/A-2570-2017 FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DH HS) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS). The authors thank Dr. Todd Gould and Dr. Kelly O'Donnell for providing access and instructions on using the flame photometer. loline Henter provided invaluable editorial assistance. NR 48 TC 9 Z9 9 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2011 VL 13 IS 3 BP 238 EP 249 DI 10.1111/j.1399-5618.2011.00915.x PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 791LF UT WOS:000292666000003 PM 21676127 ER PT J AU Parekh, AB Muallem, S AF Parekh, Anant B. Muallem, Shmuel TI Ca2+ signalling and gene regulation Introduction SO CELL CALCIUM LA English DT Editorial Material C1 [Parekh, Anant B.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England. [Muallem, Shmuel] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Parekh, AB (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Parks Rd, Oxford OX1 3PT, England. EM anant.parekh@physiol.ox.ac.uk NR 0 TC 8 Z9 8 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY PY 2011 VL 49 IS 5 SI SI BP 279 EP 279 DI 10.1016/j.ceca.2011.01.002 PG 1 WC Cell Biology SC Cell Biology GA 791ZV UT WOS:000292711200001 PM 21429578 ER PT J AU Turkel, S Henderson, DK AF Turkel, Sarah Henderson, David K. TI Current Strategies for Managing Providers Infected with Bloodborne Pathogens SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEPATITIS-C VIRUS; HEALTH-CARE WORKERS; HUMAN-IMMUNODEFICIENCY-VIRUS; HBV DNA LEVELS; B-VIRUS; PATIENT TRANSMISSION; DENTAL PRACTICE; MANAGEMENT; SURGEON; ANESTHESIOLOGIST AB BACKGROUND. In 1991 the Centers for Disease Control and Prevention issued guidelines to reduce risks for provider-to-patient transmission of bloodborne pathogens. These guidelines, unchanged since 1991, recommend management strategies for hepatitis B e antigen-positive providers and for providers infected with human immunodeficiency virus; they do not address hepatitis C virus (HCV)-infected providers. OBJECTIVE. We summarized current state practices and surveyed state health departments to determine (1) whether state policies have been modified since 1991; (2) whether state laws require prospective notification of patients and/or expert review panels to manage infected providers; (3) the frequency with which infected-providers issues come to the attention of state health departments; and (4) how state health departments intervene. METHODS. We reviewed the 50 states' laws and guidelines to determine current practices and conducted a structured telephone survey of all state health departments. RESULTS. Whereas only 19 states require infected providers to notify patients of the providers' bloodborne pathogen infection, these 19 states require notification under highly varied circumstances. Only 10 of 50 state health department officials identified these issues as requiring significant departmental effort. No state law or guideline incorporates information about providers' viral burdens as part of the risk assessment. Only 3 of 50 states have modified policies or laws since initial passage, and only 1 of 50 discusses the management of HCV-infected providers. CONCLUSIONS. These results identify a need for incorporating contemporary scientific information into guidelines and also suggest that infected-provider issues are not occurring commonly, are not being detected, or are being managed at levels below the state health department. Infect Control Hosp Epidemiol 2011;32(5):428-434 C1 [Turkel, Sarah; Henderson, David K.] NIH, Hosp Epidemiol Serv, Bethesda, MD 20892 USA. [Henderson, David K.] NIH, Off Deputy Director Clin Care, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), Bldg 10,Room 6-1480,10 Ctr Dr, Bethesda, MD 20892 USA. EM dkh@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 54 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 2011 VL 32 IS 5 BP 428 EP 434 DI 10.1086/659405 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 791GE UT WOS:000292652100003 PM 21515972 ER PT J AU Talbot, LA Metter, EJ Morrell, CH Frick, KD Weinstein, AA Fleg, JL AF Talbot, Laura A. Metter, E. Jeffrey Morrell, Christopher H. Frick, Kevin D. Weinstein, Ali A. Fleg, Jerome L. TI A Pedometer-Based Intervention to Improve Physical Activity, Fitness, and Coronary Heart Disease Risk in National Guard Personnel SO MILITARY MEDICINE LA English DT Article ID CARDIORESPIRATORY FITNESS; CARDIOVASCULAR-DISEASE; LIFE-STYLE; WOMEN; PROJECT; WALKING; SCORES; TRIAL; BOUTS AB To compare the effects of a pedometer-based behavioral intervention (Fitness for Life [FFL] program) and a traditional high-intensity fitness (TRAD) program on physical activity (PA), Army Physical Fitness Test (APFT), and coronary heart disease risk factors in Army National Guard members who failed the APFT 2-mile run. From a pool of 261 Army National Guard, a total of 156 were randomized to TRAD or FFL for 24 weeks consisting of a 12-week progressive conditioning program followed by 12 weeks of maintenance. For both groups, the total APFT score and 2-mile run time/score improved from baseline to 12 weeks (FFL: down arrow 7.4% p = 0.03; TRAD: down arrow 5%, p = 0.08) but at 24 weeks they had regressed toward baseline. PA improved modestly and coronary risk profile changed minimally in both groups. A pedometer-based exercise intervention had results similar to a high-intensity program for improving PA, APFT, and 2-mile run times/score. Neither group sustained the improved run times over the 12 weeks of maintenance. C1 [Talbot, Laura A.] Univ N Carolina, Sch Nursing, Coll Hlth & Human Serv, Charlotte, NC 28223 USA. [Metter, E. Jeffrey] Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD 21225 USA. [Morrell, Christopher H.] Loyola Univ Maryland, Dept Math Sci, Baltimore, MD 21210 USA. [Frick, Kevin D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Weinstein, Ali A.] George Mason Univ, Ctr Study Chron Illness & Disabil, Fairfax, VA 22030 USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Talbot, LA (reprint author), Univ N Carolina, Sch Nursing, Coll Hlth & Human Serv, 9201 Univ City Blvd, Charlotte, NC 28223 USA. RI Weinstein, Ali/D-3919-2012 FU TriService; USUHS; Department of Defense; U.S. Government [MDA 905-02-1-TS07, N02-007]; USUHS, Jones Bridge Rd., Bethesda [MD 20814-4799]; Department of Health and Human Services, National Institutes of Health [NIH], National Center for Research Resources [5 M01 RR0279]; NIH, National Institute on Aging; Johns Hopkins Bayview General Clinical Research Center FX We thank the ARNG Volunteers in the FFL Study. This research was sponsored by the TriService Nursing Research Program, USUHS; however, the information or content and conclusions do not necessarily represent the official positions or policies of, nor should any official endorsement be inferred by, the TriService Nursing Research Program, the USUHS, the Department of Defense, or the U.S. Government (Award no. MDA 905-02-1-TS07; Project no. N02-007). USUHS, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799, is the awarding and administering office.; We also acknowledge the Johns Hopkins Bayview General Clinical Research Center (which is funded by Department of Health and Human Services, National Institutes of Health [NIH], National Center for Research Resources, no. 5 M01 RR0279) for providing core laboratory and data management support and equipment, and the Intramural Research Program of the NIH, National Institute on Aging. Funding for this project was provided by Triservice Nursing Research Program, Johns Hopkins Bayview General Clinical Research Center, the Intramural Research Program of NIH, National Institute on Aging. NR 35 TC 8 Z9 8 U1 0 U2 4 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAY PY 2011 VL 176 IS 5 BP 592 EP 600 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 792XM UT WOS:000292783700026 PM 21634310 ER PT J AU Youngstrom, E Kenworthy, L Lipkin, PH Goodman, M Squibb, K Mattison, DR Anthony, LG Makris, SL Bale, AS Raffaele, KC LaKind, JS AF Youngstrom, Eric Kenworthy, Lauren Lipkin, Paul H. Goodman, Michael Squibb, Katherine Mattison, Donald R. Anthony, Laura Gutermuth Makris, Susan L. Bale, Ambuja S. Raffaele, Kathleen C. LaKind, Judy S. TI A proposal to facilitate weight-of-evidence assessments: Harmonization of Neurodevelopmental Environmental Epidemiology Studies (HONEES) SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Neurodevelopmental function tests; Interstudy consistency; Environmental epidemiology; Weight-of-evidence assessments; Risk assessment; Environmental chemicals ID DEVELOPMENTAL NEUROTOXICITY; DIAGNOSTIC-ACCURACY; CHILDREN; GUIDELINES; DISORDERS; CHEMICALS; EXPOSURE; ISSUES AB The ability to conduct weight-of-evidence assessments to inform the evaluation of potential environmental neurotoxicants is limited by lack of comparability of study methods, data analysis, and reporting. There is a need to establish consensus guidelines for conducting, analyzing, and reporting neurodevelopmental environmental epidemiologic studies, while recognizing that consistency is likewise needed for epidemiology studies examining other health outcomes. This paper proposes a set of considerations to be used by the scientific community at-large as a tool for systematically evaluating the quality of proposed and/or published studies in terms of their value for weight-of-evidence assessments. Particular emphasis is placed on evaluating factors influencing the risk of incorrect conclusions at the level of study findings. The proposed considerations are the first step in what must be a larger consensus-based process and can serve to catalyze such a discussion. Achieving consensus in these types of endeavors is difficult; however, opportunities exist for further interdisciplinary discussion, collaboration, and research that will help realize this goal. Broad acceptance and application of such an approach can facilitate the expanded use of environmental epidemiology studies of potential neurodevelopmental toxicants in the protection of public health, and specifically children's health. (C) 2011 Elsevier Inc. All rights reserved. C1 [LaKind, Judy S.] LaKind Associates LLC, Catonsville, MD 21228 USA. [Youngstrom, Eric] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Youngstrom, Eric] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Kenworthy, Lauren; Anthony, Laura Gutermuth] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders,Dept Pediat, Rockville, MD 20850 USA. [Kenworthy, Lauren] George Washington Univ, Dept Neurol & Psychiat, Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders,Sch Med, Rockville, MD 20850 USA. [Lipkin, Paul H.] Johns Hopkins Univ, Sch Med, Ctr Dev & Learning, Kennedy Krieger Inst,Dept Pediat, Baltimore, MD 21205 USA. [Goodman, Michael] Emory Univ, Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Squibb, Katherine] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Anthony, Laura Gutermuth] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders,Dept Psychiat, Rockville, MD 20850 USA. [Makris, Susan L.; Bale, Ambuja S.; Raffaele, Kathleen C.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [LaKind, Judy S.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21202 USA. [LaKind, Judy S.] Penn State Coll Med, Dept Pediat, Hershey, PA 17033 USA. RP LaKind, JS (reprint author), LaKind Associates LLC, 106 Oakdale Ave, Catonsville, MD 21228 USA. EM lakindassoc@comcast.net RI Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; Lipkin, Paul/0000-0002-9043-2581 FU EPA [EP10H000282]; Cefic-Long-range Research Initiative (LRI) FX The NBTS symposium was funded through EPA contract number EP10H000282. The research was supported by a grant from Cefic-Long-range Research Initiative (LRI) (DRM, SLM, ASB, and KCR did not receive support from Cefic). The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency, the National Institutes of Health, or Cefic-LRI. Cefic-LRI was not involved in the design, collection, management, analysis, or interpretation of the data; or in the preparation or approval of the manuscript. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. NR 32 TC 7 Z9 7 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2011 VL 33 IS 3 BP 354 EP 359 DI 10.1016/j.ntt.2011.01.004 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 791OB UT WOS:000292673400002 PM 21315817 ER PT J AU Graubard, BI Korn, EL AF Graubard, Barry I. Korn, Edward L. TI Conditional Logistic Regression With Survey Data SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Conditional logistic regression; Complex sample surveys; Pseudo-pairwise likelihood; Hispanic Health and Nutrition Examination Survey ID BINARY DATA; MODELS AB When data consist of clusters of potentially correlated observations then conditional logistic regression can be used to estimate the association between a binary outcome and covariates conditionally on the cluster effects. Surveys can use multistage sampling with potentially differential probabilities of sampling individuals from the same conditioning cluster (e. g., family). We show that conditional logistic regression of survey data using standard inflation (weighted) estimation (i.e., observations are weighted by the inverse of their inclusion probabilities) can result in biased estimators when the sample sizes of the observations sampled from the conditioning clusters are small. We propose using methods based on weighted pseudo-pairwise likelihoods that combine the conditional logistic likelihoods for all pairs of observations consisting of a positive and a negative outcome within a conditioning cluster and weights the pairwise likelihoods by the inverse of their joint inclusion probabilities within the cluster. Design-based variance estimators for regression coefficient estimators are provided. Limited simulations demonstrate that the proposed methods produce approximately unbiased regression coefficients and variance estimates, but can be considerably less efficient than maximum likelihood estimation when the sampling is uninformative. The proposed methods are illustrated with an analysis of data from the Hispanic Health and Nutrition Examination Survey. C1 [Graubard, Barry I.] NCI, Biostat Branch, Bethesda, MD 20892 USA. [Korn, Edward L.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Graubard, BI (reprint author), NCI, Biostat Branch, 6120 Execut Blvd,Rm 8024, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov NR 17 TC 8 Z9 8 U1 0 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD MAY PY 2011 VL 3 IS 2 BP 398 EP 408 DI 10.1198/sbr.2010.10002 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791QX UT WOS:000292680800024 ER PT J AU Sarwar, UN Sitar, S Ledgerwood, JE AF Sarwar, Uzma N. Sitar, Sandra Ledgerwood, Julie E. TI Filovirus emergence and vaccine development: A perspective for health care practitioners in travel medicine SO TRAVEL MEDICINE AND INFECTIOUS DISEASE LA English DT Article DE Filovirus vaccines; Imported Marburg infection; Glycoprotein antigen ID EBOLA HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; MARBURG VIRUS; POSTEXPOSURE PROTECTION; RISK-FACTORS; INFECTION; PROTEIN; PATHOGENESIS; APOPTOSIS; OUTBREAKS AB Recent case reports of viral hemorrhagic fever in Europe and the United States have raised concerns about the possibility for increased importation of filoviruses to non-endemic areas. This emerging threat is concerning because of the increase in global air travel and the rise of tourism in central and eastern Africa and the greater dispersion of military troops to areas of infectious disease outbreaks. Marburg viruses (MARV) and Ebola viruses (EBOV) have been associated with outbreaks of severe hemorrhagic fever involving high mortality (25-90% case fatality rates). First recognized in 1967 and 1976 respectively, subtypes of MARV and EBOV are the only known viruses of the Filoviridae family, and are among the world's most virulent pathogens. This article focuses on information relevant for health care practitioners in travel medicine to include, the epidemiology and clinical features of filovirus infection and efforts toward development of a filovirus vaccine. Published by Elsevier Ltd. C1 [Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, CRC, Bethesda, MD 20892 USA. RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, CRC, 9000 Rockville Pike,Bldg 10,Room 5-2440,40 Conven, Bethesda, MD 20892 USA. EM Ledgerwood@mail.nih.gov FU Intramural NIH HHS [ZIA AI005047-07] NR 57 TC 7 Z9 9 U1 3 U2 20 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1477-8939 EI 1873-0442 J9 TRAVEL MED INFECT DI JI Travel Med. Infect. Dis. PD MAY PY 2011 VL 9 IS 3 SI SI BP 126 EP 134 DI 10.1016/j.tmaid.2010.05.003 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 791QI UT WOS:000292679300006 PM 21208830 ER PT J AU Zilberman-Peled, B Bransburg-Zabary, S Klein, DC Gothilf, Y AF Zilberman-Peled, Bina Bransburg-Zabary, Sharron Klein, David C. Gothilf, Yoav TI Molecular Evolution of Multiple Arylalkylamine N-Acetyltransferase (AANAT) in Fish SO MARINE DRUGS LA English DT Article DE seabream; serotonin; dopamine; gene duplication ID MAMMALIAN PINEAL-GLAND; CATALYTIC MECHANISM; MELATONIN SYNTHESIS; EC 2.3.1.87; ANGSTROM RESOLUTION; EXPRESSION PATTERN; CIRCADIAN CLOCK; MESSENGER-RNA; TELEOST FISH; TROUT RETINA AB Arylalkylamine N-acetyltransferase (AANAT) catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to arylalkylamines, including indolethylamines and phenylethylamines. Multiple aanats are present in teleost fish as a result of whole genome and gene duplications. Fish aanat1a and aanat2 paralogs display different patterns of tissue expression and encode proteins with different substrate preference: AANAT1a is expressed in the retina, and acetylates both indolethylamines and phenylethylamines; while AANAT2 is expressed in the pineal gland, and preferentially acetylates indolethylamines. The two enzymes are therefore thought to serve different roles. Here, the molecular changes that led to their specialization were studied by investigating the structure-function relationships of AANATs in the gilthead seabream (sb, Sperus aurata). Acetylation activity of reciprocal mutated enzymes pointed to specific residues that contribute to substrate specificity of the enzymes. Inhibition tests followed by complementary analyses of the predicted three-dimensional models of the enzymes, suggested that both phenylethylamines and indolethylamines bind to the catalytic pocket of both enzymes. These results suggest that substrate selectivity of AANAT1a and AANAT2 is determined by the positioning of the substrate within the catalytic pocket, and its accessibility to catalysis. This illustrates the evolutionary process by which enzymes encoded by duplicated genes acquire different activities and play different biological roles. C1 [Zilberman-Peled, Bina; Gothilf, Yoav] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. [Bransburg-Zabary, Sharron] Tel Aviv Univ, George S Wise Fac Life Sci, Bioinformat Unit, IL-69978 Tel Aviv, Israel. [Klein, David C.] NICHHD, Off Sci Directory, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RP Zilberman-Peled, B (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. EM binazp@gmail.com; sharron.zabary@gmail.com; kleind@mail.nih.gov; yoavg@tauex.tau.ac.il FU Israel Science Foundation, Jerusalem [232/00-17.2] FX This research was supported by Grant No 232/00-17.2 from the Israel Science Foundation, Jerusalem. NR 53 TC 11 Z9 11 U1 1 U2 8 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD MAY PY 2011 VL 9 IS 5 BP 906 EP 921 DI 10.3390/md9050906 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 791AP UT WOS:000292632500017 PM 21673898 ER PT J AU Albert, MS DeKosky, ST Dickson, D Dubois, B Feldman, HH Fox, NC Gamst, A Holtzman, DM Jagust, WJ Petersen, RC Snyder, PJ Carrillo, MC Thies, B Phelps, CH AF Albert, Marilyn S. DeKosky, Steven T. Dickson, Dennis Dubois, Bruno Feldman, Howard H. Fox, Nick C. Gamst, Anthony Holtzman, David M. Jagust, William J. Petersen, Ronald C. Snyder, Peter J. Carrillo, Maria C. Thies, Bill Phelps, Creighton H. TI The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Mild cognitive impairment; AD dementia; Diagnosis AB The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [DeKosky, Steven T.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Dickson, Dennis] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. [Dubois, Bruno] Grp Hosp Pitie Salpetriere, Inst Memory & Alzheimers Dis, INSERM, Unit Cognit Neuroimagerie & Malad Due Cerveau, F-75634 Paris, France. [Feldman, Howard H.] Bristol Myers Squibb Neurosci, Wallingford, CT USA. [Fox, Nick C.] UCL, Inst Neurol, London, England. [Gamst, Anthony] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Holtzman, David M.] Washington Univ, Dept Neurol, St Louis, MO USA. [Holtzman, David M.] Washington Univ, Knight Alzheimers Dis Res Ctr, St Louis, MO USA. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Snyder, Peter J.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA. [Snyder, Peter J.] Brown Univ, Dept Neurol, Alpert Med Sch, Providence, RI 02912 USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Phelps, Creighton H.] NIA, Bethesda, MD 20892 USA. [DeKosky, Steven T.] Univ Virginia, Off Dean, Charlottesville, VA USA. RP Albert, MS (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. EM malbert9@jhmi.edu RI Fox, Nick/B-1319-2009; OI Fox, Nick/0000-0002-6660-657X; Dickson, Dennis W/0000-0001-7189-7917; Snyder, Peter/0000-0003-0555-4654; Feldman, Howard/0000-0002-9258-4538 FU GE Healthcare; Novartis; Roche; Eisai; Pfizer; Eli Lilly; Astra Zeneca FX With regard to potential conflicts of interest, Marilyn Albert serves as a consultant to Genentech and Eli Lilly and receives grants to her institution from GE Healthcare. Steven DeKosky serves as a consultant to Eisai, Merck, Elan/Wyeth, Novartis, he serves on the advisory board of Pfizer and provides clinical services to United Healthcare. Dennis Dickson report no conflicts. Bruno Dubois serves as a consultant to Affiris, Pierre Fabre, and Eisai, serving on a scientific advisory board for Bristol-Meyers Squibb, Roche, Pfizer, Eli Lilly, and GE Healthcare, and receives grants to his institution from Novartis, Roche, and Eisai. Howard Feldman is an employee of Bristol Meyers Squibb (BMS) and holds stock in BMS; he serves as a consultant to Servier, Glia Scientific, and Pfizer, and serves on a scientific advisory board for Elan, Janssen, Canada, and Wyeth. Nick Fox serves as a consultant (payment to Institute of Neurology) for BMS, Elan/Janssen, Eli Lilly, GE, Lundbeck, and Pfizer/Wyeth. The Institute of Neurology (Nick Fox) has conducted image analysis for Elan/Janssen, Lundbeck, and Pfizer/Wyeth. Anthony Gamst reports no conflicts. David Holtzman serves as a consultant for Bristol-Myers Squibb, Pfizer, and Innogenetics; he serves on a scientific advisory board for En Vivo, Satori, and C2N Diagnostics; and receives grants to his institution from Pfizer, Eli Lilly, and Astra Zeneca. William Jagust serves as a consultant to Genentech, Bayer Healthcare, GE Healthcare, Synarc, Otsuka Pharmaceuticals, Janssen Alzheimer Immunotherapy, Merck, and Tau Rx. Ronald Petersen serves as a consultant for Elan Pharmaceuticals and GE Healthcare and serves on data monitoring committees for Pfizer, Inc., Janssen Alzheimer Immunotherapy. Peter Snyder serves as a consultant to Cog State Ltd. Maria Carrillo is an employee of the Alzheimer's Association and reports no conflicts. Bill Thies is an employee of the Alzheimer's Association and reports no conflicts. Creighton Phelps is an employee of the U.S. Government and reports no conflicts. NR 22 TC 1934 Z9 1983 U1 30 U2 244 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 270 EP 279 DI 10.1016/j.jalz.2011.03.008 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600004 PM 21514249 ER PT J AU Phillips, MM Rimmer, CA Wood, LJ Lippa, KA Sharpless, KE Duewer, DL Sander, LC Betz, JM AF Phillips, Melissa M. Rimmer, Catherine A. Wood, Laura J. Lippa, Katrice A. Sharpless, Katherine E. Duewer, David L. Sander, Lane C. Betz, Joseph M. TI Dietary Supplement Laboratory Quality Assurance Program: The First Five Exercises SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID STANDARD REFERENCE MATERIALS; SOLID-PHASE EXTRACTION; DILUTION MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; INFANT/ADULT NUTRITIONAL FORMULA; CERTIFIED REFERENCE MATERIALS; VITAMIN-RELATED-COMPOUNDS; WATER-SOLUBLE VITAMINS; TRACE-ELEMENTS; BITTER-ORANGE AB The National Institute of Standards and Technology (NIST) has established a Dietary Supplement Laboratory Quality Assurance Program (DSQAP) in collaboration with the National Institutes of Health Office of Dietary Supplements. Program participants measure concentrations of active and/or marker compounds as well as nutritional and toxic elements in food and dietary supplements distributed by NIST. Data are compiled at NIST, where they are analyzed for accuracy relative to reference values and concordance among the participants. Performance reports and certificates of completion are provided to participants, which can be used to demonstrate compliance with current Good Manufacturing Practices as promulgated by the U.S. Food and Drug Administration. The DSQAP has conducted five exercises to date, with total participation including more than 75 different laboratories and many more individual analysts. C1 [Phillips, Melissa M.; Rimmer, Catherine A.; Wood, Laura J.; Lippa, Katrice A.; Sharpless, Katherine E.; Duewer, David L.; Sander, Lane C.] NIST, Div Analyt Chem, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Phillips, MM (reprint author), NIST, Div Analyt Chem, Mat Measurement Lab, Gaithersburg, MD 20899 USA. EM melissa.phillips@nist.gov RI Phillips, Melissa/E-8030-2013 FU NIH HHS [Y01 OD009087, Y01 OD000183] NR 73 TC 3 Z9 3 U1 0 U2 6 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2011 VL 94 IS 3 BP 803 EP 814 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 779KB UT WOS:000291775400014 PM 21797008 ER PT J AU Mikolajczyk, RT Zhang, J Betran, AP Souza, JP Mori, R Gulmezoglu, AM Merialdi, M AF Mikolajczyk, Rafael T. Zhang, Jun Betran, Ana Pilar Souza, Joao Paulo Mori, Rintaro Guelmezoglu, A. Metin Merialdi, Mario TI A global reference for fetal-weight and birthweight percentiles SO LANCET LA English DT Article ID INTRAUTERINE GROWTH-RETARDATION; PREDICTING PERINATAL-MORTALITY; GESTATIONAL-AGE; POPULATION; STANDARDS; DEFINITION; OUTCOMES; INFANTS; BORN AB Background Definition of small for gestational age in various populations worldwide remains a challenge. References based on birthweight are deficient for preterm births, those derived from ultrasound estimates might not be applicable to all populations, and the individualised reference can be too complex to use in developing countries. Our aim was to create a generic reference for fetal weight and birthweight that overcame these deficiencies and could be readily adapted to local populations. Methods We used the fetal-weight reference developed by Hadlock and colleagues and the notion of proportionality proposed by Gardosi and colleagues and made the weight reference easily adjustable according to the mean birthweight at 40 weeks of gestation for any local population. For application and validation, we used data from 24 countries in Africa, Latin America, and Asia that participated in the 2004-08 WHO Global Survey on Maternal and Perinatal Health (237025 births). We compared our reference with that of Hadlock and colleagues (non-customised) and with that of Gardosi and colleagues (individualised). For every reference, the odds ratio (OR) of adverse perinatal outcomes (stillbirths, neonatal deaths, referral to higher-level or special care unit, or Apgar score lower than 7 at 5 min) for infants who were small for gestational age versus those who were not was estimated with multilevel logistic regression. Findings OR of adverse outcomes for infants small for gestational age versus those not small for gestational age was 1.59 (95% CI 1.53-1.66) for the non-customised fetal-weight reference compared with 2.87 (2.73-3.01) for our country-specific reference, and 2.84 (2.71-2.99) for the fully individualised reference. Interpretation Our generic reference for fetal-weight and birthweight percentiles can be easily adapted to local populations. It has a better ability to predict adverse perinatal outcomes than has the non-customised fetal-weight reference, and is simpler to use than the individualised reference without loss of predictive ability. C1 [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200092, Peoples R China. [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200092, Peoples R China. [Mikolajczyk, Rafael T.] Bremen Inst Prevent Res & Social Med, Dept Clin Epidemiol, Bremen, Germany. [Mikolajczyk, Rafael T.] Univ Bielefeld, Sch Publ Hlth, Dept Publ Hlth Med, Bielefeld, Germany. [Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA. [Betran, Ana Pilar; Souza, Joao Paulo; Guelmezoglu, A. Metin; Merialdi, Mario] WHO, Dept Reprod Hlth & Res, CH-1211 Geneva, Switzerland. [Mori, Rintaro] Univ Tokyo, Grad Sch Med, Dept Global Hlth Policy, Tokyo, Japan. RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200092, Peoples R China. EM junjimzhang@gmail.com RI Souza, Joao Paulo/G-1982-2010 OI Souza, Joao Paulo/0000-0002-2288-4244 FU UNDP/UNFPA/WHO/World Bank; WHO; United States Agency for International Development (USAID); Ministry of Health, Labour and Welfare of Japan; Ministry of Public Health of the People's Republic of China; Indian Council of Medical Research, India; Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, USA FX The 2004-08 WHO Global Survey on Maternal and Perinatal Health (WHOGS) was a research project implemented by the WHO in a global network of health facilities between 2004 and 2008. The authors of this secondary analysis are grateful to all those who contributed to the project design and implementation, including researchers, study coordinators, data collectors, data clerks, and other partners such as the staff from the Ministries of Health and WHO offices. The WHOGS project was financially supported by the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (HRP); WHO; United States Agency for International Development (USAID); Ministry of Health, Labour and Welfare of Japan; Ministry of Public Health of the People's Republic of China; and the Indian Council of Medical Research, India. JZ was supported by the Intramural Programme of Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, USA. The named authors alone are responsible for the views expressed in this manuscript, which does not necessarily represent the decisions or the stated policy of the WHO. NR 29 TC 118 Z9 123 U1 4 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY-JUN PY 2011 VL 377 IS 9780 BP 1855 EP 1861 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 774UI UT WOS:000291411700031 PM 21621717 ER PT J AU Clauser, SB Wagner, EH Bowles, EJA Tuzzio, L Greene, SM AF Clauser, Steven B. Wagner, Edward H. Bowles, Erin J. Aiello Tuzzio, Leah Greene, Sarah M. TI Improving Modern Cancer Care Through Information Technology SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PATIENT-REPORTED OUTCOMES; NATIONAL TRENDS SURVEY; HEALTH INFORMATION; CLINICAL-PRACTICE; BREAST-CANCER; QUALITY IMPROVEMENT; INTERNET; IMPACT; SYSTEM; MANAGEMENT AB The cancer care system is increasingly complex, marked by multiple hand-offs between primary care and specialty providers, inadequate communication among providers, and lack of clarity about a "medical home" (the ideal accountable care provider) for cancer patients. Patients and families often cite such difficulties as information deficits, uncoordinated care, and insufficient psychosocial support. This article presents a review of the challenges of delivering well coordinated, patient-centered cancer care in a complex modern healthcare system. An examination is made of the potential role of information technology (IT) advances to help both providers and patients. Using the published literature as background, a review is provided of selected work that is underway to improve communication, coordination, and quality of care. Also discussed are additional challenges and opportunities to advancing understanding of how patient data, provider and patient involvement, and informatics innovations can support high-quality cancer care. (Am J Prev Med 2011;40(5S2):S198 -S207) (C) 2011 American Journal of Preventive Medicine C1 [Clauser, Steven B.] NCI, Outcomes Res Branch, NIH, Bethesda, MD 20892 USA. [Wagner, Edward H.; Bowles, Erin J. Aiello; Tuzzio, Leah; Greene, Sarah M.] Grp Hlth Res Inst, Seattle, WA USA. RP Clauser, SB (reprint author), NCI, Outcomes Res Branch, NIH, Execut Plaza North,Room 4086,6130 Execut Blvd,MSC, Bethesda, MD 20892 USA. EM clausers@mail.nih.gov FU National Cancer Institute [PO 263-MQ-516309, CA 79689]; National Institutes of Health FX The writing group takes sole responsibility for the content of this article. Content reflects the views of the authors only. This work was supported by the National Cancer Institute (Contract: PO 263-MQ-516309; Grant: CA 79689). We thank Beth Kirlin and Virginia Scobba for assistance with article retrieval, and Anne Rodgers for thoughtful editorial suggestions.; Publication of this article was supported by the National Institutes of Health. NR 81 TC 23 Z9 26 U1 5 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2011 VL 40 IS 5 SU 2 BP S198 EP S207 DI 10.1016/j.amepre.2011.01.014 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 754DR UT WOS:000289833200016 PM 21521595 ER PT J AU Corn, M Gustafson, DH Harris, LM Kutner, JS McFarren, AE Shad, AT AF Corn, Milton Gustafson, David H. Harris, Linda M. Kutner, Jean S. McFarren, Ann E. Shad, Aziza T. TI Survey of Consumer Informatics for Palliation and Hospice Care SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB Context: Palliation in patient care is under-utilized in part because many patients have insufficient knowledge about this management option. Information technology can improve awareness by providing access to numerous sources of trustworthy information. Evidence acquisition: To estimate what a patient interested in palliation might find online, online resources were searched in July 2010, using terms relevant to palliation. PubMed was searched for publications relevant to discussed topics. Evidence synthesis: Search engines returned vast numbers of hits, and identifying trustworthy sites was difficult. Products judged as trustworthy were classified as information, decision tool, or extended interaction tool. Sites with useful educational material were relatively plentiful; decision guides or interactive tools were much rarer. Available consumer informatics did not address some terminal illnesses very well, and some subpopulations such as children, nor was there sufficient attention to literacy levels or principles of instructional design. Online or published information about usage numbers, effectiveness, and cost/benefit considerations was scant. Many sectors, including commercial, government, healthcare, research, and wellness/advocacy groups, have created consumer informatics for palliation. Conclusions: Online information about palliation is available, although identifying trustworthy sources can be problematic. General information sites are relatively plentiful, but more tools for decision making, and interaction would increase value of web resources. More attention to literacy levels, instructional principles, and needs of special populations would improve products. Research to measure usage of such tools, ability to influence behavior, and cost/benefit issues is needed. (Am J Prev Med 2011;40(5S2):S173-S178) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Corn, Milton] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Harris, Linda M.] DHHS, Off Dis Prevent & Hlth Promot, Rockville, MD USA. [Gustafson, David H.] Univ Wisconsin Madison, Dept Ind & Syst Engn, Madison, WI USA. [Kutner, Jean S.] Univ Colorado, Dept Med, Aurora, CO USA. [McFarren, Ann E.] HealthMark Multimedia LLC, Washington, DC USA. [Shad, Aziza T.] Georgetown Univ, Dept Pediat, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Corn, M (reprint author), 8600 Rockville Pike,Bldg 38,Room 2E17C, Bethesda, MD 20894 USA. EM cornm@mail.nih.gov FU Foundation for Informed Medical Decision Making through the University of Colorado; National Institutes of Health FX JSK receives salary support for her role as a medical editor from the Foundation for Informed Medical Decision Making through a contract with the University of Colorado. AEM is president and chief financial officer of HealthMark Multimedia, LLC.; Publication of this article was supported by the National Institutes of Health. NR 26 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2011 VL 40 IS 5 SU 2 BP S173 EP S178 DI 10.1016/j.amepre.2011.01.015 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 754DR UT WOS:000289833200013 PM 21521592 ER PT J AU Goldberg, L Lide, B Lowry, S Massett, HA O'Connell, T Preece, J Quesenbery, W Shneiderman, B AF Goldberg, Larry Lide, Bettijoyce Lowry, Svetlana Massett, Holly A. O'Connell, Trisha Preece, Jennifer Quesenbery, Whitney Shneiderman, Ben TI Usability and Accessibility in Consumer Health Informatics Current Trends and Future Challenges SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COMMUNITIES AB It is a truism that, for innovative eHealth systems to have true value and impact, they must first and foremost be usable and accessible by clinicians, consumers, and other stakeholders. In this paper, current trends and future challenges in the usability and accessibility of consumer health informatics will be described. Consumer expectations of their healthcare providers and healthcare records in this new era of consumer-directed care will be explored, and innovative visualizations, assistive technologies, and other ways that healthcare information is currently being provided and/or shared will be described. Challenges for ensuring the usability of current and future systems will also be discussed. An innovative model for conducting systematic, timely, user-centered research on consumer-facing websites at the National Cancer Institute (NCI) and the ongoing efforts at the National Institute of Standards and Technology (NIST) to promote health information technology (HIT) usability standards and evaluation criteria will also be presented. (Am J Prev Med 2011;40(5S2):S187-S197) (C) 2011 American Journal of Preventive Medicine C1 [Goldberg, Larry; O'Connell, Trisha] WGBH Natl Ctr Accessible Media, Media Access Grp, Boston, MA USA. [Lide, Bettijoyce; Lowry, Svetlana] Natl Inst Stand & Technol, Informat Technol Lab, Gaithersburg, MD 20899 USA. [Massett, Holly A.] NCI, Off Commun & Educ, Bethesda, MD 20892 USA. [Preece, Jennifer] Univ Maryland, Marylands iSch, Coll Informat Studies, College Pk, MD 20742 USA. [Shneiderman, Ben] Univ Maryland, Human Comp Interact Lab, College Pk, MD 20742 USA. [Shneiderman, Ben] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Quesenbery, Whitney] Whitney Interact Design, High Bridge, NJ USA. RP Lide, B (reprint author), 100 Bur Dr,Mail Stop 8900, Gaithersburg, MD 20899 USA. EM bettijoyce.lide@nist.gov RI Sanders, Susan/G-1957-2011 FU National Science Foundation [IIS-0956571]; ONC; NIH-National Cancer Institute [CA147489]; National Institutes of Health FX BS acknowledges National Science Foundation IIS-0956571, ONC SHARP grant on Cognitive Information Design and Visualization for the National Center for Cognitive Informatics and Decision Making in Healthcare, and the Two Workshops: Technology-Mediated Social Participation and NIH-National Cancer Institute (CA147489), Interactive Exploration of Temporal Patterns in Electronic Health Records.; Publication of this article was supported by the National Institutes of Health. NR 50 TC 24 Z9 24 U1 0 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2011 VL 40 IS 5 SU 2 BP S187 EP S197 DI 10.1016/j.amepre.2011.01.009 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 754DR UT WOS:000289833200015 PM 21521594 ER PT J AU Dall'Armellina, E Karia, N Lindsay, AC Karamitsos, TD Ferreira, V Robson, MD Kellman, P Francis, JM Forfar, C Prendergast, BD Banning, AP Channon, KM Kharbanda, RK Neubauer, S Choudhury, RP AF Dall'Armellina, Erica Karia, Nina Lindsay, Alistair C. Karamitsos, Theodoros D. Ferreira, Vanessa Robson, Matthew D. Kellman, Peter Francis, Jane M. Forfar, Colin Prendergast, Bernard D. Banning, Adrian P. Channon, Keith M. Kharbanda, Rajesh K. Neubauer, Stefan Choudhury, Robin P. TI Dynamic Changes of Edema and Late Gadolinium Enhancement After Acute Myocardial Infarction and Their Relationship to Functional Recovery and Salvage Index SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE myocardial salvage; myocardial edema; late gadolinium enhancement; MRI; acute coronary syndrome ID CARDIOVASCULAR MAGNETIC-RESONANCE; ACUTE CORONARY SYNDROME; RISK; SIZE; IMPROVEMENT; PREDICTION; ISCHEMIA; NECROSIS; INJURY; AREA AB Background-Changes in the myocardium in acute ischemia are dynamic and complex, and the characteristics of myocardial tissue on cardiovascular magnetic resonance in the acute setting are not fully defined. We investigated changes in edema and late gadolinium enhancement (LGE) with serial imaging early after acute myocardial infarction, relating these to global and segmental myocardial function at 6 months. Methods and Results-Cardiovascular magnetic resonance scans were performed on 30 patients with ST-elevation-myocardial infarction treated by primary percutaneous coronary intervention at each of 4 time points: 12 to 48 hours; 5 to 7 days; 14 to 17 days; and 6 months. All patients showed edema at 24 hours. The mean volume of edema (% left ventricle) was 37 +/- 16 at 24 hours and 39 +/- 17 at 1 week, with a reduction to 24 +/- 13 (P<0.01) by 2 weeks. Myocardial segments with edema also had increased signal on LGE at 24 hours (kappa=0.77; P<0.001). The volume of LGE decreased significantly between 24 hours and 6 months (27 +/- 15% versus 22 +/- 12%; P=0.002). Of segments showing LGE at 24 hours, 50% showed resolution by 6 months. In segments with such a reduction in LGE, 65% also showed improved wall motion (P<0.0001). The area of LGE measured at 6 months correlated more strongly with troponin at 48 hours (r=0.9; P<0.01) than LGE at 24 hours (r=0.7). The difference in LGE between 24 hours and 6 months had profound effects on the calculation of salvage index (26 +/- 21% at 24 hours versus 42 +/- 23% at 6 months; P=0.02). Conclusions-Myocardial edema is maximal and constant over the first week after myocardial infarction, providing a stable window for the retrospective evaluation of area at risk. By contrast, myocardial areas with high signal intensity in LGE images recede over time with corresponding recovery of function, indicating that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium. (Circ Cardiovasc Imaging. 2011;4:228-236.) C1 [Dall'Armellina, Erica; Karia, Nina; Lindsay, Alistair C.; Karamitsos, Theodoros D.; Ferreira, Vanessa; Robson, Matthew D.; Francis, Jane M.; Channon, Keith M.; Neubauer, Stefan; Choudhury, Robin P.] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Forfar, Colin; Prendergast, Bernard D.; Banning, Adrian P.; Kharbanda, Rajesh K.] John Radcliffe Hosp, Dept Cardiol, Oxford OX3 9DU, England. RP Choudhury, RP (reprint author), Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. EM robin.choudhury@cardiov.ox.ac.uk OI Ferreira, Vanessa/0000-0002-0046-7634; Robson, Matthew/0000-0002-5902-1012; Kharbanda, Rajesh/0000-0002-5356-2395 FU Oxford Comprehensive Biomedical Research Center, NIHR; BHF Centre of Research Excellence, Oxford, United Kingdom; OCMR FX We thank the staff of the Heart Centre at John Radcliffe Hospital and OCMR for their support and help, and we gratefully acknowledge technical advice from Dr A. Arai, NIH, Bethesda, MD.; The study was funded by the Oxford Comprehensive Biomedical Research Center, NIHR funding scheme. Dr Choudhury is a Wellcome Trust Senior Research Fellow in Clinical Science. Drs Neubauer and Choudhury acknowledge the support of the BHF Centre of Research Excellence, Oxford, United Kingdom. NR 43 TC 84 Z9 85 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2011 VL 4 IS 3 BP 228 EP U67 DI 10.1161/CIRCIMAGING.111.963421 PG 17 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765NU UT WOS:000290715800008 PM 21447711 ER PT J AU Cardis, E Hatch, M AF Cardis, E. Hatch, M. TI The Chernobyl Accident - An Epidemiological Perspective SO CLINICAL ONCOLOGY LA English DT Article DE Cancer; cataracts; cardiovascular diseases; Chernobyl accident; radiation; thyroid cancer ID THYROID-CANCER INCIDENCE; POWER-STATION ACCIDENT; ATOMIC-BOMB SURVIVORS; RADIATION-INDUCED LEUKEMIA; EXPOSED IN-UTERO; CHILDHOOD LEUKEMIA; BREAST-CANCER; POST-CHERNOBYL; FOLLOW-UP; EXTERNAL RADIATION AB Twenty-five years have passed since radioactive releases from the Chernobyl nuclear accident led to the exposure of millions of people in Europe. Studies of affected populations have provided important new data on the links between radiation and cancer particularly the risk of thyroid tumours from exposure to iodine isotopes that are important not only for a fuller scientific understanding of radiation effects, but also for radiation protection. It is now well documented that children and adolescents exposed to radioiodines from Chernobyl fallout have a sizeable dose-related increase in thyroid cancer, with the risk greatest in those youngest at exposure and with a suggestion that deficiency in stable iodine may increase the risk. Data on thyroid cancer risks to other age groups are somewhat less definitive. In addition, there have been reported increases in incidence and mortality from non-thyroid cancers and non-cancer end points. Although some studies are difficult to interpret because of methodological limitations, recent investigations of Chernobyl clean-up workers (liquidators') have provided evidence of increased risks of leukaemia and other haematological malignancies and of cataracts, and suggestions of an increase in the risk of cardiovascular diseases, following low doses and low dose rates of radiation. Further careful follow-up of these populations, including the establishment and long-term support of life-span study cohorts, could provide additional important information for the quantification of radiation risks and the protection of persons exposed to low doses of radiation. (C) 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Cardis, E.] CIBERESP, Hosp Mar Res Inst IMIM, CREAL Ctr Res Environm Epidemiol, Barcelona 08003, Spain. [Hatch, M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Cardis, E (reprint author), CIBERESP, Hosp Mar Res Inst IMIM, CREAL Ctr Res Environm Epidemiol, Parc Recerca Biomed Barcelona,Doctor Aiguader 88, Barcelona 08003, Spain. EM ecardis@creal.cat RI Cardis, Elisabeth/C-3904-2017 FU US National Cancer Institute, NIH, DHHS FX This research was supported in part by the Intramural Research Program of the US National Cancer Institute, NIH, DHHS. The authors wish to acknowledge all the people in Europe-in particular in the most-affected states of Belarus, Russia and Ukraine-as well as in Japan and North America who have worked tirelessly in the last 25 years to evaluate the health impact of the Chernobyl accident and to draw lessons from this catastrophe to improve the health of the affected populations, to better understand radiation risks and to improve the basis for radiological protection of populations. A special note is made of the invaluable contributions of the late Geoffrey Howe (Columbia University) and Elaine Ron (US National Cancer Institute). NR 85 TC 65 Z9 74 U1 7 U2 23 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD MAY PY 2011 VL 23 IS 4 SI SI BP 251 EP 260 DI 10.1016/j.clon.2011.01.510 PG 10 WC Oncology SC Oncology GA 767GE UT WOS:000290842500004 PM 21396807 ER PT J AU Giaccone, G AF Giaccone, Giuseppe TI NDDO Honorary Award lecture 2011: The changing landscape of lung cancer and its treatment SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 13 EP 13 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800002 ER PT J AU Luo, J AF Luo, J. TI Targeting the Ras-MAPK pathway for cancer therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Luo, J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 14 EP 14 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800004 ER PT J AU Melillo, G AF Melillo, G. TI Targeting acquired resistance to angiogenesis inhibitors by targeting HIF-1 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Melillo, G.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 14 EP 15 PG 2 WC Oncology SC Oncology GA 773XL UT WOS:000291344800009 ER PT J AU Annunziata, CM AF Annunziata, C. M. TI PARP as a novel therapeutic target in cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Annunziata, C. M.] NCI, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 15 EP 15 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800012 ER PT J AU Neckers, L AF Neckers, L. TI Targeting the molecular chaperone Hsp90 for cancer therapy: What does the biology tell us? SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Neckers, L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 16 EP 16 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800015 ER PT J AU Fojo, T Komlodi-Pasztor, E Sackett, D AF Fojo, T. Komlodi-Pasztor, E. Sackett, D. TI "What went wrong with aurora kinase inhibitors?" SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Fojo, T.; Komlodi-Pasztor, E.] NCI, NIH, Bethesda, MD 20892 USA. [Sackett, D.] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 18 EP 18 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800027 ER PT J AU Dennis, PA AF Dennis, P. A. TI The PI3K/Akt/mTOR signaling pathway SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Dennis, P. A.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 19 EP 19 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800032 ER PT J AU Meltzer, P Killian, JK Abaan, O Pineda, M Walker, RL Zhu, J Davis, S Bilke, S AF Meltzer, P. Killian, J. K. Abaan, O. Pineda, M. Walker, R. L. Zhu, J. Davis, S. Bilke, S. TI Implications of the new sequencing technologies for clinical oncology SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Meltzer, P.; Killian, J. K.; Abaan, O.; Pineda, M.; Walker, R. L.; Zhu, J.; Davis, S.; Bilke, S.] NCI, Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 20 EP 20 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800037 ER PT J AU Bates, S Foss, F Piekarz, R Horwitz, S Pro, B Prince, M Sokol, L Greenwood, M Caballero, D Borchmann, P Morschhauser, F Wilhelm, M Pinter-Brown, L Padmanabhan, S Shustov, A Wright, J Kirschbaum, M Zain, J Allen, SL Jaffe, ES Nichols, J Wolfson, J Balser, J Coiffier, B AF Bates, Susan Foss, Francine Piekarz, Richard Horwitz, Steven Pro, Barbara Prince, Miles Sokol, Lubomir Greenwood, Matthew Caballero, Dolores Borchmann, Peter Morschhauser, Franck Wilhelm, Martin Pinter-Brown, Lauren Padmanabhan, Swaminathan Shustov, Andrei Wright, John Kirschbaum, Mark Zain, Jasmine Allen, Steven L. Jaffe, Elaine S. Nichols, Jean Wolfson, Julie Balser, John Coiffier, Bertrand TI Pooled analysis of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) following prior systemic therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Jaffe, Elaine S.] NCI, Bethesda, MD 20892 USA. [Foss, Francine] Yale Canc Ctr, New Haven, CT USA. [Piekarz, Richard; Wright, John] NCI, Canc Therapy Evaluat Program, DCTD, NIH,DHHS, Rockville, MD USA. [Horwitz, Steven] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Pro, Barbara] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Prince, Miles] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Greenwood, Matthew] Royal N Shore Hosp, Sydney, NSW, Australia. [Caballero, Dolores] Hosp Univ Salamanca, Salamanca, Spain. [Borchmann, Peter] Klinikum Univ Koln, Cologne, Germany. [Morschhauser, Franck] CHU Lille, Hop Claude Huriez, Lille, France. [Wilhelm, Martin] Klinikum Nurnberg Nord, Nurnberg, Germany. [Pinter-Brown, Lauren] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Padmanabhan, Swaminathan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shustov, Andrei] Univ Washington, Seattle, WA 98195 USA. [Kirschbaum, Mark] Nevada Canc Inst, Las Vegas, NV USA. [Zain, Jasmine] NYU, Langone Med Ctr, New York, NY USA. [Allen, Steven L.] Hofstra N Shore LIJ Sch Med, Manhasset, NY USA. [Nichols, Jean] Celgene Corp, Cambridge, MA USA. [Wolfson, Julie; Balser, John] Veristat Inc, Holliston, MA USA. [Coiffier, Bertrand] Hosp Civils Lyon, Lyon, France. RI Wilhelm, Martin/J-3964-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800040 ER PT J AU Madan, RA Palena, C Gulley, JL Hodge, JW Tsang, KY Greiner, JW Huang, J Schlom, J AF Madan, R. A. Palena, C. Gulley, J. L. Hodge, J. W. Tsang, K. Y. Greiner, J. W. Huang, J. Schlom, J. TI Novel strategies in the design and development of recombinant vaccines for cancer therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Madan, R. A.; Palena, C.; Gulley, J. L.; Hodge, J. W.; Tsang, K. Y.; Greiner, J. W.; Huang, J.; Schlom, J.] NCI, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800045 ER PT J AU Price, DK Gao, R Sissung, TM Reece, KM Rosenberg, SA Figg, WD AF Price, D. K. Gao, R. Sissung, T. M. Reece, K. M. Rosenberg, S. A. Figg, W. D. TI ERCC1 haplotypes are associated with melanoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Price, D. K.; Gao, R.; Sissung, T. M.; Reece, K. M.; Rosenberg, S. A.; Figg, W. D.] NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800050 ER PT J AU Hembrough, TA Thyparambil, S Cao, L Liao, WL Krizman, D Darfler, M Burrows, J Helman, LJ AF Hembrough, T. A. Thyparambil, S. Cao, L. Liao, W. L. Krizman, D. Darfler, M. Burrows, J. Helman, L. J. TI Quantitative analysis of IGF-1R expression and signaling pathway activation in FFPE xenograft and human tumor tissues SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Symposium on Targeted Anticancer Therapies CY MAR 07-09, 2011 CL Paris, FRANCE C1 [Hembrough, T. A.; Thyparambil, S.; Liao, W. L.; Krizman, D.; Darfler, M.; Burrows, J.] Express Pathol INC, Rockville, MD USA. [Cao, L.; Helman, L. J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 3 BP 37 EP 37 PG 1 WC Oncology SC Oncology GA 773XL UT WOS:000291344800085 ER PT J AU Peixoto, MF Pilotto, JH Stoszek, SK Kreitchmann, R Mussi-Pinhata, MM Melo, VH Joao, EC Ceriotto, M de Souza, RD Read, J AF Peixoto, Mario Ferreira Pilotto, Jose Henrique Stoszek, Sonia Karolina Kreitchmann, Regis Mussi-Pinhata, Marisa Marcia Melo, Victor Hugo Joao, Esau Custodio Ceriotto, Mariana de Souza, Ricardo da Silva Read, Jennifer TI Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities SO BRAZILIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE pregnancy; HIV; HIV protease inhibitors; drug toxicity ID LOPINAVIR-RITONAVIR; PROTEASE INHIBITORS; WOMEN; PHARMACOKINETICS; TOXICITY; EXPOSURE; BINDING; REGIMEN; TRIAL AB Objectives: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. Methods: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. Results: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts >= 500 cells/mm(3). Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. Conclusion: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants. C1 [Peixoto, Mario Ferreira] Hosp Femina, Unidade Prevencao Transmissao Vert, Porto Alegre, RS, Brazil. [Pilotto, Jose Henrique] Hosp Geral Nova Iguacu, Lab AIDS & Imunol Mol, IOC Fiocruz, Rio De Janeiro, Brazil. [Stoszek, Sonia Karolina] Westat Corp, Rockville, MD USA. [Kreitchmann, Regis] Irmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, Brazil. [Mussi-Pinhata, Marisa Marcia] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP, Brazil. [Melo, Victor Hugo] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Joao, Esau Custodio] Hosp Servidores Estado, Rio De Janeiro, Brazil. [Ceriotto, Mariana] Hosp Agudos Dra Cecilia Grierson, Buenos Aires, DF, Argentina. [de Souza, Ricardo da Silva] Univ Caxias Sul, STD HIV Clin, Caxias Do Sul, RS, Brazil. [Read, Jennifer] NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, Bethesda, MD USA. RP Peixoto, MF (reprint author), Serv Infectiol, Rua Mostardeiro,17-4 Andar, BR-90430000 Porto Alegre, RS, Brazil. EM peixoto3@terra.com.br RI Mussi-Pinhata, Marisa/G-6568-2012 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD [N01-HD-3-3345, HHSN267200800001C, N01-HD-8-0001] FX This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD Contract # N01-HD-3-3345 (2002-2007) and by NICHD Contract # HHSN267200800001C (NICHD Control #: N01-HD-8-0001) (2007-2012) NR 25 TC 5 Z9 5 U1 0 U2 2 PU CONTEXTO PI SALVADOR PA RUA ALFREDO MAGALHAES, 04-BARRA, SALVADOR, BAHIA 40140-140, BRAZIL SN 1413-8670 J9 BRAZ J INFECT DIS JI Braz. J. Infect. Dis. PD MAY-JUN PY 2011 VL 15 IS 3 BP 253 EP 261 PG 9 WC Infectious Diseases SC Infectious Diseases GA 777JY UT WOS:000291613000013 PM 21670927 ER PT J AU O'Keefe, BR AF O'Keefe, Barry R. TI Anti-HIV microbicide development: targeting the virus is the key SO FUTURE VIROLOGY LA English DT Editorial Material DE antiviral; drug development; HIV; microbicide; PrEP ID CYANOVIRIN-N; REVERSE-TRANSCRIPTASE; INACTIVATING PROTEIN; TYPE-1 INFECTION; CONTROLLED TRIAL; ENTRY INHIBITOR; VAGINAL GEL; PREVENTION; TRANSMISSION; SAFETY C1 NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP O'Keefe, BR (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Bldg 562,Room 201,NCI Frederick, Frederick, MD 21702 USA. EM okeefeba@mail.nih.gov NR 33 TC 1 Z9 1 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 J9 FUTURE VIROL JI Future Virol. PD MAY PY 2011 VL 6 IS 5 BP 553 EP 556 PG 4 WC Virology SC Virology GA 775DX UT WOS:000291439800003 ER PT J AU Latoche, JR Neely, HR Noben-Trauth, K AF Latoche, Joseph R. Neely, Harold R. Noben-Trauth, Konrad TI Polygenic inheritance of sensorineural hearing loss (Snhl2, -3, and -4) and organ of Corti patterning defect in the ALR/LtJ mouse strain SO HEARING RESEARCH LA English DT Article ID PRODUCT OTOACOUSTIC EMISSIONS; QUANTITATIVE TRAIT LOCI; MAMMALIAN INNER-EAR; INBRED STRAINS; EARLY-ONSET; DBA/2J MICE; CELL FATE; IMPAIRMENT; MODEL; POLARITY AB Progressive sensorineural hearing loss in humans is a common and debilitating impairment. Sensorineural deafness in inbred strains of mice is a similarly common and genetically diverse phenotype providing experimental models to study the underlying genetics and the biological effects of the risk factors. Here, we report that ALR/LtJ mice develop early-onset profound sensorineural hearing loss as evidenced by high-to-low frequency hearing threshold shifts, absent distortion-product otoacoustic emissions, and normal endocochlear potentials. Linkage analyses of a segregating backcross revealed three novel quantitative trait loci named sensorineural hearing loss (Snhl) -2, -3, and -4. The QTLs achieved very high LOD scores with markers on chromosome 1 (Snhl2, LOD: 12), chromosome 6 (Snhl3, LOD: 24) and chromosome 10 (Snhl4, LOD: 11). Together, they explained 90% of the phenotypic variance. While Snhl2 and Snhl3 affected hearing thresholds across a broad range of test frequencies, Snhl4 caused primarily high-frequency hearing loss. The hearing impairment is accompanied by an organ of Corti patterning defect that is characterized by the ectopic expression of supernumerary outer hair cells organized in rows along the abneural site of the sensory epithelium in the presence of unaltered planar polarity and otherwise normal cochlear duct morphology. Cloning the Snhl2, -3, and -4 genes in the ALR/LtJ mice may provide important genetic and mechanistic insights into the pathology of human progressive sensorineural deafness. Published by Elsevier B.V. C1 [Latoche, Joseph R.; Neely, Harold R.; Noben-Trauth, Konrad] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. EM nobentk@nidcd.nih.gov FU Division of Intramural Research at NIDCD FX We thank Glen Martin for help with DPOAEs and Daniel Marcus for advice on EP measurements. We thank Alain Dabdoub and Feng Qian for their comments on the manuscript. The Division of Intramural Research at NIDCD funded this work. NR 31 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2011 VL 275 IS 1-2 BP 150 EP 159 DI 10.1016/j.heares.2010.12.017 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 776WY UT WOS:000291572300016 PM 21185929 ER PT J AU Lei, P Moeslein, F Wood, BJ Shekhar, R AF Lei, Peng Moeslein, Fred Wood, Bradford J. Shekhar, Raj TI Real-time tracking of liver motion and deformation using a flexible needle SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Real-time tissue tracking; Nonrigid motion tracking; Liver motion compensation; Radiofrequency ablation; Electromagnetic tracking ID PERCUTANEOUS RADIOFREQUENCY ABLATION; CT-GUIDED INTERVENTIONS; ELECTROMAGNETIC TRACKING; SURGICAL MARGIN; REGISTRATION; SYSTEM; TUMORS; COMPENSATION; OPTIMIZATION; METASTASES AB Purpose A real-time 3D image guidance system is needed to facilitate treatment of liver masses using radiofrequency ablation, for example. This study investigates the feasibility and accuracy of using an electromagnetically tracked flexible needle inserted into the liver to track liver motion and deformation. Methods This proof-of-principle study was conducted both ex vivo and in vivo with a CT scanner taking the place of an electromagnetic tracking system as the spatial tracker. Deformations of excised livers were artificially created by altering the shape of the stage on which the excised livers rested. Free breathing or controlled ventilation created deformations of live swine livers. The positions of the needle and test targets were determined through CT scans. The shape of the needle was reconstructed using data simulating multiple embedded electromagnetic sensors. Displacement of liver tissues in the vicinity of the needle was derived from the change in the reconstructed shape of the needle. Results The needle shape was successfully reconstructed with tracking information of two on-needle points. Within 30 mm of the needle, the registration error of implanted test targets was 2.4 +/- 1.0 mm ex vivo and 2.8 +/- 1.5 mm in vivo. Conclusion A practical approach was developed to measure the motion and deformation of the liver in real time within a region of interest. The approach relies on redesigning the often-used seeker needle to include embedded electromagnetic tracking sensors. With the nonrigid motion and deformation information of the tracked needle, a single-or multimodality 3D image of the intraprocedural liver, now clinically obtained with some delay, can be updated continuously to monitor intraprocedural changes in hepatic anatomy. This capability may be useful in radiofrequency ablation and other percutaneous ablative procedures. C1 [Lei, Peng; Moeslein, Fred; Shekhar, Raj] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA. [Wood, Bradford J.] Ctr Clin, Ctr Intervent Oncol, Bethesda, MD USA. [Wood, Bradford J.] NCI, NIH, Bethesda, MD 20892 USA. [Lei, Peng; Shekhar, Raj] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. RP Shekhar, R (reprint author), Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA. EM rshekhar@umm.edu FU National Institute of Health; Center for Interventional Oncology FX This work was supported in part by the Intramural Research Program of the National Institute of Health and the Center for Interventional Oncology. We acknowledge the assistance of Timm Dickfeld, MD, PhD, Department of Cardiology and Thorsten Fleiter, MD, Department of Diagnostic Radiology and Nuclear Medicine, both of University of Maryland School of Medicine, with in vivo experiments. We also acknowledge the editorial assistance of Nancy Knight, PhD, of the Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, in the preparation of this article. NR 37 TC 9 Z9 9 U1 2 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD MAY PY 2011 VL 6 IS 3 BP 435 EP 446 DI 10.1007/s11548-010-0523-7 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA 775UU UT WOS:000291489700013 PM 20700662 ER PT J AU Aumakhan, B Gange, SJ Beyrer, C Gaydos, CA Minkoff, H Merenstein, DJ Cohen, MH Anastos, K Greenblatt, R Nowicki, MJ Quinn, TC AF Aumakhan, B. Gange, S. J. Beyrer, C. Gaydos, C. A. Minkoff, H. Merenstein, D. J. Cohen, M. H. Anastos, K. Greenblatt, R. Nowicki, M. J. Quinn, T. C. TI Quantitative and qualitative correlates of cervicovaginal herpes simplex virus type 2 shedding among HIV-infected women in the Women's Interagency HIV Study SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; women; herpes simplex; HSV-2 DNA; cervicovaginal shedding; genital herpes; cervicovaginal lavage ID GENITAL ULCER DISEASE; NORTHERN THAILAND; COINFECTED WOMEN; AFRICAN WOMEN; RISK; REACTIVATION; PLASMA; HSV-2; TIME; PCR AB We identified demographic, clinical and biological determinants of herpes simplex virus type 2 (HSV-2) shedding among HIV-infected participants in the Women's HIV Interagency Study (WIHS). Cervicovaginal lavage (CVL) specimens from 369 HIV-infected HSV seropositive women were tested with TaqMan polymerase chain reaction (PRC) for detection HSV-2 DNA. Seven percent of women tested positive for HSV-2 DNA in CVL. Significant correlates of the presence of HSV-2 DNA in CVL were being younger, African American or Hispanic race/ethnicity and injecting drugs in the past six months (P < 0.05). A borderline significant trend for reduced viral shedding with higher CD4+ T cell counts was observed (P = 0.08). All women who were never observed with any genital lesions and had consistently negative self-reported history of genital sores throughout the follow-up (n = 29, 8%) were negative for CVL HSV-2 DNA. HSV-2 DNA quantity was significantly associated with having frequent subsequent lesion recurrences (Spearman rho = 0.48, P = 0.016; adjusted prevalence ratio [APR] = 2.5, P = 0.012). Increasing the age of the host was inversely correlated with decreased viral shedding over time. However, a subset of older women continued to shed significant amounts of virus despite passage of time. This study provides genital HSV-2 DNA titre as a quantitative and symptom- and sign-based measures as qualitative predictors of HSV-2 shedding from the lower genital tract among HIV-infected women. C1 [Aumakhan, B.; Gange, S. J.; Beyrer, C.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Gaydos, C. A.; Quinn, T. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Minkoff, H.] Maimonides Hosp, Brooklyn, NY 11219 USA. [Minkoff, H.] SUNY Downstate, Brooklyn, NY USA. [Merenstein, D. J.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Cohen, M. H.] Cook Cty Med Ctr, Chicago, IL USA. [Anastos, K.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Greenblatt, R.] Univ Calif San Francisco, San Francisco Sch Pharm, San Francisco, CA 94143 USA. [Greenblatt, R.] Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA 94143 USA. [Nowicki, M. J.] Univ So Calif, Los Angeles, CA USA. [Quinn, T. C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Aumakhan, B (reprint author), Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA. EM baumakha@jhsph.edu 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]; 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 were collected by the Women's Interagency HIV Study (WTHS) Collaborative Study Group with centres (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 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. NR 36 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD MAY PY 2011 VL 22 IS 5 BP 273 EP 277 DI 10.1258/ijsa.2009.009296 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 776VT UT WOS:000291567500006 PM 21571975 ER PT J AU Kozhamkulov, U Akhmetova, A Rakhimova, S Belova, E Alenova, A Bismilda, V Chingissova, L Ismailov, S Ramanculov, E Momynaliev, K AF Kozhamkulov, Ulan Akhmetova, Ainur Rakhimova, Saule Belova, Elena Alenova, Arike Bismilda, Venera Chingissova, Lyailya Ismailov, Shahimurat Ramanculov, Erlan Momynaliev, Kuvat TI Molecular Characterization of Rifampicin- and Isoniazid-Resistant Mycobacterium tuberculosis Strains Isolated in Kazakhstan SO JAPANESE JOURNAL OF INFECTIOUS DISEASES LA English DT Article AB Kazakhstan is one of the 14 countries with a high rate of morbidity due to multidrug-resistant tuberculosis (MDR TB) in WHO European region. The aim of our study was to characterize mutations associated with drug resistance to rifampicin and isoniazid in Mycobacterium tuberculosis isolates from Kazakhstan. M. tuberculosis strains were isolated from TB patients in different regions of Kazakhstan. A drug susceptibility test was performed on Lowenstein-Jensen medium using the absolute concentration method. Sequencing analysis was performed of the rpoB rifampicin resistance-determining region and the katG gene, the oxyR-ahpC intergenic region, and the inhA promoter region in 259 MDR M. tuberculosis isolates, in 51 isoniazid-resistant isolates, and in 13 rifampicin-resistant isolates. The mutational analysis revealed that the most frequent mutations associated with rifampicin and isoniazid resistance in M. tuberculosis are the substitutions at codons 531 (82.7%) and 315 (98.4%) in the rpoB and katG genes, respectively. In addition, we have found mutations with lower frequency at codons 526 (8.4%), 533 (1.5%), and 516 (1.1%) in the rpoB gene. In 6.2% of the isolates, no mutations were found in the rpoB gene. The findings of this study provide useful data for a better understanding of the mutation spectrum of isoniazid and rifampicin resistance among strains isolated from patients in Kazakhstan. Our results are also useful for the development of diagnostic tests of MDR M. tuberculosis. C1 [Kozhamkulov, Ulan; Akhmetova, Ainur; Rakhimova, Saule; Ramanculov, Erlan; Momynaliev, Kuvat] Natl Biotechnol Ctr, Astana 010000, Kazakhstan. [Belova, Elena; Alenova, Arike; Bismilda, Venera; Chingissova, Lyailya; Ismailov, Shahimurat] Natl Ctr TB Problems, Alma Ata, Kazakhstan. RP Kozhamkulov, U (reprint author), Natl Biotechnol Ctr, Valikhanov Str 13-1, Astana 010000, Kazakhstan. EM kzulan@gmail.com RI Ramanculov, Erlan/E-2823-2013; Kozhamkulov, Ulan/H-6805-2016 FU Ministry of Education and Science of the Republic of Kazakhstan FX This study was financially supported by the Ministry of Education and Science of the Republic of Kazakhstan. NR 10 TC 12 Z9 15 U1 0 U2 4 PU NATL INST INFECTIOUS DISEASES PI TOKYO PA JPN J INFECT DIS ED OFF NATL INST INFECTIOUS DISEASES TOYAMA 1-23-1, SHINJUKU-KU, TOKYO, 162-8640, JAPAN SN 1344-6304 EI 1884-2836 J9 JPN J INFECT DIS JI Jpn. J. Infect. Dis. PD MAY PY 2011 VL 64 IS 3 BP 253 EP 255 PG 3 WC Infectious Diseases SC Infectious Diseases GA 774FN UT WOS:000291370700016 PM 21617314 ER PT J AU Cheng, XXS Bohl, DL Storch, GA Ryschkewitsch, C Gaudreault-Keener, M Major, EO Randhawa, P Hardinger, KL Brennan, DC AF Cheng, Xingxing S. Bohl, Daniel L. Storch, Gregory A. Ryschkewitsch, Caroline Gaudreault-Keener, Monique Major, Eugene O. Randhawa, Parmjeet Hardinger, Karen L. Brennan, Daniel C. TI Inhibitory Interactions between BK and JC Virus among Kidney Transplant Recipients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PREEMPTIVE IMMUNOSUPPRESSION REDUCTION; POLYOMAVIRUS-BK; RENAL-TRANSPLANTATION; ANTIBODY-TITERS; INFECTIONS; REPLICATION; NEPHROPATHY; IMPACT AB BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P = 0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P = 0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other. C1 [Cheng, Xingxing S.; Bohl, Daniel L.; Storch, Gregory A.; Brennan, Daniel C.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Storch, Gregory A.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Ryschkewitsch, Caroline; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. [Gaudreault-Keener, Monique] St Louis Childrens Hosp, Virol Lab, St Louis, MO 63178 USA. [Randhawa, Parmjeet] Univ Pittsburgh, Med Ctr, Dept Pathol, Div Transplantat Pathol, Pittsburgh, PA USA. [Hardinger, Karen L.] Univ Missouri, Dept Pharm Practice, Kansas City, MO 64110 USA. RP Brennan, DC (reprint author), Washington Univ, Renal Dept, 660 S Euclid Ave, St Louis, MO 63110 USA. EM Brennan@wudosis.wustl.edu FU NIH [2 K24-02886, DK 079333] FX This work was supported in part by NIH Grants 2 K24-02886 (D.C.B.) and DK 079333 (D.C.B.). These data were presented in part at the National Kidney Foundation 2009 Spring Clinical meeting in Nashville, TN, as Abstract 39. NR 23 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2011 VL 22 IS 5 BP 825 EP 831 DI 10.1681/ASN.2010080877 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 776FI UT WOS:000291519500009 PM 21511831 ER PT J AU Iwamoto, FM Lamborn, KR Kuhn, JG Wen, PY Yung, WKA Gilbert, MR Chang, SM Lieberman, FS Prados, MD Fine, HA AF Iwamoto, Fabio M. Lamborn, Kathleen R. Kuhn, John G. Wen, Patrick Y. Yung, W. K. Alfred Gilbert, Mark R. Chang, Susan M. Lieberman, Frank S. Prados, Michael D. Fine, Howard A. TI A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03 SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; glioma; histone deacetylase inhibitor; romidepsin ID DEPSIPEPTIDE FR901228; PROGNOSTIC-FACTORS; FK228; PHARMACOKINETICS; GLIOBLASTOMA; CELLS; CYTOCHROME-P450; IDENTIFICATION; PROGRESSION; EXPRESSION AB Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m(2)/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m(2)/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time >= 6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. C1 [Iwamoto, Fabio M.; Fine, Howard A.] NCI, Neurooncol Branch, Natl Inst Neurol Disorder & Stroke, NIH, Bethesda, MD 20892 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Houston, TX USA. [Yung, W. K. Alfred; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, Natl Inst Neurol Disorder & Stroke, NIH, 9030 Old Georgetown Rd,Bloch Bldg 82,Room 225, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU National Institutes of Health ("The North American Brain Tumor Consortium") [CA 062399] FX National Institutes of Health (CA 062399; "The North American Brain Tumor Consortium"). NR 29 TC 41 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 IS 5 BP 509 EP 516 DI 10.1093/neuonc/nor017 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 775HS UT WOS:000291450200005 PM 21377994 ER PT J AU Jack, CR Albert, MS Knopman, DS McKhann, GM Sperling, RA Carrillo, MC Thies, B Phelps, CH AF Jack, Clifford R., Jr. Albert, Marilyn S. Knopman, David S. McKhann, Guy M. Sperling, Reisa A. Carrillo, Maria C. Thies, Bill Phelps, Creighton H. TI Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Diagnostic criteria; Biomarkers; Imaging; Cerebrospinal fluid ID MILD COGNITIVE IMPAIRMENT; NEUROFIBRILLARY TANGLES; PROGRESSIVE APHASIA; AMYLOID DEPOSITION; CLINICAL DEMENTIA; SYNAPSE LOSS; LEWY BODIES; CONSORTIUM; NEUROPATHOLOGY; DEGENERATION AB Background: Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984. A broad consensus now exists that these criteria should be revised to incorporate state-of-the-art scientific knowledge. Methods: The National Institute on Aging (NIA) and the Alzheimer's Association sponsored a series of advisory round table meetings in 2009 whose purpose was to establish a process for revising diagnostic and research criteria for AD. The recommendation from these advisory meetings was that three separate work groups should be formed with each assigned the task of formulating diagnostic criteria for one phase of the disease: the dementia phase; the symptomatic, pre-dementia phase; and the asymptomatic, preclinical phase of AD. Results: Two notable differences from the AD criteria published in 1984 are incorporation of biomarkers of the underlying disease state and formalization of different stages of disease in the diagnostic criteria. There was a broad consensus within all three workgroups that much additional work is needed to validate the application of biomarkers for diagnostic purposes. In the revised NIA-Alzheimer's Association criteria, a semantic and conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes that result, whereas this distinction was blurred in the 1984 criteria. Conclusions: The new criteria for AD are presented in three documents. The core clinical criteria of the recommendations regarding AD dementia and MCI due to AD are intended to guide diagnosis in the clinical setting. However, the recommendations of the preclinical AD workgroup are intended purely for research purposes. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Jack, Clifford R., Jr.; Knopman, David S.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Albert, Marilyn S.; McKhann, Guy M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Med Sch, Boston, MA 02115 USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Phelps, Creighton H.] NIA, Div Neurosci, Baltimore, MD 21224 USA. RP Jack, CR (reprint author), Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. EM jack.clifford@mayo.edu RI Jack, Clifford/F-2508-2010 OI Jack, Clifford/0000-0001-7916-622X FU Baxter; Pfizer Inc; GE Healthcare; Elan Pharmaceuticals; Forest Pharmaceuticals; Baxter Healthcare FX Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; is an investigator in clinical trials sponsored by Baxter and Pfizer Inc; and owns stock in Johnson and Johnson. Marilyn Albert serves as a consultant to Genentech and Eli Lilly and receives grants to her institution from GE Healthcare. David Knopman serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals; is an investigator for clinical trials sponsored by Elan Pharmaceuticals, Forest Pharmaceuticals, and Baxter Healthcare; and is deputy editor of Neurology and receives compensation for editorial activities. Guy McKhann serves on a Data Safety Monitoring Board for Merck. Reisa Sperling has served as a site investigator and/or consultant to several companies developing imaging biomarkers and pharmacological treatments for early AD, including Avid, Bayer, Bristol-Myers-Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth. Maria Carrillo is an employee of the Alzheimer's Association and reports no conflicts. Bill Thies is an employee of the Alzheimer's Association and reports no conflicts. Creighton Phelps is an employee of the U.S. Government and reports no conflicts. NR 50 TC 458 Z9 477 U1 7 U2 82 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 257 EP 262 DI 10.1016/j.jalz.2011.03.004 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600002 PM 21514247 ER PT J AU McKhann, GM Knopman, DS Chertkow, H Hyman, BT Jack, CR Kawas, CH Klunk, WE Koroshetz, WJ Manly, JJ Mayeux, R Mohs, RC Morris, JC Rossor, MN Scheltens, P Carrillo, MC Thies, B Weintraub, S Phelps, CH AF McKhann, Guy M. Knopman, David S. Chertkow, Howard Hyman, Bradley T. Jack, Clifford R., Jr. Kawas, Claudia H. Klunk, William E. Koroshetz, Walter J. Manly, Jennifer J. Mayeux, Richard Mohs, Richard C. Morris, John C. Rossor, Martin N. Scheltens, Philip Carrillo, Maria C. Thies, Bill Weintraub, Sandra Phelps, Creighton H. TI The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Dementia; Diagnosis; Magnetic resonance brain imaging; Positron emission tomography; Cerebrospinal fluid ID FRONTOTEMPORAL DEMENTIA; WORK GROUP; CRITERIA; BIOMARKERS; CONSENSUS; ATROPHY AB The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [McKhann, Guy M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [McKhann, Guy M.] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Baltimore, MD 21205 USA. [Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Chertkow, Howard] McGill Univ, Dept Neurol, Sch Med, Montreal, PQ H3A 2T5, Canada. [Chertkow, Howard] Lady Davis Inst, Bloomfield Ctr Res Aging, Montreal, PQ, Canada. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Kawas, Claudia H.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia H.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Kawas, Claudia H.] Univ Calif Irvine, Alzheimer Dis Res Ctr, Irvine, CA USA. [Klunk, William E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Mohs, Richard C.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Rossor, Martin N.] UCL, Dementia Res Ctr, Dept Neurodegenerat, UCL Inst Neurol, London, England. [Scheltens, Philip] Vrije Univ Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands. [Scheltens, Philip] Vrije Univ Amsterdam, Alzheimer Ctr, Med Ctr, Amsterdam, Netherlands. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Weintraub, Sandra] NW Feinberg Sch Med, Dept Psychiat, Chicago, IL USA. [Weintraub, Sandra] NW Feinberg Sch Med, Dept Neurol, Chicago, IL USA. [Phelps, Creighton H.] NIA, Alzheimers Dis Ctr Program, Bethesda, MD 20892 USA. RP McKhann, GM (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RI Jack, Clifford/F-2508-2010; Morris, John/A-1686-2012; OI Jack, Clifford/0000-0001-7916-622X; Klunk, William/0000-0001-5512-0251 FU Elan Pharmaceuticals; Forest Pharmaceuticals; Baxter Healthcare; Pfizer Canada; NIH; Alzheimer's Association; Fidelity Biosciences; Baxter; Pfizer Inc.; Avid Radiopharmaceuticals; Eli Lilly and Co. FX Guy McKhann serves on a Data Safety Monitoring Board for Merck. David Knopman serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals and is an investigator for clinical trials sponsored by Elan Pharmaceuticals, Forest Pharmaceuticals, and Baxter Healthcare; he is deputy editor of Neurology and receives compensation for editorial activities. Howard Chertkow serves as a consultant to Pfizer Canada, Lundbeck Canada, Janssen Ortho, Novartis Canada, and Bristol Myers Squibb; he receives a research grant from Pfizer Canada. Bradley Hyman serves as a consultant to EMD Serrano, Janssen, Takeda, BMS, Neurophage, Pfizer, Quanterix, foldrx, Elan, and Link, and receives funding from the NIH, the Alzheimer's Association, and Fidelity Biosciences. Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; he is an investigator in clinical trials sponsored by Baxter and Pfizer Inc., and owns stock in Johnson and Johnson. Claudia Kawas serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals, Elan Pharmaceuticals, and Lundbeck; she is an investigator in a trial sponsored by Avid Radiopharmaceuticals. William Klunk serves as a consultant to GE Healthcare and receives research grants from the same; he also receives royalties from GE Healthcare for PiB PET technology and owns stock or options in Neuroptix, a company seeking to commercialize detection of amyloid in the eye. Walter Koroshetz are employees of the U.S. Government and report no conflicts. Jennifer Manly reports no conflicts of interests. Richard Mayeux serves on scientific advisory board of Psycho-Genics. Richard Mohs is a full-time employee of Eli Lilly and Company and holds stock in Lilly. Avid Radiopharmaceuticals is a wholly owned subsidiary of Eli Lilly and Co. John Morris serves as a consultant to Astra Zeneca, Bristol-Myers Squibb, Eisai, Janssen, Genetic, Eli Lilly, Merck, Novartis, Otsuka, Pfizer, and Schering Plough. University College London receives payment for Martin Rossor serving on the Safety Monitoring Committees for Janssen and Servier trials in AD. Philip Scheltens serves as a consultant to Pfizer Pharmaceuticals, Genetech, Danone Research, Lundbeck Pharmaceuticals, GE Healthcare, Roche, and Novartis; he also serves on a speakers bureau for Lundbeck Pharmaceuticals. Maria Carrillo and Bill Thies are employees of the Alzheimer's Association and reports no conflicts. Sandra Weintraub reports no conflicts of interest and Creighton Phelps. NR 24 TC 2377 Z9 2459 U1 77 U2 564 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 263 EP 269 DI 10.1016/j.jalz.2011.03.005 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600003 PM 21514250 ER PT J AU Sperling, RA Aisen, PS Beckett, LA Bennett, DA Craft, S Fagan, AM Iwatsubo, T Jack, CR Kaye, J Montine, TJ Park, DC Reiman, EM Rowe, CC Siemers, E Stern, Y Yaffe, K Carrillo, MC Thies, B Morrison-Bogorad, M Wagster, MV Phelps, CH AF Sperling, Reisa A. Aisen, Paul S. Beckett, Laurel A. Bennett, David A. Craft, Suzanne Fagan, Anne M. Iwatsubo, Takeshi Jack, Clifford R., Jr. Kaye, Jeffrey Montine, Thomas J. Park, Denise C. Reiman, Eric M. Rowe, Christopher C. Siemers, Eric Stern, Yaakov Yaffe, Kristine Carrillo, Maria C. Thies, Bill Morrison-Bogorad, Marcelle Wagster, Molly V. Phelps, Creighton H. TI Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Preclinical Alzheimer's disease; Biomarker; Amyloid; Neurodegeneration; Prevention ID MILD COGNITIVE IMPAIRMENT; AMYLOID DEPOSITION; OLDER-ADULTS; A-BETA; NONDEMENTED INDIVIDUALS; COMMUNITY POPULATION; BIOMARKER SIGNATURE; CSF BIOMARKERS; GENETIC RISK; DECLINE AB The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol,Med Sch, Boston, MA 02115 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Beckett, Laurel A.] Univ Calif Davis, Div Biostat, Sch Med, Davis, CA 95616 USA. [Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. [Fagan, Anne M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Iwatsubo, Takeshi] Univ Tokyo, Grad Sch Sci, Dept Neuropathol, Tokyo 113, Japan. [Jack, Clifford R., Jr.] Mayo Clin Minnesota, Dept Radiol, Rochester, MN USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Biomed Engn, Layton Aging & Alzheimers Dis Ctr, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Park, Denise C.] Univ Texas Dallas, Ctr Vital Longev, Dallas, TX 75230 USA. [Siemers, Eric] Banner Alzheimers Inst, Phoenix, AZ USA. [Rowe, Christopher C.] Univ Melbourne, Melbourne, Vic, Australia. [Siemers, Eric] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Stern, Yaakov] Columbia Univ, Coll Phys & Surg, Cognit Neurosci Div, Taub Inst, New York, NY USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Morrison-Bogorad, Marcelle; Wagster, Molly V.; Phelps, Creighton H.] NIA, Div Neurosci, Bethesda, MD 20892 USA. RP Sperling, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol,Med Sch, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu RI Jack, Clifford/F-2508-2010; OI Jack, Clifford/0000-0001-7916-622X; Beckett, Laurel/0000-0002-2418-9843; Kaye, Jeffrey/0000-0002-9971-3478 FU Pfizer Inc.; Baxter International Inc.; Baxter; Avid Pharmaceuticals; Bayer; Janssen; Eli Lilly; Elan FX Reisa Sperling has served as a site investigator and/or consultant to several companies developing imaging biomarkers and pharmacological treatments for early AD, including Avid, Bayer, Bristol-Myers-Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth. Paul Aisen serves on a scientific advisory board for NeuroPhage; serves as a consultant to Elan Corporation, Wyeth, Eisai Inc., Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck & Co., Roche, Amgen, Abbott, Pfizer Inc., Novartis, Bayer, Astellas, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, AstraZeneca, Janssen, and Medivation Inc.; receives research support from Pfizer Inc. and Baxter International Inc.; and has received stock options from Medivation Inc. and NeuroPhage. Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; is an investigator in clinical trials sponsored by Baxter and Pfizer Inc.; and owns stock in Johnson and Johnson. Denise Park has received research support from Avid Pharmaceuticals. Eric Siemers is an employee of Eli Lilly and Company, which acquired Avid Pharmaceuticals. Yaakov Stern has consulted to Bayer Pharmaceuticals and has received research support from Bayer, Janssen, Eli Lilly, and Elan. Maria Carrillo is an employee of the Alzheimer's Association and reports no conflicts. Bill Thies is an employee of the Alzheimer's Association and reports no conflicts. Creighton Phelps is an employee of the U.S. Government and reports no conflicts. NR 71 TC 1680 Z9 1721 U1 46 U2 282 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 280 EP 292 DI 10.1016/j.jalz.2011.03.003 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600005 PM 21514248 ER PT J AU Keshtkar-Jahromi, M Kuhn, JH Christova, I Bradfute, SB Jahrling, PB Bavari, S AF Keshtkar-Jahromi, Maryam Kuhn, Jens H. Christova, Iva Bradfute, Steven B. Jahrling, Peter B. Bavari, Sina TI Crimean-Congo hemorrhagic fever: Current and future prospects of vaccines and therapies SO ANTIVIRAL RESEARCH LA English DT Review DE Crimean-Congo hemorrhagic fever; Bunyavirus; Nairovirus; Priority pathogen; Ribavirin; Antiviral therapy; Viral hemorrhagic fever ID ORAL RIBAVIRIN; NOSOCOMIAL OUTBREAK; CLINICAL PATHOLOGY; BIOLOGICAL WEAPONS; VIRUS-INFECTION; EFFICACY; TURKEY; PATHOGENESIS; IRAN; MANAGEMENT AB Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by CCHF virus (CCHFV), a nairovirus in the family Bunyaviridae. CCHF occurs sporadically in a number of countries in Asia, the Middle East, southeastern Europe and Africa. Patients may develop subclinical to severe hemorrhagic disease, with fatal outcomes in a substantial percentage of cases. Transmission usually occurs through contact with viremic livestock or patients or bites by infected ticks. The number of reported cases has increased in recent years, possibly due to global climatic change and human perturbations of biocenoses that may have led to the migration of tick vectors. There is currently no FDA-approved vaccine or specific antiviral therapy for CCHF. The classification of CCHFV as a WHO Risk Group IV pathogen and the lack of suitable animal models has caused progress in developing new prophylactic and therapeutic measures to be slow. Ribavirin is active against CCHFV in vitro, but its efficacy for human therapy has not been definitively demonstrated by clinical studies. CCHF-immunoglobulin is also in use, but without clear evidence of efficacy. In this article, we review the development of prophylaxis and therapy for CCHF and discuss future prospects for vaccine and drug development. (C) 2011 Published by Elsevier B.V. C1 [Bradfute, Steven B.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Keshtkar-Jahromi, Maryam] Univ Maryland, Union Mem Hosp, Baltimore, MD 21201 USA. [Kuhn, Jens H.; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. [Christova, Iva] Natl Ctr Infect & Parasit Dis, Sofia, Bulgaria. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Frederick, MD 21702 USA. EM sina.bavari@us.army.mil RI Kuhn, Jens H./B-7615-2011 OI Kuhn, Jens H./0000-0002-7800-6045 FU Defense Threat Reduction Agency [0048-09-RD-T]; NIAID [HHSN272200200016I] FX This work was partially supported by the Defense Threat Reduction Agency, Transformational Medical Technologies project number 0048-09-RD-T (to SB). JHK performed this work as an employee of Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under Contract No. HHSN272200200016I. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the US Army, the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. NR 70 TC 34 Z9 38 U1 2 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2011 VL 90 IS 2 BP 85 EP 92 DI 10.1016/j.antiviral.2011.02.010 PG 8 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 771TB UT WOS:000291182500166 PM 21362441 ER PT J AU Selvam, P Maddali, K Marchand, C Pommier, Y AF Selvam, Periyasamy Maddali, Kasthuraiah Marchand, Christophe Pommier, Yves TI Studies of HIV Integrase Inhibitory Activity of Novel Isatine Derivatives SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 24th International Conference on Antiviral Research (ICAR) CY MAY 08-11, 2011 CL Sofia, BULGARIA SP Int Soc Antiviral Res C1 [Selvam, Periyasamy] Devaki Amma Mem Coll Pharm, Malapuram 676364, Kerala, India. [Maddali, Kasthuraiah; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2011 VL 90 IS 2 MA 80 BP A43 EP A43 DI 10.1016/j.antiviral.2011.03.066 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 771TB UT WOS:000291182500065 ER PT J AU Mosca, M Tani, C Aringer, M Bombardieri, S Boumpas, D Cervera, R Doria, A Jayne, D Khamashta, MA Kuhn, A Gordon, C Petri, M Schneider, M Shoenfeld, Y Smolen, JS Talarico, R Tincani, A Ward, MM Werth, VP Carmona, L AF Mosca, M. Tani, C. Aringer, M. Bombardieri, S. Boumpas, D. Cervera, R. Doria, A. Jayne, D. Khamashta, M. A. Kuhn, A. Gordon, C. Petri, M. Schneider, M. Shoenfeld, Y. Smolen, J. S. Talarico, R. Tincani, A. Ward, M. M. Werth, V. P. Carmona, L. TI Development of quality indicators to evaluate the monitoring of SLE patients in routine clinical practice SO AUTOIMMUNITY REVIEWS LA English DT Review DE Quality indicators; Quality of care; Systemic lupus erythematosus; Routine clinical practice ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HEALTH-CARE QUALITY; OF-CARE; RHEUMATOLOGY; RECOMMENDATIONS; IMPLEMENTATION; SET AB The assessment of systemic lupus erythematosus (SLE) patients in routine clinical practice is mainly based on the experience of the treating physician. This carries the risk of unwanted variability. Variability may have an impact on the quality of care offered to SLE patients, thereby affecting outcomes. Recommendations represent systematically developed statements to help practitioners in reducing variability. However, major difficulties arise in the application of recommendations into clinical practice. In this respect, the use of quality indicators may raise the awareness among rheumatologists regarding potential deficiencies in services and improve the quality of health care. The aim of this study was to develop a set of quality indicators (QI) for SLE by translating into QIs the recently developed EULAR Recommendations for monitoring SLE patients in routine clinical practice and observational studies. Eleven QIs have been developed referring to the use of validated activity and damage indices in routine clinical practice, general evaluation of drug toxicity, evaluation of comorbidities, eye evaluation, laboratory assessment, evaluation of the presence of chronic viral infections, documentation of vaccination and of antibody testing at baseline. A disease specific set of quality assessment tools should help physicians deliver high quality of care across populations. Routine updates will be needed. (C) 2011 Elsevier B.V. All rights reserved. C1 [Mosca, M.; Tani, C.; Bombardieri, S.; Talarico, R.] Univ Pisa, Rheumatol Unit, Dept Internal Med, Pisa, Italy. [Aringer, M.] Tech Univ Dresden, Univ Clin Ctr Carl Gustav Carus, Dresden, Germany. [Boumpas, D.] Univ Crete, Sch Med, Iraklion, Greece. [Cervera, R.] Hosp Clin Barcelona, Dept Autoimmune Dis, Barcelona, Catalonia, Spain. [Doria, A.] Univ Padua, Div Rheumatol, Padua, Italy. [Jayne, D.] Addenbrookes Hosp, Renal Unit, Cambridge, England. [Khamashta, M. A.] St Thomas Hosp, Rayne Inst, Lupus Res Unit, London SE1 7EH, England. [Kuhn, A.] Univ Munster, Dept Dermatol, D-4400 Munster, Germany. [Gordon, C.] Univ Birmingham, Sch Immun & Infect, Birmingham B15 2TT, W Midlands, England. [Petri, M.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. [Schneider, M.] Univ Dusseldorf, Clin Endocrinol Diabetol & Rheumatol, Dusseldorf, Germany. [Shoenfeld, Y.] Chaim Sheba Med Ctr, Dept Med B, IL-52621 Tel Hashomer, Israel. [Shoenfeld, Y.] Chaim Sheba Med Ctr, Ctr Autoimmune Dis, IL-52621 Tel Hashomer, Israel. [Shoenfeld, Y.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Shoenfeld, Y.] Tel Aviv Univ, Zabludowitcz Ctr Autoimmun, IL-69978 Tel Aviv, Israel. [Smolen, J. S.] Med Univ Vienna, Dept Rheumatol, Vienna, Austria. [Tincani, A.] Spedali Civil Brescia, UO Reumatol & Immunol Clin, I-25125 Brescia, Italy. [Tincani, A.] Univ Brescia, Brescia, Italy. [Ward, M. M.] NIAMSD, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Werth, V. P.] Univ Penn, Philadelphia, PA 19104 USA. [Carmona, L.] Fdn Espanola Reumatol, Res Unit, Madrid, Spain. RP Mosca, M (reprint author), Univ Pisa, Rheumatol Unit, Dept Internal Med, Pisa, Italy. EM marta.mosca@int.med.unipi.it RI Tincani, Angela/E-7608-2010; Carmona, Loreto/A-2748-2014; OI Carmona, Loreto/0000-0002-4401-2551; Aringer, Martin/0000-0003-4471-8375; Doria, Andrea/0000-0003-0548-4983 FU NIAMS NIH HHS [K24 AR002207] NR 18 TC 32 Z9 32 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD MAY PY 2011 VL 10 IS 7 BP 383 EP 388 DI 10.1016/j.autrev.2010.12.008 PG 6 WC Immunology SC Immunology GA 770XT UT WOS:000291122500003 PM 21224016 ER PT J AU Camandola, S Mattson, MP AF Camandola, Simonetta Mattson, Mark P. TI Aberrant subcellular neuronal calcium regulation in aging and Alzheimer's disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Amyloid; Calcium channels; Cognitive impairment; Endoplasmic reticulum; GLP-1; Mitochondria ID AMYLOID-BETA-PEPTIDE; LIPID-PEROXIDATION PRODUCT; MILD COGNITIVE IMPAIRMENT; GLUCAGON-LIKE PEPTIDE-1; FIBROBLAST-GROWTH-FACTOR; TRANSGENIC MOUSE MODEL; LONG-TERM POTENTIATION; HUMAN CORTICAL-NEURONS; KNOCK-IN MICE; PRECURSOR PROTEIN AB In this mini-review/opinion article we describe evidence that multiple cellular and molecular alterations in Alzheimer's disease (AD) pathogenesis involve perturbed cellular calcium regulation, and that alterations in synaptic calcium handling may be early and pivotal events in the disease process. With advancing age neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular calcium dynamics. Altered proteolytic cleavage of the beta-amyloid precursor protein (APP) in response to the aging process in combination with genetic and environmental factors results in the production and accumulation of neurotoxic forms of amyloid beta-peptide (A beta). A beta undergoes a self-aggregation process and concomitantly generates reactive oxygen species that can trigger membrane-associated oxidative stress which, in turn, impairs the functions of ion-motive ATPases and glutamate and glucose transporters thereby rendering neurons vulnerable to excitotoxicity and apoptosis. Mutations in presenilin-1 that cause early-onset AD increase A beta production, but also result in an abnormal increase in the size of endoplasmic reticulum calcium stores. Some of the events in the neurodegenerative cascade can be counteracted in animal models by manipulations that stabilize neuronal calcium homeostasis including dietary energy restriction, agonists of glucagon-like peptide 1 receptors and drugs that activate mitochondrial potassium channels. Emerging knowledge of the actions of calcium upstream and downstream of A beta provides opportunities to develop novel preventative and therapeutic interventions for AD. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. Published by Elsevier B.V. C1 [Camandola, Simonetta; Mattson, Mark P.] 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 AG000312-08, Z01 AG000313-08, Z01 AG000314-08, Z01 AG000315-08, Z01 AG000317-08] NR 161 TC 53 Z9 55 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAY PY 2011 VL 1813 IS 5 BP 965 EP 973 DI 10.1016/j.bbamcr.2010.10.005 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 770YV UT WOS:000291125300031 PM 20950656 ER PT J AU Hwang, SY Putney, JW AF Hwang, Sung-Yong Putney, James W., Jr. TI Calcium signaling in osteoclasts SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Osteoclasts; Calcium signaling; Calcium channels; Bone ID BONE-RESORPTION; RAT OSTEOCLASTS; RYANODINE RECEPTOR; CYTOSOLIC CA2+; TERMINAL DIFFERENTIATION; OSTEOPROTEGERIN LIGAND; VITRONECTIN RECEPTOR; IMMUNE-SYSTEM; MICE LACKING; KAPPA-B AB It has long been known that many bone diseases, including osteoporosis, involve abnormalities in osteoclastic bone resorption. As a result, there has been intense study of the mechanisms that regulate both the differentiation and bone resorbing function of osteoclast cells. Calcium (Ca(2+)) signaling appears to play a critical role in the differentiation and functions of osteoclasts. Cytoplasmic Ca(2+) oscillations occur during RANKL-mediated osteoclastogenesis. Ca(2+) oscillations provide a digital Ca(2+) signal that induces osteoclasts to up-regulate and autoamplify nuclear factor of activated T cells cl (NFATc1), a Ca(2+)/calcineurin-dependent master regulator of osteoclastogenesis. Here we review previous studies on Ca(2+) signaling in osteoclasts as well as recent breakthroughs in understanding the basis of RANKL-induced Ca(2+) oscillations, and we discuss possible molecular players in this specialized Ca(2+) response that appears pivotal for normal bone function. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. (C) 2010 Published by Elsevier B.V. C1 [Hwang, Sung-Yong; Putney, James W., Jr.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov FU Intramural NIH HHS [Z01 ES090087-12] NR 63 TC 32 Z9 35 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAY PY 2011 VL 1813 IS 5 BP 979 EP 983 DI 10.1016/j.bbamcr.2010.11.002 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 770YV UT WOS:000291125300033 PM 21075150 ER PT J AU Yewdell, JW Lacsina, JR Rechsteiner, MC Nicchitta, CV AF Yewdell, Jonathan W. Lacsina, Joshua R. Rechsteiner, Martin C. Nicchitta, Christopher V. TI Out with the old, in with the new? Comparing methods for measuring protein degradation SO CELL BIOLOGY INTERNATIONAL LA English DT Review DE GPSP; metabolic labelling; protein degradation; proteolysis; proteostasis; pulse-chase; SILAC ID NEWLY SYNTHESIZED PROTEINS; MAMMALIAN-CELLS; RIBOSOMAL-PROTEINS; RAPID DEGRADATION; BACTERIAL-CELLS; LIVED PROTEINS; HELA-CELLS; STABILITY; FIBROBLASTS; HYPOTHESIS AB Protein degradation is a critical factor in controlling cellular protein abundance. Here, we compare classical methods for determining protein degradation rates to a novel GFP (green fluorescent protein) fusion protein based method that assesses the intrinsic stability of cloned cDNA library products by flow cytometry [Yen et al. (2008) Science 322, 918]. While no method is perfect, we conclude that chimeric gene reporter approaches, though powerful, should be applied cautiously, due principally to OFF (or other reporter tag) interference with protein organelle targeting or incorporation into macromolecular assemblies, both of which cause spuriously high degradation rates. C1 [Yewdell, Jonathan W.] NIAID, Cell Biol Sect, Viral Dis Lab, Bethesda, MD 20892 USA. [Lacsina, Joshua R.; Nicchitta, Christopher V.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [Lacsina, Joshua R.; Nicchitta, Christopher V.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Rechsteiner, Martin C.] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA. RP Yewdell, JW (reprint author), NIAID, Cell Biol Sect, Viral Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIAID Division of Intramural Research; National Institutes of Health [GM077382, NS042892] FX Work in the authors' laboratory is supported by the NIAID Division of Intramural Research (to J.Y.) and the National Institutes of Health [grant numbers GM077382 (to C.N.), NS042892 (to MR.)]. NR 42 TC 32 Z9 32 U1 3 U2 32 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD MAY PY 2011 VL 35 IS 5 BP 457 EP 462 DI 10.1042/CBI20110055 PG 6 WC Cell Biology SC Cell Biology GA 774FD UT WOS:000291367500007 PM 21476986 ER PT J AU Palena, C Fernando, RI Litzinger, MT Hamilton, DH Huang, B Schlom, J AF Palena, Claudia Fernando, Romaine I. Litzinger, Mary T. Hamilton, Duane H. Huang, Bruce Schlom, Jeffrey TI Strategies to target molecules that control the acquisition of a mesenchymal-like phenotype by carcinoma cells SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE metastasis; epithelial-to-mesenchymal transition; EMT; cancer vaccines; Brachyury ID RESISTANT PROSTATE-CANCER; E-CADHERIN EXPRESSION; TUMOR PROGRESSION; TRANSCRIPTIONAL REPRESSOR; EPITHELIAL PLASTICITY; THERAPEUTIC TARGET; CERVICAL-CANCER; BREAST CANCERS; UP-REGULATION; BETA-CATENIN AB The switch of carcinoma cells from an epithelial to a mesenchymal-like phenotype, via a process designated 'epithelial-to-mesenchymal transition (EMT),' has been recognized as a relevant step in the metastasis of solid tumors. Additionally, this phenotypic switch of carcinoma cells has been associated with the acquisition of tumor resistance mechanisms that reduce the antitumor effects of radiation, chemotherapy and some small-molecule-targeted therapies. As multiple signaling pathways and transcriptional regulators that play a role in this phenotypic switch are being identified, novel strategies can be designed to specifically target tumor cells with this metastatic and resistant phenotype. In particular, this review focuses on the potential use of cancer vaccine strategies to target tumor cells that exhibit a mesenchymal-like phenotype, with an emphasis on the characterization of a novel tumor antigen, Brachyury, which we have identified as a critical regulator of EMT in human cancer cells. C1 [Palena, Claudia; Fernando, Romaine I.; Litzinger, Mary T.; Hamilton, Duane H.; Huang, Bruce; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX The authors thank Debra Weingarten for her editorial assistance in the preparation of this manuscript. The work was supported by Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 82 TC 19 Z9 19 U1 0 U2 3 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD MAY PY 2011 VL 236 IS 5 BP 537 EP 545 DI 10.1258/ebm.2011.010367 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 773QX UT WOS:000291324600005 PM 21427233 ER PT J AU Jochems, C Schlom, J AF Jochems, Caroline Schlom, Jeffrey TI Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE tumor immune infiltrate; T-cells; cancer prognosis; colon carcinoma; carcinoma ID CD8(+) T-CELLS; LONG-TERM SURVIVAL; HUMAN COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; HEPATOCELLULAR-CARCINOMA; DENDRITIC CELLS; CLINICAL-SIGNIFICANCE; FAVORABLE PROGNOSIS; PROSTATE-CANCER; OVARIAN-CANCER AB Numerous studies have now documented a link between the immune infiltrate in several human carcinoma types and prognosis and response to therapy. The most comprehensive of these studies were in colorectal cancer with similar conclusions by numerous groups. Analyses of immune infiltrate of several other carcinoma types also showed general correlations between immune infiltrate and prognosis, but with some conflicting results. This review will attempt to summarize the current state of this field and point out what factors may be responsible for some of the conflicting findings. Nonetheless, the breadth of reports drawing similar conclusions for some cancer cell types leads one to more seriously consider the link between immune cell infiltrate and tumor prognosis and/or response to therapy, and the potential for combining conventional cancer therapy with active immunotherapy employing therapeutic cancer vaccines. C1 [Jochems, Caroline; Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX The authors thank Debra Weingarten for her editorial assistance in the preparation of this manuscript. The work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 78 TC 76 Z9 77 U1 0 U2 5 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD MAY PY 2011 VL 236 IS 5 BP 567 EP 579 DI 10.1258/ebm.2011.011007 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 773QX UT WOS:000291324600008 PM 21486861 ER PT J AU Ahmad, I Balasubramanian, S Del Debbio, CB Parameswaran, S Katz, AR Toris, C Fariss, RN AF Ahmad, Iqbal Balasubramanian, Sudha Del Debbio, Carolina B. Parameswaran, Sowmya Katz, Allen R. Toris, Carol Fariss, Robert N. TI Regulation of Ocular Angiogenesis by Notch Signaling: Implications in Neovascular Age-Related Macular Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-VESSEL FORMATION; CHOROIDAL NEOVASCULARIZATION; VASCULAR DEVELOPMENT; EMBRYONIC LETHALITY; TUMOR ANGIOGENESIS; STEM-CELLS; VEGF; RECEPTOR; MICE AB PURPOSE. Wet age-related macular degeneration (AMD), which accounts for most AMD-related vision loss, is characterized by choroidal neovascularization (CNV). The underlying mechanism of CNV is poorly understood, but evidence indicates pathologic recruitment of normal angiogenic signaling pathways such as the VEGF pathway. Recent evidence suggests that the VEGF pathway regulates angiogenesis in concert with Notch signaling. Here, the authors examined the role of Notch signaling in CNV in the backdrop of Notch signaling-mediated regulation of retinal angiogenesis. METHODS. Choroid sclera complexes, after laser-induced CNV, were examined for changes in CNV lesion volume and in proangiogenic and antiangiogenic gene expression after perturbation in Notch signaling. Retinal vessels and angiogenic gene expression in retinal endothelial cells were analyzed in postnatal rats after perturbations in Notch signaling. Notch signaling was activated and inhibited by intravitreal or systemic injection of Jagged1 peptide and gamma secretase inhibitor DAPT, respectively. RESULTS. The authors demonstrated that activation of the canonical Notch pathway reduced the volume of CNV lesions as it attenuated the development of postnatal retinal vasculature. In contrast, inhibition of the Notch pathway exacerbated CNV lesions as it led to the development of hyperdense retinal vasculature. The authors also identified genes associated with proangiogenesis (Vegfr2, Ccr3, and Pdgfb) and antiangiogenesis (Vegfr1 and Unc5b) as targets of Notch signaling-mediated vascular homeostasis, the disruption of which might underlie CNV. CONCLUSIONS. This study suggests that Notch signaling is a key regulator of CNV and thus a molecular target for therapeutic intervention in wet AMD. (Invest Ophthalmol Vis Sci. 2011;52: 2868-2878) DOI:10.1167/iovs.10-6608 C1 [Ahmad, Iqbal; Balasubramanian, Sudha; Del Debbio, Carolina B.; Parameswaran, Sowmya; Katz, Allen R.; Toris, Carol] Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA. [Fariss, Robert N.] NEI, Biol Imaging Core Unit, Bethesda, MD 20892 USA. RP Ahmad, I (reprint author), Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA. EM iahmad@unmc.edu FU Lincy Foundation; Pearson Foundation; Nebraska Department of Health and Human Services; Research to Prevent Blindness FX Supported by the Lincy Foundation, the Pearson Foundation, the Nebraska Department of Health and Human Services, and Research to Prevent Blindness. NR 57 TC 25 Z9 29 U1 0 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 2868 EP 2878 DI 10.1167/iovs.10-6608 PG 11 WC Ophthalmology SC Ophthalmology GA 770PN UT WOS:000291100800002 PM 21228388 ER PT J AU Shen, DF Cao, XG Zhao, L Tuo, JS Wong, WT Chan, CC AF Shen, Defen Cao, Xiaoguang Zhao, Lian Tuo, Jingsheng Wong, Wai T. Chan, Chi-Chao TI Naloxone Ameliorates Retinal Lesions in Ccl2/Cx3cr1 Double-Deficient Mice via Modulation of Microglia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INDUCED PHOTORECEPTOR DEGENERATION; MACULAR DEGENERATION; NITRIC-OXIDE; NEURODEGENERATIVE DISEASES; THERAPEUTIC INTERVENTION; INTRAOCULAR-PRESSURE; SUBRETINAL MICROGLIA; ACTIVATED MICROGLIA; PARKINSONS-DISEASE; OPIOID RECEPTOR AB PURPOSE. The role of naloxone, an opioid receptor antagonist, on microglial inhibition and neuroprotective effects has been reported in lipopolysaccharide (LPS)-induced neurodegeneration and light-induced photoreceptor degeneration. The authors evaluated the effects of naloxone on Ccl2(-/-)/Cx3cr1(-/-) (DKO) mice, a murine model of age-related macular degeneration (AMD). METHODS. Two-month-old DKO and wild-type controls were given daily intraperitoneal injections of naloxone or PBS for 2 months. Animals were examined monthly by funduscopy. Ocular tissue was analyzed histologically and in retinal flat mount preparations. Ocular A2E was measured using HPLC. Quantitative RT-PCR analyzed TNF-alpha, IL-1 beta, IL-10 and TLR4 transcripts in the DKO eyes and LPS activated culture microglial cells. Serum nitrite was measured using Griess colorimetric reaction. RESULTS. Naloxone ameliorated the clinical progression and severity of retinal lesions in the DKO mice compared with those of untreated controls. Histopathology also showed less focal retinal degeneration in the treated DKO mice than in controls. The aggregation of microglia in the outer retina in DKO mice was significantly reduced in naloxone-treated animals compared with control untreated DKO. Ocular TNF-alpha, IL-1 beta, and TLR4 transcripts and A2E were significantly lower in naloxone-treated DKO animals and cultured microglial cells than in controls, as were serum nitrite levels. CONCLUSIONS. Naloxone significantly reduces the progress of retinal lesions in DKO mice. Naloxone modulates microglia accumulation and activation at the site of retinal degeneration, which may be mediated by inhibition of the proinflammatory molecules of NO, TNF-alpha, and IL-beta. The potential therapeutic effects of naloxone on retinal degeneration, including AMD, warrants further investigation. (Invest Ophthalmol Vis Sci. 2011;52:2897-2904) DOI:10.1167/iovs.10-6114 C1 [Shen, Defen; Cao, Xiaoguang; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Zhao, Lian; Wong, Wai T.] NEI, Unit Neuronal & Glial Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. [Cao, Xiaoguang] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI Wong, Wai/B-6118-2017; OI Wong, Wai/0000-0003-0681-4016; Tuo, Jingsheng/0000-0002-1372-7810 FU National Eye Institute FX Supported by the National Eye Institute Intramural Research Program. NR 55 TC 19 Z9 20 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 2897 EP 2904 DI 10.1167/iovs.10-6114 PG 8 WC Ophthalmology SC Ophthalmology GA 770PN UT WOS:000291100800005 PM 21245403 ER PT J AU Murali, D Kawaguchi-Niida, M Deng, CX Furuta, Y AF Murali, Deepa Kawaguchi-Niida, Motoko Deng, Chu-Xia Furuta, Yasuhide TI Smad4 Is Required Predominantly in the Developmental Processes Dependent on the BMP Branch of the TGF-beta Signaling System in the Embryonic Mouse Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BONE MORPHOGENETIC PROTEINS; PROGRAMMED CELL-DEATH; PRIMORDIAL GERM-CELLS; AXON GUIDANCE; HOMEOBOX GENE; CHICK-EMBRYO; OPTIC CUP; EXPRESSION; EYE; DISTINCT AB PURPOSE. The present study was aimed at defining developmental roles of Smad4, a key mediator of the TGF-beta superfamily signaling system, in the embryonic mouse retina. METHODS. Using a Cre/loxP-mediated conditional gene targeting approach, Smad4 gene function was deleted from the embryonic mouse retina. Mutant phenotypes were morphologically and molecularly examined. RESULTS. Loss of Smad4 in the developing retina led to varying degrees of microphthalmia at birth, presumably because of elevated apoptosis observed transiently at embryonic day 12.5 in the developing retina. This was also associated with an apparent delay in accumulation of retinal ganglion cells. Smad4 conditional mutants also exhibited alterations of retinal spatial patterning along the dorsal-ventral axis, consistent with a known function of BMP signaling in the embryonic retina. However, despite a known role for BMP signaling in retinal cell survival, proliferation, and differentiation, Smad4 mutant retinal progenitor cells were capable of maintaining growth and neurogenesis throughout embryonic development. We also found that the loss of Smad4 led to abnormal targeting of retinal ganglion cell axons to the optic nerve head, a phenotype consistent with reduced BMP signaling in the developing retina. CONCLUSIONS. These results suggest that Smad4 is essential for a subset of, but not all, TGF-beta/BMP-dependent developmental processes in the embryonic retina. In addition, genetic requirements for Smad4 in the embryonic retina are evident predom inantly in the developmental events regulated by the BMP branch of the TGF-beta signaling pathway. (Invest Ophthalmol Vis Sci. 2011;52:2930-2937) DOI:10.1167/iovs.10-5940 C1 [Murali, Deepa; Kawaguchi-Niida, Motoko; Furuta, Yasuhide] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Furuta, Yasuhide] Univ Texas MD Anderson Canc Ctr, Ctr Stem Cell & Dev Biol, Houston, TX 77030 USA. [Furuta, Yasuhide] Univ Texas MD Anderson Canc Ctr, Ctr Genet & Genom, Houston, TX 77030 USA. [Murali, Deepa; Furuta, Yasuhide] Univ Texas Houston, Grad Sch Biomed Sci Houston, Program Genes & Dev, Houston, TX USA. [Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Furuta, Y (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM yfuruta@mdanderson.org RI deng, chuxia/N-6713-2016 FU National Institutes of Health [EY013128, CA16672, EY010608]; American Heart Association [055037Y]; UT MD Anderson Cancer Center FX Supported by National Institutes of Health Grants EY013128 (YF), CA16672 (MD Anderson Cancer Center), and EY010608 (UT Health Sciences Center at Houston); American Heart Association Grant 055037Y (YF); and Center for Stem Cells and Developmental Biology pilot grant of UT MD Anderson Cancer Center (YF). NR 59 TC 3 Z9 3 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 2930 EP 2937 DI 10.1167/iovs.10-5940 PG 8 WC Ophthalmology SC Ophthalmology GA 770PN UT WOS:000291100800010 PM 21273545 ER PT J AU Liu, MM Agron, E Chew, E Meyerle, C Ferris, FL Chan, CC Tuo, JS AF Liu, Melissa M. Agron, Elvira Chew, Emily Meyerle, Catherine Ferris, Frederick L., III Chan, Chi-Chao Tuo, Jingsheng TI Copy Number Variations in Candidate Genes in Neovascular Age-Related Macular Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID REAL-TIME PCR; COMPLEMENT FACTOR-H; PARKINSONS-DISEASE; HUMAN GENOME; HAN CHINESE; POLYMORPHISMS; EXPRESSION; RISK; CFH; NUCLEOTIDE AB PURPOSE. The pathogenesis of age-related macular degeneration (AMD) is strongly influenced by genetic factors, and single nucleotide polymorphisms have been consistently linked to AMD. Copy number variation (CNV), or variation in the number of copies of a particular segment of DNA, may also contribute to AMD pathogenesis. This study evaluated CNVs in candidate genes that have been reported to be linked to AMD. METHODS. Study participants were 131 patients with neovascular AMD and 103 elderly persons without AMD who were evaluated by retinal specialists at the National Eye Institute. DNA was collected from peripheral whole blood, and duplex RT-PCR based copy number (CN) assays were performed for the genes CCR3, CFH, CX3CR1, ERCC6, HTRA1, and VEGF. Quantitative CNs (CN = 0, 1, 2, or 3+) were determined. RESULTS. Novel CNVs were discovered in CCR3, CX3CR1, and ERCC6. The unadjusted data suggested that CN = 3+ for CX3CR1 might be mildly protective against AMD, but this trend did not persist after adjustment for age. AMD patients appeared to have an elevated mean CFH CN relative to controls (2.13 [95% confidence interval (CI), 2.05-2.21] vs. 2.01 [95% CI, 1.92-2.09 copies]; P = 0.05). No significant associations between CNV and AMD were observed for the remaining genes. CONCLUSIONS. The methods described are suitable for quantitative characterization of CNV in candidate genes. The authors identified CNVs in AMD-associated genes but did not find strong evidence for a link with neovascular AMD. (Invest Ophthalmol Vis Sci. 2011;52:3129-3135) DOI:10.1167/iovs.10-6735 C1 [Liu, Melissa M.; Chan, Chi-Chao; Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Agron, Elvira; Chew, Emily; Meyerle, Catherine; Ferris, Frederick L., III] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Liu, Melissa M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Tuo, JS (reprint author), 10-10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM tuoj@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU National Eye Institute; American Health Assistance Foundation [M2007037] FX Supported by the National Eye Institute Intramural Research Program and American Health Assistance Foundation Grant M2007037. NR 36 TC 16 Z9 16 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 3129 EP 3135 DI 10.1167/iovs.10-6735 PG 7 WC Ophthalmology SC Ophthalmology GA 770PN UT WOS:000291100800035 PM 21273533 ER PT J AU Bull, ND Johnson, TV Welsapar, G DeKorver, NW Tomarev, SI Martin, KR AF Bull, Natalie D. Johnson, Thomas V. Welsapar, Guncha DeKorver, Nicholas W. Tomarev, Stanislav I. Martin, Keith R. TI Use of an Adult Rat Retinal Explant Model for Screening of Potential Retinal Ganglion Cell Neuroprotective Therapies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; GLYCATION END-PRODUCTS; APOPTOSIS IN-VITRO; II TYPE-1 RECEPTOR; EXPERIMENTAL GLAUCOMA; OPTIC-NERVE; PROTEIN EXPRESSION; TISSUE-CULTURE; AMACRINE CELLS; MOUSE RETINA AB PURPOSE. To validate an established adult organotypic retinal explant culture system for use as an efficient medium-throughput screening tool to investigate novel retinal ganglion cell (RGC) neuroprotective therapies. METHODS. Optimal culture conditions for detecting RGC neuroprotection in rat retinal explants were identified. Retinal explants were treated with various recognized, or purported, neuroprotective agents and cultured for either 4 or 7 days ex vivo. The number of cells surviving in the RGC layer (RGCL) was quantified using histologic and immunohistochemical techniques, and statistical analyses were applied to detect neuroprotective effects. RESULTS. The ability to replicate previously reported in vivo RGC neuroprotection in retinal explants was verified by demonstrating that caspase inhibition, brain-derived neurotrophic factor treatment, and stem cell transplantation all reduced RGCL cell loss in this model. Further screening of potential neuroprotective pharmacologic agents demonstrated that betaxolol, losartan, tafluprost, and simvastatin all alleviated RGCL cell loss in retinal explants, supporting previous reports. However, treatment with brimonidine did not protect RGCL neurons from death in retinal explant cultures. Explants cultured for 4 days ex vivo proved most sensitive for detecting neuroprotection. CONCLUSIONS. The current adult rat retinal explant culture model offers advantages over other models for screening potential neuroprotective drugs, including maintenance of neurons in situ, control of environmental conditions, and dissociation from other factors such as intraocular pressure. Verification that neuroprotection by previously identified RGC-protective therapies could be replicated in adult retinal explant cultures suggests that this model could be used for efficient medium-throughput screening of novel neuroprotective therapies for retinal neurodegenerative disease. (Invest Ophthalmol Vis Sci. 2011;52:3309-3320) DOI:10.1167/iovs.10-6873 C1 [Bull, Natalie D.; Johnson, Thomas V.; Welsapar, Guncha; Martin, Keith R.] Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 0PY, England. [Martin, Keith R.] Univ Cambridge, Dept Ophthalmol, Cambridge CB2 0PY, England. [Martin, Keith R.] Univ Cambridge, Cambridge NIHR Biomed Res Ctr, Cambridge CB2 0PY, England. [Johnson, Thomas V.; DeKorver, Nicholas W.; Tomarev, Stanislav I.] NEI, Mol Mech Glaucoma Sect, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. [Johnson, Thomas V.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Martin, KR (reprint author), Univ Cambridge, Cambridge Ctr Brain Repair, Forvie Site,Robinson Way, Cambridge CB2 0PY, England. EM krgm2@cam.ac.uk RI Johnson, Thomas/C-9351-2011; OI Johnson, Thomas/0000-0002-5372-5457; Ekheden, Isabella/0000-0003-0445-6630 FU Cambridge University Hospitals NHS Foundation Trust; Jukes Glaucoma Research Fund; Prevention of Blindness Society of Metropolitan Washington; National Eye Institute; Fight for Sight UK; National Institutes of Health; Johns Hopkins Medical Scientist Training Program/National Institutes of Health [T32-GM007309] FX Supported by funding from the Cambridge University Hospitals NHS Foundation Trust; the Jukes Glaucoma Research Fund; the Prevention of Blindness Society of Metropolitan Washington; the National Eye Institute Intramural Research Program; Fight for Sight UK (NDB); National Institutes of Health OxCam Scholarship (TVJ); and the Johns Hopkins Medical Scientist Training Program/National Institutes of Health Grant T32-GM007309 (TVJ). NR 66 TC 30 Z9 31 U1 0 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 3309 EP 3320 DI 10.1167/iovs.10-6873 PG 12 WC Ophthalmology SC Ophthalmology GA 770PN UT WOS:000291100800058 PM 21345987 ER PT J AU Vogelzangs, N Beekman, ATF Boelhouwer, IG Bandinelli, S Milaneschi, Y Ferrucci, L Penninx, BWJH AF Vogelzangs, Nicole Beekman, Aartjan T. F. Boelhouwer, Ingrid G. Bandinelli, Stefania Milaneschi, Yuri Ferrucci, Luigi Penninx, Brenda W. J. H. TI Metabolic Depression: A Chronic Depressive Subtype? Findings From the InCHIANTI Study of Older Persons SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CORONARY-HEART-DISEASE; TREATMENT PANEL-III; C-REACTIVE PROTEIN; MIDDLE-AGED WOMEN; BODY-COMPOSITION; ANXIETY NESDA; YOUNG-ADULTS; LARGE-COHORT; LATE-LIFE; SYMPTOMS AB Objective: Several studies report a cross-sectional association between metabolic syndrome and depression. Possibly, metabolic syndrome promotes onset or chronicity of depression. However, such a longitudinal link has not yet been confirmed. This study examines whether metabolic syndrome or its components are associated with onset and chronicity of depression. Method: Secondary analyses were performed on data from 823 participants (>= 65 years of age) in the InCHIANTI study, a prospective, population-based cohort study of older persons. From 1998 to 2000, the study sample was randomly selected from the population registry of 2 sites in Italy using a multistage stratified sampling method. Baseline data collection consisted of a home interview and a medical evaluation at the study clinic. Follow-up for each participant occurred after 3 years and 6 years. Metabolic syndrome at baseline was defined as >= 3 of the following: abdominal obesity, high triglycerides, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale (CES-D) at baseline and after 3 and 6 years. Sample characteristics were compared between persons with and without depression at baseline using chi(2) and t statistics. Logistic regression analyses were conducted separately in persons with and without depression at baseline to test whether metabolic syndrome at baseline could predict onset and chronicity of depression at follow-up. Results: At baseline, 235 persons had metabolic syndrome, and 168 were depressed (CES-D score >= 20). Among persons not depressed at baseline, 26.0% developed depression. Higher waist circumference increased the odds of depression onset (adjusted OR per SD increase =1.28; 95% CI, 1.05-1.56), but there was no association between other metabolic syndrome components and onset of depression. Among persons depressed at baseline, depression had a chronic character in 69.0% of persons without and 88.5% of persons with metabolic syndrome. Metabolic syndrome was associated with an almost 3-fold increase in the odds of chronicity of depression (adjusted OR = 2.66; 95% CI, 1.01-7.00), with almost every metabolic syndrome component contributing to this association. Conclusion: In late life, waist circumference, but not metabolic syndrome, predicted onset of depression. Depressed persons with metabolic syndrome were more likely to have persistent or recurrent depression. The latter may suggest that depression with metabolic abnormalities, which could be labeled metabolic depression, identifies a chronic subtype of depression. J Clin Psychiatry 2011;72(5):598-604 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Vogelzangs, Nicole; Beekman, Aartjan T. F.; Boelhouwer, Ingrid G.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands. [Vogelzangs, Nicole; Beekman, Aartjan T. F.; Boelhouwer, Ingrid G.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 HL Amsterdam, Netherlands. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil, Florence, Italy. [Milaneschi, Yuri; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Milaneschi, Yuri] Tuscany Hlth Reg Agcy, Florence, Italy. RP Vogelzangs, N (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Psychiat, AJ Ernststr 1187, NL-1081 HL Amsterdam, Netherlands. EM n.vogelzangs@vumc.nl FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [1R01-HL972972]; Italian Ministry of Health [ICS 110.1/RS97.71]; US National Institute on Aging, Bethesda, Maryland [263 MD 916413, 263 MD 821336] FX These data analyses were supported through grant 1R01-HL972972 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. The original InCHIANTI study was supported as a targeted project (ICS 110.1/RS97.71) by the Italian Ministry of Health and was supported in part by the US National Institute on Aging, Bethesda, Maryland (263 MD 916413 and 263 MD 821336). NR 52 TC 34 Z9 35 U1 1 U2 17 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 MAY PY 2011 VL 72 IS 5 BP 598 EP 604 DI 10.4088/JCP.10m06559 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600005 PM 21535996 ER PT J AU Grkovic, T Blees, JS Colburn, NH Schmid, T Thomas, CL Henrich, CJ McMahon, JB Gustafson, KR AF Grkovic, Tanja Blees, Johanna S. Colburn, Nancy H. Schmid, Tobias Thomas, Cheryl L. Henrich, Curtis J. McMahon, James B. Gustafson, Kirk R. TI Cryptocaryols A-H, alpha-Pyrone-Containing 1,3-Polyols from Cryptocarya sp Implicated in Stabilizing the Tumor Suppressor Pdcd4 SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID NF-KAPPA-B; TRANSFORMATION SUPPRESSOR; EXPRESSION; TRANSLATION; DEGRADATION; CHINENSIS; INHIBITOR; CARCINOMA; INVASION; PROTEIN AB A high-throughput cell-based reporter assay designed to identify small-molecule stabilizers of the tumor suppressor Pdcd4 was used to screer. extracts in the NCI Natural Products Repository. Bioassay-guided fractionation of an extract from a Papua New Guinea collection of the tropical tree Cryptocarya sp. provided a series of new 5,6-dihydro-alpha-pyrone-containing 1,3-polyols (1-8), named cryptocaryols A-H. Their structures were assigned from a combination of NMR, MS, and CD studies in conjunction with NMR database comparisons. Compounds 1-8 were found to rescue Pdcd4 from TPA-induced degradation with EC50 concentrations that ranged from 1.3 to 4.9 mu M. C1 [Grkovic, Tanja; Thomas, Cheryl L.; Henrich, Curtis J.; McMahon, James B.; Gustafson, Kirk R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Blees, Johanna S.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. [Blees, Johanna S.; Schmid, Tobias] Goethe Univ Frankfurt, Inst Biochem 1, Fac Med, D-60590 Frankfurt, Germany. [Henrich, Curtis J.] NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Gustafson, KR (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM gustafki@mail.nih.gov RI Grkovic, Tanja/B-8874-2012 FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We thank D. Newman (NCI) and T. McCloud (SAIC-Frederick) for the plant extract, and M. Dyba and S. Tarasov (Biophysics Resource, SBL, NCI-Frederick) for assistance with the HRLCMS studies. This research was supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. This project was also funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 26 TC 24 Z9 24 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 2011 VL 74 IS 5 BP 1015 EP 1020 DI 10.1021/np100918z PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 770ZV UT WOS:000291127900015 PM 21539301 ER PT J AU Van Wyk, AWW Zuck, KM Mckee, TC AF Van Wyk, Albert W. W. Zuck, Karina M. Mckee, Tawnya C. TI Lithothamnin A, the First Bastadin-like Metabolite from the Red Alga Lithothamnion fragilissimum SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID SPONGE IANTHELLA-BASTA; PAPUA-NEW-GUINEA; ENDOTHELIAL-CELLS; MARINE; QUADRANGULATA; DERIVATIVES; MODULATORS; CALCAREUM; COMPLEX; FKBP12 AB Lithothamnin A (1) is a new bastadin-like metabolite and represents the first report of this class of molecules from the red alga Lithothamnion fragilissimum. Lithothamnin A contains several novel structural features that distinguish it from other bastadins. These unique structural features include novel aromatic substitution patterns and the presence of a meta-meta linkage between aromatic rings, in addition to the meta-para linkage seen in the bastadins. Lithothamnin A is modestly cytotoxic in a panel of six human tumor cell lines. C1 [Van Wyk, Albert W. W.; Zuck, Karina M.; Mckee, Tawnya C.] NCI, Ctr Canc Res, Mol Discovery Program, Mol Targets Lab, Frederick, MD 21701 USA. RP Mckee, TC (reprint author), NCI, Ctr Canc Res, Mol Discovery Program, Mol Targets Lab, Frederick, MD 21701 USA. EM mckeeta@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This project has been supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. We thank D. Newman (Natural Products Branch) for coordinating collections, T. McCloud for extractions, L. Pannell and R. Ratnayake for mass spectra, T. Grkovic for NMR and MS-MS studies, and T. Ransom and J. Wilson for cytotoxicity assays. We also thank the Biophysics Resource of the Structural Biophysics Laboratory for providing technical assistance with QTOF LC-MS-MS experiments. NR 23 TC 7 Z9 7 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 2011 VL 74 IS 5 BP 1275 EP 1280 DI 10.1021/np1006795 PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 770ZV UT WOS:000291127900054 PM 21488653 ER PT J AU Palmquist, AEL Upton, R Lee, S Panter, AT Hadley, DW Koehly, LM AF Palmquist, Aunchalee E. L. Upton, Rachel Lee, Seungjin Panter, Abby T. Hadley, Don W. Koehly, Laura M. TI Beliefs About Cancer and Diet among Those Considering Genetic Testing for Colon Cancer SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE health beliefs; dietary beliefs; cancer prevention; hereditary cancer; Lynch Syndrome ID NONPOLYPOSIS COLORECTAL-CANCER; CULTURAL CONSENSUS THEORY; BREAST-CANCER; RISK; PREVENTION; HEALTH AB Objective: To assess beliefs about the role of diet in cancer prevention among individuals considering genetic testing for Lynch Syndrome. Design: Family-centered, cascade recruitment; baseline assessment of a longitudinal study. Setting: Clinical research setting. Participants: Participants were 390 persons, ages 18 and older, including persons with a Lynch Syndrome-associated cancer and suspected of carrying a disease causing mutation, and relatives at risk for inheriting a previously identified mutation. Main Outcome Measures: Assess clustering of beliefs about the role of diet in cancer prevention and predictors of class membership. Analysis: Confirmatory factor analysis; 2-class factor mixture model with binary indicators; multilevel regression analyses, individuals nested within families. Results: Women endorsed a relationship between diet and cancer prevention more often than men (P < .01). A 2-class model was used where Class 1 indicated less likely to link cancer to diet, and Class 2 indicated more likely. Factors associated with increased odds of membership in Class 1 expressed belief that nothing can prevent cancer (P < .01) and fate attribution (P < .01); Class 2 mentioned personal cancer history (P < .05) and genetic knowledge (P < .01). Conclusions and Implications: Identifying factors associated with a belief in cancer prevention through dietary behaviors can inform targeted interventions. C1 [Palmquist, Aunchalee E. L.] Yale Univ, MacMillan Ctr, New Haven, CT 06520 USA. [Upton, Rachel; Lee, Seungjin; Panter, Abby T.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Hadley, Don W.; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Palmquist, AEL (reprint author), Yale Univ, MacMillan Ctr, POB 208206, New Haven, CT 06520 USA. EM aunchalee.palmquist@yale.edu FU NIH [95-HG-0165]; NNMC [NNMC.1995.0045]; National Human Genome Research Institute; National Cancer Institute of the National Institutes of Health in Bethesda, MD [Z01HG000059-11] FX This study was supported by the NIH (protocol #95-HG-0165) and the NNMC (protocol # NNMC.1995.0045) and approved by the appropriate NIH and NNMC Institutional Review Boards. It was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Cancer Institute of the National Institutes of Health in Bethesda, MD [Z01HG000059-11:PI Koehly]. This research was conducted as part of the first author's postdoctoral work in the Social and Behavioral Research Branch of the National Human Genome Research Institute. NR 29 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 EI 1878-2620 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAY-JUN PY 2011 VL 43 IS 3 BP 150 EP 156 DI 10.1016/j.jneb.2009.12.009 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 772BB UT WOS:000291203300007 PM 21296025 ER PT J AU Robey, RW Lin, B Qiu, J Chan, LLY Bates, SE AF Robey, Robert W. Lin, Bo Qiu, Jean Chan, Leo Li-Ying Bates, Susan E. TI Rapid detection of ABC transporter interaction: Potential utility in pharmacology SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE ABCG2; Methods; MRP1; Fluorescence; P-glycoprotein; ABC transporter ID CANCER RESISTANCE PROTEIN; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; MXR ABCG2; IN-VITRO; EXPRESSION; CHEMOTHERAPY; INHIBITION; DASATINIB AB Introduction: The ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) are known to transport a wide range of structurally diverse compounds. Their high level of expression at the blood-brain, maternal-fetal, and blood-testis barriers as well as their purported roles in oral absorption suggests that ABC transporters play important pharmacologic roles. Methods: We have developed a method to characterize the function and inhibition of ABC transporters using an automated cell counter with fluorescence detection capability. The assay was performed using stably-transfected HEK293 cells expressing P-gp, MRP1, or ABCG2 and examining transport of fluorescent substrates in the presence or absence of known inhibitors and compared to results obtained with a flow cytometer. Fold increase in intracellular fluorescence was then calculated for cells incubated with fluorescent substrate in the absence of inhibitor versus in the presence of inhibitor. Results: Fold increase values obtained either with the cell counter or flow cytometer were comparable for cells expressing either MRP1 or ABCG2; slightly higher fold increase values were observed when cells expressing P-gp were read on a flow cytometer compared to the cell counter. Discussion: The assay described provides an inexpensive detection method to aid in the development of novel ABC transporter inhibitors or to characterize potential drug-drug interactions. Published by Elsevier Inc. C1 [Robey, Robert W.; Bates, Susan E.] NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Lin, Bo; Qiu, Jean; Chan, Leo Li-Ying] Nexcelom Biosci LLC, Lawrence, MA 01843 USA. RP Robey, RW (reprint author), 9000 Rockville Pike,Bldg 10,Rm 13N248, Bethesda, MD 20892 USA. EM robeyr@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This paper is subject to the NIH Public Access Policy. NR 25 TC 22 Z9 24 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8719 J9 J PHARMACOL TOX MET JI J. Pharmacol. Toxicol. Methods PD MAY-JUN PY 2011 VL 63 IS 3 BP 217 EP 222 DI 10.1016/j.vascn.2010.11.003 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 771BC UT WOS:000291131200001 PM 21112407 ER PT J AU Calzone, KA Jenkins, J Prows, CA Masny, A AF Calzone, Kathleen A. Jenkins, Jean Prows, Cynthia A. Masny, Agnes TI ESTABLISHING THE OUTCOME INDICATORS FOR THE ESSENTIAL NURSING COMPETENCIES AND CURRICULA GUIDELINES FOR GENETICS AND GENOMICS SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article DE Competency; Genetics; Genomics; Nursing education ID HEALTH AB The translation of genetics/genomics to clinical care has implications for nurses. The Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics, established by consensus, apply to all registered nurses. Learning outcomes and clinical practice indicators have been developed to provide additional guidance. The Essentials Advisory Group (EAG) established a team to establish the Outcome Indicators. A draft was developed based on published peer-reviewed documents and syllabi. The draft underwent three layers of review: (a) critique by the EAG; (b) review by representatives at a Genetics/Genomics Toolkit for Faculty meeting; and (c) review by workshop attendees of the American Association of Colleges of Nursing's baccalaureate and master's education conferences, followed by EAG's final approval. Outcome Indicators clarify specific knowledge areas and suggest clinical performance indicators for each competency. They provide the foundation to establish a competency-based education repository with outcome indicator mapping matrixes for genetic/genomic education resources. A gap analysis of education resources identified resource deficits, and online unfolding case studies were developed. Outcome Indicators assist the academic and continuing education nurse community to prepare the nursing workforce in genetics/genomics and provide a platform from which to build tools needed to achieve this goal. C1 [Calzone, Kathleen A.] NCI, NIH, Ctr Canc Res, Genet Branch, Gaithersburg, MD 20899 USA. [Jenkins, Jean] NHGRI, NIH, Bethesda, MD 20892 USA. [Prows, Cynthia A.] Childrens Hosp, Med Ctr, Div Patient Serv, Cincinnati, OH 45229 USA. [Prows, Cynthia A.] Childrens Hosp, Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Masny, Agnes] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Calzone, KA (reprint author), NCI, NIH, Ctr Canc Res, Genet Branch, 8901 Wiscinsin Ave,Bldg 8,RM 5101, Gaithersburg, MD 20899 USA. EM calzonek@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 9 TC 11 Z9 11 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 8755-7223 J9 J PROF NURS JI J. Prof. Nurs. PD MAY-JUN PY 2011 VL 27 IS 3 BP 179 EP 191 DI 10.1016/j.profnurs.2011.01.001 PG 13 WC Nursing SC Nursing GA 771UT UT WOS:000291186900009 PM 21596359 ER PT J AU Pietrzak, RH Goldstein, RB Southwick, SM Grant, BF AF Pietrzak, Robert H. Goldstein, Rise B. Southwick, Steven M. Grant, Bridget F. TI Personality disorders associated with full and partial posttraumatic stress disorder in the US population: Results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Posttraumatic stress disorder; Personality disorders; Epidemiology; Comorbidity ID DSM-IV ALCOHOL; COMORBIDITY SURVEY REPLICATION; INTERVIEW SCHEDULE AUDADIS; MAJOR DEPRESSIVE DISORDER; DRUG-USE DISORDERS; AXIS-II DISORDERS; UNITED-STATES; GENERAL-POPULATION; ANXIETY DISORDERS; TRAUMATIC EVENTS AB Background: While it is well known that personality disorders are associated with trauma exposure and PTSD, limited nationally representative data are available on DSM-IV personality disorders that co-occur with posttraumatic stress disorder (PTSD) and partial PTSD. Methods: Face-to-face interviews were conducted with 34,653 adults participating in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Logistic regression analyses controlling for sociodemographics and additional psychiatric comorbidity evaluated associations of PTSD and partial PTSD with personality disorders. Results: Prevalence rates of lifetime PTSD and partial PTSD were 6.4% and 6.6%, respectively. After adjustment for sociodemographic characteristics and additional psychiatric comorbidity, respondents with full PTSD were more likely than trauma controls to meet criteria for schizotypal, narcissistic, and borderline personality disorders (ORs = 2.1-2.5); and respondents with partial PTSD were more likely than trauma controls to meet diagnostic criteria for borderline (OR = 2.0), schizotypal (OR = 1.8), and narcissistic (OR = 1.6) PDs. Women with PTSD were more likely than controls to have obsessive compulsive PD. Women with partial PTSD were more likely than controls to have antisocial PD; and men with partial PTSD were less likely than women with partial PTSD to have avoidant PD. Conclusions: PTSD and partial PTSD are associated with borderline, schizotypal, and narcissistic personality disorders. Modestly higher rates of obsessive compulsive PD were observed among women with full PTSD, and of antisocial PD among women with partial PTSD. Published by Elsevier Ltd. C1 [Pietrzak, Robert H.; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. [Pietrzak, Robert H.; Southwick, Steven M.] VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. [Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Pietrzak, RH (reprint author), Yale Univ, Sch Med, Dept Psychiat, 950 Campbell Ave,151-E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu OI Goldstein, Rise/0000-0002-9603-9473 FU CogState, Inc.; National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institutes of Health, NIAAA FX Dr. Pietrzak receives partial salary support from CogState, Inc., for work which bears no relationship to the present study.; The National Epidemiologic Survey on Alcohol and Related Conditions is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with supplemental support from the National Institute on Drug Abuse. This research was supported in part by the Intramural Program of the National Institutes of Health, NIAAA. Preparation of this report was supported in part by the National Center for Posttraumatic Stress Disorder and a private donation. NR 116 TC 19 Z9 19 U1 5 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAY PY 2011 VL 45 IS 5 BP 678 EP 686 DI 10.1016/j.jpsychires.2010.09.013 PG 9 WC Psychiatry SC Psychiatry GA 771OR UT WOS:000291171100014 PM 20950823 ER PT J AU Cuzick, J DeCensi, A Arun, B Brown, PH Castiglione, M Dunn, B Forbes, JF Glaus, A Howell, A von Minckwitz, G Vogel, V Zwierzina, H AF Cuzick, Jack DeCensi, Andrea Arun, Banu Brown, Powel H. Castiglione, Monica Dunn, Barbara Forbes, John F. Glaus, Agnes Howell, Anthony von Minckwitz, Gunter Vogel, Victor Zwierzina, Heinz TI Preventive therapy for breast cancer: a consensus statement SO LANCET ONCOLOGY LA English DT Review ID LOW-DOSE TAMOXIFEN; HORMONE-REPLACEMENT THERAPY; SURGICAL ADJUVANT BREAST; GENOME-WIDE ASSOCIATION; POSTMENOPAUSAL WOMEN; SUSCEPTIBILITY LOCI; RANDOMIZED-TRIALS; DIABETIC-PATIENTS; CLINICAL-TRIALS; ZOLEDRONIC ACID AB In March, 2010, a group of breast cancer experts met to develop a consensus statement on breast cancer prevention, with a focus on medical and therapeutic interventions. We present the conclusions in this Review. First we agreed that the term chemoprevention is inappropriate and suggested that the term preventive therapy better represents this feature of management. Two selective oestrogen-receptor modulators-tamoxifen and raloadfene-are so far the only medical options approved by the US Food and Drug Administration for preventive therapy. Of these tamoxifen has greater efficacy and can be used in premenopausal women, but raloxifene has fewer side-effects. Two newer drugs in this class, lasofoxifene and arzoxifene, also show efficacy and possibly a better overall risk-benefit profile, but need further assessment. Aromatase inhibitors might be more efficacious, and results of prevention trials are eagerly awaited. Newer agents, notably bisphosphonates and metformin, have shown promise in observational studies and need to be assessed in randomised prevention trials. Other agents, such as aspirin, other non-steroidal anti-inflammatory drugs, COX-2 inhibitors, retinoids, rexinoids, and dietary components have limited effects or are in the early phases of investigation. New contralateral tumours in women with breast cancer might be generally useful as a model for prevention, as has been seen for tamoxifen. If valid such a model would facilitate the design of simpler, cheaper, and better-focused trials for assessing new agents. C1 [Cuzick, Jack] Queen Mary Univ London, Wolfson Inst Prevent Med, Ctr Canc Prevent, London EC1M 6BQ, England. [DeCensi, Andrea] Osped Galliera, Genoa, Italy. [DeCensi, Andrea] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy. [Brown, Powel H.] Univ Texas MD Anderson Canc Ctr, Clin Canc Prevent Dept, Houston, TX 77030 USA. [Castiglione, Monica] Brustzentrum, Zurich, Switzerland. [Castiglione, Monica] Univ Hosp Geneva, Geneva, Switzerland. [Dunn, Barbara] NCI, Basic Prevent Sci Res Grp, Bethesda, MD 20892 USA. [Forbes, John F.] Univ Newcastle, NBN Inst, Calvary Mater Hosp, Dept Surg Oncol, Newcastle, NSW 2300, Australia. [Glaus, Agnes] Tumour & Breast Ctr, St Gallen, Switzerland. [Howell, Anthony] Univ Manchester, Christie Hosp, Sch Canc & Enabling Sci, Breakthrough Breast Canc Res Unit, Manchester, Lancs, England. [Howell, Anthony] Univ Manchester, Christie Hosp, Sch Canc & Enabling Sci, Genesis Prevent Ctr, Manchester, Lancs, England. [Howell, Anthony] Univ S Manchester, Manchester, Lancs, England. [von Minckwitz, Gunter] GBG Forsch GmbH, German Breast Grp, Neu Isenburg, Germany. [Vogel, Victor] Geisinger Med Ctr, Inst Canc, Danville, PA 17822 USA. [Zwierzina, Heinz] Univ Med, Innsbruck, Austria. RP Cuzick, J (reprint author), Queen Mary Univ London, Wolfson Inst Prevent Med, Ctr Canc Prevent, Charterhouse Sq, London EC1M 6BQ, England. EM j.cuzick@qmul.ac.uk OI Howell, Anthony/0000-0002-6233-719X FU AstraZeneca; National Cancer Institute FX JC has received institutional funding and honoraria from AstraZeneca. BA has received funding from the National Cancer Institute and AstraZeneca. JFF has received honoraria from AstraZeneca. AH has received honoraria from AstraZeneca and Novartis. GvM has received institutional funding from AstraZeneca. VV has received consultancy fees from AstraZeneca and Eli Lilly. The other authors declare that they have no conflicts of interest. NR 79 TC 109 Z9 113 U1 2 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2011 VL 12 IS 5 BP 496 EP 503 DI 10.1016/S1470-2045(11)70030-4 PG 8 WC Oncology SC Oncology GA 771FQ UT WOS:000291143000027 PM 21441069 ER PT J AU Hallett, M Rothwell, J AF Hallett, Mark Rothwell, John TI Milestones in Clinical Neurophysiology SO MOVEMENT DISORDERS LA English DT Review DE transcranial magnetic stimulation; electroencephalogram; electromyogram; Parkinson's disease; dystonia ID TRANSCRANIAL MAGNETIC STIMULATION; FOCAL HAND DYSTONIA; HUMAN MOTOR CORTEX; PROGRESSIVE SUPRANUCLEAR PALSY; SPINAL-CORD-INJURY; PARKINSONS-DISEASE; WRITERS CRAMP; ESSENTIAL TREMOR; PROPRIOSPINAL MYOCLONUS; STARTLE REFLEX AB Over the last 25 years, clinical neurophysiology has made many advances in the understanding, diagnosis, and even treatment of different movement disorders. Transcranial magnetic stimulation has been the biggest technical advance. Progress in pathophysiology includes improved knowledge about bradykinesia in Parkinson's disease, loss of inhibition and increased plasticity in dystonia, abnormal startle in hyperekplexia, and various features of psychogenic movement disorders that can aid diagnosis. Studies have been done looking at the use of noninvasive brain stimulation for therapy, but effects are generally small. (C) 2011 Movement Disorder Society C1 [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Rothwell, John] UCL Inst Neurol, London WC1N 3BG, England. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Rm 7D37,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov; j.rothwell@ion.ucl.ac.uk OI Rothwell, John/0000-0003-1367-6467 FU NINDS, NIH FX Dr. Hallett's work is supported by the Intramural Program of NINDS, NIH. NR 101 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2011 VL 26 IS 6 BP 958 EP 967 DI 10.1002/mds.23572 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 774AO UT WOS:000291353900005 PM 21626542 ER PT J AU Pierson, TM Tart, G Adams, D Toro, C Golas, G Tifft, C Gahl, W AF Pierson, Tyler Mark Tart, Gary Adams, David Toro, Camilo Golas, Gretchen Tifft, Cynthia Gahl, William TI Infantile-onset spinal muscular atrophy with respiratory distress-1 diagnosed in a 20-year-old man SO NEUROMUSCULAR DISORDERS LA English DT Article DE SMARD1; IGHMBP2; Neuromuscular degeneration mouse; Motor neuron disease ID TYPE-1 SMARD1; DILATED CARDIOMYOPATHY; TRANSGENIC RESCUE; NMD MOUSE; GENE; IGHMBP2; NEUROPATHY AB Spinal muscular atrophy with respiratory distress (SMARD1) presents within the first 13 months of age with low birth weight, progressive length dependent motor neuropathy, and respiratory failure from diaphragmatic paralysis. SMARD1 is caused by mutations in IGHMBP2, encoding the immunoglobulin p.-binding protein 2. Because of the severity of the disorder, many infantile-onset SMARD1 patients do not live past the first decade of life. This report documents the clinical course of a 20-year-old man diagnosed with SMARD1. Published by Elsevier B.V. C1 [Pierson, Tyler Mark] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Pierson, Tyler Mark; Adams, David; Toro, Camilo; Golas, Gretchen; Tifft, Cynthia; Gahl, William] NIH Off Rare Dis Res & NIIGRI, NIH Undiagnosed Dis Program, Bethesda, MD USA. [Tart, Gary] Pediat NW, Tacoma, WA USA. [Adams, David; Golas, Gretchen; Tifft, Cynthia; Gahl, William] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Pierson, TM (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 35,Room 2A1012,35 Convent Dr,MSC 3705, Bethesda, MD 20892 USA. EM piersonty@ninds.nih.gov FU NIH, National Institutes of Health FX The staff of the Undiagnosed Diseases Program were all instrumental in this work and we thank them for their help and efforts. Additional thanks to Barrington Burnet for critical review of the manuscript. We would like to acknowledge the hard work and generosity of the patient, his family, and his caregivers. TMP, DA, GG, CJT, CT, and WAG were supported by the NIH Undiagnosed Diseases Program, National Institutes of Health. NR 16 TC 13 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD MAY PY 2011 VL 21 IS 5 BP 353 EP 355 DI 10.1016/j.nmd.2011.02.005 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 771YQ UT WOS:000291197000005 PM 21353777 ER PT J AU Cai, Q Davis, ML Sheng, ZH AF Cai, Qian Davis, Matthew L. Sheng, Zu-Hang TI Regulation of axonal mitochondrial transport and its impact on synaptic transmission SO NEUROSCIENCE RESEARCH LA English DT Article DE Mitochondria; Axonal transport; Docking; Synaptic plasticity; Kinesin; Motor adaptor; Anterograde transport; Retrograde transport; Stationary mitochondria; Mitochondrial mobility ID MEMBRANOUS ORGANELLES INVIVO; KINESIN HEAVY-CHAIN; CYTOPLASMIC DYNEIN; DYNACTIN COMPLEX; PROTEIN; DROSOPHILA; NEURONS; MOTOR; SYNAPSES; CALCIUM AB Mitochondria are essential organelles for neuronal survival and play important roles in ATP generation, calcium buffering, and apoptotic signaling. Due to their extreme polarity, neurons utilize specialized mechanisms to regulate mitochondrial transport and retention along axons and near synaptic terminals where energy supply and calcium homeostasis are in high demand. Axonal mitochondria undergo saltatory and bidirectional movement and display complex mobility patterns. In cultured neurons, approximately one-third of axonal mitochondria are mobile, while the rest remain stationary. Stationary mitochondria at synapses serve as local energy stations that produce ATP to support synaptic function. In addition, axonal mitochondria maintain local Ca(2+) homeostasis at presynaptic boutons. The balance between mobile and stationary mitochondria is dynamic and responds quickly to changes in axonal and synaptic physiology. The coordination of mitochondrial mobility and synaptic activity is crucial for neuronal function synaptic plasticity. In this update article, we introduce recent advances in our understanding of the motor-adaptor complexes and docking machinery that mediate mitochondrial transport and axonal distribution. We will also discuss the molecular mechanisms underlying the complex mobility patterns of axonal mitochondria and how mitochondrial mobility impacts the physiology and function of synapses. Published by Elsevier Ireland Ltd. C1 [Cai, Qian; Davis, Matthew L.; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, NIH, Bethesda, MD 20892 USA. RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, NIH, Bldg 35,Room 2B-215,35 Convent Dr, Bethesda, MD 20892 USA. EM shengz@ninds.nih.gov FU NINDS, NIH; NIH Pathway [K99] FX We thank the members of the Sheng lab for helpful discussions. The authors are supported by the Intramural Research Program of NINDS, NIH (Z.-H. Sheng) and the NIH Pathway to Independence Award K99 (Q. Cai). NR 60 TC 32 Z9 32 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD MAY PY 2011 VL 70 IS 1 BP 9 EP 15 DI 10.1016/j.neures.2011.02.005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 771RX UT WOS:000291179500003 PM 21352858 ER PT J AU Dayani, Y Simchen, G Lichten, M AF Dayani, Yaron Simchen, Giora Lichten, Michael TI Meiotic Recombination Intermediates Are Resolved with Minimal Crossover Formation during Return-to-Growth, an Analogue of the Mitotic Cell Cycle SO PLOS GENETICS LA English DT Article ID DOUBLE-STRAND-BREAK; DOUBLE HOLLIDAY JUNCTIONS; BLOOMS-SYNDROME HELICASE; TOPOISOMERASE-III-ALPHA; SACCHAROMYCES-CEREVISIAE; MEIOSIS-I; BUDDING YEAST; CROSSING-OVER; SYNAPTONEMAL COMPLEX; CHROMOSOME SYNAPSIS AB Accurate segregation of homologous chromosomes of different parental origin (homologs) during the first division of meiosis (meiosis I) requires inter-homolog crossovers (COs). These are produced at the end of meiosis I prophase, when recombination intermediates that contain Holliday junctions (joint molecules, JMs) are resolved, predominantly as COs. JM resolution during the mitotic cell cycle is less well understood, mainly due to low levels of inter-homolog JMs. To compare JM resolution during meiosis and the mitotic cell cycle, we used a unique feature of Saccharomyces cerevisiae, return to growth (RTG), where cells undergoing meiosis can be returned to the mitotic cell cycle by a nutritional shift. By performing RTG with ndt80 mutants, which arrest in meiosis I prophase with high levels of interhomolog JMs, we could readily monitor JM resolution during the first cell division of RTG genetically and, for the first time, at the molecular level. In contrast to meiosis, where most JMs resolve as COs, most JMs were resolved during the first 1.5-2 hr after RTG without producing COs. Subsequent resolution of the remaining JMs produced COs, and this CO production required the Mus81/Mms4 structure-selective endonuclease. RTG in sgs1-Delta C795 mutants, which lack the helicase and Holliday junction-binding domains of this BLM homolog, led to a substantial delay in JM resolution; and subsequent JM resolution produced both COs and NCOs. Based on these findings, we suggest that most JMs are resolved during the mitotic cell cycle by dissolution, an Sgs1 helicase-dependent process that produces only NCOs. JMs that escape dissolution are mostly resolved by Mus81/Mms4-dependent cleavage that produces both COs and NCOs in a relatively unbiased manner. Thus, in contrast to meiosis, where JM resolution is heavily biased towards COs, JM resolution during RTG minimizes CO formation, thus maintaining genome integrity and minimizing loss of heterozygosity. C1 [Dayani, Yaron; Lichten, Michael] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Dayani, Yaron; Simchen, Giora] Hebrew Univ Jerusalem, Dept Genet, IL-91904 Jerusalem, Israel. RP Dayani, Y (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM lichten@helix.nih.gov RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; Hebrew University of Jerusalem FX This work was supported by the Intramural Research Program at the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and by a travel grant from the Hebrew University of Jerusalem to YD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 102 TC 29 Z9 29 U1 0 U2 4 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 MAY PY 2011 VL 7 IS 5 AR e1002083 DI 10.1371/journal.pgen.1002083 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 769LI UT WOS:000291014600027 PM 21637791 ER PT J AU Haiman, CA Chen, GK Blot, WJ Strom, SS Berndt, SI Kittles, RA Rybicki, BA Isaacs, WB Ingles, SA Stanford, JL Diver, WR Witte, JS Chanock, SJ Kolb, S Signorello, LB Yamamura, Y Neslund-Dudas, C Thun, MJ Murphy, A Casey, G Sheng, X Wan, P Pooler, LC Monroe, KR Waters, KM Le Marchand, L Kolonel, LN Stram, DO Henderson, BE AF Haiman, Christopher A. Chen, Gary K. Blot, William J. Strom, Sara S. Berndt, Sonja I. Kittles, Rick A. Rybicki, Benjamin A. Isaacs, William B. Ingles, Sue A. Stanford, Janet L. Diver, W. Ryan Witte, John S. Chanock, Stephen J. Kolb, Suzanne Signorello, Lisa B. Yamamura, Yuko Neslund-Dudas, Christine Thun, Michael J. Murphy, Adam Casey, Graham Sheng, Xin Wan, Peggy Pooler, Loreall C. Monroe, Kristine R. Waters, Kevin M. Le Marchand, Loic Kolonel, Laurence N. Stram, Daniel O. Henderson, Brian E. TI Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; SEQUENCE VARIANTS; MULTIPLE LOCI; 8Q24; COHORT; IDENTIFICATION; POLYMORPHISM; POPULATIONS AB GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p <= 0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p <= 6x10(-4)) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry. C1 [Haiman, Christopher A.; Chen, Gary K.; Ingles, Sue A.; Casey, Graham; Sheng, Xin; Wan, Peggy; Pooler, Loreall C.; Monroe, Kristine R.; Waters, Kevin M.; Stram, Daniel O.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Haiman, Christopher A.; Chen, Gary K.; Ingles, Sue A.; Casey, Graham; Sheng, Xin; Wan, Peggy; Pooler, Loreall C.; Monroe, Kristine R.; Waters, Kevin M.; Stram, Daniel O.; Henderson, Brian E.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA. [Blot, William J.; Signorello, Lisa B.] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Div Epidemiol, Nashville, TN USA. [Blot, William J.; Signorello, Lisa B.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Strom, Sara S.; Yamamura, Yuko] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kittles, Rick A.] Univ Illinois, Dept Med, Chicago, IL USA. [Rybicki, Benjamin A.; Neslund-Dudas, Christine] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. [Isaacs, William B.] Johns Hopkins Univ Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. [Isaacs, William B.] Inst Med, Baltimore, MD 21287 USA. [Stanford, Janet L.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Witte, John S.] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Witte, John S.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Murphy, Adam] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. RP Haiman, CA (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. EM haiman@usc.edu FU NIH [CA63464, CA54281, CA1326792, CA148085, HG004726, R01 CA056678, R01 CA082664, R01 CA092579, ES011126, S06GM08016, CA092447]; Division of Cancer Epidemiology and Genetics, NCI, NIH; Cancer Research Fund [99-00524V-10258]; University of California [97-12013, 98-00924V]; NCI, NIH, Department of Health and Human Services [N01-PC-35139]; California Department of Health Services; Centers for Disease Control and Prevention [1U58DP000807-3]; DOD [W81XWH-07-1-0122, DAMD W81XWH-07-1-0203, DAMD W81XWH-06-1-0066]; [R01CA68578]; [DAMD W81XWH-07-1-0645]; [P50-CA140388] FX The MEC and the genotyping in this study were supported by NIH grants CA63464, CA54281, CA1326792, CA148085, and HG004726. Genotyping of the PLCO samples was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH. LAAPC was funded by grant 99-00524V-10258 from the Cancer Research Fund, under Interagency Agreement # 97-12013 (University of California contract # 98-00924V) with the Department of Health Services Cancer Research Program. Cancer incidence data for the MEC and LAAPC studies have been collected by the Los Angeles Cancer Surveillance Program of the University of Southern California with federal funds from the NCI, NIH, Department of Health and Human Services, under Contract No. N01-PC-35139, and the California Department of Health Services as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885, and grant number 1U58DP000807-3 from the Centers for Disease Control and Prevention. KCPCS was supported by NIH grants R01 CA056678, R01 CA082664, R01 CA092579, with additional support from the Fred Hutchinson Cancer Research Center. MDA was support by grants, R01CA68578, DAMD W81XWH-07-1-0645, and P50-CA140388. GECAP was supported by NIH grant ES011126. CaP Genes was supported by CA88164. IPCG was support by DOD grant W81XWH-07-1-0122. DCPC was supported by NIH grant S06GM08016 and DOD grants DAMD W81XWH-07-1-0203 and DAMD W81XWH-06-1-0066. SCCS is funded by NIH grant CA092447, and SCCS sample preparation was conducted at the Epidemiology Biospecimen Core Lab that is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 51 Z9 51 U1 1 U2 3 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 MAY PY 2011 VL 7 IS 5 AR e1001387 DI 10.1371/journal.pgen.1001387 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 769LI UT WOS:000291014600004 PM 21637779 ER PT J AU Chowell, G Echevarria-Zuno, S Viboud, C Simonsen, L Tamerius, J Miller, MA Borja-Aburto, VH AF Chowell, Gerardo Echevarria-Zuno, Santiago Viboud, Cecile Simonsen, Lone Tamerius, James Miller, Mark A. Borja-Aburto, Victor H. TI Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico SO PLOS MEDICINE LA English DT Article ID A H1N1 VIRUS; NEW-YORK-CITY; REPRODUCTION NUMBER; ABSOLUTE-HUMIDITY; ASIAN INFLUENZA; SCHOOL CLOSURE; UNITED-STATES; INFECTION; TRANSMISSION; IMPACT AB Background: Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April-December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission. Methods and Findings: We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April-December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April-May (Mexico City area), a second wave in June-July (southeastern states), and a geographically widespread third wave in August-December. The median age of laboratory confirmed ILI cases was similar to 18 years overall and increased to similar to 31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8-2.1, 1.6-1.9, and 1.2-1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%-37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2-5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases. Conclusions: We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics. C1 [Chowell, Gerardo] Arizona State Univ, Math Computat & Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. [Chowell, Gerardo; Viboud, Cecile; Simonsen, Lone; Tamerius, James; Miller, Mark A.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Echevarria-Zuno, Santiago] Inst Mexicano Seguro Social, Direcc Prestac Med, Mexico City, DF, Mexico. [Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA. [Tamerius, James] Univ Arizona, Sch Geog & Dev, Tucson, AZ USA. [Borja-Aburto, Victor H.] Coordinac Vigilancia Epidemiol & Apoyo Contingenc, Mexico City, DF, Mexico. RP Chowell, G (reprint author), Arizona State Univ, Math Computat & Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. EM gchowell@asu.edu RI Chowell, Gerardo/F-5038-2012; Chiang, Vincent, Ming-Hsien/D-4312-2016; OI Chowell, Gerardo/0000-0003-2194-2251; Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863; Simonsen, Lone/0000-0003-1535-8526 FU Fogarty International Center, National Institutes of Health; Science and Technology Directorate, Department of Homeland Security; Fogarty International Center; SDI, Pennsylvania; Pfizer FX This work was funded by the Fogarty International Center, National Institutes of Health (http://www.fic.nih.gov/). LS acknowledges support from the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; LS received consulting fees from SDI, a health data warehouse business in Pennsylvania, and received research support from Pfizer for a pneumococcal vaccine study, but this is not relevant to the topic of this paper. MAM has been named on a US government patent for an experimental influenza vaccine as required by Federal requirements. NR 68 TC 76 Z9 79 U1 3 U2 15 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 MAY PY 2011 VL 8 IS 5 AR e1000436 DI 10.1371/journal.pmed.1000436 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 771IW UT WOS:000291151400003 PM 21629683 ER PT J AU Anderson, JM Samake, S Jaramillo-Gutierrez, G Sissoko, I Coulibaly, CA Traore, B Soucko, C Guindo, B Diarra, D Fay, MP Lawyer, PG Doumbia, S Valenzuela, JG Kamhawi, S AF Anderson, Jennifer M. Samake, Sibiry Jaramillo-Gutierrez, Giovanna Sissoko, Ibrahim Coulibaly, Cheick A. Traore, Bourama Soucko, Constance Guindo, Boubacar Diarra, Dansine Fay, Michael P. Lawyer, Phillip G. Doumbia, Seydou Valenzuela, Jesus G. Kamhawi, Shaden TI Seasonality and Prevalence of Leishmania major Infection in Phlebotomus duboscqi Neveu-Lemaire from Two Neighboring Villages in Central Mali SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID THIES AREA SENEGAL; CUTANEOUS LEISHMANIASIS; WEST-AFRICA; CONFIDENCE-INTERVALS; VECTORS; ECOLOGY; FOCUS; RESERVOIR AB Phlebotomus duboscqi is the principle vector of Leishmania major, the causative agent of cutaneous leishmaniasis (CL), in West Africa and is the suspected vector in Mali. Although found throughout the country the seasonality and infection prevalence of P. duboscqi has not been established in Mali. We conducted a three year study in two neighboring villages, Kemena and Sougoula, in Central Mali, an area with a leishmanin skin test positivity of up to 45%. During the first year, we evaluated the overall diversity of sand flies. Of 18,595 flies collected, 12,952 (69%) belonged to 12 species of Sergentomyia and 5,643 (31%) to two species of the genus Phlebotomus, P. duboscqi and P. rodhaini. Of those, P. duboscqi was the most abundant, representing 99% of the collected Phlebotomus species. P. duboscqi was the primary sand fly collected inside dwellings, mostly by resting site collection. The seasonality and infection prevalence of P. duboscqi was monitored over two consecutive years. P. dubsocqi were collected throughout the year. Using a quasi-Poisson model we observed a significant annual (year 1 to year 2), seasonal (monthly) and village effect (Kemena versus Sougoula) on the number of collected P. duboscqi. The significant seasonal effect of the quasi-Poisson model reflects two seasonal collection peaks in May-July and October-November. The infection status of pooled P. duboscqi females was determined by PCR. The infection prevalence of pooled females, estimated using the maximum likelihood estimate of prevalence, was 2.7% in Kemena and Sougoula. Based on the PCR product size, L. major was identified as the only species found in flies from the two villages. This was confirmed by sequence alignment of a subset of PCR products from infected flies to known Leishmania species, incriminating P. duboscqi as the vector of CL in Mali. C1 [Anderson, Jennifer M.; Jaramillo-Gutierrez, Giovanna; Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Samake, Sibiry; Sissoko, Ibrahim; Coulibaly, Cheick A.; Traore, Bourama; Guindo, Boubacar; Diarra, Dansine; Doumbia, Seydou] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako, Mali. [Soucko, Constance] Univ Bamako, Fac Sci & Technol, Bamako, Mali. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD USA. [Lawyer, Phillip G.] NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, NIH, Rockville, MD USA. RP Anderson, JM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM skamhawi@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 15 Z9 15 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2011 VL 5 IS 5 AR e1139 DI 10.1371/journal.pntd.0001139 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 770OZ UT WOS:000291099100019 PM 21572984 ER PT J AU Gibson, AK Raverty, S Lambourn, DM Huggins, J Magargal, SL Grigg, ME AF Gibson, Amanda K. Raverty, Stephen Lambourn, Dyanna M. Huggins, Jessica Magargal, Spencer L. Grigg, Michael E. TI Polyparasitism Is Associated with Increased Disease Severity in Toxoplasma gondii-Infected Marine Sentinel Species SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID SEALS PHOCA-VITULINA; OTTERS ENHYDRA-LUTRIS; POLYMERASE-CHAIN-REACTION; HARBOR SEALS; IMMUNE-RESPONSES; BRITISH-COLUMBIA; DRINKING-WATER; CRYPTOCOCCUS-GATTII; RESEARCH PRIORITIES; WASHINGTON-STATE AB In 1995, one of the largest outbreaks of human toxoplasmosis occurred in the Pacific Northwest region of North America. Genetic typing identified a novel Toxoplasma gondii strain linked to the outbreak, in which a wide spectrum of human disease was observed. For this globally-distributed, water-borne zoonosis, strain type is one variable influencing disease, but the inability of strain type to consistently explain variations in disease severity suggests that parasite genotype alone does not determine the outcome of infection. We investigated polyparasitism (infection with multiple parasite species) as a modulator of disease severity by examining the association of concomitant infection of T. gondii and the related parasite Sarcocystis neurona with protozoal disease in wild marine mammals from the Pacific Northwest. These hosts ostensibly serve as sentinels for the detection of terrestrial parasites implicated in water-borne epidemics of humans and wildlife in this endemic region. Marine mammals (151 stranded and 10 healthy individuals) sampled over 6 years were assessed for protozoal infection using multi-locus PCR-DNA sequencing directly from host tissues. Genetic analyses uncovered a high prevalence and diversity of protozoa, with 147/161 (91%) of our sampled population infected. From 2004 to 2009, the relative frequency of S. neurona infections increased dramatically, surpassing that of T. gondii. The majority of T. gondii infections were by genotypes bearing Type I lineage alleles, though strain genotype was not associated with disease severity. Significantly, polyparasitism with S. neurona and T. gondii was common (42%) and was associated with higher mortality and more severe protozoal encephalitis. Our finding of widespread polyparasitism among marine mammals indicates pervasive contamination of waterways by zoonotic agents. Furthermore, the significant association of concomitant infection with mortality and protozoal encephalitis identifies polyparasitism as an important factor contributing to disease severity in marine mammals. C1 [Gibson, Amanda K.; Magargal, Spencer L.; Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Raverty, Stephen] Minist Agr & Food, Ctr Anim Hlth, Abbotsford, BC, Canada. [Raverty, Stephen] Univ British Columbia, AERL, Marine Mammal Res Unit, Fisheries Ctr, Vancouver, BC V5Z 1M9, Canada. [Lambourn, Dyanna M.] Washington Dept Fish & Wildlife, Lakewood, WA USA. [Huggins, Jessica] Cascadia Res Collect, Olympia, WA USA. RP Gibson, AK (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM griggm@niaid.nih.gov FU NIH; NIAID [AI001018]; John H. Prescott Marine Mammal Rescue Assistance Grant Program; NOAA; Washington Department of Fish and Wildlife; Cascadia Research Collective; Animal Health Center, British Columbia Ministry of Agriculture FX This study was funded by the Intramural Research Program of the NIH and NIAID (AI001018). MEG is a scholar of the Canadian Institute for Advanced Research (CIFAR) Program for Integrated Microbial Biodiversity. Stranding response and diagnostic costs were supported by the John H. Prescott Marine Mammal Rescue Assistance Grant Program, NOAA Prescott Marine Mammal Rescue Grants, the Washington Department of Fish and Wildlife, the Cascadia Research Collective and the Animal Health Center, British Columbia Ministry of Agriculture. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 30 Z9 33 U1 2 U2 26 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 MAY PY 2011 VL 5 IS 5 AR e1142 DI 10.1371/journal.pntd.0001142 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 770OZ UT WOS:000291099100021 PM 21629726 ER PT J AU Ramanathan, R Varma, S Ribeiro, JMC Myers, TG Nolan, TJ Abraham, D Lok, JB Nutman, TB AF Ramanathan, Roshan Varma, Sudhir Ribeiro, Jose M. C. Myers, Timothy G. Nolan, Thomas J. Abraham, David Lok, James B. Nutman, Thomas B. TI Microarray-Based Analysis of Differential Gene Expression between Infective and Noninfective Larvae of Strongyloides stercoralis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; PARASITIC NEMATODE; DEVELOPMENTAL VARIANT; COMPARATIVE GENOMICS; ONCHOCERCA-VOLVULUS; BINDING PROPERTIES; ANOPHELES-GAMBIAE; SECRETED PROTEIN; RATTI; IDENTIFICATION AB Background: Differences between noninfective first-stage (L1) and infective third-stage (L3i) larvae of parasitic nematode Strongyloides stercoralis at the molecular level are relatively uncharacterized. DNA microarrays were developed and utilized for this purpose. Methods and Findings: Oligonucleotide hybridization probes for the array were designed to bind 3,571 putative mRNA transcripts predicted by analysis of 11,335 expressed sequence tags (ESTs) obtained as part of the Nematode EST project. RNA obtained from S. stercoralis L3i and L1 was co-hybridized to each array after labeling the individual samples with different fluorescent tags. Bioinformatic predictions of gene function were developed using a novel cDNA Annotation System software. We identified 935 differentially expressed genes (469 L3i-biased; 466 L1-biased) having two-fold expression differences or greater and microarray signals with a p value < 0.01. Based on a functional analysis, L1 larvae have a larger number of genes putatively involved in transcription (p = 0.004), and L3i larvae have biased expression of putative heat shock proteins (such as hsp-90). Genes with products known to be immunoreactive in S. stercoralis-infected humans (such as SsIR and NIE) had L3i biased expression. Abundantly expressed L3i contigs of interest included S. stercoralis orthologs of cytochrome oxidase ucr 2.1 and hsp-90, which may be potential chemotherapeutic targets. The S. stercoralis ortholog of fatty acid and retinol binding protein-1, successfully used in a vaccine against Ancylostoma ceylanicum, was identified among the 25 most highly expressed L3i genes. The sperm-containing glycoprotein domain, utilized in a vaccine against the nematode Cooperia punctata, was exclusively found in L3i biased genes and may be a valuable S. stercoralis target of interest. Conclusions: A new DNA microarray tool for the examination of S. stercoralis biology has been developed and provides new and valuable insights regarding differences between infective and noninfective S. stercoralis larvae. Potential therapeutic and vaccine targets were identified for further study. C1 [Ramanathan, Roshan; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Varma, Sudhir] NIH, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA. [Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Myers, Timothy G.] NIH, Microarray Res Facil, Bethesda, MD 20892 USA. [Nolan, Thomas J.; Lok, James B.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Abraham, David] Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. RP Ramanathan, R (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM ramanathanr@niaid.nih.gov RI Nolan, Thomas/A-1053-2007; Varma, Sudhir/N-8763-2014; OI Varma, Sudhir/0000-0002-4096-4782; Nolan, Thomas/0000-0002-6860-7947; Ribeiro, Jose/0000-0002-9107-0818 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; NIH [AI-050688, AI-022662, AI-082548, RR02512] FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and by NIH grants AI-050688, AI-022662, AI-082548, and RR02512. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 9 Z9 10 U1 1 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 MAY PY 2011 VL 5 IS 5 AR e1039 DI 10.1371/journal.pntd.0001039 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 770OZ UT WOS:000291099100010 PM 21572524 ER PT J AU Tavares, NM Silva, RA Costa, DJ Pitombo, MA Fukutani, KF Miranda, JC Valenzuela, JG Barral, A de Oliveira, CI Barral-Netto, M Brodskyn, C AF Tavares, Natalia M. Silva, Robson A. Costa, Dirceu J. Pitombo, Maiana A. Fukutani, Kiyoshi F. Miranda, Jose C. Valenzuela, Jesus G. Barral, Aldina de Oliveira, Camila I. Barral-Netto, Manoel Brodskyn, Claudia TI Lutzomyia longipalpis Saliva or Salivary Protein LJM19 Protects against Leishmania braziliensis and the Saliva of Its Vector, Lutzomyia intermedia SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSE; MODEL; IDENTIFICATION; EXPRESSION; MICE AB Background: Leishmania transmission occurs in the presence of insect saliva. Immunity to Phlebotomus papatasi or Lutzomyia longipalpis saliva or salivary components confers protection against an infection by Leishmania in the presence of the homologous saliva. However, immunization with Lutzomyia intermedia saliva did not protect mice against Leishmania braziliensis plus Lu. intermedia saliva. In the present study, we have studied whether the immunization with Lu. longipalpis saliva or a DNA plasmid coding for LJM19 salivary protein would be protective against L. braziliensis infection in the presence of Lu. intermedia saliva, the natural vector for L. braziliensis. Methodology/Principal Findings: Immunization with Lu. longipalpis saliva or with LJM19 DNA plasmid induced a Delayed-Type Hypersensitivity (DTH) response against Lu. longipalpis as well as against a Lu. intermedia saliva challenge. Immunized and unimmunized control hamsters were then intradermally infected in the ears with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia saliva. Animals immunized with Lu. longipalpis saliva exhibited smaller lesion sizes as well as reduced disease burdens both at lesion site and in the draining lymph nodes. These alterations were associated with a significant decrease in the expression levels of IL-10 and TGF-beta. Animals immunized with LJM19 DNA plasmid presented similar findings in protection and immune response and additionally increased IFN-gamma expression. Conclusions/Significance: Immunization with Lu. longipalpis saliva or with a DNA plasmid coding LJM19 salivary protein induced protection in hamsters challenged with L. braziliensis plus Lu. intermedia saliva. These findings point out an important role of immune response against saliva components, suggesting the possibility to develop a vaccine using a single component of Lu. longipalpis saliva to generate protection against different species of Leishmania, even those transmitted by a different vector. C1 [Tavares, Natalia M.; Costa, Dirceu J.; Pitombo, Maiana A.; Fukutani, Kiyoshi F.; Miranda, Jose C.; Barral, Aldina; de Oliveira, Camila I.; Barral-Netto, Manoel; Brodskyn, Claudia] Fiocruz MS, Ctr Pesquisa Goncalo Moniz, Salvador, BA, Brazil. [Silva, Robson A.] Univ Fed Bahia, Inst Multidisciplinar Saude, Vitoria Da Conquista, BA, Brazil. [Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Barral, Aldina; de Oliveira, Camila I.; Barral-Netto, Manoel; Brodskyn, Claudia] Inst Invest Imunol, Sao Paulo, Brazil. RP Tavares, NM (reprint author), Fiocruz MS, Ctr Pesquisa Goncalo Moniz, Salvador, BA, Brazil. EM brodskyn@bahia.fiocruz.br RI Barral Netto, Manoel/B-3904-2009; de Oliveira, Camila/B-4358-2009; Imunologia, Inct/I-2124-2013; Fukutani, Kiyoshi/N-7905-2016; OI Barral Netto, Manoel/0000-0002-5823-7903; de Oliveira, Camila/0000-0002-7868-5164; Fukutani, Kiyoshi/0000-0003-2223-0918; Tavares, Natalia/0000-0002-4026-679X FU FAPESB; Renorbio [554753/2006-5]; CNPq [472973/2006-1] FX This work was supported by FAPESB, Renorbio (554753/2006-5) and CNPq (472973/2006-1). AB, CIO, MB-N and CB are senior investigators from CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 29 Z9 30 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2011 VL 5 IS 5 AR e1169 DI 10.1371/journal.pntd.0001169 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 770OZ UT WOS:000291099100037 PM 21655303 ER PT J AU Yohannes, AM Ershler, WB AF Yohannes, Abebaw Mengistu Ershler, William Baldwin TI Anemia in COPD: A Systematic Review of the Prevalence, Quality of Life, and Mortality SO RESPIRATORY CARE LA English DT Review DE anemia; COPD; quality life; morbidity; mortality; healthcare utilization ID OBSTRUCTIVE PULMONARY-DISEASE; COLONY-FORMING-UNITS; RESPIRATORY QUESTIONNAIRE; HEPCIDIN LINK; GLOBAL BURDEN; INFLAMMATION; COMORBIDITIES; INTERLEUKIN-6; EPIDEMIOLOGY; HYPOFERREMIA AB Anemia is common in patients with chronic diseases. However, little is known regarding the prevalence of comorbid anemia and its impact on quality of life, healthcare utilization, and mortality in patients with COPD. We conducted a systematic review and synthesis of the literature (1966 to March 2010). The prevalence of comorbid anemia in patients with COPD ranges from 7.5% to 34%, depending upon the populations selected and diagnostic tools employed to determine the level of hemoglobin. Comorbid anemia in patients with COPD was associated with greater healthcare resource utilization, impaired quality of life, older age, and male gender. Moreover, anemia in patients with COPD is an independent prognostic predictor of premature mortality and a greater likelihood of hospitalization. The true prevalence of anemia in patients with COPD is unknown. There is a lack of consensus agreement regarding this hematological abnormality's true frequency. Based on the findings from the existing literature, more work is necessary to establish the true prevalence of anemia in COPD. Robust and prospective clinical studies are needed to improve the management of COPD patients with comorbid anemia. C1 [Yohannes, Abebaw Mengistu] Manchester Metropolitan Univ, Dept Hlth Profess, Manchester M13 0JA, Lancs, England. [Ershler, William Baldwin] NIA, NIH, Baltimore, MD 21224 USA. [Ershler, William Baldwin] Harbor Hosp, Baltimore, MD USA. RP Yohannes, AM (reprint author), Manchester Metropolitan Univ, Dept Hlth Profess, Elizabeth Gaskell Campus,Hathersage Rd, Manchester M13 0JA, Lancs, England. EM a.yohannes@mmu.ac.uk NR 53 TC 15 Z9 19 U1 0 U2 3 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 644 EP 652 DI 10.4187/respcare.01002 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200012 PM 21276321 ER PT J AU Harper, KN Hibbeln, JR Deckelbaum, R Quesenberry, CP Schaefer, CA Brown, AS AF Harper, Kristin N. Hibbeln, Joseph R. Deckelbaum, Richard Quesenberry, Charles P., Jr. Schaefer, Catherine A. Brown, Alan S. TI Maternal serum docosahexaenoic acid and schizophrenia spectrum disorders in adult offspring SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Docosahexaenoic acid; Arachidonic acid; Schizophrenia; Prenatal ID POLYUNSATURATED FATTY-ACIDS; INTRAUTERINE GROWTH RESTRICTION; GESTATIONAL DIABETES-MELLITUS; OXIDATIVE STRESS; EICOSAPENTAENOIC ACID; SEAFOOD CONSUMPTION; FISHING COMMUNITY; FUNCTIONAL FOOD; TERM INFANTS; BIRTH-WEIGHT AB It is believed that during mid-to-late gestation, docosahexaenoic acid (DHA), an n-3 fatty acid, plays an important role in fetal and infant brain development, including neurocognitive and neuromotor functions. Deficits in several such functions have been associated with schizophrenia. Though sufficient levels of DHA appear to be important in neurodevelopment, elevated maternal DHA levels have also been associated with abnormal reproductive outcomes in both animal models and humans. Our objective was to assess whether a disturbance in maternal DHA levels, measured prospectively during pregnancy, was associated with risk of schizophrenia and other schizophrenia spectrum disorders (SSD) in adult offspring. In order to test the hypothesis that abnormal levels of DHA are associated with SSD, a case-control study nested within a large, population-based birth cohort, born from 1959 through 1967 and followed up for SSD from 1981 through 1997, was utilized. Maternal levels of both DHA and arachidonic acid (AA), an n-6 fatty acid, were analyzed in archived maternal sera from 57 cases of SSD and 95 matched controls. There was a greater than twofold increased risk of SSD among subjects exposed to maternal serum DHA in the highest tertile (OR = 2.38, 95% CI = 1.19, 4.76, p = 0.01); no such relationship was found between AA and SSD. These findings suggest that elevated maternal DHA is associated with increased risk for the development of SSD in offspring. (C) 2011 Elsevier B.V. All rights reserved. C1 [Harper, Kristin N.] Columbia Univ, Robert Wood Johnson Hlth & Soc Scholars Program, New York, NY 10032 USA. [Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, LMBB, NIH, Bethesda, MD 20892 USA. [Deckelbaum, Richard; Brown, Alan S.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Deckelbaum, Richard; Brown, Alan S.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. [Deckelbaum, Richard] Columbia Univ, Inst Human Nutr, New York, NY 10032 USA. [Quesenberry, Charles P., Jr.; Schaefer, Catherine A.] Kaiser Permanente Div Res, Oakland, CA 94612 USA. [Brown, Alan S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Harper, KN (reprint author), Columbia Univ, Robert Wood Johnson Hlth & Soc Scholars Program, 722 W 168th St,Room 1611, New York, NY 10032 USA. EM kh2383@columbia.edu; jhibbeln@mail.nih.gov; rjd20@columbia.edu; charles.quesenberry@kp.org; cathy.schaefer@kp.org; asb11@columbia.edu RI Harper, Kristin/H-3848-2012 FU National Alliance for Research on Schizophrenia and Depression [NICHD N01-HD-1-3334, NICHD NO1-HD-6-3258, NHLBI RO1 - HL-40404]; Robert Wood Johnson Foundation; [NIMH 1K02MH65422] FX This manuscript was supported by the following grants: NIMH 1K02MH65422 (A.S.B.), an Independent Investigator Award from the National Alliance for Research on Schizophrenia and Depression (AS.B.), NICHD N01-HD-1-3334, NICHD NO1-HD-6-3258 (B. Cohn), and NHLBI RO1 - HL-40404 (R.J.D.) and also received financial support from the Robert Wood Johnson Foundation (K.N.H.).These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 78 TC 8 Z9 9 U1 4 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2011 VL 128 IS 1-3 BP 30 EP 36 DI 10.1016/j.schres.2011.01.009 PG 7 WC Psychiatry SC Psychiatry GA 771QL UT WOS:000291175700007 PM 21324652 ER PT J AU Kiris, E Nuss, JE Burnett, JC Kota, KP Koh, DC Wanner, LM Torres-Melendez, E Gussio, R Tessarollo, L Bavari, S AF Kiris, Erkan Nuss, Jonathan E. Burnett, James C. Kota, Krishna P. Koh, Dawn C. Wanner, Laura M. Torres-Melendez, Edna Gussio, Rick Tessarollo, Lino Bavari, Sina TI Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery SO STEM CELL RESEARCH LA English DT Article ID SYNAPTIC PROTEIN SNAP-25; MOTOR-NEURONS; SPINAL-CORD; DIRECTED DIFFERENTIATION; CLOSTRIDIAL NEUROTOXINS; TERMINAL DOMAIN; TOXIN; RECEPTOR; PERSISTENCE; TRANSLOCATION AB Botulinum neurotoxins (BoNTs) inhibit cholinergic synaptic transmission by specifically cleaving proteins that are crucial for neurotransmitter exocytosis. Due to the lethality of these toxins, there are elevated concerns regarding their possible use as bioterrorism agents. Moreover, their widespread use for cosmetic purposes, and as medical treatments, has increased the potential risk of accidental overdosing and environmental exposure. Hence, there is an urgent need to develop novel modalities to counter BoNT intoxication. Mammalian motoneurons are the main target of BoNTs; however, due to the difficulty and poor efficiency of the procedures required to isolate the cells, they are not suitable for high-throughput drug screening assays. Here, we explored the suitability of embryonic stem (ES) cell-derived motoneurons as a renewable, reproducible, and physiologically relevant system for BoNT studies. We found that the sensitivity of ES-derived motoneurons to BoNT/A intoxication is comparable to that of primary mouse spinal motoneurons. Additionally, we demonstrated that several BoNT/A inhibitors protected SNAP-25, the BoNT/A substrate, in the ES-derived motoneuron system. Furthermore, this system is compatible with immunofluorescence-based high-throughput studies. These data suggest that ES-derived motoneurons provide a highly sensitive system that is amenable to large-scale screenings to rapidly identify and evaluate the biological efficacies of novel therapeutics. Published by Elsevier B.V. C1 [Kiris, Erkan; Nuss, Jonathan E.; Kota, Krishna P.; Wanner, Laura M.; Torres-Melendez, Edna; Bavari, Sina] USA, Med Res Inst Infect Dis, Dept Target Discovery & Expt Microbiol, Frederick, MD 21702 USA. [Kiris, Erkan; Koh, Dawn C.; Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Burnett, James C.] NCI, SAIC Frederick Inc, TSBDDG, Frederick, MD 21702 USA. [Burnett, James C.; Gussio, Rick] NCI, TSBDDG, Informat Technol Branch, Dev Therapeut Program, Frederick, MD USA. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, Dept Target Discovery & Expt Microbiol, 1425 Porter St, Frederick, MD 21702 USA. EM sina.bavari@amedd.army.mil FU Defense Threat Reduction Agency [CBS.MEDBIO_01_10_RD_014]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We are indebted to Dr. Thomas M. Jessell and Dr. Hynek Wichterle (Columbia University, New York, NY) for the generous gift of HBG3 mouse ES cell line. Also, we are grateful to Eileen Southon for kindly providing mouse embryonic fibroblast cells and helping with stem cell culture, Jodi Becker for providing assistance with microscopy and mouse spinal cord dissections, and Lyal Tressler for providing assistance with Li-Cor studies. Additionally, we thank the members of the Tessarollo, Gussio, and Bavari labs for their insightful discussion and generosity. This work was supported by Defense Threat Reduction Agency (CBS.MEDBIO_01_10_RD_014). Furthermore, for J.C.B., this project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. NR 59 TC 22 Z9 22 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD MAY PY 2011 VL 6 IS 3 BP 195 EP 205 DI 10.1016/j.scr.2011.01.002 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 773GU UT WOS:000291295800001 PM 21353660 ER PT J AU Okun, E Griffioen, KJ Mattson, MP AF Okun, Eitan Griffioen, Kathleen J. Mattson, Mark P. TI Toll-like receptor signaling in neural plasticity and disease SO TRENDS IN NEUROSCIENCES LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROGENITOR-CELL PROLIFERATION; FOCAL CEREBRAL-ISCHEMIA; ADULT HIPPOCAMPAL NEUROGENESIS; INNATE IMMUNE RECEPTOR; AMYLOID-BETA-PEPTIDE; REGULATORY T-CELLS; ALZHEIMERS-DISEASE; NEGATIVE REGULATOR AB Toll-like receptors (TLRs) are a family of innate immune system receptors that respond to pathogen-derived and tissue damage-related ligands. TLR signaling in immune cells, glia and neurons can play roles in the pathogenesis of stroke, Alzheimer's disease (AD) and multiple sclerosis (MS). Recent findings suggest that TLR signaling also influences multiple dynamic processes in the developing and adult central nervous system including neurogenesis, axonal growth and structural plasticity. In addition, TLRs are implicated in the regulation of behaviors including learning, memory and anxiety. This review describes recently discovered and unexpected roles for TLRs in neuroplasticity, and the implications of these findings for future basic and translational research studies. C1 [Okun, Eitan; Griffioen, Kathleen J.; Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Lab Neurosci, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Lab Neurosci, Biomed Res Ctr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; okun, eitan/K-1314-2016 OI okun, eitan/0000-0001-8474-1487 FU National Institute on Aging FX The authors' work was supported by the Intramural Research Program of the National Institute on Aging. NR 106 TC 154 Z9 159 U1 4 U2 25 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 2011 VL 34 IS 5 BP 269 EP 281 DI 10.1016/j.tins.2011.02.005 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 771CV UT WOS:000291135700005 PM 21419501 ER PT J AU Cai, LZ Yang, DJ Sun, ZH Tao, XC Cai, LS Pike, VW AF Cai Liangzhen Yang Dujuan Sun Zhonghua Tao Xiaochun Cai Lisheng Pike, Victor W. TI Palladium-catalyzed Coupling between Aryl Halides and Trimethylsilylacetylene Assisted by Dimethylaminotrimethyltin SO CHINESE JOURNAL OF CHEMISTRY LA English DT Article DE palladium catalysis; trimethylsilylacetylene; aryl halide; dimethylaminotrimethyltin; Sonogashira coupling ID BETA-AMYLOID PLAQUES; TERMINAL ALKYNES; SONOGASHIRA; REAGENTS; COMPLEX; VINYL AB Palladium-catalyzed coupling between aryl halides, especially less reactive ones or N-heteroaryls, and trimethylsilylacetylene in the presence of dimethylaminotrimethyltin generated the coupled products in high yields. The reaction does not need CuI and base as auxiliary agents. C1 [Cai Liangzhen; Yang Dujuan; Sun Zhonghua; Tao Xiaochun] E China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China. [Cai Lisheng; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Tao, XC (reprint author), E China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China. EM xctao@ecust.edu.cn NR 26 TC 1 Z9 1 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1001-604X J9 CHINESE J CHEM JI Chin. J. Chem. PD MAY PY 2011 VL 29 IS 5 BP 1059 EP 1062 DI 10.1002/cjoc.201190180 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 769LE UT WOS:000291014200032 ER PT J AU Lopez-Quintero, C de los Cobos, JP Hasin, DS Okuda, M Wang, S Grant, BF Blanco, C AF Lopez-Quintero, Catalina Perez de los Cobos, Jose Hasin, Deborah S. Okuda, Mayumi Wang, Shuai Grant, Bridget F. Blanco, Carlos TI Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Nicotine; Alcohol; Cannabis; Cocaine; Dependence; Racial-ethnic groups; Discrete-time time survival analyses ID DSM-IV ALCOHOL; SUBSTANCE USE DISORDERS; PSYCHIATRIC DIAGNOSTIC MODULES; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; DRUG-USE DISORDERS; UNITED-STATES; ANXIETY DISORDERS; MENTAL-DISORDERS; RISK-FACTORS AB Background: This study aims to estimate general and racial-ethnic specific cumulative probability of developing dependence among nicotine, alcohol, cannabis or cocaine users, and to identify predictors of transition to substance dependence. Methods: Analyses were done for the subsample of lifetime nicotine (n = 15,918), alcohol (n = 28,907), cannabis (n = 7389) or cocaine (n = 2259) users who participated in the first and second wave of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Discrete-time survival analyses were implemented to estimate the cumulative probability of transitioning from use to dependence and to identify predictors of transition to dependence. Results: The cumulative probability estimate of transition to dependence was 67.5% for nicotine users, 22.7% for alcohol users, 20.9% for cocaine users, and 8.9% for cannabis users. Half of the cases of dependence on nicotine, alcohol, cannabis and cocaine were observed approximately 27, 13, 5 and 4 years after use onset, respectively. Significant racial-ethnic differences were observed in the probability of transition to dependence across the four substances. Several predictors of dependence were common across the four substances assessed. Conclusions: Transition from use to dependence was highest for nicotine users, followed by cocaine, alcohol and cannabis users. Transition to cannabis or cocaine dependence occurred faster than transition to nicotine or alcohol dependence. The existence of common predictors of transition dependence across substances suggests that shared mechanisms are involved. The increased risk of transition to dependence among individuals from minorities or those with psychiatric or dependence comorbidity highlights the importance of promoting outreach and treatment of these populations. Published by Elsevier Ireland Ltd. C1 [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Lopez-Quintero, Catalina; Hasin, Deborah S.; Okuda, Mayumi; Wang, Shuai; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY 10032 USA. [Perez de los Cobos, Jose] Hosp Santa Creu & Sant Pau, Dept Psychiat, Addict Behav Unit Psychiat, Barcelona 08025, Spain. [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Lopez-Quintero, Catalina/A-2294-2013; Blanco, Carlos/I-4906-2013; Okuda, Mayumi/L-6210-2013; Perez de los Cobos, Jose/Q-2734-2016 OI Lopez-Quintero, Catalina/0000-0002-6579-6180; Blanco, Carlos/0000-0001-6187-3057; Okuda, Mayumi/0000-0002-3479-5599; Perez de los Cobos, Jose/0000-0002-9796-5823 FU NIH [DA019606, DA020783, DA023200, DA023973, MH076051, MH082773, CA133050, AA014223, DA018652, AA018111]; American Foundation for Suicide Prevention; New York State Psychiatric Institute FX This study is supported by NIH grants DA019606, DA020783, DA023200, DA023973, MH076051, MH082773 and CA133050 (Dr. Blanco) and AA014223, DA018652, and AA018111 (Dr. Hasin), a grant from the American Foundation for Suicide Prevention (Dr. Blanco), and the New York State Psychiatric Institute (Drs. Blanco and Hasin). The NIH, the American Foundation for Suicide Prevention, and the New York State Psychiatric Institute had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 109 TC 105 Z9 105 U1 15 U2 46 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2011 VL 115 IS 1-2 BP 120 EP 130 DI 10.1016/j.drugalcdep.2010.11.004 PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 770IE UT WOS:000291079400019 PM 21145178 ER PT J AU Wishart, GC Bajdik, CD Azzato, EM Dicks, E Greenberg, DC Rashbass, J Caldas, C Pharoah, PDP AF Wishart, G. C. Bajdik, C. D. Azzato, E. M. Dicks, E. Greenberg, D. C. Rashbass, J. Caldas, C. Pharoah, P. D. P. TI A population-based validation of the prognostic model PREDICT for early breast cancer SO EJSO LA English DT Article DE Breast; Prognosis; Model validation ID RANDOMIZED-TRIALS; SURVIVAL; INDEX; ADJUVANT; PROGRAM AB Introduction: Predict (www.predict.nhs.uk) is a prognostication and treatment benefit tool developed using UK cancer registry data. The aim of this study was to compare the 10-year survival estimates from Predict with observed 10-year outcome from a British Columbia dataset and to compare the estimates with those generated by Adjuvant! (www.adjuvantonline.com). Method: The analysis was based on data from 3140 patients with early invasive breast cancer diagnosed in British Columbia, Canada, from 1989-1993. Demographic, pathologic, staging and treatment data were used to predict 10-year overall survival (OS) and breast cancer specific survival (EICSS) using Adjuvant! and Predict models. Predicted outcomes from both models were then compared with observed outcomes. Results: Calibration of both models was excellent. The difference in total number of deaths estimated by Predict was 4.1 percent of observed compared to 0.7 percent for Adjuvant!. The total number of breast cancer specific deaths estimated by Predict was 3.4 percent of observed compared to 6.7 percent for Adjuvant! Both models also discriminate well with similar AUC for Predict and Adjuvant! respectively for both OS (0.709 vs 0.712) and BCSS (0.723 vs 0.727). Neither model performed well in women aged 20-35. Conclusion: In summary Predict provided accurate overall and breast cancer specific survival estimates in the British Columbia dataset that are comparable with outcome estimates from Adjuvant! Both models appear well calibrated with similar model discrimination. This study provides further validation of Predict as an effeciive predictive tool following surgery for invasive breast cancer. (c) 2011 Elsevier Ltd. All rights reserved. C1 [Azzato, E. M.; Dicks, E.; Caldas, C.; Pharoah, P. D. P.] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge CB1 8RN, England. [Wishart, G. C.; Caldas, C.] Addenbrookes Hosp, Cambridge Breast Unit, Cambridge CB2 2QQ, England. [Azzato, E. M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Greenberg, D. C.; Rashbass, J.] ECRIC, Unit C, Cambridge CB22 3AD, England. [Bajdik, C. D.] British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 1L3, Canada. [Caldas, C.] Canc Res UK Cambridge Res Inst, Funct Breast Canc Genom Lab, Li Ku Shing Ctr, Cambridge CB2 0RE, England. [Caldas, C.] Addenbrookes Hosp, NIHR, Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England. RP Pharoah, PDP (reprint author), Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge CB1 8RN, England. EM paul.pharoah@srl.cam.ac.uk RI Caldas, Carlos/A-7543-2008 FU Pfizer; Cambridge NIHR Biomedical Research Centre; National Cancer Institute; NIH-Cambridge FX The development of the PREDICT model was funded by an unrestricted educational grant from Pfizer.; GCW & CC receive research funding from the Cambridge NIHR Biomedical Research Centre. EMA was supported by the National Cancer Institute and the NIH-Cambridge Graduate Partnership Program. NR 15 TC 25 Z9 26 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 J9 EJSO-EUR J SURG ONC JI EJSO PD MAY PY 2011 VL 37 IS 5 BP 411 EP 417 DI 10.1016/j.ejso.2011.02.001 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 768FZ UT WOS:000290920400006 PM 21371853 ER PT J AU Bertherat, E Thullier, P Shako, JC England, K Kone, ML Arntzen, L Tomaso, H Koyange, L Formenty, P Ekwanzala, F Crestani, R Ciglenecki, I Rahalison, L AF Bertherat, Eric Thullier, Philippe Shako, Jean Christophe England, Kathleen Kone, Mamadou-Lamine Arntzen, Lorraine Tomaso, Herbert Koyange, Louis Formenty, Pierre Ekwanzala, Florent Crestani, Rosa Ciglenecki, Isa Rahalison, Lila TI Lessons Learned about Pneumonic Plague Diagnosis 2 Outbreaks, Democratic Republic of the Congo SO EMERGING INFECTIOUS DISEASES LA English DT Article ID MANAGEMENT; MADAGASCAR; PESTIS; ASSAY AB Pneumonic plague is a highly transmissible infectious disease for which fatality rates can be high if untreated; it is considered extremely lethal. Without prompt diagnosis and treatment, disease management can be problematic. In the Democratic Republic of the Congo, 2 outbreaks of pneumonic plague occurred during 2005 and 2006. In 2005, because of limitations in laboratory capabilities, etiology was confirmed only through retrospective serologic studies. This prompted modifications in diagnostic strategies, resulting in isolation of Yersinia pestis during the second outbreak. Results from these outbreaks demonstrate the utility of a rapid diagnostic test detecting F1 antigen for initial diagnosis and public health management, as well as the need for specialized sampling kits and trained personnel for quality specimen collection and appropriate specimen handling and preservation for plague confirmation and Y. pestis isolation. Efficient frontline management and a streamlined diagnostic strategy are essential for confirming plaque, especially in remote areas. C1 [Bertherat, Eric] WHO, HSE GAR, Dept Global Alert & Response, CH-1211 Geneva, Switzerland. [Thullier, Philippe] Ctr Rech Serv Sante Armees, Grenoble, France. [Shako, Jean Christophe] Plague Reference Lab, Bunia, Zaire. [England, Kathleen] NIH, Bethesda, MD 20892 USA. [Kone, Mamadou-Lamine] WHO, Brazzaville, Congo. [Arntzen, Lorraine] Natl Hlth Lab Serv, Johannesburg, South Africa. [Tomaso, Herbert] Bundeswehr Inst Microbiol, Munich, Germany. [Koyange, Louis] Inst Natl Rech Biomed, Kinshasa, Zaire. [Ekwanzala, Florent] WHO, Kinshasa, Zaire. [Crestani, Rosa] Med Sans Frontiere, Brussels, Belgium. [Ciglenecki, Isa] Med Sans Frontieres, Geneva, Switzerland. [Rahalison, Lila] Inst Pasteur, Antananarivo, Madagascar. RP Bertherat, E (reprint author), WHO, HSE GAR, Dept Global Alert & Response, 20 Av Appia, CH-1211 Geneva, Switzerland. EM bertherate@who.int NR 22 TC 14 Z9 14 U1 1 U2 11 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2011 VL 17 IS 5 BP 778 EP 784 DI 10.3201/eid1705.100029 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 760AB UT WOS:000290291900003 PM 21529384 ER PT J AU Sasaki, D Imaizumi, Y Hasegawa, H Osaka, A Tsukasaki, K Choi, YL Mano, H Marquez, VE Hayashi, T Yanagihara, K Moriwaki, Y Miyazaki, Y Kamihira, S Yamada, Y AF Sasaki, Daisuke Imaizumi, Yoshitaka Hasegawa, Hiroo Osaka, Akemi Tsukasaki, Kunihiro Choi, Young Lim Mano, Hiroyuki Marquez, Victor E. Hayashi, Tomayoshi Yanagihara, Katsunori Moriwaki, Yuji Miyazaki, Yasushi Kamihira, Shimeru Yamada, Yasuaki TI Overexpression of enhancer of zeste homolog 2 with trimethylation of lysine 27 on histone H3 in adult T-cell leukemia/lymphoma as a target for epigenetic therapy SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE adult T-cell leukemia/lymphoma; human T-cell leukemia virus type-1; Enhancer of zeste homolog 2; H3K27me3 ID DEACETYLASE INHIBITOR PANOBINOSTAT; GROUP PROTEIN EZH2; METHYLTRANSFERASE ACTIVITY; LEUKEMIA-LYMPHOMA; DNA METHYLATION; PROSTATE-CANCER; POLYCOMB; GENE; PROGRESSION; REPRESSION AB Background Enhancer of zeste homolog 2 is a component of the Polycomb repressive complex 2 that mediates chromatin-based gene silencing through trimethylation of lysine 27 on histone H3. This complex plays vital roles in the regulation of development-specific gene expression. Design and Methods In this study, a comparative microarray analysis of gene expression in primary adult T-cell leukemia/lymphoma samples was performed, and the results were evaluated for their oncogenic and clinical significance. Results Significantly higher levels of Enhancr of zeste homolog 2 and RING1 and YY1 binding protein transcripts with enhanced levels of trimethylation of lysine 27 on histone H3 were found in adult T-cell leukemia/lymphoma cells compared with those in normal CD4(+) T cells. Furthermore, there was an inverse correlation between the expression level of Enhancer of zeste homolog 2 and that of miR-101 or miR-128a, suggesting that the altered expression of the latter miRNAs accounts for the overexpression of the former. Patients with high Enhancer of zeste homolog 2 or RING1 and YY1 binding protein transcripts had a significantly worse prognosis than those without it, indicating a possible role of these genes in the oncogenesis and progression of this disease. Indeed, adult T-cell leukemia/lymphoma cells were sensitive to a histone methylation inhibitor, 3-deazaneplanocin A. Furthermore, 3-deazaneplanocin A and histone deacetylase inhibitor panobinostat showed a synergistic effect in killing the cells Conclusions These findings reveal that adult T-cell leukemia/lymphoma cells have deregulated Polycomb repressive complex 2 with over-expressed Enhancer of zeste homolog 2, and that there is the possibility of a new therapeutic strategy targeting histone methylation in this disease. C1 [Sasaki, Daisuke; Hasegawa, Hiroo; Osaka, Akemi; Yanagihara, Katsunori; Kamihira, Shimeru; Yamada, Yasuaki] Nagasaki Univ, Grad Sch Biomed Sci, Dept Lab Med, Nagasaki 8528501, Japan. [Imaizumi, Yoshitaka; Tsukasaki, Kunihiro; Moriwaki, Yuji; Miyazaki, Yasushi] Nagasaki Univ, Grad Sch Biomed Sci, Atom Bomb Dis Inst, Dept Hematol & Mol Med, Nagasaki 8528501, Japan. [Choi, Young Lim; Mano, Hiroyuki] Jichi Med Univ, Div Funct Genom, Shimotsuke, Tochigi, Japan. [Marquez, Victor E.] NCI, Chem Biol Lab, Frederick, MD 21701 USA. [Hayashi, Tomayoshi] Nagasaki Univ Hosp, Dept Pathol, Nagasaki, Japan. RP Yamada, Y (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Lab Med, 1-7-1 Sakamoto, Nagasaki 8528501, Japan. EM y-yamada@nagasaki-u.ac.jp FU Ministry of Health, Labour, and Welfare of Japan [04010119]; NIH, Center for Cancer Research, NCI-Frederick FX Funding: supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labour, and Welfare of Japan (N. 04010119). For VEM, this research was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick. NR 51 TC 32 Z9 35 U1 0 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAY PY 2011 VL 96 IS 5 BP 712 EP 719 DI 10.3324/haematol.2010.028605 PG 8 WC Hematology SC Hematology GA 768RN UT WOS:000290955100013 PM 21228036 ER PT J AU Leon, ME Freeman, LEB Douwes, J Hoppin, JA Kromhout, H Lebailly, P Nordby, KC Schenker, M Schuz, J Waring, SC Alavanja, MCR Annesi-Maesano, I Baldi, I Dalvie, MA Ferro, G Fervers, B Langseth, H London, L Lynch, CF McLaughlin, J Merchant, JA Pahwa, P Sigsgaard, T Stayner, L Wesseling, C Yoo, KY Zahm, SH Straif, K Blair, A AF Leon, Maria E. Freeman, Laura E. Beane Douwes, Jeroen Hoppin, Jane A. Kromhout, Hans Lebailly, Pierre Nordby, Karl-Christian Schenker, Marc Schuez, Joachim Waring, Stephen C. Alavanja, Michael C. R. Annesi-Maesano, Isabella Baldi, Isabelle Dalvie, Mohamed Aqiel Ferro, Giles Fervers, Beatrice Langseth, Hilde London, Leslie Lynch, Charles F. McLaughlin, John Merchant, James A. Pahwa, Punam Sigsgaard, Torben Stayner, Leslie Wesseling, Catharina Yoo, Keun-Young Zahm, Shelia H. Straif, Kurt Blair, Aaron TI AGRICOH: A Consortium of Agricultural Cohorts SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE agriculture; cohort studies; consortium, pesticides; occupational exposures ID FARM EXPOSURE; CANCER; HEALTH; ASTHMA; SYMPTOMS; RISK AB AGRICOH is a recently formed consortium of agricultural cohort studies involving 22 cohorts from nine countries in five continents: South Africa (1), Canada (3), Costa Rica (2), USA (6), Republic of Korea (1), New Zealand (2), Denmark (1), France (3) and Norway (3). The aim of AGRICOH, initiated by the US National Cancer Institute (NCI) and coordinated by the International Agency for Research on Cancer (IARC), is to promote and sustain collaboration and pooling of data to investigate the association between a wide range of agricultural exposures and a wide range of health outcomes, with a particular focus on associations that cannot easily be addressed in individual studies because of rare exposures (e. g., use of infrequently applied chemicals) or relatively rare outcomes (e. g., certain types of cancer, neurologic and auto-immune diseases). To facilitate future projects the need for data harmonization of selected variables is required and is underway. Altogether, AGRICOH provides excellent opportunities for studying cancer, respiratory, neurologic, and auto-immune diseases as well as reproductive and allergic disorders, injuries and overall mortality in association with a wide array of exposures, prominent among these the application of pesticides. C1 [Leon, Maria E.; Schuez, Joachim; Straif, Kurt] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon 08, France. [Leon, Maria E.; Schuez, Joachim; Straif, Kurt] Int Agcy Res Canc, Sect IARC Monographs KS, F-69372 Lyon 08, France. [Freeman, Laura E. Beane; Alavanja, Michael C. R.; Zahm, Shelia H.; Blair, Aaron] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Douwes, Jeroen] Massey Univ, Ctr Publ Hlth Res, Sch Publ Hlth, Wellington 6140, New Zealand. [Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Durham, NC 27703 USA. [Kromhout, Hans] Univ Utrecht, Environm Epidemiol Div IRAS, NL-3508 TC Utrecht, Netherlands. [Lebailly, Pierre] Univ Caen, Ctr Reg Lutte Canc Francois Baclesse, F-14000 Caen, France. [Nordby, Karl-Christian] Natl Inst Occupat Hlth, N-0033 Oslo, Norway. [Schenker, Marc] Univ Calif Davis, Dept Publ Hlth Sci, Sch Med, Davis, CA 95616 USA. [Waring, Stephen C.] Marshfield Clin Res Fdn, Epidemiol Res Ctr, Marshfield, WI 54449 USA. [Annesi-Maesano, Isabella] INSERM, Epidemiol Allerg & Resp Dis Dept, UMR S 707, F-75571 Paris 12, France. [Annesi-Maesano, Isabella] UPMC Paris 6, Med Sch St Antoine, F-75571 Paris 12, France. [Baldi, Isabelle; Ferro, Giles] Univ Bordeaux 2, Inst St Travail Environm, F-33405 Bordeaux, France. [Dalvie, Mohamed Aqiel; London, Leslie] Univ Cape Town, Ctr Occupat & Environm Hlth Res, Sch Publ Hlth & Family Med, ZA-7701 Cape Town, South Africa. [Fervers, Beatrice] Ctr Leon Berard, Unite Canc & Environm, F-69008 Lyon, France. [Langseth, Hilde] Inst Populat Based Canc Res, Canc Registry Norway, N-0304 Oslo, Norway. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [McLaughlin, John] Canc Care Ontario, Toronto, ON M5G 2L7, Canada. [Merchant, James A.] Univ Iowa, Coll Publ Hlth, Gen Hosp, Iowa City, IA 52242 USA. [Pahwa, Punam] Univ Saskatchewan, Dept Community Hlth & Epidemiol, Inst Agr Rural & Environm Hlth, Royal Univ Hosp, Saskatoon, SK S7K 5T6, Canada. [Sigsgaard, Torben] Univ Aarhus, Sch Publ Hlth, Dept Environm & Occupat Med, DK-8000 Aarhus C, Denmark. [Stayner, Leslie] Univ Illinois, Div Epidemiol & Biostat, Sch Publ Hlth, Chicago, IL 60612 USA. [Wesseling, Catharina] Univ Nacl, Cent Amer Inst Studies Tox Subst IRET, Heredia, Costa Rica. [Yoo, Keun-Young] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. RP Leon, ME (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM leonrouxm@iarc.fr; freemala@mail.nih.gov; j.douwes@massey.ac.nz; hoppin1@niehs.nih.gov; h.kromhout@uu.nl; p.lebailly@baclesse.fr; karl.c.nordby@stami.no; mbschenker@ucdavis.edu; schuzj@iarc.fr; waring.stephen@mcrf.mfldclin.edu; alavanjm@mail.nih.gov; annesimaesano@gmail.com; Isabelle.Baldi@isped.u-bordeaux2.fr; Aqiel.Dalvie@uct.ac.za; ferro@iarc.fr; fervers@lyon.fnclcc.fr; Hilde.Langseth@kreftregisteret.no; Leslie.London@uct.ac.za; charles-lynch@uiowa.edu; John.Mclaughlin@cancercare.on.ca; james-merchant@uiowa.edu; pup165@mail.usask.ca; Sigsgaard@dadlnet.dk; lstayner@uic.edu; inekewesseling@gmail.com; kyyoo@plaza.snu.ac.kr; zahms@exchange.nih.gov; straif@iarc.fr; blaira@exchange.nih.gov RI London, Leslie/G-6061-2011; Yoo, Keun-Young/J-5548-2012; McLaughlin, John/E-4577-2013; BALDI, Isabelle/P-1778-2014; Zahm, Shelia/B-5025-2015; LEBAILLY, Pierre/L-7351-2015; Annesi-Maesano, Isabella/D-9173-2016; Beane Freeman, Laura/C-4468-2015 OI Sigsgaard, Torben/0000-0002-2043-7571; Douwes, Jeroen/0000-0003-3599-4036; BALDI, Isabelle/0000-0001-6417-039X; Beane Freeman, Laura/0000-0003-1294-4124 FU US National Cancer Institute; International Agency for Research on Cancer FX The AGRICOH consortium thanks Laura Beane Freeman and Aaron Blair for initiating the first workshop and Laura Beane Freeman, Shelia Zahm, Aaron Blair, Kurt Straif and Maria E Leon for initiating the second workshop. The start up of the consortium received financial support from the US National Cancer Institute and from the International Agency for Research on Cancer. NR 26 TC 13 Z9 13 U1 1 U2 7 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD MAY PY 2011 VL 8 IS 5 BP 1341 EP 1357 DI 10.3390/ijerph8051341 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 768QK UT WOS:000290950900006 PM 21655123 ER PT J AU Carmona, R Cano, E Grueso, E Ruiz-Villalba, A Bera, TK Gaztambide, J Segovia, JC Munoz-Chapuli, R AF Carmona, R. Cano, E. Grueso, E. Ruiz-Villalba, A. Bera, T. K. Gaztambide, J. Segovia, J. C. Munoz-Chapuli, R. TI Peritoneal repairing cells: a type of bone marrow derived progenitor cells involved in mesothelial regeneration SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE peritoneum; mesothelium; regeneration; progenitor cells; bone marrow; fibrocytes ID PARIETAL PERITONEUM; STEM-CELLS; MACROPHAGES; MONOCYTES; DIFFERENTIATION; ORIGIN; TISSUE; TUMORS; RATS AB The peritoneal mesothelium exhibits a high regenerative ability. Peritoneal regeneration is concomitant with the appearance, in the coelomic cavity, of a free-floating population of cells whose origin and functions are still under discussion. We have isolated and characterized this cell population and we have studied the process of mesothelial regeneration through flow cytometry and confocal microscopy in a murine model lethally irradiated and reconstituted with GFP-expressing bone marrow cells. In unoperated control mice, most free cells positive for mesothelin, a mesothelial marker, are green fluorescent protein (GFP). However, 24 hrs after peritoneal damage, free mesothelin+/ GFP+ cells appear in peritoneal lavages. Cultured lavage peritoneal cells show colocalization of GFP with mesothelial (mesothelin, cytokeratin) and fibroblastic markers. Immunohistochemical staining of the peritoneal wall also revealed colocalization of GFP with mesothelial markers and with procollagen-1 and smooth muscle alpha-actin. This was observed in the injured area as well as in the surrounding not-injured peritoneal surfaces. These cells, which we herein call peritoneal repairing cells (PRC), are very abundant 1 week after surgery covering both the damaged peritoneal wall and the surrounding uninjured area. However, they become very scarce 1 month later, when the mesothelium has completely healed. We suggest that PRC constitute a type of monocyte-derived cells, closely related with the tissue-repairing cells known as 'fibrocytes' and specifically involved in peritoneal reparation. Thus, our results constitute a synthesis of the different scenarios hitherto proposed about peritoneal regeneration, particularly recruitment of circulating progenitor cells and adhesion of free-floating coelomic cells. C1 [Carmona, R.; Cano, E.; Ruiz-Villalba, A.; Munoz-Chapuli, R.] Univ Malaga, Fac Sci, Dept Anim Biol, E-29071 Malaga, Spain. [Grueso, E.; Segovia, J. C.] Ctr Invest Energet Medioambientales & Tecnol CIEM, Hematopoiesis & Gene Therapy Div, Differentiat & Cytometry Unit, Madrid, Spain. [Grueso, E.; Segovia, J. C.] CIBER ER, Madrid, Spain. [Bera, T. K.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Gaztambide, J.] Hosp Univ Materno Infantil, Malaga, Spain. RP Munoz-Chapuli, R (reprint author), Univ Malaga, Fac Sci, Dept Anim Biol, E-29071 Malaga, Spain. EM chapuli@uma.es RI Munoz-Chapuli, Ramon/K-7306-2014; Carmona, Rita/K-4217-2014; Segovia, Jose/L-2922-2014; OI Munoz-Chapuli, Ramon/0000-0001-6392-6802; Carmona, Rita/0000-0002-9686-473X; Segovia, Jose/0000-0003-4101-6124; , Adrian/0000-0001-8063-0317 FU Ministerio de Ciencia e Innovacion [BFU2008-02384, SAF2008-1883]; TerCel network, ISCIII [RD06/0010/0015]; Junta de Andalucia [P06-CTS-01614, P08-CTS-03618]; VI framework, UE [LSHM-CT-2005-018630] FX This work was supported by grants BFU2008-02384 and SAF2008-1883, (Ministerio de Ciencia e Innovacion), RD06/0010/0015 (TerCel network, ISCIII), P06-CTS-01614, P08-CTS-03618 (Junta de Andalucia) and LSHM-CT-2005-018630 (VI framework, UE). We thank Dr. Ira Pastan (National Cancer Institute, NIH, Bethesda) for the sending of the anti-mesothelin antibody and their useful advices. We also thank Dr. Eric G. Neilson (Vanderbilt University School of Medicine, Nashville) for the gift of the anti-FSP1 antibody. D. Navas kindly helped us with flow cytometry and confocal microscopy. The authors also thank, S. Garcia for irradiating the animals and I. Orman for his expert help with the flow cytometry procedures at the CIEMAT/CIBER-ER. NR 30 TC 2 Z9 2 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD MAY PY 2011 VL 15 IS 5 BP 1200 EP 1209 DI 10.1111/j.1582-4934.2010.01087.x PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 769VG UT WOS:000291045800019 PM 20477904 ER PT J AU Tudor-Locke, C Ainsworth, BE Washington, TL Troiano, R AF Tudor-Locke, Catrine Ainsworth, Barbara E. Washington, Tracy L. Troiano, Richard TI Assigning Metabolic Equivalent Values to the 2002 Census Occupational Classification System SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE energy expenditure; physical activity; exercise ID PHYSICAL-ACTIVITY; SITTING TIME; OBESITY; QUESTIONNAIRE; COMPENDIUM; OVERWEIGHT; PATTERNS; WORKERS; DISEASE; ADULTS AB Background: The Current Population Survey (CPS) and the American Time Use Survey (ATUS) use the 2002 census occupation system to classify workers into 509 separate occupations arranged into 22 major occupational categories. Methods: We describe the methods and rationale for assigning detailed Metabolic Equivalent (MET) estimates to occupations and present population estimates (comparing outputs generated by analysis of previously published summary MET estimates to the detailed MET estimates) of intensities of occupational activity using the 2003 ATUS data comprised of 20,720 respondents, 5323 (2917 males and 2406 females) of whom reported working 6+ hours at their primary occupation on their assigned reporting day. Results: Analysis using the summary MET estimates resulted in 4% more workers in sedentary occupations, 6% more in light, 7% less in moderate, and 3% less in vigorous compared with using the detailed MET estimates. The detailed estimates are more sensitive to identifying individuals who do any occupational activity that is moderate or vigorous in intensity resulting in fewer workers in sedentary and light intensity occupations. Conclusions: Since CPS/ATUS regularly captures occupation data it will be possible to track prevalence of the different intensity levels of occupations. Updates will be required with inevitable adjustments to future occupational classification systems. C1 [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA. [Ainsworth, Barbara E.; Washington, Tracy L.] Arizona State Univ, Dept Exercise & Wellness, Mesa, AZ USA. [Troiano, Richard] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Tudor-Locke, C (reprint author), Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA. OI Washington, Tracy L./0000-0002-0959-7320; Troiano, Richard/0000-0002-6807-989X NR 15 TC 19 Z9 19 U1 1 U2 11 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAY PY 2011 VL 8 IS 4 BP 581 EP 586 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 768YD UT WOS:000290974900015 PM 21597131 ER PT J AU Kogure, T Shirakawa, S Shimokawa, M Hosokawa, Y AF Kogure, Takamasa Shirakawa, Shuichiro Shimokawa, Masato Hosokawa, Yuji TI Automatic Sleep/Wake Scoring from Body Motion in Bed: Validation of a Newly Developed Sensor Placed under a Mattress SO JOURNAL OF PHYSIOLOGICAL ANTHROPOLOGY LA English DT Article DE actigraphy; polysomnography; sleep/wake scoring; nonwear; bed movement ID NURSING-HOME RESIDENTS; NONPHARMACOLOGICAL INTERVENTION; WAKE IDENTIFICATION; WRIST ACTIVITY; ACTIGRAPHY; PATTERNS; BALLISTOCARDIOGRAM; RESPIRATION; POPULATION; INFANTS AB The purpose of this study was to formulate a "sleep/wake" scoring algorithm for processing activity measurements obtained using a newly developed nonwear actigraphy (NWA) device, and to test its validity. The NWA device has a highly sensitive pressure sensor and is placed under a mattress. It can continuously record the activity of a person lying on the mattress and identify an "in-bed/out-of-bed" state from the vibrations of the mattress. We formulated the sleep/wake scoring algorithm by using data obtained simultaneously by wrist actigraphy (Act) and the NWA device in 33 healthy participants. Agreement rate, sensitivity, and specificity with Act were 95.7%, 97.6%, and 75.8% (33 healthy people); the corresponding values were 85.9%, 89.1%, and 79.8% for 12 nursing home residents and 93.7%, 97.2%, and 60.8% for 60 nights for 6 healthy persons who slept 10 nights on their futons. Agreement rate, sensitivity, and specificity with polysomnography were in almost perfect agreement with Act (12 nights; 6 healthy persons who slept 2 nights). All our validation results indicate that the NWA device, placed under a mattress or a futon, can produce almost identical sleep/wake scores to Act. It is expected that the NWA device, a nonwear device for scoring sleep/wake and in-bed/out-of-bed, enables convenient long-term sleep-related evaluation in various fields, including hospital settings, home-care settings, and care facility settings such as nursing homes. J Physiol Anthropol 30(3): 103-109, 2011 http://www.jstage.jst.go.jp/browse/jpa2 [DOI: 10.2114/jpa2.30.103] C1 [Kogure, Takamasa] Paramount Bed Co Ltd, Paramount Bed Sleep Res Lab, Koto Ku, Tokyo 1368670, Japan. [Shirakawa, Shuichiro] NIMH, Natl Ctr Neurol & Psychiat, Bethesda, MD USA. [Shimokawa, Masato; Hosokawa, Yuji] Paramount Bed Co Ltd, Res & Engn Dept, Tokyo 1368670, Japan. RP Kogure, T (reprint author), Paramount Bed Co Ltd, Paramount Bed Sleep Res Lab, Koto Ku, 2-14-5 Higashisuna, Tokyo 1368670, Japan. EM t.kogure@paramount.co.jp NR 27 TC 8 Z9 8 U1 3 U2 13 PU JAPAN SOC PHYSIOLOGICAL ANTHROPOLOGY PI TOKYO PA BUSINESS CENTER FOR ACADEMIC SOCIETIES JAPAN, 5-16-9 HONKOMAGOME, TOKYO, 00000, JAPAN SN 1880-6791 J9 J PHYSIOL ANTHROPOL JI J. Physiol. Anthropol. PD MAY PY 2011 VL 30 IS 3 BP 103 EP 109 DI 10.2114/jpa2.30.103 PG 7 WC Physiology SC Physiology GA 770CX UT WOS:000291065700003 PM 21636953 ER PT J AU Fielding, RA Vellas, B Evans, WJ Bhasin, S Morley, JE Newman, AB van Kan, GA Andrieu, S Bauer, J Breuille, D Cederholm, T Chandler, J De Meynard, C Donini, L Harris, T Kannt, A Guibert, FK Onder, G Papanicolaou, D Rolland, Y Rooks, D Sieber, C Souhami, E Verlaan, S Zamboni, M AF Fielding, Roger A. Vellas, Bruno Evans, William J. Bhasin, Shalender Morley, John E. Newman, Anne B. van Kan, Gabor Abelian Andrieu, Sandrine Bauer, Juergen Breuille, Denis Cederholm, Tommy Chandler, Julie De Meynard, Capucine Donini, Lorenzo Harris, Tamara Kannt, Aimo Guibert, Florence Keime Onder, Graziano Papanicolaou, Dimitris Rolland, Yves Rooks, Daniel Sieber, Cornet Souhami, Elisabeth Verlaan, Sjors Zamboni, Mauro TI Sarcopenia: An Undiagnosed Condition in Older Adults. Current Consensus Definition: Prevalence, Etiology, and Consequences. International Working Group on Sarcopenia SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Muscle; aging; body composition; function; disability ID SKELETAL-MUSCLE MASS; PERIPHERAL ARTERIAL-DISEASE; LOWER-EXTREMITY FUNCTION; BIOELECTRICAL-IMPEDANCE ANALYSIS; CONVERTING ENZYME-INHIBITION; DIFFERENT FIBER TYPES; BODY-COMPOSITION; PHYSICAL-DISABILITY; GENE-EXPRESSION; ELDERLY-MEN AB Sarcopenia, the age-associated loss of skeletal muscle mass and function, has considerable societal consequences for the development of frailty, disability, and health care planning. A group of geriatricians and scientists from academia and industry met in Rome, Italy, on November 18, 2009, to arrive at a consensus definition of sarcopenia. The current consensus definition was approved unanimously by the meeting participants and is as follows: Sarcopenia is defined as the age-associated loss of skeletal muscle mass and function. The causes of sarcopenia are multifactorial and can include disuse, altered endocrine function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. Although cachexia may be a component of sarcopenia, the 2 conditions are not the same. The diagnosis of sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health. Sarcopenia should specifically be considered in patients who are bedridden, cannot independently rise from a chair, or who have a measured gait speed less that 1 m/s(-1). Patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry with sarcopenia being defined using currently validated definitions. A diagnosis of sarcopenia is consistent with a gait speed of less than 1 m.s(-1) and an objectively measured low muscle mass (eg, appendicular mass relative to ht(2) that is <= 7.23 kg/m(2) in men and <= 5.67 kg/m(2) in women). Sarcopenia is a highly prevalent condition in older persons that leads to disability, hospitalization, and death. (J Am Med Dir Assoc 2011; 12: 249-256) C1 [Fielding, Roger A.] Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. [Vellas, Bruno] CHU Toulouse, INSERM, U558, Toulouse, France. [Evans, William J.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Bhasin, Shalender] Boston Univ, Sch Med, Boston, MA 02118 USA. [Morley, John E.] Univ Med Sch, St Louis, MO USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [van Kan, Gabor Abelian; Rolland, Yves] Hop La Grave Casselardit, Toulouse, France. [Andrieu, Sandrine] INSERM, Fac Med, U558, Toulouse, France. [Bauer, Juergen] Univ Erlangen Nurnberg, Nurnberg, Germany. [Breuille, Denis] Ctr Rech Nestle, Lausanne, Switzerland. [Cederholm, Tommy] Uppsala Univ, Uppsala, Sweden. [Chandler, Julie; Papanicolaou, Dimitris] Merck Res Labs, Rahway, NJ USA. [De Meynard, Capucine] Lab Chiesi, Courbevoie, France. [Donini, Lorenzo] Univ Roma La Sapienza, Rome, Italy. [Harris, Tamara] NIA, Bethesda, MD 20892 USA. [Kannt, Aimo] Sanofi Aventis Deutschland GmbH, Frankfurt, Germany. [Guibert, Florence Keime] Inst Rech Int SERVIER, Courbevoie, France. [Onder, Graziano] Univ Cattal Sacre Cuore, Rome, Italy. [Rooks, Daniel] Novartis Inst, Cambridge, MA USA. [Sieber, Cornet] Klinikum Nurnberg Nord, Nurnberg, Germany. [Souhami, Elisabeth] Sanofi Aventis R&D, Croix De Berny, France. [Verlaan, Sjors] Danone Res Ctr Specialised Nutr, Schiphol Airport, Netherlands. [Zamboni, Mauro] Univ Verona, I-37100 Verona, Italy. RP Fielding, RA (reprint author), Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, 711 Washington St, Boston, MA 02111 USA. EM roger.fielding@tufts.edu RI morley, john/F-9177-2011; Newman, Anne/C-6408-2013; OI morley, john/0000-0001-6444-2965; Newman, Anne/0000-0002-0106-1150; Donini, Lorenzo/0000-0003-4692-4754; ZAMBONI, Mauro/0000-0001-6961-9483 FU GlaxoSmithKline; Abbott; Chiesi; Danone; Merck; Nestle; Novartis; Sanofi Aventis FX Partial support for this meeting, in the form of travel costs, was provided by GlaxoSmithKline and Abbott, Chiesi, Danone, Merck, Nestle, Novartis, and Sanofi Aventis. NR 102 TC 574 Z9 598 U1 19 U2 130 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAY PY 2011 VL 12 IS 4 BP 249 EP 256 DI 10.1016/j.jamda.2011.01.003 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 768HK UT WOS:000290924500003 PM 21527165 ER PT J AU Hirsch, LJ Donner, EJ So, EL Jacobs, M Nashef, L Noebels, JL Buchhalter, JR AF Hirsch, L. J. Donner, E. J. So, E. L. Jacobs, M. Nashef, L. Noebels, J. L. Buchhalter, J. R. TI Abbreviated report of the NIH/NINDS workshop on sudden unexpected death in epilepsy SO NEUROLOGY LA English DT Review AB Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of epilepsy and is not rare. The NIH and National Institute of Neurological Disorders and Stroke sponsored a 3-day multidisciplinary workshop to advance research into SUDEP and its prevention. Parallel sessions were held: one with a focus on the science of SUDEP, and the other with a focus on issues related to the education of health care practitioners and people with epilepsy. This report summarizes the discussions and recommendations of the workshop, including lessons learned from investigations of sudden infant death syndrome (SIDS), sudden cardiac death, autonomic and respiratory physiology, medical devices, genetics, and animal models. Recommendations include educating all people with epilepsy about SUDEP as part of their general education on the potential harm of seizures, except in extenuating circumstances. Increasing awareness of SUDEP may facilitate improved seizure control, possibly decreasing SUDEP incidence. There have been significant advances in our understanding of the clinical and physiologic features of SIDS, sudden cardiac death, and SUDEP in both people and animals. Research should continue to focus on the cardiac, autonomic, respiratory, and genetic factors that likely contribute to the risk of SUDEP. Multicenter collaborative research should be encouraged, especially investigations with direct implications for the prevention of SUDEP. An ongoing SUDEP Coalition has been established to facilitate this effort. With the expansion of clinical, genetic, and basic science research, there is reasonable hope of advancing our understanding of SUDEP and ultimately our ability to prevent it. Neurology (R) 2011;76:1932-1938 C1 [Hirsch, L. J.] Columbia Univ, Dept Neurol, Comprehens Epilepsy Ctr, New York, NY USA. [Donner, E. J.] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Neurol, Toronto, ON M5G 1X8, Canada. [So, E. L.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. [Jacobs, M.] NINDS, Epilepsy Program, NIH, Bethesda, MD 20892 USA. [Nashef, L.] Kings Coll Hosp London, Dept Neurol, London, England. [Noebels, J. L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Noebels, J. L.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Noebels, J. L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Buchhalter, J. R.] Phoenix Childrens Hosp, Comprehens Pediat Epilepsy Program, Phoenix, AZ USA. RP Hirsch, LJ (reprint author), Yale Univ, Sch Med, Dept Neurol, POB 208018, New Haven, CT 06520 USA. EM Lawrence.Hirsch@Yale.edu OI Noebels, Jeffrey /0000-0002-2887-0839 FU NIH/NINDS; Eisai Inc.; Pfizer Inc; UCB; Lundbeck Inc.; Upsher-Smith; American Epilepsy Society; Epilepsy Foundation; Canadian Institutes of Health Research; C. U. R. E.; Blue Bird Circle Foundation for Pediatric Research FX Study funding: This workshop was supported by NIH/NINDS.; Dr. Hirsch has received speaker honoraria from UCB, GlaxoSmithKline, Pfizer Inc, and Lundbeck Inc.; serves on the editorial board of the Journal of Clinical Neurophysiology and as a contributing editor for Epilepsy Currents; receives publishing royalties for Atlas of EEG in Critical Care (Wiley-Blackwell, 2010) and UpToDate, Inc.; serves as a consultant for Lundbeck Inc. and Ikano Therapeutics Inc.; serves/has served on speakers' bureaus for GlaxoSmithKline, UCB, Pfizer Inc, and Lundbeck Inc.; and receives research support from Eisai Inc., Pfizer Inc, UCB, Lundbeck Inc., Upsher-Smith, the American Epilepsy Society, and the Epilepsy Foundation. Dr. Donner serves on the editorial board of the Journal of Child Neurology; has received speaker honoraria from Nutrica, Inc. and the American Academy of Neurology; and has received research support from the Canadian Institutes of Health Research and C. U. R. E. Dr. So serves on the editorial board of Epilepsia, Epilepsy Research, and Journal of Clinical Neurophysiology. M. Jacobs reports no disclosures. Dr. Nashef is a trustee for Epilepsy Research UK and serves on the scientific advisory committee of Epilepsy Bereaved; receives publishing royalties for Oxford Specialist Handbooks in Neurology: Epilepsy (Oxford University Press, 2009); and has attended medical conferences as a guest of pharmaceutical companies and supervised staff funded by pharmaceutical companies carrying out audits (GlaxoSmithKline, UCB, Pfizer Inc, and Eisai Inc.). Dr. Noebels served on the editorial board of the Journal of Neuroscience and receives research support from the NIH/NINDS and the Blue Bird Circle Foundation for Pediatric Research. Dr. Buchhalter serves on scientific advisory boards for the NIH and the Charlie Foundation; serves on the editorial advisory board of Clinical Neurology News; and receives research support from Lundbeck Inc, Pfizer Inc, and the NIH/NINDS. NR 5 TC 38 Z9 39 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2011 VL 76 IS 22 BP 1932 EP 1938 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 769WN UT WOS:000291049100016 PM 21543734 ER PT J AU Rochman, M Taher, L Kurahashi, T Cherukuri, S Uversky, VN Landsman, D Ovcharenko, I Bustin, M AF Rochman, Mark Taher, Leila Kurahashi, Toshihiro Cherukuri, Srujana Uversky, Vladimir N. Landsman, David Ovcharenko, Ivan Bustin, Michael TI Effects of HMGN variants on the cellular transcription profile SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INTRINSIC PROTEIN DISORDER; LINKER-HISTONE SUBTYPES; AMINO-ACID-COMPOSITION; CHROMOSOMAL-PROTEINS; CHROMATIN-STRUCTURE; BINDING; H1; EXPRESSION; NUCLEOSOMES; HMG-17 AB High mobility group N (HMGN) is a family of intrinsically disordered nuclear proteins that bind to nucleosomes, alters the structure of chromatin and affects transcription. A major unresolved question is the extent of functional specificity, or redundancy, between the various members of the HMGN protein family. Here, we analyze the transcriptional profile of cells in which the expression of various HMGN proteins has been either deleted or doubled. We find that both up- and downregulation of HMGN expression altered the cellular transcription profile. Most, but not all of the changes were variant specific, suggesting limited redundancy in transcriptional regulation. Analysis of point and swap HMGN mutants revealed that the transcriptional specificity is determined by a unique combination of a functional nucleosome-binding domain and C-terminal domain. Doubling the amount of HMGN had a significantly larger effect on the transcription profile than total deletion, suggesting that the intrinsically disordered structure of HMGN proteins plays an important role in their function. The results reveal an HMGN-variant-specific effect on the fidelity of the cellular transcription profile, indicating that functionally the various HMGN subtypes are not fully redundant. C1 [Rochman, Mark; Kurahashi, Toshihiro; Cherukuri, Srujana; Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res, Bethesda, MD 20894 USA. [Taher, Leila; Landsman, David; Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Uversky, Vladimir N.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Ctr Computat Biol & Bioinformat, Inst Intrinsically Disordered Prot Res, Indianapolis, IN 46202 USA. [Uversky, Vladimir N.] Univ S Florida, Dept Mol Med, Tampa, FL 33612 USA. [Uversky, Vladimir N.] Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142290, Moscow Region, Russia. RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20894 USA. EM bustin@helix.nih.gov RI Uversky, Vladimir/F-4515-2011; Bustin, Michael/G-6155-2015; OI Uversky, Vladimir/0000-0002-4037-5857; Landsman, David/0000-0002-9819-6675 FU CCR, NCI, NIH; National Library of Medicine, NIH; Intramural, CCR, NCI, NIH FX Intramural program of the CCR, NCI, NIH and Research Program of the National Library of Medicine, NIH. Funding for open access charge: Intramural, CCR, NCI, NIH. NR 61 TC 20 Z9 20 U1 1 U2 2 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 MAY PY 2011 VL 39 IS 10 BP 4076 EP 4087 DI 10.1093/nar/gkq1343 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 770CB UT WOS:000291063500014 PM 21278158 ER PT J AU Zampieri, C Salarian, A Carlson-Kuhta, P Nutt, JG Horak, FB AF Zampieri, Cris Salarian, Arash Carlson-Kuhta, Patricia Nutt, John G. Horak, Fay B. TI Assessing mobility at home in people with early Parkinson's disease using an instrumented Timed Up and Go test SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Home; Instrumented; Timed Up and Go ID GAIT AB Gait and mobility problems are prominent features of Parkinson's Disease (PD), and are difficult to observe clinically in early stages of PD. We previously reported that gait changes were measurable in early to mid-stage PD subjects, when we used inertial sensors during an instrumented Timed Up and Go test (iTUG). With the advent of wearable inertial sensors, home assessment of mobility has become possible. We tested six people with early PD and eight control subjects using the iTUG in the home and laboratory. Our objectives were to 1) investigate the feasibility of testing subjects at home, and 2) compare performance at home versus laboratory. We found that home iTUG testing is feasible and the patients with PD were more affected than the healthy control subjects when tested at home. Published by Elsevier Ltd. C1 [Zampieri, Cris] NCI, Funct & Appl Biomech Lab, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Salarian, Arash; Carlson-Kuhta, Patricia; Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97006 USA. RP Zampieri, C (reprint author), NCI, Funct & Appl Biomech Lab, Dept Rehabil Med, Ctr Clin, Bldg 10,MSC1604, Bethesda, MD 20892 USA. EM zampierigallac@mail.nih.gov RI Salarian, Arash/E-8311-2016 OI Salarian, Arash/0000-0001-7332-0062 FU Kinetics Foundation; National Institutes on Aging [006457]; Oregon Center for Aging and Technology [AG024978]; NIH, Clinical Center, Rehabilitation Medicine Department FX We thank our research subjects, Triana Nagel for assisting with subject scheduling and Prof. K. Aminian for providing the Physilog system. This research was supported by the Kinetics Foundation, the National Institutes on Aging (006457) and the Oregon Center for Aging and Technology (AG024978). This research was also supported in part by the Intramural Research Program of the NIH, Clinical Center, Rehabilitation Medicine Department. Dr. Horak was a consultant for the Kinetics Foundation. This potential conflict of interest has been reviewed and managed by OHSU. The technology described herein is patent pending and available for licensing from OHSU. NR 12 TC 18 Z9 20 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAY PY 2011 VL 17 IS 4 BP 277 EP 280 DI 10.1016/j.parkreldis.2010.08.001 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 770FV UT WOS:000291073300011 PM 20801706 ER PT J AU Aldworth, ZN Dimitrov, AG Cummins, GI Gedeon, T Miller, JP AF Aldworth, Zane N. Dimitrov, Alexander G. Cummins, Graham I. Gedeon, Tomas Miller, John P. TI Temporal Encoding in a Nervous System SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID CRICKET CERCAL SYSTEM; LATERAL GENICULATE-NUCLEUS; COCKROACH PERIPLANETA-AMERICANA; INFORMATION-THEORETIC ANALYSIS; PRIMARY SENSORY INTERNEURONS; TERMINAL ABDOMINAL-GANGLION; NEURAL SPIKE TRAINS; GIANT INTERNEURONS; GRYLLUS-BIMACULATUS; VISUAL INFORMATION AB We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures. C1 [Aldworth, Zane N.; Dimitrov, Alexander G.; Cummins, Graham I.; Gedeon, Tomas; Miller, John P.] Montana State Univ, Ctr Computat Biol, Bozeman, MT 59717 USA. [Gedeon, Tomas] Montana State Univ, Dept Math Sci, Bozeman, MT 59717 USA. [Dimitrov, Alexander G.; Cummins, Graham I.] Washington State Univ, Dept Math, Vancouver, WA USA. [Dimitrov, Alexander G.; Cummins, Graham I.] Washington State Univ, Sci Programs, Vancouver, WA USA. RP Aldworth, ZN (reprint author), NICHD, NIH, Lab Cellular & Synapt Physiol, Bethesda, MD 20892 USA. EM zane.aldworth@nih.gov RI Dimitrov, Alexander/E-8577-2014 OI Dimitrov, Alexander/0000-0002-8812-3536 FU National Institute of Mental Health [NIMH 2R01 MH-064416]; US National Science Foundation [EF-04252878, EIA-0129895, DMS-0818785, IGERT DGE-9972824]; Kopriva fellowship FX This work was supported by grants from the National Institute of Mental Health to JPM (NIMH 2R01 MH-064416), the US National Science Foundation to JPM (EF-04252878), to JPM and TG (EIA-0129895), to TG (DMS-0818785), and to ZNA (IGERT DGE-9972824), and by a Kopriva fellowship to ZNA The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 96 TC 7 Z9 7 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2011 VL 7 IS 5 AR e1002041 DI 10.1371/journal.pcbi.1002041 PG 19 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 769LT UT WOS:000291015800019 PM 21573206 ER PT J AU Allen, JE Wynn, TA AF Allen, Judith E. Wynn, Thomas A. TI Evolution of Th2 Immunity: A Rapid Repair Response to Tissue Destructive Pathogens SO PLOS PATHOGENS LA English DT Article ID CD4(+) T-CELLS; MACROPHAGE ACTIVATION; HELMINTH INFECTION; WOUND REPAIR; INNATE; INFLAMMATION; RESISTANCE; IMMUNOPATHOLOGY; IMMUNOLOGY; EXPRESSION C1 [Allen, Judith E.] Univ Edinburgh, Inst Evolut, Edinburgh, Midlothian, Scotland. [Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA. [Allen, Judith E.] Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh, Midlothian, Scotland. RP Allen, JE (reprint author), Univ Edinburgh, Inst Evolut, Edinburgh, Midlothian, Scotland. EM j.allen@ed.ac.uk RI Allen, Judith/C-9198-2011; Wynn, Thomas/C-2797-2011 OI Allen, Judith/0000-0002-3829-066X; FU Medical Research Council UK; NIH/NIAID FX This work was supported in part by the Medical Research Council UK and the Intramural Research Program of the NIH/NIAID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 117 Z9 119 U1 1 U2 32 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 MAY PY 2011 VL 7 IS 5 AR e1002003 DI 10.1371/journal.ppat.1002003 PG 4 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 769LC UT WOS:000291014000010 PM 21589896 ER PT J AU Gallegos, AM van Heijst, JWJ Samstein, M Su, XD Pamer, EG Glickman, MS AF Gallegos, Alena M. van Heijst, Jeroen W. J. Samstein, Miriam Su, Xiaodi Pamer, Eric G. Glickman, Michael S. TI A Gamma Interferon Independent Mechanism of CD4 T Cell Mediated Control of M. tuberculosis Infection in vivo SO PLOS PATHOGENS LA English DT Article ID NECROSIS-FACTOR-ALPHA; MYCOBACTERIUM-TUBERCULOSIS; IFN-GAMMA; PROTECTION; MICE; VACCINATION; RESPONSES; IMMUNITY; EXPRESSION; RESISTANCE AB CD4 T cell deficiency or defective IFN gamma signaling render humans and mice highly susceptible to Mycobacterium tuberculosis (Mtb) infection. The prevailing model is that Th1 CD4 T cells produce IFN gamma to activate bactericidal effector mechanisms of infected macrophages. Here we test this model by directly interrogating the effector functions of Th1 CD4 T cells required to control Mtb in vivo. While Th1 CD4 T cells specific for the Mtb antigen ESAT-6 restrict in vivo Mtb growth, this inhibition is independent of IFN gamma or TNF and does not require the perforin or FAS effector pathways. Adoptive transfer of Th17 CD4 T cells specific for ESAT-6 partially inhibited Mtb growth while Th2 CD4 T cells were largely ineffective. These results imply a previously unrecognized IFN gamma/TNF independent pathway that efficiently controls Mtb and suggest that optimization of this alternative effector function may provide new therapeutic avenues to combat Mtb through vaccination. C1 [Gallegos, Alena M.] NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Gallegos, Alena M.; van Heijst, Jeroen W. J.; Pamer, Eric G.; Glickman, Michael S.] Mem Sloan Kettering Canc Ctr, Program Immunol, Infect Dis Serv, New York, NY 10021 USA. [Samstein, Miriam; Su, Xiaodi] Weill Grad Sch Med Sci, Program Immunol & Microbial Pathogenesis, New York, NY USA. RP Gallegos, AM (reprint author), NIAID, NIH, Parasit Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pamere@mskcc.org; glickmam@mskcc.org FU National Institutes of Health [AI80619, AI0677359, GM07739]; Netherlands Organization for Scientific Research FX Funding: Financial support was received from the National Institutes of Health grant AI80619 (MG and EP) and AI0677359 (AG), the Netherlands Organization for Scientific Research (JWJvH), and NIH MSTP grant GM07739 (MS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 78 Z9 80 U1 1 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 MAY PY 2011 VL 7 IS 5 AR e1002052 DI 10.1371/journal.ppat.1002052 PG 8 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 769LC UT WOS:000291014000036 PM 21625591 ER PT J AU Markina, NA Mancuso, R Neuenswander, B Lushington, GH Larock, RC AF Markina, Nataliya A. Mancuso, Raffaella Neuenswander, Benjamin Lushington, Gerald H. Larock, Richard C. TI Solution-Phase Parallel Synthesis of a Diverse Library of 1,2-Dihydroisoquinolines SO ACS COMBINATORIAL SCIENCE LA English DT Article DE solution-phase; parallel synthesis; diverse library of 1,2-dihydroisoquinolines ID TANDEM NUCLEOPHILIC-ADDITION; ORTHO-ALKYNYLARYL ALDIMINES; CROSS-COUPLING REACTIONS; COMBINATORIAL CHEMISTRY; DEVELOPMENT SETTINGS; ESTIMATE SOLUBILITY; CONCISE SYNTHESIS; DRUG DISCOVERY; ISOQUINOLINE; CYCLIZATION AB Synthesis of a 105 membered library of 1,2-dihydroisoquinolines is described. The 1,2-dihydroisoquinoline compounds have been prepared in good yields using a Lewis acid and organocatalyst-cocatalyzed multicomponent reaction of 2-(1-alkynyl)benzaldehydes, amines, and ketones. Various indoles have also been employed as pronucleophiles, furnishing 1-(3-indolyl)-1,2-dihydroisoquinolines. The halogen functionality present in some of the synthesized compounds allows for further diversification by palladium-catalyzed Suzuki-Miyaura and Sonogashira cross-couplings to give more diversified 1,2-dihydroisoquinoline derivatives. C1 [Markina, Nataliya A.; Larock, Richard C.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Mancuso, Raffaella] Univ Calabria, Dipartimento Chim, I-87036 Arcavacata Di Rende, CS, Italy. [Neuenswander, Benjamin; Lushington, Gerald H.] Univ Kansas, NIH, Ctr Excellence Chem Methodol & Lib Dev, Lawrence, KS 66047 USA. RP Larock, RC (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. EM larock@iastate.edu FU National Institute of General Medical Sciences [GM070620, GM079593]; National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence [GM069663] FX We thank the National Institute of General Medical Sciences (GM070620 and GM079593) and the National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence (GM069663) for support of this research NR 41 TC 33 Z9 33 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2156-8952 J9 ACS COMB SCI JI ACS Comb. Sci. PD MAY-JUN PY 2011 VL 13 IS 3 BP 265 EP 271 DI 10.1021/co1000794 PG 7 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 759LO UT WOS:000290246300010 PM 21410207 ER PT J AU Kim, SE Liu, F Im, YJ Stephen, AG Fivash, MJ Waheed, AA Freed, EO Fisher, RJ Hurley, JH Burke, TR AF Kim, Sung-Eun Liu, Fa Im, Young Jun Stephen, Andrew G. Fivash, Matthew J. Waheed, Abdul A. Freed, Eric O. Fisher, Robert J. Hurley, James H. Burke, Terrence R. TI Elucidation of New Binding Interactions with the Human Tsg101 Protein Using Modified HIV-1 Gag-p6 Derived Peptide Ligands SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Protein-protein interactions; Tsg101; X-ray crystal structure; peptide analogues ID EXPEDITED LIBRARY SYNTHESIS; DRUG DISCOVERY; DOMAIN; INTERFACE; OXIME; SH3 AB Targeting protein protein interactions is gaining greater recognition as an attractive approach to therapeutic development. An example of this may be found with the human cellular protein encoded by the tumor susceptibility gene 101 (Tsg101), where interaction with the p6 C-terminal domain of the nascent viral Gag protein is required for HIV-1 particle budding and release. This association of Gag with Tsg101 is highly dependent on a "Pro-Thr-Ala-Pro" ("PTAP") peptide sequence within the p6 protein. Although p6-derived peptides offer potential starting points for developing Tsg101-binding inhibitors, the affinities of canonical peptides are outside the useful range (K(d) values greater than 50 mu M). Reported herein are crystal structures of Tsg101 in complex with two structurally modified PTAP-derived peptides. These data define new regions of ligand interaction not previously identified with canonical peptide sequences. This information could be highly useful in the design of Tsg101-binding antagonists. C1 [Kim, Sung-Eun; Liu, Fa; Burke, Terrence R.] NCI Frederick, Biol Chem Lab, Discovery Program, CCR, Frederick, MD 21702 USA. [Im, Young Jun; Hurley, James H.] Natl Inst Diabet & Digest & Kidney, Mol Biol Lab, Frederick, MD 21702 USA. [Stephen, Andrew G.; Fisher, Robert J.] NCI Frederick, Prot Chem Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Fivash, Matthew J.] NCI Frederick, Data Management Syst Inc, Frederick, MD 21702 USA. [Waheed, Abdul A.; Freed, Eric O.] NCI Frederick, HIV Drug Resistance Program, CCR, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI Frederick, Biol Chem Lab, Discovery Program, CCR, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU NIH; Center for Cancer Research; NCI-Frederick; National Cancer Institute, National Institutes of Health; NIH, NIDDK FX This work was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick, and the National Cancer Institute, National Institutes of Health, by the Intramural Research Program of the NIH, NIDDK, and by the IATAP program of the NTH Intramural Research Program Y.J.I. was supported in part an. NIH Intramural AIDS Research Fellowship. NR 25 TC 5 Z9 6 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2011 VL 2 IS 5 BP 337 EP 341 DI 10.1021/ml1002579 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 765GE UT WOS:000290691400003 PM 21643473 ER PT J AU Cardellina, JH Vieira, RC Eccard, V Skerry, J Montgomery, V Campbell, Y Roxas-Duncan, V Leister, W LeClair, CA Maloney, DJ Padula, D Pescitelli, G Khavrutskii, I Hu, X Wallqvist, A Smith, LA AF Cardellina, John H., II Vieira, Rebecca C. Eccard, Vanessa Skerry, Janet Montgomery, Vicki Campbell, Yvette Roxas-Duncan, Virginia Leister, William LeClair, Christopher A. Maloney, David J. Padula, Daniele Pescitelli, Gennaro Khavrutskii, Ilja Hu, Xin Wallqvist, Anders Smith, Leonard A. TI Separation of Betti Reaction Product Enantiomers: Absolute Configuration and Inhibition of Botulinum Neurotoxin A SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Chiral resolution; Betti reaction products; TDDFT CD calculations; molecular docking; inhibition of botulinum neurotoxin ID AUTOMATED DOCKING; FLEXIBLE LIGANDS; INVERSION; BASE; IBUPROFEN; ENERGIES; PROTEASE; AUTODOCK; SEROTYPE; KEY AB The racemic product of the Betti reaction of 5-chloro-8-hydroxyquinoline, benzaldehyde, and 2-aminopyridine was separated by chiral HPLC to determine which enantiomer inhibited botulinurn neurotoxin serotype A. When the enantiomers unexpectedly proved to have comparable activity, the absolute structures of (+)-(R)-1 and ()-(S)-1 were determined by comparison of calculated and observed circular dichroism spectra. Molecular modeling studies were undertaken in an effort to understand the observed bioactivity and revealed different ensembles of binding modes, with roughly equal binding energies, for the two enantiomers. C1 [Smith, Leonard A.] USA, Off Chief Scientist, Med Res Inst Infect Dis, Frederick, MD USA. [Cardellina, John H., II; Vieira, Rebecca C.; Eccard, Vanessa; Skerry, Janet; Montgomery, Vicki; Campbell, Yvette; Roxas-Duncan, Virginia] USA, Div Integrated Toxicol, Med Res Inst Infect Dis, Frederick, MD USA. [Leister, William; LeClair, Christopher A.; Maloney, David J.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Padula, Daniele; Pescitelli, Gennaro] Univ Pisa, Dept Chem, Pisa, Italy. [Khavrutskii, Ilja; Hu, Xin; Wallqvist, Anders] USA, Biotechnol High Performance Comp Software Applica, Telemed & Adv Technol Res Ctr, Med Res & Mat Command, Frederick, MD USA. RP Smith, LA (reprint author), USA, Off Chief Scientist, Med Res Inst Infect Dis, Frederick, MD USA. EM Leonard.Smith@amedd.army.mil RI Pescitelli, Gennaro/G-3536-2010; Padula, Daniele/F-2866-2012; OI Pescitelli, Gennaro/0000-0002-0869-5076; Padula, Daniele/0000-0002-7171-7928; wallqvist, anders/0000-0002-9775-7469 FU Defense Threat Reduction Agency [3.10037_07_RD_B]; National Research Council; U.S. Department of Defense under High Performance Computing Software Applications Institutes (HSAI) initiative FX This work was supported by a grant to L.A.S. from the Defense Threat Reduction Agency, JSTO-CBD Project Number 3.10037_07_RD_B. R.C.V. was funded by a National Research Council Research Associateship Award. This work was sponsored by the U.S. Department of Defense High Performance Computing Modernization Program (HPCMP), under the High Performance Computing Software Applications Institutes (HSAI) initiative. We thank James Bougie for help with the chiral HPLC separation. Opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the official views of the United States Department of Defense. NR 28 TC 4 Z9 4 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2011 VL 2 IS 5 BP 396 EP 401 DI 10.1021/ml200028z PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 765GE UT WOS:000290691400014 PM 22102940 ER PT J AU Shukla, GC Haque, F Tor, Y Wilhelmsson, LM Toulme, JJ Isambert, H Guo, PX Rossi, JJ Tenenbaum, SA Shapiro, BA AF Shukla, Girish C. Haque, Farzin Tor, Yitzhak Wilhelmsson, L. Marcus Toulme, Jean-Jacques Isambert, Herve Guo, Peixuan Rossi, John J. Tenenbaum, Scott A. Shapiro, Bruce A. TI A Boost for the Emerging Field of RNA Nanotechnology Report on the First International conference on RNA Nanotechnology SO ACS NANO LA English DT Article ID DNA-PACKAGING MOTOR; SINGLE-MOLECULE FLUORESCENCE; BICOID MESSENGER-RNA; NUCLEIC-ACID; BASE ANALOG; IN-VITRO; EXPONENTIAL ENRICHMENT; SYSTEMATIC EVOLUTION; STRUCTURE PREDICTION; CHEMICAL SYNTHESIS AB This Nano Focus article highlights recent advances in RNA nanotechnology as presented at the First International Conference of RNA Nanotechnology and Therapeutics, which took place in Cleveland, OH, USA (October 23-25, 2010) (http;//www.eng.uc.edu/nanomedidne/RNA2010/), chaired by Peixuan Guo and co-chaired by David Rueda and Scott Tenenbaum. The conference was the first of its kind to bring together more than 30 invited speakers in the frontier of RNA nanotechnology from France, Sweden, South Korea, China, and throughout the United States to discuss RNA nanotechnology and Its applications. It provided a platform for researchers from academia, government, and the pharmaceutical industry to share existing knowledge, vision, technology, and challenges in the field and promoted collaborations among researchers interested in advancing this emerging scientific discipline. The meeting covered a range of topics, including biophysical and single-molecule approaches for characterization of RNA nanostructures; structure studies on RNA nanoparticles by chemical or biochemical approaches, computation, prediction, and modeling of RNA nanoparticle structures; methods for the assembly of RNA nanoparticles; chemistry for RNA synthesis, conjugation, and labeling; and application of RNA nanoparticles in therapeutics. A special invited talk on the well-established principles of DNA nanotechnology was arranged to provide models for RNA nanotechnology. An Administrator from National Institutes of Health (NIH) National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer discussed the current nanocancer research directions and future funding opportunities at NCl. As indicated by the feedback received from the invited speakers and the meeting participants, this meeting was extremely successful, exciting, and informative, covering many groundbreaking findings, pioneering ideas, and novel discoveries. C1 [Tenenbaum, Scott A.] SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12203 USA. [Shukla, Girish C.] Cleveland State Univ, Dept Biol Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA. [Haque, Farzin; Guo, Peixuan] Univ Cincinnati, Coll Engn & Appl Sci, Nanobiomed Ctr, Cincinnati, OH 45267 USA. [Tor, Yitzhak] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Wilhelmsson, L. Marcus] Chalmers, Dept Chem & Biol Engn Phys Chem, SE-41296 Gothenburg, Sweden. [Toulme, Jean-Jacques] Univ Bordeaux Segalen, INSERM, U869, F-33076 Bordeaux, France. [Isambert, Herve] Inst Curie, CNRS, Div Res, UMR 168, F-75005 Paris, France. [Rossi, John J.] Beckman Res Inst City Hope, Dept Mol & Cellular Biol, Duarte, CA 91010 USA. [Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. RP Tenenbaum, SA (reprint author), SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12203 USA. EM stenenbaum@albany.edu; shapirbr@mail.nih.gov RI Wilhelmsson, L Marcus/A-9165-2008; Guo, Peixuan/I-7184-2015; OI Wilhelmsson, L Marcus/0000-0002-2193-6639; Toulme, Jean-jacques/0000-0002-8432-5034; Shukla, Girish/0000-0003-1982-2218 FU Kylin Therapeutics, Inc.; Girindus; Trilink BioTechnologies; Agilent Technologies; NIH Nanomedicine Development Center [PN2 EY 018230]; NIH [EB003730, GM059944, CA151648]; NIH, National Cancer Institute, Center for Cancer Research FX We thank the participants and sponsors of the meeting. We also wish to thank Thomas Hermann, Mark Laskovics, Christoph Flamm, Chad Schwartz, Randall Reif, and Daniel Binzel for their insightful comments. We apologize to participants whose work could not be reviewed in this article due to space limitations. The meeting was supported and sponsored by funding or donations in part from Kylin Therapeutics, Inc., Girindus, Trilink BioTechnologies, Agilent Technologies, NIH Nanomedicine Development Center of Phi29 DNA Packaging Motor for Nanomedicine (PN2 EY 018230), NIH grants EB003730, GM059944, CA151648, and funding from the laboratories of the invited speakers and the co-authors. P.G. is a co-founder and contractor of Kylin. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 136 TC 37 Z9 37 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD MAY PY 2011 VL 5 IS 5 BP 3405 EP 3418 DI 10.1021/nn200989r PG 14 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 767AD UT WOS:000290826800001 PM 21604810 ER PT J AU Suomi, SJ AF Suomi, Stephen J. TI Risk, Resilience, and Gene-Environment Interplay in Primates SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat DE anxiety; aggression; G x E; maternal buffering C1 [Suomi, Stephen J.] NICHHD, NIH, Poolesville, MD USA. NR 5 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 3 BP 1S EP 1S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800004 ER PT J AU Kleinman, JE AF Kleinman, Joel E. TI Brain Development and Risk for Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat ID EXPRESSION C1 [Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 4 BP 2S EP 2S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800005 ER PT J AU Rapoport, SI Basselin, M Ramadan, E AF Rapoport, Stanley I. Basselin, Mireille Ramadan, Epolia TI Lamotrigine, Approved for Bipolar Disorder, Interferes with Brain NMDA Receptor-Initiated Arachidonic Acid Signaling in Unanesthetized Rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Rapoport, Stanley I.; Basselin, Mireille; Ramadan, Epolia] NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 39 BP 12S EP 12S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800040 ER PT J AU Cadenhead, K Addington, J Cannon, T Cornblatt, B McGlashan, T Perkins, D Walker, E Woods, S Bachman, P Belger, A Carrion, R Donkers, F Duncan, E Johannesen, J Light, G Mathlon, D Nunag, J Roach, B Heinssen, R AF Cadenhead, Kristin Addington, Jean Cannon, Tyrone Cornblatt, Barbara McGlashan, Thomas Perkins, Diana Walker, Elaine Woods, Scott Bachman, Peter Belger, Ayse Carrion, Ricardo Donkers, Franc Duncan, Erica Johannesen, Jason Light, Gregory Mathlon, Daniel Nunag, Jason Roach, Brian Heinssen, Robert TI Greater Prepulse Inhibition Prior to the Onset of Psychosis? Findings from the North American Prodrome Longitudinal Study Consortium SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Cadenhead, Kristin; Light, Gregory; Nunag, Jason] Univ Calif San Diego, La Jolla, CA 92093 USA. [Addington, Jean] Univ Calgary, Calgary, AB, Canada. [Cannon, Tyrone; Bachman, Peter] Univ Calif Los Angeles, Los Angeles, CA USA. [Cornblatt, Barbara; Carrion, Ricardo] Zucker Hillside Hosp, Long Isl City, NY USA. [McGlashan, Thomas; Woods, Scott; Johannesen, Jason] Yale Univ, New Haven, CT USA. [Perkins, Diana; Belger, Ayse; Donkers, Franc] Univ N Carolina, Chapel Hill, NC USA. [Walker, Elaine; Duncan, Erica] Emory Univ, Atlanta, GA 30322 USA. [Mathlon, Daniel; Roach, Brian] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Heinssen, Robert] NIMH, Div Adult Translat Res, Bethesda, MD 20892 USA. RI Donkers, Franc/H-2391-2013 OI Donkers, Franc/0000-0002-8252-0426 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 41 BP 13S EP 13S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800042 ER PT J AU Weinberger, DR AF Weinberger, Daniel R. TI Epistasis and Susceptibility Genes for Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Weinberger, Daniel R.] NIMH, NIH, Inramural Res Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 61 BP 17S EP 17S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800054 ER PT J AU Young, WS AF Young, W. Scott TI Anatomy and Behavioral Roles of the Vasopressin 1b Receptor SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Young, W. Scott] NIMH, NIH, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 69 BP 19S EP 19S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800062 ER PT J AU Guha, S Lencz, T Hodgkinson, C Rosenfeld, J Yuan, QP DeRosse, P Lee, AT Kane, JM Gregersen, PK Pe'er, I Malhotra, AK Goldman, D Darvasi, A AF Guha, Saurav Lencz, Todd Hodgkinson, Colin Rosenfeld, Jeffrey Yuan, Qiaoping DeRosse, Pamela Lee, Annette T. Kane, John M. Gregersen, Peter K. Pe'er, Itsik Malhotra, Anil K. Goldman, David Darvasi, Ariel TI Genome-Wide Association Study in the Ashkenazi Jewish Population Identifies a Replicable Genetic Locus for Schizophrenia and Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Lee, Annette T.; Gregersen, Peter K.] NSLIJ, Robert S Boas Ctr Human Genet & Genom, Glen Oaks, NY USA. [Hodgkinson, Colin; Yuan, Qiaoping; Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. [Pe'er, Itsik] Columbia Univ, New York, NY USA. [Darvasi, Ariel] Hebrew Univ Jerusalem, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 89 BP 25S EP 25S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800082 ER PT J AU Fung, SJ Joshi, D Allen, K Rothwell, A Noble, PL Winslow, JT Weickert, CS AF Fung, Samantha J. Joshi, Dipesh Allen, Katherine Rothwell, Alice Noble, Pam L. Winslow, James T. Weickert, Cyndi Shannon TI White Matter Neuron Density is Increased by Adolescent Testosterone in the Prefrontal Macaque Cortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine; Rothwell, Alice; Weickert, Cyndi Shannon] Schizophrenia Res Inst, Schizophrenia Res Lab, Sydney, NSW, Australia. [Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine; Rothwell, Alice; Weickert, Cyndi Shannon] Neurosci Res Australia, Schizophrenia Res Lab, Sydney, NSW, Australia. [Fung, Samantha J.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. [Noble, Pam L.; Winslow, James T.] NIMH, IRP NonHuman Primate Core, NIH, Poolesville, MD USA. [Weickert, Cyndi Shannon] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. RI Fung, Samantha/C-9660-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 106 BP 28S EP 28S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800091 ER PT J AU Furey, M Nugent, A Speer, A Drevets, W Zarate, C AF Furey, Maura Nugent, Allison Speer, Andrew Drevets, Wayne Zarate, Carlos TI Mood State Predictors of Antidepressant Response to Scopolamine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Furey, Maura; Nugent, Allison; Zarate, Carlos] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Speer, Andrew] NIMH, Lab Brain & Cognition, NIH, Bethesda, MD 20892 USA. [Drevets, Wayne] Univ Oklahoma, Laureate Inst Brain Res, Coll Med, Tulsa, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 137 BP 38S EP 38S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800122 ER PT J AU Benson, BE Detloff, AM Plate, RC Guyer, AE Jarcho, JM Nelson, EE Pine, DS Ernst, M AF Benson, Brenda E. Detloff, Allison M. Plate, Rista C. Guyer, Amanda E. Jarcho, Johanna M. Nelson, Eric E. Pine, Daniel S. Ernst, Monique TI Unique Neural Correlates of Contingency-Based Reward in Anxious Adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Benson, Brenda E.; Plate, Rista C.; Jarcho, Johanna M.; Nelson, Eric E.; Pine, Daniel S.; Ernst, Monique] NIMH, Emot Dev Branch, Bethesda, MD 20892 USA. [Detloff, Allison M.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Guyer, Amanda E.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 140 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800125 ER PT J AU Graybeal, C Saksida, LM Bussey, TJ Holmes, A AF Graybeal, Carolyn Saksida, Lisa M. Bussey, Timothy J. Holmes, Andrew TI Touchscreen Visual Reversal Learning in Mice is Facilitated by Limited Stress or Ventromedial Prefrontal Cortex Damage, and is Rescued by Ventromedial Prefrontal Cortex BDNF Infusions SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Graybeal, Carolyn; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Rockville CB2 3EB, MD USA. [Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Dept Expt Psychol, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 141 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800126 ER PT J AU Vytal, K Cornwell, B Arkin, N Grillon, C AF Vytal, Katherine Cornwell, Brian Arkin, Nicole Grillon, Christian TI Reciprocal Effects of Anxiety and Task Difficulty on N-back Performance SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Vytal, Katherine; Cornwell, Brian; Arkin, Nicole; Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 146 BP 41S EP 41S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800131 ER PT J AU Zink, CF Kempf, L Hakimi, S Stein, JL Meyer-Lindenberg, A AF Zink, Caroline F. Kempf, Lucas Hakimi, Shabnam Stein, Jason L. Meyer-Lindenberg, Andreas TI Vasopressin Modulates Social Recognition-Related Neural Activity in the Left Temporoparietal Junction in Men SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Zink, Caroline F.; Kempf, Lucas; Hakimi, Shabnam; Stein, Jason L.] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 147 BP 41S EP 41S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800132 ER PT J AU Fowler, K Blair, J AF Fowler, Katherine Blair, James TI Youths with Conduct Disorder and Callous-Unemotional Traits Show Disrupted Amygdala, Posterior Cingulate, and Caudate Function During Decisions Regarding Environmental Threats and Rewards SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Fowler, Katherine; Blair, James] NIMH, Unit Afffect Cognit Neurosci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 156 BP 44S EP 44S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800141 ER PT J AU Geraci, MB Luckenbaugh, DA Gorodetsky, E Ernst, M Goldman, D Pine, D AF Geraci, Marilla B. Luckenbaugh, David A. Gorodetsky, Elena Ernst, Monique Goldman, David Pine, Daniel TI Adenosine Receptor A2a Polymorphisms and Caffeine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Geraci, Marilla B.; Luckenbaugh, David A.; Gorodetsky, Elena; Ernst, Monique; Goldman, David; Pine, Daniel] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 203 BP 58S EP 58S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800188 ER PT J AU Bevilacqua, L Hadjulis, M Enoch, MA New, AS Hodgkinson, CA Yuan, QP Shen, PH Siever, LJ Roy, A Goldman, D AF Bevilacqua, Laura Hadjulis, Michael Enoch, Mary-Anne New, Antonia S. Hodgkinson, Colin A. Yuan, Qiaoping Shen, Pei-Hong Siever, Larry J. Roy, Alec Goldman, David TI An HTR2B Low-expression Haplotype Predicts Risk of Cocaine Dependence and Aggression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Bevilacqua, Laura; Enoch, Mary-Anne; Hodgkinson, Colin A.; Yuan, Qiaoping; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Hadjulis, Michael; New, Antonia S.; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA. [Hadjulis, Michael; New, Antonia S.; Siever, Larry J.] James J Peters VA Med Ctr, New York, NY USA. [Roy, Alec] New Jersey VA Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 211 BP 60S EP 61S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800196 ER PT J AU Perez-Rodriguez, MM Bevilacqua, L Yuan, QP Zhou, ZF Hodgkinson, C Ripoll, L Goodman, M Koenigsberg, HW Goldman, D Siever, LJ New, AS AF Perez-Rodriguez, M. Mercedes Bevilacqua, Laura Yuan, Qiaoping Zhou, Zhifeng Hodgkinson, Colin Ripoll, Luis Goodman, Marianne Koenigsberg, Harold W. Goldman, David Siever, Larry J. New, Antonia S. TI Mu Opioid Receptor Variant Does not Predict Borderline Personality Disorder Diagnosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Perez-Rodriguez, M. Mercedes; Ripoll, Luis; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] Mt Sinai Sch Med, New York, NY USA. [Bevilacqua, Laura; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Ripoll, Luis; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, New York, NY USA. RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 221 BP 63S EP 64S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800206 ER PT J AU Jenkins, A Wang, YH Hyde, T Kleinman, J Law, A AF Jenkins, Aaron Wang, Yanhong Hyde, Thomas Kleinman, Joel Law, Amanda TI Neurexin 1 (NRXN1) Gene Expression across the Normal Human Lifespan: Implications for Neurodevelopment and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Jenkins, Aaron; Wang, Yanhong; Hyde, Thomas; Kleinman, Joel; Law, Amanda] NIMH, NIH, IRP, Bethesda, MD 20892 USA. RI Law, Amanda/G-6372-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 224 BP 65S EP 65S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800209 ER PT J AU Blair, KS Geraci, M Otero, M Blair, JR Pine, DS AF Blair, Karina S. Geraci, Marilla Otero, Marcela Blair, James R. Pine, Daniel S. TI Reduced Emotion Regulation during both Explicit and Implicit in Generalized Social Phobia (GSP), Generalized Anxiety Disorder (GAD) and Comorbid GSP/GAD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Blair, Karina S.; Geraci, Marilla; Otero, Marcela; Blair, James R.; Pine, Daniel S.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 238 BP 69S EP 69S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800223 ER PT J AU Blair, KS Geraci, M Otero, M Blair, JR Pine, DS AF Blair, Karina S. Geraci, Marilla Otero, Marcela Blair, James R. Pine, Daniel S. TI Atypical Modulation of Medial Prefrontal Cortex to Self-Referential Comments in Generalized Social Phobia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Blair, Karina S.; Geraci, Marilla; Otero, Marcela; Blair, James R.; Pine, Daniel S.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 237 BP 69S EP 69S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800222 ER PT J AU Cornwell, BR Alvarez, RP Lissek, S Ernst, M Grillon, C AF Cornwell, Brian R. Alvarez, Ruben P. Lissek, Shmuel Ernst, Monique Grillon, Christian TI Anxiety Preserves Amygdala Reactivity to Threat-related Distractors under High Perceptual Load SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Cornwell, Brian R.; Ernst, Monique; Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Alvarez, Ruben P.] Laureate Inst Brain Res, Dept Psychiat, Tulsa, OK USA. [Lissek, Shmuel] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 241 BP 70S EP 70S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800226 ER PT J AU Yu, HH Crowe, SL Wu, CC Blair, RJR AF Yu, Henry H. Crowe, Samantha L. Wu, Charlene C. Blair, R. J. R. TI Top Down and Emotional Attention Control in Post-traumatic Stress Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Yu, Henry H.; Crowe, Samantha L.; Blair, R. J. R.] NIH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA. [Wu, Charlene C.] Standford Univ, Dept Pyschol, Stanford, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 266 BP 78S EP 78S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800251 ER PT J AU Bernardi, S Anagnostou, E Shen, J Kolevzon, A Buxbaum, J Hollander, E Fan, J AF Bernardi, Silvia Anagnostou, Evdokia Shen, Jun Kolevzon, Alexander Buxbaum, Joseph Hollander, Eric Fan, Jin TI In Vivo 1h-magnetic Resonance Spectroscopy Study of the Attentional Networks in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Bernardi, Silvia] Univ Florence, Florence, Italy. [Bernardi, Silvia; Anagnostou, Evdokia; Kolevzon, Alexander; Buxbaum, Joseph; Fan, Jin] Mt Sinai Sch Med, New York, NY USA. [Bernardi, Silvia] Columbia Univ, New York, NY USA. [Shen, Jun] NIH, Sect Magnet Resonance Spect, Mol Imaging Branch, Bethesda, MD 20892 USA. [Hollander, Eric] Univ Hosp Albert Einstein Coll Med, New York, NY USA. RI Fan, Jin/A-6716-2009 OI Fan, Jin/0000-0001-9630-8330 NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 270 BP 79S EP 79S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800255 ER PT J AU Jarcho, JM Benson, BE Plate, RC Guyer, AE Detloff, AM Leibenluft, E Pine, DS Ernst, M AF Jarcho, Johanna M. Benson, Brenda E. Plate, Rista C. Guyer, Amanda E. Detloff, Allison M. Leibenluft, Ellen Pine, Daniel S. Ernst, Monique TI Differential Neural Effects of Agency on Processing Anticipated Reward in Adolescents and Adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Jarcho, Johanna M.; Benson, Brenda E.; Plate, Rista C.; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Guyer, Amanda E.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. [Detloff, Allison M.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 273 BP 80S EP 81S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800258 ER PT J AU Jarcho, JM Benson, BE Plate, RC Guyer, AE Detloff, AM Leibenluft, E Pine, DS Ernst, M AF Jarcho, Johanna M. Benson, Brenda E. Plate, Rista C. Guyer, Amanda E. Detloff, Allison M. Leibenluft, Ellen Pine, Daniel S. Ernst, Monique TI Differences in Neural Response to Reward Feedback with or without Self-Agency in Adolescents and Adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Jarcho, Johanna M.; Benson, Brenda E.; Plate, Rista C.; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Guyer, Amanda E.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. [Detloff, Allison M.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 274 BP 81S EP 81S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800259 ER PT J AU Shaw, P Sharp, W Gilliam, M Malek, M Rapoport, J AF Shaw, Philip Sharp, Wendy Gilliam, Mary Malek, Meaghan Rapoport, Judith TI Anomalous Development of Cortical Surfaces in Attention-Deficit/Hyperactivity Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Shaw, Philip; Sharp, Wendy; Gilliam, Mary; Malek, Meaghan; Rapoport, Judith] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 281 BP 83S EP 83S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800266 ER PT J AU Ben Dor, R Harsh, VL Fortinsky, P Rubinow, DR Schmidt, PJ AF Ben Dor, Rivi Harsh, Veronica L. Fortinsky, Paige Rubinow, David R. Schmidt, Peter J. TI Effects of Medically-Induced Menopause on Mood and Behavior in Healthy Young Women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Ben Dor, Rivi; Harsh, Veronica L.; Fortinsky, Paige; Schmidt, Peter J.] NIMH, NIH, Rockville, MD 20857 USA. [Rubinow, David R.] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 294 BP 87S EP 88S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800279 ER PT J AU Merikangas, KR AF Merikangas, Kathleen Ries TI Prevalence, Comorbidity, and Clinical Correlates of Bipolar and Unipolar Depression in US Youth: Results from the National Comorbidity Survey Adolescent Supplement SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Merikangas, Kathleen Ries] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 333 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800318 ER PT J AU Lipska, BK AF Lipska, Barbara K. TI Genome-Wide and Candidate Gene Studies of Alternative Splicing in Normal Development and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Lipska, Barbara K.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 339 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800324 ER PT J AU Pine, DS AF Pine, Daniel S. TI Differentiating Neural Correlates of Social Phobia, Behavioral Inhibition, and Generalized Anxiety Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 384 BP 113S EP 114S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800361 ER PT J AU Zarate, CA AF Zarate, Carlos Alberto TI A Randomized Trial of an N-methyl-D-aspartate Antagonist and Neural Correlates of Rapid Antidepressant Response in Treatment-Resistant Bipolar Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Zarate, Carlos Alberto] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 389 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800366 ER PT J AU Weinberger, D Sullivan, P Todd, J Rubinow, DR Berman, K AF Weinberger, Daniel Sullivan, Patrick Todd, John Rubinow, David R. Berman, Karen TI Whither Psychiatric Genetics? What Have we Learned from the GWAS Era? A Debate and Discussion SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Weinberger, Daniel] NIMH, NIH, Bethesda, MD 20892 USA. [Sullivan, Patrick; Rubinow, David R.] Univ N Carolina, Chapel Hill, NC USA. [Todd, John] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 417 BP 124S EP 124S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800394 ER PT J AU Kiselycznyk, CL Mishina, M Sprengel, R Delpire, E Grant, S Nakazawa, K Holmes, A AF Kiselycznyk, Carly L. Mishina, Masayoshi Sprengel, Rolf Delpire, Eric Grant, Seth Nakazawa, Kazu Holmes, Andrew TI Genetic and Pharmacological Analysis of the Role of the NMDA Receptor Glun2b Subunit in Antidepressant-sensitive Behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Kiselycznyk, Carly L.; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Rockville, MD 20892 USA. [Mishina, Masayoshi] Univ Tokyo, Dept Mol Neurobiol & Pharmacol, Tokyo, Japan. [Sprengel, Rolf] Max Planck Inst Med Res, Dept Mol Neurobiol & Pharmacol, Heidelberg, Germany. [Delpire, Eric] Vanderbilt, Anesthesiol, Nashville, TN USA. [Grant, Seth] Univ Cambridge, Wellcome Trust Sanger Inst, Cambridge, England. [Nakazawa, Kazu] NIMH, Genet Cognit & Behav Unite, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 425 BP 126S EP 127S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800402 ER PT J AU Hunsberger, J Fessler, E Leng, Y Elkahloun, A Chuang, DM AF Hunsberger, Joshua Fessler, Emily Leng, Yan Elkahloun, Abdel Chuang, De-Maw TI Profiling Micrornas Involved in the Neuroprotective Effects of Mood Stabilizers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Hunsberger, Joshua; Fessler, Emily; Leng, Yan; Chuang, De-Maw] NIMH, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 437 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800414 ER PT J AU Jimenez, D Schloesser, RJ Paredes, D Catlow, B Manji, H Martinowich, K AF Jimenez, Dennisse Schloesser, Robert J. Paredes, Daniel Catlow, Briony Manji, Husseini Martinowich, Keni TI Suppression of Adult Hippocampal Neurogenesis Leads to Changes in Cornu Ammonis Region CA3 during Recovery from Acute Stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Jimenez, Dennisse; Schloesser, Robert J.; Martinowich, Keni] NIMH, LMP, Bethesda, MD 20892 USA. [Paredes, Daniel; Catlow, Briony] NINDS, LMP, Bethesda, MD 20892 USA. [Manji, Husseini] Johnson & Johnson Pharmaceut, Neurosci Res & Dev, Titusville, NJ USA. RI Paredes , Daniel/L-6610-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 438 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800415 ER PT J AU Khairova, R Pawar, R Salvadore, G Juruena, MF Salvador, M Gattaz, WF Zarate, CA Machado-Vieira, R AF Khairova, Rushaniya Pawar, Rohit Salvadore, Giacomo Juruena, Mario F. Salvador, Mirian Gattaz, Wagner F. Zarate, Carlos A., Jr. Machado-Vieira, Rodrigo TI The Effects of Lithium on Oxidative Stress Parameters in Healthy Subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Khairova, Rushaniya; Pawar, Rohit; Salvadore, Giacomo; Zarate, Carlos A., Jr.] NIMH, NIH, Bethesda, MD 20892 USA. [Juruena, Mario F.] Univ Sao Paulo, Dept Psychiat, BR-14049 Ribeirao Preto, Brazil. [Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept Psychiat, LIM27, Sao Paulo, Brazil. RI Gattaz, Wagner/C-4456-2012; Juruena, Mario/D-5571-2009; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI Juruena, Mario/0000-0001-8558-3396; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 445 BP 132S EP 133S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800422 ER PT J AU Plate, RC Detloff, AM Jarcho, JM Pine, DS Ernst, M AF Plate, Rista C. Detloff, Allison M. Jarcho, Johanna M. Pine, Daniel S. Ernst, Monique TI Loss Aversion in Healthy and Anxious Individuals: A Developmental Investigation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Plate, Rista C.; Jarcho, Johanna M.; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Detloff, Allison M.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 457 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800434 ER PT J AU Szczepanik, J Drevets, W Nugent, A Zarate, C Furey, M AF Szczepanik, Joanna Drevets, Wayne Nugent, Allison Zarate, Carlos Furey, Maura TI Scopolamine Influences Attention and Emotional Processing Biases in Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Szczepanik, Joanna; Nugent, Allison; Zarate, Carlos; Furey, Maura] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Szczepanik, Joanna] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. [Drevets, Wayne] Laureat Inst Brain Res, Expt Therapeut & Pathophysiol Branch, Tulsa, OK USA. RI Furey, Maura/H-5273-2013 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 475 BP 142S EP 142S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800452 ER PT J AU White, SF Marsh, A Fowler, KA Schechter, JC Sinclair, S Pine, DS Blair, JR AF White, Stuart F. Marsh, Abigail Fowler, Katherine A. Schechter, Julia C. Sinclair, Stephen Pine, Daniel S. Blair, James R. TI A Test of Causal Hypotheses of Psychopathic Traits: Reduced Emotional Responsiveness or Anomalous Attentional Control? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [White, Stuart F.; Fowler, Katherine A.; Sinclair, Stephen; Blair, James R.] NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA. [Marsh, Abigail] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [Schechter, Julia C.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 484 BP 145S EP 145S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800461 ER PT J AU Lamers, F Angst, J He, JP Avenevoli, S Merikangas, K AF Lamers, Femke Angst, Jules He, Jian-ping Avenevoli, Shelli Merikangas, Kathleen TI Depressive Subtypes in Adolescents and Adults: A Comparison of NCS-R and NCS-A SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Lamers, Femke; He, Jian-ping; Merikangas, Kathleen] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. [Angst, Jules] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. [Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 497 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800473 ER PT J AU Salehi, B van der Veen, JW Shen, J Neumeister, A Drevets, W Goldman, D Hasler, G AF Salehi, Basira van der Veen, Jan Willem Shen, Jun Neumeister, Alexander Drevets, Wayne Goldman, David Hasler, Gregor TI Associations between Prefrontal GABA and a TPH2 Panic Disorder Risk Allele, and between Prefrontal NAA and a BDNF Bipolar Disorder Risk Allele SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Salehi, Basira; Hasler, Gregor] Univ Bern, Bern, 20892, Switzerland. [van der Veen, Jan Willem; Shen, Jun] NIMH, MADP, Bethesda, MD USA. [Neumeister, Alexander] MSSM, New York, NY USA. [Drevets, Wayne] Laureate Inst Brain Res, Tulsa, OK USA. [Goldman, David] NIAAA, Bethesda, MD USA. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 507 BP 151S EP 151S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800483 ER PT J AU Carlson, PJ DiazGranados, N Nugent, A Ibrahim, L Luckenbaugh, D Tinsley, R Brutsche, N Herscovitch, P Manji, HK Zarate, CA Drevets, WC AF Carlson, Paul J. DiazGranados, Nancy Nugent, Allison Ibrahim, Lobna Luckenbaugh, David Tinsley, Ruth Brutsche, Nancy Herscovitch, Peter Manji, Husseini K. Zarate, Carlos A. Drevets, Wayne C. TI Altered Habenula Activity following Ketamine Administration in Treatment-Resistant Major Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Carlson, Paul J.] Salt Lake VAMC, Salt Lake City, UT USA. [Carlson, Paul J.] Univ Utah, Sch Med, Salt Lake City, UT USA. [DiazGranados, Nancy] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Nugent, Allison; Ibrahim, Lobna; Luckenbaugh, David; Tinsley, Ruth; Brutsche, Nancy; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, DIRP, NIH, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. [Manji, Husseini K.] CNS, Titusville, NJ USA. [Manji, Husseini K.] Pain Johnson & Johnson, Titusville, NJ USA. [Drevets, Wayne C.] Univ Oklahoma, Laureate Inst Brain Res, Coll Med, Tulsa, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 537 BP 160S EP 161S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800513 ER PT J AU Savitz, J Nugent, A Neumeister, A Bogers, W Price, J Cannon, D Drevets, W AF Savitz, Jonathan Nugent, Allison Neumeister, Alexander Bogers, Wendy Price, Joseph Cannon, Dara Drevets, Wayne TI Persistent Remission of Unmedicated Patients with Major Depressive Disorder Associated with Larger Subcallosal Gyrus Volumes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Savitz, Jonathan; Bogers, Wendy; Drevets, Wayne] LIBR, Tulsa, OK USA. [Nugent, Allison] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD USA. [Neumeister, Alexander] Mt Sinai Sch Med, New York, NY USA. [Price, Joseph] Washington Univ, St Louis, MO USA. [Cannon, Dara] NUI, Galway, Ireland. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 579 BP 174S EP 174S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800555 ER PT J AU Swain, JE Kim, P Feldman, R Wang, X Mayes, L Leckman, J AF Swain, James E. Kim, Pilyoung Feldman, Ruth Wang, Xin Mayes, Linda Leckman, James TI Emotions and Behavior Affect the Brain According to Parenting, Gender, Delivery and Breastfeeding SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Swain, James E.; Wang, Xin] Univ Michigan, Ann Arbor, MI 48109 USA. [Kim, Pilyoung] NIMH, NIH, Bethesda, MD 20892 USA. [Feldman, Ruth] Bar Ilan Univ, Ramat Gan, Israel. [Mayes, Linda; Leckman, James] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 585 BP 176S EP 176S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800561 ER PT J AU Turner, AD Furey, M Drevets, W Zarate, C Nugent, A AF Turner, Arlener D. Furey, Maura Drevets, Wayne Zarate, Carlos Nugent, Allison TI Association between Hippocampal Volume and Verbal Memory in Unmedicated Depressed Patients and Healthy Controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Turner, Arlener D.; Furey, Maura; Zarate, Carlos; Nugent, Allison] NIMH, NIH, Bethesda, MD 20892 USA. [Drevets, Wayne] Laureat Inst Brain Res, Res Grp, Tulsa, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 588 BP 177S EP 178S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800564 ER PT J AU Bigos, KL Bies, RR Pollock, BG Czerminski, J Haynes, MR Zhang, FY Weinberger, DR AF Bigos, Kristin L. Bies, Robert R. Pollock, Bruce G. Czerminski, Jan Haynes, M. Ryan Zhang, Fengyu Weinberger, Daniel R. TI Genetic Variation in Cytochrome P450 Drug Metabolizing Enzymes Impacts Clearance of Antipsychotics SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Bigos, Kristin L.; Czerminski, Jan; Haynes, M. Ryan; Zhang, Fengyu; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Bies, Robert R.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Pollock, Bruce G.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 612 BP 185S EP 185S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800588 ER PT J AU Suomi, SJ AF Suomi, Stephen J. TI Gene-Environment Interplay in Primates: Protective Effects of Maternal Buffering SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Suomi, Stephen J.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 684 BP 206S EP 206S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800653 ER PT J AU Cadet, JL AF Cadet, Jean Lud TI Neurobiological Bases of Decision-Making Deficits in Marijuana Users: Therapeutic Implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Cadet, Jean Lud] NIDA, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 705 BP 213S EP 213S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800674 ER PT J AU Krasnova, I Chiflikyan, M Justinova, Z Ladenheim, B Mccoy, M Wood, W Becker, K Goldberg, S Cadet, JL AF Krasnova, Irina Chiflikyan, Margarit Justinova, Zuzana Ladenheim, Bruce McCoy, Michael Wood, William Becker, Kevin Goldberg, Steven Cadet, Jean Lud TI Methamphetamine Self-administration Alters Gene Expression in the Rat Striatum SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Krasnova, Irina; Chiflikyan, Margarit; Ladenheim, Bruce; McCoy, Michael; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Sect, NIH, DHHS, Baltimore, MD USA. [Justinova, Zuzana; Goldberg, Steven] NIDA, Preclin Pharmacol Sect, NIH, DHHS, Baltimore, MD USA. [Wood, William; Becker, Kevin] NIA, Gene Express & Genom Unit, NIH, DHHS, Baltimore, MD 21224 USA. RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 760 BP 227S EP 227S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800721 ER PT J AU Magalona, CSL Gold, I Rasetti, R Decot, H Apud, JJ Weinberger, DR Mattay, VS AF Magalona, Carmela Sophia L. Gold, Ian Rasetti, Roberta Decot, Heather Apud, Jose J. Weinberger, Daniel R. Mattay, Venkata S. TI Tolcapone Enhances Cortical Efficiency During Attentional Control In Healthy Subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Magalona, Carmela Sophia L.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 764 BP 228S EP 228S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800725 ER PT J AU Calkins, ME Richard, JA Merikangas, KR Burstein, M Heaton, L Qiu, HJ Mentch, FD Hermannsson, L Connolly, J Abrams, DJ Chiavacci, RW Grundmeier, RW Sleiman, PM Loughead, J Gur, RC Hakonarson, H Gur, RE AF Calkins, Monica E. Richard, Jan A. Merikangas, Kathleen R. Burstein, Marcy Heaton, Leanne Qiu, Haijun Mentch, Frank D. Hermannsson, L. Connolly, John Abrams, Deborah J. Chiavacci, Rosetta W. Grundmeier, R. W. Sleiman, P. M. Loughead, James Gur, Ruben C. Hakonarson, Hakon Gur, Raquel E. TI Identification of Children and Adolescents At-Risk for Psychosis: Results of a Screen for Sub-Psychotic Symptoms in a Community Sample SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Calkins, Monica E.; Richard, Jan A.; Loughead, James; Gur, Ruben C.; Gur, Raquel E.] Univ Penn, Sch Med, Neuropsychiat Program, Philadelphia, PA 19104 USA. [Merikangas, Kathleen R.; Burstein, Marcy; Heaton, Leanne] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. [Qiu, Haijun; Mentch, Frank D.; Hermannsson, L.; Connolly, John; Abrams, Deborah J.; Chiavacci, Rosetta W.; Grundmeier, R. W.; Sleiman, P. M.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 821 BP 246S EP 246S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800782 ER PT J AU Dickinson, D Trampush, J Feng, N Li, C Vakkalanka, R Rujescu, D Weinberger, D Straub, RE AF Dickinson, Dwight Trampush, J. Feng, N. Li, C. Vakkalanka, R. Rujescu, D. Weinberger, D. Straub, R. E. TI Genome-Wide Association Analysis Reveals that SCN2A, which Encodes the Alpha Subunit in Type II Voltage-gated Sodium Channels, is Associated with General Cognitive Ability in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Dickinson, Dwight; Trampush, J.; Feng, N.; Li, C.; Vakkalanka, R.; Weinberger, D.; Straub, R. E.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Rujescu, D.] Univ Munich, Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 822 BP 247S EP 247S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800783 ER PT J AU Burdick, MC Straub, RE Papaleo, F Kolachana, B Zhang, FY Mattay, VS Weinberger, DR Callicott, JH AF Burdick, Madeline C. Straub, Richard E. Papaleo, Francesco Kolachana, Bhaskar Zhang, Fengyu Mattay, Venkata S. Weinberger, Daniel R. Callicott, Joseph H. TI Genetic Interaction between COMT and Dysbindin Effects Prefrontal Cortex Function During a BOLD fMRI Working Memory Paradigm SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Burdick, Madeline C.; Straub, Richard E.; Papaleo, Francesco; Kolachana, Bhaskar; Zhang, Fengyu; Mattay, Venkata S.; Weinberger, Daniel R.; Callicott, Joseph H.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 858 BP 259S EP 259S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800819 ER PT J AU DeJong, K Geramita, M van der Veen, JW Barnett, A Shen, J Apud, J Weinberger, D Marenco, S AF DeJong, Katherine Geramita, Matthew van der Veen, Jan Willem Barnett, Alan Shen, Jun Apud, Jose Weinberger, Daniel Marenco, Stefano TI The Effects of Neuroleptics on GABA Levels in Patients with Schizophrenia Spectrum Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [DeJong, Katherine; Geramita, Matthew; Barnett, Alan; Weinberger, Daniel; Marenco, Stefano] NIMH, Genes Cognit & Psychosis Program GCAP, Bethesda, MD 20892 USA. [Apud, Jose] NIMH, Clin Brain Disorders Branch CBDB, 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 INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 859 BP 259S EP 259S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800820 ER PT J AU Feighery, EL Baranger, DAA Dickinson, D Rasetti, R Sust, S Chen, Q Rypma, B Mattay, VS Weinberger, DR Callicott, JH AF Feighery, Emer L. Baranger, David A. A. Dickinson, Dwight Rasetti, Roberta Sust, Steven Chen, Qiang Rypma, Bart Mattay, Venkata S. Weinberger, Daniel R. Callicott, Joseph H. TI A Novel Intermediate Phenotype for Prefrontal Cortical Efficiency in Schizophrenia Independent of Working Memory SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Feighery, Emer L.; Baranger, David A. A.; Dickinson, Dwight; Rasetti, Roberta; Sust, Steven; Chen, Qiang; Mattay, Venkata S.; Weinberger, Daniel R.; Callicott, Joseph H.] NIMH, Cognit Brain Disorders Branch, Bethesda, MD 20892 USA. [Rypma, Bart] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 860 BP 259S EP 259S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800821 ER PT J AU Gambale, CT Tost, H Lemaitre, H Rasetti, R Mattay, VS Weinberger, DR Marenco, S AF Gambale, Catherine T. Tost, Heike Lemaitre, Herve Rasetti, Roberta Mattay, Venkata S. Weinberger, Daniel R. Marenco, Stefano TI A Diffusion Tensor Imaging (DTI) Study of a Risk Variant for Psychosis in ZNF804a SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Gambale, Catherine T.; Tost, Heike; Rasetti, Roberta; Mattay, Venkata S.; Weinberger, Daniel R.; Marenco, Stefano] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Lemaitre, Herve] NIMH, Sect Clin Studies, 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 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 862 BP 260S EP 260S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800823 ER PT J AU Chun-Hsin, C Rawlings, B Momenan, R Walker, J Heilig, M Hommer, DW AF Chun-Hsin, Chen Rawlings, Bob Momenan, Reza Walker, Jonathan Heilig, Markus Hommer, Daniel W. TI Relationship Between Liver Function Impairment and Brain Shrinkage in Patients With Alcohol Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Chun-Hsin, Chen; Rawlings, Bob; Momenan, Reza; Walker, Jonathan; Heilig, Markus; Hommer, Daniel W.] NIAAA, LCTS, NIH, Bethesda, MD USA. [Chun-Hsin, Chen] Taipei Med Univ, WanFang Hosp, Dept Psychiat, Taipei, Taiwan. [Chun-Hsin, Chen] Taipei Med Univ, Sch Med, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 893 BP 271S EP 271S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800854 ER PT J AU Kakar, R Pao, M Akil, M AF Kakar, Rishi Pao, Maryland Akil, Mayada TI Integrating Neuroscience in the Training of Psychiatrists: An NIMH Initiative SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Kakar, Rishi; Pao, Maryland; Akil, Mayada] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 952 BP 290S EP 290S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800913 ER PT J AU Carter, TC Kay, DM Liu, A Browne, ML Romitti, PA Kuehn, D Conley, MR Caggana, M Druschel, CM Brody, LC Mills, JL AF Carter, T. C. Kay, D. M. Liu, A. Browne, M. L. Romitti, P. A. Kuehn, D. Conley, M. R. Caggana, M. Druschel, C. M. Brody, L. C. Mills, J. L. TI Hirschsprung's Disease and Variants in Genes That Regulate Enteric Neural Crest Cell Proliferation and Migration SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Carter, T. C.; Liu, A.; Kuehn, D.; Conley, M. R.; Mills, J. L.] NICHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Kay, D. M.; Caggana, M.] New York State Dept Hlth, Div Genet, Wadsworth Ctr, Albany, NY USA. [Browne, M. L.; Druschel, C. M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. [Browne, M. L.; Druschel, C. M.] SUNY Albany, Dept Epidemiol & Biostat, Albany, NY 12222 USA. [Romitti, P. A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Brody, L. C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 341 EP 341 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900067 ER PT J AU Voon, V Gao, J Brezing, C Symmonds, M Ekanayake, V Fernandez, H Dolan, RJ Hallett, M AF Voon, Valerie Gao, Jennifer Brezing, Christina Symmonds, Mkael Ekanayake, Vindhya Fernandez, Hubert Dolan, Raymond J. Hallett, Mark TI Dopamine agonists and risk: impulse control disorders in Parkinson's; disease SO BRAIN LA English DT Article DE Parkinson's; disease; dopamine; gambling; decision making; risk ID REWARD; UNCERTAINTY; BEHAVIORS; PREDICTS; INSULA AB Impulse control disorders are common in Parkinson's; disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's; disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a 'Sure' choice and a 'Gamble' choice of moderate risk. To commence each trial, in the 'Gain' condition, individuals started at $0 and in the 'Loss' condition individuals started at -$50 below the 'Sure' amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk ('Gamble Risk'). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's; disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the 'Gain' relative to the 'Loss' condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's; disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's; disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals. C1 [Voon, Valerie] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 OSZ, England. [Voon, Valerie; Gao, Jennifer; Brezing, Christina; Ekanayake, Vindhya; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. [Symmonds, Mkael; Dolan, Raymond J.] UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England. [Fernandez, Hubert] Univ Florida, Dept Neurol, Gainesville, FL 32611 USA. RP Voon, V (reprint author), Univ Cambridge, Dept Expt Psychol, Behav & Clin Neurosci Inst, Downing Site, Cambridge CB2 3EB, England. EM vv247@cam.ac.uk OI Dolan, Ray/0000-0001-9356-761X FU competitive intramural National Institute of Neurological Disorders and Stroke; intramural National Institutes of Health, Bethesda, MD, USA FX Dr Voon was a recipient of the competitive intramural National Institute of Neurological Disorders and Stroke fellowship at the time of this study. This study was conducted and funded by intramural National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. NR 26 TC 72 Z9 73 U1 0 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2011 VL 134 BP 1438 EP 1446 DI 10.1093/brain/awr080 PN 5 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 766WZ UT WOS:000290818600023 PM 21596771 ER PT J AU McDermott, MM Liu, K Carr, J Criqui, MH Tian, L Li, DB Ferrucci, L Guralnik, JM Kramer, CM Yuan, C Kibbe, M Pearce, WH Berry, J McCarthy, W Liao, YH Xu, DX Orozco, J Carroll, TJ AF McDermott, Mary M. Liu, Kiang Carr, James Criqui, Michael H. Tian, Lu Li, Debiao Ferrucci, Luigi Guralnik, Jack M. Kramer, Christopher M. Yuan, Chun Kibbe, Melina Pearce, William H. Berry, Jarett McCarthy, Walter Liao, Yihua Xu, Dongxiang Orozco, Jennifer Carroll, Timothy J. TI Superficial Femoral Artery Plaque, the Ankle-Brachial Index, and Leg Symptoms in Peripheral Arterial Disease The Walking and Leg Circulation Study (WALCS) III SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; MRI; peripheral vascular disease; plaque ID INTERMITTENT CLAUDICATION; ATHEROSCLEROTIC PLAQUE; MAGNETIC-RESONANCE; FUNCTIONAL DECLINE; HIGH-RISK; ASSOCIATIONS; CHOLESTEROL; PRESSURE AB Background-The clinical significance of magnetic resonance-imaged plaque characteristics in the superficial femoral artery (SFA) is not well established. We studied associations of the ankle-brachial index (ABI) and leg symptoms with MRI-measured plaque area and percent lumen area in the SFA in participants with and without lower-extremity peripheral arterial disease (PAD). Methods and Results-Four hundred twenty-seven participants (393 with PAD) underwent plaque imaging of the first 30 mm of the SFA. Twelve 2.5-mm cross-sectional images of the SFA were obtained. Outcomes were normalized plaque area, adjusted for artery size (0 to 1 scale, 1=greatest plaque), and lumen area, expressed as a percent of the total artery area. Adjusting for age, sex, race, smoking, statins, cholesterol, and other covariates, lower ABI values were associated with higher normalized mean plaque area (ABI <0.50:0.79; ABI 0.50 to 0.69:0.73; ABI 0.70 to 0.89:0.65; ABI 0.90 to 0.99:0.62; ABI 1.00 to 1.09:0.48; ABI 1.10 to 1.30:0.47 (P trend <0.001)) and smaller mean percent lumen area (P trend <0.001). Compared with PAD participants with intermittent claudication, asymptomatic PAD participants had lower normalized mean plaque area (0.72 versus 0.65, P=0.005) and larger mean percent lumen area (0.30 versus 0.36, P=0.01), adjusting for the ABI and other confounders. Conclusions-Lower ABI values are associated with greater MRI-measured plaque burden and smaller lumen area in the first 30 mm of the SFA. Compared with PAD participants with claudication, asymptomatic PAD participants have smaller plaque area and larger lumen area in the SFA. C1 [McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [McDermott, Mary M.; Liu, Kiang; Liao, Yihua] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Kibbe, Melina; Pearce, William H.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Kibbe, Melina; Pearce, William H.] Northwestern Univ, Feinberg Sch Med, Div Vasc Surg, Chicago, IL 60611 USA. [Carr, James; Carroll, Timothy J.] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Tian, Lu] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Li, Debiao] Cedars Sinai Med Ctr, Los Angeles, CA USA. [Ferrucci, Luigi] NIA, Lab Clin Epidemiol, Baltimore, MD 21224 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. [Kramer, Christopher M.] Univ Virginia Hlth Syst, Dept Radiol & Med, Charlottesville, VA USA. [Xu, Dongxiang] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Yuan, Chun] Univ Washington, Sch Med, Dept Radiol Elect Engn Bioengn, Seattle, WA 98195 USA. [Kibbe, Melina] Jesse Brown Vet Affairs, Med Ctr, Chicago, IL USA. [Berry, Jarett] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. [McCarthy, Walter] Rush Univ, Med Ctr, Univ Cardiovasc Surg, Chicago, IL 60612 USA. [McCarthy, Walter; Orozco, Jennifer] Rush Univ, Med Ctr, Dept Vasc Surg, Chicago, IL 60612 USA. [Carroll, Timothy J.] Northwestern Univ, Dept Biomed Engn, Chicago, IL 60611 USA. RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM mdm608@northwestern.edu RI Carroll, Timothy/B-6934-2009; Li, Debiao/B-7622-2009 FU National Heart, Lung, and Blood Institute [R01-HL083064]; National Institute on Aging; Jesse Brown VA Medical Center; VP Diagnostics; Philips Healthcare; Siemens Healthcare FX This study was supported by the National Heart, Lung, and Blood Institute (R01-HL083064), the Intramural Research Program of the National Institute on Aging, and the Jesse Brown VA Medical Center.; Dr Yuan receives research support from VP Diagnostics and from Philips Healthcare. Dr Kramer receives research support from Siemens Healthcare. Dr Xu is a technical consultant for VP Diagnostics and owner of Imaging Biomarker Solutions. NR 27 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2011 VL 4 IS 3 BP 246 EP 252 DI 10.1161/CIRCIMAGING.110.962183 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765NU UT WOS:000290715800010 PM 21436300 ER PT J AU Schonfeld, SJ Lee, C de Gonzalez, AB AF Schonfeld, S. J. Lee, C. de Gonzalez, A. Berrington TI Medical Exposure to Radiation and Thyroid Cancer SO CLINICAL ONCOLOGY LA English DT Article DE Computed tomography scans; diagnostic radiology; medical radiation; thyroid cancer ID COMPUTED-TOMOGRAPHY; UNITED-STATES; INCREASING INCIDENCE; CT EXAMINATIONS; X-RAYS; RISK; PHANTOMS; DOSIMETRY; CHILDREN AB In 2008, the worldwide estimated age-standardised incidence rates for thyroid cancer incidence were 4.7 and 1.5 per 100 000 women and men, respectively. Thyroid cancer's overall contribution to the worldwide cancer burden is relatively small, but incidence rates have increased over the last three decades throughout the world. This trend has been hypothesised to reflect a combination of technological advances enabling increased detection, but also changes in environmental factors, including population exposure to ionising radiation from fallout, diagnostic tests and treatment for benign and malignant conditions. Studies of the atomic bomb survivors and populations treated with radiotherapy have established radiation as a risk factor for thyroid cancer, particularly from early life exposure. About 0.62 mSv (20%) of the global annual per caput effective radiation dose comes from diagnostic medical and dental radiation for the period of 1997-2007, increased from 0.4 mSv for the years 1991-1996. This international trend of increasing population exposure to medical diagnostic sources of radiation, attributed in large part to the growing use of computed tomography scans, but also interventional radiology procedures, has raised concerns about exposure to radiosensitive organs such as the thyroid. Worldwide, medical and dental X-rays constitute the most common type of diagnostic medical exposures, but their contribution to the cumulative effective dose is relatively low, whereas computed tomography scans account for 7.9% of diagnostic radiology examinations but 47% of the collective effective dose from diagnostic radiation procedures in parts of the world. Although the radiation exposure from computed tomography scans is substantially lower than that from radiotherapy, multiple computed tomography scans could result in non-trivial cumulative doses to the thyroid. Studies are currently underway to assess the incidence of cancer in large cohorts of children who received computed tomography scans. National and international efforts have been developed to raise awareness and to standardise procedures for use of computed tomography and interventional radiology procedures in paediatric and general populations. (C) 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Schonfeld, S. J.; Lee, C.; de Gonzalez, A. Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Schonfeld, SJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM schonfes@mail.nih.gov RI Lee, Choonsik/C-9023-2015 OI Lee, Choonsik/0000-0003-4289-9870 FU National Cancer Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 46 TC 44 Z9 51 U1 0 U2 14 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 EI 1433-2981 J9 CLIN ONCOL-UK JI Clin. Oncol. PD MAY PY 2011 VL 23 IS 4 SI SI BP 244 EP 250 DI 10.1016/j.clon.2011.01.159 PG 7 WC Oncology SC Oncology GA 767GE UT WOS:000290842500003 PM 21296564 ER PT J AU Ferrari, R Kapogiannis, D Huey, ED Momeni, P AF Ferrari, R. Kapogiannis, D. Huey, E. D. Momeni, P. TI FTD and ALS: A Tale of Two Diseases SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE ALS; FTD; FUS; motor disease; proteinopathies; TAU; TDP-43; ubiquitin inclusions ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; MOTOR-NEURON DISEASE; VALOSIN-CONTAINING-PROTEIN; UBIQUITIN-POSITIVE INCLUSIONS; DEEP BRAIN-STIMULATION; NON-ALZHEIMER TYPE; TREATMENT-RESISTANT DEPRESSION; MUTANT SUPEROXIDE-DISMUTASE; PRIMARY PROGRESSIVE APHASIA AB The first reports of disorders that in terms of cognitive and behavioral symptoms resemble frontotemporal dementia (FTD) and in terms of motor symptoms resemble amyotrophic lateral sclerosis (ALS) bring us back to the second half of the 1800s. Over the last 150 years, and especially in the last two decades, there has been growing evidence that FTD signs can be seen in patients primarily diagnosed with ALS, implying clinical overlap among these two disorders. In the last decade pathological investigations and genetic screening have contributed tremendously in elucidating the pathology and genetic variability associated with FTD and ALS. TAR DNA binding protein [TARDBP or TDP-43] and the fused in sarcoma gene [FUS] and their implication in these disorders belong to the most important recent discoveries. FTD and ALS are the focus of this review which aims to: 1. summarize clinical features by describing the diagnostic criteria and specific symptomatology, 2. describe the morphological aspects and related pathology, 3. describe the genetic factors associated with the diseases and 4. summarize the current status of clinical trials and treatment options. A better understanding of the clinical, pathological and genetic features characterizing FTD and ALS will shed light into overlaps among these two disorders and the underpinning mechanisms that contribute to their onset and development. Advancements in the knowledge of the biology of these two disorders will help developing novel and, hopefully, more effective diagnostic and treatment options. C1 [Ferrari, R.; Momeni, P.] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79430 USA. [Kapogiannis, D.] NIA, CRB, NIH, Baltimore, MD 21225 USA. [Huey, E. D.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bethesda, MD 20892 USA. [Huey, E. D.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Huey, E. D.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Huey, E. D.] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Psychiat, New York, NY 10032 USA. [Huey, E. D.] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10032 USA. [Ferrari, R.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Ferrari, R.] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England. RP Ferrari, R (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, 3601 4th St,STOP 9410, Lubbock, TX 79430 USA. EM raffaele.ferrari@ttuhsc.edu FU Intramural NIH HHS [Z99 AG999999, ZIA AG000975-02] NR 258 TC 33 Z9 33 U1 1 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD MAY PY 2011 VL 8 IS 3 BP 273 EP 294 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 768BA UT WOS:000290905100009 PM 21222600 ER PT J AU Gallagher, PE Cook, K Soto-Pantoja, D Menon, J Tallant, EA AF Gallagher, P. E. Cook, K. Soto-Pantoja, D. Menon, J. Tallant, E. A. TI Angiotensin Peptides and Lung Cancer SO CURRENT CANCER DRUG TARGETS LA English DT Review DE Renin-angiotensin system; angiotensin; lung cancer; pulmonary cancer; angiotensin-(1-7); angiotensin converting enzyme; angiogenesis; angiotensin receptor blocker ID I-CONVERTING-ENZYME; ENDOTHELIAL GROWTH-FACTOR; VASCULAR SMOOTH-MUSCLE; HUMAN PROSTATE-CANCER; REDUCES TUMOR-GROWTH; PERMANENT CELL-LINE; NEUTRAL ENDOPEPTIDASE; EPITHELIAL-CELLS; PROSTAGLANDIN SYNTHESIS; HYPERTENSIVE-RATS AB Lung cancer is a leading cause of death in both men and women, with over 1,000,000 new cases diagnosed worldwide annually and a 5-year survival rate of only 14%, a figure that has improved little in the past thirty years. This poor prognosis suggests a need for novel approaches for the treatment and prevention of lung cancer. The renin-angiotensin system is an established, primary regulator of blood pressure, homeostasis, and natriuresis; however, compelling evidence indicates that the angiotensin peptides also play a role in cell proliferation and inflammation. Angiotensin II is a vasoconstrictor, a mitogen, and an angiogenic factor, while angiotensin-(1-7) has vasodilator, anti-proliferative, and anti-angiogenic properties. This review focuses on studies examining the renin-angiotensin system in pulmonary cancers and whether clinical intervention of this pathway may serve as an effective chemotherapeutic and/or chemopreventive modality for lung cancer. C1 [Gallagher, P. E.; Cook, K.; Tallant, E. A.] Wake Forest Univ, Bowman Gray Sch Med, Hypertens & Vasc Res Ctr, Winston Salem, NC 27157 USA. [Cook, K.; Tallant, E. A.] Wake Forest Univ, Bowman Gray Sch Med, Mol Med & Translat Sci Program, Winston Salem, NC 27157 USA. [Soto-Pantoja, D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Menon, J.] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. RP Gallagher, PE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Hypertens & Vasc Res Ctr, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM pgallagh@wfubmc.edu FU NIH [HL-51952]; Farley-Hudson Foundation; Wake Forest University Comprehensive Cancer Center FX Funding was provided by NIH grant HL-51952 as well as support from the Farley-Hudson Foundation and the Wake Forest University Comprehensive Cancer Center. P. E. Gallagher and E. A. Tallant hold a patent for the treatment of cancer with Ang-(1-7). NR 99 TC 23 Z9 23 U1 1 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD MAY PY 2011 VL 11 IS 4 BP 394 EP 404 PG 11 WC Oncology SC Oncology GA 764ED UT WOS:000290610400002 PM 21395552 ER PT J AU Malek, A Mattison, DR AF Malek, Antoine Mattison, Donald R. TI Drugs and Medicines in Pregnancy: The Placental Disposition of Opioids SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE Analgesics; drug abuse; drugs in pregnancy; drug transfer; ex vivo perfusion model; human placenta; narcotics; opioids ID CHROMATOGRAPHY-MASS SPECTROMETRY; NEONATAL ABSTINENCE SYNDROME; IN-VITRO PERFUSION; CESAREAN-SECTION; TRANSPLACENTAL TRANSFER; MATERNAL KINETICS; SUBSTANCE-ABUSE; METHADONE; FENTANYL; WOMEN AB Over the past decade therapeutic interventions during pregnancy, including the use of drugs, has increased; for example, the prescription use of opioids and nonopioid analgesics for pain management during pregnancy has increased by about 40%. Additionally, women also self-medicate during pregnancy with opioids, and are treated with methadone and buprenorphine which are used as substitution therapy for substance dependence during pregnancy. A nationally representative survey noted that similar to 74% of women of reproductive age reported substance use during the previous year, decreasing to similar to 63% amongst those who were pregnant. Substance dependence was reported by similar to 20% of women who were not pregnant, and similar to 15% of those who were pregnant. Understanding the consequences of opioid treatment or dependence during pregnancy requires an investigation of the placental disposition (metabolism and transfer), as well as of the impact of the drugs on the placental function. This review summarizes the research on the placental disposition of opioids and their impact on the placental function. C1 [Malek, Antoine] Univ Zurich Hosp, Dept Obstet, Div Res, CH-8091 Zurich, Switzerland. [Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Malek, A (reprint author), Univ Zurich Hosp, Dept Obstet, Div Res, Frauenklin Str 10, CH-8091 Zurich, Switzerland. EM antoine.malek1@gmail.com; mattisod@mail.nih.gov RI Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU NICHD FX AM and DRM have no financial or competing interests to disclose. DRM was supported in part by the intramural program of NICHD. NR 83 TC 6 Z9 6 U1 3 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD MAY PY 2011 VL 12 IS 5 BP 797 EP 803 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 764WK UT WOS:000290665000012 PM 21480827 ER PT J AU Barry, CE AF Barry, Clifton E. TI Lessons from Seven Decades of Antituberculosis Drug Discovery SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Tuberculosis; drug development; streptomycin; rifampicin; isoniazid; linezolid; nitroimidazoles; diarylquinoline; benzothiazinone ID NONREPLICATING MYCOBACTERIUM-TUBERCULOSIS; OXAZOLIDINONE ANTIBACTERIAL AGENTS; RESISTANT TUBERCULOSIS; ATP HOMEOSTASIS; ANTIBIOTICS; IDENTIFICATION; EPIDEMIOLOGY; STREPTOMYCIN; ACTIVATION; PNU-100480 AB Despite massive global efforts tuberculosis rates continue to climb and drug-resistance rates are rising to alarming levels. Discovering new agents for treating this bacterial pathogen poses unique challenges, but these challenges have been faced throughout the entire modern history of research into anti-infectives. This review looks back at every decade since the 1940s and summarizes the most important drugs developed during each decade highlighting the lessons learned during these successful medicinal chemistry programs. Looking forward we must accelerate the integration of these past lessons with the impressive advances that have been made in the basic understanding of the biology of this disease. C1 [Barry, Clifton E.] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA. RP Barry, CE (reprint author), Rm 2W20D,Bldg 33,33 North Dr,9000 Rockville Pike, Bethesda, MD 20892 USA. EM cbarry@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 NR 73 TC 17 Z9 18 U1 0 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD MAY PY 2011 VL 11 IS 10 BP 1216 EP 1225 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 764UM UT WOS:000290659800002 PM 21401509 ER PT J AU Wald, I Shechner, T Bitton, S Holoshitz, Y Charney, DS Muller, D Fox, NA Pine, DS Bar-Haim, Y AF Wald, I. Shechner, T. Bitton, S. Holoshitz, Y. Charney, D. S. Muller, D. Fox, N. A. Pine, D. S. Bar-Haim, Y. TI ATTENTION BIAS AWAY FROM THREAT DURING LIFE THREATENING DANGER PREDICTS PTSD SYMPTOMS AT ONE-YEAR FOLLOW-UP SO DEPRESSION AND ANXIETY LA English DT Article DE stress; attention bias; PTSD; threat; anxiety ID ACUTE STRESS DISORDER; RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS; SOCIAL ANXIETY; PERITRAUMATIC DISSOCIATION; INDIVIDUALS; SUPPRESSION; PHQ-9; SURVIVORS; PHOBIA AB Background: Recent studies find a correlation between attentional threat avoidance under stress and posttraumatic stress symptoms. In this study, we assessed this association longitudinally in exposed and unexposed individuals. The degree of threat avoidance during exposure was expected to predict levels of posttraumatic stress symptoms 1 year later. Methods: Thirty-two participants were recruited and followed for 12 months, including 18 subjects exposed to rocket attacks and 14 nonexposed subjects. At 1-year follow-up, participants completed self-reports and an attention dot-probe task assessing threat-related bias. Results: State anxiety decreased at follow-up in exposed participants, though posttraumatic stress disorder (PTSD) and depression symptoms remained higher in exposed than in the nonexposed group. Attentional threat avoidance during imminent danger in the exposed group changed to threat attendance a year later, such that both the exposed and the nonexposed group exhibited similar threat bias patterns. As hypothesized, in the exposed group, stronger attentional threat avoidance during stress exposure predicted higher levels of PTSD symptoms 1 year later. Conclusions: Attention bias away from threat during acute stress may relate to risk for PTSD. This suggests that neurocognitive measures may index risk for PTSD. Depression and Anxiety 28:406-411, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Wald, I.; Shechner, T.; Bitton, S.; Bar-Haim, Y.] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. [Holoshitz, Y.; Charney, D. S.; Muller, D.] Mt Sinai Sch Med, New York, NY USA. [Fox, N. A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Pine, D. S.] NIMH, Bethesda, MD 20892 USA. RP Bar-Haim, Y (reprint author), Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. EM yair1@post.tau.ac.il FU Israeli Science Foundation [964/08] FX Supported by the Israeli Science Foundation, grant no. 964/08 to Dr. Bar-Haim. NR 34 TC 32 Z9 33 U1 3 U2 26 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAY PY 2011 VL 28 IS 5 BP 406 EP 411 DI 10.1002/da.20808 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 761RN UT WOS:000290416200008 PM 21381159 ER PT J AU Nielsen, S Bruno, R AF Nielsen, Suzanne Bruno, Raimondo TI Pharmaceutical drugs: The delicate balance between reducing pain and reducing harm SO DRUG AND ALCOHOL REVIEW LA English DT Editorial Material ID UNITED-STATES; ANALGESICS; IBUPROFEN; MISUSE; ABUSE C1 [Nielsen, Suzanne] Turning Point Alcohol & Drug Ctr, Melbourne, Vic, Australia. [Nielsen, Suzanne] Univ Calif Los Angeles, NIDA Clin Trials Network INVEST, Los Angeles, CA USA. [Bruno, Raimondo] Univ Tasmania, Sch Psychol, Hobart, Tas, Australia. RP Nielsen, S (reprint author), Turning Point Alcohol & Drug Ctr, Melbourne, Vic, Australia. EM SuziN@turningpoint.org.au RI Nielsen, Suzanne/C-3256-2015; Bruno, Raimondo/A-2381-2009 OI Nielsen, Suzanne/0000-0001-5341-1055; Bruno, Raimondo/0000-0001-6673-833X NR 27 TC 4 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0959-5236 J9 DRUG ALCOHOL REV JI Drug Alcohol Rev. PD MAY PY 2011 VL 30 IS 3 BP 233 EP 235 DI 10.1111/j.1465-3362.2011.00326.x PG 3 WC Substance Abuse SC Substance Abuse GA 759SI UT WOS:000290268300001 PM 21545552 ER PT J AU Keim, SA Daniels, JL Dole, N Herring, AH Siega-Riz, AM Scheidt, PC AF Keim, Sarah A. Daniels, Julie L. Dole, Nancy Herring, Amy H. Siega-Riz, Anna Maria Scheidt, Peter C. TI A prospective study of maternal anxiety, perceived stress, and depressive symptoms in relation to infant cognitive development SO EARLY HUMAN DEVELOPMENT LA English DT Article DE Child development; Motor skills; Language; Depression; Pregnancy ID CHILD-BEHAVIOR PROBLEMS; POSTNATAL DEPRESSION; PSYCHOLOGICAL DISTRESS; PARENTING STRESS; PREGNANCY; MOTHERS; METAANALYSIS AB Aim: Our objective was to examine the associations between maternal psychological health (trait anxiety, perceived stress, and depressive symptoms) during pregnancy or postpartum and infant visual, language. motor, and overall cognitive development. Study Design and Methods: In the prospective Pregnancy. Infection, and Nutrition Study (2001-2006), central North Carolina women completed self-administered questionnaires during pregnancy to assess trait anxiety and depressive symptoms. An in-person interview assessed maternal perceived stress and depressive symptoms in the 4th postpartum month. Infant development was assessed at 12 months using the Mullen Scales of Early Learning (n = 358). Multiple linear regression with restricted cubic splines was used to examine potential non-linear associations between trait anxiety, perceived stress, and depressive symptoms in relation to Mullen sub-scales and Composite scores. Results: Increasing maternal anxiety was associated with poorer overall cognition (adjusted 13 for Composite = -0.2, 95% CI: -0.4, 0.0). Postpartum stress was positively associated with language development and general cognition (adjusted beta for Expressive Language = 0.2, 95% Cl: 0.0, 0.4; adjusted beta for Composite = 0.3. 95% CI: 0.0, 0.6). Elevated depressive symptoms throughout pregnancy and postpartum were associated with better fine motor skills (adjusted beta=9.7. 95% Cl: 3.9, 15.5). Anxiety, postpartum depressive symptoms and stress were associated with gross motor skills in a non-linear fashion, as were postpartum depressive symptoms and stress with expressive language. Conclusions: Maternal trait anxiety, depressive symptoms and stress had little negative influence on infant cognitive development. In fact, moderate psychosocial distress may slightly accelerate motor development in particular, and some aspects of language. Published by Elsevier Ireland Ltd. C1 [Keim, Sarah A.; Daniels, Julie L.; Siega-Riz, Anna Maria] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Keim, Sarah A.; Scheidt, Peter C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Daniels, Julie L.] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA. [Dole, Nancy; Herring, Amy H.; Siega-Riz, Anna Maria] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. [Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Siega-Riz, Anna Maria] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. RP Keim, SA (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Biobehav Hlth, 700 Childrens Dr, Columbus, OH 43205 USA. EM Sarah.keim@nationwidechildrens.org RI Keim, Sarah/F-8929-2013; OI Keim, Sarah/0000-0003-3490-3649; Dole, Nancy/0000-0002-2113-7984 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD37584, HD39373]; National Institute of Diabetes and Digestive and Kidney Diseases [DK61981, DK56350]; National Institute of Environmental Health Sciences of the National Institutes of Health [P30ES10126]; Carolina Population Center; NICHD FX This work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD37584, HD39373), the National Institute of Diabetes and Digestive and Kidney Diseases (DK61981, DK56350), and the National Institute of Environmental Health Sciences (P30ES10126) of the National Institutes of Health, the Carolina Population Center, and as part of the salary-supported activities of extramural staff of the NICHD. NR 33 TC 25 Z9 26 U1 3 U2 34 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD MAY PY 2011 VL 87 IS 5 BP 373 EP 380 DI 10.1016/j.earlhumdev.2011.02.004 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 767BX UT WOS:000290831400009 PM 21420261 ER PT J AU Edskes, HK Engel, A McCann, LM Brachmann, A Tsai, HF Wickner, RB AF Edskes, Herman K. Engel, Abbi McCann, Lindsay M. Brachmann, Andreas Tsai, Huei-Fung Wickner, Reed B. TI Prion-Forming Ability of Ure2 of Yeasts Is Not Evolutionarily Conserved SO GENETICS LA English DT Article ID TERMINATION FACTOR ERF3; HUMAN FUNGAL PATHOGEN; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; MESSENGER-RNA; SUP35 PROTEIN; AZOLE RESISTANCE; SPECIES BARRIER; TOR PROTEINS; GLABRATA AB [URE3] is a prion (infectious protein) of the Saccharomyces cerevisiae Ure2p, a regulator of nitrogen catabolism. We show that wild S. paradoxus can be infected with a [URE3] prion, supporting the use of S. cerevisiae as a prion test bed. We find that the Ure2p of Candida albicans and C. glabrata also regulate nitrogen catabolism. Conservation of amino acid sequence within the prion domain of Ure2p has been proposed as evidence that the [URE3] prion helps its host. We show that the C. albicans Ure2p, which does not conserve this sequence, can nonetheless form a [URE3] prion in S. cerevisiae, but the C. glabrata Ure2p, which does have the conserved sequence, cannot form [URE3] as judged by its performance in S. cerevisiae. These results suggest that the sequence is not conserved to preserve prion forming ability. C1 [Tsai, Huei-Fung; Wickner, Reed B.] NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Edskes, Herman K.; Engel, Abbi; McCann, Lindsay M.; Brachmann, Andreas; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI Brachmann, Andreas/I-2241-2013 OI Brachmann, Andreas/0000-0001-7980-8173 FU National Institute of Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health FX We thank Brendan Cormack for C. glabrata strains and plasmids, Alexander D. Johnson for C. albicans strains, Alistair J. P. Brown for the C. albicans cre-loxP plasmid system, and Janyce A. Sugui for help with microscopy. We are grateful to Michel Aigle for marked S. paradoxus strains and to Clete Kurtzman for wild S. paradoxus isolates. This work was supported by the Intramural Program of the National Institute of Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health. NR 75 TC 23 Z9 551 U1 2 U2 8 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 1943-2631 J9 GENETICS JI Genetics PD MAY PY 2011 VL 188 IS 1 BP 81 EP U127 DI 10.1534/genetics.111.127217 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 759VP UT WOS:000290276900008 PM 21368275 ER PT J AU Ting, CY Gu, S Guttikonda, S Lin, TY White, BH Lee, CH AF Ting, Chun-Yuan Gu, Stephanie Guttikonda, Sudha Lin, Tzu-Yang White, Benjamin H. Lee, Chi-Hon TI Focusing Transgene Expression in Drosophila by Coupling Gal4 With a Novel Split-LexA Expression System SO GENETICS LA English DT Article AB eHere we report the development of a ternary version of the LexA::VP16/LexAop system in which the DNA-binding and trans-activating moieties are independently targeted using distinct promoters to achieve highly restricted, intersectional expression patterns. This Split LexA system can be concatenated with the Gal4/upstream activating sequence system to refine the expression patterns of existing Gal4 lines with minimal genetic manipulations. C1 [Ting, Chun-Yuan; Gu, Stephanie; Guttikonda, Sudha; Lin, Tzu-Yang; Lee, Chi-Hon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [White, Benjamin H.] NIMH, Sect Neural Funct, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lee, CH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. EM leechih@mail.nih.gov RI Lee, Chi-Hon/G-9190-2012; Lin, Tzu-Yang/D-8300-2013; Ting, chun-yuan/F-6448-2013 FU Eunice Kennedy Shriver National Institute of Child Health and Human Developmen [HD008748]; National Institute of Mental Health [MH-002800-07] FX We thank Tzumin Lee, Thomas Clandinin, Claude Desplan, Ted Erclik, and Roderick McInnes for reagents and Haojiang Luan, Howard Nash, and Alan Hinnebusch for helpful discussion. This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD008748 to C.-H. L.) and National Institute of Mental Health (MH-002800-07 to B.H.W.). NR 10 TC 16 Z9 16 U1 0 U2 5 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 2011 VL 188 IS 1 BP 229 EP U354 DI 10.1534/genetics.110.126193 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 759VP UT WOS:000290276900019 PM 21368278 ER PT J AU Kinney, W Fetterman, B Cox, JT Lorey, T Flanagan, T Castle, PE AF Kinney, Walter Fetterman, Barbara Cox, J. Thomas Lorey, Thomas Flanagan, Tracy Castle, Philip E. TI Characteristics of 44 cervical cancers diagnosed following Pap-negative, high risk HPV-positive screening in routine clinical practice SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Cytology; Cervical cancer; Human papillomavirus (HPV); HPV testing ID HUMAN-PAPILLOMAVIRUS DNA; SQUAMOUS-CELL CARCINOMA; RANDOMIZED CONTROLLED-TRIAL; LIQUID-BASED CYTOLOGY; INTRAEPITHELIAL NEOPLASIA; UTERINE CERVIX; INTEROBSERVER REPRODUCIBILITY; ENDOCERVICAL CURETTAGE; CONVENTIONAL CYTOLOGY; INCIDENCE TRENDS AB Objective. To characterize the cervical cancers diagnosed following a Pap-negative, high risk human papillomavirus (HPV)-positive (Pap-/HPV+) screen in routine clinical practice. Methods. Using data from Kaiser Permanente Northern California, we investigated the cases of cervical cancer diagnosed between January, 2003 and January, 2009 following Pap-/HPV+ screen. Two cervical specimens were routinely collected for cervical cancer screening, one for conventional cytology and the other for high risk HPV testing using Hybrid Capture 2 (Qiagen). Results. Forty-four women (median age at diagnosis =44 years) were diagnosed with primary invasive cervical cancer with a recent history of one or more Pap-/HPV+ screens. Twenty-six women had one Pap-/HPV+ screen preceding the diagnosis of cancer, 15 had two, and three had three. There were 16 squamous cancers, one small cell cancer, 24 adenocarcinomas, 2 adenosquamous carcinomas, and one case with separate invasive squamous and adenocarcinoma. FIGO Stage was IA in 11 women, IB in 31 women and IIA in 2 women. Treatment included a pelvic node dissection in 30,2 (6.7%) of whom had positive nodes. Conclusions. HPV testing contributes to early cervical cancer diagnosis detection in women with negative Pap tests. Most women in this cohort have early stage, node negative, treatable and potentially curable disease. Adenocarcinoma predominated as might be expected because cytology misses these cancers and their precursors. The majority of cancers were diagnosed following a single Pap-/HPV+ screen, suggesting that effective triage to colposcopy of women with a Pap-/HPV+ screen would be preferable to retesting in one year as currently recommended. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. [Fetterman, Barbara; Lorey, Thomas] Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA. [Cox, J. Thomas] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Flanagan, Tracy] Kaiser Permanente Med Care Program, Womens Hlth Res Inst, Oakland, CA USA. [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Castle, PE (reprint author), Amer Soc Clin Pathologists, 1225 New York Ave NW,Suite 250, Washington, DC 20005 USA. EM philip.castle@ascp.org FU NIH, National Cancer Institute; American Cancer Society; Women's Health Research Institute at Kaiser Permanente Northern California FX Dr. Castle was supported by the Intramural Research Program of the NIH, National Cancer Institute. Dr. Kinney was supported by the American Cancer Society. The authors acknowledge the support of the Women's Health Research Institute at Kaiser Permanente Northern California. NR 43 TC 18 Z9 21 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY 1 PY 2011 VL 121 IS 2 BP 309 EP 313 DI 10.1016/j.ygyno.2010.12.361 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100013 PM 21276605 ER PT J AU Han, JJ Yu, MS Houston, N Steinberg, SM Kohn, EC AF Han, Jasmine J. Yu, Minshu Houston, Nicole Steinberg, Seth M. Kohn, Elise C. TI Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers (vol 120, pg 5, 2011) SO GYNECOLOGIC ONCOLOGY LA English DT Correction C1 [Han, Jasmine J.; Yu, Minshu; Houston, Nicole; Kohn, Elise C.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Han, Jasmine J.] NCI, Walter Reed Army Med Ctr, Gynecol Malignancies Lab, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM Kohne@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY 1 PY 2011 VL 121 IS 2 BP 427 EP 427 DI 10.1016/j.ygyno.2010.12.324 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100040 ER PT J AU Lepora, C Millum, J AF Lepora, Chiara Millum, Joseph TI The Tortured Patient: A Medical Dilemma SO HASTINGS CENTER REPORT LA English DT Article ID HUMAN-RIGHTS; INVOLVEMENT; PHYSICIANS; DOCTORS; ETHICS; COMPLICITY; REFUSAL; TREAT; DUTY C1 [Millum, Joseph] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Millum, Joseph] NIH, Fogarty Int Ctr, Bethesda, MD USA. NR 50 TC 6 Z9 6 U1 0 U2 2 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAY-JUN PY 2011 VL 41 IS 3 BP 38 EP 47 PG 10 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 765WY UT WOS:000290741300020 PM 21678814 ER PT J AU Birnbaum, LS Jung, P AF Birnbaum, Linda S. Jung, Paul TI From Endocrine Disruptors To Nanomaterials: Advancing Our Understanding Of Environmental Health To Protect Public Health SO HEALTH AFFAIRS LA English DT Article ID AIR-POLLUTION; EXPOSURE ASSESSMENT; DISEASE; POLLUTANTS; ASSOCIATION; MORTALITY; ATRAZINE AB Environmental health science is the study of the impact of the environment on human health. This paper introduces basic topics in environmental health, including clean air, clean water, and healthful food, as well as a range of current issues and controversies in environmental health. Conceptual shifts in modern toxicology have changed the field. There is a new understanding of the effects of exposure to chemicals at low doses, and in combination, and the impact on human growth and development. Other emerging topics include the role of epigenetics, or changes in genes and gene expression that can be brought about by chemical exposure; environmental justice; and potential effects of engineered nanomaterials and climate change. We review the important implications for public health policy and recommend a broad environmental health research strategy aimed at protecting and improving human health. C1 [Birnbaum, Linda S.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Birnbaum, LS (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov NR 49 TC 9 Z9 9 U1 1 U2 24 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY PY 2011 VL 30 IS 5 BP 814 EP 822 DI 10.1377/hlthaff.2010.1225 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 761WD UT WOS:000290430800003 PM 21555467 ER PT J AU de Heer, HD Balcazar, HG Rosenthal, EL Cardenas, VM Schulz, LO AF de Heer, Hendrik Dirk Balcazar, Hector G. Rosenthal, E. Lee Cardenas, Victor M. Schulz, Leslie O. TI Ethnic Pride and Cardiovascular Health Among Mexican American Adults Along the US-Mexico Border SO HISPANIC JOURNAL OF BEHAVIORAL SCIENCES LA English DT Article DE ethnic pride; diabetes; cardiovascular; metabolic syndrome; Hispanic; acculturation ID UNITED-STATES; ACCULTURATION SCALE; MENTAL-HEALTH; RISK-FACTORS; SELF-ESTEEM; NHANES-III; DRUG-USE; IDENTITY; WOMEN; HISPANICS AB This study addressed the association between items from the General Acculturation Index (GAI) and cardiovascular health. Specifically, we assessed whether ethnic pride was associated with health outcomes after controlling for items regarding language, place where the childhood was spent, and ethnic interaction. The study was a cross-sectional analysis of demographic and clinical data from a border population of Mexican American adults (n = 316) at risk for cardiovascular disease (CVD). Outcomes included smoking and diabetes status, Framingham risk, and metabolic syndrome. Ethnic pride was associated with lower diabetes prevalence, lower Framingham risk, and fewer risk factors for metabolic syndrome but was not associated with smoking status. Ethnic pride was not associated with the other acculturation items of the GAI. Among an at-risk border population, ethnic pride functioned independently of other acculturation indicators. Ethnic pride may act as a protective factor for diabetes, metabolic syndrome, and CVD risk status. C1 [de Heer, Hendrik Dirk] Univ Texas El Paso, Dept Psychol, El Paso, TX 79968 USA. [Balcazar, Hector G.; Cardenas, Victor M.] Univ Texas Houston Hlth Sci Ctr, Sch Publ Hlth, El Paso, TX USA. [Rosenthal, E. Lee] Univ Texas El Paso, Coll Hlth Sci, Dept Publ Hlth Sci, El Paso, TX 79968 USA. [Schulz, Leslie O.] No Arizona Univ, Coll Hlth & Human Serv, Flag Staff, AZ USA. RP de Heer, HD (reprint author), NHGRI, Social & Behav Res Branch, 31 Ctr Dr,Bldg 31,RM B1B37, Bethesda, MD 20892 USA. EM dirk.deheer@nih.gov RI de Heer, Hendrik/D-3192-2013 OI de Heer, Hendrik/0000-0002-9241-5021 FU NIMHD NIH HHS [R24 MD001785, R24 MD001785-01] NR 46 TC 1 Z9 1 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0739-9863 J9 HISPANIC J BEHAV SCI JI Hisp. J. Behav. Sci. PD MAY PY 2011 VL 33 IS 2 BP 204 EP 220 DI 10.1177/0739986311406068 PG 17 WC Psychology, Multidisciplinary SC Psychology GA 759XB UT WOS:000290280900005 PM 22610060 ER PT J AU Narusyte, J Neiderhiser, JM Andershed, AK D'Onofrio, BM Reiss, D Spotts, E Ganiban, J Lichtenstein, P AF Narusyte, Jurgita Neiderhiser, Jenae M. Andershed, Anna-Karin D'Onofrio, Brian M. Reiss, David Spotts, Erica Ganiban, Jody Lichtenstein, Paul TI Parental Criticism and Externalizing Behavior Problems in Adolescents: The Role of Environment and Genotype-Environment Correlation SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE parenting; externalizing behavior; twins; genotype-environment correlation ID MONOZYGOTIC-TWIN DIFFERENCES; ANTISOCIAL-BEHAVIOR; CHILD RELATIONSHIPS; EXPRESSED EMOTION; DEPRESSIVE SYMPTOMS; FAMILY ENVIRONMENT; TESTING HYPOTHESES; MIDDLE CHILDHOOD; SWEDISH TWIN; MODEL AB Genetic factors are important for the association between parental negativity and child problem behavior, but it is not clear whether this is due to passive or evocative genotype environment correlation (rGE). In this study, we applied the extended children-of-twins model to directly examine the presence of passive and evocative rGE as well as direct environmental effects in the association between parental criticism and adolescent externalizing problem behavior. The cross-sectional data come from the Twin and Offspring Study in Sweden (N = 909 pairs of adult twins) and from the Twin Study of Child and Adolescent Development (N = 915 pairs of twin children). The results revealed that maternal criticism was primarily due to evocative rGE emanating from their adolescent's externalizing behavior. On the other hand, fathers' critical remarks tended to affect adolescent problem behavior in a direct environmental way. This suggests that previously reported differences in caretaking between mothers and fathers also are reflected in differences in why parenting is associated with externalizing behavior in offspring. C1 [Narusyte, Jurgita; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Andershed, Anna-Karin] Univ Orebro, Sch Law Psychol & Social Work, Orebro, Sweden. [D'Onofrio, Brian M.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Reiss, David] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. [Spotts, Erica] NIA, NIH, Bethesda, MD 20892 USA. [Ganiban, Jody] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. RP Narusyte, J (reprint author), Karolinska Inst, Dept Clin Neurosci, Div Insurance Med, SE-17177 Stockholm, Sweden. EM jurgita.narusyte@ki.se OI lichtenstein, paul/0000-0003-3037-5287; Andershed, Anna-Karin/0000-0003-3981-0353 FU NICHD NIH HHS [R01 HD061817]; NIMH NIH HHS [R01 MH054610, R01 MH054610-09, R01MH54610] NR 64 TC 20 Z9 20 U1 3 U2 19 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2011 VL 120 IS 2 BP 365 EP 376 DI 10.1037/a0021815 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 763YP UT WOS:000290595900009 PM 21280930 ER PT J AU Alperson, SY Berger, VW AF Alperson, Sunny Y. Berger, Vance W. TI Opposing Systematic Reviews: The Effects of Two Quality Rating Instruments on Evidence Regarding T'ai Chi and Bone Mineral Density in Postmenopausal Women SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Review ID METHODOLOGICAL QUALITY; MEDICAL LITERATURE; RANDOMIZED-TRIALS; CLINICAL-TRIALS; USERS GUIDES; EXERCISE; HEALTH; CHUAN AB Purpose: This article compares and contrasts two systematic reviews of t'ai chi (TC) interventions on bone mineral density in postmenopausal women. The aim is to examine how chosen quality rating instruments can impact systematic reviews of TC literature. Methods: The rating instruments in the reviews, the three-item scale of Jadad et al. and the ad hoc checklist of Wayne et al., were analyzed using Oxman's evaluation criteria for systematic reviews regarding inclusion of articles, interpretation of results, and overall implications for the efficacy of TC on bone mineral density. Results: According to Oxman's criteria, the Jadad scale did not address advances in statistical methods and was not comprehensive enough to adapt to the clinical context or topic. In contrast, the checklist by Wayne et al. was comprehensive, adaptable to clinical context and topical relevance, and compatible with recent developments in statistics and experimental design. These quality rating instruments were critical in the inclusion of studies, analyses, and overall conclusions summarizing the TC literature. The conclusions from the two systematic reviews were starkly opposing; Lee et al. found no convincing evidence, dismissing TC studies as low quality, while Wayne et al. stated that TC may be an effective, safe, and practical intervention. Conclusions: Readers must exercise caution concerning high or low ratings from systematic reviews of TC studies because the choice of quality rating tool can dramatically influence the summary and conclusions of the reviews. There is no consensus on quality rating standards at this time. Of the two, the Jadad scale was not only inadequate but also inappropriate for reviewing TC studies, potentially misleading researchers, clinicians and policymakers. Future systematic reviews of TC should utilize instruments that are updated to current scientific standards, comprehensive, adaptable to clinical context, and relevant to the research topic. C1 [Alperson, Sunny Y.] NINR, Bethesda, MD 20892 USA. [Alperson, Sunny Y.] NIH, NIH Clin Ctr, Bethesda, MD 20892 USA. [Berger, Vance W.] NCI, NIH, Bethesda, MD 20892 USA. RP Alperson, SY (reprint author), NINR, 10 Ctr Dr,Room 2B02A MSC 11151, Bethesda, MD 20892 USA. EM alpersonsy@mail.nih.gov FU Bravewell Collaborative; National Institutes of Health; Clinical Center, NIH FX We would like to express our thanks to Karen Lewison, MD and Jay Alperson, PhD for their participation in rating the Chan et al. article with different quality rating scales. This article was supported in part by the Bravewell Collaborative, the National Institutes of Health, Intramural division of Research Program at the National Institute of Nursing Research and the Clinical Center, NIH. Its contents are solely the responsibility of the authors and do not represent views of Bravewell nor the National Institutes of Health. NR 41 TC 6 Z9 6 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD MAY PY 2011 VL 17 IS 5 BP 389 EP 395 DI 10.1089/acm.2010.0175 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 766LP UT WOS:000290784100003 PM 21548814 ER PT J AU Lee, JY Foster, HE McVary, KT Meleth, S Stavris, K Downey, J Kusek, JW AF Lee, Jeannette Y. Foster, Harris E., Jr. McVary, Kevin T. Meleth, Sreelatha Stavris, Karen Downey, Joe Kusek, John W. TI Recruitment of Participants to a Clinical Trial of Botanical Therapy for Benign Prostatic Hyperplasia SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID URINARY-TRACT SYMPTOMS; ALTERNATIVE MEDICINE; CANCER; ADULTS; COMPLEMENTARY AB Objectives: The timely recruitment of study participants is a critical component of successful trials. Benign prostatic hyperplasia (BPH), a common nonmalignant urologic condition among older men, is characterized by lower urinary tract symptoms (LUTS). Successful recruitment methods for a trial of medical therapy for BPH, Medical Therapy of Prostate Symptoms (MTOPS), were mass mailing and advertising. The Complementary and Alternative Medicines Trial for Urological Symptoms (CAMUS) was designed to evaluate a botanical therapy, saw palmetto, for the treatment of BPH. The objective of this study was to evaluate recruitment strategies for CAMUS and to contrast the baseline characteristics of CAMUS participants with those recruited to a similar trial using conventional medical therapy. Design: CAMUS is a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of saw palmetto given at escalating doses over an 18-month period on relief from LUTS. Subjects: The target enrollment goal was 350 men with LUTS from 11 clinical centers over a 12-month period. The recruitment techniques used and participants contacted, screened, and randomized through each technique were obtained from the clinical centers. Baseline characteristics of the CAMUS participants were compared with participants in the MTOPS trial who met the CAMUS eligibility criteria for LUTS. Results: The target enrollment goal was achieved in 11 months. The overall monthly recruitment rate per site was 3.7 and ranged from 2.4 to 8.0. The most successful recruitment methods were mass mailing and advertising, which accounted for 39% and 35% of the study participants, respectively. In comparison to MTOPS participants, CAMUS participants were younger, more highly educated, more diverse, and had less severe urinary symptoms. Conclusions: Successful recruitment methods for CAMUS were similar to those in MTOPS. The use of botanical therapy attracted a less symptomatic and more educated study population. C1 [Lee, Jeannette Y.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Foster, Harris E., Jr.; Stavris, Karen] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [McVary, Kevin T.] Northwestern Univ, Fineberg Sch Med, Dept Urol, Chicago, IL 60611 USA. [Meleth, Sreelatha] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Downey, Joe] Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada. [Downey, Joe] Queens Univ, Dept Urol, Kingston, ON K7L 3N6, Canada. [Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. RP Lee, JY (reprint author), Univ Arkansas Med Sci, Dept Biostat, 4301 W Markham,781, Little Rock, AR 72205 USA. EM jylee@uams.edu FU National Institutes of Health (NIH); National Institute of Diabetes, Digestive & Kidney Diseases; National Center for Complementary and Alternative Medicine; Office of Dietary Supplements; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01 DK63795, U01 DK63797, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63831, U01 DK63825, U01 DK 63883, U01 DK63778, U01 DK63788]; Office of Dietary Supplements, NIH FX Sponsors: National Institutes of Health (NIH); National Institute of Diabetes, Digestive & Kidney Diseases, John W. Kusek, PhD; National Center for Complementary and Alternative Medicine, Catherine M. Meyers, MD, Sheila Cald-well, PhD; Office of Dietary Supplements, Joseph M. Betz, PhD, Paul M. Coates, PhD.; The MTOPS study was conducted by the MTOPS investigator and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The manuscript was not prepared in collaboration with the MTOPS investigators and does not necessarily reflect the opinions or view of the MTOPS study of the NIDDK.; CAMUS is funded by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases: U01 DK63795, U01 DK63797, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63831, U01 DK63825, U01 DK 63883, U01 DK63778, and U01 DK63788. Support was provided by the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements, NIH. Saw palmetto fruit extract and matching placebo was supplied by Rottapharm/Madaus.; Kevin McVary has received grant support for or served as a consultant or speaker for Lilly/ICOS, Sanofi-Aventis, Allergan, NIDDK, Advanced Health Medical, Watson Pharmaceuticals, Neotract, and Ferring. NR 18 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD MAY PY 2011 VL 17 IS 5 BP 469 EP 472 DI 10.1089/acm.2010.0300 PG 4 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 766LP UT WOS:000290784100014 PM 21554128 ER PT J AU Abd-Elmoniem, KZ Obele, CC Sibley, CT Matta, JR Pettigrew, RI Gharib, AM AF Abd-Elmoniem, Khaled Z. Obele, Chika C. Sibley, Christopher T. Matta, Jatin R. Pettigrew, Roderic I. Gharib, Ahmed M. TI Free-Breathing Single Navigator Gated Cine Cardiac Magnetic Resonance at 3 T: Feasibility Study in Patients SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE cine cardiac MRI; free-breathing; single navigator; high field ID CORONARY MR-ANGIOGRAPHY; RESPIRATORY MOTION; REAL-TIME; BREATHHOLD AB Background: Cardiac magnetic resonance imaging (CMRI) is an important tool to assess cardiac function. However, one of the limitations of CMRI is the need for frequent breath-holding (BH) steps. This may be inconvenient to some patients and limit the use of this modality in patients unable to cooperate because of cognitive reasons or physically incapable of performing the required BH steps. The purpose of this study is to overcome the intrinsic timing and computation limitations of dual-navigator cine imaging and demonstrate the feasibility of free-breathing (FB) cine cardiac left ventricular function with a single-respiratory-navigator gating at 3 T. Results: Eight participants underwent cine CMRI with both the conventional 2-dimensional cine BH and FB navigator-gated techniques. Scan parameters were identical, except in the FB technique, in which a respiratory navigator and only 2 signal averages were used. Images were scored for quality. Left ventricular end-systolic volume and end-diastolic volume were calculated. The differences in the end-systolic volume and end-diastolic volume assessed by the BH and FB were not statistically significant with P = 0.9 and 0.2, respectively. There was a good agreement between LV volumes with the limits of agreement (+/- 2 SD = +/- 22.36 mL). Image quality score was not significantly different (P = 0.76). Conclusions: Free-breathing cine imaging utilizing a single-respiratory-navigator gating technique is comparable to conventional BH technique in both qualitative and quantitative imaging measures. Therefore, the FB cine technique can be used as an alternative for children and patients who are unable to hold their breath. C1 [Sibley, Christopher T.; Gharib, Ahmed M.] NIH, Clin Res Ctr, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA. [Abd-Elmoniem, Khaled Z.; Obele, Chika C.; Matta, Jatin R.; Pettigrew, Roderic I.; Gharib, Ahmed M.] NIDDK, Integrat Cardiovasc Imaging Sect, Bethesda, MD 20892 USA. RP Gharib, AM (reprint author), NIH, Clin Res Ctr, Radiol & Imaging Sci Dept, Bldg 10,Rm 3-5340,10 Ctr Dr, Bethesda, MD 20892 USA. EM agharib@mail.nih.gov RI Sibley, Christopher/C-9900-2013; Gharib, Ahmed/O-2629-2016; Abd-Elmoniem, Khaled/B-9289-2008; OI Gharib, Ahmed/0000-0002-2476-481X; Abd-Elmoniem, Khaled/0000-0002-1001-1702; Obele, Chika/0000-0002-6860-5490 FU National Institutes of Health; Pfizer Inc FX This research year was made possible through the Clinical Research Training Program, a public-private partnership supported jointly by the National Institutes of Health and Pfizer Inc (via a grant to the Foundation for the National Institutes of Health from Pfizer Inc). 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 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2011 VL 35 IS 3 BP 382 EP 386 DI 10.1097/RCT.0b013e31821b0ade PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 765TY UT WOS:000290732700013 PM 21586935 ER PT J AU Nwe, K Milenic, D Bryant, LH Regino, CAS Brechbiel, MW AF Nwe, Kido Milenic, Diane Bryant, L. Henry Regino, Celeste A. S. Brechbiel, Martin W. TI Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE Magnetic resonance imaging; Gadolinium-dendrimer; Gadolinium-albumin ID MAGNETIC-RESONANCE; MONOCLONAL-ANTIBODY; POLYAMIDOAMINE DENDRIMER; ANTIANGIOGENIC ACTIVITY; ENHANCEMENT PATTERNS; EXPERIMENTAL-MODEL; MOLECULAR-WEIGHT; COLON-CARCINOMA; DRUG-DELIVERY; SERUM-ALBUMIN AB We report in vivo and in vitro MRI properties of six gadolinium-dendrimer and gadolinium-albumin conjugates of derivatized acyclic diethylenetriamine-N,N',N',N '',N ''-pentaaceticacid (1B4M) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N '',N ''-tetraacetic acid (C-DOTA). The three albumin-based agents have comparable protein to chelate ratios (1:16-18) as well as molar relaxivity (8.8-10.4 mM(-1)s(-1)). The three dendrimer based agents have blood clearance half-lives ranging from 17 to 66 min while that of the three albumin-based agents are comparable to one another (40-47 mm). The dynamic image obtained from use of the albumin conjugate based on the macrocycle (C-DOTA) showed a higher contrast compared to the remaining two albumin based agents. Our conclusion from all of the results is that the macrocyclic-based (DOTA) agents are more suitable than the acyclic-based (1B4M) agent for in vivo use based on their MRI properties combined with the kinetic inertness property associated with the more stable Gd(III) DOTA complex. Published by Elsevier Inc. C1 [Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bryant, L. Henry] NIH, Lab Diagnost Radiol Res CC, Bethesda, MD 20892 USA. [Regino, Celeste A. S.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU NIH, National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and the Center for Cancer Research. NR 53 TC 18 Z9 19 U1 0 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD MAY PY 2011 VL 105 IS 5 BP 722 EP 727 DI 10.1016/j.jinorgbio.2011.01.017 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 768GX UT WOS:000290923100018 PM 21463567 ER PT J AU Forsythe, LP Thorn, B Day, M Shelby, G AF Forsythe, Laura Pence Thorn, Beverly Day, Melissa Shelby, Grace TI Race and Sex Differences in Primary Appraisals, Catastrophizing, and Experimental Pain Outcomes SO JOURNAL OF PAIN LA English DT Article DE Experimental pain; appraisals; catastrophizing; race; sex ID WORKERS-COMPENSATION CLAIMANTS; CONFIRMATORY FACTOR-ANALYSIS; VISUAL ANALOG SCALES; LOW-BACK INJURIES; COGNITIVE APPRAISAL; AFRICAN-AMERICAN; PSYCHOLOGICAL ADJUSTMENT; ETHNIC-DIFFERENCES; COPING STRATEGIES; CLINICAL PAIN AB The aims of this study were: 1) to examine race and sex differences in primary pain appraisals and catastrophizing; 2) to test the unique ability of race, sex, primary pain appraisals, and catastrophizing to predict experimental pain outcomes; and 3) to conduct mediational analyses testing pain appraisals and catastrophizing as explanatory mechanisms for race and sex differences in pain. One hundred and fifty-five college students at The University of Alabama completed a cold pressor experimental pain task and a questionnaire battery. Statistical methods included multivariable regression models and nonparametric bootstrapping methods for tests of mediation. African-Americans reported higher catastrophizing and had lower pain tolerance than white Americans. Males demonstrated higher challenge appraisals, lower pain intensity, and longer pain tolerance. Challenge appraisals were positively related to pain tolerance, threat/harm appraisals were inversely related to pain tolerance, and pain catastrophizing was positively related to both pain intensity and pain unpleasantness. Pain catastrophizing partially mediated race differences in pain tolerance and mediated sex differences in intensity, whereas primary pain appraisals did not significantly mediate race or sex differences in pain variables. Primary appraisals and catastrophizing appear to be separable constructs related to different aspects of the pain experience. Perspective: This study found that important race and sex differences exist in relation to pain appraisals and catastrophizing, and that these cognitive variables play unique roles in different aspects of the pain experience. Cognitive-behavioral therapies for pain may be enhanced by including a focus on both pain appraisals and pain catastrophizing. Published by Elsevier Inc. on behalf of the American Pain Society C1 [Forsythe, Laura Pence] NCI, Canc Prevent Fellowship Program, Off Canc Survivorship, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. [Forsythe, Laura Pence; Thorn, Beverly; Day, Melissa] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. [Shelby, Grace] Vanderbilt Univ, Med Ctr, Vanderbilt Childrens Hosp, Nashville, TN USA. RP Forsythe, LP (reprint author), NCI, Canc Prevent Fellowship Program, Off Canc Survivorship, Div Canc Control & Populat Sci,NIH, Execut Plaza S,Suite 150E,6120 Execut Blvd,MSC 71, Bethesda, MD 20892 USA. EM laura.pence@nih.gov RI Day, Melissa/B-3685-2015 NR 58 TC 24 Z9 24 U1 1 U2 10 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD MAY PY 2011 VL 12 IS 5 BP 563 EP 572 DI 10.1016/j.jpain.2010.11.003 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 766KB UT WOS:000290779900007 PM 21277836 ER PT J AU Yang, Y Gu, DY Aisa, HA Ito, Y AF Yang, Yi Gu, Dongyu Aisa, Haji Akber Ito, Yoichiro TI Studies on the performance of different coiled column configurations for compact type-I countercurrent chromatography SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Coiled column configuration; Compact type-I countercurrent chromatography; Dinitrophenyl amino acid; Dipeptide; Retention of the stationary phase; Resolution ID PLANET CENTRIFUGE; FLOW-RATE; SEPARATION; GEOMETRIES; DESIGN; TUBE AB Three types of novel coiled column configurations, i.e. a triangular coiled column and elliptical coiled columns I and II, were designed for type-I countercurrent chromatography and their performances were evaluated with two solvent systems each with suitable test samples. Three dinitrophenyl (DNP) amino acids (DNP-DL-glu, DNP-beta-ala and DNP-L-ala) were separated with a moderately hydrophobic two-phase solvent system composed of hexane-ethyl acetate-metanol-0.1M hydrochloric acid (1:1:1:1, v/v), while two dipeptides (tryptophyl-tyrosine and valyl-tyrosine) were separated with a polar solvent system composed of 1-butanol-acetic acid-water (4.75:0.25:5, v/v). The overall results indicated that the performance of compact type-I countercurrent chromatography was improved by elliptical coiled column I which was mounted with its maximum coil diameter perpendicular to the surface of the column holder. Hydrodynamic effects involved in these separations were discussed. C1 [Yang, Yi; Gu, Dongyu; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Yang, Yi; Gu, Dongyu; Aisa, Haji Akber] Chinese Acad Sci, Key Lab Xinjiang Indigenous Med Plants Resource U, Xinjiang Tech Inst Phys & Chem, Urumqi, Peoples R China. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov FU Intramural NIH HHS [ZIA HL006022-02] NR 14 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD MAY PY 2011 VL 34 IS 10 BP 1205 EP 1211 DI 10.1002/jssc.201100019 PG 7 WC Chemistry, Analytical SC Chemistry GA 764NC UT WOS:000290635400016 PM 21491597 ER PT J AU Shen, ZY Li, JF Chen, RM Zhou, QF Shung, KK AF Shen, Zong-Yang Li, Jing-Feng Chen, Ruimin Zhou, Qifa Shung, K. Kirk TI Microscale 1-3-Type (Na,K)NbO3-Based Pb-Free Piezocomposites for High-Frequency Ultrasonic Transducer Applications SO JOURNAL OF THE AMERICAN CERAMIC SOCIETY LA English DT Article ID MEDICAL IMAGING APPLICATIONS; COMPOSITES; PIEZOCERAMICS AB Fine-grained Pb-free (Na0.535K0.485)(0.95)Li-0.05(Nb0.8Ta0.2)O-3 (NKLNT) piezoceramics prepared by spark plasma sintering (SPS) technique was used to fabricate NKLNT/epoxy 1-3 composites with a modified dice-fill method. Because of its good machinability, SPSed NKLNT ceramic rods could be miniaturized to a lateral width of 50 mu m. After lapping down to 56 mu m in thickness, the composite was used to fabricate an ultrasonic transducer as the active piezoelectric element. This composite transducer showed a bandwidth at -6 dB nearly 90% at a center frequency of 29 MHz, demonstrating that this Pb-free composite thick film is very promising for the fabrication of high-frequency ultrasonic transducers in medical imaging applications. C1 [Shen, Zong-Yang; Li, Jing-Feng] Tsinghua Univ, Dept Mat Sci & Engn, State Key Lab New Ceram & Fine Proc, Beijing 100084, Peoples R China. [Shen, Zong-Yang] Jingdezhen Ceram Inst, Sch Mat Sci & Engn, Jiangxi Key Lab Adv Ceram Mat, Jingdezhen 333001, Peoples R China. [Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RP Li, JF (reprint author), Tsinghua Univ, Dept Mat Sci & Engn, State Key Lab New Ceram & Fine Proc, Beijing 100084, Peoples R China. EM jingfeng@mail.tsinghua.edu.cn RI Shen, Zong-Yang/C-9696-2014; Li, Jing-Feng/D-2770-2014 OI Shen, Zong-Yang/0000-0002-3673-225X; Li, Jing-Feng/0000-0002-0185-0512 FU MOST of China [2009CB623304]; NNSF of China [50772050, 50921061]; Tsinghua University; NIH [P41-EB2182] FX This work was financially supported by the MOST of China under the Grant 2009CB623304 and NNSF of China (Grants Nos. 50772050 and 50921061), as well as by the Tsinghua University Initiative Scientific Research Program and from NIH Grant P41-EB2182 for UTRC of the USA. NR 20 TC 26 Z9 27 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-7820 EI 1551-2916 J9 J AM CERAM SOC JI J. Am. Ceram. Soc. PD MAY PY 2011 VL 94 IS 5 BP 1346 EP 1349 DI 10.1111/j.1551-2916.2011.04508.x PG 4 WC Materials Science, Ceramics SC Materials Science GA 763CE UT WOS:000290530200012 PM 21637726 ER PT J AU Krebs-Smith, SM Kirkpatrick, SI AF Krebs-Smith, Susan M. Kirkpatrick, Sharon I. TI Methodologic Approaches Influence Assessment of Calcium Intakes SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material C1 [Krebs-Smith, Susan M.; Kirkpatrick, Sharon I.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Krebs-Smith, SM (reprint author), NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4005, Bethesda, MD 20892 USA. EM krebssms@mail.nih.gov OI Kirkpatrick, Sharon/0000-0001-9896-5975 NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 2011 VL 111 IS 5 BP 683 EP 686 DI 10.1016/j.jada.2011.02.012 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 765YO UT WOS:000290745500010 PM 21515113 ER PT J AU Cawthon, PM Fox, KM Gandra, SR Delmonico, MJ Chiou, CF Anthony, MS Caserotti, P Kritchevsky, SB Newman, AB Goodpaster, BH Satterfield, S Cummings, SR Harris, TB AF Cawthon, Peggy M. Fox, Kathleen M. Gandra, Shravanthi R. Delmonico, Matthew J. Chiou, Chiun-Fang Anthony, Mary S. Caserotti, Paolo Kritchevsky, Stephen B. Newman, Anne B. Goodpaster, Bret H. Satterfield, Suzanne Cummings, Steven R. Harris, Tamara B. CA Hlth Aging Body Composition Study TI Clustering of Strength, Physical Function, Muscle, and Adiposity Characteristics and Risk of Disability in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE lean mass; muscle; strength; disability; sarcopenia ID LOWER-EXTREMITY PERFORMANCE; SKELETAL-MUSCLE; BODY-COMPOSITION; SUBSEQUENT DISABILITY; CARDIOVASCULAR HEALTH; FAT INFILTRATION; ELDERLY-MEN; MASS; WOMEN; SARCOPENIA AB OBJECTIVES: To empirically identify groupings of strength, physical performance, adiposity, and lean mass and test how such groupings of these interrelated measures may relate to disability risk. DESIGN: Prospective Health, Aging and Body Composition Study. SETTING: Two U.S. clinical centers. PARTICIPANTS: One thousand two hundred sixty-three women and 1,221 men. MEASUREMENTS: Weight, strength (knee extension, grip); walking speed, chair stands, dual X-ray absorptiometry (fat and lean mass for total body, arm, and leg; percent fat), and thigh computed tomography scans (muscle area, muscle density). Analyses were stratified according to sex. Factor analysis reduced these variables into a smaller number of components, and proportional hazards models assessed risk of major disability for the components identified. RESULTS: In both sexes, factor analysis reduced the 14 individual variables into three components that explained 76% to 77% of the data variance: Factor 1, an adiposity component, with strong loading by fat mass, weight, and muscle density; Factor 2, a strength and lean body size component with strong loading by lean mass, weight, and strength; Factor 3, a physical performance component with positive loading by walking speed and chair stand performance. Factor 1 (adiposity) and Factor 3 (performance) but not Factor 2 (strength and lean body size) were associated with disability over 6.1 +/- 2.6 years. CONCLUSION: The adiposity and physical performance constructs but not the strength and lean body size construct were associated with disability risk, suggesting that adiposity and performance should be considered as risk factors for disability. J Am Geriatr Soc 59:781-787, 2011. C1 [Cawthon, Peggy M.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA. [Fox, Kathleen M.] Strateg Healthcare Solut LLC, Monkton, MD USA. [Gandra, Shravanthi R.; Chiou, Chiun-Fang; Anthony, Mary S.] Amgen Thousand Oaks, Thousand Oaks, CA USA. [Delmonico, Matthew J.] Univ Rhode Isl, Kingston, RI 02881 USA. [Caserotti, Paolo; Harris, Tamara B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Newman, Anne B.; Goodpaster, Bret H.] Univ Pittsburgh, Pittsburgh, PA USA. [Satterfield, Suzanne] Univ Tennessee, Memphis, TN USA. RP Cawthon, PM (reprint author), Calif Pacific Med Ctr, Res Inst, 185 Berry St,Lobby 4,Suite 5700, San Francisco, CA 94107 USA. EM pcawthon@sfcc-cpmc.net 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; Amgen; Amgen, Inc. FX This work was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the National Institutes of Health, NIA and by Amgen.; P. Cawthon received research funds from Amgen, Inc. to complete statistical analyses and prepare the manuscript. K. Fox received consultant funds from Amgen, Inc. to manage the analyses. S. Gandra, C. Chiou, and M . Anthony are employees of Amgen, Inc., and C. Chiou and M. Anthony own stock or stock options in Amgen, Inc. S. Kritchevsky is a consultant to the Egg Nutriton Center Advisory Board. Dr. Goodpaster was a consultant for the advisory meeting for GTx, Inc., May 2010. NR 29 TC 29 Z9 30 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2011 VL 59 IS 5 BP 781 EP 787 DI 10.1111/j.1532-5415.2011.03389.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 763RZ UT WOS:000290578700001 PM 21568948 ER PT J AU Mai, PL Garceau, AO Graubard, BI Dunn, M McNeel, TS Gonsalves, L Gail, MH Greene, MH Willis, GB Wideroff, L AF Mai, Phuong L. Garceau, Anne O. Graubard, Barry I. Dunn, Marsha McNeel, Timothy S. Gonsalves, Lou Gail, Mitchell H. Greene, Mark H. Willis, Gordon B. Wideroff, Louise TI Confirmation of Family Cancer History Reported in a Population-Based Survey SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COLORECTAL-CANCER; DEATH CERTIFICATE; BREAST-CANCER; UNITED-STATES; COMMUNICATION; RISK; SUSCEPTIBILITY; ACCURACY; HEALTH; INFORMATION AB Background Knowledge of family cancer history is essential for estimating an individual's cancer risk and making clinical recommendations regarding screening and referral to a specialty cancer genetics clinic. However, it is not clear if reported family cancer history is sufficiently accurate for this purpose. Methods In the population-based 2001 Connecticut Family Health Study, 1019 participants reported on 20 578 first-degree relatives (FDR) and second-degree relatives (SDR). Of those, 2605 relatives were sampled for confirmation of cancer reports on breast, colorectal, prostate, and lung cancer. Confirmation sources included state cancer registries, Medicare databases, the National Death Index, death certificates, and health-care facility records. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for reports on lung, colorectal, breast, and prostate cancer and after stratification by sex, age, education, and degree of relatedness and used to estimate report accuracy. Pairwise t tests were used to evaluate differences between the two strata in each stratified analysis. All statistical tests were two-sided. Results Overall, sensitivity and positive predictive value were low to moderate and varied by cancer type: 60.2% and 40.0%, respectively, for lung cancer reports, 27.3% and 53.5% for colorectal cancer reports, 61.1% and 61.3% for breast cancer reports, and 32.0% and 53.4% for prostate cancer reports. Specificity and negative predictive value were more than 95% for all four cancer types. Cancer history reports on FDR were more accurate than reports on SDR, with reports on FDR having statistically significantly higher sensitivity for prostate cancer than reports on SDR (58.9% vs 21.5%, P =.002) and higher positive predictive value for lung (78.1% vs 31.7%, P <.001), colorectal (85.8% vs 43.5%, P =.004), and breast cancer (79.9% vs 53.6%, P =.02). Conclusions General population reports on family history for the four major adult cancers were not highly accurate. Efforts to improve accuracy are needed in primary care and other health-care settings in which family history is collected to ensure appropriate risk assessment and clinical care recommendations. C1 [Mai, Phuong L.; Graubard, Barry I.; Gail, Mitchell H.; Greene, Mark H.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. [Garceau, Anne O.; Willis, Gordon B.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20852 USA. [Dunn, Marsha] Westat Corp, Rockville, MD USA. [McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA. [Gonsalves, Lou] Connecticut Tumor Registry, Hartford, CT USA. [Wideroff, Louise] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD USA. RP Mai, PL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7022, Bethesda, MD 20852 USA. EM maip@mail.nih.gov RI Hernandez, Jessica/G-6527-2011 FU National Cancer Institute, National Institutes of Health; Westat, Inc. [N01-PC-95039] FX This research was funded in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, and by Westat, Inc. (N01-PC-95039 to A.O.G. and M.D.). NR 38 TC 41 Z9 42 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2011 VL 103 IS 10 BP 788 EP 797 DI 10.1093/jnci/djr114 PG 10 WC Oncology SC Oncology GA 766VA UT WOS:000290813400007 PM 21562245 ER PT J AU Zervoudakis, A Strickler, HD Park, Y Xue, XN Hollenbeck, A Schatzkin, A Gunter, MJ AF Zervoudakis, Alice Strickler, Howard D. Park, Yikyung Xue, Xiaonan Hollenbeck, Albert Schatzkin, Arthur Gunter, Marc J. TI Reproductive History and Risk of Colorectal Cancer in Postmenopausal Women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ORAL-CONTRACEPTIVE USE; GROWTH-FACTOR-I; BREAST-CANCER; COLON-CANCER; PROGESTERONE-RECEPTORS; REPLACEMENT THERAPY; MENSTRUAL FACTORS; URINE ESTROGENS; SEX-HORMONES; CELL-LINES AB Background There are conflicting data regarding the role of sex hormones in colorectal cancer development. Whereas clinical trials data indicate that hormone therapy use reduces the risk of colorectal cancer, data from prospective cohort studies suggest that circulating estrogen levels are positively associated with colorectal cancer risk. A surrogate measure of lifetime estrogen exposure is reproductive history. We investigated the relationship between reproductive factors and the risk of colorectal cancer. Methods Subjects were postmenopausal women enrolled in the National Institutes of Health-American Association of Retired Persons Diet and Health Study, a cohort of 214 162 individuals (aged 50-71 years) that included 2014 incident cases of colorectal cancer that occurred over a mean follow-up of 8.2 years. Questionnaires were used to collect data on reproductive factors, including ages at menarche, birth of first child, and menopause; parity, and use of oral contraceptives. Multivariable Cox proportional hazards models were constructed to examine associations between these reproductive factors and the risk of colorectal cancer, with adjustment for established colorectal cancer risk factors. All statistical tests were two-sided. Results Age at menopause (>= 55 vs < 40 years: hazard ratio [HR] = 1.50, 95% confidence interval [CI] = 1.23 to 1.83; P(trend) =.008) and age at birth of first child (>= 30 vs <= 19 years: HR = 1.26, 95% CI = 1.01 to 1.58; P(trend) =.05) were positively associated with the risk of colorectal cancer. Among women with no history of hormone therapy use, age at menarche (>= 15 vs 11-12 years: HR = 0.73, 95% CI = 0.57 to 0.94; P(trend) =.02) and parity (>= 5 children vs no children: HR = 0.80, 95% CI = 0.63 to 1.02; P(trend) =.10) were inversely associated with the risk of colorectal cancer. Conclusion These data support a role for sex hormones in colorectal tumorigenesis and suggest that greater endogenous estrogen exposure may increase the risk of colorectal cancer in postmenopausal women. C1 [Zervoudakis, Alice; Strickler, Howard D.; Xue, Xiaonan; Gunter, Marc J.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Zervoudakis, Alice] Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Gunter, MJ (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM marc.gunter@einstein.yu.edu OI Park, Yikyung/0000-0002-6281-489X FU National Center for Research Resources, a component of the National Institutes of Health (NIH) [UL1 RR025750, KL2 RR025749, TL1 RR025748]; NIH roadmap for Medical Research FX This publication was made possible by the CTSA Grant UL1 RR025750 and KL2 RR025749 and TL1 RR025748 from the National Center for Research Resources, a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. NR 56 TC 40 Z9 40 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2011 VL 103 IS 10 BP 826 EP 834 DI 10.1093/jnci/djr101 PG 9 WC Oncology SC Oncology GA 766VA UT WOS:000290813400011 PM 21447807 ER PT J AU Nuno, T Castle, PE Harris, R Estrada, A Garcia, F AF Nuno, Tomas Castle, Philip E. Harris, Robin Estrada, Antonio Garcia, Francisco CA Yuma Project Technical Team TI Breast and Cervical Cancer Screening Utilization Among Hispanic Women Living Near the United States-Mexico Border SO JOURNAL OF WOMENS HEALTH LA English DT Article ID AFRICAN-AMERICAN WOMEN; HEALTH-CARE ACCESS; SELF-REPORTS; SOCIETY GUIDELINES; BEHAVIORAL-MODEL; MEDICAL-CARE; US; MAMMOGRAPHY; VALIDITY; OLDER AB Objective: Hispanic women who reside in low-resource settings are especially at risk for nonparticipation in cancer screening programs. The purpose of this study was to assess characteristics that influence breast and cervical cancer screening among older Hispanic women living along the United States-Mexico border. Methods: A cross-sectional study of women aged >= 50 years (n = 504) residing in Yuma County, Arizona, were randomly selected for interviews. Logistic regression analyses were conducted to identify determinants of compliance with mammography and Pap smear use. Results: Women who received a recommendation from a clinician to get both mammography and Pap smears were more likely to receive a mammogram within the past year (adjusted odds ratio [AOR] 5.1, 95% confidence interval [CI] 3.0-8.9) compared to women who received no recommendation. Likewise, women who received both recommendations were more likely to receive a Pap smear within the past 3 years (AOR 9.7, 95% CI 4.6-20.7) compared to women who received no recommendation. Other factors, such as current health insurance and a visit with their healthcare provider in the past year, were also associated with getting a mammogram within 1 year or Pap smear within 3 years. Conclusions: Enabling characteristics were significantly associated with breast and cervical cancer screening use compared to predisposing and need characteristics among older Hispanic women residing near the U.S.-Mexico border. Clinician recommendation of both mammograms and Pap smears and opportunistic clinic visits to medical providers may increase breast and cervical cancer screening coverage and reduce the burden of these two cancers in this high-risk population. C1 [Nuno, Tomas; Harris, Robin; Garcia, Francisco] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Harris, Robin; Garcia, Francisco] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Estrada, Antonio] Univ Arizona, Mexican Amer Studies & Res Ctr, Tucson, AZ USA. [Garcia, Francisco] Univ Arizona, Ctr Excellence Womens Hlth, Tucson, AZ USA. [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Garcia, F (reprint author), 1295 N Martin,POB 245209, Tucson, AZ 85724 USA. EM fcisco@email.arizona.edu FU Medicaid and Medicare Services [25-P-91062]; Centers for Disease Control and Prevention Research Center-Southwest Center for Community Health Promotion FX This work was funded by the Center for Medicaid and Medicare Services under contract number 25-P-91062, with additional support provided by the Centers for Disease Control and Prevention Research Center-Southwest Center for Community Health Promotion. We gratefully acknowledge the enthusiastic participation of the women who took part in the study survey. We also recognize the invaluable contributions of the lay community health workers (promotoras) who recruited the survey participants and conducted the interviews. We are indebted to the community of women's healthcare practitioners in Yuma County who provided access to their patients and their clinics for the purposes of this study. We are also indebted to Dr. Richard Bragg at the Centers for Medicare & Medicaid Services (CMS), who provided broad guidance and input on this project. This article was completed as part of dissertation work for the Epidemiology Graduate Program at the Mel and Enid Zuckerman College of Public Health. NR 40 TC 25 Z9 25 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2011 VL 20 IS 5 BP 685 EP 693 DI 10.1089/jwh.2010.2205 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 766MF UT WOS:000290785800007 PM 21428792 ER PT J AU Schuck, P Zhao, HY AF Schuck, Peter Zhao, Huaying TI Editorial for the special issue of methods "Modern Analytical Ultracentrifugation" SO METHODS LA English DT Editorial Material ID VELOCITY ANALYTICAL ULTRACENTRIFUGATION; SEDIMENTATION EQUILIBRIUM; MEMBRANE-PROTEINS; AGGREGATION; MACROMOLECULES; DISTRIBUTIONS C1 [Schuck, Peter; Zhao, Huaying] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. EM schuckp@mail.nih.gov; zhaoh3@mail.nih.gov RI Zhao, Huaying/F-5716-2012; OI Schuck, Peter/0000-0002-8859-6966 NR 50 TC 5 Z9 5 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2011 VL 54 IS 1 SI SI BP 1 EP 3 DI 10.1016/j.ymeth.2011.04.003 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764RJ UT WOS:000290649700001 PM 21536133 ER PT J AU Zhao, HY Balbo, A Brown, PH Schuck, P AF Zhao, Huaying Balbo, Andrea Brown, Patrick H. Schuck, Peter TI The boundary structure in the analysis of reversibly interacting systems by sedimentation velocity SO METHODS LA English DT Review DE Protein interactions; Sedimentation coefficient distributions; Gilbert-Jenkins theory; Effective particle theory; Sedimentation velocity analysis; Bayesian analysis ID PROTEIN-PROTEIN INTERACTIONS; MASS-TRANSPORT LIMITATION; ANALYTICAL ULTRACENTRIFUGATION; LAMM EQUATION; COEFFICIENT DISTRIBUTIONS; MEMBRANE-PROTEINS; BINDING; EQUILIBRIUM; COMPLEXES; MACROMOLECULES AB Sedimentation velocity (SV) experiments of heterogeneous interacting systems exhibit characteristic boundary structures that can usually be very easily recognized and quantified. For slowly interacting systems, the boundaries represent concentrations of macromolecular species sedimenting at different rates, and they can be interpreted directly with population models based solely on the mass action law. For fast reactions, migration and chemical reactions are coupled, and different, but equally easily discernable boundary structures appear. However, these features have not been commonly utilized for data analysis, for the lack of an intuitive and computationally simple model. The recently introduced effective particle theory (EFT) provides a suitable framework. Here, we review the motivation and theoretical basis of EFT, and explore practical aspects for its application. We introduce an EFT-based design tool for SV experiments of heterogeneous interactions in the software SEDPHAT. As a practical tool for the first step of data analysis, we describe how the boundary resolution of the sedimentation coefficient distribution c(s) can be further improved with a Bayesian adjustment of maximum entropy regularization to the case of heterogeneous interactions between molecules that have been previously studied separately. This can facilitate extracting the characteristic boundary features by integration of c(s). In a second step, these are assembled into isotherms as a function of total loading concentrations and fitted with EPT. Methods for addressing concentration errors in isotherms are discussed. Finally, in an experimental model system of alpha-chymotrypsin interacting with soybean trypsin inhibitor, we show that EPT provides an excellent description of the experimental sedimentation boundary structure of fast interacting systems. Published by Elsevier Inc. C1 [Zhao, Huaying; Schuck, Peter] NIH, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA. [Balbo, Andrea; Brown, Patrick H.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Schuck, P (reprint author), NIH, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, Bldg 10, Bethesda, MD 20892 USA. EM zhaoh3@mail.nih.gov; schuckp@mail.nih.gov RI Zhao, Huaying/F-5716-2012; OI Schuck, Peter/0000-0002-8859-6966 FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 57 TC 18 Z9 18 U1 0 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2011 VL 54 IS 1 SI SI BP 16 EP 30 DI 10.1016/j.ymeth.2011.01.010 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764RJ UT WOS:000290649700003 PM 21315155 ER PT J AU Harding, SE Schuck, P Abdelhameed, AS Adams, G Kok, MS Morris, GA AF Harding, Stephen E. Schuck, Peter Abdelhameed, Ali Saber Adams, Gary Kok, M. Samil Morris, Gordon A. TI Extended Fujita approach to the molecular weight distribution of polysaccharides and other polymeric systems SO METHODS LA English DT Article DE Sedimentation velocity; Power law; Polydispersity; Ideal system; SEDFIT ID SEDIMENTATION-VELOCITY DATA; SIZE-DISTRIBUTION ANALYSIS; FIELD-FLOW FRACTIONATION; LASER-LIGHT SCATTERING; ANALYTICAL ULTRACENTRIFUGATION; MUCUS GLYCOPROTEINS; SODIUM ALGINATE; CITRUS PECTINS; MODEL; MACROMOLECULES AB In 1962 H. Fujita (H. Fujita, Mathematical Theory of Sedimentation Analysis, Academic Press, New York, 1962) examined the possibility of transforming a quasi-continuous distribution g(s) of sedimentation coefficient s into a distribution f(M) of molecular weight M for linear polymers using the relation f(M) = g(s) . (ds/dM) and showed that this could be done if information about the relation between s and M is available from other sources. Fujita provided the transformation based on the scaling relation s = kappa M-s(0.5), where kappa(s) is taken as a constant for that particular polymer and the exponent 0.5 essentially corresponds to a randomly coiled polymer under ideal conditions. This method has been successfully applied to mucus glycoproteins (SE. Harding, Adv. Carbohyd. Chem. Biochem. 47 (1989) 345-381). We now describe an extension of the method to general conformation types via the scaling relation s = kappa M-b, where b = 0.4-0.5 for a coil, similar to 0.15-0.2 for a rod and similar to 0.67 for a sphere. We give examples of distributions f(M) versus M obtained for polysaccharides from SEDFIT derived least squares g(s) versus s profiles (P. Schuck, Biophys. J. 78 (2000) 1606-1619) and the analytical derivative for ds/dM performed with Microcal ORIGIN. We also describe a more direct route from a direct numerical solution of the integral equation describing the molecular weight distribution problem. Both routes give identical distributions although the latter offers the advantage of being incorporated completely within SEDFIT. The method currently assumes that solutions behave ideally: sedimentation velocity has the major advantage over sedimentation equilibrium in that concentrations less than 0.2 mg/ml can be employed, and for many systems non-ideality effects can be reasonably ignored. For large, non-globular polymer systems, diffusive contributions are also likely to be small. (C) 2011 Elsevier Inc. All rights reserved. C1 [Harding, Stephen E.; Abdelhameed, Ali Saber; Adams, Gary; Morris, Gordon A.] Univ Nottingham, Natl Ctr Macromol Hydrodynam, Loughborough LE12 5RD, England. [Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA. [Kok, M. Samil] Abant Izzet Baysal Univ AIBU, Dept Food Engn, TR-14280 Bolu, Turkey. RP Harding, SE (reprint author), Univ Nottingham, Natl Ctr Macromol Hydrodynam, Loughborough LE12 5RD, England. EM steve.harding@nottingham.ac.uk RI Abdelhameed, Ali/A-1333-2012; OI Abdelhameed, Ali/0000-0002-5910-2832; Schuck, Peter/0000-0002-8859-6966; Harding, Stephen E./0000-0002-7798-9692; Morris, Gordon/0000-0003-2588-6349 FU Biotechnology and Biological Sciences Council (UK); National Institute of Biomedical Imaging and Bioengineering, NIH (USA) FX This research was supported in part by the Biotechnology and Biological Sciences Council (UK) and the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, NIH (USA). NR 48 TC 21 Z9 22 U1 5 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD MAY PY 2011 VL 54 IS 1 SI SI BP 136 EP 144 DI 10.1016/j.ymeth.2011.01.009 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764RJ UT WOS:000290649700014 PM 21276851 ER PT J AU Ghirlando, R AF Ghirlando, Rodolfo TI The analysis of macromolecular interactions by sedimentation equilibrium SO METHODS LA English DT Article DE Analytical ultracentrifugation; Sedimentation equilibrium; Interacting systems ID PROTEIN-PROTEIN INTERACTIONS; SOYBEAN TRYPSIN-INHIBITOR; VELOCITY ANALYTICAL ULTRACENTRIFUGATION; COEFFICIENT DISTRIBUTIONS C(S); HELIX-HELIX INTERACTIONS; PARTIAL SPECIFIC VOLUMES; SELF-ASSOCIATION; QUANTITATIVE CHARACTERIZATION; ALPHA-CHYMOTRYPSIN; LIGHT-SCATTERING AB The study of macromolecular interactions by sedimentation equilibrium is a highly technical method that requires great care in both the experimental design and data analysis. The complexity of the interacting system that can be analyzed is only limited by the ability to deconvolute the exponential contributions of each of the species to the overall concentration gradient. This is achieved in part through the use of multi-signal data collection and the implementation of soft mass conservation. We illustrate the use of these constraints in SEDPHAT through the study of an A + B + B (sic) AB + B (sic) ABB system and highlight some of the technical challenges that arise. We show that both the multi-signal analysis and mass conservation result in a precise and robust data analysis and discuss improvements that can be obtained through the inclusion of data from other methods such as sedimentation velocity and isothermal titration calorimetry. Published by Elsevier Inc. C1 NIDDK, LMB, NIH, Bethesda, MD 20892 USA. RP Ghirlando, R (reprint author), NIDDK, LMB, NIH, Bldg 5,Room 208,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rodolfo.ghirlando@nih.gov RI Ghirlando, Rodolfo/A-8880-2009 FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the intramural research program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. The author thanks Dr. Marie-Paule Strub for a careful reading of the manuscript and Dr. Robert Craigie for assistance with the N-terminal protein sequencing. The author also thanks Dr. Gary Felsenfeld and members of his laboratory for their support. NR 88 TC 22 Z9 22 U1 0 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2011 VL 54 IS 1 SI SI BP 145 EP 156 DI 10.1016/j.ymeth.2010.12.005 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764RJ UT WOS:000290649700015 PM 21167941 ER PT J AU Rivas, G Minton, AP AF Rivas, German Minton, Allen P. TI Beyond the second virial coefficient: Sedimentation equilibrium in highly non-ideal solutions SO METHODS LA English DT Article DE Macromolecular crowding; Globular proteins; Polymers; Self-association; Hetero-association; Colligative properties ID PROTEIN-PROTEIN INTERACTIONS; SELF-ASSOCIATING PROTEINS; BOVINE SERUM-ALBUMIN; HARD PARTICLE MODEL; CONCENTRATED-SOLUTIONS; QUANTITATIVE CHARACTERIZATION; THERMODYNAMIC NONIDEALITY; MACROMOLECULAR SOLUTIONS; ARBITRARY CONCENTRATION; LIGHT-SCATTERING AB The general theory of sedimentation equilibrium (SE). applicable to mixtures of interacting sedimentable solutes at arbitrary concentration, is summarized. Practical techniques for the acquisition of SE data suitable for analysis are described. Experimental measurements and analyses of SE in concentrated protein solutions are reviewed. The method of non-ideal tracer sedimentation equilibrium (NITSE) is described. Experimental studies using NITSE to detect and quantitatively characterize intermolecular interactions in mixtures of dilute tracer species and concentrated proteins or polymers are reviewed. (C) 2010 Elsevier Inc. All rights reserved. C1 [Minton, Allen P.] NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. [Rivas, German] CSIC, Ctr Invest Biol, Chem & Phys Biol Programme, Madrid, Spain. RP Minton, AP (reprint author), NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM grivas@cib.csic.es; minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247; Rivas, German/0000-0003-3450-7478 FU Ministerio de Ciencia e Innovacion, Spain [BIO2008-04778-C03-03]; Comunidad de Madrid [COMBACT S-BIO-0260/2006]; European Commission [HEALTH-F3-2009-223431]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services FX G.R. acknowledges funds from Plan Nacional BIO2008-04778-C03-03 (Ministerio de Ciencia e Innovacion, Spain), COMBACT S-BIO-0260/2006 (Comunidad de Madrid) and DIVINOCELL FP7 HEALTH-F3-2009-223431 (European Commission). Research of A.P.M. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services. NR 46 TC 14 Z9 15 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2011 VL 54 IS 1 SI SI BP 167 EP 174 DI 10.1016/j.ymeth.2010.11.004 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764RJ UT WOS:000290649700017 PM 21112402 ER PT J AU Hillman, BG Gupta, SC Stairs, DJ Buonanno, A Dravid, SM AF Hillman, Brandon G. Gupta, Subhash C. Stairs, Dustin J. Buonanno, Andres Dravid, Shashank M. TI Behavioral analysis of NR2C knockout mouse reveals deficit in acquisition of conditioned fear and working memory SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE NMDA; NR2C; Knockout; Fear acquisition; Working memory ID LONG-TERM-POTENTIATION; NMDA-RECEPTOR-CHANNEL; D-ASPARTATE RECEPTORS; LATERAL AMYGDALA; D-CYCLOSERINE; PREFRONTAL CORTEX; TOPOGRAPHIC ORGANIZATION; SUBTYPE RECEPTOR; SPINAL-CORD; RAT-BRAIN AB N-methyl-D-aspartate (NMDA) receptors play an important role in excitatory neurotransmission and mediate synaptic plasticity associated with learning and memory. NMDA receptors are composed of two NR1 and two NR2 subunits and the identity of the NR2 subunit confers unique electrophysiologic and pharmacologic properties to the receptor. The precise role of NR2C-containing receptors in vivo is poorly understood. We have performed a battery of behavioral tests on NR2C knockout/n beta-galactosidase knock-in mice and found no difference in spontaneous activity, basal anxiety, forced-swim immobility, novel object recognition, pain sensitivity and reference memory in comparison to wildtype counterparts. However, NR2C knockout mice were found to exhibit deficits in fear acquisition and working memory compared to wildtype mice. Deficit in fear acquisition correlated with lack of fear conditioning-induced plasticity at the thalamo-amygdala synapse. These findings suggest a unique role of NR2C-containing receptors in associative and executive learning representing a novel therapeutic target for deficits in cognition. (C) 2011 Elsevier Inc. All rights reserved. C1 [Hillman, Brandon G.; Gupta, Subhash C.; Dravid, Shashank M.] Creighton Univ, Dept Pharmacol, Omaha, NE 68178 USA. [Stairs, Dustin J.] Creighton Univ, Dept Psychol, Omaha, NE 68178 USA. [Buonanno, Andres] NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Dravid, SM (reprint author), Creighton Univ, Dept Pharmacol, Criss 3 551,2500 Calif Plaza, Omaha, NE 68178 USA. EM shashankdravid@creighton.edu FU Health Future Foundation; National Science Foundation/Nebraska EPSCoR; Eunice Shriver Kennedy National Institute of Child Health; Human Development Intramural Research Program; National Center for Research Resources [G20RR024001] FX This work was supported by Health Future Foundation (SMD) and National Science Foundation/Nebraska EPSCoR (SMD). A. Buonanno received support from the Eunice Shriver Kennedy National Institute of Child Health and Human Development Intramural Research Program.; The project was also supported by G20RR024001 from National Center for Research Resources. The content is solely the responsibility of authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 87 TC 27 Z9 29 U1 10 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD MAY PY 2011 VL 95 IS 4 BP 404 EP 414 DI 10.1016/j.nlm.2011.01.008 PG 11 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 764AQ UT WOS:000290601200002 PM 21295149 ER PT J AU Gaykalova, DA Nagarajavel, V Bondarenko, VA Bartholomew, B Clark, DJ Studitsky, VM AF Gaykalova, Daria A. Nagarajavel, V. Bondarenko, Vladimir A. Bartholomew, Blaine Clark, David J. Studitsky, Vasily M. TI A polar barrier to transcription can be circumvented by remodeler-induced nucleosome translocation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-POLYMERASE-II; HISTONE OCTAMER; IN-VIVO; CHROMATIN; YEAST; ELONGATION; GENOME; ORGANIZATION; ACETYLATION; POSITIONS AB Many eukaryotic genes are regulated at the level of transcript elongation. Nucleosomes are likely targets for this regulation. Previously, we have shown that nucleosomes formed on very strong positioning sequences (601 and 603), present a high, orientation-dependent barrier to transcription by RNA polymerase II in vitro. The existence of this polar barrier correlates with the interaction of a 16-bp polar barrier signal (PBS) with the promoter-distal histone H3-H4 dimer. Here, we show that the polar barrier is relieved by ISW2, an ATP-dependent chromatin remodeler, which translocates the nucleosome over a short distance, such that the PBS no longer interacts with the distal H3-H4 dimer, although it remains within the nucleosome. In vivo, insertion of the 603 positioning sequence into the yeast CUP1 gene results in a modest reduction in transcription, but this reduction is orientation-independent, indicating that the polar barrier can be circumvented. However, the 603-nucleosome is present at the expected position in only a small fraction of cells. Thus, the polar barrier is probably non-functional in vivo because the nucleosome is not positioned appropriately, presumably due to nucleosome sliding activities. We suggest that interactions between PBSs and chromatin remodelers might have significant regulatory potential. C1 [Nagarajavel, V.; Clark, David J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Gaykalova, Daria A.; Bondarenko, Vladimir A.; Studitsky, Vasily M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. [Bartholomew, Blaine] So Illinois Univ, Sch Med, Dept Biochem & Mol Biol, Carbondale, IL 62901 USA. RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM clarkda@mail.nih.gov; studitvm@umdnj.edu RI Studitsky, Vasily/A-9382-2014 FU National Institutes of Health (NICHD); National Institutes of Health [GM58650, GM70864]; National Institutes of Health FX Intramural Research Program of the National Institutes of Health (NICHD); National Institutes of Health (GM58650 to V. M. S.); National Institutes of Health (GM70864 to B. B.). Funding for open access charge: Intramural Research Program of the National Institutes of Health (to D.J.C.). NR 41 TC 12 Z9 12 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 MAY PY 2011 VL 39 IS 9 BP 3520 EP 3528 DI 10.1093/nar/gkq1273 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763WD UT WOS:000290589500010 PM 21245049 ER PT J AU Zhang, YW Regairaz, M Seiler, JA Agama, KK Doroshow, JH Pommier, Y AF Zhang, Yong-Wei Regairaz, Marie Seiler, Jennifer A. Agama, Keli K. Doroshow, James H. Pommier, Yves TI Poly(ADP-ribose) polymerase and XPF-ERCC1 participate in distinct pathways for the repair of topoisomerase I-induced DNA damage in mammalian cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; ADP-RIBOSE POLYMERASE; COVALENT COMPLEXES; HOMOLOGOUS RECOMBINATION; CLEAVAGE COMPLEXES; CAMPTOTHECIN RESISTANCE; PHOSPHODIESTERASE TDP1; SPINOCEREBELLAR ATAXIA; REPLICATION FORKS; PARP INHIBITOR AB Poly(ADP-Ribose) (PAR) polymerase (PARP) inhibitors represent a promising class of novel anticancer agents. The present study explores the molecular rationale for combining veliparib (ABT-888) with camptothecin (CPT) and its clinical derivatives, topotecan and irinotecan. ABT-888 inhibited PAR induction by CPT and increased CPT-induced cell killing and histone gamma H2AX. Increased DNA breaks by ABT-888 were not associated with a corresponding increase of topoisomerase I cleavage complexes and were further increased by inactivation of tyrosyl-DNA phosphodiesterase 1. SiRNA knockdown for the endonuclease XPF-ERCC1 reduced the ABT-888-induced gamma H2AX response in non-replicating and replicating cells but enhanced the antiproliferative effect of ABT-888 in CPT-treated cells. Our findings indicate the involvement of XPF-ERCC1 in inducing gamma H2AX response and repairing topoisomerase I-induced DNA damage as an alternative pathway from PARP and tyrosyl-DNA phosphodiesterase 1. C1 [Zhang, Yong-Wei; Regairaz, Marie; Seiler, Jennifer A.; Agama, Keli K.; Doroshow, James H.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Center for Cancer Research; National Cancer Institute; National Institutes of Health; National Institutes of Health, US Government FX Center for Cancer Research; National Cancer Institute Intramural Program; National Institutes of Health. Funding for open access charge: National Institutes of Health, US Government. NR 68 TC 73 Z9 73 U1 2 U2 11 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 MAY PY 2011 VL 39 IS 9 BP 3607 EP 3620 DI 10.1093/nar/gkq1304 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763WD UT WOS:000290589500017 PM 21227924 ER PT J AU Surapureddi, S Rana, R Goldstein, JA AF Surapureddi, Sailesh Rana, Ritu Goldstein, Joyce A. TI NCOA6 differentially regulates the expression of the CYP2C9 and CYP3A4 genes SO PHARMACOLOGICAL RESEARCH LA English DT Article DE NCOA6; Co activators; PXR; HNF4 alpha; CYP2C9; Synergistic transactivation ID CONSTITUTIVE-ANDROSTANE RECEPTOR; PREGNANE-X RECEPTOR; NUCLEAR RECEPTORS; HUMAN HEPATOCYTES; SYNERGISTIC ACTIVATION; CYTOCHROMES P450; CROSS-TALK; CAR; INDUCTION; RIFAMPICIN AB CYP2Cs and CYP3A4 sub families of enzymes of the Cytochrome P450 super family metabolize clinically prescribed therapeutics. Constitutive and induced expressions of these enzymes are under the control of HNF4 alpha and rifampicin activated PXR. In the present study, we show a mechanism for ligand dependent synergistic cross talk between PXR and HNF4 alpha. Two-hybrid screening identified NCOA6 as a HNF4 alpha interacting protein. NCOA6 was also found to interact with PXR through the first LXXLL motif in GST pull down and mammalian two hybrid assays. NCOA6 enhances the synergistic activation of CYP2C9 and CYP3A4 promoter activity by PXR and HNF4 alpha in the presence of rifampicin. However silencing NCOA6 abrogated the synergistic activation and induction of CYP2C9 by PXR-HNF4 alpha but not of CYP3A4. ChIP analysis revealed that NCOA6 could bridge HNF4 alpha and PXR binding sites of the CYP2C9 promoter. Our results indicate that NCOA6 is responsible for the synergistic activation of CYP2C9 by HNF4 alpha and PXR and NCOA6 differentially regulates CYP2C9 and CYP3A4 gene expression though both the genes are regulated by the same nuclear receptors. Published by Elsevier Ltd. C1 [Surapureddi, Sailesh; Rana, Ritu; Goldstein, Joyce A.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Lab Toxicol & Pharmacol, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Rana, Ritu/F-2591-2011; Goldstein, Joyce/A-6681-2012 FU NIH, National Institute of Environmental Health Sciences [Z01ES02124] FX This study was supported by the Intramural Research Program of NIH, National Institute of Environmental Health Sciences, NIH Intramural Project Number Z01ES02124. NR 46 TC 3 Z9 4 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD MAY PY 2011 VL 63 IS 5 BP 405 EP 413 DI 10.1016/j.phrs.2011.01.013 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767XN UT WOS:000290892300008 PM 21292004 ER PT J AU Bonekamp, D Jacobs, MA El-Khouli, R Stoianovici, D Macura, KJ AF Bonekamp, David Jacobs, Michael A. El-Khouli, Riham Stoianovici, Dan Macura, Katarzyna J. TI Advancements in MR Imaging of the Prostate: From Diagnosis to Interventions SO RADIOGRAPHICS LA English DT Article ID CONTRAST-ENHANCED MRI; PHASED-ARRAY COIL; ENDORECTAL COIL; 3 T; TUMOR VOLUME; CANCER; DIFFUSION; BIOPSY; CARCINOMA; TISSUE AB Prostate cancer is the most frequently diagnosed cancer in males and the second leading cause of cancer-related death in men. Assessment of prostate cancer can be divided into detection, localization, and staging; accurate assessment is a prerequisite for optimal clinical management and therapy selection. Magnetic resonance (MR) imaging has been shown to be of particular help in localization and staging of prostate cancer. Traditional prostate MR imaging has been based on morphologic imaging with standard T1-weighted and T2-weighted sequences, which has limited accuracy. Recent advances include additional functional and physiologic MR imaging techniques (diffusionweighted imaging, MR spectroscopy, and perfusion imaging), which allow extension of the obtainable information beyond anatomic assessment. Multiparametric MR imaging provides the highest accuracy in diagnosis and staging of prostate cancer. In addition, improvements in MR imaging hardware and software (3-T vs 1.5-T imaging) continue to improve spatial and temporal resolution and the signal-to-noise ratio of MR imaging examinations. Another recent advancement in the field is MR imaging guidance for targeted prostate biopsy, which is an alternative to the current standard of transrectal ultrasonographyguided systematic biopsy. (C) RSNA, 2011 . radiographics.rsna.org C1 [Bonekamp, David; Jacobs, Michael A.; Macura, Katarzyna J.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [El-Khouli, Riham] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Stoianovici, Dan] Johns Hopkins Univ, Brady Urol Inst, Robot Program, Baltimore, MD 21287 USA. RP Macura, KJ (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 601 N Caroline St,JHOC 3140C, Baltimore, MD 21287 USA. EM kmacura@jhmi.edu RI Jacobs, Michael/G-2901-2010 FU National Institutes of Health [1R01CA100184, P50 CA103175, P50CA88843, U01CA070095]; American Roentgen Ray Society FX Supported in part by grants 1R01CA100184, P50 CA103175, P50CA88843, and U01CA070095 from the National Institutes of Health and an American Roentgen Ray Society Scholarship. NR 75 TC 72 Z9 75 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2011 VL 31 IS 3 BP 677 EP 703 DI 10.1148/rg.313105139 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 763WN UT WOS:000290590500007 PM 21571651 ER PT J AU Linet, MS Kleinerman, RA Mabuchi, K AF Linet, Martha S. Kleinerman, Ruth A. Mabuchi, Kiyohiko TI Elaine Ron, Ph.D. (1943-2010) In Memoriam SO THYROID LA English DT Biographical-Item C1 [Linet, Martha S.; Kleinerman, Ruth A.; Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2011 VL 21 IS 5 BP 567 EP 568 DI 10.1089/thy.2011.0068 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766LN UT WOS:000290783900020 ER PT J AU Clayton, JA Vitale, S Kim, J Conry-Cantilena, C Byrne, P Reed, GF Ferris, FL Leitman, SF AF Clayton, Janine A. Vitale, Susan Kim, Jonghyeon Conry-Cantilena, Cathy Byrne, Phyllis Reed, George F. Ferris, Frederick L., III Leitman, Susan F. TI Prevalence of posterior subcapsular cataracts in volunteer cytapheresis donors SO TRANSFUSION LA English DT Article ID LENS OPACITIES; EYE DISEASE; RISK; POPULATION; AUSTRALIA; EXPOSURE; AREDS AB BACKGROUND: Granulocyte donors routinely receive dexamethasone orally before donation. Steroids may increase the risk of posterior subcapsular cataract (PSC) formation. STUDY DESIGN AND METHODS: We recruited 100 granulocyte donors (four or more granulocyte donations; any number of platelet [PLT] donations) and 100 age- and sex-matched PLT donors (zero to three granulocyte donations, any number of PLT donations) to examine the risk of PSC. PSC was assessed by a masked ophthalmologist and reading center lens photograph gradings or medical record documentation of PSC as the reason for cataract extraction. RESULTS: Fourteen eyes of 10 granulocyte donors and five eyes of four PLT donors had PSCs (odds ratio [OR], 2.82; 95% confidence interval [CI], 0.83-9.61; p = 0.10). Risk of PSC increased with number of granulocyte donations: compared to zero to three donations (4.0%), the risk for four to nine, 10 to 19, and 20 or more donations was 8.6% (OR, 2.25; 95% CI, 0.31-13.99; p = 0.30), 9.5% (OR, 2.53; 95% CI, 0.44-14.20; p = 0.21), and 13.0% (OR, 3.60; 95% CI, 0.48-22.81; p = 0.11), respectively (p = 0.06 for trend). CONCLUSION: We did not demonstrate a statistically significant increased risk of PSC associated with granulocyte donation. However, although this makes a large risk unlikely, we cannot rule out a small to moderate risk and there is biologic plausibility that the steroid administration associated with granulocyte donation could be associated with PSC formation. Transfusion medicine professionals should advise granulocyte apheresis donors to maintain an appropriate frequency of eye examinations. C1 [Leitman, Susan F.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. RP Vitale, S (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, 10 Ctr Dr,Room 10D45,Mail Stop 1863, Bethesda, MD 20892 USA. EM sev@nei.nih.gov FU National Eye Institute; Department of Transfusion Medicine, National Institutes of Health FX This project was supported in whole or in part by the National Eye Institute and the Department of Transfusion Medicine, National Institutes of Health. NR 18 TC 7 Z9 7 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2011 VL 51 IS 5 BP 921 EP 928 DI 10.1111/j.1537-2995.2010.02948.x PG 8 WC Hematology SC Hematology GA 759SC UT WOS:000290267700006 PM 21091958 ER PT J AU McDermott, MM Liu, K Ferrucci, L Tian, L Guralnik, JM Tao, HM Ridker, PM Criqui, MH AF McDermott, Mary M. Liu, Kiang Ferrucci, Luigi Tian, Lu Guralnik, Jack M. Tao, Huimin Ridker, Paul M. Criqui, Michael H. TI Relation of Interleukin-6 and Vascular Cellular Adhesion Molecule-1 Levels to Functional Decline in Patients With Lower Extremity Peripheral Arterial Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MUSCLE CHARACTERISTICS; PHYSICAL PERFORMANCE; INFLAMMATION; ASSOCIATION; CHOLESTEROL; SERUM; INDEX AB The aim of this study was to determine whether persistently high levels of interleukin-6 (IL-6) or soluble vascular adhesion molecule-1 (sVCAM-1) are associated with faster functional decline compared to fluctuating or persistently low biomarker levels in 255 participants with peripheral arterial disease. Participants underwent baseline and >= 2 annual follow-up measures of IL-6 and sVCAM-1. Participants were categorized as follows: category 1, annual levels of IL-6 (or sVCAM-1) were in the lowest tertile for >= 3 study visits; category 3, annual levels of IL-6 (or sVCAM-1) were in the highest tertile for >= 3 visits. Category 2 levels of IL-6 (or sVCAM-1) did not meet criteria for group 1 or 3. Six-minute walking distance, fastest paced 4-m walking velocity, and the Short Physical Performance Battery were measured annually. Results were adjusted for age, gender, race, co-morbidities, statin use, physical activity, the ankle-brachial index, and other confounders. Across' IL-6 categories, average annual decreases in 6-minute walking distance were -21.4 feet in category 1, -49.2 feet in category 2, and -76.8 feet in category 3 (p for trend = 0.013), and average annual decreases in Short Physical Performance Battery score were -0.18, -0.45, and -0.62, respectively (p for trend = 0.022). Similar associations of IL-6 categories with decrease in fastest paced walking velocity were observed (p for trend = 0.034). There were no significant associations of sVCAM-1 categories with functional decline. In conclusion, in participants with peripheral arterial disease, persistently high IL-6 levels are associated with faster functional decline compared to those with fluctuating or persistently low IL-6 levels. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1392-1398) C1 [McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [McDermott, Mary M.; Liu, Kiang; Tao, Huimin] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Ferrucci, Luigi] NIA, Lab Clin Epidemiol, Bethesda, MD 20892 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Tian, Lu] Stanford Univ, Stanford, CA 94305 USA. [Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [R01-HL58099, R01-HL64739, R01-HL071223, R01-HL076298]; National Center for Research Resources, Bethesda, Maryland [RR-00048]; National Institute on Aging, Bethesda, Maryland FX This study was supported by grants R01-HL58099, R01-HL64739, R01-HL071223, and R01-HL076298 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland; by grant RR-00048 from the National Center for Research Resources, Bethesda, Maryland: and in part by the Intramural Research Program, National Institute on Aging, Bethesda, Maryland. NR 21 TC 9 Z9 9 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2011 VL 107 IS 9 BP 1392 EP 1398 DI 10.1016/j.amjcard.2011.01.007 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 764CI UT WOS:000290605600023 PM 21371679 ER PT J AU Davis, RM Mitchell, JB Krishna, MC AF Davis, Ryan M. Mitchell, James B. Krishna, Murali C. TI Nitroxides as Cancer Imaging Agents SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Nitroxides; oxidative stress; redox-imaging; magnetic resonance imaging; electron paramagnetic resonance ID ELECTRON-PARAMAGNETIC-RESONANCE; IN-VIVO ESR; HEXOSE-MONOPHOSPHATE SHUNT; SENSITIVE CONTRAST AGENTS; RAT-LIVER MICROSOMES; TUMOR-BEARING MICE; REDOX STATUS; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; FREE-RADICALS AB Nitroxides are low molecular weight (150-400 Da) superoxide dismutase mimics that exhibit antioxidant, radical scavenging, and radioprotective activity. Additionally, the paramagnetic nature of nitroxides makes them viable as both spin probes for electron paramagnetic resonance imaging as well as contrast agents for magnetic resonance imaging. These imaging techniques enable in vivo monitoring of nitroxide metabolism. In biological systems, nitroxide metabolism occurs predominantly via reduction of the nitroxide to a hydroxylamine. The rate of nitroxide reduction can increase or decrease due to oxidative stress, suggesting that nitroxides can provide an imaging-based assay of tissue redox status. The current review briefly summarizes the potential clinical applications of nitroxides, and focuses on the biochemical and tumor microenvironmental factors that affect the rate of nitroxide reduction. The potential therapeutic applications and bio-reduction mechanisms are discussed in the context of their relevance to oncology. C1 [Davis, Ryan M.; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Davis, RM (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM davisrm2@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 112 TC 12 Z9 12 U1 1 U2 22 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD MAY PY 2011 VL 11 IS 4 BP 347 EP 358 PG 12 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 764FL UT WOS:000290614400004 PM 21434855 ER PT J AU Rosenthal, RA Fish, B Hill, RP Huffman, KD Lazarova, Z Mahmood, J Medhora, M Molthen, R Moulder, JE Sonis, ST Tofilon, PJ Doctrow, SR AF Rosenthal, Rosalind A. Fish, Brian Hill, Richard P. Huffman, Karl D. Lazarova, Zelmira Mahmood, Javed Medhora, Meetha Molthen, Robert Moulder, John E. Sonis, Stephen T. Tofilon, Philip J. Doctrow, Susan R. TI Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Salen manganese complex; radiation injury; radiation mitigation; catalytic antioxidant ID SUPEROXIDE DISMUTASE/CATALASE MIMETICS; CHRONIC OXIDATIVE STRESS; INDUCED ORAL MUCOSITIS; IONIZING-RADIATION; CATALYTIC SCAVENGERS; CATALASE MIMETICS; GENE-EXPRESSION; REDOX CONTROL; NITRIC-OXIDE; MICE AB Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown "mito-protective" properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study. C1 [Rosenthal, Rosalind A.; Huffman, Karl D.; Doctrow, Susan R.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Sonis, Stephen T.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Dent, Boston, MA 02115 USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fish, Brian; Medhora, Meetha; Moulder, John E.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Lazarova, Zelmira] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Molthen, Robert] Med Coll Wisconsin, Dept Pulm Med, Milwaukee, WI 53226 USA. [Hill, Richard P.; Mahmood, Javed] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Tofilon, Philip J.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Doctrow, SR (reprint author), Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. EM sdoctrow@bu.edu RI Moulder, John/E-6799-2012 FU [AI067734]; [AI81294]; [CA72156] FX Development of the salen Mn complexes, including EUK-207, was funded in part by GM57770 (SRD). Renal, cutaneous, and pulmonary studies and further compound development were supported by AI067734 (JEM), including a pilot grant (RAR) to study EUK-400 compounds. Some pulmonary studies were also supported by AI81294 (MM). The mucositis study was performed by Biomodels, LLC. (Wellesley, MA) under the direction of STS. The mitochondrial injury studies were supported by CA72156 (PJT). NR 106 TC 31 Z9 32 U1 1 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD MAY PY 2011 VL 11 IS 4 BP 359 EP 372 PG 14 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 764FL UT WOS:000290614400005 PM 21453241 ER PT J AU Chio, A Borghero, G Pugliatti, M Ticca, A Calvo, A Moglia, C Mutani, R Brunetti, M Ossola, I Marrosu, MG Murru, MR Floris, G Cannas, A Parish, LD Cossu, P Abramzon, Y Johnson, JO Nalls, MA Arepalli, S Chong, S Hernandez, DG Traynor, BJ Restagno, G AF Chio, Adriano Borghero, Giuseppe Pugliatti, Maura Ticca, Anna Calvo, Andrea Moglia, Cristina Mutani, Roberto Brunetti, Maura Ossola, Irene Marrosu, Maria Giovanna Murru, Maria Rita Floris, Gianluca Cannas, Antonino Parish, Leslie D. Cossu, Paola Abramzon, Yevgeniya Johnson, Janel O. Nalls, Michael A. Arepalli, Sampath Chong, Sean Hernandez, Dena G. Traynor, Bryan J. Restagno, Gabriella CA Italian Amyotrophic Lateral Sclero TI Large Proportion of Amyotrophic Lateral Sclerosis Cases in Sardinia Due to a Single Founder Mutation of the TARDBP Gene SO ARCHIVES OF NEUROLOGY LA English DT Article ID POPULATION; DISEASE; TDP-43; DIAGNOSIS; ALS; PARKINSONISM; ASSOCIATION; FREQUENCY; CRITERIA; EUROPE AB Objective: To perform an extensive screening for mutations of amyotrophic lateral sclerosis (ALS)-related genes in a consecutive cohort of Sardinian patients, a genetic isolate phylogenically distinct from other European populations. Design: Population-based, prospective cohort study. Patients: A total of 135 Sardinian patients with ALS and 156 healthy control subjects of Sardinian origin who were age-and sex-matched to patients. Intervention: Patients underwent mutational analysis for SOD1, FUS, and TARDBP. Results: Mutational screening of the entire cohort found that 39 patients (28.7%) carried the c.1144G>A (p.A382T) missense mutation of the TARDBP gene. Of these, 15 had familial ALS (belonging to 10 distinct pedigrees) and 24 had apparently sporadic ALS. None of the 156 age-, sex-, and ethnicity-matched controls carried the pathogenic variant. Genotype data obtained for 5 ALS cases carrying the p.A382T mutation found that they shared a 94-single-nucleotide polymorphism risk haplotype that spanned 663 Kb across the TARDBP locus on chromosome 1p36.22. Three patients with ALS who carry the p.A382T mutation developed extrapyramidal symptoms several years after their initial presentation with motor weakness. Conclusions: The TARDBP p.A382T missense mutation accounts for approximately one-third of all ALS cases in this island population. These patients share a large risk haplotype across the TARDBP locus, indicating that they have a common ancestor. C1 [Chio, Adriano; Calvo, Andrea; Moglia, Cristina; Mutani, Roberto] Univ Turin, San Giovanni Univ Hosp, Dept Neurosci, ALS Ctr, I-10126 Turin, Italy. [Chio, Adriano; Calvo, Andrea; Moglia, Cristina; Mutani, Roberto] Inst Neurosci, Turin, Italy. [Borghero, Giuseppe; Marrosu, Maria Giovanna; Murru, Maria Rita; Floris, Gianluca; Cannas, Antonino] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy. [Borghero, Giuseppe; Marrosu, Maria Giovanna; Murru, Maria Rita; Floris, Gianluca; Cannas, Antonino] Univ Cagliari, Cagliari, Italy. [Pugliatti, Maura; Parish, Leslie D.; Cossu, Paola] Univ Sassari, Dept Neurosci, I-07100 Sassari, Italy. [Ticca, Anna] Azienda Osped San Francesco, Dept Neurol, Nuoro, Italy. [Brunetti, Maura; Ossola, Irene; Restagno, Gabriella] Azienda St Osped Osped Infantile Regina Margherit, Lab Mol Genet, Turin, Italy. [Abramzon, Yevgeniya; Johnson, Janel O.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Nalls, Michael A.; Arepalli, Sampath; Chong, Sean; Hernandez, Dena G.] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Traynor, Bryan J.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. RP Chio, A (reprint author), Univ Turin, San Giovanni Univ Hosp, Dept Neurosci, ALS Ctr, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI Spataro, Rossella/B-3656-2016; MANDRIOLI, JESSICA/K-7235-2016; Moglia, Cristina/K-4142-2016; Traynor, Bryan/G-5690-2010; Calvo, Andrea/K-4141-2016 OI Spataro, Rossella/0000-0002-8910-3131; Chio, Adriano/0000-0001-9579-5341; MANDRIOLI, JESSICA/0000-0002-9244-9782; Sabatelli, Mario/0000-0001-6635-4985; Moglia, Cristina/0000-0001-7377-7222; Marrosu, Maria Giovanna/0000-0003-2334-2081; Battistini, Stefania/0000-0003-2887-7624; Calvo, Andrea/0000-0002-5122-7243 FU Ministero della Salute (Ricerca Sanitaria Finalizzata); Fondazione Vialli e Mauro for ALS (amyotropic lateral sclerosis) Research Onlus, Federazione Italiana Giuoco Calcio; National Institutes of Health, National Institute on Aging [Z01-AG000949-02]; National Institute of Neurological Disorders and Stroke; ALS Association; Packard Center for ALS Research at Hopkins FX This study was supported in part by grants from Ministero della Salute (Ricerca Sanitaria Finalizzata 2007); the Fondazione Vialli e Mauro for ALS (amyotropic lateral sclerosis) Research Onlus, Federazione Italiana Giuoco Calcio; the Intramural Research Program of the National Institutes of Health, National Institute on Aging (Z01-AG000949-02); the National Institute of Neurological Disorders and Stroke; and the ALS Association and the Packard Center for ALS Research at Hopkins. NR 29 TC 62 Z9 66 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2011 VL 68 IS 5 BP 594 EP 598 DI 10.1001/archneurol.2010.352 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 761YB UT WOS:000290438000007 PM 21220647 ER PT J AU Marelli, C van de Leemput, J Johnson, JO Tison, F Thauvin-Robinet, C Picard, F Tranchant, C Hernandez, DG Huttin, B Boulliat, J Sangla, I Marescaux, C Brique, S Dollfus, H Arepalli, S Benatru, I Ollagnon, E Forlani, S Hardy, J Stevanin, G Durr, A Singleton, A Brice, A AF Marelli, Cecilia van de Leemput, Joyce Johnson, Janel O. Tison, Francois Thauvin-Robinet, Christel Picard, Fabienne Tranchant, Christine Hernandez, Dena G. Huttin, Bernard Boulliat, Jacques Sangla, Iban Marescaux, Christian Brique, Serge Dollfus, Helene Arepalli, Sampath Benatru, Isabelle Ollagnon, Elisabeth Forlani, Sylvie Hardy, John Stevanin, Giovanni Duerr, Alexandra Singleton, Andrew Brice, Alexis TI SCA15 Due to Large ITPR1 Deletions in a Cohort of 333 White Families With Dominant Ataxia SO ARCHIVES OF NEUROLOGY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; SPINOCEREBELLAR ATAXIA; MICE; NEURODEGENERATION; PHENOTYPE; BRAIN; MOUSE; GENE AB Background: Deletions in ITPR1, coding for the inositol-triphosphate receptor type 1, have been recently identified in spinocerebellar ataxia type 15 (SCA15). Objective: To determine the frequency and the phenotypical spectrum of SCA15. Design: Taqman polymerase chain reaction (258 index cases) or single-nucleotide polymorphism genome-wide genotyping (75 index cases). Setting: A collaboration between the Centre de Recherche de l'Institut de Cerveau et de la Moelle Epiniere of the Salpetriere Hospital (Paris, France) and the Molecular Genetics Unit of the National Institute of Aging (Bethesda, Maryland). Patients: Index cases of 333 families with autosomal dominant cerebellar ataxia negative for CAG repeat expansions in coding exons. Main Outcome Measures: Detection of ITPR1 copy number alterations. Results: A deletion of ITPR1 was found in 6 of 333 families (1.8%), corresponding to 13 patients with SCA15. Age at onset ranged from 18 to 66 years (mean [SD] age, 35 [16] years). The symptom at onset was cerebellar gait ataxia, except in 1 patient with isolated upper limb tremor. Although families were tested irrespective of their phenotype, patients with SCA15 had a homogeneous phenotype and were characterized by a slowly progressive cerebellar ataxia. However, pyramidal signs (2 patients) and mild cognitive problems (2 patients) were occasionally present. Radiologic findings showed global or predominant vermian cerebellar atrophy in all patients. Conclusions: In this series, ITPR1 deletions were rare and accounted for approximately 1% of all autosomal dominant cerebellar ataxias. The SCA15 phenotype mostly consists of a slowly progressive isolated cerebellar ataxia with variable age at onset; an additional pyramidal syndrome and problems in executive functions may be present. C1 [Marelli, Cecilia; Stevanin, Giovanni; Duerr, Alexandra; Brice, Alexis] Univ Paris 06, Inst Cerveau & Moelle Epiniere, Ctr Rech, UMR S975, Paris, France. [Marelli, Cecilia; Forlani, Sylvie; Stevanin, Giovanni; Duerr, Alexandra; Brice, Alexis] CNRS, UMR 7225, INSERM, U975, Paris, France. [Marelli, Cecilia; Stevanin, Giovanni; Duerr, Alexandra; Brice, Alexis] Hop La Pitie Salpetriere, Dept Genet & Cytogenet, Paris, France. [van de Leemput, Joyce; Johnson, Janel O.; Hernandez, Dena G.; Arepalli, Sampath; Singleton, Andrew] NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. [van de Leemput, Joyce; Johnson, Janel O.; Hernandez, Dena G.; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Tison, Francois] Hop Univ Bordeaux, Dept Neurol, Bordeaux, France. [Thauvin-Robinet, Christel] CHU Dijon, Dept Genet, Dijon, France. [Picard, Fabienne] Univ Hosp & Med Sch Geneva, Dept Neurol, Geneva, Switzerland. [Tranchant, Christine; Marescaux, Christian] Hop Civil, Dept Neurol, Strasbourg, France. [Huttin, Bernard] Ctr Hosp Jean Monnet, Dept Neurol, Epinal, France. [Boulliat, Jacques] Hop Fleyriat, Dept Neurol, Bourg En Bresse, France. [Sangla, Iban] Hop La Timone, Dept Neurol, Marseille, France. [Dollfus, Helene] Univ Strasbourg, Lab Physiopathol Syndromes Rares Hereditaires, AVENIR Inserm, EA3949, Strasbourg, France. [Benatru, Isabelle] CHU Dijon, Dept Neurol, Hop Gen, Dijon, France. [Ollagnon, Elisabeth] Hop Croix Rousse, Dept Genet, F-69317 Lyon, France. [Forlani, Sylvie] Univ Paris 06, DNA & Cell Bank, Ctr Rech, Inst Cerveau & Moelle Epiniere,UMR S975, Paris, France. RP Brice, A (reprint author), Grp Hosp Pitie Salpetriere, Inst Cerveau & Moelle Epiniere, Ctr Rech, INSERM,U975, 47 Bd Hop, F-75651 Paris 13, France. EM alexis.brice@upmc.fr RI Stevanin, Giovanni/E-5038-2016; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 FU European Union; Programme Hospitalier de Recherche Clinique; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000958-06] FX This work was supported in part by the European Union (to the European Integrated Project on Spinocerebellar Ataxias Network), the Programme Hospitalier de Recherche Clinique (Dr Durr), and project Z01 AG000958-06 of the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (Dr Singleton). NR 28 TC 22 Z9 22 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9942 EI 1538-3687 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2011 VL 68 IS 5 BP 637 EP 643 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 761YB UT WOS:000290438000013 PM 21555639 ER PT J AU Sojkova, J Zhou, Y An, Y Kraut, MA Ferrucci, L Wong, DF Resnick, SM AF Sojkova, Jitka Zhou, Yun An, Yang Kraut, Michael A. Ferrucci, Luigi Wong, Dean F. Resnick, Susan M. TI Longitudinal Patterns of beta-Amyloid Deposition in Nondemented Older Adults SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; REFERENCE TISSUE MODEL; 2-YEAR FOLLOW-UP; ALZHEIMERS-DISEASE; SPATIAL CONSTRAINT; DEMENTIA; PET; BIOMARKERS; BRAIN AB Background: High levels of beta-amyloid (A beta) characterize Alzheimer disease. Objective: To investigate whether longitudinal changes in A beta deposition can be detected in vivo in older adults without dementia (hereafter referred to as nondemented). Design: Prospective study. Setting: Community-dwelling older adults. Participants: Twenty-four nondemented participants (4 with a baseline Clinical Dementia Rating Scale score of 0.5; mean [SD] age, 79.2 [8.1] years) in the Baltimore Longitudinal Study of Aging underwent serial carbon 11-labeled Pittsburgh Compound B-positron emission tomography ([(11)C] PiB-PET) (follow-up at a mean [SD] of 1.5 [0.5] years), with 5 participants undergoing a third [(11)C] PiB-PET examination. Main Outcome Measures: Annual changes in distribution volume ratio (DVR) were evaluated using a global index of cortical DVR(cDVR) and region-of-interest analyses. Given the variability of cDVR at the initial PiB-PET, annual changes in cDVR in those with minimal vs those with elevated initial cDVR were compared. Results: In nondemented older adults, annual increase in [(11)C] PiB retention is 0.011 DVR per year (0.9%; P = .01), which localizes to the prefrontal, parietal, lateral temporal, occipital, and anterior and posterior cingulate cortices. Annual change in cDVR is greater in older adults with elevated cDVR than in those with a minimal initial cDVR (P = .006). Conclusions: Fibrillar A beta detected by [(11)C] PiB-PET increases over time even in nondemented older adults. Individuals with higher initial [(11)C] PiB retention have greater rates of A beta deposition, providing evidence of differential rates of A beta deposition. Moreover, regional vulner-abilities to A beta deposition allow for more targeted investigation of early A beta changes. C1 [Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Biomed Res Ctr,Intramural Res Program, Baltimore, MD 21224 USA. [Sojkova, Jitka; Zhou, Yun; Kraut, Michael A.; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Wong, Dean F.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Wong, Dean F.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Resnick, SM (reprint author), NIA, Lab Behav Neurosci, NIH, Biomed Res Ctr,Intramural Res Program, 251 Bayview Blvd,Ste 100, Baltimore, MD 21224 USA. EM resnicks@grc.nia.nih.gov FU National Institutes of Health, National Institute on Aging [N01-AG-3-2124, K24 DA000412] FX This research was supported by grants N01-AG-3-2124 and K24 DA000412 (Dr Wong) from the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 27 TC 52 Z9 53 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2011 VL 68 IS 5 BP 644 EP 649 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 761YB UT WOS:000290438000014 PM 21555640 ER PT J AU Kiernan, DF Al-Heeti, O Blair, MP Keenan, JD Lichtenstein, SJ Tsilou, ET Smaoui, N Shapiro, MJ AF Kiernan, Daniel F. Al-Heeti, Omar Blair, Michael P. Keenan, Jeremy D. Lichtenstein, Steven J. Tsilou, Ekaterini T. Smaoui, Nizar Shapiro, Michael J. TI Peripheral Retinal Nonperfusion in Septo-optic Dysplasia (de Morsier Syndrome) SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID NERVE HYPOPLASIA; APLASIA C1 [Kiernan, Daniel F.; Al-Heeti, Omar; Blair, Michael P.; Shapiro, Michael J.] Univ Illinois, Illinois Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Blair, Michael P.; Shapiro, Michael J.] Retina Consultants Ltd, Des Plaines, IL USA. [Lichtenstein, Steven J.] Illinois Eye Ctr, Peoria, IL USA. [Keenan, Jeremy D.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Tsilou, Ekaterini T.] NEI, DNA Diagnost Lab, Bethesda, MD 20892 USA. [Smaoui, Nizar] GeneDX, Gaithersburg, MD USA. RP Shapiro, MJ (reprint author), Univ Illinois, Illinois Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM michaelj.shapiro@gmail.com FU NEI NIH HHS [EY001792] NR 7 TC 3 Z9 3 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 2011 VL 129 IS 5 BP 671 EP 673 PG 4 WC Ophthalmology SC Ophthalmology GA 761XU UT WOS:000290437100026 PM 21555628 ER PT J AU Dees, C Zerr, P Tomcik, M Beyer, C Horn, A Akhmetshina, A Palumbo, K Reich, N Zwerina, J Sticherling, M Mattson, MP Distler, O Schett, G Distler, JHW AF Dees, Clara Zerr, Pawel Tomcik, Michal Beyer, Christian Horn, Angelika Akhmetshina, Alfiya Palumbo, Katrin Reich, Nicole Zwerina, Jochen Sticherling, Michael Mattson, Mark P. Distler, Oliver Schett, Georg Distler, Joerg H. W. TI Inhibition of Notch Signaling Prevents Experimental Fibrosis and Induces Regression of Established Fibrosis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GAMMA-SECRETASE INHIBITOR; SYSTEMIC-SCLEROSIS; DERMAL FIBROSIS; PATHWAY; DISEASE; CANCER; SCLERODERMA; ACTIVATION; MATRIX; SAFETY AB Objective. Tissue fibrosis caused by pathologic activation of fibroblasts with increased synthesis of extracellular matrix components is a major hallmark of systemic sclerosis (SSc). Notch signaling regulates tissue differentiation, and abnormal activation of Notch signaling has been implicated in the pathogenesis of various malignancies. The present study was undertaken to investigate the role of Notch signaling in SSc and to evaluate the therapeutic potential of Notch inhibition for the treatment of fibrosis. Methods. Activation of the Notch pathways was analyzed by staining for the Notch intracellular domain (NICD) and quantification of levels of HES-1 messenger RNA. In the mouse model of bleomycin-induced dermal fibrosis and in tight skin 1 mice, Notch signaling was inhibited by the gamma-secretase inhibitor DAPT and by overexpression of a Notch-1 antisense construct. Results. Notch signaling was activated in SSc in vivo, with accumulation of the NICD and increased transcription of the target gene HES-1. Overexpression of a Notch antisense construct prevented bleomycin-induced fibrosis and hypodermal thickening in tight skin 1 mice. Potent antifibrotic effects were also obtained with DAPT treatment. In addition to prevention of fibrosis, targeting of Notch signaling resulted in almost complete regression of established experimental fibrosis. Conclusion. The present results demonstrate that pharmacologic as well as genetic inhibition of Notch signaling exerts potent antifibrotic effects in different murine models of SSc. These findings might have direct translational implications because different inhibitors of the gamma-secretase complex are available and have yielded promising results in cancer trials. C1 [Distler, Joerg H. W.] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. [Tomcik, Michal] Charles Univ Prague, Prague, Czech Republic. [Mattson, Mark P.] NIA, NIH, Baltimore, MD 21224 USA. [Distler, Oliver] Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. [Distler, Oliver] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. RP Distler, JHW (reprint author), Univ Erlangen Nurnberg, Dept Internal Med 3, Univ Str 29, D-91054 Erlangen, Germany. EM joerg.distler@uk-erlangen.de RI Mattson, Mark/F-6038-2012; OI Beyer, Christian/0000-0003-0319-662X FU Deutsche Forschungsgesellschaft [DI 1537/2-1]; Interdisciplinary Center of Clinical Research, Erlangen [A20]; CMH [0000023728]; NIH (National Institute on Aging); Ernst Jung Foundation FX Supported by the Deutsche Forschungsgesellschaft (grant DI 1537/2-1), the Interdisciplinary Center of Clinical Research, Erlangen (IZKF grant A20), CMH Research Project 0000023728, and the NIH (National Institute on Aging Intramural Research Program). Dr. J. H. W. Distler's work was supported by a Career Support Award of Medicine from the Ernst Jung Foundation. NR 32 TC 50 Z9 51 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2011 VL 63 IS 5 BP 1396 EP 1404 DI 10.1002/art.30254 PG 9 WC Rheumatology SC Rheumatology GA 764DY UT WOS:000290609800029 PM 21312186 ER PT J AU Perkins, NJ Schisterman, EF Vexler, A AF Perkins, Neil J. Schisterman, Enrique F. Vexler, Albert TI ROC curve inference for best linear combination of two biomarkers subject to limits of detection SO BIOMETRICAL JOURNAL LA English DT Article DE Area under the curve; Best linear combinaton; Left censoring; Limit of detection; ROC ID OPERATING CHARACTERISTIC CURVE AB The receiver operating characteristic (ROC) curve is a tool commonly used to evaluate biomarker utility in clinical diagnosis of disease. Often, multiple biomarkers are developed to evaluate the discrimination for the same outcome. Levels of multiple biomarkers can be combined via best linear combination (BLC) such that their overall discriminatory ability is greater than any of them individually. Biomarker measurements frequently have undetectable levels below a detection limit sometimes denoted as limit of detection (LOD). Ignoring observations below the LOD or substituting some replacement value as a method of correction has been shown to lead to negatively biased estimates of the area under the ROC curve for some distributions of single biomarkers. In this paper, we develop asymptotically unbiased estimators, via the maximum likelihood technique, of the area under the ROC curve of BLC of two bivariate normally distributed biomarkers affected by LODs. We also propose confidence intervals for this area under curve. Point and confidence interval estimates are scrutinized by simulation study, recording bias and root mean square error and coverage probability, respectively. An example using polychlorinated biphenyl (PCB) levels to classify women with and without endometriosis illustrates the potential benefits of our methods. C1 [Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA. [Vexler, Albert] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. RP Perkins, NJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Rm 7B03, Rockville, MD 20852 USA. EM perkinson@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X FU Epidemiology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX The authors thank the Editor and reviewer for their valuable comments and suggestions that have added greatly to this manuscript. This research was supported by the Intramural Research Program of the Epidemiology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 16 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 EI 1521-4036 J9 BIOMETRICAL J JI Biom. J. PD MAY PY 2011 VL 53 IS 3 BP 464 EP 476 DI 10.1002/bimj.201000083 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 762LY UT WOS:000290481300005 PM 22223252 ER PT J AU Jamshed, S Fowler, DH Neelapu, SS Dean, RM Steinberg, SM Odom, J Bryant, K Hakim, F Bishop, MR AF Jamshed, S. Fowler, D. H. Neelapu, S. S. Dean, R. M. Steinberg, S. M. Odom, J. Bryant, K. Hakim, F. Bishop, M. R. TI EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT SO BONE MARROW TRANSPLANTATION LA English DT Article DE multiple myeloma; reduced intensity; allogeneic; transplantation ID STEM-CELL TRANSPLANTATION; DONOR LYMPHOCYTE INFUSIONS; VERSUS-HOST-DISEASE; PROGNOSTIC-FACTORS; BONE-MARROW; ANTITHYMOCYTE GLOBULIN; CHEMOTHERAPY; BORTEZOMIB; EFFICACY; RELAPSE AB There exists a need for effective salvage regimens for multiple myeloma patients being considered for reduced-intensity allogeneic hematopoietic SCT (RI-alloHSCT). We developed EPOCH-F, a regimen consisting of infusional etoposide, VCR and adriamycin with prednisone, CY and fludarabine to achieve both tumor control and host lymphocyte depletion to facilitate engraftment before RI-alloHSCT. In all, 22 multiple myeloma patients were treated with EPOCH-F before RI-alloHSCT. The median age was 53 years (range 36-65), and the median number of previous therapies was 2 (range 1-8). Patients received a median of three cycles (range 1-5) of EPOCH-F. Toxicities were primarily hematologic and manageable. Median lymphocyte counts decreased from 1423/mu L (range 335-2788) to 519/mu L (range 102-1420; P = 0.0002). The overall response (>= PR) to EPOCH-F was 22 with 13% achieving a CR/near-complete response (nCR); only 1 patient progressed while on therapy. A total of 20 patients underwent RI-alloHSCT. Median day +100 donor chimerism was 100% (range 60-100). In all, 70% of patients achieved very good partial response or better response after transplant; 40% of patients achieved CR/nCR. TRM at 100 days and 5 years was 5 and 30%, respectively. Median OS after RI-alloHSCT was 46.1 months. EPOCH-F provides disease control and host lymphocyte depletion with consistent full donor engraftment in multiple myeloma patients undergoing RI-alloHSCT. Bone Marrow Transplantation (2011) 46, 676-681; doi:10.1038/bmt.2010.173; published online 26 July 2010 C1 [Fowler, D. H.; Odom, J.; Bryant, K.; Hakim, F.; Bishop, M. R.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jamshed, S.] Georgetown Univ Hosp, Dept Med, Div Hematol & Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Neelapu, S. S.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Dean, R. M.] Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. [Steinberg, S. M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10,Hatfield CRC,Room 4-3152, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Center for Cancer Research, National Cancer Institute, NIH. NR 32 TC 3 Z9 3 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2011 VL 46 IS 5 BP 676 EP 681 DI 10.1038/bmt.2010.173 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 762JM UT WOS:000290472500007 PM 20661232 ER PT J AU El-Mallawany, NK Geller, L Bollard, CM Wistinghausen, B Mussai, F Wayne, AS Alobeid, B Cairo, MS AF El-Mallawany, N. K. Geller, L. Bollard, C. M. Wistinghausen, B. Mussai, F. Wayne, A. S. Alobeid, B. Cairo, M. S. TI Long-term remission in a child with refractory EBV+ hydroa vacciniforme-like T-cell lymphoma through sequential matched EBV+-related allogeneic hematopoietic SCT followed by donor-derived EBV-specific cytotoxic T-lymphocyte immunotherapy SO BONE MARROW TRANSPLANTATION LA English DT Letter ID LYMPHOPROLIFERATIVE DISEASE; TRANSPLANTATION C1 [El-Mallawany, N. K.; Cairo, M. S.] Columbia Univ, Dept Pediat, NewYork Presbyterian Morgan Stanley Childrens Hos, New York, NY 10027 USA. [Geller, L.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Dermatol, Kravis Childrens Hosp, New York, NY 10029 USA. [Bollard, C. M.] Texas Childrens Hosp, Houston, TX 77030 USA. [Bollard, C. M.] Methodist Hosp, Ctr Cell & Gene Therapy, Dept Pediat, Baylor Coll Med, Houston, TX 77030 USA. [Wistinghausen, B.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Pediat Hematol & Oncol, Kravis Childrens Hosp, New York, NY 10029 USA. [Mussai, F.; Wayne, A. S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Alobeid, B.; Cairo, M. S.] Columbia Univ, Dept Med, NewYork Presbyterian Morgan Stanley Childrens Hos, New York, NY 10027 USA. [Cairo, M. S.] Columbia Univ, Dept Pathol & Cell Biol, NewYork Presbyterian Morgan Stanley Childrens Hos, New York, NY 10027 USA. RP El-Mallawany, NK (reprint author), Columbia Univ, Dept Pediat, NewYork Presbyterian Morgan Stanley Childrens Hos, New York, NY 10027 USA. EM mc1310@columbia.edu OI El-Mallawany, Nader/0000-0001-6115-1046 FU NCI NIH HHS [P50 CA126752-01, P01 CA094237, P50 CA126752] NR 7 TC 3 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2011 VL 46 IS 5 BP 759 EP 761 DI 10.1038/bmt.2010.176 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 762JM UT WOS:000290472500018 PM 20661233 ER PT J AU Akilzhanova, A Meirmanov, S Zhunussova, T Nakashima, M Takamura, N Akanov, Z Masadykov, A Sandybaev, M Ramanulov, E Yamashita, S Sekine, I AF Akilzhanova, Ainur Meirmanov, Serik Zhunussova, Tamara Nakashima, Masahiro Takamura, Noboru Akanov, Zhanay Masadykov, Adilzhan Sandybaev, Marat Ramanulov, Erlan Yamashita, Shunichi Sekine, Ichiro TI Mutational Screening of the BRCA1 Gene in Sporadic Breast Cancer in Kazakhstan Population SO BREAST JOURNAL LA English DT Letter ID OVARIAN-CANCER; SERIES C1 [Akilzhanova, Ainur; Nakashima, Masahiro; Sekine, Ichiro] Nagasaki Univ, Atom Bomb Dis Inst, Div Tumor & Diagnost Pathol, Grad Sch Biomed Sci, Nagasaki 8528523, Japan. [Akilzhanova, Ainur; Nakashima, Masahiro; Sekine, Ichiro] Nagasaki Univ, Atom Bomb Dis Inst, Tissue & Histopathol Sect, Grad Sch Biomed Sci,Div Sci Data Registry, Nagasaki 8528523, Japan. [Takamura, Noboru] Nagasaki Univ, Atom Bomb Dis Inst, Dept Radiat Epidemiol, Grad Sch Biomed Sci, Nagasaki 8528523, Japan. [Sekine, Ichiro] Nagasaki Univ, Atom Bomb Dis Inst, Dept Mol Med, Grad Sch Biomed Sci, Nagasaki 8528523, Japan. [Meirmanov, Serik] Ritsumeikan Asia Pacific Univ, Coll Asia Pacific Studies, Beppu, Oita, Japan. [Zhunussova, Tamara] Sch Publ Hlth, Alma Ata, Kazakhstan. [Akilzhanova, Ainur; Akanov, Zhanay; Ramanulov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. [Masadykov, Adilzhan; Sandybaev, Marat] Semey Oncol Ctr, Semey, Kazakhstan. RP Akilzhanova, A (reprint author), Nagasaki Univ, Atom Bomb Dis Inst, Div Tumor & Diagnost Pathol, Grad Sch Biomed Sci, 1-12-4 Sakamoto, Nagasaki 8528523, Japan. EM akilzhan_ainur@mail.ru OI Meirmanov, Serik/0000-0002-1199-1263; Yamashita, Shunichi/0000-0001-6399-6261 NR 7 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1075-122X J9 BREAST J JI Breast J. PD MAY-JUN PY 2011 VL 17 IS 3 BP 328 EP 330 DI 10.1111/j.1524-4741.2011.01068.x PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 759SN UT WOS:000290268800024 PM 21410590 ER PT J AU El-Chemaly, S Ziegler, SG Calado, RT Wilson, KA Wu, HP Haughey, M Peterson, NR Young, NS Gahl, WA Moss, J Gochuico, BR AF El-Chemaly, Souheil Ziegler, Shira G. Calado, Rodrigo T. Wilson, Kirkland A. Wu, Hai Ping Haughey, Mary Peterson, Nathan R. Young, Neal S. Gahl, William A. Moss, Joel Gochuico, Bernadette R. TI Natural History of Pulmonary Fibrosis in Two Subjects With the Same Telomerase Mutation SO CHEST LA English DT Article ID REVERSE-TRANSCRIPTASE; FAMILIES; DISEASE AB Previous studies have identified subclinical lung disease in family members of probands with familial pulmonary fibrosis, but the natural history of preclinical pulmonary fibrosis is uncertain. The purpose of this study was to determine whether individuals with preclinical lung disease will develop pulmonary fibrosis. After a 27-year interval, two subjects with manifestations of preclinical familial pulmonary fibrosis, including asymptomatic alveolar inflammation and alveolar macrophage activation, were reevaluated for lung disease. CT scans of the chest, pulmonary function tests, and BAL were performed, and genomic DNA was analyzed for mutations in candidate genes associated with familial pulmonary fibrosis. One subject developed symptomatic familial pulmonary fibrosis and was treated with oxygen; her sister remained asymptomatic but had findings of pulmonary fibrosis on high-resolution CT scan of the chest. High concentrations of lymphocytes were found in BAL fluid from both subjects. Genetic sequencing and analyses identified a novel heterozygous mutation in telomerase reverse transcriptase (TERT, R1084P), resulting in telomerase dysfunction and short telomeres in both subjects. In familial pulmonary fibrosis, asymptomatic preclinical alveolar inflammation associated with mutation in TERT and telomerase insufficiency can progress to fibrotic lung disease over 2 to 3 decades. C1 [El-Chemaly, Souheil; Wu, Hai Ping; Haughey, Mary; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Calado, Rodrigo T.; Peterson, Nathan R.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Ziegler, Shira G.; Wilson, Kirkland A.; Gahl, William A.; Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Gochuico, BR (reprint author), 10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. EM gochuicb@mail.nih.gov RI Calado, Rodrigo/G-2619-2011 FU National Heart, Lung, and Blood Institute; National Human Genome Research Institute, National Institutes of Health FX This research was sponsored in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute, National Institutes of Health. NR 17 TC 22 Z9 23 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2011 VL 139 IS 5 BP 1203 EP 1209 DI 10.1378/chest.10-2048 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 763KD UT WOS:000290554300030 PM 20966039 ER PT J AU Harada, T Yatabe, Y Takeshita, M Koga, T Yano, T Wang, YS Giaccone, G AF Harada, Taishi Yatabe, Yasushi Takeshita, Masafumi Koga, Takaomi Yano, Tokujiro Wang, Yisong Giaccone, Giuseppe TI Role and Relevance of TrkB Mutations and Expression in Non-Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID NEUROTROPHIC RECEPTOR TRKB; HUMAN NEUROBLASTOMAS; KINASE; GENE; BDNF; CHEMOTHERAPY; CARCINOMA; PATHWAYS; THERAPY; PROTEIN AB Purpose: TrkB has been involved in poor cancer outcome. TrkB mutations have been reported in non-small cell lung cancer. In this study, we aimed at characterizing the role of three potentially sensitizing TrkB mutations previously reported in lung cancer. Experimental Design: We characterized three activation loop mutants of TrkB (M713I, R715G, and R734C) in terms of pathway activation/phosphorylation, migration, anchorage-independent growth, and sensitivity to a Trk inhibitor, using NIH3T3 cells and Baf3 cells. We also sequenced the tyrosine kinase domain of TrkB in a large number of lung cancer samples of East-Asian origin and cell lines. Results: None of the mutants were constitutively active in NIH3T3 transformation and migration assays. M713I and R734C mutants showed low levels of autophosphorylation in comparison with wild-type TrkB. Although R715G showed similar level of autophosphorylation to wild-type TrkB on brain-derived neurotrophic factor stimulation, the mutant was not as competent as wild-type TrkB in supporting interleukin-3-independent growth of Baf3 cells. In addition, the Trk inhibitor AZD6918 inhibited wild-type TrkB-induced cell migration and cell growth, whereas the mutants were relatively resistant to the Trk inhibitor compared with wild-type TrkB. We could not confirm the presence of nonsynonymous mutation in 78 lung cancer samples and 29 cell lines. Conclusions: Wild-type, but not mutant, TrkB enhances cell migration and transformation. Our study suggests that TrkB mutations should not be used for selection of patients with lung cancer treated with Trk inhibitors. High expression of wild-type TrkB might be beneficial for studies of Trk inhibitors. Clin Cancer Res; 17(9); 2638-45. (C)2011 AACR. C1 [Harada, Taishi; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yatabe, Yasushi] Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Nagoya, Aichi 464, Japan. [Takeshita, Masafumi] Kyushu Univ, Res Inst Dis Chest, Fukuoka 812, Japan. [Takeshita, Masafumi; Koga, Takaomi] Kyushu Univ, Div Pathophysiol & Expt Pathol, Dept Pathol, Fukuoka 812, Japan. [Yano, Tokujiro] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka 812, Japan. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU NIH FX This study and T. Harada were supported by NIH intramural fund. NR 37 TC 22 Z9 23 U1 2 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2011 VL 17 IS 9 BP 2638 EP 2645 DI 10.1158/1078-0432.CCR-10-3034 PG 8 WC Oncology SC Oncology GA 757NH UT WOS:000290093600006 PM 21242122 ER PT J AU Respa, A Bukur, J Ferrone, S Pawelec, G Zhao, YD Wang, E Marincola, FM Seliger, B AF Respa, Annedore Bukur, Juergen Ferrone, Soldano Pawelec, Graham Zhao, Yingdong Wang, Ena Marincola, Francesco M. Seliger, Barbara TI Association of IFN-gamma Signal Transduction Defects with Impaired HLA Class I Antigen Processing in Melanoma Cell Lines SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODIES; DISTINCT MECHANISMS; INTERFERON-ALPHA; STAT1; CANCER; INDUCIBILITY; EXPRESSION; RESISTANT; MOLECULES; CARCINOMA AB Purpose: Abnormalities in the constitutive and IFN-gamma-inducible HLA class I surface antigen expression of tumor cells is often associated with an impaired expression of components of the antigen processing machinery (APM). Hence, we analyzed whether there exists a link between the IFN-gamma signaling pathway, constitutive HLA class I APM component expression, and IFN-gamma resistance. Experimental Design: The basal and IFN-gamma-inducible expression profiles of HLA class I APM and IFN-gamma signal transduction cascade components were assessed in melanoma cells by real-time PCR (RT-PCR), Western blot analysis and/or flow cytometry, the integrity of the Janus activated kinase (JAK) 2 locus by comparative genomic hybridization. JAK2 was transiently overexpressed in JAK2(-) cells. The effect of IFN-gamma on the cell growth was assessed by XTT [2,3-bis(2-methoxy-4-nitro-S-sulfophenynl)-H-tetrazolium-5-carboxanilide inner salt] assay. Results: The analysis of 8 melanoma cell lines linked the IFN-gamma unresponsiveness of Colo 857 cells determined by lack of inducibility of HLA class I surface expression on IFN-gamma treatment to a deletion of JAK2 on chromosome 9, whereas other IFN-gamma signaling pathway components were not affected. In addition, the constitutive HLA class I APM component expression levels were significantly reduced in JAK2(-) cells. Furthermore, JAK2-deficient cells were also resistant to the antiproliferative effect of IFN-gamma. Transfection of wild-type JAK2 into JAK2(-) Colo 857 not only increased the basal APM expression but also restored their IFN-g sensitivity. Conclusions: Impaired JAK2 expression in melanoma cells leads to reduced basal expression of MHC class I APM components and impairs their IFN-gamma inducibility, suggesting that malfunctional IFN-gamma signaling might cause HLA class I abnormalities. Clin Cancer Res; 17(9); 2668-78. (C)2011 AACR. C1 [Respa, Annedore; Bukur, Juergen; Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06112 Halle, Saale, Germany. [Pawelec, Graham] Univ Tubingen, Dept Internal Med 2, Tuebingen Ageing & Tumor Immunol Grp TATI, Sect Transplantat Immunol & Immunohaematol,Ctr Me, Tubingen, Germany. [Ferrone, Soldano] Univ Pittsburgh, Sch Med, Dept Surg, Univ Pittsburgh Canc Inst,Canc Immunol Program, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Sch Med, Canc Immunol Program, Univ Pittsburgh Canc Inst,Dept Immunol, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Sch Med, Canc Immunol Program, Univ Pittsburgh Canc Inst,Dept Pathol, Pittsburgh, PA USA. [Zhao, Yingdong] NCI, NIH, Div Canc Treatment & Diag, Rockville, MD USA. [Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. RP Seliger, B (reprint author), Univ Halle Wittenberg, Inst Med Immunol, Magdeburger Str 2, D-06112 Halle, Saale, Germany. EM Barbara.Seliger@medizin.uni-halle.de OI Pawelec, Graham/0000-0002-3600-0163 FU DFG [SE-581-9, SE-581-11.1]; National Cancer Institute [RO1CA104947, RO1CA110249, PO1CA109688] FX This work was sponsored by DFG grant SE-581-9 and SE-581-11.1 and by PHS grants RO1CA104947 (to S. Ferrone), RO1CA110249 (to S. Ferrone), and PO1CA109688 (to S. Ferrone) awarded by the National Cancer Institute. NR 32 TC 24 Z9 25 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2011 VL 17 IS 9 BP 2668 EP 2678 DI 10.1158/1078-0432.CCR-10-2114 PG 11 WC Oncology SC Oncology GA 757NH UT WOS:000290093600009 PM 21248298 ER PT J AU Zheng, CY Cotrim, AP Rowzee, A Swaim, W Sowers, A Mitchell, JB Baum, BJ AF Zheng, Changyu Cotrim, Ana P. Rowzee, Anne Swaim, William Sowers, Anastasia Mitchell, James B. Baum, Bruce J. TI Prevention of Radiation-Induced Salivary Hypofunction Following hKGF Gene Delivery to Murine Submandibular Glands SO CLINICAL CANCER RESEARCH LA English DT Article ID KERATINOCYTE GROWTH-FACTOR; RECOMBINANT ADENOVIRAL VECTOR; INDUCED ORAL MUCOSITIS; RETRODUCTAL DELIVERY; NECK RADIOTHERAPY; LUNG INJURY; TOXICITY; MICE; PROTECTION; MORTALITY AB Purpose: Salivary glands are significantly affected when head and neck cancer patients are treated by radiation. We evaluated the effect of human keratinocyte growth factor (hKGF) gene transfer to murine salivary glands on the prevention of radiation-induced salivary hypofunction. Experimental Design: A hybrid serotype 5 adenoviral vector encoding hKGF (AdLTR(2)EF1 alpha-hKGF) was constructed. Female C3H mice, 8 weeks old, were irradiated by single (15 Gy) or fractionated (6 Gy for 5 days) doses to induce salivary hypofunction. AdLTR(2)EF1 alpha-hKGF or AdControl was administered (10(8) - 10(10) particles per gland) to both submandibular glands (SG) by retrograde ductal instillation before irradiation (IR). Salivary flow was measured following pilocarpine stimulation. Human KGF levels were measured by ELISA. SG cell proliferation was measured with bromodeoxyuridine labeling. Endothelial and progenitor or stem cells in SGs were measured by flow cytometry. The effect of SG hKGF production on squamous cell carcinoma (SCC VII) tumor growth was assessed. Results: In 3 separate single-dose IR experiments, salivary flow rates of mice administered the AdLTR(2)EF1 alpha-hKGF vector were not significantly different from nonirradiated control mice (P > 0.05). Similarly, in 3 separate fractionated IR experiments, the hKGF-expressing vector prevented salivary hypofunction dramatically. Transgenic hKGF protein was found at high levels in serum and SG extracts. AdLTR(2)EF1 alpha-hKGF-treated mice showed increased cell proliferation and numbers of endothelial cells, compared with mice treated with AdControl. hKGF gene transfer had no effect on SCC VII tumor growth +/- radiation. Conclusions: hKGF gene transfer prevents salivary hypofunction caused by either single or fractionated radiation dosing in mice. The findings suggest a potential clinical application. Clin Cancer Res; 17(9); 2842-51. (C)2011 AACR. C1 [Zheng, Changyu] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. [Sowers, Anastasia; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Zheng, CY (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1A01,MSC 1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM czheng@dir.nidcr.nih.gov OI Rowzee, Anne/0000-0003-1969-9133 FU The Divisions of Intramural Research of the National Institute of Dental and Craniofacial Research; Center for Cancer Research, NIH FX The Divisions of Intramural Research of the National Institute of Dental and Craniofacial Research and the Center for Cancer Research, NIH, provided all support for this research. NR 35 TC 31 Z9 32 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2011 VL 17 IS 9 BP 2842 EP 2851 DI 10.1158/1078-0432.CCR-10-2982 PG 10 WC Oncology SC Oncology GA 757NH UT WOS:000290093600025 PM 21367751 ER PT J AU Su, H Hu, N Yang, HH Wang, CY Takikita, M Wang, QH Giffen, C Clifford, R Hewitt, SM Shou, JZ Goldstein, AM Lee, MP Taylor, PR AF Su, Hua Hu, Nan Yang, Howard H. Wang, Chaoyu Takikita, Mikiko Wang, Quan-Hong Giffen, Carol Clifford, Robert Hewitt, Stephen M. Shou, Jian-Zhong Goldstein, Alisa M. Lee, Maxwell P. Taylor, Philip R. TI Global Gene Expression Profiling and Validation in Esophageal Squamous Cell Carcinoma and Its Association with Clinical Phenotypes SO CLINICAL CANCER RESEARCH LA English DT Article ID LYMPH-NODE METASTASIS; ACTIN-BUNDLING PROTEIN; MESSENGER-RNA; CANCER STATISTICS; CDNA MICROARRAY; BREAST-CANCER; FASCIN; CHINA; DIFFERENTIATION; OVEREXPRESSION AB Purpose: Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with poor prognosis. Understanding molecular changes in ESCC will enable identification of molecular subtypes and provide potential targets for early detection and therapy. Experimental Design: We followed up a previous array study with additional discovery and confirmatory studies in new ESCC cases by using alternative methods. We profiled global gene expression for discovery and confirmation, and validated selected dysregulated genes with additional RNA and protein studies. Results: A total of 159 genes showed differences with extreme statistical significance (P < E-15) and 2-fold differences or more in magnitude (tumor/normal RNA expression ratio, N = 53 cases), including 116 upregulated and 43 downregulated genes. Of 41 genes dysregulated in our prior array study, all but one showed the same fold change directional pattern in new array studies, including 29 with 2-fold changes or more. Alternative RNA expression methods validated array results: more than two thirds of 51 new cases examined by real-time PCR (RT-PCR) showed 2-fold differences or more for all seven genes assessed. Immunohistochemical protein expression results in 275 cases which were concordant with RNA for five of six genes. Conclusion: We identified an expanded panel of genes dysregulated in ESCC and confirmed previously identified differentially expressed genes. Microarray-based gene expression results were confirmed by RTPCR and protein expression studies. These dysregulated genes will facilitate molecular categorization of tumor subtypes and identification of their risk factors, and serve as potential targets for early detection, outcome prediction, and therapy. Clin Cancer Res; 17(9); 2955-66. (C) 2011 AACR. C1 [Su, Hua; Hu, Nan; Wang, Chaoyu; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Lee, Maxwell P.] NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Takikita, Mikiko; Hewitt, Stephen M.] NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. [Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA. [Wang, Quan-Hong] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. [Shou, Jian-Zhong] Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100037, Peoples R China. RP Taylor, PR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Rm 7006,MSC 7236, Bethesda, MD 20892 USA. EM leemax@mail.nih.gov; ptaylor@mail.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU National Cancer Institute [N02-SC-66211]; Shanxi Cancer Hospital and Institute; NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and Center for Cancer Research FX This research was supported by National Cancer Institute contract (N02-SC-66211) with the Shanxi Cancer Hospital and Institute and by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and Center for Cancer Research. NR 37 TC 58 Z9 59 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2011 VL 17 IS 9 BP 2955 EP 2966 DI 10.1158/1078-0432.CCR-10-2724 PG 12 WC Oncology SC Oncology GA 757NH UT WOS:000290093600036 PM 21385931 ER PT J AU Huestis, MA AF Huestis, M. A. TI DRUGS OF ABUSE TESTING, FROM URINE TO ORAL FLUID: SCIENTIFIC AND LEGAL RAMIFICATIONS SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Huestis, M. A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S21 EP S21 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974200015 ER PT J AU Ohlsson, C Wallaschofski, H Lunetta, KL Stolk, L Perry, JRB Annemarie, K Petersen, AK Eriksson, J Lehtimaki, T Huhtaniemi, IT Hammond, GL Maggio, M Coviello, AD Ferrucci, L Heier, M Hofman, A Holliday, KL Jansson, JO Kaakinen, M Karasik, D Karlsson, MK Kiel, DP Ljunggren, A Lorentzon, M Lyytikainen, LP Meitinger, T Mellstrom, D Melzer, D Miljkovic, I Nauck, M Nilsson, M Penninx, B Pye, SR Vasan, RS Reincke, M Tajar, A Teumer, A Uitterlinden, AG Ulloor, J Viikari, J Volker, U Volzke, H Wichmann, EH Wu, TS Zhuang, WV Ziv, E Wu, FCW Raitakari, O Eriksson, A Bidlingmaier, M Harris, TB Murray, A Jong, F Murabito, JM Bhasin, S Vandenput, L Haring, R AF Ohlsson, C. Wallaschofski, H. Lunetta, K. L. Stolk, L. Perry, J. R. B. Annemarie, K. Petersen, A. K. Eriksson, J. Lehtimaki, T. Huhtaniemi, I. T. Hammond, G. L. Maggio, M. Coviello, A. D. Ferrucci, L. Heier, M. Hofman, A. Holliday, K. L. Jansson, J. O. Kaakinen, M. Karasik, D. Karlsson, M. K. Kiel, D. P. Ljunggren, A. Lorentzon, Mattias Lyytikainen, L. P. Meitinger, T. Mellstrom, D. Melzer, D. Miljkovic, I Nauck, M. Nilsson, M. Penninx, B. Pye, S. R. Vasan, R. S. Reincke, M. Tajar, A. Teumer, A. Uitterlinden, A. G. Ulloor, J. Viikari, J. Voelker, U. Voelzke, H. Wichmann, E. H. Wu, T. S. Zhuang, W., V Ziv, E. Wu, F. C. W. Raitakari, O. Eriksson, A. Bidlingmaier, M. Harris, T. B. Murray, A. Jong, F. Murabito, J. M. Bhasin, S. Vandenput, L. Haring, R. CA EMAS Study Roup TI GENETIC DETERMINANTS OF SERUM TESTOSTERONE CONCENTRATIONS IN MEN SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Ohlsson, C.; Eriksson, J.; Lyytikainen, L. P.; Mellstrom, D.; Nilsson, M.; Eriksson, A.; Vandenput, L.] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Internal Med, Gothenburg, Sweden. [Wallaschofski, H.; Haring, R.] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, D-17487 Greifswald, Germany. [Lunetta, K. L.; Vasan, R. S.; Wichmann, E. H.; Murabito, J. M.; Bhasin, S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Lunetta, K. L.; Zhuang, W., V] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Stolk, L.; Uitterlinden, A. G.; Wichmann, E. H.] Netherlands Consortium Healthy Ageing, Rotterdam, Netherlands. [Perry, J. R. B.; Murray, A.] Univ Exeter, Peninsula Med Sch, Exeter EX4 4QJ, Devon, England. [Annemarie, K.; Harris, T. B.; Jong, F.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Petersen, A. K.; Wichmann, E. H.] Helmholtz Zentrum Munich, Inst Epidemiol, Neuherberg, Germany. [Lehtimaki, T.] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, T.] Tampere Univ Hosp, Tampere, Finland. [Huhtaniemi, I. T.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England. [Hammond, G. L.; Wu, T. S.] Univ British Columbia, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada. [Hammond, G. L.; Wu, T. S.] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Maggio, M.] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy. [Coviello, A. D.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Coviello, A. D.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Coviello, A. D.] Boston Univ, Sch Med, Dept Med, Sect Cardiol & Endocrinol, Boston, MA 02118 USA. [Coviello, A. D.] Boston Univ, Sch Med, Dept Med, Sect Diabet & Nutr, Boston, MA 02118 USA. [EMAS Study Roup] European Male Ageing Study, Warsaw, Poland. [Ferrucci, L.] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. [Heier, M.] Helmholtz Zentrum Munich, Inst Epidemiol 2, Neuherberg, Germany. [Hofman, A.; Uitterlinden, A. G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Holliday, K. L.; Pye, S. R.; Tajar, A.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthritis Res UK Epidemiol Unit, Manchester, Lancs, England. [Jansson, J. O.] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden. [Kaakinen, M.] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Karasik, D.; Kiel, D. P.] Harvard Univ, Sch Med, Boston, MA USA. [Karasik, D.; Kiel, D. P.] Hebrew Senior Life Inst Aging Res, Boston, MA USA. [Karlsson, M. K.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden. [Karlsson, M. K.] Lund Univ, Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden. [Ljunggren, A.] Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Lorentzon, Mattias] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Meitinger, T.] Tech Univ Munich, Inst Human Genet, Munich, Germany. [Meitinger, T.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Human Genet, Neuherberg, Germany. [Melzer, D.] Univ Exeter, Peninsula Med Sch, Exeter, Devon, England. [Miljkovic, I] Univ Pitt, Pittsburgh, PA 15213 USA. EM robin.haring@uni-greifswald.de RI Pye, Stephen/D-9236-2011 OI Pye, Stephen/0000-0002-7263-2897 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S424 EP S424 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974200679 ER PT J AU Zhai, G Teumer, A Stolk, L Perry, JRB Vandenput, L Coviello, AD Koster, A Bandinelli, S Bell, JT Bhasin, S Eriksson, J Eriksson, A Ernst, F Ferrucci, L Frayling, TM Glass, D Grundberg, E Haring, R Hedman, AK Hofman, A Kiel, DP Kroemer, HK Liu, Y Lunetta, L Lorentzon, M Mangino, M Melzer, D Miljkovic, I Nica, A Penninx Vasan, RS Small, KS Soranzo, N Uitterlinden, AG Volzke, H Wilson, S Xi Zhuang, WV Harris, T Murabito, JM Ohlsson, C Murray, A Jong, F Spector, TD Wallaschofski, H AF Zhai, G. Teumer, A. Stolk, L. Perry, J. R. B. Vandenput, L. Coviello, A. D. Koster, A. Bandinelli, S. Bell, J. T. Bhasin, S. Eriksson, J. Eriksson, A. Ernst, F. Ferrucci, L. Frayling, T. M. Glass, D. Grundberg, E. Haring, R. Hedman, A. K. Hofman, A. Kiel, D. P. Kroemer, H. K. Liu, Y. Lunetta, L. Lorentzon, M. Mangino, M. Melzer, D. Miljkovic, I Nica, A. Penninx Vasan, R. S. Small, K. S. Soranzo, N. Uitterlinden, A. G. Voelzke, H. Wilson, S. Xi Zhuang, W., V Harris, T. Murabito, J. M. Ohlsson, C. Murray, A. Jong, F. Spector, T. D. Wallaschofski, H. TI EIGHT COMMON GENETIC VARIANTS ASSOCIATED WITH SERUM DHEAS LEVELS SUGGESTS A KEY ROLE IN AGEING MECHANISMS SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Zhai, G.; Bell, J. T.; Glass, D.; Grundberg, E.; Mangino, M.; Small, K. S.; Soranzo, N.; Wilson, S.; Spector, T. D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Teumer, A.; Ernst, F.] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, D-17487 Greifswald, Germany. [Stolk, L.; Uitterlinden, A. G.; Jong, F.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Stolk, L.; Hofman, A.; Uitterlinden, A. G.] Netherlands Consortium Healthy Ageing, Rotterdam, Netherlands. [Perry, J. R. B.; Frayling, T. M.; Melzer, D.; Murray, A.] Univ Exeter, Peninsula Med Sch, Exeter EX4 4QJ, Devon, England. [Vandenput, L.; Eriksson, J.; Eriksson, A.; Lorentzon, M.; Ohlsson, C.] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, Gothenburg, Sweden. [Coviello, A. D.; Vasan, R. S.; Murabito, J. M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Koster, A.; Harris, T.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Bandinelli, S.] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy. [Bell, J. T.; Hedman, A. K.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Bhasin, S.] Boston Univ, Sch Med, Boston Claude D Pepper Older Amer Independence Ct, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Coviello, A. D.; Vasan, R. S.; Murabito, J. M.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Coviello, A. D.; Vasan, R. S.; Murabito, J. M.] Boston Univ, Sch Med, Dept Med, Sect Cardiol & Endocrinol, Boston, MA 02118 USA. [Coviello, A. D.; Vasan, R. S.; Murabito, J. M.] Boston Univ, Sch Med, Dept Med, Sect Diabet & Nutr, Boston, MA 02118 USA. [Ferrucci, L.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Grundberg, E.; Nica, A.; Small, K. S.; Soranzo, N.] Wellcome Trust Sanger Inst, Hixton, England. [Haring, R.; Wallaschofski, H.] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, D-17487 Greifswald, Germany. [Hofman, A.; Uitterlinden, A. G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Kiel, D. P.] Hebrew Senior Life Inst Aging Res, Boston, MA USA. [Kiel, D. P.] Harvard Univ, Sch Med, Boston, MA USA. [Kroemer, H. K.] Ernst Moritz Arndt Univ Greifswald, Dept Pharmacol, Ctr Pharmacol & Expt Therapeut, D-17487 Greifswald, Germany. [Liu, Y.] Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Lunetta, L.; Zhuang, W., V] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Miljkovic, I] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Nica, A.; Penninx] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Vasan, R. S.; Murabito, J. M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Voelzke, H.] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17487 Greifswald, Germany. [Wilson, S.] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Wilson, S.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia. [Xi] Pfizer Worldwide R&D, Mol Med Computat Biol, Groton, CT USA. EM robin.haring@uni-greifswald.de; Henri.wallaschofski@uni-greifswald.de NR 0 TC 0 Z9 0 U1 4 U2 6 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S425 EP S425 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974200680 ER PT J AU Frankola, KA Greig, NH Luo, WM Tweedie, D AF Frankola, Kathryn A. Greig, Nigel H. Luo, Weiming Tweedie, David TI Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Tumor necrosis factor-alpha; neuroinflammation; cytokine; chemokine; neurodegeneration; Alzheimer's disease; Parkinson's disease; amyotrophic lateral sclerosis; Japanese encephalitis; dementia; thalidomide; revlimid ID TUMOR-NECROSIS-FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN-INJURY; CLOSED-HEAD INJURY; INFLUENZA-ASSOCIATED ENCEPHALOPATHY; AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; SYNUCLEIN ACTIVATES MICROGLIA; ENCEPHALITIS-VIRUS INFECTION; PRO-INFLAMMATORY CYTOKINES AB Inflammatory signals generated within the brain and peripheral nervous system direct diverse biological processes. Key amongst the inflammatory molecules is tumor necrosis factor-alpha (TNF-alpha), a potent pro-inflammatory cytokine that, via binding to its associated receptors, is considered to be a master regulator of cellular cascades that control a number of diverse processes coupled to cell viability, gene expression, synaptic integrity and ion homeostasis. Whereas a self-limiting neuroinflammatory response generally results in the resolution of an intrinsically or extrinsically triggered insult by the elimination of toxic material or injured tissue to restore brain homeostasis and function, in the event of an unregulated reaction, where the immune response persists, inappropriate chronic neuroinflammation can ensue. Uncontrolled neuroinflammatory activity can induce cellular dysfunction and demise, and lead to a self-propagating cascade of harmful pathogenic events. Such chronic neuroinflammation is a typical feature across a range of debilitating common neurodegenerative diseases, epitomized by Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, in which TNF-alpha expression appears to be upregulated and may represent a valuable target for intervention. Elaboration of the protective homeostasis signaling cascades from the harmful pathogenic ones that likely drive disease onset and progression could aid in the clinical translation of approaches to lower brain and peripheral nervous system TNF-alpha levels, and amelioration of inappropriate neuroinflammation. C1 [Greig, Nigel H.] NIA, Biomed Res Ctr, Drug Design & Dev Sect, Lab Neurosci,Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Greig, NH (reprint author), NIA, Biomed Res Ctr, Drug Design & Dev Sect, Lab Neurosci,Intramural Res Program,NIH, Room 05C220,251 Bayview Blvd, Baltimore, MD 21224 USA. EM Greign@grc.nia.nih.gov FU NIH, National Institute on Aging FX This work was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 184 TC 67 Z9 70 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD MAY PY 2011 VL 10 IS 3 BP 391 EP 403 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 764EZ UT WOS:000290613100014 PM 21288189 ER PT J AU Chatterjee, K Young, MF Simon, CG AF Chatterjee, Kaushik Young, Marian F. Simon, Carl G., Jr. TI Fabricating Gradient Hydrogel Scaffolds for 3D Cell Culture SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE Combinatorial methods; high-throughput screening; hydrogels; elastic modulus; gradients; osteoblast; tissue engineering ID DIFFERENTIATION; BIOMATERIALS; SURFACES AB Optimizing cell-material interactions is critical for maximizing regeneration in tissue engineering. Combinatorial and high-throughput (CHT) methods can be used to systematically screen tissue scaffolds to identify optimal biomaterial properties. Previous CHT platforms in tissue engineering have involved a two-dimensional (2D) cell culture format where cells were cultured on material surfaces. However, these platforms are inadequate to predict cellular response in a three-dimensional (3D) tissue scaffold. We have developed a simple CHT platform to screen cell-material interactions in 3D culture format that can be applied to screen hydrogel scaffolds. Herein we provide detailed instructions on a method to prepare gradients in elastic modulus of photopolymerizable hydrogels. C1 [Chatterjee, Kaushik; Simon, Carl G., Jr.] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Chatterjee, Kaushik; Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Simon, CG (reprint author), NIST, Div Polymers, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM carl.simon@nist.gov FU National Research Council of the National Academy of Sciences in the NIH-NIBIB/NIST; NIST [NIH-NIBIB R21 EB006497-01]; NIH-NIDCR (National Institute of Dental and Craniofacial Research) FX We gratefully acknowledge technical inputs from Sheng Lin-Gibson, William E. Wallace, Kathy Flynn, Ed Parry, Kathryn L. Beers, Sapun H. Parekh, Young J. Lee and Marcus T. Cicerone at NIST. This work was performed while K. C. held a Research Associateship Award from the National Research Council of the National Academy of Sciences in the NIH-NIBIB/NIST Joint Postdoctoral Program (National Institutes of Health-National Institute of Biomedical Imaging and Bioengineering/National Institute of Standards and Technology). This work was supported by NIST, NIH-NIBIB R21 EB006497-01 and the Intramural Program of NIH-NIDCR (National Institute of Dental and Craniofacial Research). NR 24 TC 7 Z9 7 U1 0 U2 21 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD MAY PY 2011 VL 14 IS 4 BP 227 EP 236 PG 10 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 764EO UT WOS:000290611700001 PM 21143178 ER PT J AU Shukla, S Ohnuma, S Ambudkar, SV AF Shukla, S. Ohnuma, S. Ambudkar, S. V. TI Improving Cancer Chemotherapy with Modulators of ABC Drug Transporters SO CURRENT DRUG TARGETS LA English DT Review DE ABC transporters; ABCG2; blood-brain barrier; chemotherapy; modulators; multidrug resistance; oral bioavailability; P-glycoprotein ID BLOOD-BRAIN-BARRIER; MEDIATED MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN INHIBITOR; INCREASED ORAL BIOAVAILABILITY; IN-VIVO REVERSAL; BREAST-CANCER; CYCLOSPORINE-A; PROTEIN MRP; OVARIAN-CANCER; EFFLUX PUMP AB ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and ABCG2, are membrane proteins that couple the energy derived from ATP hydrolysis to efflux many chemically diverse compounds across the plasma membrane, thereby playing a critical and important physiological role in protecting cells from xenobiotics. These transporters are also implicated in the development of multidrug resistance (MDR) in cancer cells that have been treated with chemotherapeutics. One approach to blocking the efflux capability of an ABC transporter in a cell or tissue is inhibiting the activity of the transporters with a modulator. Since ABC transporter modulators can be used in combination with chemotherapeutics to increase the effective intracellular concentration of anticancer drugs, the possible impact of modulators of ABC drug transporters is of great clinical interest. Another possible clinical use of modulators that has recently attracted attention is their ability to increase oral bioavailability or increase tissue penetration of drugs transported by the transporters. Several preclinical and clinical studies have been performed to evaluate the feasibility and the safety of this approach. The primary focus of this review is to discuss progress made in recent years in the identification and applicability of compounds that may serve as ABC transporter modulators and the possible role of these compounds in altering the pharmacokinetics and pharmacodynamics of therapeutic drugs used in the clinic. C1 [Shukla, S.; Ohnuma, S.; Ambudkar, S. V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 122 TC 88 Z9 91 U1 7 U2 29 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD MAY PY 2011 VL 12 IS 5 BP 621 EP 630 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 764HB UT WOS:000290619400003 PM 21039338 ER PT J AU Bornstein, MH Hahn, CS Haynes, OM AF Bornstein, Marc H. Hahn, Chun-Shin Haynes, O. Maurice TI Maternal Personality, Parenting Cognitions, and Parenting Practices SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE mother; personality; parenting; cognitions; practices ID 5-FACTOR MODEL; INDIVIDUAL-DIFFERENCES; MOTHERS PERSONALITY; CHILD OUTCOMES; LIFE-COURSE; BIG 5; BEHAVIOR; INVENTORY; TRAITS; PERSPECTIVE AB A community sample of 262 European American mothers of firstborn 20-month-olds completed a personality inventory and measures of parenting cognitions (knowledge, self-perceptions, and reports about behavior) and was observed in interaction with their children from which measures of parenting practices (language, sensitivity, affection, and play) were independently coded. Factor analyses of the personality inventory replicated extraction of the 5-factor model of personality (Openness, Neuroticism, Extraversion, Agreeableness, and Conscientiousness). When controlling for sociodemographic characteristics, the 5 personality factors qua variables and in patterns qua clusters related differently to diverse parenting cognitions and practices, supporting the multidimensional, modular, and specific nature of parenting. Maternal personality in the normal range, a theoretically important but empirically neglected factor in everyday parenting, has meaning in studies of parenting, child development, and family process. C1 [Bornstein, Marc H.; Hahn, Chun-Shin; Haynes, O. Maurice] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030 6705,Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov FU Intramural NIH HHS [Z01 HD001119-20] NR 124 TC 28 Z9 28 U1 4 U2 30 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2011 VL 47 IS 3 BP 658 EP 675 DI 10.1037/a0023181 PG 18 WC Psychology, Developmental SC Psychology GA 757KI UT WOS:000290083500005 PM 21443335 ER PT J AU Schermerhorn, AC D'Onofrio, BM Turkheimer, E Ganiban, JM Spotts, EL Lichtenstein, P Reiss, D Neiderhiser, JM AF Schermerhorn, Alice C. D'Onofrio, Brian M. Turkheimer, Eric Ganiban, Jody M. Spotts, Erica L. Lichtenstein, Paul Reiss, David Neiderhiser, Jenae M. TI A Genetically Informed Study of Associations Between Family Functioning and Child Psychosocial Adjustment SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE family relations; child adjustment; genetics; offspring; twins ID GENOTYPE-ENVIRONMENT CORRELATION; MARITAL CONFLICT; ANTISOCIAL-BEHAVIOR; PARENTAL DIVORCE; OFFSPRING PSYCHOPATHOLOGY; ADOLESCENT PERCEPTIONS; EXTERNALIZING BEHAVIOR; EMOTIONAL SECURITY; MUTUAL INFLUENCE; TWINS DESIGN AB Research has documented associations between family functioning and offspring psychosocial adjustment, but questions remain regarding whether these associations are partly due to confounding genetic factors and other environmental factors. The current study used a genetically informed approach, the Children of Twins design, to explore the associations between family functioning (family conflict, marital quality, and agreement about parenting) and offspring psychopathology. Participants were 867 twin pairs (388 monozygotic; 479 dizygotic) from the Twin and Offspring Study in Sweden, their spouses, and children (51.7% female; M = 15.75 years). The results suggested associations between exposure to family conflict (assessed by the mother, father, and child) and child adjustment were independent of genetic factors and other environmental factors. However, when family conflict was assessed using only children's reports, the results indicated that genetic factors also influenced these associations. In addition, the analyses indicated that exposure to low marital quality and agreement about parenting was associated with children's internalizing and externalizing problems and that genetic factors also contributed to the associations of marital quality and agreement about parenting with offspring externalizing problems. C1 [Schermerhorn, Alice C.; D'Onofrio, Brian M.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Turkheimer, Eric] Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA. [Ganiban, Jody M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Spotts, Erica L.] NIA, Bethesda, MD 20892 USA. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Reiss, David] Yale Univ, Yale Child Study Ctr, New Haven, CT 06520 USA. [Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. RP Schermerhorn, AC (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 E 10th St, Bloomington, IN 47405 USA. EM alscherm@indiana.edu; jehaemn@psu.edu OI lichtenstein, paul/0000-0003-3037-5287 FU NICHD NIH HHS [HD056354, HD053550, T32HD007475, HD061817, T32 HD007475, R01 HD053550, R01 HD056354, R01 HD061817, R01 HD061384]; NIMH NIH HHS [R01 MH054610-05A1, R01MH54610, R01 MH054610] NR 98 TC 13 Z9 15 U1 5 U2 25 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2011 VL 47 IS 3 BP 707 EP 725 DI 10.1037/a0021362 PG 19 WC Psychology, Developmental SC Psychology GA 757KI UT WOS:000290083500008 PM 21142367 ER PT J AU Valentin-Blasini, L Blount, BC Otero-Santos, S Cao, Y Bernbaum, JC Rogan, WJ AF Valentin-Blasini, Liza Blount, Benjamin C. Otero-Santos, Samaret Cao, Yang Bernbaum, Judy C. Rogan, Walter J. TI Perchlorate Exposure and Dose Estimates in Infants SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID THYROID-STIMULATING HORMONE; HUMAN-MILK; BREAST-MILK; IODINE; CREATININE; EXCRETION; URINE; CHILDREN; BENEFITS; QUALITY AB Perchlorate is a naturally occurring inorganic anion used as a component of solid rocket fuel, explosives, and pyrotechnics. Sufficiently high perchlorate intakes can modify thyroid function by competitively inhibiting iodide uptake in adults; however, little is known about perchlorate exposure and health effects in infants. Food intake models predict that infants have higher perchlorate exposure doses than adults. For this reason, we measured perchlorate and related anions (nitrate, thiccyanate, and iodide) in 206 urine samples from 92 infants ages 1-377 days and calculated perchlorate intake dose for this sample of infants. The median estimated exposure dose for this sample of infants was 0.160 mu g/kg/day. Of the 205 individual dose estimates, 9% exceeded the reference dose of 0.7 mu g/kg/day; 6% of infants providing multiple samples had multiple perchlorate dose estimates above the reference dose. Estimated exposure dose differed by feeding method: breast-fed infants had a higher perchlorate exposure dose (geometric mean 0.220 mu g/kg/day) than infants consuming cow milk-based formula (geometric mean 0.103 mu g/kg/day, p < 0.0001) or soy-based formula (geometric mean 0.027 mu g/kg/day, p < 0.0001), consistent with dose estimates based on dietary intake data. The ability of perchlorate to block adequate iodide uptake by the thyroid may have been reduced by the iodine-sufficient status of the infants studied (median urinary iodide 125 mu g/L). Further research is needed to see whether these perchlorate intake doses lead to any health effects. C1 [Valentin-Blasini, Liza; Blount, Benjamin C.; Otero-Santos, Samaret] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. [Cao, Yang] Second Mil Med Univ, Fac Hlth Serv, Dept Hlth Stat, Shanghai, Peoples R China. [Bernbaum, Judy C.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Rogan, Walter J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. RP Blount, BC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. EM BBlount@cdc.gov RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Cao, Yang/0000-0002-3552-9153 FU National Institutes of Health, National Institute of Environmental Health Sciences FX This work was partially supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences NR 39 TC 14 Z9 15 U1 3 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X EI 1520-5851 J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD MAY 1 PY 2011 VL 45 IS 9 BP 4127 EP 4132 DI 10.1021/es103160j PG 6 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 753ZI UT WOS:000289819400048 PM 21449579 ER PT J AU Butrick, M Roter, D Kaphingst, K Erby, LH Haywood, C Beach, MC Levy, HP AF Butrick, Morgan Roter, Debra Kaphingst, Kimberly Erby, Lori H. Haywood, Carlton, Jr. Beach, Mary Catherine Levy, Howard P. TI Patient reactions to personalized medicine vignettes: An experimental design SO GENETICS IN MEDICINE LA English DT Article DE doctor-patient relationship; clinical vignette; genetics; race and ethnicity; personalized medicine ID AFRICAN-AMERICAN; OLDER-ADULTS; ADHERENCE; PHYSICIAN; TRUST; COMMUNICATION; DISPARITIES; BEHAVIORS; RISK; RACE AB Purpose: Translational investigation on personalized medicine is in its infancy. Exploratory studies reveal attitudinal barriers to "race-based medicine" and cautious optimism regarding genetically personalized medicine. This study describes patient responses to hypothetical conventional, race-based, or genetically personalized medicine prescriptions. Methods: Three hundred eighty-seven participants (mean age = 47 years; 46% white) recruited from a Baltimore outpatient center were randomized to this vignette-based experimental study. They were asked to imagine a doctor diagnosing a condition and prescribing them one of three medications. The outcomes are emotional response to vignette, belief in vignette medication efficacy, experience of respect, trust in the vignette physician, and adherence intention. Results: Race-based medicine vignettes were appraised more negatively than conventional vignettes across the board (Cohen's d = (-0.51)-0.57(-0.64), P < 0.001). Participants rated genetically personalized comparably with conventional medicine ((-0.14)-0.15(-0.17), P = 0.47), with the exception of reduced adherence intention to genetically personalized medicine (Cohen's d = (-0.38)-0.41(-0.44), P = 0.009). This relative reluctance to take genetically personalized medicine was pronounced for racial minorities (Cohen's d = (-0.38)-0.31(-0.25), P = 0.02) and was related to trust in the vignette physician (change in R-2 = 0.23, P < 0.001). Conclusions: This study demonstrates a relative reluctance to embrace personalized medicine technology, especially among racial minorities, and highlights enhancement of adherence through improved doctorpatient relationships. Genet Med 2011: 13(5): 421-428. C1 [Butrick, Morgan; Roter, Debra; Erby, Lori H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Butrick, Morgan] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Kaphingst, Kimberly] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Haywood, Carlton, Jr.] Johns Hopkins Univ, Sch Med, Johns Hopkins Berman Inst Bioeth, Div Hematol, Baltimore, MD USA. [Beach, Mary Catherine; Levy, Howard P.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Johns Hopkins Berman Inst Bioeth, Baltimore, MD USA. RP Butrick, M (reprint author), 920 N Calvert St, Baltimore, MD 21202 USA. EM mbutrick@jhsph.edu RI Roter, Debra/N-8830-2014; OI Haywood Jr., Carlton/0000-0002-3574-7871 FU National Human Genome Research Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Cris Price of Abt Associates provided data analysis support. These results were presented at the National Human Genome Research Scientific Retreat, Gettysburg, PA, 2009, and the National Society of Genetic Counselors Annual Education Conference, Dallas, TX, 2010. NR 41 TC 10 Z9 10 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY PY 2011 VL 13 IS 5 BP 421 EP 428 DI 10.1097/GIM.0b013e3182056133 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 761XO UT WOS:000290435700008 PM 21270639 ER PT J AU Cortes, A Danoy, P Wordsworth, B Stone, M Morgan, A Marzo-Ortega, H Ward, M Corr, M Reveille, J Weisman, M Brown, M AF Cortes, A. Danoy, P. Wordsworth, B. Stone, M. Morgan, A. Marzo-Ortega, H. Ward, M. Corr, M. Reveille, J. Weisman, M. Brown, M. TI MMP1 POLYMORPHISMS ARE ASSOCIATED WITH SEVERITY OF RADIOGRAPHIC MEASURES OF ANKYLOSING SPONDYLITIS SO INTERNAL MEDICINE JOURNAL LA English DT Meeting Abstract C1 [Cortes, A.; Danoy, P.; Brown, M.] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Wordsworth, B.] Univ Oxford, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskele, Oxford, England. [Stone, M.] Royal Natl Hosp Rheumat Dis, Bath BA1 1RL, Avon, England. [Morgan, A.; Marzo-Ortega, H.] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. [Ward, M.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Corr, M.] Univ Calif San Diego, San Diego, CA 92103 USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Weisman, M.] Cedars Sinai Med Ctr, Dept Med Rheumatol, Los Angeles, CA 90048 USA. OI Brown, Matthew A/0000-0003-0538-8211 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1444-0903 J9 INTERN MED J JI Intern. Med. J. PD MAY PY 2011 VL 41 SU 1 BP 22 EP 22 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 762OS UT WOS:000290489900074 ER PT J AU Harvie, MN Pegington, M Mattson, MP Frystyk, J Dillon, B Evans, G Cuzick, J Jebb, SA Martin, B Cutler, RG Son, TG Maudsley, S Carlson, OD Egan, JM Flyvbjerg, A Howell, A AF Harvie, M. N. Pegington, M. Mattson, M. P. Frystyk, J. Dillon, B. Evans, G. Cuzick, J. Jebb, S. A. Martin, B. Cutler, R. G. Son, T. G. Maudsley, S. Carlson, O. D. Egan, J. M. Flyvbjerg, A. Howell, A. TI The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE intermittent; continuous energy restriction; randomized; premenopausal women; insulin sensitivity ID DEPENDENT DIABETES-MELLITUS; CHRONIC CALORIC RESTRICTION; DAY FASTING REGIMENS; BREAST-CANCER; OXIDATIVE STRESS; GLYCEMIC CONTROL; GENE-EXPRESSION; HEART-DISEASE; OBESE WOMEN; BODY-WEIGHT AB Background: The problems of adherence to energy restriction in humans are well known. Objective: To compare the feasibility and effectiveness of intermittent continuous energy (IER) with continuous energy restriction (CER) for weight loss, insulin sensitivity and other metabolic disease risk markers. Design: Randomized comparison of a 25% energy restriction as IER (similar to 2710 kJ/day for 2 days/week) or CER (similar to 6276 kJ/day for 7 days/week) in 107 overweight or obese (mean (+/- s.d.) body mass index 30.6 (+/- 5.1) kg m(-2)) premenopausal women observed over a period of 6 months. Weight, anthropometry, biomarkers for breast cancer, diabetes, cardiovascular disease and dementia risk; insulin resistance (HOMA), oxidative stress markers, leptin, adiponectin, insulin-like growth factor (IGF)-1 and IGF binding proteins 1 and 2, androgens, prolactin, inflammatory markers (high sensitivity C-reactive protein and sialic acid), lipids, blood pressure and brain-derived neurotrophic factor were assessed at baseline and after 1, 3 and 6 months. Results: Last observation carried forward analysis showed that IER and CER are equally effective for weight loss: mean (95% confidence interval) weight change for IER was -6.4 (-7.9 to -4.8) kg vs -5.6 (-6.9 to -4.4) kg for CER (P-value for difference between groups 0.4). Both groups experienced comparable reductions in leptin, free androgen index, high-sensitivity C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure and increases in sex hormone binding globulin, IGF binding proteins 1 and 2. Reductions in fasting insulin and insulin resistance were modest in both groups, but greater with IER than with CER; difference between groups for fasting insulin was -1.2 (-1.4 to -1.0) mu U ml(-1) and for insulin resistance was -1.2 (-1.5 to -1.0) mu U mmol(-1) l(-1) (both P = 0.04). Conclusion: IER is as effective as CER with regard to weight loss, insulin sensitivity and other health biomarkers, and may be offered as an alternative equivalent to CER for weight loss and reducing disease risk. International Journal of Obesity (2011) 35, 714-727; doi: 10.1038/ijo.2010.171; published online 5 October 2010 C1 [Harvie, M. N.; Pegington, M.; Evans, G.; Howell, A.] Univ Hosp S Manchester NHS Fdn Trust, Genesis Prevent Ctr, Manchester M23 9LT, Lancs, England. [Mattson, M. P.; Martin, B.; Cutler, R. G.; Son, T. G.; Maudsley, S.; Carlson, O. D.; Egan, J. M.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Frystyk, J.; Flyvbjerg, A.] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark. [Frystyk, J.; Flyvbjerg, A.] Aarhus Univ Hosp, Inst Clin Med, DK-8000 Aarhus, Denmark. [Dillon, B.] Univ S Manchester Hosp, Dept Stat, Manchester M20 8LR, Lancs, England. [Cuzick, J.] Queen Marys Sch Med, Wolfson Inst Prevent Med, CRUK Ctr Epidemiol Math & Stat, London, England. [Jebb, S. A.] MRC Human Nutr Res Grp, Cambridge, England. RP Harvie, MN (reprint author), Univ Hosp S Manchester NHS Fdn Trust, Nightingale Ctr, Manchester M23 9LT, Lancs, England. EM michelle.harvie@manchester.ac.uk RI Mattson, Mark/F-6038-2012; OI Howell, Anthony/0000-0002-6233-719X; Evans, Gareth/0000-0002-8482-5784 FU Breast Cancer Campaign, World Cancer Research Fund; Genesis Appeal Manchester UK; National Institute on Aging of the NIH; Danish Research Council for Health and Disease FX Michelle N Harvie: study conception and design, trial management and manuscript preparation. Mary Pegington: running the trial, statistical analysis and manuscript preparation. Mark P Mattson: consultation, assays at NIH and manuscript preparation. Jan Frystyk and Allan Flyvbjerg: consultation, IGF-1 assays and manuscript preparation. Bernice Dillon: GEE modelling. Jack Cuzick: design of the trial, statistical advice and manuscript preparation. Gareth Evans: recruitment of subjects, consultation and manuscript preparation. Susan Jebb: MRC HNR assays, consultation and manuscript preparation. Bronwen Martin: BDNF and ghrelin assays and manuscript preparation. Roy G Cutler: AOPP and total ketone bodies assays. Tae G Son: AOPP and total ketone bodies assays. Stuart Maudsley: BDNF and ghrelin assay validation. Olga D Carlson: technical assistance with NIH assays. Josephine M Egan: BDNF and ghrelin assay validation and manuscript preparation. Anthony Howell: study conception and design, manuscript preparation. We thank Julie Morris for her invaluable statistical advice, Helen Sumner for coordinating sample storage and processing, Rosemary Greenhaugh and Jenny Affen for assisting in recruitment and sample collection, Emma Campbell for quality-of-life analysis, Lorraine Darmody, Angela Foster, Jane Eaton and Philippa Quirk for clerical support, Padraig McQuaid for help with dietary analysis. Aram Rudenski for advice on the HOMA model. We dedicate this paper to Andrew Shenton (database manager) who died tragically at a young age on 19 February 2008. Funding: Breast Cancer Campaign, World Cancer Research Fund, Genesis Appeal Manchester UK, Intramural Research Program of the National Institute on Aging of the NIH, the Danish Research Council for Health and Disease, Tanita Europe BV Middlesex UK for provision of Tanita TBF-300. NR 63 TC 96 Z9 103 U1 10 U2 81 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2011 VL 35 IS 5 BP 714 EP 727 DI 10.1038/ijo.2010.171 PG 14 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 762WX UT WOS:000290514000011 PM 20921964 ER PT J AU Persky, S Eccleston, CP AF Persky, S. Eccleston, C. P. TI Medical student bias and care recommendations for an obese versus non-obese virtual patient SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE patient-provider interaction; stigma; provider attitudes; virtual reality ID ENVIRONMENT TECHNOLOGY; GENERAL-PRACTITIONERS; PHYSICIANS ATTITUDES; WEIGHT; OVERWEIGHT; EXPERIENCES; PEOPLE; WOMEN; STIGMATIZATION; COMMUNICATION AB Objective: This study examined the independent effect of a patient's weight on medical students' attitudes, beliefs and interpersonal behavior toward the patient, in addition to the clinical recommendations they make for her care. Design: A total of 76 clinical-level medical students were randomly assigned to interact with a digital, virtual female patient who was visibly either obese or non-obese. Methods: Interactions with the patient took place in an immersive virtual (virtual reality) clinical environment that allowed standardization of all patient behaviors and characteristics except for weight. Visual contact behavior was automatically recorded during the interaction. Afterward, participants filled out a battery of self-report questionnaires. Results: Analyses revealed more negative stereotyping, less anticipated patient adherence, worse perceived health, more responsibility attributed for potentially weight-related presenting complaints and less visual contact directed toward the obese version of a virtual patient than the non-obese version of the patient. In contrast, there was no clear evidence of bias in clinical recommendations made for the patient's care. Conclusion: Biases in attitudes, beliefs and interpersonal behavior have important implications because they can influence the tone of clinical encounters and rapport in the patient-provider relationship, which can have important downstream consequences. Gaining a clear understanding of the nature and source of weight bias in the clinical encounter is an important first step toward the development of strategies to address it. International Journal of Obesity (2011) 35, 728-735; doi: 10.1038/ijo.2010.173; published online 7 September 2010 C1 [Persky, S.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Eccleston, C. P.] Syracuse Univ, Syracuse, NY USA. RP Persky, S (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Room B1B54D, Bethesda, MD 20892 USA. EM perskys@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The authors thank Colleen McBride, Nancy Stevens and Alex Cho for their insightful comments on an earlier version of this paper and Lori Bastian and Greg Feero for their valuable advice. In addition, the authors thank Laura Wagner, Studly Auguste, ShaDonna Jackson and Shea Lott for their assistance in data collection. NR 46 TC 20 Z9 20 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2011 VL 35 IS 5 BP 728 EP 735 DI 10.1038/ijo.2010.173 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 762WX UT WOS:000290514000012 PM 20820169 ER PT J AU Amoyal, NR Mason, ST Gould, NF Corry, N Mahfouz, S Barkey, A Fauerbach, JA AF Amoyal, Nicole R. Mason, Shawn T. Gould, Neda F. Corry, Nida Mahfouz, Soad Barkey, Adam Fauerbach, James A. TI Measuring Coping Behavior in Patients With Major Burn Injuries: A Psychometric Evaluation of the BCOPE SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RECENTLY DIAGNOSED PATIENTS; CLINICAL-RESEARCH; SOCIAL SUPPORT; SOUTH-AFRICA; DISTRESS; HEALTH; ADJUSTMENT; DEPRESSION; SYMPTOMS AB Burn injuries involve significant physiological, psychological, and social challenges with which individuals must cope. Although the brief COPE (BCOPE) is frequently used, knowledge of its factor structure and construct validity is limited, thus limiting confidence with interpreting results. This study assessed psychometric properties of the BCOPE in hospitalized patients with burn injury. Participants had a major burn injury (n = 362). Measures assessed coping behavior and physical, psychological, and social functioning. Exploratory factorial analysis was conducted to evaluate patterns of coping strategies. To assess construct validity, the BCOPE scale scores were correlated with the distress measures across time points. Exploratory factorial analysis revealed seven factors accounting for 51% of total variance. The pattern matrix indicated four items loaded onto factor 1 (active coping = 0.47-0.80) and four onto factor 2 (avoidant coping = 0.59-0.73). The remaining factors were consistent with original scale assignments reported by Carver (Int J Behav Med 1997; 4:92-100). Construct validity of BCOPE scales (active and avoidant) was demonstrated by their association with the Davidson trauma scale, short form-12, and satisfaction with appearance scale. The results indicate that the BCOPE is valid, reliable, and can be meaningfully interpreted. Research using these factors may improve knowledge about interrelationships among stress, coping, and outcome, thus building the evidence base for managing distress in this population. (J Burn Care Res 2011;32:392-398) C1 [Amoyal, Nicole R.] Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. [Amoyal, Nicole R.; Mason, Shawn T.; Gould, Neda F.; Corry, Nida; Mahfouz, Soad; Barkey, Adam; Fauerbach, James A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Corry, Nida] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Amoyal, NR (reprint author), Univ Rhode Isl, Canc Prevent Res Ctr, 2 Chafee Rd, Kingston, RI 02881 USA. FU National Institute on Disability and Rehabilitation Research in the Office of Special Education and Rehabilitation Services in the US Department of Education [H133A070045] FX Supported by grant H133A070045 from the National Institute on Disability and Rehabilitation Research in the Office of Special Education and Rehabilitation Services in the US Department of Education. NR 31 TC 11 Z9 11 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2011 VL 32 IS 3 BP 392 EP 398 DI 10.1097/BCR.0b013e318217f97a PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 760EZ UT WOS:000290308500021 PM 21562462 ER PT J AU De Lucca, AJ Pauli, A Schilcher, H Sien, T Bhatnagar, D Walsh, TJ AF De Lucca, Anthony J. Pauli, Alexander Schilcher, Heinz Sien, Tin Bhatnagar, Deepak Walsh, Thomas J. TI Fungicidal and Bactericidal Properties of Bisabolol and Dragosantol SO JOURNAL OF ESSENTIAL OIL RESEARCH LA English DT Article DE Arnica longifolia; Aster hesperius; Chrysothamnus nauseosus; essential oils; alpha-bisabolol; dragosantol; antimicrobial ID PSEUDOMONAS-AERUGINOSA; ANTIBACTERIAL ACTIVITY; STAPHYLOCOCCUS-AUREUS; ALPHA-BISABOLOL; ESCHERICHIA-COLI; ESSENTIAL OILS; INFECTIONS; ALCOHOLS AB alpha-Bisabolol, a natural plant sesquiterpene alcohol, and dragosantol, a racemic mixture of synthetic bisabolol, were studied for their fungicidal properties separately against the nongerminated and germinating conidia of several species of Aspergillus and Fusarium which represent problems in agriculture and medicine. Bactericidal assays against Pseudomonas aeruginosa and Staphylococcus aureus were also performed. Compared to the controls, both compounds displayed statistically significant (p < 0.001) lethality for the tested microorganisms. alpha-Bisabolol and dragosantol produced nearly 98% viability loss against the germinating conidia of A. flavus, A. fumigatus, A. niger, A. terreus, F. oxysporum, E solani, and E verticillioides (formerly E moniliforme) at, or below, 10 mu M. The viability of nongerminated E oxysporum conidia was significantly reduced. Both compounds showed very rapid and significant reduction of P. aeruginosa viability at 7.5 mu M. Staphylococcus aureus was more resistant to these compounds though significant viability loss occurred after 2 h incubation at 12.5 mu M. Minimum inhibition concentration studies (NCCIS Method-38A) showed that bisabolol inhibited the growth of clinical isolates of the dermatophytic pathogens Trichophyton tonsurans (2-8 mu g/mL), T. mentogrophytes (2-4 mu g/mL), T rubrum (0-1 mu g/mL) and Microsporum cants (0.5-2.0 mu g/mL). Results showed alpha-bisabolol and dragosantol have potent fungicidal and bactericidal properties against the tested strains. Because both compounds are safe for use in cosmetics, the data presented here suggest potential utility as antimicrobials in cosmetics, food and as a topical antifungal treatment. C1 [De Lucca, Anthony J.; Bhatnagar, Deepak] ARS, Food & Feed Res Unit, So Reg Res Ctr, USDA, New Orleans, LA USA. [Pauli, Alexander] Review Sci, Zirndorf, Germany. [Schilcher, Heinz] Free Univ Berlin, D-1000 Berlin, Germany. [Sien, Tin] NCI, NIH, Bethesda, MD 20892 USA. RP De Lucca, AJ (reprint author), ARS, Food & Feed Res Unit, So Reg Res Ctr, USDA, New Orleans, LA USA. NR 30 TC 6 Z9 6 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1041-2905 EI 2163-8152 J9 J ESSENT OIL RES JI J. Essent. Oil Res. PD MAY-JUN PY 2011 VL 23 IS 3 BP 47 EP 54 PG 8 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 762FE UT WOS:000290459400009 ER PT J AU Lamont, RF Sobel, J Mazaki-Tovi, S Kusanovic, JP Vaisbuch, E Kim, SK Uldbjerg, N Romero, R AF Lamont, Ronald F. Sobel, Jack Mazaki-Tovi, Shali Kusanovic, Juan Pedro Vaisbuch, Edi Kim, Sun Kwon Uldbjerg, Niels Romero, Roberto TI Listeriosis in human pregnancy: a systematic review SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Epidemics; foodborne; infection; Listeria monocytogenes; Listeriosis; neonate; newborn; pregnancy ID POLYMERASE-CHAIN-REACTION; HOST DEFENSE-MECHANISMS; CENTRAL-NERVOUS-SYSTEM; MONOCYTOGENES INFECTION; NEONATAL LISTERIOSIS; UNITED-STATES; PERINATAL LISTERIOSIS; EPIDEMIC LISTERIOSIS; CHANGING PATTERN; CROSS-INFECTION AB Listeria is commonly found in processed and prepared foods and listeriosis is associated with high morbidity and mortality. Preventative measures are well prescribed and monitoring and voluntary recall of contaminated products has resulted in a 44% reduction in the prevalence of perinatal listeriosis in the USA. Pregnant women are at high risk for listeriosis, but symptoms are non-specific and diagnosis is difficult. The intracellular life-cycle of Listeria protects the bacterium from host innate and adaptive immune responses. Antibiotic treatment requires agents able to penetrate, distribute, and remain stable within host cells. Prolonged use of high-dose ampicillin can significantly improve neonatal outcome. C1 [Lamont, Ronald F.; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Kim, Sun Kwon; Uldbjerg, Niels; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lamont, Ronald F.; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Kim, Sun Kwon; Uldbjerg, Niels; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Lamont, Ronald F.; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Kim, Sun Kwon; Uldbjerg, Niels; Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Sobel, Jack] Wayne State Univ, Sch Med, Dept Infect Dis, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Lamont, RF (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM rlamont@med.wayne.edu; prbchiefstaff@med.wayne.edu RI Uldbjerg, Niels/O-2038-2016; OI Uldbjerg, Niels/0000-0002-6449-6426; Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 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 159 TC 57 Z9 61 U1 2 U2 37 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD MAY PY 2011 VL 39 IS 3 BP 227 EP 236 DI 10.1515/JPM.2011.035 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 761WT UT WOS:000290432900002 PM 21517700 ER PT J AU Kirby, GM Mackay, A Grant, A Woods, P McEwen, B Khanna, C Macri, J Hayes, MA Stalker, M AF Kirby, G. M. Mackay, A. Grant, A. Woods, P. McEwen, B. Khanna, C. Macri, J. Hayes, M. A. Stalker, M. TI Concentration of Lipocalin Region of Collagen XXVII Alpha 1 in the Serum of Dogs with Hemangiosarcoma SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Article DE Cancer; Canine; Detection; Diagnosis; Prognosis ID THYMIDINE KINASE-ACTIVITY; CANINE HEMANGIOSARCOMA; LYMPHOMA; LEUKEMIA AB Background Hemangiosarcoma (HSA) is a common malignancy of dogs with characteristic early, aggressive metastasis. Diagnosis of HSA is challenging because of lack of sensitive and specific diagnostic tests. Hypothesis Specific proteins that are increased in serum of dogs with HSA might represent useful biomarkers of the disease. Animals Thirty-four dogs with HSA and 42 healthy dogs from the Ontario Veterinary College Teaching Hospital. Methods This case-control study compared serum proteins in dogs with HSA and healthy dogs. Proteins were separated by 2-dimensional difference gel electrophoresis and identified by liquid chromatography and tandem mass spectrometry. Results Western blot analysis showed that serum collagen XXVII peptide concentration in serum of dogs with large metastatic HSA burdens (1,488, 231-3,754 DU; median, minimum-maximum); was, on average, 9.5-fold higher than in healthy dogs (156; 46-2,101 DU). While concentrations for dogs with osteosarcomas (678; 124-3,251 DU), lymphomas (423; 92-2,777 DU), carcinomas (1,022; 177-3,448 DU), and inflammatory disease were also increased, values were consistently lower than those for HSA. Receiver operating characteristic curves revealed an estimated area under the curve of 83% for HSA cases whereas areas for other neoplastic and nonneoplastic diseases were nondiscriminatory. Serum collagen XXVII peptide concentration before splenectomy (1,350; 1,156-1,929 DU) was reduced after tumor removal (529; 452-562 DU) and chemotherapy but increased in 2 dogs with tumor recurrence (511-945 DU; 493-650 DU). Conclusions and Clinical Importance Collagen XXVII peptide might be useful for diagnosis and monitoring of advanced HSA. C1 [Kirby, G. M.; Mackay, A.; Grant, A.] Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. [Woods, P.] Univ Guelph, Dept Clin Studies, Guelph, ON N1G 2W1, Canada. [McEwen, B.; Stalker, M.] Univ Guelph, Hlth Anim Lab, Guelph, ON N1G 2W1, Canada. [Hayes, M. A.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Khanna, C.] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Macri, J.] McMaster Univ, Clin Prote Facil, Dept Pathol & Lab Med, Hamilton, ON, Canada. RP Kirby, GM (reprint author), Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. EM gkirby@uoguelph.ca FU OVC Pet Trust FX This research was supported by the OVC Pet Trust Fund. We thank Ann Maslen and Geraldine Higginson for their technical assistance. NR 14 TC 5 Z9 5 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAY-JUN PY 2011 VL 25 IS 3 BP 497 EP 503 DI 10.1111/j.1939-1676.2011.0709.x PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 758QE UT WOS:000290179100013 PM 21418324 ER PT J AU Kang, BT Lim, CY Gu, SH Park, HM AF Kang, B. T. Lim, C. Y. Gu, S. H. Park, H. M. TI 18F-FLUORODEOXYGLUCOSE UPTAKE OF NOMAL CANINE BRAIN WITH A HIGH-REOLUTION RESEARCH TOMOGRAPH-POSITRON EMISSION TOMOGRAPHY AND 7 T-MAGNETIC RESONANCE IMAGING FUSION SYSTEM SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kang, B. T.] NINDS, NIH, Bethesda, MD 20892 USA. [Lim, C. Y.; Gu, S. H.; Park, H. M.] Konkuk Univ, Coll Vet Med, Seoul, South Korea. RI Park, Hee-Myung/D-6222-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAY-JUN PY 2011 VL 25 IS 3 BP 731 EP 731 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 758QE UT WOS:000290179100324 ER PT J AU Paoloni, M Dhawan, D Stewart, J Nuckolls, K Lee, J Theodorescu, D Khanna, C Knapp, D AF Paoloni, M. Dhawan, D. Stewart, J. Nuckolls, K. Lee, J. Theodorescu, D. Khanna, C. Knapp, D. TI TRANSITIONAL CELL CARCINOMA COMPARATIVE GENOMICS: A MODEL FOR PERSONALIZED MEDICINE APPROACHES TO CANCER CARE SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Paoloni, M.; Nuckolls, K.; Khanna, C.] NCI, Bethesda, MD 20892 USA. [Dhawan, D.; Stewart, J.; Knapp, D.] Purdue Univ, Sch Vet Med, W Lafayette, IN 47907 USA. [Lee, J.] Univ Virginia, Charlottesville, VA USA. [Theodorescu, D.] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAY-JUN PY 2011 VL 25 IS 3 BP 746 EP 746 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 758QE UT WOS:000290179100379 ER PT J AU Sharma, CM Storz, G AF Sharma, Cynthia Mira Storz, Gisela TI Interesting twists on small RNA themes in Pseudomonas aeruginosa SO MOLECULAR MICROBIOLOGY LA English DT Editorial Material ID NONCODING RNA; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; GENE-EXPRESSION; IDENTIFICATION; TRANSLATION; ACTIVATION; REGULATOR; VIRULENCE AB P>While many of the initial studies of regulatory small RNA (sRNA) function focused on Escherichia coli and Salmonella, there is expanding characterization of sRNAs in other bacteria. These studies are revealing unique permutations of the themes found in E. coli and Salmonella. This point is nicely illustrated by the Pseudomonas aeruginosa Hfq-binding RNA, PhrS, which activates the synthesis of the key quorum sensing transcription regulator PqsR as described by Sonnleitner et al. in the current issue of Molecular Microbiology. The PhrS RNA combines features of several previously characterized sRNAs; its expression is induced by low oxygen, it encodes a small protein, and it modulates the expression of a quorum sensing regulator by preventing the formation of an inhibitory secondary structure. However, in contrast to other base pairing sRNAs that activate translation, PhrS does not act directly on pqsR but rather increases the translation of a small upstream open reading frame (uof) whose translation is coupled to pqsR. C1 [Sharma, Cynthia Mira] Univ Wurzburg, Res Ctr Infect Dis ZINF, Wurzburg, Germany. [Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD USA. RP Sharma, CM (reprint author), Univ Wurzburg, Res Ctr Infect Dis ZINF, Wurzburg, Germany. EM cynthia.sharma@uni-wuerzburg.de; storzg@mail.nih.gov RI Sharma, Cynthia/D-2869-2013; OI Sharma, Cynthia Mira/0000-0002-2321-9705; Storz, Gisela/0000-0001-6698-1241 NR 23 TC 3 Z9 3 U1 0 U2 3 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 MAY PY 2011 VL 80 IS 4 BP 855 EP 859 DI 10.1111/j.1365-2958.2011.07625.x PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 761KQ UT WOS:000290397100001 PM 21392134 ER PT J AU Chayakulkeeree, M Johnston, SA Oei, JB Lev, S Williamson, PR Wilson, CF Zuo, XM Leal, AL Vainstein, MH Meyer, W Sorrell, TC May, RC Djordjevic, JT AF Chayakulkeeree, Methee Johnston, Simon Andrew Oei, Johanes Bijosono Lev, Sophie Williamson, Peter Richard Wilson, Christabel Frewen Zuo, Xiaoming Leal, Ana Lusia Vainstein, Marilene Henning Meyer, Wieland Sorrell, Tania Christine May, Robin Charles Djordjevic, Julianne Teresa TI SEC14 is a specific requirement for secretion of phospholipase B1 and pathogenicity of Cryptococcus neoformans SO MOLECULAR MICROBIOLOGY LA English DT Article ID GPI-ANCHORED PROTEINS; CELL-WALL INTEGRITY; VIRULENCE FACTOR; LIPID RAFTS; YEAST; TRANSPORT; DISSEMINATION; MACROPHAGES; SURVIVAL; LACCASE AB P>Secreted phospholipase B1 (CnPlb1) is essential for dissemination of Cryptococcus neoformans to the central nervous system (CNS) yet essential components of its secretion machinery remain to be elucidated. Using gene deletion analysis we demonstrate that CnPlb1 secretion is dependent on the CnSEC14 product, CnSec14-1p. CnSec14-1p is a homologue of the phosphatidylinositol transfer protein ScSec14p, which is essential for secretion and viability in Saccharomyces cerevisiae. In contrast to CnPlb1, neither laccase 1-induced melanization within the cell wall nor capsule induction were negatively impacted in CnSEC14-1 deletion mutants (Cn Delta sec14-1 and Cn Delta sec14-1Cn Delta sfh5). Similar to the CnPLB1 deletion mutant (Cn Delta plb1), Cn Delta sec14-1 was hypovirulent in mice and did not disseminate to the CNS by day 14 post infection. Furthermore, macrophage expulsion of live Cn Delta sec14-1 and Cn Delta plb1 (vomocytosis) was reduced. Individual deletion of CnSEC14-2, a closely related CnSEC14-1 homologue, and CnSFH5, a distantly related SEC fourteen like homologue, did not abrogate CnPlb1 secretion or virulence. However, reconstitution of Cn Delta sec14-1 with CnSEC14-1 or CnSEC14-2 restored both phenotypes, consistent with functional genetic redundancy. We conclude that CnPlb1 secretion is SEC14-dependent and that C. neoformans preferentially exports virulence determinants to the cell periphery via distinct pathways. We also demonstrate that CnPlb1 secretion is essential for vomocytosis. C1 [Chayakulkeeree, Methee; Oei, Johanes Bijosono; Lev, Sophie; Wilson, Christabel Frewen; Zuo, Xiaoming; Leal, Ana Lusia; Meyer, Wieland; Sorrell, Tania Christine; Djordjevic, Julianne Teresa] Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, Sydney Med Sch Western, Westmead, NSW 2145, Australia. [Chayakulkeeree, Methee; Oei, Johanes Bijosono; Lev, Sophie; Wilson, Christabel Frewen; Zuo, Xiaoming; Meyer, Wieland; Sorrell, Tania Christine; Djordjevic, Julianne Teresa] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Chayakulkeeree, Methee] Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand. [Johnston, Simon Andrew; May, Robin Charles] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. [Williamson, Peter Richard] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Leal, Ana Lusia; Vainstein, Marilene Henning] Ctr Biotecnol UFRGS, Lab Biol Fungos Importancia Med & Biotecnol, BR-91501970 Porto Alegre, RS, Brazil. RP Djordjevic, JT (reprint author), Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, Sydney Med Sch Western, Westmead, NSW 2145, Australia. EM julie_djordjevic@wmi.usyd.edu.au RI Johnston, Simon/G-4515-2010; Lev, Sophie/K-3180-2012; Vainstein, Marilene/J-5452-2014; Meyer, Wieland/G-1204-2015; Leal, Ana Lusia/H-7527-2012; OI Vainstein, Marilene/0000-0002-3914-2300; Meyer, Wieland/0000-0001-9933-8340; Johnston, Simon/0000-0002-3429-9536; May, Robin/0000-0001-5364-1838 FU National Health and Medical Research Council of Australia [632634]; University of Sydney; Westmead Hospital Charitable Trust; TCS is a Sydney Medical Foundation; Medical Research Council [G0601171]; Wellcome Trust [WT088148MA]; NIH [AI45995]; Veteran's Administration; Endeavour International Postgraduate Research Scholarship (EIPRS); International Postgraduate Award (IPA); Fungal Pathogenesis; Millennium Foundation FX This work was supported by the National Health and Medical Research Council of Australia (#632634), the University of Sydney Research Grant Scheme (2008, 2009) and the Westmead Hospital Charitable Trust (2008). TCS is a Sydney Medical Foundation Fellow. RCM and SAJ are supported by the Medical Research Council (G0601171) and Wellcome Trust (WT088148MA). PRW is supported by an NIH Grant (AI45995) and a Veteran's Administration Merit Review Award. MC is supported by the Endeavour International Postgraduate Research Scholarship (EIPRS), the International Postgraduate Award (IPA), the Postgraduate Scholarship in Fungal Pathogenesis and the Millennium Foundation Stipend Enhancement Grant. We thank the Broad Institute for providing C. neoformans Serotype A sequence information, Karen Bythe-Wilson for statistical analysis, Marina Barhoumah for technical assistance and Dr Ana Traven (Monash University, Melbourne, Australia) for helpful discussion. NR 45 TC 31 Z9 32 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2011 VL 80 IS 4 BP 1088 EP 1101 DI 10.1111/j.1365-2958.2011.07632.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 761KQ UT WOS:000290397100017 PM 21453402 ER PT J AU Francis, DG Rybalchenko, V Struyk, A Cannon, SC AF Francis, David G. Rybalchenko, Volodymyr Struyk, Arie Cannon, Stephen C. TI Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia SO NEUROLOGY LA English DT Article ID GATING PORE CURRENT; SKELETAL-MUSCLE; DEPOLARIZATION; K+; CHANNELOPATHIES; INACTIVATION; TYPE-2; BRAIN; SCN4A AB Background: Hypokalemic periodic paralysis (HypoPP) is associated with mutations in either the Ca(V)1.1 calcium channel or the Na(V)1.4 sodium channel. Some Na(V)1.4 HypoPP mutations have been shown to cause an anomalous inward current that may contribute to the attacks of paralysis. Herein, we test whether disease-associated Na(V)1.4 mutations in previously untested homologous regions of the channel also give rise to the anomalous current. Methods: The functional properties of mutant Na(V)1.4 channels were studied with voltage-clamp techniques in an oocyte expression system. Results: The HypoPP mutation Na(V)1.4-R1132Q onducts an anomalous gating pore current, but the homologous R1448C mutation in paramyotonia congenita does not. Conclusions: Gating pore currents arising from missense mutations at arginine residues in the voltage sensor domains of Na V 1.4 are a common feature of HypoPP mutant channels and contribute to the attacks of paralysis. Neurology (R) 2011; 76: 1635-1641 C1 [Cannon, Stephen C.] UT SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA. [Cannon, Stephen C.] UT SW Med Ctr, Program Neurosci, Dallas, TX 75390 USA. [Francis, David G.] UT SW Med Ctr, Dept Anesthesiol, Dallas, TX 75390 USA. [Rybalchenko, Volodymyr] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Struyk, Arie] Merck Res Labs, N Wales, PA USA. RP Cannon, SC (reprint author), UT SW Med Ctr, Dept Neurol, 5323 Harry Hines, Dallas, TX 75390 USA. EM Steve.Cannon@utsouthwestern.edu FU NIH/NIAMS [AR42703]; Merck Co., Inc.; Johnson Johnson; Muscular Dystrophy Association FX Supported by the NIH/NIAMS (AR42703).; Dr. Francis and Dr. Rybalchenko report no disclosures. Dr. Struyk is an employee of Merck & Co., Inc. and receives compensation in the form of salary and stock; his spouse is an employee of Johnson & Johnson and receives compensation in the form of salary and stock; and receives research support from Merck & Co., Inc., Johnson & Johnson, and Muscular Dystrophy Association. Dr. Cannon serves on the scientific advisory board for Telethon (Italy); serves on the editorial advisory board of the Journal of General Physiology; and receives research support from the NIH/NIAMS. NR 25 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2011 VL 76 IS 19 BP 1635 EP 1641 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 761XZ UT WOS:000290437800009 PM 21490317 ER PT J AU Piknova, B Kocharyan, A Silva, A Schechter, AN AF Piknova, Barbora Kocharyan, Ara Silva, Afonso Schechter, Alan N. TI Role of nitrite in neurovascular coupling SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th Bi-Annual Conference on Approaching the Clinic - Nitrite and Nitrate Pathophysiology and Therapy CY MAY 11-13, 2011 CL Atlanta, GA C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, NIH, Bethesda, MD 20892 USA. [Kocharyan, Ara; Silva, Afonso] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY PY 2011 VL 24 SU S MA P58 BP S37 EP S37 DI 10.1016/j.niox.2011.03.289 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762HK UT WOS:000290465600059 ER PT J AU Reutov, V Sorokina, E Schechter, A AF Reutov, Valentin Sorokina, Elena Schechter, Alan TI The nitric oxide problem: From NO-synthase and nitrite-reductase systems to the nitric oxide cycle conception and cyclicity principle SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th Bi-Annual Conference on Approaching the Clinic - Nitrite and Nitrate Pathophysiology and Therapy CY MAY 11-13, 2011 CL Atlanta, GA C1 [Reutov, Valentin; Sorokina, Elena] Russian Acad Sci, Lab Funct Neurocytol, Inst Higher Nervous Act & Neurophysiol, Moscow 115569, Russia. [Schechter, Alan] NIDDKD, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY PY 2011 VL 24 SU S MA P6 BP S18 EP S18 DI 10.1016/j.niox.2011.03.237 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762HK UT WOS:000290465600007 ER PT J AU Rifkind, J Salgado, M Nagababu, E Manoharan, P AF Rifkind, Joseph Salgado, Maria Nagababu, Enika Manoharan, Periakaruppan TI The release of NO from RBCs facilitated by membrane interaction with nitrite reaction intermediates SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th Bi-Annual Conference on Approaching the Clinic - Nitrite and Nitrate Pathophysiology and Therapy CY MAY 11-13, 2011 CL Atlanta, GA C1 [Rifkind, Joseph; Salgado, Maria; Nagababu, Enika] NIA, Mol Dynam Sect, Baltimore, MD 21224 USA. [Manoharan, Periakaruppan] Indian Inst Technol, Madras 600036, Tamil Nadu, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY PY 2011 VL 24 SU S MA P56 BP S36 EP S36 DI 10.1016/j.niox.2011.03.287 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762HK UT WOS:000290465600057 ER PT J AU Sibmooh, N Srihirun, S Sriwantana, T Unchern, S Noulsri, E Pattanapanyasat, K Fucharoen, S Piknova, B Schechter, AN AF Sibmooh, Nathawut Srihirun, Sirada Sriwantana, Thanaporn Unchern, Supeenun Noulsri, Egarit Pattanapanyasat, Kovit Fucharoen, Suthat Piknova, Barbora Schechter, Alan N. TI Platelet aggregation is inhibited by nitrite reduction to nitric oxide in blood SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th Bi-Annual Conference on Approaching the Clinic - Nitrite and Nitrate Pathophysiology and Therapy CY MAY 11-13, 2011 CL Atlanta, GA C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, NIH, Mol Med Branch, Bethesda, MD 20892 USA. [Sibmooh, Nathawut; Srihirun, Sirada; Sriwantana, Thanaporn; Unchern, Supeenun] Mahidol Univ, Dept Pharmacol, Bangkok 10400, Thailand. [Noulsri, Egarit; Pattanapanyasat, Kovit] Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10400, Thailand. [Fucharoen, Suthat] Mahidol Univ, Inst Sci & Technol Res & Dev, Nakhon Pathom 10400, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY PY 2011 VL 24 SU S MA P59 BP S37 EP S37 DI 10.1016/j.niox.2011.03.290 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762HK UT WOS:000290465600060 ER PT J AU Teng, RF Sibmooh, N Piknova, B Schechter, AN Noguchi, CT AF Teng, Ruifeng Sibmooh, Nathawut Piknova, Barbora Schechter, Alan N. Noguchi, Constance Tom TI Endothelial response in acute erythropoietin treatment for cardioprotection SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th Bi-Annual Conference on Approaching the Clinic - Nitrite and Nitrate Pathophysiology and Therapy CY MAY 11-13, 2011 CL Atlanta, GA C1 [Teng, Ruifeng; Piknova, Barbora; Schechter, Alan N.; Noguchi, Constance Tom] NIDDK, NIH, Mol Med Branch, Bethesda, MD 20892 USA. [Sibmooh, Nathawut] Mahidol Univ, Fac Sci, Dept Pharmacol, Bangkok 10400, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY PY 2011 VL 24 SU S MA P53 BP S35 EP S35 DI 10.1016/j.niox.2011.03.284 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762HK UT WOS:000290465600054 ER PT J AU Tiso, M Kenney, C Tejero, J Gladwin, M AF Tiso, Mauro Kenney, Claire Tejero, Jesus Gladwin, Mark TI Deoxygenated non-symbiotic plant hemoglobins function as nitrite reductases SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th Bi-Annual Conference on Approaching the Clinic - Nitrite and Nitrate Pathophysiology and Therapy CY MAY 11-13, 2011 CL Atlanta, GA C1 [Tiso, Mauro; Tejero, Jesus; Gladwin, Mark] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA. [Tiso, Mauro] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Kenney, Claire] NHLBI, NIH, Vasc Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY PY 2011 VL 24 SU S MA P25 BP S25 EP S25 DI 10.1016/j.niox.2011.03.256 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762HK UT WOS:000290465600026 ER PT J AU Galbraith, JA Galbraith, CG AF Galbraith, James A. Galbraith, Catherine G. TI Super-resolution microscopy for nanosensing SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID STRUCTURED-ILLUMINATION MICROSCOPY; PHOTOACTIVATED LOCALIZATION MICROSCOPY; OPTICAL RECONSTRUCTION MICROSCOPY; FLUORESCENCE MICROSCOPY; STIMULATED-EMISSION; LIVING CELLS; CAULOBACTER-CRESCENTUS; DIFFRACTION-LIMIT; RESOLUTION LIMIT; STED MICROSCOPY AB The recent advances in optical microscopy enable the simultaneous visualization of thousands of structural and signaling molecules as they dynamically rearrange within living cells. Super-resolution microscopy offers an unprecedented opportunity to define the molecular mechanisms of nanosensing through direct observation of protein movement. This technology provides a real-time readout of how genetically targeted molecular perturbations affect protein interactions. As we strive to meet the challenge offered by the opportunity to ask questions about the mechanism of cell that we never thought we could answer, we need to be aware that the new technologies are still evolving. The current limitations of each technique need to be considered when matching them to specific biological questions. In this review, we briefly describe the principles of super-resolution optical microscopy and focus on comparing the characteristics of each technique that are important for their use in studying nanosensing in the cellular microenvironment. (C) 2011 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2011 3 247-255 DOI:10.1002/wnan.130 C1 [Galbraith, James A.] NINDS, NIH, Bethesda, MD 20892 USA. [Galbraith, Catherine G.] NICHD, NIH, Bethesda, MD USA. RP Galbraith, JA (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jgalbrai@ninds.nih.gov; cgalbrai@mail.nih.gov FU NINDS/NIH FX This work was supported in part by the Intramural Program of NINDS/NIH. NR 51 TC 4 Z9 4 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD MAY-JUN PY 2011 VL 3 IS 3 BP 247 EP 255 DI 10.1002/wnan.130 PG 9 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 762NI UT WOS:000290485800003 PM 21384561 ER PT J AU Lountos, GT Tropea, JE Waugh, DS AF Lountos, George T. Tropea, Joseph E. Waugh, David S. TI Structure of human dual-specificity phosphatase 27 at 2.38 angstrom resolution SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PROTEIN-TYROSINE PHOSPHATASES; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURES; CATALYTIC ROLE; DRUG TARGETS; INHIBITORS; DISEASE; GENOME; FAMILY; CANCER AB There are over 100 genes in the human genome that encode protein tyrosine phosphatases (PTPs) and approximately 60 of these are classified as dual-specificity phosphatases (DUSPs). Although many dual-specificity phosphatases are still not well characterized, novel functions have been discovered for some of them that have led to new insights into a variety of biological processes and the molecular basis for certain diseases. Indeed, as the functions of DUSPs continue to be elucidated, a growing number of them are emerging as potential therapeutic targets for diseases such as cancer, diabetes and inflammatory disorders. Here, the overexpression, purification and structure determination of DUSP27 at 2.38 angstrom resolution are presented. C1 [Lountos, George T.; Tropea, Joseph E.; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM waughd@mail.nih.gov RI Lountos, George/B-3983-2015 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX We thank Scott Cherry for technical assistance. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Electrospray mass-spectrometry experiments were conducted on the LC/ES-MS instrument maintained by the Biophysics Resource in the Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute at Frederick. X-ray diffraction data were collected on the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22-BM at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at http://www.ser-cat.org/members.html. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under contract No. W-31-109-Eng-38. NR 54 TC 10 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD MAY PY 2011 VL 67 BP 471 EP 479 DI 10.1107/S090744491100970X PN 5 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 759IY UT WOS:000290235200010 PM 21543850 ER PT J AU Lyskowski, A Oeemig, JS Jaakkonen, A Rommi, K DiMaio, F Zhou, DW Kajander, T Baker, D Wlodawer, A Goldman, A Iwai, H AF Lyskowski, Andrzej Oeemig, Jesper S. Jaakkonen, Anniina Rommi, Katariina DiMaio, Frank Zhou, Dongwen Kajander, Tommi Baker, David Wlodawer, Alexander Goldman, Adrian Iwai, Hideo TI Cloning, expression, purification, crystallization and preliminary X-ray diffraction data of the Pyrococcus horikoshii RadA intein SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID MOLECULAR-REPLACEMENT; CRYSTAL-STRUCTURE; ADENOSINE-TRIPHOSPHATASE; STRUCTURAL BASIS; PROTEIN; GENE; MECHANISM; PIPELINE; SUBUNIT; COMPLEX AB The RadA intein from the hyperthermophilic archaebacterium Pyrococcus horikoshii was cloned, expressed and purified for subsequent structure determination. The protein crystallized rapidly in several conditions. The best crystals, which diffracted to 1.75 angstrom resolution, were harvested from drops consisting of 0.1 M HEPES pH 7.5, 3.0 M NaCl and were cryoprotected with Paratone-N before flash-cooling. The collected data were processed in the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 58.1, b = 67.4, c = 82.9 angstrom. Molecular replacement with Rosetta using energy-and density-guided structure optimization provided the initial solution, which is currently under refinement. C1 [Lyskowski, Andrzej; Oeemig, Jesper S.; Jaakkonen, Anniina; Rommi, Katariina; Kajander, Tommi; Goldman, Adrian; Iwai, Hideo] Univ Helsinki, Inst Biotechnol, Res Program Struct Biol & Biophys, FIN-00014 Helsinki, Finland. [DiMaio, Frank; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Zhou, Dongwen; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Goldman, A (reprint author), Univ Helsinki, Inst Biotechnol, Res Program Struct Biol & Biophys, POB 65, FIN-00014 Helsinki, Finland. EM adrian.goldman@helsinki.fi; hideo.iwai@helsinki.fi RI Iwai, Hideo/A-6416-2009; Baker, David/K-8941-2012; OI Iwai, Hideo/0000-0001-7376-5264; Baker, David/0000-0001-7896-6217; Kajander, Tommi/0000-0002-5094-227X FU Academy of Finland [1131413]; NIH, National Cancer Institute, Center for Cancer Research; National Doctoral Programme in Informational and Structural Biology (ISB); Centre for International Mobility (CIMO); Marie Curie Fellowship under FP7 [219889] FX This work was supported in part by a grant from the Academy of Finland (1131413) and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The crystallization facility is supported by Biocenter Finland. JSO acknowledges the National Doctoral Programme in Informational and Structural Biology (ISB) and the Centre for International Mobility (CIMO) for financial support. AL was supported by Marie Curie Fellowship under FP7 (Project TrimBAT, No. 219889). NR 30 TC 2 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD MAY PY 2011 VL 67 BP 623 EP 626 DI 10.1107/S1744309111008372 PN 5 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 759JF UT WOS:000290235900023 PM 21543876 ER PT J AU Ames, NJ AF Ames, Nancy J. TI EVIDENCE TO SUPPORT TOOTH BRUSHING IN CRITICALLY ILL PATIENTS SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE-UNIT; BRONCHOALVEOLAR LAVAGE FLUID; ORAL CARE; MECHANICAL VENTILATION; PLAQUE-FORMATION; DENTAL PLAQUE; NURSING-HOMES; BACTEREMIA; HEALTH AB Tooth brushing in critically ill patients has been advocated by many as a standard of care despite the limited evidence to support this practice. Attention has been focused on oral care as the evidence accumulates to support an association between the bacteria in the oral microbiome and those respiratory pathogens that cause pneumonia. It is plausible to assume that respiratory pathogens originating in the oral cavity are aspirated into the lungs, causing infection. A recent study of the effects of a powered toothbrush on the incidence of ventilator-associated pneumonia was stopped early because of a lack of effect in the treatment group. This review summarizes the evidence that supports the effectiveness of tooth brushing in critically ill adults and children receiving mechanical ventilation. Possible reasons for the lack of benefit of tooth brushing demonstrated in clinical trials are discussed. Recommendations for future trials in critically ill patients are suggested. With increased emphasis being placed on oral care, the evidence that supports this intervention must be evaluated carefully. (American Journal of Critical Care. 2011;20:242-250) C1 NIH, Nursing & Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Ames, NJ (reprint author), NIH, Nursing & Patient Care Serv, Ctr Clin, Bldg 10,Rm 3-5627,10 Ctr Dr, Bethesda, MD 20892 USA. EM names@nih.gov FU Intramural NIH HHS [ZIA CL001143-06, ZIA CL001143-07] NR 45 TC 10 Z9 12 U1 0 U2 15 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD MAY 1 PY 2011 VL 20 IS 3 BP 242 EP 250 DI 10.4037/ajcc2011120 PG 9 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 756PO UT WOS:000290026900010 PM 21532045 ER PT J AU Fontana, RJ Sanyal, AJ Ghany, MG Bonkovsky, HL Morgan, TR Litman, HJ Reid, AE Lee, WM Naishadham, D AF Fontana, Robert J. Sanyal, Arun J. Ghany, Marc G. Bonkovsky, Herbert L. Morgan, Timothy R. Litman, Heather J. Reid, Andrea E. Lee, William M. Naishadham, Deepa CA HALT-C Trial Study Grp TI Development and Progression of Portal Hypertensive Gastropathy in Patients With Chronic Hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID VENOUS-PRESSURE GRADIENT; VIRUS-RELATED CIRRHOSIS; NATURAL-HISTORY; ADVANCED FIBROSIS; LIVER-CIRRHOSIS; THERAPY; PREVALENCE; INFECTION; TRIAL AB OBJECTIVES: The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC). METHODS: A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon alpha 2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of >= 1 point. RESULTS: During a median follow-up of 3.85 years, 50 % of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices. CONCLUSIONS: New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors. C1 [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol,Taubman Ctr 3912, Ann Arbor, MI 48109 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol, Richmond, VA USA. [Ghany, Marc G.] NIDDKD, US Dept HHS, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Internal Med, Charlotte, NC 28203 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Dept Internal Med, Long Beach, CA USA. [Litman, Heather J.; Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Reid, Andrea E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. RP Fontana, RJ (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol,Taubman Ctr 3912, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; New England Research Institutes, Watertown, MA [N01-DK-9-2328]; National Center for Research Resources, National Institutes of Health; University of Massachusetts Medical Center, Worcester, MA [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, CT [M01RR-06192]; Saint Louis University School of Medicine, St Louis, MO [N01-DK-9-2324]; Massachusetts General Hospital, Boston, MA [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center; University of Colorado Denver, School of Medicine, Aurora, CO [N01-DK-9-2327, M01RR-00051, 1 UL1 RR 025780-01]; University of California-Irvine, Irvine, CA [N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical Center, Dallas, TX [N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01]; North and Central Texas Clinical and Translational Science Initiative); University of Michigan Medical Center, Ann Arbor, MI [RR024986]; Michigan Center for Clinical and Health Research; Virginia Commonwealth University Health System, Richmond, VA [N01-DK-9-2322, M01RR-00065]; Liver Diseases Branch; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD; University of Washington, Seattle, WA [N01-DK-9-2318]; Armed Forces Institute of Pathology, Washington, DC FX This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, MEd; New England Research Institutes, Watertown, MA (contract N01-DK-9-2328): Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Linda Massey; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. by the General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional funding to conduct this study was supplied by Hoffmann-La Roche through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, MA (contract N01-DK-9-2326): Gyongyi Szabo, MD, Barbara F. Banner, MD, Maureen Cormier, RN, Donna Giansiracusa, RN; University of Connecticut Health Center, Farmington, CT (Grant no, M01RR-06192): Gloria Borders, RN, Michelle Kelley, RN, ANP; Saint Louis University School of Medicine, St Louis, MO (contract N01-DK-9-2324): Adrian M. Di Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, Debra King, RN; Massachusetts General Hospital, Boston, MA (contract N01-DK-9-2319, Grant no. M01RR-01066; Grant no. 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center): Jules L. Dienstag, MD, Raymond T. Chung, MD, Atul K. Bhan, MD, Wallis A. Molchen, David P. Lundmark; University of Colorado Denver, School of Medicine, Aurora, CO (contract N01-DK-9-2327, Grant no. M01RR-00051, Grant no. 1 UL1 RR 025780-01): Gregory T. Everson, MD, Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell Nash, MD, Jennifer DeSanto, RN, Carol McKinley, RN; University of California-Irvine, Irvine, CA (contract N01-DK-9-2320, Grant no. M01RR-00827): John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, Choon Park, RN; University of Texas Southwestern Medical Center, Dallas, TX (contract N01-DK-9-2321, Grant no. M01RR-00633, Grant no. 1 UL1 RR024982-01, North and Central Texas Clinical and Translational Science Initiative): Thomas E. Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein, RN, BSN, Nancy Liston, MPH; University of Southern California, Los Angeles, CA (contract N01-DK-9-2325, Grant no. M01RR-00043): Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol B. Jones, RN, Susan L. Milstein, RN; University of Michigan Medical Center, Ann Arbor, MI (contract N01-DK-9-2323, Grant no. M01RR-00042, Grant no. 1 UL1 RR024986, Michigan Center for Clinical and Health Research): Anna S. Lok, MD, Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, R. Tess Bonham, BS; Virginia Commonwealth University Health System, Richmond, VA (contract N01-DK-9-2322, Grant no. M01RR-00065): Mitchell L.; Shiffman, MD, RichardK. Sterling, MD, MSc, Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, Paula Smith, RN; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD: T. Jake Liang, MD, David Kleiner, MD, PhD, Yoon Park, RN, Elenita Rivera, RN, Vanessa Haynes-Williams, RN; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: James E. Everhart, MD, Leonard B. Seeff, MD, Patricia R. Robuck, PhD, Jay H. Hoofnagle, MD, Elizabeth C. Wright, PhD; University of Washington, Seattle, WA (contract N01-DK-9-2318): Chihiro Morishima, MD, David R. Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, MEd; New England Research Institutes, Watertown, MA (contract N01-DK-9-2328): Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Linda Massey; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. NR 27 TC 2 Z9 2 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2011 VL 106 IS 5 BP 884 EP 893 DI 10.1038/ajg.2010.456 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 759MP UT WOS:000290250100011 PM 21139575 ER PT J AU Esplin, S Merrell, K Goldenberg, R Lai, YL Iams, JD Mercer, B Spong, CY Miodovnik, M Simhan, HN van Dorsten, P Dombrowski, M AF Esplin, Sean Merrell, Karen Goldenberg, Robert Lai, Yinglei Iams, Jay D. Mercer, Brian Spong, Catherine Y. Miodovnik, Menachem Simhan, Hygriv N. van Dorsten, Peter Dombrowski, Mitchell CA Eunice Kennedy Shriver Natl Inst Human Dev Maternal-Fetal Med Units TI Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE amino acid sequencing; biomarker; mass spectrometry; preterm birth; proteomics ID CERVICAL-VAGINAL FLUID; INTRAAMNIOTIC INFLAMMATION; AMNIOTIC-FLUID; BIOMARKERS; INFECTION; PATTERNS AB OBJECTIVE: We sought to identify serum markers of subsequent spontaneous preterm birth (SPTB) in asymptomatic women prior to labor. STUDY DESIGN: Serum proteomics was applied to sera from 80 pregnant women sampled at 24 weeks and an additional 80 pregnant women sampled at 28 weeks. Half had uncomplicated pregnancies and half had SPTB. RESULTS: Three specific peptides arising from inter-alpha-trypsin inhibitor heavy chain 4 protein were significantly reduced in women at 24 and 28 weeks having subsequent SPTB. The most discriminating peptide had a sensitivity of 65.0% and specificity of 82.5%; odds ratio, 8.8; and 95% confidence interval, 3.1-24.8. A combination of the 3 new biomarkers and 6 previously studied biomarkers increased sensitivity to 86.5%, with a specificity of 80.6% at 28 weeks. CONCLUSION: Three novel serum markers of SPTB have been identified using serum proteomics. Using a combination of these new markers with additional markers, women at risk of SPTB can be identified weeks prior to SPTB. C1 [Esplin, Sean] Univ Utah, Hlth Sci Ctr, Sch Med, Div Maternal Fetal Med,Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Merrell, Karen] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. [Goldenberg, Robert] Univ Alabama, Birmingham, AL USA. [Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA. [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA. [Mercer, Brian] Univ Tennessee, Memphis, TN USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA. [Simhan, Hygriv N.] Univ Pittsburgh, Pittsburgh, PA USA. [van Dorsten, Peter] Med Univ S Carolina, Charleston, SC 29425 USA. [Dombrowski, Mitchell] Wayne State Univ, Detroit, MI USA. RP Esplin, S (reprint author), Univ Utah, Hlth Sci Ctr, Sch Med, Div Maternal Fetal Med,Dept Obstet & Gynecol, Room 2B200,30 N 1900 E, Salt Lake City, UT 84132 USA. EM sean.esplin@imail.org FU National Institute of Child Health and Human Development [HD21410, HD21414, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, HD27917, HD19897, HD36801]; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT FX Supported by grants from the National Institute of Child Health and Human Development (HD21410, HD21414, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, HD27917, HD19897, and HD36801). Supported in part by the Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, including fellowships to Dr Merrell, a graduate student at the time in the laboratory of Steven W. Graves, PhD. NR 15 TC 0 Z9 0 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2011 VL 204 IS 5 AR 391.e1 DI 10.1016/j.ajog.2010.09.021 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 758YZ UT WOS:000290206200019 ER PT J AU Powe, CE Ecker, J Rana, S Wang, A Ankers, E Ye, J Levine, RJ Karumanchi, A Thadhani, R AF Powe, Camille E. Ecker, Jeffrey Rana, Sarosh Wang, Alice Ankers, Elizabeth Ye, Jun Levine, Richard J. Karumanchi, Ananth Thadhani, Ravi TI Preeclampsia and the risk of large-for-gestational-age infants SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE fetal growth; gestational diabetes; large for gestational age; preeclampsia ID HEALTHY NULLIPAROUS WOMEN; FETAL GROWTH-RETARDATION; GLUCOSE-TOLERANCE; BIRTH-WEIGHT; PREGNANCY; OBESITY; CYTOTROPHOBLASTS; HYPERGLYCEMIA; HYPERTENSION; OUTCOMES AB OBJECTIVE: We sought to compare the risk of giving birth to large-for-gestational-age (LGA) infants in women with and without preeclampsia, after adjustment for obesity and glucose intolerance. STUDY DESIGN: We conducted secondary analysis of a prospective database of pregnant women with and without preeclampsia who delivered infants from 1998 through 2006 at Massachusetts General Hospital (n = 17,465). RESULTS: The risk of LGA was similar in women with and without preeclampsia (odds ratio, 0.81; 95% confidence interval, 0.59-1.14). After adjustment for body mass index, glucose intolerance, and other factors, the risk of LGA was significantly lower in women with preeclampsia compared to those without preeclampsia (odds ratio, 0.69; 95% confidence interval, 0.49-0.96). Stratified analysis in groups with a higher risk of LGA revealed that preeclampsia has a similar effect on the risk of LGA regardless of maternal obesity, glucose intolerance, parity, and race. CONCLUSION: Preeclampsia appears to be characterized by reduced, and not increased, fetal growth. C1 [Powe, Camille E.; Ankers, Elizabeth; Ye, Jun; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rana, Sarosh; Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol, Boston, MA USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. [Wang, Alice] Boston Univ, Med Ctr, Dept Pediat, Boston, MA USA. [Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, 55 Fruit St,Bullfinch 127, Boston, MA 02114 USA. EM rthadhani@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Ms Powe is a Howard Hughes Medical Institute Medical Research Training Fellow. Dr Levine receives salary support from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr Karumanchi is an investigator of the Howard Hughes Medical Institute. NR 34 TC 2 Z9 2 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2011 VL 204 IS 5 AR 425.e1 DI 10.1016/j.ajog.2010.12.030 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 758YZ UT WOS:000290206200033 PM 21371687 ER PT J AU Chantler, PD Nussbacher, A Gerstenblith, G Schulman, SP Becker, LC Ferrucci, L Fleg, JL Lakatta, EG Najjar, SS AF Chantler, Paul D. Nussbacher, Amit Gerstenblith, Gary Schulman, Steven P. Becker, Lewis C. Ferrucci, Luigi Fleg, Jerome L. Lakatta, Edward G. Najjar, Samer S. TI Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE aging; exercise ID PULSE PRESSURE RATIO; CARDIOVASCULAR-DISEASE ENTERPRISES; HEART-FAILURE; STROKE VOLUME; VASCULAR-RESISTANCE; MAJOR SHAREHOLDERS; BLOOD-VOLUME; NITRIC-OXIDE; AGE; EXERCISE AB Chantler PD, Nussbacher A, Gerstenblith G, Schulman SP, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS. Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside. Am J Physiol Heart Circ Physiol 300: H1914-H1922, 2011. First published March 4, 2011; doi:10.1152/ajpheart.01048.2010.-The coupling between arterial elastance (E(A); net afterload) and lea ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium. nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV): did not differ between old (70 +/- 8 yr. n = 15) and young (30 +/- 5 yr. n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 +/- 3.1 mmHg/ml) versus young (11.4 +/- 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 +/- 0.11) versus young (0.16 +/- 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction. C1 [Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Chantler, Paul D.] W Virginia Univ, Dept Exercise Physiol, Sch Med, Morgantown, WV 26506 USA. [Nussbacher, Amit] Univ Sao Paulo, Fac Med, Inst Heart, Div Geriatr Cardiol, Sao Paulo, Brazil. [Gerstenblith, Gary; Schulman, Steven P.; Becker, Lewis C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov FU National Institute on Aging, National Institutes of Health FX This work was supported, in part, by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 45 TC 8 Z9 8 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2011 VL 300 IS 5 BP H1914 EP H1922 DI 10.1152/ajpheart.01048.2010 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 757NA UT WOS:000290092800039 PM 21378146 ER PT J AU Gericke, A Sniatecki, JJ Mayer, VGA Goloborodko, E Patzak, A Wess, J Pfeiffer, N AF Gericke, Adrian Sniatecki, Jan J. Mayer, Veronique G. A. Goloborodko, Evgeny Patzak, Andreas Wess, Juergen Pfeiffer, Norbert TI Role of M-1, M-3, and M-5 muscarinic acetylcholine receptors in cholinergic dilation of small arteries studied with gene-targeted mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE muscarinic receptors; vasodilation; genetically altered mice ID SUBTYPES MEDIATING VASODILATION; IN-VIVO CHARACTERIZATION; MESENTERIC VASCULAR BED; KNOCKOUT MICE; CORONARY-ARTERY; BLOOD-FLOW; PHARMACOLOGICAL CHARACTERIZATION; FEMORAL-ARTERY; RELAXATION; RAT AB Gericke A, Sniatecki JJ, Mayer VG, Goloborodko E, Patzak A, Wess J, Pfeiffer N. Role of M-1, M-3, and M-5 muscarinic acetylcholine receptors in cholinergic dilation of small arteries studied with gene-targeted mice. Ant J Physiol Heart Circ Physiol 300: H1602-H1608, 2011. First published February 18, 2011; doi:10.1152/ajpheart.00982.2010.-Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of vasorelaxing agents from the endothelium. The purpose of the present study was to determine the role of M-1, M-3, and M-5 muscarinic acetylcholine receptors in vasodilation of small arteries using gene-targeted mice deficient in either of the three receptor subtypes (MIR-/-, M3R(-/-), or M5R(-/-) mice, respectively). Muscarinic receptor gene expression was determined in murine cutaneous, skeletal muscle, and renal interlobar arteries using real-time PCR. Moreover, respective arteries from M1R(-/-) M3R(-/-), M5R(-/-), and wild-type mice were isolated, cannulated with micropipettes, and pressurized. Luminal diameter was measured using video microscopy. mRNA for all five muscarinic receptor subtypes was detected in all three vascular preparations from wild-type mice. However, M-3 receptor mRNA was found to be most abundant. Acetylcholine produced dose-dependent dilation in all three vascular preparations from M1R(-/-), M5R(-/-), and wild-type mice. In contrast, cholinergic dilation was virtually abolished in arteries from M3R(-/-) mice. Deletion of either M-1, M-3, or M-5 receptor genes did not affect responses to nonmuscarinic vasodilators, such as substance P and nitroprusside. These findings provide the first direct evidence that M-3 receptors mediate cholinergic vasodilation in cutaneous, skeletal muscle, and renal interlobar arteries. in contrast, neither M-1 nor M-5 receptors appear to be involved in cholinergic responses of the three vascular preparations tested. C1 [Gericke, Adrian; Sniatecki, Jan J.; Mayer, Veronique G. A.; Goloborodko, Evgeny; Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, D-55131 Mainz, Germany. [Patzak, Andreas] Charite, Inst Vegetat Physiol, D-13353 Berlin, Germany. [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Gericke, A (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, Langenbeckstr 1, D-55131 Mainz, Germany. EM adrian.gericke@gmx.net RI Sniatecki, Jan/C-4826-2017 OI Sniatecki, Jan/0000-0001-8945-2094 FU Ernst und Berta Grimmke Foundation FX This study was supported by a grant from the Ernst und Berta Grimmke Foundation. NR 49 TC 19 Z9 21 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2011 VL 300 IS 5 BP H1602 EP H1608 DI 10.1152/ajpheart.00982.2010 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 757NA UT WOS:000290092800005 PM 21335473 ER PT J AU Chatzimoschou, A Katragkou, S Simitsopoulou, M Antachopoulos, C Georgiadou, E Walsh, TJ Roilides, E AF Chatzimoschou, Athanasios Katragkou, Spasia Simitsopoulou, Maria Antachopoulos, Charalampos Georgiadou, Elpiniki Walsh, Thomas J. Roilides, Emmanuel TI Activities of Triazole-Echinocandin Combinations against Candida Species in Biofilms and as Planktonic Cells SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL AGENTS; IN-VITRO; ALBICANS BIOFILMS; PEDIATRIC-PATIENTS; SUSCEPTIBILITY; INFECTIONS; THERAPY; EPIDEMIOLOGY; MANAGEMENT; RESISTANCE AB Biofilm formation complicates the treatment of various infections caused by Candida species. We investigated the effects of simultaneous or sequential combinations of two triazoles, voriconazole (VRC) and posaconazole (PSC), with two echinocandins, anidulafungin (AND) and caspofungin (CAS), against Candida albicans and Candida parapsilosis biofilms in comparison to their planktonic counterparts. Antifungal activity was assessed by the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide (XTT) metabolic assay. Antifungal-agent interactions were analyzed by the Bliss independence model in the simultaneous-treatment studies and by analysis of variance (ANOVA) in the sequential-treatment studies. Against C. albicans planktonic cells, the simultaneous combination of PSC (32 to 128 mg/liter) and CAS (0.008 to 0.25 mg/liter) was synergistic; the combinations of PSC (128 to 1,024 mg/liter) with AND (0.03 to 0.5 mg/liter) and VRC (32 to 512 mg/liter) with AND (0.008 to 0.03 mg/liter) were antagonistic. Against C. parapsilosis planktonic cells, the interaction between VRC (32 to 1,024 mg/liter) and CAS (1 to 16 mg/liter) was antagonistic. All simultaneous antifungal combinations demonstrated indifferent interactions against biofilms of both Candida species. Damage to biofilms of both species increased (P < 0.01) in the presence of subinhibitory concentrations of echinocandins (0.008 to 0.064 mg/liter), followed by the addition of PSC (512 mg/liter for C. albicans and 64 to 512 mg/liter for C. parapsilosis) or VRC (256 to 512 mg/liter for C. albicans and 512 mg/liter for C. parapsilosis). Triazole-echinocandin combinations do not appear to produce antagonistic effects against Candida sp. biofilms, while various significant interactions occur with their planktonic counterparts. C1 [Chatzimoschou, Athanasios; Katragkou, Spasia; Simitsopoulou, Maria; Antachopoulos, Charalampos; Georgiadou, Elpiniki; Roilides, Emmanuel] Aristotle Univ Thessaloniki, Hippokration Hosp, Infect Dis Lab, Dept Pediat 3, Thessaloniki 54642, Greece. [Walsh, Thomas J.; Roilides, Emmanuel] NIH, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Div Infect Dis, Weill Cornell Med Coll, New York, NY 10021 USA. RP Roilides, E (reprint author), Hippokrateion Hosp, Dept Pediat, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece. EM roilides@med.auth.gr FU Pfizer, Inc. FX This study was partially supported by a grant from Pfizer, Inc. NR 37 TC 22 Z9 23 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2011 VL 55 IS 5 BP 1968 EP 1974 DI 10.1128/AAC.00959-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 756NM UT WOS:000290019200019 PM 21343465 ER PT J AU Gosert, R Rinaldo, CH Wernli, M Major, EO Hirsch, HH AF Gosert, Rainer Rinaldo, Christine Hanssen Wernli, Marion Major, Eugene O. Hirsch, Hans H. TI CMX001 (1-O-Hexadecyloxypropyl-Cidofovir) Inhibits Polyomavirus JC Replication in Human Brain Progenitor-Derived Astrocytes SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACYCLIC NUCLEOSIDE PHOSPHONATES; ACTIVE ANTIRETROVIRAL THERAPY; EARLY GENE-EXPRESSION; IN-VITRO; BK REPLICATION; VIRUS MULTIPLICATION; CIDOFOVIR; CELLS; AIDS AB Polyomavirus JC (JCV) replication causes progressive multifocal leukoencephalopathy (PML), a frequently fatal brain disease in immunodeficient patients, yet antiviral drugs are lacking. We characterized the lipid conjugate 1-O-hexadecyloxypropyl-cidofovir (CMX001) regarding JCV (Mad-4) replication in human brain progenitor-derived astrocytes (PDA) and the simian virus 40 (SV40) large-T-antigen-expressing COS-7 cells up to 7 days postinfection (dpi). We examined JCV loads by PCR, the infection rate by immunofluorescence, and host cell toxicity by WST-1 and BrdU incorporation assays. Supernatants from CMX001-treated PDA demonstrated a drug concentration-dependent decrease in JCV loads and infectivity. CMX001 had only a modest effect on host cell metabolism but reduced overall BrdU incorporation. In PDA at 7 dpi, the CMX001 50% effective concentration (EC(50)) was 5.55 nM, the 50% cytotoxic concentration (CC(50)) was 184.6 nM, and the 50% selectivity index (SI(50)) was 33.3. The EC(90) was 19.7 nM, the CC(90) was 5,054 nM, and the SI(90) was 256.1. In COS-7 cells, JCV replication was faster and the EC(50) and EC(90) were 18-and 37-fold higher than those in PDA, i.e., 0.1 mu M and 0.74 mu M (CC(50), 0.67 mu M; SI(50), 6.7; CC(90), 12.2 mu M; SI(90), 16.5) at 5 dpi. We conclude that CMX001 inhibits JCV replication at concentrations in vitro that can be attained by oral administration without significant side effects in clinical studies. C1 [Gosert, Rainer; Wernli, Marion; Hirsch, Hans H.] Univ Basel, Inst Med Microbiol, Dept Biomed, CH-4003 Basel, Switzerland. [Rinaldo, Christine Hanssen] Univ Hosp N Norway, Dept Microbiol & Infect Control, Tromso, Norway. [Major, Eugene O.] NINDS, Nihon Univ, Bethesda, MD 20892 USA. [Hirsch, Hans H.] Univ Basel Hosp, CH-4031 Basel, Switzerland. RP Hirsch, HH (reprint author), Univ Basel, Inst Med Microbiol, Dept Biomed, Peterspl 10, CH-4003 Basel, Switzerland. EM hans.hirsch@unibas.ch FU Chimerix Inc. FX This work was supported by an unrestricted grant from Chimerix Inc. to H.H.H. NR 42 TC 25 Z9 25 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2011 VL 55 IS 5 BP 2129 EP 2136 DI 10.1128/AAC.00046-11 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 756NM UT WOS:000290019200040 PM 21402853 ER PT J AU Vu, BC Boyer, PL Siddiqui, MA Marquez, VE Hughes, SH AF Vu, B. Christie Boyer, Paul L. Siddiqui, Maqbool A. Marquez, Victor E. Hughes, Stephen H. TI 4 '-C-Methyl-2 '-Deoxyadenosine and 4 '-C-Ethyl-2 '-Deoxyadenosine Inhibit HIV-1 Replication SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; NUCLEOSIDE ANALOGS; MOLECULAR-MECHANISMS; STERIC HINDRANCE; DRUG-RESISTANCE; 3TC RESISTANCE; LAMIVUDINE 3TC; DNA; EXCISION AB It is important to develop new anti-HIV drugs that are effective against the existing drug-resistant mutants. Because the excision mechanism is an important pathway for resistance to nucleoside analogs, we are preparing analogs that retain a 3'-OH and can be extended after they are incorporated by the viral reverse transcriptase. We show that 4'-C-alkyl-deoxyadenosine (4'-C-alkyl-dA) compounds can be phosphorylated in cultured cells and can inhibit the replication of HIV-1 vectors: 4'-C-methyl-and 4'-C-ethyl-dA show both efficacy and selectivity against HIV-1. The compounds are also effective against viruses that replicate using reverse transcriptases (RTs) that carry nucleoside reverse transcriptase inhibitor resistance mutations, with the exception of the M184V mutant. Analysis of viral DNA synthesis in infected cells showed that viral DNA synthesis is blocked by the incorporation of either 4'-C-methyl-or 4'-C-ethyl-2'-deoxyadenosine. In vitro experiments with purified HIV-1 RT showed that 4'-C-methyl-2'-dATP can compete with dATP and that incorporation of the analog causes pausing in DNA synthesis. The 4'-C-ethyl compound also competes with dATP and shows a differential ability to block DNA synthesis on RNA and DNA templates. Experiments that measure the ability of the compounds to block DNA synthesis in infected cells suggest that this differential block to DNA synthesis also occurs in infected cells. C1 [Vu, B. Christie; Boyer, Paul L.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Siddiqui, Maqbool A.; Marquez, Victor E.] NCI, Med Chem Lab, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539, Frederick, MD 21702 USA. EM hughesst@mail.nih.gov FU NIH, National Cancer Institute; National Cancer Institute, National Institutes of Health [N01-CO-12400]; National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. This research has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. N01-CO-12400. Research in S.H.H.'s laboratory was supported by the National Cancer Institute. NR 45 TC 8 Z9 8 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2011 VL 55 IS 5 BP 2379 EP 2389 DI 10.1128/AAC.01290-10 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 756NM UT WOS:000290019200070 PM 21343443 ER PT J AU Moriyama, B Ditullio, M Wilson, E Henning, SA Penzak, SR Danner, RL Pennick, G Rinaldi, MG Zelazny, AM Gea-Banacloche, J Barrett, AJ Walsh, TJ AF Moriyama, Brad Ditullio, Marisa Wilson, Eleanor Henning, Stacey A. Penzak, Scott R. Danner, Robert L. Pennick, Gennethel Rinaldi, Michael G. Zelazny, Adrian M. Gea-Banacloche, Juan Barrett, A. John Walsh, Thomas J. TI Pharmacokinetics of Anidulafungin in Pleural Fluid during the Treatment of a Patient with Candida Empyema SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; VORICONAZOLE; PENETRATION; DIFFUSION; THORACIS AB Candida empyema is a serious complication of disseminated candidiasis. However, little is known about the intrapleural pharmacokinetics of echinocandins. We report the penetration of anidulafungin into the pleural fluid of a patient with Candida tropicalis empyema. The anidulafungin ratio for the area under the concentration-time curve from 0 h to the last measurement between pleural fluid and serum values was only 0.125 (12.5%), with pleural fluid concentrations ranging between 0.67 and 0.88 mu g/ml. C1 [Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Div Infect Dis, Weill Cornell Med Coll, New York, NY 10065 USA. New York Presbyterian Hosp, New York, NY USA. [Moriyama, Brad; Henning, Stacey A.; Penzak, Scott R.] NIH Clin Ctr, Dept Pharm, Bethesda, MD USA. [Ditullio, Marisa; Barrett, A. John] NHLBI, Bethesda, MD 20892 USA. [Wilson, Eleanor] NIAID, Bethesda, MD 20892 USA. [Danner, Robert L.] NIH Clin Ctr, Dept Crit Care Med, Bethesda, MD USA. [Pennick, Gennethel; Rinaldi, Michael G.] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. [Zelazny, Adrian M.] NIH, Ctr Clin, Microbiol Serv, Dept Lab Med, Bethesda, MD USA. [Gea-Banacloche, Juan] NCI, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), Cornell Univ, Transplantat Oncol Infect Dis Program, Div Infect Dis, Weill Cornell Med Coll, 1300 York Ave,A-421, New York, NY 10065 USA. EM thw2003@med.cornell.edu OI Wilson, Eleanor/0000-0002-4855-514X FU National Institutes of Health FX This work was supported in part by the intramural research program of the National Institutes of Health. NR 14 TC 7 Z9 7 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2011 VL 55 IS 5 BP 2478 EP 2480 DI 10.1128/AAC.01560-10 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 756NM UT WOS:000290019200095 PM 21402857 ER PT J AU Engel, KB Moore, HM AF Engel, Kelly B. Moore, Helen M. TI Effects of Preanalytical Variables on the Detection of Proteins by Immunohistochemistry in Formalin-Fixed, Paraffin-Embedded Tissue SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PATHOLOGISTS GUIDELINE RECOMMENDATIONS; MARKER-IMMUNOSTAINING INTENSITY; IN-SITU HYBRIDIZATION; NUCLEAR ANTIGEN PCNA; BREAST-CANCER; ESTROGEN-RECEPTOR; MICROWAVE FIXATION; AMERICAN-SOCIETY; CLINICAL ONCOLOGY/COLLEGE; ELECTRON-MICROSCOPY AB Context.-While formalin fixation and paraffin embedding has become a universal mechanism of tissue preservation and a gold standard for immunohistochemistry, fixation and processing variables that may confound assay effectiveness have received little attention from the scientific community. Objective.-To identify discrete steps in specimen fixation and processing that may impact immunostaining, assess the magnitude of reported effects in the literature, and highlight preanalytical variables that require further investigation. Data Sources.-Thirty-nine primary research articles that investigated immunohistochemical effects of 1 or more preanalytical variables were identified by our literature survey. Thresholds identified in the literature were then compared with published immunohistochemistry guidelines for formalin-fixed, paraffin-embedded specimens. Conclusions.-Of the 62 preanalytical variables identified, 27 were examined in published research. Meta-analysis revealed 15 preanalytical variables that were capable of impacting immunohistochemistry (including fixation delay; fixative type; time in fixative; reagents and conditions of dehydration, clearing, and paraffin impregnation; and conditions of slide drying and storage) and 12 variables with no reported influence (including the type of processor used; the number and position of specimens during dehydration, clearing, and paraffin impregnation; and the duration of paraffin block storage). Variables with antigen-dependent or inconsistent effects were highlighted. Comparison of literature-supported thresholds with published recommendations revealed (1) strong agreement among preanalytical variables for optimal immunostaining, (2) discrepancies among thresholds for adequate immunostaining, and (3) the continued need for rigorous research and comprehensive guidelines on specimen fixation, processing, and storage. C1 [Engel, Kelly B.; Moore, Helen M.] NCI, Preferred Staffing Grp, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. RP Moore, HM (reprint author), NCI, Preferred Staffing Grp, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov NR 42 TC 65 Z9 65 U1 0 U2 14 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2011 VL 135 IS 5 BP 537 EP 543 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 759DU UT WOS:000290221700005 PM 21526952 ER PT J AU Mccoy, MK Cookson, MR AF McCoy, Melissa K. Cookson, Mark R. TI DJ-1 regulation of mitochondrial function and autophagy through oxidative stress SO AUTOPHAGY LA English DT Editorial Material DE mitochondria; oxidative stress; Parkinson disease; PINK1; parkin; DJ-1 AB The dysregulation of mitochondrial function has been implicated in the pathogenesis of Parkinson disease. Mutations in the parkin, PINK1 and DJ-1 genes all result in recessive parkinsonism. Although the protein products of these genes have not been fully characterized, it has been established that all three contribute to the maintenance of mitochondrial function. PINK1 and parkin act in a common pathway to regulate the selective autophagic removal of depolarized mitochondria, but the relationship between DJ-1 and PINK1- and/or parkin-mediated effects on mitochondria and autophagy is less clear. We have shown that loss of DJ-I leads to mitochondrial phenotypes including reduced membrane potential, increased fragmentation and accumulation of autophagic markers. Supplementing DJ-1-deficient cells with glutathione reverses both mitochondrial and autophagic changes suggesting that DJ-1 may act to maintain mitochondrial function during oxidative stress and thereby alter mitochondrial dynamics and autophagy indirectly. C1 [McCoy, Melissa K.; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU Intramural NIH HHS NR 0 TC 48 Z9 49 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD MAY PY 2011 VL 7 IS 5 BP 531 EP 532 DI 10.4161/auto.7.5.14684 PG 2 WC Cell Biology SC Cell Biology GA 757LW UT WOS:000290087600009 PM 21317550 ER PT J AU Fujita, KI Srinivasula, SM AF Fujita, Ken-Ichi Srinivasula, Srinivasa M. TI TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS) SO AUTOPHAGY LA English DT Editorial Material DE p62; Nrf2; TLR4; autophagy; ALIS AB Autophagy plays an evolutionarily conserved role in host defense against pathogens. Autophagic protection mechanisms against microbes range from regulating immune signaling responses to directly targeting the pathogens for lysosomal degradation. Toll-like receptors (TLRs) that detect conserved molecular features shared by pathogens regulate several innate immune responses including autophagy. Our recent study demonstrates that autophagy reported in response to TLR4-simulation in macrophages is selective autophagy of aggresome-like induced structures (ALIS), and p62 (also known as SQSTM1) plays an essential role in this process. Treatment of macrophages with either Escherichia coli or lipopolysaccharide (LPS) results in the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), leading to an increase in the levels of p62 mRNA and protein, assembly of ALIS and their autophagic degradation. This study revealed a signaling role for p62, distinct from its known function as a bacterial-targeting factor, which might be critical for cellular stress response during infection. C1 [Fujita, Ken-Ichi; Srinivasula, Srinivasa M.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Srinivasula, SM (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. EM srinivsr@mail.nih.gov FU Intramural NIH HHS NR 0 TC 22 Z9 23 U1 1 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD MAY PY 2011 VL 7 IS 5 BP 552 EP 554 DI 10.4161/auto.7.5.15101 PG 3 WC Cell Biology SC Cell Biology GA 757LW UT WOS:000290087600017 PM 21412052 ER PT J AU Huang, J Johnson, AD O'Donnell, CJ AF Huang, Jie Johnson, Andrew D. O'Donnell, Christopher J. TI PRIMe: a method for characterization and evaluation of pleiotropic regions from multiple genome-wide association studies SO BIOINFORMATICS LA English DT Article ID GENERALIZED ESTIMATING EQUATIONS; GENETIC ASSOCIATION; CHARGE CONSORTIUM; LOCI; PHENOTYPES; TRAITS; VARIANTS; TESTS; RISK AB Motivation: The concept of pleiotropy was proposed a century ago, though up to now there have been insufficient efforts to design robust statistics and software aimed at visualizing and evaluating pleiotropy at a regional level. The Pleiotropic Region Identification Method (PRIMe) was developed to evaluate potentially pleiotropic loci based upon data from multiple genome-wide association studies (GWAS). Methods: We first provide a software tool to systematically identify and characterize genomic regions where low association P-values are observed with multiple traits. We use the term Pleiotropy Index to denote the number of traits with low association P-values at a particular genomic region. For GWAS assumed to be uncorrelated, we adopted the binomial distribution to approximate the statistical significance of the Pleiotropy Index. For GWAS conducted on traits with known correlation coefficients, simulations are performed to derive the statistical distribution of the Pleiotropy Index under the null hypothesis of no genotype-phenotype association. For six hematologic and three blood pressure traits where full GWAS results were available from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, we estimated the trait correlations and applied the simulation approach to examine genomic regions with statistical evidence of pleiotropy. We then applied the approximation approach to explore GWAS summarized in the National Human Genome Research Institute (NHGRI) GWAS Catalog. Results: By simulation, we identified pleiotropic regions including SH2B3 and BRAP (12q24.12) for hematologic and blood pressure traits. By approximation, we confirmed the genome-wide significant pleiotropy of these two regions based on the GWAS Catalog data, together with an exploration on other regions which highlights the FTO, GCKR and ABO regions. C1 [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20824 USA. [O'Donnell, Christopher J.] Harvard Univ, Div Cardiol, Sch Med, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013 FU National Heart, Lung and Blood Institute, Division of Intramural Research FX This project is supported by the National Heart, Lung and Blood Institute, Division of Intramural Research. NR 32 TC 33 Z9 36 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2011 VL 27 IS 9 BP 1201 EP 1206 DI 10.1093/bioinformatics/btr116 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 760NS UT WOS:000290331600002 PM 21398673 ER PT J AU Simon, RM Subramanian, J Li, MC Menezes, S AF Simon, Richard M. Subramanian, Jyothi Li, Ming-Chung Menezes, Supriya TI Using cross-validation to evaluate predictive accuracy of survival risk classifiers based on high-dimensional data SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE predictive medicine; survival risk classification; cross-validation; gene expression ID GENE-EXPRESSION DATA; DNA MICROARRAY DATA; ERROR ESTIMATION; MODELS; REGRESSION; SELECTION; BIAS AB Developments in whole genome biotechnology have stimulated statistical focus on prediction methods. We review here methodology for classifying patients into survival risk groups and for using cross-validation to evaluate such classifications. Measures of discrimination for survival risk models include separation of survival curves, time-dependent ROC curves and Harrell's concordance index. For high-dimensional data applications, however, computing these measures as re-substitution statistics on the same data used for model development results in highly biased estimates. Most developments in methodology for survival risk modeling with high-dimensional data have utilized separate test data sets for model evaluation. Cross-validation has sometimes been used for optimization of tuning parameters. In many applications, however, the data available are too limited for effective division into training and test sets and consequently authors have often either reported re-substitution statistics or analyzed their data using binary classification methods in order to utilize familiar cross-validation. In this article we have tried to indicate how to utilize cross-validation for the evaluation of survival risk models; specifically how to compute cross-validated estimates of survival distributions for predicted risk groups and how to compute cross-validated time-dependent ROC curves. We have also discussed evaluation of the statistical significance of a survival risk model and evaluation of whether high-dimensional genomic data adds predictive accuracy to a model based on standard covariates alone. RP Simon, RM (reprint author), NCI, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 29 TC 53 Z9 54 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 EI 1477-4054 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAY PY 2011 VL 12 IS 3 BP 203 EP 214 DI 10.1093/bib/bbr001 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 760KZ UT WOS:000290324500003 PM 21324971 ER PT J AU Moore, HM Compton, CC Alper, J Vaught, JB AF Moore, Helen M. Compton, Carolyn C. Alper, Joseph Vaught, Jimmie B. TI International Approaches to Advancing Biospecimen Science SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CANCER AB Biospecimen quality is affected by a number of preanalytical factors that may or may not be obvious to the investigator. These factors are introduced through multiple biospecimen collection, processing, and storage procedures, which can differ dramatically within and between medical institutions and biorepositories. Biospecimen Science is the emerging field of study that is attempting to quantify and control such variability. A variety of efforts are under way around the world to establish research programs, evidence-based biospecimen protocols, and standards to improve the overall quality of biospecimens for research. Cancer Epidemiol Biomarkers Prev; 20(5); 729-32. (C) 2011 AACR. C1 [Moore, Helen M.; Compton, Carolyn C.; Vaught, Jimmie B.] NCI, Off Biorepositories & Biospecimen Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Alper, Joseph] Parrottfish Consulting, Louisville, KY USA. RP Vaught, JB (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, Dept Hlth & Human Serv, 11400 Rockville Pike,Rockwall 1,Suite 700, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov; vaughtj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 15 TC 33 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 729 EP 732 DI 10.1158/1055-9965.EPI-11-0021 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000003 PM 21430299 ER PT J AU DeSantis, C Howlader, N Cronin, KA Jemal, A AF DeSantis, Carol Howlader, Nadia Cronin, Kathleen A. Jemal, Ahmedin TI Breast Cancer Incidence Rates in U.S. Women Are No Longer Declining SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN-PLUS-PROGESTIN; MENOPAUSAL HORMONE-THERAPY; POSTMENOPAUSAL WOMEN; UNITED-STATES; SCREENING MAMMOGRAPHY; RECEPTOR STATUS; COMBINED ROLES; TRENDS; TRIAL AB Background: Several publications reported breast cancer incidence rates continued to decrease among white women, following the decline of about 7% from 2002 to 2003. However, none of these reports exclusively examined the trend after 2003. In this paper, we examined breast cancer incidence rates among non-Hispanic (NH) white women from 2003 to 2007 to determine whether the decrease in breast cancer incidence rates indeed persisted through 2007. In addition, we present breast cancer incidence trends for NH black and Hispanic women and postmenopausal hormone use for all three racial/ethnic groups. Methods: Breast cancer incidence rates were calculated by race/ethnicity, age and ER status using data from the Surveillance, Epidemiology, and End Results (SEER) 12 registries for 2000 to 2007. Prevalence of postmenopausal hormone use was calculated using National Health Interview Survey data from 2000, 2005, and 2008. Results: From 2003 to 2007, overall breast cancer incidence rates did not change significantly among NH white women in any age group. However, rates increased (2.7% per year) for ER+ breast cancers in ages 40 to 49, and decreased for ER- breast cancers in ages 40 to 49 and 60 to 69. Similarly, overall breast cancer incidence rates did not change significantly for black and Hispanic women. Hormone use continued to decrease from 2005 to 2008 in all groups, although the decreases were smaller compared to those from 2000 to 2005. Conclusions: The sharp decline in breast cancer incidence rates that occurred from 2002 to 2003 among NH white women did not continue through 2007. Impact: Further studies are needed to better understand the recent breast cancer trends. Cancer Epidemiol Biomarkers Prev; 20(5); 733-9. (C) 2011 AACR. C1 [DeSantis, Carol; Jemal, Ahmedin] Amer Canc Soc, Atlanta, GA 30329 USA. [Howlader, Nadia; Cronin, Kathleen A.] NCI, Divis Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP DeSantis, C (reprint author), Amer Canc Soc, 250 Williams St NW,Suite 600, Atlanta, GA 30329 USA. EM carol.desantis@cancer.org NR 24 TC 58 Z9 59 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 733 EP 739 DI 10.1158/1055-9965.EPI-11-0061 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000004 PM 21357727 ER PT J AU Makambi, KH Agurs-Collins, T Bright-Gbebry, M Rosenberg, L Palmer, JR Adams-Campbell, LL AF Makambi, Kepher H. Agurs-Collins, Tanya Bright-Gbebry, Mireille Rosenberg, Lynn Palmer, Julie R. Adams-Campbell, Lucile L. TI Dietary Patterns and the Risk of Colorectal Adenomas: the Black Women's Health Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; COLON-CANCER RISK; POSTMENOPAUSAL BREAST-CANCER; AFRICAN-AMERICANS; PROSPECTIVE COHORT; UNITED-STATES; LIFE-STYLE; CONSUMPTION; PREVENTION; EPIDEMIOLOGY AB Background: Colorectal adenomas are benign lesions that may be precursors to colorectal cancer. No studies of African American women have investigated dietary patterns and the risk of developing colorectal adenomas. We examined data from the Black Women's Health Study to determine whether dietary patterns are associated with the risk of developing colorectal adenomas. Methods: This is a prospective cohort study of 59,000 participants followed biennially since 1995. During 155,414 person-years of follow-up from 1997 to 2007 among women who had had at least one screening colonoscopy, 620 incident cases of colorectal adenomas were identified. By using Cox regression models, we obtained incidence rate ratios (IRR) for colorectal adenoma in relation to quintiles of each of two dietary patterns, adjusting for other colorectal adenoma risk factors. Results: Two dietary patterns, Western and prudent, were utilized to assess the association between dietary intake and adenoma risk. The highest quintile of prudent diet, relative to the lowest quintile, was significantly associated with 34% lower colorectal adenoma risk overall (IRR = 0.66; 95% CI, 0.50-0.88; P(trend) < 0.01). Higher scores on the Western pattern were associated with a higher risk of developing colorectal adenoma (IRR 1.42; 95% CI, 1.09-1.85 for the highest quintile relative to the lowest; Ptrend 0.01). Conclusion: Our findings suggest that African American women may be able to reduce their risk of developing colorectal adenomas by following a prudent dietary pattern and avoiding a more Western pattern. Impact: A dietary modification could have a strong impact in colorectal adenoma prevention in African American women. Cancer Epidemiol Biomarkers Prev; 20(5); 818-25. (C)2011 AACR. C1 [Makambi, Kepher H.; Bright-Gbebry, Mireille; Adams-Campbell, Lucile L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Agurs-Collins, Tanya] NCI, Bethesda, MD 20892 USA. [Rosenberg, Lynn; Palmer, Julie R.] Boston Univ, Sch Med, Slone Epidemiol Ctr, Boston, MA 02118 USA. RP Makambi, KH (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Room 175,3800 Reservoir Rd NW, Washington, DC 20057 USA. EM khm33@georgetown.edu OI Rosenberg, Lynn/0000-0003-2760-2987; Palmer, Julie/0000-0002-6534-335X FU National Cancer Institute [CA058420] FX This study was supported by National Cancer Institute grant CA058420. NR 54 TC 11 Z9 11 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 818 EP 825 DI 10.1158/1055-9965.EPI-10-1213 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000013 PM 21357379 ER PT J AU Su, LJ Arab, L Steck, SE Fontham, ETH Schroeder, JC Bensen, JT Mohler, JL AF Su, L. Joseph Arab, Lenore Steck, Susan E. Fontham, Elizabeth T. H. Schroeder, Jane C. Bensen, Jeannette T. Mohler, James L. TI Obesity and Prostate Cancer Aggressiveness among African and Caucasian Americans in a Population-Based Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RADICAL PROSTATECTOMY; PATHOLOGICAL VARIABLES; RACIAL-DIFFERENCES; PREVENTION TRIAL; BODY-COMPOSITION; US MEN; RISK; RACE; MORTALITY; ANTIGEN AB Background: This study evaluated obesity and prostate cancer aggressiveness relationship in a population-based incident prostate cancer study. Methods: The North Carolina-Louisiana Prostate Cancer Project includes medical records data for classification of prostate cancer aggressiveness at diagnosis by using clinical criteria for 1,049 African American (AA) and 1,083 Caucasian American (CA) participants. An association between prostate cancer aggressiveness and obesity, measured using body mass indices (BMI) and waist-to-hip ratio (WHR), was assessed using ORs and 95% CIs adjusted for confounders. Results: A significantly positive association was found between prostate cancer aggressiveness and obesity. The ORs for high aggressive prostate cancer among prediagnosis obese and severely obese were 1.48 (95% CI = 1.02-2.16) and 1.98 (95% CI = 1.31-2.97), respectively, compared with normal weight research subjects. Race-stratified results suggested the association is stronger among CAs. Interaction model showed that normal weight AAs had more aggressive prostate cancer than normal weight CAs (OR = 2.69, 95% CI = 1.36-5.30); severe obesity was associated with aggressive disease in AAs (OR = 3.90, 95% CI = 1.97-7.75). WHR > 0.98 among all research subjects adjusted for race was significantly associated with high aggressive prostate cancer (OR = 1.42, 95% CI = 1.00-2.00) when compared with WHR < 0.90. The stratified result is less clear among AAs. Conclusions: This study shows a positive association between obesity and aggressive prostate cancer. AAs have more aggressive prostate cancer in general than CAs even at normal weight. Therefore, the association between obesity and aggressiveness is not as evident in AAs as in CAs. Impact: This study provides a unique opportunity to examine impact of race on obesity and high aggressive prostate cancer relationship. Cancer Epidemiol Biomarkers Prev; 20(5); 844-53. (C)2011 AACR. C1 [Su, L. Joseph; Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA USA. [Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Steck, Susan E.] Univ S Carolina, Dept Epidemiol & Biostat, Statewide Canc Prevent & Control Program, Columbia, SC 29208 USA. [Schroeder, Jane C.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Mohler, James L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Mohler, James L.] SUNY Buffalo, Sch Med & Biotechnol, Buffalo, NY 14260 USA. RP Su, LJ (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 5140, Bethesda, MD 20852 USA. EM sulj@mail.nih.gov RI Steck, Susan/G-5736-2013 FU Department of Defense [DAMD 17-03-2-0052] FX PCaP is carried out as a collaborative study supported by the Department of Defense grant DAMD 17-03-2-0052. The authors thank the staff, advisory committees, and research subjects participating in the PCaP study for their important contributions. NR 41 TC 16 Z9 17 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 844 EP 853 DI 10.1158/1055-9965.EPI-10-0684 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000016 PM 21467239 ER PT J AU Belle, FN Kampman, E McTiernan, A Bernstein, L Baumgartner, K Baumgartner, R Ambs, A Ballard-Barbash, R Neuhouser, ML AF Belle, Fabien N. Kampman, Ellen McTiernan, Anne Bernstein, Leslie Baumgartner, Kathy Baumgartner, Richard Ambs, Anita Ballard-Barbash, Rachel Neuhouser, Marian L. TI Dietary Fiber, Carbohydrates, Glycemic Index, and Glycemic Load in Relation to Breast Cancer Prognosis in the HEAL Cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID C-REACTIVE PROTEIN; WOMENS HEALTH; INSULIN-RESISTANCE; POSTMENOPAUSAL WOMEN; METABOLIC SYNDROME; SEX-HORMONES; RISK; FAT; SURVIVORS; ASSOCIATION AB Background: Dietary intake of fiber, carbohydrate, glycemic index (GI), and glycemic load (GL) may influence breast cancer survival, but consistent and convincing evidence is lacking. Methods: We investigated associations of dietary fiber, carbohydrates, GI, and GL with breast cancer prognosis among n = 688 stage 0 to IIIA breast cancer survivors in the Health, Eating, Activity, and Lifestyle (HEAL) study. Premenopausal and postmenopausal women from Western Washington State, Los Angeles County, and New Mexico participated. Usual diet was assessed with a food frequency questionnaire. Total mortality, breast cancer mortality, nonfatal recurrence, and second occurrence data were obtained from SEER (Surveillance, Epidemiology, and End Results) registries and medical records. Cox proportional hazards regression estimated multivariate-adjusted hazard ratios and 95% confidence intervals (CI). Results: During a median of 6.7 years follow-up after diagnosis, n = 106 total deaths, n = 83 breast cancer-specific deaths, and n = 82 nonfatal recurrences were confirmed. We observed an inverse association between fiber intake and mortality. Multivariate-adjusted hazard rate ratios (HRR) comparing high to low intake were 0.53 (95% CI 0.23-1.23) and 0.75 (95% CI 0.43-1.31). A threshold effect was observed whereby no additional benefit was observed for intakes of 9 g/d or more. Fiber intake was suggestively inversely associated with breast cancer-specific mortality (HRR = 0.68, 95% CI 0.27-1.70) and risk of nonfatal recurrence or second occurrence (HRR = 0.68, 95% CI 0.27-1.70), but results were not statistically significant. Conclusion: Dietary fiber was associated with a nonsignificant inverse association with breast cancer events and total mortality. Further studies to assess and confirm this relationship are needed in order to offer effective dietary strategies for breast cancer patients. Impact: Increasing dietary fiber may an effective lifestyle modification strategy for breast cancer survivors. Cancer Epidemiol Biomarkers Prev; 20(5); 890-9. (C)2011 AACR. C1 [Belle, Fabien N.; McTiernan, Anne; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Belle, Fabien N.; Kampman, Ellen] Univ Wageningen & Res Ctr, Div Human Nutr, Wageningen, Netherlands. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Baumgartner, Kathy; Baumgartner, Richard] Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY USA. [Ambs, Anita; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Neuhouser, ML (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM mneuhous@fhcrc.org RI Kampman, E./H-8057-2014; OI Belle-van Sprundel, Fabien/0000-0002-0037-4817 FU National Cancer Institute [N01-CN-75036-20, N01-PC-67010/N01-PC-35139, N01-PC-67007/N01-PC-35138, N01-PC-67009/N01-PC-35142]; NIH [T32 CA09661, M01-RR-00037]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528] FX Funding for this work was provided by National Cancer Institute contracts N01-CN-75036-20, N01-PC-67010/N01-PC-35139, N01-PC-67007/N01-PC-35138, and N01-PC-67009/N01-PC-35142 and NIH training grant T32 CA09661. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by NIH grant M01-RR-00037. Data collection for the Women's Contraceptive and Reproductive Experiences Study (CARE) at the University of Southern California was supported by the National Institute of Child Health and Human Development contract N01-HD-3-3175. Patient identification was supported in part by the California Department of Health Services grant 050Q-8709-S1528. NR 44 TC 17 Z9 17 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 890 EP 899 DI 10.1158/1055-9965.EPI-10-1278 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000021 PM 21430298 ER PT J AU Brinton, LA Gierach, GL Andaya, A Park, Y Schatzkin, A Hollenbeck, AR Spitz, MR AF Brinton, Louise A. Gierach, Gretchen L. Andaya, Abegail Park, Yikyung Schatzkin, Arthur Hollenbeck, Albert R. Spitz, Margaret R. TI Reproductive and Hormonal Factors and Lung Cancer Risk in the NIH-AARP Diet and Health Study Cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID REPLACEMENT THERAPY; CHINESE-WOMEN; POSTMENOPAUSAL WOMEN; SEX-DIFFERENCES; NURSES HEALTH; ESTROGEN; SMOKING; ADENOCARCINOMA; ASSOCIATION; PRACTITIONERS AB Background: Lung cancer exhibits unique patterns among women including high adenocarcinoma rates among nonsmokers. Inconsistent findings about hormonal factors on risk may reflect incomplete control for confounding, misclassification of exposures, or insufficient attention to variation by histology. Methods: Among 185,017 women, ages 50 to 71 years, recruited during 1995 and 1996 for the NIH-AARP (American Association of Retired Persons) Diet and Health Study, we identified 3,512 incident lung cancers (including 276 in never smokers) in follow-up through December 2006. Multivariable Cox proportional hazards models estimated relative risks (RR) and 95% CIs for self-reported hormonally related risk factors. Results: After adjustment for smoking and other confounders, subjects with late menarche were at reduced risk, with the association specific for adenocarcinomas (RR = 0.72 for menarche 15+ vs. < 11, P(trend) < 0.01). Subjects with early ages at ovarian cessation (either from natural menopause or bilateral oophorectomy) were at an increased risk for adenocarcinomas and squamous cell tumors, but the associations were strongest for smokers, suggesting either residual confounding or an enhanced effect of menopausally related factors among subjects with decreased endogenous estrogens. In contrast, we saw no relationships of risk with either parity, age at first birth, or exogenous hormone use. Conclusions: Elevated levels of hormones may adversely affect lung function early in life while assisting with cellular and immunologic responses later in life. Additional attention toward the role of hormonal factors may further our understanding of lung carcinogenesis. Impact: Our findings provide some support for a role of hormonal factors in the etiology of lung cancer, although the mechanisms appear complicated. Cancer Epidemiol Biomarkers Prev; 20(5); 900-11. (C)2011 AACR. C1 [Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Spitz, Margaret R.] Baylor Coll Med, Houston, TX 77030 USA. RP Brinton, LA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Suite 550,Room 5018, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522; Park, Yikyung/0000-0002-6281-489X FU NIH FX This investigation was supported by the intramural research program of the NIH. NR 50 TC 26 Z9 26 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 900 EP 911 DI 10.1158/1055-9965.EPI-10-1325 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000022 PM 21467241 ER PT J AU Kwon, EM Salinas, CA Kolb, S Fu, R Feng, ZD Stanford, JL Ostrander, EA AF Kwon, Erika M. Salinas, Claudia A. Kolb, Suzanne Fu, Rong Feng, Ziding Stanford, Janet L. Ostrander, Elaine A. TI Genetic Polymorphisms in Inflammation Pathway Genes and Prostate Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SIGNAL TRANSDUCER; COX-2 GENE; ASSOCIATION; CYCLOOXYGENASE-2; EXPRESSION; STAT3; CARCINOGENESIS; PROGRESSION; ACTIVATION; VARIANTS AB Background: Chronic inflammation is an important mechanism for the development and progression of prostate cancer (PC). To better understand the potential relationship between genes in the inflammation pathway and PC risk, we evaluated variants in 16 candidate genes. Methods: A total of 143 tagging and amino acid altering single nucleotide polymorphisms (SNPs) were genotyped in Caucasian and African American men participating in one of two population-based, case-control studies (n = 1,458 cases and 1,351 controls). The relative risk of PC was estimated using logistic and polytomous regression models. Results: Ten SNPs in seven genes (CXCL12, IL4, IL6, IL6ST, PTGS2, STAT3, and TNF) were nominally associated (P < 0.05) with risk of PC in Caucasians. The most significant effect on risk was seen with rs11574783 in the interleukin 6 signal transducer (IL6ST) gene (OR = 0.08, 95% CI: 0.01-0.63). Cumulatively, four SNPs in genes interleukin 4 (IL4), IL6ST, PTGS2, and signal transducer and activator of transcription 3 (STAT3) conferred a three-fold elevation in PC risk among men carrying the maximum number of high-risk alleles (OR = 2.97, 95% CI: 1.41-6.25, P(trend) = 0.0003). Risk estimates for seven SNPs varied significantly according to disease aggressiveness (P(homogeneity) < 0.05), with SNPs in AKT1, PIK3R1, and STAT3 independently associated with more aggressive PC; OR = 5.1 (95% CI: 2.29-11.40, P(trend) = 3.8 x 10(-5)) for carriers of all high-risk genotypes. Conclusions: These results suggest that variants in genes within the inflammation pathway may play a role in the development of PC, however, further studies are needed to replicate our findings. Impact: These results underline the potential importance of the inflammation pathway in PC development and progression. Cancer Epidemiol Biomarkers Prev; 20(5); 923-33. (C)2011 AACR. C1 [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Kwon, Erika M.] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD USA. [Salinas, Claudia A.; Kolb, Suzanne; Fu, Rong; Feng, Ziding; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Salinas, Claudia A.; Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Feng, Ziding; Stanford, Janet L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr,Bldg 50,Room 5351, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [RO1-CA 056678, RO1-CA092579, R03-CA121871, N01-CN-05230]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute; U.S. Department of Defense [PC06445] FX This work was supported by grants RO1-CA 056678, RO1-CA092579, and R03-CA121871 (to J.L. Stanford) and Contract N01-CN-05230 from the National Cancer Institute, with additional support provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute (E.A. Ostrander and E.M. Kwon). C.A. Salinas was supported by training grant PC06445 from the U.S. Department of Defense. NR 46 TC 31 Z9 33 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 923 EP 933 DI 10.1158/1055-9965.EPI-10-0994 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000024 PM 21430300 ER PT J AU Castle, PE Shaber, R LaMere, BJ Kinney, W Fetterma, B Poitras, N Lorey, T Schiffman, M Dunne, A Ostolaza, JM McKinney, S Burk, RD AF Castle, Philip E. Shaber, Ruth LaMere, Brandon J. Kinney, Walter Fetterma, Barbara Poitras, Nancy Lorey, Thomas Schiffman, Mark Dunne, Anne Ostolaza, Janae M. McKinney, Sharod Burk, Robert D. TI Human Papillomavirus (HPV) Genotypes in Women with Cervical Precancer and Cancer at Kaiser Permanente Northern California SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FEMALE UNIVERSITY-STUDENTS; SQUAMOUS-CELL CARCINOMA; INTRAEPITHELIAL NEOPLASIA; UNITED-STATES; INCIDENCE TRENDS; NATURAL-HISTORY; RISK-FACTORS; YOUNG-WOMEN; FOLLOW-UP; DNA AB Background: The human papillomavirus (HPV) Persistence and Progression Cohort is a natural history study of carcinogenic HPV positive women. Here, we present the HPV genotypes found in first similar to 500 cases of cervical intraepithelial neoplasia grade 3 (CIN3) or more severe disease (CIN3+) diagnosed at the study baseline. Methods: Women aged 30 and older were screened for cervical cancer using Pap smears and tested for carcinogenic HPV using Hybrid Capture 2 (HC2; Qiagen). We randomly selected women who tested HPV positive and were diagnosed with CIN3+ (n - 448) or without CIN3+ (= 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of < 3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of >= 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA. C1 [Lin, Feng-Ying C.; Chu, Chiayung; Hunt, Steven W.; Robbins, John B.; Schneerson, Rachel; Szu, Shousun C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Nguyen Duc Mao] Minist Hlth, Phu Tho Prov Hlth Serv, Hanoi, Vietnam. [Vu Dinh Thiem; Do Gia Canh; Nguyen Hong Son; Dang Duc Anh] Minist Hlth, Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. RP Lin, FYC (reprint author), NICHD, NIH, 31 Ctr Dr,Bldg 31,Rm 2A25, Bethesda, MD 20892 USA. EM Link@mail.nih.gov OI Hunt, Steven/0000-0003-3533-0627 FU Division of Intramural Research, NICHD FX We are indebted to the parents, health staff, and local leaders of Thanh Thuy District and Phu Tho Province for their support of the program and to the following contributors to the study: George Grimes, Pharmaceutical Development Section, Clinical Center, NIH; Patricia Moyer and James F. Troendle, Division of Epidemiology, Statistics and Prevention Research, NICHD; and Arthur Karpas, NICHD.; This study was supported by funds from the Division of Intramural Research, NICHD. NR 38 TC 48 Z9 50 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 730 EP 735 DI 10.1128/CVI.00532-10 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600005 PM 21411598 ER PT J AU Chandra, A Wormser, GP Marques, AR Latov, N Alaedini, A AF Chandra, Abhishek Wormser, Gary P. Marques, Adriana R. Latov, Norman Alaedini, Armin TI Anti-Borrelia burgdorferi Antibody Profile in Post-Lyme Disease Syndrome SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ANTIBIOTIC-TREATMENT; HEMATOGENOUS DISSEMINATION; MICE; OSPA; SERODIAGNOSIS; ASSOCIATION; PERSISTENCE; REACTIVITY; DIAGNOSIS; ARTHRITIS AB Patients with post-Lyme disease syndrome (PLDS) report persistent symptoms of pain, fatigue, and/or concentration and memory disturbances despite antibiotic treatment for Lyme borreliosis. The etiopathogenesis of these symptoms remains unknown and no effective therapies have been identified. We sought to examine the antiborrelia antibody profile in affected patients with the aim of finding clues to the mechanism of the syndrome and its relationship to the original spirochetal infection. Serum specimens from 54 borreliaseropositive PLDS patients were examined for antibodies to Borrelia burgdorferi proteins p18, p25, p28, p30, p31, p34, p39, p41, p45, p58, p66, p93, and VlsE by automated immunoblotting and software-assisted band analysis. The presence of serum antibodies to the 31-kDa band was further investigated by examination of reactivity against purified recombinant OspA protein. Control specimens included sera from 14 borreliaseropositive individuals with a history of early localized or disseminated Lyme disease who were symptom free (post-Lyme healthy group), as well as 20 healthy individuals without serologic evidence or history of Lyme disease. In comparison to the post-Lyme healthy group, higher frequencies of antibodies to p28 (P < 0.05), p30 (P < 0.05), p31 (P < 0.0001), and p34 (P < 0.05) proteins were found in the PLDS group. Assessment of antibody reactivity to recombinant OspA confirmed the presence of elevated levels in PLDS patients (P < 0.005). The described antiborrelia antibody profile in PLDS offers clues about the course of the antecedent infection in affected patients, which may be useful for understanding the pathogenic mechanism of the disease. C1 [Chandra, Abhishek; Latov, Norman; Alaedini, Armin] Cornell Univ, Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. [Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. [Marques, Adriana R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Alaedini, A (reprint author), Columbia Univ, Med Ctr, Dept Med, 1130 St Nicholas Ave,Room 937, New York, NY 10032 USA. EM aa819@columbia.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [AI071180-02]; NIH [N01-AI-65308] FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (grant AI071180-02 to A. Alaedini) and involved the use of specimens derived from an NIH-supported repository (contract number N01-AI-65308). It was also supported in part by the Intramural Research Program of the NIH. NR 31 TC 19 Z9 20 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 767 EP 771 DI 10.1128/CVI.00002-11 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600010 PM 21411605 ER PT J AU Zhang, SM Feng, SH Li, BJ Kim, HY Rodriguez, J Tsai, SE Lo, SC AF Zhang, Shimin Feng, Shaw-Huey Li, Bingjie Kim, Hyung-Yong Rodriguez, Joe Tsai, Shien Lo, Shyh-Ching TI In Vitro and In Vivo Studies of Monoclonal Antibodies with Prominent Bactericidal Activity against Burkholderia pseudomallei and Burkholderia mallei SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HL-60 CELLS; MELIOIDOSIS; DIFFERENTIATION; DIMETHYLSULFOXIDE; POLYSACCHARIDE; PATHOGENICITY; PROTECTION; GROWTH; SERUM; MODEL AB Our laboratory has developed more than a hundred mouse monoclonal antibodies (MAbs) against Burkholderia pseudomallei and Burkholderia mallei. These antibodies have been categorized into different groups based on their specificities and the biochemical natures of their target antigens. The current study first examined the bactericidal activities of a number of these MAbs by an in vitro opsonic assay. Then, the in vivo protective efficacy of selected MAbs was evaluated using BALB/c mice challenged intranasally with a lethal dose of the bacteria. The opsonic assay using dimethyl sulfoxide-treated human HL-60 cells as phagocytes revealed that 19 out of 47 tested MAbs (40%) have prominent bactericidal activities against B. pseudomallei and/or B. mallei. Interestingly, all MAbs with strong opsonic activities are those with specificity against either the capsular polysaccharides (PS) or the lipopolysaccharides (LPS) of the bacteria. On the other hand, none of the MAbs reacting to bacterial proteins or glycoproteins showed prominent bactericidal activity. Further study revealed that the antigenic epitopes on either the capsular PS or LPS molecules were readily available for binding in intact bacteria, while the epitopes on proteins/glycoproteins were less accessible to the MAbs. Our in vivo study showed that four MAbs reactive to either the capsular PS or LPS were highly effective in protecting mice against lethal bacterial challenge. The result is compatible with that of our in vitro study. The MAbs with the highest protective efficacy are those reactive to either the capsular PS or LPS of the Burkholderia bacteria. C1 [Zhang, Shimin; Feng, Shaw-Huey; Li, Bingjie; Kim, Hyung-Yong; Rodriguez, Joe; Tsai, Shien; Lo, Shyh-Ching] Armed Forces Inst Pathol, Amer Registry Pathol, Dept Environm & Infect Dis Sci, Washington, DC 20306 USA. RP Lo, SC (reprint author), FDA, Tissue Safety Lab Program, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 1NN06,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA. EM shyhching.lo@fda.hhs.gov RI Rodriguez Herrera, Juan Jose/I-3210-2015 FU American Registry of Pathology and Defense Threat Reduction Agency-Joint Science and Technology Office, Medical S&T Division, U.S. Department of Defense [2.10014_05_AF_B] FX This research was supported by the American Registry of Pathology and Defense Threat Reduction Agency-Joint Science and Technology Office, Medical S&T Division (2.10014_05_AF_B) of the U.S. Department of Defense. NR 30 TC 26 Z9 28 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 825 EP 834 DI 10.1128/CVI.00533-10 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600019 PM 21450976 ER PT J AU Hurst, FP Lee, JJ Jindal, RM Agodoa, LY Abbott, KC AF Hurst, Frank P. Lee, Jessica J. Jindal, Rahul M. Agodoa, Lawrence Y. Abbott, Kevin C. TI Outcomes Associated with Influenza Vaccination in the First Year after Kidney Transplantation SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ANTIBODY-RESPONSE; RECIPIENTS; DISEASE; REJECTION; MORTALITY; THERAPY; SAFE AB Background and objectives Influenza vaccination is recommended in all renal transplant recipients. However, immunosuppression in the early period post-transplant may attenuate the immunologic response to the vaccine. Additionally, it has been theorized that vaccination can induce an immune response that could trigger rejection episodes. Design, setting, participants, & measurements In a retrospective cohort of 51,730 adult Medicare primary patients who were first transplanted from January 2000 to July 2006 and followed through October 2006, we assessed Medicare claims for influenza vaccination and influenza infections, respectively. Outcomes included allograft loss and death. Results There were 9678 (18.7%) patients with claims for influenza vaccination in the first year post-transplant. Factors associated with vaccination included older age, diabetes, later year of transplant, and tacrolimus or mycophenolate at discharge. Vaccinations were less frequent among men, African Americans, highly sensitized patients, or those receiving induction immunosuppression or expanded criteria donor kidneys. Vaccination in the first year after transplant was associated with lower risk of subsequent allograft loss and death. Claims for influenza infection were reported in 310 (0.6%) patients and were not significantly associated with graft loss, although there was a trend toward death. Conclusions In the first year after renal transplantation, influenza vaccination was associated with a lower risk of subsequent allograft loss and death. Although this study cannot comment on formation of protective antibodies after vaccination, these data do not support withholding vaccination on the basis of concerns of adversely affecting allograft function. Clin J Ant Soc Nephrol 6: 1192-1197, 2011. doi: 10.2215/CJN.05430610 C1 [Hurst, Frank P.] Walter Reed Army Med Ctr, Dept Nephrol, Serv Nephrol, Washington, DC 20307 USA. [Jindal, Rahul M.] Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. [Hurst, Frank P.; Lee, Jessica J.; Abbott, Kevin C.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. [Agodoa, Lawrence Y.] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hurst, FP (reprint author), Walter Reed Army Med Ctr, Dept Nephrol, Serv Nephrol, 6900 Georgia Ave NW, Washington, DC 20307 USA. EM frank.hurst@us.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 17 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2011 VL 6 IS 5 BP 1192 EP 1197 DI 10.2215/CJN.05430610 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 761CK UT WOS:000290372600033 PM 21511837 ER PT J AU Stancakova, A Paananen, J Soininen, P Kangas, AJ Bonnycastle, LL Morken, MA Collins, FS Jackson, AU Boehnke, ML Kuusisto, J Ala-Korpela, M Laakso, M AF Stancakova, Alena Paananen, Jussi Soininen, Pasi Kangas, Antti J. Bonnycastle, Lori L. Morken, Mario A. Collins, Francis S. Jackson, Anne U. Boehnke, Michael L. Kuusisto, Johanna Ala-Korpela, Mika Laakso, Markku TI Effects of 34 Risk Loci for Type 2 Diabetes or Hyperglycemia on Lipoprotein Subclasses and Their Composition in 6,580 Nondiabetic Finnish Men SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; TRIGLYCERIDE LEVELS; CARDIOVASCULAR-DISEASE; FASTING GLUCOSE; INSULIN SENSITIVITY; REGULATORY PROTEIN; GENETIC-VARIANTS; LIPID-LEVELS; POPULATION; PLASMA AB OBJECTIVE We investigated the effects of 34 genetic risk variants for hyperglycemia/type 2 diabetes on lipoprotein subclasses and particle composition in a large population-based cohort. RESEARCH DESIGN AND METHODS The study included 6,580 nondiabetic Finnish men from the population-based Metabolic Syndrome in Men (METSIM) study (aged 57 +/- 7 years; BMI 26.8 +/- 3.7 kg/m(2)). Genotyping of 34 single nucleotide polymorphism (SNPs) for hyperglycemia/type 2 diabetes was performed. Proton nuclear magnetic resonance spectroscopy was used to measure particle concentrations of 14 lipoprotein subclasses and their composition in native serum samples. RESULTS The glucose-increasing allele of rs780094 in GCKR was significantly associated with low concentrations of VLDL particles (independently of their size) and small LDL and was nominally associated with low concentrations of intermediate-density lipoprotein, all LDL subclasses, and high concentrations of very large and large HDL particles. The glucose-increasing allele of rs174550 in FADS1 was significantly associated with high concentrations of very large and large HDL particles and nominally associated with low concentrations of all VLDL particles. SNPs rs10923931 in NOTCH2 and rs757210 in HNF1B genes showed nominal or significant associations with several lipoprotein traits. The genetic risk score of 34 SNPs was not associated with any of the lipoprotein subclasses. CONCLUSIONS Four of the 34 risk loci for type 2 diabetes or hyperglycemia (GCKR, FADS1, NOTCH2, and HNF1B) were significantly associated with lipoprotein traits. A GCKR variant predominantly affected the concentration of VLDL, and the FADS1 variant affected very large and large HDL particles. Only a limited number of risk loci for hyperglycemia/type 2 diabetes significantly affect lipoprotein metabolism. Diabetes 60:1608-1616, 2011 C1 [Stancakova, Alena; Paananen, Jussi; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Paananen, Jussi; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Soininen, Pasi; Kangas, Antti J.; Ala-Korpela, Mika] Univ Oulu, Inst Clin Med, Computat Med Res Grp, Oulu, Finland. [Soininen, Pasi; Ala-Korpela, Mika] Univ Eastern Finland, Dept Biosci, Chem Lab, NMR Metabon Lab, Kuopio, Finland. [Bonnycastle, Lori L.; Morken, Mario A.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Jackson, Anne U.; Boehnke, Michael L.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Ala-Korpela, Mika] Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland. [Ala-Korpela, Mika] Univ Oulu, Clin Res Ctr, Bioctr Oulu, Oulu, Finland. RP Laakso, M (reprint author), Univ Eastern Finland, Dept Med, Kuopio, Finland. EM markku.laakso@kuh.fi RI Soininen, Pasi/B-9716-2008; OI Paananen, Jussi/0000-0001-5100-4907 FU Academy of Finland; Finnish Diabetes Research Foundation; Finnish Cardiovascular Research Foundation; Jenny and Antti Wihuri Foundation; Kuopio University Hospital [5263, DK062370, 1Z01 HG000024] FX This work was supported by the Academy of Finland (M.L., SALVE program to M.A.K.), the Finnish Diabetes Research Foundation (M.L.), the Finnish Cardiovascular Research Foundation (M.L., M.A.-K.), the Jenny and Antti Wihuri Foundation (A.J.K.), and an EVO grant from the Kuopio University Hospital (5263), DK062370 to M.B., and 1Z01 HG000024 to F.S.C. NR 47 TC 35 Z9 38 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2011 VL 60 IS 5 BP 1608 EP 1616 DI 10.2337/db10-1655 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760UP UT WOS:000290349700030 PM 21421807 ER PT J AU Arrandale, VH Brauer, M Brook, JR Brunekreef, B Gold, DR London, SJ Miller, JD Oezkaynak, H Ries, NM Sears, MR Silverman, FS Takaro, TK AF Arrandale, Victoria H. Brauer, Michael Brook, Jeffrey R. Brunekreef, Bert Gold, Diane R. London, Stephanie J. Miller, J. David Oezkaynak, Haluk Ries, Nola M. Sears, Malcolm R. Silverman, Frances S. Takaro, Tim K. TI Exposure Assessment in Cohort Studies of Childhood Asthma SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE childhood asthma; cohort studies; exposure assessment ID GENE-ENVIRONMENT INTERACTION; GERMAN MULTICENTER ALLERGY; PIAMA BIRTH COHORT; IN-HOUSE DUST; AIR-POLLUTION; TOBACCO-SMOKE; INDOOR AIR; EARLY-LIFE; BRONCHIAL OBSTRUCTION; HOME CHARACTERISTICS AB BACKGROUND: The environment is suspected to play an important role in the development of childhood asthma. Cohort studies are a powerful observational design for studying exposure-response relationships, but their power depends in part upon the accuracy of the exposure assessment. OBJECTIVE: The purpose of this paper is to summarize and discuss issues that make accurate exposure assessment a challenge and to suggest strategies for improving exposure assessment in longitudinal cohort studies of childhood asthma and allergies. DATA SYNTHESIS: Exposures of interest need to be prioritized, because a single study cannot measure all potentially relevant exposures. Hypotheses need to be based on proposed mechanisms, critical time windows for effects, prior knowledge of physical, physiologic, and immunologic development, as well as genetic pathways potentially influenced by the exposures. Modifiable exposures are most important from the public health perspective. Given the interest in evaluating gene-environment interactions, large cohort sizes are required, and planning for data pooling across independent studies is critical. Collection of additional samples, possibly through subject participation, will permit secondary analyses. Models combining air quality, environmental, and dose data provide exposure estimates across large cohorts but can still be improved. CONCLUSIONS: Exposure is best characterized through a combination of information sources. Improving exposure assessment is critical for reducing measurement error and increasing power, which increase confidence in characterization of children at risk, leading to improved health outcomes. C1 [Brook, Jeffrey R.] Environm Canada, Air Qual Res Div, Toronto, ON M3H 5T4, Canada. [Arrandale, Victoria H.; Brook, Jeffrey R.; Silverman, Frances S.] Univ Toronto, Dalla Lana Sch Publ Hlth, Gage Occupat & Environm Hlth Unit, Toronto, ON, Canada. [Brauer, Michael] Univ British Columbia, Sch Environm Hlth, Vancouver, BC V5Z 1M9, Canada. [Brunekreef, Bert] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands. [Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Miller, J. David] Carleton Univ, Coll Nat Sci, Ottawa, ON K1S 5B6, Canada. [Oezkaynak, Haluk] US EPA, Res Triangle Pk, NC 27711 USA. [Ries, Nola M.] Univ Alberta, Hlth Law Inst, Edmonton, AB, Canada. [Ries, Nola M.] Univ Victoria, Fac Law, Victoria, BC, Canada. [Ries, Nola M.] Univ Victoria, Sch Hlth Informat Sci, Victoria, BC, Canada. [Sears, Malcolm R.] McMaster Univ, Firestone Inst Resp Hlth, Hamilton, ON, Canada. [Takaro, Tim K.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. RP Brook, JR (reprint author), Environm Canada, Air Qual Res Div, 4905 Dufferin Sreet, Toronto, ON M3H 5T4, Canada. EM Jeff.Brook@ec.gc.ca OI brunekreef, bert/0000-0001-9908-0060; Brauer, Michael/0000-0002-9103-9343; London, Stephanie/0000-0003-4911-5290 FU AllerGen NCE Inc. FX This work was supported by AllerGen NCE Inc. (the Allergy, Genes and Environment Network), a member of the Networks of Centres of Excellence Canada program. NR 99 TC 12 Z9 12 U1 1 U2 24 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2011 VL 119 IS 5 BP 591 EP 597 DI 10.1289/ehp.1002267 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 757MK UT WOS:000290089800021 PM 21081299 ER PT J AU McHale, CM Zhang, LP Lan, Q Vermeulen, R Li, GL Hubbard, AE Porter, KE Thomas, R Portier, CJ Shen, M Rappaport, SM Yin, SN Smith, MT Rothman, N AF McHale, Cliona M. Zhang, Luoping Lan, Qing Vermeulen, Roel Li, Guilan Hubbard, Alan E. Porter, Kristin E. Thomas, Reuben Portier, Christopher J. Shen, Min Rappaport, Stephen M. Yin, Songnian Smith, Martyn T. Rothman, Nathaniel TI Global Gene Expression Profiling of a Population Exposed to a Range of Benzene Levels SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE benzene; biomarker; human; microarray; transcriptomics ID NON-HODGKIN-LYMPHOMA; BONE-MARROW; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHOR; MICROARRAY; HEMATOTOXICITY; SUSCEPTIBILITY; WORKERS; RISK; TNF; CYCLOOXYGENASE-2 AB BACKGROUND: Benzene, an established cause of acute myeloid leukemia (AML), may also cause one or more lymphoid malignancies in humans. Previously, we identified genes and pathways associated with exposure to high (> 10 ppm) levels of benzene through transcriptomic analyses of blood cells from a small number of occupationally exposed workers. OBJECTIVES: The goals of this study were to identify potential biomarkers of benzene exposure and/or early effects and to elucidate mechanisms relevant to risk of hematotoxicity, leukemia, and lymphoid malignancy in occupationally exposed individuals, many of whom were exposed to benzene levels < 1 ppm, the current U.S. occupational standard. METHODS: We analyzed global gene expression in the peripheral blood mononuclear cells of 125 workers exposed to benzene levels ranging from < 1 ppm to > 10 ppm. Study design and analysis with a mixed-effects model minimized potential confounding and experimental variability. RESULTS: We observed highly significant widespread perturbation of gene expression at all exposure levels. The AML pathway was among the pathways most significantly associated with benzene exposure. Immune response pathways were associated with most exposure levels, potentially providing biological plausibility for an association between lymphoma and benzene exposure. We identified a 16-gene expression signature associated with all levels of benzene exposure. CONCLUSIONS: Our findings suggest that chronic benzene exposure, even at levels below the current U.S. occupational standard, perturbs many genes, biological processes, and pathways. These findings expand our understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia, and lymphoma and reveal relevant potential biomarkers associated with a range of exposures. C1 [McHale, Cliona M.; Zhang, Luoping; Hubbard, Alan E.; Porter, Kristin E.; Rappaport, Stephen M.; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Lan, Qing; Shen, Min; Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. [Thomas, Reuben; Portier, Christopher J.] NIEHS, Environm Syst Biol Grp, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP McHale, CM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 211 Hildebrand Hall, Berkeley, CA 94720 USA. EM cmchale@berkeley.edu RI Portier, Christopher/A-3160-2010; Vermeulen, Roel/F-8037-2011 OI Portier, Christopher/0000-0002-0954-0279; Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health (NIH) [R01ES06721, P42ES04705]; National Institute of Environmental Health Sciences [P42ES05948, P30ES10126]; National Cancer Institute; American Petroleum Institute; American Chemistry Council; law firms FX This research was supported by National Institutes of Health (NIH) grants R01ES06721 and P42ES04705 (to M.T.S.), National Institute of Environmental Health Sciences grants P42ES05948 and P30ES10126 (to S.M.R.), and the intra-mural research program of the National Cancer Institute.; G.L. has received funds from the American Petroleum Institute for consulting on benzene-related health research. S.M.R. has received consulting and expert testimony fees from law firms representing plaintiffs' cases involving exposure to benzene and has received research support from the American Petroleum Institute and the American Chemistry Council. M.T.S. has received consulting and expert testimony fees from law firms representing both plaintiffs and defendants in cases involving exposure to benzene. The other authors declare they have no actual or potential competing financial interests. NR 48 TC 34 Z9 36 U1 0 U2 18 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2011 VL 119 IS 5 BP 628 EP 634 DI 10.1289/ehp.1002546 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 757MK UT WOS:000290089800026 PM 21147609 ER PT J AU Bucher, JR Thayer, K Birnbaum, LS AF Bucher, John R. Thayer, Kristina Birnbaum, Linda S. TI The Office of Health Assessment and Translation: A Problem-Solving Resource for the National Toxicology Program SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Bucher, John R.; Thayer, Kristina; Birnbaum, Linda S.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Bucher, JR (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. EM bucher@niehs.nih.gov NR 4 TC 6 Z9 6 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2011 VL 119 IS 5 BP A196 EP A197 DI 10.1289/ehp.1103645 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 757MK UT WOS:000290089800001 PM 21531652 ER PT J AU Granata, T Cross, H Theodore, W Avanzini, G AF Granata, Tiziana Cross, Helen Theodore, William Avanzini, Giuliano TI Immune-mediated epilepsies SO EPILEPSIA LA English DT Article DE Immune-mediated disease; Inflammation; Rasmussen's encephalitis; Infantile spasms; Temporal lobe epilepsy; Hemiconvulsion-hemiplegia ID LANDAU-KLEFFNER-SYNDROME; CORTICOTROPIN-RELEASING HORMONE; ELECTRICAL STATUS EPILEPTICUS; GLUTAMIC-ACID DECARBOXYLASE; BATTEN-DISEASE; RASMUSSENS ENCEPHALITIS; LIMBIC ENCEPHALITIS; MOUSE MODEL; HEMICONVULSION-HEMIPLEGIA; TARGETED DISRUPTION AB P>A pathogenic role of immunity in epilepsies has long been suggested based on observations of the efficacy of immune-modulating treatments and, more recently, by the finding of inflammation markers including autoantibodies in individuals with a number of epileptic disorders. Clinical and experimental data suggest that both innate and adaptive immunity may be involved in epilepsy. Innate immunity represents an immediate, nonspecific host response against pathogens via activation of resident brain immune cells and inflammatory mediators. These are hypothesized to contribute to seizures and epileptogenesis. Adaptive immunity employs activation of antigen-specific B and T lymphocytes or antibodies in the context of viral infections and autoimmune disorders. In this article we critically review the evidence for pathogenic roles of adaptive immune responses in several types of epilepsy, and discuss potential mechanisms and therapeutic targets. We highlight future directions for preclinical and clinical research that are required for improved diagnosis and treatment of immune-mediated epilepsies. C1 [Granata, Tiziana] Ist Nazl Neurol Carlo Besta, Dept Child Neurol, Milan, Italy. [Cross, Helen] UCL Inst Child Hlth, Neurosci Unit, London, England. [Theodore, William] NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Avanzini, Giuliano] Ist Nazl Neurol Carlo Besta, Dept Neurophysiol, Milan, Italy. RP Granata, T (reprint author), Ist Nazl Neurol Carlo Besta, Dept Child Neurol, Milan, Italy. EM granata@istituto-besta.it OI granata, tiziana/0000-0002-0170-6836 FU Intramural NIH HHS [Z01 NS002236-32] NR 43 TC 36 Z9 39 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2011 VL 52 SU 3 BP 5 EP 11 DI 10.1111/j.1528-1167.2011.03029.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 759EY UT WOS:000290224700002 PM 21542839 ER PT J AU Kummar, S Gutierrez, ME Chen, A Turkbey, IB Allen, D Horneffer, YR Juwara, L Cao, L Yu, YK Kim, YS Trepel, J Chen, H Choyke, P Melillo, G Murgo, AJ Collins, J Doroshow, JH AF Kummar, Shivaani Gutierrez, Martin E. Chen, Alice Turkbey, Ismail B. Allen, Deborah Horneffer, Yvonne R. Juwara, Lamin Cao, Liang Yu, Yunkai Kim, Yeong Sang Trepel, Jane Chen, Helen Choyke, Peter Melillo, Giovanni Murgo, Anthony J. Collins, Jerry Doroshow, James H. TI Phase I trial of vandetanib and bevacizumab evaluating the VEGF and EGF signal transduction pathways in adults with solid tumours and lymphomas SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Clinical trial; Phase I; vandetanib; Bevacizumab; VEGF inhibitor; EGF inhibitor; ZD6474 ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; METASTATIC COLORECTAL-CANCER; FACTOR RECEPTOR; MALIGNANT-TUMORS; ZD6474; CELLS; CHEMOTHERAPY; CETUXIMAB; ANTIBODY AB Purpose: Inhibition of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) pathways may result in synergistic antitumour activity. We designed a phase I study to evaluate the combination of vandetanib, an investigational agent with activity against EGF receptor and VEGF receptor 2, and bevacizumab, a monoclonal antibody against VEGF. Experimental design: Patients with advanced solid tumours and lymphomas were enrolled. Objectives were to determine the safety and maximum tolerated dose of the combination, characterise pharmacokinetics, measure angiogenic marker changes in blood, and assess tumour blood flow using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Vandetanib was given orally once daily and bevacizumab intravenously once in every 3 weeks in 21-day cycles utilising a standard dose-escalation design. Results: Fifteen patients were enrolled, and a total of 94 cycles of therapy were administered. No protocol-defined dose-limiting toxicities were observed; due to toxicities associated with chronic dosing, hypertension, proteinuria, diarrhoea and anorexia, dose escalation was stopped at the second dose level. We observed one partial response and one minor response; 9 patients experienced stable disease. There were significant changes in plasma VEGF and placental-derived growth factor levels, and decreases in K-trans and k(ep) were observed by DCE-MRI. Conclusion: In this trial, we safely combined two targeted agents that cause dual blockade of the VEGF pathway, demonstrated preliminary evidence of clinical activity, and conducted correlative studies demonstrating anti-angiogenic effect. The recommended phase II dose was established as vandetanib 200 mg daily and bevacizumab 7.5 mg/kg every 3 weeks. Published by Elsevier Ltd. C1 [Kummar, Shivaani; Gutierrez, Martin E.; Turkbey, Ismail B.; Allen, Deborah; Horneffer, Yvonne R.; Cao, Liang; Yu, Yunkai; Kim, Yeong Sang; Trepel, Jane; Choyke, Peter; Murgo, Anthony J.; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Kummar, Shivaani; Chen, Alice; Chen, Helen; Murgo, Anthony J.; Collins, Jerry; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Juwara, Lamin; Melillo, Giovanni] NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. RP Kummar, S (reprint author), NCI, Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA. EM kummars@mail.nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [HHSN261200800001E]; PHS HHS [HHSN261200800001E] NR 25 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 2011 VL 47 IS 7 BP 997 EP 1005 DI 10.1016/j.ejca.2010.12.016 PG 9 WC Oncology SC Oncology GA 758UN UT WOS:000290192600004 PM 21247755 ER PT J AU Kataja-Tuomola, MK Kontto, JP Mannisto, S Albanes, D Virtamo, J AF Kataja-Tuomola, M. K. Kontto, J. P. Mannisto, S. Albanes, D. Virtamo, J. TI Intake of antioxidants and risk of type 2 diabetes in a cohort of male smokers SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE cohort study; epidemiology; antioxidant; diabetes ID RANDOMIZED CONTROLLED-TRIAL; POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; BETA-CAROTENE SUPPLEMENTATION; VITAMIN-E; INSULIN-RESISTANCE; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; DIETARY FLAVONOIDS; MELLITUS; WOMEN AB Background/Objectives: Oxidative stress may induce insulin resistance in peripheral tissues and impair insulin secretion from pancreatic beta-cells. Antioxidants are suggested to decrease the risk of diabetes through reduction of oxidative stress. However, only a few studies exist on dietary antioxidants and the risk of type 2 diabetes. We investigated the association of dietary antioxidants with incident type 2 diabetes in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Subject/Methods: The study cohort included 29 133 male smokers aged 50-69 years. During a median follow-up of 10.2 years 660 incident cases of diabetes were observed among the 25 505 men with a completed baseline food frequency questionnaire. Results: Dietary alpha-tocopherol, beta-tocopherol and beta-tocotrienol were positively associated with the risk of diabetes when adjusted for age and supplementation (relative risk (RR) 1.17 (95% confidence interval (CI) 0.91-1.51) P for trend 0.02; RR 1.31 (95% CI 1.02-1.68) P for trend 0.01; RR 1.28 (95% CI 1.00-1.63) P for trend 0.01, respectively), but the association disappeared after multivariate adjustment (RR 0.92 (95% CI 0.71-1.19) P for trend 0.97; RR 1.06 (95% CI 0.82-1.36) P for trend 0.48; RR 1.04 (95% CI 0.80-1.35) P for trend 0.46, respectively). Other tocopherols and tocotrienols as well as vitamin C, carotenoids, flavonols and flavones had no association with risk of diabetes. Conclusions: Dietary antioxidants were not associated with a decreased risk of incident diabetes in middle-aged male smokers. European Journal of Clinical Nutrition (2011) 65, 590-597; doi: 10.1038/ejcn.2010.283; published online 19 January 2011 C1 [Kataja-Tuomola, M. K.; Kontto, J. P.; Mannisto, S.; Virtamo, J.] Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, FIN-00300 Helsinki, Finland. [Albanes, D.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Kataja-Tuomola, MK (reprint author), Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, Mannerheimintie 164A, FIN-00300 Helsinki, Finland. EM merja.kataja-tuomola@thl.fi RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046; Kontto, Jukka/0000-0003-3899-9852 FU US Public Health Service from the National Cancer Institute, NIH [N01-CN-45165, N01-RC-45035, N01-RC-37004]; Department of Health and Human Services FX The ATBC Study was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035 and N01-RC-37004 from the National Cancer Institute, NIH and the Department of Health and Human Services. NR 41 TC 10 Z9 11 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 EI 1476-5640 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD MAY PY 2011 VL 65 IS 5 BP 590 EP 597 DI 10.1038/ejcn.2010.283 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 759MI UT WOS:000290249200005 PM 21245884 ER PT J AU Martin-Soelch, C Szczepanik, J Nugent, A Barhaghi, K Rallis, D Herscovitch, P Carson, RE Drevets, WC AF Martin-Soelch, Chantal Szczepanik, Joanna Nugent, Allison Barhaghi, Krystle Rallis, Denise Herscovitch, Peter Carson, Richard E. Drevets, Wayne C. TI Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; hemispheric; motivation; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; NUCLEUS-ACCUMBENS; C-11 RACLOPRIDE; SEX-DIFFERENCES; CONTINUOUS-INFUSION; BRAIN ASYMMETRY; PIG BRAIN; IN-VIVO; RELEASE; BINDING AB Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [11C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [11C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D(2/3) receptor binding potential (Delta BP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [11C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The Delta BP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition x lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND)) in the reward condition vs. the control condition was found only in the right ventral striatum, and the Delta BP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. C1 [Martin-Soelch, Chantal] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. [Carson, Richard E.] Yale Univ, Sch Med, PET Ctr, New Haven, CT USA. [Drevets, Wayne C.] Univ Oklahoma, Coll Med, Laureate Inst Brain Res, Dept Psychiat, Tulsa, OK USA. RP Martin-Soelch, C (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Culmannstr 8, CH-8091 Zurich, Switzerland. EM chantal.martinsoelch@usz.ch RI Carson, Richard/H-3250-2011; OI Carson, Richard/0000-0002-9338-7966; Nugent, Allison/0000-0003-2569-2480 FU National Institute of Mental Health [Z01-MH002812]; NARSAD Young Investigator Award FX We thank the staff of the PET Department for help executing the study, and Joan Williams and Michele Drevets for assistance in identifying research volunteers and evaluating their suitability for study participation. This study was supported by National Institute of Mental Health Intramural Research Program (Z01-MH002812; W. D., Principal Investigator) and a NARSAD Young Investigator Award (C.M., Principal Investigator). NR 66 TC 40 Z9 40 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2011 VL 33 IS 9 BP 1706 EP 1715 DI 10.1111/j.1460-9568.2011.07642.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 758MS UT WOS:000290169500014 PM 21453423 ER PT J AU Dunning, JP Parvaz, MA Hajcak, G Maloney, T Alia-Klein, N Woicik, PA Telang, F Wang, GJ Volkow, ND Goldstein, RZ AF Dunning, Jonathan P. Parvaz, Muhammad A. Hajcak, Greg Maloney, Thomas Alia-Klein, Nelly Woicik, Patricia A. Telang, Frank Wang, Gene-Jack Volkow, Nora D. Goldstein, Rita Z. TI Motivated attention to cocaine and emotional cues in abstinent and current cocaine users - an ERP study SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine addiction; emotional processing; human participants; late positive potential; motivated attention ID MAJOR DEPRESSIVE DISORDER; DRUG CUES; BRAIN POTENTIALS; AFFECTIVE STIMULI; VISUAL-ATTENTION; OPIATE ADDICTION; PICTURES; RESPONSES; CORTEX; DEPENDENCE AB Event-related potentials (ERPs) are a direct measure of neural activity and are ideally suited to study the time-course of attentional engagement with emotional and drug-related stimuli in addiction. In particular, the late positive potential (LPP) appears to be enhanced following cocaine-related compared with neutral stimuli in human participants with cocaine use disorders (CUD). However, previous studies have not directly compared cocaine-related with emotional stimuli while examining potential differences between abstinent and current cocaine users. The present study examined ERPs in 55 CUD (27 abstinent and 28 current users) and 29 matched healthy controls while they passively viewed pleasant, unpleasant, neutral and cocaine-related pictures. To examine the time-course of attention to these stimuli, we analysed both an early and later window in the LPP as well as the early posterior negativity (EPN), established in assessing motivated attention. Cocaine pictures elicited increased electrocortical measures of motivated attention in ways similar to affectively pleasant and unpleasant pictures in all CUD, an effect that was no longer discernible during the late LPP window for the current users. This group also exhibited deficient processing of the other emotional stimuli (early LPP window - pleasant pictures; late LPP window - pleasant and unpleasant pictures). Results were unique to the LPP and not EPN. Taken together, results support a relatively early attention bias to cocaine stimuli in cocaine-addicted individuals, further suggesting that recent cocaine use decreases such attention bias during later stages of processing but at the expense of deficient processing of other emotional stimuli. C1 [Parvaz, Muhammad A.; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Goldstein, Rita Z.] Brookhaven Natl Lab, Upton, NY 11973 USA. [Dunning, Jonathan P.; Parvaz, Muhammad A.; Hajcak, Greg] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, 30 Bell Ave, Upton, NY 11973 USA. EM rgoldstein@bnl.gov OI Parvaz, Muhammad/0000-0002-2671-2327 FU National Institute on Drug Abuse [1R01DA023579, R21DA02062]; General Clinical Research Center [5-MO1-RR-10710]; Brookhaven Science Associates, LLC. [AC02-98CHI-886]; US Department of Energy FX This study was supported by grants from the National Institute on Drug Abuse (to R.Z.G.: 1R01DA023579 and R21DA02062) and the General Clinical Research Center (5-MO1-RR-10710). This manuscript has been authored by Brookhaven Science Associates, LLC, under Contract No. DE-AC02-98CHI-886 with the US Department of Energy. The United States Government retains, and the publisher, by accepting the article for publication, acknowledges, a world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for the United States Government purposes. NR 41 TC 51 Z9 54 U1 2 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2011 VL 33 IS 9 BP 1716 EP 1723 DI 10.1111/j.1460-9568.2011.07663.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 758MS UT WOS:000290169500015 PM 21450043 ER PT J AU Rapoport, JL Gogtay, N AF Rapoport, Judith L. Gogtay, Nitin TI Childhood onset schizophrenia: support for a progressive neurodevelopmental disorder SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE Anatomic; MRI; Brain; Childhood-onset; Schizophrenia; Imaging; Progressive ID CORTICAL BRAIN-DEVELOPMENT; GRAY-MATTER LOSS; CEREBELLAR VERMIS; 1ST-EPISODE PSYCHOSIS; FUNCTIONAL CONNECTIVITY; COGNITIVE DYSMETRIA; LONGITUDINAL MRI; BIRTH-COHORT; CORTEX; ABNORMALITIES AB Structural brain abnormalities have become an established feature of schizophrenia and increasing evidence points towards the progressive nature of these abnormalities. The brain abnormalities are most profound in early onset cases, which have a severe, treatment refractory phenotype and more salient genetic features. Unique insights could thus be gained in schizophrenia pathology from studying the earliest manifestations of the illness. This paper reviews and updates the findings on anatomic brain development in patients with very early onset schizophrenia while showing preliminary data from ongoing studies. Collectively, our studies demonstrate that childhood-onset schizophrenia (COS) subjects show progressive loss of gray matter, delayed/disrupted white matter (WM) growth, and a progressive decline in cerebellar volume, some of which are shared by their healthy siblings. The developmental patterns or the 'trajectories' of brain development are often more striking than anatomic brain differences at any one point in time; highlighting the importance of longitudinal studies. The sibling findings of partially shared gray matter (GM) deficits which appear to normalize with age, along with other genetic analyses, provide evidence that the brain developmental 'patterns/trajectories' for several regions at particular ages could be useful endophenotypes (trait markers). Published by Elsevier Ltd on behalf of ISDN C1 [Rapoport, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Rm 3N202, Bethesda, MD 20892 USA. EM gogtayn@mail.nih.gov RI Gogtay, Nitin/A-3035-2008 FU Intramural NIH HHS [Z01 MH002581-17, Z99 MH999999] NR 95 TC 42 Z9 44 U1 4 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD MAY PY 2011 VL 29 IS 3 SI SI BP 251 EP 258 DI 10.1016/j.ijdevneu.2010.10.003 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 758BQ UT WOS:000290135200008 PM 20955775 ER PT J AU Thigpen, T duBois, A McAlpine, J DiSaia, P Fujiwara, K Hoskins, W Kristensen, G Mannel, R Markman, M Pfisterer, J Quinn, M Reed, N Swart, AM Berek, J Colombo, N Freyer, G Gallardo, D Plante, M Poveda, A Rubinstein, L Bacon, M Kitchener, H Stuart, GCE AF Thigpen, Tate duBois, Andreas McAlpine, Jessica DiSaia, Philip Fujiwara, Keiichi Hoskins, William Kristensen, Gunnar Mannel, Robert Markman, Maurie Pfisterer, Jacobus Quinn, Michael Reed, Nick Swart, Ann Marie Berek, Jonathan Colombo, Nicoletta Freyer, Gilles Gallardo, Dolores Plante, Marie Poveda, Andres Rubinstein, Lawrence Bacon, Monica Kitchener, Henry Stuart, Gavin C. E. CA Gynecologic Canc InterGrp TI First-Line Therapy in Ovarian Cancer Trials SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Review DE First line therapy; Ovarian cancer; Clinical trials ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; RECURRENT EPITHELIAL OVARIAN; PRIMARY PERITONEAL CANCER; PACLITAXEL-RESISTANT OVARIAN; PLATINUM-RESISTANT; OPEN-LABEL; CARCINOMA; PERSISTENT; CISPLATIN AB At the 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG) held in Vancouver, Canada, in June 2010, representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. The process focused on 13 predetermined questions. Group A, 1 of the 3 discussion groups, addressed the first 5 questions, examining first-line therapies in newly diagnosed ovarian cancer patients. A1: What are the appropriate end points for different trials (maintenance, upfront chemotherapy trials including molecular drugs)? A2: Are there any subgroups defined by tumor biology who need specific treatment options/trials? A3: Is the 2004 GCIG-recommended standard comparator arm still valid? A4: What is the role of modifying dose, schedule, and delivery of chemotherapy? A5: What role does surgery play today? C1 [Hoskins, William; Rubinstein, Lawrence] NCI, Bethesda, MD 20892 USA. RP Thigpen, T (reprint author), Univ Mississippi, Div Oncol, Sch Med, Jackson, MS 39216 USA. EM jtthigpen@att.net OI Quinn, Michael/0000-0003-0694-3870 FU Astra Zeneca; Roche; GlaxoSmithKline; Pharmamar; Ortho Biotech; Boehringer Ingelheim; Canadian Cancer Society Research Institute; Ovarian Cancer Canada; National Cancer Institute (US); Taiho; Merck; Pfizer; Amgen FX The 4th Ovarian Cancer Consensus Conference was convened by the GCIG in Vancouver, BC, Canada from June 24th-28th, 2010. Unrestricted grants were gratefully received for support of this conference from Astra Zeneca, Roche, GlaxoSmithKline, Pharmamar, Ortho Biotech, Boehringer Ingelheim, Canadian Cancer Society Research Institute, Ovarian Cancer Canada, National Cancer Institute (US), Taiho, Merck, Pfizer, and Amgen. The agenda, deliberations and final statements were developed entirely by the GCIG with no involvement from the funding sources. NR 25 TC 48 Z9 50 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAY PY 2011 VL 21 IS 4 BP 756 EP 762 DI 10.1097/IGC.0b013e31821ce75d PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 759MT UT WOS:000290250600028 PM 21543937 ER PT J AU Salo, PM Calatroni, A Gergen, PJ Hoppin, JA Sever, ML Jaramillo, R Arbes, SJ Zeldin, DC AF Salo, Paeivi M. Calatroni, Agustin Gergen, Peter J. Hoppin, Jane A. Sever, Michelle L. Jaramillo, Renee Arbes, Samuel J., Jr. Zeldin, Darryl C. TI Allergy-related outcomes in relation to serum IgE: Results from the National Health and Nutrition Examination Survey 2005-2006 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergen; allergy; allergic sensitization; serum IgE ID INHALANT ALLERGENS; NATURAL-HISTORY; UNITED-STATES; RISK-FACTORS; DUST-MITE; SKIN-TEST; US HOMES; RHINITIS; PREVALENCE; ASTHMA AB Background: The National Health and Nutrition Examination Survey (NHANES) 2005-2006 was the first population-based study to investigate levels of serum total and allergen-specific IgE in the general US population. Objective: We estimated the prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population. Methods: Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Study subjects aged 6 years and older (n = 8086) had blood taken for measurement of total IgE and 19 specific IgE levels against common aeroallergens, including Alternaria alternata, Aspergillus fumigatus, Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus), mouse and rat urine proteins, and selected foods (egg white, cow's milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgE by using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire. Results: In NHANES 2005-2006, 6.6% reported current hay fever, and 23.5% had current allergies. Allergy-related outcomes increased with increasing total IgE levels (adjusted odds ratios for a 10-fold increase in total IgE level of 1.86 [95% CI, 1.44-2.41] for hay fever and 1.64 [ 95% CI, 1.41-1.91] for allergies). Increased levels of plant-, pet-, and mold-specific IgE contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgE (adjusted odds ratio, 4.75; 95% CI, 3.83-5.88). Conclusion: In the US population self-reported allergy symptoms are most consistently associated with increased levels of plant-, pet-, and mold-specific IgE. (J Allergy Clin Immunol 2011;127:1226-35.) C1 [Salo, Paeivi M.; Hoppin, Jane A.; Sever, Michelle L.; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Calatroni, Agustin; Arbes, Samuel J., Jr.] Rho Inc, Chapel Hill, NC USA. [Gergen, Peter J.] NIAID, NIH, Bethesda, MD 20892 USA. [Jaramillo, Renee] SRA Int Inc, Durham, NC USA. RP Zeldin, DC (reprint author), NIEHS, NIH, 111 TW Alexander Dr,Room A222, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Sever, Michelle/0000-0002-2435-1214 FU National Institutes of Health, National Institute of Environmental Health Sciences FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 48 TC 72 Z9 75 U1 2 U2 21 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2011 VL 127 IS 5 BP 1226 EP U527 DI 10.1016/j.jaci.2010.12.1106 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA 756NG UT WOS:000290018600018 PM 21320720 ER PT J AU Akin, C Valent, P Metcalfe, DD AF Akin, Cem Valent, Peter Metcalfe, Dean D. TI Toward a global classification of mast cell activation diseases Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID MASTOCYTOSIS C1 [Akin, Cem] Univ Michigan, Dept Internal Med, Div Allergy & Immunol, Ann Arbor, MI 48109 USA. [Akin, Cem] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Valent, Peter] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria. [Valent, Peter] Ludwig Boltzmann Cluster Oncol, Vienna, Austria. [Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Akin, C (reprint author), Univ Michigan, Dept Internal Med, Div Allergy & Immunol, Ann Arbor, MI 48109 USA. EM dmetcalfe@niaid.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2011 VL 127 IS 5 BP 1311 EP 1312 DI 10.1016/j.jaci.2010.12.1115 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 756NG UT WOS:000290018600035 ER PT J AU Rizza, S Muniyappa, R Iantorno, M Kim, JA Chen, H Pullikotil, P Senese, N Tesauro, M Lauro, D Cardillo, C Quon, MJ AF Rizza, Stefano Muniyappa, Ranganath Iantorno, Micaela Kim, Jeong-a Chen, Hui Pullikotil, Philomena Senese, Nicoletta Tesauro, Manfredi Lauro, Davide Cardillo, Carmine Quon, Michael J. TI Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE-RATS; SERUM TRIGLYCERIDE LEVEL; CORONARY-HEART-DISEASE; GREEN TEA POLYPHENOL; GLUCOSYL HESPERIDIN; INSULIN-RESISTANCE; BLOOD-PRESSURE; VASORELAXANT ACTIVITY; FLAVONOID NARINGENIN; VASCULAR ENDOTHELIUM AB Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H(2)O(2). Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-alpha treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 +/- 1.19 vs. 7.78 +/- 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. (J Clin Endocrinol Metab 96: E782-E792, 2011) C1 [Muniyappa, Ranganath; Iantorno, Micaela; Chen, Hui; Pullikotil, Philomena; Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Rizza, Stefano; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide] Univ Roma Tor Vergata, Dept Internal Med, I-00133 Rome, Italy. [Cardillo, Carmine] Univ Cattolica Sacro Cuore, Dept Internal Med, I-00168 Rome, Italy. [Kim, Jeong-a] Univ Alabama, Div Endocrinol, Dept Med, Birmingham, AL 35294 USA. RP Quon, MJ (reprint author), Univ Maryland, Dept Med, Div Endocrinol Diabet & Nutr, 660W Redwood St,Room HH495, Baltimore, MD 21201 USA. EM quonm@medicine.umaryland.edu OI Quon, Michael/0000-0002-9601-9915; Lauro, Davide/0000-0002-8597-4415; Quon , Michael /0000-0002-5289-3707 FU National Center for Complementary and Alternative Medicine, National Institutes of Health; University of Tor Vergata FX This work was supported in part by the Intramural Research Program, National Center for Complementary and Alternative Medicine, National Institutes of Health (to M.J.Q.) and by a Fondi d'Ateneo grant from the University of Tor Vergata (to M.T.). Hesperidin was a generous gift from Blue California (Rancho Santa Margarita, CA). NR 54 TC 61 Z9 63 U1 5 U2 30 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 MAY PY 2011 VL 96 IS 5 BP E782 EP E792 DI 10.1210/jc.2010-2879 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 759AE UT WOS:000290210600003 PM 21346065 ER PT J AU Schiechl, G Bauer, B Fuss, I Lang, SA Moser, C Ruemmele, P Rose-John, S Neurath, MF Geissler, EK Schlitt, HJ Strober, W Fichtner-Feigl, S AF Schiechl, Gabriela Bauer, Bernhard Fuss, Ivan Lang, Sven A. Moser, Christian Ruemmele, Petra Rose-John, Stefan Neurath, Markus F. Geissler, Edward K. Schlitt, Hans-Juergen Strober, Warren Fichtner-Feigl, Stefan TI Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic F4/80(+)CD11b(high)Gr1(low) macrophages SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; NK-T-CELLS; COLORECTAL-CANCER; OXAZOLONE COLITIS; SUPPRESSOR-CELLS; EPITHELIAL-CELLS; MICE; ACTIVATION; MODEL AB Patients with prolonged ulcerative colitis (UC) frequently develop colorectal adenocarcinoma for reasons that are not fully clear. To analyze inflammation-associated colonic tumorigenesis, we developed a chronic form of oxazolone-induced colitis in mice that, similar to UC, was distinguished by the presence of IL-13-producing NKT cells. In this model, the induction of tumors using azotrymetharte was accompanied by the coappearance of F4/80(+)CD11b(high)Gr1(low)M2 macrophages, cells that undergo polarization by IL-13 and are absent in tumors that lack high level IL-13 production. Importantly, this subset of macrophages was a source of tumor-promoting factors, including IL-6. Similar to dextran sodium sulfate-induced colitis, F4/80(+)CD11b(high)Gr1(intermediate) macrophages were present in the mouse model of chronic oxazolone-induced colitis and may influence tumor development through production of TGF-beta 1, a cytokine that inhibits tumor immunosurveillance. Finally, while robust chronic oxazolone-induced colitis developed in myeloid differentiation primary response gene 88-deficient (Myd88(-/-)) mice, these mice did not support tumor development. The inhibition of tumor development in Myd88(-/-)mice correlated with cessation of IL-6 and TGF-beta 1 production by M2 and F4/80(+)CD11b(high)Gr1(intermediate) macrophages, respectively, and was reversed by exogenous IL-6. These data show that an UC-like inflammation may facilitate tumor development by providing a milieu favoring development of MyD88-dependent tumor-supporting macrophages. C1 [Schiechl, Gabriela; Bauer, Bernhard; Lang, Sven A.; Moser, Christian; Geissler, Edward K.; Schlitt, Hans-Juergen; Fichtner-Feigl, Stefan] Univ Regensburg, Dept Surg, D-93053 Regensburg, Germany. [Fuss, Ivan; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Ruemmele, Petra] Univ Regensburg, Dept Pathol, D-93053 Regensburg, Germany. [Rose-John, Stefan] Univ Kiel, Inst Biochem, D-2300 Kiel, Germany. [Neurath, Markus F.] Univ Hosp Erlangen, Dept Med 1, Erlangen, Germany. RP Fichtner-Feigl, S (reprint author), Univ Regensburg, Dept Surg, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM stefan.fichtner@klinik.uni-regensburg.de RI Geissler, Edward/R-4131-2016; Rose-John, Stefan/A-7998-2010 OI Rose-John, Stefan/0000-0002-7519-3279 FU Deutsche Forschungsgemeinschaft [Fi1526/1-1] FX This project was supported by grant Fi1526/1-1 from the Deutsche Forschungsgemeinschaft. The authors gratefully acknowledge this support. The authors also thank Jorg Marienhagen and Laura Cojocaru for the help with statistical calculations. NR 54 TC 43 Z9 44 U1 0 U2 4 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 MAY PY 2011 VL 121 IS 5 BP 1692 EP 1708 DI 10.1172/JCI42540 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 759LR UT WOS:000290246800007 PM 21519141 ER PT J AU Kastenmuller, K Wille-Reece, U Lindsay, RWB Trager, LR Darrah, PA Flynn, BJ Becker, MR Udey, MC Clausen, BE Igyarto, BZ Kaplan, DH Kastenmuller, W Germain, RN Seder, RA AF Kastenmueller, Kathrin Wille-Reece, Ulrike Lindsay, Ross W. B. Trager, Lauren R. Darrah, Patricia A. Flynn, Barbara J. Becker, Maria R. Udey, Mark C. Clausen, Bjorn E. Igyarto, Botond Z. Kaplan, Daniel H. Kastenmueller, Wolfgang Germain, Ronald N. Seder, Robert A. TI Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; TOLL-LIKE RECEPTOR-7; EPIDERMAL LANGERHANS CELLS; AIDED CROSS-PRESENTATION; ANTIGEN PRESENTATION; ADAPTIVE IMMUNITY; CUTTING EDGE; CONTACT HYPERSENSITIVITY; MICROBIAL ANTIGENS; EXOGENOUS ANTIGENS AB The success of a non-live vaccine requires improved formulation and adjuvant selection to generate robust T cell immunity following immunization. Here, using protein linked to a TLR7/8 agonist (conjugate vaccine), we investigated the functional properties of vaccine formulation, the cytokines, and the DC subsets required to induce protective multifunctional T cell immunity in vivo. The conjugate vaccine required aggregation of the protein to elicit potent Th1 CD4(+) and CD8(+) T cell responses. Remarkably, the conjugate vaccine, through aggregation of the protein and activation of TLR7 in vivo, led to an influx of migratory DCs to the LN and increased antigen uptake by several resident and migratory DC subsets, with the latter effect strongly influenced by vaccine-induced type I IFN. Ex vivo migratory CD8(-)DEC205(+)CD103(-)CD326(-) langerin-negative dermal DCs were as potent in cross-presenting antigen to naive CD8(+) T cells as CD11c(+)CD8(+) DCs. Moreover, these cells also influenced Th1 CD4(+) T cell priming. In summary, we propose a model in which broad-based T cell-mediated responses upon vaccination can be maximized by codelivery of aggregated protein and TLR7/8 agonist, which together promote optimal antigen acquisition and presentation by multiple DC subsets in the context of critical proinflammatory cytokines. C1 [Kastenmueller, Kathrin; Wille-Reece, Ulrike; Lindsay, Ross W. B.; Trager, Lauren R.; Darrah, Patricia A.; Flynn, Barbara J.; Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Wille-Reece, Ulrike] PATH Malaria Vaccine Initiat, Washington, DC USA. [Lindsay, Ross W. B.] AIDS Vaccine Design Lab, Int AIDS Vaccine Initiat, New York, NY USA. [Becker, Maria R.; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD USA. [Clausen, Bjorn E.] Erasmus Univ, Med Ctr, Dept Immunol, Rotterdam, Netherlands. [Igyarto, Botond Z.; Kaplan, Daniel H.] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Igyarto, Botond Z.; Kaplan, Daniel H.] Univ Minnesota, Ctr Immunol, Minneapolis, MN USA. [Kastenmueller, Wolfgang; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Germain, Ronald N.] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3025,Bldg 40,Room 3512, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov RI CLAUSEN, Bjorn/A-8229-2010; Kaplan, Daniel/N-2779-2013 OI CLAUSEN, Bjorn/0000-0002-2484-7842; Kaplan, Daniel/0000-0002-7851-7320 FU NIAID; NIH; DFG [KA 3091/1-1] FX This work was supported by the Intramural Program of NIAID, NIH, and DFG (KA 3091/1-1 to W. Kastenmuller). B.E. Clausen is a VIDI fellow of the Netherlands Organization for Scientific Research. NR 112 TC 70 Z9 72 U1 0 U2 7 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 MAY PY 2011 VL 121 IS 5 BP 1782 EP 1796 DI 10.1172/JCI45416 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 759LR UT WOS:000290246800014 PM 21540549 ER PT J AU Park, B Lizak, MJ Xiang, Y Shen, J AF Park, BuSik Lizak, Martini J. Xiang, Yun Shen, Jun TI Slice with angulated non-parallel boundaries SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Adiabatic pulse; Non-rectangular volume selection; Time-varying gradient ID SELECTIVE EXCITATION; REFOCUSING PULSES; NMR-SPECTROSCOPY; FOCI PULSES; 11.7 TESLA; RAT-BRAIN; INVERSION; LOCALIZATION AB Adiabatic pulses are widely used for spatial localization in magnetic resonance spectroscopy because of their high immunity to RF inhomogeneity and excellent slice profiles. Since non-rectangular volume is often preferred in localized spectroscopy, we propose a scheme for selecting a trapezoidal slice using adiabatic it pulses. In this scheme, a time-varying gradient orthogonal to a stationary slice selection gradient is used to change the boundaries of the slice profile from parallel to non-parallel. Numerical simulation results for the transverse and longitudinal magnetization using different RF and gradient waveforms are presented for non-parallel slice selection. Phantom imaging and in vivo H-1 MRS of rat brain using non-parallel slices are demonstrated. Published by Elsevier Inc. C1 [Park, BuSik; Xiang, Yun; Shen, Jun] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Lizak, Martini J.] Natl Inst Neurol Disorders & Stroke, Mouse Imaging Facil, NIH, Bethesda, MD USA. RP Park, B (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bldg 10,Rm 2D 50,9000 Rockville Pike, Bethesda, MD 20892 USA. EM parkb3@mail.nih.gov FU National Institutes of Health, National Institute of Mental Health FX The authors thank Mr. Chris Johnson for helping with the in vivo spectroscopy experiments, and Dr. Steve Li, Dr. Yan Zhang, and Dr. Jan Willem van der Veen for helpful discussions. The authors also thank to the National Institutes of Health Fellows Editorial Board for the editorial assistance. This work is supported by the Intramural Research Program of the National Institutes of Health, National Institute of Mental Health. NR 25 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2011 VL 210 IS 1 BP 98 EP 106 DI 10.1016/j.jmr.2011.02.016 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 757BB UT WOS:000290057800014 PM 21396862 ER PT J AU Schnall, R Cimino, JJ Currie, LM Bakken, S AF Schnall, Rebecca Cimino, James J. Currie, Leanne M. Bakken, Suzanne TI Information needs of case managers caring for persons living with HIV SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PRIMARY-CARE; CLINICAL QUESTIONS; PATIENT-CARE; PHYSICIANS; TECHNOLOGY; TAXONOMY AB Objective The goals of this study were to explore the information needs of case managers who provide services to persons living with HIV (PLWH) and to assess the applicability of the Information Needs Event Taxonomy in a new population. Design The study design was observational with data collection via an online survey. Measurements Responses to open-ended survey questions about the information needs of case managers (n=94) related to PLWH of three levels of care complexity were categorized using the Information Needs Event Taxonomy. Results The most frequently identified needs were related to patient education resources (33%), patient data (23%), and referral resources (22%) accounting for 79% of all (N=282) information needs. Limitations Study limitations include selection bias, recall bias, and a relatively narrow focus of the study on case-manager information needs in the context of caring for PLWH. Conclusion The study findings contribute to the evidence base regarding information needs in the context of patient interactions by: (1) supporting the applicability of the Information Needs Event Taxonomy and extending it through addition of a new generic question; (2) providing a foundation for the addition of context-specific links to external information resources within information systems; (3) applying a new approach for elicitation of information needs; and (4) expanding the literature regarding addressing information needs in community-based settings for HIV services. C1 [Schnall, Rebecca; Bakken, Suzanne] Columbia Univ, Sch Nursing, New York, NY 10032 USA. [Cimino, James J.] NIH Clin Ctr, Lab Informat Dev, Bethesda, MD USA. [Currie, Leanne M.] Univ British Columbia, Sch Nursing, Vancouver, BC V5Z 1M9, Canada. [Bakken, Suzanne] Columbia Univ, Dept Biomed, New York, NY USA. RP Schnall, R (reprint author), Columbia Univ, Sch Nursing, 617 W 168th St, New York, NY 10032 USA. EM rb897@columbia.edu OI Schnall, Rebecca/0000-0003-2184-4045; Cimino, James/0000-0003-4101-1622 FU National Institute of Nursing Research [P30NR010677]; Health Resources and Services Administration [D11HP07346]; NIH Clinical Center; National Library of Medicine; [R01LM007593] FX The study was supported by the National Institute of Nursing Research (P30NR010677) and the Health Resources and Services Administration Grant (D11HP07346). JJC is supported by intramural research funds from the NIH Clinical Center and the National Library of Medicine. The development of the Information Needs Event Taxonomy was funded by R01LM007593. NR 24 TC 5 Z9 5 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2011 VL 18 IS 3 BP 305 EP 308 DI 10.1136/jamia.2010.006668 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 755TT UT WOS:000289960600015 PM 21270131 ER PT J AU Lee, NR Wallace, GL Clasen, LS Lenroot, RK Blumenthal, JD White, SL Celano, MJ Giedd, JN AF Lee, Nancy Raitano Wallace, Gregory L. Clasen, Liv S. Lenroot, Rhoshel K. Blumenthal, Jonathan D. White, Samantha L. Celano, Mark J. Giedd, Jay N. TI Executive Function in Young Males with Klinefelter (XXY) Syndrome with and without Comorbid Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Sex chromosomes; Neuropsychology; Cognition; Attention Deficit Hyperactivity Disorder; Working memory; Problem solving ID SEX-CHROMOSOME ABNORMALITIES; OF-THE-LITERATURE; EXTRA X; NORMATIVE DATA; MEN 47,XXY; CHILDREN; BOYS; LANGUAGE; SKILLS; BRAIN AB Deficits in executive function (EF) are reported to occur in individuals with Klinefelter syndrome (XXY). The degree of impairment, if any, is variable and the nature of these deficits has not been clearly elucidated in young males. In this report, we (a) examine EF skills using multiple tasks in a non-clinic referred group of youth with XXY, (b) describe the extent of EF weaknesses in XXY when this group is compared with typical males of a similar SES or typical males with similar verbal abilities, and (c) evaluate the contribution of comorbid attention-deficit/hyperactivity disorder (ADHD) to EF skills. The sample included 27 males with XXY (ages 9-25), 27 typically developing age-and vocabulary-matched males, and 22 age-and socioeconomic status-matched males. EF tasks included Verbal Fluency, the Trail Making Test, and the CANTAB Spatial Working Memory and Stockings of Cambridge tasks. Mixed model analysis of variance was used to compare the groups on EF tasks and revealed a main effect of group but no group by task interaction. Overall, the XXY group performed less well than both control groups, but performance did not differ significantly as a function of task. ADHD comorbidity in males with XXY was related to poorer EF skills. (JINS, 2011, 17, 522-530) C1 [Lee, Nancy Raitano; Wallace, Gregory L.; Clasen, Liv S.; Lenroot, Rhoshel K.; Blumenthal, Jonathan D.; White, Samantha L.; Celano, Mark J.; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Lee, NR (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,4C110,MSC 1367,10 Ctr Dr, Bethesda, MD 20892 USA. EM lnancy@mail.nih.gov RI Lee, Nancy Raitano/F-2565-2011; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713; Wallace, Gregory/0000-0003-0329-5054 FU NIH, National Institute of Mental Health FX This research was supported by the Intramural Research Program of the NIH, National Institute of Mental Health. We thank the children and families who volunteered their time for this research. NR 53 TC 11 Z9 11 U1 0 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2011 VL 17 IS 3 BP 522 EP 530 DI 10.1017/S1355617711000312 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 757QU UT WOS:000290103600014 PM 21418719 ER PT J AU Kohler, BA Ward, E McCarthy, BJ Schymura, MJ Ries, LAG Eheman, C Jemal, A Anderson, RN Ajani, UA Edwards, BK AF Kohler, Betsy A. Ward, Elizabeth McCarthy, Bridget J. Schymura, Maria J. Ries, Lynn A. G. Eheman, Christie Jemal, Ahmedin Anderson, Robert N. Ajani, Umed A. Edwards, Brenda K. TI Annual Report to the Nation on the Status of Cancer, 1975-2007, Featuring Tumors of the Brain and Other Nervous System SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SERVICES TASK-FORCE; BREAST-CANCER; UNITED-STATES; PROSTATE-CANCER; RISK-FACTORS; LUNG-CANCER; INCIDENCE RATES; RECENT TRENDS; ADULT GLIOMA; ALLERGIC CONDITIONS AB Background The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year's report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Methods Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC's National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992-2007 for incidence; 1975-2007 for mortality) trends and short-term fixed interval (1998-2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980-2007; data on nonmalignant tumors were available for 2004-2007. All statistical tests were two-sided. Results Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 20032007, more than a decade after decreasing in men. During 2004-2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987-2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. Conclusions The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment. However, major challenges remain, including increasing incidence rates and continued low survival for some cancers. Malignant and nonmalignant brain tumors demonstrate differing patterns of occurrence by sex, age, and race, and exhibit considerable biologic diversity. Inclusion of nonmalignant brain tumors in cancer registries provides a fuller assessment of disease burden and medical resource needs associated with these unique tumors. C1 [Kohler, Betsy A.] N Amer Assoc Cent Canc Registries, Springfield, IL 62404 USA. [Ward, Elizabeth; Jemal, Ahmedin] Amer Canc Soc, Surveillance & Hlth Policy Res Dept, Atlanta, GA 30329 USA. [McCarthy, Bridget J.] Univ Illinois, Dept Epidemiol & Biostat, Chicago, IL USA. [Schymura, Maria J.] New York State Canc Registry, Menands, NY USA. [Ries, Lynn A. G.; Edwards, Brenda K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Eheman, Christie] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Anderson, Robert N.] Ctr Dis Control & Prevent, Div Vital Stat, Natl Ctr Hlth Stat, Hyattsville, MD USA. RP Kohler, BA (reprint author), N Amer Assoc Cent Canc Registries, 2121 W White Oaks Dr,Ste B, Springfield, IL 62404 USA. EM bkohler@naaccr.org FU American Cancer Society; National Cancer Institute of the National Institutes of Health; Centers for Disease Control and Prevention; Central Brain Tumor Registry of the United States; North American Association of Central Cancer Registries; National Cancer Institute FX The American Cancer Society, the National Cancer Institute of the National Institutes of Health, the Centers for Disease Control and Prevention, the Central Brain Tumor Registry of the United States, and the North American Association of Central Cancer Registries. Funding to pay for the Open Access publication charges associated with the article was provided by the National Cancer Institute. NR 118 TC 292 Z9 302 U1 3 U2 25 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2011 VL 103 IS 9 BP 714 EP 736 DI 10.1093/jnci/djr077 PG 23 WC Oncology SC Oncology GA 760IG UT WOS:000290317400007 PM 21454908 ER PT J AU Roberts, JN Kines, RC Katki, HA Lowy, DR Schiller, JT AF Roberts, Jeffrey N. Kines, Rhonda C. Katki, Hormuzd A. Lowy, Douglas R. Schiller, John T. TI Effect of Pap Smear Collection and Carrageenan on Cervicovaginal Human Papillomavirus-16 Infection in a Rhesus Macaque Model SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CERVICAL-CANCER; UNITED-STATES; UTERINE CERVIX; HPV INFECTION; YOUNG-WOMEN; TRENDS; ADENOCARCINOMA; TRANSMISSION; PREVALENCE AB Background Human papillomavirus (HPV) infection of the genital mucosa is thought to require trauma to the cervicovaginal epithelium. Therefore, we determined whether a cytology specimen collection procedure (Pap smear), which disrupts the epithelium by design, renders the cervix more susceptible to HPV infection in a primate model. Methods In a series of female rhesus macaques, a speculum examination was performed with (n = 8) or without (n = 4) a cytology specimen collection procedure as it is commonly practiced in a gynecology clinic. An internal digital examination was performed after specimen collection using Surgilube (n = 4) or 1% iota-carrageenan, a previously indentified HPV inhibitor (n = 4) as the lubricant. The cervix was then inoculated with HPV16 pseudovirions expressing red fluorescent protein. After 3 days, the reproductive tracts were excised and the cervix was cryosectioned. Sections were analyzed by fluorescent confocal microscopy for the number of red fluorescent protein-positive keratinocytes. Results Substantial infection of the ectocervix, the transformation zone, and the endocervix was detected, but only in conjunction with the cytology specimen collection procedure (cytology using Surgilube vs without cytology using Surgilube, mean = 84 infectious events per section vs mean = 0.05 infectious events per section, difference = 84 infectious events per section, 95% confidence interval = 19 to 384 infectious events per section). When the carrageenan gel was substituted for Surgilube for an internal digital examination, the mean number of infectious events decreased (carrageenan gel vs Surgilube, mean = 3.5 events per section vs mean = 84 infectious events per section difference = 81 events per section, 95% confidence interval = 33 to 213 events per section). Conclusions These findings indicate that cytology screening in women might lead to a transient enhancement of susceptibility to HPV infection and that use of a carrageenan-based gel during the examination might mitigate this enhancement. C1 [Roberts, Jeffrey N.; Kines, Rhonda C.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Katki, Hormuzd A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Rm 4106, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov RI Katki, Hormuzd/B-4003-2015 FU National Cancer Institute, National Institutes of Health FX This work was supported by the intramural program of the National Cancer Institute, National Institutes of Health. NR 27 TC 26 Z9 27 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2011 VL 103 IS 9 BP 737 EP 743 DI 10.1093/jnci/djr061 PG 7 WC Oncology SC Oncology GA 760IG UT WOS:000290317400008 PM 21483020 ER PT J AU Shiels, MS Pfeiffer, RM Gail, MH Hall, HI Li, JM Chaturvedi, AK Bhatia, K Uldrick, TS Yarchoan, R Goedert, JJ Engels, EA AF Shiels, Meredith S. Pfeiffer, Ruth M. Gail, Mitchell H. Hall, H. Irene Li, Jianmin Chaturvedi, Anil K. Bhatia, Kishor Uldrick, Thomas S. Yarchoan, Robert Goedert, James J. Engels, Eric A. TI Cancer Burden in the HIV-Infected Population in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED MALIGNANCIES; ANTIRETROVIRAL THERAPY; SURVEILLANCE DATA; KAPOSIS-SARCOMA; RISK-FACTORS; HAART ERA; TRENDS; ADULTS; MEN AB Background Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. Methods Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991-2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004-2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided. Results The US AIDS population expanded fourfold from 1991 to 2005 (96 179 to 413 080) largely because of an increase in the number of people aged 40 years or older. During 1991-2005, an estimated 79 656 cancers occurred in the AIDS population. From 1991-1995 to 2001-2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34 587 to 10 325 cancers; P(trend) < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10 059 cancers; P(trend) < .001). From 1991-1995 to 2001-2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers. Conclusions Over a 15-year period (1991-2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies. C1 [Shiels, Meredith S.; Chaturvedi, Anil K.; Goedert, James J.; Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Pfeiffer, Ruth M.; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Hall, H. Irene; Li, Jianmin] Centers Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. [Bhatia, Kishor; Yarchoan, Robert] NCI, Off HIV & AIDS Malignancy, Bethesda, MD 20892 USA. [Uldrick, Thomas S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20852 USA. EM shielsms@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU National Cancer Institute FX Intramural Research Program of the National Cancer Institute. NR 41 TC 261 Z9 262 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2011 VL 103 IS 9 BP 753 EP 762 DI 10.1093/jnci/djr076 PG 10 WC Oncology SC Oncology GA 760IG UT WOS:000290317400010 PM 21483021 ER PT J AU Lin, FR Thorpe, R Gordon-Salant, S Ferrucci, L AF Lin, Frank R. Thorpe, Roland Gordon-Salant, Sandra Ferrucci, Luigi TI Hearing Loss Prevalence and Risk Factors Among Older Adults in the United States SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Hearing loss; Epidemiology; Older adults; Risk factors; Race; Hearing aids ID QUALITY-OF-LIFE; FRAMINGHAM COHORT; STRIA VASCULARIS; IMPAIRMENT; HEALTH; AGE; EPIDEMIOLOGY; ASSOCIATION; PREDICTOR; DISEASE AB Background. Hearing loss has been associated with cognitive and functional decline in older adults and may be amenable to rehabilitative interventions, but national estimates of hearing loss prevalence and hearing aid use in older adults are unavailable. Methods. We analyzed data from the 2005-2006 cycle of the National Health and Nutritional Examination Survey, which is the first cycle to ever incorporate hearing assessment in adults aged 70 years and older. Audiometry was performed in 717 older adults, and data on hearing aid use, noise exposure, medical history, and demographics were obtained from interviews. Analyses incorporated sampling weights to account for the complex sampling design and yield results that are generalizable to the U.S. population. Results. The prevalence of hearing loss defined as a speech frequency pure tone average of more than 25 dB in the better ear was 63.1% (95% confidence interval: 57.4-68.8). Age, sex, and race were the factors most strongly associated with hearing loss after multivariate adjustment, with black race being substantially protective against hearing loss (odds ratio 0.32 compared with white participants [95% confidence interval: 0.19-0.53]). Hearing aids were used in 40.0% (95% confidence interval: 35.1-44.8) of adults with moderate hearing loss, but in only 3.4% (95% confidence interval: 0.8-6.0) of those with a mild hearing loss. Conclusion. Hearing loss is prevalent in nearly two thirds of adults aged 70 years and older in the U.S. population. Additional research is needed to determine the epidemiological and physiological basis for the protective effect of black race against hearing loss and to determine the role of hearing aids in those with a mild hearing loss. C1 [Lin, Frank R.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. [Lin, Frank R.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. [Thorpe, Roland] Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Ctr Hlth Dispar Solut, Baltimore, MD USA. [Thorpe, Roland] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Gordon-Salant, Sandra] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Lin, FR (reprint author), Johns Hopkins Ctr Aging & Health, 2024 E Monument St,Suite 2-700, Baltimore, MD 21287 USA. EM flin1@jhmi.edu FU National Institute on Deafness and Other Communication Disorders [1 K23DC011279]; National Institute on Aging Pepper Older Americans Independence Center FX This work was supported by the National Institute on Deafness and Other Communication Disorders (1 K23DC011279 to F.L.) and a National Institute on Aging Pepper Older Americans Independence Center Research Career Development Award (F.L.). NR 39 TC 163 Z9 169 U1 6 U2 33 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2011 VL 66 IS 5 BP 582 EP 590 DI 10.1093/gerona/glr002 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 757FG UT WOS:000290070300014 PM 21357188 ER PT J AU Fan, YG Jiang, Y Chang, RS Yao, SX Jin, P Wang, W He, J Zhou, QH Prorok, P Qiao, YL Hu, P AF Fan, Ya-Guang Jiang, Yong Chang, Run-Sheng Yao, Shu-Xiang Jin, Ping Wang, Wendy He, Jie Zhou, Qing-Hua Prorok, Philip Qiao, You-Lin Hu, Ping TI Prior lung disease and lung cancer risk in an occupational-based cohort in Yunnan, China SO LUNG CANCER LA English DT Article DE Asthma; Bronchitis; Lung diseases; Lung carcinoma ID RESPIRATORY-DISEASE; FAMILY-HISTORY; CHLAMYDIA-PNEUMONIAE; RESIDENTIAL RADON; NONSMOKING WOMEN; UNITED-STATES; TUBERCULOSIS; MORTALITY; SMOKING; METAANALYSIS AB We used the data from a prospective cohort study among tin miners in Yunnan. China to investigate whether prior lung disease is a risk factor for lung cancer. Information on prior lung disease was obtained from baseline questionnaires. The Cox proportional hazards model was used to examine the relationship between prior lung disease and lung cancer risk. From 1992 to 2001, a total of 502 lung cancer cases were confirmed among 9295 cohort participants. Prior chronic bronchitis was associated with an increase in lung cancer risk with an adjusted HR of 1.50(95% CI: 1.24-1.81). There was an increased risk of developing squamous cell carcinoma in the setting of prior chronic bronchitis and small cell carcinoma in association with asthma with an adjusted HRs of 1.57 (95% CI: 1.19-2.09) and 2.56(95% CI: 1.38-4.75), respectively. This prospective study provides further evidence that prior chronic bronchitis correlates with increased lung cancer risk, especially for squamous cell carcinoma. Asthma is associated with increased risk of small cell lung carcinoma. Published by Elsevier Ireland Ltd. C1 [Wang, Wendy; Prorok, Philip; Hu, Ping] NCI, Canc Prevent Div, Bethesda, MD USA. [Fan, Ya-Guang; Zhou, Qing-Hua] Tianjin Med Univ, Gen Hosp, Tianjin Lung Canc Inst, Tianjin Key Lab Lung Canc Metastasis & Tumor, Tianjin, Peoples R China. [Jiang, Yong; He, Jie; Qiao, You-Lin] Chinese Acad Med Sci, Dept Canc Epidemiol, Dept Thorac Surg, Inst Canc, Beijing 100037, Peoples R China. [Jiang, Yong; He, Jie; Qiao, You-Lin] Peking Union Med Coll, Beijing 100021, Peoples R China. [Chang, Run-Sheng] Third Peoples Hosp Honghe Autonomous Dist, Yunnan, Peoples R China. [Jin, Ping] Yunnan Tumor Hosp, 3rd Affiliated Hosp, Dept Pathol, Kunming Med Coll, Yunnan, Peoples R China. RP Hu, P (reprint author), NCI, NIH, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM zhouqh1016@yahoo.com.cn; pingh@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Jiang, Yong/B-4103-2012 OI Qiao, You-Lin/0000-0001-6380-0871; Jiang, Yong/0000-0002-1892-1196 FU National Cancer Institute/National Institute of Health [263-MQ-511694] FX This study was supported by the National Cancer Institute/National Institute of Health, grant No. 263-MQ-511694. We thank the staff of The Third People's Hospital of Honghe prefecture, and Labor Protection Institute of Yunnan Tin Corporation, Gejiu city, Yunnan province, P.R. China for their efforts in the collection of the baseline and follow-up data of the YTC screening cohort. We thank Drs Paul Kvale and Barbara Dunn for their critical comments. NR 45 TC 10 Z9 12 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD MAY PY 2011 VL 72 IS 2 BP 258 EP 263 DI 10.1016/j.lungcan.2011.01.032 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 758VE UT WOS:000290194300019 PM 21367481 ER PT J AU Yungher, DA Wininger, MT Barr, JB Craelius, W Threlkeld, AJ AF Yungher, Don A. Wininger, Michael T. Barr, J. B. Craelius, William Threlkeld, A. Joseph TI Surface muscle pressure as a measure of active and passive behavior of muscles during gait SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE Gait; Electromyography; Muscle; Pressure; Robotics; Prosthetics ID AVERAGED EMG PROFILES; INTRAMUSCULAR PRESSURE; QUADRICEPS MUSCLES; WALKING; FORCE; ELECTROMYOGRAPHY; VARIABILITY; CONTRACTION; ACTIVATION; TREADMILL AB While surface electromyography (SEMG) can accurately register electrical activity of muscles during gait, there are no methods to estimate muscular force non-invasively. To better understand the mechanical behavior of muscle, we evaluated surface muscle pressure (SMP) in conjunction with SEMG. Changes in anterior thigh radial pressure during isometric contractions and gait were registered by pressure sensors on the limb. During isometric knee extensions by a single subject, SMP waveforms correlated well with SEMG (r=0.97), and SEMG onsets preceded those of SMP by 35-40 ms. SMP and SEMG signals were simultaneously recorded from the quadriceps of 10 healthy subjects during gait at speeds of 0.4, 0.8, 1.1, 1.4 and 2.2 m/s. Muscle activity onset and cessation times were objectively determined for both modalities, and results showed high intra-class correlations. SMP waveforms were highly consistent from stride to stride, while SEMG waveforms varied widely. SEMG waveforms were typically brief, while SMP waveforms tended to be biphasic and outlasted the SEMG by approximately 40% of gait cycle at all speeds. These results are consistent with mechanical models of muscle, and demonstrate the use of SMP to estimate the timing of knee extensor muscle stiffness during gait. (C) 2010 IPEM. Published by Elsevier Ltd. All rights reserved. C1 [Yungher, Don A.; Wininger, Michael T.; Craelius, William] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Barr, J. B.; Threlkeld, A. Joseph] Creighton Univ, Rehabil Sci Res Lab, Omaha, NE 68178 USA. [Yungher, Don A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Wininger, Michael T.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Yungher, DA (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. EM dyungher@som.umaryland.edu FU NIDRR FX This study was supported in part by an RERC grant from NIDRR to W.C. NR 32 TC 12 Z9 14 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD MAY PY 2011 VL 33 IS 4 BP 464 EP 471 DI 10.1016/j.medengphy.2010.11.012 PG 8 WC Engineering, Biomedical SC Engineering GA 758CY UT WOS:000290139200009 PM 21176884 ER PT J AU O'Donnell, CD Subbarao, K AF O'Donnell, Christopher D. Subbarao, Kanta TI The contribution of animal models to the understanding of the host range and virulence of influenza A viruses SO MICROBES AND INFECTION LA English DT Article DE Influenza A virus; Host range; Virulence; Pathogenesis; Animal models AB Since ferrets were first used in 1933 during the initial isolation of influenza A viruses, animal models have been critical for influenza research. The following review discusses the contribution of mice, ferrets, and non-human primates to the study of influenza virus host range and pathogenicity. Published by Elsevier Masson SAS on behalf of Institut Pasteur. C1 [O'Donnell, Christopher D.; Subbarao, Kanta] NIAID, LID, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, LID, NIH, 33 North Dr,MSC 3203,Room 3E-13C-1, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU NIAID/NIH FX The authors' research was supported by the Intramural Research Program of the NIAID/NIH. NR 1 TC 42 Z9 43 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAY PY 2011 VL 13 IS 5 SI SI BP 502 EP 515 DI 10.1016/j.micinf.2011.01.014 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 757KP UT WOS:000290084200010 PM 21276869 ER PT J AU Markello, TC Pak, LK St Hilaire, C Dorward, H Ziegler, SG Chen, MY Chaganti, K Nussbaum, RL Boehm, M Gahl, WA AF Markello, Thomas C. Pak, Laura K. St Hilaire, Cynthia Dorward, Heidi Ziegler, Shira G. Chen, Marcus Y. Chaganti, Krishna Nussbaum, Robert L. Boehm, Manfred Gahl, William A. TI Vascular pathology of medial arterial calcifications in NT5E deficiency: Implications for the role of adenosine in pseudoxanthoma elasticum SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Calcification; Artery; Adenosine metabolism; Connective tissue; Pseudoxanthoma; Elastic tissue ID MUTATIONS; PROTEINS; DISEASE AB Arterial Calcification due to Deficiency of CD73 (ACDC) results from mutations in the NT5E gene encoding the 5' exonucleotidase, CD73. We now describe the third familial case of ACDC, including radiological and histopathological details of the arterial calcifications. The medial lesions involve the entire circumference of the elastic lamina, in contrast to the intimal plaque-like disease of atherosclerosis. The demonstration of broken and fragmented elastic fibers leading to generalized vascular calcification suggests an analogy to pseudoxanthoma elasticum (PXE), which exhibits similar histopathology. Classical PXE is caused by deficiency of ABCC6, a C type ABC transporter whose ligand is unknown. Other C type ABC proteins transport nucleotides, so the newly described role of adenosine in inhibiting vascular calcification, along with the similarity of ACDC and PXE with respect to vascular pathology, suggests that adenosine may be the ligand for ABCC6. Published by Elsevier Inc. C1 [Markello, Thomas C.] NHGRI, Med Genet Branch, NIH, Undiagnosed Dis Program,Off Rare Dis Res, Bethesda, MD 20892 USA. [Markello, Thomas C.; Gahl, William A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Markello, Thomas C.; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Pak, Laura K.] Cardiovasc Associates Marin & San Francis Med Grp, Larkspur, CA 94939 USA. [Pak, Laura K.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [St Hilaire, Cynthia; Chen, Marcus Y.; Boehm, Manfred] NHLBI, NIH, Bethesda, MD 20892 USA. [Chaganti, Krishna; Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP Markello, TC (reprint author), NHGRI, Med Genet Branch, NIH, Undiagnosed Dis Program,Off Rare Dis Res, 10 Ctr Dr,Bldg 10-10C103, Bethesda, MD 20892 USA. EM markellot@mail.nih.gov RI St. Hilaire, Cynthia/I-4713-2014; OI St. Hilaire, Cynthia/0000-0003-1871-6915 FU National Human Genome Research Institute; National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 21 TC 45 Z9 47 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2011 VL 103 IS 1 BP 44 EP 50 DI 10.1016/j.ymgme.2011.01.018 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 758WW UT WOS:000290199100007 PM 21371928 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, Randy J. Venditti, Charles P. TI A Barrel of Monkeys: scAAV8 Gene Therapy for Hemophilia in Nonhuman Primates SO MOLECULAR THERAPY LA English DT Editorial Material ID ADENOASSOCIATED VIRUS VECTORS; FACTOR-IX; AAV VECTOR; EFFICIENT TRANSDUCTION; SKELETAL-MUSCLE; EXPRESSION; LIVER C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20893 USA. [Chandler, Randy J.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A18,MSC 4442, Bethesda, MD 20893 USA. EM venditti@mail.nih.gov FU Intramural NIH HHS [Z01 HG200318-04, Z99 HG999999, Z01 HG200318-05] NR 14 TC 2 Z9 2 U1 0 U2 2 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 MAY PY 2011 VL 19 IS 5 BP 826 EP 827 DI 10.1038/mt.2011.73 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 758FE UT WOS:000290146200005 PM 21532610 ER PT J AU Nathwani, AC Rosales, C McIntosh, J Rastegarlari, G Nathwani, D Raj, D Nawathe, S Waddington, SN Bronson, R Jackson, S Donahue, RE High, KA Mingozzi, F Ng, CYC Zhou, JF Spence, Y McCarville, MB Valentine, M Allay, J Coleman, J Sleep, S Gray, JT Nienhuis, AW Davidoff, AM AF Nathwani, Amit C. Rosales, Cecilia McIntosh, Jenny Rastegarlari, Ghasem Nathwani, Devhrut Raj, Deepak Nawathe, Sushmita Waddington, Simon N. Bronson, Roderick Jackson, Scott Donahue, Robert E. High, Katherine A. Mingozzi, Federico Ng, Catherine Y. C. Zhou, Junfang Spence, Yunyu McCarville, M. Beth Valentine, Marc Allay, James Coleman, John Sleep, Susan Gray, John T. Nienhuis, Arthur W. Davidoff, Andrew M. TI Long-term Safety and Efficacy Following Systemic Administration of a Self-complementary AAV Vector Encoding Human FIX Pseudotyped With Serotype 5 and 8 Capsid Proteins SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRAL VECTORS; HUMAN-FACTOR-IX; NONHUMAN PRIMATE MODEL; HEMOPHILIA-B; GENE-THERAPY; EFFICIENT TRANSDUCTION; LIVER TRANSDUCTION; SKELETAL-MUSCLE; VIRUS VECTORS; LARGE-SCALE AB Adeno-associated virus vectors (AAV) show promise for liver-targeted gene therapy. In this study, we examined the long-term consequences of a single intravenous administration of a self-complementary AAV vector (scAAV2/8-LP1-hFIXco) encoding a codon optimized human factor IX (hFIX) gene in 24 nonhuman primates (NHPs). A dose-response relationship between vector titer and transgene expression was observed. Peak hFIX expression following the highest dose of vector (2 x 10(12) pcr-vector genomes (vg)/kg) was 21 +/- 3 mu g/ml (similar to 420% of normal). Fluorescent in-situ hybridization demonstrated scAAV provirus in almost 100% of hepatocytes at that dose. No perturbations of clinical or laboratory parameters were noted and vector genomes were cleared from bodily fluids by 10 days. Macaques transduced with 2 x 10(11) pcr-vg/kg were followed for the longest period (similar to 5 years), during which time expression of hFIX remained > 10% of normal level, despite a gradual decline in transgene copy number and the proportion of transduced hepatocytes. All macaques developed serotype-specific antibodies but no capsid-specific cytotoxic T lymphocytes were detected. The liver was preferentially transduced with 300-fold more proviral copies than extrahepatic tissues. Long-term biochemical, ultrasound imaging, and histologic follow-up of this large cohort of NHP revealed no toxicity. These data support further evaluation of this vector in hemophilia B patients. C1 [Nathwani, Amit C.; Rosales, Cecilia; McIntosh, Jenny; Rastegarlari, Ghasem; Nathwani, Devhrut; Raj, Deepak; Nawathe, Sushmita] UCL, UCL Canc Inst, Dept Hematol, London WC1E 6BT, England. [Nathwani, Amit C.] NHS Blood & Transplant, London, England. [Waddington, Simon N.] UCL, Inst Womens Hlth, London WC1E 6BT, England. [Bronson, Roderick; Davidoff, Andrew M.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Jackson, Scott] Univ Tennessee, Hlth Sci Ctr, Dept Comparat Med, Memphis, TN USA. [Donahue, Robert E.] NHLBI, Hematol Branch, Washington, DC USA. [High, Katherine A.; Mingozzi, Federico] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA. [High, Katherine A.] Childrens Hosp Philadelphia, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [Ng, Catherine Y. C.; Zhou, Junfang; Spence, Yunyu] St Jude Childrens Hosp, Dept Surg, Memphis, TN 38105 USA. [McCarville, M. Beth] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Valentine, Marc] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. [Allay, James; Coleman, John; Sleep, Susan] St Jude Childrens Hosp, Childrens GMP, Memphis, TN 38105 USA. [Gray, John T.; Nienhuis, Arthur W.] St Jude Childrens Hosp, Div Expt Hematol, Memphis, TN 38105 USA. RP Nathwani, AC (reprint author), UCL, UCL Canc Inst, Dept Hematol, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England. EM a.nathwani@ucl.ac.uk RI Waddington, Simon/G-3778-2011; mingozzi, federico/I-2332-2013 OI Waddington, Simon/0000-0003-4970-4730; FU Katharine Dormandy Trust, U.K., Medical Research Council, UK, Department of Health's NIHR Biomedical Research Centers; National Heart, Lung, and Blood Institute [HL073838]; National Cancer Institute Cancer Center [CA027165] FX This work was supported by The Katharine Dormandy Trust, U.K., Medical Research Council, UK, Department of Health's NIHR Biomedical Research Centers funding award to UCLH/UCL, UK, The ASSISI Foundation of Memphis, the American Lebanese Syrian Associated Charities (ALSAC), the National Heart, Lung, and Blood Institute grant HL073838 and the National Cancer Institute Cancer Center Support Grant CA027165. This report/article presents independent research commissioned by the National Institute for Health Research (NIHR), UK under its Programme Grants for Applied Research scheme (RP-PG-0310-1001). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The authors declared no conflict of interest. NR 45 TC 107 Z9 109 U1 1 U2 9 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 MAY PY 2011 VL 19 IS 5 BP 876 EP 885 DI 10.1038/mt.2010.274 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 758FE UT WOS:000290146200012 PM 21245849 ER PT J AU Yilmaz, P Kottmann, R Field, D Knight, R Cole, JR Amaral-Zettler, L Gilbert, JA Karsch-Mizrachi, I Johnston, A Cochrane, G Vaughan, R Hunter, C Park, J Morrison, N Rocca-Serra, P Sterk, P Arumugam, M Bailey, M Baumgartner, L Birren, BW Blaser, MJ Bonazzi, V Booth, T Bork, P Bushman, FD Buttigieg, PL Chain, PSG Charlson, E Costello, EK Huot-Creasy, H Dawyndt, P DeSantis, T Fierer, N Fuhrman, JA Gallery, RE Gevers, D Gibbs, RA Gil, IS Gonzalez, A Gordon, JI Guralnick, R Hankeln, W Highlander, S Hugenholtz, P Jansson, J Kau, AL Kelley, ST Kennedy, J Knights, D Koren, O Kuczynski, J Kyrpides, N Larsen, R Lauber, CL Legg, T Ley, RE Lozupone, CA Ludwig, W Lyons, D Maguire, E Methe, BA Meyer, F Muegge, B Nakielny, S Nelson, KE Nemergut, D Neufeld, JD Newbold, LK Oliver, AE Pace, NR Palanisamy, G Peplies, J Petrosino, J Proctor, L Pruesse, E Quast, C Raes, J Ratnasingham, S Ravel, J Relman, DA Assunta-Sansone, S Schloss, PD Schriml, L Sinha, R Smith, MI Sodergren, E Spor, A Stombaugh, J Tiedje, JM Ward, DV Weinstock, GM Wendel, D White, O Whiteley, A Wilke, A Wortman, JR Yatsunenko, T Glockner, FO AF Yilmaz, Pelin Kottmann, Renzo Field, Dawn Knight, Rob Cole, James R. Amaral-Zettler, Linda Gilbert, Jack A. Karsch-Mizrachi, Ilene Johnston, Anjanette Cochrane, Guy Vaughan, Robert Hunter, Christopher Park, Joonhong Morrison, Norman Rocca-Serra, Philippe Sterk, Peter Arumugam, Manimozhiyan Bailey, Mark Baumgartner, Laura Birren, Bruce W. Blaser, Martin J. Bonazzi, Vivien Booth, Tim Bork, Peer Bushman, Frederic D. Buttigieg, Pier Luigi Chain, Patrick S. G. Charlson, Emily Costello, Elizabeth K. Huot-Creasy, Heather Dawyndt, Peter DeSantis, Todd Fierer, Noah Fuhrman, Jed A. Gallery, Rachel E. Gevers, Dirk Gibbs, Richard A. Gil, Inigo San Gonzalez, Antonio Gordon, Jeffrey I. Guralnick, Robert Hankeln, Wolfgang Highlander, Sarah Hugenholtz, Philip Jansson, Janet Kau, Andrew L. Kelley, Scott T. Kennedy, Jerry Knights, Dan Koren, Omry Kuczynski, Justin Kyrpides, Nikos Larsen, Robert Lauber, Christian L. Legg, Teresa Ley, Ruth E. Lozupone, Catherine A. Ludwig, Wolfgang Lyons, Donna Maguire, Eamonn Methe, Barbara A. Meyer, Folker Muegge, Brian Nakielny, Sara Nelson, Karen E. Nemergut, Diana Neufeld, Josh D. Newbold, Lindsay K. Oliver, Anna E. Pace, Norman R. Palanisamy, Giriprakash Peplies, Joerg Petrosino, Joseph Proctor, Lita Pruesse, Elmar Quast, Christian Raes, Jeroen Ratnasingham, Sujeevan Ravel, Jacques Relman, David A. Assunta-Sansone, Susanna Schloss, Patrick D. Schriml, Lynn Sinha, Rohini Smith, Michelle I. Sodergren, Erica Spor, Ayme Stombaugh, Jesse Tiedje, James M. Ward, Doyle V. Weinstock, George M. Wendel, Doug White, Owen Whiteley, Andrew Wilke, Andreas Wortman, Jennifer R. Yatsunenko, Tanya Gloeckner, Frank Oliver TI Minimum information about a marker gene sequence (MIMARKS) and minimum information about any (x) sequence (MIxS) specifications SO NATURE BIOTECHNOLOGY LA English DT Article ID RIBOSOMAL-RNA SEQUENCES; DIVERSITY; BACTERIOPLANKTON; MICROORGANISMS; PICOPLANKTON; COMMUNITY; PLANKTON; REGIONS; PROJECT AB Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences-the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The 'environmental packages' apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere. C1 [Yilmaz, Pelin; Kottmann, Renzo; Buttigieg, Pier Luigi; Hankeln, Wolfgang; Pruesse, Elmar; Quast, Christian; Gloeckner, Frank Oliver] Max Planck Inst Marine Microbiol, Microbial Genom & Bioinformat Grp, Bremen, Germany. [Yilmaz, Pelin; Buttigieg, Pier Luigi; Hankeln, Wolfgang; Pruesse, Elmar; Gloeckner, Frank Oliver] Jacobs Univ Bremen gGmbH, Bremen, Germany. [Field, Dawn; Morrison, Norman; Sterk, Peter; Bailey, Mark; Booth, Tim; Newbold, Lindsay K.; Oliver, Anna E.; Whiteley, Andrew] Wallington CEH, Environm Bioinformat Ctr, Nat Environm Res Council, Oxford, England. [Knight, Rob; Costello, Elizabeth K.; Kennedy, Jerry; Larsen, Robert; Lozupone, Catherine A.; Nakielny, Sara; Stombaugh, Jesse; Wendel, Doug] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. [Cole, James R.] Michigan State Univ, Ribosomal Database Project, E Lansing, MI 48824 USA. [Cole, James R.; Chain, Patrick S. G.; Tiedje, James M.] Michigan State Univ, Ctr Microbial Ecol, E Lansing, MI 48824 USA. [Amaral-Zettler, Linda] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Gilbert, Jack A.] Plymouth Marine Lab, Plymouth, Devon, England. [Gilbert, Jack A.; Meyer, Folker; Wilke, Andreas] Argonne Natl Lab, Div Math & Comp Sci, Argonne, IL 60439 USA. [Gilbert, Jack A.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. [Karsch-Mizrachi, Ilene; Johnston, Anjanette] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Cochrane, Guy; Vaughan, Robert; Hunter, Christopher] European Bioinformat Inst, European Mol Biol Lab EMBL Outstn, Cambridge, England. [Park, Joonhong] Yonsei Univ, Sch Civil & Environm Engn, WCU Ctr Green Metagen, Seoul 120749, South Korea. [Morrison, Norman] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. [Rocca-Serra, Philippe; Maguire, Eamonn; Assunta-Sansone, Susanna] Univ Oxford, Oxford e Res Ctr, Oxford, England. [Arumugam, Manimozhiyan; Bork, Peer] European Mol Biol Lab, Struct & Computat Biol Unit, Heidelberg, Germany. [Baumgartner, Laura; Pace, Norman R.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Birren, Bruce W.; Gevers, Dirk; Kuczynski, Justin; Ward, Doyle V.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Birren, Bruce W.; Gevers, Dirk; Kuczynski, Justin; Ward, Doyle V.] Harvard Univ, Cambridge, MA 02138 USA. [Blaser, Martin J.] NYU, Dept Med, Langone Med Ctr, New York, NY 10016 USA. [Blaser, Martin J.] NYU, Dept Microbiol, Langone Med Ctr, New York, NY 10016 USA. [Bonazzi, Vivien; Proctor, Lita] NHGRI, NIH, Bethesda, MD 20892 USA. [Bushman, Frederic D.; Charlson, Emily; Sinha, Rohini] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Chain, Patrick S. G.; Jansson, Janet; Kyrpides, Nikos] DOE Joint Genome Inst, Walnut Creek, CA USA. [Chain, Patrick S. G.] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM USA. [Huot-Creasy, Heather; Ravel, Jacques; Schriml, Lynn; White, Owen; Wortman, Jennifer R.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Dawyndt, Peter] Univ Ghent, Dept Appl Math & Comp Sci, B-9000 Ghent, Belgium. [DeSantis, Todd] Lawrence Berkeley Natl Lab, Ctr Environm Biotechnol, Berkeley, CA USA. [Fierer, Noah; Guralnick, Robert; Legg, Teresa] Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA. [Fuhrman, Jed A.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Gallery, Rachel E.] Natl Ecol Observ Network, Boulder, CO USA. [Gibbs, Richard A.; Highlander, Sarah; Petrosino, Joseph] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Gibbs, Richard A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Gil, Inigo San] Univ New Mexico, Dept Biol, LTER Network Off, Albuquerque, NM 87131 USA. [Gonzalez, Antonio; Knights, Dan] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA. [Gordon, Jeffrey I.; Kau, Andrew L.; Muegge, Brian; Smith, Michelle I.; Yatsunenko, Tanya] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO USA. [Guralnick, Robert] Univ Colorado, Museum Nat Hist, Boulder, CO 80309 USA. [Highlander, Sarah; Petrosino, Joseph] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Hugenholtz, Philip] Univ Queensland, Sch Chem & Mol Biosci, Australian Ctr Ecogen, Brisbane, Qld, Australia. [Jansson, Janet] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Earth Sci, Berkeley, CA 94720 USA. [Kelley, Scott T.] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. [Koren, Omry; Ley, Ruth E.; Spor, Ayme] Cornell Univ, Dept Microbiol, Ithaca, NY USA. [Lauber, Christian L.; Lyons, Donna] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA. [Ludwig, Wolfgang] Tech Univ Munich, Lehrstuhl Mikrobiol, D-8050 Freising Weihenstephan, Germany. [Methe, Barbara A.; Nelson, Karen E.] J Craig Venter Inst, Rockville, MD USA. [Nemergut, Diana] Univ Colorado, Dept Environm Sci, Boulder, CO 80309 USA. [Neufeld, Josh D.] Univ Waterloo, Dept Biol, Waterloo, ON N2L 3G1, Canada. [Palanisamy, Giriprakash] Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN 37831 USA. [Peplies, Joerg] Ribocon GmbH, Bremen, Germany. [Raes, Jeroen] Vrije Univ Brussel VIB, B-1050 Brussels, Belgium. [Ratnasingham, Sujeevan] Univ Guelph, Biodivers Inst Ontario, Canadian Ctr DNA Barcoding, Guelph, ON N1G 2W1, Canada. [Relman, David A.] Stanford Univ, Dept Microbiol, Sch Med, Stanford, CA 94305 USA. [Relman, David A.] Stanford Univ, Dept Immunol, Sch Med, Stanford, CA 94305 USA. [Relman, David A.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Schloss, Patrick D.] Dept Microbiol & Immunol, Ann Arbor, MI USA. [Sodergren, Erica; Weinstock, George M.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63110 USA. RP Glockner, FO (reprint author), Max Planck Inst Marine Microbiol, Microbial Genom & Bioinformat Grp, Bremen, Germany. EM fog@mpi-bremen.de RI Ley, Ruth/M-8542-2014; Park, Joonhong/A-3520-2016; Knight, Rob/D-1299-2010; Kyrpides, Nikos/A-6305-2014; Weinstock, George/C-6314-2013; Fuhrman, Jed/C-6461-2013; Bork, Peer/F-1813-2013; Ratnasingham, Sujeevan/G-9103-2014; Arumugam, Manimozhiyan/E-1211-2011; Hugenholtz, Philip/G-9608-2011; Whiteley, Andrew/A-3395-2012; Spor, Ayme/A-6271-2012; Jansson, Janet/F-9951-2012; Park, Joonhong/G-8064-2012; bailey, mark/I-7149-2012; Dawyndt, Peter/A-1566-2013; chain, patrick/B-9777-2013 OI Koren, Omry/0000-0002-7738-1337; Maguire, Eamonn/0000-0002-7277-7834; Cochrane, Guy/0000-0001-7954-7057; Schriml, Lynn/0000-0001-8910-9851; Chain, Patrick/0000-0003-3949-3634; Bushman, Frederic/0000-0003-4740-4056; Buttigieg, Pier Luigi/0000-0002-4366-3088; Schloss, Patrick/0000-0002-6935-4275; Newbold, Lindsay/0000-0001-8895-1406; Dawyndt, Peter/0000-0002-1623-9070; Ley, Ruth/0000-0002-9087-1672; Kyrpides, Nikos/0000-0002-6131-0462; Sansone, Susanna-Assunta/0000-0001-5306-5690; Meyer, Folker/0000-0003-1112-2284; Wortman, Jennifer/0000-0002-8713-1227; Ravel, Jacques/0000-0002-0851-2233; Yilmaz, Pelin/0000-0003-4724-323X; Hunter, Christopher/0000-0002-1335-0881; Sterk, Peter/0000-0003-1668-7778; Weinstock, George/0000-0002-2997-4592; Bork, Peer/0000-0002-2627-833X; Arumugam, Manimozhiyan/0000-0002-0886-9101; Spor, Ayme/0000-0002-4707-9559; bailey, mark/0000-0002-0147-7316; FU Howard Hughes Medical Institute; NHGRI NIH HHS [R01 HG005975, R01 HG005975-02, U54 HG003273]; NHLBI NIH HHS [U01 HL098957]; NIDDK NIH HHS [K01 DK090285, UH2 DK083981] NR 30 TC 174 Z9 177 U1 4 U2 50 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2011 VL 29 IS 5 BP 415 EP 420 DI 10.1038/nbt.1823 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 760CX UT WOS:000290301700021 PM 21552244 ER PT J AU Wynn, TA Ramalingam, TR AF Wynn, Thomas A. Ramalingam, Thirumalai R. TI Shedding LIGHT on severe asthma SO NATURE MEDICINE LA English DT Editorial Material ID INFLAMMATION; ACTIVATION; EXPRESSION; FIBROSIS; AIRWAYS; DISEASE; ALPHA; CELLS; TUMOR; TNF C1 [Wynn, Thomas A.; Ramalingam, Thirumalai R.] NIAID, NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 FU Intramural NIH HHS [ZIA AI001019-04] NR 14 TC 3 Z9 3 U1 0 U2 1 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 MAY PY 2011 VL 17 IS 5 BP 547 EP 548 DI 10.1038/nm0511-547 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 759MR UT WOS:000290250400026 PM 21546971 ER PT J AU Wuest, SC Edwan, JH Martin, JF Han, S Perry, JSA Cartagena, CM Matsuura, E Maric, D Waldmann, TA Bielekova, B AF Wuest, Simone C. Edwan, Jehad H. Martin, Jayne F. Han, Sungpil Perry, Justin S. A. Cartagena, Casandra M. Matsuura, Eiji Maric, Dragan Waldmann, Thomas A. Bielekova, Bibiana TI A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy SO NATURE MEDICINE LA English DT Article ID MULTIPLE-SCLEROSIS; IL-2 RECEPTOR; ALPHA-CHAIN; CLINICAL-TRIAL; NK CELLS; LYMPHOCYTES; DEFICIENCY; ANTIBODIES; DISEASE; CD25 AB Although previous studies have described CD25 expression and production of interleukin-2 (IL-2) by mature dendritic cells (mDCs), it remains unclear how these molecules participate in the activation of T cells. In search of the mechanisms by which daclizumab, a humanized monoclonal antibody against CD25, inhibits brain inflammation in multiple sclerosis, we observed that although the drug has limited effects on polyclonal T cell activation, it potently inhibits activation of antigen-specific T cells by mDCs. We show that mDCs (and antigen-experienced T cells) secrete IL-2 toward the mDC-T cell interface in an antigen-specific manner, and mDCs 'lend' their CD25 to primed T cells in trans to facilitate early high-affinity IL-2 signaling, which is crucial for subsequent T cell expansion and development of antigen-specific effectors. Our data reveal a previously unknown mechanism for the IL-2 receptor system in DC-mediated activation of T cells. C1 [Wuest, Simone C.; Edwan, Jehad H.; Martin, Jayne F.; Han, Sungpil; Perry, Justin S. A.; Cartagena, Casandra M.; Matsuura, Eiji; Bielekova, Bibiana] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Han, Sungpil] Pusan Natl Univ, Sch Med, Yangsan, South Korea. [Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Waldmann, Thomas A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM bibi.bielekova@nih.gov RI MATSUURA, EIJI/E-1231-2013; OI MATSUURA, EIJI/0000-0001-8215-8853; Han, Sungpil/0000-0002-4674-7682 FU NINDS/NIH FX The study was supported by the intramural research program of the NINDS/NIH. We thank A. Kashani for expert technical assistance in processing apheresis samples and M. Lenardo, W. Leonard and H. McFarland for their critical review of the manuscript and helpful comments. Additionally, we are thankful to M. Lenardo and H. Su (NIH) for providing cryopreserved peripheral blood mononuclear cells (PBMCs) from the CD25- individual. Daclizumab Fab was provided by Abbott Biotherapeutics, under Material Transfer Agreement. NR 34 TC 123 Z9 126 U1 3 U2 12 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 MAY PY 2011 VL 17 IS 5 BP 604 EP U125 DI 10.1038/nm.2365 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 759MR UT WOS:000290250400037 PM 21532597 ER PT J AU Anthony, K AF Anthony, Kira TI ANTICANCER DRUGS Think globally, act globally SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. RP Anthony, K (reprint author), NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD MAY PY 2011 VL 10 IS 5 DI 10.1038/nrd3437 PG 1 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 756MX UT WOS:000290017300015 PM 21532563 ER PT J AU Pathare, SM Gerstung, M Beerenwinkel, N Schaffer, AA Kannan, S Pai, P Pathak, KA Borges, AM Mahimkar, MB AF Pathare, Swapnali M. Gerstung, Moritz Beerenwinkel, Niko Schaeffer, Alejandro A. Kannan, Sadhana Pai, Prathamesh Pathak, K. Alok Borges, Anita M. Mahimkar, Manoj B. TI Clinicopathological and prognostic implications of genetic alterations in oral cancers SO ONCOLOGY LETTERS LA English DT Article DE oral cancer; comparative genomic hybridization; prognosis; survival analysis; gain of 11q13; loss of 18q ID SQUAMOUS-CELL CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN-PAPILLOMAVIRUS; NECK-CANCER; CHROMOSOMAL IMBALANCES; MALIGNANT LESIONS; IMPROVED SURVIVAL; DNA-PLOIDY; HEAD; PROGRESSION AB This study evaluated the clinicopathological and prognostic implications of genetic alterations characterizing oral squamous cell carcinoma (OSCC). Comparative genomic hybridization was used to identify chromosomal alterations present in primary OSCCs obtained from 97 patients. In this population, tobacco use was a significant risk factor for OSCC. By contrast, the 97 samples were negative for human papillomavirus (HPV) DNA integration, which is another known risk factor for OSCC in certain populations. Results of the Fisher's exact test, followed by the Benjamini-Hochberg correction for multiple testing, showed a correlation of 7p gain and 8p loss with node-positive OSCC (p <= 0.04 for both genetic alterations) and an association of 11q13 gain with high-grade OSCC (p <= 0.05). Univariate Cox-proportional hazard models, also corrected for multiple testing, showed a significant association of 11q13 gain and 18q loss with decreased survival (p <= 0.05). The findings were supported by multivariate analysis, which revealed that 11q13 gain and 18q loss together serve as a strong bivariate predictor of poor prognosis. In conclusion, our study has identified genetic alterations that correlate significantly with nodal status, grade and the poor survival status of OSCC. These potential biomarkers may aid the current tumor node metastasis system for better prediction of clinical outcome. C1 [Pathare, Swapnali M.; Mahimkar, Manoj B.] Tata Mem Ctr TMC, Adv Ctr Treatment Res & Educ Canc ACTREC, Canc Res Inst, Kharghar Node 410210, Navi Mumbai, India. [Kannan, Sadhana] Tata Mem Ctr TMC, Adv Ctr Treatment Res & Educ Canc ACTREC, ECTU, Adv Ctr Treatment, Kharghar Node 410210, Navi Mumbai, India. [Pai, Prathamesh] Tata Mem Hosp, Tata Mem Ctr TMC, Bombay 400012, Maharashtra, India. [Borges, Anita M.] SL Raheja Hosp, Dept Pathol & Lab Med, Mumbai 400016, Maharashtra, India. [Gerstung, Moritz; Beerenwinkel, Niko] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland. [Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA. [Pathak, K. Alok] Canc Care Manitoba, Winnipeg, MB R3A 1R9, Canada. RP Mahimkar, MB (reprint author), Tata Mem Ctr TMC, Adv Ctr Treatment Res & Educ Canc ACTREC, Canc Res Inst, Kharghar Node 410210, Navi Mumbai, India. EM mmahimkar@actrec.gov.in RI Schaffer, Alejandro/F-2902-2012; OI Gerstung, Moritz/0000-0001-6709-963X FU Indian Council of Medical Research (ICMR) [5/13/2/TF/2001-NCD-III]; National Institutes of Health, NLM; CSIR FX The authors are thankful to the Indian Council of Medical Research (ICMR; Grant no.5/13/2/TF/2001-NCD-III) for funding the project. This study was also supported by the Intramural Research Program of the National Institutes of Health, NLM. We thank CSIR for providing fellowship to Ms. Swapnali Pathare during her tenure as a graduate (PhD) student. NR 46 TC 12 Z9 13 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD MAY-JUN PY 2011 VL 2 IS 3 BP 445 EP 451 DI 10.3892/ol.2011.271 PG 7 WC Oncology SC Oncology GA 758AZ UT WOS:000290133200009 PM 21546976 ER PT J AU Stoll, BJ Hansen, NI Sanchez, PJ Faix, RG Poindexter, BB Van Meurs, KP Bizzarro, MJ Goldberg, RN Frantz, ID Hale, EC Shankaran, S Kennedy, K Carlo, WA Watterberg, KL Bell, EF Walsh, MC Schibler, K Laptook, AR Shane, AL Schrag, SJ Das, A Higgins, RD AF Stoll, Barbara J. Hansen, Nellie I. Sanchez, Pablo J. Faix, Roger G. Poindexter, Brenda B. Van Meurs, Krisa P. Bizzarro, Matthew J. Goldberg, Ronald N. Frantz, Ivan D., III Hale, Ellen C. Shankaran, Seetha Kennedy, Kathleen Carlo, Waldemar A. Watterberg, Kristi L. Bell, Edward F. Walsh, Michele C. Schibler, Kurt Laptook, Abbot R. Shane, Andi L. Schrag, Stephanie J. Das, Abhik Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst C TI Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues SO PEDIATRICS LA English DT Article DE neonatal sepsis; group B streptococcal disease; Escherichia coli infection ID INTRAPARTUM ANTIBIOTIC-PROPHYLAXIS; BIRTH-WEIGHT INFANTS; INTENSIVE-CARE-UNIT; ESCHERICHIA-COLI; PRETERM INFANTS; INFECTIONS; ERA; MENINGITIS; RESISTANCE; PATTERNS AB BACKGROUND: Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen. OBJECTIVE: To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers. METHODS: Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged <= 72 hours plus treatment with antibiotic therapy for >= 5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence. RESULTS: Among 396 586 LBs (2006-2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%). CONCLUSION: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge. Pediatrics 2011;127:817-826 C1 [Stoll, Barbara J.; Hale, Ellen C.; Shane, Andi L.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Stoll, Barbara J.; Hale, Ellen C.; Shane, Andi L.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Hansen, Nellie I.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA. [Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA. [Van Meurs, Krisa P.] Stanford Univ, Med Ctr, Div Neonatol, Palo Alto, CA 94304 USA. [Bizzarro, Matthew J.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Frantz, Ivan D., III] Floating Hosp Children, Tufts Med Ctr, Dept Pediat, Boston, MA USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Kennedy, Kathleen] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA. [Watterberg, Kristi L.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. [Schibler, Kurt] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Schrag, Stephanie J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Stoll, BJ (reprint author), Emory Univ, Sch Med, Dept Pediat, 2015 Uppergate Dr, Atlanta, GA 30322 USA. EM barbara_stoll@oz.ped.emory.edu FU National Institutes of Health (NIH); National Institutes of Health, National Center for Research Resources [UL1 RR025008]; National Institutes of Health; NICHD; Centers for Disease Control and Prevention FX Funded by the National Institutes of Health (NIH).; This study was supported in part by PHS grant UL1 RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources. The National Institutes of Health, the NICHD, and the Centers for Disease Control and Prevention provided grant support for the Neonatal Research Network's Early Onset Sepsis Study. Data collected at participating sites of the NICHD NRN were transmitted to RTI International, the data coordinating center (DCC) for the network, which stored, managed, and analyzed the data for this study. On behalf of the NRN, Dr Abhik Das (DCC Principal Investigator), and Ms Nellie Hansen (DCC Statistician) had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. NR 25 TC 248 Z9 261 U1 5 U2 31 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2011 VL 127 IS 5 BP 817 EP 826 DI 10.1542/peds.2010-2217 PG 10 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800040 PM 21518717 ER PT J AU Paulson, JA Binns, HJ Brumberg, HL Forman, JA Karr, CJ Osterhoudt, KC Sandel, MT Seltzer, JM Wright, RO Mortensen, M Savage, S Rogan, WJ Pellegrini, C Spire, P AF Paulson, Jerome A. Binns, Helen J. Brumberg, Heather L. Forman, Joel A. Karr, Catherine J. Osterhoudt, Kevin C. Sandel, Megan T. Seltzer, James M. Wright, Robert O. Mortensen, Mary Savage, Sharon Rogan, Walter J. Pellegrini, Cindy Spire, Paul TI Policy Statement-Chemical-Management Policy: Prioritizing Children's Health SO PEDIATRICS LA English DT Article DE environmental health ID POLYBROMINATED DIPHENYL ETHERS; BREAST-MILK; PBDES AB The American Academy of Pediatrics recommends that chemical-management policy in the United States be revised to protect children and pregnant women and to better protect other populations. The Toxic Substance Control Act (TSCA) was passed in 1976. It is widely recognized to have been ineffective in protecting children, pregnant women, and the general population from hazardous chemicals in the marketplace. It does not take into account the special vulnerabilities of children in attempting to protect the population from chemical hazards. Its processes are so cumbersome that in its more than 30 years of existence, the TSCA has been used to regulate only 5 chemicals or chemical classes of the tens of thousands of chemicals that are in commerce. Under the TSCA, chemical companies have no responsibility to perform premarket testing or postmarket follow-up of the products that they produce; in fact, the TSCA contains disincentives for the companies to produce such data. Voluntary programs have been inadequate in resolving problems. Therefore, chemical-management policy needs to be rewritten in the United States. Manufacturers must be responsible for developing information about chemicals before marketing. The US Environmental Protection Agency must have the authority to demand additional safety data about a chemical and to limit or stop the marketing of a chemical when there is a high degree of suspicion that the chemical might be harmful to children, pregnant women, or other populations. Pediatrics 2011; 127: 983-990 C1 [Mortensen, Mary] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Savage, Sharon] NCI, Bethesda, MD 20892 USA. NR 41 TC 20 Z9 20 U1 0 U2 8 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 MAY PY 2011 VL 127 IS 5 BP 983 EP 990 DI 10.1542/peds.2011-0523 PG 8 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800060 ER PT J AU Bowers, K Liu, GS Wang, P Ye, T Tian, Z Liu, E Yu, ZJ Yang, XL Klebanoff, M Yeung, E Hu, G Zhang, CL AF Bowers, Katherine Liu, Gongshu Wang, Ping Ye, Tao Tian, Zhen Liu, Enqing Yu, Zhijie Yang, Xilin Klebanoff, Mark Yeung, Edwina Hu, Gang Zhang, Cuilin TI Birth Weight, Postnatal Weight Change, and Risk for High Blood Pressure Among Chinese Children SO PEDIATRICS LA English DT Article DE birth weight; hypertension; fetal origins ID ADULT HYPERTENSION; CARDIOVASCULAR-DISEASE; HEART-DISEASE; CHILDHOOD; OBESITY; GROWTH; DEATH; WOMEN; ASSOCIATION; OVERWEIGHT AB BACKGROUND: It is hypothesized that a physiological predisposition toward hypertension results from a combination of intrauterine growth restriction or overgrowth and excessive postnatal weight gain. Previous studies were conducted largely in Western countries however the hypothesis may also be relevant in developing countries where metabolic disorders are increasing. OBJECTIVE: We investigated the association of birth weight and postnatal weight gain with hypertension among Chinese children. METHODS: A population based study was conducted among 15 600 children aged 3 to 6 years from Tianjin, China. Weight was expressed as z scores. Postnatal weight gain was defined as changes in z scores from birth to 3 to younger than 4 years, 4 to younger than 5 years, and 5 to 6 years. Hypertension was defined as greater than the 90th percentile of either systolic or diastolic blood pressure. Logistic regression-derived odds ratios and 95% confidence intervals were generated to estimate the association between birth weight and postnatal weight gain with hypertension risk in childhood. RESULTS: Birth weight was positively associated with childhood hypertension in boys and girls (odds ratios [95% confidence interval] comparing extreme quartiles [high versus low] were 5.67 [3.83-8.39] and 2.58 [3.83-8.39], respectively). Postnatal weight gain was positively associated with hypertension and the association did not significantly vary by birth size for gestational age. CONCLUSIONS: Greater birth weight or postnatal weight gain was associated with increased childhood hypertension risk, suggesting that intrauterine growth and postnatal weight gain may have implications on health during childhood. Pediatrics 2011;127:e1272-e1279 C1 [Bowers, Katherine; Klebanoff, Mark; Yeung, Edwina; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20852 USA. [Liu, Gongshu; Wang, Ping; Ye, Tao; Tian, Zhen; Liu, Enqing] Tianjin Womens & Childrens Hlth Ctr, Tianjin, Peoples R China. [Yu, Zhijie] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai, Peoples R China. [Yang, Xilin] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Hu, Gang] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20852 USA. EM zhangcu@mail.nih.gov RI Hossain, Sarah /C-7332-2009; Bowers, Katherine/N-5226-2015; OI Hossain, Sarah /0000-0003-1355-0979; Yeung, Edwina/0000-0002-3851-2613 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX Katherine Bowers, Mark Klebanoff, Edwina Yeung, and Cuilin Zhang were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 26 TC 19 Z9 21 U1 0 U2 5 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 MAY PY 2011 VL 127 IS 5 BP E1272 EP E1279 DI 10.1542/peds.2010-2213 PG 8 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800022 PM 21502227 ER PT J AU Gaur, AH Freimanis-Hance, L Dominguez, K Mitchell, C Menezes, J Mussi-Pinhata, MM Peixoto, MF Alarcon, J Coelho, DF Read, JS AF Gaur, Aditya H. Freimanis-Hance, Laura Dominguez, Kenneth Mitchell, Charles Menezes, Jacqueline Mussi-Pinhata, Marisa M. Peixoto, Mario F. Alarcon, Jorge Coelho, Debora F. Read, Jennifer S. TI Knowledge and Practice of Prechewing/Prewarming Food by HIV-Infected Women SO PEDIATRICS LA English DT Article DE HIV; prechewing; prewarming; premastication; child ID INFANT; PREMASTICATION AB OBJECTIVE: HIV transmission has been associated with offering a child food prechewed by an HIV-infected caregiver. We assessed awareness of prechewing and oral prewarming of food by an adult before offering it to a child among HIV-infected pregnant women and clinical investigators in 3 Latin American countries. METHODS: HIV-infected pregnant women at 12 sites (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative Perinatal Longitudinal Study in Latin American Countries, a prospective cohort trial) in Argentina, Brazil, and Peru were administered a screening survey about prechewing/prewarming of infant foods and cautioned against these feeding practices. Survey responses were analyzed, overall, and stratified according to country. RESULTS: Of the 401 HIV-infected pregnant women interviewed, 34% had heard about prechewing (50% from Argentina, 32% from Brazil, and 36% from Peru), 23% knew someone who prechewed food for infants, and 4% had prechewed food in the past. Seventeen percent had heard about oral prewarming of food, 13% knew someone who prewarmed food for infants, and 3% had prewarmed food for an infant in the past. Women who reported knowing someone who prechewed were more likely to also know someone who prewarmed food (P < .0001). Few site investigators anticipated that their patients would be aware of these practices. CONCLUSIONS: Prechewing food, a potential risk factor for HIV transmission, and orally prewarming food, which has not been associated with HIV transmission but might expose a child to blood from an HIV-infected adult, are not uncommon practices in Latin America. Both practices should be further investigated. Site investigator responses underscore that health care providers could be missing information about cultural practices that patients may not report unless specifically asked. Pediatrics 2011;127:e1206-e1211 C1 [Gaur, Aditya H.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Freimanis-Hance, Laura] Westat Corp, Rockville, MD USA. [Dominguez, Kenneth] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Mitchell, Charles] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Menezes, Jacqueline] Hosp Servidores Estado, Policlin Santa Clara, Unidade Pesquisa Materno Infantil, Rio De Janeiro, Brazil. [Mussi-Pinhata, Marisa M.] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, Brazil. [Peixoto, Mario F.] Hosp Femina, Dept Infect Dis, Porto Alegre, RS, Brazil. [Alarcon, Jorge] Univ Nacl Mayor San Marcos, Inst Med Trop Daniel Alcides Carrion, Secc Epidemiol, Lima 14, Peru. [Coelho, Debora F.] Irmandade Santa Casa de Misericordia, Serv Doencas Infecciosas & Parasitarias, Porto Alegre, RS, Brazil. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. RP Gaur, AH (reprint author), St Jude Childrens Hosp, Dept Infect Dis MS 600, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM aditya.gaur@stjude.org RI Mussi-Pinhata, Marisa/G-6568-2012; OI Alarcon, Jorge/0000-0002-0800-2380 FU National Institutes of Health (NIH); NICHD [N01-HD-3-3345, HHSN267200800001C, N01-HD-8-0001] FX Funded by the National Institutes of Health (NIH).; Principal investigators, co-principal investigators, study coordinators, coordinating center representatives, and NICHD staff include: Argentina: Buenos Aires: Marcelo H. Losso, Irene Foradori, Claudia Checa, Silvina Ivalo (Hospital General de Agudos Jose Maria Ramos Mejia); Brazil: Belo Horizonte: Jorge Pinto, Victor Melo, Fabiana Kakehasi (Universidade Federal de Minas Gerais); Caxias do Sul: Ricardo da Silva de Souza, Nicole Golin, S~lvia Mariani Costamilan (Universidade de Caxias do Sul/Servico Municipal de Infectologia); Nova Iguacu: Jose Pilotto, Beatriz Grinsztejn, Valdilea Veloso, Gisely Falco (Hospital Geral Nova de Iguacu - HIV Family Care Clinic); Porto Alegre: Ricardo da Silva de Souza, Breno Riegel Santos, Rita de Cassia Alves Lira (Universidade de Caxias do Sul/Hospital Conceicao); Ricardo da Silva de Souza, Mario Ferreira Peixoto, Elizabete Teles (Universidade de Caxias do Sul/Hospital Famina); Regis Kreitchmann, Luis Carlos Ribeiro, Fabrizio Motta, Debora Fernandes Coelho (Irmandade da Santa Casa de Misericordia de Porto Alegre); Ribeirao Preto: Marisa M. Mussi-Pinhata, Geraldo Duarte, Adriana A. Tiraboschi Barbaro, Conrado Milani Coutinho, Anderson Sanches de Melo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo); Rio de Janeiro: Ricardo Hugo S. Oliveira, Elizabeth S. Machado, Maria C. Chermont Sapia (Instituto de Puericultura e Pediatria Martagao Gesteira); Esau Custodio Joao, Leon Claude Sidi, Ezequias Martins, Plinio Tostes Berardo (Hospital dos Servidores do Estado); Sao Paulo: Regina Celia de Menezes Succi, Prescilla Chow (Universidade Federal de Sao Paulo); Peru: Lima: Jorge Alarcon Villaverde (Instituto de Medicina Tropical "Daniel Alcides Carrion"-Seccion de Epidemiologia, UNMSM), Carlos Velasquez Vasquez (Instituto Nacional Materno Perinatal), Cesar Gutierrez Villafuerte (Instituto de Medicina Tropical "Daniel Alcides Carrion"-Seccion de Epidemiologia, UNMSM); Data Management and Statistical Center: Yolanda Bertucci, Laura Freimanis Hance, Rene Gonin, D. Robert Harris, Roslyn Hennessey, James Korelitz, Margot Krauss, Sharon Sothern de Sanchez, Sonia K. Stoszek (Westat, Rockville, MD, USA); NICHD: Rohan Hazra, Lynne Mofenson, Jennifer S. Read, Heather Watts, Carol Worrell (Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA). Supported by NICHD Contract # N01-HD-3-3345 (2002-2007) and by NICHD Contract # HHSN267200800001C (NICHD Control #: N01-HD-8-0001) (2007-2012). NR 18 TC 4 Z9 4 U1 0 U2 3 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 MAY PY 2011 VL 127 IS 5 BP E1206 EP E1211 DI 10.1542/peds.2010-1902 PG 6 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800014 PM 21482608 ER PT J AU Manasyan, A Chomba, E McClure, EM Wright, LL Krzywanski, S Carlo, WA AF Manasyan, Albert Chomba, Elwyn McClure, Elizabeth M. Wright, Linda L. Krzywanski, Sara Carlo, Waldemar A. CA Eunice Kennedy Shriver Natl Inst TI Cost-effectiveness of Essential Newborn Care Training in Urban First-Level Facilities SO PEDIATRICS LA English DT Article DE developing countries; low-middle income countries; neonatal mortality; perinatal mortality; midwives ID DEVELOPING-COUNTRIES; CHILD-MORTALITY; INTERVENTIONS; HEALTH; IMPACT AB OBJECTIVE: To determine the cost-effectiveness of the World Health Organization (WHO) Essential Newborn Care (ENC) training of health care providers in first-level facilities in the 2 largest cities in Zambia. METHODS: Data were extracted from a study in which the effectiveness of the ENC training was evaluated (including universal precautions and cleanliness, routine neonatal care, resuscitation, thermoregulation, breastfeeding, skin-to-skin care, care of the small infant, danger signs, and common illnesses). The costs to train an ENC instructor for each first-level delivery facility and the costs of salary/benefits for 2 coordinators responsible for maintenance of the program were recorded in 2005 US dollars. The incremental costs per life gained and per disability-adjusted life-year averted were calculated. SETTING: A 5-day ENC training-of-trainers was conducted in Lusaka, Zambia, to certify 18 college-trained midwives as ENC instructors. The instructors trained all clinic midwives working in their first-level facilities as part of a before-and-after study of the effect of ENC training on early neonatal mortality conducted from Oct 2004 to Nov 2006. RESULTS: All-cause 7-day (early) neonatal mortality decreased from 11.5 per 1000 to 6.8 per 1000 live births after ENC training of the clinic midwives (relative risk: 0.59; 95% confidence interval: 0.48-0.77; P < .001; 40 615 births). The intervention costs were $208 per life saved and $5.24 per disability-adjusted life-year averted. CONCLUSIONS: ENC training of clinic midwives who provide care in low-risk facilities is a low-cost intervention that can reduce early neonatal mortality in these settings. Pediatrics 2011;127:e1176-e1181 C1 [Carlo, Waldemar A.] Univ Alabama, Women & Infants Ctr 9380, Dept Pediat, Birmingham, AL 35233 USA. [Chomba, Elwyn; Carlo, Waldemar A.] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Chomba, Elwyn] Univ Zambia, Dept Pediat, Lusaka, Zambia. [McClure, Elizabeth M.] RTI Int, Durham, NC USA. [Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Carlo, WA (reprint author), Univ Alabama, Women & Infants Ctr 9380, Dept Pediat, 1700 6th Ave S, Birmingham, AL 35233 USA. EM wcarlo@peds.uab.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research [U01 HD043464, R01 HD053055]; Bill and Melinda Gates Foundation FX This study was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research (U01 HD043464, R01 HD053055) and the Bill and Melinda Gates Foundation. NR 21 TC 12 Z9 12 U1 0 U2 3 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 MAY PY 2011 VL 127 IS 5 BP E1176 EP E1181 DI 10.1542/peds.2010-2158 PG 6 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800010 PM 21502223 ER PT J AU Tercyak, KP Alford, SH Emmons, KM Lipkus, IM Wilfond, BS McBride, CM AF Tercyak, Kenneth P. Alford, Sharon Hensley Emmons, Karen M. Lipkus, Isaac M. Wilfond, Benjamin S. McBride, Colleen M. TI Parents' Attitudes Toward Pediatric Genetic Testing for Common Disease Risk SO PEDIATRICS LA English DT Article DE genetic testing; chronic disease; risks and benefits; children; parents ID PERSONALIZED MEDICINE; PSYCHOLOGICAL-ASPECTS; CONFOUNDER-SELECTION; GENOMICS; CHILDREN; HEALTH; CANCER; BEHAVIORS; WILL; OPPORTUNITIES AB OBJECTIVE: To describe parents' attitudes toward pediatric genetic testing for common, adult-onset health conditions and to identify factors underlying these attitudes. PARTICIPANTS AND METHODS: Parents (n = 219) enrolled in a large, group-practice health plan were offered a "multiplex" genetic test for susceptibility to 8 common, adult-onset health conditions and completed an online survey assessing attitudes and beliefs about the risks and benefits of the test for their child, their willingness to consider having their child tested, and other psychosocial variables. RESULTS: Parents viewed the benefits of pediatric testing to outweigh its risks (positive decisional balance) and were moderately interested in pediatric testing. Variables associated with positive decisional balance included greater interest in knowing about gene-health associations in their child, anticipation of less difficulty understanding their child's genetic health risks, and more positive emotional reactions to learning about their child's decreased health risks (adjusted R-2 = 0.33, P < .0001). Similarly, variables associated with greater parental willingness to test were being a mother (versus being a father), greater perceived risk of diseases in their child, greater interest in knowing about gene-health relationships in their child, anticipating less difficulty learning about their child's genetic health risks, anticipating more positive emotional reactions to learning about their child's decreased health risks, and positive decisional balance (adjusted R-2 = 0.57, P < .0001). CONCLUSIONS: As genetic susceptibility testing for common, adult-onset health conditions proliferates, pediatricians should anticipate parents' interest in testing children and be prepared to facilitate informed decision making about such testing. Pediatrics 2011;127:e1288-e1295 C1 [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hlth Outcomes & Hlth Behav,Dept Oncol, Washington, DC 20007 USA. [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lipkus, Isaac M.] Duke Univ, Sch Nursing, Durham, NC USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Seattle Childrens Hosp, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Tercyak, KP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hlth Outcomes & Hlth Behav,Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM tercyakk@georgetown.edu FU National Institutes of Health (NIH) [HHSN268200782096C]; National Human Genome Research Institute at the National Institutes of Health; National Institutes of Health/National Cancer Institute [U19CA079689]; Group Health Research Institute; Henry Ford Hospital; Center for Inherited Disease Research; National Human Genome Research Institute [R01HG002686]; National Cancer Institute [R01CA137625] FX Funded by the National Institutes of Health (NIH).; This work was supported by the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health. The research also was made possible by collaboration with the health management organization Cancer Research Network (CRN) funded by the National Institutes of Health/National Cancer Institute (U19CA079689). The overall goal of the CRN is to use a consortium of delivery systems to conduct cancer research. Additional resources were provided by the Group Health Research Institute and the Henry Ford Hospital. Genotyping services were provided by the Center for Inherited Disease Research, an entity fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). Manuscript preparation was supported by grants from the Ethical, Legal, and Social Implication Research Program of the National Human Genome Research Institute (R01HG002686) and from the National Cancer Institute (R01CA137625 to Kenneth P. Tercyak). NR 35 TC 28 Z9 28 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2011 VL 127 IS 5 BP E1288 EP E1295 DI 10.1542/peds.2010-0938 PG 8 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800024 PM 21502235 ER PT J AU Detera-Wadleigh, SD Akula, N AF Detera-Wadleigh, S. D. Akula, N. TI A Systems Approach to the Biology of Mood Disorders through Network Analysis of Candidate Genes SO PHARMACOPSYCHIATRY LA English DT Article ID BIPOLAR DISORDER; SCHIZOPHRENIA; CACNA1C AB Meta analysis of association data of mood disorders has shown evidence for the role of particular genes in genetic risk. Integration of association data from meta analysis with differential expression data in brains of mood disorder patients could heighten the level of support for specific genes. To identify molecular mechanisms that may be disrupted in disease, a systems approach that involves analysis of biological networks created by these selected genes was employed. Interaction networks of hierarchical groupings of selected genes were generated using the Michigan Molecular Interactions (MiMI) software. Large networks were deconvoluted into subclusters of core complexes by using a community clustering program, GLay. Network nodes were functionally annotated in DAVID Bioinformatics Resource to identify enriched pathways and functional clusters. MAPK and beta adrenergic receptor signaling pathways were significantly enriched in the ANK3 and CACNA1C network. The PBRM1 network bolstered the enrichment of chromatin remodeling and transcription regulation functional clusters. Lowering the stringency for inclusion of other genes in network seeds increased network complexity and expanded the recruitment of enriched pathways to include signaling by neurotransmitter and hormone receptors, neurotrophin, ErbB and the cell cycle. We present a strategy to interrogate mechanisms in the cellular system that might be perturbed in disease. Network analysis of meta analysis-generated candidate genes that exhibited differential expression in mood disorder brains identified signaling pathways and functional clusters that may be involved in genetic risk for mood disorders. C1 [Detera-Wadleigh, S. D.; Akula, N.] NIMH, Human Genet Branch, NIH, Bethesda, MD 20892 USA. RP Detera-Wadleigh, SD (reprint author), NIMH, Human Genet Branch, NIH, Bldg 35,Rm 1A205, Bethesda, MD 20892 USA. EM deteras@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health FX We wish to thank Francis McMahon for his critical reading of the manuscript. This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 18 TC 10 Z9 10 U1 0 U2 6 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD MAY PY 2011 VL 44 SU 1 BP S35 EP S42 DI 10.1055/s-0031-1275275 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 761RM UT WOS:000290416000006 PM 21547870 ER PT J AU Kim, S DeRoo, LA Sandler, DP AF Kim, Sangmi DeRoo, Lisa A. Sandler, Dale P. TI Eating patterns and nutritional characteristics associated with sleep duration SO PUBLIC HEALTH NUTRITION LA English DT Article DE Eating patterns; Sleep duration; Snack; Eating frequency; Principal component analysis ID BODY-MASS INDEX; ADULT-POPULATION; MEAL PATTERNS; WEIGHT-LOSS; OBESITY; BREAKFAST; RISK; LIFE; FREQUENCY; QUALITY AB Objective: To identify major meal and snack eating patterns, and examine their relationships with sleep duration. Design: The analyses included 27 983 participants in a prospective cohort study of women aged 35 to 74 years in the USA or Puerto Rico. Results: The principal component analysis of eight meal and snack frequency items at different times across the day yielded two major eating patterns: (i) eating during conventional eating hours (defined as times from breakfast to dinner); and (ii) dominance of snacks over meals. Comparing the identified eating patterns among women with varying sleep duration (<5, 5-5.9, 6-6.9, 7-7.9, 8-8.9, 9-9.9 and >= 10 h daily), the tendency for eating during conventional eating hours decreased with decreasing sleep duration: adjusted mean score of -0.54 (95% CI -0.68, -0.41) in women sleeping for <5 h daily v. 0.08 (95% CI 0.06, 0.11) among those with 7-7.9 h of sleep daily. The extent of snack dominance over meals increased in women with shorter sleep. Women with long (>= 10 h) sleep duration had eating patterns similar to those with short (<6 h) sleep duration. Lower tendency for eating during conventional eating hours and greater snack dominance over meals were also related to higher intakes of fat and sweets for energy and lower intakes of fruits and vegetables. Conclusions: Disrupted eating patterns and diet of poor nutritional quality may exacerbate the development of obesity and metabolic diseases in habitual short and very long sleepers. C1 [Kim, Sangmi; DeRoo, Lisa A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27599 USA. RP Sandler, DP (reprint author), NIEHS, Epidemiol Branch, NIH, POB 12233 MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27599 USA. EM sandler@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU NIH, NIEHS [Z01 ES04400509] FX This research was funded by the Intramural Research Program of the NIH, NIEHS (Z01 ES04400509) with additional support from the National Center on Minority Health and Health Disparities. NR 34 TC 30 Z9 30 U1 2 U2 19 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD MAY PY 2011 VL 14 IS 5 BP 889 EP 895 DI 10.1017/S136898001000296X PG 7 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 757SB UT WOS:000290106900018 PM 21029511 ER PT J AU Mitchel, REJ Hasu, M Bugden, M Wyatt, H Little, MP Gola, A Hildebrandt, G Priest, ND Whitman, SC AF Mitchel, R. E. J. Hasu, M. Bugden, M. Wyatt, H. Little, M. P. Gola, A. Hildebrandt, G. Priest, N. D. Whitman, S. C. TI Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; INFLAMMATORY PLAQUE PHENOTYPE; BONE-MARROW-TRANSPLANTATION; AMERICAN-HEART-ASSOCIATION; E-DEFICIENT MICE; IONIZING-RADIATION; ENHANCES ATHEROSCLEROSIS; CORONARY-ARTERIES; INDUSTRY WORKERS; INTERFERON-GAMMA AB The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed either at an early stage of disease (2 months of age) and examined 3 or 6 months later or at a late stage of disease (8 months of age) and examined 2 or 4 months later. Changes in aortic lesion frequency, size and severity as well as total serum cholesterol levels and the uptake of lesion lipids by lesion-associated macrophages were assessed. Statistically significant changes in each of these measures were observed, depending on dose, dose rate and disease stage. In all cases, the results were distinctly non-linear with dose, with maximum effects tending to occur at 25 or 50 mGy. In general, low doses given at low dose rate during either early- or late-stage disease were protective, slowing the progression of the disease by one or more of these measures. Most effects appeared and persisted for months after the single exposures, but some were ultimately transitory. In contrast to exposure at low dose rate, high-dose-rate exposure during early-stage disease produced both protective and detrimental effects, suggesting that low doses may influence this disease by more than one mechanism and that dose rate is an important parameter. These results contrast with the known, generally detrimental effects of high doses on the progression of this disease in the same mice and in humans, suggesting that a linear extrapolation of the known increased risk from high doses to low doses is not appropriate. (C) 2011 by Radiation Research Society C1 [Mitchel, R. E. J.; Bugden, M.; Wyatt, H.; Priest, N. D.] Atom Energy Canada Ltd, Radiol Protect Res & Instrumentat Branch, Chalk River, ON K0J 1J0, Canada. [Hasu, M.; Whitman, S. C.] Univ Ottawa, Dept Pathol & Lab Med, Ottawa, ON, Canada. [Hasu, M.; Whitman, S. C.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada. [Hasu, M.; Whitman, S. C.] Univ Ottawa, Inst Heart, Vasc Biol Grp, Ottawa, ON, Canada. [Little, M. P.] NCI, Radiat Epidemiol Branch, Rockville, MD USA. [Gola, A.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Biostat, London, England. [Hildebrandt, G.] Univ Hosp, Dept Radiotherapy, Rostock, Germany. RP Mitchel, REJ (reprint author), Atom Energy Canada Ltd, Radiol Protect Res & Instrumentat Branch, Chalk River, ON K0J 1J0, Canada. EM mitchelr@aecl.ca FU European Commission [FP6-036465]; Atomic Energy of Canada Limited; European Commission and Health Canada FX This work was performed as part of the European Commission FP6 NOTE project "Non-targeted effects of ionising radiation" (FP6-036465) and was funded by Atomic Energy of Canada Limited, the European Commission and Health Canada. This manuscript is dedicated to the memory of Dr. Stewart Whitman. NR 34 TC 40 Z9 45 U1 0 U2 8 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2011 VL 175 IS 5 BP 665 EP 676 DI 10.1667/RR2176.1 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 759ZZ UT WOS:000290291700014 PM 21375359 ER PT J AU Chan, CC AF Chan, Chi-Chao TI Extra-Capsular Cataract Removal-Not Couching-Pioneered by Sushruta Response SO SURVEY OF OPHTHALMOLOGY LA English DT Letter C1 NEI, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2011 VL 56 IS 3 BP 277 EP 277 DI 10.1016/j.survophthal.2011.02.008 PG 1 WC Ophthalmology SC Ophthalmology GA 758SU UT WOS:000290187600008 ER PT J AU Zakhari, S Esmat, G Friedman, S AF Zakhari, Samir Esmat, Gamal Friedman, Scott TI Introduction to the Symposium SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Liver; Alcohol; HCV; Fibrosis; Cancer C1 [Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. [Esmat, Gamal] Cairo Univ, Fac Med, Cairo, Egypt. [Friedman, Scott] Mt Sinai Sch Med, Div Liver Dis, New York, NY USA. RP Zakhari, S (reprint author), NIAAA, Div Metab & Hlth Effects, 5635 Fishers Lane,Room 2031, Bethesda, MD 20892 USA. EM szakhari@mail.nih.gov OI Esmat, Gamal/0000-0001-8614-1629 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 775 EP 775 DI 10.1111/j.1530-0277.2010.01396.x PG 1 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200001 ER PT J AU Miller, AM Horiguchi, N Jeong, WI Radaeva, S Gao, B AF Miller, Andrew M. Horiguchi, Norio Jeong, Won-Il Radaeva, Svetlana Gao, Bin TI Molecular Mechanisms of Alcoholic Liver Disease: Innate Immunity and Cytokines SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Liver Injury; IL-6; STAT3; NK Cells; IFN-gamma ID ACTIVATED STELLATE CELLS; NATURAL-KILLER-CELLS; CHRONIC HEPATITIS-C; SIGNAL TRANSDUCER; KUPFFER CELLS; TRANSCRIPTION 3; CLINICAL PROGRESSION; IL-10 PRODUCTION; RAT HEPATOCYTES; CHRONIC ETHANOL AB Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases worldwide, causing fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. In the past few decades, significant progress has been made in our understanding of the molecular mechanisms underlying alcoholic liver injury. Activation of innate immunity components such as Kupffer cells, LPS/TLR4, and complements in response to alcohol exposure plays a key role in the development and progression of alcoholic liver disease (ALD). LPS activation of Kupffer cells also produces IL-6 and IL-10 that may play a protective role in ameliorating ALD. IL-6 activates signal transducer and activator of transcription 3 (STAT3) in hepatocytes and sinusoidal endothelial cells, while IL-10 activates STAT3 in Kupffer cells/macrophages, subsequently protecting against ALD. In addition, alcohol consumption also inhibits some components of innate immunity such as natural killer (NK) cells, a type of cells that play key roles in anti-viral, anti-tumor, and anti-fibrotic defenses in the liver. Ethanol inhibition of NK cells likely contributes significantly to the pathogenesis of ALD. Understanding the roles of innate immunity and cytokines in alcoholic liver injury may provide insight into novel therapeutic targets in the treatment of alcoholic liver disease. C1 [Miller, Andrew M.; Horiguchi, Norio; Jeong, Won-Il; Radaeva, Svetlana; Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Horiguchi, Norio] Gunma Univ, Sch Med, Dept Med & Mol Sci, Gunma, Japan. [Jeong, Won-Il] Korea Adv Inst Sci & Technol, Lab Liver Res, Taejon, South Korea. [Radaeva, Svetlana] NIAAA, Div Metab & Hlth Effects, Extramural Program, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI JEONG, WON IL/B-6615-2011 FU NIAAA, NIH FX This work was supported by the intramural program of NIAAA, NIH. No conflicts of interest exist for all authors. NR 73 TC 57 Z9 62 U1 2 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 787 EP 793 DI 10.1111/j.1530-0277.2010.01399.x PG 7 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200004 PM 21284667 ER PT J AU Sirca, D Enrico, P Mereu, M Peana, AT Diana, M AF Sirca, Donatella Enrico, Paolo Mereu, Maddalena Peana, Alessandra Tiziana Diana, Marco TI l-cysteine Prevents Ethanol-Induced Stimulation of Mesolimbic Dopamine Transmission SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Ethanol; Acetaldehyde; Mesolimbic Dopamine System; Microdialysis; Rat ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; ALCOHOL-PREFERRING RATS; CENTRAL-NERVOUS-SYSTEM; GLUTAMATE TRANSPORTERS; D-PENICILLAMINE; BRAIN CATALASE; CARCINOGENIC ACETALDEHYDE; MOTIVATIONAL PROPERTIES; SEQUESTERING AGENTS AB Background: Acetaldehyde (ACD), the first metabolite of ethanol (EtOH) appears to be involved in many of the psychoactive effects of its parent compound, including EtOH-induced activation of the mesolimbic dopamine (DA) system, thereby suggesting that ACD may participate in EtOH motivational properties. l-cysteine (Lcys), a thiol compound sequestering ACD, is able to prevent the behavioral effect of EtOH and ACD. Here we show that the stimulatory effect of both EtOH and ACD on the mesolimbic DA system is prevented by Lcys pretreatment. Methods: Male Wistar rats were implanted with a microdialysis probe in the nucleus accumbens shell (NAccs), and pretreated intraperitoneally with Lcys (30 mg/kg) before intragastric administration of EtOH (1 g/kg) or ACD (20 mg/kg) or before intraperitoneal administration of morphine (2.5 mg/kg). Results: Pretreatment with Lcys prevented both EtOH and ACD-induced DA release in the NAccs without influencing morphine-induced DA release, suggesting that Lcys specifically affects EtOH-induced DA release possibly through ACD sequestering. Conclusions: Our results underscore the role of ACD on EtOH-induced stimulation of DA mesoaccumbens system and support the notion that thiol compounds such as Lcys, by modulating EtOH-derived ACD bioavailability, would blunt EtOH rewarding properties. C1 [Sirca, Donatella; Enrico, Paolo] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. [Enrico, Paolo; Peana, Alessandra Tiziana; Diana, Marco] Univ Sassari, Dept Drugs Sci, G Minardi Lab Cognit Neurosci, I-07100 Sassari, Italy. [Mereu, Maddalena] Natl Inst Drug Abuse, Baltimore, MD USA. RP Sirca, D (reprint author), Univ Sassari, Dept Biomed Sci, Vle S Pietro 43-B, I-07100 Sassari, Italy. EM dsirca@uniss.it RI Diana, Marco/D-1475-2011; ENRICO, Paolo/B-4699-2009; OI Diana, Marco/0000-0002-6561-5642; ENRICO, Paolo/0000-0002-5662-4731; PEANA, Alessandra Tiziana/0000-0002-7369-9858 FU MIUR [2006057754]; Fondazione Banco di Sardegna [2006.0454] FX This work was supported by grants PRIN 2006 to M.D. (MIUR, 2006057754) and Fondazione Banco di Sardegna (2006.0454) to A.T.P. NR 66 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 862 EP 869 DI 10.1111/j.1530-0277.2010.01416.x PG 8 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200021 PM 21303385 ER PT J AU Schneider, ML Moore, CF Barr, CS Larson, JA Kraemer, GW AF Schneider, Mary L. Moore, Colleen F. Barr, Christina S. Larson, Julie A. Kraemer, Gary W. TI Moderate Prenatal Alcohol Exposure and Serotonin Genotype Interact to Alter CNS Serotonin Function in Rhesus Monkey Offspring SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Serotonin; Rhesus Monkey; Prenatal Alcohol Exposure; Serotonin Transporter Gene; 5-Hydroxyindoleacetic Acid ID MATERNAL IPSAPIRONE TREATMENT; UTERO ETHANOL EXPOSURE; FETAL ALCOHOL; CEREBROSPINAL-FLUID; TEMPORAL VULNERABILITY; NONHUMAN-PRIMATES; MAJOR DEPRESSION; MACACA-MULATTA; BRAIN; TRANSPORTER AB Background: Moderate prenatal alcohol exposure can contribute to neurodevelopmental impairments and disrupt several neurotransmitter systems. We examined the timing of moderate level alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and levels of primary serotonin and dopamine (DA) metabolites in cerebrospinal fluid (CSF) in rhesus monkeys. Methods: Thirty-two 30-month old rhesus monkeys (Macaca mulatta) from 4 groups of females were assessed: (i) early alcohol-exposed group (n = 9), in which mothers voluntarily consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 50; (ii) middle-to-late gestation alcohol-exposed group (n = 6), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 50 to 135; (iii) a continuous-exposure group (n = 8), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 135; and (iv) controls (n = 9), mothers consumed an isocaloric control solution on gestational days 0 to 50, 50 to 135, or 0 to 135. Serotonin transporter promoter region allelic variants (homozygous s/s or heterozygous s/l vs. homozygous l/l) were determined. We examined CSF concentrations of the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively, at baseline and 50 hours after separation from cage-mates, when the monkeys were 30 months old. Results: Early- and middle-to-late gestation-alcohol exposed monkeys carrying the short allele had lower concentrations of 5-HIAA in CSF relative to other groups. Concentrations of 5-HIAA in CSF were lower for s allele carriers and increased from baseline relative to pre-separation values, whereas 5-HIAA levels in l/l allele carriers were not affected by separation. Monkeys carrying the short allele had lower basal concentrations of HVA in CSF compared with monkeys homozygous for the long allele. Conclusion: Carrying the s allele of the 5-HT transporter increased the probability of reduced 5-HIAA in early- and middle-to-late gestation alcohol-exposed monkeys and reduced HVA at baseline. These findings that prenatal alcohol exposure altered central 5-HT activity in genetically sensitive monkeys raise questions about whether abnormal serotonin biological pathways could underlie some of the psychiatric disorders reported in fetal alcohol spectrum disorder. C1 [Schneider, Mary L.] Univ Wisconsin, Dept Kinesiol, Occupat Therapy Program, Med Sci Ctr 2175, Madison, WI 53706 USA. [Moore, Colleen F.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. [Schneider, Mary L.; Larson, Julie A.] Univ Wisconsin, Harlow Ctr Biol Psychol, Madison, WI USA. [Barr, Christina S.] NIAAA, NIH, Bethesda, MD USA. [Kraemer, Gary W.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. RP Schneider, ML (reprint author), Univ Wisconsin, Dept Kinesiol, Occupat Therapy Program, Med Sci Ctr 2175, 1400 Univ Ave, Madison, WI 53706 USA. EM schneider@education.wisc.edu FU National Institute of Alcoholism and Alcohol Abuse [AA10079, AA12277] FX This study was supported by AA10079 and AA12277 from the National Institute of Alcoholism and Alcohol Abuse to M.L. Schneider. NR 72 TC 8 Z9 9 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 912 EP 920 DI 10.1111/j.1530-0277.2010.01421.x PG 9 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200026 PM 21294753 ER PT J AU Ramachandra, V Kang, F Kim, C Nova, AS Bajaj, A Hall, FS Uhl, GR Gonzales, RA AF Ramachandra, Vorani Kang, Francis Kim, Christine Nova, Alan S. Bajaj, Ankur Hall, F. Scott Uhl, George R. Gonzales, Rueben A. TI The Mu Opioid Receptor Is Not Involved in Ethanol-Stimulated Dopamine Release in the Ventral Striatum of C57BL/6J Mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE MOR; Beta Funaltrexamine; Microdialysis; Dopamine; C57BL; 6J Mice ID INCREASES EXTRACELLULAR DOPAMINE; MATERNAL METHYL SUPPLEMENTS; NUCLEUS-ACCUMBENS; KNOCKOUT MICE; MESOLIMBIC DOPAMINE; REINFORCED BEHAVIOR; ALCOHOL-DRINKING; DNA METHYLATION; NALTREXONE; CONSUMPTION AB Background: The mu opioid receptor (MOR) has previously been found to regulate ethanol-stimulated dopamine release under some, but not all, conditions. A difference in ethanol-evoked dopamine release between male and female mixed background C57BL/6J-129SvEv mice led to questions about its ubiquitous role in these effects of ethanol. Using congenic C57BL/6J MOR knockout (KO) mice and C57BL/6J mice pretreated with an irreversible MOR antagonist, we investigated the function of this receptor in ethanol-stimulated dopamine release. Methods: Microdialysis was used to monitor dopamine release and ethanol clearance in MOR -/-, +/+, and +/- . male and female mice after intraperitoneal (i.p.) injections of 1.0, 2.0, and 3.0 g/kg ethanol (or saline). We also measured the increase in dopamine release after 5 mg/kg morphine (i.p.) in male and female MOR+/+ and -/- mice. In a separate experiment, male C57BL/6J mice were pretreated with either the irreversible MOR antagonist beta funaltrexamine (BFNA) or vehicle, and dopamine levels were monitored after administration of 2 g/kg ethanol or 5 mg/kg morphine. Results: Although ethanol-stimulated dopamine release at all the 3 doses of alcohol tested, there were no differences between MOR+/+, -/-, and +/- mice in these effects. Female mice had a more prolonged effect compared to males at the 1 g/kg dose. Administration of 2 g/kg ethanol also caused a similar increase in dopamine levels in both saline-pretreated and BFNA-pretreated mice. Five mg/kg morphine caused a significant increase in dopamine levels in MOR+/+ mice but not in MOR-/- mice and in saline-pretreated mice but not in BFNA-pretreated mice. Intraperitoneal saline injections had a significant, albeit small and transient, effect on dopamine release when given in a volume equivalent to the ethanol doses, but not in a volume equivalent to the 5 mg/kg morphine dose. Ethanol pharmacokinetics were similar in all genotypes and both sexes at each dose and in both pretreatment groups. Conclusions: MOR is not involved in ethanol-stimulated dopamine release in the ventral striatum of C57BL/6J mice. C1 [Ramachandra, Vorani; Kang, Francis; Kim, Christine; Nova, Alan S.; Bajaj, Ankur; Gonzales, Rueben A.] Univ Texas Austin, PHAR Pharmacol, Austin, TX 78712 USA. [Hall, F. Scott; Uhl, George R.] NIDA, Mol Biol Branch, Intramural Res Program, NIH, Baltimore, MD USA. RP Gonzales, RA (reprint author), Univ Texas Austin, PHAR Pharmacol, 1 Univ Stn A1915, Austin, TX 78712 USA. EM rgonzales@mail.utexas.edu RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU National Institute on Alcohol Abuse and Alcoholism [RO1 AA 14874]; National Institute on Drug Abuse FX Supported by Grant RO1 AA 14874 from the National Institute on Alcohol Abuse and Alcoholism (RAG) and by funding from the Intramural Research Program of the National Institute on Drug Abuse (GRU, FSH). NR 46 TC 6 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 929 EP 938 DI 10.1111/j.1530-0277.2010.01423.x PG 10 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200028 PM 21294756 ER PT J AU Kendler, KS Kalsi, G Holmans, PA Sanders, AR Aggen, SH Dick, DM Aliev, F Shi, JX Levinson, DF Gejman, PV AF Kendler, Kenneth S. Kalsi, Gursharan Holmans, Peter A. Sanders, Alan R. Aggen, Steven H. Dick, Danielle M. Aliev, Fazil Shi, Jianxin Levinson, Douglas F. Gejman, Pablo V. TI Genomewide Association Analysis of Symptoms of Alcohol Dependence in the Molecular Genetics of Schizophrenia (MGS2) Control Sample SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Genome-Wide Association Study; Gene Ontology; Control ID AFFECTED SIB PAIR; ACTIVATED POTASSIUM CHANNELS; FAMILY-BASED ASSOCIATION; DRUG-DEPENDENCE; WIDE ASSOCIATION; ENVIRONMENTAL CONTRIBUTIONS; IDENTIFIES ASSOCIATION; LINKAGE DISEQUILIBRIUM; DIAGNOSTIC INTERVIEW; SUSCEPTIBILITY GENE AB Background: While genetic influences on alcohol dependence (AD) are substantial, progress in the identification of individual genetic variants that impact on risk has been difficult. Methods: We performed a genome-wide association study on 3,169 alcohol consuming subjects from the population-based Molecular Genetics of Schizophrenia (MGS2) control sample. Subjects were asked 7 questions about symptoms of AD which were analyzed by confirmatory factor analysis. Genotyping was performed using the Affymetrix 6.0 array. Three sets of analyses were conducted separately for European American (EA, n = 2,357) and African-American (AA, n = 812) subjects: individual single nucleotide polymorphisms (SNPs), candidate genes and enriched pathways using gene ontology (GO) categories. Results: The symptoms of AD formed a highly coherent single factor. No SNP approached genome-wide significance. In the EA sample, the most significant intragenic SNP was in KCNMA1, the human homolog of the slo-1 gene in C. Elegans. Genes with clusters of significant SNPs included AKAP9, phosphatidylinositol glycan anchor biosynthesis, class G (PIGG), and KCNMA1. In the AA sample, the most significant intragenic SNP was CEACAM6 and genes showing empirically significant SNPs included KCNQ5, SLC35B4, and MGLL. In the candidate gene based analyses, the most significant findings were with ADH1C, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1) and ankyrin repeat and kinase domain containing 1 (ANKK1) in the EA sample, and ADH5, POMC, and CHRM2 in the AA sample. The ALIGATOR program identified a significant excess of associated SNPs within and near genes in a substantial number of GO categories over a range of statistical stringencies in both the EA and AA sample. Conclusions: While we cannot be highly confident about any single result from these analyses, a number of findings were suggestive and worthy of follow-up. Although quite large samples will be needed to obtain requisite power, the study of AD symptoms in general population samples is a viable complement to case-control studies in identifying genetic risk variants for AD. C1 [Kendler, Kenneth S.; Kalsi, Gursharan; Aggen, Steven H.; Dick, Danielle M.; Aliev, Fazil] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Kendler, Kenneth S.; Kalsi, Gursharan; Aggen, Steven H.; Dick, Danielle M.; Aliev, Fazil] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23298 USA. [Kendler, Kenneth S.; Dick, Danielle M.] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Holmans, Peter A.] Cardiff Univ, Dept Psychiat, Cardiff, S Glam, Wales. [Sanders, Alan R.; Gejman, Pablo V.] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Ctr Psychiat Genet, Evanston, IL USA. [Aliev, Fazil] Ankara Univ, Dept Stat, TR-06100 Ankara, Turkey. [Shi, Jianxin] NCI, Bethesda, MD 20892 USA. [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Kendler, KS (reprint author), Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, POB 980126, Richmond, VA 23298 USA. EM kendler@vcu.edu RI Aliev, Fazil/D-7172-2013; Holmans, Peter/F-4518-2015 OI Aliev, Fazil/0000-0001-8357-4699; Holmans, Peter/0000-0003-0870-9412 FU NIH [R37AA011408, P20AA017828]; Genetic Association Information Network (GAIN) [U01MH79469, U01MH79470, R01MH81800] FX These analyses were supported in part by NIH grants R37AA011408, P20AA017828 (Kenneth S. Kendler MD). Data and biomaterials from the NIMH GI (Genetics Initiative) MGS2 (Molecular Genetics of Schizophrenia) control sample were collected by NorthShore University HealthSystem, Evanston, IL, R01 MH59571, Pablo V. Gejman, M.D. (Collaboration Coordinator; PI) as part of a collaborative R01 application comprised of 10 sites. From 2003 to 2006, the Principal Investigators and Co-Investigators were: NorthShore University HealthSystem, Evanston, IL, R01 MH59571, Pablo V. Gejman, M.D. (Collaboration Coordinator; PI), Alan R. Sanders, M.D.; Emory University School of Medicine, Atlanta, GA, R01 MH59587, Farooq Amin, M.D. (PI); University of California, San Francisco, CA, R01 MH60870, William F. Byerley, M.D. (PI); University of Iowa, Iowa, IA, R01 MH59566, Donald W. Black, M.D. (PI), Raymond R. Crowe, M.D.; Washington University, St. Louis, MO, R01 MH60879, C. Robert Cloninger, M.D. (PI); University of Colorado, Denver, CO, R01 MH59565, Robert Freedman, M.D. (PI), Ann Olincy, M.D.; Stanford University, Palo Alto, CA, R01 MH61675, Douglas F. Levinson, M.D. (PI); Louisiana State University, New Orleans, LA, R01 MH67257, Nancy G. Buccola, APRN, BC, MSN (PI); University of Queensland, Brisbane, Queensland, Australia, R01 MH59588, Bryan J. Mowry, M.D. (PI); Mt. Sinai School of Medicine, New York, NY, R01 MH59586, Jeremy M. Silverman, Ph.D. (PI). Our schizophrenia GWAS (genotyping and analyses) was supported by the Genetic Association Information Network (GAIN) and grants U01MH79469 (Pablo V. Gejman, M.D.), U01MH79470 (Douglas F. Levinson, M.D.), and R01MH81800 (Pablo V. Gejman, M.D.). We thank the individuals at each participating institution for their various contributions, especially Roberta Fishman, John Corcoran, and Douglas A. Fugman and thank the individuals who volunteered for the control sample for their participation. NR 95 TC 50 Z9 50 U1 2 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 963 EP 975 DI 10.1111/j.1530-0277.2010.01427.x PG 13 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200032 PM 21314694 ER PT J AU Schisterman, E Whitcomb, B Bowers, K AF Schisterman, Enrique Whitcomb, Brian Bowers, Katherine TI Invited Commentary: Causation or "noitasuaC"? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE breast feeding; causality; confounding ID REVERSE CAUSALITY; ASSOCIATION; MORTALITY; MODELS; BIAS AB Longitudinal studies are often viewed as the "gold standard'' of observational epidemiologic research. Establishing a temporal association is a necessary criterion to identify causal relations. However, when covariates in the causal system vary over time, a temporal association is not straightforward. Appropriate analytical methods may be necessary to avoid confounding and reverse causality. These issues come to light in 2 studies of breastfeeding described in the articles by Al-Sahab et al. (Am J Epidemiol. 2011; 173(9): 971-977) and Kramer et al. (Am J Epidemiol. 2011; 173(9): 978-983) in this issue of the Journal. Breastfeeding has multiple time points and is a behavior that is affected by multiple factors, many of which themselves vary over time. This creates a complex causal system that requires careful scrutiny. The methods presented here may be applicable to a wide range of studies that involve time-varying exposures and time-varying confounders. C1 [Schisterman, Enrique; Bowers, Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Whitcomb, Brian] Univ Massachusetts, Dept Publ Hlth, Div Biostat & Epidemiol, Amherst, MA 01003 USA. RP Schisterman, E (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B03, Rockville, MD 20854 USA. EM schistee@mail.nih.gov RI Bowers, Katherine/N-5226-2015; OI Schisterman, Enrique/0000-0003-3757-641X NR 12 TC 4 Z9 4 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2011 VL 173 IS 9 BP 984 EP 987 DI 10.1093/aje/kwq499 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 756XA UT WOS:000290046900003 PM 21430191 ER PT J AU Gao, JJ Huang, XM Park, Y Hollenbeck, A Blair, A Schatzkin, A Chen, HL AF Gao, Jianjun Huang, Xuemei Park, Yikyung Hollenbeck, Albert Blair, Aaron Schatzkin, Arthur Chen, Honglei TI Daytime Napping, Nighttime Sleeping, and Parkinson Disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Parkinson disease; prospective studies; sleep ID BEHAVIOR DISORDER; NEURODEGENERATIVE DISEASE; RISK; DURATION; DIET; ASSOCIATION; DEPRESSION; INJURY; HEALTH; MEN AB Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease. The authors examined daytime napping and nighttime sleeping durations, reported in 1996-1997 by 220,934 US NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages: established (cases diagnosed before 1995, n = 267), recent (1995-1999, n = 396), and prediagnostic (2000 and after, n = 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages: the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8, 5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases; however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases. This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early nonmotor symptoms of Parkinson disease. C1 [Gao, Jianjun; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Rockville, MD USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X FU National Institutes of Health (NIH) [R01 NS060722]; National Institute of Environmental Health Sciences [Z01-ES-101986]; National Cancer Institute [Z01 CP010196-02] FX This study was supported by the intramural research program of the National Institutes of Health (NIH), the National Institute of Environmental Health Sciences (Z01-ES-101986), the National Cancer Institute (Z01 CP010196-02), and an NIH extramural grant (R01 NS060722) to Dr. Huang. NR 24 TC 25 Z9 26 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2011 VL 173 IS 9 BP 1032 EP 1038 DI 10.1093/aje/kwq478 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 756XA UT WOS:000290046900010 PM 21402730 ER PT J AU Li, DL London, SJ Liu, JH Lee, W Jiang, XJ Van Den Berg, D Bergen, AW Nishita, D Waleh, N Swan, GE Gallaher, P Chou, CP Shih, JC Unger, JB Gauderman, WJ Gilliland, F Johnson, CA Conti, DV AF Li, Dalin London, Stephanie J. Liu, Jinghua Lee, Wonho Jiang, Xuejuan Van Den Berg, David Bergen, Andrew W. Nishita, Denise Waleh, Nahid Swan, Gary E. Gallaher, Peggy Chou, Chih-Ping Shih, Jean C. Unger, Jennifer B. Gauderman, W. James Gilliland, Frank Johnson, C. Anderson Conti, David V. TI Association of the Calcyon Neuron-Specific Vesicular Protein Gene (CALY) With Adolescent Smoking Initiation in China and California SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adolescent; dopamine; genetic association studies; smoking ID CIGARETTE-SMOKING; NICOTINE DEPENDENCE; IMPULSIVE BEHAVIOR; MAJOR DEPRESSION; TOBACCO USE; DOPAMINE; CESSATION; RISK; RECEPTORS; ALCOHOL AB Although previous investigations have indicated a role for genetic factors in smoking initiation, the underlying genetic mechanisms are still unknown. In 2,339 adolescents from a Chinese Han population in the Wuhan Smoking Prevention Trial (Wuhan, China, 1998-1999), the authors explored the association of 57 genes in the dopamine pathway with smoking initiation. Using a conservative approach for declaring significance, positive findings were further examined in an independent sample of 603 Caucasian adolescents followed for up to 10 years as part of the Children's Health Study (Southern California, 1993-2009). The authors identified 1 single nucleotide polymorphism (rs2298122) in the calcyon neuron-specific vesicular protein gene (CALY) that was positively associated with smoking initiation in females (odds ratio = 2.21, 95% confidence interval: 1.49, 3.27; P = 8.4 x 10(-5)) in the Wuhan Smoking Prevention Trial cohort, and they replicated the association in females from the Children's Health Study cohort (hazard rate ratio = 2.05, 95% confidence interval: 1.27, 3.31; P = 0.003). These results suggest that the CALY gene may influence smoking initiation in adolescents, although the potential roles of underlying psychological characteristics that may be components of the smoking-initiation phenotype, such as impulsivity or novelty-seeking, remain to be explored. C1 [Conti, David V.] Univ So Calif, Div Biostat, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [London, Stephanie J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Bergen, Andrew W.; Nishita, Denise; Waleh, Nahid; Swan, Gary E.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. [Gallaher, Peggy; Unger, Jennifer B.; Johnson, C. Anderson] Claremont Grad Univ, Sch Community & Global Hlth, Claremont, CA USA. [Shih, Jean C.] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA. RP Conti, DV (reprint author), Univ So Calif, Div Biostat, Dept Prevent Med, Keck Sch Med, 1501 San Pablo St,ZNI 101,MC 2821, Los Angeles, CA 90089 USA. EM dconti@usc.edu RI Li, Dalin/F-4266-2011; liu, jinghua/H-4516-2014; OI Bergen, Andrew/0000-0002-1237-7644; London, Stephanie/0000-0003-4911-5290; Unger, Jennifer/0000-0001-9064-6603 FU US National Institute on Drug Abuse [DA020830, CA084735]; US National Institute of Environmental Health Sciences [ES015090, GM069890]; US National Institutes of Health, National Institute of Environment Health Sciences; National Institute on Drug Abuse [DA020830] FX This work was supported by the US National Institute on Drug Abuse (grants DA020830 and CA084735 to Drs. Dalin Li and David V. Conti) and the US National Institute of Environmental Health Sciences (grants ES015090 and GM069890 to Dr. David V. Conti). This work was also supported in part by the Intramural Research Program of the US National Institutes of Health, National Institute of Environment Health Sciences. Genotyping for the example was performed as part of the Pharmacogenetics of Nicotine Addiction Treatment Program (SRI International and University of California, San Francisco), which received funding from the National Institute on Drug Abuse (grant DA020830). NR 86 TC 2 Z9 2 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2011 VL 173 IS 9 BP 1039 EP 1048 DI 10.1093/aje/kwq471 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 756XA UT WOS:000290046900011 PM 21415033 ER PT J AU Ananthanarayanan, M Li, YF Surapureddi, S Balasubramaniyan, N Ahn, J Goldstein, JA Suchy, FJ AF Ananthanarayanan, M. Li, Yanfeng Surapureddi, S. Balasubramaniyan, N. Ahn, Jaeyong Goldstein, J. A. Suchy, Frederick J. TI Histone H3K4 trimethylation by MLL3 as part of ASCOM complex is critical for NR activation of bile acid transporter genes and is downregulated in cholestasis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE hepatoma cells; microarray; epigenetics; gene regulation; activating signal cointegrator-2-containing complex; H3 lysine 4; nuclear receptors; mixed lineage leukemia 3 ID NUCLEAR RECEPTOR COREGULATORS; CLINICAL-IMPLICATIONS; MOLECULAR REGULATION; LIVER; COACTIVATORS; EXPRESSION; CHROMATIN; DISEASE; LIGAND; MICE AB The nuclear receptor Farnesoid x receptor (FXR) is a critical regulator of multiple genes involved in bile acid homeostasis. The coactivators attracted to promoters of FXR target genes and epigenetic modifications that occur after ligand binding to FXR have not been completely defined, and it is unknown whether these processes are disrupted during cholestasis. Using a microarray, we identified decreased expression of mixed lineage leukemia 3 (MLL3), a histone H3 lysine 4 (H3K4) lysine methyl transferase at 1 and 3 days of post-common bile duct ligation (CBDL) in mice. Chromatin immunoprecipitation analysis (ChIP) analysis revealed that H3K4me3 of transporter promoters by MLL3 as part of activating signal cointegrator-2 -containing complex (ASCOM) is essential for activation of bile salt export pump (BSEP), multidrug resistance associated protein 2 (MRP2), and sodium taurocholate cotransporting polypeptide (NTCP) genes by FXR and glucocorticoid receptor (GR). Knockdown of nuclear receptor coactivator 6 (NCOA6) or MLL3/MLL4 mRNAs by small interfering RNA treatment led to a decrease in BSEP and NTCP mRNA levels in hepatoma cells. Human BSEP promoter transactivation by FXR/RXR was enhanced in a dose-dependent fashion by NCOA6 cDNA coexpression and decreased by AdsiNCOA6 infection in HepG2 cells. GST-pull down assays showed that domain 3 and 5 of NCOA6 (LXXLL motifs) interacted with FXR and that the interaction with domain 5 was enhanced by chenodeoxycholic acid. In vivo ChIP assays in HepG2 cells revealed ligand-dependent recruitment of ASCOM complex to FXR element in BSEP and GR element in NTCP promoters, respectively. ChIP analysis demonstrated significantly diminished recruitment of ASCOM complex components and H3K4me3 to Bsep and Mrp2 promoter FXR elements in mouse livers after CBDL. Taken together, these data show that the "H3K4me3" epigenetic mark is essential to activation of BSEP, NTCP, and MRP2 genes by nuclear receptors and is downregulated in cholestasis. C1 [Ananthanarayanan, M.] Yale Univ, Sch Med, Dept Internal Med, Sect Digest Dis, New Haven, CT 06519 USA. [Ananthanarayanan, M.; Li, Yanfeng; Balasubramaniyan, N.; Ahn, Jaeyong; Suchy, Frederick J.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Balasubramaniyan, N.; Suchy, Frederick J.] Univ Colorado, Sch Med, Res Inst, Childrens Hosp, Denver, CO USA. [Surapureddi, S.; Goldstein, J. A.] Natl Inst Environm Hlth Sci, Pharmacol Lab, Res Triangle Pk, NC USA. RP Ananthanarayanan, M (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Digest Dis, 300 Cedar St,TACS230, New Haven, CT 06519 USA. EM mananthanarayanan@gmail.com RI Goldstein, Joyce/A-6681-2012 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-084434]; NIH, National Institute of Environmental Health Sciences [Z01ES02124] FX This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-084434 (to F. J. Suchy and M. Ananthanarayanan) and by the Intramural Research Program of NIH, National Institute of Environmental Health Sciences under NIH Intramural Project Number Z01ES02124 (to S. Surapureddi and J. A. Goldstein). NR 34 TC 28 Z9 28 U1 0 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2011 VL 300 IS 5 BP G771 EP G781 DI 10.1152/ajpgi.00499.2010 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 755NK UT WOS:000289938700012 PM 21330447 ER PT J AU Barron, L Wynn, TA AF Barron, Luke Wynn, Thomas A. TI Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Review DE inflammation; wound healing ID IDIOPATHIC PULMONARY-FIBROSIS; PROMOTES HEPATIC-FIBROSIS; L-ARGININE METABOLISM; LIVER-INJURY; MATRIX METALLOPROTEINASE-13; ALVEOLAR MACROPHAGES; MOLECULAR-MECHANISMS; GROWTH-FACTOR; INFLAMMATION; ACTIVATION AB Dysregulated wound healing leads to fibrosis, whereby fibroblasts synthesize excess extracellular matrix and scarring impairs proper organ function. Although fibrotic diseases arise from diverse causes and display heterogeneous features, fibrosis commonly associates with chronic inflammation. Recent discoveries reinforce the idea that communication between fibroblasts, macrophages, and CD4 T cells integrates the processes of wound healing and host defense. Signals between macrophages and fibroblasts can exacerbate, suppress, or reverse fibrosis. Fibroblasts and macrophages are activated by T cells, but their activation also engages negative feedback loops that reduce fibrosis by restraining the immune response, particularly when the Th2 cytokine IL-13 contributes to pathology. Thus the interactions among fibroblasts, macrophages, and CD4 T cells likely play general and critical roles in initiating, perpetuating, and resolving fibrosis in both experimental and clinical conditions. C1 [Barron, Luke; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Barron, L (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM barronl@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 47 TC 83 Z9 86 U1 1 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2011 VL 300 IS 5 BP G723 EP G728 DI 10.1152/ajpgi.00414.2010 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 755NK UT WOS:000289938700007 PM 21292997 ER PT J AU Liou, AP Chavez, DI Espero, E Hao, SZ Wank, SA Raybould, HE AF Liou, Alice P. Chavez, Diana I. Espero, Elvis Hao, Shuzhen Wank, Stephen A. Raybould, Helen E. TI Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE aromatic amino acids; enteroendocrine; peptide transporter ID SODIUM-GLUCOSE COTRANSPORTER; GLUCAGON-LIKE PEPTIDE-1; ENDOGENOUS CHOLECYSTOKININ; STC-1 CELLS; GLYCYLSARCOSINE TRANSPORT; TASTE RECEPTORS; RAT; EXPRESSION; CCK; ACTIVATION AB Dietary protein is a major stimulant for cholecystokinin (CCK) secretion by the intestinal I cell, however, the mechanism by which protein is detected is unknown. Indirect functional evidence suggests that PepT1 may play a role in CCK-mediated changes in gastric motor function. However, it is unclear whether this oligopeptide transporter directly or indirectly activates the I cell. Using both the CCK-expressing enteroendocrine STC-1 cell and acutely isolated native I cells from CCK-enhanced green fluorescent protein (eGFP) mice, we aimed to determine whether PepT1 directly activates the enteroendocrine cell to elicit CCK secretion in response to oligopeptides. Both STC-1 cells and isolated CCK-eGFP cells expressed PepT1 transcripts. STC-1 cells were activated, as measured by ERK1/2 phosphorylation, by both peptone and the PepT1 substrate Cefaclor; however, the PepT1 inhibitor 4-aminomethyl benzoic acid (AMBA) had no effect on STC-1 cell activity. The PepT1-transportable substrate glycyl-sarcosine dose-dependently decreased gastric motility in anesthetized rats but had no affect on activation of STC-1 cells or on CCK secretion by CCK-eGFP cells. CCK secretion was significantly increased in response to peptone but not to Cefaclor, cephalexin, or Phe-Ala in CCK-eGFP cells. Taken together, the data suggest that PepT1 does not directly mediate CCK secretion in response to PepT1 specific substrates. PepT1, instead, may have an indirect role in protein sensing in the intestine. C1 [Liou, Alice P.; Chavez, Diana I.; Espero, Elvis; Hao, Shuzhen; Raybould, Helen E.] Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. [Liou, Alice P.; Wank, Stephen A.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Raybould, HE (reprint author), Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, 1321 Haring Hall, Davis, CA 95616 USA. FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-41004]; California Dairy Research Foundation; Dairy Marketing Initiative FX This work was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-41004), the California Dairy Research Foundation, and the Dairy Marketing Initiative. NR 44 TC 28 Z9 29 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2011 VL 300 IS 5 BP G895 EP G902 DI 10.1152/ajpgi.00521.2010 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 755NK UT WOS:000289938700024 PM 21311026 ER PT J AU Lindemer, BJ Bongard, RD Hoffmann, R Baumgardt, S Gonzalez, FJ Merker, MP AF Lindemer, Brian J. Bongard, Robert D. Hoffmann, Raymond Baumgardt, Shelley Gonzalez, Frank J. Merker, Marilyn P. TI Genetic evidence for NAD(P)H:quinone oxidoreductase 1-catalyzed quinone reduction on passage through the mouse pulmonary circulation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE knockout mice; lung metabolism; duroquinone; isolated perfused mouse lung; coenzyme Q ID ARTERIAL ENDOTHELIAL-CELLS; IN-VIVO ROLE; NAD(P)H-QUINONE OXIDOREDUCTASE; COMPLEX-I; REDOX STATUS; MITOMYCIN-C; COENZYME-Q; SUBMITOCHONDRIAL PARTICLES; DUROQUINONE REDUCTION; METABOLIC-ACTIVATION AB Lindemer BJ, Bongard RD, Hoffmann R, Baumgardt S, Gonzalez FJ, Merker MP. Genetic evidence for NAD(P)H: quinone oxidoreductase 1-catalyzed quinone reduction on passage through the mouse pulmonary circulation. Am J Physiol Lung Cell Mol Physiol 300: L773-L780, 2011. First published February 4, 2011; doi:10.1152/ajplung.00394.2010.-The quinones duroquinone (DQ) and coenzyme Q(1) (CoQ(1)) and quinone reductase inhibitors have been used to identify reductases involved in quinone reduction on passage through the pulmonary circulation. In perfused rat lung, NAD(P)H:quinone oxidoreductase 1 (NQO1) was identified as the predominant DQ reductase and NQO1 and mitochondrial complex I as the CoQ(1) reductases. Since inhibitors have nonspecific effects, the goal was to use Nqo1-null (NQO1(-/-)) mice to evaluate DQ as an NQO1 probe in the lung. Lung homogenate cytosol NQO1 activities were 97 +/- 11, 54 +/- 6, and 5 +/- 1 (SE) nmol dichlorophenolindophenol reduced.min(-1).mg protein(-1) for NQO1(+/+), NQO1(+/-), and NQO1(-/-) lungs, respectively. Intact lung quinone reduction was evaluated by infusion of DQ (50 mu M) or CoQ(1) (60 mu M) into the pulmonary arterial inflow of the isolated perfused lung and measurement of pulmonary venous effluent hydroquinone (DQH(2) or CoQ(1)H(2)). DQH(2) efflux rates for NQO1(+/+), NQO1(+/-), and NQO1(-/-) lungs were 0.65 +/- 0.08, 0.45 +/- 0.04, and 0.13 +/- 0.05 (SE) mu mol.min(-1).g dry lung(-1), respectively. DQ reduction in NQO1(+/+) lungs was inhibited by 90 +/- 4% with dicumarol; there was no inhibition in NQO1(-/-) lungs. There was no significant difference in CoQ(1)H(2) efflux rates for NQO1(+/+) and NQO1(-/-) lungs. Differences in DQ reduction were not due to differences in lung dry weights, wet-to-dry weight ratios, perfusion pressures, perfused surface areas, or total DQ recoveries. The data provide genetic evidence implicating DQ as a specific NQO1 probe in the perfused rodent lung. C1 [Merker, Marilyn P.] Med Coll Wisconsin, Zablocki VAMC, Res Serv 151, Milwaukee, WI 53295 USA. [Lindemer, Brian J.; Baumgardt, Shelley; Merker, Marilyn P.] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53295 USA. [Bongard, Robert D.] Med Coll Wisconsin, Dept Pulm Med, Milwaukee, WI 53295 USA. [Hoffmann, Raymond] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53295 USA. [Merker, Marilyn P.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53295 USA. [Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. RP Merker, MP (reprint author), Med Coll Wisconsin, Zablocki VAMC, Res Serv 151, Milwaukee, WI 53295 USA. EM mmerker@mcw.edu FU National Institutes of Health [R01 HL-5065537]; Childrens Environmental Health Core Center [ES-004184-23]; National Cancer Institute Intramural Research Program; Department of Veterans Affairs FX This work was supported by National Institutes of Health Grant R01 HL-5065537 and Childrens Environmental Health Core Center Grant ES-004184-23, the National Cancer Institute Intramural Research Program, and the Department of Veterans Affairs (VA Medical Research Funds). NR 44 TC 1 Z9 1 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAY PY 2011 VL 300 IS 5 BP L773 EP L780 DI 10.1152/ajplung.00394.2010 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 757MF UT WOS:000290088800011 PM 21296895 ER PT J AU Blum, N Katz, E Fee, E AF Blum, Nava Katz, Ehud Fee, Elizabeth TI PROFESSOR NATAN GOLDBLUM AND THE COMBINED VACCINATION PROGRAM IN GAZA RESPONSE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 [Blum, Nava] Univ Haifa, Sch Publ Hlth, Fac Social Welf & Hlth Sci Studies, IL-31905 Haifa, Israel. [Katz, Ehud] Hebrew Univ Jerusalem, Dept Biochem, Jerusalem, Israel. [Katz, Ehud] Hebrew Univ Jerusalem, Dept Mol Biol, Jerusalem, Israel. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Blum, N (reprint author), Univ Haifa, Sch Publ Hlth, Fac Social Welf & Hlth Sci Studies, IL-31905 Haifa, Israel. EM navablum@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2011 VL 101 IS 5 BP 775 EP 775 DI 10.2105/AJPH.2011.300160 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 753GT UT WOS:000289761000004 ER PT J AU Parry, M AF Parry, Manon TI Benjamin Spock: Pediatrician and Anti-War Activist SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 [Parry, Manon] Univ Maryland, College Pk, MD 20742 USA. RP Parry, M (reprint author), Natl Lib Med, Exhibit Program, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA. EM parrym@mail.nlm.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2011 VL 101 IS 5 BP 802 EP 803 DI 10.2105/AJPH.2010.191403 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 753GT UT WOS:000289761000017 PM 21490334 ER PT J AU Reddy, N Rezyani, K Barrett, AJ Savani, BN AF Reddy, Nishitha Rezyani, Katayoun Barrett, A. John Savani, Bipin N. TI Strategies to Prevent EBV Reactivation and Posttransplant Lymphoproliferative Disorders (PTLD) after Allogeneic Stem Cell Transplantation in High-Risk Patients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE EBV reactivation; PTLD; Stem cell transplantation; Rituximab; Sirolimus; Long-term survivors ID EPSTEIN-BARR-VIRUS; BONE-MARROW-TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; NON-HODGKIN-LYMPHOMA; VERSUS-HOST-DISEASE; CYTOTOXIC T-CELLS; ADOPTIVE IMMUNOTHERAPY; ANTITHYMOCYTE GLOBULIN; PREEMPTIVE RITUXIMAB; POST TRANSPLANT AB Epstein-Barr virus (EBV)-associated postallogeneic stem cell transplantation (SCT) lymphoproliferative disorder (PTLD) is often life threatening. The risk of EBV reactivation is highest in older patients, T cell-depleted SCT (in vivo or vitro), and in unrelated or mismatched SCT. Cumulative numbers of patients with EBV reactivation and PTLD are rising as more patients at high risk for EBV reactivation and PTLD are receiving allo-SCT. Novel but easily applicable strategies are needed to prevent EBV reactivation and PTLD to serve the needs of the increasingly enlarging population of high-risk SCT recipients across the globe. Biol Blood Marrow Transplant 17: 591-597 (2011) Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation C1 [Reddy, Nishitha; Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Div Hematol Oncol,Dept Med, Nashville, TN 37232 USA. [Rezyani, Katayoun] Univ London Imperial Coll Sci Technol & Med, Dept Hematol, Hammersmith Hosp Trust, London, England. [Barrett, A. John] NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Savani, BN (reprint author), Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Div Hematol Oncol,Dept Med, 3927 Vanderbilt Clin, Nashville, TN 37232 USA. EM Bipin.Savani@Vanderbilt.Edu FU Intramural NIH HHS [ZIA HL006105-02, ZIA HL002342-16, ZIA HL006106-02] NR 80 TC 29 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2011 VL 17 IS 5 BP 591 EP 597 DI 10.1016/j.bbmt.2010.08.007 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 757CK UT WOS:000290061500001 PM 20732435 ER PT J AU Mariotti, J Taylor, J Massey, PR Ryan, K Foley, J Buxhoeveden, N Felizardo, TC Amarnath, S Mossoba, ME Fowler, DH AF Mariotti, Jacopo Taylor, Justin Massey, Paul R. Ryan, Kaitlyn Foley, Jason Buxhoeveden, Nicole Felizardo, Tania C. Amarnath, Shoba Mossoba, Miriam E. Fowler, Daniel H. TI The Pentostatin Plus Cyclophosphamide Nonmyeloablative Regimen Induces Durable Host T Cell Functional Deficits and Prevents Murine Marrow Allograft Rejection SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Fludarabine; Immune suppression; Immune depletion; Preparative regimen; Mixed chimerism ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PURINE NUCLEOSIDE ANALOGS; DEAMINASE DEFICIENCY; GRAFT-REJECTION; IN-VIVO; TRANSPLANTATION; ADENOSINE; FLUDARABINE; 9-BETA-D-ARABINOFURANOSYL-2-FLUOROADENINE; IRRADIATION AB We describe a novel animal model of nonmyeloablative bone marrow transplantation (BMT) using the purine analog pentostatin. Other cohorts of mice received another purine analog, fludarabine, which we and others have previously evaluated in nonmyeloablative murine models. We evaluated pentostatin for its ability to (1) operate synergistically with cyclophosphamide to induce host T cell depletion; (2) induce host T cell suppression, as defined by modulation of cytokine secretion in vitro and abrogation of host-versus-graft reactivity in vivo; (3) constrain host T cell recovery post-therapy; and (4) prevent the rejection of T cell depleted, fully major histocompatibility complex mismatched bone marrow allografts. Relative to single-agent regimens, combination regimens with pentostatin and cyclophosphamide (PC) and with fludarabine and cyclophosphamide (FC) worked synergistically to deplete host CD4(+) and CD8(+) T cells. PC and FC regimens were developed that yielded similar levels of host T cell and myeloid cell depletion. In the setting of these generally comparable states of host T cell and myeloid cell depletion, the PC regimen was found to be highly immunosuppressive, as evidenced by a reduced host T cell capacity to secrete interleukin-2 and interferon-gamma in vitro, to mediate host-versus-graft reactivity in vivo, and to recover numerically and functionally during a 2-week observation period after chemotherapy. Finally, using B6 hosts treated with the 14-day chemotherapy regimens, the PC regimen more consistently prevented the rejection of BALB/c T cell depleted allografts compared with the FC regimen (rate of alloengraftment, 14/15 [93%] of PC-treated recipients vs 8/14 [57%] of FC-treated recipients; P<.05); similar results were observed using an 8-day conditioning regimen. These data suggest that host T cell suppression, distinct from T cell depletion, may be a critical determinant of engraftment after purine analog based regimens and also may be preferentially attained by the use of pentostatin. Biol Blood Marrow Transplant 17: 620-631 (2011) Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation C1 [Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr,East Labs 3, Bethesda, MD 20892 USA. [Taylor, Justin] NCI, Clin Res Training Program, NIH, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr,East Labs 3, Bethesda, MD 20892 USA. EM fowlerda@mail.nih.gov FU Center for Cancer Research, National Cancer Institute FX This work was supported by the Center for Cancer Research, National Cancer Institute, Intramural Research Program. NR 30 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2011 VL 17 IS 5 BP 620 EP 631 DI 10.1016/j.bbmt.2010.11.029 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 757CK UT WOS:000290061500004 PM 21130889 ER PT J AU Pollack, M Heugel, J Xie, H Leisenring, W Storek, J Young, JA Kukreja, M Gress, R Tomblyn, M Boeckh, M AF Pollack, Margaret Heugel, Judson Xie, Hu Leisenring, Wendy Storek, Jan Young, Jo-Anne Kukreja, Manisha Gress, Ronald Tomblyn, Marcie Boeckh, Michael CA CIMBTR Infection Immune TI An International Comparison of Current Strategies to Prevent Herpesvirus and Fungal Infections in Hematopoietic Cell Transplant Recipients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Cytomegalovirus disease; Hematopoietic stem cell transplanation; Herpesvirus infection; Antifungal porphylaxis ID LATE CYTOMEGALOVIRUS DISEASE; MARROW-TRANSPLANTATION; GLOBAL PERSPECTIVE; AMERICAN-SOCIETY; PROPHYLAXIS; GUIDELINES; RECOMMENDATIONS; COMPLICATIONS; THERAPY; IMPACT AB Herpes virus (cytometalovirus [CMV], herpes simplex virus, varicella zoster virus) and invasive fungal infections continue to cause significant morbidity and mortality in allogeneic hematopoietic cell transplant (HCT) recipients despite the availability of effective therapies. In this study, we developed an Internet-based survey, which was distributed to all hematopoietic cell transplant centers participating in the Center for International Blood and Marrow Transplant Research (CIBMTR) program, to gather information on strategies utilized for the prevention of disease caused by herpes viruses and fungal infections between 1999 and 2003. The survey response rate was 72%, representing 175 programs from 32 countries. Generally, reported center strategies were in accord with the Center for Disease Control and Prevention guidelines published in 2000, with 81% of programs using low-dose acyclovir prophylaxis for herpes simplex virus seropositive patients, 99% of programs reporting use of a CMV prevention strategy during the first 100 days posttransplant for all patients at risk of CMV disease, and 90% of programs using antifungal prophylaxis. Seventy percent of programs reported routine use of a CMV prevention strategy in high-risk patients after day 100. The greatest departure from published guidelines was the use of acyclovir prophylaxis for varicella zoster virus seropositive recipients in 75% of programs. There were very few reported changes within centers in practices over the study time period. Significant regional variations were found with regard to surveillance procedures and treatment durations. There were no significant differences in treatment practices by center size and very few differences found between those centers that reported treating primarily pediatric patients versus primarily adult patients. In summary, our survey demonstrates overall agreement with published guidelines for the prevention of disease because of herpesviruses and fungal infections with significant regional differences found in duration of antiviral prophylaxis, duration of preemptive therapy, and duration and dosing of antifungal prophylaxis. Center size and age of primary patient population were not associated with many reported differences in strategies. Biol Blood Marrow Transplant 17: 664-673 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Pollack, Margaret; Heugel, Judson; Xie, Hu; Leisenring, Wendy; Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Heugel, Judson] Johns Hopkins Univ, Baltimore, MD USA. [Storek, Jan] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Young, Jo-Anne] Univ Minnesota, Minneapolis, MN USA. [Kukreja, Manisha] CIBMTR, Milwaukee, WI USA. [Gress, Ronald] NIH, Bethesda, MD 20892 USA. [Tomblyn, Marcie] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Boeckh, M (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D3-100, Seattle, WA 98109 USA. EM mboeckh@fhcrc.org RI Young, Jo-Anne/G-2617-2013; OI Young, Jo-Anne/0000-0003-4182-341X; Green, Margaret/0000-0002-5591-0779 FU Public Health Service from National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Allos, Inc.; Amgen, Inc.; Astellas Pharma US, Inc.; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc.; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kirin Brewery Co., Ltd.; Leukemia & Lymphoma Society; Merck Company; Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix, Inc; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Allos, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc.; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. This article received additional support from NTH CA 18029, HL093294, NIH CA 15704. NR 14 TC 34 Z9 35 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2011 VL 17 IS 5 BP 664 EP 673 DI 10.1016/j.bbmt.2010.07.026 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 757CK UT WOS:000290061500009 PM 20699126 ER PT J AU Hosing, C Nash, R McSweeney, P Mineishi, S Seibold, J Griffith, LM Shulman, H Goldmuntz, E Mayes, M Parikh, CR Crofford, L Keyes-Elstein, L Furst, D Steen, V Sullivan, KM AF Hosing, Chitra Nash, Richard McSweeney, Peter Mineishi, Shin Seibold, James Griffith, Linda M. Shulman, Howard Goldmuntz, Ellen Mayes, Maureen Parikh, Chirag R. Crofford, Leslie Keyes-Elstein, Lynette Furst, Daniel Steen, Virginia Sullivan, Keith M. TI Acute Kidney Injury in Patients with Systemic Sclerosis Participating in Hematopoietic Cell Transplantation Trials in the United States SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Renal Complications; Scleroderma ID BONE-MARROW-TRANSPLANTATION; SCLERODERMA RENAL CRISIS; THROMBOTIC THROMBOCYTOPENIC PURPURA; TOTAL-BODY IRRADIATION; HEMOLYTIC-UREMIC SYNDROME; VON-WILLEBRAND-FACTOR; DOSE D-PENICILLAMINE; VERSUS-HOST-DISEASE; TERM-FOLLOW-UP; RISK-FACTORS AB Recipients of hematopoietic cell transplantation may be at risk for developing acute kidney injury (AKI), and this risk may be increased in patients who undergo transplantation for severe systemic sclerosis (SSc) due to underlying scleroderma renal disease. AKI after transplantation can increase treatment-related mortality. To better define these risks, we analyzed 91 patients with SSc who were enrolled in 3 clinical trials in the United States of autologous or allogeneic hematopoietic cell transplantation (HCT). Eleven (12%) of the 91 patients with SSc in these studies (8 undergoing autologous HCT, I undergoing allogeneic HCT, 1 pretransplantation, 1 given cyclophosphamide on a transplantation trial) experienced AKI, of whom 8 required dialysis and/or therapeutic plasma exchange. AKI injury in the 9 HCT recipients developed a median of 35 days (range, 0-90 days) after transplantation. Ten of 11 patients with AKI received angiotensin-converting enzyme inhibitor (ACE-I) therapy. The etiology of AKI was attributed to scleroderma renal crisis in 6 patients (including 2 with normotensive renal crisis), to AKI of uncertain etiology in 2 patients, and to AKI superimposed on scleroderma kidney disease in 3 patients. Eight of the 11 patients died, one each because of progression of SSc, multiorgan failure, gastrointestinal and pulmonary bleeding, pericardial tamponade and pulmonary complications, diffuse alveolar hemorrhage, pulmonary embolism, graft-versus-host disease, and malignancy. Limiting nephrotoxins, cautious use of corticosteroids, renal shielding during total body irradiation, strict control of blood pressure, and aggressive use of ACE-Is may be of importance in preventing renal complications after HCT for SSc. Biol Blood Marrow Transplant 17: 674-681 (2011) (C) 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Hosing, Chitra] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Nash, Richard] Fred Hutchinson Canc Res Ctr, Div Clin Res, Dept Med, Seattle, WA 98104 USA. [McSweeney, Peter] Rocky Mt Canc Ctr, Blood & Marrow Transplant Program, Denver, CO USA. [Mineishi, Shin] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Seibold, James] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Griffith, Linda M.] NIAID, Clin Immunol Branch, Div Allergy, NIH, Bethesda, MD 20892 USA. [Shulman, Howard] Fred Hutchinson Canc Res Ctr, Dept Med, Seattle, WA 98104 USA. [Mayes, Maureen] Univ Texas Houston, Div Rheumatol, Houston, TX USA. [Parikh, Chirag R.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Crofford, Leslie] Univ Kentucky, Div Rheumatol, Lexington, KY USA. [Keyes-Elstein, Lynette] Rho Inc, Chapel Hill, NC USA. [Furst, Daniel] Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA USA. [Steen, Virginia] Georgetown Univ, Div Rheumatol, Washington, DC USA. [Sullivan, Keith M.] Duke Univ, Med Ctr, Div Cellular Therapy, Durham, NC USA. RP Hosing, C (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd,Unit 423, Houston, TX 77030 USA. EM cmhosing@mdanderson.org RI Crofford, Leslie/J-8010-2013; OI Hosing, Chitra/0000-0003-0409-5556 FU National Institute of Allergy and Infectious Diseases [AI005419] FX This work, was supported in part by award AI005419 from the National Institute of Allergy and Infectious Diseases. NR 51 TC 9 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2011 VL 17 IS 5 BP 674 EP 681 DI 10.1016/j.bbmt.2010.08.003 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 757CK UT WOS:000290061500010 PM 20708086 ER PT J AU Trabert, B Longnecker, MP Graubard, BI Klebanoff, MA Stanczyk, FZ McGlynn, KA AF Trabert, Britton Longnecker, Matthew P. Graubard, Barry I. Klebanoff, Mark A. Stanczyk, Frank Z. McGlynn, Katherine A. TI Placental characteristics as a proxy measure of serum hormone and protein levels during pregnancy with a male fetus SO CANCER CAUSES & CONTROL LA English DT Article DE Cancer risk; Placental weight; Birth weight; Maternal hormones ID TESTICULAR CANCER; BREAST-CANCER; ESTRIOL LEVELS; BIRTH-WEIGHT; PERINATAL CHARACTERISTICS; UNITED-STATES; MATERNAL RISK; ESTRADIOL; ESTROGEN; AGE AB Objective In utero exposure to steroid hormones may be related to risk of some cancers such as testicular germ cell tumors (TGCT). To determine whether placental characteristics are good surrogate measures of maternal biomarker levels, we evaluated the correlations in mothers of sons at higher (whites, n = 150) and lower (blacks, n = 150) risk of TGCT. Associations with birth weight were also examined. Methods All mothers, participants in the Collaborative Perinatal Project, were primigravidas who gave birth to male singletons. Associations between placental weight and placental thickness and third-trimester biomarker levels were evaluated using linear regression. Partial correlation coefficients for placental characteristics and birth weight were also estimated. Results Placental weight was positively correlated with alpha-fetoprotein (AFP), sex hormone-binding globulin (SHBG), testosterone, estradiol and estriol in whites, and AFP and estriol in blacks. Placental thickness was not associated with any biomarker. After adjustment for placental weight, birth weight was not correlated with any biomarker. Conclusions In these data, placental weight was modestly correlated with third-trimester biomarker level; however, it appeared to be a better surrogate for third-trimester biomarker level than birth weight. Placental thickness had limited utility as a surrogate measure for biomarker levels. C1 [Trabert, Britton; McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. [Longnecker, Matthew P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA. [Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. [Klebanoff, Mark A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Trabert, B (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Executive Blvd,Suite 550, Rockville, MD 20852 USA. EM trabertbl@mail.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; Trabert, Britton/F-8051-2015; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Longnecker, Matthew/0000-0001-6073-5322 FU Intramural Research Programs of the National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences of the National Institutes of Health (NIH) FX Support for this research was provided by the Intramural Research Programs of the National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences of the National Institutes of Health (NIH). NR 40 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2011 VL 22 IS 5 BP 689 EP 695 DI 10.1007/s10552-011-9741-8 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 754IO UT WOS:000289848500003 PM 21336590 ER PT J AU Brown, LM Check, DP Devesa, SS AF Brown, Linda Morris Check, David P. Devesa, Susan S. TI Oropharyngeal cancer incidence trends: diminishing racial disparities SO CANCER CAUSES & CONTROL LA English DT Article DE Oropharyngeal cancer; Human papillomavirus (HPV); Descriptive epidemiology; Incidence; Health disparities ID SQUAMOUS-CELL CARCINOMA; PAPILLOMAVIRUS-ASSOCIATED CANCERS; NECK-CANCER; UNITED-STATES; ORAL-CAVITY; SEXUAL-BEHAVIORS; RISK-FACTORS; HEAD; EPIDEMIOLOGY; PREVALENCE AB Objective The aim of this article is to evaluate oral cavity/pharyngeal cancer (OCPC) trends that may reflect changes in cigarette smoking, alcohol consumption, and human papillomavirus (HPV) infection. Methods We used Surveillance, Epidemiology, and End Results program data for 58,204 cases diagnosed during 1977-2007 to classify if squamous cell carcinomas of the OCP by anatomic site are potentially HPV-related. Results OCPC rates among men peaked during 1982-1986 before declining, most rapidly (46%) among blacks. Rates decreased least rapidly among white males while declining at intermediate paces among other ethnic groups (Asian/Pacific Islanders and Hispanics) and females. Among the men during the recent 16-year time period, the annual percent change for HPV-unrelated sites was much steeper [-6.0% (95% CI = -7.2 to -4.9)] among blacks than whites [-2.5% (95% CI = -2.9 to -2.1)]; for HPV-related sites, it was -1.7% (95% CI = -2.6 to -0.7) among blacks, in striking contrast to +3.3% (95% CI = 2.5-4.0) among whites. HPV-related rates rose rapidly among the white men born since the mid-1940s, tripling among those aged 25-44 and recently surpassing the black male rate. Relative survival rates rose over the study period due to improvements among HPV-related cases. Conclusions The OCPC decreases found among all the race/sex groups reflect reductions in smoking prevalence and alcohol consumption. Rising HPV-related cancers among white men may reflect changes in sexual practices since the mid-1960s. C1 [Brown, Linda Morris] RTI Int, Rockville, MD 20852 USA. [Brown, Linda Morris; Check, David P.; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), RTI Int, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. EM lindabrown@rti.org RI Check, David/J-7184-2015 OI Check, David/0000-0003-3887-0493 FU Division of Cancer Epidemiology and Genetics; National Cancer Institute (NCI); National Institutes of Health FX This study was supported by the Intramural Program of the Division of Cancer Epidemiology and Genetics, the National Cancer Institute (NCI), and National Institutes of Health. NR 49 TC 36 Z9 37 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2011 VL 22 IS 5 BP 753 EP 763 DI 10.1007/s10552-011-9748-1 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 754IO UT WOS:000289848500009 PM 21380619 ER PT J AU Green, CE Swezey, R Bakke, J Shinn, W Furimsky, A Bejugam, N Shankar, GN Jong, L Kapetanovic, IM AF Green, Carol E. Swezey, Robert Bakke, James Shinn, Walter Furimsky, Anna Bejugam, Naveen Shankar, Gita N. Jong, Ling Kapetanovic, Izet M. TI Improved oral bioavailability in rats of SR13668, a novel anti-cancer agent SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE SR13668; Formulation; Pharmacokinetics; Absorption enhancer; Bioavailability; Chemoprevention; Rat; Drug metabolism ID INDOLE-3-CARBINOL; PHARMACOKINETICS; DELIVERY; SYSTEMS; ACID AB Purpose SR13668, a bis-indole with potent activity in vitro and in vivo against various cancers and promising cancer chemopreventive activity, was found to have very low oral bioavailability, < 1%, in rats during pilot pharmacokinetic studies. The objective of these studies was to better understand the source of low oral exposure and to develop a formulation that could be used in preclinical development studies. Methods An automated screening system for determining solubility in lipid-based vehicles, singly and in combination, was used to identify formulations that might enhance absorption by improving solubility of SR13668, and these results were confirmed in vivo using Sprague-Dawley rats. Pharmacokinetics of SR13668 was then determined in male and female Sprague-Dawley rats administered 1 mg/kg iv, 1, 10, and 30 mg/kg po formulated in PEG400:LabrasolA (R) (1:1 v/v). Blood was collected at time points through 24 h and the concentration of SR13668 determined using HPLC with UV and fluorescence detection. Results SR13668 was found to be resistant to plasma esterases in vitro and relatively stable to rat and human liver microsomal metabolism. SR13668 concentrates in tissues as indicated by significantly higher levels in lung compared to blood, blood concentrations similar to 2.5-fold higher than plasma levels, and apparent volume of distribution (V) of similar to 5 l/kg. A marked sex difference was observed in exposure to SR13668 with area under the curve (AUC) significantly higher and clearance (CL) lower for female compared to male rats, after both iv and oral administration. The oral bioavailability (F) of SR13668 was 25.4 +/- A 3.8 and 27.7 +/- A 3.9% (30 mg/kg), for males and females, respectively. A putative metabolite (M1), molecular weight of 445 in the negative ion mode (i.e., SR13668 + 16), was identified in blood samples from both the iv and po routes, as well as in vitro microsomal samples. Conclusions In summary, while SR13668 does undergo metabolism, probably by the liver, the oral bioavailability of SR13668 in rats was dramatically improved by the use of formulation that contained permeation enhancers and promoted better solubilization of the drug. C1 [Green, Carol E.; Swezey, Robert; Bakke, James; Shinn, Walter; Furimsky, Anna; Bejugam, Naveen; Shankar, Gita N.; Jong, Ling] SRI Int, Biosci Div, Menlo Pk, CA 94025 USA. [Kapetanovic, Izet M.] NCI, NIH CADRG, DCP, Bethesda, MD 20892 USA. RP Green, CE (reprint author), SRI Int, Biosci Div, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. EM carol.green@sri.com FU National Cancer Institute, National Institutes of Heath, Department of Health and Human Services [HHSN261200433005C] FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Heath, Department of Health and Human Services, under Contract No. HHSN261200433005C. NR 11 TC 4 Z9 4 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2011 VL 67 IS 5 BP 995 EP 1006 DI 10.1007/s00280-010-1395-9 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 754ZX UT WOS:000289897500003 PM 20623225 ER PT J AU Mazzola, EP Parkinson, A Kennelly, EJ Coxon, B Einbond, LS Freedberg, DI AF Mazzola, Eugene P. Parkinson, Ainsley Kennelly, Edward J. Coxon, Bruce Einbond, Linda S. Freedberg, Daron I. TI Utility of coupled-HSQC experiments in the intact structural elucidation of three complex saponins from Blighia sapida SO CARBOHYDRATE RESEARCH LA English DT Article DE Ackee; Blighia sapida; Coupled-HSQC; Triterpene glycosides; Saponins ID MAGNETIC RESONANCE SPECTRA; NMR-SPECTROSCOPY; CANCER-CELLS; ACKEE; ASSIGNMENT; CONSTANTS; VACCINES; SEEDS; H-1 AB The structures of three complex saponins from the fruit pods of Blighia sapida have been elucidated and their (1)H and (13)C NMR spectra assigned employing a variety of one- and two-dimensional NMR techniques without degradative chemistry. The saponins have either four or six monosaccharide units linked to a triterpene aglycone. High-resolution, proton-coupled-HSQC spectra were important for determining both the identities of the intact monosaccharide units and coupling constants in strongly coupled proton spin systems. These NMR experiments will prove crucial as the complexity of saponin structures reaches the limit that can be determined solely by NMR. (C) 2011 Published by Elsevier Ltd. C1 [Mazzola, Eugene P.] Univ Maryland, FDA Joint Inst, College Pk, MD 20742 USA. [Parkinson, Ainsley; Kennelly, Edward J.] CUNY Herbert H Lehman Coll, Bronx, NY 10468 USA. [Coxon, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Einbond, Linda S.] Columbia Univ Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Freedberg, Daron I.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mazzola, EP (reprint author), Univ Maryland, FDA Joint Inst, College Pk, MD 20742 USA. EM emazzola@umd.edu; ainsley.parkinson@lehman.cuny.edu; Edward.kennelly@lehman.cuny.edu; coxonb@mail.nih.gov; l.einbond@gmail.com; daron-freedberg@nih.gov FU Intramural NIH HHS [Z01 HD008849-01] NR 35 TC 8 Z9 8 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 1 PY 2011 VL 346 IS 6 BP 759 EP 768 DI 10.1016/j.carres.2011.02.019 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 754AB UT WOS:000289821900010 PM 21439554 ER PT J AU Lungu, C Tarulli, AW Tarsy, D Mongiovi, P Vanderhorst, VG Rutkove, SB AF Lungu, Codrin Tarulli, Andrew W. Tarsy, Daniel Mongiovi, Phillip Vanderhorst, Veronique G. Rutkove, Seward B. TI Quantifying muscle asymmetries in cervical dystonia with electrical impedance: A preliminary assessment SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Dystonia; Electrical impedance myography; Diagnosis; Botulinum toxin ID CLINICAL RATING-SCALES; DEEP BRAIN-STIMULATION; BOTULINUM TOXIN; NEUROMUSCULAR DISEASE; SPASMODIC TORTICOLLIS; MYOGRAPHY; PREVALENCE AB Objective: Cervical dystonia (CD) lacks an objective quantitative measure. Electrical impedance myography (EIM) is a non-invasive assessment method sensitive to changes in muscle structure and physiology. We evaluate the potential role of EIM in quantifying CD, hypothesizing that patients would demonstrate differences in the symmetry of muscle electrical resistance compared to controls, and that this asymmetry would decrease after botulinum neurotoxin (BoNT) treatment. Methods: EIM was performed on the sternocleidomastoid (SCM) and cervical paraspinal (PS) muscles of CD patients and age-matched controls. 50 kHz resistance was analyzed, comparing side-to-side asymmetry in patients and controls, and, in patients, before and after BoNT treatment. Results: Sixteen patients and 10 controls were included. Resistance asymmetry was on average 3-5 times higher in patients than controls. Receiver operating characteristic analysis demonstrated 91% accuracy of discriminating CD from normal. From pre-treatment to maximum BoNT effect, asymmetry decreased from 20.8(13.9-26.1)% to 6.2(3.1-9.9)% (SCM), and from 16.0(14.3-16.0)% to 8.4(7.0-9.2)% (PS), p < 0.05 (median, interquartile range). Conclusions: EIM effectively differentiates normal subjects from CD patients by revealing asymmetries in resistance values and detects improvement in muscle symmetry after treatment. Significance: These results suggest that EIM, a painless, non-invasive measure, can provide a useful quantitative metric in CD evaluation and deserves further study. Published by Elsevier Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 [Lungu, Codrin] NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Tarulli, Andrew W.; Tarsy, Daniel; Mongiovi, Phillip; Vanderhorst, Veronique G.; Rutkove, Seward B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. RP Lungu, C (reprint author), NINDS, Med Neurol Branch, NIH, Bldg 10,Room 7D37,MSC 1428,10 Ctr Dr, Bethesda, MD 20892 USA. EM lunguci@ninds.nih.gov FU NIH [K24NS060951, RO1NS042037] FX This project is supported by NIH grants K24NS060951, RO1NS042037. NR 33 TC 6 Z9 7 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2011 VL 122 IS 5 BP 1027 EP 1031 DI 10.1016/j.clinph.2010.09.013 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 757OX UT WOS:000290098700025 PM 20943436 ER PT J AU Franke, RM Lancaster, CS Peer, CJ Gibson, AA Kosloske, AM Orwick, SJ Mathijssen, RH Figg, WD Baker, SD Sparreboom, A AF Franke, R. M. Lancaster, C. S. Peer, C. J. Gibson, A. A. Kosloske, A. M. Orwick, S. J. Mathijssen, R. H. Figg, W. D. Baker, S. D. Sparreboom, A. TI Effect of ABCC2 (MRP2) Transport Function on Erythromycin Metabolism SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ORGANIC ANION TRANSPORTER-2; CYTOCHROME-P450 3A ACTIVITY; CELL LUNG-CANCER; BREATH TEST; P-GLYCOPROTEIN; IRINOTECAN-PHARMACOKINETICS; IN-VIVO; EXPORT PUMPS; PROTEIN; POLYMORPHISMS AB The macrolide antiobiotic erythromycin undergoes extensive hepatic metabolism and is commonly used as a probe for cytochrome P450 (CYP) 3A4 activity. By means of a transporter screen, erythromycin was identified as a substrate for the transporter ABCC2 (MRP 2) and its murine ortholog, Abcc2. Because these proteins are highly expressed on the biliary surface of hepatocytes, we hypothesized that impaired Abcc2 function may influence the rate of hepatobiliary excretion and thereby enhance erythromycin metabolism. Using Abcc2 knockout mice, we found that Abcc2 deficiency was associated with a significant increase in erythromycin metabolism, whereas murine Cyp3a protein expression and microsomal Cyp3a activity were not affected. Next, in a cohort of 108 human subjects, we observed that homozygosity for a common reduced-function variant in ABCC2 (rs717620) was also linked to an increase in erythromycin metabolism but was not correlated with the clearance of midazolam. These results suggest that impaired ABCC2 function can alter erythromycin metabolism, independent of changes in CYP 3A4 activity. C1 [Franke, R. M.; Lancaster, C. S.; Gibson, A. A.; Kosloske, A. M.; Orwick, S. J.; Baker, S. D.; Sparreboom, A.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Peer, C. J.; Figg, W. D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Mathijssen, R. H.] Erasmus MC Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. RP Sparreboom, A (reprint author), St Jude Childrens Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA. EM alex.sparreboom@stjude.org RI Figg Sr, William/M-2411-2016 FU American Lebanese Syrian Associated Charities; US Public Health Service Cancer Center [3P30CA021765] FX This work was supported in part by the American Lebanese Syrian Associated Charities and US Public Health Service Cancer Center Support Grant 3P30CA021765 (S. D. B.). We thank Erin Schuetz and Lubin Lan for their assistance with performing the transcellular transport assays and the erythromycin breath test in mice. NR 44 TC 16 Z9 16 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2011 VL 89 IS 5 BP 693 EP 701 DI 10.1038/clpt.2011.25 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 754DP UT WOS:000289833000017 PM 21451505 ER PT J AU Stunkel, L Grady, C AF Stunkel, Leanne Grady, Christine TI More than the money: A review of the literature examining healthy volunteer motivations SO CONTEMPORARY CLINICAL TRIALS LA English DT Review DE Motivations; Human subjects; Clinical trials ID DECISION-MAKING PROCESS; CLINICAL-TRIALS; PHASE-I; PARTICIPATION; DRUG; INCENTIVES; ATTITUDES; CONSENT; PAYMENT AB Background and objective: Few existing data report the motivations of healthy volunteers in clinical research trials. Some worry that volunteers consider only financial motivations. This study summarized and analyzed existing empirical research on self-reported motivations of healthy volunteers participating in studies not intended to offer benefit from participation. Study selection: A systematic PubMed search was conducted. Inclusion criteria captured English-language empirical studies on the self-reported motivations, reasons, or factors influencing the decision of healthy volunteers to enroll in clinical research. Thirteen studies involving more than 2000 healthy volunteers met the criteria and were included in this review. Data extraction: Independent review by the authors and extraction of information about the sample, methodology and objectives of the motivations study, description of the clinical trial and whether participation was actual or hypothetical, reported primary and secondary motivations of the healthy volunteers, risk evaluation, and reported differences in motivations related to sociodemographic variables. Results: This review showed that although financial reward is the primary motivation for healthy volunteers to participate in clinical trials, financial motivations are one among many other reported motivations, including contributing to science or the health of others, accessing ancillary healthcare benefits, scientific interest or interest in the goals of the study, as well as meeting people and curiosity. Volunteers consider risk when making a decision about participation. Conclusions: Although financial incentives are important in recruiting healthy volunteers, their motivations are not limited to financial motivations. Further research is needed to examine motivations in different contexts and countries, the decision making of healthy volunteers, and the dynamics of repeat participation. Published by Elsevier Inc. C1 [Stunkel, Leanne; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10-1C118, Bethesda, MD 20892 USA. EM ldstunkel@gmail.com; cgrady@cc.nih.gov NR 31 TC 35 Z9 37 U1 4 U2 39 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2011 VL 32 IS 3 BP 342 EP 352 DI 10.1016/j.cct.2010.12.003 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 757EO UT WOS:000290068200008 PM 21146635 ER PT J AU Beleslin-Cokic, BB Cokic, VP Wang, L Piknova, B Teng, RF Schechter, AN Noguchi, CT AF Beleslin-Cokic, Bojana B. Cokic, Vladan P. Wang, Li Piknova, Barbora Teng, Ruifeng Schechter, Alan N. Noguchi, Constance T. TI Erythropoietin and hypoxia increase erythropoietin receptor and nitric oxide levels in lung microvascular endothelial cells SO CYTOKINE LA English DT Article DE Erythropoietin; Erythropoietin receptor; NO; Hypoxia; HMVEC-L ID PULMONARY-HYPERTENSION; CARDIAC-FUNCTION; GROWTH-FACTOR; OVINE FETUS; SYNTHASE; RATS; EXPRESSION; TONE; NO; SYSTEM AB Acute lung exposure to low oxygen results in pulmonary vasoconstriction and redistribution of blood flow. We used human microvascular endothelial cells from lung (HMVEC-L) to study the acute response to oxygen stress. We observed that hypoxia and erythropoietin (EPO) increased erythropoietin receptor (EPOR) gene expression and protein level in HMVEC-L In addition, EPO dose- and time-dependently stimulated nitric oxide (NO) production. This NO stimulation was evident despite hypoxia induced reduction of endothelial NO synthase (eNOS) gene expression. Western blot of phospho-eNOS (serine1177) and eNOS and was significantly induced by hypoxia but not after EPO treatment. However, iNOS increased at hypoxia and with EPO stimulation compared to normal oxygen tension. In accordance with our previous results of NO induction by EPO at low oxygen tension in human umbilical vein endothelial cells and bone marrow endothelial cells, these results provide further evidence in HMVEC-L for EPO regulation of NO production to modify the effects of hypoxia and cause compensatory vasoconstriction. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Wang, Li; Piknova, Barbora; Teng, Ruifeng; Schechter, Alan N.; Noguchi, Constance T.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Beleslin-Cokic, Bojana B.] Clin Ctr Serbia, Inst Endocrinol Diabet & Metab Dis, Belgrade 11000, Serbia. [Cokic, Vladan P.] Inst Med Res, Lab Expt Hematol, Belgrade 11129, Serbia. RP Noguchi, CT (reprint author), NIDDK, Mol Cell Biol Branch, Bldg 10,Room 9N319,10 Ctr Dr,MSC-1822, Bethesda, MD 20892 USA. EM cnoguchi@helix.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 FU National Institute of Diabetes and Digestive and Kidney Diseases; Serbian Ministry of Science and Technological Development [175053] FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and by a grant from the Serbian Ministry of Science and Technological Development [175053]. NR 37 TC 15 Z9 16 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 2011 VL 54 IS 2 BP 129 EP 135 DI 10.1016/j.cyto.2011.01.015 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 757CZ UT WOS:000290063200005 PM 21324713 ER PT J AU Biesecker, LG AF Biesecker, Leslie G. TI Polydactyly: How Many Disorders and How Many Genes? 2010 Update SO DEVELOPMENTAL DYNAMICS LA English DT Review DE malformations; genetic heterogeneity; medical diagnosis; pleiotropism ID BARDET-BIEDL-SYNDROME; MCKUSICK-KAUFMAN-SYNDROME; SMITH-LEMLI-OPITZ; PHENOTYPIC SPECTRUM; MUTATIONS; GLI3; MALFORMATIONS; OVERLAP; MODELS AB Limb development is clinically and biologically important. Polydactyly is common and caused by aberrant anterior-posterior patterning. Human disorders that include polydactyly are diverse. To facilitate an understanding of the biology of limb development, cataloging the genes that are mutated in patients with polydactyly would be useful. In 2002, I characterized human phenotypes that included polydactyly. Subsequently, many advances have occurred with refinement of clinical entities and identification of numerous genes. Here, I update human polydactyly entities by phenotype and mutated gene. This survey demonstrates phenotypes with overlapping manifestations, genetic heterogeneity, and distinct phenotypes generated from mutations in single genes. Among 310 clinical entities, 80 are associated with mutations in 99 genes. These results show that knowledge of limb patterning genetics is improving rapidly. Soon, we will have a comprehensive toolkit of genes important for limb development, which will lead to regenerative therapies for limb anomalies. Developmental Dynamics 240:931-942, 2011. (C) 2011 Wiley-Liss, Inc. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49,Room 4A56, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov FU Intramural NIH HHS [ZIA HG200328-06] NR 28 TC 16 Z9 17 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2011 VL 240 IS 5 SI SI BP 931 EP 942 DI 10.1002/dvdy.22609 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 755OJ UT WOS:000289942300004 PM 21445961 ER PT J AU Hopyan, S Sharpe, J Yang, YZ AF Hopyan, Sevan Sharpe, James Yang, Yingzi TI Budding Behaviors: Growth of the Limb as a Model of Morphogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Review DE limb bud; morphogenesis; elongation; cell polarity; directional cell movement; protrusive activity; mesoderm; anlage; growth plate; oriented cell division; cell movement; oriented cell division; planar cell polarity; cell shape; noncanonical Wnt signalling; Wnt5a; Fgf signalling; Vangl2 ID APICAL ECTODERMAL RIDGE; ORIENTED CELL-DIVISION; CHICK LIMB; MOUSE LIMB; XENOPUS GASTRULATION; EXTERNAL GENITALIA; BUD MESENCHYME; OUTGROWTH; POLARITY; CARTILAGE AB Questions regarding morphogenesis have played second fiddle to those pertaining to pattern formation among the limb development set for some time. A recent series of publications has reinvigorated the search for mechanisms by which the limb bud arises, elongates and acquires its peculiar shape. While there are stage-specific variations, the theme that resonates across these studies is that mesoderm and cartilage cells in the limb bud exhibit polarity that drives directional movement and oriented division. Noncanonical Wnt signalling is important for these cell behaviors at all stages of limb development. While the emerging morphogenetic mechanisms underlying limb bud outgrowth are partly analogous to those of other developing structures, insights from the limb have the potential to reveal intriguing new mechanisms by which three dimensional mesoderm changes shape. Developmental Dynamics 240:1054-1062, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Hopyan, Sevan] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 1X8, Canada. [Hopyan, Sevan] Hosp Sick Children, Div Orthopaed, Toronto, ON M5G 1X8, Canada. [Sharpe, James] UPF, EMBL CRG Syst Biol Res Unit, CRG, Barcelona, Spain. [Yang, Yingzi] NHGRI, Dev Genet Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Hopyan, S (reprint author), Hosp Sick Children, Dev & Stem Cell Biol Program, 555 Univ Ave,Suite S107, Toronto, ON M5G 1X8, Canada. EM sevan.hopyan@sickkids.ca RI Sharpe, James/L-1150-2014 OI Sharpe, James/0000-0002-1434-9743 NR 75 TC 20 Z9 20 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2011 VL 240 IS 5 SI SI BP 1054 EP 1062 DI 10.1002/dvdy.22601 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 755OJ UT WOS:000289942300013 PM 21384474 ER PT J AU Zhu, JJ Mackem, S AF Zhu, Jianjian Mackem, Susan TI Analysis of Mutants With Altered Shh Activity and Posterior Digit Loss Supports a Biphasic Model for Shh Function as a Morphogen and Mitogen SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Sonic hedgehog; limb development; digit patterning ID VERTEBRATE LIMB DEVELOPMENT; SONIC HEDGEHOG; CHOLESTEROL MODIFICATION; MOUSE LIMB; BUD; EXPRESSION; RECOMBINASE; RESTRICTS; SKELETON AB Sonic hedgehog (Shh) controls the number and type of digits formed. Using a conditional genetic approach for timed removal of Shh, we previously proposed a biphasic model of Shh function: a transient patterning phase, during which digit progenitors are specified, and an extended proliferative phase, during which expansion of progenitor pools enables digit formation. Other models favor a close integration of digit patterning and expansion, with sequential promotion to more posterior identity over time, apparently supported by some mutants with selective posterior digit loss. To further test these models, we analyzed the dynamics of Shh activity in several oligodactylous mutants with different types of digit loss. The profile of Shh activity and phenotypic outcome in these mutants supports a biphasic over an integrated temporal model. Eomesodermin expression, as an independent marker of posterior digit identity, confirmed that proper digit 4 specification requires only the transient phase of Shh activity. Developmental Dynamics 240:1303-1310, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Zhu, Jianjian; Mackem, Susan] NCI Frederick, CCR, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Mackem, S (reprint author), NCI Frederick, CCR, Canc & Dev Biol Lab, 1050 Boyles St,Bldg539 Room121A, Frederick, MD 21702 USA. EM mackems@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX Grant sponsor: Center for Cancer Research, National Cancer Institute, NIH. NR 24 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2011 VL 240 IS 5 SI SI BP 1303 EP 1310 DI 10.1002/dvdy.22637 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 755OJ UT WOS:000289942300035 PM 21509901 ER PT J AU Yang, CH Zhang, MS Li, J Zhang, XP Wang, H Hao, YB AF Yang, Cai-Hong Zhang, Ming-Sheng Li, Jie Zhang, Xuan-Ping Wang, Hang Hao, Yi-Bin TI Monophosphoryl Lipid A-Induced Delayed Preconditioning in Rat Small Intestine Is Mediated by Calcitonin Gene-Related Peptide SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Monophosphoryl lipid A; Delayed preconditioning; CGRP (calcitonin gene-related peptide); CGRP-(8-37); Capsaicin; Rat small intestine ID ISCHEMIA-REPERFUSION INJURY; K-ATP CHANNELS; NITRIC-OXIDE; CARDIAC ISCHEMIA; NITROGLYCERIN; EXPRESSION; PROTECTION; CGRP; CARDIOPROTECTION; PATHWAY AB Protective effects of ischemic preconditioning in rat small intestine have been shown to be related to the release of calcitonin gene-related peptide. The purpose of the present study was to explore whether monophosphoryl lipid A participated in the protective process of the delayed ischemic preconditioning in the peripheral vascular bed (the anse intestinalis of rat), and whether endogenous calcitonin gene-related peptide is a mediator in this process. Intestinal ischemia was induced by occlusion of the superior mesenteric artery for 30 min, followed by reperfusion for 60 min. The intestinal lesions were evaluated by the measurement of serum lactate dehydrogenase, myeloperoxidase levels, and small intestine tissue contents of malondialdehyde. In addition, calcitonin gene-related peptide in plasma and superior mesenteric vein effluent were also examined. Pretreatment with monophosphoryl lipid A (500 mu g/kg. i.p.) 24 h prior to ischemia-reperfusion significantly alleviated the intestinal tissue histology lesions, decreased serum levels of lactate dehydrogenase, myeloperoxidase, and reduced tissue content of malondialdehyde. Moreover, monophosphoryl lipid A markedly increased plasma concentrations of calcitonin gene-related peptide. Pretreatment with capsaicin, which specifically depletes the neurotransmitter content of sensory nerves or calcitonin gene-related peptide-(8-37), a selective calcitonin gene-related peptide receptor antagonist, inhibited the increased calcitonin gene-related peptide release and subsequently abrogated the protection by monophosphoryl lipid A. In conclusion, monophosphoryl lipid A pharmacologically mimics delayed preconditioning and the protective effects are related to the stimulation of calcitonin gene-related peptide release in rat small intestine. C1 [Yang, Cai-Hong; Zhang, Ming-Sheng; Li, Jie; Zhang, Xuan-Ping; Hao, Yi-Bin] Shanxi Med Univ, Dept Pharmacol, Taiyuan 030001, Shanxi, Peoples R China. [Wang, Hang] NHGRI, NIH, Bethesda, MD 20892 USA. RP Hao, YB (reprint author), Shanxi Med Univ, Dept Pharmacol, Taiyuan 030001, Shanxi, Peoples R China. EM hyb4690740@yahoo.com.cn NR 34 TC 1 Z9 2 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2011 VL 56 IS 5 BP 1333 EP 1341 DI 10.1007/s10620-010-1428-6 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 755AO UT WOS:000289899200013 PM 20936354 ER PT J AU Gonzalez, FJ Cheng, J Ma, XC AF Gonzalez, Frank J. Cheng, Jie Ma, Xiaochao TI Pregnane X receptor-humanized mice SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 4th Asia Pacific Meeting of the International-Society-for-the-Study-of -Xenobiotics (ISSX) CY APR 22-25, 2011 CL Tainan, TAIWAN SP Int Soc Study Xenobiot C1 [Gonzalez, Frank J.; Cheng, Jie] NCI, Lab Metab, Bethesda, MD 20892 USA. [Ma, Xiaochao] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD MAY PY 2011 VL 43 SU 1 BP 7 EP 8 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 751PG UT WOS:000289629400013 ER PT J AU Gonzalez, FJ Patterson, AD Krausz, KW Idle, JR AF Gonzalez, Frank J. Patterson, Andrew D. Krausz, Kristopher W. Idle, Jeffrey R. TI Predictive toxicology using metabolomics SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 4th Asia Pacific Meeting of the International-Society-for-the-Study-of -Xenobiotics (ISSX) CY APR 22-25, 2011 CL Tainan, TAIWAN SP Int Soc Study Xenobiot C1 [Gonzalez, Frank J.; Patterson, Andrew D.; Krausz, Kristopher W.] NCI, Lab Metab, Bethesda, MD 20892 USA. [Idle, Jeffrey R.] Univ Bern, Inst Clin Pharmacol, Bern, Switzerland. RI Patterson, Andrew/G-3852-2012 OI Patterson, Andrew/0000-0003-2073-0070 NR 0 TC 0 Z9 0 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD MAY PY 2011 VL 43 SU 1 BP 12 EP 13 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 751PG UT WOS:000289629400023 ER PT J AU Kim, HJ Miron, VE Dukala, D Proia, RL Ludwin, SK Traka, M Antel, JP Soliven, B AF Kim, Hye Jung Miron, Veronique E. Dukala, Danuta Proia, Richard L. Ludwin, Samuel K. Traka, Maria Antel, Jack P. Soliven, Betty TI Neurobiological effects of sphingosine 1-phosphate receptor modulation in the cuprizone model SO FASEB JOURNAL LA English DT Article DE FTY720; fingolimod; oligodendrocytes; multiple sclerosis; demyelination; remyelination ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MATURE OLIGODENDROCYTE APOPTOSIS; IMMUNOMODULATORY DRUG FTY720; RELAPSING MULTIPLE-SCLEROSIS; PROTEIN-COUPLED RECEPTORS; PRIMARY DEMYELINATION; SIGNAL-TRANSDUCTION; ORAL FINGOLIMOD; GENE-EXPRESSION AB Fingolimod (FTY720) is a sphingosine 1-phosphate (S1P) receptor modulator that regulates lymphocyte trafficking and exerts pleiotropic actions on oligodendrocytes (OLGs) and other neural cells. The purpose of this study was to investigate the role of S1P receptors in a non-T-cell model of demyelination, the cuprizone (cupr) model in C57BL/6 mice. Treatment with FTY720 (1 mg/kg) led to attenuated injury to OLGs, myelin, and axons in the corpus callosum (percentage of myelinated fibers was 44.7% in cupr-water and 63% in cupr-FTY720). Reactive astrogliosis and microgliosis were ameliorated when FTY720 was given from d 1, but astrogliosis was augmented when FTY720 was given from wk 4-9. FTY720 did not promote remyelination in this model. The protective effect of FTY720 was associated with decreased interleukin-1 beta and CCL2 transcripts in the corpus callosum, as well as altered S1P1 expression. Targeted deletion of S1P1 in OLG lineage cells did not lead to obvious clinical phenotype, but resulted in subtle abnormalities in myelin and an increased susceptibility to cupr-induced demyelination. We conclude that S1P receptors expressed by neuroglia are involved in regulating the response to injury, and CNS effects of FTY720 could contribute to its favorable therapeutic response in multiple sclerosis.-Kim, H. J., Miron, V. E., Dukala, D., Proia, R. L., Ludwin, S. K., Traka, M., Antel, J. P., Soliven, B. Neurobiological effects of sphingosine 1-phosphate receptor modulation in the cuprizone model. FASEB J. 25, 1509-1518 (2011). www.fasebj.org C1 [Kim, Hye Jung; Dukala, Danuta; Traka, Maria; Soliven, Betty] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Miron, Veronique E.; Antel, Jack P.] McGill Univ, Dept Neuroimmunol, Montreal, PQ, Canada. [Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. [Ludwin, Samuel K.] Queens Univ, Dept Neuropathol, Kingston, ON, Canada. RP Soliven, B (reprint author), Univ Chicago, Dept Neurol MC2030, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM bsoliven@neurology.bsd.uchicago.edu RI Proia, Richard/A-7908-2012 FU U.S. National Institute of Neurological Disorders and Stroke [R21 NS049014]; National MS Society [RG3951A7/1, TR3762-A-1]; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; MS Society of Canada; Novartis; Canadian Institutes of Health FX The authors thank Dr. B. Popko, Dr. N. Turgut, Dr. T. Johnson, and B. Durafourt for their assistance or advice in some experiments. This work was supported by the U.S. National Institute of Neurological Disorders and Stroke (R21 NS049014), the National MS Society (RG3951A7/1), and a gift from M. P. Miller (B. S.); the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R. L. P.); the National MS Society (TR3762-A-1), a grant from the MS Society of Canada, and a grant from Novartis (J.P.A.); and a Canadian Institutes of Health Research studentship (V. E. M.). NR 61 TC 40 Z9 40 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2011 VL 25 IS 5 BP 1509 EP 1518 DI 10.1096/fj.10-173203 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 756OU UT WOS:000290023800009 PM 21248243 ER PT J AU Kobrinsky, E Duong, SQ Sheydina, A Soldatov, NM AF Kobrinsky, Evgeny Duong, Son Q. Sheydina, Anna Soldatov, Nikolai M. TI Microdomain organization and frequency-dependence of CREB-dependent transcriptional signaling in heart cells SO FASEB JOURNAL LA English DT Article DE cardiac myocytes; wavelet transform analysis; Ca(v)1.2 calcium channel; FRET microscopy; patch clamp ID ELEMENT-BINDING PROTEIN; TARGET GENE ACTIVATION; TERM CARDIAC MEMORY; CALCIUM OSCILLATIONS; WAVELET TRANSFORM; PHOSPHORYLATION; EXPRESSION; CHANNEL; CAMP; CARDIOMYOCYTES AB Voltage-gated Ca(v)1.2 calcium channels couple membrane depolarization to cAMP response-element-binding protein (CREB)-dependent transcriptional activation. To investigate the spatial and temporal organization of CREB-dependent transcriptional nuclear microdomains, we combined perforated patch-clamp technique and FRET microscopy for monitoring CREB and CREB-binding protein interaction in the nuclei of live cells. The experimental approach to the quantitative assessment of CREB-dependent transcriptional signaling evoked by cAMP-and Ca(v)1.2-dependent mechanisms was devised in COS1 cells expressing recombinant Ca(v)1.2 calcium channels. Using continuous 2-dimensional wavelet transform and time series analyses, we found that nuclear CREB-dependent transcriptional signaling is organized differentially in spatially and temporally separated microdomains of 4 distinct types. In rat neonatal cardiomyocytes, CREB-dependent transcription is mediated by the cAMP-initiated CaMKII-sensitive and Ca(v)1.2-initiated CaMKII-insensitive mechanisms. The latter microdomains show a tendency to exhibit periodic behavior correlated with spontaneous contraction of myocytes suggestive of frequency-dependent CREB-dependent transcriptional regulation in the heart.-Kobrinsky, E., Duong, S. Q., Sheydina, A., Soldatov, N. M. Microdomain organization and frequency-dependence of CREB-dependent transcriptional signaling in heart cells. FASEB J. 25, 1544-1555 (2011). www.fasebj.org C1 [Kobrinsky, Evgeny; Duong, Son Q.; Sheydina, Anna; Soldatov, Nikolai M.] NIA, NIH, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), Humgenex Inc, 3105 Starner Ct, Kensington, MD 20895 USA. EM soldatovn.humgenex@verizon.net FU National Institute on Aging [Z01 AG000294-08] FX This study was supported by the National Institute on Aging Intramural Research Program (Z01 AG000294-08 to NMS). The authors thank Dr. Mark R. Montminy (The Salk Institute for Biological Studies, La Jolla, CA, USA) for providing KID and KIX constructs and Dr. Kenneth R. Boheler (National Institute on Aging, U.S. National Institutes of Health, Baltimore, MD, USA) for providing rat cardiac myocytes. NR 60 TC 6 Z9 6 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2011 VL 25 IS 5 BP 1544 EP 1555 DI 10.1096/fj.10-176198 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 756OU UT WOS:000290023800012 PM 21248242 ER PT J AU Gildea, DE Luetkemeier, ES Bao, XZ Loftus, SK Mackem, S Yang, YZ Pavan, WJ Biesecker, LG AF Gildea, Derek E. Luetkemeier, Erin S. Bao, Xiaozhong Loftus, Stacie K. Mackem, Susan Yang, Yingzi Pavan, William J. Biesecker, Leslie G. TI The pleiotropic mouse phenotype extra-toes spotting is caused by translation initiation factor Eif3c mutations and is associated with disrupted sonic hedgehog signaling SO FASEB JOURNAL LA English DT Article DE development; polydactyly; positional cloning; GLI3 processing ID GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; DEVELOPING NEURAL-TUBE; LIMB DEVELOPMENT; POLARIZING ACTIVITY; FEEDBACK LOOP; IN-VIVO; GLI3; GENE; EXPRESSION; DELETION AB Polydactyly is a common malformation and can be an isolated anomaly or part of a pleiotropic syndrome. The elucidation of the mutated genes that cause polydactyly provides insight into limb development pathways. The extra-toes spotting (Xs) mouse phenotype manifests anterior polydactyly, predominantly in the forelimbs, with ventral hypopigmenation. The mapping of Xs(J) to chromosome 7 was confirmed, and the interval was narrowed to 322 kb using intersubspecific crosses. Two mutations were identified in eukaryotic translation initiation factor 3 subunit C (Eif3c). An Eif3c c.907C > T mutation (p.Arg303X) was identified in Xs(J), and a c.1702_1758del mutation (p.Leu568_Leu586del) was identified in extra-toes spotting-like (Xsl), an allele of Xs(J). The effect of the Xs(J) mutation on the SHH/GLI3 pathway was analyzed by in situ hybridization analysis, and we show that Xs mouse embryos have ectopic Shh and Ptch1 expression in the anterior limb. In addition, anterior limb buds show aberrant Gli3 processing, consistent with perturbed SHH/GLI3 signaling. Based on the occurrence of Eif3c mutations in 2 Xs lines and haploinsufficiency of the Xs(J) allele, we conclude that the Xs phenotype is caused by a mutation in Eif3c, a component of the translation initiation complex, and that the phenotype is associated with aberrant SHH/GLI3 signaling.-Gildea, D. E., Luetkemeier, E. S., Bao, X., Loftus, S. K., Mackem, S., Yang, Y., Pavan, W. J., Biesecker, L. G. The pleiotropic mouse phenotype extra-toes spotting is caused by translation initiation factor Eif3c mutations and is associated with disrupted sonic hedgehog signaling. FASEB J. 25, 1596-1605 (2011). www.fasebj.org C1 [Gildea, Derek E.; Luetkemeier, Erin S.; Loftus, Stacie K.; Yang, Yingzi; Pavan, William J.; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Gildea, Derek E.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. [Bao, Xiaozhong; Mackem, Susan] NCI, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, NIH, Bldg 49,Rm 4A56, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov FU National Human Genome Research Institute; National Cancer Institute FX The authors thank Arturo Incao, Marjorie Lindhurst, and Julie Nadel for assistance with animal husbandry. The authors also thank Julia Fekecs for help with generating figures. This research was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Cancer Institute. Information on Xsl can be found online (http://mousemutant.jax.org/articles/mmrmutantxsl.html). NR 37 TC 4 Z9 4 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2011 VL 25 IS 5 BP 1596 EP 1605 DI 10.1096/fj.10-169771 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 756OU UT WOS:000290023800017 PM 21292980 ER PT J AU Grover, M Farrugia, G Lurken, MS Bernard, CE Faussone-Pellegrini, MS Smyrk, TC Parkman, HP Abell, TL Snape, WJ Hasler, WL Unalp-Arida, A Nguyen, L Koch, KL Calles, J Lee, L Tonascia, J Hamilton, FA Pasricha, PJ AF Grover, Madhusudan Farrugia, Gianrico Lurken, Matthew S. Bernard, Cheryl E. Faussone-Pellegrini, Maria Simonetta Smyrk, Thomas C. Parkman, Henry P. Abell, Thomas L. Snape, William J. Hasler, William L. Unalp-Arida, Aynur Nguyen, Linda Koch, Kenneth L. Calles, Jorges Lee, Linda Tonascia, James Hamilton, Frank A. Pasricha, Pankaj J. CA NIDDK Gastroparesis Clinical Res TI Cellular Changes in Diabetic and Idiopathic Gastroparesis SO GASTROENTEROLOGY LA English DT Article DE Gastric Emptying; Smooth Muscle; Interstitial Cells of Cajal; Enteric Nerves ID NEURONAL NITRIC-OXIDE; INTERSTITIAL-CELLS; OXIDATIVE STRESS; PATHOLOGICAL FINDINGS; MYENTERIC PLEXUS; NERVOUS-SYSTEM; ANIMAL-MODEL; CAJAL; ASSOCIATION; MECHANISMS AB BACKGROUND & AIMS: Cellular changes associated with diabetic and idiopathic gastroparesis are not well described. The aim of this study was to describe histologic abnormalities in gastroparesis and compare findings in idiopathic versus diabetic gastroparesis. METHODS: Full-thickness gastric body biopsy specimens were obtained from 40 patients with gastroparesis (20 diabetic) and matched controls. Sections were stained for H&E and trichrome and immunolabeled with antibodies against protein gene product (PGP) 9.5, neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide, substance P, and tyrosine hydroxylase to quantify nerves, S100 beta for glia, Kit for interstitial cells of Cajal (ICC), CD45 and CD68 for immune cells, and smoothelin for smooth muscle cells. Tissue was also examined by transmission electron microscopy. RESULTS: Histologic abnormalities were found in 83% of patients. The most common defects were loss of ICC with remaining ICC showing injury, an abnormal immune infiltrate containing macrophages, and decreased nerve fibers. On light microscopy, no significant differences were found between diabetic and idiopathic gastroparesis with the exception of nNOS expression, which was decreased in more patients with idiopathic gastroparesis (40%) compared with diabetic patients (20%) by visual grading. On electron microscopy, a markedly increased connective tissue stroma was present in both disorders. CONCLUSIONS: This study suggests that on full-thickness biopsy specimens, cellular abnormalities are found in the majority of patients with gastroparesis. The most common findings were loss of Kit expression, suggesting loss of ICC, and an increase in CD45 and CD68 immunoreactivity. These findings suggest that examination of tissue can lead to valuable insights into the pathophysiology of these disorders and offer hope that new therapeutic targets can be found. C1 [Grover, Madhusudan; Farrugia, Gianrico; Lurken, Matthew S.; Bernard, Cheryl E.; Smyrk, Thomas C.] Mayo Clin, Rochester, MN 55905 USA. [Faussone-Pellegrini, Maria Simonetta] Univ Florence, Florence, Italy. [Parkman, Henry P.] Temple Univ, Philadelphia, PA 19122 USA. [Abell, Thomas L.] Univ Mississippi, Jackson, MS 39216 USA. [Snape, William J.] Calif Pacific Med Ctr, San Francisco, CA USA. [Hasler, William L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Unalp-Arida, Aynur; Lee, Linda; Tonascia, James] Johns Hopkins Univ, Baltimore, MD USA. [Nguyen, Linda; Pasricha, Pankaj J.] Stanford Univ, Palo Alto, CA 94304 USA. [Koch, Kenneth L.; Calles, Jorges] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hamilton, Frank A.] NIDDK, Bethesda, MD USA. RP Farrugia, G (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM farrugia.gianrico@mayo.edu RI Vaughn, Ivana/B-6138-2016 OI Vaughn, Ivana/0000-0002-7201-0289 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974, U01DK074008]; [DK57061]; [PO1 DK68055] FX The Gastroparesis Clinical Research Consortium is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974, and U01DK074008). This work was also supported by grants DK57061 and PO1 DK68055. NR 51 TC 103 Z9 109 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2011 VL 140 IS 5 BP 1575 EP U296 DI 10.1053/j.gastro.2011.01.046 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756QA UT WOS:000290028200038 PM 21300066 ER PT J AU Strober, W Fuss, IJ AF Strober, Warren Fuss, Ivan J. TI Proinflammatory Cytokines in the Pathogenesis of Inflammatory Bowel Diseases SO GASTROENTEROLOGY LA English DT Article DE Crohn's Disease; Ulcerative Colitis; Cytokines; IL-12; IL-23; IFN-gamma; IL-17; IL-22; TL1A ID CELL-DEPENDENT COLITIS; ACTIVE CROHNS-DISEASE; CD4(+) T-CELLS; ROR-GAMMA-T; INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; TGF-BETA; CUTTING EDGE; TH17 CELLS; IFN-GAMMA AB The cytokine responses characterizing the inflammatory bowel diseases are the key pathophysiologic elements that govern the initiation, evolution, and, ultimately, the resolution of these forms of inflammation. Studies during the last 2 decades now provide a detailed (but not yet complete) picture of the nature of these responses. The first tier of cytokine responses are governed by the T-cell differentiation patterns dominating the disease. In Crohn's disease, the major cytokines arise from T-helper cell (Th) 1 and Th17 CD4(+) T-cell differentiation and consist of interferon-gamma and interleukin (IL)-17/IL-22 generated by these types of differentiation. The relative importance of these cytokines to Crohn's inflammation is still unclear, although evidence is mounting that interferon-gamma is primus inter pare (first among equals). In contrast, in ulcerative colitis, a Th2-like differentiation process is paramount, which results in expansion of natural killer T cells producing IL-13 (and perhaps IL-5). These disease-specific cytokine patterns give rise to a second tier of cytokines that span the Th1/Th17-Th2 divide and act as upstream facilitators and downstream mediators of inflammation. These cytokines include the well-known tumor necrosis factor-alpha, IL-1 beta, IL-6 triumphirate, as well as a more recently studied cytokine known as TL1A (tumor necrosis factor-like ligand). In this review, we will explore this cytokine landscape with the view of providing an understanding of how recent and future anticytokine therapies actually function. C1 [Strober, Warren; Fuss, Ivan J.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, 10 Ctr Dr,CRC Bldg,5 W Labs Rm 3940, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000432-23] NR 88 TC 345 Z9 370 U1 12 U2 56 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2011 VL 140 IS 6 BP 1756 EP U82 DI 10.1053/j.gastro.2011.02.016 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756MT UT WOS:000290016700008 PM 21530742 ER PT J AU Ichijima, Y Ichijima, M Lou, ZK Nussenzweig, A Camerini-Otero, RD Chen, JJ Andreassen, PR Namekawa, SH AF Ichijima, Yosuke Ichijima, Misako Lou, Zhenkun Nussenzweig, Andre Camerini-Otero, R. Daniel Chen, Junjie Andreassen, Paul R. Namekawa, Satoshi H. TI MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells SO GENES & DEVELOPMENT LA English DT Article DE germ cells; meiosis; meiotic sex chromosome inactivation; DNA damage response; MDC1; gamma H2AX ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; IMPRINTED X-INACTIVATION; DNA-DAMAGE CHECKPOINT; MAMMALIAN MEIOSIS; MEIOTIC CHROMOSOMES; GENOME INTEGRITY; MOUSE; CHROMATIN; MICE AB Chromosome-wide inactivation is an epigenetic signature of sex chromosomes. The mechanism by which the chromosome-wide domain is recognized and gene silencing is induced remains unclear. Here we identify an essential mechanism underlying the recognition of the chromosome-wide domain in the male germline. We show that mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (gamma H2AX), defines the chromosome-wide domain, initiates meiotic sex chromosome inactivation (MSCI), and leads to XY body formation. Importantly, MSCI consists of two genetically separable steps. The first step is the MDC1-independent recognition of the unsynapsed axis by DNA damage response (DDR) factors such as ataxia telangiectasia and Rad3-related (ATR), TOPBP1, and gamma H2AX. The second step is the MDC1-dependent chromosome-wide spreading of DDR factors to the entire chromatin. Furthermore, we demonstrate that, in somatic cells, MDC1-dependent amplification of the gamma H2AX signal occurs following replicative stress and is associated with transcriptional silencing. We propose that a common DDR pathway underlies both MSCI and the response of somatic cells to replicative stress. These results establish that the DDR pathway centered on MDC1 triggers epigenetic silencing of sex chromosomes in germ cells. C1 [Ichijima, Yosuke; Ichijima, Misako; Namekawa, Satoshi H.] Cincinnati Childrens Hosp, Med Ctr, Div Reprod Sci, Perinatal Inst, Cincinnati, OH 45229 USA. [Ichijima, Yosuke; Ichijima, Misako; Andreassen, Paul R.; Namekawa, Satoshi H.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA. [Lou, Zhenkun] Mayo Clin, Div Oncol Res, Dept Oncol, Rochester, MN 55905 USA. [Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Camerini-Otero, R. Daniel] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. [Chen, Junjie] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Andreassen, Paul R.] Cincinnati Childrens Hosp, Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. RP Namekawa, SH (reprint author), Cincinnati Childrens Hosp, Med Ctr, Div Reprod Sci, Perinatal Inst, Cincinnati, OH 45229 USA. EM satoshi.namekawa@cchmc.org FU Developmental Fund and Trustee Grant at Cincinnati Children's Hospital Medical Center; NCI (NIH); NIDDK (NIH); NIH [CA130996, CA092312, HL085587] FX We thank Mary Ann Handel, Xiaochun Yu, Denise Escalier, and James Ingles for providing antibodies; Yuya Ogawa, Ho-Su Sin, and Fumika N. Hamada for discussion and helpful comments regarding the manuscript; Marina A. Bellani, Katherine Minter Dykhouse, and Margarida Almeida Santos for help in transferring mice; S. Steven Potter and Shawn Smith for help with the microarray analysis; and Erin L. Adams for editing the manuscript. S.H.N. is deeply grateful to S.K. Dey and Jeannie T. Lee for their support of the initial stage of the Namekawa laboratory. This work was supported by the Developmental Fund and Trustee Grant at Cincinnati Children's Hospital Medical Center (to S.H.N.), the NCI (NIH) Intramural Research Program (A.N.), the NIDDK (NIH) Intramural Research Program (R.D.C.-O.), and NIH grants CA130996 (to Z.L.), CA092312 (to J.C.), and HL085587 (to P.R.A.). NR 70 TC 66 Z9 67 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 2011 VL 25 IS 9 BP 959 EP 971 DI 10.1101/gad.2030811 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 757LU UT WOS:000290087300009 PM 21536735 ER PT J AU Hakim, O Sung, MH Voss, TC Splinter, E John, S Sabo, PJ Thurman, RE Stamatoyannopoulos, JA de Laat, W Hager, GL AF Hakim, Ofir Sung, Myong-Hee Voss, Ty C. Splinter, Erik John, Sam Sabo, Peter J. Thurman, Robert E. Stamatoyannopoulos, John A. de Laat, Wouter Hager, Gordon L. TI Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements SO GENOME RESEARCH LA English DT Article ID LONG-RANGE INTERACTIONS; GLUCOCORTICOID-RECEPTOR; NUCLEAR-ORGANIZATION; GENOME; LOCUS; ACTIVATION; TRANSCRIPTION; HEPATOCYTES; ASSOCIATION; EXPRESSION AB The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. Contradicting results have been reported to date, with little consensus about the dynamics of nuclear organization and the features of the contact loci. In this study, we investigated the properties and dynamics of genomic loci that are in contact with glucocorticoid receptor (GR)-responsive loci. We took a systematic approach, combining genome-wide interaction profiling by the chromosome conformation capture on chip (4C) technology with expression, protein occupancy, and chromatin accessibility profiles. This approach allowed a comprehensive analysis of how distinct features of the linear genome are organized in the three-dimensional nuclear space in the context of rapid gene regulation. We found that the transcriptional response to GR occurs without dramatic nuclear reorganization. Moreover, contrary to the view of transcription-driven organization, even genes with opposite transcriptional responses colocalize. Regions contacting GR-regulated genes are not particularly enriched for GR-regulated loci or for any functional group of genes, suggesting that these subnuclear environments are not organized to respond to a specific factor. The contact regions are, however, highly enriched for DNase I-hypersensitive sites that comprehensively mark cell-type-specific regulatory sites. These findings indicate that the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming, and this organization is significantly correlated with cell-type-specific chromatin sites accessible to regulatory factors. Numerous open chromatin loci may be arranged in nuclear domains that are poised to respond to diverse signals in general and to permit efficient gene regulation. C1 [Hakim, Ofir; Sung, Myong-Hee; Voss, Ty C.; John, Sam; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Splinter, Erik; de Laat, Wouter] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. [Splinter, Erik; de Laat, Wouter] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. [Sabo, Peter J.; Thurman, Robert E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov RI Hakim, Ofir/A-6239-2012; cheng, yong/I-4270-2012 FU National Institute of Health, National Cancer Institute, Center for Cancer Research FX We acknowledge A. Indrawan for technical help; T. Karpova for help with microscopy; Y. Dalal and K. Gardner for helpful discussions; D. Meerzaman and R.L. Walker for help with the microarray scanner; S. Baek for submitting motif analysis jobs to the NIH supercomputing cluster; and K. Meaburn for help with DNA FISH. Fluorescence imaging was performed at the National Cancer Institute Fluorescence Imaging Facility. This work was supported in part by the Intramural Research Program of the National Institute of Health, National Cancer Institute, Center for Cancer Research. NR 32 TC 71 Z9 73 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 2011 VL 21 IS 5 BP 697 EP 706 DI 10.1101/gr.111153.110 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 757LZ UT WOS:000290088000007 PM 21471403 ER PT J AU Mensa, L Crespo, G Gastinger, MJ Kabat, J Perez-del-Pulgar, S Miquel, R Emerson, SU Purcell, RH Forns, X AF Mensa, Laura Crespo, Gonzalo Gastinger, Matthew J. Kabat, Juraj Perez-del-Pulgar, Sofia Miquel, Rosa Emerson, Suzanne U. Purcell, Robert H. Forns, Xavier TI Hepatitis C Virus Receptors Claudin-1 and Occludin After Liver Transplantation and Influence on Early Viral Kinetics SO HEPATOLOGY LA English DT Article ID B TYPE-I; SCAVENGER RECEPTOR; CELL ENTRY; EXPRESSION; CD81; INFECTION; PROTEIN; STEP; LOCALIZATION; RECURRENCE AB Liver transplantation (LT) is a unique model to study hepatitis C virus (HCV) entry into hepatocytes. Recent in vitro studies suggest significant changes in the expression of the HCV receptors claudin-1 and occludin after HCV infection. Our aims were: (1) to characterize claudin-1 and occludin expression in grafts from LT recipients and (2) to explore their potential influence on early HCV kinetics and their changes after HCV infection. We included 42 HCV-infected LT recipients and 19 uninfected controls. Claudin-1 and occludin were detected in paraffin-embedded liver biopsies obtained during reperfusion and 3 and 12 months after LT. HCV receptors were characterized by confocal immunofluorescence microscopy; quantification and colocalization studies were performed with dedicated software. Claudin-1 and occludin expression were restricted to the apical pole of hepatocytes. There was a significant correlation between the amount of scavenger receptor B1 at the time of reperfusion and the HCV-RNA decay during the first 24 hours following LT (r = 5 0.55, P = 5 0.007). Similarly, there was a significant correlation between the levels of claudin and occludin and the slope of HCV-RNA increase during the first week after LT (r = 5 0.63, P = 5 0.005). Occludin and claudin-1 levels increased significantly 12 months after LT (P = 5 0.03 and P = 5 0.007, respectively). The expression pattern of both proteins, however, remained unchanged, colocalizing strongly (60%-94%) at the apical membrane of hepatocytes. Conclusions. HCV receptor levels at the time of LT seem to modulate early HCV kinetics. Hepatitis C recurrence after LT was associated with increased levels of claudin-1 and occludin in the hepatocyte cell membrane, although it did not alter their localization within the tight junctions. (HEPATOLOGY 2011;53:1436-1445) C1 [Forns, Xavier] IDIBAPS, Hosp Clin, Inst Malalties Digest, Liver Unit, Barcelona 08036, Spain. [Miquel, Rosa] IDIBAPS, Hosp Clin, Dept Pathol, Barcelona 08036, Spain. [Gastinger, Matthew J.; Kabat, Juraj] NIAID, Biol Imaging Facil, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Emerson, Suzanne U.; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Forns, X (reprint author), IDIBAPS, Hosp Clin, Inst Malalties Digest, Liver Unit, Villarroel 170, Barcelona 08036, Spain. EM xforns@clinic.ub.es OI Perez-del-Pulgar, Sofia/0000-0002-9890-300X FU Instituto de Salud Carlos III [PI080239]; European Regional Development Fund (ERDF); Spanish Association for the Study of Liver Diseases (AEEH, Beca Hernandez-Guio); Hospital Clinic (Ajut a la Recerca Josep Font); Fundacion BBVA; Instituto de Salud Carlos III (PFIS); National Institute of Allergy and Infectious Diseases, National Institutes of Health FX X. Forns received support in part by a grant from Instituto de Salud Carlos III (PI080239), cofunded by the European Regional Development Fund (ERDF), and by the Spanish Association for the Study of Liver Diseases (AEEH, Beca Hernandez-Guio). G. Crespo was supported by Hospital Clinic (Ajut a la Recerca Josep Font) and Fundacion BBVA. L. Mensa was supported by Instituto de Salud Carlos III (PFIS). This study was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 31 TC 22 Z9 22 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2011 VL 53 IS 5 BP 1436 EP 1445 DI 10.1002/hep.24110 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 755SG UT WOS:000289956100005 PM 21294144 ER PT J AU Rodrigue, JR Balistreri, W Haber, B Jonas, MM Mohan, P Molleston, JP Murray, KF Narkewicz, MR Rosenthal, P Smith, LJ Lobritto, SJ Schwarz, KB Robuck, PR Barton, B Gonzalez-Peralta, RP AF Rodrigue, James R. Balistreri, William Haber, Barbara Jonas, Maureen M. Mohan, Parvathi Molleston, Jean P. Murray, Karen F. Narkewicz, Michael R. Rosenthal, Philip Smith, Lesley J. Lobritto, Steven J. Schwarz, Kathleen B. Robuck, Patricia R. Barton, Bruce Gonzalez-Peralta, Regino P. TI Peginterferon With or Without Ribavirin Has Minimal Effect on Quality of Life, Behavioral/Emotional, and Cognitive Outcomes in Children SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; VIRUS-INFECTION; PLUS RIBAVIRIN; INDUCED DEPRESSION; INTERFERON; IMPACT; ALPHA; COMBINATION; IMPAIRMENT; THERAPY AB The aim of this study was to prospectively assess the quality of life (QOL), behavioral/emotional functioning, and cognitive status of children undergoing treatment for hepatitis C virus (HCV) infection. In all, 114 children (5 to 18 years old) enrolled in a multisite randomized clinical trial (Peds-C) to evaluate peginterferon alpha 2a (PEG 2a) with ribavirin (RV) or with placebo (PL) completed several standardized measures prior to treatment and at 24 weeks, 48 weeks, 6 months following treatment, and at two annual follow-up visits. After 24 weeks of treatment, mean physical QOL scores declined significantly for both groups from baseline to 24 weeks of treatment (F = 5.8, P = 0.004), although scores remained in the average range. There were no significant time or group effects for behavioral/emotional or cognitive functioning. Three children (5%) in the PEG 2a + RV group and no children in the PEG 2a 1 PL group had a clinically significant increase in depression symptoms. For those children who received 48 weeks of treatment, there were no significant time or group effects on any of the outcome measures (P > 0.05). A majority of children in both the PEG 2a 1 RV and PEG 2a 1 PL groups experienced no clinically significant change in physical QOL, behavioral adjustment, depression, or cognitive functioning during or after treatment. Conclusion: Overall QOL and psychosocial functioning are not deleteriously impacted by PEG 2a 1 RV or PL treatment of children with HCV. (HEPATOLOGY 2011;53:1468-1475) C1 [Rodrigue, James R.] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. [Balistreri, William] Childrens Hosp Med Ctr, Cincinnati, OH USA. [Haber, Barbara] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Jonas, Maureen M.] Childrens Hosp Boston, Boston, MA USA. [Mohan, Parvathi] George Washington Univ, Washington, DC USA. [Molleston, Jean P.] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. [Murray, Karen F.] Childrens Hosp & Reg Med Ctr, Seattle, WA USA. [Narkewicz, Michael R.] Univ Colorado Denver Sch Med, Childrens Hosp, Aurora, CO USA. [Rosenthal, Philip] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Smith, Lesley J.; Lobritto, Steven J.] Columbia Univ, New York, NY USA. [Schwarz, Kathleen B.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Robuck, Patricia R.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA. [Barton, Bruce] Univ Massachusetts, Sch Med, Worcester, MA USA. [Gonzalez-Peralta, Regino P.] Univ Florida, Coll Med, Gainesville, FL USA. [Gonzalez-Peralta, Regino P.] Shands Childrens Hosp, Gainesville, FL USA. RP Rodrigue, JR (reprint author), Beth Israel Deaconess Med Ctr, Transplant Inst, 110 Francis St,7th Floor, Boston, MA 02215 USA. EM jrrodrig@bidmc.harvard.edu OI Barton, Bruce/0000-0001-7878-8895 FU National Institute of Diabetes and Digestive and Kidney Diseases [1UO1DK067767]; Office of Orphan Products Development, Food and Drug Administration FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases, grant number 1UO1DK067767, with additional support from the Office of Orphan Products Development, Food and Drug Administration. Contents herein are the authors' sole responsibility and do not necessarily represent official NIH views. Additional support is provided by Hoffman-La Roche for the study medications, data coordinating center, and central laboratory costs. NR 29 TC 11 Z9 11 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2011 VL 53 IS 5 BP 1468 EP 1475 DI 10.1002/hep.24248 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 755SG UT WOS:000289956100008 PM 21351116 ER PT J AU Calado, RT Brudno, J Mehta, P Kovacs, JJ Wu, C Zago, MA Chanock, SJ Boyer, TD Young, NS AF Calado, Rodrigo T. Brudno, Jennifer Mehta, Paulomi Kovacs, Joseph J. Wu, Colin Zago, Marco A. Chanock, Stephen J. Boyer, Thomas D. Young, Neal S. TI Constitutional Telomerase Mutations Are Genetic Risk Factors for Cirrhosis SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; IDIOPATHIC PULMONARY-FIBROSIS; GENOME-WIDE ASSOCIATION; BONE-MARROW FAILURE; DYSKERATOSIS-CONGENITA; APLASTIC-ANEMIA; LIVER FIBROSIS; REVERSE-TRANSCRIPTASE; SUSCEPTIBILITY LOCI; DISEASE AB Some patients with liver disease progress to cirrhosis, but the risk factors for cirrhosis development are unknown. Dyskeratosis congenita, an inherited bone marrow failure syndrome associated with mucocutaneous anomalies, pulmonary fibrosis, and cirrhosis, is caused by germline mutations of genes in the telomerase complex. We examined whether telomerase mutations also occurred in sporadic cirrhosis. In all, 134 patients with cirrhosis of common etiologies treated at the Liver Research Institute, University of Arizona, between May 2008 and July 2009, and 528 healthy subjects were screened for variation in the TERT and TERC genes by direct sequencing; an additional 1,472 controls were examined for the most common genetic variation observed in patients. Telomere length of leukocytes was measured by quantitative polymerase chain reaction. Functional effects of genetic changes were assessed by transfection of mutation-containing vectors into telomerase-deficient cell lines, and telomerase activity was measured in cell lysates. Nine of the 134 patients with cirrhosis (7%) carried a missense variant in TERT, resulting in a cumulative carrier frequency significantly higher than in controls (P = 0.0009). One patient was homozygous and eight were heterozygous. The allele frequency for the most common missense TERT variant was significantly higher in patients with cirrhosis (2.6%) than in 2,000 controls (0.7%; P = 0.0011). One additional patient carried a TERC mutation. The mean telomere length of leukocytes in patients with cirrhosis, including six mutant cases, was shorter than in age-matched controls (P = 0.0004). Conclusion: Most TERT gene variants reduced telomerase enzymatic activity in vitro. Loss-of-function telomerase gene variants associated with short telomeres are risk factors for sporadic cirrhosis. (HEPATOLOGY 2011;53:1600-1607) C1 [Calado, Rodrigo T.; Brudno, Jennifer; Mehta, Paulomi; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Brudno, Jennifer; Mehta, Paulomi] NIH, Clin Res Training Program, Bethesda, MD 20892 USA. [Kovacs, Joseph J.; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Wu, Colin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Zago, Marco A.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Div Hematol, BR-14049 Ribeirao Preto, SP, Brazil. [Boyer, Thomas D.] Univ Arizona, Sch Med, Liver Res Inst, Tucson, AZ USA. RP Calado, RT (reprint author), 10 Ctr Dr,Bldg 10-CRC,Rm 3E-5140, Bethesda, MD 20892 USA. EM calador@nhlbi.nih.gov RI Calado, Rodrigo/G-2619-2011; Celulas tronco, Inct/I-1921-2013; ZAGO, MARCO/E-9442-2017 FU National Institutes of Health (NIH); Pfizer FX Supported by the National Institutes of Health (NIH) Intramural Research Program. J.B. and P.M.'s research years were made possible through the Clinical Research Training Program (CRTP), a public-private partnership supported jointly by the NIH and Pfizer (grant to the Foundation for NIH from Pfizer). NR 51 TC 58 Z9 58 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2011 VL 53 IS 5 BP 1600 EP 1607 DI 10.1002/hep.24173 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 755SG UT WOS:000289956100021 PM 21520173 ER PT J AU Sha, J Endsley, JJ Kirtley, ML Foltz, SM Huante, MB Erova, TE Kozlova, EV Popov, VL Yeager, LA Zudina, IV Motin, VL Peterson, JW DeBord, KL Chopra, AK AF Sha, Jian Endsley, Janice J. Kirtley, Michelle L. Foltz, Sheri M. Huante, Matthew B. Erova, Tatiana E. Kozlova, Elena V. Popov, Vsevolod L. Yeager, Linsey A. Zudina, Irina V. Motin, Vladimir L. Peterson, Johnny W. DeBord, Kristin L. Chopra, Ashok K. TI Characterization of an F1 Deletion Mutant of Yersinia pestis CO92, Pathogenic Role of F1 Antigen in Bubonic and Pneumonic Plague, and Evaluation of Sensitivity and Specificity of F1 Antigen Capture-Based Dipsticks SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MURINE PERITONEAL-MACROPHAGES; POLYMERASE-CHAIN-REACTION; LINKED-IMMUNOSORBENT-ASSAY; PASTEURELLA-PESTIS; IN-VITRO; PRESUMPTIVE IDENTIFICATION; HUMAN INTERLEUKIN-1-BETA; DIAGNOSTIC-TEST; VIRULENCE; FRACTION-1 AB We evaluated two commercial F1 antigen capture-based immunochromatographic dipsticks, Yersinia Pestis (F1) Smart II and Plague BioThreat Alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected with Yersinia pestis CO92. To assess the specificities of these dipsticks, an in-frame F1-deficient mutant of CO92 (Delta caf) was generated by homologous recombination and used as a negative control. Based on genetic, antigenic/immunologic, and electron microscopic analyses, the Delta caf mutant was devoid of a capsule. The growth rate of the Delta caf mutant generally was similar to that of the wild-type (WT) bacterium at both 26 and 37 degrees C, although the mutant's growth dropped slightly during the late phase at 37 degrees C. The Delta caf mutant was as virulent as WT CO92 in the pneumonic plague mouse model; however, it was attenuated in developing bubonic plague. Both dipsticks had similar sensitivities, requiring a minimum of 0.5 mu g/ml of purified F1 antigen or 1 x 10(5) to 5 x 10(5) CFU/ml of WT CO92 for positive results, while the blood samples were negative for up to 1 x 10(8) CFU/ml of the Delta caf mutant. Our studies demonstrated the diagnostic potential of two plague dipsticks in detecting capsular-positive strains of Y. pestis in bubonic and pneumonic plague. C1 [Sha, Jian; Endsley, Janice J.; Kirtley, Michelle L.; Foltz, Sheri M.; Huante, Matthew B.; Erova, Tatiana E.; Kozlova, Elena V.; Yeager, Linsey A.; Zudina, Irina V.; Motin, Vladimir L.; Peterson, Johnny W.; Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Endsley, Janice J.; Yeager, Linsey A.; Motin, Vladimir L.; Peterson, Johnny W.; Chopra, Ashok K.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Endsley, Janice J.; Popov, Vsevolod L.; Motin, Vladimir L.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Endsley, Janice J.; Motin, Vladimir L.; Peterson, Johnny W.; Chopra, Ashok K.] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX 77555 USA. [DeBord, Kristin L.] NIH, Bethesda, MD 20892 USA. RP Chopra, AK (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA. EM achopra@utmb.edu RI Motin, Vladimir/O-1535-2013 FU NIH/NIAID [N01 AI40097, AI064389] FX This work was supported by NIH/NIAID contract N01 AI40097 and grant AI064389. Our studies were conducted in the Galveston National Laboratory, and we acknowledge the UC7 grant awarded by NIH/NIAID. NR 56 TC 18 Z9 18 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2011 VL 49 IS 5 BP 1708 EP 1715 DI 10.1128/JCM.00064-11 PG 8 WC Microbiology SC Microbiology GA 755OA UT WOS:000289941000002 PM 21367990 ER PT J AU Saleeb, PG Drake, SK Murray, PR Zelazny, AM AF Saleeb, Paul G. Drake, Steven K. Murray, Patrick R. Zelazny, Adrian M. TI Identification of Mycobacteria in Solid-Culture Media by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INTACT MYCOBACTERIA; MUCOGENICUM; ABSCESSUS; BACTERIA; YEAST; DNA AB Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been introduced into the clinical microbiology laboratory as a rapid and accurate method to identify bacteria and yeasts. In this paper we describe our work on the use of MALDI-TOF MS for the identification of mycobacterial isolates. We developed a protocol for protein extraction from mycobacteria and utilized it to construct a database containing 42 clinically relevant type and reference strains of mycobacteria. The database was used to identify 104 clinical isolates of mycobacteria. All members of the Mycobacterium tuberculosis complex were identified accurately at the complex level but could not be separated at the species level. All other organisms were identified at the species level, with the exception of one strain of M. kansasii (accurately identified but with a low spectral score) and three pairs of closely related strains: M. abscessus and M. massiliense, M. mucogenicum and M. phocaicum, and M. chimaera and M. intracellulare. These pairs of organisms can currently be identified only by multilocus gene sequence analysis. We conclude that MALDI-TOF MS analysis can be incorporated into the work flow of the microbiology laboratory for rapid and accurate identification of most strains of mycobacteria isolated from solid growth media. C1 [Murray, Patrick R.; Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Saleeb, Paul G.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Drake, Steven K.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Zelazny, AM (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM azelazny@mail.nih.gov FU Laboratory of Clinical Infectious Diseases; NIH Clinical Center, Department of Laboratory Medicine FX This research was supported by the Laboratory of Clinical Infectious Diseases and the Intramural Research Program of the NIH Clinical Center, Department of Laboratory Medicine. NR 22 TC 101 Z9 104 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2011 VL 49 IS 5 BP 1790 EP 1794 DI 10.1128/JCM.02135-10 PG 5 WC Microbiology SC Microbiology GA 755OA UT WOS:000289941000014 PM 21411597 ER PT J AU Korn, EL Freidlin, B AF Korn, Edward L. Freidlin, Boris TI On the Usefulness of Outcome-Adaptive Randomization Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CLINICAL-TRIALS C1 [Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NR 5 TC 9 Z9 9 U1 1 U2 3 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 MAY 1 PY 2011 VL 29 IS 13 BP E393 EP E393 DI 10.1200/JCO.2011.34.6726 PG 1 WC Oncology SC Oncology GA 757MN UT WOS:000290090400014 ER PT J AU Wu, V Barbash, IM Ratnayaka, K Saikus, CE Sonmez, M Kocaturk, O Lederman, RJ Faranesh, AZ AF Wu, Vincent Barbash, Israel M. Ratnayaka, Kanishka Saikus, Christina E. Sonmez, Merdim Kocaturk, Ozgur Lederman, Robert J. Faranesh, Anthony Z. TI Adaptive Noise Cancellation to Suppress Electrocardiography Artifacts During Real-Time Interventional MRI SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE electrocardiogram; MRI; gradient artifacts; adaptive filter ID MAGNETIC-FIELD GRADIENTS; STEADY-STATE; ACQUISITION; RESTORATION; SYSTEM AB Purpose: To develop a system for artifact suppression in electrocardiogram (ECG) recordings obtained during interventional real-time magnetic resonance imaging (MRI). Materials and Methods: We characterized ECG artifacts due to radiofrequency pulses and gradient switching during MRI in terms of frequency content. A combination of analog filters and digital least mean squares adaptive filters were used to filter the ECG during in vivo experiments and the results were compared with those obtained with simple low-pass filtering. The system performance was evaluated in terms of artifact suppression and ability to identify arrhythmias during real-time MRI. Results: Analog filters were able to suppress artifacts from high-frequency radiofrequency pulses and gradient switching. The remaining pulse artifacts caused by intermittent preparation sequences or spoiler gradients required adaptive filtering because their bandwidth overlapped with that of the ECG. Using analog and adaptive filtering, a mean improvement of 38 dB (n = 11, peak QRS signal to pulse artifact noise) was achieved. This filtering system was successful in removing pulse artifacts that obscured arrhythmias such as premature ventricular complexes and complete atrioventricular block. Conclusion: We have developed an online ECG monitoring system employing digital adaptive filters that enables the identification of cardiac arrhythmias during real-time MRI-guided interventions. C1 [Wu, Vincent; Barbash, Israel M.; Ratnayaka, Kanishka; Saikus, Christina E.; Sonmez, Merdim; Kocaturk, Ozgur; Lederman, Robert J.; Faranesh, Anthony Z.] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Faranesh, AZ (reprint author), NHLBI, Div Intramural Res, NIH, Bldg 10,Room 2C713,10 Ctr Dr,MSC-1538, Bethesda, MD 20892 USA. EM faranesh@nih.gov RI Kocaturk, Ozgur/A-1419-2016; OI lederman, robert/0000-0003-1202-6673 FU National Institutes of Health (NIH) [1ZIA HL005062] FX Contract grant sponsor: National Institutes of Health (NIH): Contract grant number: 1ZIA HL005062. NR 32 TC 9 Z9 9 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2011 VL 33 IS 5 BP 1184 EP 1193 DI 10.1002/jmri.22530 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 756GM UT WOS:000289999700023 PM 21509878 ER PT J AU Beydoun, MA Shroff, MR Chen, XL Beydoun, HA Wang, YF Zonderman, AB AF Beydoun, May A. Shroff, Monal R. Chen, Xiaoli Beydoun, Hind A. Wang, Youfa Zonderman, Alan B. TI Serum Antioxidant Status Is Associated with Metabolic Syndrome among US Adults in Recent National Surveys SO JOURNAL OF NUTRITION LA English DT Article ID NUTRITION EXAMINATION SURVEY; BETA-CAROTENE SUPPLEMENTATION; DEPENDENT DIABETES-MELLITUS; ARTERY RISK DEVELOPMENT; FASTING PLASMA-GLUCOSE; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; UNITED-STATES; CARDIOVASCULAR-DISEASE; VITAMIN-D AB Potential antiinflammatory and antioxidant effects were recently ascribed to naturally occurring micronutrients. The extent and magnitudes of their differential effects on the metabolic syndrome (MetS) are still unknown. We examined the association between serum antioxidant status and MetS. NHANES 2001-2006 cross-sectional data among adults aged 20-85 y were analyzed (n= 3008-9099). MetS was defined with the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and also by elevated homeostatic model assessment insulin resistance (HOMA-IR), C-reactive protein (CRP) and hyperuricemia. Serum antioxidants included retinol, retinyl esters, carotenoids [alpha-carotene, beta-carotene (cis+trans), beta-cryptoxanthin, lutein+zeaxanthin, total lycopene], vitamin E, and vitamin C. MetS (NCEP ATP Ill) prevalence in U.S. adults was 32.0% among men and 29.5% among women. Adults with MetS had consistently lower serum carotenoid concentrations compared with those without MetS, even after controlling for total cholesterol and TG among other potential confounders. Vitamin E had no significant relationship with MetS in the full multiple logistic regression model, whereas retinol+retinyl esters were inversely related to MetS among men only. The latter were also inversely related to elevated CRP and positively associated with hyperuricemia. Vitamin C exhibited a similar pattern to serum caratenoids with an inverse linear association with MetS (binary), HOMA-IR, and hyperuricemia. Future intervention studies of dietary and lifestyle change must be conducted to assess the utility of modifying serum antioxidant concentrat ons, especially carotenoids, given their suboptimal levels among U.S. adults with MetS, for the prevention of type 2 diabetes and various cardiovascular endpoints. J. Nutr. 141 903-913, 2011. C1 [Beydoun, May A.; Zonderman, Alan B.] NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Shroff, Monal R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Chen, Xiaoli; Wang, Youfa] Johns Hopkins Med Inst, Ctr Human Nutr, Dept Int Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. RP Beydoun, MA (reprint author), NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. EM baydounm@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging; NIH/NIDDK [R01DK81335-01A1] FX Supported ay the National Institute on Aging, Intramural Research Program. X.C. and Y.W.'s related work was supported by the NIH/NIDDK (R01DK81335-01A1). 2 Author disclosures: M. A. Beydoun, M. R. Shroff, X. Chen, H. A. Beydoun, Y. Wang, and A. B. Zonderman, no conflicts of interest. NR 76 TC 49 Z9 51 U1 2 U2 14 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 MAY PY 2011 VL 141 IS 5 BP 903 EP 913 DI 10.3945/jn.110.136580 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 754CF UT WOS:000289828800021 PM 21451127 ER EF