FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gao, B Jeong, WI Tian, ZG AF Gao, Bin Jeong, Won-Il Tian, Zhigang TI Liver: An organ with predominant innate immunity SO HEPATOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; PATTERN-RECOGNITION RECEPTORS; ACTIVATED STELLATE CELLS; C VIRUS-INFECTION; HEPATITIS-C; T-CELLS; NK CELLS; ACETAMINOPHEN HEPATOTOXICITY; TUMOR-CELLS; FATTY LIVER AB Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and gamma delta T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells. In addition, the liver also plays an important role in controlling systemic innate immunity through the biosynthesis of numerous soluble pathogen-recognition receptors and complement components. Conclusion: The liver is an organ with predominant innate immunity, playing an important role not only in host defenses against invading microorganisms and tumor transformation but also in liver injury and repair. Recent evidence suggests that innate immunity is also involved in the pathogenesis of liver fibrosis, providing novel therapeutic targets to treat such a liver disorder. C1 [Gao, Bin; Jeong, Won-Il] NIAAA, NIH, Sect Liver Biol, Lab Physiol Studies, Bethesda, MD 20892 USA. [Tian, Zhigang] Univ Sci & Technol China, Sch Life Sci, Inst Immunol, Hefei 230026, Peoples R China. RP Gao, B (reprint author), NIAAA, NIH, Sect Liver Biol, Lab Physiol Studies, 5625 Fishers Lane,Room 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI JEONG, WON IL/B-6615-2011; Tian, Zhigang/J-3512-2013 NR 56 TC 290 Z9 317 U1 8 U2 43 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2008 VL 47 IS 2 BP 729 EP 736 DI 10.1002/hep.22034 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 259KZ UT WOS:000252939500042 PM 18167066 ER PT J AU Martin, B Golden, E Keselman, A Stone, M Mattson, MP Egan, JM Maudsley, S AF Martin, Bronwen Golden, Erin Keselman, Alex Stone, Matthew Mattson, Mark P. Egan, Josephine M. Maudsley, Stuart TI Therapeutic perspectives for the treatment of Huntington's disease: Treating the whole body SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE Huntingtin; therapeutic; aggregation; polyglutamine; expansion ID TRANSGENIC MOUSE MODEL; HYPERKINETIC MOVEMENT-DISORDERS; 1ST CASE-REPORT; KNOCK-IN MICE; MUTANT HUNTINGTIN; STRIATAL NEURONS; CREATINE SUPPLEMENTATION; INTRANUCLEAR INCLUSIONS; SELECTIVE VULNERABILITY; WIDESPREAD EXPRESSION AB Huntington's disease (HD) is a tremendously debilitating disorder that strikes relatively young individuals and progresses rapidly over the next ten to fifteen years inducing a loss of cognitive and motor skills and eventually death occurs. The primary locus of the disorder is a polyglutamine expansion of the protein product of the huntingtin (htt) gene. The htt protein appears to be a scaffolding protein that orchestrates the complex assembly of multiple intracellular proteins involved in multiple processes, including vesicular movement and cell metabolism. The htt protein is ubiquitously expressed in human tissues but the predominance of the interest in the pathology lies in its effects on the central nervous system (CNS). Most of the current therapeutics for HD thus have been targeted at preventing neuronal damage in the CNS, however, a considerable body of evidence has been accumulating to suggest that the maintenance of a healthy nervous system is tightly linked with peripheral physiological health. Therefore treatment of both the peripheral and central pathophysiologies of HD could form the basis of a more effective HD therapeutic strategy. C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, NIH, Gerontol Res Ctr, 5600 Nathan Schock Dr, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000318-01] NR 127 TC 31 Z9 34 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD FEB PY 2008 VL 23 IS 2 BP 237 EP 250 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 238PI UT WOS:000251459300013 PM 17999380 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Hormesis and disease resistance: activation of cellular stress response pathways SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE exercise; sirtuins; phytochemicals; chaperone; antioxidant ID NF-KAPPA-B; ELEMENT-BINDING PROTEIN; CARBON-MONOXIDE; NITRIC-OXIDE; NEURODEGENERATIVE DISORDERS; NEURONAL PLASTICITY; CALORIE RESTRICTION; LIFE-SPAN; CAENORHABDITIS-ELEGANS; HIPPOCAMPAL-NEURONS AB The survival of all organisms depends upon their ability to overcome stressful conditions, an ability that involves adaptive changes in cells and molecules. Findings from studies of animal models and human populations suggest that hormesis (beneficial effects of low levels of stress) is an effective means of protecting against many different diseases including diabetes, cardiovascular disease, cancers and neuro degenerative disorders. Such stress resistance mechanisms can be bolstered by diverse environmental factors including exercise, dietary restriction, cognitive stimulation and exposure to low levels of toxins. Some commonly used vitamins and dietary supplements may also induce beneficial stress responses. Several interrelated cellular signaling molecules are involved in the process of hormesis. Examples include the gases oxygen, carbon monoxide and nitric oxide, the neurotransmitter glutamate, the calcium ion and tumor necrosis factor. In each case low levels of these signaling molecules are beneficial and protect against disease, whereas high levels can cause the dysfunction and/or death of cells. The cellular and molecular mechanisms of hormesis are being revealed and include activation of growth factor signaling pathways, protein chaperones, cell survival genes and enzymes called sirtuins. Knowledge of hormesis mechanisms is leading to novel approaches for preventing and treating a range of human diseases. C1 [Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 66 TC 44 Z9 45 U1 1 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0960-3271 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD FEB PY 2008 VL 27 IS 2 BP 155 EP 162 DI 10.1177/0960327107083417 PG 8 WC Toxicology SC Toxicology GA 310KG UT WOS:000256527200015 PM 18480142 ER PT J AU Johanneson, B McDonnell, SK Karyadi, DM Hebbring, SJ Wang, L Deutsch, K McIntosh, L Kwon, EM Suuriniemi, M Stanford, JL Schaid, DJ Ostrander, EA Thibodeau, SN AF Johanneson, Bo McDonnell, Shannon K. Karyadi, Danielle M. Hebbring, Scott J. Wang, Liang Deutsch, Kerry McIntosh, Laura Kwon, Erika M. Suuriniemi, Miia Stanford, Janet L. Schaid, Daniel J. Ostrander, Elaine A. Thibodeau, Stephen N. TI Fine mapping of familial prostate cancer families narrows the interval for a susceptibility locus on chromosome 22q12.3 to 1.36 Mb SO HUMAN GENETICS LA English DT Article ID AUTOSOMAL-DOMINANT INHERITANCE; SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME LINKAGE SCREEN; SEGREGATION ANALYSIS; INTERNATIONAL CONSORTIUM; GENES; RISK; SCAN; GENETICS; PEDIGREES AB Genetic studies suggest that hereditary prostate cancer is a genetically heterogeneous disease with multiple contributing loci. Studies of high-risk prostate cancer families selected for aggressive disease, analysis of large multigenerational families, and a meta-analysis from the International Consortium for Prostate Cancer Genetics (ICPCG), all highlight chromosome 22q12.3 as a susceptibility locus with strong statistical significance. Recently, two publications have narrowed the 22q12.3 locus to a 2.18 Mb interval using 54 high-risk families from the ICPCG collaboration, as defined by three recombination events on either side of the locus. In this paper, we present the results from fine mapping studies at 22q12.3 using both haplotype and recombination data from 42 high-risk families contributed from the Mayo Clinic and the Prostate Cancer Genetic Research Study (PROGRESS) mapping studies. No clear consensus interval is present when all families are used. However, in the subset of 14 families with >= 5 affected men per family, a 2.53-Mb shared consensus segment that overlaps with the previously published interval is identified. Combining these results with data from the earlier ICPCG study reduces the three-recombination interval at 22q12.3 to approximately 1.36 Mb. C1 [Hebbring, Scott J.; Wang, Liang; Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Johanneson, Bo; Karyadi, Danielle M.; Kwon, Erika M.; Suuriniemi, Miia; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [McDonnell, Shannon K.; Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Deutsch, Kerry] Inst Syst Biol, Seattle, WA USA. [McIntosh, Laura; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. RP Thibodeau, SN (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 1st St SW,920 Hilton Bldg, Rochester, MN 55905 USA. EM sthibodeau@mayo.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU NCI NIH HHS [R01 CA72818, R01 CA089600, R01 CA78836, R01 CA80122] NR 47 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 2008 VL 123 IS 1 BP 65 EP 75 DI 10.1007/s00439-007-0451-y PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 257KY UT WOS:000252799200006 PM 18066601 ER PT J AU Simon-Sanchez, J Scholz, S Matarin, MDM Fung, HC Hernandez, D Gibbs, JR Britton, A Hardy, J Singleton, A AF Simon-Sanchez, Javier Scholz, Sonia Matarin, Maria Del Mar Fung, Hon-Chung Hernandez, Dena Gibbs, J. Raphael Britton, Angela Hardy, John Singleton, Andrew TI Genomewide SNP assay reveals mutations underlying Parkinson disease SO HUMAN MUTATION LA English DT Article DE PARK2; genomewide; Parkinson; duplication; deletion; SNP; CNV ID EARLY-ONSET PARKINSONISM; COPY NUMBER; GENE; POLYMORPHISM; PINK1; DNA AB Technologies that allow genotyping of more than 100,000 polymorphisms in a single assay enable the execution of genomewide SNP (GWSNP) association studies to identify common genetic variants underlying traits. Less appreciated is the ability of GWSNP assays to map and directly identify rare mutations that cause disease. Here we show the use of this approach in identifying rare structural mutations involved in disease using a large cohort of Parkinson disease (PD) patients and neurologically normal controls by examination of genotype data and copy number metrics. This approach revealed a patient with homozygous mutation at the PARK2 locus. In addition, two heterozygous deletion mutations and five heterozygous duplication mutations within PARK2 were identified in PD subjects and controls. All mutations were confirmed by independent gene dosage experiments. These data demonstrate the utility of this approach in the direct detection of mutations that underlie disease. C1 [Simon-Sanchez, Javier; Scholz, Sonia; Matarin, Maria Del Mar; Hernandez, Dena; Britton, Angela; Singleton, Andrew] NIH, Mol Genet Unit, Bethesda, MD 20892 USA. [Simon-Sanchez, Javier] Inst Biomed Valencia, Consejo Super Invest Sientificas, Dept Genom & Proteom, Mol Genet Unit, Valencia, Spain. [Scholz, Sonia; Fung, Hon-Chung; Gibbs, J. Raphael; Hardy, John] Reta Lila Weston Inst, Inst Neurol, Dept Mol Neurosci, Dept Neurodegenerat Dis, London, England. [Fung, Hon-Chung] NIH, NIA, Neurogenet Lab, Bethesda, MD USA. [Gibbs, J. Raphael] NIH, Computat Biol Core, Bethesda, MD USA. RP Singleton, A (reprint author), NIH, Mol Genet Unit, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Gibbs, J. Raphael/A-3984-2010; Hardy, John/C-2451-2009; Matarin, Mar/F-1771-2016; OI Matarin, Mar/0000-0002-4717-5735; Scholz, Sonja/0000-0002-6623-0429 FU Intramural NIH HHS; Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 19 TC 31 Z9 31 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD FEB PY 2008 VL 29 IS 2 BP 315 EP 322 DI 10.1002/humu.20626 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 260TJ UT WOS:000253033000015 PM 17994548 ER PT J AU Wang, H Sammel, MD Tromp, G Gotsch, F HaIder, I Shriver, MD Romero, R Strauss, JE AF Wang, Hongyan Sammel, Mary D. Tromp, Gerard Gotsch, Francesca HaIder, Indrani Shriver, Mark D. Romero, Roberto Strauss, Jerome E., III TI A 12-bp deletion in the 5'-flanking region of the SERPINH1 gene affects promoter activity and protects against preterm premature rupture of membranes in African Americans SO HUMAN MUTATION LA English DT Article DE SERPINH1; preterm premature rupture of membranes; promoter function; African-Americans AB We identified a novel 12-bp deletion NT_033927.7: g.5495364_5495375del in the 5'-flanking region of the SERPINH1 gene that increases promoter activity. The 12-bp deletion is in linkage disequilibrium with the minor "T" allele of the -656 C/T SNP (NT_033927.7(SERPINHI):g.5495402C>T) that reduces promoter activity in amnion fibroblast cells and is associated with a significantly increased risk of preterm birth as a result of premature rupture of membranes. In a case-control study, fetal carriage of the 12-bp deletion was found to protect against PPROM, apparently overcoming the influence of the SERPINHI -656 "T" allele. These studies define a new haplotype in the SERPINHI gene that modifies risk of an adverse obstetrical outcome. (C) 2007 Wiley-Liss, Inc. C1 [Wang, Hongyan] Fudan Univ, Sch Life Sci, Inst Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Sammel, Mary D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Tromp, Gerard; Gotsch, Francesca; Romero, Roberto] Hutzel Hosp, NICHD, Perinatol Res Branch, Detroit, MI 48201 USA. [HaIder, Indrani] Univ Pittsburgh, Behav Physiol Lab, Cardiovasc Behav Med Program, Pittsburgh, PA 15260 USA. [Shriver, Mark D.] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. [Strauss, Jerome E., III] Virginia Commonwealth Univ, Dept Obstet & Gynecol, Richmond, VA 23298 USA. RP Strauss, JE (reprint author), MCV Campus, Sanger Hall, 1st Fl, Rm 1-071, 1101 E, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu RI Tromp, Gerard/B-2677-2017 OI Tromp, Gerard/0000-0002-7761-0806 FU NIMHD NIH HHS [P60 MD002256] NR 0 TC 13 Z9 13 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD FEB PY 2008 VL 29 IS 2 BP 332 EP 332 DI 10.1002/humu.9522 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 260TJ UT WOS:000253033000021 PM 18205191 ER PT J AU Nepomnaschy, PA Weinberg, CR Wilcox, AJ Baird, DD AF Nepomnaschy, P. A. Weinberg, C. R. Wilcox, A. J. Baird, D. D. TI Urinary hCG patterns during the week following implantation SO HUMAN REPRODUCTION LA English DT Article DE pregnancy; hCG; spontaneous abortion; twins; fetal sex ID HUMAN CHORIONIC-GONADOTROPIN; IN-VITRO FERTILIZATION; EARLY-PREGNANCY; PROGESTERONE METABOLITES; ECTOPIC PREGNANCY; EMBRYOS INVITRO; DOUBLING TIME; DOWN-SYNDROME; BETA-SUBUNIT; SERUM AB Background: Human chorionic gonadotrophin (hCG) is used to monitor pregnancy status. Yet the pattern of hCG excretion in the first week following implantation has not been adequately described. Therefore the aim of this study was to describe the average profile of hCG and its variability during the 7 days following estimated implantation in a population of naturally conceived pregnancies. Methods: We measured daily hCG concentrations in first-morning urine for 142 clinical pregnancies from women with no known fertility problems. Mixed-effects regression models were used to estimate the hCG trajectory and its variability in relation to pregnancy outcomes. Results: hCG rose 3-fold between the day of detection and the next day (95% CI = 2.7-3.4). The relative rate of rise decreased thereafter, reaching 1.6-fold (95% CI = 1.5-1.8) between days 6 and 7. HCG levels followed a log-quadratic trajectory, and the patterns of rise were unrelated to number of fetuses, risk of spontaneous abortion or sex of the baby. Later implantations (after 10 luteal days) produced slower rates of increase. Conclusions: Although mean hCG follows a log-quadratic trajectory during the first week of detectability, there is high variability across pregnancies. Later implantation may reflect characteristics of the uterus or conceptus that slow hCG production. C1 [Nepomnaschy, P. A.; Wilcox, A. J.; Baird, D. D.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Weinberg, C. R.] NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Nepomnaschy, PA (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05,Rm 309,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM pablo_nepomnaschy@sfu.com RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS [, ZIA ES049003-23] NR 62 TC 14 Z9 16 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 2008 VL 23 IS 2 BP 271 EP 277 DI 10.1093/humrep/dem397 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 253UY UT WOS:000252544300006 PM 18083748 ER PT J AU Tapia, A Gangi, LM Zegers-Hochschild, F Balmaceda, J Pommer, R Trejo, L Pacheco, IM Salvatierra, AM Henriquez, S Quezada, M Vargas, M Rios, M Munroe, DJ Croxatto, HB Velasquez, L AF Tapia, Alejandro Gangi, Lisa M. Zegers-Hochschild, Fernando Balmaceda, Jose Pommer, Ricardo Trejo, Leon Margarita Pacheco, Isabel Maria Salvatierra, Ana Henriquez, Soledad Quezada, Marisol Vargas, Macarena Rios, Miguel Munroe, David J. Croxatto, Horacio B. Velasquez, Luis TI Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy SO HUMAN REPRODUCTION LA English DT Article DE endometrium; implantation; microarrays; oocyte donation; uterine receptivity ID PROTEINASE-INHIBITOR 9; GRANZYME-B INHIBITOR; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; MONOAMINE-OXIDASE; MENSTRUAL-CYCLE; BLASTOCYST IMPLANTATION; CYTOTOXIC LYMPHOCYTES; CHEMOKINE RECEPTORS; MEDIATED APOPTOSIS AB Background: Gene expression profiling of normal receptive endometrium has been characterized, but intrinsic defects in endometrial gene expression associated with implantation failure have not been reported. Methods: Women who had previously participated as recipients in oocyte donation cycles and repeatedly exhibited implantation failure (Group A, study group) or had at least one successful cycle (Group B, control group) and spontaneously fertile women (Group C, normal fertility group) were recruited. All were treated with exogenous estradiol and progesterone to induce an endometrial cycle, and an endometrial biopsy was taken on the seventh day of progesterone administration. RNA from each sample was analysed by cDNA microarrays to identify differentially expressed genes between groups. Results: 63 transcripts were differentially expressed (>= 2-fold) between Groups A and B, of which 16 were subjected to real time RT-PCR. Eleven of these were significantly decreased in Group A with regard to Groups B and C. Among the dysregulated genes were MMP-7, CXCR4, PAEP and C4BPA. Conclusions: Repeated implantation failure in some oocyte recipients is associated with an intrinsic defect in the expression of multiple genes in their endometrium. Significantly decreased levels of several transcripts in endometria without manifest abnormalities is demonstrated for the first time and shown to be associated with implantation failure. C1 [Tapia, Alejandro; Henriquez, Soledad; Quezada, Marisol; Vargas, Macarena; Rios, Miguel; Croxatto, Horacio B.; Velasquez, Luis] Univ Santiago Chile, Dept Biol, Santiago, Chile. [Gangi, Lisa M.; Munroe, David J.] Sci Applicat Int Corp, Lab Mol Technol, NCI, Frederick, MD USA. [Zegers-Hochschild, Fernando; Balmaceda, Jose; Margarita Pacheco, Isabel] Clin Las Condes, Reprod Med Unit, Santiago, Chile. [Pommer, Ricardo; Trejo, Leon] Univ Chile, Inst Invest Maternoinfantil, Santiago, Chile. [Maria Salvatierra, Ana; Croxatto, Horacio B.] Inst Chileno Med Reprod ICMER, Santiago, Chile. [Croxatto, Horacio B.] Millenium Inst Fundamental & Appl Biol, Santiago, Chile. RP Tapia, A (reprint author), Prince Henrys Inst Med Res, 246 Clayton Rd,POB 5152, Clayton, Vic 3168, Australia. EM atapiap@gmail.com FU NCI NIH HHS [N01-CO-12400] NR 83 TC 35 Z9 36 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 2008 VL 23 IS 2 BP 340 EP 351 DI 10.1093/humrep/dem319 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 253UY UT WOS:000252544300017 PM 18077318 ER PT J AU Farasat, SM Morrell, CH Scuteri, A Ting, CT Yin, FCP Spurgeon, HA Chen, CH Lakatta, EG Najjar, SS AF Farasat, S. Morteza Morrell, Christopher H. Scuteri, Angelo Ting, Chih-Tai Yin, Frank C. P. Spurgeon, Harold A. Chen, Chen-Huan Lakatta, Edward G. Najjar, Samer S. TI Pulse pressure is inversely related to aortic root diameter implications for the pathogenesis of systolic hypertension SO HYPERTENSION LA English DT Article DE aorta; sinus of Valsalva; pulse pressure; systolic hypertension ID CARDIOVASCULAR-DISEASE ENTERPRISES; ARTERIAL STIFFNESS; PULSATILE HEMODYNAMICS; MAJOR SHAREHOLDERS; FLOW RELATIONSHIP; HEART-FAILURE; AGE; DETERMINANTS; DILATATION; DIMENSIONS AB Hypertension accelerates the age-associated increase in aortic root diameter ( AoD), likely because of chronically elevated distending pressures. However, the pulsatile component of blood pressure may have a different relationship with AoD. We sought to assess the relationship between AoD and pulse pressure ( PP) while accounting for left ventricular and central arterial structural and functional properties, which are known to influence PP. The study population was composed of 1256 individuals, aged 30 to 79 years ( 48% women and 48% hypertensive), none of whom were on antihypertensive medications. Blood pressure was measured in the sitting position with conventional sphygmomanometry. PP was calculated as the difference between systolic and diastolic blood pressures. AoD was measured at end diastole at the level of the sinuses of Valsalva with echocardiography. The relationship between AoD and PP was evaluated with multiple regression analyses. PP was 50 +/- 14 mm Hg in men and 54 +/- 18 mm Hg in women, and AoD was 31.9 +/- 3.5 mm in men and 28.9 +/- 3.5 mm in women. After adjusting for age, age(2), height, weight, and mean arterial pressure, AoD was independently and inversely associated with PP in both sexes. After further adjustments for central arterial stiffness and wall thickness, reflected waves, and left ventricular geometry, AoD remained inversely associated with PP in both men ( coefficient =-0.48; P=0.0003; model R-2=0.51) and women ( coefficient =-0.40; P=0.01; model R-2=0.61). Thus, AoD is inversely associated with PP, suggesting that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility. C1 [Farasat, S. Morteza; Morrell, Christopher H.; Spurgeon, Harold A.; Lakatta, Edward G.; Najjar, Samer S.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21225 USA. [Farasat, S. Morteza] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA. [Morrell, Christopher H.] Loyola Coll, Dept Math Sci, Baltimore, MD 21210 USA. [Scuteri, Angelo] Ist Nazl Ricovero E Cura Anziani, Unita Operat, Rome, Italy. [Ting, Chih-Tai] Natl Yang Ming Univ, Taipei 112, Taiwan. [Ting, Chih-Tai; Chen, Chen-Huan] Inst Clin Med & Cardiovasc Res Inst, Taipei 112, Taiwan. [Farasat, S. Morteza; Morrell, Christopher H.; Scuteri, Angelo; Ting, Chih-Tai; Yin, Frank C. P.; Spurgeon, Harold A.; Chen, Chen-Huan; Lakatta, Edward G.; Najjar, Samer S.] Taichung Vet Gen Hosp, Taichung, Taiwan. [Yin, Frank C. P.] Washington Univ, Dept Biomed Engn, St Louis, MO USA. RP Najjar, SS (reprint author), NIA, Cardiovasc Sci Lab, NIH, 3001 S Hanover St, Baltimore, MD 21225 USA. EM najjarsa@mail.nih.gov FU Intramural NIH HHS; NIA NIH HHS [N01-AG-1-2118] NR 37 TC 33 Z9 34 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB 1 PY 2008 VL 51 IS 2 BP 196 EP 202 DI 10.1161/HYPERTENSIONAHA.107.099515 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254QK UT WOS:000252602200009 PM 18158348 ER PT J AU Faustini, MC Neptune, RR Crawford, RH Stanhope, SJ AF Faustini, Mario C. Neptune, Richard R. Crawford, Richard H. Stanhope, Steven J. TI Manufacture of passive dynamic ankle-foot orthoses using selective laser sintering SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE design automation; freeform fabrication; orthotics ID STIFFNESS CONTROL; OIL DAMPER; PROSTHESES; TRIMLINE; AMPUTEES; WALKING; DESIGN; GAIT AB Ankle-foot orthosis (AFO) designs vary in size, shape, and functional characteristics depending on the desired clinical application. Passive Dynamic (PD) Response ankle-foot orthoses (PD-AFOs) constitute a design that seeks to improve walking ability for persons with various neuromuscular disorders by passively (like a spring) providing variable levels of support during the stance phase of gait. Current PD-AFO manufacturing technology is either labor intensive or not well suited for the detailed refinement of PD-AFO bending stiffness characteristics. The primary objective of this study was to explore the feasibility of using a rapid freeform prototyping technique, selective laser sintering (SLS), as a PD-AFO manufacturing process. Feasibility was determined by replicating the shape and functional characteristics of a carbon fiber AFO (CF-AFO). The study showed that a SLS-based framework is ideally suited for this application. A second objective was to determine the optimal SLS material for PD-AFOs to store and release elastic energy; considering minimizing energy dissipation through internal friction is a desired material characteristic. This study compared the mechanical damping of the CF-AFO to PD-AFOs manufactured by SLS using three different materials. Mechanical damping evaluation ranked the materials as Rilsan (TM) D80 (best), followed by DuraForm (TM) PA and DuraForm (TM) GF. In addition, Rilsan (TM) D80 was the only SLS material able to withstand large deformations. C1 [Faustini, Mario C.; Neptune, Richard R.; Crawford, Richard H.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Stanhope, Steven J.] NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Faustini, MC (reprint author), Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. EM faustini@alumni.utexas.net; rnep-tune@mail.utexas.edu; rhc@mail.utexas.edu; steven_stanhope@nih.gov NR 24 TC 40 Z9 44 U1 8 U2 32 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 2008 VL 55 IS 2 BP 784 EP 790 DI 10.1109/TBME.2007.912638 PN 1 PG 7 WC Engineering, Biomedical SC Engineering GA 254XV UT WOS:000252622200044 PM 18270017 ER PT J AU Thakor, NV He, JP AF Thakor, Nitish V. He, Jiping TI Special theme on neural and myoelectric control of prostheses SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Editorial Material C1 [Thakor, Nitish V.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Thakor, Nitish V.] IEEE Transact Neural & Rehabil Engn, New York, NY USA. [Thakor, Nitish V.] NIH Training Grant Neuroengn, Bethesda, MD USA. [He, Jiping] Arizona State Univ, Ira A Fulton Sch Engn, Tempe, AZ 85287 USA. RP Thakor, NV (reprint author), Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. RI Thakor, Nitish/G-9110-2015 OI Thakor, Nitish/0000-0002-9981-9395 NR 0 TC 1 Z9 1 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD FEB PY 2008 VL 16 IS 1 BP 1 EP 2 DI 10.1109/TNSRE.2008.918238 PG 2 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 266NH UT WOS:000253442400001 ER PT J AU Egen, JG Rothfuchs, AG Feng, CG Winter, N Sher, A Germain, RN AF Egen, Jackson G. Rothfuchs, Antonio Gigliotti Feng, Carl G. Winter, Nathalie Sher, Alan Germain, Ronald N. TI Macrophage and T cell dynamics during the development and disintegration of mycobacterial Granulomas SO IMMUNITY LA English DT Article ID BACILLUS-CALMETTE-GUERIN; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; IN-VIVO; BOVIS BCG; LYMPH-NODE; IMMUNE-RESPONSE; AUTOIMMUNE ENCEPHALOMYELITIS; BACTERIAL-INFECTIONS; DENDRITIC CELLS AB Granulomas play a key role in host protection againstmycobacterial pathogens, with their breakdown contributing to exacerbated disease. To better understand the initiation and maintenance of these structures, we employed both high-resolution multiplex static imaging and intravital multiphoton microscopy of Mycobacterium bovis BCG-induced liver granulomas. We found that Kupffer cells directly capture blood-borne bacteria and subsequently nucleate formation of a nascent granuloma by recruiting both uninfected liver-resident macrophages and blood-derived monocytes. Within the mature granuloma, these myeloid cell populations formed a relatively immobile cellular matrix that interacted with a highly dynamic effector T cell population. The efficient recruitment of these T cells was highly dependent on TNF-alpha-derived signals, which also maintained the granuloma structure through preferential effects on uninfected macrophage populations. By characterizing the migration of both innate and adaptive immune cells throughout the process of granuloma development, these studies provide a new perspective on the cellular events involved in mycobacterial containment and escape. C1 [Egen, Jackson G.; Germain, Ronald N.] NIAID, Natl Inst Hlth, Immunol Lab, Lymphocyte Biol Sect, Bethesda, MD 20892 USA. [Rothfuchs, Antonio Gigliotti; Feng, Carl G.; Sher, Alan] NIAID, Natl Inst Hlth, Parasit Dis Lab, Immunobiol Sect, Bethesda, MD 20892 USA. [Winter, Nathalie] Inst Pasteur, Mycobacterial Genet Unit, F-7724 Paris, France. RP Germain, RN (reprint author), NIAID, Natl Inst Hlth, Immunol Lab, Lymphocyte Biol Sect, Bethesda, MD 20892 USA. EM asher@niaid.nih.gov; rgermain@nih.gov RI Rothfuchs, Antonio/F-5981-2013; OI Rothfuchs, Antonio/0000-0001-6001-7240; Egen, Jackson/0000-0003-2053-0837 FU Intramural NIH HHS [Z01 AI000545-19] NR 50 TC 199 Z9 204 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 2008 VL 28 IS 2 BP 271 EP 284 DI 10.1016/i.immuni.2007.12.010 PG 14 WC Immunology SC Immunology GA 264GH UT WOS:000253275000016 PM 18261937 ER PT J AU Tolar, P Sohn, HW Pierce, SK AF Tolar, Pavel Sohn, Hae Won Pierce, Susan K. TI Viewing the antigen-induced initiation of B-cell activation in living cells SO IMMUNOLOGICAL REVIEWS LA English DT Review DE B cells; live cell imaging; signal transduction; membrane microdomains ID RESONANCE ENERGY-TRANSFER; IG-ALPHA/IG-BETA; LIPID RAFTS; SYNAPSE FORMATION; RECEPTOR; TRAFFICKING; PROTEINS; DISSOCIATION; ORGANIZATION; LYMPHOCYTES AB The binding of antigen to the B-cell receptor (BCR) induces BCR clustering and signaling cascades that lead to the activation of a variety of genes associated with B-cell activation. Over the last several years, our understanding of the molecular details of the BCR signaling pathways have been considerably advanced; what remains only poorly understood are the molecular events that initiate BCR clustering and how clustering leads to activation. Here, we review our progress using live cell imaging technologies to view the earliest events that follow the B cell's binding of antigen. We provide a model for BCR clustering and B-cell activation that involves an intrinsic tendency of the BCR to cluster and does not require direct crosslinking of the BCR by multivalent antigens. We suggest that local membrane topology and lipid composition play key roles in BCR clustering and initiation of signaling. We believe that our model for B-cell activation, in which receptor interactions with monovalent antigens on membrane surfaces lead to receptor clustering, may be highly relevant to the mechanisms by which other immune receptors cluster including the T-cell receptor in response to monovalent peptide-major histocompatibility complex complexes. C1 [Tolar, Pavel; Sohn, Hae Won; Pierce, Susan K.] NIAID, NIH, Immunogenet Lab, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, NIH, Immunogenet Lab, Twinbrook 2 12441 Parklawn Dr,Room 213, Rockville, MD 20852 USA. EM spierce@nih.gov NR 32 TC 36 Z9 38 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2008 VL 221 BP 64 EP 76 DI 10.1111/j.1600-065X.2008.00583.x PG 13 WC Immunology SC Immunology GA 260WZ UT WOS:000253042400005 PM 18275475 ER PT J AU Germain, RN Bajenoff, M Castellino, F Chieppa, M Egen, JG Huang, AYC Ishii, M Koo, LY Qi, H AF Germain, Ronald N. Bajenoff, Marc Castellino, Flora Chieppa, Marcello Egen, Jackson G. Huang, Alex Y. C. Ishii, Masaru Koo, Lily Y. Qi, Hai TI Making friends in out-of-the-way places: how cells of the immune system get together and how they conduct their business as revealed by intravital imaging SO IMMUNOLOGICAL REVIEWS LA English DT Review DE B cells; T cells; dendritic cells; stromal cells; in vivo imaging; cell trafficking ID CD8(+) T-CELLS; HIGH-ENDOTHELIAL VENULES; LYMPH-NODE CORTEX; BEARING DENDRITIC CELLS; TOLL-LIKE RECEPTOR-5; CLASS-II TRANSPORT; IN-VIVO; B-CELLS; 2-PHOTON MICROSCOPY; ANTIBODY-RESPONSES AB A central characteristic of the immune system is the constantly changing location of most of its constituent cells. Lymphoid and myeloid cells circulate in the blood, and subsets of these cells enter, move, and interact within, then leave organized lymphoid tissues. When inflammation is present, various hematopoietic cells also exit the vasculature and migrate within non-lymphoid tissues, where they carry out effector functions that support host defense or result in autoimmune pathology. Effective innate and adaptive immune responses involve not only the action of these individual cells but also productive communication among them, often requiring direct membrane contact between rare antigen-specific or antigen-bearing cells. Here, we describe our ongoing studies using two-photon intravital microscopy to probe the in situ behavior of the cells of the immune system and their interactions with non-hematopoietic stromal elements. We emphasize the importance of non-random cell migration within lymphoid tissues and detail newly established mechanisms of traffic control that operate at multiple organizational scales to facilitate critical cell contacts. We also describe how the methods we have developed for imaging within lymphoid sites are being applied to other tissues and organs, revealing dynamic details of host-pathogen interactions previously inaccessible to direct observation. C1 [Germain, Ronald N.; Bajenoff, Marc; Chieppa, Marcello; Egen, Jackson G.; Ishii, Masaru; Qi, Hai] NIAID, NIH,DHHS, Immunol Lab, Lymphocyte Biol Sect,Program Syst Immunol &Infect, Bethesda, MD 20892 USA. [Castellino, Flora] Novartis Vaccines, Siena, Italy. [Bajenoff, Marc] Univ Nice, CNRS, IPMC,U 344, INSERM, Valbonne, France. [Huang, Alex Y. C.] Case Western Reserve Univ, Sch Med, Rainbow Babies & Childrens Hosp, Div Pediat Hematol, Cleveland, OH 44106 USA. [Koo, Lily Y.] NIAID, NIH, Biol Imaging Facil, Res Tech Branch, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, NIH,DHHS, Immunol Lab, Lymphocyte Biol Sect,Program Syst Immunol &Infect, Bldg 10 Rm 11N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. EM rgermain@nih.gov RI Qi, Hai/A-3955-2009; Ishii, Masaru/D-2361-2009; Chieppa, Marcello/K-4846-2012; OI Egen, Jackson/0000-0003-2053-0837; Huang, Alex/0000-0002-5701-4521 FU Intramural NIH HHS NR 111 TC 59 Z9 59 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2008 VL 221 BP 163 EP 181 DI 10.1111/j.1600-065X.2008.00591.x PG 19 WC Immunology SC Immunology GA 260WZ UT WOS:000253042400011 PM 18275481 ER PT J AU Ellison, DW Clark, TR Sturdevant, DE Virtaneva, M Porcella, SF Hackstadt, T AF Ellison, Damon W. Clark, Tina R. Sturdevant, Daniel E. Virtaneva, Mmmo Porcella, Stephen F. Hackstadt, Ted TI Genomic comparison of virulent Rickettsia rickettsii Sheila Smith and avirulent Rickettsia rickettsii Iowa SO INFECTION AND IMMUNITY LA English DT Article ID SPOTTED-FEVER GROUP; MONOCLONAL-ANTIBODIES; ARP2/3 COMPLEX; SEQUENCE; PROTEIN; STRAINS; CONORII; CELLS; MECHANISMS; PROWAZEKII AB Rickettsia rickettsii is an obligate intracellular pathogen that is the causative agent of Rocky Mountain spotted fever. To identify genes involved in the virulence of R. rickettsii, the genome of an avirulent strain, R. rickettsii Iowa, was sequenced and compared to the genome of the virulent strain R. rickettsii Sheila Smith. R. rickettsii Iowa is avirulent in a guinea pig model of infection and displays altered plaque morphology with decreased lysis of infected host cells. Comparison of the two genomes revealed that R. rickettsii Iowa and R. rickettsii Sheila Smith share a high degree of sequence identity. A whole-genome alignment comparing R. rickettsii Iowa to R. rickettsii Sheila Smith revealed a total of 143 deletions; for the two strains. A subsequent single-nucleotide polymorphism (SNP) analysis comparing Iowa to Sheila Smith revealed 492 SNPs for the two genomes. One of the deletions in R. rickettsii Iowa truncates rompA, encoding a major surface antigen (rickettsial outer membrane protein A [rOmpA]) and member of the autotransporter family, 660 bp from the start of translation. Immunoblotting and immunofluorescence confirmed the absence of rOmpA from R. rickettsii Iowa. In addition, R. rickettsii Iowa is defective in the processing of rOmpB, an autotransporter and also a major surface antigen of spotted fever group rickettsiae. Disruption of rompA and the defect in rOmpB processing are most likely factors that contribute to the avirulence of R. rickettsii Iowa. Genomic differences between the two strains do not significantly alter gene expression as analysis of microarrays revealed only four differences in gene expression between R. rickettsii Iowa and R. rickettsii strain R. Although R. rickettsii Iowa does not cause apparent disease, infection of guinea pigs with this strain confers protection against subsequent challenge with the virulent strain R. rickettsii Sheila Smith. C1 [Ellison, Damon W.; Clark, Tina R.; Hackstadt, Ted] NIH, NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. [Sturdevant, Daniel E.; Virtaneva, Mmmo; Porcella, Stephen F.] NIH, NIAID, Rocky Mt Labs, Res Technol Sect,Genome Unit, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIH, NIAID, Rocky Mt Labs, Intracellular Parasites Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM thackstadt@niaid.nih.gov FU Intramural NIH HHS NR 34 TC 62 Z9 277 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2008 VL 76 IS 2 BP 542 EP 550 DI 10.1128/IAI.00952-07 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 259ZE UT WOS:000252978600010 PM 18025092 ER PT J AU Bartra, SS Styer, KL O'Bryant, DM Nilles, ML Hinnebusch, BJ Aballay, A Plano, GV AF Bartra, Sara Schesser Styer, Katie L. O'Bryant, Deanna M. Nilles, Matthew L. Hinnebusch, B. Joseph Aballay, Alejandro Plano, Gregory V. TI Resistance of Yersinia pestis to complement-dependent killing is mediated by the Ail outer membrane protein SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; CAENORHABDITIS-ELEGANS; VIRULENCE PLASMID; SERUM RESISTANCE; GENOME SEQUENCE; ENTEROCOLITICA; PLAGUE; LIPOPOLYSACCHARIDE; INVASION AB Yersinia pestis, the causative agent of plague, must survive in blood in order to cause disease and to be transmitted from host to host by fleas. Members of the Ail/Lom family of outer membrane proteins provide protection from complement-dependent killing for a number of pathogenic bacteria. The Y. pestis KIM genome is predicted to encode four Ail/Lom family proteins. Y. pestis mutants specifically deficient in expression of each of these proteins were constructed using lambda Red-mediated recombination. The Ail outer membrane protein was essential for Y. pestis to resist complement-mediated killing at 26 and 37 degrees C. Ail was expressed at high levels at both 26 and 37 degrees C, but not at 6 degrees C. Expression of Ail in Escherichia coli provided protection from the bactericidal activity of complement. High-level expression of the three other Y. pestis Ail/Lom family proteins (the y1682, y2034, and y2446 proteins) provided no protection against complement-mediated bacterial killing. A Y. pestis ail deletion mutant was rapidly killed by sera obtained from all mammals tested except mouse serum. The role of Ail in infection of mice, Caenorhabditis elegans, and fleas was investigated. C1 [Bartra, Sara Schesser; Plano, Gregory V.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. [Styer, Katie L.; Aballay, Alejandro] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [O'Bryant, Deanna M.; Nilles, Matthew L.] Univ N Dakota, Sch Med & Hlth Sci, Dept Microbiol & Immunol, Grand Forks, ND 58202 USA. [Hinnebusch, B. Joseph] NIAID, NIH, Rocky Mt Labs, Lab Zoon Pathogens, Hamilton, MT 59840 USA. [Bartra, Sara Schesser] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden. RP Plano, GV (reprint author), Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. EM gplano@med.miami.edu OI Nilles, Matthew/0000-0002-2235-8682 FU NIAID NIH HHS [R01 AI051520-05, R21 AI074820, R21 AI074820-02, R01 AI051520, R01 AI039575]; NIGMS NIH HHS [R01 GM070977] NR 44 TC 84 Z9 90 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2008 VL 76 IS 2 BP 612 EP 622 DI 10.1128/IAI.01125-07 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 259ZE UT WOS:000252978600017 PM 18025094 ER PT J AU Leaf, WA Simons-Morton, BG Hartos, JL Northrup, VS AF Leaf, W. A. Simons-Morton, B. G. Hartos, J. L. Northrup, V. Shabanova TI Driving miles estimates by teen drivers: how accurate are they? SO INJURY PREVENTION LA English DT Article ID PROGRAM; CRASHES AB The objective of this study was to determine how accurately teens can report miles driven. Participants were 118 drivers in Connecticut (average age 17 1/2 years; average time licensed 11 months). Half had their own vehicle; half shared family vehicles. Teens completed a telephone survey about their preceding week's driving, then completed a daily trip log for the next week and a second survey about the details of the logged week's trips and miles. Teens with their own vehicle provided odometer readings. Summing the miles for every trip was generally consistent with estimates from odometer readings. Overall mileage estimates were 20-30% lower than those from trip-by-trip listings, except for very low estimates for the first week by teens who shared vehicles. The results indicate that single overall estimates frequently understate total miles driven, but that prompted reviews of each trip can provide valid and detailed information. C1 [Leaf, W. A.; Northrup, V. Shabanova] Preusser Res Grp Inc, Trumbull, CT 06611 USA. [Simons-Morton, B. G.] NICHHD, Bethesda, MD 20892 USA. [Hartos, J. L.] Univ N Carolina, Charlotte, NC 28223 USA. RP Leaf, WA (reprint author), Preusser Res Grp Inc, 7100 Main St, Trumbull, CT 06611 USA. EM wleaf@preussergroup.com OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z01 HD001707-09]; NICHD NIH HHS [1-HD-8-3285, F32 HD008318, Y3-HD8318] NR 12 TC 7 Z9 7 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD FEB PY 2008 VL 14 IS 1 BP 59 EP 61 DI 10.1136/ip.2007.016097 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 258LB UT WOS:000252868300013 PM 18245317 ER PT J AU Assumpcao, TCF Francischetti, IMB Andersen, JF Schwarz, A Santana, JM Ribeiro, JMC AF Assumpcao, Teresa C. F. Francischetti, Ivo M. B. Andersen, John F. Schwarz, Alexandra Santana, Jaime M. Ribeiro, Jose M. C. TI An insight into the sialome of the blood-sucking bug Triatoma infestans, a vector of Chagas' disease SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE hematophagy; saliva; transcriptome; salivary gland; Triatoma infestans; feeding; sialome ID ADULT FEMALE MOSQUITO; MULTIPLE SEQUENCE ALIGNMENT; ESCHERICHIA-COLI HEMOLYSIN; SALIVARY-GLAND TRANSCRIPTS; LEECH HIRUDO-MEDICINALIS; LIPOCALIN PROTEIN FAMILY; ODORANT-BINDING PROTEINS; BLOOD-FEEDING INSECT; KAZAL-TYPE INHIBITOR; MAST-CELL TRYPTASE AB Triatoma infestans is a hemiptera, vector of Chagas' disease that feeds exclusively on vertebrate blood in all life stages. Hematophagous insects' salivary glands (SG) produce potent pharmacological compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. To obtain a further insight into the salivary biochemical and pharmacological complexity of this insect, a cDNA library from its SG was randomly sequenced. Also, salivary proteins were submitted to two-dimensional gel (2D-gel) electrophoresis followed by MS analysis. We present the analysis of a set of 1534 (SG) cDNA sequences, 645 of which coded for proteins of a putative secretory nature. Most salivary proteins described as lipocalins matched peptide sequences obtained from proteomic results. Published by Elsevier Ltd. C1 [Francischetti, Ivo M. B.; Andersen, John F.; Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Assumpcao, Teresa C. F.; Santana, Jaime M.] Univ Brasilia, Lab Host Parasite Interface, BR-70910900 Brasilia, DF, Brazil. [Schwarz, Alexandra] Ruhr Univ Bochum, Dept Special Zool, D-44780 Bochum, Germany. RP Ribeiro, JMC (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM tecris@unb.br; ifrancischetti@niaid.nih.gov; jandersen@niaid.nih.gov; a.schwarz@abdn.ac.uk; jsantana@unb.br; jribeiro@niaid.nih.gov RI Santana, Jaime/H-5319-2013; OI Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [Z01 AI000810-11] NR 126 TC 69 Z9 71 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD FEB PY 2008 VL 38 IS 2 BP 213 EP 232 DI 10.1016/j.ibmb.2007.11.001 PG 20 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 268FJ UT WOS:000253564200009 PM 18207082 ER PT J AU Ioannidis, JPA Boffetta, P Little, J O'Brien, TR Uitterlinden, AG Vineis, P Balding, DJ Chokkalingam, A Dolan, SM Flanders, WD Higgins, JPT McCarthy, MI McDermott, DH Page, GP Rebbeck, TR Seminara, D Khoury, MJ AF Ioannidis, John P.A. Boffetta, Paolo Little, Julian O'Brien, Thomas R. Uitterlinden, Andre G. Vineis, Paolo Balding, David J. Chokkalingam, Anand Dolan, Siobhan M. Flanders, W. Dana Higgins, Julian P. T. McCarthy, Mark I. McDermott, David H. Page, Grier P. Rebbeck, Timothy R. Seminara, Daniela Khoury, Muin J. TI Assessment of cumulative evidence on genetic associations: interim guidelines SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE epidemiologic methods; genetics; genomics; causality; evidence ID GENOME-WIDE ASSOCIATION; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; COMPLEX DISEASES; BREAST-CANCER; ENVIRONMENT INTERACTIONS; NO ASSOCIATION; LARGE-SCALE; EPIDEMIOLOGY; SUSCEPTIBILITY AB Established guidelines for causal inference in epidemiological studies may be inappropriate for genetic associations. A consensus process was used to develop guidance criteria for assessing cumulative epidemiologic evidence in genetic associations. A proposed semi-quantitative index assigns three levels for the amount of evidence, extent of replication, and protection from bias, and also generates a composite assessment of strong, moderate or weak epidemiological credibility. In addition, we discuss how additional input and guidance can be derived from biological data. Future empirical research and consensus development are needed to develop an integrated model for combining epidemiological and biological evidence in the rapidly evolving field of investigation of genetic factors. C1 [Ioannidis, John P.A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Ioannina 45110, Greece. [Ioannidis, John P.A.] Fdn Res Technol, Biomed Res Inst, Ioannina 45110, Greece. [Ioannidis, John P.A.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Boffetta, Paolo] Int Agcy Res Canc, F-69008 Lyon, France. [Little, Julian] Univ Ottawa, Dept Epidemiol & Commun Med, Ottawa, ON K1H 8M5, Canada. [O'Brien, Thomas R.] NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Dept Epidemiol & Biostat, NL-3000 CA Rotterdam, Netherlands. [Vineis, Paolo; Balding, David J.] Imperial Coll, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Chokkalingam, Anand] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94707 USA. [Dolan, Siobhan M.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10461 USA. [Flanders, W. Dana] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30327 USA. [Higgins, Julian P. T.] Univ Forvie Site, Inst Publ Hlth, MRC Biostat Unit, Cambridge CB2 0SR, England. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet, Oxford OX3 7LJ, England. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BM, England. [McDermott, David H.] NIH, Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bethesda, MD 20892 USA. [Page, Grier P.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Seminara, Daniela] NIH, Natl Canc Inst, Div Canc Control & Populat Sci, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA. RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Ioannina 45110, Greece. EM jioannid@cc.uoi.gr RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Balding, David/G-9898-2011; OI Higgins, Julian/0000-0002-8323-2514; Balding, David/0000-0002-1480-6115; McDermott, David/0000-0001-6978-0867 FU Intramural NIH HHS; Medical Research Council [MC_U105285807] NR 83 TC 314 Z9 314 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2008 VL 37 IS 1 BP 120 EP 132 DI 10.1093/ije/dym159 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 258YP UT WOS:000252906600022 PM 17898028 ER PT J AU Rastogi, T Devesa, S Mangtani, P Mathew, A Cooper, N Kao, R Sinha, R AF Rastogi, Tanuja Devesa, Susan Mangtani, Punam Mathew, Aleyamma Cooper, Nicola Kao, Roy Sinha, Rashmi TI Cancer incidence rates among South Asians in four geographic regions: India, singapore, UK and US SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cancer incidence; India; Asian Indians; South Asians; Singapore Indians ID UNITED-STATES; BREAST-CANCER; CERVICAL-CANCER; STOMACH-CANCER; ORAL-CANCER; EPIDEMIOLOGY; RISK; POPULATION; CALIFORNIA; SURVIVAL AB Background Data are limited regarding cancer incidence among Indians residing in different geographic regions around the world. Examining such rates may provide us with insights into future aetiological research possibilities as well as screening and prevention. Methods Incidence rates for all cancers combined and 19 specific cancers were obtained for India from Globocan 2002, for Indians in Singapore from Cancer Incidence in Five Continents (VIII), and from national data sources for South Asians (SA) in the United Kingdom (UK) and for Asian Indians/Pakistanis (AIP) and whites in the United States (US). Results We observed the lowest total cancer incidence rates in India (111 and 116 per 100 000 among males and females, respectively, age-standardized to the 1960 world population) and the highest among US whites (362 and 296). Cancer incidence rates among Indians residing outside of India were: intermediate Singapore (102 and 132), UK (173 and 179) and US ranges 152176 and 142164. A similar pattern was observed for cancers of the colorectum, prostate, thyroid, pancreas, lung, breast and non-Hodgkin lymphoma. In contrast, rates for cancers of the oral cavity, oesophagus, larynx and cervix uteri were highest in India. Although little geographic variability was apparent for stomach cancer incidence, Indians in Singapore had the highest rates compared with any other region. The UK SA and the US AIP appear with adopt the cancer patterns of their host country. Conclusions Variations in environmental exposures such as tobacco use, diet and infection, as well as better health care access and knowledge may explain some of the observed incidence differences. C1 [Sinha, Rashmi] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Rastogi, Tanuja; Devesa, Susan; Sinha, Rashmi] NIH, DHHS, NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Mangtani, Punam] London Sch Hyg & Trop Med, London, England. [Mathew, Aleyamma] Reg Canc Ctr, Trivandrum, Kerala, India. [Cooper, Nicola] Off Natl Stat, London, England. [Kao, Roy] Alfred I duPont Hosp Children, Wilmington, DE USA. RP Sinha, R (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 3046,EPS, Rockville, MD 20852 USA. EM sinhar@nih.gov RI Sinha, Rashmi/G-7446-2015; Osborne, Nicholas/N-4915-2015 OI Sinha, Rashmi/0000-0002-2466-7462; Osborne, Nicholas/0000-0002-6700-2284 FU Intramural NIH HHS; NCI NIH HHS [N01-PC-35136, N01-PC-35139, N02-PC-15105]; PHS HHS [U55/CCR921930-02] NR 48 TC 82 Z9 84 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2008 VL 37 IS 1 BP 147 EP 160 DI 10.1093/ije/dym219 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 258YP UT WOS:000252906600025 PM 18094016 ER PT J AU Johnson, BA Ait-Daoud, N Elkashef, AM Smith, EV Kahn, R Vocci, F Li, SH Bloch, DA AF Johnson, Bankole A. Ait-Daoud, Nassima Elkashef, Ahmed M. Smith, Edwina V. Kahn, Roberta Vocci, Francis Li, Shou-Hua Bloch, Daniel A. CA Methamphetamine Study Grp TI A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of methamphetamine dependence SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE clinical trial; cognitive behavioural therapy; humans; methamphetamine dependence; ondansetron ID 5-HT3 RECEPTOR ANTAGONIST; RISK-TAKING BEHAVIOR; HEALTHY-VOLUNTEERS; MESOLIMBIC SYSTEM; NUCLEUS-ACCUMBENS; CONTROLLED-TRIAL; AMPHETAMINE; ABUSE; DOPAMINE; NEUROBIOLOGY AB Methamphetamine dependence is an increasing public health problem in the United States. No efficacious medication for methamphetamine dependence has been developed. As ondansetron, a 5-HT(3) receptor antagonist and modulator of cortico-mesolimbic dopamine function, has been shown to reduce some of the rewarding effects of d-amphetamine in animal and human laboratory studies, we decided to test whether it would be superior to placebo at reducing methamphetamine use. In a preliminary, multi-site, randomized, double-blind, 8-wk controlled trial, 150 methamphetamine-dependent men and women received ondansetron (0.25 mg, 1 mg, or 4 mg b.i.d.) or placebo. Participants were assessed on several measures of methamphetamine use including urine methamphetamine level up to three times per week. As a psychosocial adjunct to the medication condition, cognitive behavioural therapy also was administered three times per week. Ondansetron was well tolerated and was less likely than placebo to be associated with serious adverse events. Nevertheless, none of the ondansetron doses was superior to placebo at decreasing any of the measures of methamphetamine use, withdrawal, craving, or clinical severity of methamphetamine dependence. Our preliminary results do not support the utility of ondansetron, at the doses tested, as a treatment for methamphetamine dependence. These findings should be viewed in light of the possibility that a less intensive cognitive behavioural therapy regimen might have yielded more positive results in this initial phase II trial exploring for the efficacy of ondansetron. C1 [Johnson, Bankole A.; Ait-Daoud, Nassima] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22908 USA. [Elkashef, Ahmed M.; Smith, Edwina V.; Kahn, Roberta; Vocci, Francis; Li, Shou-Hua] Natl Inst Drug Abuse, Natl Inst Hlth, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD USA. [Bloch, Daniel A.] Stanford Univ, Dept Hlth Res & Policy, Div Biostat, Stanford, CA 94305 USA. RP Johnson, BA (reprint author), Univ Virginia, Dept Psychiat & Neurobehav Sci, POB 800623, Charlottesville, VA 22908 USA. EM bankolejohnson@virginia.edu OI newton, thomas/0000-0002-3198-5901 FU NIDA NIH HHS [N01DA-0-8804, N01DA-9-8101] NR 45 TC 37 Z9 38 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD FEB PY 2008 VL 11 IS 1 BP 1 EP 14 DI 10.1017/S1461145707007778 PG 14 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 262SH UT WOS:000253167800001 PM 17470315 ER PT J AU Xia, GH Gajwani, P Muzina, DJ Kemp, DE Gao, K Ganocy, SJ Calabrese, JR AF Xia, Guohua Gajwani, Prashant Muzina, David J. Kemp, David E. Gao, Keming Ganocy, Stephen J. Calabrese, Joseph R. TI Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE bipolar disorders; depression; major depressive disorders; repetitive transcranial magnetic stimulation (rTMS); treatment-emergent mania/hypomania ID TREATMENT-RESISTANT DEPRESSION; PLACEBO-CONTROLLED TRIAL; VAGUS NERVE-STIMULATION; SHAM-CONTROLLED TRIAL; DOUBLE-BLIND; MAJOR DEPRESSION; MOOD STABILIZERS; I DEPRESSION; ELECTROCONVULSIVE-THERAPY; MAINTENANCE TREATMENT AB This review focused on the treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS) treatment of depression. English-language literature published from 1966-2006 and indexed in Medline was searched. Ten of 53 randomized controlled trials on rTMS treatment of depression specifically addressed TEM. The pooled TEM rate is 0.84% for the active treatment group and 0.73% for the sham group. The difference is not statistically significant. Along with case reports, a total of 13 cases of TEM associated with rTMS treatment of depression have been published. Most of these patients were diagnosed with bipolar disorder and the majority of patients experiencing TEM took medication concurrent with rTMS. The parameters of rTMS used in these cases were scattered over the spectrum of major parameters explored in previous studies. Most train durations and intervals were within the published safety guidelines of the field. Reducing the frequency of sessions from two per day to one per day might be associated with a lower likelihood of TEM recurrence. The severity of manic symptoms varied significantly, but all cases responded to treatment that included a decrease or discontinuation of antidepressant and/or rTMS treatment and/or use of anti-manic medication. Current data suggests that rTMS treatment carries a slight risk of TEM that is not statistically higher than that associated with sham treatment. More systematic studies are needed to better understand TEM associated with rTMS. Special precautions and measures should be adopted to prevent, monitor, and manage TEM in research and practice. C1 [Xia, Guohua; Gajwani, Prashant; Kemp, David E.; Gao, Keming; Ganocy, Stephen J.; Calabrese, Joseph R.] Case Western Reserve Univ, Dept Psychiat, NIMH, Ctr Bipolar Disorders, Cleveland, OH 44106 USA. [Muzina, David J.] Cleveland Clin, Dept Psychiat & Psychol, Cleveland, OH 44106 USA. RP Xia, GH (reprint author), Case Western Reserve Univ, Dept Psychiat, NIMH, Ctr Bipolar Disorders, 11400 Euclid Ave,Suite 200, Cleveland, OH 44106 USA. EM guohua.xia@case.edu NR 61 TC 52 Z9 54 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD FEB PY 2008 VL 11 IS 1 BP 119 EP 130 DI 10.1017/S1461145707007699 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 262SH UT WOS:000253167800012 PM 17335643 ER PT J AU Kim, MK Kim, YA Kim, YJ Soung, NK Yi, TH Kim, SY Yang, DC AF Kim, Myung Kyum Kim, Young-Ae Kim, Yu-Jin Soung, Nak-Kyun Yi, Tae-Hoo Kim, Se-Young Yang, Deok-Chun TI Parapedobacter soli sp nov., isolated from soil of a ginseng field SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SPHINGOBACTERIUM-SPIRITIVORUM; GEN. NOV.; COMB-NOV; BACTERIA AB Strain DCY14(T), a Gram-negative, non-spore-forming, rod-shaped, non-motile bacterium, was isolated from soil from a ginseng field in Korea and was characterized in order to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain DCY14T belongs to the family Sphingobacteriaceae, the highest degree of sequence similarity being found with respect to Parapeclobacter koreensis Jip14(T) (95.8%). Chemotaxonomic data revealed that strain DCY14(T) possesses MK-7 as the major menaquinone. The major fatty acids present were anteiso-C-13:0, iso-C-15:0, iSo-C-17:0 3-OH and summed feature 4(C-16:1 omega 7c/iso-C-15:0 2-OH). The results of physiological and biochemical tests clearly demonstrated that strain DCY14T represents a distinct species. On the basis of these data, DCY14(T) represents a novel species of the genus Parapedobacter, for which the name Parapedobacter soli sp. nov. is proposed. The type strain is DCY14(T) (=KCTC 12984(T)=LMG 24069(T)). C1 [Kim, Myung Kyum; Kim, Young-Ae; Kim, Yu-Jin; Yi, Tae-Hoo; Kim, Se-Young; Yang, Deok-Chun] Kyung Hee Univ, Korean Ginseng Ctr & Ginseng Genet Resource Bank, Yongin 449701, Kyunggi Do, South Korea. [Soung, Nak-Kyun] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yang, DC (reprint author), Kyung Hee Univ, Korean Ginseng Ctr & Ginseng Genet Resource Bank, 1 Seocheon Dong, Yongin 449701, Kyunggi Do, South Korea. EM dcyang@khu.ac.kr NR 19 TC 5 Z9 5 U1 1 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD FEB PY 2008 VL 58 BP 337 EP 340 DI 10.1099/ijs.065249-0 PN 2 PG 4 WC Microbiology SC Microbiology GA 268FF UT WOS:000253563800004 PM 18218927 ER PT J AU Park, MJ Kim, MK Kim, HB Im, WT Yi, TH Kim, SY Soung, NK Yang, DC AF Park, Min-Ju Kim, Myung Kyum Kim, Ho-Bin Im, Wan-Taek Yi, Tae-Hoo Kim, Se-Young Soung, Nak-Kyun Yang, Deok-Chun TI Microbacterium ginsengisoli sp nov., a beta-glucosidase-producing bacterium isolated from soil of a ginseng field SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; REDEFINED GENUS MICROBACTERIUM; DEOXYRIBONUCLEIC-ACID; SEQUENCE ALIGNMENT; ORLA-JENSEN; SYSTEMATICS AB Strain Gsoil 259(T), a beta-glucosidase-producing bacterium, was isolated from a soil sample from a ginseng field in the Republic of Korea and characterized in order to determine its taxonomic position. Cells were Gram-positive, heterotrophic, strictly aerobic, non-motile short rods. 16S rRNA gene sequence analysis revealed that strain Gsoil 259(T) belonged to the genus Microbacterium and was closely related to Microbacterium arborescens IFO 3750(T) (98.5%) and Microbacterium imperiale IFO 12610(T) (97.9%). However, it has low values for DNA-DNA relatedness with the above strains (20.7 and 17.5 %, respectively). Strain Gsoil 259(T) possessed chemotaxonomic markers that were consistent with classification in the genus Microbacterium, i.e. MK-11 and MK-12 were the major menaquinones and anteiso-C-17:0, anteiso-C-15:0 and iso-C-16:0 were the predominant cellular fatty acids. The DNA G + C content was 69.4 mol%. The cell-wall sugar was rhamnose and the diamino acid in the cell-wall pepticloglycan was ornithine. On the basis of data from this polyphasic study, strain Gsoil 259(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium ginsengisoli sp. nov. is proposed. The type strain is Gsoil 259(T) (=KCTC 19189(T) =DSM 18659(T)). C1 [Park, Min-Ju; Kim, Myung Kyum; Kim, Ho-Bin; Yi, Tae-Hoo; Kim, Se-Young; Yang, Deok-Chun] Kyung Hee Univ, Dept Oriental Med Mat, Yongin 446701, Gyeonggi Do, South Korea. [Park, Min-Ju; Kim, Myung Kyum; Kim, Ho-Bin; Yi, Tae-Hoo; Kim, Se-Young; Yang, Deok-Chun] Kyung Hee Univ, Proc Coll Life Sci, Yongin 446701, Gyeonggi Do, South Korea. [Im, Wan-Taek] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. [Soung, Nak-Kyun] NCI, NIH, Ctr Canc Res, Lab Metab, Bethesda, MD 20892 USA. RP Yang, DC (reprint author), Kyung Hee Univ, Dept Oriental Med Mat, 1 Seocheon Dong, Yongin 446701, Gyeonggi Do, South Korea. EM dcyang@khu.ac.kr NR 27 TC 10 Z9 10 U1 1 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD FEB PY 2008 VL 58 BP 429 EP 433 DI 10.1099/ijs.0.65226-0 PN 2 PG 5 WC Microbiology SC Microbiology GA 268FF UT WOS:000253563800021 PM 18218944 ER PT J AU Csaky, KG Richman, EA Ferris, FL AF Csaky, Karl G. Richman, Elaine A. Ferris, Frederick L., III TI Report from the NEI/FDA ophthalmic clinical trial design and endpoints symposium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Editorial Material ID DIABETIC MACULAR EDEMA; ENDOTHELIAL GROWTH-FACTOR; DEGENERATION; RANIBIZUMAB; RETINOPATHY; TRIAMCINOLONE; COMPLICATIONS; VERTEPORFIN; PROGRESSION; PEGAPTANIB C1 [Csaky, Karl G.] Duke Univ, Med Ctr, Ophthalm Unit, DCRI, Durham, NC 27710 USA. [Richman, Elaine A.] Richman Associates LLC, Baltimore, MD USA. [Ferris, Frederick L., III] NEI, NIH, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. RP Csaky, KG (reprint author), Duke Univ, Med Ctr, Ophthalm Unit, DCRI, Durham, NC 27710 USA. EM karl.csaky@duke.edu NR 16 TC 86 Z9 87 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2008 VL 49 IS 2 BP 479 EP 489 DI 10.1167/iovs.07-1132 PG 11 WC Ophthalmology SC Ophthalmology GA 256RK UT WOS:000252747100001 PM 18234989 ER PT J AU Chouker, A Lizak, M Schimel, D HeImberger, T Ward, JM Despres, D Kaufmann, I Bruns, C Lohe, F Ohta, A Sitkovsky, MV Klaunberg, B Thiel, M AF Chouker, Alexander Lizak, Martin Schimel, Daniel HeImberger, Thomas Ward, Jerrold M. Despres, Daryl Kaufmann, Ines Bruns, Christiane Lohe, Florian Ohta, Akio Sitkovsky, Michael V. Klaunberg, Brenda Thiel, Manfred TI Comparison of Fenestra VC contrast-enhanced computed tomography imaging with gadopentetate dimeglumine and Ferucarbotran magnetic resonance imaging for the in vivo evaluation of murine liver damage after ischemia and reperfusion SO INVESTIGATIVE RADIOLOGY LA English DT Article DE liver ischemia reperfusion; MicroCT; MRI; contrast media ID GD-EOB-DTPA; POLYIODINATED TRIGLYCERIDE ANALOGS; PRECLINICAL EVALUATION; CT DETECTION; IRON-OXIDE; RAT-LIVER; AGENT; INJURY; LESIONS; TRANSPLANTATION AB Objectives: Comparison of intravenous Fenestra VC-enhanced computed tomography (CT) with gadopentetate dimeglumine and Ferucarbotran contrast-enhanced magnetic resonance imaging (MRI) for the in vivo imaging of hepatic ischemia/reperfusion injury (IRI) in a murine model. Material and Methods: After induction of hepatic IRI by left liver lobe (LLL) ischernia (30, 45, and 75 minutes) and reperfusion (4 hours and 24 hours), a total of 130 mice were imaged either by Fenestra VC-enhanced 3-D CT or by dynamic, T2*-weighed gadopentetafe dimeglumine or static, T2*-weighed Ferucarbotran 2-D MRI (4.7 T). Results: Detection of liver tissue damage as a consequence of IRI was not possible by CT or MRI without the use of contrast media. (1) Mice subjected to liver IRI (45 minutes of ischemia) and injected with Fenestra VC showed a distinct liver enhancement of the viable liver tissue or a nonenhancement of the necrotic tissue. The Fenestra VC CT-unenhanced liver volume increased as a function of time of ischemia and reperfusion. The unenhanced liver volume also correlated positively with serum liver enzyme activities and damage scores from liver histology. (2) The signal intensities (SI) between normal liver tissue and livers subjected to 30 minutes of ischemia were not different on dynamic gadopentetate dimeglumine-enhanced magnetic resonance images. More severe IRI as induced by 45 or 75 minutes of ischemia was characterized by (a) early hyperenhancement of regions in the LLL with rapid increase of SI higher than that observed in the undamaged liver within the first few minutes and (b) delayed hyperenhancement in the later course after gadopentetate dimeglumine injection, respectively. (3) Ferucarbotran MRI detected signs of IRI after only 30 minutes of liver ischemia and hence detected IRI earlier than Fenestra VC or gadopentetate dimeglumine. With longer duration of ischemia, Ferucarbotran SI increased in the LLL, but viable and necrotic tissues were not clearly distinguishable. Conclusions: MicroCT with Fenestra VC enhancement and MRI using either gadopentetate dimeglumine or Ferucarbotran enhancement of the liver revealed that all techniques allow in vivo determination of hepatic IRI as a function of the duration of ischemia and reperfusion of the liver. However, Fenestra VC-enhanced CT of the murine liver is superior to gadopentetate dimeglumine and Ferucarbotran for localization, quantification, and differentiation of viable from metabolically inactive/damaged liver tissue after hepatic ischemia/reperfasion but Fenestra VC is less sensitive than Ferucarbotran to detect the early onset of subtle consequences of hepatic IRI. C1 [Chouker, Alexander; Kaufmann, Ines; Thiel, Manfred] Univ Munich, Klinikum Grosshadern, Dept Anesthesiol, D-81377 Munich, Germany. [Chouker, Alexander; Ward, Jerrold M.] NIAID, Bethesda, MD 20892 USA. [Lizak, Martin; Schimel, Daniel; Despres, Daryl; Klaunberg, Brenda] NINDS, NIH, Bethesda, MD 20892 USA. [HeImberger, Thomas] Univ Lubeck, Inst Radiol, Lubeck, Germany. [Bruns, Christiane; Lohe, Florian] Univ Munich, Klinikum Grosshadern, Dept Visceral Surg, Munich, Germany. [Ohta, Akio; Sitkovsky, Michael V.] Northeastern Univ, New England Inflammat & Tissue Protect Inst Conso, Boston, MA 02115 USA. RP Thiel, M (reprint author), Univ Munich, Klinikum Grosshadern, Dept Anesthesiol, D-81377 Munich, Germany. EM mthiel@med.uni-muenchen.de FU Intramural NIH HHS NR 45 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD FEB PY 2008 VL 43 IS 2 BP 77 EP 91 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 254EN UT WOS:000252569300001 PM 18197060 ER PT J AU Joy, T Keogh, HM Hadigan, C Dolan, SE Fitch, K Liebau, J Johnsen, S Lo, J Grinspoon, SK AF Joy, Tisha Keogh, Hester M. Hadigan, Colleen Dolan, Sara E. Fitch, Kathleen Liebau, James Johnsen, Stine Lo, Janet Grinspoon, Steven K. TI Relation of body composition to body mass index in HIV-infected patients with metabolic abnormalities SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE body composition; body mass index; HIV; visceral adiposity ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; FAT DISTRIBUTION; ABDOMINAL ADIPOSITY; GLUCOSE-TOLERANCE; RANDOMIZED-TRIAL; LIPODYSTROPHY; WOMEN; MEN AB Objective: To determine visceral adiposity (VAT), subcutaneous adiposity (SAT), and regional body adipose differences between HIV-infected and non-HIV-infected subjects in relation to body mass index (BMI) and World Health Organization BMI categories. Design, Setting, and Participants: Analyses were conducted of 306 HIV-infected and 107 community-derived HIV-negative subjects evaluated for metabolic studies between 1999 and 2006. Analyses were stratified by gender. Additional analyses were performed stratifying subjects by metabolic syndrome status. Results: HIV-infected men and women demonstrated decreased total extremity fat by 1.1 kg and 0.85 kg, respectively, relative to non-HIV-infected control subjects. VAT was increased among HIV-infected men and women in the normal (18.5 to 24.9 kg/m(2)) and overweight (25.0 to 29.9 kg/m(2)) categories relative to control subjects but not among those in the obese category ( >= 30.0 kg/m(2)). In contrast, abdominal SAT was reduced among HIV-infected men in the normal and overweight categories but was similar among HIV-infected women and control subjects in these categories. Abdominal SAT was increased among HIV-infected women in the obese category relative to control subjects. Similar results were obtained limiting the analysis to HIV-infected (n = 204) and control subjects (n = 89) without the metabolic syndrome. Conclusions: Peripheral lipoatrophy is a consistent finding among HIV-infected men and women with metabolic abnormalities. Relative increases in VAT are most pronounced among male and female HIV-infected subjects in the normal weight and overweight categories. Gender differences in abdominal SAT accumulation are observed, with preservation of SAT among HIV-infected women relative to control subjects. C1 [Joy, Tisha; Keogh, Hester M.; Hadigan, Colleen; Dolan, Sara E.; Fitch, Kathleen; Liebau, James; Johnsen, Stine; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Joy, Tisha; Keogh, Hester M.; Hadigan, Colleen; Dolan, Sara E.; Fitch, Kathleen; Liebau, James; Johnsen, Stine; Lo, Janet; Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hadigan, Colleen] NIH, Bethesda, MD USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066, M01 RR001066]; NICHD NIH HHS [T32 HD052961, T32HD-052961]; NIDDK NIH HHS [DK-02844, R01 DK049302, K23 DK002844, P30 DK040561-12, P30 DK040561]; PHS HHS [DKR01-49302] NR 40 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2008 VL 47 IS 2 BP 174 EP 184 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 255VA UT WOS:000252684600006 PM 17971710 ER PT J AU Cohen, SG AF Cohen, Sheldon G. TI Measles and immunomodulation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID REACTIVITY; VACCINE C1 NIH, NIAID, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIH, NIAID, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 BP 543 EP 544 DI 10.1016/j.jaci.2007.12.1152 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 265CX UT WOS:000253337800052 PM 18269930 ER PT J AU Bencharitiwong, R Sampson, HA Schwartz, J Shreffler, WG Gergen, P Mitchell, H Esch, RE Nowak-Wegrzyn, AH AF Bencharitiwong, R. Sampson, H. A. Schwartz, J. Shreffler, W. G. Gergen, P. Mitchell, H. Esch, R. E. Nowak-Wegrzyn, A. H. TI In vitro assessment of cockroach allergenic extract potency utilizing sera from cockroach-allergic individuals SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Bencharitiwong, R.; Sampson, H. A.; Shreffler, W. G.; Nowak-Wegrzyn, A. H.] Mt Sinai Sch Med, New York, NY USA. [Schwartz, J.; Mitchell, H.] Rho Inc, Chapel Hill, NC USA. [Gergen, P.] NIAID, NIH, DAIT, Bethesda, MD USA. [Esch, R. E.] Greer Labs, Lenoir, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 896 BP S233 EP S233 DI 10.1016/j.jaci.2007.12.920 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401360 ER PT J AU Brown, JM Soule, BP Mitchell, JB Metcalfe, DD AF Brown, J. M. Soule, B. P. Mitchell, J. B. Metcalfe, D. D. TI Mast cell survival following gamma-irradiation is dependent on Bcl-2 and Bcl-xL SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Brown, J. M.; Soule, B. P.; Mitchell, J. B.; Metcalfe, D. D.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 47 BP S13 EP S13 DI 10.1016/j.jaci.2007.12.052 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400048 ER PT J AU Gan, PS Mathias, RA Rafaels, NM Grant, AV Hand, T Hansel, N Diette, G Adkinson, NF Liu, MC Faruque, M Dunston, GM Scott, AF Ruczinski, I Beaty, TH Barnes, KC AF Gan, P. S. Mathias, R. A. Rafaels, N. M. Grant, A. V. Hand, T. Hansel, N. Diette, G. Adkinson, N. F. Liu, M. C. Faruque, M. Dunston, G. M. Scott, A. F. Ruczinski, I. Beaty, T. H. Barnes, K. C. TI A genome-wide association study of cockroach sensitization among African American asthmatics SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Gan, P. S.; Rafaels, N. M.; Grant, A. V.; Hand, T.; Adkinson, N. F.; Barnes, K. C.] Johns Hopkins Univ, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21218 USA. [Mathias, R. A.] NHGRI, NIH, Inherited Dis Res Branch, Baltimore, MD USA. [Hansel, N.; Diette, G.; Liu, M. C.] Johns Hopkins Univ, Sch Med, Dept Pulm Med, Baltimore, MD 21218 USA. [Faruque, M.; Dunston, G. M.] Howard Univ, Natl Human Genome Ctr, Washington, DC USA. [Scott, A. F.] Johns Hopkins Univ, Sch Med, Genet Resiurces Core Facil, Baltimore, MD 21218 USA. [Ruczinski, I.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA. [Beaty, T. H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 312 BP S81 EP S81 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400313 ER PT J AU Gao, L Grigoryev, DN Cheadle, C Grant, AV Rafaels, NM Hand, TA Hansel, N Diette, G Adkinson, NF Liu, MC Togias, A Faruque, M Watson, H Rabb, H Reddy, SP Simon, BA King, LS Scott, AF Ruczinski, I Mathias, RA Dunston, G Brower, RG Beaty, TH Barnes, KC AF Gao, L. Grigoryev, D. N. Cheadle, C. Grant, A. V. Rafaels, N. M. Hand, T. A. Hansel, N. Diette, G. Adkinson, N. F. Liu, M. C. Togias, A. Faruque, M. Watson, H. Rabb, H. Reddy, S. P. Simon, B. A. King, L. S. Scott, A. F. Ruczinski, I. Mathias, R. A. Dunston, G. Brower, R. G. Beaty, T. H. Barnes, K. C. TI Co-associations between candidate genes in acute lung injury models and asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Gao, L.; Grigoryev, D. N.; Cheadle, C.; Grant, A. V.; Rafaels, N. M.; Hand, T. A.; Adkinson, N. F.; Togias, A.; Barnes, K. C.] Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. [Hansel, N.; Diette, G.; Liu, M. C.; King, L. S.; Brower, R. G.] JHU, Div Pulm & Crit Care Med, Baltimore, MD USA. [Faruque, M.] Howard Univ, Washington, DC 20059 USA. [Watson, H.] Univ W Indies, W Indies, Barbados. [Rabb, H.] JHU, Div Nephrol, Baltimore, MD USA. [Reddy, S. P.; Ruczinski, I.; Beaty, T. H.] JHU, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Simon, B. A.] JHU, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Scott, A. F.] JHU, Genet Resources Core Facil, Baltimore, MD USA. [Mathias, R. A.] Natl Human Genome Res Inst, Baltimore, MD USA. [Dunston, G.] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 247 BP S64 EP S64 DI 10.1016/j.jaci.2007.12.256 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400248 ER PT J AU Grayson, MH Bauer-Sardina, I Visness, C Wood, R Witter, F O'Connor, GT Sandel, M Kattan, M Sampson, H Togias, A Gern, JE Bloomberg, G AF Grayson, M. H. Bauer-Sardina, I. Visness, C. Wood, R. Witter, F. O'Connor, G. T. Sandel, M. Kattan, M. Sampson, H. Togias, A. Gern, J. E. Bloomberg, G. TI Relationship between cord blood sCD14 levels, ethnicity, sex, and prenatal smoke exposure in a population of "At-Risk" infants SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Grayson, M. H.; Bauer-Sardina, I.; Bloomberg, G.] Washington Univ, Sch Med, St Louis, MO USA. [Visness, C.] Rho, Chapel Hill, NC USA. [Wood, R.; Witter, F.] Johns Hopkins Univ, Baltimore, MD USA. [O'Connor, G. T.; Sandel, M.] Boston Univ, Boston, MA 02215 USA. [Kattan, M.] Childrens Hosp New York, New York, NY USA. [Sampson, H.] Mt Sinai Sch Med, New York, NY USA. [Togias, A.] NIH, Bethesda, MD 20892 USA. [Gern, J. E.] Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 14 BP S4 EP S4 DI 10.1016/j.jaci.2007.12.019 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400015 ER PT J AU Grigoryev, DN Watkins, T Gao, L Grant, AV Stockton-Porter, M Watson, H Mathias, RA Gittens, M Cheadle, C Barnes, KC AF Grigoryev, D. N. Watkins, T. Gao, L. Grant, A. V. Stockton-Porter, M. Watson, H. Mathias, R. A. Gittens, M. Cheadle, C. Barnes, K. C. TI Transcriptomics of peripheral blood from asthmatics living in Barbados SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Grigoryev, D. N.; Watkins, T.; Gao, L.; Grant, A. V.; Stockton-Porter, M.; Cheadle, C.; Barnes, K. C.] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Baltimore, MD 21218 USA. [Watson, H.; Gittens, M.] Univ W Indies, Sch Clin Med & Res, Bridgetown, W Ind Assoc St. [Mathias, R. A.] NIH, NHGRI, Genometric Sect, Inherited Dis Res Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 1001 BP S259 EP S259 DI 10.1016/j.jaci.2007.12.1027 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401464 ER PT J AU Heller, NM Qi, X Junttila, I Paul, WE Keegan, AD AF Heller, N. M. Qi, X. Junttila, I. Paul, W. E. Keegan, A. D. TI The type III-4 receptor complex selectively activates the tyrosine phosphorylation of IRS-2 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Heller, N. M.; Qi, X.; Keegan, A. D.] Univ Maryland, Baltimore, MD USA. [Junttila, I.; Paul, W. E.] NIH, NIAID, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 188 BP S48 EP S48 DI 10.1016/j.jaci.2007.12.196 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400189 ER PT J AU Hosen, J Perzanowski, M Carter, MC Odhiambo, J Ng'ang'a, L Ngari, P Satinover, S Platts-Mills, TAE AF Hosen, J. Perzanowski, M. Carter, M. C. Odhiambo, J. Ng'ang'a, L. Ngari, P. Satinover, S. Platts-Mills, T. A. E. TI IgE antibodies to helminths and the cross-reactive oligosaccharide galactose-alpha-1,3-galactose (alphaGal) among children in a village in Africa SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Hosen, J.; Satinover, S.; Platts-Mills, T. A. E.] Univ Virginia, Charlottesville, VA USA. [Perzanowski, M.] Columbia Univ, New York, NY USA. [Carter, M. C.] NIAID, Bethesda, MD 20892 USA. [Carter, M. C.] NIAID, Nairobi, Kenya. [Odhiambo, J.] US Ctr Dis Control & Prevent, Nairobi, Kenya. [Ng'ang'a, L.; Ngari, P.] Kenya Govt Med Res Ctr, Nairobi, Kenya. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 542 BP S140 EP S140 DI 10.1016/j.jaci.2007.12.1097 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401006 ER PT J AU Ishmael, F Fang, X Atasoy, U Gorospe, M Cheadle, C Stellato, C AF Ishmael, F. Fang, X. Atasoy, U. Gorospe, M. Cheadle, C. Stellato, C. TI Characterization of the glucocorticoid response for transcripts associated with the RNA-binding protein tristetraprolin SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Ishmael, F.; Fang, X.; Cheadle, C.; Stellato, C.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Atasoy, U.] Columbia Univ, Columbia, MO USA. [Gorospe, M.] NIA, NIH, Cellular & Mol Biol Lab, Baltimore, MD USA. RI Stellato, Cristiana/P-3001-2015 OI Stellato, Cristiana/0000-0002-1294-8355 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 1059 BP S274 EP S274 DI 10.1016/j.jaci.2007.12.1087 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401522 ER PT J AU Kim, N Foster, B Prussin, C AF Kim, N. Foster, B. Prussin, C. TI Detection of influenza specific T-Cell response in allergic and healthy controls SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Kim, N.; Foster, B.; Prussin, C.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 474 BP S123 EP S123 DI 10.1016/j.jaci.2007.12.488 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400475 ER PT J AU Kirshenbaum, AS Hair, GA Ansari, AA Secor, WE Gilfillan, AM Metcalfe, DD Sundstrom, JB AF Kirshenbaum, A. S. Hair, G. A. Ansari, A. A. Secor, W. E. Gilfillan, A. M. Metcalfe, D. D. Sundstrom, J. B. TI Demonstration that IgE influences HIV coreceptor usage and viral phenotype during ontogeny of human mast cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Kirshenbaum, A. S.; Gilfillan, A. M.; Metcalfe, D. D.] NIH, NIAID, Bethesda, MD 20892 USA. [Hair, G. A.; Ansari, A. A.; Sundstrom, J. B.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Secor, W. E.] Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 541 BP S140 EP S140 DI 10.1016/j.jaci.2007.12.1142 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401005 ER PT J AU Lajoie, S Herman, NS Dienger, KM Sproles, A Pesce, J Wynn, T Grusby, M Wills-Karp, M AF Lajoie, S. Herman, N. S. Dienger, K. M. Sproles, A. Pesce, J. Wynn, T. Grusby, M. Wills-Karp, M. TI IL-21 receptor signaling partially mediates Th2-mediated allergic airway responses SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Lajoie, S.; Herman, N. S.; Dienger, K. M.; Sproles, A.; Wills-Karp, M.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Pesce, J.; Wynn, T.] NIAID, Parasit Dis Lab, Immunopathogenesis Sect, Baltimore, MD USA. [Grusby, M.] Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 560 BP S145 EP S145 DI 10.1016/j.jaci.2007.12.1115 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401024 ER PT J AU Lee, J Foster, B Prussin, C AF Lee, J. Foster, B. Prussin, C. TI CD4+T lymphocyte dysregulation in food allergy and eosinophilic gastroenteritis (EG) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Lee, J.; Foster, B.; Prussin, C.] NIH, NIAID, Lab Alleg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 405 BP S105 EP S105 DI 10.1016/j.jaci.2007.12.418 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400407 ER PT J AU Meyer-Manlapat, AK Segal, DM AF Meyer-Manlapat, A. K. Segal, D. M. TI Mast cell degranulation inhibits Th1 and promotes Th2 responses SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Meyer-Manlapat, A. K.; Segal, D. M.] NIH, NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 441 BP S114 EP S114 DI 10.1016/j.jaci.2007.12.455 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400443 ER PT J AU Nguyen, KD Krensky, AM Nadeau, KC AF Nguyen, K. D. Krensky, A. M. Nadeau, K. C. TI Increased cytotoxicity of CD4+invariant NKT in allergic asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Nguyen, K. D.; Nadeau, K. C.] Stanford Univ, Stanford, CA 94305 USA. [Krensky, A. M.] Natl Inst Hlth, Bethesda, MD USA. RI Krensky, Alan/F-7956-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 1054 BP S273 EP S273 DI 10.1016/j.jaci.2007.12.1082 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401518 ER PT J AU Ogbogu, PU Brown, M Nutruan, TB Klion, AD AF Ogbogu, P. U. Brown, M. Nutruan, T. B. Klion, A. D. TI Eosinophils from patients with FIP1L1/PDGFRA-Positive chronic eosinophilic leukemia show increased activation and granule protein turnover SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Ogbogu, P. U.; Brown, M.; Nutruan, T. B.; Klion, A. D.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 170 BP S44 EP S44 DI 10.1016/j.jaci.2007.12.178 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400171 ER PT J AU Pomes, A Li, M Wuenschmann, S King, EM Alexandratos, J Chapman, MD Wlodawer, A Gustchina, A AF Pomes, A. Li, M. Wuenschmann, S. King, E. M. Alexandratos, J. Chapman, M. D. Wlodawer, A. Gustchina, A. TI The crystal structure of the complex of Bla g 2 with an antibody fragment reveals cation-pi and sugar interactions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Pomes, A.; Wuenschmann, S.; King, E. M.; Chapman, M. D.] INDOOR Biotechnol Inc, Charlottesville, VA USA. [Li, M.] SAIC Frederick, Bas Res Program, Frederick, MD USA. [Li, M.; Alexandratos, J.; Wlodawer, A.; Gustchina, A.] Natl Canc Inst, Macromol Crystallography Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 819 BP S213 EP S213 DI 10.1016/j.jaci.2007.12.796 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401283 ER PT J AU Prussin, C Foster, B Foroughi, S AF Prussin, C. Foster, B. Foroughi, S. TI Anti-IgE therapy does not have immunomodulatory activity on allergen specific T cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Prussin, C.; Foster, B.; Foroughi, S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 446 BP S116 EP S116 DI 10.1016/j.jaci.2007.12.460 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400448 ER PT J AU Rafaels, NM Mathias, RA Grant, AV Hand, T Tsai, YJ Gao, PS Hansel, N Diette, G Adkinson, NF Liu, MC Watson, H Faruque, M Dunston, GM Scott, AF Ruczinski, I Togias, A Beaty, TH Barnes, KC AF Rafaels, N. M. Mathias, R. A. Grant, A. V. Hand, T. Tsai, Y. J. Gao, P. S. Hansel, N. Diette, G. Adkinson, N. F. Liu, M. C. Watson, H. Faruque, M. Dunston, G. M. Scott, A. F. Ruczinski, I. Togias, A. Beaty, T. H. Barnes, K. C. TI Validation of previously reported genetic associations for asthma using a genome-wide association approach among a large population of African descent SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Rafaels, N. M.; Grant, A. V.; Hand, T.; Tsai, Y. J.; Gao, P. S.; Adkinson, N. F.; Togias, A.; Barnes, K. C.] Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. [Mathias, R. A.] NIH, NHGRI, Inherted Dis Res Branch, Baltimore, MD USA. [Hansel, N.; Diette, G.; Liu, M. C.] Johns Hopkins Univ, Sch Med, Dept Pulm Med, Baltimore, MD USA. [Watson, H.] Univ W Indies, Cave Hill, Barbados. [Faruque, M.; Dunston, G. M.] Howard Univ, Natl Human Genome Ctr, Coll Med, Washington, DC 20059 USA. [Scott, A. F.] Johns Hopkins Univ, Sch Med, Genet Resources Core Facil, Baltimore, MD USA. [Ruczinski, I.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Beaty, T. H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 0 TC 0 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 244 BP S63 EP S63 DI 10.1016/j.jaci.2007.12.253 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400245 ER PT J AU Salo, PM Cohn, RD Zeldin, DC AF Salo, P. M. Cohn, R. D. Zeldin, D. C. TI Exposure to mouse allergen in US homes is associated with asthma symptoms SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Salo, P. M.; Zeldin, D. C.] NIEHS, Res Triangle Pk, NC USA. [Cohn, R. D.] Constella, Durham, NC USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 891 BP S231 EP S231 DI 10.1016/j.jaci.2007.12.915 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401355 ER PT J AU Sever, ML Salo, PM Cohn, RD Zeldin, DC AF Sever, M. L. Salo, P. M. Cohn, R. D. Zeldin, D. C. TI Relationship of active asthma and current dog and cat allergen exposure in beds SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Sever, M. L.; Salo, P. M.; Zeldin, D. C.] NIEHS, Res Triangle Pk, NC 27709 USA. [Cohn, R. D.] Constella Grp LLC, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 363 BP S94 EP S94 DI 10.1016/j.jaci.2007.12.375 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400364 ER PT J AU Slager, RE Poole, JA Levan, TD Hoppin, JA AF Slager, R. E. Poole, J. A. Levan, T. D. Hoppin, J. A. TI Occupational rhinitis is associated with pesticide exposure among commercial pesticide applicators in the agricultural health study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Slager, R. E.; Poole, J. A.; Levan, T. D.] Univ Nebraska Med Ctr, Omaha, NE USA. [Hoppin, J. A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 902 BP S234 EP S234 DI 10.1016/j.jaci.2007.12.926 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401366 ER PT J AU Sorkness, CA Bloomberg, G Calatroni, A Curry, M Gergen, P Keresmar, C Kim, J Neaville, W Steinbach, S AF Sorkness, C. A. Bloomberg, G. Calatroni, A. Curry, M. Gergen, P. Keresmar, C. Kim, J. Neaville, W. Steinbach, S. TI Comparison of asthma phenotypic characteristics to exhaled nitric oxide: Observations from the ACE trial SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Sorkness, C. A.] Univ Wisconsin, Madison, WI 53706 USA. [Bloomberg, G.] Washington Univ, Sch Med, St Louis Childrens Hosp, St Louis, MO USA. [Calatroni, A.; Curry, M.] Rho Inc, Chapel Hill, NC USA. [Gergen, P.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Keresmar, C.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Kim, J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Neaville, W.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Steinbach, S.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 18 BP S5 EP S5 DI 10.1016/j.jaci.2007.12.023 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400019 ER PT J AU Stohr, L Wuenschmann, S Chapman, MD Li, M Wlodawer, A Gustchina, A Pomes, A AF Stohr, L. Wuenschmann, S. Chapman, M. D. Li, M. Wlodawer, A. Gustchina, A. Pomes, A. TI Does the structural symmetry of cockroach allergen Bla g 2 determine symmetry of antigenic determinants for IgE antibody binding? SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Stohr, L.; Wuenschmann, S.; Chapman, M. D.; Pomes, A.] INDOOR Biotechnol Inc, Charlottesville, VA USA. [Li, M.] SAIC Frederick, Bas Res Program, Frederick, MD USA. [Li, M.; Wlodawer, A.; Gustchina, A.] Natl Canc Inst, Macromol Crystallography Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 818 BP S213 EP S213 DI 10.1016/j.jaci.2007.12.795 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401282 ER PT J AU Swindle, EJ Deleo, FR Metcalfe, DD AF Swindle, E. J. DeLeo, F. R. Metcalfe, D. D. TI Intracellular superoxide production by mast cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Swindle, E. J.; Metcalfe, D. D.] NIH, NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [DeLeo, F. R.] NIH, NIAID, RML, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 428 BP S111 EP S111 DI 10.1016/j.jaci.2007.12.441 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400430 ER PT J AU Tran, DQ Glass, DD Shevach, EM AF Tran, D. Q. Glass, D. D. Shevach, E. M. TI The suppressive function of human T regulatory cells is contact-mediated and requires interleukin-2 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Tran, D. Q.; Glass, D. D.; Shevach, E. M.] NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 870 BP S226 EP S226 DI 10.1016/j.jaci.2007.12.893 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401334 ER PT J AU Tsai, YJ Mathias, R Grant, A Rafaels, N Hand, T Togias, A Hansel, N Diette, G Adkinson, NF Liu, MC Faruque, M Watson, H Scott, A Ruczinski, I Dunston, G Beaty, T Barnes, KC AF Tsai, Y. J. Mathias, R. Grant, A. Rafaels, N. Hand, T. Togias, A. Hansel, N. Diette, G. Adkinson, N. F., Jr. Liu, M. C. Faruque, M. Watson, H. Scott, A. Ruczinski, I. Dunston, G. Beaty, T. Barnes, K. C. TI A genome wide approach to identify genetic determinants of asthma traits related to airway function in populations of African descent SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Tsai, Y. J.; Grant, A.; Rafaels, N.; Hand, T.; Togias, A.; Hansel, N.; Diette, G.; Adkinson, N. F., Jr.; Liu, M. C.; Watson, H.; Scott, A.; Ruczinski, I.; Beaty, T.; Barnes, K. C.] Johns Hopkins Univ, Baltimore, MD USA. [Mathias, R.] Natl Human Genome Res Inst, Baltimore, MD USA. [Faruque, M.; Dunston, G.] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 249 BP S65 EP S65 DI 10.1016/j.jaci.2007.12.258 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400250 ER PT J AU Uzzaman, A Hu, T Brittain, E Carter, MC Metcalfe, DD Komarow, HD AF Uzzaman, A. Hu, Z. Brittain, E. Carter, M. C. Metcalfe, D. D. Komarow, H. D. TI Serum tryptase levels in atopic and non-atopic children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Uzzaman, A.; Hu, Z.; Brittain, E.; Carter, M. C.; Metcalfe, D. D.; Komarow, H. D.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 439 BP S114 EP S114 DI 10.1016/j.jaci.2007.12.453 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400441 ER PT J AU Wilson, TM Wu, Y Fu, W Bai, Y Noel, P Marie, I Robyn, J Metcalfe, DD AF Wilson, T. M. Wu, Y. Fu, W. Bai, Y. Noel, P. Marie, I. Robyn, J. Metcalfe, D. D. TI Acquired activating NRAS mutations associated with aggressive systemic mastocytosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Wilson, T. M.; Wu, Y.; Bai, Y.; Robyn, J.; Metcalfe, D. D.] NIH, NIAID, Lab Allerg Dis, Bethesda, MD USA. [Fu, W.; Noel, P.; Marie, I.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 423 BP S110 EP S110 DI 10.1016/j.jaci.2007.12.436 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400425 ER PT J AU Wu, CC Pritsch, T Shehadeh, A Bickels, J Malawer, MM AF Wu, Chia-Chun Pritsch, Tamir Shehadeh, Ahmad Bickels, Jacob Malawer, Martin M. TI The anterior popliteal approach for popliteal exploration, distal femoral resection, and endoprosthetic reconstruction SO JOURNAL OF ARTHROPLASTY LA English DT Article DE distal femoral resection; surgical approach; endoprosthesis; anterior popliteal approach; myocutaneous flap; vastus medialis ID LIMB-SPARING SURGERY; BONE SARCOMAS; PROSTHETIC RECONSTRUCTION; MYOCUTANEOUS FLAP; SALVAGE SURGERY; MUSCLE FLAP; FEMUR; KNEE; TUMORS; REPLACEMENT AB Distal femoral resection and endoprosthetic reconstruction are sometimes associated with flap necrosis and inadequate soft tissue coverage. We evaluated the anterior popliteal surgical approach, which was designed to reduce those complications by using a posteromedial myocutaneous flap based upon the vastus medialis. A retrospective analysis of 46 consecutive patients was performed, and results were compared with historical controls. Compared with 19.4% with wound complications and 22.7% with gastrocnemius flap transfers in previous series by the senior author, 7.8% of patients in the present study had minimal superficial flap necrosis, and no gastrocnemius transfers for soft tissue coverage were required. The median Musculoskeletal Tumor Society score was 26, and the local recurrence rate 2 years or more after resection of osteosarcoma was 4%. The anterior popliteal approach to the distal femur limited wound complications and provided good soft tissue coverage of the endoprostheses. C1 [Pritsch, Tamir; Shehadeh, Ahmad; Malawer, Martin M.] Washington Hosp Ctr, Washington Canc Inst, Dept Orthoped Oncol, Washington, DC 20010 USA. [Wu, Chia-Chun] Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Orthoped Surg, Taipei, Taiwan. [Bickels, Jacob] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Natl Unit Orthoped Oncol, IL-69978 Tel Aviv, Israel. [Malawer, Martin M.] Georgetown Univ, Dept Orthoped, Washington, DC USA. [Malawer, Martin M.] Natl Canc Inst, Pediat & Surg Branch, Bethesda, MD USA. RP Pritsch, T (reprint author), Washington Hosp Ctr, Washington Canc Inst, Dept Orthoped Oncol, C2173,110 Irving St NW, Washington, DC 20010 USA. NR 27 TC 2 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 2008 VL 23 IS 2 BP 254 EP 262 DI 10.1016/j.arth.2007.01.005 PG 9 WC Orthopedics SC Orthopedics GA 269KZ UT WOS:000253649200016 PM 18280421 ER PT J AU Bender, RA Downs, D Kiley, P LaRossa, RA Sonenshein, AL Storz, G AF Bender, Robert A. Downs, Diana Kiley, Patricia LaRossa, Robert A. Sonenshein, Abraham L. Storz, Gisela TI Bridges and chasms: Summary of the IMAGE 2 meeting in Montreal, Canada, 30 April to 3 May 2007 SO JOURNAL OF BACTERIOLOGY LA English DT Editorial Material C1 [Bender, Robert A.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Downs, Diana; Kiley, Patricia] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. [LaRossa, Robert A.] DuPont Co Inc, Cent Res & Dev, Wilmington, DE 19880 USA. [Sonenshein, Abraham L.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Storz, Gisela] Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bender, RA (reprint author), Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. EM rbender@umich.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2008 VL 190 IS 3 BP 792 EP 797 DI 10.1128/JB.01097-07 PG 6 WC Microbiology SC Microbiology GA 254VT UT WOS:000252616800003 PM 17827302 ER PT J AU Durfee, T Hansen, AM Zhi, H Blattner, FR Jin, DJ AF Durfee, Tim Hansen, Anne-Marie Zhi, Huijun Blattner, Frederick R. Jin, Ding Jun TI Transcription profiling of the stringent response in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Review ID RIBOSOMAL-RNA TRANSCRIPTION; GUANOSINE 5'-DIPHOSPHATE 3'-DIPHOSPHATE; PHASE-DEPENDENT REGULATION; GLOBAL GENE-EXPRESSION; TOXIN-ANTITOXIN SYSTEM; STATIONARY-PHASE; GROWTH-PHASE; IN-VIVO; INORGANIC POLYPHOSPHATE; PROTEIN-SYNTHESIS AB The bacterial stringent response serves as a paradigm for understanding global regulatory processes. It can be triggered by nutrient downshifts or starvation and is characterized by a rapid RelA-dependent increase in the alarmone (p)ppGpp. One hallmark of the response is the switch from maximum-growth-promoting to biosynthesis-related gene expression. However, the global transcription patterns accompanying the stringent response in Escherichia coli have not been analyzed comprehensively. Here, we present a time series of gene expression profiles for two serine hydroxymate-treated cultures: (i) MG1655, a wild-type E. coli K-12 strain, and (ii) an isogenic relA Delta 251 derivative defective in the stringent response. The stringent response in MG1655 develops in a hierarchical manner, ultimately involving almost 500 differentially expressed genes, while the relA Delta 251 mutant response is both delayed and limited in scope. We show that in addition to the down-regulation of stable RNA-encoding genes, flagellar and chemotaxis gene expression is also under stringent control. Reduced transcription of these systems, as well as metabolic and transporter-encoding genes, constitutes much of the down-regulated expression pattern. Conversely, a significantly larger number of genes are up-regulated. Under the conditions used, induction of amino acid biosynthetic genes is limited to the leader sequences of attenuator-regulated operons. Instead, up-regulated genes with known functions, including both regulators (e.g., rpoE, rpoH, and rpoS) and effectors, are largely involved in stress responses. However, one-half of the up-regulated genes have unknown functions. How these results are correlated with the various effects of (p)ppGpp (in particular, RNA polymerase redistribution) is discussed. C1 [Durfee, Tim; Blattner, Frederick R.] Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. [Hansen, Anne-Marie; Zhi, Huijun; Jin, Ding Jun] NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. RP Durfee, T (reprint author), Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. EM durf@genome.wisc.edu; djjin@helix.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM35682-17S1, R01 GM035682]; NLM NIH HHS [T15 LM007359, 5T15LM007359] NR 105 TC 149 Z9 153 U1 5 U2 45 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2008 VL 190 IS 3 BP 1084 EP 1096 DI 10.1128/JB.01092-07 PG 13 WC Microbiology SC Microbiology GA 254VT UT WOS:000252616800034 PM 18039766 ER PT J AU Irarrazabal, CE Williams, CK Ely, MA Birrer, MJ Garcia-Perez, A Burg, MB Ferraris, JD AF Irarrazabal, Carlos E. Williams, Chester K. Ely, Megan A. Birrer, Michael J. Garcia-Perez, Arlyn Burg, Maurice B. Ferraris, Joan D. TI Activator protein-1 contributes to high NaCl-induced increase in tonicity-responsive enhancer/osmotic response element-binding protein transactivating activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALDOSE REDUCTASE GENE; NF-KAPPA-B; INOSITOL COTRANSPORTER GENE; OSMOTIC RESPONSE; C-JUN; DNA-BINDING; TRANSCRIPTIONAL REGULATION; STIMULATES TRANSCRIPTION; STRUCTURAL ORGANIZATION; HYPEROSMOTIC STRESS AB Tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP) is a Rel protein that activates transcription of osmoprotective genes at high extracellular NaCl. Other Rel proteins NFAT1-4 and NF-kappa B complex with activator protein-1 (AP-1) to transactivate target genes through interaction at composite NFAT/NF-kappa B center dot AP-1 sites. TonEBP/OREBP target genes commonly have one or more conserved AP-1 binding sites near TonEBP/OREBPcognateelements(OREs). Also, TonEBP/OREBP and the AP-1 proteins c-Fos and c-Jun are all activated by high NaCl. We now find, using an ORE center dot AP-1 reporter from the target aldose reductase gene or the same reporter with a mutated AP-1 site, that upon stimulation by high extracellular NaCl, 1) the presence of a wild type, but not a mutated, AP-1 site contributes to TonEBP/OREBP-dependent transcription and 2) AP-1 dominant negative constructs inhibit TonEBP/OREBP-dependent transcription provided the AP-1 site is not mutated. Using supershifts and an ORE center dot AP-1 probe, we find c-Fos and c-Jun present in combination with TonEBP/ OREBP. Also, c-Fos and c-Jun coimmunoprecipitate with TonEBP/ OREBP, indicating physical association. Small interfering RNA knockdown of either c-Fos or c-Jun inhibits high NaCl-induced increase of mRNA abundance of the TonEBP/ OREBP target genes AR and BGT1. Furthermore, a dominant negative AP-1 also reduces high NaCl-induced increase of TonEBP/ OREBP transactivating activity. Inhibition of p38, which is known to stimulate TonEBP/OREBP transcriptional activity, reduces high NaCl-dependent transcription of anORE center dot AP-1 reporter only if the AP-1 site is intact. Thus, AP-1 is part of the TonEBP/ OREBP enhanceosome, and its role in high NaCl-induced activation of TonEBP/ OREBP may require p38 activity. C1 [Irarrazabal, Carlos E.; Williams, Chester K.; Ely, Megan A.; Garcia-Perez, Arlyn; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Birrer, Michael J.] NCI, Cell & Canc Biol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ferraris, JD (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM ferraris@nhlbi.nih.gov NR 61 TC 23 Z9 23 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 1 PY 2008 VL 283 IS 5 BP 2554 EP 2563 DI 10.1074/jbc.M703490200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254XW UT WOS:000252622300012 PM 18056707 ER PT J AU Cuthbertson, BJ Liao, Y Birnbaumer, L Blackshear, PJ AF Cuthbertson, Brandon J. Liao, Yanhong Birnbaumer, Lutz Blackshear, Perry J. TI Characterization of zfs1 as an mRNA-binding and -destabilizing protein in Schizosaccharomyces pombe SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AU-RICH ELEMENT; ZINC-FINGER PROTEINS; GENE-EXPRESSION; FISSION YEAST; CONFORMATIONAL-CHANGES; IRON-DEFICIENCY; GLOBAL ANALYSIS; HUMAN HOMOLOG; SWISS-MODEL; TRISTETRAPROLIN AB Tristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a protein containing the critical features of the tristetraprolin zinc finger domain. zfs1 has been linked to pheromone signal transduction control and to the coordination of mitosis, but no biological function has been ascribed to the zfs1 protein. Through a functional genomics approach we compared transcript levels in wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1-deficient strain were examined for the presence of potential tristetraprolin-like binding sites. One such potential target transcript was encoded by arz1, a gene encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA decay was inhibited in the zfs1-deficient strain when it was expressed under the control of a thiamine-repressible promoter. Mutations within one AU-rich element present in the arz1 3 '- untranslated region protected this transcript from zfs1-promoted decay, whereas mutating another potential binding site had no effect. Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based probes; this interaction was eliminated when key residues were mutated in either zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model system for studies of zinc finger protein/AU-rich element interactions that result in mRNA decay. C1 [Cuthbertson, Brandon J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Liao, Yanhong; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Blackshear, Perry J.] NIEHS, Clin Res Program, NIH, Res Triangle Pk, NC 27709 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 TW Alexander Dr,MD A2-05, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU Intramural NIH HHS [Z01 ES101684-05, Z99 ES999999, Z01 ES101643-05] NR 44 TC 15 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 1 PY 2008 VL 283 IS 5 BP 2586 EP 2594 DI 10.1074/jbc.M707154200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254XW UT WOS:000252622300015 PM 18042546 ER PT J AU Alter-Koltunoff, M Goren, S Nousbeck, J Feng, CG Sher, A Ozato, K Azriel, A Levi, BZ AF Alter-Koltunoff, Michal Goren, Sigal Nousbeck, Janna Feng, Carl G. Sher, Alan Ozato, Keiko Azriel, Aviva Levi, Ben-Zion TI Innate immunity to intraphagosomal pathogens is mediated by interferon regulatory factor 8 (IRF-8) that stimulates the expression of macrophage-specific Nramp1 through antagonizing repression by c-Myc SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; INFECTIOUS-DISEASE SUSCEPTIBILITY; INTRACELLULAR IRON TRANSPORT; MYELOID PROGENITOR CELLS; NATURAL-RESISTANCE; GENE-EXPRESSION; INTERLEUKIN-12 EXPRESSION; TRANSCRIPTION FACTOR; LEISHMANIA-DONOVANI; DENDRITIC CELLS AB Macrophages are a central arm of innate immune defense against intracellular pathogens. They internalize microbes into phagosomes where the invaders are being killed by oxygen and nitrogen reactive species. Despite this battery of antimicrobial molecules, some are able to thrive within the phagosome thus termed intraphagosomal pathogens among which are Salmonella, Leishmania, and Mycobacteria. In mice, a single dominant gene termed Nramp1/Slc11a1 controls innate resistance to such pathogens. This gene is expressed exclusively in myeloid cells. Previously, we have shown that the restricted expression of Nramp1 is regulated by a myeloid cell-specific transcription factor termed IRF-8/ICSBP. It is demonstrated here that the induction of Nramp1 expression in activated macrophages is accompanied by a promoter shift from a repression state elicited by c-Myc to an activation state elicited by the induction of IRF-8 in activated macrophages. This transition from repression to activation is facilitated by a competitive protein-protein interaction with the transcription factor Miz-1. To show that IRF-8 is directly involved in the elimination of intraphagosomal pathogens through the regulation of Nramp1 gene expression, we bred wild type as well as IRF-8 and Nramp1 null mouse strains and examined macrophages derived from bone marrow and peritoneum. Our results clearly show that the absence of IRF-8 and Nramp1 leads to the same phenotype; defective killing of intraphagosomal Salmonella enterica serovar typhimurium and Mycobacterium bovis. Thus, interplay between repression and activation state of the Nramp1 promoter mediated by IRF-8 provides the molecular basis by which macrophages resist intraphagosomal pathogens at early stage after infection. C1 [Alter-Koltunoff, Michal; Goren, Sigal; Nousbeck, Janna; Azriel, Aviva; Levi, Ben-Zion] Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. [Ozato, Keiko] NICHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. [Feng, Carl G.; Sher, Alan] NIAID, Immunol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Levi, BZ (reprint author), Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. EM blevi@technion.ac.il NR 51 TC 38 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 1 PY 2008 VL 283 IS 5 BP 2724 EP 2733 DI 10.1074/jbc.M707704200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254XW UT WOS:000252622300030 PM 18045875 ER PT J AU Esser, L Elberry, M Zhou, F Yu, CA Yu, L Xia, D AF Esser, Lothar Elberry, Maria Zhou, Fei Yu, Chang-An Yu, Linda Xia, Di TI Inhibitor-complexed structures of the cytochrome bc(1) from the photosynthetic bacterium Rhodobacter sphaeroides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IRON-SULFUR PROTEIN; MITOCHONDRIAL RESPIRATORY-CHAIN; BOVINE HEART-MITOCHONDRIA; QUINOL OXIDATION SITE; ELECTRON-TRANSFER; B(6)F COMPLEX; CRYSTAL-STRUCTURE; EXTRA FRAGMENT; C REDUCTASE; B GENE AB The cytochrome bc(1) complex (bc(1)) is a major contributor to the proton motive force across the membrane by coupling electron transfer to proton translocation. The crystal structures of wild type and mutant bc(1) complexes from the photosynthetic purple bacterium Rhodobacter sphaeroides(Rsbc(1)), stabilized with the quinol oxidation (Q(P)) site inhibitor stigmatellin alone or in combination with the quinone reduction (Q(N)) site inhibitor antimycin, were determined. The high quality electron density permitted assignments of a new metal-binding site to the cytochrome c(1) subunit and a number of lipid and detergent molecules. Structural differences between Rsbc(1) and its mitochondrial counterparts are mostly extra membranous and provide a basis for understanding the function of the predominantly longer sequences in the bacterial subunits. Functional implications for the bc(1) complex are derived from analyses of 10 independent molecules in various crystal forms and from comparisons with mitochondrial complexes. C1 [Esser, Lothar; Xia, Di] NCI, Natl Inst Hlth, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Elberry, Maria; Zhou, Fei; Yu, Chang-An; Yu, Linda] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. RP Xia, D (reprint author), NCI, Natl Inst Hlth, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM dixia@helix.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM 30721] NR 58 TC 89 Z9 89 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 1 PY 2008 VL 283 IS 5 BP 2846 EP 2857 DI 10.1074/jbc.M708608200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254XW UT WOS:000252622300042 PM 18039651 ER PT J AU Gabel, SA London, RE AF Gabel, Scott A. London, Robert E. TI Ternary borate-nucleoside complex stabilization by ribonuclease A demonstrates phosphate mimicry SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE nuclear magnetic resonance; nucleic acid; ribonuclease A; borate; B-11 NMR ID BOVINE PANCREATIC RIBONUCLEASE; GAMMA-GLUTAMYL-TRANSPEPTIDASE; NUCLEAR-MAGNETIC-RESONANCE; TRANSITION-STATE ANALOGS; MYOSIN MOTOR DOMAIN; CRYSTAL-STRUCTURE; BORIC-ACID; RNASE-A; ALCOHOL-DEHYDROGENASE; CATALYTIC ACTIVITY AB Phosphate esters play a central role in cellular energetics, biochemical activation, signal transduction and conformational switching. The structural homology of the borate anion with phosphate, combined with its ability to spontaneously esterify hydroxyl groups, suggested that phosphate ester recognition sites on proteins might exhibit significant affinity for nonenzymatically formed borate esters. B-11 NMR studies and activity measurements on ribonuclease A (RNase A) in the presence of borate and several cytidine analogs demonstrate the formation of a stable ternary RNase A center dot 3'-deoxycytidine-2'-borate ternary complex that mimics the complex formed between RNase A and a 2'-cytidine monophosphate (2'-CMP) inhibitor. Alternatively, no slowly exchanging borate resonance is observed for a ternary RNase A, borate, 2'-deoxycytidine mixture, demonstrating the critical importance of the 2'-hydroxyl group for complex formation. Titration of the ternary complex with 2'-CMP shows that it can displace the bound borate ester with a binding constant that is close to the reported inhibition constant of RNase A by 2'-CMP. RNase A binding of a cyclic cytidine-2',3'-borate ester, which is a structural homolog of the cytidine-2',3'-cyclic phosphate substrate, could also be demonstrated. The apparent dissociation constant for the cytidine-2',3'-borate center dot RNase A complex is 0.8 mM, which compares with a Michaelis constant of 11 mM for cytidine-2',3'-cyclic phosphate at pH 7, indicating considerably stronger binding. However, the value is 1,000-fold larger than the reported dissociation constant of the RNase A complex with uridine-vanadate. These results are consistent with recent reports suggesting that in situ formation of borate esters that mimic the corresponding phosphate esters supports enzyme catalysis. C1 [Gabel, Scott A.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, MR-01,111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050110-19] NR 51 TC 7 Z9 7 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD FEB PY 2008 VL 13 IS 2 BP 207 EP 217 DI 10.1007/s00775-007-0311-1 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 255QV UT WOS:000252673400005 PM 17957392 ER PT J AU Komatsoulis, GA Warzel, DB Hartel, FW Shanbhag, K Chilukuri, R Fragoso, G de Coronado, S Reeves, DM Hadfield, JB Ludet, C Covitz, PA AF Komatsoulis, George A. Warzel, Denise B. Hartel, Francis W. Shanbhag, Krishnakant Chilukuri, Ram Fragoso, Gilberto de Coronado, Sherri Reeves, Dianne M. Hadfield, Jillaine B. Ludet, Christophe Covitz, Peter A. TI caCORE version 3: Implementation of a model driven, service-oriented architecture for semantic interoperability SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE semantic interoperability; Model Driven Architecture; metadata; controlled terminology; ISO 11179 ID CANCER-RESEARCH; NCI THESAURUS; INFORMATICS; RESOURCE; ONTOLOGY; PROJECT AB One of the requirements for a federated information system is interoperability, the ability of one computer system to access and use the resources of another system. This feature is particularly important in biomedical research systems, which need to coordinate a variety of disparate types of data. In order to meet this need, the National Cancer Institute Center for Bioinformatics (NCICB) has created the cancer Common Ontologic Representation Environment (caCORE), an interoperability infrastructure based on Model Driven Architecture. The caCORE infrastructure provides a mechanism to create interoperable biomedical information systems. Systems built using the caCORE paradigm address both aspects of interoperability: the ability to access data (syntactic interoperability) and understand the data once retrieved (semantic interoperability). This infrastructure consists of an integrated set of three major components: a controlled terminology service (Enterprise Vocabulary Services), a standards-based metadata repository (the cancer Data Standards Repository) and an information system with an Application Programming Interface (API) based on Domain Model Driven Architecture. This infrastructure is being leveraged to create a Semantic Service-Oriented Architecture (SSOA) for cancer research by the National Cancer Institute's cancer Biomedical Informatics Grid (caBIG (TM)). Published by Elsevier Inc. C1 [Komatsoulis, George A.; Warzel, Denise B.; Hartel, Francis W.; Shanbhag, Krishnakant; Fragoso, Gilberto; de Coronado, Sherri; Reeves, Dianne M.; Hadfield, Jillaine B.; Covitz, Peter A.] NCI, Ctr Bioinformat, Rockville, MD 20852 USA. [Chilukuri, Ram; Ludet, Christophe] Semant Bits LLC, Reston, VA 20191 USA. RP Komatsoulis, GA (reprint author), NCI, Ctr Bioinformat, 2115 E Jefferson St,Suite 5000, Rockville, MD 20852 USA. EM komatsog@mail.nih.gov RI Smith, Barry/A-9525-2011; OI Smith, Barry/0000-0003-1384-116X; Komatsoulis, George/0000-0001-6967-7085 FU Intramural NIH HHS [Z99 CA999999] NR 30 TC 52 Z9 53 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 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD FEB PY 2008 VL 41 IS 1 BP 106 EP 123 DI 10.1016/j.jbi.2007.03.009 PG 18 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 292IR UT WOS:000255260200010 PM 17512259 ER PT J AU Grishaev, A Tugarinov, V Kay, LE Trewhella, J Bax, A AF Grishaev, Alexander Tugarinov, Vitali Kay, Lewis E. Trewhella, Jill Bax, Ad TI Refined solution structure of the 82-kDa enzyme malate synthase G from joint NMR and synchrotron SAXS restraints SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE NMR; protein structure; SAXS; RDC; malate synthase G ID ANGLE X-RAY; MOLECULAR-WEIGHT PROTEINS; RESIDUAL DIPOLAR COUPLINGS; SOLUTION SCATTERING DATA; CHEMICAL-SHIFT ANISOTROPY; BIOLOGICAL MACROMOLECULES; ANGSTROM RESOLUTION; DOMAIN-STRUCTURE; ATOMIC MOTIONS; SPECTROSCOPY AB Determination of the accurate three-dimensional structure of large proteins by NMR remains challenging due to a loss in the density of experimental restraints resulting from the often prerequisite perdeuteration. Solution small-angle scattering, which carries long-range translational information, presents an opportunity to enhance the structural accuracy of derived models when used in combination with global orientational NMR restraints such as residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs). We have quantified the improvements in accuracy that can be obtained using this strategy for the 82 kDa enzyme Malate Synthase G (MSG), currently the largest single chain protein solved by solution NMR. Joint refinement against NMR and scattering data leads to an improvement in structural accuracy as evidenced by a decrease from similar to 4.5 to similar to 3.3 angstrom of the backbone rmsd between the derived model and the high-resolution X-ray structure, PDB code 1D8C. This improvement results primarily from medium-angle scattering data, which encode the overall molecular shape, rather than the lowest angle data that principally determine the radius of gyration and the maximum particle dimension. The effect of the higher angle data, which are dominated by internal density fluctuations, while beneficial, is also found to be relatively small. Our results demonstrate that joint NMR/SAXS refinement can yield significantly improved accuracy in solution structure determination and will be especially well suited for the study of systems with limited NMR restraints such as large proteins, oligonucleotides, or their complexes. C1 [Grishaev, Alexander; Bax, Ad] NIH, Chem Phys Lab, NIDDK, Bethesda, MD 20892 USA. [Tugarinov, Vitali; Kay, Lewis E.] Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada. [Tugarinov, Vitali; Kay, Lewis E.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. [Tugarinov, Vitali; Kay, Lewis E.] Univ Toronto, Dept Chem, Toronto, ON M5S 1A8, Canada. [Trewhella, Jill] Univ Sydney, Sch Mol & Microbial Biosci, Sydney, NSW 2006, Australia. RP Grishaev, A (reprint author), NIH, Chem Phys Lab, NIDDK, Bldg 5, Bethesda, MD 20892 USA. EM alexanderg@intra.niddk.nih.gov OI Trewhella, Jill/0000-0002-8555-6766 FU Intramural NIH HHS NR 49 TC 69 Z9 71 U1 3 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD FEB PY 2008 VL 40 IS 2 BP 95 EP 106 DI 10.1007/s10858-007-9211-5 PG 12 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 249JF UT WOS:000252223400002 PM 18008171 ER PT J AU Titus, S Neumann, S Zheng, W Southall, N Michael, S Klumpp, C Yasgar, A Shinn, P Thomas, CJ Inglese, J Gershengorn, MC Austin, CP AF Titus, Steve Neumann, Susanne Zheng, Wei Southall, Noel Michael, Sam Klumpp, Carleen Yasgar, Adam Shinn, Paul Thomas, Craig J. Inglese, James Gershengorn, Marvin C. Austin, Christopher P. TI Quantitative high-throughput screening using a live-cell cAMP assay identifies small-molecule Agonists of the TSH receptor SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE thyroid-stimulating hormone; TSH; TSHR; TSHR agonist; quantitative high-throughput screening; qHTS; HTS; probe identification; CNG; PubChem ID THYROTROPIN RECEPTOR; TECHNOLOGIES AB The thyroid-stimulating hormone (TSH; thyrotropin) receptor belongs to the glycoprotein hormone receptor subfamily of 7-transmembrane spanning receptors. TSH receptor (TSHR) is expressed mainly in thyroid follicular cells and is activated by TSH. which regulates the growth and function of thyroid follicular cells. Recombinant TSH is used in diagnostic screens for thyroid cancer. especially in patients after thyroid cancer surgery. Currently, no selective small-molecule agonists of the TSHR are available. To screen for novel TSHR agonists, the authors miniaturized a commercially available cell-based cyclic adenosine 3 ',5 ' monophosphate (cAMP) assay into a 1536-well plate format. This assay uses an HEK293 cell line stably transfected with the TSHR coupled to a cyclic nucleotide gated ion channel as a biosensor. From a quantitative high-throughput screen of 73,180 compounds in parallel with a parental cell line (without the TSHR), 276 primary active compounds were identified. The activities of the selected active compounds were further confirmed in an orthogonal homogeneous time-resolved fluorescence cAMP-based assay. Forty-nine compounds in several structural classes have been confirmed as the small-molecule TSHR agonists that will serve as a starting point for chemical optimization and studies of thyroid physiology in health and disease. C1 [Titus, Steve; Zheng, Wei; Southall, Noel; Michael, Sam; Klumpp, Carleen; Yasgar, Adam; Shinn, Paul; Thomas, Craig J.; Inglese, James; Austin, Christopher P.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Austin, CP (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM austinc@mail.nih.gov RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU Intramural NIH HHS [Z01 HG200319-04] NR 18 TC 30 Z9 31 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD FEB PY 2008 VL 13 IS 2 BP 120 EP 127 DI 10.1177/1087057107313786 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 264DP UT WOS:000253266100003 PM 18216391 ER PT J AU Day, TF Yang, YZ AF Day, Timothy F. Yang, Yingzi TI Wnt and hedgehog signaling pathways in bone development SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT American-Academy-of-Orthopaedic-Surgeons Research Symposium on Fracture Repair: Challenges and Opportunities CY APR 25-28, 2007 CL Natl Inst Hlth, Miami Beach, FL SP Amer Acad Orthopaed Surg, Natl Inst Arthritis & Musculoskeletal & Skin Dis HO Natl Inst Hlth ID RECEPTOR-RELATED PROTEIN-5; SYNOVIAL JOINT FORMATION; INDIAN HEDGEHOG; MULTIPLE ROLES; BETA-CATENIN; DIFFERENTIATION; OSTEOBLAST; GENE; IHH; PROLIFERATION AB Cell-cell signaling is a major strategy that vertebrate embryos employ to coordinately control cell proliferation, differentiation, and survival in many developmental processes. Similar cell signaling pathways also control adult tissue regeneration and repair. We demonstrated in the developing skeletal system that the Wnt/beta-catenin signaling controls the differentiation of progenitor cells into either osteoblasts or chondrocytes. Genetic ablation of beta-catenin in the developing mouse embryo resulted in ectopic formation of chondrocytes at the expense of osteoblast differentiation during both intramembranous and endochondral ossification. Conversely, ectopic upregulation of the canonical Wnt signaling led to suppression of chondrocyte formation and enhanced ossification. As other signaling pathways also play critical roles in controlling skeletal development, to gain a full picture of the molecular regulatory network of skeletal development, we investigated how the Wnt/beta-catenin signaling is integrated with Indian hedgehog (Ihh) signaling in controlling various aspects of skeletal development. We found that Wnt signaling acts downstream of Ihh signaling and is required in osteoblasts after Osterix expression to promote osteoblast maturation during endochondral bone formation. Since similar controlling mechanisms of osteoblast proliferation and differentiation may be employed by adult mesenchymal progenitor cells during fracture repair, these studies suggest that, to enhance fracture repair or bone formation, Ihh signaling needs to be enhanced at early stages, whereas Wnt signaling should be upregulated slightly later in differentiated osteoblasts. C1 [Day, Timothy F.; Yang, Yingzi] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, Bldg 49,Room 4A68,Convent Dr,MSC 4472, Bethesda, MD 20892 USA. EM yingzi@mail.nih.gov NR 40 TC 92 Z9 101 U1 0 U2 20 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2008 VL 90A SU 1 BP 19 EP 24 DI 10.2106/JBJS.G.01174 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 260AE UT WOS:000252981300005 PM 18292352 ER PT J AU Wakita, H Ruetzler, C Illoh, KO Chen, Y Takanohashi, A Spatz, M Hallenbeck, JM AF Wakita, Hideaki Ruetzler, Christl Illoh, Kachikwu O. Chen, Yong Takanohashi, Asako Spatz, Maria Hallenbeck, John M. TI Mucosal tolerization to E-selectin protects against memory dysfunction and white matter damage in a vascular cognitive impairment model SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE E-selectin; immunomodulation; mucosal tolerance; vascular cognitive impairment ID CHRONIC CEREBRAL HYPOPERFUSION; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; RAT-BRAIN; ADHESION MOLECULES; ORAL TOLERANCE; FACTOR-ALPHA; BLOOD-FLOW; ACTIVATION; CELL AB Vascular cognitive impairment (VCI) is the second most prevalent type of dementia in the world. The white matter damage that characterizes the common subcortical ischemic form of VCI can be modeled by ligating both common carotid arteries in the Wistar rat to induce protracted cerebral hypoperfusion. In this model, we find that repetitive intranasal administration of recombinant E-selectin to induce mucosal tolerance and to target immunomodulation to activating blood vessels potently suppresses both white matter (and possibly gray matter) damage and markers of vessel activation (tumor necrosis factor and E-selectin); it also preserves behavioral function in T-maze spontaneous alternation, T-maze spatial discrimination memory retention, and object recognition tests. Immunomodulation may be an effective novel strategy to prevent progression of VCI. C1 [Spatz, Maria; Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, Bldg 49,Room 2A10,49 Convent Dr, Bethesda, MD 20892 USA. EM Hallenbj@ninds.nih.gov OI Takanohashi, Asako/0000-0003-3292-1595 FU Intramural NIH HHS [Z99 NS999999] NR 44 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2008 VL 28 IS 2 BP 341 EP 353 DI 10.1038/sj.jcbfm.9600528 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 255MS UT WOS:000252662700012 PM 17637705 ER PT J AU Daly, JW Garraffo, HM Spande, TF Giddings, LA Saporito, RA Vieites, DR Vences, M AF Daly, John W. Garraffo, H. Martin Spande, Thomas F. Giddings, Lesley-Ann Saporito, Ralph A. Vieites, David R. Vences, Miguel TI Individual and geographic variation of skin alkaloids in three species of madagascan poison frogs (Mantella) SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE alkaloids; ants; chemical defense; chemical sequestration; mantellid frogs; mites; trophic relationships; vertebrate ID BUFONID TOADS MELANOPHRYNISCUS; DENDROBATID FROGS; DIETARY ALKALOIDS; ARTHROPOD SOURCE; AMPHIBIAN SKIN; PUMILIOTOXINS; ANURA; ANTS; QUINOLIZIDINES; INDOLIZIDINES AB Alkaloid profiles for 81 individual mantellid frogs, Mantella baroni (Boulenger 1988) (N=19), M. bernhardi (N=51), and M. madagascariensis (Grandidier 1877) (N=11), from six different populations from Madagascar were examined. Marked individual differences in alkaloid composition (number, type, and amount) were observed between different species and between populations of the same species. Disjunct populations of each of the three species differed significantly in alkaloid composition. Sympatric populations of M. baroni and M. madagascariensis also differed significantly in alkaloid composition. In M. bernhardi, differences in alkaloid composition were marginally associated with different sexes. A total of 111 alkaloids, including isomers, were detected in analysis of the individuals from the three species. The majority (47%) appear likely to be obtained from dietary mites, whereas many of the others (18%) are presumed to be from ants, and a few (4%) are from millipedes. Putative dietary sources for the remaining alkaloids are generally unknown, but beetles are probably the source of at least some of the tricyclic alkaloids (6%). In addition, alkaloid compositions from extracts of groups of individuals from five additional populations of M. baroni and from one population of M. bernhardi (Vences et al. 1994) and one population of M. cowanii (Boulenger 1882) were examined. An additional 50 alkaloids, including isomers, were detected in the combined samples, bringing the total number of alkaloids identified from these four species of mantellid frogs to 161. Alkaloid compositions in mantellid poison frogs are diverse and highly dependent on geographic location that appear to be largely determined by the nature and availability of alkaloid-containing prey items. C1 [Daly, John W.; Garraffo, H. Martin; Spande, Thomas F.; Giddings, Lesley-Ann] NIDDK, Bioorgan Chem Lab, NIH, HHS, Bethesda, MD 20892 USA. [Vences, Miguel] Tech Univ Carolo Wilhelmina Braunschweig, Inst Zool, Div Evolutionary Biol, D-38106 Braunschweig, Germany. [Saporito, Ralph A.] Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. [Vieites, David R.] Univ Calif Berkeley, Museum Vertebrate Zool, Berkeley, CA 94720 USA. [Vieites, David R.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. RP Vences, M (reprint author), NIDDK, Bioorgan Chem Lab, NIH, HHS, Bethesda, MD 20892 USA. EM m.vences@tu-bs.de RI Vieites, David/B-4481-2009; OI Vieites, David/0000-0001-5551-7419; Vences, Miguel/0000-0003-0747-0817 FU Intramural NIH HHS NR 43 TC 19 Z9 19 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD FEB PY 2008 VL 34 IS 2 BP 252 EP 279 DI 10.1007/s10886-007-9396-9 PG 28 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA 261AD UT WOS:000253050600015 PM 18196341 ER PT J AU Rodriguez-Ropero, F Zanuy, D Casanovas, J Nussinov, R Aleman, C AF Rodriguez-Ropero, Francisco Zanuy, David Casanovas, Jordi Nussinov, Ruth Aleman, Carlos TI Application of 1-aminocyclohexane carboxylic acid to protein nanostructure computer design SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID MOLECULAR-DYNAMICS; C-ALPHA,ALPHA-DIALKYLATED GLYCINES; CONFORMATIONAL PROPERTIES; STRUCTURAL VERSATILITY; LINEAR OLIGOPEPTIDES; AMINO-ACIDS; PEPTIDES; HOMOPEPTIDES; DENSITY; ANALOGS AB Conformationally restricted amino acids are promising candidates to serve as basic pieces in redesigned protein motifs which constitute the basic modules in synthetic nanoconstructs.. Here we study the ability of constrained cyclic amino acid 1-aminocyclohexane-1-carboxylic acid (AC(6)c) to stabilize highly regular eta-helical motifs excised from naturally occurring Proteins. Calculations indicate that the conformational flexibility observed in both the ring and the main chain is significantly higher than that detected for other 1-aminocycloalkane-1-carboxylic acids (Ac(n)c, where n refers to the size of the ring) with smaller cycles. Incorporation of Ac(6)c into the flexible loops of P-helical motifs indicates that the stability of such excised building blocks as well as the nanoassemblies derived from them is significantly enhanced. Thus, the intrinsic Ac(6)c tendency to adopt folded conformations combined with the low structural strain of the cyclohexane ring confers the ability to both self-adapt to the beta-helix motif and to stabilize the overall structure by absorbing part of its conformational fluctuations. Comparison with other Ac(n)c residues indicates that the ability to adapt to the targeted position improves considerably with the ring size, i.e., when the rigidity introduced by the strain of the ring decreases. C1 [Rodriguez-Ropero, Francisco] Univ Politecn Cataluna, ETS Engn Ind Barcelona, Dept Engn, E-08028 Barcelona, Spain. [Casanovas, Jordi] Univ Lledia, Escola Politecn Super, Dept Quim, E-25001 Lleida, Spain. [Nussinov, Ruth] NCI FCRDC, Nanobiol Program, Ctr Canc Res, Basic Res Program,SAIC Frederick Inc, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Zanuy, D (reprint author), Univ Politecn Cataluna, ETS Engn Ind Barcelona, Dept Engn, E-08028 Barcelona, Spain. EM david.zanuy@upc.edu; carlos.aleman@upe.edu RI Rodriguez-Ropero, Francisco/F-2458-2011; Casanovas, Jordi/B-5435-2013; Zanuy, David/G-3930-2014 OI Rodriguez-Ropero, Francisco/0000-0001-7435-8986; Casanovas, Jordi/0000-0002-4914-9194; Zanuy, David/0000-0001-7704-2178 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01 CO012400, N01-CO-12400] NR 30 TC 15 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD FEB PY 2008 VL 48 IS 2 BP 333 EP 343 DI 10.1021/ci700291x PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 266IT UT WOS:000253428400010 PM 18201062 ER PT J AU Bhatia, SK Rezac, AJ Vitiello, B Sitorius, MA Buehler, BA Kratochvil, CJ AF Bhatia, Supriya K. Rezac, Amy J. Vitiello, Benedetto Sitorius, Michael A. Buehler, Bruce A. Kratochvil, Christopher J. TI Antidepressant prescribing practices for the treatment of children and adolescents SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; PEDIATRIC DEPRESSION; DOUBLE-BLIND; SUICIDE ATTEMPTS; RISK; FLUOXETINE; SERTRALINE AB Objective: This study evaluates pediatric antidepressant prescribing practices of Nebraska clinicians. Methods: Surveys were sent in July, :2005, to 1,521 prescribing clinicians throughout Nebraska to assess pediatric antidepressant use along with any practice changes following the U.S. Food and Drug Administration (FDA) "'black box" warning issued in October, 2004. Results: Over half (n = 866) of the clinicians responded to the survey, of which 96.8% reported awareness of the FDA "black box" warning. Of the respondents, 76.9% (n = 666) were prescribing antidepressants to children and/or adolescents. Clinicians reported decreased prescribing frequency for both children (15.5%) and adolescents (36.6%), with 36% having increased referrals to specialists. While 31.9% reported seeing patients more frequently upon initiation of antidepressants, only 7.5% reported weekly visits for the first month of treatment, as recommended by the FDA. Over one fifth (21.9%) reported a caregiver or patient had refused antidepressant medication treatment due to the FDA's warning. Conclusion: Clinicians in Nebraska report changes in clinical practice due to the issuance of the FDA "black box" warning, with at decrease in prescribing antidepressants to pediatric patients and an increase in referrals to specialists. Although awareness of the FDA's warning was evident among clinicians and patients, adherence to recommended guidelines was low. C1 [Bhatia, Supriya K.; Rezac, Amy J.; Sitorius, Michael A.; Buehler, Bruce A.; Kratochvil, Christopher J.] Univ Nebraska Med Ctr, Omaha, NE USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. RP Kratochvil, CJ (reprint author), Psychopharamacol Res Ctr, 985581 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ckratoch@unmc.edu NR 36 TC 23 Z9 24 U1 4 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB PY 2008 VL 18 IS 1 BP 70 EP 80 DI 10.1089/cap.2007.0049 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 273CC UT WOS:000253907000008 PM 18294090 ER PT J AU Maletkovic, J Schiffmann, R Gorospe, JR Gordon, ES Mintz, M Hoffman, EP Alper, G Lynch, DR Singhal, BS Harding, C Amartino, H Brown, CM Chan, A Renaud, D Geraghty, M Jensen, L Senbil, N Kadom, N Nazarian, J Feng, YJ Wang, ZY Hartka, T Morizono, H Vanderver, A AF Maletkovic, Jelena Schiffmann, Raphael Gorospe, J. Rafael Gordon, Erynn S. Mintz, Michelle Hoffman, Eric P. Alper, Gulay Lynch, David R. Singhal, Bhim S. Harding, Cary Amartino, Hernan Brown, Candida M. Chan, Alicia Renaud, Deborah Geraghty, Michael Jensen, Lloyd Senbil, Nesrin Kadom, Nadja Nazarian, Javad Feng, Yuanjian Wang, Zuyi Hartka, Thomas Morizono, Hiroki Vanderver, Adeline TI Genetic and clinical heterogeneity in eIF2B-related disorder SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE eIF2B; leukodystrophy; vanishing white matter disease; leukoencephalopathy ID VANISHING WHITE-MATTER; ADULT-ONSET LEUKOENCEPHALOPATHY; GUANINE-NUCLEOTIDE EXCHANGE; UNFOLDED PROTEIN RESPONSE; INITIATION-FACTOR EIF2B; CHILDHOOD ATAXIA; DISEASE; MUTATIONS; ACTIVATION; LEUKODYSTROPHIES AB Eukaryotic initiation factor 2B (eIF2B)-related disorders are heritable white matter disorders with a variable clinical phenotype (including vanishing white matter disease and ovarioleukodystrophy) and an equally heterogeneous genotype. We report 9 novel mutations in the EIF2B genes in our subject population, increasing the number of known mutations to more than 120. Using homology modeling, we have analyzed the impact of novel mutations on the 5 subunits of the eIF2B protein. Although recurrent mutations have been found at CpG dinucleotides in the EIF2B genes, the high incidence of private or low frequency mutations increases the challenge of providing rapid genetic confirmation of this disorder, and limits the application of EIF2B screening in cases of undiagnosed leukodystrophy. C1 [Maletkovic, Jelena; Gorospe, J. Rafael; Gordon, Erynn S.; Mintz, Michelle; Hoffman, Eric P.; Nazarian, Javad; Feng, Yuanjian; Wang, Zuyi; Hartka, Thomas; Morizono, Hiroki; Vanderver, Adeline] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Genet Med, Washington, DC 20010 USA. [Kadom, Nadja] Dept Radiol, Washington, DC USA. [Schiffmann, Raphael] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. [Alper, Gulay] Childrens Hosp Pittsburgh, Div Child Neurol, Pittsburgh, PA USA. [Lynch, David R.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Singhal, Bhim S.] Bombay Hosp Inst Med Sci, Dept Neurol, Bombay, Maharashtra, India. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Amartino, Hernan] Fdn Estudio Enfermedades Neurometab, Buenos Aires, DF, Argentina. [Brown, Candida M.] Childrens Hosp Oakland, Div Neurol, Oakland, CA USA. [Chan, Alicia] Univ Alberta, Med Genet Clin, Edmonton, AB, Canada. [Renaud, Deborah] Mayo Clin, Dept Neurol, Rochester, MN USA. [Geraghty, Michael] Childrens Hosp Eastern Ontario, Genet Clin, Ottawa, ON K1H 8L1, Canada. [Jensen, Lloyd] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Senbil, Nesrin] Dr Sami Ulus Childrens Hosp, Dept Child Neurol, Ankara, Turkey. RP Vanderver, A (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Genet Med, 111 Michigan Ave NW, Washington, DC 20010 USA. EM avanderv@cnmc.org OI Kadom, Nadja/0000-0002-7073-956X FU Intramural NIH HHS; NICHD NIH HHS [HD-P30-40677, 1P30HD40677-01, K12HD001399] NR 53 TC 28 Z9 31 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD FEB PY 2008 VL 23 IS 2 BP 205 EP 215 DI 10.1177/0883073807308705 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 275FK UT WOS:000254057100012 PM 18263758 ER PT J AU Lau, JYF Eley, TC AF Lau, Jennifer Y. F. Eley, Thalia C. TI Disentangling gene-environment correlations and interactions on adolescent depressive symptoms SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE gene-environment interaction; gene-environment correlation; adolescence; depressive symptoms ID LIFE EVENTS; CHILDHOOD; TWIN; PSYCHOPATHOLOGY; MODERATION; ETIOLOGY; STRESS; SAMPLE; GIRLS; MOOD AB Background: Genetic risks for depression may be expressed through greater exposure towards environmental stressors (gene-environment correlation, rGE) and increased susceptibility to these stressors (gene-environment interaction, G x E). While these effects are often studied independently, evidence supports their co-occurrence on depression. Methods: Adolescent twin and sibling data was used to assess correlations and interactions between genetic risks for depressive symptoms and two putative environmental stressors: dependent negative life events and maternal punitive discipline. Results: Moderate genetic effects influenced each environmental risk factor, consistent with rGE. Genetic effects on environmental risks also contributed to depressive outcomes, implying genetic correlations between measures. Genetic effects on depressive symptoms changed across levels of negative life events and maternal punitive discipline, consistent with G x E. Finally, G x E co-occurred with rGE on depressive outcomes. Conclusions: Adolescents at genetic risk for depressive phenotypes may be exposed to increased social adversity (rGE) and more susceptible to developing symptoms in response to these risks (G x E). C1 [Lau, Jennifer Y. F.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Lau, Jennifer Y. F.; Eley, Thalia C.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. RP Lau, JYF (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K N Dr, Bethesda, MD 20892 USA. EM lauj@mail.nih.gov RI Eley, Thalia/D-4811-2011 FU Medical Research Council [G120/635] NR 29 TC 46 Z9 48 U1 1 U2 18 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD FEB PY 2008 VL 49 IS 2 BP 142 EP 150 DI 10.1111/j.1469-7610.2007.01803.x PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 279KI UT WOS:000254353700005 PM 18211276 ER PT J AU Parise, RA Beumer, JH Kangani, CO Holleran, JL Eiseman, JL Smith, NF Covey, JA Perrine, SP Egorin, MJ AF Parise, Robert A. Beumer, Jan H. Kangani, Cyrous O. Holleran, Julianne L. Eiseman, Julie L. Smith, Nicola F. Covey, Joseph A. Perrine, Susan P. Egorin, Merrill J. TI Liquid chromatography-mass spectrometric assay for quantitation of the short-chain fatty acid, 2,2-dimethylbutyrate (NSC 741804), in rat plasma SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE dimethylbutyrate; metabolism; mass spectrometry; validation; fatty acid; sickle cell disease; thalassemia ID FETAL-HEMOGLOBIN PRODUCTION; ORAL SODIUM PHENYLBUTYRATE; BETA-THALASSEMIA MAJOR; GLOBIN GENE-EXPRESSION; ERYTHROID PROGENITORS; BUTYRATE THERAPY; DERIVATIVES; INDUCTION; PROGRESS AB 2,2-Dimethylbutyrate (DNM) is a potential treatment for thalassemia and hemoglobinopathies. To facilitate pharmacokinetic evaluation of DMB, we developed an LC-MS assay and quantitated DMB in plasma of rats after an oral dose of 500 mg/kg. After acetonitrile protein precipitation, DMB and dimethylvaleric acid (DMV) internal standard were derivatized to benzylamides, chromatographed on a Hydro-RP column with acetonitrile, water, and 0.1% formic acid, and detected by electrospray positive-mode ionization mass spectrometry. The assay was accurate (97-107%) and precise (3.4-6.2%) between 100 and 10,000 ng/mL. Recovery from plasma was >62%. Plasma freeze-thaw and room temperature stability were acceptable. (c) 2007 Elsevier B.V. All rights reserved. C1 [Parise, Robert A.; Beumer, Jan H.; Holleran, Julianne L.; Eiseman, Julie L.; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. [Parise, Robert A.; Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. [Kangani, Cyrous O.] Univ Pittsburgh, Sch Med, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15213 USA. [Eiseman, Julie L.; Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. [Smith, Nicola F.; Covey, Joseph A.] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. [Perrine, Susan P.] Boston Univ, Sch Med, Canc Res Ctr, Boston, MA 02118 USA. [Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Med, Pittsburgh, PA 15213 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G27E,Hillman Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM egorinmj@msx.upmc.edu OI Beumer, Jan/0000-0002-8978-9401 FU NCI NIH HHS [N01 CM052202, N01-CM52202, N01CM52202, P30 CA047904, P30 CA047904-209021, P30 CA47904] NR 25 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD FEB 1 PY 2008 VL 862 IS 1-2 BP 168 EP 174 DI 10.1016/j.jchromb.2007.12.002 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 265JF UT WOS:000253354200020 PM 18155649 ER PT J AU Gardner, ER Dahut, W Figg, WD AF Gardner, Erin R. Dahut, William Figg, William D. TI Quantitative determination of total and unbound paclitaxel in human plasma following Abraxane treatment SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE albumin; nanoparticle; paclitaxel; taxane; anticancer; formulation; LC-MS/MS; unbound fraction; free fraction ID CANCER AB A simple, rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay was developed and validated for the quantification of both unbound and total paclitaxel in plasma following treatment with Abraxane (ABI-007) or Taxol. Accurate and reproducible analysis of ABI-007, an albumin nanoparticle formulation of paclitaxel could not be achieved using previously published methodology designed for Taxol. The final validated method involved protein precipitation followed by vacuum filtration, in a 96-well format for rapid processing. The 4 min run employed gradient elution on a Waters SymmetryShield C8 (2.1 mm x 50 mm, 3.5 mu m) column, followed by tandem mass spectrometric detection, in electrospray positive mode. Calibrator samples were prepared daily with paclitaxel and analyzed with both ABI-007 and paclitaxel quality control samples. To measure unbound drug, sample preparation was preceded by ultrafiltration. The assay was linear over the range of 10-2500 ng/mL, with dilution providing measurement up to 50,000 ng/mL. Within-run and between-run precision for all QC samples was less than 5.0% and 10.4%, respectively. Accuracy was high, with deviation of less than 6.1% for all QCs. Measurement of unbound paclitaxel was precise (BRP and WRP <10%). (C) 2008 Elsevier B.V. All rights reserved. C1 [Dahut, William; Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Med Oncol Div, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, SAIC Frederick Inc, Clin Pharmacol Program, Frederick, MD 21702 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Ctr Canc Res, Med Oncol Div, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [NIH0011335962, Z01 SC006536-06]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 10 TC 28 Z9 33 U1 2 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD FEB 1 PY 2008 VL 862 IS 1-2 BP 213 EP 218 DI 10.1016/j.jchromb.2007.12.013 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 265JF UT WOS:000253354200026 PM 18191625 ER PT J AU Nesterova, M Bossis, I Wen, F Horvath, A Matyakhina, L Stratakis, CA AF Nesterova, Maria Bossis, Ioannis Wen, Feng Horvath, Anelia Matyakhina, Ludmila Stratakis, Constantine A. TI An immortalized human cell line bearing a PRKAR1A-inactivating mutation: Effects of overexpression of the wild-type allele and other protein kinase A subunits SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NODULAR ADRENOCORTICAL DISEASE; CARNEY COMPLEX; REGULATORY SUBUNIT; CUSHINGS-SYNDROME; PRKAR1A GENE; ADRENAL-HYPERPLASIA; ENDOCRINE; TUMORS; 1A; PROLIFERATION AB Context: Inactivating mutations of PRKAR1A, the regulatory subunit type 1 A (RI alpha) of protein kinase A (PKA), are associated with tumor formation. Objective: Our objective was to evaluate the role of PKA isozymes on proliferation and cell cycle. Methods: A cell line with RI alpha haploinsufficiency due to an inactivating PRKAR1A mutation (IVS2+1 G -> A) was transfected with constructs encoding PKA subunits. Genetics, PKA subunit mRNA and protein expression and proliferation, aneuploidy, and cell cycle status were assessed. To identify factors that mediate PKA-associated cell cycle changes, we studied E2F and cyclins expression in transfected cells and E2F's role by small interfering RNA; we also assessed cAMP levels and baseline and stimulated cAMP signaling in transfected cells. Results: Introduction of PKA subunits led to changes in proliferation and cell cycle: a decrease in aneuploidy and G(2)/M for the PRKAR1A-transfected cells and an increase in S phase and aneuploidy for cells transfected with PRKAR2B, a known PRKAR1A mutant (RI alpha P), and the PKA catalytic subunit. There were alterations in cAMP levels, PKA subunit expression, cyclins, and E2F factors; E2F1 was shown to possibly mediate PKA effects on cell cycle by small interfering RNA studies. cAMP levels and constitutive and stimulated cAMP signaling were altered in transfected cells. Conclusion: This is the first immortalized cell line with a naturally occurring PRKAR1A-inactivating mutation that is associated in vivo with tumor formation. PKA isozyme balance is critical for the control of cAMP signaling and related cell cycle and proliferation changes. Finally, E2F1 may be a factor that mediates dysregulated PKA's effects on the cell cycle. C1 [Nesterova, Maria; Bossis, Ioannis; Horvath, Anelia; Matyakhina, Ludmila; Stratakis, Constantine A.] NICHD, NIH, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet,Dev Endrocrinol Branch, Bethesda, MD 20892 USA. [Wen, Feng] NCI, NIH, Basic Res Lab, Cellular Biochem Sect, Bethesda, MD 20892 USA. RP Nesterova, M (reprint author), NICHD, NIH, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet,Dev Endrocrinol Branch, Bldg 10,CRC,Room 1-3216,Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM nesterom@mail.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD000642, Z01-HD-000642-04] NR 30 TC 22 Z9 23 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2008 VL 93 IS 2 BP 565 EP 571 DI 10.1210/jc.2007-1902 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 262RN UT WOS:000253165800036 PM 18056771 ER PT J AU Watanabe, T Asano, N Murray, PJ Ozato, K Tailor, P Fuss, IJ Kitani, A Strober, W AF Watanabe, Tomohiro Asano, Naolki Murray, Peter J. Ozato, Keiko Tailor, Prafullakurnar Fuss, Ivan J. Kitani, Atsushi Strober, Warren TI Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; IFN REGULATORY FACTOR-4; TOLL-LIKE RECEPTORS; CROHNS-DISEASE; T-CELLS; NEGATIVE REGULATOR; DENDRITIC CELLS; NOD2; INDUCTION; RESPONSES AB The mechanisms underlying the susceptibility of individuals with caspase recruitment domain 15 (CARD15) mutations and corresponding abnormalities of nucleotide-binding oligomerization domain 2 (NOD2) protein to Crohn disease are still poorly understood. One possibility is based on previous studies showing that muramyl dipeptide (MDP) activation of NOD2 negatively regulates TLR2 responses and that absence of such regulation leads to heightened Th1 responses. We now report that administration of MDP protects mice from the development of experimental colitis by downregulating multiple TLR responses, not just TLR2. The basis of these in vivo findings was suggested by in vitro studies of DCs, in which we showed that prestimulation of cells with MDP reduces cytokine responses to multiple TLR ligands and this reduction is dependent on enhanced IFN regulatory factor 4 (IRF4) activity. Further studies of mouse models of colitis showed that this inhibitory role of IRF4 does in fact apply to MDP-mediated protection from colitis, since neither IRF4-deficient mice nor mice treated with siRNA specific for IRF4 were protected. These findings indicate that MDP activation of NOD2 regulates innate responses to intestinal microflora by downregulating multiple TLR responses and suggest that the absence of such regulation leads to increased susceptibility to Crohn disease. C1 [Watanabe, Tomohiro; Asano, Naolki; Fuss, Ivan J.; Kitani, Atsushi] NIAID, NIH, Host Def Lab, Mucosal Immun Sect, Bethesda, MD 20892 USA. [Watanabe, Tomohiro] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan. [Murray, Peter J.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Ozato, Keiko; Tailor, Prafullakurnar] NICHHD, NIH, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, NIH, Host Def Lab, Mucosal Immun Sect, Bldg 10-CRC Room 5W940,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov OI Asano, Naoki/0000-0003-4452-8459 NR 48 TC 200 Z9 203 U1 1 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 FEB PY 2008 VL 118 IS 2 BP 545 EP 559 DI 10.1172/JC133145 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 257CS UT WOS:000252777400023 PM 18188453 ER PT J AU Zudaire, E Cuesta, N Murty, V Woodson, K Adarns, L Gonzalez, N Martinez, A Narayan, G Kirsch, I Franklin, W Hirsch, F Birrer, M Cuttittal, F AF Zudaire, Enrique Cuesta, Natalia Murty, Vundavalli Woodson, Karen Adarns, Lisa Gonzalez, Nieves Martinez, Alfredo Narayan, Gopeshwar Kirsch, Ilan Franklin, Wilbur Hirsch, Fred Birrer, Michael Cuttittal, Frank TI The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID AH DIOXIN RECEPTOR; GERM-CELL TUMORS; COLORECTAL-CANCER; CHROMOSOME 5P; HUMAN OVARIAN; EXPRESSION; HETEROZYGOSITY; DELETION; GROWTH; MICE AB The aryl hydrocarbon receptor repressor (AHRR) is a bHLH/Per-ARNT-Sim transcription factor located in a region of chromosome 5 (5p15.3) that has been proposed to contain one or more tumor suppressor genes. We report here consistent downregulation of AHRR mRNA in human malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, and ovary, and demonstrate DNA hypermethylation as the regulatory mechanism of AHRR gene silencing. Knockdown of AHRR gene expression in a human lung cancer cell line using siRNA significantly enhanced in vitro anchorage-dependent and -independent cell growth as well as cell growth after transplantation into immunocompromised mice. In addition, knockdown of AHRR in non-clonable normal human mammary epithelial cells enabled them to grow in an anchorage-independent manner. Further, downregulation of AHRR expression in the human lung cancer cell line conferred resistance to apoptotic signals and enhanced motility and invasion in vitro and angiogenic potential in vivo. Ectopic expression of AHRR in tumor cells resulted in diminished anchorage-dependent and -independent cell growth and reduced angiogenic potential. These results therefore demonstrate that AHRR is a putative new tumor suppressor gene in multiple types of human cancers. C1 [Zudaire, Enrique; Cuttittal, Frank] NCI, NIH, Gaithersburg, MD USA. [Cuesta, Natalia] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Murty, Vundavalli; Narayan, Gopeshwar] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. [Woodson, Karen; Adarns, Lisa] NCI, Genet Branch, Bethesda, MD 20892 USA. [Gonzalez, Nieves] NIDDK, NIH, Bethesda, MD USA. [Martinez, Alfredo] CSIC, Inst Cajal, Dept Cell Biol & Neuroanat, E-28002 Madrid, Spain. [Kirsch, Ilan; Birrer, Michael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Franklin, Wilbur; Hirsch, Fred] Univ Colorado, Ctr Canc, Aurora, CO USA. RP Zudaire, E (reprint author), NCI, Ctr Adv Technol, NIH, NCI Angiogenesis Core Facil, Suite 115, Bethesda, MD 20892 USA. EM zudairee@mail.nih.gov RI Cuesta, Natalia/C-1358-2012; Martinez, Alfredo/A-3077-2013; Cuesta, Natalia/J-7761-2015; Cuttitta, Frank/B-4758-2016 OI Martinez, Alfredo/0000-0003-4882-4044; Cuesta, Natalia/0000-0003-0809-2934; FU NCI NIH HHS [5P50 CA 058187, P50 CA058187] NR 51 TC 94 Z9 97 U1 0 U2 6 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 FEB PY 2008 VL 118 IS 2 BP 640 EP 650 DI 10.1172/JCI30024 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 257CS UT WOS:000252777400031 PM 18172554 ER PT J AU Tanaka, N Moriya, K Kiyosawa, K Koike, K Gonzalez, FJ Aoyama, T AF Tanaka, Naoki Moriya, Kyoji Kiyosawa, Kendo Koike, Kazuhiko Gonzalez, Frank J. Aoyama, Toshifurni TI PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID C VIRUS-INFECTION; DENSITY LIPOPROTEIN SECRETION; X-RECEPTOR-ALPHA; PEROXISOME-PROLIFERATOR; TRANSGENIC MICE; TRANSCRIPTIONAL ACTIVITY; INSULIN-RESISTANCE; UNITED-STATES; MOUSE-LIVER; HEPATOCARCINOGENESIS AB Transgenic mice expressing HCV core protein develop hepatic steatosis and hepatocellular carcinoma (HCC), but the mechanism underlying this process remains unclear. Because PPAR alpha is a central regulator of triglyceride homeostasis and mediates hepatocarcinogenesis in rodents, we determined whether PPAR alpha contributes to HCV core protein-induced diseases. We generated PPAR alpha-homozygous, -heterozygous, and -null mice with liver-specific transgenic expression of the core protein gene (Ppara(+/+):HCVcpTg, Ppara(-/-):HCVcpTg, and Ppara(-/-):HCVcpTg mice. Severe steatosis was unexpectedly observed only in Ppara+/+:HCVcpTg mice, which resulted from enhanced fatty acid uptake and decreased mitochondrial beta-oxidation due to breakdown of mitochondrial outer membranes. Interestingly, HCC developed in approximately 35% of 24-month-old Pparat(+/+): HCVcpTg mice, but tumors were not observed in the other genotypes. These phenomena were found to be closely associated with sustained PPAR alpha activation. In Ppara(+/-):HCVcpTg mice, PPAR alpha activation and the related changes did not occur despite the presence of a functional Ppara allele. However, long-term treatment of these mice with clofibrate, a PPAR alpha activator, induced HCC with mitochondrial abnormalities and hepatic steatosis. Thus, our results indicate that persistent activation of PPAR alpha is essential for the pathogenesis of hepatic steatosis and HCC induced by HCV infection. C1 [Tanaka, Naoki; Aoyama, Toshifurni] Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metabol Regulat, Matsumoto, Nagano 3908621, Japan. [Tanaka, Naoki; Kiyosawa, Kendo] Shinshu Univ, Sch Med, Dept Internal Med, Div Gastroenterol, Matsumoto, Nagano 3908621, Japan. [Moriya, Kyoji; Koike, Kazuhiko] Univ Tokyo, Grad Sch Med, Dept Infect Dis Internal Med, Tokyo, Japan. [Gonzalez, Frank J.] NCI, Met Lab, NIH, Bethesda, MD 20892 USA. RP Tanaka, N (reprint author), Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metabol Regulat, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan. EM naopi@hsp.md.shinshu-u.ac.jp NR 54 TC 137 Z9 139 U1 2 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 FEB PY 2008 VL 118 IS 2 BP 683 EP 694 DI 10.1172/JCI33594 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 257CS UT WOS:000252777400035 PM 18188449 ER PT J AU Santos, N Honma, S Timenetsky, MDST Linhares, AC Ushijima, H Armah, GE Gentsch, JR Hoshino, Y AF Santos, Norma Honma, Shinjiro Timenetsky, Maria do Carmo S. T. Linhares, Alexandre C. Ushijima, Hiroshi Armah, George E. Gentsch, Jon R. Hoshino, Yasutaka TI Development of a microtiter plate hybridization-based PCR-enzyme-linked Immunosorbent assay for identification of clinically relevant human group A rotavirus G and P genotypes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; HIGH-FREQUENCY; VP7 GENE; MOLECULAR EPIDEMIOLOGY; HUMAN PAPILLOMAVIRUSES; REASSORTANT VACCINE; MIXED INFECTIONS; UNUSUAL STRAINS; UNITED-STATES; CHILDREN AB A microtiter plate hybridization-based PCR-enzyme-linked immunosorbent assay (PCR-ELISA) has been used for the detection and identification of a variety of microorganisms. Here, we report the development of a PCR-ELISA for the identification of clinically relevant human rotavirus VP7 (G1 to G6, G8 to G10, and G12) and VP4 (P[4], P[6], P[8], P[9], and P[14]) genotypes. The G and P types of reference human and animal rotavirus strains for which specific probes were available were correctly identified by the PCR-ELISA. In addition, reference strains bearing G or P genotypes for which specific probes were unavailable, such as G11, G14, P[3], P[10], and P[11], did not display any cross-reactivity to the probes. The usefulness of the assay was further evaluated by analyzing a total of 396 rotavirus-positive stool samples collected in four countries: Brazil, Ghana, Japan, and the United States. The results of this study showed that the PCR-ELISA was sensitive and easy to perform without the use of any expensive and sophisticated equipment, the reagents used are easy to obtain commercially and advantageous over multiplex PCR since more than one type-specific probe is used and the selection of probes is more flexible. C1 [Santos, Norma] Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, BR-21941590 Rio De Janeiro, Brazil. [Santos, Norma; Honma, Shinjiro; Hoshino, Yasutaka] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Timenetsky, Maria do Carmo S. T.] Inst Adolfo Lutz Registro, Sao Paulo, Brazil. [Linhares, Alexandre C.] Secretaria Vigilancia Saude, Inst Evandro Chagas, Belem, Para, Brazil. [Ushijima, Hiroshi] Univ Tokyo, Tokyo, Japan. [Armah, George E.] Univ Ghana, Noguchi Mem Inst Med Res, Legon, Ghana. [Gentsch, Jon R.] CDC, Coordinating Ctr Infect Dis, Natl Ctr Immunizat & Resp Dis, Div Viral Dis,Gastroenteritis & Resp Viruses Lab, Atlanta, GA 30333 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, Cidade Univ,CCS-Bl I, BR-21941590 Rio De Janeiro, Brazil. EM nsantos@micro.ufrj.br RI TIMENETSKY, MARIA/I-7593-2013; Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 FU Intramural NIH HHS NR 83 TC 23 Z9 26 U1 0 U2 0 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 FEB PY 2008 VL 46 IS 2 BP 462 EP 469 DI 10.1128/JCM.01361-07 PG 8 WC Microbiology SC Microbiology GA 261SM UT WOS:000253100300010 PM 18057127 ER PT J AU Page-Shafer, K Pappalardo, BL Tobler, LH Phelps, BH Edlin, BR Moss, AR Wright, TL Wright, DJ O'Brien, TR Caglioti, S Busch, MP AF Page-Shafer, Kimberly Pappalardo, Brandee L. Tobler, Leslie H. Phelps, Bruce H. Edlin, Brian R. Moss, Andrew R. Wright, Teresa L. Wright, David J. O'Brien, Thomas R. Caglioti, Sally Busch, Michael P. TI Testing strategy to identify cases of acute hepatitis C virus (HCV) infection and to project HCV incidence rates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INJECTION-DRUG USERS; SAN-FRANCISCO; BLOOD-DONORS; RISK-FACTORS; HIV-1 INFECTION; UNITED-STATES; PREVALENCE; ANTIBODY; VIREMIA; RNA AB Surveillance for hepatitis C virus (HCV) is limited by the challenge of differentiating between acute and chronic infections. In this study, we evaluate a cross-sectional testing strategy that identifies individuals with acute HCV infection and we estimate HCV incidence. Anti-HCV-negative persons from four populations with various risks, i.e., blood donors, Veterans Administration (VA) patients, young injection drug users (IDU), and older IDU, were screened for HCV RNA by minipool or individual sample nucleic acid testing (NAT). The number of detected viremic seronegative infections was combined with the duration of the preseroconversion NAT-positive window period (derived from analysis of frequent serial samples from plasma donors followed from NAT detection to seroconversion) to estimate annual HCV incidence rates. Projected incidence rates were compared to observed incidence rates. Projected HCV incidence rates per 100 person-years were 0.0042 (95% confidence interval [95% CI], 0.0025 to 0.007) for blood donors, 0.86 (95% CI, 0.02 to 0.71) for VA patients, 39.8 (95% CI, 25.9 to 53.7) for young IDU, and 53.7 (95% CI, 23.4 to 108.8) for older IDU. Projected rates were most similar to observed incidence rates for young IDU (33.4; 95% CI, 28.0 to 39.9). This study demonstrates the value of applying a cross-sectional screening strategy to detect acute HCV infections and to estimate HCV incidence. C1 [Pappalardo, Brandee L.; Tobler, Leslie H.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Page-Shafer, Kimberly; Edlin, Brian R.; Moss, Andrew R.; Wright, Teresa L.; Busch, Michael P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Phelps, Bruce H.] Chiron Corp, Emeryville, CA 94608 USA. [Edlin, Brian R.] Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY USA. [Wright, Teresa L.] Vet Adm Med Ctr, San Francisco, CA 94121 USA. [Wright, Teresa L.] Westat Corp, Rockville, MD USA. [O'Brien, Thomas R.] NCI, Natl Inst Hlth, Div Canc Epidemiol & Genet, Viral Epidemiol Branch,Dept Hlth & Human Serv, Rockville, MD USA. [Caglioti, Sally; Busch, Michael P.] Blood Syst Inc, Scottsdale, AZ USA. RP Busch, MP (reprint author), Blood Syst Res Inst, 270 Mason Ave, San Francisco, CA 94118 USA. EM Mbusch@bloodsystems.org OI Edlin, Brian/0000-0001-8172-8797; Page, Kimberly/0000-0002-7120-1673 FU CSAT SAMHSA HHS [H79-TI1Z103]; NHLBI NIH HHS [R01 HL076902, R01-HL-076902-01]; NIDA NIH HHS [R01 DA009532, R01 DA013245, R01 DA016017, R01 DA016159, R01-DA-016017-03A1, R01-DA09532, R01-DA13245, R01-DA16159] NR 54 TC 60 Z9 60 U1 1 U2 1 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 FEB PY 2008 VL 46 IS 2 BP 499 EP 506 DI 10.1128/JCM.01229-07 PG 8 WC Microbiology SC Microbiology GA 261SM UT WOS:000253100300016 PM 18032621 ER PT J AU Wood, BJ Rizzo-Price, P Holden, J Hardick, A Quinn, TC Gaydos, CA AF Wood, Billie Jo Rizzo-Price, Patricia Holden, Jeff Hardick, Andrew Quinn, Thomas C. Gaydos, Charlotte A. TI The microbicide tenofovir does not inhibit nucleic acid amplification tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine samples SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; SIMIAN IMMUNODEFICIENCY VIRUS; VAGINAL TRANSMISSION; NEWBORN MACAQUES; HIV-INFECTION; PREVENTION; SPECIMENS; EFFICACY; SAFETY; WOMEN AB The potential inhibitory effects of tenofovir and a placebo were examined using the Becton Dickinson ProbeTec, Gen-Probe Aptima Combo 2, and Roche Amplicor tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae. Concentrations of 5% to 0% of tenofovir and the placebo were added to dilutions of C. trachomatis and N. gonorrhoeae. No appreciable inhibition was observed. C1 [Wood, Billie Jo; Rizzo-Price, Patricia; Holden, Jeff; Hardick, Andrew; Quinn, Thomas C.; Gaydos, Charlotte A.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Gaydos, CA (reprint author), 720 Rutland Ave,1159 Ross, Baltimore, MD 21205 USA. EM cgaydos@jhmi.edu RI Gaydos, Charlotte/E-9937-2010 FU NIAID NIH HHS [U01 AI068613, U01 AI 68613-01C, U01 AI068613-02] NR 20 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2008 VL 46 IS 2 BP 763 EP 765 DI 10.1128/JCM.01867-07 PG 3 WC Microbiology SC Microbiology GA 261SM UT WOS:000253100300056 PM 18057133 ER PT J AU Korn, EL Liu, PY Lee, SJ Chapman, JAW Niedzwiecki, D Suman, VJ Moon, J Sondak, VK Atkins, MB Eisenhauer, EA Parulekar, W Markovic, SN Saxman, S Kirkwood, JM AF Korn, Edward L. Liu, Ping-Yu Lee, Sandra J. Chapman, Judith-Anne W. Niedzwiecki, Donna Suman, Vera J. Moon, James Sondak, Vernon K. Atkins, Michael B. Eisenhauer, Elizabeth A. Parulekar, Wendy Markovic, Svetomir N. Saxman, Scott Kirkwood, John M. TI Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AMERICAN JOINT COMMITTEE; SOUTHWEST-ONCOLOGY-GROUP; PROGNOSTIC-FACTORS; MALIGNANT-MELANOMA; CLINICAL-TRIALS; END-POINT; DESIGNS AB Purpose Objective tumor response rates observed in phase II trials for metastatic melanoma have historically not provided a reliable indicator of meaningful survival benefits. To facilitate using overall survival ( OS) or progression-free survival ( PFS) as an endpoint for future phase II trials, we evaluated historical data from cooperative group phase II trials to attempt to develop benchmarks for OS and PFS as reference points for future phase II trials. Patients and Methods Individual-level and trial-level data were obtained for patients enrolled onto 42 phase II trials ( 70 trial arms) that completed accrual in the years 1975 through 2005 and conducted by Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, North Central Cancer Treatment Group, and the Clinical Trials Group of the National Cancer Institute of Canada. Univariate and multivariate analyses were performed to identify prognostic variables, and between-trial(-arm) variability in 1-year OS rates and 6-month PFS rates were examined. Results Statistically significant individual-level and trial-level prognostic factors found in a multivariate survival analysis for OS were performance status, presence of visceral disease, sex, and whether the trial excluded patients with brain metastases. Performance status, sex, and age were statistically significant prognostic factors for PFS. Controlling for these prognostic variables essentially eliminated between-trial variability in 1-year OS rates but not in 6-month PFS rates. Conclusion Benchmarks are provided for 1-year OS or OS curves that make use of the distribution of prognostic factors of the patients in the phase II trial. A similar benchmark for 6-month PFS is provided, but its use is more problematic because of residual between-trial variation in this endpoint. C1 [Korn, Edward L.] NCI, Biometr Res Branch, EPN 8129, Div Canc Treatment & Diagnost, Bethesda, MD 20892 USA. SW Oncol Grp, Stat Off, Seattle, WA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. Queens Univ, Canc Clin Trials Grp, NCI, Kingston, ON, Canada. Canc & Leukemia Grp Stat Ctr B, Durham, NC USA. Mayo Clin, Rochester, MN USA. Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Peace Corps, Washington, DC USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN 8129, Div Canc Treatment & Diagnost, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov FU NCATS NIH HHS [UL1 TR000005] NR 29 TC 319 Z9 327 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 527 EP 534 DI 10.1200/JCO.2007.12.7837 PG 8 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400006 PM 18235113 ER PT J AU Ramanathan, RK Egorin, MJ Takimoto, CHM Remick, SC Doroshow, JH LoRusso, PA Mulkerin, DL Grem, JL Hamilton, A Murgo, AJ Potter, DM Belani, CP Hayes, MJ Peng, B Ivy, SP AF Ramanathan, Ramesh K. Egorin, Merrill J. Takimoto, Chris H. M. Remick, Scot C. Doroshow, James H. LoRusso, Patricia A. Mulkerin, Daniel L. Grem, Jean L. Hamilton, Anne Murgo, Anthony J. Potter, Douglas M. Belani, Chandra P. Hayes, Michael J. Peng, Bin Ivy, S. Percy TI Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction: A study by the National Cancer Institute Organ Dysfunction Working Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID CHRONIC MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR; MAIN METABOLITE CGP-74588; HEPATIC-DYSFUNCTION; ANTICANCER AGENTS; C-KIT; TRIAL; DISPOSITION; PACLITAXEL AB Purpose To develop dosing guidelines and to evaluate the pharmacokinetics of imatinib in patients with liver dysfunction ( LD). Patients and Methods Patients ( N = 89) with varying solid tumors and liver function were stratified into four groups according to serum total bilirubin and AST and were treated with escalating doses of imatinib. Plasma and urine were assayed for concentrations of imatinib and its active metabolite, CGP74588. Results In the mild LD group, dose-limiting toxicity, specifically nausea/vomiting and fatigue, occurred in two patients at the 600 mg/d dose level. In the moderate and severe LD groups, the maximal dose evaluated was 300 mg/d. Grade 3 to 4 toxicities consisted primarily of liver function test elevations ( 24%), nausea/vomiting ( 10%), fatigue ( 6%), and edema ( 5%). After the first imatinib dose, the mean ( +/- SD) dose-normalized areas under the plasma concentration- time curve from time 0 to infinity ( AUC(0-infinity)) were 162 +/- 155, 171 +/- 72, 182 +/- 157, and 185 +/- 172 ( mu g/mL x h)/mg for normal, mild, moderate, and severe LD groups, respectively. Renal excretion of imatinib was less than 10% of the total dose in all groups. Conclusion Imatinib exposure ( as measured by the dose-normalized AUC) did not differ between patients with normal liver function and those with LD. The maximal recommended dose of imatinib for patients with mild LD is 500 mg/d. Dosing guidelines for patients with moderate and severe LD remain undetermined. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. Univ Texas San Antonio, San Antonio, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Wayne State Univ, Detroit, MI USA. Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. NYU, New York, NY USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD USA. Novartis Pharmaceut, E Hanover, NJ USA. RP Ramanathan, RK (reprint author), Translat Genom Res Inst, 13208 E Shea Blvd,Ste 100, Scottsdale, AZ 85259 USA. EM rramanathan@tgen.org OI Belani, Chandra/0000-0001-5049-5329 FU NCI NIH HHS [P30CA47904, U01 -CA62505, 5U0-1CA062487-14, U01 CA062491, U01-CA069853, U01-CA76642, UO1-CA062491, UO1-CA69855]; NCRR NIH HHS [5M01 RR 00056, M01 RR03186] NR 33 TC 45 Z9 45 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 563 EP 569 DI 10.1200/JCO.2007.11.0304 PG 7 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400011 PM 18235115 ER PT J AU Gibbons, J Egorin, MJ Ramanathan, RK Fu, PF Mulkerin, DL Shibata, S Takimoto, CHM Mani, S LoRusso, PA Grem, JL Pavlick, A Lenz, HJ Flick, SM Reynolds, S Lagattuta, TF Parise, RA Wang, YF Murgo, AJ Ivy, SP Remick, SC AF Gibbons, Joseph Egorin, Merrill J. Ramanathan, Ramesh K. Fu, Pingfu Mulkerin, Daniel L. Shibata, Stephen Takimoto, Chris H. M. Mani, Sridhar LoRusso, Patricia A. Grem, Jean L. Pavlick, Anna Lenz, Heinz-Josef Flick, Susan M. Reynolds, Sherrie Lagattuta, Theodore F. Parise, Robert A. Wang, Yanfeng Murgo, Anthony J. Ivy, S. Percy Remick, Scot C. TI Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of renal dysfunction: A study by the National Cancer Institute Organ Dysfunction Working Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; DERMATOFIBROSARCOMA PROTUBERANS; ALPHA-1-ACID GLYCOPROTEIN; SOLID TUMORS; C-KIT; GROWTH; STI571; FAILURE AB Purpose This study was undertaken to determine the safety, dose-limiting toxicities ( DLT), maximum-tolerated dose ( MTD), and pharmacokinetics of imatinib in cancer patients with renal impairment and to develop dosing guidelines for imatinib in such patients. Patients and Methods Sixty adult patients with advanced solid tumors and varying renal function ( normal, creatinine clearance [ CrCL] >= 60 mL/min; mild dysfunction, CrCL 40 to 59 mL/min; moderate dysfunction, CrCL 20 to 39 mL/min; and severe dysfunction, CrCL < 20 mL/min) received daily imatinib doses of 100 to 800 mg. Treatment cycles were 28 days long. Results The MTD was not reached for any group. DLTs occurred in two mild group patients ( 600 and 800 mg) and two moderate group patients ( 200 and 600 mg). Serious adverse events ( SAEs) were more common in the renal dysfunction groups than in the normal group ( P =.0096). There was no correlation between dose and SAEs in any group. No responses were observed. Several patients had prolonged stable disease. Imatinib exposure, expressed as dose-normalized imatinib area under the curve, was significantly greater in the mild and moderate groups than in the normal group. There was a positive correlation between serum alpha-1 acid glycoprotein ( AGP) concentration and plasma imatinib, and an inverse correlation between plasma AGP concentration and imatinib clearance. Urinary excretion accounted for 3% to 5% of the daily imatinib dose. Conclusion Daily imatinib doses up to 800 or 600 mg were well tolerated by patients with mild and moderate renal dysfunction, respectively, despite their having increased imatinib exposure. C1 Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Case Med Ctr, Univ Hosp, Ireland Canc Ctr, Case Comprehens Canc Ctr,Dev Therapeut Program, Cleveland, OH USA. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NYU, Kaplan Comprehens Canc Ctr, New York, NY USA. Wayne State Univ, Detroit, MI USA. NCI, Med Branch, Natl Naval Med Ctr, Bethesda, MD 20892 USA. NCI, Ctr Treatment & Evaluat Program, Div Canc Diag & Treatment, Rockville, MD USA. Novartis Pharmaceut, Florham Pk, NJ USA. RP Remick, SC (reprint author), W Virginia Univ, Mary Babb Randolph Canc Ctr, 1801 Hlth Sci S,POB 9300, Morgantown, WV 26506 USA. EM sremick@hsc.wvu.edu FU NCI NIH HHS [U01 CA062491, 5 U01 CA62505, 5U01CA069853, P30 CA043703, P30 CA47904, U01 CA062502, U01 CA099168, U01 CA62502, P30 CA43703]; NCRR NIH HHS [5M01 RR-00056, M01 RR-000080] NR 44 TC 59 Z9 61 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 570 EP 576 DI 10.1200/JCO.2007.13.3819 PG 7 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400012 PM 18235116 ER PT J AU Chaturvedi, AK Engels, EA Anderson, WF Gillison, ML AF Chaturvedi, Anil K. Engels, Eric A. Anderson, William F. Gillison, Maura L. TI Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID NECK-CANCER; ACCELERATED RADIOTHERAPY; OROPHARYNGEAL CANCERS; PROGNOSTIC-FACTOR; TONGUE CANCER; BIRTH COHORT; HEAD; RATES; SURVIVAL; INFECTION AB Purpose To investigate the impact of human papillomavirus ( HPV) on the epidemiology of oral squamous cell carcinomas ( OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival between potentially HPV-related and HPV-unrelated OSCC sites. Patients and Methods Data from nine Surveillance, Epidemiology, and End Results program registries ( 1973 to 2004) were used to classify OSCCs by anatomic site as potentially HPV-related ( n = 17,625) or HPV-unrelated ( n = 28,144). Joinpoint regression and age-period-cohort models were used to assess incidence trends. Life-table analyses were used to compare 2-year overall survival for HPV-related and HPV-unrelated OSCCs. Results HPV-related OSCCs were diagnosed at younger ages than HPV-unrelated OSCCs ( mean ages at diagnosis, 61.0 and 63.8 years, respectively; P <.001). Incidence increased significantly for HPV-related OSCC from 1973 to 2004 ( annual percentage change [ APC] = 0.80; P <.001), particularly among white men and at younger ages. By contrast, incidence for HPV-unrelated OSCC was stable through 1982 ( APC = 0.82; P =.186) and declined significantly during 1983 to 2004 ( APC = -1.85; P <.001). When treated with radiation, improvements in 2-year survival across calendar periods were more pronounced for HPV-related OSCCs ( absolute increase in survival from 1973 through 1982 to 1993 through 2004 for localized, regional, and distant stages = 9.9%, 23.1%, and 18.6%, respectively) than HPV-unrelated OSCCs ( 5.6%, 3.1%, and 9.9%, respectively). During 1993 to 2004, for all stages treated with radiation, patients with HPV-related OSCCs had significantly higher survival rates than those with HPV-unrelated OSCCs. Conclusion The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Gillison, ML (reprint author), Johns Hopkins Univ, Canc Res Bldg 1,Rm 3M 54A,1650 Orleans St, Baltimore, MD 21231 USA. EM gillima@jhmi.edu RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU Intramural NIH HHS NR 38 TC 657 Z9 671 U1 3 U2 37 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2008 VL 26 IS 4 BP 612 EP 619 DI 10.1200/JCO.2007.14.1713 PG 8 WC Oncology SC Oncology GA 276XQ UT WOS:000254177400018 PM 18235120 ER PT J AU Tagliaferro, P Morales, M AF Tagliaferro, Patricia Morales, Marisela TI Synapses between corticotropin-releasing factor-containing axon terminals and dopaminergic neurons in the ventral tegmental area are predominantly glutamatergic SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE dopamine; stress; reward; mesolimbic dopamine system ID STRESS-INDUCED RELAPSE; SELECTIVE ACTIVATION; BEHAVIORAL-RESPONSES; VESICULAR GLUTAMATE; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; DRUG SEEKING; RAT-BRAIN; COCAINE; SYSTEM AB Interactions between stress and the mesocorticolimbic dopamine (DA) system have been suggested from behavioral and electrophysiological studies. Because corticotropin-releasing factor (CRF) plays a role in stress responses, we investigated possible interactions between neurons containing CRF and those producing DA in the ventral tegmental area (VTA). We first investigated the cellular distribution of CRF in the VTA by immunolabeling VTA sections with anti-CRF antibodies and analyzing these sections by electron microscopy. We found CRF immunoreactivity present mostly in axon terminals establishing either symmetric or asymmetric synapses with VTA dendrites. We established that nearly all CRF asymmetric synapses are glutamatergic, insofar as the CRF-immunolabeled axon terminals in these synapses coexpressed the vesicular glutamate transporter 2, and that the majority of CRF symmetric synapses are GABAergic, insofar as the CRF-immunolabeled axon terminals in these synapses coexpressed glutamic acid decarboxylase, findings that are of functional importance. We then looked for synaptic interactions between CRF- and DA-containing neurons, by using antibodies against CRF and tyrosine hydroxylase (TH; a marker for DA neurons). We found that most synapses between CRF-immunoreactive axon terminals and TH neurons are asymmetric (in the majority likely to be glutamatergic) and suggest that glutamatergic neurons containing CRF may be part of the neuronal circuitry that mediates stress responses involving the mesocorticolimbic DA system. The presence of CRF synapses in the VTA offers a mechanism for interactions between the stress-associated neuropeptide CRF and the mesocorticolimbic DA system. C1 [Tagliaferro, Patricia; Morales, Marisela] Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Morales, M (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mmorales@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000508-01, NIH0011712076] NR 40 TC 61 Z9 61 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD FEB 1 PY 2008 VL 506 IS 4 BP 616 EP 626 DI 10.1002/cne.21576 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 246JH UT WOS:000252002800007 PM 18067140 ER PT J AU Johnson, L Genco, RJ Damsky, C Haden, NK Hart, S Hart, TC Shuler, CF Tedesco, LA AF Johnson, Lynn Genco, Robert J. Damsky, Caroline Haden, N. Karl Hart, Suzanne Hart, Thomas C. Shuler, Charles F. Tedesco, Lisa A. TI Genetics and its implications for clinical dental practice and education - Report of panel 3 of the Macy study SO JOURNAL OF DENTAL EDUCATION LA English DT Article ID SEVERE CHRONIC PERIODONTITIS; PATIENT SIMULATIONS; SUSCEPTIBILITY TEST C1 [Genco, Robert J.] SUNY Buffalo, Sch Dent Med, Buffalo, NY 14260 USA. [Genco, Robert J.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Damsky, Caroline] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hart, Thomas C.] NHGRI, NIH, Off Director, Bethesda, MD USA. [Shuler, Charles F.] Univ British Columbia, Fac Dent, Vancouver, BC V5Z 1M9, Canada. [Tedesco, Lisa A.] Emory Univ, Acad Affairs Grad Studies, Atlanta, GA 30322 USA. [Tedesco, Lisa A.] Emory Univ, Grad Sch, Atlanta, GA 30322 USA. RP Johnson, L (reprint author), Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. FU NIDCR NIH HHS [R13 DE017508-01] NR 32 TC 4 Z9 4 U1 0 U2 1 PU AMER DENTAL EDUCATION ASSOC PI WASHINGTON PA 1400 K STREET, NW, STE 1100, WASHINGTON, DC 20005 USA SN 0022-0337 J9 J DENT EDUC JI J. Dent. Educ. PD FEB PY 2008 VL 72 IS 2 SU S BP 86 EP 94 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 281NU UT WOS:000254505200016 PM 18250384 ER PT J AU Sonoyama, W Liu, Y Yamaza, T Tuan, RS Wang, S Shi, S Huang, GTJ AF Sonoyama, Wataru Liu, Yi Yamaza, Takayoshi Tuan, Rocky S. Wang, Songlin Shi, Songtao Huang, George T. -J. TI Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: A pilot study SO JOURNAL OF ENDODONTICS LA English DT Article DE apexogenesis; apical papilla; bone marrow mesenchymal stem cells; dental pulp stem cells; immature teeth; immunocytofluorescence; immunohistochemistry; mesenchymal stem cells; stem cells from the apical papilla ID DENTAL-PULP CELLS; IN-VITRO; BONE-MARROW; DIFFERENTIATION; PERIODONTITIS; REVASCULARIZATION; VIVO AB Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells or DPSCs) and deciduous teeth (stem cells from human exfoliated deciduous teeth). We recently discovered another type of MSCs in the apical papilla of human immature permanent teeth termed stem cells from the apical papilla (SCAP). Here, we further characterized the apical papilla tissue and stem cell properties of SCAP using histologic, immunohistochemical, and immunocytofluorescent analyses. We found that the apical papilla is distinctive to the pulp in terms of containing less cellular and vascular components than those in the pulp. Cells in the apical papilla proliferated 2- to 3-fold greater than those in the pulp in organ cultures. Both SCAP and DPSCs were as potent in osteo/dentinogenic differentiation as MSCs from bone marrows, whereas they were weaker in adipogenic potential. The immunophenotype of SCAP is similar to that of DPSCs on the osteo/dentinogenic and growth factor receptor gene profiles. Double-staining experiments showed that STRO-1 coexpressed with dentinogenic markers such as bone sialophosphoprotein, osteocalcin, and growth factors FGFR1 and TGF beta R1 in cultured SCAR Additionally, SCAP express a wide variety of neurogenic markers such as nestin and neurofilament M upon stimulation with a neurogenic medium. We conclude that SCAP are similar to DPSCs but a distinct source of potent dental stem/progenitor cells. Their implications in root development and apexogenesis are discussed. C1 [Huang, George T. -J.] Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Endodont Prosthodont & Operat Dent, Baltimore, MD 21201 USA. [Sonoyama, Wataru; Yamaza, Takayoshi; Shi, Songtao] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90089 USA. [Sonoyama, Wataru] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral & Maxillofacial Rehabil, Okayama, Japan. [Liu, Yi; Wang, Songlin] Capital Med Univ, Sch Stomatol, Salivary Gland Dis Ctr, Beijing, Peoples R China. [Liu, Yi; Wang, Songlin] Capital Med Univ, Sch Stomatol, Mol Lab Gene Therapy, Beijing, Peoples R China. [Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Huang, GTJ (reprint author), Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Endodont Prosthodont & Operat Dent, 650 W Baltimore St, Baltimore, MD 21201 USA. EM ghuang@umaryland.edu FU Intramural NIH HHS [NIH0011027684, Z01 AR041131-06]; NIDCR NIH HHS [R01 DE017449, R01 DE019156, R01 DE019156-05, R01 DE17449] NR 24 TC 353 Z9 383 U1 14 U2 58 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD FEB PY 2008 VL 34 IS 2 BP 166 EP 171 DI 10.1016/j.joen.2007.11.021 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 259PP UT WOS:000252951500010 PM 18215674 ER PT J AU Weng, XH Piermarini, PM Yamahiro, A Yu, MJ Aneshansley, DJ Beyenbach, KW AF Weng, Xing-He Piermarini, Peter M. Yamahiro, Atsuko Yu, Ming-Jiun Aneshansley, Daniel J. Beyenbach, Klaus W. TI Gap junctions in Malpighian tubules of Aedes aegypti SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE Malpighian tubule; yellow fever mosquito; electrical coupling; gap-junction resistance; innexin; circuit analysis; cable analysis; ATP ID YELLOW-FEVER MOSQUITO; DROSOPHILA-MELANOGASTER; PRINCIPAL CELLS; EPITHELIAL TRANSPORT; CHANNELS; PERMEABILITY; LEUCOKININ; FAMILY; CONDUCTANCE; MEMBRANES AB We present electrical, physiological and molecular evidence for substantial electrical coupling of epithelial cells in Malpighian tubules via gap junctions. Current was injected into one principal cell of the isolated Malpighian tubule and membrane voltage deflections were measured in that cell and in two neighboring principal cells. By short-circuiting the transepithelial voltage with the diuretic peptide leucokinin-VIII we largely eliminated electrical coupling of principal cells through the tubule lumen, thereby allowing coupling through gap junctions to be analyzed. The analysis of an equivalent electrical circuit of the tubule yielded an average gap-junction resistance (R-gj) of 431 k Omega between two cells. This resistance would stem from 6190 open gap- junctional channels, assuming the high single gap- junction conductance of 375 pS found in vertebrate tissues. The addition of the calcium ionophore A23187 (2 mu mol l(-1)) to the peritubular Ringer bath containing 1.7 mmol l(-1) Ca2+ did not affect the gap- junction resistance, but metabolic inhibition of the tubule with dinitrophenol (0.5 mmol l(-1)) increased the gap- junction resistance 66-fold, suggesting the regulation of gap junctions by ATP. Lucifer Yellow injected into a principal cell did not appear in neighboring principal cells. Thus, gap junctions allow the passage of current but not Lucifer Yellow. Using RT-PCR we found evidence for the expression of innexins 1, 2, 3 and 7 (named after their homologues in Drosophila) in Malpighian tubules. The physiological demonstration of gap junctions and the molecular evidence for innexin in Malpighian tubules of Aedes aegypti call for the double cable model of the tubule, which will improve the measurement and the interpretation of electrophysiological data collected from Malpighian tubules. C1 [Weng, Xing-He; Piermarini, Peter M.; Yamahiro, Atsuko; Beyenbach, Klaus W.] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. [Yu, Ming-Jiun] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Aneshansley, Daniel J.] Cornell Univ, Dept Biol Environm Engn, Ithaca, NY 14853 USA. RP Beyenbach, KW (reprint author), Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. EM kwb1@cornell.edu OI YU, MING-JIUN/0000-0003-0393-4696 NR 56 TC 21 Z9 21 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD FEB 1 PY 2008 VL 211 IS 3 BP 409 EP 422 DI 10.1242/jeb.011213 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 263CY UT WOS:000253196400025 PM 18203997 ER PT J AU Hajduch, J Dolensky, B Yoshida, S Fan, J Kirk, KL AF Hajduch, Jan Dolensky, Bohumil Yoshida, Shinichi Fan, Junfa Kirk, Kenneth L. TI Synthesis of (E)- and (Z)-alpha,beta-difluorourocanic acid SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE fluoroimidazole; urocanic acid; fluoroolefins; FBr addition; regiochemistry ID FLUOROUROCANIC ACIDS; UROCANIC ACID; FLUORINATION; SUPPRESSION AB Horner-Emmons fluoroolefination of an aryl aldehyde followed by introduction of a second fluorine via "FBr" addition provides an original approach to the preparation of 1-alkyl-2-aryl-1,2-difluoroethenes. The utility of this procedure is demonstrated by the preparation of (E and Z)-alpha,beta-difluorourocanic acid. Published by Elsevier B.V. C1 [Hajduch, Jan; Dolensky, Bohumil; Yoshida, Shinichi; Fan, Junfa; Kirk, Kenneth L.] NIDDKD, NIH, Lab Bioorgan Chem, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, NIH, Lab Bioorgan Chem, Bethesda, MD 20892 USA. EM kennethk@intra.niddk.nih.gov FU Intramural NIH HHS [Z01 DK031113-31] NR 13 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD FEB PY 2008 VL 129 IS 2 BP 112 EP 118 DI 10.1016/j.jfluchem.2007.09.006 PG 7 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 264WW UT WOS:000253322100006 PM 19190713 ER PT J AU Dwyer, JT Picciano, MF Betz, JM Fisher, KD Saldanha, LG Yetley, EA Coates, PM Milner, JA Whitted, J Burt, V Radimer, K Wilger, J Sharpless, KE Holden, JM Andrews, K Roseland, J Zhao, C Schweitzer, A Harnly, J Wolf, WR Perry, CR AF Dwyer, Johanna T. Picciano, Mary Frances Betz, Joseph M. Fisher, Kenneth D. Saldanha, Leila G. Yetley, Elizabeth A. Coates, Paul M. Milner, John A. Whitted, Jackie Burt, Vicki Radimer, Kathy Wilger, Jaimie Sharpless, Katherine E. Holden, Joanne M. Andrews, Karen Roseland, Janet Zhao, Culwei Schweitzer, Amy Harnly, James Wolf, Wayne R. Perry, Charles R. TI Progress in developing analytical and label-based dietary supplement databases at the NIH Office of Dietary Supplements SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 30th National Nutrient Databank Conference CY SEP 19-20, 2006 CL Honolulu, HI DE dietary supplements; analytical substantiation; dietary supplement composition; dietary supplement ingredient database; NHANES; DSID; NHANES-DSLD; DSLD-USA; dietary supplement labels; standard reference materials (R); certified reference materials ID NUTRIENT ANALYSIS PROGRAM; VITAMIN-D SUPPLEMENTATION; NATIONAL-HEALTH; FOOD; CALCIUM; TRIALS; RISK AB Although an estimated 50% of adults in the United States consume dietary supplements, analytically substantiated data on their bioactive constituents are sparse. Several programs funded by the Office of Dietary Supplements (ODS) at the National Institutes of Health enhance dietary supplement database development and help to better describe the quantitative and qualitative contributions of dietary supplements to total dietary intakes. ODS, in collaboration with the United States Department of Agriculture, is developing a Dietary Supplement Ingredient Database (DSID) verified by chemical analysis. The products chosen initially for analytical verification are adult multivitamin-mineral supplements (MVMs). These products are widely used, analytical methods are available for determining key constituents, and a certified reference material is in development. Also MVMs have no standard scientific, regulatory, or marketplace definitions and have widely varying compositions, characteristics, and bioavailability. Furthermore, the extent to which actual amounts of vitamins and minerals in a product deviate from label values is not known. Ultimately, DSID will prove useful to professionals in permitting more accurate estimation of the contribution of dietary supplements to total dietary intakes of nutrients and better evaluation of the role of dietary supplements in promoting health and well-being. ODS is also collaborating with the National Center for Health Statistics to enhance the National Health and Nutrition Examination Survey dietary supplement label database. The newest ODS effort explores the feasibility and practicality of developing a database of all dietary supplement labels marketed in the US. This article describes these and supporting projects. Published by Elsevier Inc. C1 [Dwyer, Johanna T.; Picciano, Mary Frances; Betz, Joseph M.; Fisher, Kenneth D.; Saldanha, Leila G.; Yetley, Elizabeth A.; Coates, Paul M.] US Dept HHS, Natl Inst Hlth, Off Dietary Supplement, Bethesda, MD USA. [Milner, John A.; Whitted, Jackie] US Dept HHS, Natl Canc Inst, Nutr Sci Res Grp, Bethesda, MD USA. [Burt, Vicki; Radimer, Kathy; Wilger, Jaimie] US Dept HHS, Natl Ctr Hlth Stat, Ctr Dis Control & Prevent, Natl Hlth & Nutr Exam Survey, Hyattsville, MD USA. [Sharpless, Katherine E.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. [Holden, Joanne M.; Andrews, Karen; Roseland, Janet; Zhao, Culwei; Schweitzer, Amy] USDA ARS, Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD USA. [Harnly, James; Wolf, Wayne R.] USDA ARS, Human Nutr Res Ctr, Food Compos Lab, Beltsville, MD USA. [Perry, Charles R.] USDA, Natl Agr Stat Serv, Div Res & Dev, Fairfax, VA USA. RP Dwyer, JT (reprint author), US Dept HHS, Natl Inst Hlth, Off Dietary Supplement, Bethesda, MD USA. EM dwyerjl@od.nih.gov OI Sharpless, Katherine/0000-0001-6569-198X; Dwyer, Johanna/0000-0002-0783-1769 FU NIH HHS [Y01 OD001298-01] NR 40 TC 14 Z9 14 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD FEB PY 2008 VL 21 SU S BP S83 EP S93 DI 10.1016/j.jfca.2007.07.010 PG 11 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 240TR UT WOS:000251610800013 PM 25346570 ER PT J AU Harnack, L Stevens, M Van Heel, N Schakel, S Dwyer, JT Himes, J AF Harnack, Lisa Stevens, Mary Van Heel, Nancy Schakel, Sally Dwyer, Johanna T. Himes, John TI A computer-based approach for assessing dietary supplement use in conjunction with dietary recalls SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 30th National Nutrient Databank Conference CY SEP 19-20, 2006 CL Honolulu, HI DE NDSR; nutrition data system for research; DSAM; dietary supplement assessment module; supplement inventory methodology; dietary supplement inventory; NHANES dietary supplement database; vitamins; minerals ID CARDIOVASCULAR DRUGS; QUESTIONNAIRE; MEDICATIONS; VALIDITY; VITAMIN; ADULTS; HEALTH; NHANES; WOMEN AB In response to the need to assess both food and supplemental sources of nutrients, we have expanded the capabilities of nutrition data system for research (NDSR) software to allow for assessing dietary supplement use. A Dietary Supplement Assessment Module allows for the automated collection and coding of dietary supplement use. The module is designed for use in conjunction with the software's 24-hour dietary recall features. The medication inventory method, commonly used in pharmaceutical research, served as the basis for the module's assessment approach. In adapting this approach for use in our software we designed a tiered structure that involves first screening for use of dietary supplements, then collecting product detail (e.g. full name of product, number of times taken, etc.), and finally reviewing the information with the participant. Results from a demonstration study conducted to evaluate the module indicate the assessment approach is acceptable to both participants and interviewers. Collecting dietary supplement use information significantly increases interview time, especially for those using multiple products. A validation study is needed to determine whether the new method results in accurate estimation of nutrient intake from supplemental sources. (C) 2007 Elsevier Inc. All rights reserved. C1 [Harnack, Lisa; Stevens, Mary; Van Heel, Nancy; Schakel, Sally; Himes, John] Univ Minnesota, Div Epidemiol & Commun Hlth, Minneapolis, MN 55454 USA. [Dwyer, Johanna T.] Natl Inst Hlth, Off Dietary Supplement, Bethesda, MD USA. RP Harnack, L (reprint author), Univ Minnesota, Div Epidemiol & Commun Hlth, 1300 S 2nd St Suite 300, Minneapolis, MN 55454 USA. EM harnack@epi.umn.edu OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [U24 HL061778-09, U24 HL061778] NR 17 TC 13 Z9 14 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 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD FEB PY 2008 VL 21 SU S BP S78 EP S82 DI 10.1016/j.jfca.2007.05.004 PG 5 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 240TR UT WOS:000251610800012 PM 19190705 ER PT J AU Pennington, JAT AF Pennington, Jean A. T. TI Applications of food composition data: Data sources and considerations for use SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 30th National Nutrient Databank Conference CY SEP 19-20, 2006 CL Honolulu, HI DE food composition data; data sources; data uses; food databases; documentation; quality; reliability; variability; limitations; food analysis; appropriate food data utilization ID ANTIOXIDANT ACTIVITY; DIETARY-SUPPLEMENTS; SEASONAL-VARIATIONS; HUMAN HEALTH; NIH OFFICE; POLYPHENOLS; FLAVANONES; VEGETABLES; COMPONENTS; PRODUCTS AB Sources of food composition data for nutrition professionals include electronic and hardcopy databases, which may be listed in database directories, and data from the food industry and the scientific literature. When data are not available from these sources, it may be necessary to impute or calculate values for a food, and the procedures used should be documented. Considerations for selecting data from various sources for a particular food include the food name and description, reliability of the source, data quality, and data variability. Food composition data are used for many purposes-dietary intake surveys/studies, reference work, patient care, student education, product development, dietary assessment, and clinical research. Understanding of the limitations of the data should be considered before using them for these various purposes. For example, it may not be appropriate to use data from a reference database for clinical studies where food component intakes are related to physiological measurements. More precise data from direct analysis of the food(s) under study may be required. Using food composition data from other countries may be appropriate, but might require modification for local ingredients or preparation methods. The many and varied sources of food composition data should be used with consideration for their appropriateness in national surveys, patient care, education, clinical practice, clinical research, and product development. (C) 2007 Elsevier Inc. All rights reserved. C1 [Pennington, Jean A. T.] Natl Inst Hlth, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. RP Pennington, JAT (reprint author), Natl Inst Hlth, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. EM jp157d@nih.gov NR 68 TC 39 Z9 40 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD FEB PY 2008 VL 21 SU S BP S3 EP S12 DI 10.1016/j.jfca.2007.02.005 PG 10 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 240TR UT WOS:000251610800002 ER PT J AU Pennington, JAT Stumbo, PJ AF Pennington, Jean A. T. Stumbo, Phyllis J. TI Food composition data: The foundation of dietary assessment SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Editorial Material DE American Dietetic Association; ADA; National Nutrient Databank Conference; Databank Conference; NNDC; food composition; databases AB The 30th National Nutrient Databank Conference was held as a two-day meeting in conjunction with the American Dietetic Association Food and Nutrition Conference and Exposition on September 19-20, 2006 in Honolulu, Hawaii. The 17 papers in this supplement bring together various issues of interest to database users and developers with a particular slant towards the data needs of dietitians. (C) 2007 Elsevier Inc. All rights reserved. C1 [Pennington, Jean A. T.] Natl Inst Hlth, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Stumbo, Phyllis J.] Univ Iowa, Gen Clin Res Ctr, Iowa City, IA USA. RP Pennington, JAT (reprint author), Natl Inst Hlth, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. EM jpl57d@nih.gov NR 18 TC 2 Z9 2 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD FEB PY 2008 VL 21 SU S BP S1 EP S2 DI 10.1016/j.jfca.2007.05.001 PG 2 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 240TR UT WOS:000251610800001 ER PT J AU Roseland, JM Holden, JM Andrews, KW Zhao, C Schweitzer, A Harnly, J Wolf, WR Perry, CR Dwyer, JT Picciano, MF Betz, JM Saldanha, LG Yetley, EA Fisher, KD Sharpless, KE AF Roseland, Janet M. Holden, Joanne M. Andrews, Karen W. Zhao, Cuiwei Schweitzer, Amy Harnly, James Wolf, Wayne R. Perry, Charles R. Dwyer, Johanna T. Picciano, Mary Frances Betz, Joseph M. Saldanha, Leila G. Yetley, Elizabeth A. Fisher, Kenneth D. Sharpless, Katherine E. TI Dietary supplement ingredient database (DSID): Preliminary USDA studies on the composition of adult multivitamin/mineral supplements SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 30th National Nutrient Databank Conference CY SEP 19-20, 2006 CL Honolulu, HI DE dietary supplements; analytical database; DSID; multivitamin; pilot study; nutrients ID AMERICA-NHANES; EAT AB The Nutrient Data Laboratory of the United States Department of Agriculture (USDA) is collaborating with the Office of Dietary Supplements (ODS), the National Center for Health Statistics (NCHS), and other government agencies to design and populate a dietary supplement ingredient database (DSID). This analytically based, publicly available database will provide reliable estimates of vitamin and mineral content of dietary supplement (DS) products. The DSID will initially be populated with multivitamin/mineral (MVM) products because they are the most commonly consumed supplements. Challenges associated with the analysis of MVMs were identified and investigated. A pilot study addressing the identification of appropriate analytical methods, sample preparation protocols, and experienced laboratories for the analysis of 12 vitamins and 11 minerals in adult MVM supplement products was completed. Preliminary studies support the development of additional analytical studies with results that can be applied to the DSID. Total intakes from foods and supplements are needed to evaluate the associations between dietary components and health. The DSID will provide better estimates of actual nutrient intake from supplements than databases that rely on label values alone. (C) 2007 Elsevier Inc. All rights reserved. C1 [Roseland, Janet M.; Holden, Joanne M.; Andrews, Karen W.; Zhao, Cuiwei; Schweitzer, Amy] USDA ARS, Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD 20705 USA. [Harnly, James; Wolf, Wayne R.] USDA ARS, Human Nutr Res Ctr, Food Compos Lab, Beltsville, MD USA. [Perry, Charles R.] USDA, Nat Agr Stat Serv, Div Res & Dev, Fairfax, VA USA. [Dwyer, Johanna T.; Picciano, Mary Frances; Betz, Joseph M.; Saldanha, Leila G.; Yetley, Elizabeth A.; Fisher, Kenneth D.] US Dept HHS, Natl Inst Hlth, Off Dietary Supplement, Bethesda, MD USA. [Sharpless, Katherine E.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RP Roseland, JM (reprint author), USDA ARS, Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD 20705 USA. EM janct.roseland@ars.usda.gov OI Sharpless, Katherine/0000-0001-6569-198X; Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [Y04 HV0051]; NIH HHS [Y01 OD001298-01] NR 23 TC 20 Z9 20 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD FEB PY 2008 VL 21 SU S BP S69 EP S77 DI 10.1016/j.jfca.2007.07.009 PG 9 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 240TR UT WOS:000251610800011 PM 24307755 ER PT J AU Sen, S Conroy, S Hynes, SO McMahon, J O'Doherty, A Bartlett, JS Akhtar, Y Adegbola, T Connolly, CE Sultan, S Barry, F Katusic, ZS O'Brien, T AF Sen, S. Conroy, S. Hynes, S. O. McMahon, J. O'Doherty, A. Bartlett, J. S. Akhtar, Y. Adegbola, T. Connolly, C. E. Sultan, S. Barry, F. Katusic, Z. S. O'Brien, T. TI Gene delivery to the vasculature mediated by low-titre adeno-associated virus serotypes 1 and 5 SO JOURNAL OF GENE MEDICINE LA English DT Article DE AAV serotypes; gene transfer; cardiovascular ID WALL IN-VIVO; ENDOTHELIAL-CELLS; EFFICIENT TRANSDUCTION; ARTERIAL-WALL; VECTORS; INFECTION; THERAPY; TYPE-2; EXPRESSION; MUSCLE AB Background Vascular gene therapy requires safe and efficient gene transfer in vivo. Recombinant adeno-associated virus (AAV) is a promising viral vector but its use in the vasculature has produced conflicting results and serotypes other than AAV2 have not been intensively studied. We investigated the efficiency of alternative AAV serotypes for vascular gene delivery in vitro and in vivo. Methods Vascular cell lines were transduced in vitro with AAV vectors. Rabbit carotid arteries were transduced with AAV1, 2 and 5 encoding enhanced green fluorescent protein (eGFP) (similar to 1.4 x 10(9) DNAse-resistant particles (drp)). Gene transfer in vivo was assessed at 14 and 28 days. High-titre doses of AAV2 encoding beta-galactosidase in vivo were also studied. Results In vitro, transgene expression was not observed in endothelial cells using AAV2 whereas the use of serotypes 1 and 5 resulted in detectable levels of transgene expression. Coronary artery smooth muscle cells (CASMCs) transduced with AAV2 demonstrated higher levels of GFP expression than AAV1 or 5. Transgene expression in vivo was noted using low-titre AAV1 and AAV5 (similar to 1.4 x 10(9) drp) in the media and adventitia. Only delivery of AAV1eGFP resulted in neointimal formation (3/7 vessels examined), with transgene expression noted in the neointima. Transgene expression with AAV2 was not detected in any layer of the blood vessel wall using low titre (similar to 10(9) drp). However, high-titre (similar to 10(11) drp) AAV2 resulted in transduction of cells in the media and adventitia but not the endothelium. Conclusions AAV1 and AAV5 have advantages over AAV2 for vascular gene delivery at low titres. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Sen, S.; Conroy, S.; Hynes, S. O.; McMahon, J.; O'Doherty, A.; O'Brien, T.] Univ Coll Hosp Galway, Dept Med, Inst Clin Sci, Galway, Ireland. [Sen, S.; Conroy, S.; Hynes, S. O.; McMahon, J.; O'Doherty, A.; Barry, F.; O'Brien, T.] Natl Univ Ireland Univ Coll Galway, Regenerat Med Inst, Galway, Ireland. [Sen, S.; Conroy, S.; Hynes, S. O.; McMahon, J.; O'Doherty, A.; O'Brien, T.] Natl Univ Ireland Univ Coll Galway, Dept Med, Galway, Ireland. [Bartlett, J. S.] Columbus Childrens Hosp, Childrens Res Inst, Gene Therapy Ctr, Columbus, OH USA. [Bartlett, J. S.] Ohio State Univ, Sch Med & Publ Hlth, Columbus, OH 43210 USA. [Akhtar, Y.; Sultan, S.] Univ Coll Hosp Galway, Dept Vasc Surg, Galway, Ireland. [Adegbola, T.; Connolly, C. E.] Univ Coll Hosp Galway, Dept Pathol, Galway, Ireland. [Katusic, Z. S.] Mayo Clin, Dept Anaesthesiol, Rochester, MN USA. [Sen, S.] NIDDK, NIH, Bethesda, MD USA. RP O'Brien, T (reprint author), Univ Coll Hosp Galway, Dept Med, Inst Clin Sci, Galway, Ireland. EM timothy.obrien@nuigalway.ie RI Barry, Frank/K-5960-2013; O'Brien, Timothy/N-7112-2014 OI O'Brien, Timothy/0000-0001-9028-5481 NR 33 TC 7 Z9 8 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD FEB PY 2008 VL 10 IS 2 BP 143 EP 151 DI 10.1002/jgm.1133 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 266JC UT WOS:000253430100004 PM 18067196 ER PT J AU Walker, B Spann, M AF Walker, Bailus Spann, Melvin TI The need for diversity in the environmental health workforce SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE diversity; environmental health; workforce; public health ID CARE AB Epidemiologic evidence makes clear that the likelihood of exposure to environmental contaminants increases in most poor and underserved communities. Despite progress in reducing a number of environmental risk factors for disease, serious environmental problems persist, and those remaining problems are highly complex. Their solution requires meaningful community engagement as well as a diverse environmental health workforce. Demographic data, and related social and economic developments, strongly indicate that such a workforce must include underrepresented minorities. While the problem has not been solved, select programs have made impressive contributions to meeting this need, an example of which is described in this paper. C1 [Walker, Bailus] Howard Univ, Coll Med, Washington, DC 20059 USA. [Walker, Bailus; Spann, Melvin] Natl Lib Med, Specialized Informat Serv, Bethesda, MD 20894 USA. RP Walker, B (reprint author), Howard Univ, Coll Med, Washington, DC 20059 USA. EM bwalker@howard.edu NR 27 TC 1 Z9 1 U1 0 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2008 VL 19 IS 1 BP 16 EP 25 DI 10.1353/hpu.2008.0009 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 262LC UT WOS:000253149000004 PM 18263983 ER PT J AU Galazka, M Groves, S Corcoran, T Johnson, B Suffredini, A Britt, E Sherman, B Augustine, S Moainie, S Todd, N Griffith, B Iacono, A AF Galazka, M. Groves, S. Corcoran, T. Johnson, B. Suffredini, A. Britt, E. Sherman, B. Augustine, S. Moainie, S. Todd, N. Griffith, B. Iacono, A. TI Preservation of pulmonary function by inhaled cyclosporine in lung transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Galazka, M.; Groves, S.; Britt, E.; Sherman, B.; Augustine, S.; Moainie, S.; Todd, N.; Griffith, B.; Iacono, A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Suffredini, A.] NIH, Bethesda, MD 20892 USA. [Corcoran, T.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 403 BP S206 EP S206 DI 10.1016/j.healun.2007.11.415 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300404 ER PT J AU Goldstein, D Naka, Y Icenogle, T Slaughter, M Pagani, E Choe, J Rose, E Desvigne-Nickens, P Parides, M Rawiel, U Guerchicoff, A Ascheim, D Moskowitz, A Gelijns, A Schmidt, AM AF Goldstein, D. Naka, Y. Icenogle, T. Slaughter, M. Pagani, E. Choe, J. Rose, E. Desvigne-Nickens, P. Parides, M. Rawiel, U. Guerchicoff, A. Ascheim, D. Moskowitz, A. Gelijns, A. Schmidt, A. M. TI The epidemiology of bleeding and clotting in pulsatile and continuous flow LVAD patients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Goldstein, D.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Naka, Y.; Schmidt, A. M.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Icenogle, T.] Sacred Heart Med Ctr, Spokane, WA USA. [Slaughter, M.] Advocate Christ Med Ctr, Oak Lawn, IL USA. [Pagani, E.] Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. [Choe, J.; Parides, M.; Rawiel, U.; Guerchicoff, A.; Ascheim, D.; Moskowitz, A.; Gelijns, A.] Int Ctr Hlth Outcomes & Innovat Res, New York, NY USA. [Desvigne-Nickens, P.] 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 342 BP S184 EP S184 DI 10.1016/j.healun.2007.11.352 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300343 ER PT J AU Holman, WL Kormos, RL Miller, MA Pagani, FD Blume, E Cleeton, T Koenig, SC Naftel, DC Kirklin, JK Edwards, L AF Holman, W. L. Kormos, R. L. Miller, M. A. Pagani, F. D. Blume, E. Cleeton, T. Koenig, S. C. Naftel, D. C. Kirklin, J. K. Edwards, L. TI Predictors of death and transplant in patients with a mechanical circulatory support device: A multi-institutional study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Holman, W. L.; Naftel, D. C.; Kirklin, J. K.] Univ Alabama Birmingham, Birmingham, AL USA. [Kormos, R. L.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Miller, M. A.] NHLBI, Rockville, MD USA. [Pagani, F. D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Blume, E.] Childrens Hosp, Boston, MA USA. [Cleeton, T.] Univ Florida, Shands Hosp, Gainesville, FL USA. [Koenig, S. C.] Univ Louisville, Jewish Hosp Louisville, Louisville, KY 40292 USA. [Edwards, L.] United Network Organ Sharing, Richmond, VA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 512 BP S244 EP S244 DI 10.1016/j.healun.2007.11.526 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300513 ER PT J AU Jessup, M Stevenson, LW Desvigne-Nickens, P Young, J Acker, M Milano, C Wissman, S Frazier, OH Naftel, DC Kirklin, JK AF Jessup, M. Stevenson, L. Warner Desvigne-Nickens, P. Young, J. Acker, M. Milano, C. Wissman, S. Frazier, O. H. Naftel, D. C. Kirklin, J. K. TI Patients with mechanical circulatory support (MCSD): Is implant strategy static or dynamic? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Jessup, M.; Acker, M.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Stevenson, L. Warner] Brigham & Womens Hosp, Boston, MA 02115 USA. [Desvigne-Nickens, P.] NHLBI, Washington, DC USA. [Young, J.] Cleveland Clin, Cleveland, OH 44106 USA. [Milano, C.] Duke Univ, Med Ctr, Durham, NC USA. [Wissman, S.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Frazier, O. H.] Texas Heart Inst, Houston, TX 77025 USA. [Naftel, D. C.; Kirklin, J. K.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 4 BP S61 EP S61 DI 10.1016/j.healun.2007.11.008 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300005 ER PT J AU Naftel, DC Rogers, JG Young, JB Baldwin, T Chen, E Sapirstein, W Kormos, RL Ascheim, DV Chisholm, KA AF Naftel, D. C. Rogers, J. G. Young, J. B. Baldwin, T. Chen, E. Sapirstein, W. Kormos, R. L. Ascheim, D. V. Chisholm, K. A. TI The use of the interagency registry for mechanically assisted circulatory support (INTERMACS) to generate objective performance criteria (OPCs) for use in MCSD trials SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Naftel, D. C.] Univ Alabama Birmingham, Birmingham, AL USA. [Rogers, J. G.] Duke Univ, Med Ctr, Durham, NC USA. [Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Baldwin, T.] Natl Heart Lung & Blood Inst, Bethesda, MD USA. [Chen, E.; Sapirstein, W.] US FDA, Rockville, MD USA. [Kormos, R. L.] Univ Pittsburgh, Pittsburgh, PA USA. [Ascheim, D. V.] Columbia Univ, New York, NY USA. [Chisholm, K. A.] Univ Arizona, Med Ctr, Tucson, AZ 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 297 BP S167 EP S167 DI 10.1016/j.healun.2007.11.306 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300298 ER PT J AU Pagani, FD Stevenson, LW Ulisney, KL Jeevanandam, V Teuteberg, JJ Camacho, MT Martin, T Aaronson, K Naftel, DC Kirklin, JK AF Pagani, F. D. Stevenson, L. Warner Ulisney, K. L. Jeevanandam, V. Teuteberg, J. J. Camacho, M. T. Martin, T. Aaronson, K. Naftel, D. C. Kirklin, J. K. TI Pre-implant patient triage using patient status with INTERMACS patient profiles: Can we refine selection strategy for MCS? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Pagani, F. D.; Aaronson, K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Stevenson, L. Warner] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ulisney, K. L.] NHLBI, Bethesda, MD 20892 USA. [Jeevanandam, V.] Univ Chicago, Chicago, IL 60637 USA. [Teuteberg, J. J.] Univ Pittsburgh, Pittsburgh, PA USA. [Camacho, M. T.; Martin, T.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Naftel, D. C.; Kirklin, J. K.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 3 BP S60 EP S61 DI 10.1016/j.healun.2007.11.007 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300004 ER PT J AU Pipeling, MR West, EE Lechtzin, N Migueles, SA Connors, M McDyer, JF AF Pipeling, M. R. West, E. E. Lechtzin, N. Migueles, S. A. Connors, M. McDyer, J. F. TI Dissecting CMV-specific immunity in high-risk lung transplant recipients: Differences between the lung allograft and blood effector memory T cells SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Pipeling, M. R.; West, E. E.; Lechtzin, N.; McDyer, J. F.] Johns Hopkins Univ, Baltimore, MD USA. [Migueles, S. A.; Connors, M.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 119 BP S102 EP S102 DI 10.1016/j.healun.2007.11.125 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300120 ER PT J AU Sugimoto, R Nakao, A Kohmoto, J Wang, Y Gladivin, MT Billiar, TR McCurry, KR AF Sugimoto, R. Nakao, A. Kohmoto, J. Wang, Y. Gladivin, M. T. Billiar, T. R. McCurry, K. R. TI Nitrite protects rat lung grafts from ischemia/reperfusion injury via xanthlne oxidoreductase (XOR) SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Sugimoto, R.; Nakao, A.; Kohmoto, J.; Wang, Y.; McCurry, K. R.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Heart Lung & Esophageal Surg Inst, Dept Surg, Pittsburgh, PA USA. [Gladivin, M. T.] NIH, Vasc Med Branch, Crit Care Med Dept, Bethesda, MD 20892 USA. [Billiar, T. R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 32 BP S71 EP S71 DI 10.1016/j.healun.2007.11.036 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300033 ER PT J AU Deola, S Panelli, MC Maric, D Selleri, S Dmitrieva, NI Voss, CY Klein, H Stroncek, D Wang, E Marincola, FM AF Deola, Sara Panelli, Monica C. Maric, Dragan Selleri, Silvia Dmitrieva, Natalia I. Voss, Ching Y. Klein, Harvey Stroncek, David Wang, Ena Marincola, Francesco M. TI Helper B cells promote cytotoxic T cell survival and proliferation independently of antigen presentation through CD27/CD70 interactions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR3; ALLOGRAFT-REJECTION; DENDRITIC CELLS; CENTRAL-MEMORY; CC-CHEMOKINE; CD8(+); EFFECTOR; SUBSETS; DIFFERENTIATION; GENERATION AB CD8-expressing cytotoxic T cell (CTL) interactions with APCs and helper T cells determine their function and ability to survive. In this study, we describe a novel interaction independent of Ag presentation between activated CTLs and bystander CD19-expressing B lymphocytes. Ag-stimulated CTLs serially engage autologous B lymphocytes through CD27/CD70 contact that promotes their survival and proliferation. Moreover, these interactions induce the release of proinflammatory cytokines that follows two general patterns: 1) an epitope-dependent enhancement of cytokine release, and 2) a previously undiscovered coordinate release of cytokines independent of epitope exposure. The latter includes chemoattractants targeting activated T cells. As a result, activated T cells are attracted to B cells, which exert a "helper" role in lymphatic organs or in areas of inflammation. This observation provides a mechanistic explanation to previously reported experimental observations suggesting that B cells are required for T cell priming in vivo. C1 [Deola, Sara; Panelli, Monica C.; Selleri, Silvia; Klein, Harvey; Stroncek, David; Wang, Ena; Marincola, Francesco M.] NIH, Ctr Clin, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA. [Voss, Ching Y.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Facil, NIH, Bethesda, MD 20892 USA. [Dmitrieva, Natalia I.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Selleri, Silvia] Univ Milan, Dept Human Morphol, Milan, Italy. RP Marincola, FM (reprint author), NIH, Ctr Clin, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bldg 10,Room 1N224,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fmarincola@mailnih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 NR 39 TC 28 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2008 VL 180 IS 3 BP 1362 EP 1372 PG 11 WC Immunology SC Immunology GA 255BY UT WOS:000252632900009 PM 18209030 ER PT J AU Huaman, MC Martin, LB Malkin, E Narum, DL Miller, LH Mahanty, S Long, CA AF Huaman, Maria Cecilia Martin, Laura B. Malkin, Elissa Narum, David L. Miller, Louis H. Mahanty, Siddhartha Long, Carole A. TI Ex vivo cytokine and memory T cell responses to the 42-kDa fragment of Plasmodium falciparum merozoite surface protein-1 in vaccinated volunteers SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MALARIA-NAIVE; RECEPTOR EXPRESSION; DIFFERENT REGIONS; IMMUNE-RESPONSES; DISULFIDE BONDS; FLOW-CYTOMETRY; IFN-GAMMA; IN-VIVO; CD4(+); PROTECTION AB A number of blood-stage malaria Ags are under development as vaccine candidates, but knowledge of the cellular responses to these vaccines in humans is limited. We evaluated the nature and specificity of cellular responses in healthy American volunteers vaccinated with a portion of the major merozoite surface protein-1 (MSP1) of Plasmodium falciparum, MSP1(42), formulated on Alhydrogel. Volunteers were vaccinated three times with 80 mu g of either MSP1(42)-FVO/Alhydrogel or MSP1(42)-3D7/Alhydrogel. Cells collected 2 wk after the third vaccination produced Th1 cytokines, including IFN-gamma and IL-2 following Ag stimulation, and greater levels of the Th2 cytokines IL-5 and IL-13; the anti-inflammatory cytokine IL-10 and the molecule CD25 (IL-2R alpha) were also detected. The volunteers were evaluated for the MSP1(42)-FVO or MSP1(42)-3D7 specificity of their T cell responses. Comparison of their responses to homologous and heterologous Ags showed ex vivo IFN-gamma and IL-5 levels that were significantly higher to homologous rather than to heterologous Ags. The epitopes involved in this stimulation were shown to be present in the dimorphic MSP1(33) portion of the larger MSP1(42)-3D7 polypeptide, and indirect experiment suggests the same for the MSP1(42)-FVO polypeptide. This contrasts with B cell responses, which were primarily directed to the conserved MSPI,, portion. Furthermore, we explored the maturation of memory T cells and found that 46% of vaccinees showed specific memory T cells defined as CD4(+)CD45RO(+)CD40L(+) after long-term in vitro culture. The identification of human-specific CD4(+) memory T cells provides the foundation for future studies of these cells both after vaccination and in field studies. C1 [Huaman, Maria Cecilia; Martin, Laura B.; Malkin, Elissa; Narum, David L.; Miller, Louis H.; Mahanty, Siddhartha; Long, Carole A.] NIAID, NIH, Lab Malaria & Vector Res, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. [Huaman, Maria Cecilia; Long, Carole A.] NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Mahanty, Siddhartha] NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Long, CA (reprint author), NIAID, NIH, Lab Malaria & Vector Res, Malaria Vaccine Dev Branch, Twinbrook 3,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM calong@niaid.nih.gov RI Martin, Laura/N-1789-2013; OI Martin, Laura/0000-0002-4431-4381; Mahanty, Siddhartha/0000-0003-1068-0524 FU Intramural NIH HHS NR 60 TC 29 Z9 29 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2008 VL 180 IS 3 BP 1451 EP 1461 PG 11 WC Immunology SC Immunology GA 255BY UT WOS:000252632900019 PM 18209040 ER PT J AU Powell, DJ Attia, P Ghetie, V Schindler, J Vitetta, ES Rosenberg, SA AF Powell, Daniel J., Jr. Attia, Peter Ghetie, Victor Schindler, John Vitetta, Ellen S. Rosenberg, Steven A. TI Partial reduction of human FOXP3+ CD4 T cells in vivo after CD25-directed recombinant immunotoxin administration SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE human; immunotoxin; RFT5-SMPT-dgA; CD25; regulatory T cell; depletion ID RICIN A-CHAIN; REFRACTORY HODGKINS LYMPHOMA; TOXIN FUSION PROTEIN; METASTATIC MELANOMA; DENILEUKIN DIFTITOX; TUMOR-IMMUNITY; REGULATORY-CELLS; PHASE-I; LYMPHODEPLETING CHEMOTHERAPY; INTERLEUKIN-2 RECEPTOR AB The regulation of tolerance to self-proteins and the suppression of T-cell responses have in part been attributed to the activity of CD25(+)CD4(+) T regulatory (T-reg) cells. Further, Treg cells can inhibit the antitumor effectiveness of adoptive immunotherapy and active immunization approaches in preclinical models. In an effort to selectively eliminate T-reg cells from human peripheral blood mononuclear cell to potentially bolster antitumor responses, we have evaluated the T-reg-cell depleting capacity of the CD25-directed immunotoxin, RFT5-SMPT-dgA. In preclinical studies, incubation of human peripheral blood mononuclear cell with RFT5-SMPT-dgA mediated a partial reduction in the levels of CD25(+), Foxp3-expressing CD4(+) T cells in vitro. Administration of RFT5-SMPT-dgA to 6 patients with metastatic melanoma induced a transient but robust reduction in the number of CD25(high) CD4(+) T cells in vivo (a 97.5% mean reduction at nadir; from 69.4 +/- 12.4cells/mu L to 1.7 +/- 0.3 cells/mu L). The reduction in FOXP3(+) CD4+ T-cell number was less comprehensive (a 71.3% mean reduction at nadir; from 66.6 +/- 16.5 cells/mu L to 14.2 +/- 3.9 cells/mu L). This resulted in the selective persistence of a stable number of CD25(low/neg) FOXP3(+) CD4(+) T cells in vivo. No objective antitumor responses were seen in any patient. Our results indicate that the CD25-directed, RFT5-SMPT-dgA immunotoxin can mediate a transient, partial reduction in Treg-cell frequency and number in vitro and in vivo and suggest that comprehensive eradication of human T-reg cells in vivo may require the ability to target and eliminate FOXP3(+) cells expressing both high and low levels of CD25. C1 [Powell, Daniel J., Jr.; Attia, Peter; Rosenberg, Steven A.] Natl Canc Inst, Surg Branch, NIH, Bethesda, MD USA. [Ghetie, Victor; Schindler, John; Vitetta, Ellen S.] Univ Texas SW Med Ctr Dallas, Canc Immunobiol Ctr, Dallas, TX 75390 USA. RP Powell, DJ (reprint author), Univ Penn, Abramson Canc Ctr, 421 Curie Blvd,1313 Biomed Res Bldg 1-2, Philadelphia, PA 19104 USA. EM poda@mail.med.upenn.edu FU Intramural NIH HHS [Z01 SC003811-33] NR 52 TC 41 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD FEB-MAR PY 2008 VL 31 IS 2 BP 189 EP 198 DI 10.1097/CJI.0b013e31815dc0e8 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 266KE UT WOS:000253433300008 PM 18481388 ER PT J AU D'Souza, MP Altfeld, M AF D'Souza, M. Patricia Altfeld, Marcus TI Measuring HIV-1-specific T cell immunity: How valid are current assays? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VACCINE EFFICACY; HIV-1 INFECTION; TYPE-1; LYMPHOCYTES; RESPONSES; VIREMIA; ESCAPE C1 [Altfeld, Marcus] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Altfeld, Marcus] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. [D'Souza, M. Patricia] NIAID, Vaccine Clin Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM maltfeld@partners.org NR 21 TC 19 Z9 19 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2008 VL 197 IS 3 BP 337 EP 339 DI 10.1086/525288 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 262EK UT WOS:000253131600003 PM 18184092 ER PT J AU Kari, L Whitmire, WM Carlson, JH Crane, DD Reveneau, N Nelson, DE Mabey, DCW Bailey, RL Holland, MJ McClarty, G Caldwell, HD AF Kari, Laszlo Whitmire, William M. Carlson, John H. Crane, Deborah D. Reveneau, Nathalie Nelson, David E. Mabey, David C. W. Bailey, Robin L. Holland, Martin J. McClarty, Grant Caldwell, Harlan D. TI Pathogenic diversity among Chlamydia trachomatis ocular strains in nonhuman primates is affected by subtle genomic variations SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting of the Chlamydia-Basic-Research-Society CY MAR, 2007 CL Louisville, KY SP Chlamydia Basic Res Soc ID GAMMA-INTERFERON; TRYPTOPHAN SYNTHASE; MEMBRANE-PROTEINS; TISSUE TROPISM; ANIMAL-MODEL; AMINO-ACID; POLYMORPHISMS; RISK; INFECTIONS; RESISTANCE AB Chlamydia trachomatis is the etiological agent of trachoma, the leading cause of preventable blindness. Trachoma presents distinct clinical syndromes ranging from mild and self-limiting to severe inflammatory disease. The underlying host and pathogen factors responsible for these diverse clinical outcomes are unclear. To assess the role played by pathogen variation in disease outcome, we analyzed the genomes of 4 trachoma strains representative of the 3 major trachoma serotypes, using microarray-based comparative genome sequencing. Outside of ompA, trachoma strains differed primarily in a very small subset of genes (n = 22). These subtle genetic variations were manifested in profound differences in virulence as measured by in vitro growth rate, burst size, plaque morphology, and interferon-gamma sensitivity but most importantly in virulence as shown by ocular infection of non-human primates. Our findings are the first to identify genes that correlate with differences in pathogenicity among trachoma strains. C1 [Kari, Laszlo; Whitmire, William M.; Carlson, John H.; Crane, Deborah D.; Reveneau, Nathalie; Caldwell, Harlan D.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. [Nelson, David E.] Indiana Univ, Dept Biol, Bloomington, IN USA. [Mabey, David C. W.; Bailey, Robin L.; Holland, Martin J.] London Sch Hyg & Trop Med, Infect Trop Dis Dept, Clin Res Unit, London WC1, England. [Holland, Martin J.] MRC Labs, Viral Dis Programme, Banjul, Gambia. [McClarty, Grant] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. RP Caldwell, HD (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov OI Mabey, David/0000-0002-0031-8276 FU Intramural NIH HHS; Medical Research Council [MC_U190081961] NR 46 TC 62 Z9 63 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2008 VL 197 IS 3 BP 449 EP 456 DI 10.1086/525285 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 262EK UT WOS:000253131600018 PM 18199030 ER PT J AU Kirkpatrick, BD Haque, R Duggal, P Mondal, D Larsson, C Peterson, K Akter, J Lockhart, L Khan, S Petri, WA AF Kirkpatrick, Beth D. Haque, Rashidul Duggal, Priya Mondal, Dinesh Larsson, Cathy Peterson, Kristine Akter, Jasmin Lockhart, Lauren Khan, Salwa Petri, William A., Jr. TI Association between Cryptosporidium infection and human leukocyte antigen class I and class II alleles SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BANGLADESHI CHILDREN; BRAZILIAN CHILDREN; PARVUM INFECTION; IMMUNE-RESPONSES; DIARRHEA; VIRUS; SUSCEPTIBILITY; MICE AB Background. Cryptosporidium species are a common cause of diarrhea, which can be severe and protracted in young children and immunocompromised individuals. Methods. A cohort of 226 Bangladeshi children aged 2-5 years was prospectively followed for >3 years to study the role of host genetics in susceptibility to infection, as well as the community impact of cryptosporidiosis on this population. Results. Ninety-six children (42.5%) received a diagnosis of Cryptosporidium infection. A total of 51 (22.6%) had asymptomatic infection. Fifty-eight (25.7%) had cryptosporidiosis, of whom 17 (29.3%) had recurrent disease. Children with cryptosporidiosis presented early, and most had abdominal pain and a short course of diarrhea. Infected children were more likely to carry the human leukocyte antigen (HLA) class II DQB1*0301 allele, particularly those with asymptomatic and symptomatic infection (P = .009); a strong association was found between carriage of the DQB1*0301/DRB1*1101 haplotype and development of both asymptomatic and symptomatic infection (P = .008). Infected children were also more likely to carry the B*15 HLA class I allele. Conclusions. This is the first study to describe a possible genetic component of the immune response to Cryptosporidium infection, which includes HLA class I and II alleles. Cryptosporidiosis in Bangladeshi children aged 2-5 years is common and often recurrent, but the duration is shorter and the abdominal pain greater than that described in children aged <2 years. C1 [Kirkpatrick, Beth D.; Larsson, Cathy; Khan, Salwa] Univ Vermont, Coll Med, Infect Dis Unit, Burlington, VT 05405 USA. [Duggal, Priya] NHGRI, NIH, Baltimore, MD USA. [Peterson, Kristine; Lockhart, Lauren; Petri, William A., Jr.] Univ Virginia, Charlottesville, VA USA. [Haque, Rashidul; Mondal, Dinesh; Akter, Jasmin] Int Ctr Diarrhoeal Dis Res, Ctr Hlth & Populat Res, Dhaka 1000, Bangladesh. RP Kirkpatrick, BD (reprint author), Univ Vermont, Coll Med, Infect Dis Unit, 110 Stafford Hall,95 Carrigan Ln, Burlington, VT 05405 USA. EM beth.kirkpatrick@uvm.edu FU Intramural NIH HHS; NIAID NIH HHS [AI0143596, R01 AI043596, U54 AI057168, U54 AI57168] NR 20 TC 16 Z9 16 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2008 VL 197 IS 3 BP 474 EP 478 DI 10.1086/525284 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 262EK UT WOS:000253131600021 PM 18248305 ER PT J AU Zeytin, H Reali, E Zaharoff, DA Rogers, CJ Schlom, J Greiner, JW AF Zeytin, Hasan Reali, Eva Zaharoff, David A. Rogers, Connie J. Schlom, Jeffrey Greiner, John W. TI Targeted delivery of murine IFN-gamma using a recombinant fowlpox virus: NK cell recruitment to regional lymph nodes and priming of tumor-specific host immunity SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID NATURAL-KILLER-CELLS; COLONY-STIMULATING FACTOR; PHASE-I TRIAL; DENDRITIC CELLS; INTERFERON-GAMMA; T-CELLS; RESPONSES; ANTIGEN; ACTIVATION; INDUCTION AB Interferon-gamma (IFN-gamma) is a proinflammatory cytokine that also acts as a potent immunomodulatory agent. In this study, a replication-deficient recombinant avian (fowlpox) virus was engineered to express the murine IFN-gamma gene (rF-MuIFN-gamma) with the rationale of delivering concentrated levels of the cytokine to a local tissue microenvironment. Subcutaneous (s.c.) rF-MuIFN-gamma administration resulted in IFN-gamma production that (1) was restricted to the tissue microenvironment of the injection site and (2) was biologically active, as evidenced by a significant increase of class 1 MHC expression levels in s.c. growing tumors following rF-MuIFN-gamma administration. Infection of a highly tumorigenic murine cell line, MC38, with rF-MuIFN-y functioned as an effective tumor cell-based vaccine by protecting mice from the formation of primary tumors and from subsequent tumor challenge. The cell-based vaccine was completely ineffective if mice were vaccinated with MC38 cells either pretreated with rIFN-gamma or infected with the wild-type fowlpox virus (FP-WT). Analysis of the regional lymph nodes draining the site of injection of the rF-MuIFN-gamma-based tumor cell vaccine revealed the presence of tumor-specific cell lysis (CTL) as well as a significant amount of lysis directed at natural killer (NK)-sensitive YAC-1 cells. Flow cytometric analyses coupled with functional assays confirmed the sustained presence of Nk1.1(+) cells within those draining lymph nodes for up to 5 days after rF-MuIFN-y injection. Mice treated with NK cell-depleting antibodies prior to the injection of the rF-MuIFN-gamma-infected MC38 tumor cells were not protected from primary tumor growth; analysis of the lymph nodes draining the injection site in NK-depleted mice revealed an accompanying loss of the tumor-specific CTL activity. The findings provide evidence that NK cells, known for their contributions to host innate immunity, also provide immunoregulatory signals required for the development of an adaptive immune response, which, in turn, protected vaccinated mice against tumor growth. C1 [Zeytin, Hasan; Reali, Eva; Zaharoff, David A.; Rogers, Connie J.; Schlom, Jeffrey; Greiner, John W.] NIH, NCI, Canc Res Ctr, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. [Reali, Eva] Natl Inst Mol Genet, INGM, I-20122 Milan, Italy. RP Zeytin, H (reprint author), NIH, NCI, Canc Res Ctr, Lab Tumor Immunol & Biol, Bldg 10, Bethesda, MD 20892 USA. RI Reali, Eva/Q-1161-2016; OI Reali, Eva/0000-0003-1900-1356; Zaharoff, David/0000-0001-6885-6727 FU Intramural NIH HHS [Z01 BC010598-04] NR 48 TC 11 Z9 11 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD FEB PY 2008 VL 28 IS 2 BP 73 EP 87 DI 10.1089/jir.2007.0063 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 269DO UT WOS:000253629900003 PM 18279103 ER PT J AU Davey, RT Pertel, PE Benson, A Cassell, DJ Gazzard, BG Holodniy, M Lalezari, JP Levy, Y Mitsuyasu, RT Palella, FJ Pollard, RB Rajagopalan, P Saag, MS Salata, RA Sha, BE Choudhri, S AF Davey, Richard T. Pertel, Peter E. Benson, Alice Cassell, Delanie J. Gazzard, Brian G. Holodniy, Mark Lalezari, Jacob P. Levy, Yves Mitsuyasu, Ronald T. Palella, Frank J. Pollard, Richard B. Rajagopalan, Prabhu Sagg, Michael S. Salata, Robert A. Sha, Beverly E. Choudhri, Shurjeel TI Safety, tolerability, pharmacokinetics, and efficacy of an interleukin-2 agonist among HIV-infected patients receiving highly active antiretroviral therapy SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL; DOSE RECOMBINANT INTERLEUKIN-2; INTRAVENOUS INTERLEUKIN-2; SUBCUTANEOUS INTERLEUKIN-2; INTERMITTENT INTERLEUKIN-2; T-LYMPHOCYTES; BETA-CHAIN; IN-VIVO; IL-2 AB We sought to determine the safety, maximum tolerated dose, optimal dose, and preliminary dose efficacy of intermittent subcutaneously (s.c.) administered BAY 50-4798 among patients with HIV infection receiving highly active antiretroviral therapy (HAART) compared with patients receiving HAART alone. A phase I/II randomized, double-blind, dose-escalation study was conducted of the safety, tolerability, pharmacokinetics, and efficacy of s.c. BAY 50-4798 administered to HIV-infected patients already receiving stable HAART. There were no unexpected safety findings in a population of HIV-infected patients receiving HAART plus SC BAY 50-4798 as adjunctive therapy. BAY 50-4798 exhibited nearly dose-proportional pharmacokinetics, and accumulation was minimal during multiple-dose treatment. Limited efficacy data indicated that treatment with BAY 50-4798 caused at least a transient increase in CD4(+) T cell counts in some recipients, particularly at the early time points. In general, this effect appeared to increase with increasing dose. Bay 50-4798 was generally well tolerated across the dose range tested, but a lack of potent, sustained immunologic activity suggests that further optimization of dose and schedule will be necessary. C1 [Davey, Richard T.] NIAID, NIH, DHHS, Bethesda, MD 20892 USA. [Pertel, Peter E.; Benson, Alice; Rajagopalan, Prabhu; Choudhri, Shurjeel] Bayer Healthcare Pharmaceut, West Haven, CT 06516 USA. [Cassell, Delanie J.] Bayer Biotechnol Div, Berkeley, CA 94710 USA. [Gazzard, Brian G.] Chelsea & Westminster Hosp, London, England. [Holodniy, Mark] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Holodniy, Mark] Stanford Univ, Div Infect Dis & Geograph Med, Palo Alto, CA 94304 USA. [Lalezari, Jacob P.] Quest Clin Res, San Francisco, CA 94115 USA. [Levy, Yves] Hop Henri Mondor, Creteil, France. [Mitsuyasu, Ronald T.] Univ Calif Los Angeles, Med Ctr, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Palella, Frank J.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Pollard, Richard B.] Univ Calif Davis, Med Ctr, Sch Med, Div Infect Dis, Sacramento, CA 95817 USA. [Sagg, Michael S.] Univ Alabama, Birmingham Div Infect Dis, Birmingham, AL 35249 USA. [Salata, Robert A.] Case Western Reserve Univ Hosp, Sch Med, Div Infect Dis, Cleveland, OH 44106 USA. [Sha, Beverly E.] Rush Univ, Med Ctr, Sect Infect Dis, Chicago, IL 60612 USA. RP Davey, RT (reprint author), NIAID, NIH, DHHS, 10 Ctr Dr,Rm 4-1479,MSC 1460, Bethesda, MD 20892 USA. EM rdavey@niaid.nih.gov NR 27 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD FEB PY 2008 VL 28 IS 2 BP 89 EP 100 DI 10.1089/jir.2007.0064 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 269DO UT WOS:000253629900004 PM 18279104 ER PT J AU Shawl, F Lederman, RJ AF Shawl, Fayaz Lederman, Robert J. TI Prophylactic, Standby, or Rescue Support for High-Risk PCI: Who Knows? SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material C1 [Shawl, Fayaz; Lederman, Robert J.] Washington Adventist Hosp, Div Intervent Cardiol, Takoma Pk, MD USA. [Shawl, Fayaz] George Washington Univ, Sch Med, Washington, DC USA. [Lederman, Robert J.] NHLBI, Cardiovasc Branch, Div Intramaral Res, NIH, Bethesda, MD 20892 USA. RP Shawl, F (reprint author), 7600 Carroll Ave, Takoma Pk, MD 20912 USA. EM fshawlmd@aol.com FU Intramural NIH HHS [Z01 HL005062-05] NR 6 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD FEB PY 2008 VL 20 IS 2 BP 73 EP 74 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V14MM UT WOS:000207738500007 PM 18252971 ER PT J AU Lee, J Wu, W Kopan, R AF Lee, Jonghyeob Wu, Wei Kopan, Raphael TI Murine vibrissae cultured in serum-free medium reinitiate anagen SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID HAIR-FOLLICLES; IN-VITRO; GROWTH; CYCLE; MORPHOGENESIS; RAT C1 [Lee, Jonghyeob; Kopan, Raphael] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. [Lee, Jonghyeob; Kopan, Raphael] Washington Univ, Sch Med, Dept Med, Div Dermatol, St Louis, MO 63110 USA. [Wu, Wei] NINDS, Synapt Transmiss Unit, Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Stanford Univ, Dept Dev Biol, Sch Med, 279 Campus Dr, Stanford, CA 94305 USA. EM kopan@wustl.edu FU NIGMS NIH HHS [R01 GM055479-08, R01 GM055479, R01 GM55479] NR 11 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2008 VL 128 IS 2 BP 482 EP 485 DI 10.1038/sj.jid.5701024 PG 5 WC Dermatology SC Dermatology GA 252NH UT WOS:000252452700033 PM 17687387 ER PT J AU Chen, GJ Han, GC Wang, JN Wang, RX Xu, RN Shen, BF Qian, JH Li, Y AF Chen, Guojiang Han, Gencheng Wang, Jianan Wang, Renxi Xu, Ruonan Shen, Beifen Qian, Jiahua Li, Yan TI Essential roles of TGF-beta in anti-CD3 antibody therapy: reversal of diabetes in nonobese diabetic mice independent of Foxp3(+) CD4(+) regulatory T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE autoimmunity; immunotherapy; cytokine; regulatory lymphocyte ID GROWTH-FACTOR-BETA; IMMUNE-RESPONSES; AUTOIMMUNE ENCEPHALOMYELITIS; ACTIVE TOLERANCE; SELF-TOLERANCE; MECHANISMS; TGF-BETA-1; RECEPTOR; DISEASE; IMMUNOSUPPRESSION AB Anti-CD3 mAb have potentials to treat overt autoimmunity as reported recently. However, the underlying mechanisms remain unclear. In this report, using an animal model of type 1 diabetes, we found that TGF-beta 1, an important immunoregulatory cytokine, plays a critical role in anti-CD3-mediated diabetes reversion and immune tolerance. Anti-CD3 treatment increased the TGF-beta 1 production, lasting for a long period of time, which contributed to maintaining peripheral tolerance by controlling pathogenic cells. Furthermore, we found that anti-CD3 treatment did not increase the forkhead box p3 + (Foxp3(+)) CD4(+) regulatory T cells (Tregs). When fractionated from anti-CD3-treated, remitting mice and cotransferred with splenic cells from diabetic NOD mice, these Tregs failed to inhibit diabetes development in NOD. scid mice. Moreover, we found that the depletion of these Tregs did not affect an anti-CD3-mediated, therapeutic effect and the level of TGF-beta 1, production, which suggested that an increased level of TGF-beta 1 may not derive from these Tregs. Thus, our data showed a dispensable role of Foxp3(+) CD4(+) Tregs in anti-CD3 antibody-reversed diabetes in NOD mice. These findings may have an important implication for understanding the involved mechanisms responsible for immunomodulatory function of anti-CD3 antibody on autoimmune diseases. C1 [Chen, Guojiang; Han, Gencheng; Wang, Jianan; Wang, Renxi; Xu, Ruonan; Shen, Beifen; Li, Yan] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. [Qian, Jiahua] NCI, Vaccine Branch, Bethesda, MD 20892 USA. RP Li, Y (reprint author), Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Taiping Rd,27, Beijing 100850, Peoples R China. EM liyan62033@yahoo.com.cn NR 41 TC 20 Z9 20 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB 1 PY 2008 VL 83 IS 2 BP 280 EP 287 DI 10.1189/jlb.0707498 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 257AR UT WOS:000252772100008 PM 18029395 ER PT J AU Hyodo, F Subramanian, S Devasahayam, N Murugesan, R Matsumoto, K Mitchell, JB Krishna, MC AF Hyodo, F. Subramanian, S. Devasahayam, N. Murugesan, R. Matsumoto, K. Mitchell, J. B. Krishna, M. C. TI Evaluation of sub-microsecond recovery resonators for in vivo electron paramagnetic resonance imaging SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE EPR; EPRI; Litz coil; parallel coil; in vivo imaging ID LOOP-GAP RESONATOR; SPECTROSCOPY; FIELD; RATS AB Time-domain (TD) electron paramagnetic resonance (EPR) imaging at 300 MHz for in vivo applications requires resonators with recovery times less than I Vs after pulsed excitation to reliably capture the rapidly decaying free induction decay (FID). In this study, we tested the suitability of the Litz foil coil resonator (LCR), commonly used in MRI, for in vivo EPR/EPRI applications in the TD mode and compared with parallel coil resonator (PCR). In TD mode, the sensitivity of LCR was lower than that of the PCR. However, in continuous wave (CW) mode, the LCR showed better sensitivity. The RF homogeneity was similar in both the resonators. The axis of the RF magnetic field is transverse to the cylindrical axis of the LCR, making the resonator and the magnet co-axial. Therefore, the loading of animals, and placing of the anesthesia nose cone and temperature monitors was more convenient in the LCR compared to the PCR whose axis is perpendicular to the magnet axis. Published by Elsevier Inc. C1 [Hyodo, F.; Subramanian, S.; Devasahayam, N.; Mitchell, J. B.; Krishna, M. C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Murugesan, R.] Madurai Kamaraj Univ, Sch Chem, Madurai 625021, Tamil Nadu, India. [Matsumoto, K.] Natl Inst Radiol Sci, Heavy Ion Radiobiol Res Grp, Chiba 260, Japan. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3 B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov FU Intramural NIH HHS [Z01 BC010476-04] NR 19 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD FEB PY 2008 VL 190 IS 2 BP 248 EP 254 DI 10.1016/j.jmr.2007.11.004 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 256TL UT WOS:000252752700008 PM 18042414 ER PT J AU Gozalo, AS Chavera, A Montoya, EJ Takano, J Weller, RE AF Gozalo, Alfonso S. Chavera, Alfonso Montoya, Enrique J. Takano, Juan Weller, Richard E. TI Relationship of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and proteinuria to cardiomyopathy in the owl monkey (Aotus vociferans) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Workshop for the Association-of-Primate-Veterinarians CY OCT 12-14, 2006 CL Park City, UT SP Assoc Primate Veterinarians, Alpha Genesis, ANILAB LLC, Bio-Serv, Charles River BRF, Covance Res Prod Inc, RC Hartelust BV, Shared Enterprises Ltd, VRL Lab, Three Spring Sci Inc, BioReliance Inc, Suburban Surg Co Inc, Allentown Inc, Animal Specialties & Provis LLC, Frames Animal Transportat, Buckshire Corp, Instech Solomon, Brain & Software Int, Purina Lab Diets, Lab Prod Inc, Zoologix Inc, Mannheimers Fdn DE Cebidae; hypertension; primates; serum chemistry; urinalysis ID URINARY ALBUMIN EXCRETION; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; DNA VACCINE; JOB STRAIN; TRIVIRGATUS; NANCYMAE; CHALLENGE; LESIONS; VIRUS AB Background The purpose of this study was to determine serum reference values for creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in captive-born and wild-caught owl monkeys to assess their usefulness for diagnosing myocardial disease. Methods Blood samples were collected for CK, AST and LDH determinations. In addition, urine samples were collected and semiquantitative tests performed. Results There was no statistically significant difference between CK, AST and LDH when comparing both groups. However, when comparing monkeys with proteinuria to those without proteinuria, a statistically significant difference in CK value was observed (P = 0.021). In addition the CK/AST ratio revealed that 29% of the animals included in this study had values suggesting cardiac infarction. Grossly, cardiac concentric hypertrophy of the left ventricle and small, pitted kidneys were the most common findings. Microscopically, myocardial fibrosis, contraction band necrosis, hypertrophy and hyperplasia of coronary arteries, medium-sized renal arteries and afferent glomerular arteriolae were the most significant lesions, along with increased mesangial matrix and hypercellularity of glomeruli, Bowman's capsule and peritubular space fibroplasia. Conclusions These findings suggest that CK, AST and LDH along with urinalysis provide a reliable method for diagnosing cardiomyopathies in the owl monkey. In addition, CK/AST ratio, proteinuria and the observed histological and ultrastructural changes suggest that Aotus vociferans suffer from arterial hypertension and chronic myocardial infarction. C1 [Gozalo, Alfonso S.; Montoya, Enrique J.] Univ Nacl Mayor San Marcos, Inst Vet Invest Trop & Altura, Fac Med Vet, Iquitos, Peru. [Chavera, Alfonso; Takano, Juan] Univ Nacl Mayor San Marcos, Fac Med Vet, Dept Patol, Lima 14, Peru. [Weller, Richard E.] Pacific NW Natl Lab, Richland, WA 99352 USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, Bldg 14B S,Room 228,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov NR 46 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB PY 2008 VL 37 SU 1 BP 29 EP 38 DI 10.1111/j.1600-0684.2007.00258.x PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 261ZE UT WOS:000253117700007 PM 18269526 ER PT J AU Strech, D Synofzik, M Marckmann, G AF Strech, Daniel Synofzik, Matthis Marckmann, Georg TI How physicians allocate scarce resources at the bedside: A systematic review of qualitative studies SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE clinical ethics; health-care rationing; medical decision making; qualitative research; systematic review ID HEALTH-CARE; GENERAL-PRACTICE; DECISION-MAKING; INSTITUTIONS; PRINCIPLES; BARRIERS; JUSTICE; ETHICS; VIEWS; TRUST AB Although rationing of scarce health-care resources is inevitable in clinical practice, there is still limited and scattered information about bow physicians perceive and execute this bedside rationing (BSR) and how it can be performed in an ethically fair way. This review gives a systematic overview on physicians' perspectives on influences, strategies, and consequences of health-care rationing. Relevant references as identified by systematically screening major electronic databases and manuscript references were synthesized by thematic analysis. Retrieved studies focused on themes that fell under three major headings: (i) conditions and influences of BSR, (ii) strategies of BSR, and (iii) consequences of BSR. The range of themes indicates that physicians' rationing behavior is highly variable, strongly influenced by context-related factors, and consists mainly of implicit rationing strategies. Torn between patient advocacy and the obligation to contain costs, physicians experience various role conflicts. The development of explicit rationing strategies seems necessary to avoid arbitrary BSR and allow a fair allocation of health-care resources. C1 [Strech, Daniel] Univ Tubingen, Inst Eth & Geschichte Med, D-72076 Tubingen, Germany. [Strech, Daniel] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Strech, D (reprint author), Univ Tubingen, Inst Eth & Geschichte Med, Schleichstr 8, D-72076 Tubingen, Germany. EM daniel.strech@uni-tuebingen.de OI Strech, Daniel/0000-0002-9153-079X NR 31 TC 53 Z9 53 U1 3 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD FEB PY 2008 VL 33 IS 1 BP 80 EP 99 DI 10.1093/jmp/jhm007 PG 20 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 305PF UT WOS:000256189600006 PM 18420552 ER PT J AU Wolf, CM Wang, L Alcalai, R Pizard, A Burgon, PG Ahmad, F Sherwood, M Branco, DM Wakimoto, H Fishman, GI See, V Stewart, CL Conner, DA Berul, CI Seidman, CE Seidman, JG AF Wolf, Cordula M. Wang, Libin Alcalai, Ronny Pizard, Anne Burgon, Patrick G. Ahmad, Ferhaan Sherwood, Megan Branco, Dorothy M. Wakimoto, Hiroko Fishman, Glenn I. See, Vincent Stewart, Colin L. Conner, David A. Berul, Charles I. Seidman, Christine E. Seidman, J. G. TI Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE cardiac conduction system; arrhythmia; heart block; laminopathies; dilated cardiomyopathy ID DREIFUSS MUSCULAR-DYSTROPHY; N-TERMINAL KINASE; A-TYPE LAMINS; ATRIOVENTRICULAR-BLOCK; NUCLEAR MECHANICS; LMNA MUTATIONS; SUDDEN-DEATH; GENE; ACTIVATION; DEFECTS AB Mutations in the lamin A/C (LMNA) gene, which encodes nuclear membrane proteins, cause a variety of human conditions including dilated cardiomyopathy (DCM) with associated cardiac conduction system disease. To investigate mechanisms responsible for electrophysiologic and myocardial phenotypes caused by dominant human LAMA mutations, we performed longitudinal evaluations in heterozygous Lmna(+/-) mice. Despite one normal allele, Lmna(+/-) mice had 50% of normal cardiac lamin A/C levels and developed cardiac abnormalities. Conduction system function was normal in neonatal Lmna(+/-) mice but, by 4 weeks of age, attioventricular (AV) nodal myocytes had abnormally shaped nuclei and active apoptosis. Telemetric and in vivo electrophysiologic studies in 10-week-old Lmna(+/-) mice showed AV conduction defects and both atrial and ventricular arrhythmias, analogous to those observed in humans with heterozygous LANA mutations. Isolated myocytes from 12-month-old Lmna(+/-) mice exhibited impaired contractility. In vivo cardiac studies of aged Lmna(+/-) mice revealed DCM; in some mice this occurred without overt conduction system disease. However, neither histopathology nor serum CK levels indicated skeletal muscle pathology. These data demonstrate cardiac pathology due to heterozygous Lmna mutations reflecting a 50% reduction in lamin protein levels. Lamin haploinsufficiency caused early-onset programmed cell death of AV nodal myocytes and progressive electrophysiologic disease. While lamin haploinsufficiency was better tolerated by non-conducting myocytes, ultimately, these too succumbed to diminished lamin levels leading to dilated cardiomyopathy, which presumably arose independently from conduction system disease. (c) 2007 Elsevier Inc. All rights reserved. C1 [Wolf, Cordula M.; Sherwood, Megan; Branco, Dorothy M.; Wakimoto, Hiroko; Berul, Charles I.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Cardiol Childrens Hosp, Boston, MA 02115 USA. [Wang, Libin; Alcalai, Ronny; Pizard, Anne; Burgon, Patrick G.; Ahmad, Ferhaan; Conner, David A.; Seidman, Christine E.; Seidman, J. G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Pizard, Anne] INSERM, Unite 652, Inst Cordeliers, Paris, France. [Burgon, Patrick G.] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada. [Ahmad, Ferhaan] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15213 USA. [Ahmad, Ferhaan] Univ Pittsburgh, Dept Med & Genet, Pittsburgh, PA 15213 USA. [Sherwood, Megan] Childrens Hosp Westmead, Dept Pediat, Sydney, NSW, Australia. [Fishman, Glenn I.] NYU, Sch Med, Leon H Cahrney Div Cardiol, New York, NY 10016 USA. [See, Vincent] Boston Univ, Sch Med, Boston, MA 02118 USA. [See, Vincent] Med Ctr, Boston, MA 02118 USA. [Stewart, Colin L.] NCI, Canc & Dev Biol OLab, Frederick, MD 21702 USA. [Seidman, Christine E.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Berul, CI (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Cardiol Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM charles.berul@cardio.chboston.org FU NHLBI NIH HHS [R01 HL084553-02, R01 HL080494, R01 HL080494-03, R01 HL084553, U01 HL066582, U01 HL066582-04] NR 41 TC 70 Z9 72 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD FEB PY 2008 VL 44 IS 2 BP 293 EP 303 DI 10.1016/j.yjmcc.2007.11.008 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 275AC UT WOS:000254043300009 PM 18182166 ER PT J AU Garron, ML Arthos, J Guichou, JF McNally, J Cicala, C Arold, ST AF Garron, Marie-Line Arthos, James Guichou, Jean-Francois McNally, Jonathan Cicala, Claudia Arold, Stefan T. TI Structural basis for the interaction between focal adhesion kinase and CD4 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CD4; focal adhesion kinase; HIV; gp120; Nef ID HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGE-TROPIC HIV; T-CELLS; TARGETING DOMAIN; DOWN-REGULATION; RAPID INTERNALIZATION; CHEMOKINE RECEPTOR; NEF PROTEIN; SH3 DOMAIN; BINDING AB Focal adhesion kinase (FAK) and CD4 fulfil vital functions in cellular signal transduction: FAK is a central component in integrin signalling, whereas CD4 plays essential roles in the immune defence. In T lymphocytes, FAK and CD4 localise to the same signalling complexes after stimulation by either the human immunodeficiency virus (HIV) gp120 glycoprotein or an antigen, suggesting the concerted action of FAK and CD4 in these cells. Using crystallography and microcalorimetry, we here show that the focal adhesion targeting (FAT) domain of FAK binds specifically to the CD4 endocytosis motif in vitro. This FAT-CD4 complex is structurally and thermodynamically similar to the one FAT forms with paxillin LD motifs. The CD4 binding site on FAT presents the same features as the established CD4 binding site on the HIV-1 Nef protein. The binding of FAT to CD4 is incompatible with the binding of Lck to CD4. We further show that HIV-1 gp120 triggers the association of CD4 with FAK in T cells, under conditions that are known to dissociate Lck from CD4. Our results suggest that the FAK-CD4 complex represents an alternative route for eliciting T-cell-specific signals and that it links gp120 engagement to distinctive T-cell signalling during HIV infection. In infected cells, HIV-1 Net may displace FAK from CD4 to protect the cells from apoptosis. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Garron, Marie-Line; Guichou, Jean-Francois; Arold, Stefan T.] Univ Montpellier 1 & 2, CNRS, UMR 5048, CBS, F-34090 Montpellier, France. [Garron, Marie-Line; Guichou, Jean-Francois; Arold, Stefan T.] INSERM, UMR 554, F-34090 Montpellier, France. [Arthos, James; McNally, Jonathan; Cicala, Claudia] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Arold, ST (reprint author), Univ Montpellier 1 & 2, CNRS, UMR 5048, CBS, 29 Rue Navacelles, F-34090 Montpellier, France. EM Stefan.Arold@cbs.cnrs.fr RI FIP, BM30A/I-5166-2015; OI Arold, Stefan T/0000-0001-5278-0668 NR 40 TC 26 Z9 29 U1 0 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 1 PY 2008 VL 375 IS 5 BP 1320 EP 1328 DI 10.1016/j.jmb.2007.11.040 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261RQ UT WOS:000253098100013 PM 18078954 ER PT J AU Kim, YC Hummer, G AF Kim, Young C. Hummer, Gerhard TI Coarse-grained models for simulations of multiprotein complexes: application to ubiquitin binding SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein-protein interactions; protein-protein docking; Vps27/Hse1; ubiquitin binding domain; energy function ID PROTEIN-PROTEIN INTERACTIONS; CYTOCHROME-C PEROXIDASE; QUASI-CHEMICAL APPROXIMATION; SIDE-CHAIN FLEXIBILITY; 2ND VIRIAL-COEFFICIENT; CRYSTAL-STRUCTURE; CONTACT ENERGIES; PAIR POTENTIALS; FERRICYTOCHROME-C; TRANSITION-STATES AB We develop coarse-grained models and effective energy functions for simulating thermodynamic and structural properties of multiprotein complexes with relatively low binding affinity (K-d > 1 mu M) and apply them to binding of Vps27 to membrane-tethered ubiquitin. Folded protein domains are represented as rigid bodies. The interactions between the domains are treated at the residue level with amino-acid-dependent pair potentials and Debye-Huckel-type electrostatic interactions. Flexible linker peptides connecting rigid protein domains are represented as amino acid beads on a polymer with appropriate stretching, bending, and torsion-angle potentials. In simulations of membrane-attached protein complexes, interactions between amino acids and the membrane are described by residue-dependent short-range potentials and long-range electrostatics. We parameterize the energy functions by fitting the osmotic second virial coefficient of lysozyme and the binding affinity of the ubiquitin-CUE complex. For validation, extensive replica-exchange Monte Carlo simulations are performed of various protein complexes. Binding affinities for these complexes are in good agreement with the experimental data. The simulated structures are clustered on the basis of distance matrices between two proteins and ranked according to cluster population. In similar to 70% of the complexes, the distance root-mean-square is less than 5 angstrom from the experimental structures. In similar to 90% of the complexes, the binding interfaces on both proteins are predicted correctly, and in all other cases at least one interface is correct. Transient and nonspecifically bound structures are also observed. With the validated model, we simulate the interaction between the Vps27 multiprotein complex and a membrane-tethered ubiquitin. Ubiquitin is found to bind preferentially to the two UIM domains of Vps27, but transient interactions between ubiquitin and the VHS and FYVE domains are observed as well. These specific and nonspecific interactions are found to be positively cooperative, resulting in a substantial enhancement of the overall binding affinity beyond the similar to 300 mu M of the specific domains. We also find that the interactions between ubiquitin and Vps27 are highly dynamic, with conformational rearrangements enabling binding of Vps27 to diverse targets as part of the multivesicular-body protein-sorting pathway. Published by Elsevier Ltd. C1 [Kim, Young C.; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS [Z01 DK029033-08] NR 87 TC 91 Z9 91 U1 5 U2 37 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 1 PY 2008 VL 375 IS 5 BP 1416 EP 1433 DI 10.1016/j.jmb.2007.11.063 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261RQ UT WOS:000253098100020 PM 18083189 ER PT J AU Pomeroy, LW Bjornstad, ON Holmes, EC AF Pomeroy, Laura W. Bjornstad, Ottar N. Holmes, Edward C. TI The evolutionary and epidemiological dynamics of the paramyxoviridae SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE paramyxovirus; coalescent; population bottleneck; measles virus; mumps virus; canine distemper virus ID CANINE-DISTEMPER VIRUS; POPULATION HISTORY; GENETIC DIVERSITY; PROTEIN GENE; RNA VIRUSES; MEASLES; SUBSTITUTION; GLYCOPROTEIN; SELECTION; GENOTYPES AB Paramyxoviruses are responsible for considerable disease burden in human and wildlife populations: measles and mumps continue to affect the health of children worldwide, while canine distemper virus causes serious morbidity and mortality in a wide range of mammalian species. Although these viruses have been studied extensively at both the epidemiological and the phylogenetic scales, little has been done to integrate these two types of data. Using a Bayesian coalescent approach, we infer the evolutionary and epidemiological dynamics of measles, mumps and canine distemper viruses. Our analysis yielded data on viral substitution rates, the time to common ancestry, and elements of their demographic history. Estimates of rates of evolutionary change were similar to those observed in other RNA viruses, ranging from 6.585 to 11.350 x 10(-4) nucleotide substitutions per site, per year. Strikingly, the mean Time to the Most Recent Common Ancestor (TMRCA) was both similar and very recent among the viruses studied, ranging from only 58 to 91 years (1908 to 1943). Worldwide, the paramyxoviruses studied here have maintained a relatively constant level of genetic diversity. However, detailed heterchronous samples illustrate more complex dynamics in some epidemic populations, and the relatively low levels of genetic diversity (population size) in all three viruses is likely to reflect the population bottlenecks that follow recurrent outbreaks. C1 [Pomeroy, Laura W.; Bjornstad, Ottar N.; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. [Bjornstad, Ottar N.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. RP Pomeroy, LW (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, 501 ASI Bldg, University Pk, PA 16802 USA. EM LPomeroy@psu.edu RI Bjornstad, Ottar/I-4518-2012; OI Holmes, Edward/0000-0001-9596-3552 FU NIGMS NIH HHS [GM080533-01, R01 GM080533, R01 GM080533-02] NR 34 TC 47 Z9 48 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD FEB PY 2008 VL 66 IS 2 BP 98 EP 106 DI 10.1007/s00239-007-9040-x PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 277HE UT WOS:000254202500002 PM 18217182 ER PT J AU Toth, ZE Zelena, D Mergl, Z Kirilly, E Varnai, P Mezey, E Makara, GB Palkovits, M AF Toth, Zsuzsanna E. Zelena, Dora Mergl, Zsuzsa Kirilly, Eszter Varnai, Peter Mezey, Eva Makara, Gabor B. Palkovits, Miklos TI Chronic repeated restraint stress increases prolactin-releasing peptide/tyrosine-hydroxylase ratio with gender-related differences in the rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE estrogen receptor alpha; gender-related difference; hypothalamic paraventricular nucleus lesion; in situ hybridization; rat ID DORSOMEDIAL HYPOTHALAMIC NUCLEUS; MESSENGER-RNA EXPRESSION; PARAVENTRICULAR NUCLEUS; FOOD-INTAKE; BODY-WEIGHT; IMMUNOREACTIVE NEURONS; NORADRENERGIC NEURONS; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; PEPTIDE NEURONS AB In this study, we investigated the effect of chronic repeated restraint (RR) on prolactin-releasing peptide (PrRP) expression. In the brainstem, where PrRP colocalize with norepinephrine in neurons of the A1 and A2 catecholaminergic cell groups, the expression of tyrosine hydroxylase (TH) has also been examined. In the brainstem, but not in the hypothalamus, the basal PrRP expression in female rats was higher than that in the males that was abolished by ovariectomy. RR evoked an elevation of PrRP expression in all areas investigated, with smaller reaction in the brainstems of females. There was no gender-related difference in the RR-evoked TH expression. Elevation of PrRP was relatively higher than elevation of TH, causing a shift in PrRP/TH ratio in the brainstem after RR. Estrogen alpha receptors were found in the PrRP neurons of the A1 and A2 cell groups, but not in the hypothalamus. Bilateral lesions of the hypothalamic paraventricular nucleus did not prevent RR-evoked changes. Elevated PrRP production parallel with increased PrRP/TH ratio in A1/A2 neurons indicate that: (i) there is a clear difference in the regulation of TH and PrRP expression after RR, and (ii) among other factors this may also contribute to the changed sensitivity of the hypothalamo-pituitary-adrenal axis during chronic stress. C1 [Toth, Zsuzsanna E.; Palkovits, Miklos] Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, H-1085 Budapest, Hungary. [Zelena, Dora; Mergl, Zsuzsa; Makara, Gabor B.] Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary. [Kirilly, Eszter] Semmelweis Univ, Fac Med, Dept Pharmacol & Pharmacotherapy, H-1085 Budapest, Hungary. [Kirilly, Eszter] Natl Inst Psychiat & Neurol, Lab Neurochem & Expt Med, Budapest, Hungary. [Varnai, Peter] Semmelweis Univ, Fac Med, Dept Physiol, H-1085 Budapest, Hungary. [Mezey, Eva] NIDCR, CSDB, NIH, Bethesda, MD USA. RP Toth, ZE (reprint author), Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, Tuzolto Utca 58, H-1085 Budapest, Hungary. EM tothzs@ana.sote.hu RI Palkovits, Miklos/F-2707-2013; Makara, Gabor/H-8397-2013; OI Makara, Gabor/0000-0001-9220-0373; Palkovits, Miklos/0000-0003-0578-0387 NR 59 TC 9 Z9 11 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2008 VL 104 IS 3 BP 653 EP 666 DI 10.1111/j.1471-4159.2007.05069.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 250TD UT WOS:000252322600007 PM 18199117 ER PT J AU Tamagno, E Guglielmotto, M Aragno, M Borghi, R Autelli, R Giliberto, L Muraca, G Danni, O Zhu, XW Smith, MA Perry, G Jo, DG Mattson, MP Tabaton, M AF Tamagno, Elena Guglielmotto, Michela Aragno, Manuela Borghi, Roberta Autelli, Riccardo Giliberto, Luca Muraca, Giuseppe Danni, Oliviero Zhu, Xiongwei Smith, Mark A. Perry, George Jo, Dong-Gyu Mattson, Mark P. Tabaton, Massimo TI Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; BACE1; JNK pathway oxidative stress; gamma-secretase ID N-TERMINAL KINASE; ISCHEMIC BRAIN-INJURY; ALZHEIMERS-DISEASE; C-JUN; LIPID-PEROXIDATION; CEREBRAL-ISCHEMIA; A-BETA; NEURONAL APOPTOSIS; EXPRESSION; PEPTIDE AB Sequential cleavages of the beta-amyloid precursor protein cleaving enzyme 1 (BACE1) by beta-secretase and gamma-secretase generate the amyloid beta-peptides, believed to be responsible of synaptic dysfunction and neuronal cell death in Alzheimer's disease (AD). Levels of BACE1 are increased in vulnerable regions of the AD brain, but the underlying mechanism is unknown. Here we show that oxidative stress (OS) stimulates BACE1 expression by a mechanism requiring gamma-secretase activity involving the c-jun N-terminal kinase (JNK)/c-jun pathway. BACE1 levels are increased in response to OS in normal cells, but not in cells lacking presenilins or amyloid precursor protein. Moreover, BACE1 is induced in association with OS in the brains of mice subjected to cerebral ischaemia/reperfusion. The OS-induced BACE1 expression correlates with an activation of JNK and c-jun, but is absent in cultured cells or mice lacking JNK. Our findings suggest a mechanism by which OS induces BACE1 transcription, thereby promoting production of pathological levels of amyloid beta in AD. C1 [Tamagno, Elena; Guglielmotto, Michela; Aragno, Manuela; Autelli, Riccardo; Danni, Oliviero] Univ Turin, Dept Expt Med & Oncol, Turin, Italy. [Borghi, Roberta; Giliberto, Luca; Tabaton, Massimo] Univ Genoa, Dept Neurosci, Genoa, Italy. [Muraca, Giuseppe] Univ Turin, Dept Anat Pharmacol & Forens Med, Turin, Italy. [Zhu, Xiongwei; Smith, Mark A.; Perry, George] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Jo, Dong-Gyu; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Jo, Dong-Gyu] Sungkyunkwan Univ, Coll Pharm, Suwon, South Korea. RP Tamagno, E (reprint author), Univ Turin, Dept Expt Med & Oncol, Corso Raffaello 30, Turin, Italy. EM elena.tamagno@unito.it RI Smith, Mark/A-9053-2009; Zhu, Xiongwei/A-9629-2009; Perry, George/A-8611-2009; Mattson, Mark/F-6038-2012 OI Perry, George/0000-0002-6547-0172; FU Intramural NIH HHS; NIA NIH HHS [AG024028, R01 AG024028, R01 AG024028-02]; Telethon [GGP06009] NR 64 TC 202 Z9 210 U1 3 U2 19 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2008 VL 104 IS 3 BP 683 EP 695 DI 10.1111/j.1471-4159.2007.05072.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 250TD UT WOS:000252322600009 PM 18005001 ER PT J AU Schepers, RJF Mahoney, JL Zapata, A Chefer, V Shippenberg, TS AF Schepers, Raf Jan-Filip Mahoney, Janet Lynn Zapata, Agustin Chefer, Vladimir Shippenberg, Toni Shaun TI The effects of local perfusion of DAMGO on extracellular GABA and glutamate concentrations in the rostral ventromedial medulla SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE analgesia; GABA glutamate; microdialysis; rostral ventromedial medulla ID NUCLEUS RAPHE MAGNUS; MESENCEPHALIC MORPHINE ANALGESIA; COLUMN LIQUID-CHROMATOGRAPHY; PERIAQUEDUCTAL GRAY-MATTER; OPIOID RECEPTOR AGONISTS; D-ASPARTATE RECEPTORS; BRAIN-STEM; RAT-BRAIN; NOCICEPTIVE MODULATION; MICRODIALYSIS SAMPLES AB Electrophysiological data suggest an involvement of rostral ventromedial medulla (RVM) GABA and glutamate (GLU) neurons in morphine analgesia. Direct evidence that extracellular concentrations of GABA or GLU are altered in response to mu opioid receptor (MOP-R) activation is, however, lacking. We used in vivo microdialysis to investigate this issue. Basal GABA overflow increased in response to intra-RVM perfusion of KCl (60 mmol/L). Reverse microdialysis of the MOP-R agonist D-Ala(2),NMePhe(4),Gly-ol(5)]enkephalin (DAMGO) (20-500 mu mol/L) produced a concentration-dependent decrease of RVM GABA overflow. Behavioral testing revealed that concentrations that decreased GABA levels increased thermal withdrawal thresholds. A lower agonist concentration that did not increase GABA failed to alter thermal thresholds. DAMGO did not alter GLU concentrations. However, KCl also failed to modify GLU release. Since rapid, transporter-mediated uptake may mask the detection of changes in GLU release, the selective excitatory amino acid transporter inhibitor pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mmol/L) was added to the perfusion medium for subsequent studies. tPDC increased GLU concentrations, confirming transport inhibition. KCl increased GLU dialysate levels in the presence of tPDC, demonstrating that transport inhibition permits detection of depolarization-evoked GLU overflow. In the presence of tPDC, DAMGO increased GLU overflow in a concentration-dependent manner. These data demonstrate that MOP-R activation decreases GABA and increases GLU release in the RVM. We hypothesize that the opposing effects of MOP-R on GLU and GABA transmission contribute to opiate antinociception. C1 [Schepers, Raf Jan-Filip; Mahoney, Janet Lynn; Zapata, Agustin; Chefer, Vladimir; Shippenberg, Toni Shaun] NIH, Integrat Neurosci Program, Behav Neurosci Branch, NIDA,Intramural Res Program, Baltimore, MD 21224 USA. [Schepers, Raf Jan-Filip] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Shippenberg, TS (reprint author), NIH, Integrat Neurosci Program, Behav Neurosci Branch, NIDA,Intramural Res Program, 333 Cassell Dr, Baltimore, MD 21224 USA. EM tshippen@mail.nih.gov NR 64 TC 9 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2008 VL 104 IS 3 BP 806 EP 817 DI 10.1111/j.1471-4159.2007.05017.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 250TD UT WOS:000252322600019 PM 17961151 ER PT J AU Yue, C Mutsuga, N Sugimura, Y Verbalis, J Gainer, H AF Yue, C. Mutsuga, N. Sugimura, Y. Verbalis, J. Gainer, H. TI Differential kinetics of oxytocin and vasopressin heteronuclear RNA expression in the rat supraoptic nucleus in response to chronic salt loading In vivo SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE heteronuclear RNA; mRNA; gene expression; secretion; oxytocin; vasopressin; in situ hybridisation ID INTRON-SPECIFIC PROBES; GENE-EXPRESSION; INSITU HYBRIDIZATION; OSMOTIC STIMULATION; HYPOTHALAMUS; SECRETION; NEURONS; SYSTEM; LEVEL; CELLS AB Previous studies have shown that the secretion of oxytocin and vasopressin from the posterior pituitary always accompanies systemic hyperosmotic stimuli in rats, and that oxytocin and vasopressin mRNAs consistently increase in response to prolonged hyperosmotic stimuli. Hence, it has been widely interpreted that oxytocin and vasopressin secretion and gene expression are closely coupled. In the present study, we used both vasopressin and oxytocin intron- specific probes to measure vasopressin and oxytocin heteronuclear RNA (hnRNA) levels, respectively, by in situ hybridisation in the rat supraoptic nucleus (SON) in conjunction with radioimmunoassays of vasopressin and oxytocin peptide levels in plasma and in the posterior pituitary in normally hydrated rats and after 1-5 days of salt loading. Increased oxytocin secretion in response to hyperosmotic stimuli exceeded vasopressin secretion at every time point studied. Vasopressin hnRNA in the SON increased to near maximal levels within minutes after the hyperosmotic stimulus, and was maintained throughout all 5 days of salt loading. By contrast, oxytocin hnRNA did not significantly change from control levels until approximately 2 days after hyperosmotic stimulation, and was not maximal until 3 days. In summary, increases in oxytocin gene transcription in response to osmotic stimuli are dramatically delayed compared to increases in vasopressin gene transcription under the same conditions. These data indicate that oxytocin gene transcription is not as closely correlated with pituitary peptide secretion as is vasopressin gene transcription, and suggests that there is a fundamental difference in excitation-secretion-transcription coupling mechanisms that regulate these two closely related genes in the rat magnocellular neurones in the SON. C1 [Yue, C.; Mutsuga, N.; Gainer, H.] NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Mutsuga, N.; Sugimura, Y.] Nagoya Univ, Grad Sch Med, Dept Endocrinol & Diabet, Showa Ku, Nagoya, Aichi, Japan. [Sugimura, Y.; Verbalis, J.] Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC USA. RP Gainer, H (reprint author), NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bldg 49,Rm 5A78, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL083428] NR 22 TC 18 Z9 18 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD FEB PY 2008 VL 20 IS 2 BP 227 EP 232 DI 10.1111/j.1365-2826.2007.01640.x PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 254LK UT WOS:000252587900009 PM 18088359 ER PT J AU Shaikh, AG Jinnah, HA Tripp, RM Optican, LM Ramat, S Lenz, FA Zee, DS AF Shaikh, A. G. Jinnah, H. A. Tripp, R. M. Optican, L. M. Ramat, S. Lenz, F. A. Zee, D. S. TI Irregularity distinguishes limb tremor in cervical dystonia from essential tremor SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID SPASMODIC TORTICOLLIS AB Introduction: Patients with cervical dystonia (CD) often have limb tremor that is clinically indistinguishable from essential tremor (ET). Whether a common central mechanism underlies the tremor in these conditions is unknown. We addressed this issue by quantifying limb tremor in 19 patients with CD and 35 patients with ET. Method: Postural, resting and kinetic tremors were quantified (amplitude, mean frequency and regularity) using a three-axis accelerometer. Results: The amplitude of limb tremor in ET was significantly higher than in CD, but the mean frequency was not significantly different between the groups. The cycle-to-cycle variability of the frequency (ie the tremor irregularity), however, was significantly greater (similar to 50%) in CD. Analysis of covariance excluded the possibility that the increased irregularity was related to the smaller amplitude of tremor in CD (ANCOVA: p = 0.007, F = 5.31). Discussion: We propose that tremor in CD arises from oscillators with different dynamic characteristics, producing a more irregular output, whereas the tremor in ET arises from oscillators with similar dynamic characteristics, producing a more regular output. We suggest that variability of tremor is an important parameter for distinguishing tremor mechanisms. It is possible that changes in membrane kinetics based on the pattern of ion channel expression underlie the differences in tremor in some diseases. C1 [Shaikh, A. G.; Jinnah, H. A.; Zee, D. S.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Tripp, R. M.] FlexAble Syst, Fountain Hills, AZ USA. [Optican, L. M.] DHHS, NEI, Natl Inst Hlth, Bethesda, MD USA. [Ramat, S.] Univ Pavia, I-27100 Pavia, Italy. [Lenz, F. A.] Johns Hopkins Univ Hosp, Dept Neurosurg, Baltimore, MD 21287 USA. RP Shaikh, AG (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. EM aasefshaikh@gmail.com RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X FU Intramural NIH HHS [Z01 EY000302-13] NR 14 TC 21 Z9 21 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD FEB PY 2008 VL 79 IS 2 BP 187 EP 189 DI 10.1136/jnnp.2007.131110 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 261PG UT WOS:000253091900020 PM 17872981 ER PT J AU Jagannathan, J Lonser, RR Smith, R Devroom, HL Oldfield, EH AF Jagannathan, Jay Lonser, Russell R. Smith, Rene Devroom, Hetty L. Oldfield, Edward H. TI Surgical management of cerebellar hemangioblastomas in patients with von Hippel-Lindau disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebellar hemangioblastoma; surgery; tumor; von Hippel-Lindau disease ID CENTRAL-NERVOUS-SYSTEM; POSTERIOR-FOSSA HEMANGIOBLASTOMAS; RENAL-CELL CARCINOMA; ENDOLYMPHATIC SAC TUMORS; OF-THE-LITERATURE; NATURAL-HISTORY; SPINAL-CORD; TRANSTENTORIAL APPROACH; SUPPRESSOR GENE; METASTASIS AB Object. Despite the frequency of cerebellar hemangioblastomas in von Hippel-Lindau (VHL) disease, their optimum contemporary management has not been defined, and is made complex because of the multiple, progressive, and protean nature of the tumors found in patients with this disorder. To examine modem management and outcomes of cerebellar hemangioblastomas in VHL disease, the authors reviewed findings in patients with this disease who underwent resection of cerebellar hemangioblastomas. Methods. Consecutive patients with VHL disease who underwent surgery for cerebellar hemangioblastoma(s) at the National Institutes of Health were included. Eighty consecutive patients (44 female and 36 male patients) underwent 126 operations for removal of 164 cerebellar hemangioblastomas (age at surgery 37.8 +/- 10.3 years, follow-up duration 96.0 +/- 60.3 months). Serial clinical examinations, imaging studies, and operative records were analyzed. Results. Symptoms and signs included headache (94 operations; 75%), ataxia (55%), dysmetria (29%), and hydrocephalus (28%). Although the primary objective of surgery was resection of the hemangioblastoma considered responsible for symptoms (136 of the hemangioblastomas [83%]), 28 additional hemangioblastomas (17%) were removed during the same surgeries. Tumors associated with symptoms were larger (diameter 1.8 +/- 1.9 cm; volume 2.8 +/- 3.4 cm(3). p < 0.05) and more likely to be associated with peritumoral edema or peritumoral cysts (100% associated with edema and/or cyst; p < 0.05) than asymptomatic tumors (diameter 1.1 +/- 0.9 cm; volume 0.7 +/- 0.4 cm(3); 18%). More tumors were located in the posterior (74%) compared with the anterior (26%) half of the cerebellum (p < 0.05). Three months after resection, symptom improvement/stabilization had occurred following 124 of the operations (98%). Preoperative hydrocephalus resolved after tumor removal in 33 cases (94%) and did not require cerebrospinal fluid diversion. Long-term imaging follow-up (61.5 +/- 15.0 months) revealed no recurrences. Conclusions. Symptoms and signs caused by cerebellar hemangioblastomas in VHL disease are associated with edema and peritumoral cyst formation/propagation and are treated safely and effectively with resection. Cerebrospinal fluid diversion is rarely necessary after complete tumor removal in patients with preoperative hydrocephalus. Cerebellar hemangioblastomas are preferentially distributed in the posterior half of the cerebellum, as they are in the brainstem and spinal cord. Tumor recurrence is avoided by meticulous extracapsular resection. C1 [Jagannathan, Jay; Lonser, Russell R.; Smith, Rene; Devroom, Hetty L.; Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Jagannathan, Jay] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov FU Intramural NIH HHS NR 68 TC 62 Z9 69 U1 0 U2 3 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 FEB PY 2008 VL 108 IS 2 BP 210 EP 222 DI 10.3171/JNS/2008/108/2/0210 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 259JB UT WOS:000252934500003 PM 18240914 ER PT J AU Wetjen, NM Heiss, JD Oldfield, EH AF Wetjen, Nicholas M. Heiss, John D. Oldfield, Edward H. TI Time course of syringomyelia resolution following decompression of Chiari malformation Type I SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE Chiari malformation Type I; outcome assessment; pediatric neurosurgery; syringomyelia ID POSTERIOR CRANIAL FOSSA; CEREBELLAR TONSILS; PATHOPHYSIOLOGY; PATHOGENESIS; MANAGEMENT; ADULTS AB Object. To better understand syrinx pathophysiology, the authors performed a prospective study in which they used findings from serial clinical and magnetic resonance (MR) imaging examinations performed before and after cranio-cervical decompression to establish the time course of syrinx narrowing: Methods. Serial clinical examinations and cervical MR imaging were performed in 29 consecutive patients with Chiari malformation Type I (CM-I) and syringomyelia before surgery, 1 week, and 3-6 months after surgery, and then annually. Time to narrowing of the syrinx (> 50% decrease in maximal anteroposterior diameter) following surgery was calculated using the Kaplan-Meier method. Results. All syringes decreased in diameter and length (number of segments) on MR images at 3-6 months, I year, and 2 years or later. The syrinx diameter decreased from 6.9 +/- 2.1 mm (mean +/- standard deviation) preoperatively to < 1.5 mm at last evaluation (p < 0.0001). The median time to syrinx narrowing was 3.6 months following CM-I decompression (95% confidence interval 3.0-6.5 months). After surgery 94% of patients had improved symptoms, but symptoms resolved incompletely in 68% of patients; 52 and 59% of patients had residual dysesthesias and sensory loss, respectively. Clinical improvement occurred before partial or complete disappearance of the syrinx on MR images. Patient age, duration of symptoms, sex, preoperative syrinx diameter, and length of syrinx were unrelated to time to syrinx narrowing. Conclusions. Most patients improve after decompression for CM-I, but many have residual symptoms. Syringes may continue to diminish for months to years after surgical decompression. A collapsed syrinx (absence of distention of the spinal cord) indicates that the pathophysiology has been reversed by treatment regardless of the completeness of elimination of the cavity on MR images. C1 [Wetjen, Nicholas M.; Heiss, John D.; Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Wetjen, Nicholas M.] Mayo Clin, Dept Neurol Surg, Rochester, MN USA. RP Heiss, JD (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM heissj@ninds.nih.gov OI Heiss, John/0000-0002-3890-0165 FU Intramural NIH HHS [ZIA NS003050-05] NR 16 TC 32 Z9 34 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROS-PEDIATR JI J. Neurosurg.-Pediatr. PD FEB PY 2008 VL 1 IS 2 BP 118 EP 123 DI 10.3171/PED/2008/1/2/118 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 306WF UT WOS:000256277900003 PM 18352779 ER PT J AU Khaibullina, A Jang, BS Sun, H Lee, N Yu, S Frenkel, V Carrasquillo, JA Pastan, I Li, KCP Paik, CH AF Khaibullina, Alfia Jang, Beom-Su Sun, Haihao Lee, Nhat Yu, Sarah Frenkel, Victor Carrasquillo, Jorge A. Pastan, Ira Li, King C. P. Paik, Chang H. TI Pulsed high-intensity focused ultrasound enhances uptake of radiolabeled monoclonal antibody to human epidermoid tumor in nude mice SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE pulsed-HIFU; enhanced tumor uptake; In-111-MX-B3; A431 tumor ID REFRACTORY LOW-GRADE; SINGLE-CHAIN FV; SOLID TUMORS; IN-VIVO; CARCINOMA XENOGRAFTS; CANCER XENOGRAFTS; COMPARATIVE BIODISTRIBUTION; BIOLOGICAL IMPEDIMENTS; PHASE-I; RADIOIMMUNOTHERAPY AB The aim of this study was to determine if pulsed high-intensity focused ultrasound (HIFU) exposures could enhance tumor uptake of In-111-MX-B3, a murine IgG1(K) monoclonal antibody directed against the Le(y) antigen. Methods: MX-B3 was labeled with In-111, purified, and confirmed for its binding to the antigen-positive A431 cell line. Groups of nude mice were inoculated subcutaneously with A431 tumor cells on both hind flanks. A tumor on one flank was treated with pulsed-HIFU; the other tumor was used as an untreated control. Within 10 min after the HIFU exposure, the mice received intravenous In-111-MX-B3 for imaging and biodistribution studies. Mice were euthanized at 1, 24, 48, and 120 h after injection for biodistribution studies. Results: The HIFU exposure shortened the peak tumor uptake time (24 vs. 48 h for the control) and increased the peak tumor uptake value (38 vs. 25 %ID/g [percentage injected dose per gram] for the control). The HIFU effect on enhancing tumor uptake was greater at earlier times up to 24 h, but the effect was gradually diminished thereafter. The HIFU effect on enhancing tumor uptake was substantiated by nuclear imaging studies. HIFU also increased the uptake of the antibody in surrounding tissues, but the net increase was marginal compared with the increase in tumor uptake. Conclusion: This study demonstrates that pulsed-HIFU significantly enhances the delivery of In-111-MX-B3 in human epidermoid tumors xenografted in nude mice. The results of this pilot study warrant further evaluation of other treatment regimens, such as repeated HIFU exposures for greater delivery enhancement of antibodies labeled with cytotoxic radioisotopes or pulsed-HIFU exposure in addition to a combined therapy of Y-90-B3 and taxol to enhance the synergistic effect. C1 [Jang, Beom-Su; Lee, Nhat; Yu, Sarah; Carrasquillo, Jorge A.; Paik, Chang H.] NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. [Jang, Beom-Su; Lee, Nhat; Yu, Sarah; Carrasquillo, Jorge A.; Paik, Chang H.] NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. [Pastan, Ira] NIH, Natl Canc Inst, Mol Biol Lab, Bethesda, MD 20892 USA. RP Paik, CH (reprint author), NIH, Ctr Clin, Dept Nucl Med, Bldg 21,Room 136, Bethesda, MD 20892 USA. EM cpaik@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 40 TC 43 Z9 47 U1 0 U2 11 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 2008 VL 49 IS 2 BP 295 EP 302 DI 10.2967/jnumed.107.046888 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258KH UT WOS:000252866300038 PM 18199622 ER PT J AU O'Neil, C Fisher, C AF O'Neil, Carol Fisher, Cheryl TI Should I take this course online? SO JOURNAL OF NURSING EDUCATION LA English DT Article ID WORLD-WIDE-WEB; NURSING-RESEARCH; EDUCATION; UNDERGRADUATE; INSTRUCTION; STUDENTS; INTERNET; FACULTY AB As the number of online nursing courses increases, students are faced with the daunting question, "Should I take this course online?" Although online courses are convenient, convenience should not be the sole factor for making this decision. Students and their advisors should discuss the characteristics of successful online students before deciding to take a course online. A study was conducted in which the same face-to-face and online version of a course were compared using Ragan's framework. The results of the study describe characteristics that can serve as useful criteria for predicting student success in an online course. C1 [O'Neil, Carol] Univ Maryland, Sch Nursing, Dept Family & Community Hlth, Inst Educators Nursing & Hlth Profess, Baltimore, MD 21201 USA. [Fisher, Cheryl] NIH, Ctr Clin, Program Manager Practice Dev, Bethesda, MD 20892 USA. RP O'Neil, C (reprint author), Univ Maryland, Sch Nursing, Dept Family & Community Hlth, Inst Educators Nursing & Hlth Profess, 655,W Lombard St, Baltimore, MD 21201 USA. EM oneil@son.umaryland.edu NR 23 TC 7 Z9 7 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD FEB PY 2008 VL 47 IS 2 BP 53 EP 58 PG 6 WC Nursing SC Nursing GA 257SJ UT WOS:000252818500002 PM 18320955 ER PT J AU DeRosa, F Keefer, LK Hrabie, JA AF DeRosa, Frank Keefer, Larry K. Hrabie, Joseph A. TI Nitric oxide reacts with methoxide SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID FUNCTIONAL-GROUP; CHEMISTRY; CARBON AB CH3ONa ->(NO) HCOONa Despite over a century of reports to the contrary, sodium methoxide has been found to react with nitric oxide (NO). The reaction, whose final organic product is sodium formate, is postulated to occur via an intermediate O-bound diazeniumdiolate [CH3O-N(O)=NO-] that decomposes to formaldehyde and nitrous oxide. Sodium formate forms from the aldehyde via a Cannizzaro reaction. Carboxylate salts have similarly been obtained by exposing sodium benzylate and sodium neopentoxide to NO in dioxane solution. Accordingly, sodium trimethylsilanoate should be considered as a substitute for sodium methoxide as the base used to accomplish the replacement of active hydrogens by the diazeniumdiolate functional group via the Traube reaction. C1 [Hrabie, Joseph A.] SAIC Frederick Inc, Natl Canc Inst, Basic Res Program, Frederick, MD 21702 USA. [DeRosa, Frank; Keefer, Larry K.] Natl Canc Inst, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Hrabie, JA (reprint author), SAIC Frederick Inc, Natl Canc Inst, Basic Res Program, Frederick, MD 21702 USA. EM hrabie@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 23 TC 10 Z9 10 U1 1 U2 6 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 FEB 1 PY 2008 VL 73 IS 3 BP 1139 EP 1142 DI 10.1021/jo7020423 PG 4 WC Chemistry, Organic SC Chemistry GA 255VQ UT WOS:000252686400048 PM 18184006 ER PT J AU Dworkin, RH Turk, DC Wyrwich, KW Beaton, D Cleeland, CS Farrar, JT Haythornthwaite, JA Jensen, MP Kerns, RD Ader, DN Brandenburg, N Burke, LB Cella, D Chandler, J Cowan, P Dimitrova, R Dionne, R Hertz, S Jadad, AR Katz, NP Kehlet, H Kramer, LD Manning, DC McCormick, C McDermott, MP McQuay, HJ Patel, S Porter, L Quessy, S Rappaport, BA Rauschkolb, C Revickl, DA Rothman, M Schmader, KE Stacey, BR Stauffer, JW Von Stein, T White, RE Witter, J Zavislc, S AF Dworkin, Robert H. Turk, Dennis C. Wyrwich, Kathleen W. Beaton, Dorcas Cleeland, Charles S. Farrar, John T. Haythornthwaite, Jennifer A. Jensen, Mark P. Kerns, Robert D. Ader, Deborah N. Brandenburg, Nancy Burke, Laurie B. Cella, David Chandler, Julie Cowan, Penny Dimitrova, Rozalina Dionne, Raymond Hertz, Sharon Jadad, Alejandro R. Katz, Nathaniel P. Kehlet, Henrik Kramer, Lynn D. Manning, Donald C. McCormick, Cynthia McDermott, Michael P. McQuay, Henry J. Patel, Sanjay Porter, Linda Quessy, Steve Rappaport, Bob A. Rauschkolb, Christine Revickl, Dennis A. Rothman, Margaret Schmader, Kenneth E. Stacey, Brett R. Stauffer, Joseph W. Von Stein, Thorsten White, Richard E. Witter, James Zavislc, Stojan TI Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations SO JOURNAL OF PAIN LA English DT Review DE chronic pain; randomized clinical trials; outcome measures; clinical importance; assessment; quality of life; physical functioning; emotional functioning; global ratings ID QUALITY-OF-LIFE; LOW-BACK-PAIN; VISUAL ANALOG SCALE; RANDOMIZED CONTROLLED-TRIAL; PATIENT-REPORTED OUTCOMES; MINIMALLY IMPORTANT DIFFERENCES; BECK DEPRESSION INVENTORY; HEALTH-STATUS MEASURES; SPINAL-CORD-INJURY; IMPORTANT DIFFERENCE AB A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. Perspective: Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments. (c) 2008 by the American Pain Society. C1 [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Dept Neurol, Rochester, NY 14627 USA. [Turk, Dennis C.; Jensen, Mark P.] Univ Washington, Seattle, WA 98195 USA. [Wyrwich, Kathleen W.] St Louis Univ, St Louis, MO 63103 USA. [Beaton, Dorcas] Univ Toronto, Inst Work & Hlth, Toronto, ON, Canada. [Cleeland, Charles S.] MD Anderson Canc Ctr, Houston, TX USA. [Farrar, John T.] Univ Penn, Philadelphia, PA 19104 USA. [Haythornthwaite, Jennifer A.] Johns Hopkins Univ, Baltimore, MD USA. [Kerns, Robert D.] Yale Univ, VA Connecticut Hlthcare Syst, New Haven, CT 06520 USA. [Ader, Deborah N.] NIAMSD, Bethesda, MD USA. [Brandenburg, Nancy] Pfizer Inc, New York, NY USA. [Burke, Laurie B.; Hertz, Sharon; Rappaport, Bob A.; Witter, James] US FDA, Rockville, MD USA. [Cella, David] Northwestern Univ, Evanston Nothwestern Hlthcare, Evanston, IL 60208 USA. [Chandler, Julie] Merck & Co Inc, Blue Bell, PA USA. [Cowan, Penny] Amer Chron Pain Assoc, Rocklin, CA USA. [Dimitrova, Rozalina] Allergan Pharmaceut Inc, Irvine, CA USA. [Dionne, Raymond] NINR, Bethesda, MD USA. [Jadad, Alejandro R.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Katz, Nathaniel P.] Analgesic Res, Needham, MA USA. [Kehlet, Henrik] Univ Copenhagen, Rigshosp, DK-1168 Copenhagen, Denmark. [Kramer, Lynn D.] Purdue Pharma, Stamford, CT USA. [Manning, Donald C.] Celgene Corp, Warren, NJ USA. [McCormick, Cynthia] McCormick Consultat, Bethesda, MD USA. [McDermott, Michael P.] Univ Rochester, Rochester, NY 14627 USA. [McQuay, Henry J.] Univ Oxford, Oxford OX1 2JD, England. [Patel, Sanjay] Elan Pharmaceut Inc, San Diego, CA USA. [Porter, Linda] NINDS, Bethesda, MD USA. [Quessy, Steve] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Rauschkolb, Christine; Rothman, Margaret] Johnson & Johnson, Raritan, NJ USA. [Revickl, Dennis A.] United Biosource Corp, Hlth Care Anal Grp, Bethesda, MD USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, VA Med ctr, GRECC, Durham, NC USA. [Stacey, Brett R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Stauffer, Joseph W.] Alpharma, Elizabeth, NJ USA. [Von Stein, Thorsten] Tercica, Brisbane, CA USA. [White, Richard E.] Endo Pharmaceut Inc, Chadds Ford, PA USA. [Zavislc, Stojan] AstraZeneca, Sodertalje, Sweden. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Dept Neurol, Rochester, NY 14627 USA. EM robert-dworkin@urmc.rochester.edu RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 NR 163 TC 910 Z9 921 U1 11 U2 66 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 FEB PY 2008 VL 9 IS 2 BP 105 EP 121 DI 10.1016/j.jpain.2007.09.005 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 263MF UT WOS:000253220500002 PM 18055266 ER PT J AU Huang, TTK AF Huang, Terry T-K TI Finding thresholds of risk for components of the pediatric metabolic syndrome SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID ASSOCIATION; STATEMENT C1 NICHHD, Ctr Res Mothers & Childre, Growth Branch, Rockville, MD 20852 USA. RP Huang, TTK (reprint author), NICHHD, Ctr Res Mothers & Childre, Growth Branch, 6100 Execut Blvd,4B11, Rockville, MD 20852 USA. EM huangter@mail.nih.gov NR 11 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD FEB PY 2008 VL 152 IS 2 BP 158 EP 159 DI 10.1016/j.jpeds.2007.09.032 PG 2 WC Pediatrics SC Pediatrics GA 257ST UT WOS:000252819500004 PM 18206680 ER PT J AU Huang, TTK Nansel, TR Bielsheim, AR Morrison, JA AF Huang, Terry T-K Nansel, Tonia R. Bielsheim, Allen R. Morrison, John A. TI Sensitivity, specificity, and predictive values of pediatric metabolic syndrome components in relation to adult metabolic syndrome: The princeton LRC follow-up study SO JOURNAL OF PEDIATRICS LA English DT Article ID TYPE-2 DIABETES-MELLITUS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; SCHOOL-CHILDREN; RISK-FACTORS; ADOLESCENTS; PREVALENCE; CHILDHOOD AB Objective To estimate the sensitivity, specificity, and predictive values of pediatric metabolic syndrome (MetS) components (obesity, fasting glucose, triglycerides, high-density lipoprotein, and blood pressure) at various cutoff points in relation to adult metS. Study design Data from the National Heart, Lung, and Blood Institute Lipid Research Clinics Princeton Prevalence Study (1973-1976) and the Princeton Follow-tip Stud), (2000-2004) were used to calculate sensitivity, specificity, and positive and negative predictive values for each component at a given cutoff point and for aggregates of components. Results Individual pediatric components alone showed low to moderate sensitivity, high specificity, and moderate predictive values in relation to adult MetS. When all 5 pediatric MetS components were considered, the presence of at least I abnormality had higher sensitivity for adult MetS than individual components alone. When multiple abnormalities were mandatory for MetS, positive predictive value was high and sensitivity was low. Childhood body mass alone showed neither high sensitivity nor high positive predictive value for adult MetS. Conclusions Considering multiple metabolic variables in childhood can improve the predictive usefulness for adult MetS, compared with each component or body mass alone. MetS variables may be useful for identifying some children who are at risk for prevention interventions. C1 [Huang, Terry T-K] NICHHD, Endocrinol Nutr & Growth Branch, Rockville, MD 20852 USA. [Nansel, Tonia R.; Bielsheim, Allen R.] NICHHD, Prevent Res Branch, Bethesda, MD USA. [Morrison, John A.] Cincinnati Childrens Hosp, Med Ctr, Div Cardiol, Cincinnati, OH USA. RP Huang, TTK (reprint author), NICHHD, Endocrinol Nutr & Growth Branch, 6100 Esecut Blvd,4B11, Rockville, MD 20852 USA. EM huangter@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS [Z99 HD999999]; NHLBI NIH HHS [N01-HV22914-L, R01 HL062394, R01-HL62394] NR 28 TC 27 Z9 29 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD FEB PY 2008 VL 152 IS 2 BP 185 EP 190 DI 10.1016/j.jpeds.2007.08.007 PG 6 WC Pediatrics SC Pediatrics GA 257ST UT WOS:000252819500011 PM 18206687 ER PT J AU Sun, SS Liang, R Huang, TTK Daniels, SR Arslanan, S Liu, K Grave, GD Siervogel, RM AF Sun, Shumei S. Liang, Ruohong Huang, Terry T-K Daniels, Stephen R. Arslanan, Silva Liu, Kiang Grave, Gilman D. Siervogel, Roger M. TI Childhood obesity predicts adult metabolic syndrome: The fels longitudinal study SO JOURNAL OF PEDIATRICS LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; ADOLESCENTS; PREVALENCE; CHILDREN AB Objectives To determine the age of significant divergence in body mass index (BMI) mid waist circumference in adults with and without the metabolic syndrome, mid to provide age- and sex-specific childhood values that predict adult metabolic syndrome. Study design Part I of this study is a retrospective cohort study of 92 men and 59 women (mean age, 51 years) who had metabolic syndrome and 154 randomly selected adults matched for age and sex who did not have the syndrome. Part 2 is a study of predictive accuracy in a validation sample of 743 participants. Results The first appearance of differences between adults with and without metabolic syndrome occurred at ages 8 and 13 for BMI and 6 and 13 for waist circumference in boys and girls, respectively. Odds ratios (ORs) for the metabolic syndrome at 30 years and older ranged from 1.4 to 1.9 across age groups in boys and from 0.8 to 2.8 across age groups in girls if 1311,11 exceeded criterion values in childhood. The corresponding ORs for waist circumference ranged from 2.5 to 31.4 in boys and 1.7 to 2.5 in girls. These ORs increased with the number of examinations. Conclusions Children with BMI and waist circumference values exceeding the established criterion values are at increased risk for the adult metabolic syndrome. C1 [Sun, Shumei S.; Liang, Ruohong; Siervogel, Roger M.] Wright State Univ, Boonshaft Sch Med, Lifespan Hlth Res Ctr, Dept Community Hlth, Dayton, OH 45420 USA. [Huang, Terry T-K; Grave, Gilman D.] NICHHD, Endocrinol Nutr & Growth Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD USA. [Daniels, Stephen R.] Univ Colorado, Dept Pediat, Denver, CO 80202 USA. [Arslanan, Silva] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. [Liu, Kiang] Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Sun, SS (reprint author), Wright State Univ, Boonshaft Sch Med, Lifespan Hlth Res Ctr, Dept Community Hlth, 3171 Res Blvd, Dayton, OH 45420 USA. EM shumei.sun@wright.edu FU NHLBI NIH HHS [R01 HL072838, HL 072838]; NICHD NIH HHS [R01 HD012252, HD 12252, R01 HD060913]; NIDDK NIH HHS [DK 071485, R01 DK071485] NR 14 TC 118 Z9 123 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD FEB PY 2008 VL 152 IS 2 BP 191 EP 200 DI 10.1016/j.jpeds.2007.07.055 PG 10 WC Pediatrics SC Pediatrics GA 257ST UT WOS:000252819500012 PM 18206688 ER PT J AU Gonzalez, N Hocart, SJ Portal-Nunez, S Mantey, SA Nakagawa, T Zudaire, E Coy, DH Jensen, RT AF Gonzalez, Nieves Hocart, Simon J. Portal-Nunez, Sergio Mantey, Samuel A. Nakagawa, Tomoo Zudaire, Enrique Coy, David H. Jensen, Robert T. TI Molecular basis for agonist selectivity and activation of the orphan bombesin receptor subtype 3 receptor SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NEUROMEDIN-B RECEPTOR; 2ND EXTRACELLULAR LOOP; HIGH-AFFINITY BINDING; PEPTIDE RECEPTOR; AMINO-ACIDS; CHOLECYSTOKININ RECEPTOR; TRANSMEMBRANE SEGMENT; IDENTIFICATION; DOMAINS; LIGAND AB Bombesin receptor subtype (BRS)-3, a G-protein-coupled orphan receptor, shares 51% identity with the mammalian bombesin (Bn) receptor for gastrin-releasing peptide. There is increasing interest in BRS-3 because it is important in energy metabolism, glucose control, motility, and tumor growth. BRS-3 has low affinity for all Bn-related peptides; however, recently synthetic high-affinity agonists, [D-Tyr(6)/D-Phe(6), beta Ala(11), Phe(13), Nle(14)] Bn-(6-14), were described, but they are nonselective for BRS-3 over other Bn receptors. Based on these peptides, three BRS-3-selective ligands were developed: peptide 2, [D-Tyr(6)(R)-3-amino-propionic acid(11), Phe(13), Nle(14)]Bn(6-14); peptide 3, [D-Tyr(6),(R)-Apa(11),4Cl-Phe(13), Nle(14)]Bn(6-14); and peptide 4, acetyl-Phe-Trp-Ala-His(tBzl)-piperidine-3 carboxylic acid-Gly-Arg-NH2. Their molecular determinants of selectivity/high affinity for BRS-3 are unknown. To address this, we used a chimeric/site mutagenesis approach. Substitution of extracellular domain 2 (EC2) of BRS-3 by the comparable gastrin-releasing peptide receptor (GRPR) domain decreased 26-, 4-, and 0-fold affinity for peptides 4, 3, and 2. Substitution of EC3 decreased affinity 4-, 11-, and 0-fold affinity for peptides 2 to 4. Ten-point mutations in the EC2 and adjacent transmembrane regions (TM2) 2 and 3 of BRS-3 were made. His107 (EC2-BRS-3) for lysine (H107K) (EC2-GRPR) decreased affinity (25- and 0-fold) for peptides 4 and 1; however, it could not be activated by either peptide. Its combination with Val101 (TM2), Gly112 (EC2), and Arg127 (TM3) resulted in complete loss-ofaffinity of peptide 4. Receptor-modeling showed that each of these residues face inward and are within 4 angstrom of the binding pocket. These results demonstrate that Val101, His107, Gly112, and Arg127 in the EC2/adjacent upper TMs of BRS-3 are critical for the high BRS3 selectivity of peptide 4. His107 in EC2 is essential for BRS-3 activation, suggesting amino-aromatic ligand/receptor interactions with peptide 4 are critical for both binding and activation. Furthermore, these result demonstrate that even though these three BRS-3-selective agonists were developed from the same template peptide, [D-Phe(6), beta Ala(11), Phe(13), Nle(14)] Bn(6-14), their molecular determinants of selectivity/high affinity varied considerably. C1 [Gonzalez, Nieves; Hocart, Simon J.; Nakagawa, Tomoo; Jensen, Robert T.] NIH, NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. [Hocart, Simon J.; Coy, David H.] Tulane Univ, Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA USA. [Portal-Nunez, Sergio; Zudaire, Enrique] NIH, Natl Canc Inst, Angiogenesis Core Facility, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIH, NIDDK, Digest Dis Branch, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Portal-Nunez, Sergio/L-7391-2014 OI Portal-Nunez, Sergio/0000-0003-0659-1545 FU Intramural NIH HHS [Z01 DK053101-19, Z01 DK053100-19] NR 40 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2008 VL 324 IS 2 BP 463 EP 474 DI 10.1124/jpet.107.132332 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255CB UT WOS:000252633200008 PM 18006692 ER PT J AU Wang, T Ma, XC Krausz, KW Idle, JR Gonzalez, FJ AF Wang, Ting Ma, Xiaochao Krausz, Kristopher W. Idle, Jeffrey R. Gonzalez, Frank J. TI Role of pregnane X receptor in control of all-trans retinoic acid (ATRA) metabolism and its potential contribution to ATRA resistance SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; HUMAN HEPATOCYTES; GENE-EXPRESSION; CYTOCHROME-P450; CELLS; LIVER; IDENTIFICATION; INDUCTION; CYP26; DEXAMETHASONE AB Although all-trans-retinoic acid (ATRA) is an effective treatment for acute promyelocytic leukemia and several solid tumors, its use is limited by resistance due to increased metabolism. The most studied mechanism for ATRA resistance is the autoinduced metabolism regulated by the retinoic acid receptor-CYP26 pathway. However, treatment of cancer is usually not done with a single antineoplastic agent, but with a variety of combined chemotherapy regimens, including several anticancer drugs, and other concomitantly administered supportive drugs. Pregnane X receptor (PXR), an orphan nuclear receptor that functions as a ligand-activated transcription factor, serves as an important xenobiotic sensor regulating metabolism and elimination. Many prescription drugs are PXR ligands, which can activate PXR target genes, including phase I enzyme, phase II enzyme, and transporter genes. The present study was designed to examine the role of PXR in ATRA metabolism. Due to the marked species differences in response to PXR ligands, Pxr-null, wild-type, and PXR-humanized transgenic mouse models were used. In addition to pregnenolone 16 alpha-carbonitrile, several clinically relevant PXR ligands (rifampicin and dexamethasone) all increased ATRA metabolism both in vitro and in vivo, which was PXR-dependent, and upregulation of Cyp3a was the major contributor. Furthermore, induction of the Mdr1a, Mrp3, and Oatp2 genes was also observed. This study suggested that coadministration of PXR ligands can increase ATRA metabolism through activation of the PXR-CYP3A pathway, which might be a mechanism for some form of ATRA resistance. Other PXR target transporters might also be involved. C1 [Wang, Ting; Ma, Xiaochao; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Idle, Jeffrey R.] Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS [Z01 BC005562-19] NR 35 TC 30 Z9 33 U1 0 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2008 VL 324 IS 2 BP 674 EP 684 DI 10.1124/jpet.107.131045 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255CB UT WOS:000252633200029 PM 17962516 ER PT J AU Jutkiewicz, EM Baladi, MG Folk, JE Rice, KC Woods, JH AF Jutkiewicz, Emily M. Baladi, Michelle G. Folk, John E. Rice, Kenner C. Woods, James H. TI The delta-opioid receptor agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S, 5R)4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N, N-diethylbenzamide] synergistically enhances the locomotor-activating effects of some psychomotor stimulants, but not direct dopamine agonists, in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VENTRAL TEGMENTAL AREA; SPRAGUE-DAWLEY RATS; NUCLEUS-ACCUMBENS; RELEASE; MODULATION; MICRODIALYSIS; SENSITIZATION; COCAINE; LOCALIZATION; AMPHETAMINE AB The nonpeptidic delta-opioid agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S, 5R)4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N, N-diethylbenzamide] produces many stimulant-like behavioral effects in rodents and monkeys, such as locomotor stimulation, generalization to cocaine in discrimination procedures, and antiparkinsonian effects. Tolerance to the locomotor-stimulating effects of SNC80 develops after a single administration of SNC80 in rats; it is not known whether cross-tolerance develops to the effects of other stimulant compounds. In the initial studies to determine whether SNC80 produced cross-tolerance to other stimulant compounds, it was discovered that amphetamine-stimulated locomotor activity was greatly enhanced in SNC80-pretreated rats. This study evaluated acute cross-tolerance between delta-opioid agonists and other locomotor-stimulating drugs. Locomotor activity was measured in male Sprague-Dawley rats implanted with radiotransmitters, and activity levels were recorded in the home cage environment. Three-hour SNC80 pretreatment produced tolerance to further delta-opioid receptor stimulation but also augmented greatly amphetamine-stimulated locomotor activity in a dose-dependent manner. Pretreatments with other delta-opioid agonists, (+) BW373U86 [(+)-4-[delta(R)-alpha-[(2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N, N-diethylbenzamide] and oxymorphindole (17-methyl-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7,2', 3'-indolomorphinan), also modified amphetamine-induced activity levels. SNC80 pretreatment enhanced the stimulatory effects of the dopamine/norepinephrine transporter ligands cocaine and nomifensine (1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinanmine maleate salt), but not the direct dopamine receptor agonists SKF81297 [ R-(+)-6-chloro-7,8-dihydroxy1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] and quinpirole [trans-(-)-(4 alpha R)-4,4a, 5,6,7,8,8a, 9-octahydro5-propyl-1H-pyrazolo[3,4-g] quinoline monohydrochloride]. In conclusion, SNC80 enhanced the locomotor-stimulating effects of monoamine transporter ligands suggesting that delta-opioid receptor activation might alter the functional activity of monoamine transporters or presynaptic monoamine terminals. C1 [Jutkiewicz, Emily M.; Woods, James H.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Baladi, Michelle G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Folk, John E.; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, NIH, Bethesda, MD USA. RP Jutkiewicz, EM (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 Med Sci Res Bldg 3,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM ejutkiew@umich.edu FU Intramural NIH HHS; NIDA NIH HHS [T32 DA07267, T32 DA07268, DA00254, DA020669]; NIGMS NIH HHS [T32 GM07767] NR 36 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2008 VL 324 IS 2 BP 714 EP 724 DI 10.1124/jpet.107.123844 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255CB UT WOS:000252633200033 PM 17986650 ER PT J AU Gomaraschi, M Calabresi, L Rossoni, G Iametti, S Franceschini, G Stonik, JA Remaley, AT AF Gomaraschi, Monica Calabresi, Laura Rossoni, Giuseppe Iametti, Stefania Franceschini, Guido Stonik, John A. Remaley, Alan T. TI Anti-inflammatory and cardioprotective activities of synthetic high-density lipoprotein containing apolipoprotein A-I mimetic peptides SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; NF-KAPPA-B; MYOCARDIAL ISCHEMIA/REPERFUSION INJURY; RANDOMIZED CONTROLLED-TRIAL; CORONARY ATHEROSCLEROSIS; PROSTACYCLIN RELEASE; ENDOTHELIAL-CELLS; HDL; MILANO; CHOLESTEROL AB Apolipoprotein A-I (apoA-I) mimetic peptides may represent an alternative to apoA-I for large-scale production of synthetic high-density lipoproteins (sHDL) as a therapeutic agent. In this study, the cardioprotective activity of sHDL made with either L37pA peptide or its D-stereoisomer, D37pA, was compared to sHDL made with apoA-I. The peptides were reconstituted with palmitoyl-oleoyl-phosphatidylcholine, which yielded sHDL particles comparable to apoA-I sHDL in diameter, molecular weight, and alpha-helical content. Pretreatment of endothelial cells with either peptide sHDL reduced tumor necrosis factor alpha-stimulated vascular cell adhesion molecule-1 expression to the same extent as apoA-I sHDL. In an isolated rat heart model of ischemia/reperfusion (I/R) injury, L37pA and D37pA sHDL significantly reduced postischemic cardiac contractile dysfunction compared to the saline control, as indicated by a 49.7 +/- 6.4% (L37pA; P < 0.001) and 53.0 +/- 9.1% (D37pA; P < 0.001) increase of left ventricular-developed pressure (LVDP) after reperfusion and by a 45.4 +/- 3.4% (L37pA; P < 0.001) and 49.6 +/- 2.6% (D37pA; P < 0.001) decrease of creatine kinase (CK) release. These effects were similar to the 51.3 +/- 3.0% (P < 0.001) increase of LVDP and 51.3 +/- 3.0 (P < 0.001) reduction of CK release induced by apoA-I sHDL. Consistent with their cardioprotective effects, all three types of sHDL particles mediated an approximate 20% (P < 0.001) reduction of cardiac tumor necrosis factor alpha (TNF alpha) content and stimulated an approximate 35% (P < 0.05) increase in postischemic release of prostacyclin. In summary, L37pA and D37pA peptides can form sHDL particles that retain a similar level of protective activity as apoA-I sHDL on the endothelium and the heart; thus, apoA-I mimetic peptides may be useful therapeutic agents for the prevention of cardiac I/R injury. C1 [Stonik, John A.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gomaraschi, Monica; Calabresi, Laura; Franceschini, Guido] Univ Milan, Dept Pharmacol Sci, Ctr E Grossi Paoletti, Milan, Italy. [Rossoni, Giuseppe] Univ Milan, Dept Pharmacol Chemotherapy & Med Toxicol, Mol Dis Sect, Milan, Italy. [Iametti, Stefania] Univ Milan, Dept Mol & Agroalimentary Sci, Milan, Italy. RP Remaley, AT (reprint author), NHLBI, Lipoprot Metab Sect, Vasc Med Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 2C-433, Bethesda, MD 20892 USA. EM aremaley@nih.gov RI Gomaraschi, Monica/A-3601-2014; OI Gomaraschi, Monica/0000-0003-3082-2120; FRANCESCHINI, GUIDO/0000-0003-2687-1771; Calabresi, Laura/0000-0001-5042-9532; Iametti, Stefania/0000-0002-4159-3768 FU Intramural NIH HHS NR 41 TC 36 Z9 37 U1 2 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2008 VL 324 IS 2 BP 776 EP 783 DI 10.1124/jpet.107.129411 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255CB UT WOS:000252633200040 PM 18042829 ER PT J AU Saji, T Kikuchi, R Kusuhara, H Kim, I Gonzalez, FJ Sugiyama, Y AF Saji, Takami Kikuchi, Ryota Kusuhara, Hiroyuki Kim, Insook Gonzalez, Frank J. Sugiyama, Yuichi TI Transcriptional regulation of human and mouse organic anion transporter 1 by hepatocyte nuclear factor 1 alpha/beta SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ORGANIC ANION TRANSPORTER; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; DNA METHYLATION; EXPRESSED GENES; KIDNEY; MEMBER; HNF1; HOMEOPROTEIN; NETWORK; KINASE AB Organic anion transporter 1 (OAT1/SLC22A6) is predominantly expressed in the proximal tubules of the kidney. Cumulative studies have shown its critical role in the tubular secretion of a variety of organic anions, including several clinically important drugs. In addition, OAT1 is also involved in the pharmacological effect of diuretics and the nephrotoxicity of antiviral drugs. In contrast to these functional characterizations, the regulatory mechanism of OAT1 expression is poorly understood. It was recently demonstrated that the expression of Oat1 was markedly reduced in the kidneys of hepatocyte nuclear factor 1 alpha (Hnf1 alpha)-null mice. However, in vitro evidence for the involvement of HNF1 alpha and further analyses are required to illustrate the transcriptional regulation of OAT1 genes in more detail. Computational analysis of the potential transcription factor binding sites revealed that the HNF1-motif was conserved in the proximal-promoter region of human and mouse OAT1 genes. The mRNA expression of mouse organic anion transporter 1 was drastically reduced in Hnf1 alpha-null mice compared with that in wild-type mice, which was consistent with a previous report (Maher et al., 2006). Forced expression of HNF1 alpha alone or both HNF1 alpha and HNF1 beta enhanced the activity of human and mouse OAT1 promoters in the transactivation assays, whereas HNF1 beta alone was not active. Mutations in the HNF1-motif significantly reduced this transactivation. Direct binding of HNF1 alpha/HNF1 alpha homodimer and HNF1 alpha/HNF1 beta heterodimer to the HNF1-motif found in the human OAT1 promoter was demonstrated by electrophoretic mobility shift assays. These results provide convincing evidence for the involvement of HNF1 alpha/beta in the constitutive expression of human and mouse OAT1 in the kidney. C1 [Saji, Takami; Kikuchi, Ryota; Kusuhara, Hiroyuki; Sugiyama, Yuichi] Univ Tokyo, Dept Mol Pharmacokinet, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. [Kim, Insook; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Sugiyama, Y (reprint author), Univ Tokyo, Dept Mol Pharmacokinet, Grad Sch Pharmaceut Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM sugiyama@mol.f.u-tokyo.ac.jp NR 33 TC 35 Z9 36 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2008 VL 324 IS 2 BP 784 EP 790 DI 10.1124/jpet.107.128249 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255CB UT WOS:000252633200041 PM 18029548 ER PT J AU Zolkowska, D Baumann, MH Rothman, RB AF Zolkowska, Dorota Baumann, Michael H. Rothman, Richard B. TI Chronic fenfluramine administration increases plasma serotonin (5-hydroxytryptamine) to nontoxic levels SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PULMONARY-HYPERTENSION; PLATELET SEROTONIN; CARCINOID-TUMORS; HEART-DISEASE; PHENTERMINE; FLUOXETINE; RECEPTORS; DIAGNOSIS; BRAIN; BLOOD AB Large elevations in blood serotonin (5-hydroxytryptamine; 5-HT) can produce valvular heart disease in humans and laboratory animals. In accordance, one prevailing hypothesis (i. e., the "5-HT hypothesis") suggests that 5-HT transporter substrates like fenfluramine increase the risk for valvular heart disease by elevating plasma 5-HT, secondary to the release of 5-HT from platelets. The main purpose of this study was to determine whether chronic administration of fenfluramine increases plasma 5-HT to concentrations that are associated with the development of valvular heart disease. To the best of our knowledge, this is the first study to address this issue using an in vivo microdialysis method that measures plasma 5-HT in nonhypoxic rats. We examined the effects of chronic (+/-)-fenfluramine and fluoxetine on plasma levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in blood samples from conscious catheterized rats. Plasma indoles were measured by high-performance liquid chromatography with electrochemical detection in the dialysates of whole blood. The baseline plasma 5-HT level was < 1.0 nM. Chronic fenfluramine (14-day minipump infusion) produced small increases in baseline plasma 5-HT (similar to 2-4-fold), whereas chronic fluoxetine had no effect. Chronic fenfluramine and fluoxetine markedly decreased whole-blood 5-HT and reduced the ability of acute fenfluramine to evoke 5-HT release. Elevations in baseline plasma 5-HT produced by chronic fenfluramine are far below the micromolar levels necessary to produce valvular heart disease. Furthermore, chronic fenfluramine reduces the ability of acute fenfluramine to increase plasma 5-HT, suggesting that the 5-HT hypothesis cannot explain the increased risk of valvular heart disease in patients treated with fenfluramine. C1 [Zolkowska, Dorota; Baumann, Michael H.; Rothman, Richard B.] Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov FU Intramural NIH HHS NR 27 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2008 VL 324 IS 2 BP 791 EP 797 DI 10.1124/jpet.107.132654 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255CB UT WOS:000252633200042 PM 18032571 ER PT J AU Li, JX Rice, KC France, CP AF Li, Jun-Xu Rice, Kenner C. France, Charles P. TI Discriminative stimulus effects of 1-(2,5-dimethoxy-4methylphenyl)-2-aminopropane in rhesus monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LYSERGIC-ACID DIETHYLAMIDE; SALVINORIN-A; ATYPICAL ANTIPSYCHOTICS; SALVIA-DIVINORUM; NMDA ANTAGONISTS; TRAINED SUBJECTS; RECEPTOR; LSD; DOM; HALLUCINOGEN AB Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)2-aminopropane (DOM) and related drugs have been studied extensively in rodents, although the generality of those findings across species is not known. The goals of this study were to see whether monkeys could discriminate DOM and to characterize the DOM discriminative stimulus by studying a variety of drugs, including those with hallucinogenic activity in humans. Four rhesus monkeys discriminated between 0.32 mg/ kg s. c. DOM and vehicle after an average of 116 (range = 85-166) sessions while responding under a fixed ratio 5 schedule of stimulus shock termination. Increasing doses of DOM occasioned increased responding on the drug lever with the training dose occasioning DOM-lever responding for up to 2 h. The serotonin (5-HT) 2A/2C receptor antagonists ritanserin and ketanserin, the 5-(HT/ 2A) receptor antagonist (+) 2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL100907), and its (-) stereoisomer MDL100009 [(-) 2,3-dimethoxyphenyl1-[2-(4-piperidine)-methanol], but not haloperidol, completely blocked the discriminative stimulus effects of DOM. Quipazine as well as several drugs with hallucinogenic activity in humans, including (+) lysergic acid diethylamide, (-) DOM, and 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), occasioned DOM-lever responding. The kappa-opioid receptor agonists U-50488 and salvinorin A (a hallucinogen) did not exert DOM-like effects and neither did ketamine, phencyclidine, amphetamine, methamphetamine, cocaine, morphine, yohimbine, fenfluramine, 8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8OH-DPAT), or (+/-)-2-(N-phenethyl-N-1'-propyl) amino-5-hydroxytetralin hydrochloride (N-0434). These data confirm in nonhuman primates a prominent role for 5-HT2A receptors in the discriminative stimulus effects of some drugs with hallucinogenic activity in humans. The failure of another drug with hallucinogenic activity (salvinorin A) to substitute for DOM indicates that different classes of hallucinogens exert qualitatively different discriminative stimulus effects in nonhumans. C1 [Li, Jun-Xu; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu RI Li, Jun-Xu/K-9192-2013 FU NIDA NIH HHS [DA17918, K05 DA017918] NR 41 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2008 VL 324 IS 2 BP 827 EP 833 DI 10.1124/jpet.107.130625 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255CB UT WOS:000252633200046 PM 17993605 ER PT J AU Sun, H Hu, XQ Emerit, MB Schoenebeck, JC Kimmel, CE Peoples, RW Miko, A Zhang, L AF Sun, Hui Hu, Xiang-Qun Emerit, Michel B. Schoenebeck, Jeffrey C. Kimmel, Cassin E. Peoples, Robert W. Miko, Angela Zhang, Li TI Modulation of 5-HT3 receptor desensitization by the light chain of microtubule-associated protein 1B expressed in HEK 293 cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; GATED ION-CHANNEL; RECOMBINANT GABA(A) CHANNELS; HIPPOCAMPAL-NEURONS; BINDING DOMAIN; NERVOUS-SYSTEM; SPINAL NEURONS; MAP1B; CONDUCTANCE; TRAFFICKING AB Regulation of ligand-gated ion channel (LGIC) function and trafficking by cytoskeleton proteins has been the topic of recent research. Here, we report that the light chain (LC1) of microtubule-associated protein 1B (MAP1B) specifically interacted with the 5-HT3A receptor, a predominant serotonin-gated ion channel in the brain. LCI and 5-HT3A receptors were colocalized in central neurons and in HEK 293 cells expressing 5-HT3A receptors. LC1 reduced the steady-state density of 5-HT3A receptors at the membrane surface of HEK 293 cells and significantly accelerated receptor desensitization time constants from 3.8 +/- 0.3 s to 0.8 +/- 0.1 s. However, LC1 did not significantly alter agonist binding affinity and single-channel conductance of 5-HT3A receptors. On the other hand, application of specific LC1 antisense oligonucleotides and nocodazole, a microtubule disruptor, significantly prolonged the desensitization time of the recombinant and native neuronal 5-HT3 receptors by 3- to 6-fold. This kinetic change induced by nocodazole was completely rescued by addition of LC1 but not GABA(A) receptor-associated protein (GABARAP), suggesting that LC1 can specifically interact with 5-HT3A receptors. These observations suggest that the LC1-5-HT3A receptor interaction contributes to a mechanism that regulates receptor desensitization kinetics. Such dynamic regulation may play a role in reshaping the efficacy of 5-HT3 receptor-mediated synaptic transmission. C1 [Sun, Hui; Hu, Xiang-Qun; Schoenebeck, Jeffrey C.; Kimmel, Cassin E.; Miko, Angela; Zhang, Li] NIAAA, NIH, Lab Integrat Neurosci, Bethesda, MD 20892 USA. [Emerit, Michel B.] CHU Pitie Salpetriere, INSERM, U677, F-75634 Paris 13, France. [Peoples, Robert W.] Marquette Univ, Coll Hlth Sci, Dept Biomed Sci, Milwaukee, WI 53201 USA. RP Zhang, L (reprint author), NIAAA, NIH, Lab Integrat Neurosci, 5625 Fishers Lane,TS24, Bethesda, MD 20892 USA. EM lzhang@mail.nih.gov FU Intramural NIH HHS NR 53 TC 20 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 1 PY 2008 VL 586 IS 3 BP 751 EP 762 DI 10.1113/jphysiol.2007.136440 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 265PL UT WOS:000253373300011 PM 18063656 ER PT J AU Ressom, HW Varghese, RS Goldman, L An, Y Loffredo, CA Abdel-Hamid, M Kyselova, Z Mechref, Y Novotny, M Drake, SK Goldman, R AF Ressom, Habtorn W. Varghese, Rency S. Goldman, Lenka An, Yanming Loffredo, Christopher A. Abdel-Hamid, Mohamed Kyselova, Zuzana Mechref, Yehia Novotny, Milos Drake, Steven K. Goldman, Radoslav TI Analysis of MALDI-TOF mass spectrometry data for discovery of peptide and glycan biomarkers of hepatocellular carcinoma SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE liver cancer; proteomics; glycomics; peak selection ID CHRONIC HEPATITIS-C; SERUM; SELECTION; CANCER; HCV; GLYCOSYLATION; GLYCOPROTEINS; CIRRHOSIS; PROTEINS AB This paper presents computational methods to analyze MALDI-TOF mass spectrometry data for quantitative comparison of peptides and glycans in serum. The methods are applied to identify candidate biomarkers in serum samples of 203 participants from Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD) consisting of cirrhosis and fibrosis cases, and 78 population controls. Two complementary sample preparation methods were applied prior to generating mass spectra: (1) low molecular weight (LMW) enrichment of each serum sample was carried out for MALDI-TOF quantification of peptides, and (2) glycans were enzymatically released from proteins in each serum sample and permethylated for MALDI-TOF quantification of glycans. A peak selection algorithm was applied to identify the most useful peptide and glycan peaks for accurate detection of HCC cases from high-risk population of patients with CLD. In addition to global peaks selected by the whole population based approach, where identically labeled patients are treated as a single group, subgroup-specific peaks were identified by searching for peaks that are differentially abundant in a subgroup of patients only. The peak selection process was preceded by peak screening, where we eliminated peaks that have significant association with covariates such as age, gender, and viral infection based on the peptide and glycan spectra from population controls. The performance of the selected peptide and glycan peaks was evaluated in terms of their ability in detecting HCC cases from patients with CLD in a blinded validation set and through the cross-validation method. Finally, we investigated the possibility of using both peptides and glycans in a panel to enhance the diagnostic capability of these candidate markers. Further evaluation is needed to examine the potential clinical utility of the candidate peptide and glycan markers identified in this study. C1 [Ressom, Habtorn W.; Varghese, Rency S.; Goldman, Lenka; An, Yanming; Loffredo, Christopher A.; Goldman, Radoslav] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Abdel-Hamid, Mohamed] Menia Univ, Cairo, Egypt. [Abdel-Hamid, Mohamed] NHTMRI, Viral Hepatitis Res Lab, Cairo, Egypt. [Kyselova, Zuzana; Mechref, Yehia; Novotny, Milos] Natl Ctr Glycom & Glycoprote, Dept Chem, Bloomington, IN USA. [Drake, Steven K.] NIH, Clin Chem Serv, Dept Lab Med, Bethesda, MD 20892 USA. RP Ressom, HW (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. EM hwr@georgetown.edu RI Varghese, Rency/A-8770-2012; OI Mechref, Yehia/0000-0002-6661-6073 FU NCI NIH HHS [R01 CA115625, R03 CA119288, R03 CA119313, R03 CA119313-01A2] NR 25 TC 37 Z9 37 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD FEB PY 2008 VL 7 IS 2 BP 603 EP 610 DI 10.1021/pr0705237 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 258JO UT WOS:000252864400013 PM 18189345 ER PT J AU Van, QN Issaq, HJ Jiang, QJ Li, QL Muschik, GM Waybright, TJ Lou, H Dean, M Uitto, J Veenstra, TD AF Van, Que N. Issaq, Haleem J. Jiang, Qiujie Li, Qiaoli Muschik, Gary M. Waybright, Timothy J. Lou, Hong Dean, Michael Uitto, Jouni Veenstra, Timothy D. TI Comparison of 1D and 2D NMR spectroscopy for metabolic profiling SO JOURNAL OF PROTEOME RESEARCH LA English DT Article ID GAS-LIQUID-CHROMATOGRAPHY; CASSETTE ABC TRANSPORTER; PSEUDOXANTHOMA ELASTICUM; H-1-NMR SPECTROSCOPY; MASS-SPECTROMETRY; PATTERN-RECOGNITION; CONNECTIVE TISSUES; BIOLOGICAL-FLUIDS; MOUSE URINE; LC-NMR AB High-resolution, liquid state nuclear magnetic resonance (NMR) spectroscopy is a popular platform for metabolic profiling because the technique is nondestructive, quantitative, reproducible, and the spectra contain a wealth of biochemical information. Because of the large dynamic range of metabolite concentrations in biofluids, statistical analyses of one-dimensional (1D) proton NMR data tend to be biased toward selecting changes in more abundant metabolites. Although two-dimensional (2D) proton-proton experiments can alleviate spectral crowding, they have been mainly used for structural determination. In this study, 2D total correlation spectroscopy NMR was used to compare the global metabolic profiles of urine obtained from wild-type and Abcc6-knockout mice. The 2D data were compared to an improved 1D experiment in which signal contributions from macromolecules and the urea peak have been spectroscopically removed for more accurate quantitation of low-abundance metabolites. Although statistical models from both 1D and 2D data could differentiate samples acquired from the two groups of mice, only the 2D spectra allowed the characterization of statistically relevant changes in the low-abundance metabolites. While acquisition of the 2D data require more time, the data obtained resulted in a more meaningful and comprehensive metabolic profile, aided in metabolite identifications, and minimized ambiguities in peak assignments. C1 [Van, Que N.; Issaq, Haleem J.; Muschik, Gary M.; Waybright, Timothy J.; Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, NCI, Ft Detrick, MD 21702 USA. [Jiang, Qiujie; Li, Qiaoli; Uitto, Jouni] Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. [Lou, Hong; Dean, Michael] NCI, Lab Gen Divers, Ft Detrick, MD 21702 USA. RP Van, QN (reprint author), SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, NCI, Ft Detrick, MD 21702 USA. EM qvan@ncifcrf.gov RI Dean, Michael/G-8172-2012; Li, Qiaoli/F-8383-2013 OI Dean, Michael/0000-0003-2234-0631; FU NIAMS NIH HHS [R01AR28450]; PHS HHS [N01-C0-12400] NR 57 TC 26 Z9 27 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD FEB PY 2008 VL 7 IS 2 BP 630 EP 639 DI 10.1021/pr700594s PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 258JO UT WOS:000252864400016 PM 18081246 ER PT J AU Nishizuka, S Ramalingam, S Spurrier, B Washburn, FL Krishna, R Honkanen, P Young, L Shimura, T Steeg, PS Austin, J AF Nishizuka, Satoshi Ramalingam, Sundhar Spurrier, Brett Washburn, Frank L. Krishna, Ramya Honkanen, Peter Young, Lynn Shimura, Tsutomu Steeg, Patricia S. Austin, John TI Quantitative protein network monitoring in response to DNA damage SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE "reverse-phase" protein lysate microarrays; DNA damage; dose-response curves; quantitative analysis; protein microarrayer; high-dimensional data; cell cycle; apoptosis ID LYSATE MICROARRAYS; P53; PHOSPHORYLATION; APOPTOSIS; ATR; PATHWAYS; INHIBITION; ACTIVATION; DATABASE; TUMOR AB Conventional molecular biology techniques have identified a large number of cell signaling pathways; however, the importance of these pathways often varies, depending on factors such as treatment type, dose, time after treatment, and cell type. Here, we describe a technique using "reverse-phase" protein lysate microarrays. (RPAs) to acquire multiple dimensions of information on protein dynamics in response to DNA damage. Whole-cell lysates from three cellular stress treatments (IR, UV, and ADR) were collected at four doses per treatment, and each, in turn, at 10 time points, resulting in a single-slide RPA consisting of 10 240 features, including replicates. The dynamic molecular profile of 18 unique protein species was compared to phenotypic fate by FACS analysis for corresponding stress conditions. Our initial quantitative results in this new platform confirmed that (1) there is clear stress dose-response effect in p53 protein and (2) a comparison of the rates of increase of p21 and Cyclin D3/p53-Ser15 in response to DNA damage may be associated with the pattern of DNA content. This method, offering a quantitative time-course monitoring of protein expression levels, can provide an experimental reference for developing mathematical models of cell signaling dynamics. Although the present study focuses on the DNA damage-repair pathway, the technique is generally useful to the study of protein signaling.. C1 [Nishizuka, Satoshi; Ramalingam, Sundhar; Spurrier, Brett; Washburn, Frank L.; Krishna, Ramya; Steeg, Patricia S.] NCI, Mol Therapeut Program, NIH, Bethesda, MD 20892 USA. [Nishizuka, Satoshi] NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. [Honkanen, Peter; Austin, John] Aushon BioSyst, Burlington, MA 01803 USA. [Young, Lynn] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Steeg, Patricia S.] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Nishizuka, S (reprint author), Iwate Med Univ, Sch Med, Dept Surg, Uchimaru 19-1, Morioka, Iwate 0208505, Japan. EM nishizus@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 28 TC 11 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD FEB PY 2008 VL 7 IS 2 BP 803 EP 808 DI 10.1021/pr0702971 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 258JO UT WOS:000252864400035 PM 18173236 ER PT J AU Moore, AB Flake, GP Swartz, CD Heartwell, G Cousins, D Hasernan, JK Kissling, GE Sidawy, MK Dixon, D AF Moore, Alicia B. Flake, Gordon P. Swartz, Carol D. Heartwell, Glenn Cousins, Deborah Hasernan, Joseph K. Kissling, Grace E. Sidawy, Mary K. Dixon, Darlene TI Association of race, age and body mass index with gross pathology of uterine fibroids SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE age; body mass index; fibroids; uterine; race ID UNITED-STATES; ETHNIC-DIFFERENCES; PREMENOPAUSAL WOMEN; RISK-FACTORS; HYSTERECTOMY; LEIOMYOMATA; ESTROGEN; METABOLISM; OBESITY AB OBJECTIVE: To determine the associations of race, age and body mass index (BMI) with the gross pathology parameters of uterine leiomyomas in premenopausal women undergoing hysterectomy or myomectomy. STUDY DESIGN: Participants (N = 107) were recruited from surgical rosters of the George Washington University (GWU) Medical Center Gynecology Department as part of the National Institute of Environmental Health Sciences Fibroid Study. Tumor data and patient demographics were obtained from clinical reports, pathology forms and interviews. RESULTS: Surgical cases consisted of 78% African Americans, 13% Caucasians and 9% others (non-African American, non-Caucasian or race unknown). This proportion of African Americans was significantly higher than the distribution of GWU health plan participants. Fibroids were localized predominantly within the intramural region. Subserosal tumors were more common in patients with more than 9 tumors. African Americans had the highest mean BMI and mean myomatous uterine weight. CONCLUSION: African Americans were the disproportionate majority coming to surgery for fibroids. The average BMI and uterine weight were greater in African Americans than in Caucasians, although these differences were marginal. Race did not influence the size, location or number of fibroids in these surgical cases. Subserosal tumors were more common in patients with more than 9 tumors. C1 Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, NIH, Biostat Branch,Lab Expt Pathol, Res Triangle Pk, NC USA. CODA Res Inc, Durham, NC USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. RP Dixon, D (reprint author), Natl Inst Environm Hlth Sci, Lab Expt Pathol, PO Box 12233, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov FU Intramural NIH HHS NR 33 TC 15 Z9 17 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD FEB PY 2008 VL 53 IS 2 BP 90 EP 96 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 265FX UT WOS:000253345600003 PM 18357799 ER PT J AU Ludlow, CL Hoit, J Kent, R Ramig, LO Shrivastav, R Strand, E Yorkston, K Sapienza, CM AF Ludlow, Christy L. Hoit, Jeannette Kent, Raymond Ramig, Lorraine O. Shrivastav, Rahul Strand, Edythe Yorkston, Kathryn Sapienza, Christine M. TI Translating principles of neural plasticity into research on speech motor control recovery and rehabilitation SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Plasticity/Rehabilitation Research CY APR 10-13, 2005 CL Univ Florida, Gainesville, FL SP Brain Rehabil Res Ctr, Vet Adm Res & Dev Ctr Excellence HO Univ Florida DE brain imaging; brain reorganization; dysarthria; dyspraxia; dysphonia ID TRANSCRANIAL MAGNETIC STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; AMYOTROPHIC-LATERAL-SCLEROSIS; PRIMARY SOMATOSENSORY CORTEX; REPETITIVE STRAIN INJURY; VOXEL-BASED MORPHOMETRY; VOICE TREATMENT LSVT(R); ADULT SQUIRREL-MONKEYS; ISCHEMIC BRAIN-INJURY; DIFFUSION TENSOR MRI AB Purpose: To review the principles of neural plasticity and make recommendations for research on the neural bases for rehabilitation of neurogenic speech disorders. Method: A working group in speech motor control and disorders developed this report, which examines the potential relevance of basic research on the brain mechanisms involved in neural plasticity and discusses possible similarities and differences for application to speech motor control disorders. The possible involvement of neural plasticity in changes in speech production in normalcy, development, aging, and neurological diseases and disorders was considered. This report focuses on the appropriate use of functional and structural neuroimaging and the design of feasibility studies aimed at understanding how brain mechanisms are altered by environmental manipulations such as training and stimulation and how these changes might enhance the future development of rehabilitative methods for persons with speech motor control disorders. Conclusions: Increased collaboration with neuroscientists working in clinical research centers addressing human communication disorders might foster research in this area. It is hoped that this article will encourage future research on speech motor control disorders to address the principles of neural plasticity and their application for rehabilitation. C1 [Ludlow, Christy L.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Hoit, Jeannette] Univ Arizona, Tucson, AZ USA. [Kent, Raymond] Univ Wisconsin, Madison, WI USA. [Ramig, Lorraine O.] Univ Colorado, Boulder, CO 80309 USA. [Shrivastav, Rahul] Univ Florida, Gainesville, FL USA. [Strand, Edythe] Mayo Clin, Rochester, MI USA. [Yorkston, Kathryn] Univ Washington, Seattle, WA 98195 USA. [Sapienza, Christine M.] Univ Florida, Gainesville, FL USA. RP Ludlow, CL (reprint author), 10 Ctr Dr MSC 1416,Bldg 10,Rm 5D-38, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [Z01 NS002980-09] NR 155 TC 35 Z9 37 U1 1 U2 15 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD FEB PY 2008 VL 51 IS 1 BP S240 EP S258 DI 10.1044/1092-4388(2008/019) PG 19 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 265PN UT WOS:000253373500019 PM 18230849 ER PT J AU Simon, R AF Simon, Richard TI Development and validation of biomarker classifiers for treatment selection SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE pharmacogenomics; biomarker; genomics; DNA microarray; clinical trial design validation ID GENE-EXPRESSION DATA; DNA MICROARRAY DATA; PROGNOSTIC CLASSIFICATION; CLASS PREDICTION; ERROR ESTIMATION; CLINICAL-TRIALS; BREAST-CANCER; ALGORITHMS; EFFICIENCY; DISCOVERY AB Many syndromes traditionally viewed as individual diseases are heteroaeneous in molecular pathogenesis and treatment responsiveness. This often leads to the conduct of large clinical trials to identify small average treatment benefits for heterogeneous groups of patients. Drugs that demonstrate effectiveness in such trials may subsequently he used broadly, resulting in ineffective treatment of many patients. New genomic and proteornic technologies provide powerful tools for the selection of patients likely to benefit from a therapeutic without unacceptable adverse events. In spite of the large literature on developing predictive biomarkers, there is considerable confusion about the development and validation of biomarker-based diagnostic classifiers for treatment selection. In this paper we attempt to clarify some of these issues and to provide guidance on the design of clinical trials for evaluating the clinical utility and robustness of pharmacogenomic classifiers. Published by Elsevier B.V. C1 NCI, Biomet Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biomet Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 38 TC 37 Z9 37 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD FEB 1 PY 2008 VL 138 IS 2 BP 308 EP 320 DI 10.1016/j.jspi.2007.06.010 PG 13 WC Statistics & Probability SC Mathematics GA 261GN UT WOS:000253067200002 PM 19190712 ER PT J AU Jiang, W Kalbfleisch, JD AF Jiang, Wenyu Kalbfleisch, John D. TI Permutation methods in relative risk regression models SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE permutation test; resampling; relative risk regression; Cox model; studentization; martingale; partial likelihood; counting process ID PROPORTIONAL HAZARDS MODELS; BOOTSTRAP AB In this paper, we develop a weighted permutation (WP) method to construct confidence intervals for regression parameters in relative risk regression models. The WP method is a generalized permutation approach. It constructs a resampled history which mimics the observed history for individuals under study. Inference procedures are based on studentized score statistics that are insensitive to the forms of the relative risk function. This makes the WP method appealing in the general framework of the relative risk regression model. First-order accuracy of the WP method is established using counting process approach with a partial likelihood filtration. A simulation study indicates that the method typically improves accuracy over asymptotic confidence intervals. (C) 2007 Elsevier B.V. All rights reserved. C1 [Kalbfleisch, John D.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Jiang, Wenyu] NCI, NIH, Div Canc Treatment & Diag, Biomet Res Branch, Rockville, MD 20852 USA. RP Kalbfleisch, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, 1420 Washington Heights, Ann Arbor, MI 48109 USA. EM jiangwen@mail.nih.gov; jdkalbfl@umich.edu NR 15 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD FEB 1 PY 2008 VL 138 IS 2 BP 416 EP 431 DI 10.1016/j.jspi.2007.06.001 PG 16 WC Statistics & Probability SC Mathematics GA 261GN UT WOS:000253067200009 ER PT J AU Martin, A Faraone, SV Henderson, SW Hudziak, JJ Leibenluft, E Piacentini, J Stein, B Todd, RD Walkup, J AF Martin, Andres Faraone, Stephen V. Henderson, Schuyler W. Hudziak, James J. Leibenluft, Ellen Piacentini, John Stein, Bradley Todd, Richard D. Walkup, John TI Conflict of interest SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 [Martin, Andres] Yale Univ, New Haven, CT 06520 USA. [Faraone, Stephen V.] SUNY Upstate, New York, NY USA. [Henderson, Schuyler W.] Columbia Univ, New York, NY 10027 USA. [Hudziak, James J.] Univ Vermont, Burlington, VT 05405 USA. [Leibenluft, Ellen] NIMH, Bethesda, MD 20892 USA. [Piacentini, John] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Stein, Bradley] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Todd, Richard D.] Washington Univ, St Louis, MO 63130 USA. [Walkup, John] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Martin, A (reprint author), Yale Univ, New Haven, CT 06520 USA. RI Piacentini, John/C-4645-2011; OI Hudziak, James/0000-0001-9653-758X; Faraone, Stephen/0000-0002-9217-3982 NR 5 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2008 VL 47 IS 2 BP 119 EP 120 DI 10.1097/chi.0b013e31815d6dba PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 253MR UT WOS:000252522800002 PM 18216711 ER PT J AU Kishor, S Turner, ML Borg, BB Kleiner, DE Cowen, EW AF Kishor, Sowmya Turner, Maria L. Borg, Brian B. Kleiner, David E. Cowen, Edward W. TI Cutaneous sarcoidosis and primary biliary cirrhosis: A chance association or related diseases? SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PULMONARY INVOLVEMENT; HEPATIC SARCOIDOSIS; PATIENT; GRANULOMAS; MANIFESTATIONS; CHOLESTASIS; COEXISTENCE; THERAPY; LESIONS; LIVER AB Sarcoidosis and primary biliary cirrhosis (PBC) are thought to be two distinct disorders of unknown origin. However, both are characterized by hepatic granuloma formation and may also manifest Cutaneous granulomatous inflammation. In this report, we describe two cases of cutaneous sarcoidosis occurring in the setting of PBC and review 7 additional cases from the literature of granulomatous skin disease associated with PBC. Although the pathogenesis of both sarcoidosis and PBC remains elusive, the simultaneous occurrence of these uncommon diseases suggests a common pathway may contribute to granuloma formation in both disorders. C1 [Turner, Maria L.; Cowen, Edward W.] Natl Canc Inst, Dermatol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. [Kishor, Sowmya] Eastern Virginia Med Sch, Dermatol Branch, Norfolk, VA 23501 USA. [Kleiner, David E.] Natl Canc Inst, Pathol Lab, Bethesda, MD 20892 USA. [Borg, Brian B.] Washington Univ, Sch Med, Dept Gastroenterol, St Louis, MO 63130 USA. RP Cowen, EW (reprint author), Natl Canc Inst, Dermatol Branch, Canc Res Ctr, Bldg 10 Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 34 TC 9 Z9 9 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2008 VL 58 IS 2 BP 326 EP 335 DI 10.1016/j.jaad.2007.07.031 PG 10 WC Dermatology SC Dermatology GA 253HJ UT WOS:000252509000020 PM 18222332 ER PT J AU Clark, JA Yao, L Turner, ML Cowen, EW AF Clark, Jason A. Yao, Lawrence Turner, Maria L. Cowen, Edward W. TI Magnetic resonance imaging for the diagnosis of subcutaneous involvement in patients with chronic graft-versus-host disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Dermatology CY FEB 01-05, 2008 CL San Antonio, TX SP Amer Acad Dermatol C1 [Clark, Jason A.] Natl Inst Hlth, Bethesda, MD USA. [Yao, Lawrence] Dept Diagnost Radiol, Bethesda, MD USA. [Turner, Maria L.; Cowen, Edward W.] Dermatol Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2008 VL 58 IS 2 SU 2 BP AB85 EP AB85 PG 1 WC Dermatology SC Dermatology GA 256AT UT WOS:000252700800338 ER PT J AU Pan, Y Pratt, CA AF Pan, Yang Pratt, Charlotte A. TI Metabolic syndrome and its association with diet and physical activity in US adolescents SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID INSULIN-RESISTANCE-SYNDROME; SYNDROME SYNDROME-X; YOUNG-ADULTS; CARDIOVASCULAR SYNDROME; SYNDROME PHENOTYPE; OBESE CHILDREN; RISK-FACTORS; OVERWEIGHT; CHILDHOOD; PATTERNS AB Background Research on the metabolic syndrome and its association with lifestyle behaviors in adolescents is important for identifying subgroups of youth at whom interventions should be targeted. Objective To examine the relationship of metabolic syndrome with diet and physical activity in US adolescents. Design A sample of 4,450 12- to 19-year-olds was obtained from 4-year combined data of the National Health and Nutrition Examination Survey 1999-2002. Method The metabolic syndrome was defined as having three or more of the following conditions: waist circumference >= 90th percentile for age/sex, fasting blood glucose >= 100 mg/dL (5.6 mmoUL), blood triglycerides >= 110 mg/dL (>= 1.2 mmol/L), HDL cholesterol <= 35 mg/dL (0.9 mmol/L), and systolic/diastolic blood pressure >= 90th percentile for height or taking antihypertensive drugs. Diet quality was assessed using the Healthy Eating Index and its components, and nutrient intakes. The association between the metabolic syndrome and physical activity was presented as the prevalence of metabolic syndrome by different physical activity levels. Results Overall prevalence of metabolic syndrome among US adolescents was 3.5%. More males than females (5.1% vs 1.7%; P<0.0001) had metabolic syndrome. The metabolic syndrome was 16 times higher in overweight adolescents (body mass index >= 95th percentile) compared to those with body mass index <85th percentile (14.5% vs 0.9%; P<0.0001). Prevalence of metabolic syndrome decreased with increments of overall Healthy Eating Index and fruit score quartiles. Higher overall Healthy Eating Index and fruit scores were associated with lower metabolic syndrome (P<0.001). There was a trend toward lower prevalence of metabolic syndrome in adolescents with high physical activity levels (2.6%) compared to those who had low (4.3%) or moderate (3.1%) physical activity levels. Conclusion Results support the need to engage adolescents in regular physical activity and healthful dietary practices to prevent excessive weight gain. Weight control should be recommended as the first-line intervention to decrease metabolic syndrome in adolescents. C1 [Pan, Yang] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Pratt, Charlotte A.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD USA. RP Pan, Y (reprint author), Coca Cola Co, 2000 St James Pl,Suite 534, Houston, TX 77056 USA. EM yapan@na.ko.com NR 39 TC 109 Z9 115 U1 1 U2 15 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 2008 VL 108 IS 2 BP 276 EP 286 DI 10.1016/j.jada.2007.10.049 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 260HW UT WOS:000253002400018 PM 18237576 ER PT J AU Stein, JH Korcarz, CE Hurst, RT Lonn, E Kendall, CB Mohler, ER Najjar, SS Rembold, CM Post, WS AF Stein, James H. Korcarz, Claudia E. Hurst, R. Todd Lonn, Eva Kendall, Christopher B. Mohler, Emile R. Najjar, Samcr S. Rembold, Christopher M. Post, Wendy S. TI Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force endorsed by the society for vascular medicine SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE atherosclerosis; cardiovascular disease; carotid arteries; carotid intima-media thickness; risk factors; ultrasound diagnosis; ultrasound ID CORONARY-HEART-DISEASE; B-MODE ULTRASOUND; BORDER DETECTION PROGRAM; ARTERIAL-WALL THICKNESS; COLLEGE-OF-CARDIOLOGY; HEALTHY-YOUNG ADULTS; MIDDLE-AGED ADULTS; ATHEROSCLEROSIS RISK; COMPUTED-TOMOGRAPHY; MYOCARDIAL-INFARCTION AB Continuing Medical Education Course for "Use of Carotid Ultrasound to Identify Subdinical Vascular Disease and Evaluate Cardiovascular Disease Risk: A Consensus Statement for the American Society of Echocardiography Carotid Intima-Media Thickness Task Force" Accreditation Statement: The American Society of Echocardiography is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Society of Echocardiography designates this educational activity for a maximum of 1 AMA PRA Category 1 Credits (TM). Physicians should only claim credit commensurate with the extent of their participation in the activity. ARDMS and CCI recognize ASE's certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The American Society of Echocardiography is committed to resolving all conflict of interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. Target Audience: 1. Physicians, physicians' assistants, and nurses with an interest in cardiac and vascular imaging, preventive cardiology, and cardiovascular disease risk assessment. 2. Ultrasonographers with interest in vascular imaging and cardiovascular disease risk assessment. Objectives: Upon completing this activity, participants will be able to: 1. Describe the rationale for using carotid ultrasound to identify subdinical vascular disease and to evaluate cardiovascular disease risk. 2. Explain the application of carotid ultrasound to cardiovascular disease risk assessment. 3. Describe the scanning technique for identifying subdinical vascular disease using carotid ultrasound. 4. Explain the key components of interpreting carotid ultrasound studies for cardiovascular disease risk assessment. C1 [Stein, James H.; Korcarz, Claudia E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Hurst, R. Todd; Kendall, Christopher B.] Mayo Clin, Scottsdale, AZ USA. [Lonn, Eva] McMaster Univ, Fac Hlth Sci, Hamilton, ON, Canada. [Mohler, Emile R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Najjar, Samcr S.] Natl Inst Hlth, NIA, Baltimore, MD USA. [Rembold, Christopher M.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Post, Wendy S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Post, Wendy S.] Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Stein, JH (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, 600 Highland Ave,G7-341 CSC MC 3248, Madison, WI 53792 USA. EM jhs@medicine.wisc.edu RI Rembold, Christopher/K-8359-2013 NR 96 TC 771 Z9 817 U1 7 U2 40 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD FEB PY 2008 VL 21 IS 2 BP 93 EP 111 DI 10.1016/j.echo.2007.11.011 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 266GW UT WOS:000253423500001 PM 18261694 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI The Asian Century: The changing geography of science SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 NIAID, NIH, LMM, Mol Virol Sect, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, NIH, LMM, Mol Virol Sect, 9000 Rockville Pike,Bldg 4,Room 306, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 4 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SINGAPORE PTE LTD PI SINGAPORE PA 3 KILLINEY ROAD 08-01, WINSLAND HOUSE 1, SINGAPORE, 239519, SINGAPORE SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD FEB PY 2008 VL 107 IS 2 BP 101 EP 102 DI 10.1016/S0929-6646(08)60122-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 267IX UT WOS:000253503800001 PM 18285241 ER PT J AU Greenfield, SP Chesney, RW Carpenter, M Moxey-Mims, M Nyberg, L Hoberman, A Keren, R Matthews, R Mattoo, T AF Greenfield, Saul P. Chesney, Russell W. Carpenter, Myra Moxey-Mims, Marva Nyberg, Leroy Hoberman, Alejandro Keren, Ron Matthews, Ranjiv Mattoo, Tej CA RIVUR Steering Comm TI Vesicoureteral reflux: The RIVUR study and the way forward SO JOURNAL OF UROLOGY LA English DT Editorial Material ID PROPHYLACTIC ANTIBIOTICS; CHILDREN C1 [Chesney, Russell W.] Lebonheur Childrens Hosp & Med Ctr, Memphis, TN USA. [Carpenter, Myra] Univ N Carolina, Chapel Hill, NC USA. [Moxey-Mims, Marva; Nyberg, Leroy; RIVUR Steering Comm] NIH, NIDDK, Bethesda, MD 20892 USA. [Hoberman, Alejandro] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Keren, Ron] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Matthews, Ranjiv] Johns Hopkins Sch Med, Baltimore, MD USA. [Mattoo, Tej] Wayne State Univ, Sch Med, Detroit, MI USA. RP Greenfield, SP (reprint author), Womens & Childrens Hosp, Dept Pediat Urol, Buffalo, NY 14222 USA. NR 12 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2008 VL 179 IS 2 BP 405 EP 407 DI 10.1016/j.juro.2007.10.100 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 251JP UT WOS:000252369600003 PM 18076937 ER PT J AU Woodson, K O'Reilly, KJ Hanson, JC Nelson, D Walk, EL Tangrea, JA AF Woodson, Karen O'Reilly, Keith J. Hanson, Jefirey C. Nelson, Dayne Walk, Elyse L. Tangrea, Joseph A. TI The usefulness of the detection of GSTP1 methylation in urine as a biomarker in the diagnosis of prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; methylation; prostate-specific antigen; mass screening ID POLYMERASE-CHAIN-REACTION; DNA-BASED DETECTION; MOLECULAR-DETECTION; HYPERMETHYLATION; SECRETIONS; BIOPSY AB Purpose: Prostate cancer has a unique set of problems associated with its early detection and diagnosis that might be aided by the addition of molecular markers, such as DNA hypermethylation. DNA methylation is an important epigenetic mechanism of gene regulation that has a critical role in normal developmental processes. Aberrant DNA methylation is a hallmark of carcinogenesis and GSTP1 hypermethylation is the most common molecular alteration in human prostate cancer. To our knowledge the clinical usefulness of the detection of gene methylation is yet to be established. Materials and Methods: We evaluated GSTP1 hypermethylation in urine collected after prostatic massage and in core needle biopsies from 100 men referred for diagnostic biopsy. Results: Methylation of GSTP1 in urine specimens had 75% sensitivity and 98% specificity for prostate cancer. GSTP1 methylation in the biopsy had 88% specificity and 91% sensitivity. Interestingly we observed a higher frequency of GSTP1 methylation in the urine of men with stage III vs II disease (100% vs 20%, p = 0.05). Conclusions: This study suggests that the detection of GSTP1 methylation in prediagnostic urine may improve the specificity of PSA and help distinguish men with prostate cancer from those with benign prostatic hyperplasia. This finding should be further explored in a larger, prospective screening trial. C1 [Woodson, Karen; Hanson, Jefirey C.; Walk, Elyse L.] NCI, Genet Branch, Ctr Canc Res, Ctr Adv Technol,NIH, Bethesda, MD 20892 USA. [Tangrea, Joseph A.] NCI, Div Canc Prevent, NIH, Bethesda, MD USA. [O'Reilly, Keith J.; Nelson, Dayne] Madigan Army Med Ctr, Urol Serv, Tacoma, WA 98431 USA. [O'Reilly, Keith J.; Nelson, Dayne] Madigan Army Med Ctr, Dept Anat Pathol, Tacoma, WA 98431 USA. RP Woodson, K (reprint author), NCI, Genet Branch, Ctr Canc Res, Ctr Adv Technol,NIH, 8717 Grovemont Cir, Bethesda, MD 20892 USA. EM kw114v@nih.gov NR 18 TC 51 Z9 57 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2008 VL 179 IS 2 BP 508 EP 511 DI 10.1016/j.juro.2007.09.073 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 251JP UT WOS:000252369600030 PM 18076912 ER PT J AU Propert, KJ Mayer, R Nickel, JC Payne, CK Peters, KM Teal, V Burks, D Kusek, JW Nyberg, LM Foster, HE AF Propert, Kathleen Joy Mayer, Robert Nickel, J. Curtis Payne, Christopher K. Peters, Kenneth M. Teal, Valerie Burks, David Kusek, John W. Nyberg, Leroy M. Foster, Harris E. CA Interstitial Cystitis Clin Trials TI Followup of patients with interstitial cystitis responsive to treatment with intravesical bacillus Calmette-Guerin or placebo SO JOURNAL OF UROLOGY LA English DT Article DE bladder; cystitis; interstitial; Mycobacterium bovis; pain; quality of life ID BENIGN PROSTATIC HYPERPLASIA; CLINICAL-TRIAL; THERAPY AB Purpose: We evaluated the longer term response in patients with interstitial cystitis who initially responded to intravesical bacillus Calmette-Guerin or placebo in a randomized clinical trial. Materials and Methods: Patients with interstitial cystitis who responded positively to treatment with bacillus Calmette-Guerin or placebo after 34 weeks of followup in a double-blind clinical trial were followed for an additional 34 weeks in an observational study to assess response durability. Outcomes at 68 weeks included a patient reported global response assessment, 24-hour voiding diary, and pain, urgency and validated interstitial cystitis symptom indexes. Results: Of responders to bacillus Calmette-Guerin or placebo in the clinical trial 38 continued extended followup in the observational study. A total of 12 (75%) responders who received placebo and 19 (86%) who received bacillus Calmette-Guerin considered themselves to remain moderately or markedly improved at week 68. Improved symptom outcomes were also generally maintained during followup in the 2 groups. Conclusions: Most patients who respond to therapy with intravesical bacillus Calmette-Guerin or placebo maintain improved symptoms for up to 68 weeks after the initiation of therapy. However, initial response rates are low and placebo responders demonstrated essentially the same durability of response as bacillus Calmette-Guerin responders. These results argue against the routine use of bacillus Calmette-Guerin in this patient group. C1 [Propert, Kathleen Joy; Teal, Valerie] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mayer, Robert] Univ Rochester, Rochester, NY USA. [Nickel, J. Curtis] Queens Univ, Kingston, ON, Canada. [Payne, Christopher K.] Stanford Univ, Stanford, CA 94305 USA. [Peters, Kenneth M.] William Beaumont Hosp, Detroit, MI USA. [Burks, David] Royal Oak & Henry Ford Hosp, Detroit, MI USA. [Kusek, John W.; Nyberg, Leroy M.] NIDDK, NIH, Bethesda, MD USA. [Foster, Harris E.] Yale Univ, New Haven, CT USA. RP Propert, KJ (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Blockey Hall,6th Floor,423 Guardian Dr, Philadelphia, PA 19104 USA. EM propert@mail.med.upenn.edu OI Teal, Valerie/0000-0001-7116-5353 FU NCRR NIH HHS [M01 RR016500-05, M01 RR 16500, M01 RR016500-08, M01 RR016500-06, M01 RR016500-07, M01 RR016500]; NIDDK NIH HHS [U01 DK54158, U01 DK054158-04, U01 DK054138-05S1, U01 DK54108, U01 DK054138-04, U01 DK054108-05, U01 DK054108-04, U01 DK054108-02, U01 DK054133-02, U01 DK54125, U01 DK054133-05, U01 DK54133, U01 DK054108-03, U01 DK054158-02, U01 DK054133-04, U01 DK054133-03, U01 DK054158-05S1, U01 DK054108-05S1, U01 DK054125-05S1, U01 DK054125-02, U01 DK054127-05, U01 DK54138, U01 DK054138-03, U01 DK054127, T32 DK060455, U01 DK054158-05, U01 DK054125-03, U01 DK54127, U01 DK054158-03, U01 DK054125-05, U01 DK054138-02, U01 DK054108, U01 DK054138-05, U01 DK054125-04, U01 DK054133-05S1] NR 9 TC 17 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2008 VL 179 IS 2 BP 552 EP 555 DI 10.1016/j.juro.2007.09.035 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 251JP UT WOS:000252369600044 PM 18082224 ER PT J AU Mosley, JW Operskalski, EA Tobler, LH Buskell, ZJ Andrews, WW Phelps, B Dockter, J Giachetti, C Seeff, LB Busch, MP AF Mosley, J. W. Operskalski, E. A. Tobler, L. H. Buskell, Z. J. Andrews, W. W. Phelps, B. Dockter, J. Giachetti, C. Seeff, L. B. Busch, M. P. CA Transfusion-Transmitted Viruses St TI The course of hepatitis C viraemia in transfusion recipients prior to availability of antiviral therapy SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE alanine aminotransferase; blood transfusion; hepatitis C infection; prospective studies; transcription-mediated amplification; viral RNA ID T-CELL RESPONSE; INTERFERON-ALPHA THERAPY; HCV VIRAL LOAD; VIRUS-INFECTION; AMINOTRANSFERASE LEVELS; TRANSAMINASE-ACTIVITY; DRUG-USERS; CLEARANCE; TRANSMISSION; RNA AB Knowing the likely distribution of intervals from hepatitis C infection to first RNA-negativity is important in deciding about therapeutic intervention. Prospectively collected sera and data from the Transfusion-transmitted Viruses Study (1974-1980) provide specific dates of infection and pattern of alanine aminotransferase (ALT) elevations. We examined frequency, timing and correlates of spontaneous resolution for 94 acutely infected transfusion recipients followed for a median of 9.5 months. Later, follow-up sera (>10 years) were available for 27 of the 94 cases from a Veterans Administration (VA) Study (1989-1990). Twenty-five (27%) of the 94 cases were classified as probably resolved during the episode itself. First RNA negativity occurred at 6-50 weeks (median, 19.5 weeks) after infection, and 5-43 weeks (median, 11 weeks) after ALT elevation. Thirteen of the 25 cases remained RNA-negative subsequently; 12 others had 1-6 RNA-positive sera intercalated between first and last RNA-negative results. RNA negativity, therefore, began variably and was interrupted in 12 cases of 25 (48%) by transient RNA-positive sera. Five of these 25 patients who were RNA-negative in the last study specimen had late, Veterans Administration Study follow-up; none showed viraemia. Of the remaining 69 transfusion transmitted virus study recipients, whose last serum was RNA-positive, two cleared viraemia after the last study serum but before late follow-up. Eleven (16%) had 23 intercalated RNA-negative sera before last positivity. RNA status, therefore, needs monitoring for many months before judging the spontaneous outcome as transient negativity may occur. Resolution was significantly more common in women and symptomatic cases; it was not associated with viral load in the infectious donation, HCV genotype, or the recipient's age. C1 [Mosley, J. W.; Operskalski, E. A.] Univ So Calif, Keck Sch Med, Los Angeles, CA USA. [Tobler, L. H.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA. [Buskell, Z. J.; Seeff, L. B.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Andrews, W. W.; Phelps, B.] Chiron Corp, Emeryville, CA 94608 USA. [Dockter, J.; Giachetti, C.] Gen Probe Incorp, San Diego, CA USA. [Seeff, L. B.] NIDDK, Bethesda, MD USA. [Busch, M. P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Mosley, JW (reprint author), 3627 Los Amigos St, La Crescenta, CA 91214 USA. EM mosley@usc.edu FU NHLBI NIH HHS [N01-HB-37093, R01-HL-076902, N01-HB-42972, N01-HB-9-7074, N01-HB-87047, N01-HB-47114] NR 42 TC 30 Z9 31 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD FEB PY 2008 VL 15 IS 2 BP 120 EP 128 DI 10.1111/j.1365-2893.2007.00900.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 246LY UT WOS:000252009700006 PM 18184195 ER PT J AU Kaur, A Di Mascio, M Barabasz, A Rosenzweig, M McClure, HM Perelson, AS Ribeiro, RM Johnson, RP AF Kaur, Amitinder Di Mascio, Michele Barabasz, Amy Rosenzweig, Michael McClure, Harold M. Perelson, Alan S. Ribeiro, Ruy M. Johnson, R. Paul TI Dynamics of T- and B-lymphocyte turnover in a natural host of simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; SOOTY MANGABEYS; RHESUS MACAQUES; SIV INFECTION; RAPID TURNOVER; CELL TURNOVER; IN-VIVO; CD4(+); CD8(+) AB Increased lymphocyte turnover is a hallmark of pathogenic lentiviral infection. To investigate perturbations in lymphocyte dynamics in natural hosts with nonpathogenic simian immunodeficiency virus (SIV) infection, the nucleoside analog bromodeoxyuridine (BrdU) was administered to six naturally SIV-infected and five SIV-negative sooty mangabeys. As a measure of lymphocyte turnover, we estimated the mean death rate by fitting a mathematical model to the fraction of BrdU-labeled cells during a 2-week labeling and a median 10-week delabeling period. Despite significantly lower total T- and B-lymphocyte counts in SIV-infected sooty mangabeys than in SIV-negative mangabeys, the turnover rate of B lymphocytes and CD4(+) and CD8(+) T lymphocytes was not increased in the SIV-infected animals. A small, rapidly proliferating CD45RA(+) memory subset and a large, slower-proliferating CD45RA(-) central memory subset of CD4(+) T lymphocytes identified in the peripheral blood of sooty mangabeys also did not show evidence of increased turnover in the context of SIV infection. Independently of SIV infection, the turnover of CD4(+) T lymphocytes in sooty mangabeys was significantly higher (P < 0.01) than that of CD8(+) T lymphocytes, a finding hitherto not reported in rhesus macaques or humans. The absence of aberrant T-lymphocyte turnover along with an inherently high rate of CD4(+) T-lymphocyte turnover may help to preserve the pool of central memory CD4(+) T lymphocytes in viremic SIV-infected sooty mangabeys and protect against progression to AIDS. C1 [Kaur, Amitinder; Barabasz, Amy; Rosenzweig, Michael; Johnson, R. Paul] Harvard Univ, Sch Med, Div Immunol, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Di Mascio, Michele] NIAID, NIH, Off Clin Res, Biostat Res Branch, Bethesda, MD 20892 USA. [McClure, Harold M.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Perelson, Alan S.; Ribeiro, Ruy M.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Kaur, A (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Reg Primate Res Ctr, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. EM amitinder_kaur@hms.harvard.edu OI Ribeiro, Ruy/0000-0002-3988-8241 FU NCRR NIH HHS [K26 RR000168, P20 RR018754, P20-RR18754, P51 RR000168, R01 RR006555, RR 00168, RR06555]; PHS HHS [A149809] NR 32 TC 33 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2008 VL 82 IS 3 BP 1084 EP 1093 DI 10.1128/JVI.02197-07 PG 10 WC Virology SC Virology GA 253JH UT WOS:000252514000003 PM 18032490 ER PT J AU Lindwasser, OW Smith, WJ Chaudhuri, R Yang, P Hurley, JH Bonifacino, JS AF Lindwasser, O. Wolf Smith, William J. Chaudhuri, Rittik Yang, Peter Hurley, James H. Bonifacino, Juan S. TI A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2 SO JOURNAL OF VIROLOGY LA English DT Article ID CD4 DOWN-REGULATION; ADAPTER PROTEIN COMPLEXES; HIV-1 NEF; CLATHRIN ADAPTER; DILEUCINE MOTIF; PLASMA-MEMBRANE; SH3 DOMAIN; RAPID INTERNALIZATION; CYTOPLASMIC DOMAIN; ACIDIC SEQUENCE AB A key function of the Nef protein of immunodeficiency viruses is the downregulation of the T-cell and macrophage coreceptor, CD4, from the surfaces of infected cells. CD4 downregulation depends on a conserved (D/E)XXXL(L/I)-type dileucine motif in the C-terminal, flexible loop of Nef, which mediates binding to the clathrin adaptor complexes AP-1, AP-2, and AP-3. We now report the identification of a consensus (D/E)D motif within this loop as a second, conserved determinant of interaction of Nef with A-P-2, though not with AP-1 and AP-3. Mutations in this diacidic motif abrogate both AP-2 binding and CD4 downregulation. We also show that a dileucine motif from tyrosinase, both in its native context and in the context of Nef, can bind to AP-2 independently of a diacidic motif. These results thus identify a novel type of AP-2 interaction determinant, support the notion that AP-2 is the key clathrin adaptor for the downregulation of CD4 by Nef, and reveal a previously unrecognized diversity among dileucine sorting signals. C1 [Lindwasser, O. Wolf; Smith, William J.; Chaudhuri, Rittik; Yang, Peter; Bonifacino, Juan S.] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. [Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU Intramural NIH HHS; NICHD NIH HHS [K22 HD54602] NR 55 TC 57 Z9 58 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2008 VL 82 IS 3 BP 1166 EP 1174 DI 10.1128/JVI.01874-07 PG 9 WC Virology SC Virology GA 253JH UT WOS:000252514000011 PM 18032517 ER PT J AU Graff, J Zhou, YH Torian, U Nguyen, H Claire, MS Yu, C Purcell, RH Emerson, SU AF Graff, Judith Zhou, Yi-Hua Torian, Udana Nguyen, Hanh Claire, Marisa St. Yu, Claro Purcell, Robert H. Emerson, Suzanne U. TI Mutations within potential glycosylation sites in the capsid protein of hepatitis E virus prevent the formation of infectious virus particles SO JOURNAL OF VIROLOGY LA English DT Article ID CIS-REACTIVE ELEMENT; NON-B-HEPATITIS; ORF2 PROTEIN; ENDOPLASMIC-RETICULUM; HEPATOMA-CELLS; INSECT CELLS; FULL-LENGTH; IN-VITRO; NON-A; HEV AB Hepatitis E virus is a nonenveloped RNA virus. However, the single capsid protein resembles a typical glycoprotein in that it contains a signal sequence and potential glycosylation sites that are utilized when recombinant capsid protein is overexpressed in cell culture. In order to determine whether these unexpected observations were biologically relevant or were artifacts of overexpression, we analyzed capsid protein produced during a normal viral replication cycle. In vitro transcripts from an infectious cDNA clone mutated to eliminate potential glycosylation sites were transfected into cultured Huh-7 cells and into the livers of rhesus macaques. The mutations did not detectably affect genome replication or capsid protein synthesis in cell culture. However, none of the mutants infected rhesus macaques. Velocity sedimentation analyses of transfected cell lysates revealed that mutation of the first two glycosylation sites prevented virion assembly, whereas mutation of the third site permitted particle formation and RNA encapsidation, but the particles were not infectious. However, conservative mutations that did not destroy glycosylation motifs also prevented infection. Overall, the data suggested that the mutations were lethal because they perturbed protein structure rather than because they eliminated glycosylation. C1 [Graff, Judith; Zhou, Yi-Hua; Torian, Udana; Nguyen, Hanh; Emerson, Suzanne U.] NIAID, Mol Hepatitis Sect, LID, NIH, Bethesda, MD 20892 USA. [Yu, Claro; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Claire, Marisa St.] Bioqual Inc, Rockville, MD 20850 USA. RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, LID, NIH, Room 6537,Bldg 50,50 South Dr,MSC 8009, Bethesda, MD 20892 USA. EM semerson@niaid.nih.gov FU Intramural NIH HHS NR 48 TC 49 Z9 51 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2008 VL 82 IS 3 BP 1185 EP 1194 DI 10.1128/JVI.01219-07 PG 10 WC Virology SC Virology GA 253JH UT WOS:000252514000013 PM 18032496 ER PT J AU Schmidt, M Voutetakis, A Afione, S Zheng, C Mandikian, D Chiorini, JA AF Schmidt, Michael Voutetakis, Antonis Afione, Sandra Zheng, Changyu Mandikian, Danielle Chiorini, John A. TI Adeno-associated virus Type 12 (AAV12): A novel AAV serotype with sialic acid- and heparan sulfate proteoglycan-independent transduction activity SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS TYPE-16; INFECTIOUS ENTRY; GENE-TRANSFER; CELL; REPLICATION; VECTORS; BINDING; IDENTIFICATION; PARVOVIRUS; EVOLUTION AB Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy. Recent isolations of novel AAV serotypes have led to significant advances by broadening the tropism and increasing the efficiency of gene transfer to the desired target cell. However, a major concern that remains is the strong preexisting immune responses to several vectors. In this paper, we describe the isolation and characterization of AAV12, an AAV serotype with unique biological and immunological properties. In contrast to those of all other reported AAVs, AAV12 cell attachment and transduction do not require cell surface sialic acids or heparan sulfate proteoglycans. Furthermore, rAAV12 is resistant to neutralization by circulating antibodies from human serum. The feasibility of rAAV12 as a vector was demonstrated in a mouse model in which muscle and salivary glands were transduced. These characteristics make rAAV12 an interesting candidate for gene transfer applications. C1 [Schmidt, Michael; Voutetakis, Antonis; Afione, Sandra; Zheng, Changyu; Mandikian, Danielle; Chiorini, John A.] NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Chiorini, JA (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, 10-1N113,10 Ctr Dr,MSC1190, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov FU Intramural NIH HHS NR 31 TC 75 Z9 78 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2008 VL 82 IS 3 BP 1399 EP 1406 DI 10.1128/JVI.02012-07 PG 8 WC Virology SC Virology GA 253JH UT WOS:000252514000034 PM 18045941 ER PT J AU Motomura, K Chen, JB Hu, WS AF Motomura, Kazushi Chen, Jianbo Hu, Wei-Shau TI Genetic recombination between human immunodeficiency virus type 1 (HIV-1) and HIV-2, two distinct human lentiviruses SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RETROVIRAL RECOMBINATION; REVERSE TRANSCRIPTION; VIRAL REPLICATION; PREFERRED REGION; TARGET-CELLS; RNA; INFECTION; GAG; SENEGAL AB Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are genetically distinct viruses that each can cause AIDS. Approximately 1 million people are infected with both HIV-1 and HIV-2. Additionally, these two viruses use the same receptor and coreceptors and can therefore infect the same target cell populations. To explore potential genetic interactions, we first examined whether RNAs from HfV-1 and HIV-2 can be copackaged into the same virion. We used modified near-full-length viruses that each contained a green fluorescent protein gene (gfp) with a different inactivating mutation. Thus, a functional gfp could be reconstituted via recombination, which was used to detect the copackaging of HIV-1 and HIV-2 RNAs. The GFP-positive (GFP(+)) phenotype was detected in approximately 0.2% of the infection events, which was 35-fold lower than the intrasubtype HIV-1 rates. We isolated and characterized 54 GFP(+) single-cell clones and determined that all of them contained proviruses with reconstituted gfp. We then mapped the general structures of the recombinant viruses and characterized the recombination junctions by DNA sequencing. We observed several different recombination patterns, including those that had crossovers only in gfp. The most common hybrid genomes had heterologous long terminal repeats. Although infrequent, crossovers in the viral sequences were also identified. Taken together, our study demonstrates that HIV-1 and HIV-2 can recombine, albeit at low frequencies. These observations indicate that multiple factors are likely to restrict the generation of viable hybrid HIV-1 and HIV-2 viruses. However, considering the large coinfected human population and the high viral load in patients, these rare events could provide the basis for the generation of novel human immunodeficiency viruses. C1 [Motomura, Kazushi; Chen, Jianbo; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU Intramural NIH HHS NR 47 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2008 VL 82 IS 4 BP 1923 EP 1933 DI 10.1128/JVI.01937-07 PG 11 WC Virology SC Virology GA 258ZQ UT WOS:000252909300027 PM 18057256 ER PT J AU Stanley, LR Comello, MLG Edwards, RW Marquart, BS AF Stanley, Linda R. Comello, Maria Leonora G. Edwards, Ruth W. Marquart, Beverly S. TI School adjustment in rural and urban communities: Do students from "Timbuktu" differ from their "City Slicker" peers? SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE school adjustment; school liking; rural; urban ID PARENTAL INVOLVEMENT; SUBSTANCE USE; ACADEMIC-ACHIEVEMENT; MIDDLE SCHOOL; ADOLESCENT; PARTICIPATION; DELINQUENCY; MOTIVATION; EDUCATION; FAMILY AB The primary purpose of our study was to explore the effects of rurality on school adjustment and other school-related variables. Using data from 167,738 7th-12th graders located in a national sample of 185 predominantly white communities, multilevel models were estimated for perceived school performance and school liking using a variety of individual-level (e.g., gender, ethnicity, and peer school performance) and community/school-level variables (e.g., school size, rurality, and percentage free/reduced lunch) as predictor variables. Rurality was not significantly related to school adjustment, but rather, the characteristics of individuals living within those communities were. Results also indicated that participation in school and non-school activities, a strength of rural schools, can play a positive role in school adjustment. Given the significant relationships of income and parental education to all of the school-related variables, a key long-term strategy may lie in improving the economic climate of rural areas. C1 [Stanley, Linda R.; Edwards, Ruth W.; Marquart, Beverly S.] Colorado State Univ, Triethn Ctr Prevent Res, Ft Collins, CO 80523 USA. [Comello, Maria Leonora G.] Ohio State Univ, Dept Commun, Columbus, OH 43210 USA. [Marquart, Beverly S.] NIDA, Bethesda, MD 20892 USA. RP Stanley, LR (reprint author), Colorado State Univ, Triethn Ctr Prevent Res, Ft Collins, CO 80523 USA. EM linda.stanley@colostate.edu RI Price, Katie/H-1931-2012 NR 80 TC 10 Z9 11 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD FEB PY 2008 VL 37 IS 2 BP 225 EP 238 DI 10.1007/s10964-007-9180-8 PG 14 WC Psychology, Developmental SC Psychology GA 243KR UT WOS:000251795800009 ER PT J AU Ferrucci, L AF Ferrucci, Luigi TI Throwing pots and commitments for 2008 SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID CONTROLLED-TRIALS; FRAILTY; SYSTEMS C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIA ASTRA Unit,Harbor Hosp, Baltimore, MD 21225 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIA ASTRA Unit,Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 15 TC 1 Z9 1 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2008 VL 63 IS 2 BP 157 EP 159 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 301FV UT WOS:000255882700007 PM 18314450 ER PT J AU Dayhoff-Brannigan, M Ferrucci, L Sun, K Fried, LP Walston, J Varadhan, R Guralnik, JM Semba, RD AF Dayhoff-Brannigan, Margaret Ferrucci, Luigi Sun, Kai Fried, Linda P. Walston, Jeremy Varadhan, Ravi Guralnik, Jack M. Semba, Richard D. TI Oxidative protein damage is associated with elevated serum interleukin-6 levels among older moderately to severely disabled women living in the community SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE inflammation; interleukin-6; oxidative stress; protein carbonyls ID C-REACTIVE PROTEIN; KAPPA-B; CARDIOVASCULAR-DISEASE; INFLAMMATORY MARKERS; ALZHEIMERS-DISEASE; GENE-EXPRESSION; CARBONYL GROUPS; STRESS; ATHEROSCLEROSIS; MALONDIALDEHYDE AB Background. Elevated interleukin (IL)-6 is associated with adverse outcomes. Our objective was to determine whether serum protein carbonyls, an indicator of oxidative protein damage and oxidative stress, were associated with IL-6. Methods. Serum protein carbonyls and IL-6 were measured in 739 women, age >= 65 years, in the Women's Health and Aging Study I. Results. Geometric mean of protein carbonyls was 0.082 nmol/mg. After adjusting for age and smoking status, log, serum protein carbonyls were associated with log, IL-6 (beta = 0.143, standard error [SE] = 0.048, p =.003) in linear regression analyses and with elevated IL-6 (>= 2.5 pg/mL) (odds ratio = 1.38, 95% confidence interval, 1.02-1.86, p = .037) in logistic regression analyses. Conclusion. Oxidative damage to proteins is independently associated with serum IL-6 among older women living in the community. Increased oxidative stress may be a factor involved in the pathogenesis of the proinflammatory state that occurs in older adults. C1 [Dayhoff-Brannigan, Margaret; Sun, Kai; Fried, Linda P.; Walston, Jeremy; Varadhan, Ravi; Semba, Richard D.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. [Guralnik, Jack M.] NIA, Epidemiol Demog & Biometry Branch, Bethesda, MD 20892 USA. RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000722]; NIA NIH HHS [R01 AG011703, N01 AG012112, N01-AG12112, AG11703-01A1, R01 AG027012]; NIAID NIH HHS [R01 AI41956, R01 AI041956] NR 42 TC 10 Z9 11 U1 1 U2 1 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 FEB PY 2008 VL 63 IS 2 BP 179 EP 183 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 301FV UT WOS:000255882700011 PM 18314454 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, US Dept HHS, OER, OLAW, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, US Dept HHS, OER, OLAW, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD FEB PY 2008 VL 37 IS 2 BP 63 EP 63 DI 10.1038/laban0208-63 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 260WC UT WOS:000253040100005 PM 18216794 ER PT J AU Fowler, CB Cunningham, RE Waybright, TJ Blonder, J Veenstra, TD O'Leary, TJ Mason, JT AF Fowler, Carol B. Cunningham, Robert E. Waybright, Timothy J. Blonder, Josip Veenstra, Timothy D. O'Leary, Timothy J. Mason, Jeffrey T. TI Elevated hydrostatic pressure promotes protein recovery from formalin-fixed, paraffin-embedded tissue surrogates SO LABORATORY INVESTIGATION LA English DT Article DE antigen retrieval; formalin-fixed; paraffin-embedded tissue; high-pressure protein extraction; lysozyme; mass spectrometry; proteomics ID FORMALDEHYDE-INDUCED MODIFICATIONS; MOLECULAR-MECHANISM; PROTEOMIC ANALYSIS; ANTIGEN RETRIEVAL; MASS-SPECTROMETRY; ASPARTIC-ACID; IDENTIFICATION; FIXATION; SECTIONS; CLEAVAGE AB High-throughput proteomic studies on formalin-fixed, paraffin-embedded (FFPE) tissues have been hampered by inefficient methods to extract proteins from archival tissue and by an incomplete knowledge of formaldehyde-induced modifications to proteins. We previously reported a method for the formation of 'tissue surrogates' as a model to study formalin fixation, histochemical processing, and protein retrieval from FFPE tissues. In this study, we demonstrate the use of high hydrostatic pressure as a method for efficient protein recovery from FFPE tissue surrogates. Reversal of formaldehyde-induced protein adducts and crosslinks was observed when lysozyme tissue surrogates were extracted at 45 000 psi and 80-100 degrees C in Tris buffers containing 2% sodium dodecyl sulfate and 0.2M glycine at pH 4. These conditions also produced peptides resulting from acid-catalyzed aspartic acid cleavage. Additives such as trimethylamine N-oxide or copper (II) chloride decreased the total percentage of these aspartic acid cleavage products, while maintaining efficient reversal of intermolecular crosslinks in the FFPE tissue surrogates. Mass spectrometry analysis of the recovered lysozyme yielded 70% sequence coverage, correctly identified all formaldehyde-reactive amino acids, and demonstrated hydrolysis at all of the expected trypsin cleavage sites. This study demonstrates that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues for proteomic analysis. C1 [Fowler, Carol B.; Cunningham, Robert E.; Mason, Jeffrey T.] Armed Forces Inst Pathol, Dept Biophys, Rockville, MD 20850 USA. [Waybright, Timothy J.; Blonder, Josip; Veenstra, Timothy D.] Natl Canc Inst, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, Frederick, MD USA. [O'Leary, Timothy J.] Vet Hlth Adm, Biomed Lab Res & Dev Serv, Washington, DC USA. RP Mason, JT (reprint author), Armed Forces Inst Pathol, Dept Biophys, 1413 Res Blvd,Bldg 101,Room 1057D, Rockville, MD 20850 USA. EM mason@afip.osd.mil FU NCI NIH HHS [N01-CO-12400, 1R33 CA 107844] NR 35 TC 23 Z9 25 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2008 VL 88 IS 2 BP 185 EP 195 DI 10.1038/labinvest.3700708 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 255MT UT WOS:000252662800009 PM 18158558 ER PT J AU Hughes, RAC Donofrio, P Bril, V Dolakas, MC Deng, CQ Hanna, K Hartung, HP Latov, N Merkies, ISJ van Doom, PA AF Hughes, Richard A. C. Donofrio, Peter Bril, Vera Dolakas, Marinos C. Deng, Chunqin Hanna, Kim Hartung, Hans-Peter Latov, Norman Merkies, Ingemar S. J. van Doom, Pieter A. CA ICE Study Grp TI Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial SO LANCET NEUROLOGY LA English DT Article ID MEDIATED POLYNEUROPATHIES; IMMUNOGLOBULIN TREATMENT; DOUBLE-BLIND; CRITERIA; DIAGNOSIS; STRENGTH; CIDP AB Background Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyetinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. Methods 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740. Findings During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33.5%, 95% CI 15.4-51.7; p=0.0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10.9 kPa, 4.6-17.2; p=0.0008) and the non-dominant hand (8.6 kPa, 2.6-14.6; p=0.005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0.011). The incidence of serious adverse events per infusion was 0.8% (9/1096) with IGIV-C versus 1.9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension. Interpretation This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP. C1 [Hughes, Richard A. C.] Kings Coll London, Guy Hosp, Dept Clin Neurosci, London SE1 1UL, England. [Donofrio, Peter] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Bril, Vera] Univ Hlth Network, Toronto, ON, Canada. [Dolakas, Marinos C.] NIH, Neuromuscular Dis Sect, Bethesda, MD USA. [Deng, Chunqin; Hanna, Kim] Talecris Biotherapeut, Res Triangle Pk, NC USA. [Hartung, Hans-Peter] Univ Dusseldorf, Dusseldorf, Germany. [Latov, Norman] Cornell Univ, Peripheral Neuropathy Ctr, New York, NY USA. [Merkies, Ingemar S. J.; van Doom, Pieter A.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. RP Hughes, RAC (reprint author), Kings Coll London, Dept Clin Neurosci, Hodgkin Bldg,Guys Campus, London SE1 1UL, England. EM richard.a.hughes@kci.ac.uk RI riva, nilo/J-7187-2012 OI riva, nilo/0000-0002-0513-9517 NR 26 TC 250 Z9 253 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2008 VL 7 IS 2 BP 136 EP 144 DI 10.1016/S1474-4422(07)70329-0 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 261PY UT WOS:000253093700014 PM 18178525 ER PT J AU Brigman, JL Feyder, M Saksida, LM Bussey, TJ Mishina, M Holmes, A AF Brigman, Jonathan L. Feyder, Michael Saksida, Lisa M. Bussey, Timothy J. Mishina, Masayoshi Holmes, Andrew TI Impaired discrimination learning in mice lacking the NMDA receptor NR2A subunit SO LEARNING & MEMORY LA English DT Article ID LONG-TERM POTENTIATION; EPSILON-1 SUBUNIT; VISUAL-CORTEX; TETRAMERIC STRUCTURE; ALZHEIMERS-DISEASE; HIPPOCAMPAL LTP; FRONTAL-CORTEX; IN-VIVO; MEMORY; EXPRESSION AB N-Methyl-D-aspartate receptors (NMDARs) mediate certain forms of synaptic plasticity and learning. We used a touchscreen system to assess NR2A subunit knockout mice (KO) for (1) pairwise visual discrimination and reversal learning and (2) acquisition and extinction of an instrumental response requiring no pairwise discrimination. NR2A KO mice exhibited significantly retarded discrimination learning. Performance on reversal was impaired in NR2A KO mice during the learning phase of the task; with no evidence of heightened perseverative responses. Acquisition and extinction of an instrumental behavior requiring no pairwise discrimination was normal in NR2A KO mice. The present findings demonstrate a significant and selective deficit in discrimination learning following loss of NR2A. C1 [Brigman, Jonathan L.; Feyder, Michael; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Saksida, Lisa M.; Bussey, Timothy J.] MRC, Cambridge CB2 3EB, England. [Saksida, Lisa M.; Bussey, Timothy J.] Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Mishina, Masayoshi] Univ Tokyo, Grad Sch Med, Dept Mol Neurobiol & Pharmacol, Tokyo 1130033, Japan. RP Brigman, JL (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. EM brigmanj@mail.nih.gov RI Brigman, Jonathan/O-4978-2016; Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016 OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041 FU Intramural NIH HHS [ZIA AA000411-09]; Medical Research Council [G0001354] NR 43 TC 67 Z9 69 U1 0 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD FEB PY 2008 VL 15 IS 2 BP 50 EP 54 DI 10.1101/lm.777308 PG 5 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 257BR UT WOS:000252774700002 PM 18230672 ER PT J AU Winslow, JT Noble, PL Davis, M AF Winslow, James T. Noble, Pamela L. Davis, Michael TI AX+/BX- discrimination learning in the fear-potentiated startle paradigm in monkeys SO LEARNING & MEMORY LA English DT Article ID CONDITIONED INHIBITION; RHESUS-MONKEYS; EXTINCTION; RATS AB Individuals with anxiety disorders often do not respond to safety signals and hence continue to be afraid and anxious. Consequently, it is important to develop paradigms in animals that can directly study brain systems involved in learning about, and responding to, safety signals. We previously developed a discrimination procedure in rats of the form AX+/BX-, where cues A and X presented together are paired with an aversive stimulus and cues B and X presented together predict the absence of an aversive stimulus. The present experiment adapted this procedure to the fear-potentiated startle paradigm in rhesus monkeys. C1 [Winslow, James T.; Noble, Pamela L.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. [Davis, Michael] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Davis, Michael] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Davis, Michael] Emory Univ, Yerkes Natl Primate Ctr, Ctr Behav Neurosci, Atlanta, GA 30322 USA. RP Winslow, JT (reprint author), NIMH, Intramural Res Program, Bethesda, MD 20892 USA. EM jameswinslow@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [MH 47840, MH 58922]; PHS HHS [RROO165] NR 14 TC 9 Z9 9 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD FEB PY 2008 VL 15 IS 2 BP 63 EP 66 DI 10.1101/lm.843308 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 257BR UT WOS:000252774700004 PM 18230674 ER PT J AU Shukla, S Sauna, ZE Ambudkar, SV AF Shukla, S. Sauna, Z. E. Ambudkar, S. V. TI Evidence for the interaction of imatinib at the transport-substrate site(s) of the multidrug-resistance-linked ABC drug transporters ABCB1 (P-glycoprotein) and ABCG2 SO LEUKEMIA LA English DT Letter ID HIGH-AFFINITY INTERACTION; INTRACELLULAR LEVELS; TYROSINE KINASE; IN-VITRO; CELLS; MESYLATE; MECHANISM; INCREASE; REVERSAL; STI571 C1 [Shukla, S.; Sauna, Z. E.; Ambudkar, S. V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Shukla, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI Ambudkar, Suresh/B-5964-2008 FU Intramural NIH HHS NR 13 TC 45 Z9 47 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 2008 VL 22 IS 2 BP 445 EP 447 DI 10.1038/sj.leu.2404897 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 262RY UT WOS:000253166900035 PM 17690695 ER PT J AU Bosetti, F Toscano, CD AF Bosetti, Francesca Toscano, Christopher D. TI Is it time to standardize ethics guiding the peer review process? SO LIPIDS LA English DT Letter DE ethics; conflict of interest; peer review AB While most scientific journals have well defined ethics requirements for authors, very few journals explicitly specify the ethics standards that govern the actions of editors, editorial board members, and reviewers. We believe it is time to create a standardized policy for all medical and scientific journals that guides the ethical conduct of all stakeholders in the peer review process. C1 [Bosetti, Francesca; Toscano, Christopher D.] NIA, NIH, Brain Physiol & Medabol Sect, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), NIA, NIH, Brain Physiol & Medabol Sect, Bethesda, MD 20892 USA. EM frances@mail.nih.gov FU Intramural NIH HHS [Z01 AG000425-01, Z01 AG000423-04, NIH0011410670] NR 4 TC 6 Z9 7 U1 2 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PD FEB PY 2008 VL 43 IS 2 BP 107 EP 108 DI 10.1007/s11745-007-3134-5 PG 2 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 259YM UT WOS:000252976800002 PM 18046592 ER PT J AU Masood, MA Salem, N AF Masood, M. Athar Salem, Norman, Jr. TI High-throughput analysis of plasma fatty acid methyl esters employing robotic transesterification and fast gas chromatography SO LIPIDS LA English DT Article DE robotic transesterification; plasma fatty acid methyl esters; fast gas chromatographic; high throughput sample preparation; high throughput gas chromatography; essential fatty acids ID ALPHA-LINOLENIC ACID; OMEGA-3-FATTY-ACID DEFICIENCY; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; DOCOSAHEXAENOIC ACID; CONTROLLED-TRIAL; HEART-DISEASE; TERM INFANTS; SUDDEN-DEATH; BRAIN AB Fatty acid analysis is an important research tool, and indices derived from essential fatty acid contents serve as useful biomarkers related to cardiovascular and other chronic disease risk. Both clinical and basic studies of essential fatty acid composition are becoming ever larger in magnitude leading to delays while the rather laborious lipid analyses are performed. A robotic transesterification procedure has been developed for high-throughput analysis of plasma fatty acid methyl esters. In this approach, robots perform most steps including plasma and reagent transfer, transesterification reaction via heating at 80 degrees C in open tubes with multiple reagent additions, followed by two-phase extraction and transfer of lipid extracts to GC vials. The vials are then placed directly onto a GC autosampler carousel for robotic sample injection. An improved fast GC method is presented in which the peaks of interest are eluted within 6 min. This method is readily scalable to prepare and analyze 200 samples per day (1,000 samples per week) so that large clinical trials can be accommodated. C1 [Masood, M. Athar; Salem, Norman, Jr.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Masood, MA (reprint author), 5625 Fishers Lane,Room 3N-07,MSC 9410, Bethesda, MD 20892 USA. EM masoodaa@mail.nih.gov; nsalem@niaaa.nih.gov FU Intramural NIH HHS NR 40 TC 32 Z9 32 U1 1 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 EI 1558-9307 J9 LIPIDS JI Lipids PD FEB PY 2008 VL 43 IS 2 BP 171 EP 180 DI 10.1007/s11745-007-3130-9 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 259YM UT WOS:000252976800010 PM 18084789 ER PT J AU Reynolds, HY AF Reynolds, Herbert Y. TI In choosing a research health career, mentoring is essential SO LUNG LA English DT Article DE mentoring; minorities; scholastic programs; clinical skills ID PHYSICIAN-SCIENTISTS; VISION AB An academic career in medical research can be wonderfully rewarding if the new biologic and health knowledge one discovers is later translated into the design of better health care strategies or clinical therapy. With so many new investigative methods available, this seems to be an opportune time to enter the research field. However, the seemingly limitless possibilities for discovery might not be realized if an ample new investigator work force is not maintained. Preparing and training young investigators are included in the primary mission of the National Institutes of Health (NIH),which is to support and facilitate scientific research. The National Heart, Lung, and Blood Institute (NHLBI) is very involved in research training, as are the professional pulmonary societies, patient disease-related organizations, and pharmaceutical companies who support this partnership. This perspective will review ways, young students initially may become interested in science and perhaps medicine through the help of mentors, and exposure to early research opportunities that allow them to experience the excitement of science. Then, later career development strategies will be presented that might further the interest of undergraduate and young health professionals to pursue medical research. As creative and spirited mentoring efforts are often very important in career selection, current approaches need to be critiqued for improvement. C1 [Reynolds, Herbert Y.] NHLBI, Dept Hlth, Div Lung Dis, Rockledge Ctr 2,NIH, Bethesda, MD 20892 USA. [Reynolds, Herbert Y.] NHLBI, Human Serv, Div Lung Dis, Rockledge Ctr 2,NIH, Bethesda, MD 20892 USA. RP Reynolds, HY (reprint author), NHLBI, Dept Hlth, Div Lung Dis, Rockledge Ctr 2,NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM Reynoldh@nhlbi.nih.gov NR 37 TC 23 Z9 23 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD FEB PY 2008 VL 186 IS 1 BP 1 EP 6 DI 10.1007/s00408-007-9050-x PG 6 WC Respiratory System SC Respiratory System GA 257NX UT WOS:000252806900001 PM 17990035 ER PT J AU Aletras, AH Kellman, P Derbyshire, JA Arai, AE AF Aletras, Anthony H. Kellman, Peter Derbyshire, J. Andrew Arai, Andrew E. TI ACUT(2)E TSE-SSFP: A hybrid method for T2-weighted Imaging of edema in the heart SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE edema; infarction; T2; ACUT(2)E; ACUTE; C-TIDE; myocardium; heart ID CARDIOVASCULAR MAGNETIC-RESONANCE; ACUTE MYOCARDIAL-INFARCTION; TURBO SPIN-ECHO; MR; CONTRAST; ENHANCEMENT; ANGIOGRAPHY; RESOLUTION; IMAGES; NMR AB ACUT(2)E TSE-SSFP is a hybrid between steady state free precession (SSFP) and turbo spin echo (TSE) for bright-blood T2-weighted imaging with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) similar to dark-blood TSE. TSE-SSFP uses a segmented SSFP readout during diastole with 180 pulses following a 90 preparation. The 180 refocusing pulses make TSE-SSFP similar to TSE but TSE-SSFP uses gradient moment nulling, whereas TSE uses gradient crushing. TSE-SSFP produced T2-weighted images with minimal T1 weighting. TSE-SSFP and TSE had similar SNR (155.9 +/- 6.0 vs 160.9 +/- 7.0; P = NS) for acute myocardial infarction (MI) and twice the SNR of T2-prepared SSFP (73.1 +/- 3.4, P < 0.001). TSE-SSFP and TSE had approximately double the CNR of T2-prepared SSFP for differentiating acute MI from normal myocardium. Imperfect blood suppression, present in all animals on some TSE images, was a problem eliminated by TSE-SSFP and T2-prepared SSFP. C1 [Aletras, Anthony H.; Kellman, Peter; Derbyshire, J. Andrew; Arai, Andrew E.] NHLBI, NIH, LCE, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Aletras, AH (reprint author), NHLBI, NIH, LCE, US Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA. EM aletrasa@nhibi.nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS NR 28 TC 73 Z9 75 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2008 VL 59 IS 2 BP 229 EP 235 DI 10.1002/mrm.21490 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258WV UT WOS:000252901700001 PM 18228588 ER PT J AU Yang, SL Hu, JN Kou, ZF Yang, YH AF Yang, Shaolin Hu, Jiani Kou, Zhifeng Yang, Yihong TI Spectral simplification for resolved glutamate and glutamine measurement using a standard STEAM sequence with optimized timing parameters at 3, 4, 4.7, 7, and 9.4 T SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE glutamate; glutamine; H-1 MR spectroscopy; STEAM ID MAGNETIC-RESONANCE SPECTROSCOPY; HUMAN BRAIN; IN-VIVO; MR SPECTROSCOPY; H-1-NMR SPECTROSCOPY; RELAXATION-TIMES; COUPLED SPINS; QUANTIFICATION; METABOLITES; PRESS AB The C4 multiplet proton resonances of glutamate (Glu) around 2.35 ppm and glutamine (Gin) around 2.45 ppm usually overlap in MR spectra, particularly at low- and mid-field strengths (1.54.7T). A spectral simplification approach is introduced that provides unobstructed Glu and Gin measurement using a standard STEAM localization sequence with optimized interpulse timings. The underlying idea is to exploit the dependence of response of a coupled spin system on the echo time (TE) and mixing time (TM) to find an optimum timing set (TE, TM), at which the outer-wings of C4 "pseudo-triplet" proton resonances of Glu and Gin are significantly suppressed while the central peaks are maintained. The spectral overlap is thus resolved as the overlap exists exclusively at the outer-wings and the central peaks are readily separated due to the approximate 0.1-ppm difference in chemical shift. Density matrix simulation for Glu, Gin, and other overlapping metabolites at 2.3-2.5 ppm was conducted to predict the optimum timing sets. The simulated, phantom, and in vivo results demonstrated that the C4 multiplet proton resonances of Glu and Gin can be resolved for unobstructed detection at 3T, 4T, and 4.7T. For simplicity, only simulated data are illustrated at 7T and 9AT. C1 [Yang, Shaolin; Yang, Yihong] Natl Inst Drug Abuse, NIH, Neuroimaging Res Branch, Baltimore, MD 21224 USA. [Hu, Jiani; Kou, Zhifeng] Wayne State Univ, Dept Radiol, Detroit, MI USA. RP Yang, YH (reprint author), Natl Inst Drug Abuse, NIH, Neuroimaging Res Branch, 5500 Nathan Shock Dr,Room 383, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov FU Intramural NIH HHS NR 38 TC 31 Z9 32 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2008 VL 59 IS 2 BP 236 EP 244 DI 10.1002/mrm.21463 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258WV UT WOS:000252901700002 PM 18228589 ER PT J AU Francischetti, IMB Seydel, KB Monteiro, RQ AF Francischetti, Ivo M. B. Seydel, Karl B. Monteiro, Robson Q. TI Blood coagulation, inflammation, and malaria SO MICROCIRCULATION LA English DT Review DE endothelium; tissue factor; prothroinbinase; apoptosis; sepsis ID PLASMODIUM-FALCIPARUM MALARIA; TUMOR-NECROSIS-FACTOR; HUMAN CEREBRAL MALARIA; DISSEMINATED INTRAVASCULAR COAGULATION; INTERCELLULAR-ADHESION MOLECULE-1; TISSUE FACTOR EXPRESSION; FACTOR PATHWAY INHIBITOR; HUMAN ENDOTHELIAL-CELLS; ESCHERICHIA-COLI SEPSIS; PLASMINOGEN-ACTIVATOR RECEPTOR AB Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year. Plasmodium falciparum, infection is often associated with a procoagulant tonus characterized by thrombocytopenia and activation of the coagulation cascade and fibrinolytic svstem; however, bleeding and hemorrhage are uncommon events, suggesting that a compensated state of blood coagulation activation occurs in malaria. This article (i) reviews the literature related to blood coagulation and malaria in a historic perspective., (ii) describes basic mechanisms of coagulation, anticoagulation and fibrinolysis., (iii) explains the laboratory changes in acute and compensated disseminated intravascular coagulation (DIC), (iv) discusses the implications of tissue factor (TF) expression in the endothelium of P. falctiparum infected patients, and (v) emphasizes the procoagulant role of parasitized red blood cells (RBCs) and activated platelets in the pathogenesis of malaria. This article also presents the Tissue Factor Model (TFM) for malaria pathogenesis, which places TF as the interface between sequestration, endothelial cell (EC) activation, blood coagulation disorder., and inflammation often associated with the disease. The relevance of the coagulation-inflammation cycle for the multiorgan dysfunction and coma is discussed in the context of malaria pathogenesis. C1 [Francischetti, Ivo M. B.] NIAID, LMVR, Vector Biol Sect, NIH, Bethesda, MD 20892 USA. [Seydel, Karl B.] NIAID, LMVR, Malaria Cell Biol Sect, NIH, Bethesda, MD 20892 USA. [Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil. RP Francischetti, IMB (reprint author), NIAID, LMVR, Vector Biol Sect, NIH, 12735 Twinbrook Pkwy,Room 2E28 MSC 8132, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov RI Inbeb, Inct/K-2317-2013; Monteiro, Robson/B-8007-2014 FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999] NR 292 TC 65 Z9 68 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD FEB PY 2008 VL 15 IS 2 BP 81 EP 107 DI 10.1080/10739680701451516 PG 27 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 268ML UT WOS:000253583800001 PM 18260002 ER PT J AU Kanungo, J AF Kanungo, Jyotshnabala TI DNase I-resistant DNA-dependent protein kinase activity in Xenopus oocytes SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Ku; DNA-PK activation; Xenopus oocyte ID HUMAN KU-AUTOANTIGEN; PHOSPHORYLATION ACTIVITY; COMPLEX; ANTIGEN; REPAIR; CELLS; RECOMBINATION; ASSOCIATION; NUCLEI; GENE AB DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase consisting of a catalytic subunit p460 (DNA-PKcs), and a DNA binding component termed Ku. DNA-PK plays a role in transcription, nonhomologous recombination, and DNA repair. Several reports have demonstrated that binding to double-stranded DNA (dsDNA) is required for the activation of DNA-PK. To date, very few reports suggest the possibility that an alternative pathway of DNA-PK activation exists without the requirement of dsDNA. In this study, direct biochemical evidence is presented to support this notion. Here, Xenopus oocytes were used as a model system because they offer the advantage of a manual enucleation process providing an extract that can be termed purely 'cytoplasmic' and the isolated nuclei (germinal vesicles) can be used to make nuclear extracts. Specific antibody-mediated pulled-down DNA-PK activity was assayed in the cytoplasmic extracts to evaluate the enzyme activity in the presence and absence of DNA. DNase I treatment did not affect the DNA-PK activity. Analyses of the association of nicked DNA with the pulled-down DNA-PK by radiolabeling the associated nicked DNA provided evidence that the cytoplasmic DNA-PK is catalytically active in absence of DNA. These results suggest that potential mechanisms occurring outside of the nucleus might activate DNA-PK, and therefore, could reveal novel functions of this enzyme. C1 NIH, NHGRI, Bethesda, MD 20892 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Kanungo, J (reprint author), NIH, NHGRI, 50 S Dr,Room 5232, Bethesda, MD 20892 USA. EM kanungoj@mail.nih.gov NR 28 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD FEB PY 2008 VL 309 IS 1-2 BP 33 EP 40 DI 10.1007/s11010-007-9640-1 PG 8 WC Cell Biology SC Cell Biology GA 255DW UT WOS:000252638200004 PM 17973081 ER PT J AU Ge, K Cho, YW Guo, H Hong, TB Guermah, M Ito, M Yu, H Kalkum, M Roeder, RG AF Ge, Kai Cho, Young-Wook Guo, Hong Hong, Teresa B. Guermah, Mohamed Ito, Mitsuhiro Yu, Hong Kalkum, Markus Roeder, Robert G. TI Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; NUCLEAR RECEPTORS; PPAR-GAMMA; COACTIVATOR COMPLEX; TRANSCRIPTIONAL REGULATION; GLUCOCORTICOID-RECEPTOR; DEPENDENT TRANSCRIPTION; C/EBP-ALPHA; TRAP220; TRAP/MEDIATOR AB Mediator is a general coactivator complex connecting transcription activators and RNA polymerase II. Recent work has shown that the nuclear receptor-interacting MED1/TRAP220 subunit of Mediator is required for peroxisome pro] iferator-activated receptor gamma (PPAR gamma)-stimulated adipogenesis of mouse embryonic fibroblasts (MEFs). However, the molecular mechanisms remain undefined. Here, we show an intracellular PPAR gamma-Mediator interaction that requires the two LXXLL nuclear receptor recognition motifs on MED1/TRAP220 and, furthermore, we show that the intact LXXLL motifs are essential for optimal PPAR gamma function in a reconstituted cell-free transcription system. Surprisingly, a conserved N-terminal region of MED1/TRAP220 that lacks the LXXLL motifs but gets incorporated into Mediator fully supports PPAR gamma-stimulated adipogenesis. Moreover, in undifferentiated MEFs, MED1/TRAP220 is dispensable both for PPAR gamma-mediated target gene activation and for recruitment of Mediator to a PPAR response element on the aP2 target gene promoter. However, PPAR gamma shows significantly reduced transcriptional activity in cells deficient for a subunit (MED24/ TRAP100) important for the integrity of the Mediator complex, indicating a general Mediator requirement for PPAR gamma function. These results indicate that there is a conditional requirement for MED1/TRAP220 and that a direct interaction between PPAR gamma and Mediator through MED1/TRAP220 is not essential either for PPAR gamma-stimulated adipogenesis or for PPAR gamma target gene expression in cultured fibroblasts. As Mediator is apparently essential for PPAR gamma transcriptional activity, our data indicate the presence of alternative mechanisms for Mediator recruitment, possibly through intermediate cofactors or other cofactors that are functionally redundant with MED1/TRAP220. C1 [Ge, Kai; Cho, Young-Wook; Guo, Hong; Yu, Hong] NIDDKD, Nucl Receptor Biol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Ge, Kai; Guermah, Mohamed; Ito, Mitsuhiro; Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. [Hong, Teresa B.; Kalkum, Markus] City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. RP Ge, K (reprint author), NIDDKD, Nucl Receptor Biol Sect, Clin Endocrinol Branch, NIH, Bldg 10,Room 8N307C, Bethesda, MD 20892 USA. EM kaig@niddk.nih.gov; roeder@mail.rockefeller.edu RI Cho, Young-Wook /F-8269-2011; OI Ge, Kai/0000-0002-7442-5138 FU Intramural NIH HHS [Z01 DK047055-01, Z01 DK047056-01, Z01 DK047056-02, Z99 DK999999]; NIDDK NIH HHS [ZIADK047055-03, DK07190, ZIADK075017-01] NR 44 TC 50 Z9 53 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2008 VL 28 IS 3 BP 1081 EP 1091 DI 10.1128/MCB.00967-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 254RQ UT WOS:000252606100019 PM 18039840 ER PT J AU Trotter, KW Fan, HY Ivey, ML Kingston, RE Archer, TK AF Trotter, Kevin W. Fan, Hua-Ying Ivey, Melissa L. Kingston, Robert E. Archer, Trevor K. TI The HSA domain of BRG1 mediates critical interactions required for glucocorticoid receptor-dependent transcriptional activation in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN-REMODELING COMPLEX; BREAST-CANCER CELLS; NUCLEAR RECEPTORS; ESTROGEN-RECEPTOR; SWI/SNF COMPLEXES; RESPONSIVE GENES; SUBUNITS; PROTEINS; FAMILY; DNA AB The packaging of eukaryotic DNA into chromatin can create an impediment to transcription by hindering binding of essential factors required for transcription. The mammalian SWI/SNF remodeling complex has been shown to alter local chromatin structure and facilitate recruitment of transcription factors. BRG1 (or hBrm), the central ATPase of the human SWI/SNF complex, is a critical factor for the functional activity of nuclear receptor complexes. Analysis using BRG1/SNF2h chimeras suggests BRG1 may contain previously uncharacterized functional motifs important for SWI/SNF. To identify these regions, BRG1 truncation and deletion mutants were designed, characterized, and utilized in a series of assays to evaluate transcriptional activation and chromatin remodeling by the glucocorticoid receptor. We identified a domain within the N terminus of BRG1 that mediates critical protein interactions within SWI/SNF. We find the HSA domain of BRG1 is required to mediate the interaction with BAF250a/ARIDIA and show this association is necessary for transcriptional activation from chromatin mouse mammary tumor virus or endogenous promoters in vivo. These studies suggest BAF250a is a necessary facilitator of BRG1-mediated chromatin remodeling required for SWI/SNF-dependent transcriptional activation. C1 [Trotter, Kevin W.; Ivey, Melissa L.; Archer, Trevor K.] NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Fan, Hua-Ying; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fan, Hua-Ying] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. [Fan, Hua-Ying; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Archer, TK (reprint author), NIEHS, NIH, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM archer1@me.nih.gov FU Intramural NIH HHS; NCI NIH HHS [K01 CA093660, CA-093660] NR 40 TC 30 Z9 31 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2008 VL 28 IS 4 BP 1413 EP 1426 DI 10.1128/MCB.01301-07 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 260SD UT WOS:000253029800020 PM 18086889 ER PT J AU Irimia, M Rukov, JL Penny, D Garcia-Fernandez, J Vinther, J Roy, SW AF Irimia, Manuel Rukov, Jakob L. Penny, David Garcia-Fernandez, Jordi Vinther, Jeppe Roy, Scott W. TI Widespread evolutionary conservation of alternatively spliced exons in Caenorhabditis SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE alternative splicing; Coenorhabditis; cassette exon; evolution; genome ID MESSENGER-RNA; INTRON POSITIONS; GENE DUPLICATION; C-ELEGANS; GENOME; MOUSE; GAIN; EVENTS; EUKARYOTES; DROSOPHILA AB Alternative splicing (AS) contributes to increased transcriptome and proteome diversity in various eukaryotic lineages. Previous studies showed low levels of conservation of alternatively spliced (cassette) exons within mammals and within dipterans. We report a strikingly different pattern in Caenorhabditis nematodes-more than 92% of cassette exons from Caenorhabditis elegans are conserved in Caenorhabditis briggsae and/or Caenorhabditis remanei. High levels of conservation extend to minor-form exerts (present in a minority of transcripts) and are particularly pronounced for exons showing complex patterns of splicing. The functionality of the vast majority of cassette exons is underscored by various other features. We suggest that differences in conservation between lineages reflect differences in levels of functionality and further suggest that these differences are due to differences in intron length and the strength of consensus boundaries across lineages. Finally, we demonstrate an inverse relationship between AS and gene duplication, suggesting that the latter may be primarily responsible for the emergence of new functional transcripts in nematodes. C1 [Irimia, Manuel; Garcia-Fernandez, Jordi] Univ Barcelona, Dept Genet, Barcelona, Spain. [Rukov, Jakob L.; Vinther, Jeppe] Univ Copenhagen, Dept Mol Biol, Mol Evolut Grp, Copenhagen, Denmark. [Penny, David; Roy, Scott W.] Massey Univ, Allan Wilson Ctr Mol Evolut & Ecol, Palmerston North, New Zealand. [Roy, Scott W.] Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Irimia, M (reprint author), Univ Barcelona, Dept Genet, Barcelona, Spain. EM mirimia@gmail.com; scottwroy@gmail.com RI Irimia, Manuel/E-3040-2010; Penny, David/E-9410-2011; Vinther, Jeppe/A-8172-2012; Garcia-Fernandez, Jordi/B-3839-2013 OI Irimia, Manuel/0000-0002-2179-2567; Vinther, Jeppe/0000-0002-3847-3853; Garcia-Fernandez, Jordi/0000-0001-5677-5970 NR 50 TC 32 Z9 32 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD FEB PY 2008 VL 25 IS 2 BP 375 EP 382 DI 10.1093/molbev/msm262 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 269FL UT WOS:000253634800015 PM 18048400 ER PT J AU Balla, A Kim, YJ Varnai, P Szentpetery, Z Knight, Z Shokat, KM Balla, T AF Balla, Andras Kim, Yeun Ju Varnai, Peter Szentpetery, Zsofia Knight, Zachary Shokat, Kevan M. Balla, Tamas TI Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylinositol 4-kinase III alpha SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; PH DOMAINS; 4-KINASE; GOLGI; RECEPTOR; BINDING; CELLS; 4-PHOSPHATE; SECRETION; 4,5-BISPHOSPHATE AB Type III phosphatidylinositol (PtdIns) 4-kinases (PI4Ks) have been previously shown to support plasma membrane phosphoinositide synthesis during phospholipase C activation and Ca2+ signaling. Here, we use biochemical and imaging tools to monitor phosphoinositide changes in the plasma membrane in combination with pharmacological and genetic approaches to determine which of the type III PI4Ks (alpha or beta) is responsible for supplying phosphoinositides during agonist-induced Ca2+ signaling. Using inhibitors that discriminate between the alpha- and beta-isoforms of type III PI4Ks, PI4KIII alpha was found indispensable for the production of phosphatidylinositol 4-phosphate (PtdIns4P), phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2], and Ca2+ signaling in angiotensin II (AngII)-stimulated cells. Downregulation of either the type II or type III PI4K enzymes by small interfering RNA ( siRNA) had small but significant effects on basal PtdIns4P and PtdIns( 4,5) P2 levels in P-32-labeled cells, but only PI4KIII alpha down-regulation caused a slight impairment of PtdIns4P and PtdIns(4,5)P-2 resynthesis in AngII-stimulated cells. None of the PI4K siRNA treatments had a measurable effect on AngII-induced Ca2+ signaling. These results indicate that a small fraction of the cellular PI4K activity is sufficient to maintain plasma membrane phosphoinositide pools, and they demonstrate the value of the pharmacological approach in revealing the pivotal role of PI4KIII alpha enzyme in maintaining plasma membrane phosphoinositides. C1 [Balla, Andras; Kim, Yeun Ju; Varnai, Peter; Szentpetery, Zsofia; Balla, Tamas] NICHHD, Sect Mol Signal Transduct, NIH, Bethesda, MD 20892 USA. [Balla, Andras; Varnai, Peter] Semmelweis Univ, Sch Med, Dept Physiol, H-1086 Budapest, Hungary. [Knight, Zachary] Univ Calif San Francisco, Program Chem & Chem Biol, San Francisco, CA 94158 USA. [Shokat, Kevan M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA. [Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. RP Balla, T (reprint author), NICHHD, Sect Mol Signal Transduct, NIH, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793 FU Intramural Research Program of the National Institute of Child Health and Human Development of the National Institutes of Health; NIH; Hungarian Scientific Research fund [OTKA NF-68563, PF 63893]; Medical Research Council [ETT 440/2006] FX We are grateful to Dr. Roger Y. Tsien for the monomeric red fluorescent protein, Dr. Philip W. Majerus for the human type-IV 5-ptase clone, and Drs. Alberto-Jesus Olivares-Reyes and Kevin J. Catt for the HEK-293-AT1 cells. The confocal imaging was performed at the Microscopy and Imaging Core of the National Institute of Child Health and Human Development, National Institutes of Health (NIH), with the kind assistance of Drs. Vincent Schram and James T. Russell. This research was supported in part by the Intramural Research Program of the National Institute of Child Health and Human Development of the National Institutes of Health, and by an appointment of P. V. to the Senior Fellowship Program at the NIH. This latter program is administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the National Institutes of Health. A. B and P. V. are also Bolyai Fellows of the Hungarian Academy of Science and were supported by the Hungarian Scientific Research fund (OTKA NF-68563 and PF 63893) and the Medical Research Council (ETT 440/2006). NR 34 TC 95 Z9 96 U1 3 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB PY 2008 VL 19 IS 2 BP 711 EP 721 DI 10.1091/mbc.E07-07-0713 PG 11 WC Cell Biology SC Cell Biology GA 344TX UT WOS:000258951300026 PM 18077555 ER PT J AU Nakamura, G Maruyama, H Ishii, S Shimotori, M Kameda, S Kono, T Miyazaki, JI Kulkarni, AB Gejyo, F AF Nakamura, Gen Maruyama, Hiroki Ishii, Satoshi Shimotori, Masaaki Kameda, Shigemi Kono, Toru Miyazaki, Jun-Ichi Kulkarni, Ashok B. Gejyo, Fumitake TI Naked plasmid DNA-based alpha-galactosidase A gene transfer partially reduces systemic accumulation of globotriaosylceramide in Fabry mice SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE naked plasmid DNA; Fabry disease; catheter-based gene transfer; renal vein injection; CAG promoter; hydrodynamics-based transfection ID ENZYME REPLACEMENT THERAPY; ADENOASSOCIATED VIRUS; GLYCOLIPID STORAGE; DEFICIENT MICE; RENAL-VEIN; DISEASE; EXPRESSION; VECTORS; KIDNEY; ADENOVIRUS AB Fabry disease is an X-linked recessive inborn metabolic disorder in which a deficiency in lysosomal enzyme alpha-galactosidase A (Gal A) causes the systemic accumulation of globotriaosylceramide (Gb3). Although many investigators have attempted to treat alpha-Gal A knock-out mice (Fabry mice) with gene therapy, no report has demonstrated therapeutic effects by the retrograde renal vein injection of naked DNA. We recently developed a naked plasmid vector-mediated kidney-targeted gene transfer technique. A solution containing naked plasmid DNA encoding human alpha-Gal A (pKSCX-alpha-Gal A) was rapidly injected into the left kidney of Fabry mice (pKSCX-alpha-Gal A mice). pKSCX was used for mock transfections (pKSCX mice). We confirmed that vector-derived human alpha-Gal A mRNA was present in the left kidney but not in other tissues, by reverse transcriptase polymerase chain reaction. Compared with the pKSCX mice, the pKSCX-alpha-Gal A mice showed partial therapeutic effects: increased alpha-Gal A activity in the injected kidney and in the liver, heart, and plasma, and decreased Gb3 in the injected kidney, contralateral kidney, liver, heart, and spleen. Our results demonstrated that, although further studies are needed to improve the outcome, this method has promise as a potential treatment option for Fabry disease. C1 [Nakamura, Gen; Maruyama, Hiroki; Shimotori, Masaaki; Kameda, Shigemi; Gejyo, Fumitake] Niigata Univ, Grad Sch Med & Dent Sci, Dept Clin Nephrosci, Div Clin Nephrol & Rheumatol, Niigata 9518510, Japan. [Ishii, Satoshi] Obihiro Univ Agr & Vet Med, Dept Agr & Life Sci, Obihiro, Hokkaido 0808555, Japan. [Kono, Toru] Asahikawa Med Coll, Dept Gastroenterol, Dept Surg 2, Asahikawa, Hokkaido 0788510, Japan. [Miyazaki, Jun-Ichi] Osaka Univ, Sch Med, Div Stem Cell Regulat, Suita, Osaka 5650871, Japan. [Kulkarni, Ashok B.] CDBRB NIDCR, Funct Genom Sect, NIH, Bethesda, MD 20892 USA. RP Maruyama, H (reprint author), Niigata Univ, Grad Sch Med & Dent Sci, Dept Clin Nephrosci, Div Clin Nephrol & Rheumatol, 1-757 Asahimachi Dori, Niigata 9518510, Japan. EM hirokim@med.niigata-u.ac.jp RI Miyazaki, Jun-ichi/N-1976-2015 OI Miyazaki, Jun-ichi/0000-0003-2475-589X NR 39 TC 9 Z9 11 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD FEB PY 2008 VL 38 IS 2 BP 109 EP 119 DI 10.1007/s12033-007-9008-5 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 255RP UT WOS:000252675400003 PM 18219591 ER PT J AU Ricciardi, A Elia, AR Cappello, P Puppo, M Vann, C Fardin, P Eva, A Munroe, D Wu, XL Giovarelli, M Varesio, L AF Ricciardi, Annamaria Elia, Angela Rita Cappello, Paola Puppo, Maura Vann, Cristina Fardin, Paolo Eva, Alessandra Munroe, David Wu, Xiaolin Giovarelli, Mirella Varesio, Luigi TI Transcriptome of hypoxic immature dendritic cells: Modulation of chemokine/receptor expression SO MOLECULAR CANCER RESEARCH LA English DT Article ID OXIDE SYNTHASE PROMOTER; AIRWAY EPITHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; GENE-EXPRESSION; GROWTH-FACTOR; NITRIC-OXIDE; HUMAN MONOCYTES; INDUCIBLE FACTOR-1-ALPHA; RESPONSIVE ELEMENT; RECEPTOR CCR3 AB Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues. Dendritic cells (DC) are professional antigen-presenting cells whose differentiation, migration, and activities are intrinsically linked to the microenvironment. DCs will home and migrate through pathologic tissues before reaching their final destination in the lymph node. We studied the differentiation of human monocytes into immature DCs (iDCs) in a hypoxic microenvironment. We generated iDC in vitro under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and examined the hypoxia-responsive element in the promoter, gene expression, and biochemical KEGG pathways. Hi-DCs had an interesting phenotype represented by up-regulation of genes associated with cell movement/migration. In addition, the Hi-DC cytokine/receptor pathway showed a dichotomy between down-regulated chemokines and up-regulated chemokine receptor mRNA expression. We showed that CCR3, CX3CR1, and CCR2 are hypoxia-inducible genes and that CCL18, CCL23, CCL26, CCL24, and CCL14 are inhibited by hypoxia. A strong chemotactic response to CCR2 and CXCR4 agonists distinguished Hi-DCs from iDCs at a functional level. The hypoxic microenvironment promotes the differentiation of Hi-DCs, which differs from iDCs for gene expression profile and function. The most prominent characteristic of Hi-DCs is the expression of a mobility/migratory rather than inflammatory phenotype. We speculate that Hi-DCs have the tendency to leave the hypoxic tissue and follow the chemokine gradient toward normoxic areas where they can mature and contribute to the inflammatory process. C1 [Ricciardi, Annamaria] Ist Giannina Gaslini, I-16147 Genoa, Italy. [Ricciardi, Annamaria; Puppo, Maura; Vann, Cristina; Fardin, Paolo; Eva, Alessandra; Varesio, Luigi] Ist Giannina Gaslini, Mol Biol Lab, Genoa, Italy. [Elia, Angela Rita; Cappello, Paola; Giovarelli, Mirella] Univ Turin, Dept Med & Expt Oncol, Turin, Italy. [Munroe, David; Wu, Xiaolin] NCI, Sci Applicat Int Corp Frederick Inc, Lab Mol Technol, Frederick, MD 21701 USA. RP Ricciardi, A (reprint author), Ist Giannina Gaslini, Largo Gaslini 5, I-16147 Genoa, Italy. EM annamariaricciardi@ospedale-gaslini.ge.it RI Eva, Alessandra/J-8268-2016; varesio, luigi/J-8261-2016; OI Eva, Alessandra/0000-0003-2949-078X; varesio, luigi/0000-0001-5659-2218; Cappello, Paola/0000-0002-5321-7794; Giovarelli, Mirella/0000-0002-7397-3466 FU NCI NIH HHS [N01 CO 12400]; Associazione Italiana per la Ricerca sul Cancro NR 68 TC 44 Z9 48 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2008 VL 6 IS 2 BP 175 EP 185 DI 10.1158/1541-7786.MCR-07-0391 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 268TP UT WOS:000253602800001 PM 18314479 ER PT J AU Huppi, K Volfovsky, N Runfola, T Jones, TL Macklewicz, M Martin, SE Mushinski, JF Stephens, R Caplen, NJ AF Huppi, Konrad Volfovsky, Natalia Runfola, Timothy Jones, Tamara L. Macklewicz, Mark Martin, Scott E. Mushinski, J. Frederic Stephens, Robert Caplen, Natasha J. TI The identification of microRNAs in a genomically unstable region of human chromosome 8q24 SO MOLECULAR CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; C-MYC; CELL-PROLIFERATION; MOUSE; GENE; AMPLIFICATION; EXPRESSION; TRANSLOCATIONS; TRANSCRIPTION; ACTIVATION AB The PVT1 locus is identified as a cluster of T(2;8) and T(8;22) "variant" MYC-activating chromosomal translocation breakpoints extending 400 kb downstream of MYC in a subset (approximate to 20%) of Burkitt's lymphoma (vBL). Recent reports that microRNAs (miRNA) may be associated with fragile sites and cancer-associated genomic regions prompted us to investigate whether the PVT1 region on chromosome 8q24 may contain miRNAs. Computational analysis of the genomic sequence covering the PVT1 locus and experimental verification identified seven miRNAs. One miRNA, hsa-miR-1204, resides within a previously described PVT1 exon (1b) that is often fused to the immunoglobulin light chain constant region in vBLs and is present in high copy number in MYC/PVT1-amplified tumors. Like its human counterpart, mouse mmu-miR-1204 represents the closest miRNA to Myc (similar to 50 kb) and is found only 1 to 2 kb downstream of a cluster of retroviral integration sites. Another miRNA, mmu-miR-1206, is close to a cluster of variant translocation breakpoints associated with mouse plasmacytoma and exon 1 of mouse Pvt1. Virtually all the miRNA precursor transcripts are expressed at higher levels in late-stage B cells (including plasmacytoma and vBL cell lines) compared with immature B cells, suggesting possible roles in lymphoid development and/or lymphoma. In addition, lentiviral vector-mediated overexpression of the miR-1204 precursor (human and mouse) in a mouse pre-B-cell line increased expression of Myc. High levels of expression of the hsa-miR-1204 precursor is also seen in several epithelial cancer cell lines with MYC/PVT1 coamplification, suggesting a potentially broad role for these miRNAs in tumorigenesis. C1 [Huppi, Konrad; Runfola, Timothy; Jones, Tamara L.; Macklewicz, Mark; Martin, Scott E.; Caplen, Natasha J.] NCI, NIH, Ctr Canc Res, Genet Branch,Gene Silencing Sect, Bethesda, MD 20892 USA. [Mushinski, J. Frederic] NCI, NIH, Ctr Canc Res, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Stephens, Robert] Sci Applicat Int Corp Frederick Inc, Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD USA. RP Huppi, K (reprint author), NCI, NIH, Ctr Canc Res, Genet Branch,Gene Silencing Sect, Bldg 37,Room 6128, Bethesda, MD 20892 USA. EM huppi@helix.nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU Intramural NIH HHS; NCI NIH HHS [N01 CO 012400, N01 CO012400] NR 46 TC 76 Z9 84 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2008 VL 6 IS 2 BP 212 EP 221 DI 10.1158/1541-7786.MCR-07-0105 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 268TP UT WOS:000253602800005 PM 18314482 ER PT J AU Mishra, MV Bisht, KS Sun, L Muldoon-Jacobs, K Awwad, R Kaushal, A Nguyen, P Huang, L Pennington, JD Markovina, S Bradbury, CM Gius, D AF Mishra, Mark V. Bisht, Kheern S. Sun, Lunching Muldoon-Jacobs, Kristi Awwad, Rania Kaushal, Aradhana Nguyen, Phuongmai Huang, Lei Pennington, J. Daniel Markovina, Stephanie Bradbury, C. Matthew Gius, David TI DNMT1 as a molecular target in a multimodality-resistant phenotype in tumor cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; OXIDATIVE STRESS; HEAT-SHOCK; HYDROGEN-PEROXIDE; GENE-EXPRESSION; CELLULAR-RESISTANCE; HAMSTER FIBROBLASTS; CANCER EPIGENETICS; DNA METHYLATION; SUPPRESSOR GENE AB We have previously shown that hydrogen peroxide-resistant permanent (OC-14) cells are resistant to the cytotoxicity of several exogenous oxidative and anticancer agents including H2O2, etoposide, and cisplatin; and we refer to this process as an oxidative multi modality-resistant phenotype (MMRP). Furthermore, OC-14 cells contain increased activator protein 1 activity, and inhibition of activator protein 1 reversed the MMRP. In this study, we show that permanent Rat-1 cell lines genetically altered to overexpress c-Fos also displayed a similar MMRP to H2O2, etoposide, and cisplatin as OC-14 cells. Gene expression analysis of the OC-14 cells and c-Fos-overexpressing cells showed increased DNMT1 expression. Where OC-14 and c-Fos-overexpressing cells were exposed to 5-aza-2'-deoxycytidine, which inhibits DNMT activity, a significant but incomplete reversal of the MMRP was observed. Thus, it seems logical to suggest that DNMT1 might be at least one target in the MMRP. Rat-1 cells genetically altered to overexpress DNMT1 were also shown to be resistant to the cytotoxicity of H2O2, etoposide, and cisplatin. Finally, somatic HCT116 knockout cells that do not express either DNMT1 (DNMT1(-/-)) or DNMT3B (DNMT3B(-/-)) were shown to be more sensitive to the cytotoxicity of H2O2, etoposide, and cisplatin compared with control HCT116 cells. This work is the first example of a role for the epigenome in tumor cell resistance to the cytotoxicity of exogenous oxidative (H2O2) or systemic (etoposide and cisplatin) agents and highlights a potential role for DNMT1 as a potential molecular target in cancer therapy. C1 [Mishra, Mark V.; Bisht, Kheern S.; Sun, Lunching; Muldoon-Jacobs, Kristi; Awwad, Rania; Kaushal, Aradhana; Nguyen, Phuongmai; Huang, Lei; Pennington, J. Daniel; Markovina, Stephanie; Bradbury, C. Matthew; Gius, David] NCI, NIH, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Mishra, MV (reprint author), NCI, NIH, Radiat Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov FU Intramural NIH HHS NR 45 TC 29 Z9 30 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2008 VL 6 IS 2 BP 243 EP 249 DI 10.1158/1541-7786.MCR-07-0373 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 268TP UT WOS:000253602800008 PM 18314485 ER PT J AU Kim, HH Gorospe, M AF Kim, Hlyeon Ho Gorospe, Myriam TI GU-rich RNA: Expanding CUGBP1 function, broadening mRNA turnover SO MOLECULAR CELL LA English DT Editorial Material ID DEGRADATION; SEQUENCE AB In this issue of Molecular Cell, Vlasova et al. (2008) identify the GU-rich element (GRE) as a novel, widespread, degradation-promoting sequence through which the RNA-binding protein CUGBP1 elicits mRNA decay. C1 [Kim, Hlyeon Ho; Gorospe, Myriam] NIA, Intramural Res Program, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Intramural Res Program, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov NR 10 TC 11 Z9 11 U1 3 U2 4 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 FEB 1 PY 2008 VL 29 IS 2 BP 151 EP 152 DI 10.1016/j.molcel.2008.01.005 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 259MZ UT WOS:000252944700002 PM 18243108 ER PT J AU Nanavati, D Gucek, M Milne, JLS Subramaniam, S Markey, SP AF Nanavati, Dhaval Gucek, Marjan Milne, Jacqueline L. S. Subramaniam, Srirarn Markey, Sanford P. TI Stoichiometry and absolute quantification of proteins with mass spectrometry using fluorescent and isotope-labeled concatenated peptide standards SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID SIGNATURE PEPTIDES; COMPLEXES; PROTEOMICS AB We have explored a general approach for the determination of absolute amounts and the relative stoichiometry of proteins in a mixture using fluorescence and mass spectrometry. We engineered a gene to express green fluorescent protein (GFP) with a synthetic fusion protein (GAB-GFP) in Escherichia coli to function as a spectroscopic standard for the quantification of an analogous stable isotope-labeled, non-fluorescent fusion protein (GAB*) and for the quantification and stoichiometric analysis of purified transducin, a heterotrimeric G-protein complex. Both GAB-GFP and GAB* contain concatenated sequences of specific proteotypic peptides that are derived from the alpha, beta, and gamma protein subunits of transducin and that are each flanked by spacer regions that maintain the native proteolytic properties for these peptide fragments. Spectroscopic quantification of GAB-GFP provided a molar scale for mass spectrometric ratios from tryptic peptides of GAB* and defined molar responses for mass spectrometric signal intensities from a purified transducin complex. The stoichiometry of transducin subunits alpha, beta, and gamma was measured to be 1:1.1:1.15 over a 5-fold range of labeled internal standard with a relative standard deviation of 9%. Fusing a unique genetically coded spectroscopic signal element with concatenated proteotypic peptides provides a powerful method to accurately quantify and determine the relative stoichiometry of multiple proteins present in complexes or mixtures that cannot be readily assessed using classical gravimetric, enzymatic, or antibody-based technologies. C1 [Nanavati, Dhaval; Gucek, Marjan; Markey, Sanford P.] NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. [Milne, Jacqueline L. S.; Subramaniam, Srirarn] NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Markey, SP (reprint author), NIMH, Lab Neurotoxicol, 10 Ctr Dr,Rm 3D42, Bethesda, MD 20892 USA. EM markeys@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [1 Z01 MH000274] NR 18 TC 33 Z9 34 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD FEB PY 2008 VL 7 IS 2 BP 442 EP 447 DI 10.1074/mcp.M700345-MCP200 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 266EM UT WOS:000253417300018 PM 18029347 ER PT J AU Shrivastav, S Kino, T Cunningham, T Ichijo, T Schubert, U Heinklein, P Chrousos, GP Kopp, JB AF Shrivastav, Shashi Kino, Tomoshige Cunningham, Tshaka Ichijo, Takamasa Schubert, Ulrich Heinklein, Peter Chrousos, George P. Kopp, Jeffrey B. TI Human immunodeficiency virus (HIV)-1 viral protein R suppresses transcriptional activity of peroxisome proliferator-activated receptor gamma and inhibits adipocyte differentiation: Implications for HIV-associated lipodystrophy SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CELL-CYCLE ARREST; NUCLEAR HORMONE RECEPTORS; PPAR-GAMMA; RESISTANCE/HYPERSENSITIVITY SYNDROMES; GLUCOCORTICOID-RECEPTOR; INSULIN-RESISTANCE; GENE-EXPRESSION; VPR ARRESTS; BODY-FAT; TYPE-1 AB HIV-1-infected patients may develop lipodystrophy and insulin resistance. We investigated the effect of the HIV-1 accessory protein viral protein R (Vpr) on the activity of the peroxisome proliferator-activating receptor-gamma (PPAR gamma), a key regulator of adipocyte differentiation and tissue insulin sensitivity. We studied expression of PPAR gamma-responsive reporter genes in 3T3-L1 mouse adipocytes. We investigated Vpr interaction with the PPAR/ retinoid X receptor (RXR)-binding site of the c-Cbl-associating protein (CAP) gene using the chromatin immunoprecipitation assay as well as the interaction of Vpr and PPAR gamma using coimmunoprecipitation. Finally, we studied the ability of exogenous Vpr protein to enter cultured adipocytes and retard differentiation. We found that Vpr suppressed PPAR gamma-induced transactivation in both undifferentiated and differentiated 3T3-L1 cells. Transcriptional suppression by Vpr required an intact LXXLL coactivator motif. Vpr suppressed mRNA expression of PPAR gamma-responsive genes in undifferentiated 3T3-L1 cells and associated with the PPAR/ RXR-binding site located in the promoter region of the CAP gene. Vpr interacted with the ligand-binding domain of PPAR gamma in an agonist-dependent fashion in vitro. Vpr delivered either by an expression plasmid or as protein added to media suppressed PPAR gamma agonist-induced adipocyte differentiation, assessed as lipid accumulation and mRNA expression of the adipocyte differentiation marker adipocyte P2 in 3T3-L1 cells. In conclusion, circulating Vpr or, alternatively, Vpr produced as a consequence of direct infection of adipocytes could suppress in vivo differentiation of preadipocytes by acting as a corepressor of PPAR gamma-mediated gene transcription. Vpr may alter sensitivity to insulin and thereby contribute to the development of lipodystrophy and insulin resistance observed in HIV-1-infected patients. C1 [Shrivastav, Shashi; Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, Bethesda, MD 20892 USA. [Kino, Tomoshige; Ichijo, Takamasa; Chrousos, George P.] NICHHD, Sect Pediat Endocrinol, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Cunningham, Tshaka; Schubert, Ulrich] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Schubert, Ulrich] Univ Erlangen Nurnberg, Inst Virol, D-91054 Erlangen, Germany. [Heinklein, Peter] Humboldt Univ, Inst Biochem, D-10115 Berlin, Germany. [Chrousos, George P.] Univ Athens, Dept Pediat 1, Athens 11527, Greece. RP Kopp, JB (reprint author), 10 Ctr Dr MSC 1268, Bethesda, MD 20892 USA. EM jbkopp@nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [R01 DK 59537, R01 DK059537] NR 51 TC 43 Z9 43 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2008 VL 22 IS 2 BP 234 EP 247 DI 10.1210/me.2007-0124 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255SV UT WOS:000252678600003 PM 17932108 ER PT J AU Yin, ZR Williams-Simons, L Parlow, AF Asa, S Kirschner, LS AF Yin, Zhirong Williams-Simons, Lisa Parlow, A. F. Asa, Sylvia Kirschner, Lawrence S. TI Pituitary-specific knockout of the carney complex gene Prkar1a leads to pituitary tumorigenesis SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CRE-MEDIATED RECOMBINATION; STIMULATORY G-PROTEIN; REGULATORY SUBUNIT; TUMOR-DEVELOPMENT; EXPRESSION; MUTATIONS; ADENOMAS; MOUSE; MICE; PROLIFERATION AB Carney complex (CNC) is an inherited neoplasia syndrome characterized by spotty skin pigmentation, myxomas, endocrine tumors, and schwannomas. Among the endocrine tumors that comprise the syndrome, GH- producing pituitary tumors are seen in approximately 10% of patients, although biochemical abnormalities of the GH axis are much more common. To explore the role of loss of the CNC gene PRKAR1A on pituitary tumorigenesis, we produced a tissue- specific knockout (KO) of this gene in the mouse. For these studies, we generated a mouse line expressing the cre recombinase in pituitary cells using the rat GHRH receptor promoter. These mice were then crossed with Prkar1a conditional null animals to produce tissue-specific KOs. Although prolactinomas were observed in KO and control mice, the KO mice exhibited a significantly increased frequency of pituitary tumors compared with wild- type or conventional Prkar1a(+/-) mice. Characterization of the tumors demonstrated they were composed of cells of the Pit1 lineage that stained for GH, prolactin, and TSH. At the biochemical level, levels of GH in the serum of KO animals were markedly elevated compared with controls, regardless of the presence of a frank tumor. These data indicate that complete loss of Prkar1a is sufficient to allow the formation of pituitary tumors and abnormalities of the GH axis, in close analogy to human patients with CNC. C1 [Yin, Zhirong; Kirschner, Lawrence S.] Ohio State Univ, Dept Internal Med, Dept Mol Virol Immunol & Mol Genet, Columbus, OH 43210 USA. [Kirschner, Lawrence S.] Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Williams-Simons, Lisa] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. [Parlow, A. F.] Univ Calif Los Angeles, Harbor Med Ctr, Natl Hormone & Peptide Program, Torrance, CA 90502 USA. [Asa, Sylvia] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 2C4, Canada. RP Kirschner, LS (reprint author), 544 TMRF,420 W 12th Ave, Columbus, OH 43210 USA. EM Lawrence.Kirschner@osumc.edu FU NCI NIH HHS [R01 CA112268, P30 CA016058, CA 112268, CA 16058] NR 40 TC 40 Z9 41 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2008 VL 22 IS 2 BP 380 EP 387 DI 10.1210/me.2006-0428 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255SV UT WOS:000252678600013 PM 17975024 ER PT J AU Nazarian, R Huizing, M Helip-Wooley, A Starcevic, M Gahl, WA Dell'Angelica, EC AF Nazarian, Ramin Huizing, Marian Helip-Wooley, Amanda Starcevic, Marta Gahl, William A. Dell'Angelica, Esteban C. TI An immunoblotting assay to facilitate the molecular diagnosis of Hermansky-Pudlak syndrome SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE AP-3; BLOC-1; BLOC-2; BLOC-3; hermansky-pudlak syndrome; Immunoblotting; molecular diagnosis ID LYSOSOME-RELATED ORGANELLES; STORAGE-POOL DEFICIENCY; PLATELET-DENSE GRANULES; SYNDROME TYPE-1; PROTEIN TRAFFICKING; PULMONARY-FIBROSIS; BETA-3A SUBUNIT; AP-3 ADAPTER; COMPLEX; BIOGENESIS AB Hermansky-Pudlak syndrome (HPS) comprises a constellation of human autosomal recessive disorders characterized by albinism and platelet storage pool deficiency. At least eight types of HPS have been defined based on the identity of the mutated gene. These genes encode components of four ubiquitously expressed protein complexes, named Adaptor Protein (AP)-3 and Biogenesis of Lysosomerelated Organelles Complex (BLOC)-1 through -3. In patients of Puerto Rican origin, the molecular diagnosis can be based on analysis of two founder mutations. On the other hand, identification of the HPS type in other patients relies on the sequencing of all candidate genes. In this work, we have developed a biochemical assay to minimize the number of candidate genes to be sequenced per patient. The assay consists of immunoblotting analysis of extracts prepared from skin fibroblasts, using antibodies to one subunit per protein complex. The assay allowed us to determine which complex was defective in each of a group of HPS patients with unknown genetic lesions, thus subsequent sequencing was limited to genes encoding the corresponding subunits. Because no mutations within the two genes encoding BLOC-3 subunits could be found in two patients displaying reduced BLOC-3 levels, the possible existence of additional subunits was considered. Through size-exclusion chromatography and sedimentation velocity analysis, the native molecular mass of BLOC-3 was estimated to be 140 +/- 30 kDa, a value most consistent with the idea that BLOC-3 is a HPSI.HPS4 heterodirner (similar to 156 kDa) albeit not inconsistent with the putative existence of a relatively small third subunit. (C) 2007 Elsevier Inc. All rights reserved. C1 [Nazarian, Ramin; Starcevic, Marta; Dell'Angelica, Esteban C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Huizing, Marian; Helip-Wooley, Amanda; Gahl, William A.] NIH, Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD 20892 USA. RP Dell'Angelica, EC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. EM Edellangelica@mednet.ucla.edu FU Intramural NIH HHS; NEI NIH HHS [R01 EY015143, R01 EY015143-05] NR 53 TC 8 Z9 8 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 BP 134 EP 144 DI 10.1016/j.ymgme.2007.09.001 PG 11 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500005 PM 17933573 ER PT J AU Alpan, OG Samaddar, T Stubblefiled, B Cuervo, AM Giasson, B Sidransky, E AF Alpan, Ozlem Goker Samaddar, Ted Stubblefiled, Barbara Cuervo, Ann-Marie Giasson, Benoit Sidransky, Ellen TI The contribution of lysosomal pathways to the pathogenesis of common neurodegenerative disorders: Glucocerebrosidase and the synucleinopathies SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Alpan, Ozlem Goker; Samaddar, Ted; Stubblefiled, Barbara; Sidransky, Ellen] NIH, NHGRI, MGB, Bethesda, MD 20892 USA. [Cuervo, Ann-Marie] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. [Giasson, Benoit] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 34 BP S22 EP S22 DI 10.1016/j.ymgme.2007.10.046 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500051 ER PT J AU Hermoni, YB Goldin, E Motabar, O Sidransky, E AF Hermoni, Yotam Blech Goldin, Ehud Motabar, Omid Sidransky, Ellen TI Analysis of enzyme activities of different lysosomal enzymes in brain samples from subjects with Parkinson disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Hermoni, Yotam Blech; Goldin, Ehud; Motabar, Omid; Sidransky, Ellen] NIH, NGHRI, MGB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 BP S17 EP S17 DI 10.1016/j.ymgme.2007.10.024 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500029 ER PT J AU Hruska, K Blech-Hermont, Y Ziegler, S Stubblefield, B Sidransky, E AF Hruska, Kathleen Blech-Hermont, Yotam Ziegler, Shira Stubblefield, Barbara Sidransky, Ellen TI Functional evaluation of predicted regulatory sequences at the GBA locus SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Hruska, Kathleen; Blech-Hermont, Yotam; Ziegler, Shira; Stubblefield, Barbara; Sidransky, Ellen] NIH, NHGRI, MGB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 43 BP S25 EP S25 DI 10.1016/j.ymgme.2007.10.055 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500060 ER PT J AU Pierson, TM Zeng, BJ Torres, P Pastores, G Finkel, R Mahuran, D Kolodny, E Tennekoon, G AF Pierson, Tyler Mark Zeng, Bai Jin Torres, Paola Pastores, Gregory Finkel, Richard Mahuran, Don Kolodny, Edwin Tennekoon, Gihan TI Novel mutations in juvenile Sandhoff disease presenting as motor neuron disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Pierson, Tyler Mark] NIH, NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. [Zeng, Bai Jin; Torres, Paola; Pastores, Gregory; Kolodny, Edwin] NYU Med Ctr, Dept Neurol, New York, NY 10016 USA. [Finkel, Richard; Tennekoon, Gihan] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Mahuran, Don] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 74 BP S33 EP S33 DI 10.1016/j.ymgme.2007.10.086 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500091 ER PT J AU Raben, N Plotz, P AF Raben, Nina Plotz, Paul TI A new took at pathogenesis of Pompe disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Raben, Nina; Plotz, Paul] NIH, Natl Inst Arthritis & Musculoskeletal & Skin Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 78 BP S34 EP S34 DI 10.1016/j.ymgme.2007.10.090 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500095 ER PT J AU Sidransky, E Alpan, OG Urban, D Zheng, W Austin, C AF Sidransky, Ellen Alpan, Ozlem Goker Urban, Daniel Zheng, Wei Austin, Christopher TI The association between mutant glucocerebrosidase and parkinsonism SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Sidransky, Ellen; Alpan, Ozlem Goker; Urban, Daniel] NGHRI, NIH, MGB, Bethesda, MD USA. [Zheng, Wei; Austin, Christopher] NGHRI, NIH, NCGC, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 90 BP S37 EP S37 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500107 ER PT J AU Slaugenhatipt, S Curcio-Morelli, C Venugopal, B Varro, A Michaud, N Nanthakumar, N Walkley, S Pickel, J Marsha, B AF Slaugenhatipt, Susan Curcio-Morelli, Cyntia Venugopal, Bhuvaramurthy Varro, Andrea Michaud, Norman Nanthakumar, Nanda Walkley, Steven Pickel, James Marsha, Browning TI A murine model for mucolipidosis type IV SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Slaugenhatipt, Susan; Curcio-Morelli, Cyntia; Venugopal, Bhuvaramurthy; Nanthakumar, Nanda; Marsha, Browning] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Varro, Andrea] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Michaud, Norman] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Walkley, Steven] Albert Einstein Coll Med, Bronx, NY USA. [Pickel, James] Natl Inst Hlth, Bethesda, MD USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 92 BP S38 EP S38 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500109 ER PT J AU Wu, XY Moscioli, K Katz, E Chang, HH Shin, SH Kluepfel-Stahl, S Murray, G Schiffmann, R Valenzano, K Lockhart, D Benjamin, E AF Wu, Xiaoyang Moscioli, Kirsten Katz, Evan Chang, Hui-Hwa Shin, Sang-Hoon Kluepfel-Stahl, Stefanie Murray, Gary Schiffmann, Raphael Valenzano, Kenneth Lockhart, David Benjamin, Elfrida TI Identification of Fabry disease-causing mutations that are responsive to the pharmacological chaperone ATI001 SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Wu, Xiaoyang; Moscioli, Kirsten; Katz, Evan; Chang, Hui-Hwa; Valenzano, Kenneth; Lockhart, David; Benjamin, Elfrida] Amicus Therapeut, Cranbury, NJ USA. [Shin, Sang-Hoon; Kluepfel-Stahl, Stefanie; Murray, Gary; Schiffmann, Raphael] NIH, NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 113 BP S43 EP S44 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500130 ER PT J AU Yanjanin, N Brewer, C King, K Pavan, W Gropman, A Patterson, M Porter, F AF Yanjanin, Nicole Brewer, Carmen King, Kelly Pavan, William Gropman, Andrea Patterson, Marc Porter, Forbes TI Disease progression in Niemann-Pick disease, type C: Longitudinal SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2008 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Yanjanin, Nicole; Brewer, Carmen; King, Kelly; Porter, Forbes] NIH, NICHD, DHHS, Bethesda, MD 20892 USA. [Pavan, William] NIH, NHGRI, DHHS, Bethesda, MD 20892 USA. [Gropman, Andrea] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Patterson, Marc] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2008 VL 93 IS 2 MA 115 BP S44 EP S44 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 265KT UT WOS:000253358500132 ER PT J AU Feinerman, O Germain, RN Altan-Bonnet, G AF Feinerman, Ofer Germain, Ronald N. Altan-Bonnet, Gregoire TI Quantitative challenges in understanding ligand discrimination by alpha beta T cells SO MOLECULAR IMMUNOLOGY LA English DT Review ID MHC CLASS-I; IMMUNOLOGICAL SYNAPSE; CONFORMATIONAL-CHANGE; NEGATIVE SELECTION; SEGREGATION MODEL; RECEPTOR ZETA; LYMPH-NODES; ACTIVATION; TCR; ANTIGEN C1 Mem Sloan Kettering Canc Ctr, Program Computat Biol & Immunol, ImmunoDynam Grp, New York, NY 10021 USA. NIH, NIAID, Lymphocyte Biol Sect, Bethesda, MD USA. RP Altan-Bonnet, G (reprint author), Mem Sloan Kettering Canc Ctr, Program Computat Biol & Immunol, ImmunoDynam Grp, New York, NY 10021 USA. EM altanbog@mskcc.org FU Intramural NIH HHS [Z01 AI000403-24] NR 65 TC 39 Z9 39 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 2008 VL 45 IS 3 BP 619 EP 631 DI 10.1016/j.molimm.2007.03.028 PG 13 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 237CQ UT WOS:000251350900005 PM 17825415 ER PT J AU Muegge, K Xi, SC Geiman, T AF Muegge, Kathrin Xi, Sichuan Geiman, Theresa TI The see-saw of differentiation: Tipping the chromatin balance SO MOLECULAR INTERVENTIONS LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; EPIGENETIC MEMORY; DNA METHYLATION; DEFINED FACTORS; IN-VITRO; PLURIPOTENT; FIBROBLASTS; COMPLEX; STATE C1 [Muegge, Kathrin; Xi, Sichuan; Geiman, Theresa] NCI, Lab Canc Prevent, SAIC, FCRDC, Frederick, MD 21701 USA. RP Muegge, K (reprint author), NCI, Lab Canc Prevent, SAIC, FCRDC, Frederick, MD 21701 USA. FU Intramural NIH HHS NR 32 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD FEB 1 PY 2008 VL 8 IS 1 BP 15 EP 18 DI 10.1124/mi.8.1.4 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 279RP UT WOS:000254372600003 PM 18332479 ER PT J AU Adhya, SL Court, DL Friedman, DI Gottesman, ME AF Adhya, Sankar L. Court, Donald L. Friedman, David I. Gottesman, Max E. TI Amos Oppenheim (31 October 1934 to 24 September 2006) - Obituary SO MOLECULAR MICROBIOLOGY LA English DT Biographical-Item C1 [Adhya, Sankar L.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Court, Donald L.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA. [Friedman, David I.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Gottesman, Max E.] Columbia Univ Coll Phys & Surg, Canc Res Inst, New York, NY 10032 USA. RP Adhya, SL (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 2008 VL 67 IS 4 BP 685 EP 686 DI 10.1111/j.1365-2958.2007.06097.x PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 264TD UT WOS:000253312400001 PM 18237367 ER PT J AU Hanssen, E Sougrat, R Frankland, S Deed, S Klonis, N Lippincott-Schwartzand, J Tilley, L AF Hanssen, Eric Sougrat, Rachid Frankland, Sarah Deed, Samantha Klonis, Nectarios Lippincott-Schwartzand, Jennifer Tilley, Leann TI Electron tomography of the Maurer's cleft organelles of Plasmodium falciparum-infected erythrocytes reveals novel structural features SO MOLECULAR MICROBIOLOGY LA English DT Article ID VESICLE-MEDIATED TRAFFICKING; RED-BLOOD-CELLS; HISTIDINE-RICH PROTEIN; MALARIA PARASITES; HOST-CELL; PARASITOPHOROUS VACUOLE; MEMBRANE-PROTEINS; SURFACE-MEMBRANE; RING STAGE; TRANSPORT AB During intraerythrocytic development, the human malaria parasite, plasmodium falciparum, establishes membrane-bound compartments, known as Maurer's clefts, outside the confines of its own plasma membrane. The Maurer's compartments are thought to be a crucial component of the machinery for protein sorting and trafficking; however, their ultrastructure is only partly defined. We have used electron tomography to image Maurer's clefts of 3D7 strain parasites. The compartments are revealed as flattened structures with a translucent lumen and a more electron-dense coat. They display a complex and convoluted morphology, and some regions are modified with surface nodules, each with a circular cross-section of similar to 25 nm. Individual 25 nm vesicle-like structures are also seen in the erythrocyte cytoplasm and associated with the red blood cell membrane. The Maurer's clefts are connected to the red blood cell membrane by regions with extended stalk-like profiles. Immunogold labelling with specific antibodies confirms differential labelling of the Maurer's clefts and the parasitophorous vacuole and erythrocyte membranes. Spot fluorescence photobleaching was used to demonstrate the absence of a lipid continuum between the Maurer's clefts and parasite membranes and the host plasma membrane. C1 [Hanssen, Eric; Frankland, Sarah; Deed, Samantha; Klonis, Nectarios; Tilley, Leann] La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia. [Hanssen, Eric; Deed, Samantha; Klonis, Nectarios; Tilley, Leann] La Trobe Univ, Ctr Excellence Coherent Xray Sci, Melbourne, Vic 3086, Australia. [Sougrat, Rachid; Lippincott-Schwartzand, Jennifer] NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Tilley, L (reprint author), La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia. EM L.Tilley@latrobe.edu.au RI Hanssen, Eric/A-7217-2013; OI Hanssen, Eric/0000-0002-4064-1844; Sougrat, Rachid/0000-0001-6476-1886 NR 70 TC 59 Z9 61 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 2008 VL 67 IS 4 BP 703 EP 718 DI 10.1111/j.1365-2958.2007.06063.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 264TD UT WOS:000253312400004 PM 18067543 ER PT J AU Bair, CL Oppenheim, A Trostel, A Prag, G Adhya, S AF Bair, Catherine L. Oppenheim, Amos Trostel, Andrei Prag, Gali Adhya, Sankar TI A phage display system designed to detect and study protein-protein interactions SO MOLECULAR MICROBIOLOGY LA English DT Article ID BACTERIOPHAGE-LAMBDA; FILAMENTOUS BACTERIOPHAGE; BINDING MOTIF; CUE DOMAIN; IN-VITRO; LIBRARIES; BACTERIAL; RECOGNITION; SELECTION; PEPTIDES AB Analysing protein-protein interactions is critical in proteomics and drug discovery. The usage of 2-Hybrid (2 lambda) systems is limited to an in vivo environment. We describe a bacteriophage 2-Hybrid system for studying protein interactions in vitro. Bait and prey are displayed as fusions to the surface of phage A. that are marked with different selectable drug-resistant markers. An interaction of phages in vitro through displayed proteins allows bacterial infection by two phages resulting in double drug-resistant bacterial colonies at very low multiplicity of infections. We demonstrate interaction of the protein sorting signal Ubiquitin with the Vps9-CUE, a Ubiquitin binding domain, and by the interaction of (Gly-Glu)(4) and (Gly-Arg)(4) peptides. Interruptions of the phage interactions by non-fused (free) bait or prey molecules show how robust and unique our approach is. We also demonstrate the use of Ubiquitin and CUE display phages to find binding partners in a lambda-display library. The unique usefulness to 2 lambda is also described. C1 [Bair, Catherine L.; Oppenheim, Amos; Trostel, Andrei; Adhya, Sankar] NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Oppenheim, Amos] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. [Prag, Gali] Tel Aviv Univ, Dept Biochem, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM adhyas@mail.nih.gov FU Intramural NIH HHS NR 44 TC 8 Z9 11 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 2008 VL 67 IS 4 BP 719 EP 728 DI 10.1111/j.1365-2958.2007.06077.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 264TD UT WOS:000253312400005 PM 18179417 ER PT J AU Xiong, W Hosoi, M Koo, BN Zhang, L AF Xiong, Wei Hosoi, Masako Koo, Bon-Nyeo Zhang, Li TI Anandamide inhibition of 5-HT3A receptors varies with receptor density and desensitization SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-KINASE-C; SEROTONIN RECEPTOR; GENE HTR3A; MEDIATED RESPONSES; GLYCINE RECEPTORS; XENOPUS OOCYTES; NERVOUS-SYSTEM; VARIANT C178T; RAT-BRAIN; MICE AB Converging evidence has suggested that anandamide (AEA), an endogenous agonist of cannabinoid (CB) receptors, can directly interact with certain types of ligand-gated ion channels (LGICs). However, little is known about the molecular and cellular mechanisms of AEA-induced direct effects on LGICs. Here, we report that AEA inhibited the function of serotonin-gated ion channels (5-HT3A) expressed in Xenopus laevis oocytes and human embryonic kidney 293 cells in a manner that was dependent on the steady-state receptor density at the cell surface. The magnitude of AEA inhibition was inversely correlated with the expression levels of receptor protein and function. With increasing surface receptor expression, the magnitude of AEA inhibition decreased. Consistent with this idea, pretreatment with actinomycin D, which inhibits transcription, decreased the amplitude of current activated by maximal concentrations of 5-hydroxytryptamine (5-HT) and increased the magnitude of AEA inhibition. AEA did not significantly alter 5-HT3A receptor trafficking. However, AEA accelerated 5-HT3A receptor desensitization time in a concentration-dependent manner without significantly changing receptor activation and deactivation time. The desensitization time was correlated with the AEA-induced inhibiting effect and mean 5-HT current density. Applications of 5-hydroxyindole and nocodazole, a microtubule disruptor, significantly slowed 5-HT3A receptor desensitization and reduced the magnitude of AEA inhibition. These observations suggest that 5-HT3 receptor density at the steady state regulates receptor desensitization kinetics and the potency of AEA-induced inhibiting effect on the receptors. The inhibition of 5-HT3 receptors by AEA may contribute to its physiological roles in control of pain and emesis. C1 [Xiong, Wei; Hosoi, Masako; Koo, Bon-Nyeo; Zhang, Li] Natl Inst Hlth, Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), Natl Inst Hlth, Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM lzhang@mail.nih.gov RI Xiong, Wei/F-8251-2011 FU Intramural NIH HHS NR 49 TC 19 Z9 19 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2008 VL 73 IS 2 BP 314 EP 322 DI 10.1124/mol.107.039149 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254PA UT WOS:000252597300006 PM 17993512 ER PT J AU Liao, Z Robey, RW Guirouilh-Barbat, J To, KKW Polgar, O Bates, SE Pommier, Y AF Liao, Zhiyong Robey, Robert W. Guirouilh-Barbat, Josee To, Kenneth K. W. Polgar, Orsolya Bates, Susan E. Pommier, Yves TI Reduced expression of DNA topoisomerase I in SF295 human glioblastoma cells selected for resistance to homocamptothecin and diflomotecan SO MOLECULAR PHARMACOLOGY LA English DT Article ID RING-MODIFIED CAMPTOTHECIN; HUMAN COLON-CARCINOMA; MULTIDRUG-RESISTANCE; PHASE-I; MALIGNANT GLIOMA; HALF-TRANSPORTER; CANCER CELLS; SOLID TUMORS; PROTEIN; ABCG2 AB Homocamptothecins (hCPTs) are a novel class of topoisomerase I (Top1) inhibitors with enhanced chemical stability compared with the currently used camptothecin (CPT) analogs irinotecan and topotecan. The hCPT derivative diflomotecan (BN80915) is currently in clinical trials. We established two resistant human glioblastoma cell lines, SF295/hCPT50 and SF295/BN50, by stepwise exposure of the parental SF295 line to increasing concentrations of hCPT and BN80915, respectively. The two resistant cell lines were 15- to 22-fold resistant to hCPT and BN80915 as well as 7- to 27-fold cross-resistant to other Top1 inhibitors, including CPT, topotecan, and the indenoisoquinolines MJ-III-65 (NSC 706744) and NSC 724998, but sensitive to the topoisomerase II inhibitors mitoxantrone and etoposide. Neither of the resistant cell lines displayed any detectable expression of the three major drug transporters P-glycoprotien, multidrug resistance-associated protein 1, or ATP-binding cassette, subfamily G (WHITE), member 2, as assessed by immunoblot or flow cytometry. Reduced expression of Top1 protein occurred at the transcriptional level in both of the resistant cell lines, consistent with the reduction of Top1 enzyme level as the major contribution to the resistance phenotype in SF295/hCPT50 and SF295/BN50 cells. Treatment of the resistant cell lines with the histone deacetylase inhibitor depsipeptide or the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine alone or concomitantly did not result in re-expression of Top1. Our studies suggest that selection for resistance to hCPT or BN80915 is primarily related to reduced Top1 expression at the transcriptional level, resulting in reduced enzyme levels. C1 [Liao, Zhiyong; Guirouilh-Barbat, Josee; Pommier, Yves] NIH, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Robey, Robert W.; To, Kenneth K. W.; Polgar, Orsolya; Bates, Susan E.] NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NIH, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37 Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU Intramural NIH HHS [Z01 BC010622-04] NR 40 TC 26 Z9 29 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2008 VL 73 IS 2 BP 490 EP 497 DI 10.1124/mol.107.041178 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254PA UT WOS:000252597300023 PM 17984197 ER PT J AU Zhao, CQ Fernandes, MJ Prestwich, GD Turgeon, M Di Battista, J Clair, T Poubelle, PE Bourgoin, SG AF Zhao, Chenqi Fernandes, Maria J. Prestwich, Glenn D. Turgeon, Melanie Di Battista, John Clair, Timothy Poubelle, Patrice E. Bourgoin, Sylvain G. TI Regulation of lysophosphatidic acid receptor expression and function in human synoviocytes: Implications for rheumatoid arthritis? SO MOLECULAR PHARMACOLOGY LA English DT Article ID FIBROBLAST-LIKE SYNOVIOCYTES; CYCLIC PHOSPHATIDIC-ACID; GENE-EXPRESSION; PHOSPHONATE ANALOGS; OVARIAN-CANCER; MESSENGER-RNA; EDG FAMILY; CELLS; AUTOTAXIN; PROTEIN AB Lysophosphatidic acid (LPA), via interaction with its G-protein coupled receptors, is involved in various pathological conditions. Extracellular LPA is mainly produced by the enzyme autotaxin (ATX). Using fibroblast-like synoviocytes (FLS) isolated from synovial tissues of patients with rheumatoid arthritis (RA), we studied the expression profile of LPA receptors, LPA-induced cell migration, and interleukin (IL)-8 and IL-6 production. We report that FLS express LPA receptors LPA(1-3). More-over, exogenously applied LPA induces FLS migration and secretion of IL-8/IL-6, whereas the LPA(3) agonist L-sn-1-O-oleoyl-2- methyl-glyceryl-3-phosphothionate (2S-OMPT) stimulates cytokine synthesis but not cell motility. The LPA-induced FLS motility and cytokine production are suppressed by LPA(1/3) receptor antagonists diacylglycerol pyrophosphate and (S)phosphoric acid mono-(2-octadec-9-enoylamino-3-[4-(pyridine2- ylmethoxy)-phenyl]-propyl) ester (VPC32183). Signal transduction through p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and Rho kinase is involved in LPA-mediated cytokine secretion, whereas LPA-induced cell motility requires p38 MAPK and Rho kinase but not p42/44 MAPK. Treatment of FLS with tumor necrosis factor-alpha (TNF-alpha) increases LPA(3) mRNA expression and correlates with enhanced LPA-or OMPT-induced cytokine production. LPA-mediated superproduction of cytokines by TNF-alpha-primed FLS is abolished by LPA(1/3) receptor antagonists. We also report the presence of ATX in synovial fluid of patients with RA. LPA(1/3) receptor antagonists and ATX inhibitors reduce the synovial fluid-induced cell motility. Together the data suggest that LPA(1) and LPA(3) may contribute to the pathogenesis of RA through the modulation of FLS migration and cytokine production. The above results provide novel insights into the relevance of LPA receptors in FLS biology and as potential therapeutic targets for the treatment of RA. C1 [Zhao, Chenqi; Turgeon, Melanie] Ctr Rech CHUQ CHUL, Ctr Rech Rhumatol & Immunol, Quebec City, PQ G1V 4G2, Canada. [Poubelle, Patrice E.] Univ Laval, Fac Med, Dept Med, Quebec City, PQ G1K 7P4, Canada. [Fernandes, Maria J.; Bourgoin, Sylvain G.] Univ Laval, Dept Anat Physiol, Quebec City, PQ, Canada. [Di Battista, John] Ctr Univ McGill, Dept Rhumatol & Immunol, Montreal, PQ, Canada. [Clair, Timothy] NCI, Pathol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Prestwich, Glenn D.] Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA. RP Bourgoin, SG (reprint author), Ctr Rech CHUQ CHUL, Ctr Rech Rhumatol & Immunol, Local T1-49,2705 Boul Laurier, Quebec City, PQ G1V 4G2, Canada. EM sylvain.bourgoin@crchul.ulaval.ca FU Intramural NIH HHS; NINDS NIH HHS [NS29632] NR 40 TC 44 Z9 46 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2008 VL 73 IS 2 BP 587 EP 600 DI 10.1124/mol.107.038216 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254PA UT WOS:000252597300032 PM 18006645 ER PT J AU Baum, AE Akula, N Cabanero, M Cardona, I Corona, W Klemens, B Schulze, TG Cichon, S Rietschel, M Nothen, MM Georgi, A Schumacher, J Schwarz, M Abou Jamra, R Hofels, S Propping, P Satagopan, J Detera-Wadleigh, SD Hardy, J McMahon, FJ AF Baum, A. E. Akula, N. Cabanero, M. Cardona, I. Corona, W. Klemens, B. Schulze, T. G. Cichon, S. Rietschel, M. Noethen, M. M. Georgi, A. Schumacher, J. Schwarz, M. Abou Jamra, R. Hoefels, S. Propping, P. Satagopan, J. Detera-Wadleigh, S. D. Hardy, J. McMahon, F. J. CA NIMH Genetics Initiative Bipolar TI A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE mania; DFNB31; whirlin; Wnt; DAG; SORCS2 ID LARGE-SCALE ASSOCIATION; USHERS SYNDROME; COMPLEX TRAITS; LINKAGE; SCHIZOPHRENIA; POPULATION; IDENTIFICATION; POLYMORPHISM; METAANALYSIS; POWER AB The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550 000 single-nucleotide polymorphisms (SNPs) in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA, and selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost saving and gain in efficiency. A total of 88 SNPs, representing 80 different genes, met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of diacylglycerol kinase eta (DGKH; P = 1.5 x 10(-8), experiment-wide P < 0.01, OR = 1.59). This gene encodes DGKH, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease. C1 [Baum, A. E.; Akula, N.; Cabanero, M.; Cardona, I.; Corona, W.; Klemens, B.; Detera-Wadleigh, S. D.; McMahon, F. J.; NIMH Genetics Initiative Bipolar] NIMH, Unit Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, US Dept HHS,NIH, Bethesda, MD 20892 USA. [Klemens, B.] Ctr Social & Econ Dynam, Brookings Inst, Washington, DC USA. [Schulze, T. G.; Rietschel, M.; Georgi, A.] Univ Heidelberg, Cent Inst Mental Hlth, Dept Genet Epidemiol, D-6800 Mannheim, Germany. [Cichon, S.; Noethen, M. M.; Schumacher, J.; Abou Jamra, R.; Propping, P.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Cichon, S.; Noethen, M. M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Schwarz, M.] Univ Heidelberg, Acad Teaching Hosp, Psychiat Zent Nordbaden, Wiesloch, Germany. [Hoefels, S.] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. [Satagopan, J.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [NIMH Genetics Initiative Bipolar] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [NIMH Genetics Initiative Bipolar] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [NIMH Genetics Initiative Bipolar] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. [NIMH Genetics Initiative Bipolar] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [NIMH Genetics Initiative Bipolar] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [NIMH Genetics Initiative Bipolar] NIMH, Clin Sci Lab, US Dept HHS, Intramural Res Program,NIH, Bethesda, MD USA. [NIMH Genetics Initiative Bipolar] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL USA. [NIMH Genetics Initiative Bipolar] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [NIMH Genetics Initiative Bipolar] Univ Iowa, Sch Med, Dept Psychiat, Iowa City, IA 52242 USA. [NIMH Genetics Initiative Bipolar] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Hardy, J.] NIA, Neurogenet Lab, US Dept HHS, NIH, Bethesda, MD USA. RP McMahon, FJ (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, US Dept HHS,NIH, 35 Convent Dr,1A-202, Bethesda, MD 20892 USA. EM mcmahonf@mail.nih.gov RI McMahon, Francis/A-7290-2009; Hardy, John/C-2451-2009; Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schumacher, Johannes/F-4970-2015; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399; Schumacher, Johannes/0000-0001-9217-6457; Georgi, Alexander/0000-0002-1499-8524; Satagopan, Jaya/0000-0001-7102-5633; McMahon, Francis/0000-0002-9469-305X; Nothen, Markus/0000-0002-8770-2464 FU Intramural NIH HHS [Z01 MH002810-05, Z01 MH002842-04, Z01 MH002843-04]; Medical Research Council [G0701075, MR/K01417X/1]; NCI NIH HHS [R01 CA098438]; NIGMS NIH HHS [R01 GM60457]; NIMH NIH HHS [R01 MH059533, R01 MH059534, R01 MH059535, R01 MH059545, R01 MH059548, R01 MH059553, R01 MH059556, R01 MH059565, R01 MH059566, R01 MH059567, R01 MH059571, R01 MH059586, R01 MH059587, R01 MH059588, R01 MH060068, R01 MH060870, R01 MH060879, R01 MH061675, R01 MH067257, Z01 MH002810] NR 54 TC 380 Z9 392 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2008 VL 13 IS 2 BP 197 EP 207 DI 10.1038/sj.mp.4002012 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 252OG UT WOS:000252455200010 PM 17486107 ER PT J AU Lupu, VD Danielian, L Johnsen, JA Vasconcelos, OM Prokhorenko, OA Jabbari, B Campbell, WW Floeter, MK AF Lupu, Vitalie D. Danielian, Laura Johnsen, Jacqueline A. Vasconcelos, Olavo M. Prokhorenko, Olga A. Jabbari, Bahman Campbell, William W. Floeter, Mary Kay TI Physiology of the motor cortex in polio survivors SO MUSCLE & NERVE LA English DT Article DE intracortical facilitation; intracortical inhibition; plasticity; postpolio syndrome; transcranial magnetic stimulation ID POSTPOLIO SYNDROME; CORTICOSPINAL PROJECTIONS; TWITCH INTERPOLATION; MUSCLE PERFORMANCE; EVOKED-POTENTIALS; REORGANIZATION; INHIBITION; FATIGUE; POLIOMYELITIS; ASSESSMENTS AB We hypothesized that the corticospinal system undergoes functional changes in long-term polio survivors. Central motor conduction times (CMCTs) to the four limbs were measured in 24 polio survivors using transcranial magnetic stimulation (TMS). Resting motor thresholds and CMCTs were normal. In 17 subjects whose legs were affected by polio and 13 healthy controls, single- and paired-pulse TMS was used to assess motor cortex excitability while recording from tibialis anterior (TA) muscles at rest and following maximal contraction until fatigue. In polio survivors the slope of the recruitment curve was normal, but maximal motor evoked potentials (MEPs) were larger than in controls. MEPs were depressed after fatiguing exercise. Three patients with central fatigue by twitch interpolation had a trend toward slower recovery. There was no association with symptoms of post-polio syndrome. These changes occurring after polio may allow the motor cortex to activate a greater proportion of the motor neurons innervating affected muscles. C1 [Lupu, Vitalie D.; Danielian, Laura; Johnsen, Jacqueline A.; Floeter, Mary Kay] NINDS, NIH, EMG Sect, Bethesda, MD 20892 USA. [Vasconcelos, Olavo M.; Prokhorenko, Olga A.; Campbell, William W.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD USA. [Jabbari, Bahman] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Floeter, MK (reprint author), NINDS, NIH, EMG Sect, Bldg 10,CRC,7-5680,10 Ctr Dr,MSC-1404, Bethesda, MD 20892 USA. EM flooterm@ninds.nih.gov FU Intramural NIH HHS NR 28 TC 3 Z9 4 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD FEB PY 2008 VL 37 IS 2 BP 177 EP 182 DI 10.1002/mus.20913 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 258WK UT WOS:000252900500004 PM 17990291 ER PT J AU Butler, LM Millikan, RC Sinha, R Keku, TO Winkel, S Harlan, B Eaton, A Gammon, MD Sandler, RS AF Butler, Lesley M. Millikan, Robert C. Sinha, Rashmi Keku, Temitope O. Winkel, Scott Harlan, Brent Eaton, Allison Gammon, Marilie D. Sandler, Robert S. TI Modification by N-acetyltransferase 1 genotype on the association between dietary heterocyclic amines and colon cancer in a multiethnic study SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE acetyltransferases; amines; colon cancer; meat; polymorphism; genetic ID ARYLAMINE N-ACETYLTRANSFERASES; GENE-ENVIRONMENT INTERACTIONS; GLUTATHIONE S-TRANSFERASES; DONE RED MEAT; COLORECTAL-CANCER; AFRICAN-AMERICANS; METABOLIC PHENOTYPES; MOLECULAR-GENETICS; CIGARETTE-SMOKING; BREAST-CANCER AB Objective: Colorectal cancer incidence is greater among African Americans, compared to whites in the U.S., and may be due in part to differences in diet, genetic variation at metabolic loci, and/or the joint effect of diet and genetic susceptibility. We examined whether our previously reported associations between meat-derived heterocyclic amine (HCA) intake and colon cancer were modified by N-acetyltransferase 1 (NAT1) or 2 (NAT2) genotypes and whether there were differences by race. Methods: In a population-based, case-control study of colon cancer, exposure to HCAs was assessed using a food-frequency questionnaire with a meat-cooking and doneness module, among African Americans (217 cases and 315 controls) and whites (290 cases and 534 controls). Results: There was no association with NAT1*10 versus NAT1-non*10 genotypes for colon cancer. Among whites, there was a positive association for NAT2-"rapid/intermediate" genotype [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.0, 1.8], compared to the NAT2-"slow" that was not observed among African Americans. Colon cancer associations with HCA intake were modified by NAT1, but not NAT2, regardless of race. However, the "at-risk" NAT1 genotype differed by race. For example, among African Americans, the positive association with 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) was confined to those with NAT1*10 genotype (OR = 1.8; 95% CI = 1.0, 3.3; P for interaction = 0.02, comparing highest to lowest intake), but among whites, an association with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was confined to those with NAT1-non*10 genotype (OR = 1.9; 95% CI = 1.1, 3.1; P for interaction = 0.03). Conclusions: Our data indicate modification by NATI for HCA and colon cancer associations, regardless of race. Although the at-risk NATI genotype differs by race, the magnitude of the individual HCA-related associations in both race groups are similar. Therefore, our data do not support the hypothesis that NATI by HCA interactions contribute to differences in colorectal cancer incidence between African Americans and whites. (C) 2007 Elsevier B.V. All rights reserved. C1 [Butler, Lesley M.] Univ Calif Davis, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA. [Millikan, Robert C.; Winkel, Scott; Harlan, Brent; Eaton, Allison; Gammon, Marilie D.; Sandler, Robert S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Keku, Temitope O.; Sandler, Robert S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Sinha, Rashmi] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Butler, LM (reprint author), Univ Calif Davis, Dept Publ Hlth Sci, 1 Shields Ave, Davis, CA 95616 USA. EM lmbutler@ucdavis.edu RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [P30-CA16086, R01 CA66635]; NICHD NIH HHS [K12 HD051958]; NIDDK NIH HHS [T32 DK007634, P30-DK34987, T32 DK007634-09, T32 DK07634]; NIEHS NIH HHS [P30-ES10126] NR 78 TC 26 Z9 26 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD FEB 1 PY 2008 VL 638 IS 1-2 BP 162 EP 174 DI 10.1016/j.mrfmmm.2007.10.002 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 260TT UT WOS:000253034000020 PM 18022202 ER PT J AU Lengyel, JS Milne, JLS Subramaniam, S AF Lengyel, Jeffrey S. Milne, Jacqueline L. S. Subramaniam, Sriram TI Electron tomography in nanoparticle imaging and analysis SO NANOMEDICINE LA English DT Review DE 3D electron microscopy; AIDS virus; cryo-electron tomography; Doxil (R); liposomes; nanoparticle characterization; nanoparticle standardization ID 3-DIMENSIONAL STRUCTURE; INSIGHTS AB A wide range of medically important nanosized biological assemblies are not amenable to study by standard structural techniques, such as x-ray crystallography or nuclear magnetic resonance spectroscopy, either owing to their large size or the intrinsic heterogeneity of the specimen. The emerging technique of cryo-electron tomography is being applied actively to study these nanoparticles and has the potential of providing high-resolution structural information on these heterogeneous assemblies. Although the majority of structural methods involve the averaging of large numbers of structurally homogeneous molecules, tomography enables the visualization and quantitation of variation in a mixed population. Here, we present a review of the principles of cryo-electron tomography as applied to the 3D analysis of nanoparticles and illustrate applications where it can be used for visualizing the architecture of enveloped viruses and for the analysis of size and compositional variation of Doxil (R), a commonly used, US FDA-approved nanomedicine. C1 [Lengyel, Jeffrey S.; Milne, Jacqueline L. S.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. EM lengyelj@mail.nih.gov; jmilne@nih.gov; ss1@nih.gov FU Intramural NIH HHS [Z01 BC010278-10, Z01 BC010826-01] NR 16 TC 25 Z9 25 U1 1 U2 12 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD FEB PY 2008 VL 3 IS 1 BP 125 EP 131 DI 10.2217/17435889.3.1.125 PG 7 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 331EE UT WOS:000257994700015 PM 18393671 ER PT J AU Mathivanan, S Ahmed, M Ahn, NG Hainard, A Amanchy, R Andrews, PC Bader, JS Balgley, BM Bantscheff, M Bennett, KL Bjorling, E Blagoev, B Bose, R Brahmachari, SK Burlingame, AS Bustelo, XR Cagney, G Cantin, GT Cardasis, HL Celis, JE Chaerkady, R Chu, FX Cole, PA Costello, CE Cotter, RJ Crockett, D DeLany, JP De Marzo, AM DeSouza, LV Deutsch, EW Dransfield, E Drewes, G Droit, A Dunn, MJ Elenitoba-Johnson, K Ewing, RM Van Eyk, J Faca, V Falkner, J Fang, XM Fenselau, C Figeys, D Gagne, P Gelfi, C Gevaert, K Gimble, JM Gnad, F Goel, R Gromov, P Hanash, SM Hancock, WS Harsha, HC Hart, G Hays, F He, FC Hebbar, P Helsens, K Hermeking, H Hide, W Hjerno, K Hochstrasser, DF Hofmann, O Horn, DM Hruban, RH Ibarrola, N James, P Jensen, ON Jensen, PH Jung, P Kandasamy, K Kheterpal, I Kikuno, RF Korf, U Korner, R Kuster, B Kwon, MS Lee, HJ Lee, YJ Lefevre, M Lehvaslaiho, M Lescuyer, P Levander, F Lim, MS Lobke, C Loo, JA Mann, M Martens, L Martinez-Heredia, J McComb, M McRedmond, J Mehrle, A Menon, R Miller, CA Mischak, H Mohan, SS Mohmood, R Molina, H Moran, MF Morgan, JD Moritz, R Morzel, M Muddiman, DC Nalli, A Navarro, JD Neubert, TA Ohara, O Oliva, R Omenn, GS Oyama, M Paik, YK Pennington, K Pepperkok, R Periaswamy, B Petricoin, EF Poirier, GG Prasad, TSK Purvine, SO Rahiman, BA Ramachandran, P Ramachandra, YL Rice, RH Rick, J Ronnholm, RH Salonen, J Sanchez, JC Sayd, T Seshi, B Shankari, K Sheng, SJ Shetty, V Shivakumar, K Simpson, RJ Sirdeshmukh, R Siu, KWM Smith, JC Smith, RD States, DJ Sugano, S Sullivan, M Superti-Furga, G Takatalo, M Thongboonkerd, V Trinidad, JC Uhlen, M Vandekerckhove, J Vasilescu, J Veenstra, TD Vidal-Taboada, JM Vihinen, M Wait, R Wang, XY Wiemann, S Wu, B Xu, T Yates, JR Zhong, J Zhou, M Zhu, YP Zurbig, P Pandey, A AF Mathivanan, Suresh Ahmed, Mukhtar Ahn, Natalie G. Hainard, Alexandre Amanchy, Ramars Andrews, Philip C. Bader, Joel S. Balgley, Brian M. Bantscheff, Marcus Bennett, Keiryn L. Bjoerling, Erik Blagoev, Blagoy Bose, Ron Brahmachari, Samir K. Burlingame, Alma S. Bustelo, Xose R. Cagney, Gerard Cantin, Greg T. Cardasis, Helene L. Celis, Julio E. Chaerkady, Raghothama Chu, Feixia Cole, Philip A. Costello, Catherine E. Cotter, Robert J. Crockett, David DeLany, James P. De Marzo, Angelo M. DeSouza, Leroi V. Deutsch, Eric W. Dransfield, Eric Drewes, Gerard Droit, Arnaud Dunn, Michael J. Elenitoba-Johnson, Kojo Ewing, Rob M. Van Eyk, Jennifer Faca, Vitor Falkner, Jayson Fang, Xiangming Fenselau, Catherine Figeys, Daniel Gagne, Pierre Gelfi, Cecilia Gevaert, Kris Gimble, Jeffrey M. Gnad, Florian Goel, Renu Gromov, Pavel Hanash, Samir M. Hancock, William S. Harsha, H. C. Hart, Gerald Hays, Faith He, Fuchu Hebbar, Prashantha Helsens, Kenny Hermeking, Heiko Hide, Winston Hjerno, Karin Hochstrasser, Denis F. Hofmann, Oliver Horn, David M. Hruban, Ralph H. Ibarrola, Nieves James, Peter Jensen, Ole N. Jensen, Pia Honnerup Jung, Peter Kandasamy, Kumaran Kheterpal, Indu Kikuno, Reiko F. Korf, Ulrike Koerner, Roman Kuster, Bernhard Kwon, Min-Seok Lee, Hyoung-Joo Lee, Young-Jin Lefevre, Michael Lehvaslaiho, Minna Lescuyer, Pierre Levander, Fredrik Lim, Megan S. Loebke, Christian Loo, Joseph A. Mann, Matthias Martens, Lennart Martinez-Heredia, Juan McComb, Mark McRedmond, James Mehrle, Alexander Menon, Rajasree Miller, Christine A. Mischak, Harald Mohan, S. Sujatha Mohmood, Riaz Molina, Henrik Moran, Michael F. Morgan, James D. Moritz, Robert Morzel, Martine Muddiman, David C. Nalli, Anuradha Navarro, J. Daniel Neubert, Thomas A. Ohara, Osamu Oliva, Rafael Omenn, Gilbert S. Oyama, Masaaki Paik, Young-Ki Pennington, Kyla Pepperkok, Rainer Periaswamy, Balamurugan Petricoin, Emanuel F. Poirier, Guy G. Prasad, T. S. Keshava Purvine, Samuel O. Rahiman, B. Abdul Ramachandran, Prasanna Ramachandra, Y. L. Rice, Robert H. Rick, Jens Ronnholm, Ragna H. Salonen, Johanna Sanchez, Jean-Charles Sayd, Thierry Seshi, Beerelli Shankari, Kripa Sheng, Shi Jun Shetty, Vivekananda Shivakumar, K. Simpson, Richard J. Sirdeshmukh, Ravi Siu, K. W. Michael Smith, Jeffrey C. Smith, Richard D. States, David J. Sugano, Sumio Sullivan, Matthew Superti-Furga, Giulio Takatalo, Maarit Thongboonkerd, Visith Trinidad, Jonathan C. Uhlen, Mathias Vandekerckhove, Joel Vasilescu, Julian Veenstra, Timothy D. Vidal-Taboada, Jose-Manuel Vihinen, Mauno Wait, Robin Wang, Xiaoyue Wiemann, Stefan Wu, Billy Xu, Tao Yates, John R. Zhong, Jun Zhou, Ming Zhu, Yunping Zurbig, Petra Pandey, Akhilesh TI Human Proteinpedia enables sharing of human protein data SO NATURE BIOTECHNOLOGY LA English DT Letter C1 [Mathivanan, Suresh; Ahmed, Mukhtar; Chaerkady, Raghothama; Goel, Renu; Harsha, H. C.; Hebbar, Prashantha; Kandasamy, Kumaran; Mohan, S. Sujatha; Nalli, Anuradha; Navarro, J. Daniel; Periaswamy, Balamurugan; Prasad, T. S. Keshava; Shankari, Kripa; Shivakumar, K.] Inst Bioinformat, Bangalore 560066, Karnataka, India. [Amanchy, Ramars; Chaerkady, Raghothama; Molina, Henrik; Zhong, Jun; Pandey, Akhilesh] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Amanchy, Ramars; Chaerkady, Raghothama; Molina, Henrik; Zhong, Jun; Pandey, Akhilesh] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. [Amanchy, Ramars; Chaerkady, Raghothama; Molina, Henrik; Zhong, Jun; Pandey, Akhilesh] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. [Mathivanan, Suresh; Kandasamy, Kumaran; Mohmood, Riaz; Periaswamy, Balamurugan; Rahiman, B. Abdul; Ramachandra, Y. L.; Shivakumar, K.] Kuvempu Univ, Dept Biotechnol, Shankaraghatta 577451, Karnataka, India. [Ahn, Natalie G.] Univ Colorado, Howard Hughes Med Inst, Dept Chem & Biochem, Boulder, CO 80309 USA. [Hainard, Alexandre; Hochstrasser, Denis F.; Lescuyer, Pierre; Sanchez, Jean-Charles] Univ Geneva, Fac Med, Dept Struct Biol & Bioinformat, Biomed Proteom Res Grp, CH-1211 Geneva, Switzerland. [Andrews, Philip C.; Falkner, Jayson] Univ Colorado, Dept Biol Chem, Ann Arbor, MI 48109 USA. [Bader, Joel S.] Johns Hopkins Univ, High Throughput Biol Ctr, Baltimore, MD 21205 USA. [Bader, Joel S.; Balgley, Brian M.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. [Balgley, Brian M.] Calbrant Biosyst, Gaithersburg, MD 20878 USA. [Bantscheff, Marcus; Drewes, Gerard; Kuster, Bernhard; Rick, Jens] Cellzone AG, D-69117 Heidelberg, Germany. [Bennett, Keiryn L.; Superti-Furga, Giulio] Res Ctr Mol Med, A-1090 Vienna, Austria. [Bjoerling, Erik; Uhlen, Mathias] AlbaNova Univ Ctr, Royal Inst Technol, Sch Biotechnol, SE-10691 Stockholm, Sweden. [Blagoev, Blagoy; Hjerno, Karin; Jensen, Ole N.; Jensen, Pia Honnerup; Mann, Matthias] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark. [Bose, Ron; Cole, Philip A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA. [Bose, Ron; Brahmachari, Samir K.; Cole, Philip A.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Brahmachari, Samir K.] CSIR, GN Ramchandran Knowledge Ctr Genome Informat, Inst Genome & Integrat Biol, Delhi 110007, India. [Burlingame, Alma S.; Chu, Feixia; Trinidad, Jonathan C.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. [Bustelo, Xose R.; Ibarrola, Nieves] Univ Salamanca, CSIC, Ctr Invest Canc, E-37007 Salamanca, Spain. [Bustelo, Xose R.; Ibarrola, Nieves] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, E-37007 Salamanca, Spain. [Cagney, Gerard; Dunn, Michael J.; McRedmond, James; Pennington, Kyla; Sullivan, Matthew] UCD Conway Inst Biomol & Biomed Res, Proteome Res Ctr, Dublin 4, Ireland. [Cantin, Greg T.; Xu, Tao; Yates, John R.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. [Cardasis, Helene L.; Neubert, Thomas A.; Shetty, Vivekananda] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA. [Cardasis, Helene L.; Neubert, Thomas A.; Shetty, Vivekananda] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. [Celis, Julio E.; Gromov, Pavel] Danish Ctr Translat Breast Canc Res, DK-2100 Copenhagen, Denmark. [Celis, Julio E.; Gromov, Pavel] Danish Canc Soc, Inst Canc Biol, Dept Proteom Canc, DK-2100 Copenhagen, Denmark. [Costello, Catherine E.; McComb, Mark] Boston Univ, Sch Med, Cardiovasc Proteom Ctr, Boston, MA 02118 USA. [Cotter, Robert J.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Ann Arbor, MI 48109 USA. [Crockett, David; Elenitoba-Johnson, Kojo; Lim, Megan S.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [DeLany, James P.] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15213 USA. [De Marzo, Angelo M.; Morgan, James D.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21287 USA. [De Marzo, Angelo M.; Morgan, James D.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [DeSouza, Leroi V.; Siu, K. W. Michael] York Univ, Ctr Res Mass Spect, N York, ON M3J 1P3, Canada. [DeSouza, Leroi V.; Siu, K. W. Michael] York Univ, Dept Chem, N York, ON M3J 1P3, Canada. [Deutsch, Eric W.] Inst Syst Biol, Seattle, WA 98103 USA. [Dransfield, Eric; Sayd, Thierry] Wageningen Ctr Food Sci, NL-6700 AN Wageningen, Netherlands. [Droit, Arnaud; Gagne, Pierre; Poirier, Guy G.] Univ Laval, CHU Laval, Med Res Ctr, Environm & Hlth Unit,Fac Med, Quebec City, PQ G1V 4G2, Canada. [Ewing, Rob M.] Protana Transit Therapeut, Toronto, ON M5G 1L7, Canada. [Ewing, Rob M.] Infochrom, Toronto, ON M5G 1L7, Canada. [Van Eyk, Jennifer; Sheng, Shi Jun] Johns Hopkins Univ, Johns Hopkins Bayview Proteom Ctr, Dept Med, Baltimore, MD 21224 USA. [Faca, Vitor; Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Fang, Xiangming] GenWay Biotech Inc, San Diego, CA 92121 USA. [Fenselau, Catherine; Hays, Faith] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Figeys, Daniel; Smith, Jeffrey C.; Vasilescu, Julian] Univ Ottawa, Ottawa Inst Syst Biol, Ottawa, ON K1H 8M5, Canada. [Gelfi, Cecilia] Univ Milan, Fac Med, Dept Biomed Sci & Technol, Milan, Italy. [Gevaert, Kris; Helsens, Kenny; Martens, Lennart; Vandekerckhove, Joel] Univ Ghent, Fac Med, Dept Biochem & Med Prot Res, B-9000 Ghent, Belgium. [Gimble, Jeffrey M.; Lefevre, Michael] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Stem Cell Lab, Baton Rouge, LA 70808 USA. [Gimble, Jeffrey M.; Kheterpal, Indu; Ohara, Osamu] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Cell Biol Core Facil, Baton Rouge, LA 70808 USA. [Gnad, Florian; Mann, Matthias] Max Planck Inst Biochem, Dept Proteom & Signal Transduct, D-82152 Martinsried, Germany. [Hancock, William S.; Wu, Billy] NE Univ, Barnett Inst, Boston, MA 02115 USA. [Hancock, William S.; Wu, Billy] NE Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [He, Fuchu; Zhu, Yunping] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, Beijing 100850, Peoples R China. [He, Fuchu] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Hermeking, Heiko; Jung, Peter] Max Planck Inst Biochem, Independent Max Planck Res Grp, D-82152 Martinsried, Germany. [Hide, Winston; Hofmann, Oliver; Lehvaslaiho, Minna] Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa. [Hochstrasser, Denis F.] Univ Hosp Geneva, Cent Lab Clin Chem, Geneva, Switzerland. [Horn, David M.; Miller, Christine A.] Agilent Technol, Santa Clara, CA 95051 USA. [Hruban, Ralph H.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol & Oncol, Baltimore, MD 21231 USA. [James, Peter; Levander, Fredrik] Lund Univ, Lund, Sweden. [Kikuno, Reiko F.] Kazusa DNA Res Inst, Dept Human Genome Technol, Chiba 2920818, Japan. [Korf, Ulrike; Loebke, Christian; Mehrle, Alexander; Wiemann, Stefan] DKFZ Heidelberg, German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany. [Koerner, Roman] Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany. [Kwon, Min-Seok; Lee, Hyoung-Joo; Paik, Young-Ki] Yonsei Univ, Dept Biochem, Yonsei Proteome Res Ctr, Seoul 120749, South Korea. [Kwon, Min-Seok; Lee, Hyoung-Joo; Paik, Young-Ki] Yonsei Univ, Biomed Proteome Res Ctr, Seoul 120749, South Korea. [Lee, Young-Jin; Rice, Robert H.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. [Lefevre, Michael] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Lipoprot Lab, Baton Rouge, LA 70808 USA. [Loo, Joseph A.; Ramachandran, Prasanna] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Loo, Joseph A.; Ramachandran, Prasanna] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. [Martens, Lennart] European Bioinformat Inst, EMBL Outstn, Cambridge CB10 1SD, England. [Martinez-Heredia, Juan; Oliva, Rafael; Vidal-Taboada, Jose-Manuel] Univ Barcelona, Fac Med, Human Genet Res Grp, IDIBAPS, Barcelona 08023, Spain. [Menon, Rajasree; States, David J.] Univ Michigan, Bioinformat Program, Ann Arbor, MI 48109 USA. [Mischak, Harald; Zurbig, Petra] Mosaiques Diag & Therapeut AG, D-30625 Hannover, Germany. [Moran, Michael F.] Hosp Sick Children, Canc Program, Toronto, ON M5G 1L7, Canada. [Moran, Michael F.] Hosp Sick Children, McLaughlin Ctr Mol Med, Toronto, ON M5G 1L7, Canada. [Moran, Michael F.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada. [Moran, Michael F.] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1L6, Canada. [Moritz, Robert; Simpson, Richard J.] Ludwig Inst Canc Res, Joint Proteom Lab, Melbourne Branch, Melbourne, Vic 3050, Australia. [Moritz, Robert; Simpson, Richard J.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. [Morzel, Martine] INRA, UR 370, F-63122 St Genes Champanelle, France. [Muddiman, David C.] N Carolina State Univ, Dept Chem, WM Keck FT ICR Mass Spect Lab, Raleigh, NC 27695 USA. [Ohara, Osamu] RIKEN, Yokohama Inst, Res Ctr Allergy & Immunol, Lab Immunogenom,Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Omenn, Gilbert S.] Univ Michigan, Dept Internal Med, Ctr Comp Med & Biol Proteom Alliance Canc Res, Ann Arbor, MI 48109 USA. [Oyama, Masaaki; Sugano, Sumio] Univ Tokyo, Inst Med Sci, Med Proteom Lab, Tokyo 1088639, Japan. [Pepperkok, Rainer] European Mol Biol Lab, Cell Biol & Biophys Programme, D-69117 Heidelberg, Germany. [Petricoin, Emanuel F.] George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA 20110 USA. [Purvine, Samuel O.; Smith, Richard D.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. [Purvine, Samuel O.; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Ronnholm, Ragna H.; Takatalo, Maarit] Univ Helsinki, Dept Biol & Environm Sci, Div Biochem, FI-00014 Helsinki, Finland. [Salonen, Johanna; Vihinen, Mauno] Univ Tampere, Inst Med Technol, FI-33014 Tampere, Finland. [Seshi, Beerelli] Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Dept Pathol,Los Angeles Biomed Res Inst Harbor, Torrance, CA 90502 USA. [Sirdeshmukh, Ravi] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. [Thongboonkerd, Visith] Mahidol Univ, Siriraj Hosp, Off Res & Dev, Med Mol Biol Unit,Fac Med, Bangkok 10700, Thailand. [Veenstra, Timothy D.; Zhou, Ming] NCI Frederick, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Ft Detrick, MD 21702 USA. [Wait, Robin] Univ London Imperial Coll Sci Technol & Med, Fac Med, Kennedy Inst Rheumatol, London SW7 2AZ, England. [Amanchy, Ramars; Harsha, H. C.; Hart, Gerald; Molina, Henrik; Wang, Xiaoyue; Pandey, Akhilesh] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21205 USA. RP Mathivanan, S (reprint author), Inst Bioinformat, Int Tech Pk, Bangalore 560066, Karnataka, India. EM pandey@jhmi.edu RI Korner, Roman/G-8565-2011; Bader, Joel/A-1818-2009; Cagney, Gerard/A-4648-2009; Pandey, Akhilesh/B-4127-2009; THONGBOONKERD, VISITH /C-6920-2009; Hide, Winston Hide/C-7217-2009; Kandasamy, Kumaran/C-8981-2009; Ahmed, Dr. Mukhtar/F-7056-2010; Wang, Xiaoyue/D-1046-2010; Oliva, Rafael/C-9741-2009; Xu, Tao/A-9353-2009; Chaerkady, Raghothama/D-5718-2011; Mischak, Harald/E-8685-2011; Vidal-Tabaoada, Jose Manuel/L-4777-2014; Wiemann, Stefan/E-4424-2013; Prasad, T. S. Keshava/F-7631-2010; Mann, Matthias/A-3454-2013; Superti-Furga, Giulio/F-4755-2015; Lee, Young Jin/F-2317-2011; Ohara, Osamu/G-5448-2015; Gelfi, Cecilia/L-1490-2016; Kuster, Bernhard/Q-6031-2016; Lefevre, Michael/B-5030-2014; Gevaert, Kris/D-6489-2017; Vihinen, Mauno/A-8452-2012; Ohara, Osamu/A-9119-2012; Simpson, Richard/A-6947-2012; Zhong, Jun/D-1662-2010; Martens, Lennart/E-8816-2010; Smith, Richard/J-3664-2012; Jensen, Ole/J-1763-2012; Faca, Vitor/A-3989-2013; Hofmann, Oliver/F-1800-2013; Korf, Ulrike/G-2795-2013; DeSouza, Leroi/H-3831-2013; Gevaert, Kris/H-3637-2013; Mathivanan, Suresh/D-2045-2009; OI Korner, Roman/0000-0001-9285-9290; Bader, Joel/0000-0002-6020-4625; Pandey, Akhilesh/0000-0001-9943-6127; Hide, Winston Hide/0000-0002-8621-3271; Oliva, Rafael/0000-0003-4876-2410; Vidal-Tabaoada, Jose Manuel/0000-0001-5667-4133; Wiemann, Stefan/0000-0003-4683-3174; Prasad, T. S. Keshava/0000-0002-6206-2384; Mann, Matthias/0000-0003-1292-4799; Superti-Furga, Giulio/0000-0002-0570-1768; Lee, Young Jin/0000-0002-2533-5371; Ohara, Osamu/0000-0002-3328-9571; Gelfi, Cecilia/0000-0002-2996-6912; Kuster, Bernhard/0000-0002-9094-1677; Lefevre, Michael/0000-0002-2046-3593; Gevaert, Kris/0000-0002-4237-0283; Ewing, Rob/0000-0001-6510-4001; Pepperkok, Rainer/0000-0002-9762-3583; Vihinen, Mauno/0000-0002-9614-7976; Zhong, Jun/0000-0003-3148-4143; Martens, Lennart/0000-0003-4277-658X; Smith, Richard/0000-0002-2381-2349; Jensen, Ole/0000-0003-1862-8528; Hofmann, Oliver/0000-0002-7738-1513; Gevaert, Kris/0000-0002-4237-0283; Mathivanan, Suresh/0000-0002-7290-5795; Balgley, Brian/0000-0002-3509-4567; Costello, Catherine/0000-0003-1594-5122; Blagoev, Blagoy/0000-0002-3596-0066; Amanchy, Ramars/0000-0001-9315-8488; Lescuyer, Pierre/0000-0001-6986-8738; Levander, Fredrik/0000-0002-0710-9792; KEERTHIKUMAR, SHIVAKUMAR/0000-0001-9865-9767; Cagney, Gerard/0000-0001-7189-9496; Takatalo, Maarit/0000-0003-4825-6358 FU NCI NIH HHS [R01 CA073735]; NCRR NIH HHS [U54 RR020839]; NHLBI NIH HHS [P01 HL081427-040003, N01 HV028178, N01 HV028180, N01-HV-28180, P01 HL077180, P01 HL077180-010001, P01 HL077180-020001, P01 HL077180-030001, P01 HL077180-040001, P01 HL077180-050001, P01 HL081427, P01 HL081427-010003, P01 HL081427-020003, P01 HL081427-030003, P01 HL081427-050003, P50 HL084946, P50 HL084946-019003, P50 HL084946-029003, P50 HL084946-039003] NR 0 TC 103 Z9 107 U1 3 U2 44 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 2008 VL 26 IS 2 BP 164 EP 167 DI 10.1038/nbt0208-164 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 263BQ UT WOS:000253193000013 PM 18259167 ER PT J AU Aulehla, A Wiegraebe, W Baubet, V Wahl, MB Deng, CX Taketo, M Lewandoski, M Pourquie, O AF Aulehla, Alexander Wiegraebe, Winfried Baubet, Valerie Wahl, Matthias B. Deng, Chuxia Taketo, Makoto Lewandoski, Mark Pourquie, Olivier TI A beta-catenin gradient links the clock and wavefront systems in mouse embryo segmentation SO NATURE CELL BIOLOGY LA English DT Article ID ANTEROPOSTERIOR AXIS ELONGATION; PRESOMITIC MESODERM; SOMITE SEGMENTATION; GENE-EXPRESSION; LUNATIC-FRINGE; TRANSCRIPTION FACTORS; FLUORESCENT PROTEIN; IN-VIVO; NOTCH; WNT AB Rhythmic production of vertebral precursors, the somites, causes bilateral columns of embryonic segments to form. This process involves a molecular oscillator - the segmentation clock - whose signal is translated into a spatial, periodic pattern by a complex signalling gradient system within the presomitic mesoderm (PSM). In mouse embryos, Wnt signalling has been implicated in both the clock and gradient mechanisms, but how the Wnt pathway can perform these two functions simultaneously remains unclear. Here, we use a yellow fluorescent protein (YFP)-based, real-time imaging system in mouse embryos to demonstrate that clock oscillations are independent of beta-catenin protein levels. In contrast, we show that the Wnt-signalling gradient is established through a nuclear beta-catenin protein gradient in the posterior PSM. This gradient of nuclear beta-catenin defines the size of the oscillatory field and controls key aspects of PSM maturation and segment formation, emphasizing the central role of Wnt signalling in this process. C1 [Aulehla, Alexander; Wiegraebe, Winfried; Wahl, Matthias B.; Pourquie, Olivier] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Baubet, Valerie] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Deng, Chuxia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Taketo, Makoto] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Lewandoski, Mark] NCI, Lab Canc & Dev Biol, NIH, Frederick, MD 21702 USA. [Pourquie, Olivier] Howard Hughes Med Inst, Kansas City, MO 64110 USA. RP Pourquie, O (reprint author), Stowers Inst Med Res, Kansas City, MO 64110 USA. EM olp@stowers-institute.org RI deng, chuxia/N-6713-2016; OI Pourquie, Olivier/0000-0001-5189-1227 NR 50 TC 151 Z9 155 U1 2 U2 6 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 FEB PY 2008 VL 10 IS 2 BP 186 EP U56 DI 10.1038/ncb1679 PG 16 WC Cell Biology SC Cell Biology GA 258VO UT WOS:000252897800014 PM 18157121 ER PT J AU Dupre, A Boyer-Chatenet, L Sattler, RM Modi, AP Lee, JH Nicolette, ML Kopelovich, L Jasin, M Baer, R Paull, TT Gautier, J AF Dupre, Aude Boyer-Chatenet, Louise Sattler, Rose M. Modi, Ami P. Lee, Ji-Hoon Nicolette, Matthew L. Kopelovich, Levy Jasin, Maria Baer, Richard Paull, Tanya T. Gautier, Jean TI A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex SO NATURE CHEMICAL BIOLOGY LA English DT Article ID CHROMOSOMAL DNA-REPLICATION; DOUBLE-STRAND BREAKS; ATM ACTIVATION; DEPENDENT PHOSPHORYLATION; MRE11/RAD50/NBS1 COMPLEX; MRE11 COMPLEX; DAMAGE; PROTEIN; CHECKPOINT; REPAIR AB The MRN (Mre11-Rad50-Nbs1)-ATM (ataxia-telangiectasia mutated) pathway is essential for sensing and signaling from DNA double-strand breaks. The MRN complex acts as a DNA damage sensor, maintains genome stability during DNA replication, promotes homology-dependent DNA repair and activates ATM. MRN is essential for cell viability, which has limited functional studies of the complex. Small-molecule inhibitors of MRN could circumvent this experimental limitation and could also be used as cellular radio- and chemosensitization compounds. Using cell-free systems that recapitulate faithfully the MRN-ATM signaling pathway, we designed a forward chemical genetic screen to identify inhibitors of the pathway, and we isolated 6-(4-hydroxyphenyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone (mirin, 1) as an inhibitor of MRN. Mirin prevents MRN-dependent activation of ATM without affecting ATM protein kinase activity, and it inhibits Mre11-associated exonuclease activity. Consistent with its ability to target the MRN complex, mirin abolishes the G2/M checkpoint and homology-dependent repair in mammalian cells. C1 [Dupre, Aude; Boyer-Chatenet, Louise; Sattler, Rose M.; Modi, Ami P.; Baer, Richard; Gautier, Jean] Columbia Univ, Inst Canc Genet, Irving Canc Res Ctr, New York, NY 10032 USA. [Lee, Ji-Hoon; Nicolette, Matthew L.; Paull, Tanya T.] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA. [Lee, Ji-Hoon; Nicolette, Matthew L.; Paull, Tanya T.] Univ Texas Austin, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. [Kopelovich, Levy] NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. [Jasin, Maria] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA. RP Gautier, J (reprint author), Columbia Univ, Inst Canc Genet, Irving Canc Res Ctr, 1130 St Nicholas Ave,Room 602, New York, NY 10032 USA. EM jg130@columbia.edu FU NCI NIH HHS [CA92245, CA95866, CA97403, P01 CA097403, R01 CA092245, R01 CA092245-06, R01 CA095866]; NIGMS NIH HHS [R01 GM054668, GM54668, R01 GM054668-11] NR 40 TC 159 Z9 159 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD FEB PY 2008 VL 4 IS 2 BP 119 EP 125 DI 10.1038/nchembio.63 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254KL UT WOS:000252585400011 PM 18176557 ER PT J AU Willer, CJ Sanna, S Jackson, AU Scuteri, A Bonnycastle, LL Clarke, R Heath, SC Timpson, NJ Najjar, SS Stringham, HM Strait, J Duren, WL Maschio, A Busonero, F Mulas, A Albai, G Swift, AJ Morken, MA Narisu, N Bennett, D Parish, S Shen, HQ Galan, P Meneton, P Hercberg, S Zelenika, D Chen, WM Li, Y Scott, LJ Scheet, PA Sundvall, J Watanabe, RM Nagaraja, R Ebrahim, S Lawlor, DA Ben-Shlomo, Y Davey-Smith, G Shuldiner, AR Collins, R Bergman, RN Uda, M Tuomilehto, J Cao, A Collins, FS Lakatta, E Lathrop, GM Boehnke, M Schlessinger, D Mohlke, KL Abecasis, GR AF Willer, Cristen J. Sanna, Serena Jackson, Anne U. Scuteri, Angelo Bonnycastle, Lori L. Clarke, Robert Heath, Simon C. Timpson, Nicholas J. Najjar, Samer S. Stringham, Heather M. Strait, James Duren, William L. Maschio, Andrea Busonero, Fabio Mulas, Antonella Albai, Giuseppe Swift, Amy J. Morken, Mario A. Narisu, Narisu Bennett, Derrick Parish, Sarah Shen, Haiqing Galan, Pilar Meneton, Pierre Hercberg, Serge Zelenika, Diana Chen, Wei-Min Li, Yun Scott, Laura J. Scheet, Paul A. Sundvall, Jouko Watanabe, Richard M. Nagaraja, Ramaiah Ebrahim, Shah Lawlor, Debbie A. Ben-Shlomo, Yoav Davey-Smith, George Shuldiner, Alan R. Collins, Rory Bergman, Richard N. Uda, Manuela Tuomilehto, Jaakko Cao, Antonio Collins, Francis S. Lakatta, Edward Lathrop, G. Mark Boehnke, Michael Schlessinger, David Mohlke, Karen L. Abecasis, Goncalo R. TI Newly identified loci that influence lipid concentrations and risk of coronary artery disease SO NATURE GENETICS LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; GENOME-WIDE ASSOCIATION; ISCHEMIC-HEART-DISEASE; OLD ORDER AMISH; MYOCARDIAL-INFARCTION; NONFASTING TRIGLYCERIDES; ANTIOXIDANT VITAMINS; GENETIC-VARIANTS; METAANALYSIS; POPULATION AB To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls. C1 [Willer, Cristen J.; Sanna, Serena; Jackson, Anne U.; Stringham, Heather M.; Duren, William L.; Chen, Wei-Min; Li, Yun; Scott, Laura J.; Scheet, Paul A.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Sanna, Serena; Maschio, Andrea; Busonero, Fabio; Mulas, Antonella; Albai, Giuseppe; Uda, Manuela; Cao, Antonio] Citta Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy. [Scuteri, Angelo; Najjar, Samer S.; Strait, James; Nagaraja, Ramaiah; Lakatta, Edward; Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Scuteri, Angelo] Ist Patol Endocrina & Metab, Unita Operat Geriatr, Rome, Italy. [Bonnycastle, Lori L.; Swift, Amy J.; Morken, Mario A.; Narisu, Narisu; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Clarke, Robert; Bennett, Derrick; Parish, Sarah; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England. [Heath, Simon C.; Zelenika, Diana; Lathrop, G. Mark] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, F-91057 Evry, France. [Timpson, Nicholas J.; Lawlor, Debbie A.; Ben-Shlomo, Yoav; Davey-Smith, George] Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. [Shen, Haiqing; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Galan, Pilar] INSERM, U872, F-75270 Paris, France. [Galan, Pilar] Fac Med Rene Descartes, Dept Sante Publ & Informat Med, F-75270 Paris, France. [Meneton, Pierre; Hercberg, Serge] CRNH, F-93017 Bobigny, France. [Meneton, Pierre; Hercberg, Serge] INSERM, U557, F-93017 Bobigny, France. [Meneton, Pierre; Hercberg, Serge] INRA, U1125, F-93017 Bobigny, France. [Meneton, Pierre; Hercberg, Serge] Cnam, F-93017 Bobigny, France. [Meneton, Pierre; Hercberg, Serge] Univ Paris 13, F-93017 Bobigny, France. [Sundvall, Jouko] Natl Publ Hlth Inst, Dept Hlth & Funct Capac, Lab Analyt Biochem, SF-00300 Helsinki, Finland. [Watanabe, Richard M.; Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Ebrahim, Shah] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England. [Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP Abecasis, GR (reprint author), Univ Michigan, Dept Biostat, Ctr Stat Genet, 1420 Washington Hts, Ann Arbor, MI 48109 USA. EM mohlke@med.unc.edu; goncalo@umich.edu RI Chen, Wei-Min/A-8469-2009; Abecasis, Goncalo/B-7840-2010; Heath, Simon/J-4138-2012; Davey Smith, George/A-7407-2013; OI Davey Smith, George/0000-0002-1407-8314; Willer, Cristen/0000-0001-5645-4966; sanna, serena/0000-0002-3768-1749; Mulas, Antonella/0000-0002-6856-1483; Abecasis, Goncalo/0000-0003-1509-1825; Timpson, Nicholas/0000-0002-7141-9189; Lawlor, Debbie A/0000-0002-6793-2262 FU Intramural NIH HHS [, Z01 AG000235-01]; Medical Research Council [G0600705, G9815508, MC_U137686857]; NHGRI NIH HHS [N01HG65403, N01-HG-65403)]; NIDDK NIH HHS [R01 DK029867, R01 DK072193]; Wellcome Trust [076113] NR 49 TC 934 Z9 947 U1 4 U2 86 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2008 VL 40 IS 2 BP 161 EP 169 DI 10.1038/ng.76 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 256MJ UT WOS:000252732900014 PM 18193043 ER PT J AU Sanna, S Jackson, AU Nagaraja, R Willer, CJ Chen, WM Bonnycastle, LL Shen, HQ Timpson, N Lettre, G Usala, G Chines, PS Stringham, HM Scott, LJ Dei, M Lai, S Albai, G Crisponi, L Naitza, S Doheny, KF Pugh, EW Ben-Shlomo, Y Ebrahim, S Lawlor, DA Bergman, RN Watanabe, RM Uda, M Tuomilehto, J Coresh, J Hirschhorn, JN Shuldiner, AR Schlessinger, D Collins, FS Smith, GD Boerwinkle, E Cao, A Boehnke, M Abecasis, GR Mohlke, KL AF Sanna, Serena Jackson, Anne U. Nagaraja, Ramaiah Willer, Cristen J. Chen, Wei-Min Bonnycastle, Lori L. Shen, Haiqing Timpson, Nicholas Lettre, Guillaume Usala, Gianluca Chines, Peter S. Stringham, Heather M. Scott, Laura J. Dei, Mariano Lai, Sandra Albai, Giuseppe Crisponi, Laura Naitza, Silvia Doheny, Kimberly F. Pugh, Elizabeth W. Ben-Shlomo, Yoav Ebrahim, Shah Lawlor, Debbie A. Bergman, Richard N. Watanabe, Richard M. Uda, Manuela Tuomilehto, Jaakko Coresh, Josef Hirschhorn, Joel N. Shuldiner, Alan R. Schlessinger, David Collins, Francis S. Smith, George Davey Boerwinkle, Eric Cao, Antonio Boehnke, Michael Abecasis, Goncalo R. Mohlke, Karen L. TI Common variants in the GDF5-UQCC region are associated with variation in human height SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; OLD ORDER AMISH; SUSCEPTIBILITY; OSTEOARTHRITIS; EXPRESSION; ADULT; CHONDROGENESIS; HERITABILITY; CARTILAGE; RISK AB Identifying genetic variants that influence human height will advance our understanding of skeletal growth and development. Several rare genetic variants have been convincingly and reproducibly associated with height in mendelian syndromes, and common variants in the transcription factor gene HMGA2 are associated with variation in height in the general population(1). Here we report genome-wide association analyses, using genotyped and imputed markers, of 6,669 individuals from Finland and Sardinia, and follow-up analyses in an additional 28,801 individuals. We show that common variants in the osteoarthritis-associated locus(2) GDF5-UQCC contribute to variation in height with an estimated additive effect of 0.44 cm (overall P < 10(-15)). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development. C1 [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Sanna, Serena; Jackson, Anne U.; Willer, Cristen J.; Chen, Wei-Min; Stringham, Heather M.; Scott, Laura J.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Sanna, Serena; Usala, Gianluca; Dei, Mariano; Lai, Sandra; Albai, Giuseppe; Crisponi, Laura; Naitza, Silvia; Uda, Manuela; Cao, Antonio] Citta Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy. [Nagaraja, Ramaiah; Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Chen, Wei-Min] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. [Bonnycastle, Lori L.; Chines, Peter S.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Shen, Haiqing; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Timpson, Nicholas; Ben-Shlomo, Yoav; Lawlor, Debbie A.; Smith, George Davey] Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. [Timpson, Nicholas; Lawlor, Debbie A.; Smith, George Davey] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 2PR, Avon, England. [Lettre, Guillaume; Hirschhorn, Joel N.] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Doheny, Kimberly F.; Pugh, Elizabeth W.] Johns Hopkins Univ, Sch Med, Inst Med Genet, CIDR, Baltimore, MD 21224 USA. [Ebrahim, Shah] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Bergman, Richard N.; Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. [Coresh, Josef] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Ctr, Baltimore, MD 21201 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77225 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX 77225 USA. RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. EM goncalo@umich.edu; mohlke@med.unc.edu RI Chen, Wei-Min/A-8469-2009; Abecasis, Goncalo/B-7840-2010; Fox, Laura /C-6249-2016; Davey Smith, George/A-7407-2013; Naitza, Silvia/D-5620-2017; OI Abecasis, Goncalo/0000-0003-1509-1825; Davey Smith, George/0000-0002-1407-8314; Willer, Cristen/0000-0001-5645-4966; Timpson, Nicholas/0000-0002-7141-9189; Lawlor, Debbie A/0000-0002-6793-2262; sanna, serena/0000-0002-3768-1749; Monsalve, Beatriz Elena/0000-0002-5994-866X FU Intramural NIH HHS; Medical Research Council [G0000934, G0600705]; NCRR NIH HHS [M01 RR 16500, M01 RR016500]; NHGRI NIH HHS [HG002651, N01HG65403, R01 HG002651, R01 HG002651-05S2, Z01 HG000024]; NHLBI NIH HHS [N01HC55019, HL084729, HL72515, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC55015, N01HC55016, N01HC55018, N01HC55020, N01HC55021, N01HC55022, U01 HL072515, U01 HL084729, U01 HL084729-03]; NIA NIH HHS [AG18728, R01 AG018728]; NIAMS NIH HHS [AR046838, R01 AR046838]; NIDDK NIH HHS [DK062370, DK072193, DK54361, P30 DK072488, R01 DK029867, R01 DK062370, R01 DK072193, R01 DK072193-04, R56 DK062370, U01 DK062370]; Wellcome Trust [068545/Z/02] NR 29 TC 239 Z9 249 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2008 VL 40 IS 2 BP 198 EP 203 DI 10.1038/ng.74 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 256MJ UT WOS:000252732900018 PM 18193045 ER PT J AU Hickman, HD Takeda, K Skon, CN Murray, FR Hensley, SE Loomis, J Barber, GN Bennink, JR Yewdell, JW AF Hickman, Heather D. Takeda, Kazuyo Skon, Cara N. Murray, Faith R. Hensley, Scott E. Loomis, Joshua Barber, Glen N. Bennink, Jack R. Yewdell, Jonathan W. TI Direct priming of antiviral CD8(+) T cells in the peripheral interfollicular region of lymph nodes SO NATURE IMMUNOLOGY LA English DT Article ID CD8-ALPHA(+) DENDRITIC CELLS; HIGH ENDOTHELIAL VENULES; IN-VIVO; B-CELLS; ANTIGEN PRESENTATION; SUBCAPSULAR SINUS; IMMUNE-RESPONSE; VIRUS INFECTION; ACTIVATION; TRAFFICKING AB It is uncertain how antiviral lymphocytes are activated in draining lymph nodes, the site where adaptive immune responses are initiated. Here, using intravital microscopy we show that after infection of mice with vaccinia virus (a large DNA virus) or vesicular stomatitis virus (a small RNA virus), virions drained to the lymph node and infected cells residing just beneath the subcapsular sinus. Naive CD8(+) T cells rapidly migrated to infected cells in the peripheral interfollicular region and then formed tight interactions with dendritic cells, leading to complete T cell activation. Thus, antigen presentation at the lymph node periphery, not at lymphocyte exit sites in deeper lymph node venules, as dogma dictates, has a dominant function in antiviral CD8(+) T cell activation. C1 [Hickman, Heather D.; Takeda, Kazuyo; Skon, Cara N.; Murray, Faith R.; Hensley, Scott E.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. [Loomis, Joshua; Barber, Glen N.] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Loomis, Joshua; Barber, Glen N.] Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jyewdell@mail.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS NR 41 TC 136 Z9 137 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2008 VL 9 IS 2 BP 155 EP 165 DI 10.1038/ni1557 PG 11 WC Immunology SC Immunology GA 253FB UT WOS:000252503000012 PM 18193049 ER PT J AU Barrett, T Edgar, R AF Barrett, Tanya Edgar, Ron TI Reannotation of array probes at NCBI's GEO database SO NATURE METHODS LA English DT Letter ID TO-GENE ANNOTATIONS; INCONSISTENCIES; TIME C1 [Barrett, Tanya; Edgar, Ron] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Barrett, T (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. EM edgar@ncbi.nlm.nih.gov NR 5 TC 10 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2008 VL 5 IS 2 BP 117 EP 117 DI 10.1038/nmeth0208-117b PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 256SR UT WOS:000252750700003 PM 18235428 ER PT J AU Manley, S Gillette, JM Patterson, GH Shroff, H Hess, HF Betzig, E Lippincott-Schwartz, J AF Manley, Suliana Gillette, Jennifer M. Patterson, George H. Shroff, Hari Hess, Harald F. Betzig, Eric Lippincott-Schwartz, Jennifer TI High-density mapping of single-molecule trajectories with photoactivated localization microscopy SO NATURE METHODS LA English DT Article ID PLASMA-MEMBRANE; PARTICLE TRACKING; CELLS; DIFFUSION; MICRODOMAINS; PROTEINS; SURFACE; HIV-1 AB We combined photoactivated localization microscopy (PALM) with live-cell single-particle tracking to create a new method termed sptPALM. We created spatially resolved maps of single-molecule motions by imaging the membrane proteins Gag and VSVG, and obtained several orders of magnitude more trajectories per cell than traditional single-particle tracking enables. By probing distinct subsets of molecules, sptPALM can provide insight into the origins of spatial and temporal heterogeneities in membranes. C1 [Manley, Suliana; Gillette, Jennifer M.; Patterson, George H.; Lippincott-Schwartz, Jennifer] NICHHD, NIH, Bethesda, MD 20892 USA. [Shroff, Hari; Hess, Harald F.; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov RI Manley, Suliana/D-3818-2012; Shroff, Hari/E-7247-2016 OI Manley, Suliana/0000-0002-4755-4778; Shroff, Hari/0000-0003-3613-8215 FU Intramural NIH HHS NR 14 TC 454 Z9 460 U1 24 U2 182 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2008 VL 5 IS 2 BP 155 EP 157 DI 10.1038/NMETH.1176 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 256SR UT WOS:000252750700015 PM 18193054 ER PT J AU Koenigs, M Huey, ED Raymont, V Cheon, B Solomon, J Wassermann, EM Grafman, J AF Koenigs, Michael Huey, Edward D. Raymont, Vanessa Cheon, Bobby Solomon, Jeffrey Wassermann, Eric M. Grafman, Jordan TI Focal brain damage protects against post-traumatic stress disorder in combat veterans SO NATURE NEUROSCIENCE LA English DT Article ID MEDIAL PREFRONTAL CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; DOUBLE-BLIND; AMYGDALA; PTSD; VIETNAM; ACTIVATION; DEPRESSION; SOFTWARE; MEMORY AB Post-traumatic stress disorder ( PTSD) is an often debilitating mental illness that is characterized by recurrent distressing memories of traumatic events. PTSD is associated with hypoactivity in the ventromedial prefrontal cortex ( vmPFC), hyperactivity in the amygdala and reduced volume in the hippocampus, but it is unknown whether these neuroimaging findings reflect the underlying cause or a secondary effect of the disorder. To investigate the causal contribution of specific brain areas to PTSD symptoms, we studied a unique sample of Vietnam War veterans who suffered brain injury and emotionally traumatic events. We found a substantially reduced occurrence of PTSD among those individuals with damage to one of two regions of the brain: the vmPFC and an anterior temporal area that included the amygdala. These results suggest that the vmPFC and amygdala are critically involved in the pathogenesis of PTSD. C1 [Koenigs, Michael; Huey, Edward D.; Raymont, Vanessa; Wassermann, Eric M.; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Raymont, Vanessa; Cheon, Bobby] Natl Naval Med Ctr, Henry M Jackson Fdn, Vietnam Head Injury Study, Bethesda, MD 20889 USA. [Solomon, Jeffrey] Med Numer, Germantown, MD 20876 USA. RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, US Natl Inst Hlth, 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457; Koenigs, Michael/0000-0002-5799-4881 FU Intramural NIH HHS [Z01 NS002792-19, Z01 NS003024-01] NR 38 TC 118 Z9 125 U1 5 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 2008 VL 11 IS 2 BP 232 EP 237 DI 10.1038/nn2032 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 256FC UT WOS:000252712100018 PM 18157125 ER PT J AU Paoloni, M Khanna, C AF Paoloni, Melissa Khanna, Chand TI Science and society - Translation of new cancer treatments from pet dogs to humans SO NATURE REVIEWS CANCER LA English DT Review ID MAST-CELL TUMORS; ENCAPSULATED MURAMYL TRIPEPTIDE; COLONY-STIMULATING FACTOR; GASTROINTESTINAL STROMAL TUMORS; SPONTANEOUSLY OCCURRING TUMORS; PHASE-I; MALIGNANT-MELANOMA; C-KIT; INTERLEUKIN-2 LIPOSOMES; CANINE LYMPHOSARCOMA AB Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. the value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics. C1 [Paoloni, Melissa; Khanna, Chand] NCI, Ctr Canc Res, Comparat Oncol Program, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Ctr Canc Res, Comparat Oncol Program, 37 Convent Dr,Room 2144, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov NR 111 TC 266 Z9 269 U1 2 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD FEB PY 2008 VL 8 IS 2 BP 147 EP 156 DI 10.1038/nrc2273 PG 11 WC Oncology SC Oncology GA 255RA UT WOS:000252673900016 PM 18202698 ER PT J AU Lundberg, JO Weitzberg, E Gladwin, MT AF Lundberg, Jon O. Weitzberg, Eddie Gladwin, Mark T. TI The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID K-ATP CHANNELS; ISCHEMIA-REPERFUSION INJURY; DECREASES INFARCTION SIZE; URINARY-TRACT-INFECTIONS; MITOCHONDRIAL COMPLEX-I; CORONARY HEART-DISEASE; REGIONAL BLOOD-FLOW; DIETARY NITRATE; ACIDIFIED NITRITE; XANTHINE OXIDOREDUCTASE AB The inorganic anions nitrate (NO3-) and nitrite (NO2-) were previously thought to be inert end products of endogenous nitric oxide (NO) metabolism. However, recent studies show that these supposedly inert anions can be recycled in vivo to form NO, representing an important alternative source of NO to the classical L-arginine-NO-synthase pathway, in particular in hypoxic states. This Review discusses the emerging important biological functions of the nitrate-nitrite-NO pathway, and highlights studies that implicate the therapeutic potential of nitrate and nitrite in conditions such as myocardial infarction, stroke, systemic and pulmonary hypertension, and gastric ulceration. C1 [Lundberg, Jon O.; Weitzberg, Eddie] Karolinska Inst, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care, SE-17177 Stockholm, Sweden. [Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Gladwin, Mark T.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Lundberg, JO (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care, SE-17177 Stockholm, Sweden. EM jon.lundberg@ki.se; eddie.weitzberg@ki.se; mgladwin@mail.nih.gov NR 134 TC 842 Z9 856 U1 25 U2 189 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 FEB PY 2008 VL 7 IS 2 BP 156 EP 167 DI 10.1038/nrd2466 PG 12 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 257NT UT WOS:000252806500014 PM 18167491 ER PT J AU Hedestam, GBK Fouchier, RAM Phogat, S Burton, DR Sodroski, J Wyatt, RT AF Hedestam, Gunilla B. Karlsson Fouchier, Ron A. M. Phogat, Sanjay Burton, Dennis R. Sodroski, Joseph Wyatt, Richard T. TI The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; CORECEPTOR BINDING-SITE; X-RAY CRYSTALLOGRAPHY; T-CELL RESPONSES; RECEPTOR-BINDING; PROTECTIVE IMMUNITY; PANDEMIC INFLUENZA; VACCINE DESIGN AB The ability to elicit broadly neutralizing antibody responses against HIV-1 is a crucial goal for a prophylactic HIV-1 vaccine. Here, we discuss the difficulties of achieving broad HIV-1 neutralization in the context of both the effective annual human influenza virus vaccine and the need to develop a pandemic influenza vaccine. Immunogen-design strategies are underway to target functionally conserved regions of the HIV-1 envelope glycoproteins, and similar strategies might be applicable to pandemic influenza virus vaccine development. Efforts to develop broadly neutralizing vaccines against either HIV-1 or influenza virus might establish a paradigm for future vaccines against highly variable pathogens. C1 [Phogat, Sanjay; Wyatt, Richard T.] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm 17177, Sweden. [Hedestam, Gunilla B. Karlsson] Swedish Inst Infect Dis Control, Solna 17182, Sweden. [Fouchier, Ron A. M.] Erasmus MC, Natl Influenza Ctr, NL-3015GE Rotterdam, Netherlands. [Fouchier, Ron A. M.] Erasmus MC, Dept Virol, NL-3015GE Rotterdam, Netherlands. [Burton, Dennis R.] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Div AIDS, Dana Farber Canc Inst,Dept Cancer Immunol & AIDS, Boston, MA 02115 USA. RP Wyatt, RT (reprint author), NIAID, NIH, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov RI Fouchier, Ron/A-1911-2014 OI Fouchier, Ron/0000-0001-8095-2869 NR 134 TC 169 Z9 170 U1 3 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD FEB PY 2008 VL 6 IS 2 BP 143 EP 155 DI 10.1038/nrmicro1819 PG 13 WC Microbiology SC Microbiology GA 252DZ UT WOS:000252426700013 ER PT J AU Murphy, DL Lesch, KP AF Murphy, Dennis L. Lesch, Klaus-Peter TI Targeting the murine serotonin transporter: insights into human neurobiology SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID KNOCK-OUT MICE; OBSESSIVE-COMPULSIVE DISORDER; ENTERIC NERVOUS-SYSTEM; 5-HT TRANSPORTER; MAJOR DEPRESSION; DEFICIENT MICE; PROMOTER POLYMORPHISM; NEUROTRANSMITTER TRANSPORTERS; NEUROENDOCRINE RESPONSES; PULMONARY-HYPERTENSION AB Mutations resulting in reduced or completely abrogated serotonin-transporter (SERT) function in mice have led to the identification of more than 50 different phenotypic changes, ranging from increased anxiety and stress-related behaviours to gut dysfunction, bone weakness and late-onset obesity with metabolic syndrome. These multiple effects, which can be amplified by gene-environment and gene-gene interactions, are primarily attributable to altered intracellular and extracellular serotonin concentrations during development and adulthood. Much of the human data relating to altered expression of the gene that encodes SERT are based on genetic-association findings or correlations and are therefore not as robust as the experimental mouse results. Nevertheless, SERT-function-modifying gene variants in humans apparently produce many phenotypes that are similar to those that manifest themselves in mice. C1 [Murphy, Dennis L.] NIMH, NIH, Lab Clin Sci Intramural Res Program, Bethesda, MD 20892 USA. [Lesch, Klaus-Peter] Univ Wurzburg, Dept Psychiat & Psychotherapy, D-97080 Wurzburg, Germany. RP Murphy, DL (reprint author), NIMH, NIH, Lab Clin Sci Intramural Res Program, Bethesda, MD 20892 USA. EM DennisMurphy@mail.nih.gov; kplesch@mail.uni-wuerzburg.de RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 132 TC 246 Z9 251 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD FEB PY 2008 VL 9 IS 2 BP 85 EP 96 DI 10.1038/nrn2284 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 253FE UT WOS:000252503300011 PM 18209729 ER PT J AU Kouzine, F Sanford, S Elisha-Feil, Z Levens, D AF Kouzine, Fedor Sanford, Suzanne Elisha-Feil, Zichrini Levens, David TI The functional response of upstream DNA to dynamic supercoiling in vivo SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID C-MYC EXPRESSION; SHOCK GENE LOCUS; TOPOISOMERASE-I; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; CHROMATIN-STRUCTURE; HISTONE RELEASE; BETA-LAPACHONE; RNA-POLYMERASE; HUMAN-CELLS AB Because RNA polymerase is a powerful motor, transmission of transcription-generated forces might directly alter DNA structure, chromatin or gene activity in mammalian cells. Here we show that transcription-generated supercoils streaming dynamically from active promoters have considerable consequences for DNA structure and function in cells. Using a tamoxifen-activatable Cre recombinase to excise a test segment of chromatin positioned between divergently transcribed metallothionein-IIa promoters, we found the degree of dynamic supercoiling to increase as transcription intensified, and it was very sensitive to the specific arrangement of promoters and cis elements. Using psoralen as an in vivo probe confirmed that, during transcription, sufficient supercoiling is produced to enable transitions to conformations other than B-DNA in elements such as the human MYC far upstream element (FUSE), which in turn recruit structure-sensitive regulatory proteins, such as FUSE Binding Protein (FBP) and FBP-Interacting Repressor (FIR). These results indicate that mechanical stresses, constrained by architectural features of DNA and chromatin, may broadly contribute to gene regulation. C1 [Kouzine, Fedor; Sanford, Suzanne; Elisha-Feil, Zichrini; Levens, David] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Levens, D (reprint author), NCI, Pathol Lab, 10 Ctr Dr,Bldg 10,Room 2N106, Bethesda, MD 20892 USA. EM levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU Intramural NIH HHS NR 60 TC 143 Z9 144 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2008 VL 15 IS 2 BP 146 EP 154 DI 10.1038/nsmb.1372 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 259IG UT WOS:000252932400014 PM 18193062 ER PT J AU Li, J Yin, CY Okamoto, H Balgley, BM Lee, CS Yuan, K Ikejiri, B Glasker, S Vortmeyer, AO Oldfield, EH Weil, RJ Zhuang, ZP AF Li, Jie Yin, Chunyue Okamoto, Hiroaki Balgley, Brian M. Lee, Cheng S. Yuan, Kristy Ikejiri, Barbara Glasker, Sven Vortmeyer, Alexander O. Oldfield, Edward H. Weil, Robert J. Zhuang, Zhengping TI Identification of a novel proliferation-related protein, WHSC1 4a, in human gliomas SO NEURO-ONCOLOGY LA English DT Article DE expression; glioma; proliferation proteomic; profiling; WHSC1 ID SYNDROME CRITICAL REGION; MULTIPLE-MYELOMA; EXPRESSION; CANCER; PATTERNS; GENE AB Dynamic changes in the expression of multiple genes appear to be common features that distinguish transformed cells from their normal counterparts. We compared the proteomic profiles of four glioblastoma multiforme (GBM) tissue samples and four normal brain cortex samples to examine the molecular basis of gliomagenesis. Trypsin-digested protein samples were separated by capillary isoelectric focusing with nano-reversed-phase liquid chromatography and were profiled by mass spectrometric sequencing. Wolf-Hirschhorn syndrome candidate 1 (WHSC1), along with 103 other proteins, was found only in the GBM proteomes. Western blot and immunohistochemistry verified our proteomic findings and demonstrated that 30-kDa WHSC1 expression increases with ascending tumor proliferation activity. RNA interference could suppress glioma cell growth by blocking WHSC1 expression. Our novel findings encourage the application of proteomic techniques in cancer research. C1 [Li, Jie; Yin, Chunyue; Okamoto, Hiroaki; Yuan, Kristy; Ikejiri, Barbara; Glasker, Sven; Vortmeyer, Alexander O.; Oldfield, Edward H.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Balgley, Brian M.; Lee, Cheng S.] Calibrant Biosyst, Gaithersburg, MD USA. [Weil, Robert J.] Cleveland Clin, Dept Neurosurg, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. RP Zhuang, ZP (reprint author), Bldg 10,Roon 5D37,10 Ctr Dr, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov OI Balgley, Brian/0000-0002-3509-4567 FU Intramural NIH HHS NR 14 TC 18 Z9 20 U1 0 U2 3 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD FEB PY 2008 VL 10 IS 1 BP 45 EP 51 DI 10.1215/15228517-2007-036 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 259WI UT WOS:000252971200006 PM 18182627 ER PT J AU Schneider, AB Ron, E Lubin, J Stovall, M Shore-Freedman, E Tolentino, J Collins, BJ AF Schneider, Arthur B. Ron, Elaine Lubin, Jay Stovall, Marilyn Shore-Freedman, Eileen Tolentino, Jocelyn Collins, Barbara J. TI Acoustic neuromas following childhood radiation treatment for benign conditions of the head and neck SO NEURO-ONCOLOGY LA English DT Article DE acoustic neuromas; dose-response relationships; radiation-related neoplasms ID DOSE-RESPONSE RELATIONSHIPS; CENTRAL-NERVOUS-SYSTEM; SALIVARY-GLAND TUMORS; THYROID-CANCER; RISK-FACTORS; IRRADIATION; NEOPLASMS; SCHWANNOMAS; SURVIVORS; RADIOTHERAPY AB Childhood radiation exposure has been associated with an increased risk for developing several neoplasms, particularly benign and malignant thyroid tumors, but little is known about the risk of developing acoustic neuromas. The aim of this study was to confirm whether there is a risk for acoustic neuromas and, if so, to determine its magnitude and duration. We investigated the time trend and dose-response relationships for acoustic neuroma incidence in a cohort of 3,112 individuals who were irradiated as children between 1939 and 1962. Most of the patients were treated to reduce the size of their tonsils and adenoids and received substantial radiation exposure to the cerebellopontine angle, the site of acoustic neuromas. Forty-three patients developed benign acoustic neuromas, forty of them surgically resected, far in excess of what might be expected from data derived from brain tumor registries. The mean dose (+/- SD) to the cerebellopontine angle was 4.6 +/- 1.9 Gy. The relative risk per Gy was 1.14 (95% confidence interval 1.0-1.3). The earliest case occurred 20.4 years after exposure and the latest 55 years after exposure (mean 38.3 +/- 10.1 years). Our study provides support for an association between acoustic neuromas and childhood radiation exposure. Although acoustic neuromas are usually benign and often asymptomatic, many cause significant morbidity. Following childhood radiation exposure, they appear after a long latency and continue to occur many decades afterward. Any symptoms of an acoustic neuroma in a patient with a history of radiation to the head and neck area should be investigated carefully, and the threshold for employing imaging should be lowered. C1 [Schneider, Arthur B.; Shore-Freedman, Eileen; Tolentino, Jocelyn; Collins, Barbara J.] Univ Illinois, Coll Med, Sect Endocrinol & Metab, Chicago, IL USA. [Ron, Elaine; Lubin, Jay] NCI, Div Epidemiol & Genet, Rockville, MD USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. RP Schneider, AB (reprint author), Univ Illinois, Coll Med, Sect Endocrinol Diab & Metab MC 640, 1819 W Polk St, Chicago, IL 60612 USA. EM abschnei@uic.edu OI Shore-Freedman, Eileen/0000-0001-6194-1814 FU Intramural NIH HHS; NCI NIH HHS [N01-CP-85604, N01-CP-95614, CA-21518] NR 31 TC 12 Z9 12 U1 1 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD FEB PY 2008 VL 10 IS 1 BP 73 EP 78 DI 10.1215/15228517-2007-047 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 259WI UT WOS:000252971200009 PM 18079359 ER PT J AU Floel, A Garraux, G Xu, B Breitenstein, C Knecht, S Herscovitch, P Cohen, LG AF Floel, A. Garraux, G. Xu, B. Breitenstein, C. Knecht, S. Herscovitch, P. Cohen, L. G. TI Levodopa increases memory encoding and dopamine release in the striatum in the elderly SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; motor; memory formation; positron emission tomography; neuropharmacology; neurotransmitter; neurorehabilitation ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; HUMAN MOTOR CORTEX; USE-DEPENDENT PLASTICITY; PARKINSONS-DISEASE; PREFRONTAL CORTEX; SYNAPTIC PLASTICITY; BASAL GANGLIA; CLINICAL-APPLICATION; CONTINUOUS-INFUSION AB Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized that levodopa would (a) ameliorate aging-dependent deficits in motor memory formation, and (b) increase dopamine availability at the dopamine type 2-like (D2) receptor during training in task-relevant brain structures. The effects of training plus levodopa (100 mg, plus 25 mg carbidopa) on motor memory formation and striatal dopamine availability were measured with [C-11]raclopride (RAC) positron emission tomography (PET). We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal caudate nucleus. Motor memory formation during training correlated with the increase of dopamine release in the caudate nucleus. These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores, actively engaged in phasic dopamine release during motor training. (C) 2006 Elsevier Inc. All rights reserved. C1 [Floel, A.; Garraux, G.; Xu, B.; Cohen, L. G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. [Floel, A.; Breitenstein, C.; Knecht, S.] Univ Munster, Dept Neurol, D-48129 Munster, Germany. [Floel, A.; Breitenstein, C.; Knecht, S.] Univ Munster, IMF Munster, Munster, Germany. [Herscovitch, P.] NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Floel, A (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM floeel@uni-muenster.de RI Garraux, Gaetan/G-9050-2011; Floel, Agnes/A-9426-2017; OI Knecht, Stefan/0000-0003-1056-9228 FU Intramural NIH HHS [Z01 NS002978-09] NR 79 TC 32 Z9 32 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2008 VL 29 IS 2 BP 267 EP 279 DI 10.1016/j.neurobiolaging.2006.10.009 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 254AX UT WOS:000252559800011 PM 17098331 ER PT J AU Chen, XH Johnson, GS Schnabel, RD Taylor, JF Johnson, GC Parker, HG Patterson, EE Katz, ML Awano, T Khan, S O'Brien, DP AF Chen, Xuhua Johnson, Gary S. Schnabel, Robert D. Taylor, Jeremy F. Johnson, Gayle C. Parker, Heidi G. Patterson, Edward E. Katz, Martin L. Awano, Tomoyuki Khan, Shahwanaz O'Brien, Dennis P. TI A neonatal encephalopathy with seizures in standard poodle dogs with a missense mutation in the canine ortholog of ATF2 SO NEUROGENETICS LA English DT Article DE ATF2; activating transcription factor 2; neonatal encephalopathy; seizures; dogs ID ACTIVATING TRANSCRIPTION FACTOR-2; JUN NH2-TERMINAL KINASE; CYCLIN-A PROMOTER; NEWBORN ENCEPHALOPATHY; GENOTYPE PROBABILITIES; EFFICIENT COMPUTATION; PROTEIN-KINASES; RISK-FACTORS; PHOSPHORYLATION; GENE AB Neonatal encephalopathy with seizures (NEWS) is a previously undescribed autosomal recessive disease of standard poodle puppies. Affected puppies are small and weak at birth. Many die in their first week of life. Those surviving past 1 week develop ataxia, a whole-body tremor, and, by 4 to 6 weeks of age, severe generalized clonic-tonic seizures. None have survived to 7 weeks of age. Cerebella from affected puppies were reduced in size and often contained dysplastic foci consisting of clusters of intermixed granule and Purkinje neurons. We used deoxyribonucleic acid samples from related standard poodles to map the NEWS locus to a 2.87-Mb segment of CFA36, which contains the canine ortholog of ATF2. This gene encodes activating transcription factor 2 (ATF-2), which participates in the cellular responses to a wide variety of stimuli. We amplified and sequenced all coding regions of canine ATF2 from a NEWS-affected puppy and identified a T > G transversion that predicts a methionine-to-arginine missense mutation at amino acid position 51. Methionine-51 lies within a hydrophobic docking site for mitogen-activated protein kinases that activate ATF-2 so the arginine substitution is likely to interfere with ATF-2 activation. All 20 NEWS-affected puppies in the standard poodle family were homozygous for the mutant G allele. The 58 clinically normal family members were either G/T heterozygotes or homozygous for the ancestral T allele. There are no previous reports of spontaneous ATF2 mutations in people or animals; however, atf2-knockout mice have cerebellar lesions that are similar to those in puppies with NEWS. C1 [Chen, Xuhua; Johnson, Gary S.; Johnson, Gayle C.; Katz, Martin L.; Awano, Tomoyuki; Khan, Shahwanaz] Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. [Schnabel, Robert D.; Taylor, Jeremy F.] Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA. [Parker, Heidi G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Patterson, Edward E.] Univ Minnesota, Dept Vet Clin Sci, St Paul, MN 55108 USA. [Katz, Martin L.] Univ Missouri, Mason Eye Inst, Columbia, MO 65211 USA. [O'Brien, Dennis P.] Univ Missouri, Dept Vet Med & Surg, Columbia, MO 65211 USA. RP Johnson, GS (reprint author), Univ Missouri, Dept Vet Pathobiol, 322 Connaway Hall, Columbia, MO 65211 USA. EM johnsongs@missouri.edu OI Schnabel, Robert/0000-0001-5018-7641 NR 40 TC 9 Z9 9 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD FEB PY 2008 VL 9 IS 1 BP 41 EP 49 DI 10.1007/s10048-007-0112-2 PG 9 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 255EC UT WOS:000252638800005 PM 18074159 ER PT J AU Goense, JBM Ku, SP Merkle, H Tolias, AS Logothetis, NK AF Goense, Jozien B. M. Ku, Shih-Pi Merkle, Hellmut Tolias, Andreas S. Logothetis, Nikos K. TI fMRI of the temporal lobe of the awake monkey at 7 T SO NEUROIMAGE LA English DT Article ID IMAGE DISTORTION CORRECTION; HUMAN BRAIN ACTIVATION; ECHO-PLANAR IMAGES; FUNCTIONAL MRI; HIGH-RESOLUTION; SPIN-ECHO; MAGNETIC-FIELD; LAMINAR SPECIFICITY; AUDITORY-CORTEX; MACAQUE MONKEY AB Increasingly 7 T scanners are used for fMRI of humans and non-human primates, promising improvements in signal-to-noise, spatial resolution and specificity. A disadvantage of fMRI at 7 T, but already at 3 T, is that susceptibility artifacts from air-filled cavities like the ear canal and nasal cavity cause signal loss and distortion. This limits the applicability of fMRI in these areas, thereby limiting study of these areas, but it also limits study of processes that span large-scale cortical networks or the entire brain. Our goal is to study the inferior temporal (IT) lobe in awake monkeys because of its importance in object perception and recognition, but the functional signal is degraded by strong susceptibility gradients. To allow fMRI of this region, we used an optimized SE-EPI, which recovers signal lost with GE-EPI and we corrected for susceptibility-induced image distortion. SE-EPI has the added advantage that, in contrast to GE-EPI, where the functional signal derives to a large extent from veins, the SE-EPI signal arises from the microvasculature, and hence it better represents the neural activation. We show fMRI at 7 T of the entire visual pathway in the awake primate with robust and widespread activation in all ventral areas of the brain, including areas adjacent to the ear canal. This allows fMRI of areas that normally suffer from artifact and thus more reliable whole-brain studies. (c) 2007 Elsevier Inc. All rights reserved. C1 [Goense, Jozien B. M.; Ku, Shih-Pi; Tolias, Andreas S.; Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. [Merkle, Hellmut] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Logothetis, Nikos K.] Univ Manchester, Manchester, Lancs, England. RP Goense, JBM (reprint author), Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, Spemannstr 38, D-72076 Tubingen, Germany. EM jozien.goense@tuebingen.mpg.de FU Intramural NIH HHS NR 74 TC 20 Z9 20 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2008 VL 39 IS 3 BP 1081 EP 1093 DI 10.1016/j.neuroimage.2007.09.038 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 255XN UT WOS:000252691800017 PM 18024083 ER PT J AU Volkow, ND Wang, GJ Telang, F Fowler, JS Logan, J Childress, AR Jayne, M Wong, C Ma, YM AF Volkow, Nora D. Wang, Gene-Jack Telang, Frank Fowler, Joanna S. Logan, Jean Childress, Anna-Rose Jayne, Millard Wong, Christopher Ma, Yeming TI Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues SO NEUROIMAGE LA English DT Article DE PET imaging; raclopride; addiction; caudate; putamen; conditioned responses; D2 receptors ID VENTRAL TEGMENTAL AREA; HUMAN BRAIN; NUCLEUS-ACCUMBENS; SEEKING BEHAVIOR; DORSAL STRIATUM; EXTRACELLULAR DOPAMINE; INTRAVENOUS COCAINE; PREFRONTAL CORTEX; C-11 RACLOPRIDE; BED NUCLEUS AB Imaging studies have shown an association between dopamine increases in striatum and cue induced craving in cocaine abusers. However, the extent to which dopamine increases reflect a primary rather than a secondary response to the cues remains unclear. Here we evaluated the extent to which dopamine increases by themselves can induce craving in cocaine abusers. Using PET and [C-11]raclopride (D2 receptor radioligand sensitive to competition with endogenous dopamine) we show that in cocaine abusers (n=20) oral methylphenidate (20 mg), which significantly increased dopamine in striatum, did not induce craving unless subjects were concomitantly exposed to cocaine cues (video scenes of subjects self-administering cocaine). This suggests that dopamine increases associated with conditioned cues are not primary responses but reflect downstream stimulation of dopamine cells (presumably glutamatergic afferents from prefrontal cortex and/or amygdala). Inasmuch as afferent stimulation of dopamine neurons results in phasic cell firing these findings suggest that "fast" dopamine increases, in contrast to the "slow" dopamine increases as achieved when using oral methylphenidate (mimicking tonic dopamine cell firing), are required for cues to trigger craving. The fact that methylphenidate induced craving only when given with the cocaine cues highlights the context dependency of methylphenidate's effects and suggests that its use for the treatment of ADHD subjects with co-morbid drug abuse should not increase craving. Published by Elsevier Inc. C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Volkow, Nora D.; Telang, Frank; Jayne, Millard; Ma, Yeming] NIAAA, Bethesda, MD 20892 USA. [Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Childress, Anna-Rose] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Childress, Anna-Rose] Philadelphia Dept Vet Affairs, Philadelphia, PA 19104 USA. [Fowler, Joanna S.; Logan, Jean; Wong, Christopher] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov OI Logan, Jean/0000-0002-6993-9994 FU Intramural NIH HHS [Z01 DA*00001-05]; NCRR NIH HHS [M01 RR010710, M01RR10710]; NIDA NIH HHS [DA06278-15, R01 DA006278] NR 60 TC 92 Z9 93 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2008 VL 39 IS 3 BP 1266 EP 1273 DI 10.1016/j.neuroimage.2007.09.059 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 255XN UT WOS:000252691800032 PM 18024160 ER PT J AU Imaizumi, M Briard, E Zoghbi, SS Gourley, JP Hong, J Fujimura, Y Pike, VW Innis, RB Fujita, M AF Imaizumi, Masao Briard, Emmanuelle Zoghbi, Sami S. Gourley, Jonathan P. Hong, Jinsoo Fujimura, Yota Pike, Victor W. Innis, Robert B. Fujita, Masahiro TI Brain and whole-body imaging in nonhuman primates of [C-11]PBR28, a promising PET radioligand for peripheral benzodiazepine receptors SO NEUROIMAGE LA English DT Article ID IN-VIVO; AUTORADIOGRAPHIC LOCALIZATION; BINDING; NOMENCLATURE; ACTIVATION; DAA1106; LIGAND; SITES; MODEL; RAT AB Objectives: Peripheral benzodiazepine receptors (PBRs) are upregulated on activated microglia and are thereby biomarkers of neuroinflammation. We developed a PET ligand with an aryloxyanilide structure, [O-methyl-C-11]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine ([C-11]PBR28), to image PBRs. The objectives of the current study were to evaluate kinetics of brain uptake, and the influence of the peripheral binding on the arterial input function in rhesus monkey. Methods: Brain (baseline: n=6, blocking: n=1) and whole-body PET imaging (baseline: n=3, blocking: n=1) of [C-11]PBR28 were performed with the measurement of radio metabolite-corrected arterial input function in all brain and two whole body scans. Results: Saturating doses of nonradioactive PBR ligands markedly increased [C-11]PBR28 in plasma (similar to 400% increase) and brain (similar to 200%) at 2 min by displacing radioligand from PBRs in peripheral organs. Brain uptake of radioactivity peaked in baseline scans at similar to 40 min after injection of [C-11]PBR28 and was high (similar to 300% standardized uptake value). The images showed no receptor-free region that could be used for reference tissue analysis. Thus, quantitation of receptor density required measurement of parent radioligand in arterial plasma. Nondisplaceable uptake was estimated from the blocked scans and was only similar to 5% of total distribution volume measured under baseline conditions. Distribution volume of [C-11]PBR28 was stably determined within 110 min of scanning. Conclusions: Regional brain uptake of [C-11]PBR28 in monkey could be quantified as a value proportional to the density of receptors-namely, as equilibrium distribution volume. [C-11]PBR28 had high levels of specific binding in brain and should provide a sensitive measure of changes in PBRs. Published by Elsevier Inc. C1 [Imaizumi, Masao; Briard, Emmanuelle; Zoghbi, Sami S.; Gourley, Jonathan P.; Hong, Jinsoo; Fujimura, Yota; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Natl Inst Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Natl Inst Hlth, Mol Imaging Branch, Bldg 31,Rm B2B37,31 Ctr Dr MSC,2035, Bethesda, MD 20892 USA. EM fujitam@mail.nih.gov FU Intramural NIH HHS [Z01 MH002795-06]; NIMH NIH HHS [N01MH32004, Z01 MH002795, Z01-MH-002795-04] NR 33 TC 65 Z9 65 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2008 VL 39 IS 3 BP 1289 EP 1298 DI 10.1016/j.neuroimage.2007.09.063 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 255XN UT WOS:000252691800034 PM 18024084 ER PT J AU Chang, SE Erickson, KI Ambrose, NG Hasegawa-Johnson, MA Ludlow, CL AF Chang, Soo-Eun Erickson, Kirk I. Ambrose, Nicoline G. Hasegawa-Johnson, Mark A. Ludlow, Christy L. TI Brain anatomy differences in childhood stuttering SO NEUROIMAGE LA English DT Article DE stuttering; gray matter; white matter fiber tracts; diffusion tensor imaging; voxel-based morphometry; speech disorders; fractional anisotropy ID VOXEL-BASED MORPHOMETRY; DIFFUSION-TENSOR MRI; PLANUM TEMPORALE; CEREBRAL DOMINANCE; FLUENT SPEAKERS; GRAY-MATTER; LANGUAGE; SPEECH; CHILDREN; ADULTS AB Stuttering is a developmental speech disorder that occurs in 5% of children with spontaneous remission in approximately 70% of cases. Previous imaging studies in adults with persistent stuttering found left white matter deficiencies and reversed right-left asymmetries compared to fluent controls. We hypothesized that similar differences might be present indicating brain development differences in children at risk of stuttering. Optimized voxel-based morphometry compared gray matter volume (GMV) and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts in 3 groups: children with persistent stuttering, children recovered from stuttering, and fluent peers. Both the persistent stuttering and recovered groups had reduced GMV from normal in speech-relevant regions: the left inferior frontal gyros and bilateral temporal regions. Reduced FA was found in the left white matter tracts underlying the motor regions for face and larynx in the persistent stuttering group. Contrary to previous findings in adults who stutter, no increases were found in the right hemisphere speech regions in stuttering or recovered children and no differences in right-left asymmetries. Instead, a risk for childhood stuttering was associated with deficiencies in left gray matter volume while reduced white matter integrity in the left hemisphere speech system was associated with persistent stuttering. Anatomical increases in right hemisphere structures previously found in adults who stutter may have resulted from a lifetime of stuttering. These findings point to the importance of considering the role of neuroplasticity during development when studying persistent forms of developmental disorders in adults. (c) 2007 Elsevier Inc. All rights reserved. C1 [Chang, Soo-Eun; Ludlow, Christy L.] Nat Inst Neurol Disorders & Stroke, Natl Inst Hlth, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. [Erickson, Kirk I.] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. [Erickson, Kirk I.; Hasegawa-Johnson, Mark A.] Bekman Inst Adv Sci & Technol, Urbana, IL USA. [Ambrose, Nicoline G.] Univ Illinois, Dept Speech & Hearing Sci, Urbana, IL 61801 USA. [Hasegawa-Johnson, Mark A.] Univ Illinois, Dept Elect & Comp Engn, Champaign, IL 61820 USA. RP Chang, SE (reprint author), Nat Inst Neurol Disorders & Stroke, Natl Inst Hlth, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. EM changsoo@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [NIH0012332320, Z01 NS002980-09]; NIDCD NIH HHS [R01 DC005210, R01 DC05210] NR 56 TC 108 Z9 112 U1 2 U2 34 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2008 VL 39 IS 3 BP 1333 EP 1344 DI 10.1016/j.neuroimage.2007.09.067 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 255XN UT WOS:000252691800039 PM 18023366 ER PT J AU Bruzzo, AA Gesierich, B Santi, M Tassinari, CA Birbaumer, N Rubboli, G AF Bruzzo, Angela A. Gesierich, Benno Santi, Maurizio Tassinari, Carlo Alberto Birbaumer, Niels Rubboli, Guido TI Permutation entropy to detect vigilance changes and preictal states from scalp EEG in epileptic patients. A preliminary study SO NEUROLOGICAL SCIENCES LA English DT Article DE drug-resistant focal epilepsy; permutation entropy; preictal phase; scalp-electroencephalogram; seizure prediction; state of vigilance ID SEIZURE ANTICIPATION; PREDICTABILITY; PREDICTION; EPILEPSIES; RECORDINGS; SERIES; LONG AB Permutation entropy (PE) was recently introduced as a very fast and robust algorithm to detect dynamic complexity changes in time series. It was also suggested as a useful screening algorithm for epileptic events in EEG data. In the present work, we tested its efficacy on scalp EEG data recorded from three epileptic patients. With a receiver operating characteristics (ROC) analysis, we evaluated the separability of amplitude distributions of PE resulting from preictal and interictal phases. Moreover, the dependency of PE on vigilance state was tested by correlation coefficients. A good separability of interictal and preictal phase was found, nevertheless PE was shown to be sensitive to changes in vigilance state. The changes of PE during the preictal phase and at seizure onset coincided with changes in vigilance state, restricting its possible use for seizure prediction on scalp EEG; this finding however suggests its possible usefulness for an automated classification of vigilance states. C1 [Bruzzo, Angela A.] Univ Bologna, Dept Psychol, I-40100 Bologna, Italy. [Gesierich, Benno] Univ Trent, Ctr Mind Brain Sci, Rovereto, Italy. [Bruzzo, Angela A.; Santi, Maurizio; Tassinari, Carlo Alberto; Rubboli, Guido] Univ Bologna, Bellaria Hosp, Dept Neurosci, I-40100 Bologna, Italy. [Bruzzo, Angela A.; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. [Birbaumer, Niels] NINDS, NIH, Cort Physiol Unit, Bethesda, MD 20892 USA. RP Bruzzo, AA (reprint author), Univ Bologna, Dept Psychol, Viale Carlo Berti Pichat 5, I-40100 Bologna, Italy. EM angela.bruzzo@libero.it NR 25 TC 79 Z9 80 U1 1 U2 13 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 1590-1874 EI 1590-3478 J9 NEUROL SCI JI Neurol. Sci. PD FEB PY 2008 VL 29 IS 1 BP 3 EP 9 DI 10.1007/s10072-008-0851-3 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 275BW UT WOS:000254047900002 PM 18379733 ER PT J AU Yang, HYT Tao, T Iadarola, MJ AF Yang, Hsiu-Ying T. Tao, Tao Iadarola, Michael J. TI Modulatory role of neuropeptide FF system in nociception and opiate analgesia SO NEUROPEPTIDES LA English DT Review DE NPFF; nociception; opiate analgesia; RFamide peptides; asic channels ID RAT SPINAL-CORD; PROTEIN-COUPLED RECEPTOR; CENTRAL-NERVOUS-SYSTEM; MAMMALIAN FMRF-NH2-LIKE PEPTIDE; PROLACTIN-RELEASING PEPTIDE; SENSORY NEURON EXCITABILITY; SENSING ION CHANNELS; REDUCES FOOD-INTAKE; GENE-EXPRESSION; GANGLION NEURONS AB The tetra-peptide FMRF-NH2 is a cardioexcitatory peptide in the clam. Using the antibody against this peptide, FMRF-NH2-like immunoreactive material was detected in mammalian CNS. Subsequently, mammalian FMRF-NH2 immunoreactive peptides were isolated from bovine brain and characterized to be FLFQPQRF-NH2 (NPFF) and AGEGLSSPFWSLAAPQRF-NH2 (NPAF). The genes encoding NPFF precursor proteins and NPFF receptors I and 2 are expressed in all vertebrate species examined to date and are highly conserved. Among many biological roles suggested for the NPFF system, the possible modulatory role of NPFF in nocicetion and opiate analgesia has been most widely investigated. Pharmacologically, NPFF-related peptides were found to exhibit analgesia and also potentiate the analgesic activity of opiates when administered intrathecally but attenuate the opiate induced analgesia when administered intracerebroventricularly. RF-NH2 peptides including NPFF-related peptides were found to delay the rate of acid sensing ion channels (ASIC) desensitization resulting in enhancing acid gated currents, raising the possibility that NPFF also may have a pain modulatory role through ASIC. The genes for NPFF as well as NPFF-R2, preferred receptor for NPFF, are highly unevenly expressed in the rat CNS with the highest levels localized to the superficial layers of the dorsal spinal cord. These two genes are also present in the dorsal root ganglia (DRG), though at low levels in normal rats. NPFF and NPFF-R2 mRNAs were found to be coordinately up-regulated in spinal cord and DRG of rats with peripheral inflammation. In addition, NPFF-R2 immunoreactivity in the primary afferents was increased by peripheral inflammation. The findings from the early studies on the analgesic and morphine modulating activities suggested a role for NPFF in pain modulation and this possibility is further supported by the distribution of NPFF and its receptor and the regulation of the NPFF system in vivo. Published by Elsevier Ltd. C1 [Yang, Hsiu-Ying T.; Iadarola, Michael J.] NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Bethesda, MD 20892 USA. [Tao, Tao] NIH, Natl Ctr Biotechnol Informat, Informat Resources Branch, Bethesda, MD USA. RP Yang, HYT (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Bldg 49,Room 1A07,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. EM hyang@dir.nider.nih.gov FU Intramural NIH HHS NR 107 TC 49 Z9 50 U1 0 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD FEB PY 2008 VL 42 IS 1 BP 1 EP 18 DI 10.1016/j.npep.2007.06.004 PG 18 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 277QZ UT WOS:000254231100001 PM 17854890 ER PT J AU Wank, SA Feng, JY Lu, XP Anthony, ST Peterson, CD Jiang, J Thomas, C AF Wank, Stephen A. Feng, Jianying Lu, Xinping Anthony, Shari T. Peterson, Clark D. Jiang, Jack Thomas, Craig TI The calcium-sensing receptor (CaSR) mediates meal stimulated gastrin secretion SO NEUROPEPTIDES LA English DT Meeting Abstract CT Summer Neuropeptide Conference CY SEP 08-09, 2007 CL Essex, VT C1 [Wank, Stephen A.; Feng, Jianying; Lu, Xinping; Anthony, Shari T.; Peterson, Clark D.; Jiang, Jack; Thomas, Craig] NIDDK, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. [Wank, Stephen A.; Feng, Jianying; Lu, Xinping; Anthony, Shari T.; Peterson, Clark D.; Jiang, Jack; Thomas, Craig] NIDDK, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD FEB PY 2008 VL 42 IS 1 BP 112 EP 112 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 277QZ UT WOS:000254231100017 ER PT J AU Loh, YP Koshimizu, H Kim, T AF Loh, Y. Peng Koshimizu, Hisatsugu Kim, Taeyoon TI Role of chromogranin a in peptidergic granule biogenesis SO NEUROPEPTIDES LA English DT Meeting Abstract CT Summer Neuropeptide Conference CY SEP 08-09, 2007 CL Essex, VT C1 [Loh, Y. Peng; Koshimizu, Hisatsugu; Kim, Taeyoon] NICHHD, Cellular Neurobiol Sect, Bethesda, MD 20892 USA. RI Koshimizu, Hisatsugu/G-5536-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD FEB PY 2008 VL 42 IS 1 BP 115 EP 116 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 277QZ UT WOS:000254231100025 ER PT J AU Gehlert, DR Cippitelli, A Thorsell, A Le, AD Hipskind, PA Hamdouchi, C Lu, J Hembre, EJ Cramer, J Song, M McKinzie, D Morin, M Ciccocioppo, R Heilig, M AF Gehlert, D. R. Cippitelli, A. Thorsell, A. Le, A. D. Hipskind, P. A. Hamdouchi, C. Lu, J. Hembre, E. J. Cramer, J. Song, M. McKinzie, D. Morin, M. Ciccocioppo, R. Heilig, M. TI MTIP: A novel brain penetrant, orally available corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist for treatment of alcoholism SO NEUROPEPTIDES LA English DT Meeting Abstract CT Summer Neuropeptide Conference CY SEP 08-09, 2007 CL Essex, VT C1 [Gehlert, D. R.; Cippitelli, A.; Thorsell, A.; Le, A. D.; Hipskind, P. A.; Hamdouchi, C.; Lu, J.; Hembre, E. J.; Cramer, J.; Song, M.; McKinzie, D.; Morin, M.; Ciccocioppo, R.; Heilig, M.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Gehlert, D. R.; Cippitelli, A.; Thorsell, A.; Le, A. D.; Hipskind, P. A.; Hamdouchi, C.; Lu, J.; Hembre, E. J.; Cramer, J.; Song, M.; McKinzie, D.; Morin, M.; Ciccocioppo, R.; Heilig, M.] NIAAA, NIH, Lab Clin & Translat Studies, Bethesda, MD USA. [Gehlert, D. R.; Cippitelli, A.; Thorsell, A.; Le, A. D.; Hipskind, P. A.; Hamdouchi, C.; Lu, J.; Hembre, E. J.; Cramer, J.; Song, M.; McKinzie, D.; Morin, M.; Ciccocioppo, R.; Heilig, M.] Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, Italy. [Gehlert, D. R.; Cippitelli, A.; Thorsell, A.; Le, A. D.; Hipskind, P. A.; Hamdouchi, C.; Lu, J.; Hembre, E. J.; Cramer, J.; Song, M.; McKinzie, D.; Morin, M.; Ciccocioppo, R.; Heilig, M.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD FEB PY 2008 VL 42 IS 1 BP 117 EP 117 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 277QZ UT WOS:000254231100028 ER PT J AU Myers, CS Taylor, RC Moolchan, ET Heishman, SJ AF Myers, Carol S. Taylor, Richard C. Moolchan, Eric T. Heishman, Stephen J. TI Dose-related enhancement of mood and cognition in smokers administered nicotine nasal spray SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE nicotine nasal spray; performance; sustained attention; information processing; working memory; plasma nicotine ID SPATIAL WORKING-MEMORY; TRANSDERMAL NICOTINE; ATTENTIONAL PERFORMANCE; ACETYLCHOLINE-RECEPTORS; CIGARETTE-SMOKING; NEVER-SMOKERS; RATS; TASK; NONSMOKERS; TOBACCO AB The discovery of the role of nicotinic receptors in attention and memory has led to the testing of nicotinic analogs as cognitive enhancing agents in patient populations. Empirical information about nicotine's ability to enhance elements of attention and memory in normal individuals might guide development of therapeutic uses of nicotine in cognitively impaired populations. The purpose of this study was to determine the effect of nicotine on continuous attention, working memory, and computational processing in tobacco-deprived and nondeprived smokers. A total of 28 smokers (14 men, 14 women) participated in a double-blind, placebo-controlled, within-subject study, in which they were overnight (12 h) tobacco deprived at one session and smoked ad libitum before the other session. At each session, participants received 0, 1, and 2mg nicotine via nasal spray in random order at 90 min intervals. Before and after each dose, a battery of cognitive, subjective, and physiological measures was administered, and blood samples were taken for plasma nicotine concentration. Overnight tobacco deprivation resulted in impaired functioning on all cognitive tests and increased self-reports of tobacco craving and negative mood; nicotine normalized these deficits. In the nondeprived condition, nicotine enhanced performance on the continuous performance test (CPT) and an arithmetic test in a dose-related manner, but had no effect on working memory. In general, women were more sensitive than men to the subjective effects of nicotine. These results provide an unequivocal determination that nicotine enhanced attentional and computational abilities in nondeprived smokers and suggest these cognitive domains as substrates for novel therapeutic indications. C1 [Myers, Carol S.; Taylor, Richard C.; Moolchan, Eric T.; Heishman, Stephen J.] NIDA, Nicotine Psychopharmacol Unit, Intramural Res Program, Clin Pharmacol & Therapeut Branch,NIH, Baltimore, MD 21224 USA. RP Myers, CS (reprint author), NIDA, Nicotine Psychopharmacol Unit, Intramural Res Program, Clin Pharmacol & Therapeut Branch,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM cmyers@intra.nida.nih.gov FU Intramural NIH HHS NR 67 TC 66 Z9 67 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2008 VL 33 IS 3 BP 588 EP 598 DI 10.1038/sj.npp.1301425 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 250LE UT WOS:000252300700013 PM 17443125 ER PT J AU Borycz, J Zapata, A Quiroz, C Volkow, ND Ferre, S AF Borycz, Janusz Zapata, Agustin Quiroz, Cesar Volkow, Nora D. Ferre, Sergi TI 5-HT(1B) receptor-mediated serotoninergic modulation of methylphenidate-induced locomotor activation in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE methylphenidate; methamphetamine; fluoxetine; dopamine; serotonin; 5-HT(1B) receptor ID REUPTAKE INHIBITORS ENHANCE; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; MONOAMINE TRANSPORTERS; 5-HYDROXYTRYPTAMINE(1B) RECEPTORS; ACUTE RESPONSE; COCAINE; METHAMPHETAMINE; AMPHETAMINE; RELEASE AB Previous studies have shown that the dopamine (DA) uptake blocker methylphenidate, a psychostimulant widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), prevents the neurotoxic effects of the highly abused DA releaser methamphetamine. However, there is a lack of information about the pharmacological interactions of these two drugs at the behavioral level. When systemically administered within an interval of 2h, previous administration of methylphenidate (10mg/kg, intraperitoneal (i.p.)) did not modify locomotor activation induced by methamphetamine. On the other hand, previous administration of methamphetamine (1mg/kg,i.p.) markedly potentiated methylphenidate-induced motor activation. With in vivo microdialysis experiments, methamphetamine and methylphenidate were found to increase DA extracellular levels in the nucleus accumbens (NAs). Methamphetamine, but not methylphenidate, significantly increased the extracellular levels of serotonin (5-HT) in the NAs. Methamphetamine-induced 5-HT release remained significantly elevated for more than 2h after its administration, suggesting that the increased 5-HT could be responsible for the potentiation of methylphenidate-induced locomotor activation. In fact, previous administration of the 5-HT uptake blocker fluoxetine (10mg/kg,i.p.) also potentiated the motor activation induced by methylphenidate. A selective 5-HT(1B) receptor antagonist (GR 55562; 1mg/kg), but not a 5-HT(2) receptor antagonist (ritanserin;2mg/kg,i.p.), counteracted the effects of methamphetamine and fluoxetine on the motor activation induced by methylphenidate. Furthermore, a 5-HT(1B) receptor agonist (CP94253;1-10mg/kg,i.p.) strongly and dose-dependently potentiated methylphenidate-induced locomotor activation. The 5-HT(1B) receptor-mediated modulation of methylphenidate-induced locomotor activation in rat could have implications for the treatment of ADHD. C1 [Borycz, Janusz; Zapata, Agustin; Quiroz, Cesar; Volkow, Nora D.; Ferre, Sergi] NIDA, Dept Hlth & Human Serv, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Volkow, Nora D.] NIAAA, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Ferre, S (reprint author), NIDA, Dept Hlth & Human Serv, Intramural Res Program, NIH, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU Intramural NIH HHS NR 52 TC 23 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2008 VL 33 IS 3 BP 619 EP 626 DI 10.1038/sj.npp.1301445 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 250LE UT WOS:000252300700016 PM 17487226 ER PT J AU Chen, KJ Piknova, B Pittman, RN Schechter, AN Popel, AS AF Chen, Kejing Piknova, Barbora Pittman, Roland N. Schechter, Alan N. Popel, Aleksander S. TI Nitric oxide from nitrite reduction by hemoglobin in the plasma and erythrocytes SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE computational model; nitric oxide; nitrite reduction; intraerythrocytic hemoglobin; cell-free hemoglobin ID SOLUBLE GUANYLATE-CYCLASE; BLOOD-FLOW REGULATION; BIOCHEMICAL PATHWAYS; S-NITROSOHEMOGLOBIN; OXYGEN CARRIER; L-ARGININE; IN-VIVO; MODEL; NO; TRANSPORT AB Experimental evidence has shown that nitrite anion plays a key role in one of the proposed mechanisms for hypoxic vasodilation, in which the erythrocyte acts as a NO generator and deoxygenated hemoglobin in pre-capillary arterioles reduces nitrite to NO, which contributes to vascular smooth muscle relaxation. However, because of the complex reactions among nitrite, hemoglobin, and the NO that is formed, the amount of NO delivered by this mechanism under various conditions has not been quantified experimentally. Furthermore, paracrine NO is scavenged by cell-free hemoglobin, as shown by studies of diseases characterized by extensive hemolysis (e.g., sickle cell disease) and the administration of hemoglobin-based oxygen carriers. Taking into consideration the free access of cell-free hemoglobin to the vascular wall and its ability to act as a nitrite reductase, we have now examined the hypothesis that in hypoxia this cell-free hemoglobin could serve as an additional endocrine source of NO. In this study, we constructed a multicellular model to characterize the amount of NO delivered by the reaction of nitrite with both intraerythrocytic and cell-free hemoglobin, while intentionally neglecting all other possible sources of NO in the vasculature. We also examined the roles of hemoglobin molecules in each compartment as nitrite reductases and NO scavengers using the model. Our calculations show that: (1) similar to 0.04 pM NO from erythrocytes could reach the smooth muscle if free diffusion were the sole export mechanism; however, this value could rise to similar to 43 pM with a membrane-associated mechanism that facilitated NO release from erythrocytes; the results also strongly depend on the erythrocyte membrane permeability to NO, (2) despite the closer proximity of cell-free hemoglobin to the smooth muscle, cell-free hemoglobin reaction with nitrite generates approximately 0.02 pM of free NO that can reach the vascular wall, because of a strong self-capture effect. However, it is worth noting that this value is in the same range as erythrocytic hemoglobin-generated NO that is able to diffuse freely out of the cell, despite the tremendous difference in hemoglobin concentration in both cases (pM hemoglobin in plasma vs. mM in erythrocyte); (3) intraerythrocytic hemoglobin encapsulated by a NO-resistant membrane is the major source of NO from nitrite reduction, and cell-free hemoglobin is a significant scavenger of both paracrine and endocrine NO. (c) 2007 Elsevier Inc. All rights reserved. C1 [Chen, Kejing; Popel, Aleksander S.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Piknova, Barbora; Schechter, Alan N.] NIH, Natl Inst Diab Digest & Kidney Dis, Mol Med Branch, Bethesda, MD 20892 USA. [Pittman, Roland N.] Virginia Commonwealth Univ, Med Coll Virginia Campus, Dept Physiol, Richmond, VA 23298 USA. RP Chen, KJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Biomed Engn, 613 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM kchen21@jhu.edu OI Schechter, Alan N/0000-0002-5235-9408 FU NHLBI NIH HHS [R01 HL018292, R01 HL018292-29, R01 HL079087, R01 HL079087-03] NR 49 TC 35 Z9 37 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD FEB PY 2008 VL 18 IS 1 BP 47 EP 60 DI 10.1016/j.niox.2007.09.088 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 254SP UT WOS:000252608600006 PM 17964300 ER PT J AU Hsu, LY Wragg, A Anderson, SA Balaban, RS Boehm, M Arai, AE AF Hsu, Li-Yueh Wragg, Andrew Anderson, Stasia A. Balaban, Robert S. Boehm, Manfred Arai, Andrew E. TI Automatic assessment of dynamic contrast-enhanced MRI in an ischemic rat hindlimb model: an exploratory study of transplanted multipotent progenitor cells SO NMR IN BIOMEDICINE LA English DT Article DE image analysis; MRI; contrast agent; perfusion; late enhancement; stem cell; skeletal muscle ID SKELETAL-MUSCLE PERFUSION; MESENCHYMAL STEM-CELLS; IN-VIVO ASSESSMENT; ABSOLUTE PERFUSION; ARTERIAL WATER; MARROW; FLOW; INVERSION; OCCLUSION; EXERCISE AB This study presents computerized automatic image analysis for quantitatively evaluating dynamic contrast-enhanced MRI in an ischemic rat hindlimb model. MRI at 7 T was performed on animals in a blinded placebo-controlled experiment comparing multipotent adult progenitor cell-derived progenitor cell (MDPC)-treated, phosphate buffered saline (PBS)-injected, and sham-operated rats. Ischemic and non-ischemic limb regions of interest were automatically segmented from time-series images for detecting changes in perfusion and late enhancement. In correlation analysis of the time-signal intensity histograms, the MDPC-treated limbs correlated well with their corresponding non-ischemic limbs. However, the correlation coefficient of the PBS control group was significantly lower than that of the MDPC-treated and sham-operated groups. In semi-quantitative parametric maps of contrast enhancement, there was no significant difference in hypo-enhanced area between the MDPC and PBS groups at early perfusion-dependent time frames. However, the late-enhancement area was significantly larger in the PBS than the MDPC group. The results of this exploratory study show that MDPC-treated rats could be objectively distinguished from PBS controls. The differences were primarily determined by late contrast enhancement of PBS-treated limbs. These computerized methods appear promising for assessing perfusion and late enhancement in dynamic contrast-enhanced MRI. Published in 2007 by John Wiley & Sons, Ltd. C1 [Hsu, Li-Yueh; Wragg, Andrew; Anderson, Stasia A.; Balaban, Robert S.; Boehm, Manfred; Arai, Andrew E.] NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA. EM araia@nih.gov FU Intramural NIH HHS NR 26 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD FEB PY 2008 VL 21 IS 2 BP 111 EP 119 DI 10.1002/nbm.1166 PG 9 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 272EM UT WOS:000253842700004 PM 17506036 ER PT J AU Todd, BA Rau, DC AF Todd, Brian A. Rau, Donald C. TI Interplay of ion binding and attraction in DNA condensed by multivalent cations SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HELIX-COIL TRANSITION; POLYELECTROLYTE SOLUTIONS; EQUILIBRIUM DIALYSIS; FINE-STRUCTURE; SPERMIDINE; AGGREGATION; PRECIPITATION; COUNTERIONS; COBALT(III); POLYAMINES AB We have measured forces generated by multivalent cation-induced DNA condensation using single-molecule magnetic tweezers. In the presence of cobalt hexammine, spermidine, or spermine, stretched DNA exhibits an abrupt configurational change from extended to condensed. This occurs at a well-defined condensation force that is nearly equal to the condensation free energy per unit length. The multivalent cation concentration dependence for this condensation force gives the apparent number of multivalent cations that bind DNA upon condensation. The measurements show that the lower critical concentration for cobalt hexammine as compared to spermidine is due to a difference in ion binding, not a difference in the electrostatic energy of the condensed state as previously thought. We also show that the resolubilization of condensed DNA can be described using a traditional Manning-Oosawa cation adsorption model, provided that cation-anion pairing at high electrolyte concentrations is taken into account. Neither overcharging nor significant alterations in the condensed state are required to describe the resolubilization of condensed DNA. The same model also describes the spermidine(3)/Na+ phase diagram measured previously. C1 [Todd, Brian A.; Rau, Donald C.] NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Todd, BA (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM toddba@mail.nih.gov FU Intramural NIH HHS NR 43 TC 59 Z9 60 U1 4 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB PY 2008 VL 36 IS 2 BP 501 EP 510 DI 10.1093/nar/gkm1038 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 260PG UT WOS:000253021600015 PM 18048417 ER PT J AU Entezam, A Usdin, K AF Entezam, Ali Usdin, Karen TI ATR protects the genome against CGG.CCG-repeat expansion in Fragile X premutation mice SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUNTINGTONS-DISEASE GENE; CAG TRIPLET REPEATS; DM1 TRANSGENIC MICE; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; MISMATCH-REPAIR; CGG REPEAT; TRINUCLEOTIDE REPEATS; DEPENDENT MANNER; FULL MUTATION AB Fragile X mental retardation syndrome is a repeat expansion disease caused by expansion of a CGG.CCG-repeat tract in the 5' UTR of the FMR1 gene. In humans, small expansions occur more frequently on paternal transmission while large expansions are exclusively maternal in origin. It has been suggested that expansion is the result of aberrant DNA replication, repair or recombination. To distinguish amongst these possibilities we crossed mice containing 120 CGG.CCG-repeats in the 5' UTR of the mouse Fmr1 gene to mice with mutations in ATR, a protein important in the cellular response to stalled replication forks and bulky DNA lesions. We show here that ATR heterozygosity results in increased expansion rates of maternally, but not paternally, transmitted alleles. In addition, age-related somatic expansions occurred in mice of both genders that were not seen in ATR wild-type animals. Some ATR-sensitive expansion occurs in postmitotic cells including haploid gametes suggesting that aberrant DNA repair is responsible. Our data suggest that two mechanisms of repeat expansion exist that may explain the small and large expansions seen in humans. In addition, our data provide an explanation for the maternal bias of large expansions in humans and the lower incidence of these expansions in mice. C1 [Entezam, Ali; Usdin, Karen] NIDDK, Sect Gene Struct & Dis, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDK, Sect Gene Struct & Dis, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM ku@helix.nih.gov FU Intramural NIH HHS NR 67 TC 33 Z9 34 U1 1 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 FEB PY 2008 VL 36 IS 3 BP 1050 EP 1056 DI 10.1093/nar/gkm1136 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 267EC UT WOS:000253491300038 PM 18160412 ER PT J AU Flegal, KM Graubard, BI Williamson, DF Gail, MH AF Flegal, Katherine M. Graubard, Barry I. Williamson, David F. Gail, Mitchell H. TI Correcting bias, or biased corrections? SO OBESITY LA English DT Article ID BODY-MASS INDEX; FOLLOW-UP; MORTALITY; OBESITY; DEATHS; POPULATION; REGRESSION; OVERWEIGHT; WEIGHT; MEN C1 [Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Graubard, Barry I.; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Williamson, David F.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. EM KFlegal@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 20 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD FEB PY 2008 VL 16 IS 2 BP 229 EP 231 DI 10.1038/oby.2007.41 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 258QU UT WOS:000252883600003 PM 18239628 ER PT J AU Fuemmeler, BF Agurs-Collins, TD Mcclernon, FJ Kollins, SH Kail, ME Bergen, AW Ashley-Koch, AE AF Fuemmeler, Bernard F. Agurs-Collins, Tanya D. Mcclernon, F. Joseph Kollins, Scott H. Kail, Melanie E. Bergen, Andrew W. Ashley-Koch, Allison E. TI Genes implicated in serotonergic and dopaminergic functioning predict BMI categories SO OBESITY LA English DT Article ID 5-HT2A RECEPTOR GENE; BODY-MASS INDEX; D2 RECEPTOR; ADOLESCENT HEALTH; PROMOTER POLYMORPHISM; TAQI POLYMORPHISM; MONOAMINE-OXIDASE; ABDOMINAL OBESITY; SMOKING-BEHAVIOR; BRAIN-SEROTONIN AB Objective: This study addressed the hypothesis that variation in genes associated with dopamine function (SLC6A3, DRD2, DRD4), serotonin function (SLC6A4, and regulation of monoamine levels (MAOA) may be predictive of BMI categories (obese and overweight + obese) in young adulthood and of changes in BMI as adolescents transition into young adulthood. Interactions with gender and race/ethnicity were also examined. Methods and Procedures: Participants were a subsample of individuals from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset of 1,584 unrelated individuals with genotype data. Multiple logistic regressions were conducted to evaluate the associations between genotypes and obesity (BMI > 29.9) or overweight + obese combined (BMI >= 25) with normal weight (BMI = 18.5-24.9) as a referent. Linear regression models were used to examine change in BMI from adolescence to young adulthood. Results: Significant associations were found between SLC6A4 5HTTLPR and categories of BMI, and between MAOA promoter variable number tandem repeat (VNTR) among men and categories of BMI. Stratified analyses revealed that the association between these two genes and excess BMI was significant for men overall and for white and Hispanic men specifically. Linear regression models indicated a significant effect of SLC6A4 5HTTLPR on change in BMI from adolescence to young adulthood. Discussion: Our findings lend further support to the involvement of genes implicated in dopamine and serotonin regulation on energy balance. C1 [Fuemmeler, Bernard F.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Agurs-Collins, Tanya D.] NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA. [Mcclernon, F. Joseph; Kollins, Scott H.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Kail, Melanie E.; Ashley-Koch, Allison E.] Duke Univ, Med Ctr, Ctr Human Genet, Dept Med, Durham, NC 27710 USA. [Bergen, Andrew W.] NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. [Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. RP Fuemmeler, BF (reprint author), Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. EM bernard.fuemmeler@duke.edu RI Kollins, Scott/G-2965-2012; OI Bergen, Andrew/0000-0002-1237-7644; Ashley-Koch, Allison/0000-0001-5409-9155 FU NCI NIH HHS [K07 CA124905-01A1, K07 CA124905]; NICHD NIH HHS [P01 HD 31921, P01 HD031921]; NIDA NIH HHS [K23 DA 017261, K23 DA017261]; NINDS NIH HHS [NS 049067, R01 NS049067] NR 70 TC 55 Z9 55 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD FEB PY 2008 VL 16 IS 2 BP 348 EP 355 DI 10.1038/oby.2007.65 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 258QU UT WOS:000252883600018 PM 18239643 ER PT J AU Considine, RV Premkumar, A Reynolds, JC Sebring, NG Ricks, M Sumner, AE AF Considine, Robert V. Premkumar, Ahalya Reynolds, James C. Sebring, Nancy G. Ricks, Madia Sumner, Anne E. TI Adiponectin and leptin in African Americans SO OBESITY LA English DT Article ID VISCERAL ADIPOSE-TISSUE; INSULIN-RESISTANCE ATHEROSCLEROSIS; MECHANISMS LINKING OBESITY; BODY-FAT DISTRIBUTION; RACIAL-DIFFERENCES; PLASMA ADIPONECTIN; METABOLIC SYNDROME; SERUM ADIPONECTIN; CIRCULATING CONCENTRATIONS; SUBCUTANEOUS ADIPOCYTES AB Objective: African Americans (AAs) have less visceral and more subcutaneous fat than whites, thus the relationship of adiponectin and leptin to body fat and insulin sensitivity in AA may be different from that in whites. Methods and Procedures: Sixty-nine non-diabetic AA (37 men and 32 women), aged 33 +/- 1 year participated. The percent fat was determined by dual-energy X-ray absorptiometry, abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume by computerized tomography (CT), and insulin sensitivity by homeostasis model assessment (HOMA). Results: VAT was greater in men (1,619 +/- 177 cm(3) vs. 1,022 +/- 149 cm(3); P = 0.01); women had a higher percentage of body fat (34.1 +/- 1.4 vs. 24.0 +/- 1.2; P < 0.0001), adiponectin (15.8 +/- 1.2 mu g/ml vs. 10.4 +/- 0.8 mu g/ml; P = 0.0004) and leptin (23.2 +/- 15.8 ng/ml vs. 9.2 +/- 7.2 ng/ml; P < 0.0001). SAT and HOMA did not differ because of the sex. Adiponectin negatively correlated with VAT (r = -0.41, P < 0.05) in men, and with VAT (r = -0.55, P < 0.01), and SAT (r = -0.35, P < 0.05) in women. Adiponectin negatively correlated with HOMA in men (r = -0.38, P < 0.05) and women (r = -0.44, P < 0.05). In multiple regression, sex (P = 0.02), HOMA (P = 0.03) and VAT (P = 0.003) were significant predictors of adiponectin (adj R-2 = 0.38, P < 0.0001). Leptin positively correlated with VAT, SAT, percent fat and HOMA in men (r = 0.79, r = 0.86, r = 0.89, and r = 0.53; P < 0.001) and women (r = 0.62, r = 0.75, r = 0.83, and r = 0.55; P < 0.01). In multiple regression VAT (P = 0.04), percent body fat (P < 0.0001) and sex (P = 0.01), but not HOMA were significant predictors of serum leptin (adj R-2= 0.82, P < 0.0001). Discussion: The relationship of adiponectin and leptin to body fat content and distribution in AA is dependent on sex. Although VAT and insulin sensitivity are significant determinants of adiponectin, VAT and percent body fat determine leptin. C1 [Considine, Robert V.] Indiana Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Indianapolis, IN 46204 USA. [Premkumar, Ahalya] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. [Sebring, Nancy G.] NIH, Ctr Clin, Dept Nutr, Bethesda, MD 20892 USA. [Ricks, Madia; Sumner, Anne E.] NIDDK, Clin Endocrinol Branch, Bethesda, MD USA. RP Considine, RV (reprint author), Indiana Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Indianapolis, IN 46204 USA. EM rconsidi@iupui.edu FU Intramural NIH HHS NR 62 TC 14 Z9 16 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD FEB PY 2008 VL 16 IS 2 BP 428 EP 434 DI 10.1038/oby.2007.80 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 258QU UT WOS:000252883600030 PM 18239655 ER PT J AU Freiberg, MS Pencina, MJ D'Agostino, RB Lanier, K Wilson, PWF Vasan, RS AF Freiberg, Matthew S. Pencina, Michael J. D'Agostino, Ralph B. Lanier, Katherine Wilson, Peter W. F. Vasan, Ramachandran S. TI BMI vs. waist circumference for identifying vascular risk SO OBESITY LA English DT Article ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; AGE-RELATED-CHANGES; ABDOMINAL ADIPOSITY; WHOLE-BODY; US ADULTS; OBESITY; PREVALENCE AB Objective: Current guidelines recommend measurement of both BMI and waist circumference (WC) in individuals with BMI between 25.0 and 34.9 kg/m(2). We investigated the relative contributions of BMI and WC toward identifying risk of adverse vascular events in a community-based sample. Methods and Procedures: We evaluated Framingham Study participants (n = 4,195 person-examinations, 53% women) using pooled logistic regression to assess the incremental prognostic utility of WC in predicting risk of a first cardiovascular disease (CVD) event in the three BMI categories (normal, <25 kg/m(2); overweight, 25 to <30 kg/m(2); obese, = 30 kg/m(2)) and to assess the incremental prognostic utility of BMI and WC separately for predicting risk of a first cardiovascular event. Results: On follow-up (16 years), 430 participants (158 women) had experienced a first CVD event. In overweight women, but not in overweight men, larger WC was found to be an independent predictor of CVD incidence, longitudinally (in women, multivariable-adjusted odds ratio (OR) per s.d. increment in WC 1.86, 95% confidence interval (CI) = 1.03-3.36, P = 0.04; in men adjusted OR per s.d. increment in WC 0.91, 95% CI 0.60-1.38, P = 0.66). In obese individuals and in those with normal BMI, WC was not associated independently with incident CVD. When BMI and WC were analyzed separately for predicting risk of a first cardiovascular event, the c statistics associated with the multivariable CVD models incorporating BMI vs. WC were nearly identical in men and women. Discussion: Knowledge of WC aids identification of vascular risk among overweight women. Among normal weight or obese women and men (regardless of BMI category) WC did not appear to substantially add to prediction of risk of vascular events. C1 [Freiberg, Matthew S.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. [Freiberg, Matthew S.; Pencina, Michael J.; D'Agostino, Ralph B.; Vasan, Ramachandran S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Pencina, Michael J.; D'Agostino, Ralph B.; Lanier, Katherine] Boston Univ, Dept Math, Boston, MA 02215 USA. [Wilson, Peter W. F.] Med Coll S Carolina, Dept Med, Sect Endocrinol & GCRC, Charleston, SC USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Freiberg, MS (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. EM freibergms@upmc.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2 K24 HL 04334, N01 HC 25195]; NIAAA NIH HHS [1 K23 AA 015914-01]; PHS HHS [2 T32 HP 100028-06] NR 41 TC 46 Z9 48 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD FEB PY 2008 VL 16 IS 2 BP 463 EP 469 DI 10.1038/oby.2007.75 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 258QU UT WOS:000252883600035 PM 18239660 ER PT J AU Mercer, BM Gilbert, S Landon, MB Spong, CY Leveno, KJ Rouse, DJ Harner, MW Moawad, AH Simhan, HN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, A O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM AF Mercer, Brian M. Gilbert, Sharon Landon, Mark B. Spong, Catherine Y. Leveno, Kenneth J. Rouse, Dwight J. Harner, Michael W. Moawad, Atef H. Simhan, Hyagriv N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. CA Natl Inst Child Hlth Human Dev Ma TI Labor outcomes with increasing number of prior vaginal births after cesarean delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecol Invest ID UTERINE RUPTURE; TRIAL; MULTIPLE; SUCCESS; WOMEN; RISK AB OBJECTIVE: To estimate the success rates and risks of an attempted vaginal birth after cesarean delivery (VBAC) according to the number of prior successful VBACs. METHODS: From a prospective multicenter registry collected at 19 clinical centers from 1999 to 2002, we selected women with one or more prior low transverse cesarean deliveries who attempted a VBAC in the current pregnancy. Outcomes were compared according to the number of prior VBAC attempts subsequent to the last cesarean delivery. RESULTS: Among 13,532 women meeting eligibility criteria, VBAC success increased with increasing number of prior VBACs: 63.3%, 87.6%, 90.9%, 90.6%, and 91.6% for those with 0, 1, 2, 3, and 4 or more prior VBACs, respectively (P<.001). The rate of uterine rupture decreased after the first successful VBAC and did not increase thereafter: 0.87%, 0.45%, 0.38%, 0.54%, 0.52% (P=.03). The risk of uterine dehiscence and other peripartum complications also declined statistically after the first successful VBAC. No increase in neonatal morbidities was seen with increasing VBAC number thereafter. CONCLUSION: Women with prior successful VBAC attempts are at low risk for maternal and neonatal complications during subsequent VBAC attempts. An increasing number of prior VBACs is associated with a greater probability of VBAC success, as well as a lower risk of uterine rupture and perinatal complications in the current pregnancy. C1 Case Western Reserve Univ, MetroHlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH 44109 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Alabama, Birmingham, AL USA. Univ Utah, Salt Lake City, UT USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ Chicago, Chicago, IL 60637 USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ Pittsburgh, Pittsburgh, PA USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Wake Forest Univ, Winston Salem, NC 27109 USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Wayne State Univ, Detroit, MI USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ Cincinnati, Cincinnati, OH USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Columbia Univ, New York, NY USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Brown Univ, Providence, RI USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Northwestern Univ, Chicago, IL 60611 USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ Miami, Miami, FL 33152 USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ Tennessee, Memphis, TN USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ Texas San Antonio, San Antonio, TX USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ N Carolina, Chapel Hill, NC USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] Univ Texas Houston, Houston, TX USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] George Washington Univ, Ctr Biostat, Washington, DC USA. [Mercer, Brian M.; Gilbert, Sharon; Landon, Mark B.; Spong, Catherine Y.; Leveno, Kenneth J.; Rouse, Dwight J.; Harner, Michael W.; Moawad, Atef H.; Simhan, Hyagriv N.; Harper, Margaret; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Ramin, Susan M.; Natl Inst Child Hlth Human Dev Ma] NICHHD, Bethesda, MD 20892 USA. RP Mercer, BM (reprint author), Case Western Reserve Univ, MetroHlth Med Ctr, Dept Obstet & Gynecol, G240,2500 MetroHlth Dr, Cleveland, OH 44109 USA. RI Varner, Michael/K-9890-2013; OI Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NIAID NIH HHS [P01 AI057005, R56 AI049170]; NICHD NIH HHS [HD27869, HD21410, HD21414, HD27860, HD27861, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, U10 HD040544] NR 21 TC 29 Z9 32 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2008 VL 111 IS 2 BP 285 EP 291 DI 10.1097/AOG.0b013e31816102b9 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 256XD UT WOS:000252762300005 PM 18238964 ER PT J AU Mikolajczyk, RT DiSilvesto, A Zhang, J AF Mikolajczyk, Rafael T. DiSilvesto, Alexis Zhang, Jun TI Evaluation of logistic regression reporting in current obstetrics and gynecology SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MEDICAL-RESEARCH; EXTERNAL VALIDATION; MODELS; BIAS; PREDICTION; SIMULATION AB OBJECTIVE: To evaluate the quality of logistic regression reporting in the obstetrics and gynecology literature. METHODS: All original papers published in 2005 and 2006 in four leading obstetrics and gynecology journals were manually searched for the use of logistic regression. One hundred four articles that used logistic regression were randomly selected (13 from each journal and each year) and evaluated according to previously established criteria for reporting logistic regression analyses. Rates of compliance with these criteria were calculated separately for each journal and weighted according to the number of articles using logistic regression in each of the journals in the same period to obtain an overall estimate. RESULTS: Logistic regression was used in 34.2% of all original research articles (724 of 2,234) in the four journals for the study period. Statistical significance of estimates was reported in 96% of examined articles. Criteria of variable selection for the logistic regression model were reported in 76% of articles, and coding of variables was described in 83%. Overfitting (models with too many variables for the number of outcome events) occurred in 57% of studies. The majority of examined articles insufficiently reported information for the remaining criteria-testing for interactions (18%), conformity to a linear gradient of continuous variables (9%), goodness of fit (3.6%), assessment of multi-collinearity (0.46%), and validation of the model (0%). CONCLUSION: Logistic regression has become a standard statistical method in obstetrics and gynecology literature. Although some standards are mostly fulfilled, there is still considerable room for improvement. C1 [Mikolajczyk, Rafael T.; DiSilvesto, Alexis; Zhang, Jun] NIH, Natl Inst Child Hlth & Human Dev, Epidemiol Branch, Bethesda, MD 20892 USA. RP Mikolajczyk, RT (reprint author), NIH, Natl Inst Child Hlth & Human Dev, Epidemiol Branch, 6100 Execut Blvd,Room 7B03,MSC 7510, Bethesda, MD 20892 USA. EM mikorafa@mail.nih.gov FU Intramural NIH HHS NR 23 TC 20 Z9 21 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2008 VL 111 IS 2 BP 413 EP 419 DI 10.1097/AOG.0b013e318160f38e PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 256XD UT WOS:000252762300021 PM 18238980 ER PT J AU Stein, U Arlt, F Walther, W Harris, ED Smith, J Fichtner, I Herrmann, P Birchmeier, W Schlag, PM Shoemaker, RH AF Stein, U. Arlt, F. Walther, W. Harris, E. D. Smith, J. Fichtner, I. Herrmann, P. Birchmeier, W. Schlag, P. M. Shoemaker, R. H. TI Prognostic and diagnostic relevance of s100A4, a newly identified target gene of beta-catenin/TCF signalling, for colon cancer metastasis SO ONKOLOGIE LA English DT Meeting Abstract C1 [Stein, U.; Arlt, F.; Walther, W.; Smith, J.; Fichtner, I.; Birchmeier, W.] Max Delbruck Ctr Mol Med, Berlin, Germany. [Harris, E. D.; Shoemaker, R. H.] Natl Canc Inst, Frederick, MD USA. [Herrmann, P.; Schlag, P. M.] Robert Rossle Klin, Berlin, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD FEB PY 2008 VL 31 SU 1 BP 54 EP 54 PG 1 GA 265PG UT WOS:000253372800171 ER PT J AU Habermann, JK Roblick, U Luke, B Prieto, D Finlay, W Oevermann, E Schiedeck, T Homann, N Conrads, T Veenstra, T Burt, S Bruch, HP Auer, G Ried, T AF Habermann, J. K. Roblick, U. Luke, B. Prieto, D. Finlay, W. Oevermann, E. Schiedeck, T. Homann, N. Conrads, T. Veenstra, T. Burt, S. Bruch, H. -P. Auer, G. Ried, T. TI Serum-test for C3A anaphylatoxin makes possible minimal invasive screening for colorectal tumors SO ONKOLOGIE LA German DT Meeting Abstract C1 [Habermann, J. K.; Roblick, U.; Oevermann, E.; Schiedeck, T.; Bruch, H. -P.] Univ Klinikum Schleswig Holstein, Chirurg Klin, Chirurg Forschungslab, Lubeck, Germany. [Luke, B.; Prieto, D.; Conrads, T.; Veenstra, T.; Auer, G.] Natl Canc Inst, Frederick, MD USA. [Luke, B.; Auer, G.] Adv Biomed Computing Ctr, Frederick, MD USA. [Prieto, D.; Conrads, T.; Veenstra, T.] Lab Proteom & Analyt Technol, Frederick, MD USA. [Finlay, W.] Dublin City Univ, Biomed Diagnost Grp, Dublin, Ireland. [Homann, N.] Univ Klinikum Schleswig Holstein, Dept Internal Med, Lubeck, Germany. [Auer, G.] Karolinska Inst, Dept Pathol & Oncol, S-10401 Stockholm, Sweden. [Ried, T.] Natl Canc Inst, Human Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD FEB PY 2008 VL 31 SU 1 BP 65 EP 65 PG 1 GA 265PG UT WOS:000253372800206 ER PT J AU Mansky, P Wallerstedt, D Monahan, B Lee, C Sannes, T Stagl, J Blackman, M Swain, S Grem, J AF Mansky, P. Wallerstedt, D. Monahan, B. Lee, C. Sannes, T. Stagl, J. Blackman, M. Swain, S. Grem, J. TI Phase I study of Mistletoe extract/gemcitabine combination treatment in patients with advanced solid tumors SO ONKOLOGIE LA English DT Meeting Abstract C1 [Mansky, P.; Wallerstedt, D.; Lee, C.; Sannes, T.; Stagl, J.] Natl Inst Hlth, Natl Ctr Complementary & Alternative Med, Bethesda, MD USA. [Monahan, B.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD USA. [Blackman, M.] Washington DC Vet Affairs, Med Ctr, ACOS Res, Washington, DC USA. [Swain, S.] George Washington Univ, Washington Canc Inst, Washington, DC USA. [Grem, J.] Univ Nebraska Med Ctr, Hematol Oncol Sect, Omaha, NE USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD FEB PY 2008 VL 31 SU 1 BP 200 EP 200 PG 1 GA 265PG UT WOS:000253372800618 ER PT J AU Janket, SJ Jones, JA Meurman, JH Baird, AE Van Dyke, TE AF Janket, Sok-Ja Jones, Judith A. Meurman, Jukka H. Baird, Alison E. Van Dyke, Thomas E. TI Oral infection, hyperglycemia, and endothelial dysfunction SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; DEPENDENT DIABETES-MELLITUS; CARDIOVASCULAR RISK-FACTORS; C-REACTIVE PROTEIN; GLYCEMIC INDEX; DIETARY FIBER; PERIODONTAL-DISEASE; SYNDROME-X; ATHEROSCLEROSIS; INFLAMMATION AB Metabolic syndrome and type 2 diabetes ( T2DM) resulting from sustained hyperglycemia are considered as risk factors for cardiovascular disease ( CVD) but the mechanism for their contribution to cardiopathogenesis is not well understood. Hyperglycemia induces nonenzymatic glycation of protein-yielding advanced glycation end products ( AGE), which are postulated to stimulate interleukin-6 ( IL-6) expression, triggering the liver to secrete tissue necrosis factor alpha ( TNF-alpha) and C-reactive protein ( CRP) that contribute to CVD pathogenesis. Although the high prevalence of periodontitis among individuals with diabetes is well known by dental researchers, it is relatively unrecognized in the medical community. The expression of the same proinflammatory mediators implicated in hyperglycemia ( i.e., IL-6, TNF-alpha, and CRP) have been reported to be associated with periodontal disease and increased risk for CVD. We will review published evidence related to these 2 pathways and offer a consensus. C1 [Janket, Sok-Ja; Jones, Judith A.] Boston Univ, Sch Dent Med, Dept Gen Dent, Boston, MA 02118 USA. [Meurman, Jukka H.] Univ Helsinki, Cent Hosp, Inst Dent, Helsinki, Finland. [Baird, Alison E.] Natl Inst Neurol Disorders & Stroke, Stroke Div, NIH, Bethesda, MD USA. [Van Dyke, Thomas E.] Boston Univ, Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. RP Janket, SJ (reprint author), Boston Univ, Sch Dent Med, Dept Gen Dent, 100 E Newton St,Rm G-619, Boston, MA 02118 USA. EM skjanket@bu.edu OI Janket, Sok-Ja/0000-0003-0078-3992; Jones, Judith/0000-0002-0126-0790; Meurman, Jukka/0000-0001-6702-6836 FU Intramural NIH HHS; NIDCR NIH HHS [P01 DE013191, R01 DE015566, R01 DE015566-01A1] NR 44 TC 35 Z9 38 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD FEB PY 2008 VL 105 IS 2 BP 173 EP 179 DI 10.1016/j.tripleo.2007.06.027 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 262EQ UT WOS:000253132200009 PM 17905606 ER PT J AU Woo, CW Tan, F Cassano, H Lee, J Lee, KC Thiele, CJ AF Woo, Chan-Wook Tan, Fei Cassano, Hope Lee, JungHwa Lee, Kwang Chul Thiele, Carol J. TI Use of RNA interference to elucidate the effect of MYCN on cell cycle in neuroblastoma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE MYCN; neuroblastoma; cell cycle; p27; CDK6 ID HUMAN NEURO-BLASTOMA; N-MYC; MAMMALIAN-CELLS; ID2 EXPRESSION; E GENE; AMPLIFICATION; ASSOCIATION; DEGRADATION; PROGRESSION; ONCOGENE AB Background MYCN amplification marks poor prognosis in neuroblastoma (NB) tumors. In evaluating the mechanisms by which retinoic acid (RA) or nerve growth factor (NGF) decrease cell number in MYCN amplified NB cells, we have identified a number of proteins whose expression either decreases (E2F, CDC2, CDK6, cyclin dependent kinase activity) or increases (p27) in association with a decrease in MYCN expression. However, it was still unclear which were MYCN dependent effects or not. Procedure. This study aimed to determine which changes in cell cycle gene expression are modulated as a consequence of the decrease in MYCN. We silenced MYCN expression using siRNA targeted to the coding region of MYCN. Then, by using siRNA transient transfections, we analyzed the change of cell cycle related genes and cell cycle in MYCN amplified NB cell lines. Results. We demonstrate that expression of MYCN can be suppressed by almost 60% in MYCN amplified NB cell using siRNAs targeted to MYCN. Functionally, the decrease in MYCN leads to a decrease in cells in the S-phase of the cell cycle. Decreases in MYCN are associated with decreases in E2F1-2 and ID2 along with increases in p27 protein levels by post-transcriptional modification. Moreover, we find that a decrease in MYCN is accompanied by a decrease in cdk6 mRNA and protein expression. Conclusions. These results show that E2F and ID2 expression is associated with MYCN regulation and that cdk6 is a possible new transcriptional target of MYCN. C1 [Woo, Chan-Wook; Lee, JungHwa; Lee, Kwang Chul] Korea Univ, Coll Med, Dept Pediat, Seoul 152703, South Korea. [Tan, Fei; Cassano, Hope; Thiele, Carol J.] NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Woo, CW (reprint author), Korea Univ, Ansan Hosp, Coll Med, Dept Pediat, 516 Gojan-1-Dong, Ansan 425707, Kyungki Do, South Korea. EM wooc@korea.ac.kr FU Intramural NIH HHS NR 30 TC 18 Z9 18 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2008 VL 50 IS 2 BP 208 EP 212 DI 10.1002/pbc.21195 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 246KN UT WOS:000252006000005 PM 17420990 ER PT J AU Hoffman, KE Derdak, J Bernstein, D Reynolds, JC Avila, NA Gerber, L Steinberg, SM Chrousos, G Mackall, CL Mansky, PJ AF Hoffman, Karen E. Derdak, Joanne Bernstein, Donna Reynolds, James C. Avila, Nilo A. Gerber, Lynn Steinberg, Seth M. Chrousos, George Mackall, Crystal L. Mansky, Patrick J. TI Metabolic syndrome traits in long-term survivors of pediatric sarcoma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cancer survivors; cardiovascular; endocrine; insulin resistance; late effects; metabolic; treatment ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GROWTH-HORMONE DEFICIENCY; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; ADULT SURVIVORS; INSULIN-RESISTANCE; CHILDHOOD-CANCER; INCREASED RISK; US ADULTS; DISTURBANCES AB Purpose. The metabolic syndrome (MS), a cluster of central obesity, dyslipidemia, hyperglycemia, and hypertension, conveys an increased risk of type 2 diabetes and cardiovascular disease. This cross-sectional study investigated the prevalence of metabolic syndrome traits (MST) in long-term survivors of pediatric sarcoma (SARC) who received multi-modality therapy (MMT). Methods. Thirty-two SARC survivors (predominantly Ewings; median age 36.5; median age at MMT 15) underwent body composition, activity, and psychosocial analysis. Serum endocrine and inflammatory parameters and urine beta(2)-microglobulin (132M) were evaluated. The prevalence of MST was compared to age- and gender-matched U.S. population data. Results. SARC survivors were more likely to have two or more MST (OR 2.38 95% Cl: [1.14, 5.04]). Analysis of individual MST demonstrated higher prevalence of hypertension (OR 2.61 95% Cl: 11.20, 5.591]), hypertriglyceridemia (OR 3.63 95% Cl: [1.75, 7.60]), and male visceral abdominal obesity (20-39 years old OR 4.63 95% Cl: [0.91, 21.63], 40-59 years old OR infinity). Survivors 18-39 years old had a higher prevalence of the MS (OR 4.29 95% Cl: [1.50, 11.21]), defined as three or more MST. Plasminogen activator inhibitory activity (P = 0.016) and 132M (P = 0.027) increased with increasing numbers of MST. In males,total testosterone declined (P = 0.0027) as the number of MST increased. Average (P = 0.014) and maximum (P = 0.021) activity levels decreased as the number of MST increased. Conclusion. After a median follow up of 17 years, adult SARC survivors of MMT had an increased prevalence of MST, especially those less than 40 years old. The development of MST in this population was associated with decreased testosterone and activity levels. Pediatr Blood Cancer 2008;50:341-346. (c) 2007 Wiley-Liss, Inc. C1 [Hoffman, Karen E.; Derdak, Joanne; Bernstein, Donna; Steinberg, Seth M.; Mackall, Crystal L.] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Dept Nucl Med, CC, Bethesda, MD USA. [Avila, Nilo A.] NIH, Dept Diagnost Radiol, CC, Bethesda, MD 20892 USA. [Gerber, Lynn] George Mason Univ, Fairfax, VA 22030 USA. [Chrousos, George] NICHHD, NIH, Bethesda, MD 20892 USA. [Mansky, Patrick J.] NIH, NCCAM, Div Intramural Res, Bethesda, MD USA. RP Mansky, PJ (reprint author), Natl Ctr Complementary & Alternat Med, NIH, DHHS, 10 Ctr Dr,Bldg 10,CRC,Room 4-1741,MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov FU Intramural NIH HHS NR 38 TC 30 Z9 30 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2008 VL 50 IS 2 BP 341 EP 346 DI 10.1002/pbc.21363 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 246KN UT WOS:000252006000032 PM 17918262 ER PT J AU Lee, BH Stoll, BJ McDonald, SA Higgins, RD AF Lee, Ben H. Stoll, Barbara J. McDonald, Scott A. Higgins, Rosemary D. CA NICHHDNRN TI Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone SO PEDIATRICS LA English DT Article DE prenatal glucocorticoid treatment; dexamethasone; betamethasone; extremely low birth weight; neurodevelopmental outcome ID RESPIRATORY-DISTRESS SYNDROME; GLUCOCORTICOID TREATMENT; ANTENATAL DEXAMETHASONE; PREMATURE-INFANTS; CONTROLLED TRIAL; LUNG-DISEASE; SCHOOL-AGE; RETINOPATHY; EXPRESSION; CORTICOSTEROIDS AB OBJECTIVE. We compared the development of adverse neurodevelopmental outcomes at corrected ages of 18 to 22 months for extremely low birth weight infants exposed prenatally to dexamethasone, betamethasone, or no steroid. METHODS. Study infants were extremely low birth weight (401-1000 g) infants who were in the care of National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 2002, and April 30, 2003; they were assessed neurodevelopmentally at corrected ages of 18 to 22 months. Outcomes were defined as Bayley Scales of Infant Development-II Mental Development Index of < 70, Bayley Scales of Infant Development-II Psychomotor Development Index of < 70, bilateral blindness, bilateral hearing aid use, cerebral palsy, and neurodevelopmental impairment. Neurodevelopmental impairment was defined as >= 1 of the aforementioned outcomes. RESULTS. A total of 1124 infants met entry criteria. There were no statistically significant associations between prenatal dexamethasone exposure and any follow-up outcome, compared with no prenatal steroid exposure. Prenatal betamethasone exposure was associated with reduced risks of hearing impairment and neurodevelopmental impairment and with increased likelihood of unimpaired status, compared with no prenatal steroid exposure. Compared with betamethasone, dexamethasone was associated with a trend for increased risk of Psychomotor Development Index of < 70, increased risk of hearing impairment, and decreased likelihood of unimpaired status. CONCLUSIONS. Prenatal betamethasone exposure was associated with increased likelihood of unimpaired neurodevelopmental status and reduced risk of hearing impairment at corrected ages of 18 to 22 months among extremely low birth weight infants, compared with prenatal dexamethasone exposure or no prenatal steroid exposure. Pending a randomized, clinical trial, it may be in the best interests of infants to receive betamethasone, rather than dexamethasone, when possible. C1 [Lee, Ben H.; Stoll, Barbara J.] Mid Atlantic Neonatol Associates, Morristown, NJ 07960 USA. [Lee, Ben H.] Emory Univ, Sch Med, Div Neonatal Perinatal Med, Atlanta, GA 30322 USA. [McDonald, Scott A.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Higgins, Rosemary D.] NICHHD, Washington, DC USA. RP Lee, BH (reprint author), Mid Atlantic Neonatol Associates, 100 Madison Ave,Box 85, Morristown, NJ 07960 USA. EM ben.lee@atlantichealth.org FU NICHD NIH HHS [U10 HD27856, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40521, U10 HD40689] NR 33 TC 47 Z9 47 U1 0 U2 2 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 FEB PY 2008 VL 121 IS 2 BP 289 EP 296 DI 10.1542/peds.2007-1103 PG 8 WC Pediatrics SC Pediatrics GA 258OQ UT WOS:000252877600009 PM 18245420 ER PT J AU Lukacik, M Thomas, RL Aranda, JV AF Lukacik, Marek Thomas, Ronald L. Aranda, Jacob V. TI A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea SO PEDIATRICS LA English DT Article DE diarrhea; zinc ID RANDOMIZED CONTROLLED-TRIAL; MALNOURISHED BANGLADESHI CHILDREN; VITAMIN-A SUPPLEMENTATION; ACUTE WATERY DIARRHEA; YOUNG-CHILDREN; DEVELOPING-COUNTRIES; POOLED ANALYSIS; DOUBLE-BLIND; EFFICACY; INFANTS AB OBJECTIVE. Children in developing countries are at a high risk for zinc deficiency. Supplemental zinc has previously been shown to provide therapeutic benefits in diarrhea. The objective of this study was to examine the efficacy and safety of supplemental oral zinc therapy during recovery from acute or persistent diarrhea. METHODS. We conducted a meta-analysis of randomized, controlled trials to compare the efficacy and safety of supplementary oral zinc with placebo in children with acute and persistent diarrhea. Results were reported using a pooled relative risk or a weighted mean difference. A total of 22 studies were identified for inclusion: 16 examined acute diarrhea (n = 15 231), and 6 examined persistent diarrhea (n = 2968). RESULTS. Mean duration of acute diarrhea and persistent diarrhea was significantly lower for zinc compared with placebo. Presence of diarrhea between zinc and placebo at day 1 was not significantly different in acute diarrhea or persistent diarrhea trials. At day 3, presence was significantly lower for zinc in persistent diarrhea trials (n = 221) but not in acute diarrhea trials. Vomiting after therapy was significantly higher for zinc in 11 acute diarrhea trials (n = 4438) and 4 persistent diarrhea trials (n = 2969). Those who received zinc gluconate in comparison with zinc sulfate/acetate vomited more frequently. Overall, children who received zinc reported an 18.8% and 12.5% reduction in average stool frequency, 15.0% and 15.5% shortening of diarrhea duration, and a 17.9% and 18.0% probability of reducing diarrhea over placebo in acute and persistent trials, respectively. CONCLUSIONS. Zinc supplementation reduces the duration and severity of acute and persistent diarrhea; however, the mechanisms by which zinc exerts its antidiarrheal effect have not been fully elucidated. C1 [Lukacik, Marek] Med Coll Georgia, Childrens Med Ctr, Dept Pediat, Augusta, GA 30912 USA. [Thomas, Ronald L.; Aranda, Jacob V.] Wayne State Univ, Sch Med, Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48202 USA. [Thomas, Ronald L.; Aranda, Jacob V.] Wayne State Univ, NICHHD, Pediat Pharmacol Res Unit Network, Detroit, MI 48202 USA. RP Lukacik, M (reprint author), Med Coll Georgia, Childrens Med Ctr, Dept Pediat, 1120 15th St, Augusta, GA 30912 USA. EM mlukacik@mcg.edu NR 43 TC 68 Z9 72 U1 0 U2 11 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 FEB PY 2008 VL 121 IS 2 BP 326 EP 336 DI 10.1542/peds.2007-0921 PG 11 WC Pediatrics SC Pediatrics GA 258OQ UT WOS:000252877600013 PM 18245424 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI Late-preterm births: Challenges and opportunities SO PEDIATRICS LA English DT Editorial Material ID NEAR-TERM INFANTS; RESPIRATORY-FAILURE; PREMATURE RUPTURE; GESTATIONAL-AGE; MEMBRANES; FETUS; LABOR C1 [Raju, Tonse N. K.] NIH, NICHHD, Ctr Dev Biol & Perinatal Med, Bethesda, MD 20952 USA. RP Raju, TNK (reprint author), NIH, NICHHD, Ctr Dev Biol & Perinatal Med, 6100 Execut Blvd,Room 4BD3, Bethesda, MD 20952 USA. EM rajut@mail.nih.gov NR 20 TC 17 Z9 17 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 FEB PY 2008 VL 121 IS 2 BP 402 EP 403 DI 10.1542/peds.2007-2357 PG 2 WC Pediatrics SC Pediatrics GA 258OQ UT WOS:000252877600020 PM 18245431 ER PT J AU Golub, MS Collman, GW Foster, PMD Kimmel, CA Meyts, ERD Reiter, EO Sharpe, RM Skakkebaek, NE Toppari, J AF Golub, Mari S. Collman, Gwen W. Foster, Paul M. D. Kimmel, Carole A. Meyts, Ewa Rajpert-De Reiter, Edward O. Sharpe, Richard M. Skakkebaek, Niels E. Toppari, Jorma TI Public health implications of altered puberty timing SO PEDIATRICS LA English DT Review DE puberty; precocious puberty; adrenarche; growth and development; breast cancer; testicular cancer; polycystic ovary; syndrome; infertility; behavioral symptoms; risk assessment ID ENDOCRINE-DISRUPTING CHEMICALS; CENTRAL PRECOCIOUS PUBERTY; PROSTATE-CANCER RISK; LEVEL LEAD TOXICITY; IN-UTERO EXPOSURE; TESTICULAR CANCER; PREMATURE ADRENARCHE; SEXUAL-MATURATION; ADOLESCENT GIRLS; POLYBROMINATED BIPHENYLS AB Changes in puberty timing have implications for the treatment of individual children, for the risk of later adult disease, and for chemical testing and risk assessment for the population. Children with early puberty are at a risk for accelerated skeletal maturation and short adult height, early sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated with an increased risk for testicular cancer according to several, but not all, epidemiologic studies. Girls and, possibly, boys who exhibit premature adrenarche are at a higher risk for developing features of metabolic syndrome, including obesity, type 2 diabetes, and cardiovascular disease later in adulthood. Altered timing of puberty also has implications for behavioral disorders. For example, an early maturation is associated with a greater incidence of conduct and behavior disorders during adolescence. Finally, altered puberty timing is considered an adverse effect in reproductive toxicity risk assessment for chemicals. Recent US legislation has mandated improved chemical testing approaches for protecting children's health and screening for endocrine-disrupting agents, which has led to changes in the US Environmental Protection Agency's risk assessment and toxicity testing guidelines to include puberty-related assessments and to the validation of pubertal male and female rat assays for endocrine screening. C1 [Toppari, Jorma] Univ Turku, Dept Physiol, FI-20520 Turku, Finland. [Toppari, Jorma] Univ Turku, Dept Pediat, FI-20520 Turku, Finland. [Golub, Mari S.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. [Golub, Mari S.] California Environm Protect Agcy, Sacramento, CA USA. [Collman, Gwen W.] Div Extramural Res & Training, Res Triangle Pk, NC USA. [Foster, Paul M. D.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Kimmel, Carole A.] US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Skakkebaek, Niels E.] Rigshosp, Dept Growth & Reprod, DK-2100 Copenhagen, Denmark. [Reiter, Edward O.] Baystate Childrens Hosp, Dept Pediat, Springfield, MA USA. [Sharpe, Richard M.] Univ Edinburgh, MRC, Human Reprod Sci Unit, Edinburgh, Midlothian, Scotland. RP Toppari, J (reprint author), Univ Turku, Dept Physiol, Kiinamyllynkatu 10, FI-20520 Turku, Finland. EM jorma.toppari@utu.fi RI Sharpe, Richard/D-2725-2013 OI Sharpe, Richard/0000-0003-1686-8085 FU Medical Research Council [MC_U127684422]; NCRR NIH HHS [RR00169] NR 146 TC 141 Z9 149 U1 7 U2 24 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 FEB PY 2008 VL 121 SU S BP S218 EP S230 DI 10.1542/peds.2007-1813G PG 13 WC Pediatrics SC Pediatrics GA 271MN UT WOS:000253792600005 PM 18245514 ER PT J AU Louis, GMB Gray, LE Marcus, M Ojeda, SR Pescovitz, OH Witchel, SF Sippell, W Abbott, DH Soto, A Tyl, RW Bourguignon, JP Skakkebaek, NE Swan, SH Golub, MS Wabitsch, M Toppari, J Euling, SY AF Louis, Germaine M. Buck Gray, L. Earl Marcus, Michele Ojeda, Sergio R. Pescovitz, Ora H. Witchel, Selma Feldman Sippell, Wolfgang Abbott, David H. Soto, Ana Tyl, Rochelle W. Bourguignon, Jean-Pierre Skakkebaek, Niels E. Swan, Shanna H. Golub, Mari S. Wabitsch, Martin Toppari, Jorma Euling, Susan Y. TI Environmental factors and puberty timing: Expert panel research needs SO PEDIATRICS LA English DT Review DE human puberty; puberty timing; breast development; menarche; pubic hair development; genital development; endocrine disruptors; body fat ID POLYCYSTIC-OVARY-SYNDROME; IN-UTERO EXPOSURE; FEMALE RHESUS-MONKEYS; DOSE-RESPONSE ANALYSIS; SPRAGUE-DAWLEY RATS; BISPHENOL-A ALTERS; SEXUAL-MATURATION; REPRODUCTIVE DEVELOPMENT; THYROID-FUNCTION; POLYCHLORINATED-BIPHENYLS AB Serono Symposia International convened an expert panel to review the impact of environmental influences on the regulation of pubertal onset and progression while identifying critical data gaps and future research priorities. An expert panel reviewed the literature on endocrine-disrupting chemicals, body size, and puberty. The panel concluded that available experimental animal and human data support a possible role of endocrine-disrupting chemicals and body size in relation to alterations in pubertal onset and progression in boys and girls. Critical data gaps prioritized for future research initiatives include (1) etiologic research that focus on environmentally relevant levels of endocrine-disrupting chemicals and body size in relation to normal puberty as well as its variants, (2) exposure assessment of relevant endocrine-disrupting chemicals during critical windows of human development, and (3) basic research to identify the primary signal(s) for the onset of gonadotropin-releasing hormone-dependent/central puberty and gonadotropin-releasing hormone -independent/peripheral puberty. Prospective studies of couples who are planning pregnancies or pregnant women are needed to capture the continuum of exposures at critical windows while assessing a spectrum of pubertal markers as outcomes. Coupled with comparative species studies, such research may provide insight regarding the causal ordering of events that underlie pubertal onset and progression and their role in the pathway of adult-onset disease. C1 [Louis, Germaine M. Buck] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. [Gray, L. Earl] US EPA, Endocrinol Branch, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Marcus, Michele] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Ojeda, Sergio R.] Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Pescovitz, Ora H.] Indiana Univ, Sch Med, James Whitcomb Riley Hosp Children, Dept Pediat & Cellular & Integrat Physiol, Indianapolis, IN 46204 USA. [Witchel, Selma Feldman] Childrens Hosp Pittsburgh, Div Endocrinol, Pittsburgh, PA 15213 USA. [Sippell, Wolfgang] Univ Kiel, Dept Pediat, Div Endocrinol, D-2300 Kiel, Germany. [Abbott, David H.] Univ Wisconsin, Dept Obstet Gynecol, Madison, WI USA. [Soto, Ana] Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA. [Tyl, Rochelle W.] RTI Int, Ctr Life Sci & Toxicol, Res Triangle Pk, NC USA. [Bourguignon, Jean-Pierre] Univ Liege, CHU Sart Tilman, B-4000 Liege, Belgium. [Skakkebaek, Niels E.] Rigshosp, Univ Dept Growth & Reprod, DK-2100 Copenhagen, Denmark. [Swan, Shanna H.] Univ Missouri, Dept Family & Community Med, Columbia, MO USA. [Golub, Mari S.] California Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Sacramento, CA USA. [Wabitsch, Martin] Univ Ulm, Dept Pediat & Adolescent Med, Ulm, Germany. [Toppari, Jorma] Univ Turku, Dept Physiol, Turku, Finland. [Toppari, Jorma] Univ Turku, Dept Pediat, Turku, Finland. [Euling, Susan Y.] US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Abbott, David H.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA. RP Louis, GMB (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov RI Marcus, Michele/J-2746-2015; OI Buck Louis, Germaine/0000-0002-1774-4490 NR 123 TC 95 Z9 96 U1 7 U2 23 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 FEB PY 2008 VL 121 SU S BP S192 EP S207 DI 10.1542/peds.1813E PG 16 WC Pediatrics SC Pediatrics GA 271MN UT WOS:000253792600003 PM 18245512 ER PT J AU Oner, O Alkar, OY Oner, P AF Oner, Ozgur Alkar, Ozden Yalcinkaya Oner, Pinar TI Relation of ferritin levels with symptom ratings and cognitive performance in children with attention deficit-hyperactivity disorder SO PEDIATRICS INTERNATIONAL LA English DT Article DE attention deficit hyperactivity disorder; ferritin; iron deficiency; neuropsychological assessment ID SPONTANEOUSLY HYPERTENSIVE-RAT; IRON-DEFICIENCY; EXECUTIVE FUNCTIONS; DEFICIT/HYPERACTIVITY DISORDER; NUCLEUS-ACCUMBENS; ANIMAL-MODEL; BRAIN IRON; ADOLESCENTS; DOPAMINE; ADHD AB Background: The aim of the present paper was to investigate the relationship between behavioral symptoms and attentional and executive functions and hematological variables related to iron deficiency and anemia, ferritin, hemoglobin, mean corpuscular volume (MCV), and red cell distribution width (RDW) in children and adolescents with attention deficit-hyperactivity disorder (ADHD). Methods: The sample consisted of 52 ADHD children (42 boys, 10 girls; age 7-13 years; mean +/- SD, 9.9 +/- 2.1 years). Conners Parent and Teacher Rating Scales were obtained. The neuropsychological test battery included Wisconsin Card-Sorting Test (WCST), Stroop, Continuous Performance Test, Digit Symbol and Digit Span subtests of the Wechsler Intelligence Scale for Children Revised (WISC-R), and Trail Making Test A and B, which taps abstraction-flexilibity (WCST), sustained attention (CPT), mental tracking and complex attention (WISC-R Digit Span, Digit Symbol, Trail Making A and B) and interference control (Stroop). Multiple linear regression was used to evaluate the relation of ferritin, hemoglobin, MCV, RDW, age, gender, and presence of comorbidity. Results: While seven children had iron deficiency, none of them was anemic. Lower ferritin levels were associated with higher hyperactivity scores in parental ratings. While performance increased with age for most of the neuropsychological tests utilized, ferritin, hemoglobin, MCV and RDW and gender were not significantly related with cognitive performance in this sample. Conclusions: At least for the present clinical sample, ferritin levels might be related with behavioral but not cognitive measures in ADHD cases. C1 [Oner, Ozgur] SB Diskapi Childerns Hosp, Dept Child Psychiat, Ankara, Turkey. [Alkar, Ozden Yalcinkaya] Etlik Ihtisas Hosp, Dept Child Psychiat, Ankara, Turkey. [Oner, Pinar] Mersin Univ, Sch Med, Dept Child Psychiat, Mersin, Turkey. [Oner, Ozgur] Childrens Hosp, Fogarty Int Ctr, Mental Hlth & Dev Disabil Program, Boston, MA USA. RP Oner, O (reprint author), Gelincik Sok 11-10 A, Ankara, Turkey. EM ozz_oner@yahoo.com FU FIC NIH HHS [D43 TW005807, D43 TW005807-05S1, D43 TW005807-06, D43 TW005807-04, D43 TW005807-05, D43TW05807] NR 34 TC 33 Z9 35 U1 2 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1328-8067 J9 PEDIATR INT JI Pediatr. Int. PD FEB PY 2008 VL 50 IS 1 BP 40 EP 44 DI 10.1111/j.1442-200X.2007.02496.x PG 5 WC Pediatrics SC Pediatrics GA 262AO UT WOS:000253121600008 PM 18279203 ER PT J AU Adib, AB AF Adib, Artur B. TI Random-walk approach to the d-dimensional disordered Lorentz gas SO PHYSICAL REVIEW E LA English DT Article ID ANALYTIC DENSITY BEHAVIOUR; DIFFUSION COEFFICIENT; DIVERGENCIES; EXPANSION AB A correlated random walk approach to diffusion is applied to the disordered nonoverlapping Lorentz gas. By invoking the Lu-Torquato theory for chord-length distributions in random media [J. Chem. Phys. 98, 6472 (1993)], an analytic expression for the diffusion constant in arbitrary number of dimensions d is obtained. The result corresponds to an Enskog-like correction to the Boltzmann prediction, being exact in the dilute limit, and better or nearly exact in comparison to renormalized kinetic theory predictions for all allowed densities in d=2,3. Extensive numerical simulations were also performed to elucidate the role of the approximations involved. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Adib, AB (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM adiba@mail.nih.gov FU Intramural NIH HHS NR 17 TC 6 Z9 6 U1 0 U2 0 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 FEB PY 2008 VL 77 IS 2 AR 021118 DI 10.1103/PhysRevE.77.021118 PN 1 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 271BK UT WOS:000253763700032 PM 18351998 ER PT J AU Wildman, DE AF Wildman, D. E. TI Sources for comparative studies of placentation. II. Genomic resources SO PLACENTA LA English DT Article DE placentation; phylogenomics; mammalia ID EVOLUTION; SEQUENCE; INSIGHTS; MAMMALS AB The genomes of over a dozen placental mammal species are now publicly available. These genome sequences have the potential to provide insight into the development and evolution of the placenta. In particular, the variable anatomy of the placenta has likely been affected by natural selection on the genomes of living and extinct mammals. In this note the current availability of mammal genome sequences is reviewed, and strengths and limitations of these data are discussed. Additionally, museums, zoos, and commercial entities are available to provide genomic resources to the placental research community. Recommendations for tissue storage conditions of placentas in genomic research are given. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Wildman, D. E.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Wildman, D. E.] NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Wildman, DE (reprint author), Wayne State Univ, Ctr Mol Med & Genet, 540 E Canfield Ave, Detroit, MI 48201 USA. EM dwildman@med.wayne.edu FU Intramural NIH HHS [Z99 HD999999, Z01 HD002400-16] NR 18 TC 3 Z9 3 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD FEB PY 2008 VL 29 IS 2 BP 144 EP 147 DI 10.1016/j.placenta.2007.11.005 PG 4 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 267FZ UT WOS:000253496200002 PM 18155141 ER PT J AU Klausmeyer, P McCloud, TG Uranchimeg, B Melillo, G Scudiero, DA Cardellina, JH Shoemaker, RH AF Klausmeyer, Paul McCloud, Thomas G. Uranchimeg, Badarch Melillo, Giovanni Scudiero, Dominic A. Cardellina, John H., II Shoemaker, Robert H. TI Separation and SAR study of HIF-1 alpha inhibitory tubulosines form Alangium cf. longiflourm SO PLANTA MEDICA LA English DT Article DE alongium cf. longiflorum; Alangiaceae; tubulosine; U251 human cancer cells; HIF-1 alpha; chiral chromatography ID PROTEIN-SYNTHESIS INHIBITORS; SMALL-MOLECULE INHIBITORS; INDUCIBLE FACTOR-I; IDENTIFICATION; ALKALOIDS; ACTIVATION; EMETINE; CELLS AB A crude organic solvent extract of Alangium cf. longiflorum exhibited potent inhibition of hypoxia-incluced HIF-1 transcriptional activity in human U251 glioma cells. Dereplication and bioactivity-guided fractionation, including Sephadex LH-20 and chiral HPLC chromatographies, led to the isolation of tubulosine (1), 9-desmethyltubulosine (2), and isotubulosine (3). Structures were verified by complete H-1 and C-13 assignments using 1D- and 2D-NMR techniques. Tubulosine strongly inhibited HIF-1 transcriptional activity, iscrtubulosine was devoid of activity, and 9-desmethyltubulosine possessed 6-fold less potency than tubulosine. C1 [Klausmeyer, Paul; McCloud, Thomas G.] NCI Frederick, SAIC Frederick Inc, Nat Prod Suppourt Grp, Frederick, MD 21702 USA. [Uranchimeg, Badarch; Melillo, Giovanni] NCI Frederick, DTP Tumor Hypoxia Lab, Frederick, MD 21702 USA. [Scudiero, Dominic A.] NCI Frederick, SAIC Frederick, Mol Target Screening Program, Frederick, MD 21702 USA. [Cardellina, John H., II; Shoemaker, Robert H.] NCI Frederick, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Screening Technol Branch, Frederick, MD 21702 USA. RP McCloud, TG (reprint author), NCI Frederick, SAIC Frederick Inc, Nat Prod Suppourt Grp, Frederick, MD 21702 USA. EM mccloud@dtpax2.ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 11 TC 6 Z9 6 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 BP 258 EP 263 DI 10.1055/s-2008-1034315 PG 6 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300010 PM 18302092 ER PT J AU Cragg, GM Newman, DJ AF Cragg, G. M. Newman, D. J. TI International collaboration in drug discovery and development - Abstracts SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Newman, D. J.] NCI, Div Canc Treatment & Diagnosis, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA S2 BP 307 EP 307 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300023 ER PT J AU Brown, PN Betz, JM AF Brown, P. N. Betz, J. M. TI Guidelines for analytical method selection & appropriate use when determining chemical constituents in dietary supplements SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Brown, P. N.] Ctr Technol, Nat Hlth Prod Res Grp, BC Inst Technol, Burnaby, BC V5G 3H2, Canada. [Betz, J. M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA S21 BP 313 EP 313 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300044 ER PT J AU Swanson, CA AF Swanson, C. A. TI NIH botanical research Centers program (BRCP) SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Swanson, C. A.] NIH, Off Dietary Supplements, Bethesda, MD 20895 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA S24 BP 314 EP 314 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300047 ER PT J AU Burdick, T Kotadia, A Pauli, GF AF Burdick, T. Kotadia, A. Pauli, G. F. TI NAPRABASE an open analytical database for natural products SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Burdick, T.; Kotadia, A.] Univ Illinois, Coll Pharm, Coll Engn, NIH, Chicago, IL 60612 USA. [Burdick, T.; Pauli, G. F.] Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL 60612 USA. [Kotadia, A.; Pauli, G. F.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. [Pauli, G. F.] Univ Illinois, Coll Pharm, Ctr Bot Dietary Supplements Res, NIH, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA P12 BP 326 EP 326 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300088 ER PT J AU Ejamo, YM Takahashi, Y Strunnikov, A AF Ejamo, Y. M. Takahashi, Y. Strunnikov, A. TI Investigating factors that affect chromosomal localization of essential chromosomal proteins SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Ejamo, Y. M.] Towson Univ, Towson, MD 21252 USA. [Takahashi, Y.; Strunnikov, A.] NICHD, NIH, LGRD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA P34 BP 333 EP 333 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300110 ER PT J AU Ungessa, S Lee, CH Lei, X Chen, T AF Ungessa, S. Lee, C. H. Lei, X. Chen, T. TI Genetic screen for visual system connectivity mutants in drosophila SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Ungessa, S.] Towson Univ, Towson, MD 21252 USA. [Lee, C. H.; Lei, X.; Chen, T.] NICHD, NIH, LGRD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA P36 BP 334 EP 334 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300112 ER PT J AU Meragelman, TL Cardellina, JH Britt, JR Shipley, SM McCloud, TG Newman, DJ Shoemaker, RH AF Meragelman, T. L. Cardellina, J. H. Britt, J. R. Shipley, S. M. McCloud, T. G. Newman, D. J. Shoemaker, R. H. TI Bacterial histone deacetylase inhibitor isolated from several Rubiaceae species. A mutualistic association? SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Meragelman, T. L.; Newman, D. J.] NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21702 USA. [Cardellina, J. H.; Shoemaker, R. H.] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. [Britt, J. R.; Shipley, S. M.; McCloud, T. G.] SAIC Frederick Inc, Nat Prod Suport Grp, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA P40 BP 335 EP 335 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300116 ER PT J AU Imai, A Yao, P Overk, C Bolton, JL Nikolic, DS van Breemen, RB Pauli, GF AF Imai, A. Yao, P. Overk, C. Bolton, J. L. Nikolic, D. S. van Breemen, R. B. Pauli, G. F. TI Phytochemical investigation of the estrogenic aerial parts of Cimicifuga racemosa (L.) Nutt (Ranunculaceae) SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Imai, A.; Yao, P.; Overk, C.; Bolton, J. L.; Nikolic, D. S.; van Breemen, R. B.; Pauli, G. F.] Univ Illinois, Coll Pharm, NIH,Dept Med Chem & Pharmacognosy, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA P45 BP 336 EP 336 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300121 ER PT J AU Klausmeyer, P Cardellina, JH Scudiero, DA Shoemaker, RH McCloud, TG AF Klausmeyer, P. Cardellina, J. H. Scudiero, D. A. Shoemaker, R. H. McCloud, T. G. TI HIF-1 alpha active components of the unstudied plant, Crossosoma bigelovii SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Klausmeyer, P.; McCloud, T. G.] NCI, Nat Prod Support Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. [Cardellina, J. H.; Shoemaker, R. H.] NCI, Screening Technol Branch, Dev Therapeut Program,FCRDC, Div Canc Treatment & Diagnost, Frederick, MD 21702 USA. [Scudiero, D. A.] NCI, Vitro Cell Line Screening Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA P84 BP 348 EP 348 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300160 ER PT J AU Sivertsen, A Wilcox, A Johnson, GE Abyholm, F Vindenes, HA Lie, RT AF Sivertsen, Ase Wilcox, Allen Johnson, Gunnar Espolin Abyholm, Frank Vindenes, Hallvard Andreas Lie, Rolv Terje TI Prevalence of major anatomic variations in oral clefts SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PALATE; LIP; CLP AB Background: The authors describe morphologic variations of oral clefts in a large population-based sample, especially variations in severity and laterality. The authors present 3616 cleft cases treated in Norway for oral clefts between 1967 and 1998. Methods: Classification of cleft morphology was based on clefting in 9 anatomical focal areas. A three-digit coding system provides a total of 63 possible cleft combinations. Their distribution in the population is presented as a whole and stratified by the baby's sex and the presence of accompanying malformations. The relative proportion of cleft types is illustrated in modified striped Y Kernahan diagrams. Results: Clefts of the lip or palate are more severe when both cleft types are present. Among babies with cleft lip, 18 percent of lips were severe (i.e., complete cleft of the primary palate) in the absence of cleft palate, compared with 81 percent severe when cleft palate was also present. Similarly, among babies with cleft palate, 40 percent were severe (complete cleft of the secondary palate) in the absence of cleft lip, compared with 93 percent when cleft lip was also present. The more severe the cleft lip, the more likely that the baby had an accompanying cleft palate. Girls were more likely to have severe clefts, as were patients who had other types of congenital disabilities. Although cleft lip was more frequent on the left side, clefts were not more severe on the left side. In bilateral cleft lip, the severity was similar on both sides. Conclusion: The authors' data provide a population-based reference for common and rare variants of oral clefts. C1 [Sivertsen, Ase; Wilcox, Allen; Johnson, Gunnar Espolin; Abyholm, Frank; Vindenes, Hallvard Andreas; Lie, Rolv Terje] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, NO-5018 Bergen, Norway. [Sivertsen, Ase; Wilcox, Allen; Johnson, Gunnar Espolin; Abyholm, Frank; Vindenes, Hallvard Andreas; Lie, Rolv Terje] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, NO-5018 Oslo, Norway. [Sivertsen, Ase; Wilcox, Allen; Johnson, Gunnar Espolin; Abyholm, Frank; Vindenes, Hallvard Andreas; Lie, Rolv Terje] Haukeland Hosp, Dept Plast Surg, N-5021 Bergen, Norway. [Sivertsen, Ase; Wilcox, Allen; Johnson, Gunnar Espolin; Abyholm, Frank; Vindenes, Hallvard Andreas; Lie, Rolv Terje] Haukeland Hosp, Dept Plast Surg, Oslo, Norway. [Sivertsen, Ase; Wilcox, Allen; Johnson, Gunnar Espolin; Abyholm, Frank; Vindenes, Hallvard Andreas; Lie, Rolv Terje] NIEHS, Epidemiol Branch, NIH, Durham, NC USA. [Sivertsen, Ase; Wilcox, Allen; Johnson, Gunnar Espolin; Abyholm, Frank; Vindenes, Hallvard Andreas; Lie, Rolv Terje] Rikshosp, Dept Plast Surg, Durham, NC USA. RP Sivertsen, A (reprint author), Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Kalfarveien 31, NO-5018 Bergen, Norway. EM ase.sivertsen@isf.uib.no OI Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 21 TC 23 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2008 VL 121 IS 2 BP 587 EP 595 DI 10.1097/01.prs.0000297839.78179.f5 PG 9 WC Surgery SC Surgery GA 261KC UT WOS:000253076500029 PM 18300979 ER PT J AU Elango, N Kim, SH Vigoda, E Yi, SV AF Elango, Navin Kim, Seong-Ho Vigoda, Eric Yi, Soojin V. CA NISC Comparative Sequencing Progra TI Mutations of Different Molecular Origins Exhibit Contrasting Patterns of Regional Substitution Rate Variation SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID HUMAN GENOME; DNA METHYLATION; GC-CONTENT; CYTOSINE DEAMINATION; VERTEBRATE GENOMES; MAMMALIAN GENOME; CPG-ISLANDS; EVOLUTION; SEQUENCE; SCALE AB Transitions at CpG dinucleotides, referred to as "CpG substitutions", are a major mutational input into vertebrate genomes and a leading cause of human genetic disease. The prevalence of CpG substitutions is due to their mutational origin, which is dependent on DNA methylation. In comparison, other single nucleotide substitutions (for example those occurring at GpC dinucleotides) mainly arise from errors during DNA replication. Here we analyzed high quality BAC-based data from human, chimpanzee, and baboon to investigate regional variation of CpG substitution rates. We show that CpG substitutions occur approximately 15 times more frequently than other single nucleotide substitutions in primate genomes, and that they exhibit substantial regional variation. Patterns of CpG rate variation are consistent with differences in methylation level and susceptibility to subsequent deamination. In particular, we propose a "distance-decaying" hypothesis, positing that due to the molecular mechanism of a CpG substitution, rates are correlated with the stability of double-stranded DNA surrounding each CpG dinucleotide, and the effect of local DNA stability may decrease with distance from the CpG dinucleotide. Consistent with our "distance-decaying" hypothesis, rates of CpG substitution are strongly (negatively) correlated with regional G+C content. The influence of G+C content decays as the distance from the target CpG site increases. We estimate that the influence of local G+C content extends up to 1,500,2,000 bps centered on each CpG site. We also show that the distance-decaying relationship persisted when we controlled for the effect of long-range homogeneity of nucleotide composition. GpC sites, in contrast, do not exhibit such "distance-decaying" relationship. Our results highlight an example of the distinctive properties of methylation-dependent substitutions versus substitutions mostly arising from errors during DNA replication. Furthermore, the negative relationship between G+C content and CpG rates may provide an explanation for the observation that GC-rich SINEs show lower CpG rates than other repetitive elements. C1 [Elango, Navin; Kim, Seong-Ho; Yi, Soojin V.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Vigoda, Eric] Georgia Inst Technol, Coll Comp, Atlanta, GA 30332 USA. RP Elango, N (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. EM soojinyi@gatech.edu FU Georgia Institute of Technology; NSF; National Human Genome Research Institute; National Institutes of Health FX SVY is supported by funds from the Georgia Institute of Technology. EV is supported by NSF career grant. This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 47 TC 51 Z9 52 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD FEB PY 2008 VL 4 IS 2 AR e1000015 DI 10.1371/journal.pcbi.1000015 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 492WI UT WOS:000269692800015 PM 18463707 ER PT J AU Listgarten, J Brumme, Z Kadie, C Gao, XJ Walker, B Carrington, M Goulder, P Heckerman, D AF Listgarten, Jennifer Brumme, Zabrina Kadie, Carl Gao Xiaojiang Walker, Bruce Carrington, Mary Goulder, Philip Heckerman, David TI Statistical Resolution of Ambiguous HLA Typing Data SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID EXPECTATION-MAXIMIZATION ALGORITHM; HAPLOTYPE FREQUENCY ESTIMATION; MAXIMUM-LIKELIHOOD-ESTIMATION; C VIRUS-INFECTION; POPULATION-DATA; INFORMATION; INFERENCE; ALLELES; POLYMORPHISMS; GENOTYPE AB High-resolution HLA typing plays a central role in many areas of immunology, such as in identifying immunogenetic risk factors for disease, in studying how the genomes of pathogens evolve in response to immune selection pressures, and also in vaccine design, where identification of HLA-restricted epitopes may be used to guide the selection of vaccine immunogens. Perhaps one of the most immediate applications is in direct medical decisions concerning the matching of stem cell transplant donors to unrelated recipients. However, high-resolution HLA typing is frequently unavailable due to its high cost or the inability to re-type historical data. In this paper, we introduce and evaluate a method for statistical, in silico refinement of ambiguous and/or low-resolution HLA data. Our method, which requires an independent, high-resolution training data set drawn from the same population as the data to be refined, uses linkage disequilibrium in HLA haplotypes as well as four-digit allele frequency data to probabilistically refine HLA typings. Central to our approach is the use of haplotype inference. We introduce new methodology to this area, improving upon the Expectation-Maximization (EM)based approaches currently used within the HLA community. Our improvements are achieved by using a parsimonious parameterization for haplotype distributions and by smoothing the maximum likelihood (ML) solution. These improvements make it possible to scale the refinement to a larger number of alleles and loci in a more computationally efficient and stable manner. We also show how to augment our method in order to incorporate ethnicity information (as HLA allele distributions vary widely according to race/ethnicity as well as geographic area), and demonstrate the potential utility of this experimentally. A tool based on our approach is freely available for research purposes at http://microsoft.com/science. C1 [Listgarten, Jennifer; Kadie, Carl; Heckerman, David] Microsoft Res, Redmond, WA USA. [Brumme, Zabrina; Walker, Bruce; Goulder, Philip] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Gao Xiaojiang; Carrington, Mary] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Walker, Bruce] Howard Hughes Med Inst, Frederick, MD USA. [Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. RP Listgarten, J (reprint author), Microsoft Res, Redmond, WA USA. EM jennl@microsoft.com; heckerma@microsoft.com FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; Center for Cancer Research FX This publication has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. NR 48 TC 35 Z9 35 U1 0 U2 1 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 FEB PY 2008 VL 4 IS 2 AR e1000016 DI 10.1371/journal.pcbi.1000016 PG 15 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 492WI UT WOS:000269692800016 PM 18392148 ER PT J AU Kimura, M Cherkas, LF Kato, BS Demissie, S Hjelmborg, JB Brimacombe, M Cupples, A Hunkin, JL Gardner, JP Lu, XB Cao, XJ Sastrasinh, M Province, MA Hunt, SC Christensen, K Levy, D Spector, TD Aviv, A AF Kimura, Masayuki Cherkas, Lynn F. Kato, Bernet S. Demissie, Serkalem Hjelmborg, Jacob B. Brimacombe, Michael Cupples, Adrienne Hunkin, Janice L. Gardner, Jefferey P. Lu, Xiaobin Cao, Xiaojian Sastrasinh, Malinee Province, Michael A. Hunt, Steven C. Christensen, Kaare Levy, Daniel Spector, Tim D. Aviv, Abraham TI Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm SO PLOS GENETICS LA English DT Article ID INSULIN-RESISTANCE; OLDEST-OLD; PULSE PRESSURE; MALE GERMLINE; CELLS; ASSOCIATION; MORTALITY; LIFE; POPULATION; CHROMOSOME AB Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (< 30 years) and older (> 50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study. C1 [Kimura, Masayuki; Brimacombe, Michael; Gardner, Jefferey P.; Lu, Xiaobin; Cao, Xiaojian; Sastrasinh, Malinee; Aviv, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [Cherkas, Lynn F.; Kato, Bernet S.; Hunkin, Janice L.; Spector, Tim D.] Kings Coll London, Twin Res & Genet Epidemiol Unit, London WC2R 2LS, England. [Demissie, Serkalem; Cupples, Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Hjelmborg, Jacob B.; Christensen, Kaare] Univ So Denmark, Inst Publ Hlth Epidemiol & Stat, Odense, Denmark. [Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Hunt, Steven C.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Levy, Daniel] NHLBI, Framingham Heart Study, Boston, MA USA. RP Aviv, A (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, 185 S Orange Ave, Newark, NJ 07103 USA. EM avivab@umdnj.edu RI Christensen, Kaare/C-2360-2009; OI Christensen, Kaare/0000-0002-5429-5292; Atkins, Janice/0000-0003-4919-9068; Brimacombe, Michael/0000-0002-3276-9071 FU NHLBI NIH HHS [U01 HL067901, N0HC25195, U01 HL 67893, U01 HL056567, U01 HL067893, U01 HL067894, U01 HL067895, U01 HL067896, U01 HL067897, U01 HL067898, U01 HL067899, U01 HL067900, U01 HL067902, U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, U01 HL56569, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, U01 HL67902]; NIA NIH HHS [P01-AG0876, R01 AG020132, R01 AG021593, R01-AG020132, R01-AG021593]; Wellcome Trust [074951] NR 59 TC 90 Z9 91 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD FEB PY 2008 VL 4 IS 2 AR e37 DI 10.1371/journal.pgen.0040037 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 294EC UT WOS:000255386100025 PM 18282113 ER PT J AU Shifman, S Johannesson, M Bronstein, M Chen, SX Collier, DA Craddock, NJ Kendler, KS Li, T O'Donovan, M O'Neill, FA Owen, MJ Walsh, D Weinberger, DR Sun, C Flint, J Darvasi, A AF Shifman, Sagiv Johannesson, Martina Bronstein, Michal Chen, Sam X. Collier, David A. Craddock, Nicholas J. Kendler, Kenneth S. Li, Tao O'Donovan, Michael O'Neill, F. Anthony Owen, Michael J. Walsh, Dermot Weinberger, Daniel R. Sun, Cuie Flint, Jonathan Darvasi, Ariel TI Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women SO PLOS GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE-POLYMORPHISM; POOLED DNA; EXTRACELLULAR-MATRIX; SEX-DIFFERENCES; LARGE SAMPLES; REGION; MICROARRAYS; REPEAT; ARRAYS; MOUSE AB Sex differences in schizophrenia are well known, but their genetic basis has not been identified. We performed a genome-wide association scan for schizophrenia in an Ashkenazi Jewish population using DNA pooling. We found a female-specific association with rs7341475, a SNP in the fourth intron of the reelin ( RELN) gene (p = 2.9 x 10(-5) in women), with a significant gene-sex effect (p = 1.8 x 10(-4)). We studied rs7341475 in four additional populations, totaling 2,274 cases and 4,401 controls. A significant effect was observed only in women, replicating the initial result (p = 2.1 x 10(-3) in women; p = 4.2 x 10(-3) for gene-sex interaction). Based on all populations the estimated relative risk of women carrying the common genotype is 1.58 (p = 8.8 x 10(-7); p = 1.6 x 10(-5) for gene-sex interaction). The female-specific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease. C1 [Shifman, Sagiv; Johannesson, Martina; Flint, Jonathan] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Bronstein, Michal; Darvasi, Ariel] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Chen, Sam X.; Kendler, Kenneth S.; Sun, Cuie] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Chen, Sam X.; Kendler, Kenneth S.; Sun, Cuie] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behavior Genet, Richmond, VA USA. [Collier, David A.; Li, Tao] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England. [Craddock, Nicholas J.; O'Donovan, Michael; Owen, Michael J.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. [Li, Tao] Sichuan Univ, Psychiat Lab, W China Hosp, Chengdu, Peoples R China. [Li, Tao] Sichuan Univ, Dept Psychiat, W China Hosp, Chengdu, Peoples R China. [Li, Tao] Sichuan Univ, State Key Lab Biotherapy, W China Hosp, Chengdu, Peoples R China. [O'Neill, F. Anthony] Queens Univ Belfast, Dept Psychiat, Belfast, Antrim, North Ireland. [Walsh, Dermot] Hlth Res Board, Dublin, Ireland. [Weinberger, Daniel R.] US Dept Hlth & Human Serv, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIMH,NIH, Bethesda, MD USA. RP Shifman, S (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM sagiv@vms.huji.ac.il RI turton, miranda/F-4682-2011; johannesson, martina/F-4131-2011; Shifman, Sagiv/D-8749-2017; OI johannesson, martina/0000-0002-4353-7583; Shifman, Sagiv/0000-0003-4071-5361; O'Donovan, Michael/0000-0001-7073-2379; Flint, Jonathan/0000-0002-9427-4429; O'Neill, Francis Anthony/0000-0002-7531-7657 FU Medical Research Council [G9309834, G9810900]; Wellcome Trust [079912, ] NR 37 TC 202 Z9 215 U1 1 U2 18 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 FEB PY 2008 VL 4 IS 2 AR e28 DI 10.1371/journal.pgen.0040028 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 294EC UT WOS:000255386100019 PM 18282107 ER PT J AU Silver, DL Hou, L Somerville, R Young, ME Apte, SS Pavan, WJ AF Silver, Debra L. Hou, Ling Somerville, Robert Young, Mary E. Apte, Suneel S. Pavan, William J. TI The secreted metalloprotease ADAMTS20 is required for melanoblast survival SO PLOS GENETICS LA English DT Article ID CREST CELL-MIGRATION; C-KIT EXPRESSION; CHONDROITIN SULFATE PROTEOGLYCAN; EPIDERMAL-GROWTH-FACTOR; MELANOCYTE PRECURSORS; PG-M/VERSICAN; CAENORHABDITIS-ELEGANS; MOUSE EMBRYO; STEEL FACTOR; IN-VIVO AB ADAMTS20 (A disintegrin-like and metalloprotease domain with thrombospondin type-1 motifs) is a member of a family of secreted metalloproteases that can process a variety of extracellular matrix (ECM) components and secreted molecules. Adamts20 mutations in belted (bt) mice cause white spotting of the dorsal and ventral torso, indicative of defective neural crest (NC)-derived melanoblast development. The expression pattern of Adamts20 in dermal mesenchymal cells adjacent to migrating melanoblasts led us to initially propose that Adamts20 regulated melanoblast migration. However, using a Dct-LacZ transgene to track melanoblast development, we determined that melanoblasts were distributed normally in whole mount E12.5 bt/bt embryos, but were specifically reduced in the trunk of E13.5 bt/bt embryos due to a seven- fold higher rate of apoptosis. The melanoblast defect was exacerbated in newborn skin and embryos from bt/bt animals that were also haploinsufficient for Adamts9, a close homolog of Adamts20, indicating that these metalloproteases functionally overlap in melanoblast development. We identified two potential mechanisms by which Adamts20 may regulate melanoblast survival. First, skin explant cultures demonstrated that Adamts20 was required for melanoblasts to respond to soluble Kit ligand (sKitl). In support of this requirement, bt/bt;Kit(tm1Alf)/+ and bt/bt;Kitl(Sl)/+ mice exhibited synergistically increased spotting. Second, ADAMTS20 cleaved the aggregating proteoglycan versican in vitro and was necessary for versican processing in vivo, raising the possibility that versican can participate in melanoblast development. These findings reveal previously unrecognized roles for Adamts proteases in cell survival and in mediating Kit signaling during melanoblast colonization of the skin. Our results have implications not only for understanding mechanisms of NC-derived melanoblast development but also provide insights on novel biological functions of secreted metalloproteases. C1 [Silver, Debra L.; Hou, Ling; Pavan, William J.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Somerville, Robert; Young, Mary E.; Apte, Suneel S.] Cleveland Clin Fdn ND20, Dept Biomed Engn, Cleveland, OH USA. RP Silver, DL (reprint author), NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. EM bpavan@mail.nih.gov OI Hou, Ling/0000-0003-0705-8099 FU Intramural NIH HHS; NIAMS NIH HHS [AR49930, R01 AR049930, R56 AR049930] NR 92 TC 46 Z9 46 U1 1 U2 5 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 FEB PY 2008 VL 4 IS 2 AR e1000003 DI 10.1371/journal.pgen.1000003 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 294EC UT WOS:000255386100004 PM 18454205 ER PT J AU Couper, KN Blount, DG Wilson, MS Hafalla, JC Belkaid, Y Kamanaka, M Flavell, RA De Souza, JB Riley, EM AF Couper, Kevin N. Blount, Daniel G. Wilson, Mark S. Hafalla, Julius C. Belkaid, Yasmine Kamanaka, Masahito Flavell, Richard A. De Souza, J. Brian Riley, Eleanor M. TI IL-10 from CD4(+)CD25(-)Foxp3(-)CD127(-) adaptive regulatory T cells modulates parasite clearance and pathology during malaria infection SO PLOS PATHOGENS LA English DT Article ID GROWTH-FACTOR-BETA; PLASMODIUM-CHABAUDI-CHABAUDI; INNATE IMMUNE-RESPONSES; TGF-BETA; MONOCLONAL-ANTIBODY; CYTOKINE PRODUCTION; LEISHMANIA-MAJOR; CUTTING EDGE; YOELII INFECTION; CEREBRAL MALARIA AB The outcome of malaria infection is determined, in part, by the balance of pro-inflammatory and regulatory immune responses. Failure to develop an effective pro-inflammatory response can lead to unrestricted parasite replication, whilst failure to regulate this response leads to the development of severe immunopathology. IL-10 and TGF-beta are known to be important components of the regulatory response, but the cellular source of these cytokines is still unknown. Here we have examined the role of natural and adaptive regulatory T cells in the control of malaria infection and find that classical CD4(+)CD25(hi) ( and Foxp3(+)) regulatory T cells do not significantly influence the outcome of infections with the lethal (17XL) strain of Plasmodium yoelii (PyL). In contrast, we find that adaptive IL-10-producing, CD4(+) T cells ( which are CD25(-), Foxp3(-), and CD127(-) and do not produce Th1, Th2, or Th17 associated cytokines) that are generated during both PyL and non-lethal P. yoelii 17X (PyNL) infections are able to down-regulate pro-inflammatory responses and impede parasite clearance. In summary, we have identified a population of induced Foxp3(-) regulatory (Tr1) T cells, characterised by production of IL-10 and down regulation of IL-7R alpha, that modulates the inflammatory response to malaria. C1 [Couper, Kevin N.; Blount, Daniel G.; Hafalla, Julius C.; De Souza, J. Brian; Riley, Eleanor M.] London Sch Hyg & Trop Med, Immunol Unit, Dept Infect & Trop Dis, London WC1, England. [Wilson, Mark S.; Belkaid, Yasmine] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Kamanaka, Masahito; Flavell, Richard A.] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. [De Souza, J. Brian] UCL, Sch Med, Dept Immunol & Mol Pathol, London W1N 8AA, England. RP Couper, KN (reprint author), London Sch Hyg & Trop Med, Immunol Unit, Dept Infect & Trop Dis, London WC1, England. EM eleanor.riley@lshtm.ac.uk RI Couper, Kevin/C-2419-2009; de Souza, Joseph/D-4979-2009; Riley, Eleanor/C-8960-2013; OI Riley, Eleanor/0000-0003-3447-3570; Couper, Kevin/0000-0003-4659-8960 FU Wellcome Trust [074538] NR 66 TC 129 Z9 131 U1 3 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2008 VL 4 IS 2 AR e1000004 DI 10.1371/journal.ppat.1000004 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 294OR UT WOS:000255415900005 PM 18401464 ER PT J AU Nelson, MI Viboud, C Simonsen, L Bennett, RT Griesemer, SB George, KS Taylor, J Spiro, DJ Sengamalay, NA Ghedin, E Taubenberger, JK Holmes, EC AF Nelson, Martha I. Viboud, Cecile Simonsen, Lone Bennett, Ryan T. Griesemer, Sara B. George, Kirsten St. Taylor, Jill Spiro, David J. Sengamalay, Naomi A. Ghedin, Elodie Taubenberger, Jeffery K. Holmes, Edward C. TI Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918 SO PLOS PATHOGENS LA English DT Article ID POSITIVE SELECTION; UNITED-STATES; EPIDEMIC; PANDEMICS; STRAINS; 20TH-CENTURY; MORTALITY; REVEALS; EXPLAIN; VACCINE AB The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized. C1 [Nelson, Martha I.; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Viboud, Cecile; Holmes, Edward C.] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA. [Bennett, Ryan T.] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [Bennett, Ryan T.; Griesemer, Sara B.; George, Kirsten St.; Taylor, Jill] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Spiro, David J.] J Craig Venter Inst, Rockville, MD USA. [Sengamalay, Naomi A.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Ghedin, Elodie] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Nelson, MI (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552; Simonsen, Lone/0000-0003-1535-8526 FU Intramural NIH HHS; NIGMS NIH HHS [GM080533-01, R01 GM080533] NR 39 TC 132 Z9 137 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2008 VL 4 IS 2 AR e1000012 DI 10.1371/journal.ppat.1000012 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 294OR UT WOS:000255415900012 PM 18463694 ER PT J AU Persky, S Blascovich, J AF Persky, Susan Blascovich, Jim TI Immersive virtual video game play and presence: Influences on aggressive feelings and behavior SO PRESENCE-TELEOPERATORS AND VIRTUAL ENVIRONMENTS LA English DT Article ID PHYSIOLOGICAL AROUSAL; CONSTRUCT-VALIDITY; VIOLENT; ENVIRONMENT; PARADIGMS; COGNITION; MODEL AB Immersive virtual environment technology (IVET) allows developers to create simulated environments that can engage users in context relevant behaviors and that can produce relatively intense user experiences for purposes such as entertainment (e.g., video games), phobia desensitization, and training. We predicted that playing a violent video game using an IVET platform would lead to increased presence and aggressive feelings and behavior compared to playing on a less immersive desktop platform. The results of two experiments supported this hypothesis. The data suggest that presence mediated the relationship between playing platform and aggressive feelings but not the relationship between playing platform and aggressive behavior. Finally, we explored the utility of using cardiovascular measures within this research paradigm. C1 [Persky, Susan] NHGRI, Bethesda, MD 20892 USA. [Blascovich, Jim] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. RP Persky, S (reprint author), NHGRI, 31 Ctr Dr,Bldg 31,Room B1B54D, Bethesda, MD 20892 USA. EM perskys@mail.nih.gov NR 49 TC 32 Z9 32 U1 5 U2 12 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 1054-7460 J9 PRESENCE-TELEOP VIRT JI Presence-Teleoper. Virtual Env. PD FEB PY 2008 VL 17 IS 1 BP 57 EP 72 DI 10.1162/pres.17.1.57 PG 16 WC Computer Science, Cybernetics; Computer Science, Software Engineering SC Computer Science GA 255OJ UT WOS:000252667000005 ER PT J AU Rao, RP Acharya, JK AF Rao, Raghavendra Pralhada Acharya, Jairaj K. TI Sphingolipids and membrane biology as determined from genetic models SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Review DE sphingolipids; membrane biology; animal models; genetics ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; PROTEIN-COUPLED RECEPTOR; SPHINGOMYELINASE-DEFICIENT MICE; GLOBOID-CELL LEUKODYSTROPHY; CENTRAL-NERVOUS-SYSTEM; GPI-ANCHORED PROTEINS; NIEMANN-PICK-DISEASE; HAMSTER OVARY CELLS; LONG-CHAIN BASE; SACCHAROMYCES-CEREVISIAE AB The importance of sphingolipids in membrane biology was appreciated early in the twentieth century when several human inborn errors of metabolism were linked to defects in sphingolipid degradation. The past two decades have seen an explosion of information linking sphingolipids with cellular processes. Studies have unraveled mechanistic details of the sphingolipid metabolic pathways, and these findings are being exploited in the development of novel therapies, some now in clinical trials. Pioneering work in yeast has laid the foundation for identifying genes encoding the enzymes of the pathways. The advent of the era of genomics and bioinformatics has led to the identification of homologous genes in other species and the subsequent creation of animal knock-out lines for these genes. Discoveries from these efforts have re-kindled interest in the role of sphingolipids in membrane biology. This review highlights some of the recent advances in understanding sphingolipids' roles in membrane biology as determined from genetic models. Published by Elsevier Inc. C1 [Rao, Raghavendra Pralhada; Acharya, Jairaj K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. RP Acharya, JK (reprint author), NCI, Lab Cell & Dev Signaling, Room 22-6,Bldg 560,1050 Boyle St, Frederick, MD 21702 USA. EM acharyaj@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010331-07, Z99 CA999999] NR 209 TC 9 Z9 9 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD FEB PY 2008 VL 85 IS 1-2 BP 1 EP 16 DI 10.1016/j.prostaglandins.2007.10.002 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 264EN UT WOS:000253268900001 PM 18035569 ER PT J AU Bian, XW Xu, JP Ping, YF Wang, Y Chen, JH Xu, CP Wu, YZ Wu, J Zhou, XD Chen, YS Shi, JQ Wang, JM AF Bian, Xiu-Wu Xu, Jian-Ping Ping, Yi-Fang Wang, Yan Chen, Jian-Hong Xu, Cheng-Ping Wu, Yu-Zhang Wu, Jun Zhou, Xiang-Dong Chen, Yi-Sheng Shi, Jing-Quan Wang, Ji Ming TI Unique proteomic features induced by a potential antiglioma agent, Nordy (dl-nordihydroguaiaretic acid), in glioma cells SO PROTEOMICS LA English DT Article DE apoptosis; differentiation therapy; glioma; lipoxygenase inhibitor; proliferation ID MALIGNANT HUMAN GLIOMAS; CHEMOKINE RECEPTOR CXCR4; LIPOXYGENASE INHIBITORS; FORMYLPEPTIDE RECEPTOR; GENE-EXPRESSION; HUMAN UP1; IN-VITRO; GROWTH; CANCER; ELECTROPHORESIS AB Nordy is a chirally synthesized compound of a natural lipoxygenase inhibitor nordihydroguaiaretic acid. In this study, we found that Nordy inhibited the growth of human glioma cell lines in vitro and their tumorigenicity in mice. In addition, Nordy promoted differentiation of highly malignant human glioma cells. Investigation into the mechanistic basis of Nordy activities revealed that it altered the pattern of protein expression profiles in tumor cells. By using 2-DE, we found that in human glioma cell lines, at least six proteins were down-regulated after Nordy treatment, while four proteins were elevated in the same cells. Among the six down-regulated proteins, microsequencing with MALDI TOF MS confirmed the identity of five: proliferation-associated gene A (PAG-A), alternative splicing factor-3 (ASF-3), P-galactoside binding lectin, eukaryotic translation initiation factor 5A (eIF-5A), and coffilin-1 (nonmuscle). Four upregulated proteins were GST-pi, glyceraldehyde-3-phosphate dehydrogenase, alpha-enolase, and cyclophilin. All these proteins have been reported to participate in key cellular functions including proliferation, metabolism, differentiation, apoptosis, and gene transcription. Our results suggest that Nordy may constitute a promising drug lead for the development of novel antitumor agents targeting proteins that control tumor cell function at multiple levels. C1 [Bian, Xiu-Wu; Xu, Jian-Ping; Ping, Yi-Fang; Chen, Jian-Hong; Xu, Cheng-Ping; Chen, Yi-Sheng; Shi, Jing-Quan] Third Mil Med Univ, SW Hosp, Inst Pathol, Chongqing, Peoples R China. [Wang, Yan] Third Mil Med Univ, Dept Med Genet, Div Basic Med Sci, Chongqing, Peoples R China. [Wu, Yu-Zhang] Third Mil Med Univ, Inst Immunol, Div Basic Med Sci, Chongqing, Peoples R China. [Wu, Jun] Third Mil Med Univ, Inst Burn Res, Chongqing, Peoples R China. [Zhou, Xiang-Dong] Third Mil Med Univ, Dept Pharm, Div Basic Med Sci, Chongqing, Peoples R China. [Wang, Ji Ming] NCI, Canc Res Ctr, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD USA. RP Bian, XW (reprint author), Third Mil Med Univ, SW Hosp, Inst Pathol, Chongqing, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 38 TC 13 Z9 15 U1 1 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD FEB PY 2008 VL 8 IS 3 BP 484 EP 494 DI 10.1002/pmic.200700054 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 263VA UT WOS:000253243400007 PM 18232056 ER PT J AU Abu-Asab, M Chaouchi, M Amri, H AF Abu-Asab, Mones Chaouchi, Mohamed Amri, Hakima TI Evolutionary medicine: A meaningful connection between omics, disease, and treatment SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Review DE biomarkers; cancer; early detection; evolution; omics; parsimony; phylogenetics ID GENE-EXPRESSION; PHYLOGENETIC ANALYSIS; SERUM PROTEOMICS; MICROARRAY DATA; LIKELIHOOD; PARSIMONY; CLASSIFICATION; NEUROBLASTOMA; PATHOGENESIS; CONGRUENCE AB The evolutionary nature of diseases requires that their omics be analyzed by evolution-compatible analytical tools such as parsimony phylogenetics in order to reveal common mutations and pathways' modifications. Since the heterogeneity of the omics data renders some analytical tools such as phenetic clustering and Bayesian likelihood inefficient, a parsimony phylogenetic paradigm seems to connect between the omics and medicine. It offers a seamless, dynamic, predictive, and multidimensional analytical approach that reveals biological classes, and disease ontogenies; its analysis can be translated into practice for early detection, diagnosis, biomarker identification, prognosis, and assessment of treatment. Parsimony phylogenetics identifies classes of specimens, the clades, by their shared derived expressions, the synapomorphies, which are also the potential biomarkers for the classes that they delimit. Synapomorphies are determined through polarity assessment (ancestral vs. derived) of m/z or gene-expression values and parsimony analysis; this process also permits intra and interplatform comparability and produces higher concordance between platforms. Furthermore, major trends in the data are also interpreted from the graphical representation of the data as a tree diagram termed cladogram; it depicts directionality of change, identifies the transitional patterns from healthy to diseased, and can be developed into a predictive tool for early detection. C1 [Abu-Asab, Mones] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Chaouchi, Mohamed; Amri, Hakima] Georgetown Univ, Sch Med, Dept Phys & Biophys, Washington, DC USA. RP Abu-Asab, M (reprint author), NCI, Pathol Lab, NIH, Bldg 10-rM 2a33, Bethesda, MD 20892 USA. EM mones@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 40 TC 14 Z9 15 U1 2 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD FEB PY 2008 VL 2 IS 2 BP 122 EP 134 DI 10.1002/prca.200780047 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266XN UT WOS:000253471200002 PM 18458745 ER PT J AU Amano, K Yamada, K Iwayama, Y Detera-Wadleigh, SD Hattori, E Toyota, T Tokunaga, K Yoshikawa, T Yamakawa, K AF Amano, Kenji Yamada, Kazuo Iwayama, Yoshimi Detera-Wadleigh, Sevilla D. Hattori, Eiji Toyota, Tomoko Tokunaga, Katsushi Yoshikawa, Takeo Yamakawa, Kazuhiro TI Association study between the Down syndrome cell adhesion molecule (DSCAM)gene and bipolar disorder SO PSYCHIATRIC GENETICS LA English DT Article DE case-control association; chromosome 21; family-based association; gene expression; linkage; postmortem brain ID PEDIGREE DISEQUILIBRIUM TEST; SUSCEPTIBILITY LOCUS; CHROMOSOME 21Q22.3; LINKAGE ANALYSIS; AXON GUIDANCE; GENOME SCAN; N-CAM; DSCAM; GENE; SCHIZOPHRENIA AB Objectives Defects of neurodevelopmental processes are suggested to underlie the pathogenesis of bipolar disorder. Down syndrome cell adhesion molecule (DSCAM), a member of neural immunoglobulin superfamily playing a diverse role for neural development, is mapped to chromosome 21q22, a linkage locus for bipolar disorder, and is, therefore, an interesting candidate for the disease. Methods We performed a variation screening of the gene and association studies in 22 multiplex bipolar pedigrees of Caucasian descent and 119 Japanese patients with bipolar disorder and 140 controls. Expression levels of DSCAM were also examined in postmortem brains from the Stanley Medical Research Institute. Results We found 27 single nucleotide polymorphisms in DSCAM. Possible associations of SNP DC141 (IVS27-15A > G; P=0.042) and DC142 (IVS29+328C > A; P=0.036) were observed in pedigree samples, and G allele of DC141 was correlated with increased expression levels of DSCAM (P=0.038) in postmortem brains. Possible association of DC136 (4749C > T), which is in the same haplotype block with DC141 and DC142, was detected in Japanese populations (P=0.049). Conclusions These results suggest the possible contribution of DSCAM gene in bipolar disorder, and warrant further investigations. C1 [Yamada, Kazuo; Iwayama, Yoshimi; Hattori, Eiji; Toyota, Tomoko; Yoshikawa, Takeo] RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama 3510198, Japan. [Amano, Kenji; Yamakawa, Kazuhiro] RIKEN, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. [Yoshikawa, Takeo] Japan Sci & Technol Agcy, CREST, Tokyo, Saitama, Japan. [Tokunaga, Katsushi] Univ Tokyo, Dept Human Genet, Grad Sch Med, Bunkyo Ku, Tokyo, Japan. [Tokunaga, Katsushi] Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo, Japan. [Detera-Wadleigh, Sevilla D.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Yoshikawa, T (reprint author), RIKEN, Brain Sci Inst, Lab Mol Psychiat, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM takeo@brain.riken.jp; yamakawa@brain.riken.jp RI Yamakawa, Kazuhiro/N-5050-2015 NR 36 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD FEB PY 2008 VL 18 IS 1 BP 1 EP 10 PG 10 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 256JD UT WOS:000252723700001 PM 18197079 ER PT J AU Wendland, JR DeGuzman, TB McMahon, F Rudnick, G Detera-Wadleigh, SD Murphy, DL AF Wendland, Jens R. DeGuzman, Theresa B. McMahon, Francis Rudnick, Gary Detera-Wadleigh, Sevilla D. Murphy, Dennis L. TI SERT IIeu425Val in autism, Asperger syndrome and obsessive-compulsive disorder SO PSYCHIATRIC GENETICS LA English DT Article DE autism; genetics; obsessive-compulsive disorder; serotonin ID SEROTONIN TRANSPORTER GENE; 5-HT2A PROMOTER POLYMORPHISM; PSYCHIATRIC-DISORDERS; SUSCEPTIBILITY LOCI; REPETITIVE THOUGHTS; GENOMEWIDE SCREEN; REGULATORY REGION; ANOREXIA-NERVOSA; LINKAGE ANALYSIS; ASSOCIATION AB Background SERT 1425V, an uncommon missense single nucleotide polymorphism producing a gain-of-function of the serotonin transporter (SERT), was originally found to segregate with a primarily obsessive-compulsive disorder (OCD) but complexly comorbid phenotype in two unrelated families. Objective As two individuals with SERT 1425V and OCD also had Asperger syndrome (AS), an autism spectrum disorder, and as other rare SERT variants have recently shown significant associations with autism, we set out to extend our original OCD study by genotyping additional autism/AS and OCD samples. Methods Case-control association study of SERT 1425V in 210 AS/autism probands and 215 controls, plus 335 OCD probands and their family members. Results SERT 1425V was not found in any of the individuals with AS/autism, OCD alone or OCD comorbid with AS and other disorders, or in controls. This results in new estimates of SERT 1425V having a 1.5% prevalence in 530 individuals with OCD from five unrelated families genotyped by us and by one other group and a 0.23% frequency in four control populations totaling 1300 individuals, yielding a continuing significant OCD-control difference (Fisher's exact test corrected for family coefficient of identity P=0.004, odds ratio=6.54). Conclusion As several other uncommon, less well quantitated genetic variations occur with an OCD phenotype, including chromosomal anomalies and some other rare gene variants (SGCE, GCH1 and SLITRK1), a tentative conclusion is that OCD resembles other complex disorders in being etiologically heterogeneous and in having both highly penetrant familial subtypes associated with rare alleles or chromosomal anomalies, as well as having a more common, polygenetic form that may involve polymorphisms in such genes as BDNF, COMT, GRIN2 beta, TPH2, HTR2A and SLC1A1. C1 [Wendland, Jens R.; DeGuzman, Theresa B.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [McMahon, Francis; Detera-Wadleigh, Sevilla D.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Rudnick, Gary] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41,10 Ctr Dr, Bethesda, MD 20892 USA. EM DennisMurphy@mail.nih.gov RI McMahon, Francis/A-7290-2009; Wendland, Jens/A-1809-2012 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA008213] NR 78 TC 19 Z9 21 U1 5 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD FEB PY 2008 VL 18 IS 1 BP 31 EP 39 PG 9 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 256JD UT WOS:000252723700005 PM 18197083 ER PT J AU Woodman, GF Kang, MS Thompson, K Schall, JD AF Woodman, Geoffrey F. Kang, Min-Suk Thompson, Kirk Schall, Jeffrey D. TI The effect of visual search efficiency on response preparation - Neurophysiological evidence for discrete flow SO PSYCHOLOGICAL SCIENCE LA English DT Article ID FRONTAL EYE FIELD; SACCADE TARGET SELECTION; PROCESSING STAGES; MENTAL PROCESSES; PARTIAL INFORMATION; CENTRAL BOTTLENECK; CONTINUOUS MODELS; DUAL-TASK; CORTEX; ACTIVATION AB Most models assume that response time (RT) comprises the time required for successive processing stages, but they disagree about whether information is transmitted continuously or discretely between stages. We tested these alternative hypotheses by measuring when movement-related activity began in the frontal eye field (FEF) of macaque monkeys performing visual search. Previous work showed that RT was longer when visual neurons in FEF took longer to select the target, a finding consistent with prolonged perceptual processing during less efficient search. We now report that the buildup of saccadic movement-related activity in FEF is delayed in inefficient visual search. Variability in the delay of movement-related activity accounted for the difference in RT between search conditions and for the variability of RT within conditions. These findings provide neurophysiological support for the hypothesis that information is transmitted discretely between perceptual and response stages of processing during visual search. C1 [Woodman, Geoffrey F.; Kang, Min-Suk; Schall, Jeffrey D.] Vanderbilt Univ, Dept Psychol, Ctr Integrat & Cognit Neurosci, Nashville, TN 37240 USA. [Woodman, Geoffrey F.; Kang, Min-Suk; Schall, Jeffrey D.] Vanderbilt Univ, Vanderbilt Vis Res Ctr, Nashville, TN 37240 USA. [Thompson, Kirk] NEI, NIH, Bethesda, MD 20892 USA. RP Woodman, GF (reprint author), Vanderbilt Univ, Dept Psychol, Ctr Integrat & Cognit Neurosci, Wilson Hall,111 21st Ave South, Nashville, TN 37240 USA. EM geoffrey.f.woodman@vanderbilt.edu FU NEI NIH HHS [F32 EY015043, R01-EY08890, P30-EY08126, P30 EY008126, T32 EY07135, R01 EY008890, T32 EY007135]; NICHD NIH HHS [P30 HD015052, P30-HD015052] NR 41 TC 37 Z9 37 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD FEB PY 2008 VL 19 IS 2 BP 128 EP 136 DI 10.1111/j.1467-9280.2008.02058.x PG 9 WC Psychology, Multidisciplinary SC Psychology GA 259TR UT WOS:000252964300008 PM 18271860 ER PT J AU Maheu, FS Merke, DP Schroth, EA Keil, MF Hardin, J Poeth, K Pine, DS Ernst, M AF Maheu, Francoise S. Merke, Deborah P. Schroth, Elizabeth A. Keil, Margaret F. Hardin, Julie Poeth, Kaitlin Pine, Daniel S. Ernst, Monique TI Steroid abnormalities and the developing brain: Declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE development; glucocorticoids; declarative memory; congenital adrenal hyperplasia; steroid hormones ID CORTICOTROPIN-RELEASING HORMONE; MORRIS WATER MAZE; LONG-TERM-MEMORY; SEXUAL-DIFFERENTIATION; PRENATAL DEXAMETHASONE; COGNITIVE FUNCTION; AMYGDALA FUNCTION; STRESS HORMONES; GENE-EXPRESSION; DENTATE GYRUS AB Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effects of these hormones on the neural networks underlying memory. Using Congenital adrenal hyperplasia (CAH) as a naturalistic mode( of early steroid abnormalities, this study examines the consequences of CAH on memory and its neural correlates for emotionally arousing and neutral material in children. Seventeen patients with CAH and 17 age- and sex-matched healthy children (ages 12-14 years) completed the study. Subjects were presented positive, negative and neutral pictures. Memory recall occurred about 30 min after viewing the picture. Children with CAH showed memory deficits for negative pictures compared to healthy children (p<0.01). There were no group differences on memory performance for either positive or neutral pictures (p>0.1). In patients, 24 h urinary-free cortisol levels (reflecting glucocorticoid replacement therapy) and testosterone levels were not associated with memory performance. These findings suggest that early steroid imbalances affect memory for negative material in children with CAH. Such memory impairments may result from abnormal brain organization and function following hormonal dysfunction during critical periods of development. Published by Elsevier Ltd. C1 [Maheu, Francoise S.; Schroth, Elizabeth A.; Poeth, Kaitlin; Pine, Daniel S.; Ernst, Monique] NIMH, NIH, Emot Dev & Affect Neurosci Sect, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Merke, Deborah P.; Keil, Margaret F.; Hardin, Julie] NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Merke, Deborah P.; Keil, Margaret F.; Hardin, Julie] NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Maheu, FS (reprint author), NIMH, NIH, Emot Dev & Affect Neurosci Sect, Mood & Anxiety Disorders Program, 15K N Dr,Room 333-C, Bethesda, MD 20892 USA. EM maheufra@mail.nih.gov FU Intramural NIH HHS [Z01 MH002780-06] NR 67 TC 9 Z9 9 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD FEB PY 2008 VL 33 IS 2 BP 238 EP 245 DI 10.1016/j.psyneuen.2007.11.006 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 265MH UT WOS:000253362600011 PM 18162329 ER PT J AU Kiyatkin, EA Bae, D AF Kiyatkin, Eugene A. Bae, David TI Behavioral and brain temperature responses to salient environmental stimuli and intravenous cocaine in rats: effects of diazepam SO PSYCHOPHARMACOLOGY LA English DT Article DE benzodiazepines; brain temperature recording; stress; arousal; metabolic brain activation; vasoconstriction; rats ID FREELY MOVING RATS; BODY-TEMPERATURE; BLOOD-PRESSURE; HEART-RATE; BENZODIAZEPINE RECEPTORS; SEXUAL INTERACTION; INITIAL-VALUE; DOPAMINE; STRESS; PHARMACOKINETICS AB Rationale While diazepam is an effective anxiolytic and somnolent drug in humans, its physiological and behavioral effects in animals are often variable. Differences in basal activity state (basal arousal) may be important in determining both this response variability and the pattern of drug influence on behavioral and physiological responses to natural arousing stimuli and other drugs. Objectives To evaluate the changes in brain, muscle, and skin temperatures, and in locomotion induced in rats by several arousing stimuli and intravenous (i.v.) cocaine; and to assess how these responses are modulated by diazepam at a relatively low dose (1 mg/kg, i.p.). Materials and methods Male rats were implanted with thermal probes in the nucleus accumbens (NAcc), temporal muscle, and subcutaneously, and equipped with a chronic i.v. catheter. They were exposed to 1-min tail-pinch, 1-min social interaction with another male and cocaine (1 mg/kg, i.v.) after administration of diazepam or saline. Results While the injection of either diazepam or saline resulted in similar locomotor activation and temperature responses, diazepam decreased basal brain and muscle temperatures for about 3 h; the temperature-decreasing effect of diazepam was oppositely related to basal brain temperature (r=-0.51). After diazepam, rats also showed weaker temperature and locomotor responses to both arousing stimuli; the effect was stronger for tail-pinch and for absolute temperature increases than relative changes. Although diazepam significantly decreased cocaine-induced locomotor activation, it had virtually no effects on cocaine-induced temperature responses in all locations. Conclusions In accordance with the "law of initial values", the temperature-increasing effects of all tested arousing stimuli and temperature-decreasing effect of diazepam depend upon basal brain temperature. The greatest temperature effects are seen with arousing stimuli at low basal arousal (increases) and with diazepam at high basal arousal (decreases). This is a likely explanation for the variability seen with the physiological and behavioral effects of diazepam in animals. C1 [Kiyatkin, Eugene A.; Bae, David] DHHS, Behav Neurosci Branch, Natl Inst Drug Abuse, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), DHHS, Behav Neurosci Branch, Natl Inst Drug Abuse, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural NIH HHS NR 40 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2008 VL 196 IS 3 BP 343 EP 356 DI 10.1007/s00213-007-0965-y PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 257OG UT WOS:000252807800002 PM 17938891 ER PT J AU Panlilio, LV Thorndike, EB Schindler, CW AF Panlilio, Leigh V. Thorndike, Eric B. Schindler, Charles W. TI A stimulus-control account of regulated drug intake in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE self-administration; incentive learning; titration; cocaine; remifentanil; food ID COMPOUNDING DISCRIMINATIVE STIMULI; D-AMPHETAMINE; SET-POINT; COCAINE; REINFORCEMENT; ESCALATION; SCHEDULES; REMIFENTANIL; TRANSITION; ADDICTION AB Rationale Patterns of drug self-administration are often highly regular, with a consistent pause after each self-injection. This pausing might occur because the animal has learned that additional injections are not reinforcing once the drug effect has reached a certain level, possibly due to the reinforcement system reaching full capacity. Thus, interoceptive effects of the drug might function as a discriminative stimulus, signaling when additional drug will be reinforcing and when it will not. Objective This hypothetical stimulus control aspect of drug self-administration was emulated using a schedule of food reinforcement. Materials and methods Rats' nose-poke responses produced food only when a cue light was present. No drug was administered at any time. However, the state of the light stimulus was determined by calculating what the whole-body drug level would have been if each response in the session had produced a drug injection. The light was only presented while this virtual drug level was below a specific threshold. A range of doses of cocaine and remifentanil were emulated using parameters based on previous self-administration experiments. Results Response patterns were highly regular, dose-dependent, and remarkably similar to actual drug self-administration. Conclusion This similarity suggests that the emulation schedule may provide a reasonable model of the contingencies inherent in drug reinforcement. Thus, these results support a stimulus control account of regulated drug intake in which rats learn to discriminate when the level of drug effect has fallen to a point where another self-injection will be reinforcing. C1 [Panlilio, Leigh V.; Thorndike, Eric B.; Schindler, Charles W.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. RP Panlilio, LV (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lpanlili@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000001-23, Z99 DA999999] NR 31 TC 13 Z9 13 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2008 VL 196 IS 3 BP 441 EP 450 DI 10.1007/s00213-007-0978-6 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 257OG UT WOS:000252807800011 PM 17957355 ER PT J AU Ironson, GH O'Cleirigh, C Weiss, A Schneiderman, N Costa, PT AF Ironson, Gail H. O'Cleirigh, Conall Weiss, Alexander Schneiderman, Neil Costa, Paul T., Jr. TI Personality and HIV disease progression: Role of NEO-PI-R openness, extraversion, and profiles of engagement SO PSYCHOSOMATIC MEDICINE LA English DT Article DE personality; HIV/AIDS; disease progression; Five-Factor Model; openness; conscientiousness ID CORONARY HEART-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM SURVIVAL; PSYCHOSOCIAL FACTORS; HEALTH BEHAVIORS; 5-FACTOR MODEL; VIRAL LOAD; MORTALITY; CANCER; RISK AB Objective: To examine the role of the big five personality domains (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness) and their respective facets and profiles on change in CD4 and log HIV-RNA copies/ml (VL) over 4 years. The examination of psychosocial predictors of disease progression in human immunodeficiency virus (HIV) has focused primarily on depression, coping, and stress, with little attention paid to stable individual differences. Methods: A diverse sample of HIV-seropositive patients (n = 104) completed personality assessment (NEO-PI-R), under-went comprehensive psychological assessment and blood samples every 6 months for 4 years. Linear rates of change for CD4 cells and VL were modeled using Hierarchical Linear Modeling controlling for antiretrovirals (time dependent covariate), initial disease status, age, gender, ethnicity, and education. Results: Domains that were significantly associated with slower disease progression over 4 years included Openness (CD4, VL), Extraversion (CD4, VL), and Conscientiousness (VL). Facets of the above domains that were significantly related to slower disease progression were assertiveness, positive emotions, and gregariousness (Extraversion); ideas, esthetics (Openness); achievement striving and order (Conscientiousness). In addition, profile analyses suggested personality styles which seem to underscore the importance of remaining engaged (e.g., Creative Interactors (E+O+), Upbeat Optimists (N-E+), Welcomers (E+A+), Go Getters (C+E+), and Directed (N-C+)) had slower disease progression, whereas the "homebody" profile (Low Extraversion-Low Openness) was significantly associated with faster disease progression. Conclusions: These results provide good initial evidence of the relationship between personality and disease progression in HIV and suggest protective aspects of profiles of engagement. These finding may help identify those individuals at risk for poorer disease course and specify targets for psychosocial interventions. C1 [Ironson, Gail H.; O'Cleirigh, Conall; Schneiderman, Neil] Univ Miami, Dept Psychiat & Psychol, Coral Gables, FL 33124 USA. [Weiss, Alexander; Costa, Paul T., Jr.] NIA, NIH, Lab Personal & Cognit, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ironson, GH (reprint author), Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. EM gironson@aol.com OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS; NIMH NIH HHS [R01 MH066697, R01 MH066697-05, R01MH066697, R01MH53791, T32 MH018917, T32MH18917] NR 44 TC 38 Z9 39 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD FEB-MAR PY 2008 VL 70 IS 2 BP 245 EP 253 DI 10.1097/PSY.0b013e31816422fc PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 263UU UT WOS:000253242800015 PM 18256349 ER PT J AU Eidemuller, M Ostroumova, E Krestinina, L Akleyev, A Jacob, P AF Eidemueller, M. Ostroumova, E. Krestinina, L. Akleyev, A. Jacob, P. TI Analysis of solid cancer mortality in the Techa River cohort using the two-step clonal expansion model SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; DOSIMETRY SYSTEM; MAYAK WORKERS; LUNG-CANCER; FOLLOW-UP; CARCINOGENESIS; RADIATION; RISK; EXPOSURE; AGE AB In this study the solid cancer mortality data in the Techa River Cohort in the Southern Urals region of Russia was analyzed. The cohort received protracted exposure in the 1950s due to the releases of radioactive materials from the Mayak plutonium complex. The Extended Techa River Cohort includes 29,849 people who resided along the Techa River between 1950 and 1960 and were followed from January 1, 1950 through December 31, 1999. The analysis was done within the framework of the biologically based two-stage clonal expansion (TSCE) model. It was found that about 2.6% of the 1854 solid cancer deaths (excluding 18 bone cancer cases) could be related to radiation exposure. At age 63, which is the mean age for solid cancer deaths, the excess relative risk (ERR) and excess absolute risk (EAR) were found to be 0.76 Gy(-1) (95% CI 0.23; 1.29) and 33.0 (10(4) PY Gy)(-1) (95% CI 9.8; 52.6), respectively. These risk estimates are consistent with earlier excess relative risk analyses for the same cohort. The change in the ERR with age was investigated in detail, and an increase in risk with attained age was observed. Furthermore, the data were tested for possible signs of genomic instability, and it was found that the data could be described equally well by a model incorporating effects of genomic instability. Results from the TSCE models indicated that radiation received at older ages might have stronger biological effects than exposure at younger ages. (C) 2008 by Radiation Research Society. C1 [Eidemueller, M.; Jacob, P.] Inst Radiat Protect, GSF Natl Res Ctr Environm & Hlth, D-85764 Neuherberg, Germany. [Ostroumova, E.] NCI, Bethesda, MD 20892 USA. [Ostroumova, E.; Krestinina, L.; Akleyev, A.] Urals Res Ctr Radiat Med, Chelyabinsk 454076, Russia. RP Eidemuller, M (reprint author), GSF Natl Res Ctr, Inst Radiat Protect, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM markus.eidemueller@asf.de RI Akleyev, Alexander/Q-1891-2015 OI Akleyev, Alexander/0000-0003-2583-5808 NR 29 TC 9 Z9 9 U1 0 U2 4 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 FEB PY 2008 VL 169 IS 2 BP 138 EP 148 DI 10.1667/RR1157.1 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 255BZ UT WOS:000252633000002 PM 18220471 ER PT J AU Unoki, M Bronner, C Mousli, M AF Unoki, Motoko Bronner, Christian Mousli, Marc TI A concern regarding the current confusion with the human homolog of mouse Np95, ICBP90/UHRF1 SO RADIATION RESEARCH LA English DT Editorial Material ID PROTEIN; EXPRESSION; UHRF1; GENE AB ICBP90/UHRF1, which is overexpressed in cancer cells and is down-regulated by p53, possesses a methylated CpG binding affinity and binds to the methylated promoters of tumor suppressor genes in cancer cells with HDAC1 and DNMT1, suggesting suppression of these genes and maintenance of methylation status which leads to carcinogenesis. Recently, it was reported that the human homolog of Np95 is different from ICBP90 but not from UHRF1. Because UHRF1 is the gene symbol of ICBP90, the claim is a little confusing; that is, UHRF1 and ICBP90 are identical. Because the previously published genomic structure of the ICBP90 gene needed to be revised and the registered ICBP90 sequence (AF129507) contains two rare polymorphisms or sequence errors, we think that confusion could occur. Here we show the revised ICBP90 gene structure and 366 polymorphisms in this gene. Our conclusion is that the human homolog of Np95 is ICBP90, whose gene symbol is UHRF1. (C) 2008 by Radiation Research Society. C1 [Unoki, Motoko] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bronner, Christian] CNRS, Dept Pharmacol & Pharmacochim Interact Mol & Cell, Fac Pharm, F-67401 Illkirch Graffenstaden, France. [Mousli, Marc] Univ Strasbourg 1, Fac Med, UPRES EA Interact Cellulaires & Mol Hote Parasite, Inst Parasitol & Pathol Trop Stasbourg, F-67000 Strasbourg, France. RP Unoki, M (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 3060, Bethesda, MD 20892 USA. EM unokim@mail.nih.gov NR 9 TC 4 Z9 4 U1 0 U2 2 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 FEB PY 2008 VL 169 IS 2 BP 240 EP 244 DI 10.1667/RR1209.1 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 255BZ UT WOS:000252633000013 PM 18220474 ER PT J AU Feinendegen, LE Paretzke, H Neumann, RD AF Feinendegen, Ludwig E. Paretzke, Herwig Neumann, Ronald D. TI Two principal considerations are needed after low doses of ionizing radiation SO RADIATION RESEARCH LA English DT Letter ID ADAPTIVE RESPONSE C1 [Feinendegen, Ludwig E.] Univ Dusseldorf, Dept Nucl Med, D-88131 Lindau, Germany. [Paretzke, Herwig] Res Ctr Hlth & Environm Sci GSF, Inst Radioprotect, Munich, Germany. [Neumann, Ronald D.] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Feinendegen, LE (reprint author), Univ Dusseldorf, Dept Nucl Med, Wannental 45, D-88131 Lindau, Germany. NR 5 TC 10 Z9 11 U1 1 U2 6 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 FEB PY 2008 VL 169 IS 2 BP 247 EP 248 DI 10.1667/RR1123.1d PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 255BZ UT WOS:000252633000017 PM 18220467 ER PT J AU Chang, R Chen, CC Kam, A Mao, E Shawker, TH Horne, MK AF Chang, Richard Chen, Clam C. Kam, Anthony Mao, Edict Shawker, Thomas H. Horne, McDonald K., III TI Deep vein thrombosis of lower extremity: Direct intraclot injection of alteplase once daily with systemic anti coagulation-results of pilot study SO RADIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; VENOUS THROMBOSIS; THROMBOLYTIC THERAPY; PERIPHERAL ARTERIAL; HEPARIN-THERAPY; CLINICAL COURSE; FOLLOW-UP; T-PA; STREPTOKINASE; REFLUX AB Purpose: To prospectively evaluate the outcome of patients with acute deep vein thrombosis (DVT) of the lower extremity treated with "lacing" of the thrombus with alteplase (recombinant tissue plasminogen activator, or rTPA). Materials and Methods: This HIPAA-compliant study was approved by the Institutional Review Board of the National Heart, Lung, and Blood Institute and was funded by the National Institutes of Health. After giving written consent, 20 patients with first-onset acute DVT were treated with direct intraclot lacing of the thrombus with alteplase (maximum daily dose, 50 mg per log per day; maximum of four treatments) and full systemic anticoagulation. Alteplase was chosen because its high fibrin affinity obviates continuous infusion of this thrombolytic agent. Ventilation-perfusion (V/Q) scans were performed for evaluation of embolic risks, and clinical and imaging examinations were supplemented with pharmacokinetic studies to enable further assessment of treatment Outcomes. Results: The 20 patients included 13 men and seven women aged 18-79 years. Antegrade blood flow was restored throughout the deep venous system in 16 patients (80%) during thrombolytic therapy, with complete resolution of symptoms in 18 patients (90%) after 6 months of anticoagulation. Pharmacokinetic studies showed rapid clearance of circulating alteplase and recovery of plasminogen activator inhibitor-1 levels within 2 hours after termination of alteplase treatment. V/Q scans revealed a 40% incidence of pulmonary embolism before treatment and a 15% incidence of asymptomatic pulmonary embolism during thrombolytic therapy. There were no cases of clinically important pulmonary embolism or serious bleeding during thrombolytic therapy. During a mean follow-up period of 3.4 years, no patient developed a postthrombotic syndrome or recurrent thromboembolism. Conclusion: Intraclot injection or lacing of the thrombus with a fibrin-binding thrombolytic agent such as alteplase is an alternative to continuous-infusion thrombolytic regimens and minimizes the duration of systemic exposure to thrombolytic agents. (C) RSNA, 2008. C1 [Chang, Richard; Kam, Anthony; Mao, Edict; Shawker, Thomas H.] NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Chen, Clam C.] NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. [Horne, McDonald K., III] NIH, Warren G Magnuson Clin Ctr, Imaging Sci Program, Bethesda, MD 20892 USA. [Horne, McDonald K., III] NIH, Warren G Magnuson Clin Ctr, Hematol Serv, Dept Lab Med,Clin Pathol Dept, Bethesda, MD 20892 USA. RP Chang, R (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rchang@cc.nih.gov FU Intramural NIH HHS NR 52 TC 8 Z9 11 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2008 VL 246 IS 2 BP 619 EP 629 DI 10.1148/radiol.2461062076 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JW UT WOS:000252796300034 PM 18227550 ER PT J AU Black, WC Aberle, DR Berg, CD AF Black, William C. Aberle, Denise R. Berg, Christine D. TI Will the national lung screening trial be able to demonstrate a mortality reduction? Response SO RADIOLOGY LA English DT Letter C1 [Black, William C.] Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03756 USA. [Aberle, Denise R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. [Berg, Christine D.] Natl Canc Inst, Div Canc Prevent, Bethesda, MD USA. RP Black, WC (reprint author), Dartmouth Hitchcock Med Ctr, Dept Radiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM william.black@hitchcock.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2008 VL 246 IS 2 BP 654 EP 654 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JW UT WOS:000252796300059 ER PT J AU Pilotto, A Ferrucci, L Franceschi, M D'Ambrosio, LP Scarcelli, C Cascavilla, L Paris, F Placentino, G Seripa, D Dallapiccola, B Leandro, G AF Pilotto, Alberto Ferrucci, Luigi Franceschi, Marilisa D'Ambrosio, Luigi P. Scarcelli, Carlo Cascavilla, Leandro Paris, Francesco Placentino, Giuliana Seripa, Davide Dallapiccola, Bruno Leandro, Gioacchino TI Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients SO REJUVENATION RESEARCH LA English DT Article ID MINI NUTRITIONAL ASSESSMENT; ILLNESS RATING-SCALE; FRAILTY INDEX; COLORECTAL-CANCER; CUMULATIVE INDEX; ELDERLY PATIENTS; HEALTH; POPULATION; COMMUNITY; PEOPLE AB Our objective was to construct and validate a Multidimensional Prognostic Index (MPI) for 1-year mortality from a Comprehensive Geriatric Assessment (CGA) routinely carried out in elderly patients in a geriatric acute ward. The CGA included clinical, cognitive, functional, nutritional, and social parameters and was carried out using six standardized scales and in formation on medications and social support network, for a total of 63 items in eight domains. A MPI was developed from CGA data by aggregating the total scores of the eight domains and expressing it as a score from 0 to 1. Three grades of MPI were identified: low risk, 0.0-0.33; moderate risk, 0.34-0.66; and severe risk, 0.67-1.0. Using the proportional hazard models, we studied the predictive value of the MPI for all causes of mortality over a 12-month follow-up period. MPI was then validated in a different cohort of consecutively hospitalized patients. The development cohort included 838 and the validation cohort 857 elderly hospitalized patients. Of the patients in the two cohorts, 53.3 and 54.9% were classified in the low-risk group, respectively (MPI mean value, 0.18 +/- 0.09 and 0.18 +/- 0.09); 31.2 and 30.6% in the moderaterisk group (0.48 +/- 0.09 and 0.49 +/- 0.09); 15.4 and 14.2% in the severe-risk group (0.77 +/- 0.08 and 0.75 +/- 0.07). In both cohorts, higher MPI scores were significantly associated with older age (p = 0.0001), female sex (p = 0.0001), lower educational level (p = 0.0001), and higher mortality (p = 0.0001). In both cohorts, a close agreement was found between the estimated mortality and the observed mortality after both 6 months and 1 year of follow-up. The discrimination of the MPI was also good, with a ROC area of 0.751 (95%CI, 0.70-0.80) at 6 months and 0.751 (95%CI, 0.71-0.80) at 1 year of follow-up. We conclude that this MPI, calculated from in formation collected in a standardized CGA, accurately stratifies hospitalized elderly patients into groups at varying risk of mortality. C1 [Pilotto, Alberto; Franceschi, Marilisa; D'Ambrosio, Luigi P.; Scarcelli, Carlo; Cascavilla, Leandro; Paris, Francesco; Placentino, Giuliana; Seripa, Davide] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, I-71013 San Giovanni Rotondo, FG, Italy. [Pilotto, Alberto; Franceschi, Marilisa; D'Ambrosio, Luigi P.; Scarcelli, Carlo; Cascavilla, Leandro; Paris, Francesco; Placentino, Giuliana; Seripa, Davide] IRCCS Casa Sollievo Sofferenza, Res Dept, Gerontol & Geriatr Lab, I-71013 San Giovanni Rotondo, FG, Italy. [Ferrucci, Luigi] Harbor Hosp Ctr, Longitudinal Studies Sect, NIA, Baltimore, MD USA. [Dallapiccola, Bruno] CSS Mendel Inst, Dept Res, Rome, Italy. [Leandro, Gioacchino] IRCCS Saverio Bellis, Biostat & Gastroenterol Unit, Castellana Grotte, Italy. RP Pilotto, A (reprint author), IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, Viale Cappuccini, I-71013 San Giovanni Rotondo, FG, Italy. EM alberto.pilotto@operapadrepio.it RI Dallapiccola, Bruno/K-8692-2016 OI Dallapiccola, Bruno/0000-0002-5031-1013 FU Intramural NIH HHS [Z99 AG999999] NR 35 TC 105 Z9 106 U1 5 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD FEB PY 2008 VL 11 IS 1 BP 151 EP 161 DI 10.1089/rei.2007.0569 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 268GC UT WOS:000253566300013 PM 18173367 ER PT J AU Levens, ED Xu, XL Munson, PJ Nelson, LM DeChemey, AH Nieman, LK AF Levens, Eric D. Xu, Xiuli Munson, Peter J. Nelson, Lawrence M. DeChemey, Alan H. Nieman, Lynnette K. TI Novel autosomal target genes may be responsible for SRY positive sex-reversal: The results of exon expression analysis SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Levens, Eric D.; Nelson, Lawrence M.; DeChemey, Alan H.; Nieman, Lynnette K.] NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Xu, Xiuli] NIH, NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Munson, Peter J.] NIH, CIT, Math & Stat Comp Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 40 BP 72A EP 72A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600042 ER PT J AU Kohn, MJ Yagi, R Ullah, Z De Pamphilis, ML AF Kohn, Matthew J. Yagi, Rieko Ullah, Zakir De Pamphilis, Melvin L. TI Specification of the trophectoderm lineage and production of trophoblast giant cells SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Kohn, Matthew J.; Yagi, Rieko; Ullah, Zakir; De Pamphilis, Melvin L.] NICHD, LMGR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 57 BP 77A EP 77A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600059 ER PT J AU Montenegro, D Romero, R Kim, SS Tarca, A Draghici, S Kusanovic, JP Kim, JS Erez, O Gotsch, F Hassan, SS Kim, CJ AF Montenegro, Daniel Romero, Roberto Kim, Sung-Su Tarca, Adi Draghici, Sorin Kusanovic, Juan Pedro Kim, Jun-Sun Erez, Offer Gotsch, Francesca Hassan, Sonia S. Kim, Chong Jai TI A role for microRNAs in human parturition SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Montenegro, Daniel; Romero, Roberto; Kim, Sung-Su; Tarca, Adi; Kusanovic, Juan Pedro; Kim, Jun-Sun; Erez, Offer; Gotsch, Francesca; Hassan, Sonia S.; Kim, Chong Jai] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Romero, Roberto; Kim, Chong Jai] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Tarca, Adi; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI USA. [Kim, Jun-Sun] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 61 BP 78A EP 78A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600063 ER PT J AU Jessmon, PA Kilburn, BA Romero, R Leach, RE Armant, DR AF Jessmon, P. A. Kilburn, B. A. Romero, R. Leach, R. E. Armant, D. R. TI HBEGF-induced downstream regulators of trophoblast functions SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Jessmon, P. A.; Kilburn, B. A.; Armant, D. R.] Wayne State Univ, Detroit, MI USA. [Romero, R.] NICHHD, NICHD, NIH, Bethesda, MD USA. [Leach, R. E.] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Armant, D. R.] NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 75 BP 82A EP 82A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600077 ER PT J AU Caritis, SN Simhan, H AF Caritis, Steve N. Simhan, Hyagriv TI Relationship of 17 alpha hydroxyprogesterone caproate (17-OHPC) concentrations and gestational age at delivery in twins SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Caritis, Steve N.; Simhan, Hyagriv] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Caritis, Steve N.; Simhan, Hyagriv] NICHD, Maternal Fetal Med Units Network, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 139 BP 100A EP 100A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600141 ER PT J AU Caritis, SN Venkat, R AF Caritis, Steve N. Venkat, Raman TI Impact of body mass index (BMI) on plasma concentrations of 17 alpha hydroxyprogesterone caproate (17-OHPC). SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Caritis, Steve N.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Venkat, Raman] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. [Caritis, Steve N.] NICHD, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 138 BP 100A EP 100A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600140 ER PT J AU Simhan, HN Caritis, SN AF Simhan, Hyagriv N. Caritis, Steve N. TI The effect of 17-alpha hydroxyprogesterone caproate (17-OHPC) on maternal plasma CRP levels in twin pregnancies SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Simhan, Hyagriv N.; Caritis, Steve N.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Simhan, Hyagriv N.; Caritis, Steve N.] NICHD, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 140 BP 100A EP 101A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600142 ER PT J AU Romero, V Hassan, S Ward, C Kusanovic, JP Nikita, L Mazaki-Tovi, S Camacho, N Mittal, P Romero, R AF Romero, Vivian Hassan, Sonia Ward, Clara Kusanovic, Juan Pedro Nikita, Lorraine Mazaki-Tovi, Shali Camacho, Natalia Mittal, Pooja Romero, Roberto TI Does a short cervix increase the risk for a small for gestational age neonate? SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Romero, Vivian; Hassan, Sonia; Ward, Clara; Nikita, Lorraine; Mazaki-Tovi, Shali; Camacho, Natalia; Mittal, Pooja] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Kusanovic, Juan Pedro; Romero, Roberto] NIH, NICHD, DHHS, Perinatol Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 220 BP 123A EP 124A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600222 ER PT J AU Sundell, IB Romero, R Kim, SK Kim, JS Kusanovic, JP Gotsch, F Erez, O Hassan, S Kim, CJ AF Sundell, I. Birgitta Romero, Roberto Kim, Sun Kwon Kim, Jung-Sun Kusanovic, Juan Pedro Gotsch, Francesca Erez, Offer Hassan, Sonia Kim, Chong Jai TI Fetal carriage of the 4G/4G plasminogen activator inhibitor type 1 (PAI-1) genotype is a risk factor for fetal thrombotic vasculopathy and has functional consequences SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Sundell, I. Birgitta; Romero, Roberto; Kim, Sun Kwon; Kim, Jung-Sun; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Hassan, Sonia; Kim, Chong Jai] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 259 BP 134A EP 135A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600261 ER PT J AU Imudia, AN Kilburn, BA Petkova, A Edwin, SS Romero, R Armant, DR AF Imudia, Anthony N. Kilburn, Brian A. Petkova, Anelia Edwin, Samuel S. Romero, Roberto Armant, D. Randall TI Expression of heparin-binding EGF-Like growth factor (HBEGF) in term chorionic villous explants and its role in trophoblast survival. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Imudia, Anthony N.; Kilburn, Brian A.; Petkova, Anelia; Armant, D. Randall] Wayne State Univ, Sch Med, Detroit, MI USA. [Edwin, Samuel S.; Romero, Roberto] NICHD, Perinatol Res Branch, Bethesda, MD USA. [Armant, D. Randall] NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 288 BP 142A EP 142A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600290 ER PT J AU Than, NG Romero, R Erez, O Weckle, A Hotra, J Abbas, A Kim, CJ Kusanovic, JP Gotsch, F Santolaya-Forgas, J Benirschke, K Papp, Z Grossman, LI Goodman, M Wildman, DE AF Than, Nandor G. Romero, Roberto Erez, Offer Weckle, Amy Hotra, John Abbas, Asad Kim, Chong Jai Kusanovic, Juan Pedro Gotsch, Francesca Santolaya-Forgas, Joaquin Benirschke, Kurt Papp, Zoltan Grossman, Lawrence I. Goodman, Morris Wildman, Derek E. TI Evidence that galectin-1 has undergone intense purifying selection in placental mammals: A potential link between placentation and immune response SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Than, Nandor G.; Romero, Roberto; Erez, Offer; Weckle, Amy; Hotra, John; Abbas, Asad; Kusanovic, Juan Pedro; Gotsch, Francesca] NIH, NICHD, DHHS, Perinatol Res Branch, Bethesda, MD 20892 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Santolaya-Forgas, Joaquin] Brigham & Womens Hosp, Harvard Med Sch, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benirschke, Kurt] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary. [Grossman, Lawrence I.; Goodman, Morris; Wildman, Derek E.] Wayne State Univ, Dept Med & Mol Genet, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S BP 151A EP 151A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600320 ER PT J AU Kim, SK Romero, R Edwin, S Kim, JS Kim, YM Kusanovic, JP Gotsch, F Erez, O Hassan, S Kim, CJ AF Kim, Sun Kwon Romero, Roberto Edwin, Sam Kim, Jung-Sun Kim, Yeon Mee Kusanovic, Juan Pedro Gotsch, Francesca Erez, Offer Hassan, Sonia Kim, Chong Jai TI Novel observations on surfactant protein-D (SP-D) in human pregnancy: Human neutrophils are a source of SP-D. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Kim, Sun Kwon; Romero, Roberto; Edwin, Sam; Kim, Jung-Sun; Kim, Yeon Mee; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Hassan, Sonia; Kim, Chong Jai] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 324 BP 152A EP 152A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600326 ER PT J AU Cormier, CM AF Cormier, Clint M. TI Relationship between severity of maternal diabetes and VBAC success in women undergoing trial of labor. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Cormier, Clint M.] Univ Texas Houston Hlth Sci Ctr, Houston, TX USA. [Cormier, Clint M.] NICHD, MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 411 BP 176A EP 177A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600413 ER PT J AU Vora, S Ackerman, WE Kniss, DA Abbas, A Kim, CJ Romero, R AF Vora, Sonali Ackerman, William E. Kniss, Douglas A. Abbas, Asad Kim, Chong Jai Romero, Roberto TI Nuclear localization of NF kappa B in full-thickness fetal membranes, decidua, and myometrium in term and preterm labor. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Vora, Sonali; Ackerman, William E.; Kniss, Douglas A.] Ohio State Univ, Columbus, OH 43210 USA. [Abbas, Asad; Kim, Chong Jai; Romero, Roberto] NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. RI Ackerman, William/E-2612-2011 NR 0 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 450 BP 187A EP 188A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600452 ER PT J AU Erez, O Vaisbuch, E Gotsch, F Kusanovic, JP Mazaki-Tovi, S Kim, CJ Kim, JS Chaiworapongsa, T Hoppensteadt, D Fareed, J Than, NG Nhan-Chang, CL Mazor, M Mittal, P Hassan, SS Romero, R AF Erez, Offer Vaisbuch, Edi Gotsch, Francesca Kusanovic, Juan Pedro Mazaki-Tovi, Shali Kim, Chong Jai Kim, Jung-Sun Chaiworapongsa, Tinnakorn Hoppensteadt, Deborah Fareed, Jawed Than, Nandor G. Nhan-Chang, Chia-Ling Mazor, Moshe Mittal, Pooja Hassan, Sonia S. Romero, Roberto TI Protein Z plasma concentrations in the umbilical cord of patients with Preeclampsia and SGA. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Erez, Offer; Vaisbuch, Edi; Gotsch, Francesca; Kusanovic, Juan Pedro; Than, Nandor G.; Romero, Roberto] NIH, NICHD, DHHS, Perinatol Res Branch, Bethesda, MD USA. [Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA. [Kim, Chong Jai; Kim, Jung-Sun] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Hoppensteadt, Deborah; Fareed, Jawed] Loyola Univ, Dept Pathol, Maywood, IL 60153 USA. [Mazor, Moshe] Soroka Univ, Med Ctr, Dept Ob Gyn, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 543 BP 213A EP 213A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600545 ER PT J AU Bytautiene, E Maner, WL Romero, R Saade, GR Garfield, RE AF Bytautiene, Egle Maner, William L. Romero, Roberto Saade, George R. Garfield, Robert E. TI Uterine electromyographic activity in pregnant women with asthma SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Bytautiene, Egle; Maner, William L.; Saade, George R.; Garfield, Robert E.] Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77550 USA. [Romero, Roberto] NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 579 BP 223A EP 223A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600581 ER PT J AU Harvey, AJ Armant, DR Brenner, CA AF Harvey, A. J. Armant, D. R. Brenner, C. A. TI Stem cell markers of embryonic and trophoblast lineages in rhesus macaque blastocysts. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Harvey, A. J.; Armant, D. R.; Brenner, C. A.] Wayne State Univ, Detroit, MI USA. [Armant, D. R.] NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 611 BP 232A EP 232A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600613 ER PT J AU Manipalviratn, S Tong, ZB Widra, E DeCherney, AH AF Manipalviratn, Somjate Tong, Zhi-Bin Widra, Eric DeCherney, Alan H. TI Comparison of intracellullar ATP levels between non-vitrified and surviving post-vitrification/thawed human oocytes. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Manipalviratn, Somjate; Tong, Zhi-Bin; DeCherney, Alan H.] NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Widra, Eric] Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. [Widra, Eric] Shady Grove Reprod Sci Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 623 BP 236A EP 236A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600625 ER PT J AU Browne, H McCarthy-Keith, D Stegmann, B Armstrong, A AF Browne, Hyacinth McCarthy-Keith, Desiree Stegmann, Barbara Armstrong, Alicia TI Ovarian response in patients undergoing ovarian stimulation after myomectomy. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Browne, Hyacinth; McCarthy-Keith, Desiree; Stegmann, Barbara; Armstrong, Alicia] NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Browne, Hyacinth; McCarthy-Keith, Desiree; Stegmann, Barbara; Armstrong, Alicia] Walter Reed Army Med Ctr, Reprod Endocrinol & Infertil, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 636 BP 239A EP 240A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600638 ER PT J AU Yauger, BJ Henne, MB Armstrong, AY Chason, R Stegmann, BJ Queenan, JT Segars, JH AF Yauger, Belinda J. Henne, Melinda B. Armstrong, Alicia Y. Chason, Rebecca Stegmann, Barbara J. Queenan, John T. Segars, James H. TI Cost analysis of outpatient management of OHSS via paracentesis: 'Tap early and often' versus hospitalization. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Yauger, Belinda J.; Henne, Melinda B.; Armstrong, Alicia Y.; Chason, Rebecca; Stegmann, Barbara J.; Segars, James H.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Yauger, Belinda J.; Armstrong, Alicia Y.; Stegmann, Barbara J.; Segars, James H.] NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Queenan, John T.] Univ Rochester, Med Ctr, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 634 BP 239A EP 239A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600636 ER PT J AU Vaisbuch, E Kusanovic, JP Erez, O Gotsch, F Mazaki-Tovi, S Kim, CJ Kim, JS Chaiworapongsa, T Edwin, SS Than, NG Nhan-Chang, CL Mazor, M Mittal, P Hassan, S Romero, R AF Vaisbuch, Edi Kusanovic, Juan Pedro Erez, Offer Gotsch, Francesca Mazaki-Tovi, Shali Kim, Chong Jai Kim, Jung-Sun Chaiworapongsa, Tinnakom Edwin, Samuel S. Than, Nandor G. Nhan-Chang, Chia-Ling Mazor, Moshe Mittal, Pooja Hassan, Sonia Romero, Roberto TI Fetal hemoglobin concentration in amniotic fluid is elevated in preterm labor or prelabor rupture of membranes. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Edwin, Samuel S.; Than, Nandor G.; Romero, Roberto] NIH, NICHD, DHHS, Perinatol Res Branch, Bethesda, MD 20892 USA. [Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakom; Mittal, Pooja; Hassan, Sonia] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA. [Kim, Chong Jai; Kim, Jung-Sun] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. Soroka Univ Med Ctr, Dept Ob Gyn, Beer Sheva, Israel. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 686 BP 254A EP 254A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600688 ER PT J AU Erez, O Gotsch, F Kusanovic, JP Mazaki-Tovi, S Vaisbuch, E Kim, CJ Chaiworapongsa, T Hoppensteadt, D Fareed, J Than, NG Nhan-Chang, CL Mazor, M Hassan, SS Mittal, P Romero, R AF Erez, Offer Gotsch, Francesca Kusanovic, Juan Pedro Mazaki-Tovi, Shali Vaisbuch, Edi Kim, Chong Jai Chaiworapongsa, Tinnakorn Hoppensteadt, Deborah Fareed, Jawed Than, Nandor G. Nhan-Chang, Chia-Ling Mazor, Moshe Hassan, Sonia S. Mittal, Pooja Romero, Roberto TI Is tissue factor responsible for the consumption coagulopathy associated with fetal death? SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Erez, Offer; Gotsch, Francesca; Kusanovic, Juan Pedro; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Than, Nandor G.; Romero, Roberto] NIH, NICHD, DHHS, Perinatol Res Branch, Bethesda, MD 20892 USA. [Mazaki-Tovi, Shali] Wayne State Univ, Dept ObGyn, Detroit, MI 48202 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Hoppensteadt, Deborah; Fareed, Jawed] Loyola Univ Hlth Syst, Dept Pathol, Maywood, IL USA. [Mazor, Moshe] Beer Sheva Univ Negev, Soroka Med Ctr, Dept ObGyn, Beer Sheva, Israel. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 703 BP 259A EP 259A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600705 ER PT J AU Walsh, LH Lu, MY Sammel, MD Romero, R Strauss, JF AF Walsh, Lori H. Lu Minyan Sammel, Mary D. Romero, Roberto Strauss, Jerome F., III TI A polymorphism in the fetal COMT gene is associated with preeclampsia. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Walsh, Lori H.; Lu Minyan; Strauss, Jerome F., III] Virginia Commonwealth Univ, Richmond, VA USA. [Sammel, Mary D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Romero, Roberto] Hutzel Hosp, NICHD, Perinatol Res Branch, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 804 BP 287A EP 287A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600806 ER PT J AU Norian, JM Stratton, P AF Norian, John M. Stratton, Pamela TI Labial fusion: A rare complication of chronic graft versus host disease SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Norian, John M.; Stratton, Pamela] NIH, Natl Inst Child Hlth & Human Dev, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Norian, John M.] Combined Fed Fellowship Program Reprod Endocrinol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 827 BP 293A EP 293A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600829 ER PT J AU Malik, M Norian, JM Britten, J Joseph, D Catherino, WH AF Malik, Minnie Norian, John M. Britten, Joy Joseph, Doina Catherino, William H. TI Novel therapeutic interventions for uterine leiomyomas: Opposing roles for retinoic acid and TGF-beta on leiomyoma development SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Malik, Minnie; Norian, John M.; Britten, Joy; Joseph, Doina; Catherino, William H.] Uninformed Serv Univ, Bethesda, MD USA. [Norian, John M.; Catherino, William H.] NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 843 BP 297A EP 297A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600845 ER PT J AU Barad, DH Bevers, TB Coker, LH Espeland, MA Jaramillo, SA Limacher, M Lane, DS Rapp, S Maki, P Resnick, S Shumaker, SA Stefianick, ML AF Barad, David H. Bevers, Therese B. Coker, Laura H. Espeland, Mark A. Jaramillo, Sarah A. Limacher, Marian Lane, Dorothy S. Rapp, Stephen Maki, Pauline Resnick, Susan Shumaker, Sally A. Stefianick, Marcia L. TI Relative effects of tamoxifen, raloxifene, and estrogen therapy on cognition: Results from the Women's Health Initiative Memory Study (WHIMS) and the cognition in the study of tamoxifen and raloxifene (CoSTAR) clinical trials. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Barad, David H.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Bevers, Therese B.] Univ Texas Houston, Houston, TX USA. [Coker, Laura H.; Espeland, Mark A.; Jaramillo, Sarah A.; Rapp, Stephen; Shumaker, Sally A.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Limacher, Marian] Univ Florida, Gainesville, FL USA. [Lane, Dorothy S.] SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. [Maki, Pauline] Univ Illinois, Chicago, IL USA. [Maki, Pauline; Resnick, Susan] NIH, NIA, Gerontol Res Ctr, Baltimore, MD USA. [Stefianick, Marcia L.] Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 886 BP 309A EP 309A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600888 ER PT J AU Stegmann, B Frank, B Gemmill, J Chrousos, G Ballweg, M Stratton, P AF Stegmann, B. Frank, B. Gemmill, J. Chrousos, G. Ballweg, M. Stratton, P. TI The HPA axis and depression/anxiety scores in chronic pelvic pain patients. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Stegmann, B.; Gemmill, J.; Chrousos, G.; Stratton, P.] NIH, NICHD, RBMB, Bethesda, MD USA. [Frank, B.] Wake Forest Univ, SOM, Winston Salem, NC 27109 USA. [Ballweg, M.] Endometrios Assoc, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 905 BP 314A EP 315A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600907 ER PT J AU Devasahayam, N Subramanian, S Krishna, MC AF Devasahayam, N. Subramanian, S. Krishna, M. C. TI A novel programmable pulse generator with nanosecond resolution for pulsed electron paramagnetic resonance applications SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID EPR SPECTROSCOPY; SYSTEM; SPECTROMETER; DESIGN AB A pulse programmer with nanosecond time resolution needed for time-domain electron paramagnetic resonance (EPR) spectroscopic applications is described. This unit uses commercially available timing and input-output port modules and control software developed in our laboratory. The pulse programmer is operated through a personal computer front panel graphic user interface (GUI) inputs to control pulse widths, delays, and the associated acquisition trigger timings. Based on these parameters, all other associated gate and trigger timings are internally generated automatically without the need to enter them explicitly. The excitahon pulse widths were of nanosecond resolution while all other gate pulses can be incremented in steps of 20 ns without compromising spectrometer performance. In the current configuration, the pulse programmer permits generation of a single pulse or multiple pulse sequences for EPR imaging with minimal data entry via the front panel GUI. (C) 2008 American Institute of Physics. C1 [Devasahayam, N.; Subramanian, S.; Krishna, M. C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD FEB PY 2008 VL 79 IS 2 AR 026106 DI 10.1063/1.2839398 PN 1 PG 4 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 277EB UT WOS:000254194400063 PM 18315338 ER PT J AU Thurman, AR Shain, RN Holden, AEC Champion, JD Perdue, ST Piper, JM AF Thurman, Andrea Ries Shain, Rochelle N. Holden, Alan E. C. Champion, Jane Dimmitt Perdue, Sondra T. Piper, Jeanna M. TI Partner notification of sexually transmitted infections: A large cohort of Mexican American and African American women SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID CHLAMYDIA-TRACHOMATIS INFECTION; MINORITY WOMEN; PRIVATE-SECTOR; UNITED-STATES; GONORRHEA; RECURRENT; STD; PREVENTION; SEATTLE; TRIAL AB Objectives: To determine factors associated with partner notification (PN) of sexually transmitted infection (STI) exposure among low-income Mexican American and African American women and their male sexual partners. Goal: To identify women most likely to notify their partners about an STI exposure. Study Design: Cross-sectional analysis of 775 women with a non-viral STI. The primary outcome, PN, is notification of, or intent to notify male sexual partner(s) of STI exposure. A comprehensive intake interview was used to obtain sociodemographic, psychosocial, communication, and relationship information for the patients and each male sexual partner. Chi square analysis and multivariate logistic regres- sion analysis were used to determine factors independently associated with PN. Results: The 775 women identified 1122 male sexual partners. Of women with 1, 2, and 3 or more partners, 87.9%, 41.4%, and 25.0% reported PN for all partners respectively. Logistic regression demonstrated that 5 variables independently predicted PN: a "steady" relationship (OR: 5.25; CI: 2.82-4.91), 1 partner (OR: 2.10; CI: 1.71-2.56), recent intercourse (OR: 1.37; CI: 1.21-1.54), anticipated ongoing sexual activity (OR: 1.48; CI: 1.04-2.10), and/or desire for pregnancy with that partner (OR: 1.68; CI: 1.10-2.58). Patient and partner sociodemographic vati ables were not significantly associated with PN. Responses to specific relationship and communication variables, although significant, did not remain independent in the final logistic regression model. Conclusion: Among low-income Mexican American and African American women, the perception that a relationship with individual partner(s) was committed was predictive of PN. C1 [Thurman, Andrea Ries; Shain, Rochelle N.; Holden, Alan E. C.; Champion, Jane Dimmitt; Perdue, Sondra T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Piper, Jeanna M.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Thurman, AR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, 7703 Floyd Curl Dr,Mail Code 7836, San Antonio, TX 78229 USA. EM thurmana@uthscsa.edu FU NIAID NIH HHS [U01 AI40029] NR 26 TC 8 Z9 9 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD FEB PY 2008 VL 35 IS 2 BP 136 EP 140 DI 10.1097/OLQ.0b013e318151498f PG 5 WC Infectious Diseases SC Infectious Diseases GA 254GC UT WOS:000252573400006 PM 17898679 ER PT J AU McBride, CM Puleo, E Pollak, KI Clipp, EC Woolford, S Emmons, KM AF McBride, Colleen M. Puleo, Elaine Pollak, Kathryn I. Clipp, Elizabeth C. Woolford, Sam Emmons, Karen M. TI Understanding the role of cancer worry in creating a "teachable moment" for multiple risk factor reduction SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE worry; teachable moment; behavior change; USA; colon cancer ID POSSIBLE SELVES; BREAST-CANCER; SCREENING BEHAVIOR; PROJECT PREVENT; HEALTH-STATUS; COLON-CANCER; OUTCOMES; SMOKING; WOMEN; LIFE AB The manuscript examines the influence of contextual factors on whether and for whom a colon polyp diagnosis might be a teachable moment, as indicated by engagement with a proactively delivered intervention. Baseline and 8-month follow-up data were analyzed from a two-site behavioral intervention trial with patients in Massachusetts and North Carolina, USA who had recently undergone polypectomy for pre-cancerous colon polyps and were randomized to a behavior change intervention condition (N = 591). Intervention "buy-in" was used as an indicator of response consistent with the polyp identification serving as a teachable moment. Cancer worry, personal risk, health-related self-identity and other sociodemographic factors were tested to predict intervention buy-in. As predicted, those who were most worried about colon cancer were most likely to engage in the intervention. One indicator of personal risk, number of risk behaviors, was significantly and negatively associated with buy-in. Predictors of intervention buy-in and cancer worry were not consistent. We recommend that expanded measures of affect and health-related self-identity should be considered in future research to understand the motivational potential of health events for increasing engagement in effective behavior change interventions. (C) 2007 Elsevier Ltd. All rights reserved. C1 [McBride, Colleen M.] NHGRI, Social Behav Res Branch, Bethesda, MD 20892 USA. [Puleo, Elaine] Univ Massachusetts, Amherst, MA 01003 USA. [Clipp, Elizabeth C.] Duke Univ, Ctr Med, Div Geriatr, Dept Med, Durham, NC 27706 USA. [Clipp, Elizabeth C.] Duke Univ, Med Ctr, Sch Nursing, Duke Comprehens Canc Ctr, Durham, NC 27706 USA. [Woolford, Sam] Bentley Coll, Waltham, MA 02154 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP McBride, CM (reprint author), NHGRI, Social Behav Res Branch, 2 Ctr Dr,Bldg 2,Room E408, Bethesda, MD 20892 USA. EM cmcbride@mail.nih.gov FU Intramural NIH HHS [Z01 HG200315-04] NR 43 TC 36 Z9 37 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 2008 VL 66 IS 3 BP 790 EP 800 DI 10.1016/j.socscimed.2007.10.014 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 261SA UT WOS:000253099100026 PM 18037204 ER PT J AU Thorpe, RJ Kasper, JD Szanton, SL Frick, KD Fried, LP Simonsick, EM AF Thorpe, Roland James, Jr. Kasper, Judith D. Szanton, Sarah L. Frick, Kevin D. Fried, Linda P. Simonsick, Eleanor M. TI Relationship of race and poverty to lower extremity function and decline: Findings from the women's health and aging study SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE health disparities; poverty status; functional decline; race; functional status; lower extremity functioning; women; USA ID BLACK-WHITE DIFFERENCES; DISABLED OLDER WOMEN; PHYSICAL PERFORMANCE; SOCIOECONOMIC-STATUS; RACIAL DISPARITIES; AFRICAN-AMERICANS; UNITED-STATES; DISABILITY; AGE; SEGREGATION AB Race- and poverty-related disparities in physical function are well documented, though little is known about effects of race and poverty on functional decline and the progression of disability. We examined cross-sectional and longitudinal relationships between race, poverty and lower extremity function using data from moderately to severely disabled women in the U.S. Women's Health and Aging Study. Severity of lower extremity functional limitation was determined from scaled responses of reported difficulty walking 4 mile, walking across a room, climbing stairs, and stooping, crouching or kneeling. Usual walking speed assessed over 4 m was our objective measure of function. Of the 996 women who described themselves as black or white, 284 (29%) were black and 367 (37%) were living at or below 100% of the federal poverty level. Independent of demographic and health-related factors, among white women, the poor exhibited consistently worse lower extremity function than the non-poor; this association, however, was not observed in black women. Among the non-poor, black women had slower walking speeds, and reported more limitation in lower extremity function than their non-poor white counterparts, even after adjusting for demographic variables and health-related characteristics. After 3 years, accounting for baseline function, demographic and health-related factors, race and poverty status were unrelated to functional decline. Thus, while race and poverty status were associated with functional deficits in old age, they do not appear to impact the rate of functional decline or progression of disability over 3 years. Published by Elsevier Ltd. C1 [Thorpe, Roland James, Jr.; Fried, Linda P.] Johns Hopkins Med Inst, Hopkins Ctr Hlth Dispar Solut, Baltimore, MD 21205 USA. [Kasper, Judith D.; Frick, Kevin D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Szanton, Sarah L.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21205 USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Simonsick, Eleanor M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Thorpe, RJ (reprint author), Johns Hopkins Med Inst, Hopkins Ctr Hlth Dispar Solut, 624 N Broadway,Ste 441, Baltimore, MD 21205 USA. EM rthorpe@jhsph.edu; jkasper@jhsph.edu; sszanton@son.jhmi.edu; kfrick@jhsph.edu; lfried@jhmi.edu; simonsickel@grc.nia.nih.gov FU NIA NIH HHS [N01AG12112, N01 AG012112, T32 AG000120, T32-AG-000120]; NIMHD NIH HHS [L60 MD001407, L60 MD001407-01] NR 51 TC 26 Z9 26 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 2008 VL 66 IS 4 BP 811 EP 821 DI 10.1016/j.socscimed.2007.11.005 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 276RJ UT WOS:000254159500002 PM 18164113 ER PT J AU Allen, M Lau, CY AF Allen, Mary Lau, Chuen-Yen TI Social impact of preventive HIV vaccine clinical trial participation: A model of prevention, assessment and intervention SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE social impact; social harm; HIV vaccine; clinical trial; USA; NIAID ID DISCRIMINATION; VOLUNTEERS; RISKS AB Preventive HIV vaccine trial participants may experience problems related to trial participation, including difficulties with personal relationships, employment, education, health care, housing, health insurance, disability insurance, life insurance, travel or immigration. During the 19 years that the U.S.-based National Institute of Allergy and Infectious Diseases (NIAID) has conducted preventive HIV vaccine trials, we have developed a model to prevent and resolve social impact related to study participation and assist study participants who report such events. Key elements of the model include: informing potential volunteers of risks prior to enrollment; standardizing data collection methods on social impact events; reviewing and following-up on reported social impact events; assisting participants, including provision of free HIV testing to differentiate HIV infection from vaccine-induced HIV antibody; implementing broad-based and targeted community education programs for achieving community support; communicating with scientific and health care communities; and working with government agencies, non-government agencies and industry on mechanisms to address SI. This approach, established in collaboration with NIAID-funded clinical trial groups, serves as a model for prevention, assessment, monitoring, and intervention for social impact related to preventive HIV vaccine clinical trial participation. Although further research is necessary, this model could be adapted for use in different clinical trials. Published by Elsevier Ltd. C1 [Allen, Mary; Lau, Chuen-Yen] NIAID, NIH, Div AIDS, Vaccine Res Program, Bethesda, MD 20817 USA. RP Lau, CY (reprint author), NIAID, NIH, Div AIDS, Vaccine Res Program, 6700 B Rockledge Dr, Bethesda, MD 20817 USA. EM mallen@niaid.nih.gov; lauc@niaid.nih.gov OI Allen, Mary/0000-0001-8163-0714 NR 9 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 2008 VL 66 IS 4 BP 945 EP 951 DI 10.1016/j.socscimed.2007.10.019 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 276RJ UT WOS:000254159500013 PM 18162272 ER PT J AU Wasserman, BA Sharrett, R Lai, S Gomes, AS Cushman, M Folsom, AR Bild, DE Kronmal, RA Sinha, S Bluemke, DA AF Wasserman, Bruce A. Sharrett, Richey Lai, Shenghan Gomes, Antoinette S. Cushman, Mary Folsom, Aaron R. Bild, Diane E. Kronmal, Richard A. Sinha, Shantanu Bluemke, David A. TI Risk factor associations with the presence of a lipid core in carotid plaque of asymptomatic individuals using high-resolution MRI - The Multi-Ethnic Study of Atherosclerosis (MESA) SO STROKE LA English DT Article DE atherosclerosis; carotid artery; cholesterol; lipid core; magnetic resonance; MRI; risk factors; stroke ID C-REACTIVE PROTEIN; DENSITY-LIPOPROTEIN CHOLESTEROL; INTIMA-MEDIA THICKNESS; SUDDEN CORONARY DEATH; IN-VIVO; MYOCARDIAL-INFARCTION; ARTERY STENOSIS; RUPTURE; ECHOLUCENT; MORPHOLOGY AB Background and Purpose-Atheroma vulnerability to rupture is increased in the presence of a large lipid core. Factors associated with a lipid core in the general population have not been studied. Methods-The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study of individuals free of clinical cardiovascular disease designed to include a high proportion of ethnic minorities. We selected MESA participants from the top 15th percentile of maximum carotid intima media thickness by ultrasound and acquired high-resolution black blood MRI images through their carotid plaque before and after the intravenous administration of gadodiamide (0.1 mmol/kg). Lumen and outer wall contours were defined using semiautomated analysis software. We analyzed only plaques with a maximum thickness >= 1.5 mm by MRI (n=214) and assessed cross-sectional risk factor associations with lipid core presence by multivariable logistic regression. Results-A lipid core was present in 151 (71%) of the plaques. After controlling for age, ethnicity, sex, maximum arterial wall thickness, hypertension, cigarette smoking, diabetes, and C-reactive protein, compared with participants in the lowest tertile of total plasma cholesterol, the ORs of having a lipid core for participants in the middle and highest tertiles were 2.76 (95% CI: 1.01 to 7.51) and 4.63 (95% CI: 1.56 to 13.75), respectively. None of the other risk factors was associated with lipid core. Conclusions-In persons with thickened carotid walls, plasma total cholesterol, but not other established coronary heart disease risk factors, is strongly associated with lipid core presence by MRI. High total cholesterol may be associated with rupture proneness of atherosclerotic lesions in the general population. C1 [Wasserman, Bruce A.; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA. [Lai, Shenghan] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. [Gomes, Antoinette S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gomes, Antoinette S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA USA. [Cushman, Mary] Univ Vermont, Dept Med, Dept Pathol, Burlington, VT USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. [Bild, Diane E.] NHLBI, Div Prevent & Populat Studies, Bethesda, MD USA. [Kronmal, Richard A.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Sinha, Shantanu] Univ Calif San Diego, Med Ctr, Dept Radiol, San Diego, CA USA. RP Wasserman, BA (reprint author), Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Phipps B-100, 600 N Wolfe St, Baltimore, MD 21287 USA. EM bwasser@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU NHLBI NIH HHS [N01-HC-95159, N01-HC-95166, N01-HC-95168, R01-HL-69905]; NIDA NIH HHS [R01 DA012777] NR 32 TC 71 Z9 79 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 BP 329 EP 335 DI 10.1161/STROKEAHA.107.498634 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100021 PM 18174475 ER PT J AU Ay, H Arsava, EM Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, E. Murat Koroshetz, Walter J. Sorensen, A. Gregory TI Middle cerebral artery infarcts encompassing the insula are more prone to growth SO STROKE LA English DT Article DE cerebral infarct; diffusion-weighted imaging; heart-brain relationships; insula; MRI; neurocardiology; sympathetic nervous system ID PATHOLOGICAL SYMPATHETIC ACTIVATION; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; ACUTE ISCHEMIC-STROKE; BLOOD-FLOW; SUDDEN-DEATH; CORTEX STIMULATION; BRAIN; TISSUE; HYPERGLYCEMIA AB Background and Purpose - Based on previous observations that infarcts encompassing the insula were linked to unfavorable clinical outcome, we hypothesized that insular damage was directly associated with worsened infarction in ischemic but potentially viable neighboring brain tissue. Methods - Using acute diffusion- and perfusion-weighted MRI within the first 12 hours of symptom onset and a follow-up MRI on day 5 or later, we calculated the percentage of mismatch lost (PML) in 61 consecutive patients with ischemic stroke within the middle cerebral artery territory. PML denoted the percentage of mismatch tissue between diffusion- weighted imaging and mean transit time maps that eventually underwent infarction. We explored the relationship between PML and insular location using a regression model. Results - The median PML was 17.7% (interquartile range, 3.5% to 54.2%) in insular and 2.5% (0.0% to 12.7%) in noninsular infarcts (P < 0.01). The PML correlated with the volume of abnormal regions on diffusion- weighted imaging (P < 0.01), mean transit time (P < 0.01), cerebral blood flow maps (P < 0.01), and cerebral blood volume maps (P < 0.01). A linear regression model with PML as response and with acute MRI volumes, age, and the site of vascular occlusion as covariates showed that insular involvement was an independent predictor of PML (P < 0.01). The regression model predicted an approximately 3.2-fold increase in PML with insular involvement. Conclusions - Infarction of the insula is associated with increased conversion of ischemic but potentially viable neighboring tissues into infarction. The unfavorable tissue outcome in insular infarcts may not be a mere bystander effect from proximal middle cerebral artery occlusions. C1 [Ay, Hakan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Ay, Hakan; Arsava, E. Murat; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomed Ctr Imging,Dept Radiol, Boston, MA 02129 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomed Ctr Imging, 149 13th St,Rm 2301, Boston, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013 OI Arsava, Ethem Murat/0000-0002-6527-4139 FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R01-NS38477-04, NS38477] NR 47 TC 24 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 BP 373 EP 378 DI 10.1161/STROKEAHA.107.499095 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100028 PM 18174474 ER PT J AU Kim, YR van Meer, MPA Tejima, E Murata, Y Mandeville, JB Dai, G Chuang, DM Rosen, BR Lo, EH AF Kim, Young R. van Meer, Maurits P. A. Tejima, Emiri Murata, Yoshi Mandeville, Joseph B. Dai, George Chuang, De-Maw Rosen, Bruce R. Lo, Eng H. TI Functional MRI of delayed chronic lithium treatment in rat focal cerebral ischemia SO STROKE LA English DT Article DE BOLD; CBV; fMRI; focal ischemia; neuroprotective agents; rat; treatment ID GLYCOGEN-SYNTHASE KINASE-3-BETA; ARTERY OCCLUSION; FOREPAW STIMULATION; TEMPORAL EVOLUTION; ANIMAL-MODELS; STROKE; ANGIOGENESIS; SURVIVAL; BRAIN; RECOVERY AB Background and Purpose - The use of lithium as a neuroprotective agent has been demonstrated using various models in which improvements in infarct size, DNA damage, and neurological function were reported. We further investigated neurohemodynamic aspects of the treatment-associated recovery by assessing the therapeutic efficacy of delayed chronic lithium treatment using functional MRI. Methods - Ipsilesional functional MRI activations in the somatosensory cortex, acquired 2 weeks after the 90-minute transient middle cerebral artery occlusion, were compared between lithium- and saline-treated rats. Specifically, MRI signal changes based on blood oxygenation level dependence and functional cerebral blood volume responses were examined using electrical stimulation of forelimbs. Additional immunohistochemical assays were performed. Results - The ratio of ipsilesional to contralesional blood oxygenation level dependence response magnitudes significantly improved with lithium treatments. In contrast, the increase of the functional cerebral blood volume response magnitude ratio was not statistically significant. Nonetheless, the lithium treatment induced significant enhancements of total functional MRI activation (defined as a product of activation volume and response magnitude) for both blood oxygenation level dependence and functional cerebral blood volume methods. Increased cerebral blood volume in periinfarct tissues suggests a possible stroke-induced vascular transformation in both saline- and lithium-treated rats; however, other MRI-derived vascular parameters (vascular size index and microvascular volume) and immunohistochemical staining (CD31, glia fibrillary-associated protein, and matrix metalloproteinase-9) may imply that the neoformation of vasculature was differently affected by the lithium treatment. Conclusions - The delayed chronic lithium treatment enhanced the blood oxygenation level dependence functional MRI response magnitude in the absence of neurological improvement and influenced vascular formation in poststroke animal models. C1 [Kim, Young R.; van Meer, Maurits P. A.; Mandeville, Joseph B.; Dai, George; Rosen, Bruce R.] Massachusetts Gen Hosp, Ctr Biomed Imaging, Boston, MA 02129 USA. [Kim, Young R.; van Meer, Maurits P. A.; Tejima, Emiri; Murata, Yoshi; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprtect Res Lab, Boston, MA 02129 USA. [van Meer, Maurits P. A.] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands. [Chuang, De-Maw] NIH, NIMH, Mol Neurobiol Sect, Bethesda, MD USA. RP Kim, YR (reprint author), Massachusetts Gen Hosp, Ctr Biomed Imaging, 149 13th St,Rm 2301, Boston, MA 02129 USA. EM spmn@nmr.mgh.harvard.edu FU NIBIB NIH HHS [5R01EB002066, R01 EB002066, 17 R01-EB002066]; NINDS NIH HHS [R01 NS053560, P01 NS055104, P50-NS10828, R01-NS48422, R01 NS048422, P50 NS010828, R01-NS37074, R01 NS056458, R01-NS56458, R01 NS037074, P01-NS55104] NR 24 TC 25 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 BP 439 EP 447 DI 10.1161/STROKEAHA.107.492215 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100039 PM 18187690 ER PT J AU Tsivgoulis, G Alexandrov, AV Wadley, VV Unverzagt, FV Go, RC Moy, CS Kissela, B Howard, G AF Tsivgoulis, Georgios Alexandrov, Andrei V. Wadley, Virginia V. Unverzagt, Frederick V. Go, Rodney C. Moy, Claudia S. Kissela, Brett Howard, George TI Association between increased diastolic blood pressure levels and cognitive impairment: the reasons for geographic and racial differences in stroke (REGARDS) study. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Tsivgoulis, Georgios; Alexandrov, Andrei V.] Univ Alabama, Birmingham Hosp, Comprehens Stroke Ctr, Birmingham, AL USA. [Wadley, Virginia V.] Univ Alabama, Dept Med, Birmingham, AL USA. [Unverzagt, Frederick V.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN USA. [Go, Rodney C.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Moy, Claudia S.] Natl Inst Hlth, NINDS, Bethesda, MD USA. [Kissela, Brett] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. [Howard, George] Univ Alabama, Dept Biostat, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 66 BP 544 EP 544 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100127 ER PT J AU Worrall, BB Brown, WM Brott, TG Brown, RD Hardy, J Matarin, M Rich, SS Singleton, A Meschia, JF AF Worrall, Bradford B. Brown, W. M. Brott, Thomas G. Brown, Robert D., Jr. Hardy, John Matarin, Mar Rich, Stephen S. Singleton, Andrew Meschia, James F. CA ISGS Invest TI Analysis of the age-at-onset phenotype in a pilot genome-wide association study of ischemic stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Worrall, Bradford B.; Rich, Stephen S.] Univ Virginia, Charlottesville, VA 22903 USA. [Brown, W. M.] Wake Forest Sch Med, Winston Salem, NC USA. [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Jacksonville, FL USA. [Brown, Robert D., Jr.] Mayo Clin, Rochester, MN USA. [Hardy, John] Queen Square, London, England. [Matarin, Mar; Singleton, Andrew] NIA, Bethesda, MD USA. RI Singleton, Andrew/C-3010-2009; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 98 BP 552 EP 552 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100159 ER PT J AU Howard, G Wadley, VG Unverzagt, FW Jenny, N Go, RC Cushman, M Moy, CS AF Howard, George Wadley, Virginia G. Unverzagt, Frederick W. Jenny, Nancy Go, Rodney C. Cushman, Mary Moy, Claudia S. CA REGARDS TI Stroke risk factors are predictive of cognitive decline in the absence of clinically diagnosed incident stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Howard, George; Wadley, Virginia G.; Go, Rodney C.] Univ Alabama, Birmingham, AL USA. [Unverzagt, Frederick W.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Jenny, Nancy; Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA. [Moy, Claudia S.] NINDS, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 125 BP 559 EP 559 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100186 ER PT J AU Nyquist, PA Winkler, CA McKenzie, LM Yanek, LR Becker, LC Becker, DM AF Nyquist, Paul A. Winkler, Cherie A. McKenzie, Louise M. Yanek, Lisa R. Becker, Lewis C. Becker, Diane M. TI Variants in the monocyte chemoattractant protein-1 (MCP-1) and chemokine receptor-2 (CCR2) genes act synergistically to increase the risk of carotid atherosclerosis SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Nyquist, Paul A.; Yanek, Lisa R.; Becker, Lewis C.; Becker, Diane M.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Winkler, Cherie A.; McKenzie, Louise M.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 126 BP 559 EP 559 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100187 ER PT J AU Barr, TL Latour, LL Lee, KY Schaewe, TJ Luby, M Chang, G El-Zammar, Z Alam, S Kidwell, CS Warach, S AF Barr, Taura L. Latour, Lawrence L. Lee, Kyung-Yul Schaewe, Timothy J. Luby, Marie Chang, George El-Zammar, Ziad Alam, Shaista Kidwell, Chelsea S. Warach, Steven CA NIH Natural Hist Stroke Invest TI Early blood brain barrier disruption is associated with plasma matrix metalloproteinase-9 concentration in acute stroke patients SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Barr, Taura L.] NINR, NINDS, Bethesda, MD USA. [Latour, Lawrence L.; Lee, Kyung-Yul; Schaewe, Timothy J.; Luby, Marie; Chang, George; El-Zammar, Ziad; Alam, Shaista; Warach, Steven] Natl Inst Hlth, NINDS, Bethesda, MD USA. [Kidwell, Chelsea S.] Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 157 BP 566 EP 567 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100217 ER PT J AU Kidwell, CS Singleton, KW Schaewe, TJ Luby, M Warach, S Alger, J AF Kidwell, Chelsea S. Singleton, Kyle W. Schaewe, Timothy J. Luby, Marie Warach, Steven Alger, Jeffry CA NIH Nat Hist Stroke Invest TI Neuroanatomic representation of NIHSS sub-items employing acute diffusion imaging: Developing a predictive atlas of clinical outcome SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Kidwell, Chelsea S.] Georgetown Univ, Washington, DC 20057 USA. [Singleton, Kyle W.; Luby, Marie] NIH, NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD USA. [Schaewe, Timothy J.; Alger, Jeffry] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P4 BP 570 EP 570 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100225 ER PT J AU Latour, LL Kidwell, CS Lee, KY Schaewe, TJ Merino, JG Warach, S AF Latour, Lawrence L. Kidwell, Chelsea S. Lee, Kyung-Yul Schaewe, Timothy J. Merino, Jose G. Warach, Steven TI Blood brain barrier disruption in acute stroke prior to therapy is evident on immediate post-contrast FLAIR MRI SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Latour, Lawrence L.; Lee, Kyung-Yul; Merino, Jose G.; Warach, Steven] NINDS, Bethesda, MD USA. [Kidwell, Chelsea S.] Georgetown Univ, Washington, DC USA. [Schaewe, Timothy J.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P5 BP 570 EP 570 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100226 ER PT J AU Benameur, K Merino, J Kidwell, CS Warach, S Latour, L AF Benameur, Karima Merino, Jose Kidwell, Chelsea S. Warach, Steven Latour, Lawrence TI Small cortical lesions visible on acute DWI are not visible on 90 day FLAIR. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Benameur, Karima; Merino, Jose; Warach, Steven; Latour, Lawrence] NINDS, NIH, Bethesda, MD USA. [Kidwell, Chelsea S.] Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P70 BP 587 EP 587 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100290 ER PT J AU Lee, KY Latour, LL Merino, JG Warach, S AF Lee, Kyung-Yul Latour, Lawrence L. Merino, Jose G. Warach, Steven CA NIH NHS Invest TI Parenchymal enhancement on T1-weighted MRI predicts subsequent hemorrhagic transformation in acute ischemic stroke. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Lee, Kyung-Yul; Latour, Lawrence L.; Merino, Jose G.; Warach, Steven] NINDS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P77 BP 588 EP 588 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100297 ER PT J AU Luby, M Jothen, JL Merino, JG Bykowski, JL Schellinger, PD Warach, S AF Luby, Marie Jothen, Jennifer L. Merino, Jose G. Bykowski, Julie L. Schellinger, Peter D. Warach, Steven CA NIH NHS Invest TI Neural network model for prediction of final infarct volume in treated versus untreated stroke patients. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Luby, Marie; Jothen, Jennifer L.; Merino, Jose G.; Bykowski, Julie L.; Warach, Steven] Natl Inst Hlth, Bethesda, MD USA. [Schellinger, Peter D.] Neurol Clin, Erlangen, Germany. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P78 BP 588 EP 589 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100298 ER PT J AU Taylor, AM Castle, AB Hsia, AW Merino, JG Kidwell, CS Warach, S AF Taylor, Alexis M. Castle, Amanda B. Hsia, Amie W. Merino, Jose G. Kidwell, Chelsea S. Warach, Steven CA NIH NHS Invest TI Spectrm - Stroke patients eligible for clinical trials - A regression model SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Taylor, Alexis M.; Castle, Amanda B.; Merino, Jose G.; Warach, Steven] NINDS, NIH, Sect Stroke Diagnost & Therapeut, Bethesda, MD USA. [Hsia, Amie W.] Washington Hosp Ctr, Washington, DC USA. [Kidwell, Chelsea S.] Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P109 BP 596 EP 597 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100329 ER PT J AU Lyden, P Raman, R Liu, L Rapp, K Emr, M Warren, M Marler, J AF Lyden, Patrick Raman, Rema Liu, Lin Rapp, Karen Emr, Marion Warren, Margo Marler, John TI Reliability of NIHSS training and certification in across multiple venues SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Lyden, Patrick; Raman, Rema; Liu, Lin; Rapp, Karen] Univ Calif San Diego, San Diego, CA USA. [Emr, Marion; Warren, Margo; Marler, John] NINDS, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P115 BP 598 EP 598 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100335 ER PT J AU Ay, H Arsava, EM Gungor, L Furie, KL Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, Ethem Murat Gungor, Levent Furie, Karen L. Koroshetz, Walter J. Sorensen, A. Gregory TI Imaging-based estimation of stroke recurrence risk SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Ay, Hakan; Arsava, Ethem Murat; Gungor, Levent; Sorensen, A. Gregory] Massachusetts Gen Hosp, AA Martinos Cntr BioMed Imaging, Boston, MA 02114 USA. [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koroshetz, Walter J.] NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P226 BP 625 EP 626 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100445 ER PT J AU Ovbiagele, B Drogan, O Koroshetz, WJ Fayad, P Saver, JL AF Ovbiagele, Bruce Drogan, Oksana Koroshetz, Walter J. Fayad, Pierre Saver, Jeffrey L. TI Post stroke hospitalization practice patterns: A survey of neurologists. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Ovbiagele, Bruce; Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Drogan, Oksana] Amer Acad Neurol, St Paul, MN USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Fayad, Pierre] Univ Nebraska Med Ctr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P268 BP 636 EP 636 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100487 ER PT J AU Ishibashi, S Maric, D Ohtani, R Lee-Wickner, YJ Mou, Y Hallenbeck, JM AF Ishibashi, Satoru Maric, Dragan Ohtani, Ryo Lee-Wickner, Yang-Ja Mou, Yongshan Hallenbeck, John M. TI Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T cell induction after stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Ishibashi, Satoru; Ohtani, Ryo; Lee-Wickner, Yang-Ja; Mou, Yongshan; Hallenbeck, John M.] Nih Ninds Stroke Branch, Bethesda, MD USA. [Maric, Dragan] Nih Ninds Lab Neurophysiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P363 BP 658 EP 658 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100576 ER PT J AU Charoen, D Raman, M Olfman, L AF Charoen, Danuvasin Raman, Murali Olfman, Lorne TI Improving end user behaviour in password utilization: An action research initiative SO SYSTEMIC PRACTICE AND ACTION RESEARCH LA English DT Article DE action research; security; passwords; memory; training ID INFORMATION; SYSTEMS; PRINCIPLES AB This paper is about the design and implementation of techniques and strategies to improve end user behavior in the utilization of passwords within a formal setting. The researchers were requested to investigate the issues inherent in the password management and utilization procedure within the client organization and thereby improve end user behavior in utilization of passwords within the organization. The researchers completed an action research study and successfully implemented a training program to improve system users' behavior related to passwords. They used a unique approach by designing training for creating passwords to fit with theories pertaining to human memory. In addition, the researchers also created and delivered security awareness training. The end users of the target information systems reported that after training they were able to use strong passwords (A strong password in our organization is one that has 15 characters with at least two numbers and one symbol) without writing them down. Requests to the help desk for password resets decreased. Users also reported that they are much more aware of security threats. C1 [Charoen, Danuvasin] NIDA, Grad Sch Business Adm, Bangkok, Thailand. [Raman, Murali] Monash Univ, Sch Business & Econ, Selangor, Malaysia. [Olfman, Lorne] Claremont Grad Univ, Sch Informat Syst & Technol, Claremont, CA USA. RP Charoen, D (reprint author), NIDA, Grad Sch Business Adm, Bangkok, Thailand. EM danuvasin@gmail.com; Murali.raman@buseco.monash.edu.my; Lorne.olfman@cgu.edu NR 15 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-429X J9 SYST PRACT ACT RES JI Syst. Pract. Action Res. PD FEB PY 2008 VL 21 IS 1 BP 55 EP 72 DI 10.1007/s11213-007-9082-4 PG 18 WC Management SC Business & Economics GA 248NB UT WOS:000252159100004 ER PT J AU Li, G Citrin, D Camphausen, K Mueller, B Burman, C Mychalczak, B Miller, RW Song, YL AF Li, Guang Citrin, Deborah Camphausen, Kevin Mueller, Boris Burman, Chandra Mychalczak, Borys Miller, Robert W. Song, Yulin TI Advances in 4D medical imaging and 4D radiation therapy SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Review DE 4D medical imaging; multiple imaging modalities; image-guided radiation therapy (IGRT); adaptive radiation therapy (ART); 4D radiation therapy (4DRT) ID CONE-BEAM CT; COMPUTED-TOMOGRAPHY IMAGES; INTERNAL TARGET VOLUME; MOTION-TRACKING SYSTEM; LUNG-CANCER PATIENTS; REAL-TIME MRI; RF COIL ARRAY; DEFORMABLE REGISTRATION; INITIAL-EXPERIENCE; PROSTATE-CANCER AB This paper reviews recent advances in 4D medical imaging (4DMI) and 4D radiation therapy (4DRT), which study, characterize, and minimize patient motion during the processes of imaging and radiotherapy. Patient motion is inevitably present in these processes, producing artifacts and uncertainties in target (lesion) identification, delineation, and localization. 4DMI includes time-resolved volumetric CT, MRI, PET, PET/CT, SPECT, and US imaging. To enhance the performance of these volumetric imaging techniques, parallel multi-detector array has been employed for acquiring image projections and the volumetric image reconstruction has been advanced from the 2D to the 3D tomography paradigm. The time information required for motion characterization in 4D imaging can be obtained either prospectively or retrospectively using respiratory gating or motion tracking techniques. The former acquires snapshot projections for reconstructing a motion-free image. The latter acquires image projections continuously with an associated timestamp indicating respiratory phases using external surrogates and sorts these projections into bins that represent different respiratory phases prior to reconstructing the cyclical series of 3D images. These methodologies generally work for all imaging modalities with variations in detailed implementation. In 4D CT imaging, both multi-slice CT (MSCT) and cone-beam CT (CBCT) are applicable in 4D imaging. In 4D MR imaging, parallel imaging with multi-coil-detectors has made 4D volumetric MRI possible. In 4D PET and SPECT, rigid and non-rigid motions can be corrected with aid of rigid and deformable registration, respectively, without suffering from low statistics due to signal binning. In 4D PET/CT and SPECT/CT, a single set of 4D images can be utilized for motion-free image creation, intrinsic registration, and attenuation correction. In 4D US, volumetric ultrasonography can be employed to monitor fetal heart beating with relatively high temporal resolution. 4DRT aims to track and compensate for target motion during radiation treatment, minimizing normal tissue injury, especially critical structures adjacent to the target, and/or maximizing radiation dose to the target. 4DRT requires 4DMI, 4D radiation treatment planning (4D RTP), and 4D radiation treatment delivery (4D RTD). Many concepts in 4DRT are borrowed, adapted and extended from existing image-guided radiation therapy (IGRT) and adaptive radiation therapy (ART). The advantage of 4DRT is its promise of sparing additional normal tissue by synchronizing the radiation beam with the moving target in real-time. 4DRT can be implemented differently depending upon how the time information is incorporated and utilized. In an ideal situation, the motion adaptive approach guided by 4D imaging should be applied to both RTP and RTD. However, until new automatic planning and motion feedback tools are developed for 4DRT, clinical implementation of ideal 4DRT will meet with limited success. However, simplified forms of 4DRT have been implemented with minor modifications of existing planning and delivery systems. The most common approach is the use of gating techniques in both imaging and treatment, so that the planned and treated target localizations are identical. In 4D planning, the use of a single planning CT image, which is. representative of the statistical respiratory mean, seems preferable. In 4D delivery, on-site CBCT imaging or 3D US localization imaging for patient setup and internal fiducial markers for target motion tracking can significantly reduce the uncertainty in treatment delivery, providing improved normal tissue sparing. Most of the work on 4DRT can be regarded as a proof-of-principle and 4DRT is still in its early stage of development. C1 [Li, Guang; Citrin, Deborah; Camphausen, Kevin; Miller, Robert W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Mueller, Boris; Mychalczak, Borys] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Burman, Chandra; Song, Yulin] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. RP Song, YL (reprint author), NCI, Radiat Oncol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM songy@mskcc.org NR 124 TC 86 Z9 90 U1 2 U2 42 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD FEB PY 2008 VL 7 IS 1 BP 67 EP 81 PG 15 WC Oncology SC Oncology GA 260JJ UT WOS:000253006300009 PM 18198927 ER PT J AU Margolis, RN AF Margolis, Ronald N. TI The Nuclear Receptor Signaling Atlas: Catalyzing understanding of thyroid hormone signaling and metabolic control SO THYROID LA English DT Article ID UNION-OF-PHARMACOLOGY; ESTROGEN-RECEPTOR; CIRCADIAN CLOCK; SUPERFAMILY; ACTIVATION; EXPRESSION; TRANSCRIPTION; COACTIVATORS; CHOLESTEROL; PHYSIOLOGY AB The Nuclear Receptor Signaling Atlas (NURSA) was established as a trans-National Institutes of Health resource to develop, accrue, and communicate information about the nuclear receptor (NR) superfamily of ligand-dependent and -independent transcription factors. NRs have broad involvement in the regulation of development, reproduction, and metabolism. Receptors for thyroid hormones represent important members of the NR superfamily with key roles in development and homeostasis. NURSA has attempted to create a resource for information on NRs, associated coregulators, and ligands. The Web portal (www.NURSA.org) creates a window through which the general research community can gain access to data generated by NURSA investigators and linked from other sources. The molecule pages provide detailed curated information about the NR superfamily and allow the user to search for information useful to their own specific research problems. With the application of bioinformatics solutions, analyses of large amounts of data can be utilized to validate and/or create hypotheses that will ultimately lead to translational opportunities to take information about NRs, in general, and thyroid receptors, in particular to potential clinical applications. C1 NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Margolis, RN (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Democracy 2,Room 693,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM margolisr@nih.gov OI Margolis, Ronald/0000-0002-8956-0455 FU NIDDK NIH HHS [U19DK62434] NR 39 TC 4 Z9 4 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 FEB PY 2008 VL 18 IS 2 BP 113 EP 122 DI 10.1089/thy.2007.0247 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270LR UT WOS:000253722800004 PM 18279012 ER PT J AU Stout, MD Bodes, E Schoonhoven, R Upton, PB Travlos, GS Swenberg, JA AF Stout, Matthew D. Bodes, Elmarie Schoonhoven, Robert Upton, Patricia B. Travlos, Gregory S. Swenberg, James A. TI Toxicity, DNA Binding, and Cell Proliferation in Male F344 Rats following Short-term Gavage Exposures to Trans-2-Hexenal SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Hexenal; rat; forestomach; DNA adduct; mass spectrometry; proliferating cell nuclear antigen ID ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; SUBSTITUTED ACROLEIN CONGENERS; LIVER ALDEHYDE DEHYDROGENASES; ZERO DOSE CONTROL; LIPID-PEROXIDATION; MAMMALIAN-CELLS; MASS-SPECTROMETRY; ALDOSE REDUCTASE; V79 CELLS; ADDUCTS AB Hexenal is a genotoxic compound to which humans are exposed daily through the consumption of foods and beverages. The present studies were conducted to examine the relationships between the dose-responses of trans-2-hexenal-induced toxicity, DNA adduct formation, and cell proliferation. Male F344 rats were exposed by gavage to single doses of up to 500 mg/kg and killed 1, 2, or 4 days after dosing or were exposed to repeat doses of up to 100 mg/kg once daily for 5 days or 5 days per week for 4 weeks and killed 1 day after the end of the dosing period. Histologically, the primary observations were necroulcerative lesions, inflammation, and hyperplasia in the forestomach and inflammation in the glandular stomach. Hexenal-derived DNA adduct formation and cell proliferation were induced in the forestomach at doses of hexenal that also induced gastric toxicity; DNA adducts were not observed in the glandular stomach. These findings suggest that the toxicity of hexenal was limited to the site of contact ( stomach) and that the observed DNA adduct formation and cell proliferation occurred in the setting of severe tissue damage. C1 [Swenberg, James A.] Univ N Carolina, Michael Hooker Res Ctr, Curriculum Toxicol, Chapel Hill, NC 27599 USA. [Schoonhoven, Robert; Upton, Patricia B.; Swenberg, James A.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Travlos, Gregory S.] NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Swenberg, JA (reprint author), Univ N Carolina, Michael Hooker Res Ctr, Curriculum Toxicol, Chapel Hill, NC 27599 USA. EM james_swenberg@unc.edu FU NIH [P30-ES10126, T32-CA72319, T32-ES07126, ES11746]; Flavor and Extract Manufacturers Association; National Institute of Environmental Health Sciences, Division of Intramural Research FX We thank Ralph Wilson and Sandy Ward for skilled technical assistance with clinical chemistry and hematology, Norris Flagler for preparation of figures for publication, and Drs. Louise M. Ball and Po Chan for critical review of the manuscript. The mass spectrometry facility at the University of North Carolina at Chapel Hill is partly funded by NIH Grant P30-ES10126. Additional support was provided by NIH Grants T32-CA72319, T32-ES07126, and ES11746, the Flavor and Extract Manufacturers Association, and the National Institute of Environmental Health Sciences, Division of Intramural Research. NR 55 TC 10 Z9 12 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2008 VL 36 IS 2 BP 232 EP 246 DI 10.1177/0192623307311758 PG 15 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UK UT WOS:000267457400005 PM 18362197 ER PT J AU Wancket, LM Devor-Henneman, D Ward, JM AF Wancket, Lyn M. Devor-Henneman, Deborah Ward, Jerrold M. TI Fibro-osseous (FOL) and Degenerative Joint Lesions in Female Outbred NIH Black Swiss Mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Bone disease; bone marrow; mice; Swiss mice; degenerative joint disease ID DIETHYLSTILBESTROL; STRAIN AB A review of spontaneous bone and joint lesions in female aging NIH Black Swiss mice (Cr:NIH BL[S]) revealed a high incidence of fibro-osseous lesions (FOL; 89%) and degenerative joint lesions (90%). FOL was characterized by the replacement of bone marrow by fibrovascular tissue and was first seen at 59 weeks of age, most commonly in the nasal bone, femur, and tibia. FOL in female Black Swiss was often accompanied by reproductive-tract lesions, including ovarian atrophy and uterine cervical dysplasia with hydrometra. Mild degenerative femorotibial joint lesions developed by 59 weeks and progressed to full-thickness articular cartilage ulceration and osteophyte development by 75 weeks; joint inflammation was minimal. Although the underlying etiology of FOL remains unknown, an accurate assessment of FOL and degenerative joint disease as background lesions in this stock is necessary to interpret lesions in genetically engineered mice produced from this outbred line. C1 [Devor-Henneman, Deborah] Ohio State Univ, Dept Vet Biosci, Coll Vet Med, Columbus, OH 43210 USA. [Wancket, Lyn M.] Univ Illinois, Coll Vet Med, Urbana, IL 61801 USA. [Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Wancket, LM (reprint author), Ohio State Univ, Dept Vet Biosci, Coll Vet Med, 1925 Coffey Rd, Columbus, OH 43210 USA. EM wancket.1@osu.edu FU NIAID; Intramural Research Program of the NIH (NIAID); National Cancer Institute (NCI) FX This work was supported, in part, by a NIAID contract to SoBran, Inc., and by the Intramural Research Program of the NIH ( NIAID) and the National Cancer Institute ( NCI). The NIH Black Swiss were created by Dr. Carl Hansen, NIH. The aging study was performed at NCI Frederick. The histotechnology support of Keith Rogers and his staff and the editorial review of Drs. Charles Capen and Steve Weisbrode are gratefully acknowledged. NR 10 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2008 VL 36 IS 2 BP 362 EP 365 DI 10.1177/0192623307312697 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UK UT WOS:000267457400017 PM 18362198 ER PT J AU Berman, RF Pessah, IN Mouton, PR Mav, D Harry, J AF Berman, Robert F. Pessah, Isaac N. Mouton, Peter R. Mav, Deepak Harry, Jean TI Low-level neonatal thimerosal exposure: Further evaluation of altered neurotoxic potential in SJL mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE thimerosal; mercury; SJL mice; locomotor behavior; social behavior; hippocampus; stereology ID BEHAVIORAL TASKS RELEVANT; KAINATE RECEPTOR SUBUNITS; SPATIAL WORKING-MEMORY; MOSSY FIBER SYNAPSES; NERVOUS-SYSTEM; MERCURY CONCENTRATIONS; STEREOLOGICAL ANALYSIS; PREPULSE INHIBITION; DOPAMINE-RECEPTORS; PREFRONTAL CORTEX AB Ethylmercury in thimerosal-preserved childhood vaccines has been suggested to be neurotoxic and to contribute to the etiology of neurodevelopmental disorders, including autism. Immune system function may be an important factor influencing vulnerability of the developing nervous system to thimerosal. This possibility is based in part on a report by Hornig et al. (2004, Mol. Psychiatry 9, 833-845) of neurodevelomental toxicity in SJL/J mice that develop autoantibodies when exposed to organic mercury. The present study reexamined this possibility by injecting neonatal SJL/J mice with thimerosal, with and without combined HiB and DTP vaccines. Injections modeled childhood vaccination schedules, with mice injected on postnatal days 7, 9, 11, and 15 with 14.2, 10.8, 9.2, and 5.6 mu g/kg mercury from thimerosal, respectively, or vehicle. Additional groups received vaccine only or a 10 times higher thimerosal 1 vaccine dose. Low levels of mercury were found in blood, brain, and kidneys 24 h following the last thimerosal injection. Survival, body weight, indices of early development (negative geotaxis, righting) and hippocampal morphology were not affected. Performance was unaffected in behavioral tests selected to assess behavioral domains relevant to core deficits in neurodevelopmental disorders such as autism (i.e., social interaction, sensory gating, anxiety). In an open-field test the majority of behaviors were unaffected by thimerosal injection, although thimerosal-injected female mice showed increased time in the margin of an open field at 4 weeks of age. Considered together the present results do not indicate pervasive developmental neurotoxicity following vaccine-level thimerosal injections in SJL mice, and provide little if any support for the hypothesis that thimerosal exposure contributes to the etiology of neurodevelopmental disorders. C1 [Berman, Robert F.] Univ Calif Davis, Dept Neurol Surg, Davis, CA 95616 USA. [Berman, Robert F.; Pessah, Isaac N.] Univ Calif Davis, Ctr Childrens Environm Hlth, Davis, CA 95616 USA. [Pessah, Isaac N.] Univ Calif Davis, Dept Mol Biosci, Davis, CA 95616 USA. [Mouton, Peter R.] NIH, NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Mav, Deepak] LLC, Constella Grp, Durham, NC 27713 USA. [Harry, Jean] NIH, Neurobiol Lab, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Berman, RF (reprint author), Univ Calif Davis, Dept Neurol Surg, 1515 Newton Court,Room 502C, Davis, CA 95616 USA. EM rfberman@ucdavis.edu FU NIEHS NIH HHS [P42 ES04699, N02-ES65554, 1P01 ES11269, P42 ES05707]; PHS HHS [HHSN291200555547C] NR 75 TC 33 Z9 34 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2008 VL 101 IS 2 BP 294 EP 309 DI 10.1093/toxsci/kfm265 PG 16 WC Toxicology SC Toxicology GA 250NE UT WOS:000252306100012 PM 17977901 ER PT J AU Tilley, L Sougrat, R Lithgow, T Hanssen, E AF Tilley, Leann Sougrat, Rachid Lithgow, Trevor Hanssen, Eric TI The twists and turns of Maurer's cleft trafficking in P-Falciparum-infected erythrocytes SO TRAFFIC LA English DT Review DE electron tomography; green fluorescent protein; Maurer's clefts; Plasmodium falciparum; protein trafficking ID RED-BLOOD-CELLS; PARASITE PLASMODIUM-FALCIPARUM; HISTIDINE-RICH PROTEIN; TRANSFECTED MALARIA PARASITES; CAVEOLA-VESICLE COMPLEXES; HOST-CELL; MEMBRANE-PROTEINS; GENE FAMILY; PARASITOPHOROUS VACUOLE; TARGETING SIGNAL AB The malaria parasite, Plasmodium falciparum, invades the red blood cells (RBCs) of its human host and initiates a series of morphological rearrangements within the host cell cytoplasm. The mature RBC has no endogenous trafficking machinery; therefore, the parasite generates novel structures to mediate protein transport. These include compartments called the Maurer's clefts (MC), which play an important role in the trafficking of parasite proteins to the surface of the host cell. Recent electron tomography studies have revealed MC as convoluted flotillas of flattened discs that are tethered to the RBC membrane, prompting speculation that the MC could, in one respect, represent an extracellular equivalent of the Golgi apparatus. Visualization of both resident and cargo proteins has helped decipher the signals and routes for trafficking of parasite proteins to the MC and beyond. C1 [Tilley, Leann; Hanssen, Eric] La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia. [Tilley, Leann; Hanssen, Eric] La Trobe Univ, Ctr Excellence Coherent Xray Sci, Melbourne, Vic 3086, Australia. [Sougrat, Rachid] NIH, NICHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. [Lithgow, Trevor] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia. [Lithgow, Trevor] Univ Melbourne, Bio Mol Sci & Biotechnol Inst 21, Parkville, Vic 3010, Australia. RP Tilley, L (reprint author), La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia. EM l.tilley@latrobe.edu.au RI Hanssen, Eric/A-7217-2013; OI Hanssen, Eric/0000-0002-4064-1844; Sougrat, Rachid/0000-0001-6476-1886 NR 89 TC 49 Z9 51 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-9219 J9 TRAFFIC JI Traffic PD FEB PY 2008 VL 9 IS 2 BP 187 EP 197 DI 10.1111/j.1600-0854.2007.00684.x PG 11 WC Cell Biology SC Cell Biology GA 254LY UT WOS:000252589300004 PM 18088325 ER PT J AU Denholm, EM Martin, WJ AF Denholm, Elizabeth M. Martin, William J., II TI Translational research in environmental health sciences SO TRANSLATIONAL RESEARCH LA English DT Editorial Material C1 [Denholm, Elizabeth M.; Martin, William J., II] NIEHS, Off Translat Res, Res Triangle Pk, NC 27709 USA. RP Denholm, EM (reprint author), NIEHS, Off Translat Res, POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z99 HD999999] NR 4 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 J9 TRANSL RES JI Transl. Res. PD FEB PY 2008 VL 151 IS 2 BP 57 EP 58 DI 10.1016/j.trs1.2007.09.005 PG 2 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 255JF UT WOS:000252653600001 PM 18201672 ER PT J AU Jang, HB Zheng, J Lal, R Nussinov, R AF Jang, Hyunbum Zheng, Jie Lal, Ratnesh Nussinov, Ruth TI New structures help the modeling of toxic amyloid beta ion channels SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID SOLID-STATE NMR; PROTEIN MISFOLDING DISEASES; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; LIPID-BILAYERS; PARKINSONS-DISEASE; 3D STRUCTURE; NEURODEGENERATIVE DISEASE; CORTICAL-NEURONS; FIBRIL FORMATION AB The mechanism of amyloid toxicity is poorly understood and there are two schools of thought in this hotly debated field: the first favors membrane destabilization by intermediate-to-large amyloid oligomers, with consequent thinning and non-specific ion leakage; the second favors ion-specific permeable channels lined by small amyloid oligomers. Published results currently support both mechanisms. However, the amyloid beta (A beta) peptide has recently been shown to form a U-shaped 'beta-strand-turn-beta-strand' structure. This structure and the available physiological data present a challenge for computational biology - to provide candidate models consistent with the experimental data. Modeling based on small AP oligomers containing extramembranous N-termini predicts channels with shapes and dimensions consistent with experimentally derived channel structures. These results support the hypothesis that small A beta oligomers can form ion channels. Molecular dynamics modeling can provide blueprints of 3D structural conformations for many other amyloids whose membrane association is key to their toxicity. C1 [Jang, Hyunbum; Zheng, Jie; Nussinov, Ruth] NCI Frederick, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Lal, Ratnesh] Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. [Lal, Ratnesh] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI Frederick, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Zheng, Jie/B-5057-2013 OI Zheng, Jie/0000-0003-1547-3612 FU Intramural NIH HHS; NCI NIH HHS [N01 CO12400] NR 74 TC 102 Z9 102 U1 4 U2 25 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 2008 VL 33 IS 2 BP 91 EP 100 DI 10.1016/j.tibs.2007.10.007 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 268BH UT WOS:000253552400006 PM 18182298 ER PT J AU Kovacic, JC Moore, J Herbert, A Ma, D Boehm, M Graham, RM AF Kovacic, Jason C. Moore, John Herbert, Andrea Ma, David Boehm, Manfred Graham, Robert M. TI Endothelial progenitor cells, angioblasts, and angiogenesis - Old terms reconsidered from a current perspective SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID STEM-CELLS; POSTNATAL VASCULOGENESIS; VESSEL FORMATION; BLOOD-VESSELS; NEOVASCULARIZATION; OUTGROWTH; MONOCYTES; ORIGIN; MONOCYTES/MACROPHAGES; DIFFERENTIATION AB When the term 'angioblast' was initially used, almost a century ago, the cells bearing this name were thought to give rise to plasma, red blood cells and endothelium, with new blood vessels arising from 'Within the (cell) bodies of these angioblasts'. More recently, putative circulating 'progenitor p endothelial cells, often also refer-red to as angioblasts, were first described in the adult human a mere decade ago. Therefore, while our understanding of progenitor cell biology and other relevant vascular developmental programs has progressed enormously, key terms such as 'angioblast' and 'angiogenesis' have remained constant. With the recent intense interest in angioblasts and endothelial progenitor cells, and their potential with respect to cardiovascular regenerative medicine, our knowledge of how these and other nonprogenitor cells might contribute to new vessel formation has taken a further leap in understanding. In this review, we focus on the controversial use and definition of these terms based upon our current understanding of vascular biology and progenitor cells. C1 [Graham, Robert M.] Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia. [Kovacic, Jason C.; Boehm, Manfred] Natl Inst Hlth, Cardiol Branch, Div Intramural Res, Bethesda, MD USA. [Herbert, Andrea; Ma, David; Graham, Robert M.] Univ New S Wales, St Vincent Hosp, Fac Med, Kensington, NSW 2033, Australia. RP Kovacic, JC (reprint author), Bldg 10-CRC,Room 5E-3232,MSC 1454,10 Ctr Dr, Bethesda, MD 20892 USA. EM kovacicj@mail.nih.gov; r.graham@victorchang.edu.au NR 48 TC 44 Z9 49 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD FEB PY 2008 VL 18 IS 2 BP 45 EP 51 DI 10.1016/j.tcm.2007.12.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 277BR UT WOS:000254188200002 PM 18308194 ER PT J AU Gorospe, M de Cabot, R AF Gorospe, Myriam de Cabot, Rafael TI AsSIRTing the DNA damage response SO TRENDS IN CELL BIOLOGY LA English DT Review ID BINDING PROTEIN HUR; MESSENGER-RNA STABILITY; FOXO TRANSCRIPTION FACTORS; BREAKAGE SYNDROME PROTEIN; PANCREATIC BETA-CELLS; ATM ACTIVATION; OXIDATIVE STRESS; REGULATES SIRT1; ATAXIA-TELANGIECTASIA; DEACETYLASE ACTIVITY AB In mammalian cells, changes in signaling networks and expressed proteins ensure the adequate detection and management of damaged macromolecules. Here, we review an emergent pathway of maintenance of homeostasis following genotoxic stress. The RNA-binding protein HuR associates with sirtuin (SIRT)1 mRNA and maintains constitutively elevated levels of SIRT1 protein, a deacetylase that elicits a prosurvival function. SIRT1 was recently shown to deacetylate the Nijmegen breakage syndrome (NBS1) protein, thereby rendering it phosphorylatable by ataxia telangiectasia mutated protein (ATM). A component of the MRN (MRE11-RAD50-NBS1) nuclease complex, NBS1 is crucial for sensing DNA damage and mounting a genotoxic response. This article covers the regulatory pathway of HuR -> SIRT1 -> NBS1, through which post-transcriptional and post-translational effectors contribute to the maintenance of genomic integrity. C1 [Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [de Cabot, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 97 TC 38 Z9 39 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD FEB PY 2008 VL 18 IS 2 BP 77 EP 83 DI 10.1016/j.tcb.2007.11.007 PG 7 WC Cell Biology SC Cell Biology GA 273OZ UT WOS:000253942600006 PM 18215521 ER PT J AU Kusanovic, JP Nien, JK Goncalves, LF Espinoza, J Lee, W Balasubramaniam, M Soto, E Erez, O Romero, R AF Kusanovic, J. P. Nien, J. K. Goncalves, L. F. Espinoza, J. Lee, W. Balasubramaniam, M. Soto, E. Erez, O. Romero, R. TI The use of inversion mode and 3D manual segmentation in volume measurement of fetal fluid-filled structures: comparison with Virtual Organ Computer-aided AnaLysis (VOCAL (TM)) SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE 3D US; fetal bladder; fetal stomach; three-dimensional ultra sonography; volume measurements ID TRANSVAGINAL 3-DIMENSIONAL ULTRASOUND; OVARIAN VOLUME; INTEROBSERVER RELIABILITY; ULTRASONOGRAPHY; ACCURACY; ECHOCARDIOGRAPHY; ALGORITHM; VALIDITY; DISTANCE; BLADDER AB Objective Volume measurements by three-dimensional (3D) ultrasonograpby are considered more accurate than those performed by two-dimensional (2D) ultrasonograpby. The purpose of this study was to compare the agreement of three techniques, as well as the inter- and intraobserver agreements for volume measurements of fetal fluid-filled structures. Methods Fifty 3D volume datasets of fetal stomachs and bladders were explored. Volume measurements were performed independently by two observers using: (1) Virtual Organ Computer-aided AnaLysis (VOCAL (TM)); (2) inversion mode; and (3) 'manual segmentation'. Reliability was evaluated using intraclass correlation coefficient (ICC), and Bland-Altman plots were generated to examine bias and agreement. The time required to complete the measurements was compared using Student's t-test or the Wilcoxon Signed Rank Test, and P-values < 0.025 or < 0.05 were considered statistically significant. Results All volume datasets could be measured using the three techniques. A high degree of reliability was observed between: (1) VOCAL and inversion mode (ICC, 0.99s; 95% CI, 0.992-0.997); (2) VOCAL and manual segmentation (ICC, 0.997; 95% CI, 0.995-0.998); and (3) inversion mode and manual segmentation (ICC, 0.99s; 9S% CI, 0.992-0.997). There was good agreement between VOCAL and inversion mode (mean, -2.4%; 95% limits of agreement, -20.1 to 15.3%), VOCAL and manual segmentation (mean, -8.3%; 95% limits of agreement, -28.8 to 12.2%) as well as between inversion mode and manual segmentation (mean, 5.9%, 95% limits of agreement: -14.3 to 26%). Manual segmentation and inversion mode measurements were obtained significantly faster than those by VOCAL. Conclusions Volume measurements of fetal fluid-filled structures of relatively regular shape with inversion mode and manual segmentation are feasible. Both techniques have good agreement with VOCAL and are significantly faster than VOCAL. Inversion mode is a reliable method for volume calculations of fluid-filled organs, whereas manual segmentation can be used when volume measurements by VOCAL or inversion mode are technically difficult to obtain, such as solid structures with poorly defined borders as the volume dataset is rotated, like the uterine cervix. Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd. C1 [Kusanovic, J. P.; Nien, J. K.; Goncalves, L. F.; Espinoza, J.; Soto, E.; Erez, O.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Kusanovic, J. P.; Nien, J. K.; Goncalves, L. F.; Espinoza, J.; Soto, E.; Erez, O.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Goncalves, L. F.; Espinoza, J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Balasubramaniam, M.] William Beaumont Hosp, Res Inst, Div Biostat, Royal Oak, MI 48072 USA. [Lee, W.] William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, DHHS, NIH,NICHD,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002401-15, Z99 HD999999] NR 31 TC 28 Z9 32 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD FEB PY 2008 VL 31 IS 2 BP 177 EP 186 DI 10.1002/uog.5242 PG 10 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 267LU UT WOS:000253511300011 PM 18254130 ER PT J AU Espinoza, J Romero, R Kusanovic, JP Gotsch, F Lee, W Goncalves, LF Hassan, SS AF Espinoza, J. Romero, R. Kusanovic, J. P. Gotsch, F. Lee, W. Goncalves, L. F. Hassan, S. S. TI Standardized views of the fetal heart using four-dimensional sonographic and tomographic imaging SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE algorithm; congenital heart disease; four dimensional; prenatal diagnosis; spatiotemporal; spatiotemporal image correlation; three dimensional; tomographic ultrasound imaging ID COLOR DOPPLER ULTRASOUND; 3-DIMENSIONAL ULTRASOUND; PRENATAL-DIAGNOSIS; ECHOCARDIOGRAPHIC ANALYSIS; GREAT-ARTERIES; 4D ULTRASOUND; ULTRASONOGRAPHY; DISEASE; 3D; DISPLAY C1 [Espinoza, J.; Kusanovic, J. P.; Gotsch, F.; Goncalves, L. F.; Hassan, S. S.] Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, Detroit, MI 48201 USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Lee, W.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Espinoza, J.; Goncalves, L. F.; Hassan, S. S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002401-15] NR 60 TC 8 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD FEB PY 2008 VL 31 IS 2 BP 233 EP 242 DI 10.1002/uog.5250 PG 10 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 267LU UT WOS:000253511300026 PM 18254137 ER PT J AU McGlynn, KA Devesa, SS AF McGlynn, Katherine A. Devesa, Susan S. TI Re: Nguyen MM, Ellison LM: Testicular cancer patterns in Asian-American males : An opportunity for public health education to impact outcomes (Urology 66 : 606-609, 2005) and Gajendran VK, Nguyen M, Ellison LM : Testicular cancer patterns in African-American men (Urology 66 : 602-605, 2005) SO UROLOGY LA English DT Letter ID GERM-CELL TUMORS; UNITED-STATES C1 [McGlynn, Katherine A.; Devesa, Susan S.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. RP McGlynn, KA (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. FU Intramural NIH HHS [Z99 CA999999] NR 5 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 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2008 VL 71 IS 2 BP 356 EP 357 DI 10.1016/j.urology.2006.01.094 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 265CZ UT WOS:000253338000054 PM 18308129 ER PT J AU Singh, G Klar, AJS AF Singh, Gurjeet Klar, Amar J. S. TI Mutations in deoxyribonucleotide biosynthesis pathway cause spreading of silencing across heterochromatic barriers at the mating-type region of the fission yeasty SO YEAST LA English DT Article DE heterochromatin barriers; fission yeast; ribonucleoside reductase; thymidylate synthase; epigenetic ID DNA-POLYMERASE-ALPHA; SCHIZOSACCHAROMYCES-POMBE; NUCLEAR-ORGANIZATION; CHROMATIN DOMAINS; LYSINE-9 METHYLATION; CHROMODOMAIN PROTEIN; EPIGENETIC CONTROL; BOUNDARIES; TRANSCRIPTION; EXPRESSION AB The mat2,3-region of Schizosaccharomyces pombe is flanked by two inverted repeat elements, IRL and IRR, which define the boundaries of the silent domain resulting from heterochromatin assembly in the region. We employed a genetic screen to isolate factors whose mutations allowed spreading of heterochromatin across boundary elements. Surprisingly, this screen revealed that mutations in the genes required for deoxyribonucleotide biosynthesis, cdc22 (encoding the large subunit of ribonucleotide reductase) and tdsl (putative thymidylate synthase), cause silencing of marker genes inserted outside of the silent domain. Chromatin-immunoprecipitation analysis showed that histone H3 lysine 9 methylation modification, an epigenetic mark associated with gene silencing, is enriched by two- to three-fold in the cdc22 mutant as compared to the level found in the wild-type strain in regions outside the silent domain. The spreading of heterochromatin across barriers required functional Atf1/Pcr1, ATF-CREB family proteins, but not the RNA-interference Dcr1, Ago1, or Rdp1 factors, previously implicated in silencing. These results implicate the deoxyribonucleotide biosynthesis pathway in limiting epigenetic controls at barrier elements at the mating-type region, but the mechanism remains unknown. Published in 2007 by John Wiley & Sons, Ltd. C1 [Singh, Gurjeet; Klar, Amar J. S.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Klar, AJS (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, POB B,Bldg 539, Ft Detrick, MD 21702 USA. EM klar@ncircrf.gov FU Intramural NIH HHS NR 53 TC 13 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD FEB PY 2008 VL 25 IS 2 BP 117 EP 128 DI 10.1002/yea.1569 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 271JL UT WOS:000253784600004 PM 18030666 ER PT J AU Hunter, L Lu, Z Firby, J Baumgartner, WA Johnson, HL Ogren, PV Cohen, KB AF Hunter, Lawrence Lu, Zhiyong Firby, James Baumgartner, William A., Jr. Johnson, Helen L. Ogren, Philip V. Cohen, K. Bretonnel TI OpenDMAP: An open source, ontology-driven concept analysis engine, with applications to capturing knowledge regarding protein transport, protein interactions and cell-type-specific gene expression SO BMC BIOINFORMATICS LA English DT Article ID BIOMEDICAL TEXT; ARGUMENT STRUCTURES; INFORMATION; EXTRACTION; SYSTEM; DATABASE; NETWORK; BIOLOGY; TOOL AB Background: Information extraction (IE) efforts are widely acknowledged to be important in harnessing the rapid advance of biomedical knowledge, particularly in areas where important factual information is published in a diverse literature. Here we report on the design, implementation and several evaluations of OpenDMAP, an ontology-driven, integrated concept analysis system. It significantly advances the state of the art in information extraction by leveraging knowledge in ontological resources, integrating diverse text processing applications, and using an expanded pattern language that allows the mixing of syntactic and semantic elements and variable ordering. Results: OpenDMAP information extraction systems were produced for extracting protein transport assertions (transport), protein-protein interaction assertions (interaction) and assertions that a gene is expressed in a cell type (expression). Evaluations were performed on each system, resulting in F-scores ranging from .26-.72 (precision .39-.85, recall .16-.85). Additionally, each of these systems was run over all abstracts in MEDLINE, producing a total of 72,460 transport instances, 265,795 interaction instances and 176,153 expression instances. Conclusion: OpenDMAP advances the performance standards for extracting protein-protein interaction predications from the full texts of biomedical research articles. Furthermore, this level of performance appears to generalize to other information extraction tasks, including extracting information about predicates of more than two arguments. The output of the information extraction system is always constructed from elements of an ontology, ensuring that the knowledge representation is grounded with respect to a carefully constructed model of reality. The results of these efforts can be used to increase the efficiency of manual curation efforts and to provide additional features in systems that integrate multiple sources for information extraction. The open source OpenDMAP code library is freely available at http://bionlp.sourceforge.net/. C1 [Hunter, Lawrence; Baumgartner, William A., Jr.; Johnson, Helen L.; Cohen, K. Bretonnel] Univ Colorado, Sch Med, Ctr Computat Pharmacol, Aurora, CO 80045 USA. [Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Firby, James] PowerSet Inc, San Francisco, CA 94107 USA. [Ogren, Philip V.] Univ Colorado, Dept Comp Sci, Boulder, CO 80303 USA. RP Hunter, L (reprint author), Univ Colorado, Sch Med, Ctr Computat Pharmacol, Aurora, CO 80045 USA. EM Larry.Hunter@uchsc.edu; luzh@ncbi.nlm.nih.gov; Jim.Firby@gmail.com; William.Baumgartner@uchsc.edu; Helen.Johnson@uchsc.edu; Philip@Ogren.info; Kevin.Cohen@gmail.com OI Hunter, Lawrence/0000-0003-1455-3370 FU Intramural NIH HHS; NLM NIH HHS [R01 LM008111, R01 LM009254]; PHS HHS [R01NLM008111, R01NLM009254] NR 58 TC 59 Z9 61 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 31 PY 2008 VL 9 AR 78 DI 10.1186/1471-2105-9-78 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 280OP UT WOS:000254436400001 PM 18237434 ER PT J AU Sam, V Tai, CH Garnier, J Gibrat, JF Lee, B Munson, PJ AF Sam, Vichetra Tai, Chin-Hsien Garnier, Jean Gibrat, Jean-Francois Lee, Byungkook Munson, Peter J. TI Towards an automatic classification of protein structural domains based on structural similarity SO BMC BIOINFORMATICS LA English DT Article ID STRUCTURE ALIGNMENT; MATHEMATICAL-THEORY; SCOP; DATABASE; FSSP; FOLD; CATH; COMMUNICATION; SEQUENCES AB Background: Formal classification of a large collection of protein structures aids the understanding of evolutionary relationships among them. Classifications involving manual steps, such as SCOP and CATH, face the challenge of increasing volume of available structures. Automatic methods such as FSSP or Dali Domain Dictionary, yield divergent classifications, for reasons not yet fully investigated. One possible reason is that the pairwise similarity scores used in automatic classification do not adequately reflect the judgments made in manual classification. Another possibility is the difference between manual and automatic classification procedures. We explore the degree to which these two factors might affect the final classification. Results: We use DALI, SHEBA and VAST pairwise scores on the SCOP C class domains, to investigate a variety of hierarchical clustering procedures. The constructed dendrogram is cut in a variety of ways to produce a partition, which is compared to the SCOP fold classification. Ward's method dendrograms led to partitions closest to the SCOP fold classification. Dendrogram- or tree-cutting strategies fell into four categories according to the similarity of resulting partitions to the SCOP fold partition. Two strategies which optimize similarity to SCOP, gave an average of 72% true positives rate (TPR), at a 1% false positive rate. Cutting the largest size cluster at each step gave an average of 61% TPR which was one of the best strategies not making use of prior knowledge of SCOP. Cutting the longest branch at each step produced one of the worst strategies. We also developed a method to detect irreducible differences between the best possible automatic partitions and SCOP, regardless of the cutting strategy. These differences are substantial. Visual examination of hard-to-classify proteins confirms our previous finding, that global structural similarity of domains is not the only criterion used in the SCOP classification. Conclusion: Different clustering procedures give rise to different levels of agreement between automatic and manual protein classifications. None of the tested procedures completely eliminates the divergence between automatic and manual protein classifications. Achieving full agreement between these two approaches would apparently require additional information. C1 [Sam, Vichetra; Garnier, Jean; Munson, Peter J.] NIH, DHHS, DCB, Mth & Stat Comp Lab, Bethesda, MD 20892 USA. [Tai, Chin-Hsien; Lee, Byungkook] NCI, DHHS, CCR, Mol Biol Lab,NIH, Bethesda, MD 20892 USA. [Garnier, Jean; Gibrat, Jean-Francois] INRA, Lab Math Informat & Genome, Jouy En Josas, France. RP Munson, PJ (reprint author), NIH, DHHS, DCB, Mth & Stat Comp Lab, Bldg 10, Bethesda, MD 20892 USA. EM vsam@mail.nih.gov; taic@mail.nih.gov; jean.garnier@jouy.inra.fr; jean-francois.gibrat@jouy.inra.fr; BKLee@mail.nih.gov; munson@helix.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [P41 RR-01081, P41 RR001081] NR 36 TC 15 Z9 15 U1 0 U2 2 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 JAN 31 PY 2008 VL 9 AR 74 DI 10.1186/1471-2105-9-74 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 274OQ UT WOS:000254011000001 PM 18237410 ER PT J AU Baldwin, GS Brooks, NJ Robson, RE Wynveen, A Goldar, A Leikin, S Seddon, JM Kornyshev, AA AF Baldwin, Geoff S. Brooks, Nicholas J. Robson, Rebecca E. Wynveen, Aaron Goldar, Arach Leikin, Sergey Seddon, John M. Kornyshev, Alexei A. TI DNA double helices recognize mutual sequence homology in a protein free environment SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID OSMOTIC-STRESS; CONDENSATION; ORGANIZATION; MOLECULES; DENSITY; ORDER AB The structure and biological function of the DNA double helix are based on interactions recognizing sequence complementarity between two single strands of DNA. A single DNA strand can also recognize the double helix sequence by binding in its groove and forming a triplex. We now find that sequence recognition occurs between intact DNA duplexes without any single-stranded elements as well. We have imaged a mixture of two fluorescently tagged, double helical DNA molecules that have identical nucleotide composition and length (50% GC; 294 base pairs) but different sequences. In electrolytic solution at minor osmotic stress, these DNAs form discrete liquid-crystalline aggregates (spherulites). We have observed spontaneous segregation of the two kinds of DNA within each spherulite, which reveals that nucleotide sequence recognition occurs between double helices separated by water in the absence of proteins, consistent with our earlier theoretical hypothesis. We thus report experimental evidence and discuss possible mechanisms for the recognition of homologous DNAs from a distance. C1 [Baldwin, Geoff S.; Robson, Rebecca E.] Univ London Imperial Coll Sci Technol & Med, Div Mol Biosci, London SW7 2AZ, England. [Brooks, Nicholas J.; Robson, Rebecca E.; Wynveen, Aaron; Goldar, Arach; Seddon, John M.; Kornyshev, Alexei A.] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AZ, England. [Leikin, Sergey] NICHHD, Sect Phys Biochem, NIH, DHHS, Bethesda, MD 20892 USA. RP Baldwin, GS (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Mol Biosci, London SW7 2AZ, England. EM g.baldwin@imperial.ac.uk; leikins@mail.nih.gov; j.seddon@irnperial.ac.uk RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008; Brooks, Nicholas/H-3717-2011; OI Leikin, Sergey/0000-0001-7095-0739; Brooks, Nicholas/0000-0002-1346-9559; Baldwin, Geoffrey/0000-0003-4800-023X FU Intramural NIH HHS NR 25 TC 47 Z9 50 U1 2 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 31 PY 2008 VL 112 IS 4 BP 1060 EP 1064 DI 10.1021/jp7112297 PG 5 WC Chemistry, Physical SC Chemistry GA 254WP UT WOS:000252619000004 PM 18181611 ER PT J AU Volkow, ND Swanson, JM AF Volkow, Nora D. Swanson, James M. TI The action of enhancers can lead to addiction SO NATURE LA English DT Letter C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Swanson, James M.] Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. NR 1 TC 13 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 31 PY 2008 VL 451 IS 7178 BP 520 EP 520 DI 10.1038/451520a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 256OQ UT WOS:000252739900016 PM 18235477 ER PT J AU Ying, H Willingham, MC Cheng, SY AF Ying, H. Willingham, M. C. Cheng, S-Y TI The steroid receptor coactivator-3 is a tumor promoter in a mouse model of thyroid cancer SO ONCOGENE LA English DT Article DE thyroid carcinogenesis; SRC-3; apoptosis; cell cycles; thyroid hormone receptor mutant; mouse model of thyroid cancer ID TRANSCRIPTIONAL ACTIVITY; HORMONE RESISTANCE; CELL-PROLIFERATION; SIGNALING PATHWAY; LIGAND-BINDING; BETA-RECEPTOR; GENE; CARCINOGENESIS; GROWTH; SRC-3 AB The molecular genetic events underlying thyroid carcinogenesis are not well understood. Mice harboring a dominant-negative mutant thyroid hormone receptor-beta (TR beta(PV/PV) mice) spontaneously develop follicular thyroid carcinoma similar to human cancer. The present study aimed to elucidate the role of the steroid receptor coactivator-3 (SRC-3) in thyroid carcinogenesis in vivo by using the offspring from the cross of TR beta(PV/PV) and SRC-3(-/-) mice. TR beta PV/PV mice deficient in SRC-3 (TRb beta(SRC)-S-PV/PV-3(-/-) mice) had significantly increased survival, decreased thyroid tumor growth, delayed tumor progression and lower incidence of distant metastasis as compared with TR beta(PV/PV) mice with SRC-3 (TR beta(SRC)-S-PV/PV-3(-/-) mice). Further, in vivo nd in vitro analyses of multiple signaling pathways indicated that SRC-3 deficiency could lead to (1) inhibition of cell cycle progression at the G(1)/S transition via controlling the expression of cell cycle regulators, such as E2F1; (2) induction of apoptosis by controlling the expression of the Bcl-2 and caspase-3 genes and (3) suppression of neovascularization and metastasis, at least in part, through modulating the vascular endothelial growth factor gene expression. Taken together, SRC-3 could play important roles through regulating multiple target genes and signaling pathways during thyroid carcinogenesis, understanding of which should direct future therapeutic options for thyroid cancer. C1 [Ying, H.; Cheng, S-Y] NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Willingham, M. C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bldg 37,Room 5128,37 Convent Dr, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural NIH HHS NR 24 TC 17 Z9 19 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 31 PY 2008 VL 27 IS 6 BP 823 EP 830 DI 10.1038/sj.onc.1210680 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 258QZ UT WOS:000252884500011 PM 17653082 ER PT J AU Martin-Jimenez, T Lindeblad, M Kapetanovicc, IM Chen, Y Lyubimov, A AF Martin-Jimenez, T. Lindeblad, M. Kapetanovicc, I. M. Chen, Y. Lyubimov, A. TI Comparing pharmacokinetic and pharmacodynamic profiles in female rats orally exposed to lovastatin by gavage versus diet SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Conference on Frontiers of Pharmacology and Toxicology CY AUG 28-31, 2006 CL Chicago, IL SP Univ Illinois, Toxicol Res Lab, Dept Pharmacol & Canc Res Ctr, Appl Biosyst, Elsevier, Soc Toxicol, Labcat, Waters Corp, Hilltop Lab Anim, Bristol Myers Squibb, Marshall Farms, Thermo Electron N Amer LLC, AniLytics, EMKA Technologies, Perkin Elmer, Life & Analyt Sci DE lovastatin; gavage; diet; pharmacokinetics; pharmacodynamics; preclinical ID METABOLISM; SPARSE AB The objective of this study was to assess how the dosing method (i.e., gavage versus diet) affects the absorption and disposition of lovastatin, as well as its effect on two biological markers of exposure, such as serum levels of cholesterol and triglycerides. In preclinical safety studies the test agent is normally administered by gavage, but in chemoprevention efficacy studies the test agent is usually administered with the diet. Therefore, extrapolation of safety and efficacy data from laboratory animals to humans should consider the influence of the method of administration on the absorption, disposition and effect of the drug. Lovastatin, a blood cholesterol-lowering drug with a short elimination half-life in humans, was used to assess the influence of two different dosing methods on the drug pharmacokinetics and pharmacodynamics. Plasma and liver concentrations of lovastatin and its active metabolite lovastatin-Na were measured in female rats at sequential times after administration. Serum concentrations of triglycerides and cholesterol were measured at similar times and used as biomarkers of effect. Significant differences in pharmacokinetics and pharmacodynamics were observed after administration of lovastatin by the two oral dosing paradigms. In general, oral gavage resulted in higher peak and lower trough concentrations of lovastatin and lovastatin-Na in plasma and liver, lower area under the concentration-time curve of lovastatin-Na in plasma and liver, and less of an effect on the serum concentrations of triglycerides and cholesterol than the corresponding diet dosing. Although no inverse linear relationship was observed between pharmacokinetic and pharmacodynamic markers, in the case of serum cholesterol a visual trend could be observed which might have proven significant had data from a larger number of dose levels been available. As in our previous study with sulindac, this study illustrates potential limitations in trying to extrapolate from data obtained using different dosing schemes to potential safety and efficacy in humans. (c) 2007 Elsevier Ireland Ltd. All fights reserved. C1 [Martin-Jimenez, T.] Univ Tennessee, Coll Vet Med, Dept Comparat & Expt Med, Knoxville, TN 37996 USA. [Lindeblad, M.; Chen, Y.; Lyubimov, A.] Univ Illinois, Dept Pharmacol, Toxicol Res Lab, Chicago, IL 60612 USA. [Kapetanovicc, I. M.] NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Martin-Jimenez, T (reprint author), Univ Tennessee, Coll Vet Med, Dept Comparat & Expt Med, 2407 River Dr, Knoxville, TN 37996 USA. EM tmartinj@utk.edu NR 13 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JAN 30 PY 2008 VL 171 IS 2 BP 142 EP 151 DI 10.1016/j.cbi.2007.07.010 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 265MN UT WOS:000253363400004 PM 17854789 ER PT J AU Kabirov, KK Kapetanovic, IM Lyubimov, AV AF Kabirov, K. K. Kapetanovic, I. M. Lyubimov, A. V. TI Direct determination of selenium in rat blood plasma by Zeeman atomic absorption spectrometry SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Conference on Frontiers of Pharmacology and Toxicology CY AUG 28-31, 2006 CL Chicago, IL SP Univ Illinois, Toxicol Res Lab, Dept Pharmacol & Canc Res Ctr, Appl Biosyst, Elsevier, Soc Toxicol, Labcat, Waters Corp, Hilltop Lab Anim, Bristol Myers Squibb, Marshall Farms, Thermo Electron N Amer LLC, AniLytics, EMKA Technologies, Perkin Elmer, Life & Analyt Sci DE selenium; rat plasma; atomic absorption ID TISSUE DISTRIBUTION; MAMMARY-CANCER; SE; SUPPLEMENTATION; CHEMOPREVENTION; METABOLISM; SPECIATION; EXCRETION; SERUM AB The method was developed to be applied for direct determination of selenium in rat plasma by graphite-furnace atomic absorption spectrometry with Zeeman background correction. Blood was obtained from CD (R) rats of both sexes 2 h after dosing in weeks 7 and 13 in order to acquire data on the levels of selenium in these animals during 13-week gavage administration Of L-selenomethylselenocysteine (SeMC), a new candidate chemopreventive agent under development. Application of the commonly used method of standard addition was found to be unsuitable to calculate the selenium content in rat plasma (within-run and between-run accuracy and precision parameters were less than 85%). Therefore, a new analytical method was developed. In this method, samples of rat plasma (50 mu L) were diluted 10-fold with a reducing agent containing L-ascorbic acid, a modifier solution containing palladium chloride and Triton X-100. Samples were atomized in pyrolytically coated graphite tubes and peak height signals were measured. Selenium concentrations were determined by linear least squares regression analysis based on the standard curve generated in pooled rat blank plasma. Since selenium is normally present in plasma, a three-step approach was used to calculate selenium plasma levels. Initially selenium levels were determined based on the standard curve with selenium-spiked pool plasma. In the second step, background selenium levels in the pooled plasma were determined based on the same standard curve. In the third step, background level was added to the previously derived number. The relative errors were in the range from -4.6 to 11.4% (intra-day assay) and from -0.4 to 8.8% (inter-day assay) which proved good accuracy. The relative standard deviations were in the range from 1.88 to 4.70% (intra-day precision) and from 3.28 to 5.38% (inter-day precision). In rat plasma, the following dose-dependent selenium levels (mean +/- S.D.) in males and females, respectively, were observed at 13 weeks: 655.5 +/- 48.8 and 595.8 +/- 43.9 ng/mL (control group), 927.9 +/- 85.3 and 859.3 +/- 164.3 ng/mL (0.4 mg/kg per day dose group), 1238.9 +/- 182.4 and 1169.9:+/- 112.6 ng/mL (0.8 mg/kg per day dose group), and 1476.5 +/- 138.1 and 1320.1 +/- 228.6 ng/mL (2.0 mg/kg per day dose group). No significant sex differences in selenium plasma levels were seen in the SeMC-treated groups. No significant differences in selenium plasma levels were seen between mean plasma levels at 7 and 13 weeks. The described method is simple, rapid, accurate, precise and can be easily applied in other laboratories for a large number of samples. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Kabirov, K. K.; Lyubimov, A. V.] Univ Illinois, Dept Pharmacol, Toxicol Res Lab, Chicago, IL 60612 USA. [Kapetanovic, I. M.] NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Kabirov, KK (reprint author), Univ Illinois, Dept Pharmacol, Toxicol Res Lab, 808 S Wood St, Chicago, IL 60612 USA. EM kabirov@uic.edu FU NCI NIH HHS [N01-CN-43306] NR 30 TC 4 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JAN 30 PY 2008 VL 171 IS 2 BP 152 EP 158 DI 10.1016/j.cbi.2007.11.011 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 265MN UT WOS:000253363400005 PM 18155186 ER PT J AU Robles, AI Varticovski, L AF Robles, Ana I. Varticovski, Lyuba TI Harnessing genetically engineered mouse models for preclinical testing SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Conference on Frontiers of Pharmacology and Toxicology CY AUG 28-31, 2006 CL Chicago, IL SP Univ Illinois, Toxicol Res Lab, Dept Pharmacol & Canc Res Ctr, Appl Biosyst, Elsevier, Soc Toxicol, Labcat, Waters Corp, Hilltop Lab Anim, Bristol Myers Squibb, Marshall Farms, Thermo Electron N Amer LLC, AniLytics, EMKA Technologies, Perkin Elmer, Life & Analyt Sci DE gene expression; breast cancer; microarray; MMTV-PyMT; MMTV-wntl; transgenics; transplantation; xenografts ID GENE-EXPRESSION PATTERNS; HUMAN TUMOR XENOGRAFTS; WNT SIGNALING PATHWAY; IN-VIVO; CANCER MODELS; DRUG DEVELOPMENT; TRANSGENIC MICE; CLINICAL-TRIALS; MAMMARY-TUMORS; CELLS AB Recent studies cast doubt on the value of traditionally used models as tools for testing therapies for human cancer. Although the standard practice of xenograffing tumors into immunocompromised mice generates reproducible tumors, drug testing in these models has low predictive power when compared to the clinical responses in Phase II trials. The use of tumor-bearing genetically engineered mouse models holds promise for improving preclinical testing. These models recapitulate specific molecular pathways in tumor initiation or progression and provide a biological system in which to study the disease process for assessing efficacy of new therapies and proof-of-principle for testing molecularly targeted drugs. In this review, we discuss the advantages and limitations of genetically engineered mice and plausible solutions for adapting these valuable tumors for wider use in preclinical testing by transplantation into naive recipients. We also provide examples of comparative molecular analysis of mammary tumors from MMTV-Polyoma Middle-T antigen and MMTV-wntl models as tools for finding clinical correlates, validating existing models and guiding the development of new genetically engineered mouse models for cancer. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Robles, Ana I.; Varticovski, Lyuba] NCI, NIH, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Varticovski, L (reprint author), NCI, NIH, Human Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Room 3060, Bethesda, MD 20892 USA. EM varticol@mail.nih.gov NR 32 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JAN 30 PY 2008 VL 171 IS 2 BP 159 EP 164 DI 10.1016/j.cbi.2007.01.014 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 265MN UT WOS:000253363400006 PM 17362899 ER PT J AU Kapetanovic, IM AF Kapetanovic, I. M. TI Computer-aided drug discovery and development (CADDD): In silico-chemico-biological approach SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Conference on Frontiers of Pharmacology and Toxicology CY AUG 28-31, 2006 CL Chicago, IL SP Univ Illinois, Toxicol Res Lab, Dept Pharmacol & Canc Res Ctr, Appl Biosyst, Elsevier, Soc Toxicol, Labcat, Waters Corp, Hilltop Lab Anim, Bristol Myers Squibb, Marshall Farms, Thermo Electron N Amer LLC, AniLytics, EMKA Technologies, PerkinElmer, Life & Analyt Sci DE drug discovery; drug development; molecular modeling; virtual screening; computational modeling; in silico drug design; QSAP/QSPR; predictive toxicology ID BETA SELECTIVE LIGANDS; LEAD STRUCTURE DISCOVERY; SYSTEMS BIOLOGY; PHARMACOPHORE IDENTIFICATION; RECEPTOR ANTAGONISTS; KINASE INHIBITORS; NATURAL-PRODUCTS; DOCKING; DESIGN; PROTEIN AB It is generally recognized that drug discovery and development are very time and resources consuming processes. There is an ever growing effort to apply computational power to the combined chemical and biological space in order to streamline drug discovery, design, development and optimization. In biomedical arena, computer-aided or in silico design is being utilized to expedite and facilitate hit identification, hit-to-lead selection, optimize the absorption, distribution, metabolism, excretion and toxicity profile and avoid safety issues. Commonly used computational approaches include ligand-based drug design (pharmacophore, a 3D spatial arrangement of chemical features essential for biological activity), structure-based drug design (drug-target docking), and quantitative structure-activity and quantitative structure-property relationships. Regulatory agencies as well as pharmaceutical industry are actively involved in development of computational tools that will improve effectiveness and efficiency of drug discovery and development process, decrease use of animals, and increase predictability. It is expected that the power of CADDD will grow as the technology continues to evolve. Published by Elsevier Ireland Ltd. C1 NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, 6130 Execut Bldg,Suit 2117,MSC 7322, Bethesda, MD 20892 USA. EM kapetani@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 94 TC 117 Z9 126 U1 3 U2 32 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JAN 30 PY 2008 VL 171 IS 2 BP 165 EP 176 DI 10.1016/j.cbi.2006.12.006 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 265MN UT WOS:000253363400007 PM 17229415 ER PT J AU Huestis, MA Scheidweiler, KB Saito, T Fortner, N Abraham, T Gustafson, RA Smith, ML AF Huestis, Marilyn A. Scheidweiler, Karl B. Saito, Takeshi Fortner, Neil Abraham, Tsadik Gustafson, Richard A. Smith, Michael L. TI Excretion of Delta(9)-tetrahydrocannabinol in sweat SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE THC; sweat; excretion; GC/MS; cannabinoid; marijuana ID ORAL FLUID; COCAINE USE; GC-MS; CANNABINOIDS; PATCHES; URINE; ABUSE; DISPOSITION; METABOLITES; MARIJUANA AB Sweat testing is a noninvasive technique for monitoring drug exposure over a 7-day period in treatment, criminal justice, and employment settings. We evaluated Delta(9)-tetrahydrocannabinol (THC) excretion in 11 daily cannabis users after cessation of drug use. PharmChek(R) sweat patches worn for 7 days were analyzed for THC by gas chromatography-mass spectrometry (GC/MS). The limit of quantification (LOQ) for the method was 0.4 ng THC/patch. Sweat patches worn the first week of continuously monitored abstinence had THC above the United States Substance Abuse Mental Health Services Administration's proposed cutoff concentration for federal workplace testing of 1 ng THC/patch. Mean +/- S.E.M. THC concentrations were 3.85 +/- 0.86 ng THC/patch. Eight of 11 subjects had negative patches the second week and one produced THC positive patches for 4 weeks of monitored abstinence. We also tested daily and weekly sweat patches from seven subjects who were administered oral doses of up to 14.8 mg THC/day for five consecutive days. In this oral THC administration study, no daily or weekly patches had THC above the LOQ; concurrent plasma THC concentrations were all less than 6.1 mu g/L. In conclusion, using proposed federal cutoff concentrations, most daily cannabis users will have a positive sweat patch in the first week after ceasing drug use and a negative patch after subsequent weeks, although patches may remain positive for 4 weeks or more. Oral ingestion of up to 14.8 mg THC daily does not produce a THC positive sweat patch test. Published by Elsevier Ireland Ltd. C1 [Huestis, Marilyn A.; Scheidweiler, Karl B.; Saito, Takeshi; Abraham, Tsadik] NIH, Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. [Saito, Takeshi] Tokai Univ, Sch Med, Kanagawa 2591100, Japan. [Fortner, Neil] ChoicePoint Inc, Alpharetta, GA USA. [Gustafson, Richard A.] USN, Navy Drug Screening Lab, Jacksonville, FL USA. [Smith, Michael L.] Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, Rockville, MD USA. RP Huestis, MA (reprint author), NIH, Natl Inst Drug Abuse, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000414-10, Z01 DA000412-10] NR 27 TC 27 Z9 27 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD JAN 30 PY 2008 VL 174 IS 2-3 BP 173 EP 177 DI 10.1016/j.forsciint.2007.04.002 PG 5 WC Medicine, Legal SC Legal Medicine GA 260TR UT WOS:000253033800015 PM 17481836 ER PT J AU Willenbring, ML AF Willenbring, Mark L. TI Topiramate as treatment for alcohol dependence - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Willenbring, ML (reprint author), NIAAA, NIH, Bethesda, MD 20892 USA. EM mlw@niaaa.hih.gov NR 2 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 30 PY 2008 VL 299 IS 4 BP 407 EP 407 DI 10.1001/jama.299.4.407-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 256JK UT WOS:000252724500013 ER PT J AU Schetter, AJ Leung, SY Sohn, JJ Zanetti, KA Bowman, ED Yanaihara, N Yuen, ST Chan, TL Kwong, DLW Au, GKH Liu, CG Calin, GA Croce, CM Harris, CC AF Schetter, Aaron J. Leung, Suet Yi Sohn, Jane J. Zanetti, Krista A. Bowman, Elise D. Yanaihara, Nozomu Yuen, Siu Tsan Chan, Tsun Leung Kwong, Dora L. W. Au, Gordon K. H. Liu, Chang-Gong Calin, George A. Croce, Carlo M. Harris, Curtis C. TI MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CELL-PROLIFERATION; HUMAN CANCERS; C-ELEGANS; GENE; DIFFERENTIATION; CLUSTER; ANTAGOMIRS; DROSOPHILA; SIGNATURE AB Context MicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome. Objective To identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome. Design, Setting, and Patients MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow- up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort. Main Outcome Measures MicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point. Results Thirty- seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR- 20a, miR- 21, miR- 106a, miR- 181b, and miR- 203, and all 5 were enriched in tumors from the validation cohort ( P <. 001). Higher miR- 21 expression was present in adenomas ( P =.006) and in tumors with more advanced TNM staging ( P <. 001). In situ hybridization demonstrated miR- 21 to be expressed at high levels in colonic carcinoma cells. The 5- year cancer- specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR- 21 expression was associated with poor survival in both the training ( hazard ratio, 2.5; 95% confidence interval, 1.2- 5.2) and validation cohorts ( hazard ratio, 2.4; 95% confidence interval, 1.4- 3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome. Conclusions Expression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR- 21 expression is associated with poor survival and poor therapeutic outcome. C1 [Schetter, Aaron J.; Sohn, Jane J.; Zanetti, Krista A.; Bowman, Elise D.; Yanaihara, Nozomu; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Schetter, Aaron J.; Zanetti, Krista A.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Leung, Suet Yi; Yuen, Siu Tsan; Chan, Tsun Leung] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Pokfulam, Hong Kong, Peoples R China. [Kwong, Dora L. W.; Au, Gordon K. H.] Univ Hong Kong, Queen Mary Hosp, Dept Clin Oncol, Pokfulam, Hong Kong, Peoples R China. [Liu, Chang-Gong; Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Calin, George A.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 3068A, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov RI Yuen , Siu /K-6311-2014; Leung, Suet Yi/C-4340-2009 FU Intramural NIH HHS [Z01 BC005480-22] NR 43 TC 980 Z9 1069 U1 10 U2 68 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 30 PY 2008 VL 299 IS 4 BP 425 EP 436 DI 10.1001/jama.299.4.425 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 256JK UT WOS:000252724500020 PM 18230780 ER PT J AU Jiang, XY Tian, F Du, Y Copeland, NG Jenkins, NA Tessarollo, L Wu, X Pan, HN Hu, XZ Xu, K Kenney, H Egan, SE Turley, H Harris, AL Marini, AM Lipsky, RH AF Jiang, Xueying Tian, Feng Du, Yang Copeland, Neal G. Jenkins, Nancy A. Tessarollo, Lino Wu, Xuan Pan, Hongna Hu, Xian-Zhang Xu, Ke Kenney, Heather Egan, Sean E. Turley, Helen Harris, Adrian L. Marini, Ann M. Lipsky, Robert H. TI BHLHB2 controls Bdnf promoter 4 activity and neuronal excitability SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain-derived neurotrophic factor; BDNF; neuronal excitability; BHLHB2; DEC1/Sharp2/Stra13; transcription ID NF-KAPPA-B; METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; MESSENGER-RNA EXPRESSION; NEUROTROPHIC FACTOR GENE; HIPPOCAMPAL-NEURONS; SYNAPTIC PLASTICITY; BINDING PROTEIN; NMDA RECEPTOR; REPRESSES TRANSCRIPTION AB Brain-derived neurotrophic factor (BDNF), via activation of TrkB receptors, mediates vital physiological functions in the brain, ranging from neuronal survival to synaptic plasticity, and has been implicated in the pathophysiology of neurodegenerative disorders. Although transcriptional regulation of the BDNF gene (Bdnf) has been extensively studied, much remains to be understood. We discovered a sequence within Bdnf promoter 4 that binds the basic helix-loop-helix protein BHLHB2 and is a target for BHLHB2-mediated transcriptional repression. NMDA receptor activation de-repressed promoter 4-mediated transcription and correlated with reduced occupancy of the promoter by BHLHB2 in cultured hippocampal neurons. Bhlhb2 gene -/- mice showed increased hippocampal exon 4-specific Bdnf mRNA levels compared with +/+ littermates under basal and activity-dependent conditions. Bhlhb2 knock-out mice also showed increased status epilepticus susceptibility, suggesting that BHLHB2 alters neuronal excitability. Together, these results support a role for BHLHB2 as a new modulator of Bdnf transcription and neuronal excitability. C1 [Jiang, Xueying; Tian, Feng; Hu, Xian-Zhang; Kenney, Heather; Lipsky, Robert H.] NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Xu, Ke] NIAAA, Sect Human Genet, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Du, Yang; Copeland, Neal G.; Jenkins, Nancy A.; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Wu, Xuan; Pan, Hongna; Marini, Ann M.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. [Egan, Sean E.] Univ Toronto, Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada. [Egan, Sean E.] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada. [Turley, Helen; Harris, Adrian L.] Univ Oxford, John Radcliffe Hosp, Mol Oncol Lab, Watherall Inst Mol Med, Oxford OX3 9DS, England. RP Lipsky, RH (reprint author), 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM rlipsky@mail.nih.gov OI Lipsky, Robert/0000-0001-7753-1473; Harris, Adrian/0000-0003-1376-8409 FU Intramural NIH HHS NR 78 TC 44 Z9 46 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 30 PY 2008 VL 28 IS 5 BP 1118 EP 1130 DI 10.1523/JNEUROSCI.2262-07.2008 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 257CY UT WOS:000252778000012 PM 18234890 ER PT J AU Silva, AC Lee, JH Wu, CWH Tucciarone, J Pelled, G Aoki, L Koretsky, AP AF Silva, Afonso C. Lee, Jung Hee Wu, Carolyn W. -H. Tucciarone, Jason Pelled, Galit Aoki, Lchio Koretsky, Alan P. TI Detection of cortical laminar architecture using manganese-enhanced MRI SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE brain; cortical layers; neuroarchitecture; neuronal tract tracing; somatosensory cortex ID RESONANCE-IMAGING MEMRI; BLOOD-BRAIN-BARRIER; IN-VIVO; MOUSE-BRAIN; 3D MRI; DEPENDENT CONTRAST; ANTEROGRADE TRACER; OCULAR DOMINANCE; FUNCTIONAL MRI; VISUAL-CORTEX AB Changes in manganese-enhanced MRI (MEMRI) contrast across the rodent somatosensory cortex were compared to the cortical laminae as identified by tissue histology and administration of an anatomical tracer to cortex and thalamus. Across the cortical thickness, MEMRI signal intensity was low in layer I, increased in layer II, decreased in layer III until mid-layer IV, and increased again, peaking in layer V, before decreasing through layer VI. The reeler mouse mutant was used to confirm that the cortical alternation in MEMRI contrast was related to laminar architecture. Unlike in wild-type mice, the reeler cortex showed no appreciable changes in MEMRI signal, consistent with absence of cortical laminae in histological slides. The tract tracing ability of MEMRI was used to further confirm assignments and demonstrate laminar specificity. Twelve to 16 It after stereotaxic injections of MnCl2 to the ventroposterior thalamic nuclei, an overall increase in signal intensity was detected in primary somatosensory cortex compared to other brain regions. Maximum intensity projection images revealed a distinctly bright stripe located 600-700 mu m below the pial surface, in layer IV. The data show that both systemic and tract tracing forms of MEMRI are useful for studying laminar architecture in the brain. Published by Elsevier B.V. C1 [Silva, Afonso C.; Lee, Jung Hee; Wu, Carolyn W. -H.; Tucciarone, Jason; Pelled, Galit; Aoki, Lchio; Koretsky, Alan P.] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Lab Funct & Mol Imaging, Cerebral Microcirculat Unit, Bethesda, MD 20892 USA. RP Silva, AC (reprint author), Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Lab Funct & Mol Imaging, Cerebral Microcirculat Unit, 10 Ctr Dr,10-B 1D118, Bethesda, MD 20892 USA. EM SilvaA@ninds.nih.gov RI Silva, Afonso/A-7129-2009; Aoki, Ichio/G-2529-2011; Koretsky, Alan/C-7940-2015 OI Aoki, Ichio/0000-0002-4429-5053; Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 59 TC 46 Z9 47 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 30 PY 2008 VL 167 IS 2 BP 246 EP 257 DI 10.1016/j.jneumeth.2007.08.020 PG 12 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 259KO UT WOS:000252938400015 PM 17936913 ER PT J AU Camargos, ST Cardoso, F Momeni, P Gianetti, JG Lees, A Hardy, J Singleton, A AF Camargos, Sarah Teixeira Cardoso, Francisco Momeni, Parastoo Gianetti, Juliana Gurgel Lees, Andrew Hardy, John Singleton, Andrew TI Novel GCH1 mutation in a Brazilian family with dopa-responsive dystonia SO MOVEMENT DISORDERS LA English DT Article DE dopa-responsive dystonia; Segawa disease; GCH1; GTP-cyclohydrolase; Brazilian families ID GTP-CYCLOHYDROLASE-I; GENE-MUTATIONS AB Dopa responsive Dystonia (DRD) was first described in 1971 and typically begins at childhood with gait dysfunction caused by foot dystonia progressing to affect other extremities. There is marked diurnal fluctuation and sustained improvement of symptoms with low dose levodopa therapy. Heterozygous mutation of the gene GCH1 has been shown to cause DRD. We studied GCH1 in nine patients with DRD from six families of Federal University of Minas Gerais Movement Disorders Clinic. We identified three mutations; two affected siblings carried a novel T209P mutation and two siblings from another family were compound heterozygous carriers of Met211Val and Lys224Arg mutations. To our knowledge this is the first report of GCH1 mutations underlying DRD in patients from Brazil. (C) 2007 Movement Disorder Society. C1 [Momeni, Parastoo; Hardy, John; Singleton, Andrew] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. [Camargos, Sarah Teixeira; Cardoso, Francisco; Gianetti, Juliana Gurgel] Univ Fed Minas Gerais, Dept Clin & Neurol Sci, Movement Disorders Grp, Belo Horizonte, MG, Brazil. [Momeni, Parastoo] Texas Tech Univ, Dept Neurol, Lubbock, TX 79409 USA. [Lees, Andrew] UCL, Reta Lila Weston Inst Neurol Studies, London, England. [Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. RP Singleton, A (reprint author), NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Lees, Andrew/A-6605-2009; Cardoso, Francisco/A-2285-2014; CAMARGOS, SARAH/O-4670-2014 OI Cardoso, Francisco/0000-0003-0808-0116; CAMARGOS, SARAH/0000-0001-9829-6783 FU Intramural NIH HHS; Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 14 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN 30 PY 2008 VL 23 IS 2 BP 299 EP 302 DI 10.1002/mds.21842 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 258ME UT WOS:000252871200027 PM 18044725 ER PT J AU Wang, H Chen, HL Gao, X McGrath, M Deer, D De Vivo, I Schwarzschild, MA Ascherio, A AF Wang, Hao Chen, Honglei Gao, Xiang McGrath, Monica Deer, Dwayne De Vivo, Immaculata Schwarzschild, Michael A. Ascherio, Alberto TI Telomere length and risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE nested case-control study; Parkinson's disease; telomere length; relative risk ID OXIDATIVE STRESS; CIGARETTE-SMOKING; MORTALITY; CONSUMPTION; DEMENTIA; CELLS; WOMEN; MEN AB We investigated whether telomere length was associated with the risk of Parkinson's disease (PD) in a case-control study (96 cases and 172 age-matched controls) nested within the Health Professionals Follow-up Study. Relative ratio of telomere repeat copy number to single-gene copy number in peripheral blood leukocytes was determined by quantitative real time PCR. Men with shorter telomeres had a lower PD risk (multivariate adjusted relative risk for the lowest vs. the highest quartile 0.33; 95% confidence interval: 0.12-0.90). Our results suggest that, contrary to telomere attrition observed in several aging-related diseases, shorter telomeres are not associated with an increased risk of PD. (C) 2007 Movement Disorder Society. C1 [Wang, Hao; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [McGrath, Monica; De Vivo, Immaculata; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [McGrath, Monica; Deer, Dwayne; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [McGrath, Monica; Deer, Dwayne; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Deer, Dwayne] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [De Vivo, Immaculata] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Wang, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM hwangi@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [R01 NS048517-01A2, R01 NS048517] NR 17 TC 38 Z9 39 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN 30 PY 2008 VL 23 IS 2 BP 302 EP 305 DI 10.1002/mds.21867 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 258ME UT WOS:000252871200028 PM 18044760 ER PT J AU Vexler, A Schisterman, EF Liu, A AF Vexler, Albert Schisterman, Enrique F. Liu, Aiyi TI Estimation of ROC curves based on stably distributed biomarkers subject to measurement error and pooling mixtures SO STATISTICS IN MEDICINE LA English DT Article DE deconvolution; design of experiments; Fourier inversion; infinitely divisible distribution; measurement error; pooling blood samples; receiver operating characteristic curves; stable distribution; summand's distribution ID NONPARAMETRIC DECONVOLUTION; STATISTICAL-INFERENCE; POOLED ASSESSMENTS; DIAGNOSTIC-TESTS; PARAMETERS; SAMPLES; AREA; LAWS AB Additive measurement errors and pooling design are objectively two different issues, which have been separately and extensively dealt with in the biostatistics literature. However, these topics usually correspond to problems of reconstructing a summand's distribution of the biomarker by the distribution of the convoluted observations. Thus, we associate the two issues into one stated problem. The integrated approach creates an opportunity to investigate new fields, e.g. a subject of pooling errors, issues regarding pooled data affected by measurement errors. To be specific, we consider the stated problem in the context of the receiver operating characteristic (ROC) curves analysis, which is the well-accepted tool for evaluating the ability of a biomarker to discriminate between two populations. The present paper considers a wide family of biospecimen distributions. In addition, applied assumptions, which are related to distribution functions of biomarkers, are mainly conditioned by the reconstructing problem. We propose and examine maximum likelihood techniques based on the following data: a biomarker with measurement error; pooled samples; and pooled samples with measurement error. The obtained methods are illustrated by applications to real data studies. Published in 2007 by John Wiley & Sons, Ltd. C1 [Vexler, Albert; Schisterman, Enrique F.; Liu, Aiyi] NICHHD, Bethesda, MD 20892 USA. RP Schisterman, EF (reprint author), 6100 Execut Blvd, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [NIH0014367067, Z01 HD008761-05] NR 31 TC 22 Z9 22 U1 0 U2 3 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 JAN 30 PY 2008 VL 27 IS 2 BP 280 EP 296 DI 10.1002/sim.3035 PG 17 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 261RY UT WOS:000253098900014 PM 17721905 ER PT J AU Schisterman, EF Faraggi, D Reiser, B Hu, J AF Schisterman, Enrique F. Faraggi, David Reiser, Benjamin Hu, Jessica TI Youden Index and the optimal threshold for markers with mass at zero SO STATISTICS IN MEDICINE LA English DT Article DE Box-Cox power transformations; Coronary Calcium Score; diagnostic markers; mixture model; ROC curve; sensitivity; specificity ID OPERATING CHARACTERISTIC CURVES; OPTIMAL CUT-POINT; TRANSFORMATION MODELS; DIAGNOSTIC-TESTS; ROC ANALYSIS; MORTALITY; DISEASE; SERUM AB The Youden Index is often used as a summary measure of the receiver operating characteristic curve. It measures the effectiveness of a diagnostic marker and permits the selection of an optimal threshold value or cutoff point for the biomarker of interest. Some markers, while basically continuous and positive, have a spike or positive mass of probability at the value zero. We provide a flexible modeling approach for estimating the Youden Index and its associated cutoff point for such spiked data and compare it with the standard empirical approach. We show how this modeling approach can be adjusted to take covariate information into account. This approach is applied to data on the Coronary Calcium Score, a marker for atherosclerosis. Published in 2007 by John Wiley & Sons, Ltd. C1 [Faraggi, David; Reiser, Benjamin] Univ Haifa, Dept Stat, IL-31999 Haifa, Israel. [Schisterman, Enrique F.] NICHD, Div Epidemiol Stat & Prevent, NIH, Rockville, MD USA. [Hu, Jessica] Glotech Inc, Rockville, MD USA. RP Reiser, B (reprint author), Univ Haifa, Dept Stat, IL-31999 Haifa, Israel. EM reiser@stat.haifa.ac.il RI Reiser, Benjamin/G-6591-2012; OI Reiser, Benjamin/0000-0002-9797-9029; Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [Z01 HD008761-05] NR 27 TC 31 Z9 32 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2008 VL 27 IS 2 BP 297 EP 315 DI 10.1002/sim.2993 PG 19 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 261RY UT WOS:000253098900015 PM 17624866 ER PT J AU Kestler, HA Muller, A Kraus, JM Buchholz, M Gress, TM Liu, HF Kane, DW Zeeberg, BR Weinstein, JN AF Kestler, Hans A. Mueller, Andre Kraus, Johann M. Buchholz, Malte Gress, Thomas M. Liu, Hongfang Kane, David W. Zeeberg, Barry R. Weinstein, John N. TI VennMaster: Area-proportional Euler diagrams for functional GO analysis of microarrays SO BMC BIOINFORMATICS LA English DT Article ID RESOURCE AB Background: Microarray experiments generate vast amounts of data. The functional context of differentially expressed genes can be assessed by querying the Gene Ontology ( GO) database via GoMiner. Directed acyclic graph representations, which are used to depict GO categories enriched with differentially expressed genes, are difficult to interpret and, depending on the particular analysis, may not be well suited for formulating new hypotheses. Additional graphical methods are therefore needed to augment the GO graphical representation. Results: We present an alternative visualization approach, area-proportional Euler diagrams, showing set relationships with semi-quantitative size information in a single diagram to support biological hypothesis formulation. The cardinalities of sets and intersection sets are represented by area-proportional Euler diagrams and their corresponding graphical ( circular or polygonal) intersection areas. Optimally proportional representations are obtained using swarm and evolutionary optimization algorithms. Conclusion: VennMaster's area-proportional Euler diagrams effectively structure and visualize the results of a GO analysis by indicating to what extent flagged genes are shared by different categories. In addition to reducing the complexity of the output, the visualizations facilitate generation of novel hypotheses from the analysis of seemingly unrelated categories that share differentially expressed genes. C1 [Kestler, Hans A.; Kraus, Johann M.] Univ Ulm, D-89069 Ulm, Germany. [Kestler, Hans A.; Mueller, Andre; Kraus, Johann M.; Buchholz, Malte; Gress, Thomas M.] Univ Hosp Ulm, Ulm, Germany. [Buchholz, Malte; Gress, Thomas M.] Univ Hosp Marburg, Dept Gastroenterol & Endocrinol, Marburg, Germany. [Liu, Hongfang] George Washington Univ, Washington, DC USA. [Kane, David W.] SRA Int, Fairfax, VA 22033 USA. [Liu, Hongfang; Zeeberg, Barry R.; Weinstein, John N.] NCI, NIH, Mol Pharmacol Lab, Genom & Bioinformat Grp, Bethesda, MD 20892 USA. RP Kestler, HA (reprint author), Univ Ulm, D-89069 Ulm, Germany. EM hans.kestler@uni-ulm.de; andre.mueller@uniklinik-ulm.de; johann.kraus@uni-ulm.de; malte.buchholz@staff.uni-marburg.de; thomas.gress@med.uni-marburg.de; hl224@georgetown.edu; David_Kane@sra.com; zeebergb@mail.nih.gov; weinstein@dtpax2.ncifcrf.gov RI Kestler, Hans/D-5799-2012 OI Kestler, Hans/0000-0002-4759-5254 FU Intramural NIH HHS; NLM NIH HHS [R01 LM009959] NR 23 TC 37 Z9 37 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 JAN 29 PY 2008 VL 9 AR 67 DI 10.1186/1471-2105-9-67 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 277GD UT WOS:000254199800001 PM 18230172 ER PT J AU Goldstein, DS AF Goldstein, David S. TI Genotype and vascular phenotype linked by catecholamine systems SO CIRCULATION LA English DT Editorial Material DE editorials; catecholamines; nervous system, sympathetic; norepinephrine; vasoconstriction; veins; tyramine ID BLOOD-PRESSURE; PLASMA NOREPINEPHRINE; NORADRENALINE RELEASE; HYPERTENSIVE SUBJECTS; AUTONOMIC ACTIVITY; HUMANS; TYRAMINE; DIHYDROXYPHENYLGLYCOL; RESPONSIVENESS; POLYMORPHISM C1 NINDS, Clin Neurocardiol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, Natl Inst Hlth, 10 Ctr Dr,MSC-1620,Bldg 10,Room 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS [, Z01 NS003033-02, Z01 NS003034-01, Z01 NS003033-01, Z99 NS999999] NR 35 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 29 PY 2008 VL 117 IS 4 BP 458 EP 461 DI 10.1161/CIRCULATIONAHA.107.745737 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 256FA UT WOS:000252711900002 PM 18227395 ER PT J AU Han, GC Wang, RX Chen, GJ Wang, RN Xu, RN Feng, JN Yu, M Wu, XB Qian, JH Shen, BF Li, Y AF Han, Gencheng Wang, Renxi Chen, Guojiang Wang, Ranan Xu, Ruonan Feng, Jiannan Yu, Ming Wu, Xiaobing Qian, Jiahua Shen, Beifen Li, Yan TI Gene delivery GAD(500) autoantigen by AAV serotype 1 prevented diabetes in NOD mice: Transduction efficiency do not play important roles SO IMMUNOLOGY LETTERS LA English DT Article DE autoimmune diabetes; gene therapy; AAV-1; AAV-2 ID RECOMBINANT ADENOASSOCIATED VIRUS; SKELETAL-MUSCLE; HEMOPHILIA-B; VECTORS; THERAPY; EXPRESSION; ANTIGENS; MELLITUS; MURINE; TYPE-1 AB We previously found that adeno-associated viral vector serotype 2 (AAV-2) muscle gene delivery of GAD(500-585) autoantigen efficiently prevented autoimmune diabetes in NOD mice. Recent reports suggest that AAV vectors based on serotype 1 (AAV-1) transduce murine skeletal muscle much more efficiently than AAV-2, with reported increases in expression ranging from 2 to 1000-fold. To determine whether this increased efficacy of AAV-1 could result in increased therapeutic effects in mice, we constructed rAAV(1)/GAD(500-585) vectors and compared their effects in preventing autoimmune diabetes in NOD mice with those of rAAV(2)/GAD(500-585) after muscle injection. rAAV(1)/GAD(500-585) gene therapy prevented diabetes in NOD mice. However, although much higher level of GAD500-585 expression was found in mice using AAV-1 as gene delivery vector than those using AAV-2, no increased efficiency of AAV-1 vectors were found in their capability to prevent autoimmune diabetes, as higher titers of rAAV1/GAD(500-585) virus (3 x 10(11) v.g./mouse) were needed to obtain therapeutic effects in NOD mice, a titer not different from that of AAV2. Protection resulted from rAAV(1)/GAD(500-585) gene therapy were marked by enhanced Th2 immune response and up-regulated CD4(+)Foxp(3+)T regulatory cells, which might actively suppress effector T cells in NOD mice. As here we found that the therapeutic effects of AAV1 were not positively correlated to it's transduction efficiency, our data suggested that the safety and other factors besides efficiency should be considered when use different AAV serotype to treat autoimmune disease. (C) 2007 Elsevier B.V. All rights reserved. C1 [Han, Gencheng; Wang, Renxi; Chen, Guojiang; Wang, Ranan; Xu, Ruonan; Feng, Jiannan; Yu, Ming; Shen, Beifen; Li, Yan] Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. [Wu, Xiaobing] Natl Key Lab Mol Virol & Genet Engn, Beijing, Peoples R China. [Qian, Jiahua] Natl Canc Inst, Vaccine Branch, Bethesda, MD 20889 USA. RP Li, Y (reprint author), Inst Basic Med Sci, Dept Mol Immunol, Taiping Rd 27, Beijing 100850, Peoples R China. EM liyan62033@yahoo.com.cn NR 24 TC 10 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JAN 29 PY 2008 VL 115 IS 2 BP 110 EP 116 DI 10.1016/j.imlet.2007.10.004 PG 7 WC Immunology SC Immunology GA 260TF UT WOS:000253032600006 PM 18045698 ER PT J AU Illes, J Kirschen, MP Edwards, E Bandettini, P Cho, MK Ford, PJ Glover, GH Kulynych, J Macklin, R Michael, DB Wolf, SM Grabowski, T Seto, B AF Illes, J. Kirschen, M. P. Edwards, E. Bandettini, P. Cho, M. K. Ford, P. J. Glover, G. H. Kulynych, J. Macklin, R. Michael, D. B. Wolf, S. M. Grabowski, T. Seto, B. TI Practical approaches to incidental findings in brain imaging research SO NEUROLOGY LA English DT Review ID CARE RESPONSIBILITIES; NEUROIMAGING RESEARCH; MEDICAL RESEARCHERS; CLINICAL CARE; MR-IMAGES; ETHICS AB A decade of empirical work in brain imaging, genomics, and other areas of research has yielded new knowledge about the frequency of incidental findings, investigator responsibility, and risks and benefits of disclosure. Straightforward guidance for handling such findings of possible clinical significance, however, has been elusive. In early work focusing on imaging studies of the brain, we suggested that investigators and institutional review boards must anticipate and articulate plans for handling incidental findings. Here we provide a detailed analysis of different approaches to the problem and evaluate their merits in the context of the goals and setting of the research and the involvement of neurologists, radiologists, and other physicians. Protecting subject welfare and privacy, as well as ensuring scientific integrity, are the highest priorities in making choices about how to handle incidental findings. Forethought and clarity will enable these goals without overburdening research conducted within or outside the medical setting. C1 [Illes, J.; Kirschen, M. P.; Cho, M. K.] Stanford Univ, Stanford Ctr Biomed Eth, Stanford, CA 94305 USA. [Illes, J.; Cho, M. K.] Stanford Univ, Dept Pediat Med Genet, Stanford, CA 94305 USA. [Kirschen, M. P.; Glover, G. H.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Kirschen, M. P.] Stanford Univ, Program Neurosci, Stanford, CA 94305 USA. [Edwards, E.] NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Bandettini, P.] NIH, NIMH, Bethesda, MD 20892 USA. [Seto, B.] NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. [Ford, P. J.] Cleveland Clin Fdn, Dept Bioeth, Cleveland, OH 44195 USA. [Kulynych, J.] Johns Hopkins Hosp & Hlth Syst, Legal Dept, Baltimore, MD USA. [Macklin, R.] Albert Einstein Coll Med, Dept Bioeth, Bronx, NY 10467 USA. [Wolf, S. M.] Univ Minnesota, Sch Med, Sch Law, Minneapolis, MN 55455 USA. [Wolf, S. M.] Univ Minnesota, Ctr Bioeth, Minneapolis, MN 55455 USA. [Grabowski, T.] Univ Iowa Hosp, Iowa City, IA USA. RP Illes, J (reprint author), Univ British Columbia, Natl Core Neuroeth, 2211 Wesbrook Mall,Koerner S124, Vancouver, BC V6T 2BS, Canada. EM jilles@interchange.ubc.ca RI Kam, Grace/F-5364-2012; Bandettini, Peter/F-5871-2012 FU NHGRI NIH HHS [1R01 HG003178, P50 HG003389, P50 HG003389-03, P50 HG003389-03S1, P50 HG003389-04, R01 HG003178]; NIMH NIH HHS [R01 MH084282, R01 MH084282-04A1]; NINDS NIH HHS [R01 NS045831, R01 NS045831-01A1, R01 NS045831-02, R01 NS045831-02S1, R01 NS045831-03] NR 24 TC 54 Z9 54 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 29 PY 2008 VL 70 IS 5 BP 384 EP 390 DI 10.1212/01.wnl.0000280469.17461.94 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 256HQ UT WOS:000252719500010 PM 18227420 ER PT J AU Gottfredsson, M Halldorsson, BV Jonsson, S Kristjansson, M Kristjansson, K Kristinsson, KG Love, A Blondal, T Viboud, C Thorvaldsson, S Helgason, A Gulcher, JR Stefansson, K Jonsdottir, I AF Gottfredsson, Magnus Halldorsson, Bjarni V. Jonsson, Stefan Kristjansson, Mar Kristjansson, Kristleifur Kristinsson, Karl G. Love, Arthur Blondal, Thorsteinn Viboud, Cecile Thorvaldsson, Sverrir Helgason, Agnar Gulcher, Jeffrey R. Stefansson, Kari Jonsdottir, Ingileif TI Lessons from the past: Familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heritability; host factors; medical history; mortality; transmission ID H5N1 VIRUS-INFECTION; MORTALITY; RESPONSES; IMMUNE AB The pandemic influenza of 1918 (Spanish flu) killed 21-50 million people globally, including in Iceland, where the characteristics and spread of the epidemic were well documented. It has been postulated that genetic host factors may have contributed to this high mortality. We identified 455 individuals who died of the Spanish flu in Iceland during a 6-week period during the winter of 1918, representing >92% of all fatal domestic cases mentioned by historical accounts. The highest case fatality proportion was 2.8%, and peak excess mortality was 162/100,000/week. Fatality proportions were highest among infants, young adults, and the elderly. A genealogical database was used to study relatedness and relative risk (RR) of the fatal influenza victims and relatives of their unaffected mates. The significance of these RR computations was assessed by drawing samples randomly from the genealogical database matched for age, sex, and geographical distribution. Familial aggregation of fatalities was seen, with RRs for death ranging from 3.75 for first-degree relatives(P < 0.0001) to 1.82 (P= 0.005), 1.12 (P = 0.252), and 1.47 (P = 0.0001) for second- to fourth-degree relatives of fatal influenza victims, respectively. The RRs within the families of unaffected mates of fatal influenza victims were 2.95 (P < 0.0001), 1.27 (P = 0.267),1.35 (P = 0.04), and 1.42 (P = 0.001), for first- to fourth-degree relatives, respectively. In conclusion, the risk of death from the Spanish flu was similar within families of patients who succumbed to the illness and within families of their mates who survived. Our data do not provide conclusive evidence for the role of genetic factors in susceptibility to the Spanish flu. C1 [Gottfredsson, Magnus; Kristjansson, Kristleifur; Kristinsson, Karl G.; Love, Arthur; Blondal, Thorsteinn; Jonsdottir, Ingileif] Landspitali Univ Hosp, IS-108 Reykjavik, Iceland. [Gottfredsson, Magnus; Kristinsson, Karl G.; Love, Arthur; Helgason, Agnar; Stefansson, Kari; Jonsdottir, Ingileif] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Halldorsson, Bjarni V.; Jonsson, Stefan; Kristjansson, Kristleifur; Thorvaldsson, Sverrir; Helgason, Agnar; Gulcher, Jeffrey R.; Stefansson, Kari; Jonsdottir, Ingileif] DeCODE Genet, IS-101 Reykjavik, Iceland. [Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Gottfredsson, M (reprint author), Landspitali Univ Hosp, IS-108 Reykjavik, Iceland. EM magnusgo@landspitali.is RI Helgason, Agnar/K-1522-2015; OI Gottfredsson, Magnus/0000-0003-2465-0422; Halldorsson, Bjarni/0000-0003-0756-0767 FU PHS HHS [HHSN266200400064C] NR 29 TC 35 Z9 38 U1 1 U2 7 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 JAN 29 PY 2008 VL 105 IS 4 BP 1303 EP 1308 DI 10.1073/pnas.0707659105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 258NF UT WOS:000252873900040 PM 18216264 ER PT J AU Kennedy, AD Otto, M Braughton, KR Whitney, AR Chen, L Mathema, B Mediavilla, JR Byrne, KA Parkins, LD Tenover, FC Kreiswirth, BN Musser, JM DeLeo, FR AF Kennedy, Adam D. Otto, Michael Braughton, Kevin R. Whitney, Adeline R. Chen, Liang Mathema, Barun Mediavilla, Jose R. Byrne, Kelly A. Parkins, Larye D. Tenover, Fred C. Kreiswirth, Barry N. Musser, James M. DeLeo, Frank R. TI Epidemic community-associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genomics; phylogeny; virulence; single-nucleotide polymorphism ID SOFT-TISSUE INFECTIONS; GROUP-A STREPTOCOCCUS; UNITED-STATES; VIRULENCE; GENOME; EVOLUTION; STRAINS; MRSA; EMERGENCE; TIME AB Emerging and re-emerging infectious diseases, especially those caused by drug-resistant bacteria, are a major problem worldwide. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) appeared rapidly and unexpectedly in the United States, resulting in an epidemic caused primarily by isolates classified as USA300. The evolutionary and molecular underpinnings of this epidemic are poorly understood. Specifically, it is unclear whether there has been clonal emergence of USA300 isolates or evolutionary convergence toward a hypervirulent phenotype resulting in the independent appearance of similar organisms. To definitively resolve this issue and understand the phylogeny of USA300 isolates, we used comparative whole-genome sequencing to analyze 10 USA300 patient isolates from eight states in diverse geographic regions of the United States and multiple types of human infection. Eight of 10 isolates analyzed had very few single nucleotide polymorphisms (SNPs) and thus were closely related, indicating recent diversification rather than convergence. Unexpectedly, 2 of the clonal isolates had significantly reduced mortality in a mouse sepsis model compared with the reference isolate (P = 0.0002), providing strong support to the idea that minimal genetic change in the bacterial genome can have profound effects on virulence. Taken together, our results demonstrate that there has been recent clonal expansion and diversification of a subset of isolates classified as USA300. The findings add an evolutionary dimension to the epidemiology and emergence of USA300 and suggest a similar mechanism for the pandemic occurrence and spread of penicillin-resistant S. aureus (known as phage-type 80/81 S. aureus) in the 1950s. C1 [Kennedy, Adam D.; Otto, Michael; Braughton, Kevin R.; Whitney, Adeline R.; Parkins, Larye D.; DeLeo, Frank R.] NIAID, NIH, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. [Mathema, Barun; Mediavilla, Jose R.; Kreiswirth, Barry N.] Publ Hlth Res Inst, Int Ctr Publ Hlth, Newark, NJ 07103 USA. [Tenover, Fred C.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Musser, James M.] Methodist Hosp, Res Inst, Ctr ol & Translat Human Infect Dis Res, Dept Pathol, Houston, TX 77030 USA. RP DeLeo, FR (reprint author), NIAID, NIH, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov RI Chen, Liang/D-3583-2009; OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS NR 29 TC 209 Z9 217 U1 4 U2 20 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 JAN 29 PY 2008 VL 105 IS 4 BP 1327 EP 1332 DI 10.1073/pnas.0710217105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 258NF UT WOS:000252873900044 PM 18216255 ER PT J AU Guralnih, JM AF Guralnih, Jack M. TI Successful aging - Is it in our future? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID BODY-COMPOSITION; CYSTATIN-C; BIOMARKERS; ASSOCIATION; DISEASE; HEALTH C1 NIA, Lab Epidemiol Demograph & Biometry, Bethesda, MD 20892 USA. RP Guralnih, JM (reprint author), NIA, Lab Epidemiol Demograph & Biometry, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. EM Jack.Guralnik@nih.gov FU Intramural NIH HHS NR 11 TC 4 Z9 5 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 28 PY 2008 VL 168 IS 2 BP 131 EP 132 DI 10.1001/archinternmed.2007.11 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 254NR UT WOS:000252593800002 PM 18227356 ER PT J AU Gochuico, BR Avila, NA Chow, CK Novero, LJ Wu, HP Ren, P MacDonald, SD Travis, WD Stylianou, MP Rosas, IO AF Gochuico, Bernadette R. Avila, Nilo A. Chow, Catherine K. Novero, Levi J. Wu, Hai-Ping Ren, Ping MacDonald, Sandra D. Travis, William D. Stylianou, Mario P. Rosas, Ivan O. TI Progressive preclinical interstitial lung disease in rheumatoid arthritis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; IDIOPATHIC PULMONARY-FIBROSIS; GROWTH-FACTOR RECEPTORS; ALVEOLAR MACROPHAGES; FUNCTION TESTS; PIRFENIDONE; RADIOGRAPHY; PNEUMONIA; GENE; CT AB Background: Early detection and treatment for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objective of this study was to identify asymptomatic lung disease and potential therapeutic targets in patients having RA and preclinical ILD (RA-ILD). Methods: Sixty-four adults with RA and 10 adults with RA and pulmonary fibrosis (RAPF) were referred to the National Institutes of Health, Bethesda, Maryland, and underwent high-resolution computed tomography (HRCT) and pulmonary physiology testing. Proteins capable of modulating fibrosis were quantified in alveolar fluid. Results: Twenty-one of 64 patients (33%) having RA without dyspnea or cough had preclinical ILD identified by HRCT. Compared with patients without lung disease, patients with RA-ILD had statistically significantly longer histories of cigarette smoking (P<.001), increased frequencies of crackles (P=.02), higher alveolararterial oxygen gradients (P=.004), and higher HRCT scores (P<.001). The HRCT abnormalities progressed in 12 of 21 patients (57%) with RA-ILD. The alveolar concentrations of platelet-derived growth factor-AB and platelet-derived growth factor-BB were statistically significantly higher in patients having RA-ILD (mean [SE], 497.3 [78.6] and 1473 [2641 pg/mL, respectively) than in patients having RA without ILD (mean [SE], 24.9 [42.4] and 792.7 [195.0] pg/mL, respectively) (P<.001 and P=.047, respectively). The concentrations of interferon gamma and transforming growth factor beta(2) were statistically significantly lower in patients having RAPF (mean [SE], 5.59 [1.11] pg/mL and 0.94 [0.46] ng/mL, respectively) than in patients having RA without ILD (mean [SE], 14.1 [1.9] pg/mL and 2.30 [0.39] ng/mL, respectively) (P=.001 and P=.006, respectively) or with preclinical ILD (mean [SD], 11.4 [2.6] pg/mL and 3.63 [0.66] ng/mL, respectively) (P=.04 and P=.007, respectively). Compared with patients having stable RA-ILD, patients having progressive RA-ILD had statistically significantly higher frequencies of treatment using methotrexate and higher alveolar concentrations of interferon gamma and transforming growth factor beta(1), (P=.046, P=.04, and P=.04, respectively). Conclusions: Asymptomatic preclinical ILD, which is detectable by HRCT, may be prevalent and progressive among patients having RA. Cigarette smoking seems to be associated with preclinical ILD in patients having RA, and treatment using methotrexate may be a risk factor for progression of preclinical ILD. Quantification of alveolar proteins indicates that potential pathogenic mechanisms seem to differ in patients having RA-ILD and symptomatic RAPF. C1 [Gochuico, Bernadette R.; Novero, Levi J.; Wu, Hai-Ping; Ren, Ping; MacDonald, Sandra D.] NHLBI, NIH, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. [Stylianou, Mario P.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Avila, Nilo A.; Chow, Catherine K.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Travis, William D.] Armed Forces Inst Pathol, Pulm & Mediastinal Dept, Washington, DC 20306 USA. RP Gochuico, BR (reprint author), NHLBI, NIH, Pulm Crit Care Med Branch, 10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. EM gochuicb@mail.nih.gov FU Intramural NIH HHS NR 23 TC 108 Z9 123 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 28 PY 2008 VL 168 IS 2 BP 159 EP 166 DI 10.1001/archinternmed.2007.59 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 254NR UT WOS:000252593800008 PM 18227362 ER PT J AU Wright, JT Harris-Haywood, S Pressel, S Barzilay, J Bairnbridge, C Bareis, CJ Basile, JN Black, HR Dart, R Gupta, AK Hamilton, BP Einhorn, PT Haywood, LJ Jafri, SZA Louis, GT Whelton, PK Scott, CL Sinnnons, DL Stanford, C Davis, BR AF Wright, Jackson T. Harris-Haywood, Sonja Pressel, Sara Barzilay, Joshua Bairnbridge, Charles Bareis, Charles J. Basile, Jan N. Black, Henry R. Dart, Richard Gupta, Alok K. Hamilton, Bruce P. Einhorn, Paula T. Haywood, L. Julian Jafri, Syed Z. A. Louis, Gail T. Whelton, Paul K. Scott, Cranford L. Sinnnons, Debra L. Stanford, Carol Davis, Barry R. TI Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the International-Society-for-Hypertension-in-Blacks CY JUN 23, 2006 CL Atlanta, GA ID CALCIUM-CHANNEL BLOCKER; PROSPECTIVELY-DESIGNED OVERVIEWS; ISOLATED SYSTOLIC HYPERTENSION; MAJOR CARDIOVASCULAR EVENTS; CONVERTING ENZYME-INHIBITOR; DIABETES-MELLITUS; RANDOMIZED-TRIALS; RISK; ASSOCIATION; GLUCOSE AB Background: Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcornes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an a-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Methods: A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 4.18 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women. Results: Significantly higher rates of heart failure were consistent across all treatment comparisons those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.1.8-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.081.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS a] so had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone. Conclusions: The ALLHAT findings fail to support the preference for calcium channel blockers, alpha-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants. C1 [Pressel, Sara; Bairnbridge, Charles; Davis, Barry R.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Coordnating Ctr Clin Trials, Houston, TX 77030 USA. [Wright, Jackson T.] Case Western Reserve Univ, Dept Med, Gen Clin Res Ctr, Cleveland, OH 44106 USA. [Harris-Haywood, Sonja] Case Western Reserve Univ, Dept Family Med, Cleveland, OH 44106 USA. [Barzilay, Joshua] Kaiser Permanente, Tucker, GA USA. [Bareis, Charles J.] MacNeal Ctr Clin Res, Dept Med, Berwyn, IL USA. [Basile, Jan N.] Med Univ S Carolina, Charleston, SC 29425 USA. [Basile, Jan N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Black, Henry R.] NYU, Dept Internal Med, Cardiol Sect, New York, NY USA. [Dart, Richard] Marshfield Clin Fdn Med Res & Educ, Dept Nephrol, Marshfield, WI USA. [Gupta, Alok K.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Hamilton, Bruce P.] Vet Affairs Med Ctr, Endocrine Hypertens Unit, Baltimore, MD USA. [Einhorn, Paula T.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Haywood, L. Julian] Univ So Calif, Div Cardiovasc Med, Los Angeles, CA USA. [Jafri, Syed Z. A.] Vet Affairs Med Ctr, Dept Cardiol, Fargo, ND USA. [Louis, Gail T.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA USA. [Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Sinnnons, Debra L.] Univ Arkansas Med Sci, Dept Endocrinol, Little Rock, AR 72205 USA. [Stanford, Carol] Univ Missouri, Sch Med, Kansas City, MO USA. RP Pressel, S (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Coordnating Ctr Clin Trials, 1200 Herman Pressel St,Ste E801, Houston, TX 77030 USA. EM Sara.L.Pressel@uth.tmc.edu FU NHLBI NIH HHS [N01 HC035130, N01HC35130, N01-HC-35130]; NIMHD NIH HHS [P60 MD002265] NR 35 TC 54 Z9 54 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 28 PY 2008 VL 168 IS 2 BP 207 EP 217 DI 10.1001/archinternmed.2007.66 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 254NR UT WOS:000252593800016 PM 18227370 ER PT J AU Shi, J Zhao, LY Copersino, ML Fang, YX Chen, Y Tian, A Deng, YP Shuai, YH Jin, J Lu, L AF Shi, Jie Zhao, Li-Yan Copersino, Marc L. Fang, Yu-Xia Chen, Yingmao Tian, Aahe Deng, Yanping Shuai, Yinhang Jin, Jun Lu, Lin TI PET imaging of dopamine transporter and drug craving during methadone maintenance treatment and after prolonged abstinence in heroin users SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE heroin abuse; craving; anxiety; prolonged withdrawal; dopamine transporter; positron emission tomography; methadone maintenance treatment ID OPIATE-DEPENDENT SUBJECTS; OPIOID ADDICTION; LONG-TERM; COCAINE; STRESS; SPECT; AMPHETAMINE; TOMOGRAPHY; WITHDRAWAL; MECHANISM AB It has been documented that methadone maintenance treatment is effective in reducing drug craving and relevant risk behaviors in heroin users. However, it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum. To establish whether chronic opiate use might impair brain dopamine neurons in humans, we assessed dopamine transporter (DAT) uptake function in the striatum (caudate and putamen), and analyzed the correlation between DAT in the striatum and heroin craving and subjective anxiety in former heroin users with prolonged abstinence and in patients receiving methadone maintenance treatment. Binding of [C-11]-2 beta-carbomethoxy-3 beta-aryltropane ([C-11] CFT) as a brain dopamine transporter ligand was measured with positron emission tomography (PET) in eleven former heroin users with prolonged abstinence, ten patients receiving methadone maintenance treatment and ten healthy control subjects. Heroin craving and subjective anxiety in prolonged abstinence and methadone maintenance treatment groups were assessed and the correlations between DAT of striatum and heroin craving or subjective anxiety were determined. In comparison with healthy control subjects, methadone maintenance treatment subjects had lower DAT uptake function in the bilateral caudate and putamen and prolonged abstinence subjects showed significantly lower DAT uptake function in the bilateral caudate. Moreover, in comparison to the prolonged abstinence subjects, the methadone maintenance treatment subjects showed significant decreases of DAT uptake in the bilateral putamen. DAT uptake function in bilateral striatum was not associated with heroin craving in prolonged abstinence or in methadone maintenance treatment subjects; however, DAT uptake function in the bilateral caudate was significantly correlated with subjective anxiety in methadone maintenance treatment subjects. Our findings suggest that chronic opioid use induces long-lasting striatum dopamine neuron impairment, and prolonged withdrawal from opioids can benefit the recovery of impaired dopamine neurons in the brain. (C) 2007 Elsevier B.V All rights reserved. C1 [Shi, Jie; Zhao, Li-Yan; Deng, Yanping; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100871, Peoples R China. [Copersino, Marc L.] Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Treatment Program, Belmont, MA 02478 USA. [Fang, Yu-Xia] NIH, Intramural Res Program, Natl Inst Drug Abuse, Baltimore, MD 21224 USA. [Deng, Yanping; Shuai, Yinhang] China PLA Gen Hosp, Beijing 100062, Peoples R China. [Shuai, Yinhang; Jin, Jun] Beijing Ankang Hosp, Beijing 102406, Peoples R China. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xueyuan Rd, Beijing 100871, Peoples R China. EM llu@bjmu.edu.cn NR 42 TC 48 Z9 57 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 28 PY 2008 VL 579 IS 1-3 BP 160 EP 166 DI 10.1016/j.ejphar.2007.09.042 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 259ZK UT WOS:000252979200021 PM 17977528 ER PT J AU Berezhkovskii, AM Weissa, GH AF Berezhkovskii, Alexander M. Weissa, George H. TI Propagators and related descriptors for non-Markovian asymmetric random walks with and without boundaries SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID FLUCTUATION THEOREM; DYNAMICAL ENSEMBLES; MOLECULAR MOTORS; STEADY-STATES; SYMMETRY AB There are many current applications of the continuous-time random walk (CTRW), particularly in describing kinetic and transport processes in different chemical and biophysical phenomena. We derive exact solutions for the Laplace transforms of the propagators for non-Markovian asymmetric one-dimensional CTRW's in an infinite space and in the presence of an absorbing boundary. The former is used to produce exact results for the Laplace transforms of the first two moments of the displacement of the random walker, the asymptotic behavior of the moments as t-->infinity, and the effective diffusion constant. We show that in the infinite space, the propagator satisfies a relation that can be interpreted as a generalized fluctuation theorem since it reduces to the conventional fluctuation theorem at large times. Based on the Laplace transform of the propagator in the presence of an absorbing boundary, we derive the Laplace transform of the survival probability of the random walker, which is then used to find the mean lifetime for terminated trajectories of the random walk. C1 [Berezhkovskii, Alexander M.; Weissa, George H.] Natl Inst Hlth, Ctr Informat Technol, Div Comp Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), Natl Inst Hlth, Ctr Informat Technol, Div Comp Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA. EM weissgh@mail.nih.gov FU Intramural NIH HHS NR 27 TC 9 Z9 9 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 28 PY 2008 VL 128 IS 4 AR 044914 DI 10.1063/1.2830254 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 257TK UT WOS:000252821200088 PM 18248007 ER PT J AU Ohrt, C O'Meara, WP Remich, S McEvoy, P Ogutu, B Mtalib, R Odera, JS AF Ohrt, Colin O'Meara, Wendy Prudhomme Remich, Shon McEvoy, Peter Ogutu, Bernhards Mtalib, Ramadan Odera, James Sande TI Pilot assessment of the sensitivity of the malaria thin film SO MALARIA JOURNAL LA English DT Article ID PARASITE DENSITY; BLOOD FILMS; MICROSCOPY; DIAGNOSIS; KENYA AB Background: Malaria microscopy remains the reference standard for malaria diagnosis in clinical trials (drug and vaccine), new diagnostic evaluation, as well as in clinical care in much of the world today. It is known that microscopy is an imperfect gold standard, and that very low false positive rates can dramatically lower protective efficacy estimates in malaria prevention trials. Although new methods are now available, including malaria rapid diagnostic tests and PCR, neither is as yet validated in the clinical trial setting and both have limitations. Surprisingly, the sensitivity of thin smears is not well established and thin smears are not commonly used in the developing world. Methods: Malaria thick and thin films were collected in the lowlands of Western Kenya. All had density determined by four readings with two methods, as well as species identified. Thirty-six with low density parasitaemia had the thin smear read by five independent microscopists, two were expert and three were qualified. Microscopists read the entire thin film. For the first 10 parasites seen, they reported the species, appearance, time, field number, and red blood cells in the field. Total parasites, total fields, and total time to examine the smear were also recorded. Results: Median parasitaemia was 201 parasites/mu l, mean 1,090 +/- 2,195, range 6-11,124 parasites/mu l for the 36 smears evaluated. The data revealed a density dependent increase in sensitivity, with 100% sensitivity achieved at > 200 parasites/mu l for experts and > 500 parasites/mu l for qualified readers. Thin film readings confirmed parasitaemia 74% of the time by experts, and 65% of the time for qualified microscopists. The 95(th) percentile for time to detect parasitaemia was 15 minutes for experts, 17 minutes for qualified microscopists. This decreased to 4-10 minutes for experts at densities of > 200 parasites/mu l. Additionally, substantial discordance for species identification was observed. Conclusion: The thin film is sensitive enough to be a useful tool to confirm malaria diagnosis in study subjects in some settings. Specificity of the thin film and its utility for confirming thick film or other diagnostic test results should be assessed further. C1 [Ohrt, Colin] Walter Reed Army Inst Res, Silver Spring, MD USA. [O'Meara, Wendy Prudhomme] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Remich, Shon; Ogutu, Bernhards; Odera, James Sande] USA, Med Unit Kenya, Clin Res Ctr, Kenya Med Res Inst, Kisumu, Kenya. [McEvoy, Peter] Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Ohrt, C (reprint author), Walter Reed Army Inst Res, Silver Spring, MD USA. EM colin.ohrt@us.army.mil; prudhomw@mail.nih.gov; shon.remich2@amedd.army.mil; mcevoy@afip.osd.mil; bogutu@wrp-ksm.org; rama_mtalib@yahoo.com; jsande@wrp-ksm.org NR 17 TC 15 Z9 15 U1 0 U2 2 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 JAN 28 PY 2008 VL 7 AR 22 DI 10.1186/1475-2875-7-22 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 272MG UT WOS:000253862900002 PM 18226243 ER PT J AU Ise, T Das, S Nagata, S Maeda, H Lee, Y Onda, M Anver, MR Bera, TK Pastan, I AF Ise, Tomoko Das, Sudipto Nagata, Satoshi Maeda, Hiroshi Lee, Yoomi Onda, Masanori Anver, Miriam R. Bera, Tapan K. Pastan, Ira TI Expression of POTE protein in human testis detected by novel monoclonal antibodies SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE POTE paralogs; primary spermatocytes; spermatogenesis ID ANKYRIN REPEAT; PROSTATE; PARALOGS; GENES AB The POTE gene family is composed of 13 highly homologous paralogs preferentially expressed in prostate, ovary, testis, and placenta. We produced 10 monoclonal antibodies (MAbs) against three representative POTE paralogs: POTE-21, POTE-2 gamma C, and POTE-22. One reacted with all three paralogs, six MAbs reacted with POTE-2 gamma C and POTE-22, and three MAbs were specific to POTE-21. Epitopes of all 10 MAbs were located in the cysteine-rich repeats (CRRs) motifs located at the N-terminus of each POTE paralog. Testing the reactivity of each MAb with 12 different CRRs revealed slight differences among the antigenic determinants, which accounts for differences in cross-reactivity. Using MAbs HP8 and PG5 we were able to detect a POTE-actin fusion protein in human testis by immunoprecipitation followed by Western blotting. By immunohistochemistry we demonstrated that the POTE protein is expressed in primary spermatocytes, implying a role in spermatogenesis. Published by Elsevier Inc. C1 [Ise, Tomoko; Das, Sudipto; Nagata, Satoshi; Maeda, Hiroshi; Lee, Yoomi; Onda, Masanori; Bera, Tapan K.; Pastan, Ira] NCI, NIH, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA. [Anver, Miriam R.] NCI, SAIC Frederick, Pathol Histotechnol Lab, Frederick, MD 21702 USA. RP Pastan, I (reprint author), NCI, NIH, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU Intramural NIH HHS [Z01 BC010298-09]; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 14 TC 9 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 25 PY 2008 VL 365 IS 4 BP 603 EP 608 DI 10.1016/j.bbrc.2007.10.195 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 244LJ UT WOS:000251867100001 PM 17996727 ER PT J AU Podar, M Wall, MA Makarova, KS Koonin, EV AF Podar, Mircea Wall, Mark A. Makarova, Kira S. Koonin, Eugene V. TI The prokaryotic V4R domain is the likely ancestor of a key component of the eukaryotic vesicle transport system SO BIOLOGY DIRECT LA English DT Article ID TRAPP; MODEL; COMPLEXES; EVOLUTION; SUGGESTS; BET3; FORM AB Intracellular vesicle traffic that enables delivery of proteins between the endoplasmic reticulum, Golgi and various endosomal subcompartments is one of the hallmarks of the eukaryotic cell. Its evolutionary history is not well understood but the process itself and the core vesicle traffic machinery are believed to be ancient. We show here that the 4-vinyl reductase (V4R) protein domain present in bacteria and archaea is homologous to the Bet3 subunit of the TRAPP1 vesicle-tethering complex that is conserved in all eukaryotes. This suggests, for the first time, a prokaryotic origin for one of the key eukaryotic trafficking proteins. C1 [Podar, Mircea] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. [Podar, Mircea] Oak Ridge Natl Lab, Bioenergy Sci Ctr, Oak Ridge, TN 37831 USA. [Wall, Mark A.] Verenium Corp, Bioinformat Dept, San Diego, CA 92121 USA. [Makarova, Kira S.; Koonin, Eugene V.] Natl Lib Med, Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Podar, M (reprint author), Oak Ridge Natl Lab, Biosci Div, 1 Bethel Valley Rd, Oak Ridge, TN 37831 USA. EM podarm@ornl.gov; mark.wall@verenium.com; makarova@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov OI Podar, Mircea/0000-0003-2776-0205 FU Intramural NIH HHS NR 18 TC 14 Z9 14 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD JAN 25 PY 2008 VL 3 AR 2 DI 10.1186/1745-6150-3-2 PG 4 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274QR UT WOS:000254016400001 PM 18221539 ER PT J AU Zdanov, A Wlodawer, A AF Zdanov, Alexander Wlodawer, Alexander TI A new look at cytokine signaling SO CELL LA English DT Editorial Material ID CRYSTAL-STRUCTURE; RECEPTOR; COMPLEX; INTERLEUKIN-4; HORMONE AB Signal transduction is initiated when a cytokine binds to the extracellular domains of its receptors, bringing them together and triggering a complicated sequence of events inside the cell. In this issue, LaPorte et al. ( 2008) present crystal structures of three signaling complexes of the cytokines interleukin-4 and interleukin-13 with their receptors, showing how events taking place outside the cell may affect the specificity of signal transduction. C1 [Zdanov, Alexander; Wlodawer, Alexander] NCI, CCR, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Zdanov, A (reprint author), NCI, CCR, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM zdanov@ncifcrf.gov; wlodawer@ncifcrf.gov FU Intramural NIH HHS NR 11 TC 3 Z9 4 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 25 PY 2008 VL 132 IS 2 BP 179 EP 181 DI 10.1016/j.cell.2008.01.006 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 266IM UT WOS:000253427700003 PM 18243092 ER PT J AU Barabas, O Ronning, DR Guynet, C Hickman, AB Ton-Hoang, B Chandler, M Dyda, F AF Barabas, Orsolya Ronning, Donald R. Guynet, Catherine Hickman, Alison Burgess Ton-Hoang, Bao Chandler, Michael Dyda, Fred TI Mechanism of IS200/IS605 family DNA transposases: Activation and transposon-directed target site selection SO CELL LA English DT Article ID GROUP-II INTRONS; CRYSTAL-STRUCTURE; DEINOCOCCUS-RADIODURANS; HELICOBACTER-PYLORI; INSERTION SEQUENCES; BINDING; RECOMBINATION; SPECIFICITY; ISHP608; DOMAIN AB The smallest known DNA transposases are those from the IS200/IS605 family. Here we show how the interplay of protein and DNA activates TnpA, the Helicobacter pylori IS608 transposase, for catalysis. First, transposon end binding causes a conformational change that aligns catalytically important protein residues within the active site. Subsequent precise cleavage at the left and right ends, the steps that liberate the transposon from its donor site, does not involve a site-specific DNA-binding domain. Rather, cleavage site recognition occurs by complementary base pairing with a TnpA-bound subterminal transposon DNA segment. Thus, the enzyme active site is constructed from elements of both protein and DNA, reminiscent of the interdependence of protein and RNA in the ribosome. Our structural results explain why the transposon ends are asymmetric and how the transposon selects a target site for integration, and they allow us to propose a molecular model for the entire transposition reaction. C1 [Barabas, Orsolya; Ronning, Donald R.; Hickman, Alison Burgess; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Guynet, Catherine; Ton-Hoang, Bao; Chandler, Michael] Natl Rech Sci, Microbiol Lab, F-31062 Toulouse, France. [Guynet, Catherine; Ton-Hoang, Bao; Chandler, Michael] Natl Rech Sci, Ctr Mol Genet, F-31062 Toulouse, France. RP Dyda, F (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM fred.dyda@nih.gov RI Guynet, Catherine/A-4815-2011; Barabas, Orsolya/F-3961-2012; OI Barabas, Orsolya/0000-0002-2873-5872; Chandler, Michael/0000-0002-0292-6662 FU Intramural NIH HHS [Z01 DK036154-01] NR 32 TC 59 Z9 60 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 25 PY 2008 VL 132 IS 2 BP 208 EP 220 DI 10.1016/j.cell.2007.12.029 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 266IM UT WOS:000253427700008 PM 18243097 ER PT J AU Boyle, AP Davis, S Shulha, HP Meltzer, P Margulies, EH Weng, Z Furey, TS Crawford, GE AF Boyle, Alan P. Davis, Sean Shulha, Hennady P. Meltzer, Paul Margulies, Elliott H. Weng, Zhiping Furey, Terrence S. Crawford, Gregory E. TI High-resolution mapping and characterization of open chromatin across the genome SO CELL LA English DT Article ID DNASE HYPERSENSITIVE SITES; REGULATORY ELEMENTS; INTERFERON-GAMMA; NUCLEOSOME CORE; BINDING SITES; PROTEIN CTCF; GENE; TRANSCRIPTION; ENHANCER; IDENTIFICATION AB Mapping DNase I hypersensitive (HS) sites is an accurate method of identifying the location of genetic regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions. We employed high-throughput sequencing and whole-genome tiled array strategies to identify DNase I HS sites within human primary CD4(+) T cells. Combining these two technologies, we have created a comprehensive and accurate genome-wide open chromatin map. Surprisingly, only 16%-21% of the identified 94,925 DNase I HS sites are found in promoters or first exons of known genes, but nearly half of the most open sites are in these regions. In conjunction with expression, motif, and chromatin immunoprecipitation data, we find evidence of cell-type-specific characteristics, including the ability to identify transcription start sites and locations of different chromatin marks utilized in these cells. In addition, and unexpectedly, our analyses have uncovered detailed features of nucleosome structure. C1 [Boyle, Alan P.; Furey, Terrence S.; Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. [Shulha, Hennady P.; Weng, Zhiping] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA. [Davis, Sean; Meltzer, Paul] NCI, Natl Inst Hlth, Ctr Canc Res, Bethesda, MD 20892 USA. [Margulies, Elliott H.] NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Crawford, GE (reprint author), Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. EM terry.furey@duke.edu; greg.crawford@duke.edu RI Boyle, Alan/I-1848-2014; OI Boyle, Alan/0000-0002-2081-1105; Davis, Sean/0000-0002-8991-6458 FU Intramural NIH HHS; NHGRI NIH HHS [HG003169, K22 HG003169, K22 HG003169-03] NR 42 TC 502 Z9 518 U1 6 U2 43 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 25 PY 2008 VL 132 IS 2 BP 311 EP 322 DI 10.1016/j.cell.2007.12.014 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 266IM UT WOS:000253427700016 PM 18243105 ER PT J AU Zhang, Y Zhou, Y Schweizer, U Savaskan, NE Hua, D Kipnis, J Hatfield, DL Gladyshev, VN AF Zhang, Yan Zhou, You Schweizer, Ulrich Savaskan, Nicolai E. Hua, Deame Kipnis, Jonathan Hatfield, Dolph L. Gladyshev, Vadim N. TI Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTATHIONE-PEROXIDASE; TYPE-2 DEIODINASE; TARGET TISSUES; GLIAL-CELLS; RICH DOMAIN; RAT-BRAIN; THIOREDOXIN; MECHANISM; PATTERNS; MICE AB Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss. To address the basis for the critical role of Se in brain function, we carried out comparative gene expression analyses for the complete selenoproteome and associated biosynthetic factors. Using the Allen Brain Atlas, we evaluated 159 regions of adult mouse brain and provided experimental analyses of selected selenoproteins. All 24 selenoprotein mRNAs were expressed in the mouse brain. Most strikingly, neurons in olfactory bulb, hippocampus, cerebral cortex, and cerebellar cortex were exceptionally rich in selenoprotein gene expression, in particular in GPx4, SelK, SelM, SelW, and Sep15. Over half of the selenoprotein genes were also expressed in the choroid plexus. A unique expression pattern was observed for one of the highly expressed selenoprotein genes, SelP, which we suggest to provide neurons with Se. Cluster analysis of the expression data linked certain selenoproteins and selenocysteine machinery genes and suggested functional linkages among selenoproteins, such as that between SelM and Sep15. Overall, this study suggests that the main functions of selenium in mammals are confined to certain neurons in the brain. C1 [Zhang, Yan; Hua, Deame; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Zhou, You] Univ Nebraska, Ctr Biotechnol, Lincoln, NE 68588 USA. [Schweizer, Ulrich] Charite Univ Med Berlin, Neurosci Res Ctr, D-10117 Berlin, Germany. [Savaskan, Nicolai E.] ETH & Univ Zurich, Brain Res Inst, Dept Neuromorphol, CH-8057 Zurich, Switzerland. [Kipnis, Jonathan] Univ Virginia, Dept Neurosci, Charlottesville, VA 22908 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), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu OI Savaskan, Nicolai/0000-0003-1348-094X; Schweizer, Ulrich/0000-0003-1380-4780 FU Intramural NIH HHS NR 63 TC 62 Z9 64 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 2008 VL 283 IS 4 BP 2427 EP 2438 DI 10.1074/jbc.M707951200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253EH UT WOS:000252501000069 PM 18032379 ER PT J AU Shimura, T Torres, MJ Martin, MM Rao, VA Pommier, Y Katsura, M Miyagawa, K Aladjerm, MI AF Shimura, Tsutomu Torres, Michael J. Martin, Melvenia M. Rao, V. Ashutosh Pommier, Yves Katsura, Mari Miyagawa, Kiyoshi Aladjerm, Mirit I. TI Bloom's syndrome helicase and Mus81 are required to induce transient double-strand DNA breaks in response to DNA replication stress SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE bLM; Mus81; ATR; double-strand breaks; replication fork blockage; aphidicolin ID S-PHASE ARREST; CHECKPOINT ACTIVATION; POLYMERASE-ALPHA; SYNDROME PROTEIN; RECQ HELICASES; HUMAN-CELLS; ATAXIA-TELANGIECTASIA; HOLLIDAY JUNCTIONS; BLM HELICASE; DAMAGE AB Perturbed DNA replication either activates a cell cycle checkpoint, which halts DNA replication, or decreases the rate of DNA synthesis without activating a checkpoint. Here we report that at low doses, replication inhibitors did not activate a cell cycle checkpoint, but they did activate a process that required functional Bloom's syndrome-associated (BLM) helicase, Mus81 nuclease and ataxia telangiectasia mutated and Rad3-related (ATR) kinase to induce transient double-stranded DNA breaks. The induction of transient DNA breaks was accompanied by dissociation of proliferating cell nuclear antigen (PCNA) and DNA polymerase a from replication forks. In cells with functional BLM, Mus81 and ATR, the transient breaks were promptly repaired and DNA continued to replicate at a slow pace in the presence of replication inhibitors. In cells that lacked BLM, Mus81, or AIR, transient breaks did not form, DNA replication did not resume, and exposure to low doses of replication inhibitors was toxic. These observations suggest that BLM helicase, ATR kinase, and Mus81 nuclease are required to convert perturbed replication forks to DNA breaks when cells encounter conditions that decelerate DNA replication, thereby leading to the rapid repair of those breaks and resumption of DNA replication without incurring DNA damage and without activating a cell cycle checkpoint. Published by Elsevier Ltd. C1 [Shimura, Tsutomu; Torres, Michael J.; Martin, Melvenia M.; Rao, V. Ashutosh; Pommier, Yves; Aladjerm, Mirit I.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shimura, Tsutomu] Tohoku Univ, Dept Pathol, Inst Dev Aging & Canc, Sendai, Miyagi 980, Japan. [Katsura, Mari; Miyagawa, Kiyoshi] Univ Tokyo, Grad Sch Med, Sect Radiat Biol, Bunkyo Ku, Tokyo 1130033, Japan. RP Aladjerm, MI (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM aladjemm@mail.nih.gov FU Intramural NIH HHS [Z01 BC010411-07, Z99 CA999999] NR 45 TC 45 Z9 46 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 25 PY 2008 VL 375 IS 4 BP 1152 EP 1164 DI 10.1016/j.jmb.2007.11.006 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261RP UT WOS:000253098000022 PM 18054789 ER PT J AU Berezhkovskii, AM Bezrukov, SM AF Berezhkovskii, Alexander M. Bezrukov, Sergey M. TI Counting translocations of strongly repelling particles through single channels: Fluctuation theorem for membrane transport SO PHYSICAL REVIEW LETTERS LA English DT Article ID DYNAMICAL ENSEMBLES; STOCHASTIC DYNAMICS; STATES AB Transport of strongly repelling particles through a single membrane channel is analyzed assuming that the channel cannot be occupied by more than one particle. An exact solution is found for the Laplace transform of the probability P(n)(t) that n particles have been transported in time t. This transform is used to find the flux through the channel and to show that P(n)(t) and P(-n)(t) are related by the fluctuation theorem. The solution is obtained using an observation that P(n)(t) is the propagator for a non-Markovian random walk, which can be found by solving a set of integral equations. C1 [Berezhkovskii, Alexander M.] NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comput Lab, Bethesda, MD 20892 USA. [Bezrukov, Sergey M.] NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comput Lab, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 32 TC 19 Z9 19 U1 0 U2 1 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD JAN 25 PY 2008 VL 100 IS 3 AR 038104 DI 10.1103/PhysRevLett.100.038104 PG 4 WC Physics, Multidisciplinary SC Physics GA 255ZU UT WOS:000252698100097 PM 18233042 ER PT J AU Karpova, TS Kim, MJ Spriet, C Nalley, K Stasevich, TJ Kherrouche, Z Heliot, L McNally, JG AF Karpova, Tatiana S. Kim, Min J. Spriet, Corentin Nalley, Kip Stasevich, Timothy J. Kherrouche, Zoulika Heliot, Laurent McNally, James G. TI Concurrent fast and slow cycling of a transcriptional activator at an endogenous promoter SO SCIENCE LA English DT Article ID ESTROGEN-RECEPTOR; LIVING CELLS; IN-VIVO; GENE-EXPRESSION; DYNAMICS; RECRUITMENT; EXCHANGE; COMPLEX; BINDING; YEAST AB For gene regulation, some transcriptional activators bind periodically to promoters with either a fast (similar to 1 minute) or a slow (similar to 15 to 90 minutes) cycle. It is uncertain whether the fast cycle occurs on natural promoters, and the function of either cycle in transcription remains unclear. We report that fast and slow cycling can occur simultaneously on an endogenous yeast promoter and that slow cycling in this system reflects an oscillation in the fraction of accessible promoters rather than the recruitment and release of stably bound transcriptional activators. This observation, combined with single- cell measurements of messenger RNA ( mRNA) production, argues that fast cycling initiates transcription and that slow cycling regulates the quantity of mRNA produced. These findings counter the prevailing view that slow cycling initiates transcription. C1 [Karpova, Tatiana S.; Kim, Min J.; Nalley, Kip; Stasevich, Timothy J.; McNally, James G.] NCI, Ctr Canc Res, Core Imaging Facil, Lab Receptor Biol & Gene Express,NIH, Bethesda, MD 20892 USA. [Spriet, Corentin; Heliot, Laurent] Lille Univ Sci & Technol, Interdisciplinary Res Inst, CNRS, USR 3078, F-59021 Lille, France. [Kherrouche, Zoulika] Inst Pasteur, UMR 8161, Inst Biol Lille, F-59021 Lille, France. RP McNally, JG (reprint author), NCI, Ctr Canc Res, Core Imaging Facil, Lab Receptor Biol & Gene Express,NIH, 41 Lib Dr, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov NR 22 TC 89 Z9 90 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 25 PY 2008 VL 319 IS 5862 BP 466 EP 469 DI 10.1126/science.1150559 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 254HB UT WOS:000252576600039 PM 18218898 ER PT J AU Peluso, M Srivatanakul, P Munnia, A Jedpiyawongse, A Meunier, A Sangrajrang, S Piro, S Ceppi, M Boffetta, P AF Peluso, Marco Srivatanakul, Petcharin Munnia, Armelle Jedpiyawongse, Adisorn Meunier, Aurelie Sangrajrang, Suleeporn Piro, Sara Ceppi, Marcello Boffetta, Paolo TI DNA adduct formation among workers in a Thai industrial estate and nearby residents SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE Map Tha Put; air pollution; industrialized area; bulky DNA adducts; P-32-postlabelling assay ID POLYCYCLIC AROMATIC-HYDROCARBONS; LUNG-CANCER RISK; AIR-POLLUTION; EXPOSURE; REFINERY; PLANT; 1-HYDROXYPYRENE; ASSOCIATION; LYMPHOCYTES; BIOMARKER AB The genotoxic effects of air pollutant exposures have been studied in people living and working in Map Ta Phut, Rayong province, Thailand, a site where is located the Map Ta Phut Industrial Estate (MIE) one of the largest steel, refinery and petrochemical complex in the South-Eastern Asia. This was done by the conduction of a transversal study aimed to compare the prevalence of bulky DNA adducts in groups of subjects experiencing various degree of air pollution. DNA adduct analysis was performed in the leukocytes of 201 volunteers by the P-32-postlabelling assay: 79 were workers in the MIE complex, including 24 refinery workers, 40 steel workers and 15 tinplate workers, 72 were people residing downwind in the MIE area and 50 were residents in a control district of the same Rayong province but without industrial exposures. The groups of workers were analyzed separately to evaluate if DNA adduct formation differs by the type of industry. The levels of bulky DNA adducts were 1.17 +/- 0.17 (SE) adduCtS/10(8) nucleotides in refineryworkers, 1.19 +/- 0.19 (SE) in steel workers, 0.87 +/- 0.17 (SE) in tinplate workers, 0.85 +/- 0.07 (SE) in MIE residents and 0.53 +/- 0.05 (SE) in district controls. No effects of smoking habits on DNA adducts was found. The multivariate regression analysis shows that the levels of DNA adducts were significantly increased among the individuals living near the MIE industrial complex in respect to those resident in a control district (p<0.05). in the groups of occupationally exposed workers, the highest levels of DNA adducts were found among the workers experiencing an occupational exposure to polycyclic aromatic hydrocarbons, e.g. the steel factory and refinery workers. When we have evaluated if the levels of DNA adducts of the PAH exposed workers were different from those of the MIE residents, a statistical significantly difference was found (p<0.05). Our present study indicates that people living near point sources of industrial air pollution can experiment an excess of DNA adduct formation. The emissions from the MIE complex are the main source of air pollution in this area and can be the cause of such increment in the levels of DNA damage. (c) 2007 Elsevier B.V. All rights reserved. C1 [Peluso, Marco; Munnia, Armelle; Piro, Sara] Ist Sci Reg Toscana, CSPO, Canc Risk Factor Branch, Analyt & Biomol Cytol Unit, I-50139 Florence, Italy. [Srivatanakul, Petcharin; Jedpiyawongse, Adisorn; Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok 10400, Thailand. [Meunier, Aurelie; Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Ceppi, Marcello] Natl Canc Inst, I-16132 Genoa, Italy. RP Peluso, M (reprint author), Ist Sci Reg Toscana, CSPO, Canc Risk Factor Branch, Analyt & Biomol Cytol Unit, Via Cosimo Vecchio 2, I-50139 Florence, Italy. EM m.peluso@cspo.it OI PIRO, SARA/0000-0003-4198-7035 FU Associazione Italiana per la Ricerca sul Cancro NR 33 TC 32 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD JAN 25 PY 2008 VL 389 IS 2-3 BP 283 EP 288 DI 10.1016/j.scitotenv.2007.09.012 PG 6 WC Environmental Sciences SC Environmental Sciences & Ecology GA 243WB UT WOS:000251826900009 PM 17935758 ER PT J AU Zhao, XZ Semenova, EA Vu, BC Maddali, K Marchand, C Hughes, SH Pommier, Y Burke, TR AF Zhao, Xue Zhi Semenova, Elena A. Vu, B. Christie Maddali, Kasthuraiah Marchand, Christophe Hughes, Stephen H. Pommier, Yves Burke, Terrence R., Jr. TI 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one-based HIV-1 integrase inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 INTEGRASE; IN-VITRO; DESIGN; REPLICATION; LENNOXAMINE; CELLS AB The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3'-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors. C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Canc Res Ctr, Med Chem Lab, Frederick, MD 21701 USA. [Vu, B. Christie; Hughes, Stephen H.] NCI, Canc Res Ctr, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Zhao, Xue Zhi; Semenova, Elena A.; Vu, B. Christie; Maddali, Kasthuraiah; Marchand, Christophe; Hughes, Stephen H.; Pommier, Yves; Burke, Terrence R., Jr.] Natl Inst Hlth, Frederick, MD 21702 USA. [Semenova, Elena A.; Maddali, Kasthuraiah; Marchand, Christophe; Pommier, Yves] NCI, NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Canc Res Ctr, Med Chem Lab, Frederick, MD 21701 USA. EM tburke@helix.nih.gov RI Zhao, Xue Zhi/N-9594-2014; Burke, Terrence/N-2601-2014; Marchand, Christophe/D-8559-2016 OI Zhao, Xue Zhi/0000-0003-1006-6364; FU Intramural NIH HHS NR 34 TC 33 Z9 35 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 24 PY 2008 VL 51 IS 2 BP 251 EP 259 DI 10.1021/jm070715d PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 253LL UT WOS:000252519600007 PM 18095643 ER PT J AU Cam, HP Noma, K Ebina, H Levin, HL Grewal, SIS AF Cam, Hugh P. Noma, Ken-ichi Ebina, Hirotaka Levin, Henry L. Grewal, Shiv I. S. TI Host genome surveillance for retrotransposons by transposon-derived proteins SO NATURE LA English DT Article ID HUMAN CENTROMERE PROTEIN; FISSION YEAST; CENP-B; SCHIZOSACCHAROMYCES-POMBE; CHROMOSOME SEGREGATION; MOLECULAR-CLONING; DNA METHYLATION; HETEROCHROMATIN; SEQUENCE; ELEMENTS AB Transposable elements and their remnants constitute a substantial fraction of eukaryotic genomes. Host genomes have evolved defence mechanisms, including chromatin modifications and RNA interference, to regulate transposable elements. Here we describe a genome surveillance mechanism for retrotransposons by transposase- derived centromeric protein CENP- B homologues of the fission yeast Schizosaccharomyces pombe. CENP- B homologues of S. pombe localize at and recruit histone deacetylases to silence Tf2 retrotransposons. CENP- Bs also repress solo long terminal repeats ( LTRs) and LTR- associated genes. Tf2 elements are clustered into 'Tf' bodies, the organization of which depends on CENP- Bs that display discrete nuclear structures. Furthermore, CENP- Bs prevent an 'extinct' Tf1 retrotransposon from re- entering the host genome by blocking its recombination with extant Tf2, and silence and immobilize a Tf1 integrant that becomes sequestered into Tf bodies. Our results reveal a probable ancient retrotransposon surveillance pathway important for host genome integrity, and highlight potential conflicts between DNA transposons and retrotransposons, major transposable elements believed to have greatly moulded the evolution of genomes. C1 [Cam, Hugh P.; Noma, Ken-ichi; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Ebina, Hirotaka; Levin, Henry L.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov FU Intramural NIH HHS NR 50 TC 94 Z9 96 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 24 PY 2008 VL 451 IS 7177 BP 431 EP U2 DI 10.1038/nature06499 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 253YS UT WOS:000252554100037 PM 18094683 ER PT J AU Reti, IM Miskimon, M Dickson, M Petralia, RS Takamiya, K Bland, R Saini, J During, MJ Huganir, RL Baraban, JM AF Reti, I. M. Miskimon, M. Dickson, M. Petralia, R. S. Takamiya, K. Bland, R. Saini, J. During, M. J. Huganir, R. L. Baraban, J. M. TI Activity-dependent secretion of neuronal activity regulated pentraxin from vasopressin neurons into the systemic circulation SO NEUROSCIENCE LA English DT Article DE pituitary; hypovolemia; dehydration; hypothalamus; plasma; hypophysectomy ID ARGININE VASOPRESSIN; SYNAPTIC PLASTICITY; HUMAN-PLASMA; NARP; EXPRESSION; RECEPTORS; OXYTOCIN; RELEASE; PROTEIN; RAT AB Neuronal activity regulated pentraxin (Narp) is a secreted, synaptic protein that has been implicated in modulating synaptic transmission. However, it is unclear how Narp secretion is regulated. Since we noted prominent Narp immunostaining in vasopressin neurons of the hypothalamus and in the posterior pituitary, we assessed whether it, like vasopressin, is released into the systemic circulation in an activity-dependent fashion. Consistent with this hypothesis, electron microscopic studies of the posterior pituitary demonstrated that Narp is located in secretory vesicles containing vasopressin. Using affinity chromatography, we detected Narp in plasma and found that these levels are markedly decreased by hypophysectomy. In addition, we confirmed that injection of a viral Narp construct into the hypothalamus restores plasma Narp levels in Narp knockout mice. In checking for activity-dependent secretion of Narp from the posterior pituitary, we found that several stimuli known to trigger vasopressin release, i.e. hypovolemia, dehydration and endotoxin, elevate plasma Narp levels. Taken together, these findings provide compelling evidence that Narp is secreted from vasopressin neurons in an activity-dependent fashion. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Reti, I. M.; Baraban, J. M.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Reti, I. M.; Miskimon, M.; Dickson, M.; Takamiya, K.; Huganir, R. L.; Baraban, J. M.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA. [Petralia, R. S.] NIH, NIDCD, Bethesda, MD USA. [Bland, R.] Neurologix Inc, Ft Lee, NJ USA. [Saini, J.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [During, M. J.] Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA. RP Reti, IM (reprint author), Johns Hopkins Univ Hosp, Dept Psychiat, Meyer 3-181,600 N Wolfe St, Baltimore, MD 21205 USA. EM imreti@jhmi.edu OI Baraban, Jay/0000-0002-8165-2638 FU Intramural NIH HHS; NIDA NIH HHS [5P50DA000266-35, P50 DA000266, R01 DA016303-01A2, P50 DA000266-35, R01 DA016303, R01DA016303]; NINDS NIH HHS [R01 NS044576-06, R01 NS044576] NR 31 TC 11 Z9 12 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN 24 PY 2008 VL 151 IS 2 BP 352 EP 360 DI 10.1016/j.neuroscience.2007.10.040 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 255GB UT WOS:000252644600005 PM 18082971 ER PT J AU Han, SU Kwak, TH Her, KH Cho, YH Choi, C Lee, HJ Hong, S Park, YS Kim, YS Kim, TA Kim, SJ AF Han, S-U Kwak, T-H Her, K. H. Cho, Y-H Choi, C. Lee, H-J Hong, S. Park, Y. S. Kim, Y-S Kim, T-A Kim, S-J TI CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling SO ONCOGENE LA English DT Article DE carcinoembryonic antigen; TGF-beta; Smad3; gastric cancer ID GROWTH-FACTOR-BETA; HUMAN GASTRIC-CANCER; BILIARY GLYCOPROTEIN CD66A; CELL-ADHESION MOLECULE-1; HUMAN-TUMOR-MARKER; CARCINOEMBRYONIC ANTIGEN; CARCINOMA-CELLS; CEA FAMILY; EXPRESSION; SMAD3 AB The carcinoembryonic antigen (CEAs) family consists of a large group of evolutionarily and structurally divergent glycoproteins. The transforming growth factor-beta (TGF-beta) signaling pathway has been implicated in the stimulation of CEA secretion in TGF-beta-sensitive colon cells, thereby possibly modulating cell adhesion and differentiation. However, the specific CEAs targeted by TGF-beta signaling or underlying mechanism of the expression of CEAs has not yet been clarified. In this study, we investigated the specific CEAs targeted by the TGF-beta signaling pathway. In nine human gastric cancer cell lines examined, TGF-beta-responsive cell lines showed positive expression of CEAs. Expression patterns of CEA proteins correlated well with the level of CEA (CEACAM5) and CEACAM6 transcripts in these cell lines, but CEACAM1 expression was not observed in all of these cells. To investigate the role of TGF-beta signaling in CEA expression, we selected two TGF-beta unresponsive gastric cancer cell lines; SNU638 cells that contain a mutation in the TGF-beta type II receptor and SNU484 cells that express low to undetectable level of the TGF-beta pathway intermediate protein, Smad3. Restoration of TGF-beta signaling in these cells induced expression of the CEAs and increased activity of both CEA (CEACAM5) and CEACAM6 promoters. CEA expression was observed in the epithelium of the stomach of wild-type mice, but was markedly decreased in Smad3 null mice. These findings suggest that CEA (CEACAM5) and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling. C1 [Han, S-U; Kwak, T-H; Her, K. H.; Cho, Y-H; Choi, C.; Lee, H-J; Hong, S.; Park, Y. S.; Kim, T-A; Kim, S-J] Natl Canc Inst, Lab Canc Biol & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lee, H-J] KRIBB, Div Mol Therapeut, Taejon, South Korea. [Kim, Y-S] Hanyang Univ, Coll Med, Dept Biochem, Seoul 133791, South Korea. [Kim, S-J] Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Lab Cell Regulat & Carcinogenesis, Inchon, South Korea. RP Kim, SJ (reprint author), Natl Canc Inst, Lab Canc Biol & Genet, Natl Inst Hlth, Bldg 37,Room 5046D,900 Rockville Pike, Bethesda, MD 20892 USA. EM kims@mail.nih.gov FU Intramural NIH HHS NR 33 TC 24 Z9 26 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 24 PY 2008 VL 27 IS 5 BP 675 EP 683 DI 10.1038/sj.onc.1210686 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 255RK UT WOS:000252674900011 PM 17653079 ER PT J AU Wyatt, LS Earl, PL Vogt, J Eller, LA Chandran, D Liu, JY Robinson, HL Moss, B AF Wyatt, Linda S. Earl, Patricia L. Vogt, Jennifer Eller, Leigh Anne Chandran, Dev Liu, Jinyan Robinson, Harriet L. Moss, Bernard TI Correlation of immunogenicities and in vitro expression levels of recombinant modified vaccinia virus Ankara HIV vaccines SO VACCINE LA English DT Article DE MVA vaccine; recombinant MVA expression; HIV Env ID ATTENUATED MVA STRAIN; T-CELL INDUCTION; RHESUS-MONKEYS; GAG-POL; ENVELOPE GLYCOPROTEIN; PROTECTIVE IMMUNITY; DNA/MVA VACCINE; INFLUENZA-VIRUS; HOST-RANGE; MACAQUES AB The purpose of the present study was to correlate the in vitro Level. of HIV Env expression by recombinant modified vaccinia virus Ankara (rMVA) with immunogenicity in mice. A 5-fold difference in Env synthesis was achieved at the translational level by the presence or absence of an out-of-frame initiation codon upstream of the env gene. This perturbation had no effect on the size or processing of Env. In contrast to the variation in Env synthesis, the rMVAs produced similar amounts of HIV Gag, which were expressed from identical cassettes. Mice immunized with the higher Env expressing. rMVAs had about 15-fold higher titers of Env antibodies and several fold higher frequencies of Env-specific CD8+ and CD4+ T cells than mice immunized with the low expresser. The greater immune response achieved by high expression was maintained over a 100-fold dose range. Importantly, enhanced Env immune responses did not come at the expense of tower Gag T cell responses. These data suggest that for high immunogenicity, rMVAs should be engineered to produce the most recombinant protein that can be achieved without compromising the growth and stability of the rMVA. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Wyatt, Linda S.; Earl, Patricia L.; Vogt, Jennifer; Chandran, Dev; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Eller, Leigh Anne] Henry M Jackson Fdn, Rockville, MD USA. [Liu, Jinyan; Robinson, Harriet L.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Robinson, Harriet L.] Emory Vaccine Ctr, Atlanta, GA 30322 USA. RP Wyatt, LS (reprint author), NIAID, Viral Dis Lab, NIH, 33 N Dr,MSC 3210, Bethesda, MD 20892 USA. EM lwyatt@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000416-24] NR 38 TC 22 Z9 22 U1 0 U2 1 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 JAN 24 PY 2008 VL 26 IS 4 BP 486 EP 493 DI 10.1016/j.vaccine.2007.11.036 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 260IY UT WOS:000253005200006 PM 18155813 ER PT J AU Bernstein, MB Chakraborty, M Wansley, EK Guo, Z Franzusoff, A Mostbock, S Sabzevari, H Schlom, J Flodge, JW AF Bernstein, Michael B. Chakraborty, Mala Wansley, Elizabeth K. Guo, Zhimin Franzusoff, Alex Mostboeck, Sven Sabzevari, Helen Schlom, Jeffrey Flodge, James W. TI Recombinant Saccharomyces cerevisiae (yeast-CEA) as a potent activator of murine dendritic cells SO VACCINE LA English DT Article DE Saccharomyces cerevisiae; yeast; CEA; dendritic cells ID COSTIMULATORY MOLECULES SYNERGIZE; COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN; CANCER VACCINES; TUMOR-ANTIGENS; RESPONSES; IMMUNOTHERAPY; INDUCTION; VECTOR; TRIAD AB Recombinant Saccharomyces cerevisiae (yeast) represents a unique and attractive vehicle to deliver antigens in vaccine immunotherapy protocols for cancer or infectious disease, in that it has been shown to be extremely safe and can be administered multiple times to hosts. In the studies reported here, we describe the effects of treatment with recombinant yeast on murine immature dendritic cells (DCs). Yeast expressing human carcinoembryonic antigen (CEA) as a model antigen was studied. Injection of mice subcutaneously with yeast-CEA resulted in rapid increases in MHC class II+ cells and total antigen-presenting cells in draining lymph nodes. Post-treatment with yeast-CEA, DCs rapidly elevated both MHC class I and class II, numerous costimulatory molecules and other DC maturation markers, and secreted a range of Type I inflammatory cytokines. Gene expression arrays also revealed the rapid up-regulation of numerous cytokine and chemokine mRNAs, as well as genes involved in signal transduction and antigen uptake. Functional studies demonstrated enhanced allospecific reactivity of DCs following treatment with yeast-CEA or control yeast. Additionally, treatment of DCs with yeast-CEA resulted in specific activation of CEA-specific CD8(+) T cells in an MHC-restricted manner in vitro. Lastly, vaccination of CEA-transgenic mice with yeast-CEA elicited antigen-specific CD4(+) and CD8(+) immune responses in vivo. Thus, these studies taken together form a scientific rationale for the use of recombinant yeast in vaccination protocots for cancer or infectious diseases. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Bernstein, Michael B.; Chakraborty, Mala; Wansley, Elizabeth K.; Mostboeck, Sven; Sabzevari, Helen; Schlom, Jeffrey; Flodge, James W.] NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. [Guo, Zhimin; Franzusoff, Alex] Globel Immune Inc, Louisville, CO 80027 USA. RP Schlom, J (reprint author), NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM jsl41lc@nih.gov OI Wansley, Elizabeth/0000-0002-0110-7550 FU Intramural NIH HHS NR 40 TC 43 Z9 46 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 JAN 24 PY 2008 VL 26 IS 4 BP 509 EP 521 DI 10.1016/j.vaccine.2007.11.033 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 260IY UT WOS:000253005200009 PM 18155327 ER PT J AU Ragert, P Kalisch, T Bliem, B Franzkowiak, S Dinse, HR AF Ragert, Patrick Kalisch, Tobias Bliem, Barbara Franzkowiak, Stephanie Dinse, Hubert R. TI Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects SO BMC NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; SOMATOSENSORY CORTEX; CORTICAL REORGANIZATION; SYNAPTIC TRANSMISSION; PERCEPTION; PERFORMANCE; IMPROVEMENT; DEPRESSION; EXCITABILITY; MODULATION AB Background: Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior. Results: Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm(2) on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm(2)) indicating special requirements for spatial summation. Conclusion: Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects. C1 [Ragert, Patrick; Kalisch, Tobias; Bliem, Barbara; Franzkowiak, Stephanie; Dinse, Hubert R.] Ruhr Univ Bochum, Expt Neurobiol Lab, Dept Theoret Biol, Inst Neuroinformat, D-44780 Bochum, Germany. [Ragert, Patrick] Ruhr Univ Bochum, BG Kliniken Bergmannsheil, Dept Neurol, D-44789 Bochum, Germany. [Ragert, Patrick] NINCDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. RP Ragert, P (reprint author), Ruhr Univ Bochum, Expt Neurobiol Lab, Dept Theoret Biol, Inst Neuroinformat, D-44780 Bochum, Germany. EM patrick.ragert@uni-duesseldorf.de; tobias.kalisch@neuroinformatik.rub.de; barbara.bliem@rub.de; stephanie.franzkowiak@rub.de; hubert.dinse@neuroinformatik.rub.de NR 29 TC 27 Z9 27 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD JAN 23 PY 2008 VL 9 AR 9 DI 10.1186/1471-2202-9-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 267VI UT WOS:000253536900001 PM 18215277 ER PT J AU Bartali, B Frongillo, EA Guralnik, JM Stipanuk, MH Allore, HG Cherubini, A Bandinelli, S Ferrucci, L Gill, TM AF Bartali, Benedetta Frongillo, Edward A. Guralnik, Jack M. Stipanuk, Martha H. Allore, Heather G. Cherubini, Antonio Bandinelli, Stefania Ferrucci, Luigi Gill, Thomas M. TI Serum micronutrient concentrations and decline in physical function among older persons SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MINI-MENTAL-STATE; OXIDATIVE STRESS; VITAMIN-E; DISABILITY; HEALTH; PERFORMANCE; INCHIANTI; DAMAGE; AGE; ANTIOXIDANTS AB Context Maintaining independence of older persons is a public health priority, and identifying the factors that contribute to decline in physical function is needed to prevent or postpone the disablement process. The potential deleterious effect of poor nutrition on decline in physical function in older persons is unclear. Objective To determine whether a low serum concentration of micronutrients is associated with subsequent decline in physical function among older men and women living in the community. Design, Setting, and Participants Longitudinal study of 698 community- living persons 65 years or older who were randomly selected from a population registry in Tuscany, Italy. Participants completed the baseline examination from November 1, 1998, through May 28, 2000, and the 3- year follow- up assessments from November 1, 2001, through March 30, 2003. Main Outcome Measure Decline in physical function was defined as a loss of at least 1 point in the Short Physical Performance Battery during the 3- year follow- up. Odds ratios ( ORs) were calculated for the lowest quartile of each nutrient using the other 3 quartiles combined as the reference group. Two additional and complementary analytical approaches were used to confirm the validity of the results. Results The mean decline in the Short Physical Performance Battery score was 1.1 point. In a logistic regression analysis that was adjusted for potential confounders, only a low concentration of vitamin E ( < 1.1 mu g/ mL [ < 24.9 mu mol/L]) was significantly associated with subsequent decline in physical function ( OR, 1.62; 95% confidence interval, 1.11- 2.36; P=. 01 for association of lowest alpha-tocopherol quartile with at least a 1- point decline in physical function). In a general linear model, the concentration of vitamin E at baseline, when analyzed as a continuous measure, was significantly associated with the Short Physical Performance Battery score at follow- up after adjustment for potential confounders and Short Physical Performance Battery score at baseline ( beta=.023; P=. 01). In a classification and regression tree analysis, age older than 81 years and vitamin E ( in participants aged 70- 80 years) were identified as the strongest determinants of decline in physical function ( physical decline in 84% and 60%, respectively; misclassification error rate, 0.33). Conclusions These results provide empirical evidence that a low serum concentration of vitamin E is associated with subsequent decline in physical function among community-living older adults. Clinical trials may be warranted to determine whether an optimal concentration of vitamin E reduces functional decline and the onset of disability in older persons. C1 [Bartali, Benedetta; Allore, Heather G.; Gill, Thomas M.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06504 USA. [Bartali, Benedetta; Frongillo, Edward A.; Stipanuk, Martha H.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. [Cherubini, Antonio] Univ Perugia, Sch Med, Monteluce Policlin, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy. RP Bartali, B (reprint author), Yale Univ, Sch Med, Dept Internal Med, 20 York St,TMP 17B, New Haven, CT 06504 USA. EM benedetta.bartali@yale.edu OI Cherubini, Antonio/0000-0003-0261-9897; Allore, Heather/0000-0001-7685-8175 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [K24AG021507, P30 AG021342, P30AG21342, K24 AG021507]; NIMHD NIH HHS [R01 MD009164] NR 39 TC 54 Z9 57 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 23 PY 2008 VL 299 IS 3 BP 308 EP 315 DI 10.1001/jama.299.3.308 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 253DB UT WOS:000252497800022 PM 18212315 ER PT J AU Barnett, CF Hsue, PY Machado, RF AF Barnett, Christopher F. Hsue, Priscilla Y. Machado, Roberto F. TI Pulmonary hypertension - An increasingly recognized complication of hereditary hemolytic anemias and HIV infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SICKLE-CELL-DISEASE; CLINICAL-PRACTICE GUIDELINES; ARTERIAL-HYPERTENSION; NITRIC-OXIDE; FREE HEMOGLOBIN; GROWTH-FACTOR; RISK-FACTOR; THERAPY; EXPRESSION; SURVIVAL AB Modern health care has greatly increased longevity for patients with congenital hemolytic anemias ( such as sickle cell disease and thalassemia) and human immunodeficiency virus ( HIV) infection. It is estimated that 10% of patients with hemoglobinopathies and 0.5% of patients with HIV infection develop moderate to severe pulmonary hypertension. Pulmonary hypertension is a relentlessly progressive disease leading to right heart failure and death. Worldwide, there are an estimated 30 million patients with sickle cell disease or thalassemia and 40 million patients with HIV disease. Considering the prevalence of pulmonary vascular disease in these populations, sickle cell disease and HIV disease may be the most common causes of pulmonary hypertension worldwide. In this review, the available data on epidemiology, hemodynamics, mechanisms, and therapeutic strategies for these diseases are summarized. Because therapy is likely to reduce morbidity and prolong survival, efforts to screen, diagnose, and treat these patients represent a global health opportunity. C1 [Barnett, Christopher F.; Machado, Roberto F.] NHLBI, Pulm & Vasc Med Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. [Barnett, Christopher F.; Machado, Roberto F.] NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Hsue, Priscilla Y.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. RP Machado, RF (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Ctr Clin, Bldg 10-CRC,Room 5-5140, Bethesda, MD 20892 USA. EM robertom@nhlbi.nih.gov NR 56 TC 43 Z9 45 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 23 PY 2008 VL 299 IS 3 BP 324 EP 331 DI 10.1001/jama.299.3.324 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 253DB UT WOS:000252497800024 PM 18212317 ER PT J AU Rhee, HW Lee, CR Cho, SH Song, MR Cashel, M Choy, HE Seok, YJ Hong, JI AF Rhee, Hyun-Woo Lee, Chang-Ro Cho, Seung-Hyon Song, Mi-Ryung Cashel, Michael Choy, Hyon E. Seok, Young-Jae Hong, Jong-In TI Selective fluorescent chemosensor for the bacterial alarmone (p)ppGpp SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID GUANOSINE 5'-DIPHOSPHATE 3'-DIPHOSPHATE; ESCHERICHIA-COLI; PYROPHOSPHATE SENSOR; TRANSCRIPTION REGULATION; INVITRO DEGRADATION; EXCIMER FORMATION; AQUEOUS-SOLUTION; PPGPP; ACCUMULATION; WATER AB We have developed the first selective fluorescent chemosensor (PyDPA) for (p)ppGpp, a bacterial and plant alarmone. By using pyrene-excimer fluorescence, PyDPA shows very good selectivity for (p)ppGpp from among other nucleotides in water. PyDPA was used for the real-time detection of in vitro ppGpp synthesis by bacterial ribosomal complexes. C1 [Rhee, Hyun-Woo; Hong, Jong-In] Seoul Natl Univ, Coll Nat Resources, Dept Chem, Seoul 151747, South Korea. [Lee, Chang-Ro; Cho, Seung-Hyon; Seok, Young-Jae] Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea. [Song, Mi-Ryung; Choy, Hyon E.] Chonnam Natl Univ, Sch Med, Dept Microbiol, Kwangju 501746, South Korea. [Cashel, Michael] Natl Inst Hlth, NICHD, Mol Genet Lab, Bethesda, MD 20892 USA. RP Rhee, HW (reprint author), Seoul Natl Univ, Coll Nat Resources, Dept Chem, Seoul 151747, South Korea. RI Rhee, Hyun-Woo/A-6861-2013 FU Intramural NIH HHS NR 29 TC 70 Z9 70 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 23 PY 2008 VL 130 IS 3 BP 784 EP + DI 10.1021/ja0759139 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 252DW UT WOS:000252426300003 PM 18166051 ER PT J AU Sucato, CA Upton, TG Kashemirov, BA Osuna, J Oertell, K Beard, WA Wilson, SH Florian, J Warshel, A McKenna, CE Goodman, MF AF Sucato, Christopher A. Upton, Thomas G. Kashemirov, Boris A. Osuna, Jorge Oertell, Keriann Beard, William A. Wilson, Samuel H. Florian, Jan Warshel, Arieh McKenna, Charles E. Goodman, Myron F. TI DNA polymerase beta fidelity: Halomethylene-modified leaving groups in pre-steady-state kinetic analysis reveal differences at the chemical transition state SO BIOCHEMISTRY LA English DT Article ID INDUCED-FIT MECHANISM; CATALYTIC MECHANISM; REPLICATION FIDELITY; STRUCTURAL INSIGHTS; CRYSTAL-STRUCTURES; ENZYME CATALYSIS; ALPHA-S; EFFICIENCY; MUTATIONS; COMPLEXES AB The mechanism of DNA polymerase beta-catalyzed nucleotidyl transfer consists of chemical steps involving primer 3' OH deprotonation, nucleophilic attack, and pyrophosphate leaving-group elimination, preceded by dNTP binding which induces a large-amplitude conformational change for Watson-Crick nascent base pairs. Ambiguity in the nature of the rate-limiting step and active-site structural differences between correct and incorrect base-paired transition states remain obstacles to understanding DNA replication fidelity. Analogues of dGTP where the beta-gamma bridging oxygen is replaced with fluorine-substituted methylene groups have been shown to probe the contribution of leaving-group elimination to the overall catalytic rate (Biochemistry 46, 461-471). Here, the analysis is expanded substantially to include a broad range of halogen substituents with disparate steric and electronic properties. Evaluation of linear free energy relationships for incorporation of dGTP analogues opposite either template base C or T reveals a strong correlation of log(k(pol)) to leaving group pK(a). Significantly different k(pol) behavior is observed with a subset of the analogues, with magnitude dependent on the identity of the nascent base pair. This observation, and the absence of an analogous effect on ground state analogue binding (K-d values), points to active-site structural differences at the chemical transition state. Reduced catalysis with bulky halo-containing substrates is manifested in the fidelity of T-G incorporation, where the CCl2-bridging analogue shows a 27-fold increase in fidelity over the natural dGTP. Solvent pH and deuterium isotope-effect data are also used to evaluate mechanistic differences between correct and mispaired incorporation. C1 [Sucato, Christopher A.; Upton, Thomas G.; Kashemirov, Boris A.; Osuna, Jorge; Oertell, Keriann; Warshel, Arieh; McKenna, Charles E.; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Florian, Jan] Loyola Univ, Dept Chem, Chicago, IL 60626 USA. [Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. EM mgoodman@usc.edu RI Florian, Jan/E-1554-2012; Upton, Thomas/E-3749-2012 OI Florian, Jan/0000-0003-2669-4293; FU Intramural NIH HHS; NCI NIH HHS [1U19CA10501]; NIGMS NIH HHS [R37GM21422] NR 51 TC 51 Z9 52 U1 1 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 22 PY 2008 VL 47 IS 3 BP 870 EP 879 DI 10.1021/bi7014162 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 251ZV UT WOS:000252415500002 PM 18161950 ER PT J AU Bras, J Guerreiro, R Ribeiro, M Morgadinho, A Januario, C Dias, M Calado, A Semedo, C Oliveira, C Hardy, J Singleton, A AF Bras, Jose Guerreiro, Rita Ribeiro, Maria Morgadinho, Ana Januario, Cristina Dias, Margarida Calado, Ana Semedo, Cristina Oliveira, Catarina Hardy, John Singleton, Andrew TI Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2 SO BMC NEUROLOGY LA English DT Article ID EARLY-ONSET PARKINSONISM; ALPHA-SYNUCLEIN; GENE; G2019S; PARK7 AB Background: Mutations in the genes PRKN and LRRK2 are the most frequent known genetic lesions among Parkinson's disease patients. We have previously reported that in the Portuguese population the LRRK2 c.6055G > A; p.G2019S mutation has one of the highest frequencies in Europe. Methods: Here, we follow up on those results, screening not only LRRK2, but also PRKN, SNCA and PINK1 in a cohort of early-onset and late-onset familial Portuguese Parkinson disease patients. This series comprises 66 patients selected from a consecutive series of 132 patients. This selection was made in order to include only early onset patients (age at onset below 50 years) or late-onset patients with a positive family history (at least one affected relative). All genes were sequenced bi-directionally, and, additionally, SNCA, PRKN and PINK1 were subjected to gene dosage analysis. Results: We found mutations both in LRRK2 and PRKN, while the remaining genes yielded no mutations. Seven of the studied patients showed pathogenic mutations, in homozygosity or compound heterozygosity for PRKN, and heterozygosity for LRRK2. Conclusion: Mutations are common in Portuguese patients with Parkinson's disease, and these results clearly have implications not only for the genetic diagnosis, but also for the genetic counseling of these patients. C1 [Bras, Jose; Guerreiro, Rita; Hardy, John; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Bras, Jose; Guerreiro, Rita; Ribeiro, Maria; Oliveira, Catarina] Univ Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Ribeiro, Maria; Morgadinho, Ana; Januario, Cristina; Oliveira, Catarina] Coimbra Univ Hosp, Neurol Serv, Coimbra, Portugal. [Dias, Margarida; Calado, Ana; Semedo, Cristina] Lisbon Hosp Ctr, Neurol Serv, Ctr Reg EPE, Lisbon, Portugal. RP Singleton, A (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM brasj@nia.nih.gov; portalegrer@nia.nih.gov; mhgarrucho@huc.min-saude.pt; anamorgadinho@portugalmail.pt; cristinajanuario@gmail.com; msilvadias@netcabo.pt; al_calado@yahoo.com; crissemedo@gmail.com; catarina@cnc.uc.pt; hardyj@mail.nih.gov; singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Bras, Jose/D-3366-2009; Oliveira, Catarina/F-3685-2010; Bras, Jose/A-1428-2011; Hardy, John/C-2451-2009; Guerreiro, Rita/A-1327-2011; Januario Santos, Maria Cristina/O-5939-2015; OI Januario Santos, Maria Cristina/0000-0001-5402-3978; Oliveira, Catarina/0000-0001-6942-4328 FU Intramural NIH HHS; Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 23 TC 15 Z9 15 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD JAN 22 PY 2008 VL 8 AR 1 DI 10.1186/1471-2377-8-1 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 279OS UT WOS:000254365100001 PM 18211709 ER PT J AU Pearce, CL Wu, AH Gayther, SA Bale, AE Beck, P Beesley, J Chanock, S Cramer, D DiCioccio, R Edwards, R Fredericksen, ZS Garcia-Closas, M Goode, EL Green, AC Hartmann, LC Hogdall, E Kjaer, SK Lissowska, J McGuire, V Modugno, F Moysich, K Ness, RB Ramus, SJ Risch, HA Sellers, TA Song, H Stram, DO Terry, KL Webb, PM Whiteman, DC Whittemore, AS Zheng, W Pharoah, PDP Chenevix-Trench, G Pike, MC Schildkraut, J Berchuck, A AF Pearce, C. L. Wu, A. H. Gayther, S. A. Bale, A. E. Beck, P. A. Beesley, J. Chanock, S. Cramer, D. W. DiCioccio, R. Edwards, R. Fredericksen, Z. S. Garcia-Closas, M. Goode, E. L. Green, A. C. Hartmann, L. C. Hogdall, E. Kjaer, S. K. Lissowska, J. McGuire, V. Modugno, F. Moysich, K. Ness, R. B. Ramus, S. J. Risch, H. A. Sellers, T. A. Song, H. Stram, D. O. Terry, K. L. Webb, P. M. Whiteman, D. C. Whittemore, A. S. Zheng, W. Pharoah, P. D. P. Chenevix-Trench, G. Pike, M. C. Schildkraut, J. Berchuck, A. CA Australian Canc Study Ovarian Ctr Australian Ovarian Canc Study Grp Ovarian Canc Assoc Consortium TI Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the ovarian cancer association consortium pooled analysis SO BRITISH JOURNAL OF CANCER LA English DT Article DE ovarian cancer; progesterone receptor; SNPs; PROGINS; pooled analyses; endometrioid ovarian cancer ID FRAGMENT-LENGTH-POLYMORPHISM; ORAL-CONTRACEPTIVES; GENE POLYMORPHISM; COMMON VARIANTS; BREAST-CANCER; REPAIR GENES; CARCINOMA; ESTROGEN; PROGINS; MUTATIONS AB There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 30 variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n = 651, OR = 1.17, 95% CI = 1.01-1.36, P = 0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n 725 cases; OR = 0.80, 95% CI 0.62-1.04, P = 0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer. C1 [Pearce, C. L.; Wu, A. H.; Stram, D. O.; Pike, M. C.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Gayther, S. A.; Ramus, S. J.] UCL, Windeyer Inst, Translat Res Lab, London W1T 4JE, England. [Bale, A. E.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Beesley, J.; Green, A. C.; Whiteman, D. C.; Chenevix-Trench, G.] Queensland Inst Med Res, Post Off Royal Brisbane Hosp, Herston, Qld 4029, Australia. [Chanock, S.] NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Cramer, D. W.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [DiCioccio, R.; Moysich, K.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Edwards, R.] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA 15213 USA. [Fredericksen, Z. S.; Goode, E. L.; Hartmann, L. C.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Garcia-Closas, M.] NCI, Div Canc Genet & Epidemiol, NIH, Rockville, MD 20852 USA. [Hogdall, E.; Kjaer, S. K.] Rigshosp, Danish Canc Soc, Inst Canc Epidemiol, Dept Virus Hormones & Canc, DK-2100 Copenhagen, Denmark. [Lissowska, J.] Ctr Canc, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lissowska, J.] M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland. [McGuire, V.; Whittemore, A. S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol & Biostat, Stanford, CA 94305 USA. [Risch, H. A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Sellers, T. A.] H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL 33612 USA. [Song, H.; Pharoah, P. D. P.] Univ Cambridge, Strangeways Res Lab, CR UK Dept Oncol, Cambridge CB1 8RN, England. [Zheng, W.] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85724 USA. [Schildkraut, J.; Berchuck, A.] Duke Comprehens Canc Ctr, Div Prevent Med, Durham, NC 27710 USA. [Modugno, F.; Ness, R. B.] Univ Pittsburgh, Dept Epidemiol, Inst Canc, Pittsburgh, PA 15261 USA. RP Pearce, CL (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, 1441 Eastlake Ave,Room 4415A, Los Angeles, CA 90089 USA. EM cpearce@usc.edu RI Susan, Ramus/C-1607-2008; Webb, Penelope/D-5736-2013; Garcia-Closas, Montserrat /F-3871-2015; Whiteman, David/P-2728-2014; OI Webb, Penelope/0000-0003-0733-5930; Garcia-Closas, Montserrat /0000-0003-1033-2650; Whiteman, David/0000-0003-2563-9559; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS; NCI NIH HHS [CA17054, 5R01-CA074850, 5R01-CA080742, CA14089, CA16056, CA61132, CA63464, CA71966, N01 PC067010, N01-PC-6710, P01 CA017054, P30 CA014089, P30 CA016056, R01 CA 61107, R01 CA063464, R01 CA074850, R01 CA080742, R03 CA113148, R03-CA113148, U01 CA063464] NR 44 TC 38 Z9 39 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 22 PY 2008 VL 98 IS 2 BP 282 EP 288 DI 10.1038/sj.bjc.6604170 PG 7 WC Oncology SC Oncology GA 259IQ UT WOS:000252933400007 PM 18219286 ER PT J AU Zlobec, I Vuong, T Compton, CC Lugli, A Michel, RP Hayashi, S Jass, JR AF Zlobec, I. Vuong, T. Compton, C. C. Lugli, A. Michel, R. P. Hayashi, S. Jass, J. R. TI Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy SO BRITISH JOURNAL OF CANCER LA English DT Article DE rectal cancer; VEGF; EGFR; immunohistochemistry; pre-operative radiotherapy; brachytherapy ID GROWTH-FACTOR RECEPTOR; ACCELERATED RADIATION-THERAPY; TOTAL MESORECTAL EXCISION; AMERICAN JOINT COMMITTEE; COLORECTAL-CANCER; ENDORECTAL BRACHYTHERAPY; STAINING INTENSITY; COLON-CANCER; EXPRESSION; CHEMORADIOTHERAPY AB The ability to predict complete pathologic response or sensitivity to radiation before treatment would have a significant impact on the selection of patients for preoperative radiotherapy or chemo-radiation therapy schedules. The aim of this study was to determine the value of epidermal growth factor receptor ( EGFR), vascular endothelial growth factor ( VEGF), p53, Bcl-2 and apoptosis protease-activating factor-1 (APAF-1) as predictors of complete pathologic tumour regression in patients undergoing preoperative radiotherapy for advanced rectal cancer. Pretreatment tumour biopsies from predominantly cT3 patients undergoing a preoperative high-dose-rate brachytherapy protocol were immunostained for EGFR, VEGF, p53, Bcl-2 and APAF-1. Immunoreactivity was evaluated by three pathologists. Cut-off scores for tumour marker positivity were obtained by receiver-operating characteristic (ROC) curve analysis. The association of marker expression with complete pathologic response was analysed in univariate and multivariable analysis. Multi-marker phenotypes of the independent protein markers were evaluated. In multivariable analysis, loss of VEGF (P-value 0.009; odds ratio ( OR) (95% CI) 0.24 (0.08-0.69)) and positive EGFR (P-value = 0.01; OR ( 95% CI) = 3.82 (1.37-10.6)) both demonstrated independent predictive value for complete pathologic response. The odds of complete response were 12.8 for the multi-marker combination of VEGF-negative and EGFR-positive tumours. Of the 34 EGFR-negative- and VEGF-positive cases, 32 (94.1%) had no complete pathologic response. The combined analysis of VEGF and EGFR is predictive of complete pathologic response in patients undergoing preoperative radiotherapy. In addition, the findings of this study have identified a subgroup of simultaneous EGFR-negative and VEGF-positive patients who are highly resistant to radiotherapy and should perhaps be considered candidates for innovative neoadjuvant combined modalities. C1 [Zlobec, I.; Lugli, A.] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland. [Vuong, T.] McGill Univ, Dept Radiat Oncol, Montreal, PQ H3G 1A4, Canada. [Compton, C. C.] NCI, NIH, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Michel, R. P.] McGill Univ, Dept Pathol, Montreal, PQ H3A 2B4, Canada. [Hayashi, S.] Toyama Univ, Dept Pathol, Toyama 9300194, Japan. [Jass, J. R.] Univ London Imperial Coll Sci Technol & Med, St Marks Hosp, Dept Pathol, Harrow HA1 3UJ, Middx, England. RP Zlobec, I (reprint author), Univ Basel Hosp, Inst Pathol, Schonbeinstr 40, CH-4031 Basel, Switzerland. EM izlobec@uhbs.ch NR 54 TC 51 Z9 56 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 22 PY 2008 VL 98 IS 2 BP 450 EP 456 DI 10.1038/sj.bjc.6604172 PG 7 WC Oncology SC Oncology GA 259IQ UT WOS:000252933400028 PM 18182986 ER PT J AU Jain, L Gardner, ER Venitz, J Dahut, W Figg, WD AF Jain, Lokesh Gardner, Erin R. Venitz, Juergen Dahut, William Figg, William D. TI Development of a rapid and sensitive LC-MS/MS assay for the determination of sorafenib in human plasma SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE BAY43-9006; kinase inhibitor ID MULTIKINASE INHIBITOR; BAY-43-9006 AB A rapid and sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) assay was developed for the quantitative determination of sorafenib in human plasma. Sample pretreatment involved simple protein precipitation by the addition of 0.5 mL acetonitrile, containing internal standard ([H-2(3), N-15] sorafenib), to 50 mu L of plasma sample volume. Separation was achieved on a Waters SymmetryShield RP8 (2.1 mm x 50 mm, 3.5 mu m) column at room temperature using an isocratic elution method with acetonitrile/0.1% formic acid in water: 65/35 (v/v) at a flow rate of 0.25 mL/min. Detection was per-formed using electrospray ionization in positive ion multiple reaction monitoring (MRM) mode by monitoring the ion transitions from m/z 464.9 --> 252.0 (sorafenib) and m/z 469.0 --> 259.0 (internal standard). Calibration curves were linear in the concentration range of 5-2000 ng/mL. The accuracy and precision values, calculated from three different sets of quality control samples analyzed in quintuplicate on six different days, ranged from 92.86% to 99.88% and from 1.19% to 4.53%, respectively. (C)- 2007 Elsevier B.V. All rights reserved. C1 [Jain, Lokesh; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Jain, Lokesh; Venitz, Juergen] Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA 23298 USA. [Gardner, Erin R.] NCI Frederick, SAIC Frederick Inc, Clin Pharmacol Program, Ft Detrick, MD 21702 USA. [Dahut, William] NCI, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [NIH0011335962, Z01 SC006536-06]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 7 TC 42 Z9 42 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JAN 22 PY 2008 VL 46 IS 2 BP 362 EP 367 DI 10.1016/j.jpba.2007.10.027 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 260LI UT WOS:000253011400022 PM 18309574 ER PT J AU Levitzky, YS Pencina, MJ D'Agostino, RB Meigs, JB Murabito, JM Vasan, RS Fox, CS AF Levitzky, Yamini S. Pencina, Michael J. D'Agostino, Ralph B. Meigs, James B. Murabito, Joanne M. Vasan, Ramachandran S. Fox, Caroline S. TI Impact of impaired fasting glucose on cardiovascular disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; DIABETES-MELLITUS; RISK-FACTORS; FOLLOW-UP; DIAGNOSTIC-CRITERIA; OLDER-ADULTS; FRAMINGHAM; TOLERANCE; MORTALITY; POPULATION AB Objectives We sought to determine whether impaired fasting glucose (IFG) predicts cardiovascular disease (CVD) events. Background It is unclear which glucose threshold should define prediabetes. We compared the 1997 and 2003 American Diabetes Association (ADA) definitions of IFG to predict CVD. Methods Framingham offspring participants free of CVD, categorized by the 1997 ADA IFG definition (fasting plasma glucose 110 to 125 mg/dI; 6.1 to 6.9 mmol/l) or the 2003 definition (100 to 125 mg/dI; 5.6 to 6.9 mmol/1), were followed from 1983 to 2004. Pooled logistic regression was used to calculate multivariable-adjusted odds ratios (ORs) for incident coronary heart disease (CHD; 291 events) or CVD (423 events). Results Four-year CHD event rates among women were 1.3% (100 to 109 mg/dl), 2.3% (110 to 125 mg/dI), and 2.9% (diabetes); whereas corresponding rates in men were 2.9%, 3.0%, and 8.7%. For the 2003 IFG definition, the OR for CHD among women was 1.7 (95% confidence interval [CI] 1.0 to 3.0, p = 0.048), whereas for the 1997 IFG definition, the OR for CHD in women was 2.2 (95% Cl 1.1 to 4.4, p = 0.02), which was almost as high as for women with diabetes (OR 2.5, 95% Cl 1.2 to 5.2, p = 0.01). For CVD, only the 1997 IFG definition yielded significantly greater odds of CVD in women (OR 2.1, 95% Cl 1.2 to 3.6, p = 0.01). Men were not at increased odds of developing CVD or CHD by either definition. Conclusions In women, both IFG definitions were associated with increased CHD risk, whereas neither IFG definition identified men at increased short-term risk for CHD or CVD. The finding that: women with FPG 110 to 125 mg/dI had similar CHD risk compared with women with diabetes suggests that CHD risk in women may be elevated at a lower glucose level than for men. C1 [Levitzky, Yamini S.; Murabito, Joanne M.; Vasan, Ramachandran S.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA. [Pencina, Michael J.; D'Agostino, Ralph B.] Boston Univ, Dept Mathemat, Stat & Consulting Unit, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Med Ctr, Dept Med, Sect Gen Internal Med, Boston, MA USA. [Fox, Caroline S.] Harvard Med Sch, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Diabet Endocrinol & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite No 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195, 2K24 HL4334] NR 32 TC 122 Z9 135 U1 0 U2 4 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 JAN 22 PY 2008 VL 51 IS 3 BP 264 EP 270 DI 10.1016/j.jace.2007.09.039 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 254DD UT WOS:000252565700004 PM 18206734 ER PT J AU Abbas, A Roth, BL AF Abbas, Atheir Roth, Bryan L. TI Arresting serotonin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID MEDIATED SIGNALING PATHWAYS; FUNCTIONAL SELECTIVITY; BETA-ARRESTINS; RECEPTORS; HALLUCINOGENS; ARIPIPRAZOLE; PHARMACOLOGY; MECHANISM; EFFICACY; UNIQUE C1 [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Dept Med Chem, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Abbas, Atheir] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU NIGMS NIH HHS [T32 GM007250] NR 18 TC 24 Z9 24 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 22 PY 2008 VL 105 IS 3 BP 831 EP 832 DI 10.1073/pnas.0711335105 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900002 PM 18195368 ER PT J AU Liu, J Nussinov, R AF Liu, Jin Nussinov, Ruth TI Allosteric effects in the marginally stable von Hippel-Lindau tumor suppressor protein and allostery-based rescue mutant design SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allosteric site prediction; drug design; E3 ubiquitin ligase; HIF; molecular dynamics simulations ID UBIQUITIN-PROTEASOME PATHWAY; HYPOXIA-INDUCIBLE FACTOR-1; P53 CORE DOMAIN; VHL GENE; GERMLINE MUTATIONS; FACTOR 1-ALPHA; COMPLEX; BINDING; STABILITY; DISEASE AB Many multifunctional tumor suppressor proteins have low stability, a property linked to cancer development. The von Hippel-Lindau tumor suppressor protein (pVHL) is one of these proteins. pVHL forms part of the E3 ubiquitin ligase complex that regulates the degradation of the hypoxia-inducible factor (HIF). Under native conditions, free pVHL is a molten globule, but it is stabilized in the E3 complex. By using molecular dynamics simulations, we observed that the interface between the two pVHL domains is the least stable region in unbound pVHL. We designed five stable mutants: one with a mutation at the interdomain interface and the others in the alpha- or beta-domains. Experimentally, type 2B pVHL disease mutant Y98N at the HIF binding site was shown to destabilize pVHL and decrease its binding affinity to HIF. Our simulations showed that the decrease in pVHL stability and binding affinity are allosterically regulated. The mutations designed to stabilize unbound wild-type pVHL, which are away from the elongin C and HIF binding sites, successfully stabilized the Y98N pVHL-elongin C complex and lowered the binding free energy of pVHL with HIF. Our results indicated both the enthalpic and dynamic allosteric components between the elongin C and HIF binding sites in pVHL, in the alpha- and beta-domains, respectively, mediated by the interdomain interface and linker. Drugs mimicking the allosteric effects of these mutants may rescue pVHL function in von Hippel-Lindau disease. C1 [Liu, Jin; Nussinov, Ruth] NCI, Basic Res Program, SAIC, Frederick Inc,Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC, Frederick Inc,Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 45 TC 52 Z9 52 U1 1 U2 4 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 JAN 22 PY 2008 VL 105 IS 3 BP 901 EP 906 DI 10.1073/pnas.0707401105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900015 PM 18195360 ER PT J AU Jegga, AG Inga, A Menendez, D Aronow, BJ Resnick, MA AF Jegga, Anil G. Inga, Alberto Menendez, Daniel Aronow, Bruce J. Resnick, Michael A. TI Functional evolution of the p53 regulatory network through its target response elements SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR-BINDING-SITES; TRANSCRIPTION-FACTOR; HUMAN GENOME; GENE; SEQUENCE; CONSERVATION; P63; HUMANS; TRANSACTIVATION; IDENTIFICATION AB Transcriptional network evolution is central to the development of complex biological systems. Networks can evolve through variation of master regulators and/or by changes in regulation of genes within networks. To gain insight into meaningful evolutionary differences in large networks, it is essential to address the functional consequences of sequence differences in response elements (REs) targeted by transcription factors. Using a combination of custom bioinformatics and multispecies alignment of promoter regions, we investigated the functional evolution of REs in terms of responsiveness to the sequence-specific transcription factor p53, a tumor suppressor and master regulator of stress responses. We identified REs orthologous to known p53 targets in human and rodent cells or alternatively REs related to the established p53 consensus. The orthologous REs were assigned p53 transactivation capabilities based on rules determined from model systems, and a functional heat map was developed to visually summarize conservation of sequence and relative level of responsiveness to p53 for 47 REs in 14 species. Individual REs exhibited marked differences in transactivation potentials and widespread evolutionary turnover. Functional differences were often not predicted from consensus sequence evaluations. Of the established human p53 REs analyzed, 91% had sequence conservation in at least one nonprimate species compared with 67.5% for functional conservation. Surprisingly, there was almost no conservation of functional REs for genes involved in DNA metabolism or repair between humans and rodents, suggesting important differences in p53 stress responses and cancer development. C1 [Menendez, Daniel; Resnick, Michael A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Jegga, Anil G.; Aronow, Bruce J.] Cincinnati Childrens Hosp, Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA. [Jegga, Anil G.; Aronow, Bruce J.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45267 USA. [Inga, Alberto] Ist Nazl Ric Canc, Mol Mutagenesis Unit, I-16132 Genoa, Italy. RP Resnick, MA (reprint author), NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov OI Jegga, Anil/0000-0002-4881-7752 FU Intramural NIH HHS; NCI NIH HHS [U01 CA084291, UO1 CA84291-07]; Associazione Italiana per la Ricerca sul Cancro NR 43 TC 43 Z9 44 U1 0 U2 4 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 JAN 22 PY 2008 VL 105 IS 3 BP 944 EP 949 DI 10.1073/pnas.0704694105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900023 PM 18187580 ER PT J AU Akilesh, S Huber, TB Wu, H Wang, G Hartleben, B Kopp, JB Miner, JH Roopenian, DC Unanue, ER Shaw, AS AF Akilesh, Shreeram Huber, Tobias B. Wu, Hui Wang, Gary Hartleben, Bjoern Kopp, Jeffrey B. Miner, Jeffrey H. Roopenian, Derry C. Unanue, Emil R. Shaw, Andrey S. TI Podocytes use FcRn to clear IgG from the glomerular basement membrane SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Fc receptor; glomerulonephritis ID VISCERAL EPITHELIAL-CELL; RAT RENAL-VEIN; KIDNEY GLOMERULUS; FERRITIN TRANSFER; FILTERED ALBUMIN; CAPILLARY WALL; NEONATAL RAT; SERUM IGG; RECEPTOR; MICE AB The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here, we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GEM as they aged, and tracer studies showed delayed clearance of IgG from the kidneys of FcRn-deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases. C1 [Akilesh, Shreeram; Huber, Tobias B.; Wu, Hui; Wang, Gary; Hartleben, Bjoern; Unanue, Emil R.; Shaw, Andrey S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Miner, Jeffrey H.] Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA. [Kopp, Jeffrey B.] NIH, Nat Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA. [Roopenian, Derry C.] Jackson Lab, Bar Harbor, ME 04609 USA. RP Unanue, ER (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM unanue@pathology.wustl.edu; shaw@wustl.edu OI Akilesh, Shreeram/0000-0003-3152-7991; Kopp, Jeffrey/0000-0001-9052-186X FU NIGMS NIH HHS [T32 GM007200, T32 GM07200]; PHS HHS [52701, 56597] NR 45 TC 115 Z9 124 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 22 PY 2008 VL 105 IS 3 BP 967 EP 972 DI 10.1073/pnas.0711515105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900027 PM 18198272 ER PT J AU Cholera, R Brittain, NJ Gillriet, MR Lopera-Mesa, TM Diakite, SAS Arie, T Krause, MA Guindo, A Tubman, A Fujioka, H Diallo, DA Doumbo, OK Ho, M Wellems, TE Fairhurst, RM AF Cholera, Rushina Brittain, Nathaniel J. Gillriet, Mark R. Lopera-Mesa, Tatiana M. Diakite, Seidina A. S. Arie, Takayuki Krause, Michael A. Guindo, Aldiouma Tubman, Abby Fujioka, Hisashi Diallo, Dapa A. Doumbo, Ogobara K. Ho, May Wellems, Thomas E. Fairhurst, Rick M. TI Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE disease severity; malaria; PfEMP-1; hemoglobin S; hemoglobin C ID HUMAN CEREBRAL MALARIA; CELL TRAIT; RED-CELLS; PROTECTION; SEQUESTRATION; RESISTANCE; MECHANISM; SURFACE; GENE; CHILDREN AB Sickle trait, the heterozygous state of normal hemoglobin A (HbA) and sickle hemoglobin S (HbS), confers protection against malaria in Africa. AS children infected with Plasmodium falciparum are less likely than AA children to suffer the symptoms or severe manifestations of malaria, and they often carry lower parasite densities than AA children. The mechanisms by which sickle trait might confer such malaria protection remain unclear. We have compared the cytoadherence properties of parasitized AS and AA erythrocytes, because it is by these properties that parasitized erythrocytes can sequester in postcapillary microvessels of critical tissues such as the brain and cause the life-threatening complications of malaria. Our results show that the binding of parasitized AS erythrocytes to microvascular endothelial cells and blood monocytes is significantly reduced relative to the binding of parasitized AA erythrocytes. Reduced binding correlates with the altered display of P, falciparum erythrocyte membrane protein-1 (PfEMP-1), the parasite's major cytoadherence ligand and virulence factor on the erythrocyte surface. These findings identify a mechanism of protection for HbS that has features in common with that of hemoglobin C (HbC). Coinherited hemoglobin polymorphisms and naturally acquired antibodies to PfEMP-1 may influence the degree of malaria protection-in AS children by further weakening cytoadherence interactions. C1 [Cholera, Rushina; Brittain, Nathaniel J.; Lopera-Mesa, Tatiana M.; Arie, Takayuki; Krause, Michael A.; Tubman, Abby; Wellems, Thomas E.; Fairhurst, Rick M.] NIH, Natl Inst Allergy & Infect Dis, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Gillriet, Mark R.] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada. [Diakite, Seidina A. S.; Guindo, Aldiouma; Diallo, Dapa A.] Univ Bamako, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali. [Fujioka, Hisashi] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. RP Wellems, TE (reprint author), NIH, Natl Inst Allergy & Infect Dis, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov; rfairhurst@niaid.nih.gov FU Intramural NIH HHS NR 42 TC 110 Z9 112 U1 3 U2 26 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 JAN 22 PY 2008 VL 105 IS 3 BP 991 EP 996 DI 10.1073/pnas.0711401105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900031 PM 18192399 ER PT J AU Scheel, TKH Gottwein, JM Jensen, TB Prentoe, JC Hoeght, AM Alter, HJ Eugen-Olsen, J Bukh, J AF Scheel, Troels K. H. Gottwein, Judith M. Jensen, Tanja B. Prentoe, Jannick C. Hoeght, Anne M. Alter, Harvey J. Eugen-Olsen, Jesper Bukh, Jens TI Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE egypt; hepatitis C virus strain ED43; in vitro infection; intergenotypic recombinant; vaccine ID INFECTION IN-VITRO; EGYPT; REPLICATION; RECOMBINANT; ANTIBODY; IMMUNITY; STRAIN; ENTRY; HOST; NS2 AB Efficient in vitro systems to study the life cycle of hepatitis C virus (HCV) were recently developed for JFH1 (genotype 2a), which has unique replication capacity in Huh7 cells. We developed 4a/JFH1 intergenotypic recombinants containing the structural genes (Core, E1, and E2), p7, and all or part of NS2 of the 4a prototype strain ED43 that, after transfection of Huh7.5 cells with RNA transcripts, produced infectious viruses. Compared with the J6/JFH control virus, production of viruses was delayed. However, efficient spread of infection and high HCV RNA and infectivity titers were obtained in serial passages. Sequence analysis of recovered viruses and subsequent reverse genetic studies revealed a vital dependence on one or two N52 mutations, depending on the 4a/2a junction. Infectivity of ED43/JFH1 viruses was CD81 dependent. The genotype 4 cell culture systems permit functional analyses as well as drug and vaccine research on an increasingly important genotype in the Middle East, Africa, and Europe. We also developed genotype 1a intergenotypic recombinants from H77C with vital mutations in NS3. Using H77C/JFH1 and ED43/JFH1 viruses, we demonstrated high homologous neutralizing antibody titers in 1a and 4a patient sera, respectively. Furthermore, availability of JFH1 viruses with envelope proteins of the six major HCV genotypes permitted cross-neutralization studies; 1a and 4a serum cross-neutralized 1a, 4a, 5a,and 6a but not 2a and 3a viruses. Thus, the JFH1 intergenotypic recombinants will be of importance for future studies of HCV neutralization and accelerate the development of passive and active immunoprophylaxis. C1 [Alter, Harvey J.] NIAID, Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. [Bukh, Jens] NIAID, Natl Inst Hlth, Infect Dis Lab, Bethesda, MD 20892 USA. [Scheel, Troels K. H.; Gottwein, Judith M.; Jensen, Tanja B.; Prentoe, Jannick C.; Eugen-Olsen, Jesper; Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program, Dept Infect Dis, DK-2650 Hvidovre, Denmark. [Scheel, Troels K. H.; Gottwein, Judith M.; Jensen, Tanja B.; Hoeght, Anne M.; Eugen-Olsen, Jesper; Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program, Clin Res Ctr, DK-2650 Hvidovre, Denmark. [Hoeght, Anne M.] Copenhagen Univ Hosp, Dept Clin Microbiol, DK-2650 Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen, Denmark. RP Alter, HJ (reprint author), NIAID, Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. EM halter@mail.nih.gov; jbukh@niaid.nih.gov OI Eugen-Olsen, jesper/0000-0002-4630-4275; Prentoe, Jannick/0000-0003-2203-9478; Scheel, Troels/0000-0003-1545-4067 NR 28 TC 106 Z9 114 U1 0 U2 10 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 JAN 22 PY 2008 VL 105 IS 3 BP 997 EP 1002 DI 10.1073/pnas.0711044105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900032 PM 18195353 ER PT J AU Fearon, P Cohen-Fix, O AF Fearon, Paula Cohen-Fix, Orna TI The Endoplasmic Reticulum Takes Center Stage in Cell Cycle Regulation SO SCIENCE SIGNALING LA English DT Article AB Cell cycle progression is controlled by the action of cyclins and their partners, the cyclin-dependent kinases (CDKs). Although many of the cyclin/CDK targets are in the nucleus,some cyclins spend part of their time in the cytoplasm. Until recently, it was not clear what happens to these cyclins while they are in the cytoplasm; now, two different cyclins have been found to be associated with the endoplasmic reticulum. The question is why. C1 [Fearon, Paula; Cohen-Fix, Orna] NIDDK, Mol & Cellular Biol Lab, Bethesda, MD 20892 USA. RP Cohen-Fix, O (reprint author), NIDDK, Mol & Cellular Biol Lab, Bethesda, MD 20892 USA. EM ornacf@helix.nih.gov NR 11 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JAN 22 PY 2008 VL 1 IS 3 AR pe4 DI 10.1126/stke.13pe4 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10UV UT WOS:000207489800001 PM 18272469 ER PT J AU Nelson, A Garraffo, HM Spande, TF Daly, JW Stevenson, PJ AF Nelson, Angela Garraffo, H. Martin Spande, Thomas F. Daly, John W. Stevenson, Paul J. TI Facile synthesis of two diastereomeric indolizidines corresponding to the postulated structure of alkaloid 5,9E-259B from a Bufonid toad (Melanophryniscus) SO BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID POISON-FROG ALKALOIDS; NICOTINIC ACETYLCHOLINE-RECEPTORS; DIELS-ALDER REACTION; ENANTIOSELECTIVE SYNTHESIS; STEREOSELECTIVE-SYNTHESIS; (-)-INDOLIZIDINE 209B; (+/-)-INDOLIZIDINES 167B; OLEFIN METATHESIS; (-)-209B; (-)-235B AB A short synthesis of the postulated structure for indolizidine alkaloid 259B with the hydrogens at C5 and C9 entgegen has been achieved with complete control of stereochemistry at C5. Both diastereoisomers at C8 were obtained, but neither proved to be the natural product. The comparison of the mass and FTIR spectral properties of the synthetic compounds to those of the natural material strongly suggest that the gross structure is correct and that the difference may be a branch in the C5 alkyl side-chain. The GC-retention times of the two synthetic compounds were markedly longer than that of the natural 5,9E-259B. C1 [Nelson, Angela; Stevenson, Paul J.] Queens Univ Belfast, Sch Chem & Chem Engn, Belfast BT9 5AG, Antrim, North Ireland. [Garraffo, H. Martin; Spande, Thomas F.; Daly, John W.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Stevenson, PJ (reprint author), Queens Univ Belfast, Sch Chem & Chem Engn, Belfast BT9 5AG, Antrim, North Ireland. EM p.stevenson@qub.ac.uk; garraffo@helix.nih.gov; thomassp@bdg8.niddk.nih.gov; jdaly@nih.gov; p.stevenson@qub.ac.uk NR 50 TC 1 Z9 1 U1 0 U2 4 PU BEILSTEIN-INSTITUT PI FRANKFURT AM MAIN PA TRAKEHNER STRASSE 7-9, FRANKFURT AM MAIN, 60487, GERMANY SN 1860-5397 J9 BEILSTEIN J ORG CHEM JI Beilstein J. Org. Chem. PD JAN 21 PY 2008 VL 4 AR 6 DI 10.1186/1860-5397-4-6 PG 6 WC Chemistry, Organic SC Chemistry GA 263HE UT WOS:000253207400001 PM 18208586 ER PT J AU Yang, D Chen, Q Su, SB Zhang, P Kurosaka, K Caspi, RR Michalek, SM Rosenberg, HF Zhang, N Oppenheim, JJ AF Yang, De Chen, Qian Su, Shao Bo Zhang, Ping Kurosaka, Kahori Caspi, Rachel R. Michalek, Suzanne M. Rosenberg, Helene F. Zhang, Ning Oppenheim, Joost J. TI Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOLL-LIKE RECEPTOR-4; HEAT-SHOCK PROTEINS; GROUP BOX-1 PROTEIN; CUTTING EDGE; REGULATED KINASE; ANTIMICROBIAL PEPTIDES; TRANSDUCTION PATHWAYS; CATIONIC PROTEIN; CHILDHOOD ASTHMA; GRANULE PROTEINS AB Eosinophil-derived neurotoxin (EDN) is an eosinophil granule-derived secretory protein with ribonuclease and antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2-myeloid differentiation factor 88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independently of TLR1 or TLR6. When mice were immunized with ovalbumin (OVA) together with EDN or with EDN-treated OVA-loaded DCs, EDN enhanced OVA-specifi c T helper (Th)2-biased immune responses as indicated by predominant production of OVA-specifi c interleukin (IL)-5, IL-6, IL-10, and IL-13, as well as higher levels of immunoglobulin (Ig)G1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen-specifi c immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen-specifi c Th2 immune responses. C1 [Yang, De; Chen, Qian; Kurosaka, Kahori; Zhang, Ning; Oppenheim, Joost J.] Natl Canc Inst, Ctr Canc Res, Canc Inflammat Program, Lab Mol Immunoregulat, Ft Detrick, MD 21702 USA. [Su, Shao Bo; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, Eosinophil Biol Sect, NIH, Bethesda, MD 20892 USA. [Zhang, Ping; Michalek, Suzanne M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Zhang, Ning] Tianjin Med Univ Canc Inst & Hosp, Tianjin 300060, Peoples R China. [Yang, De] Natl Canc Inst, Ctr Canc Res, Basic Res Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. RP Yang, D (reprint author), Natl Canc Inst, Ctr Canc Res, Basic Res Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. EM dyang@ncifcrf.gov; oppenhei@ncifcrf.gov; oppenhei@ncifcrf.gov OI Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 69 TC 178 Z9 187 U1 1 U2 13 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 JAN 21 PY 2008 VL 205 IS 1 BP 79 EP 90 DI 10.1084/jem.20062027 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253GQ UT WOS:000252507100010 PM 18195069 ER PT J AU Bender, JLG Adamson, PC Reid, JM Xu, L Baruchel, S Shaked, Y Kerbel, RS Cooney-Qualter, EM Stempak, D Chen, HX Nelson, MD Krailo, MD Ingle, AM Blaney, SM Kandel, JJ Yamashiro, DJ AF Bender, Julia L. Glade Adamson, Peter C. Reid, Joel M. Xu, Lu Baruchel, Sylvain Shaked, Yuval Kerbel, Robert S. Cooney-Qualter, Erin M. Stempak, Diana Chen, Helen X. Nelson, Marvin D. Krailo, Mark D. Ingle, Ashish M. Blaney, Susan M. Kandel, Jessica J. Yamashiro, Darrell J. TI Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: A children's oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID ENDOTHELIAL GROWTH-FACTOR; FACTOR MONOCLONAL-ANTIBODY; CELL LUNG-CANCER; COLORECTAL-CANCER; BREAST-CANCER; VEGF ANTIBODY; ANGIOGENESIS; MODEL; CHEMOTHERAPY; SUPPRESSION AB Purpose We conducted a pediatric phase I trial of the vascular endothelial growth factor ( VEGF)-neutralizing antibody bevacizumab (BV). Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer. Patients and Methods BV ( 5, 10, 15 mg/kg) was administered intravenously every 2 weeks in 28-day courses to children with refractory solid tumors. Results Twenty-one patients enrolled, 20 ( median age, 13 years) were eligible, and 18 completed one course and were fully assessable for toxicity. A total of 67 courses were administered ( median, three courses per patient; range, one to 16 courses). Treatment was well tolerated with no DLTs observed. Non-DLTs included infusional reaction, rash, mucositis, proteinuria, and lymphopenia. Increases in systolic and diastolic blood pressure not meeting Common Terminology Criteria for Adverse Events (CTCAEv3) pediatric-specific criteria for hypertension were observed. There was no hemorrhage or thrombosis. Growth perturbation was not detected in a limited sample over the first course. The serum exposure to BV as measured by area under the concentration-time curve (AUC) seemed to increase in proportion to dose. The median clearance of BV was 4.1 mL/d/kg ( range, 3.1 to 15.5 mL/d/kg), and the median half-life was 11.8 days (range, 4.4 to 14.6 days). No objective responses were observed. Exploratory analyses on circulating endothelial mobilization and viability are consistent with the available adult data. Conclusion BV is well tolerated in children. Phase II pediatric studies of BV in combination with chemotherapy in dosing schedules similar to adults are planned. C1 Columbia Univ, Coll Physicians & Surgeons, New York, NY USA. Childrens Hosp, Philadelphia, PA 19104 USA. Mayo Clin & Mayo Fdn, Rochester, MN USA. Genectech Inc, San Francisco, CA USA. Childrens Hosp, Los Angeles, CA 90027 USA. Childrens Oncol Grp, Arcadia, CA USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Sunnybrook & Womens Coll, Ctr Hlth Sci, Toronto, ON, Canada. NCI, Bethesda, MD USA. Texas Childrens Canc Ctr, Houston, TX USA. RP Bender, JLG (reprint author), Irving Pavilion 7,169 Ft Washington Ave, New York, NY 10032 USA. EM jg589@columbia.edu NR 32 TC 106 Z9 109 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2008 VL 26 IS 3 BP 399 EP 405 DI 10.1200/JCO.2007.11.9230 PG 7 WC Oncology SC Oncology GA 276XO UT WOS:000254177200013 ER PT J AU Jeong, SJ Dasgupta, A Jung, KJ Um, JH Burke, A Park, HU Brady, JN AF Jeong, Soo-Jin Dasgupta, Arindarn Jung, Kyung-Jin Um, Jee-Hyun Burke, Aileen Park, Hyeon Ung Brady, John N. TI PI3K/AKT inhibition induces caspase-dependent apoptosis in HTLV-1-transformed cells SO VIROLOGY LA English DT Article DE AKT; HTLV-1; apoptosis; LYZ9400Z; AKT inhibitor II ID NF-KAPPA-B; VIRUS TYPE-I; AKT/PROTEIN-KINASE-B; LEUKEMIA-VIRUS; TAX PROTEIN; T-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; P53 INHIBITION; CANCER-CELLS; CYCLIN D1 AB The phosphatidylinositol-3-kinase (PI3K) and AKT (protein kinase B) signaling pathways play an important role in regulating cell cycle progression and cell survival. In previous studies, we demonstrated that AKT is activated in HTLV-1-transformed cells and that Tax activation of A AKT is linked to p53 inhibition and cell survival. In the present study, we extend these observations to identify regulatory pathways affected by AKT in HTLV-1-transformed cells. We demonstrate that inhibition of AKT reduces the level of phosphorylated Bad, an important member of the proapoptotic family of proteins. Consistent with the decrease of phosphorylated Bad, cytochrome c is released from the mitochondria and caspase-9 is activated. Pretreatment of the cells with caspase-9 specific inhibitor z-LEHD-FMK or pan caspase inhibitor Ac-DEVD-CHO prevented LY294002-induced apoptosis. Of interest, p53 siRNA prevents LY294002-induced apoptosis in HTLV-1-transformed cells, suggesting that p53 reactivation is linked to apoptosis. In conclusion, the AKT pathway is involved in targeting multiple proteins which regulate caspase- and p53-dependent apoptosis in HTLV-1-transformed cells. Since AKT inhibitors simultaneously inhibit NF-kappa B and activate p53, these drugs should be promising candidates for HTLV-1-associated cancer therapy. Published by Elsevier Inc. C1 [Jeong, Soo-Jin; Dasgupta, Arindarn; Jung, Kyung-Jin; Burke, Aileen; Park, Hyeon Ung; Brady, John N.] NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Um, Jee-Hyun] Natl Heart Lung & Blood Inst, Lab Biochem Genet, NIH, Bethesda, MD USA. [Park, Hyeon Ung] Univ Maryland, Dept Pathol, Sch Med, Baltimore, MD 21201 USA. RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov FU Intramural NIH HHS [Z99 OD999999, Z01 BC005691-15] NR 56 TC 45 Z9 47 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 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 2008 VL 370 IS 2 BP 264 EP 272 DI 10.1016/j.virol.2007.09.003 PG 9 WC Virology SC Virology GA 242BF UT WOS:000251698800006 PM 17931677 ER PT J AU Murata, H Peden, K Lewis, AM AF Murata, Haruhiko Peden, Keith Lewis, Andrew M., Jr. TI Identification of a mutation in the SV40 capsid protein VP1 that influences plaque morphology, vacuolization, and receptor usage SO VIROLOGY LA English DT Article DE polyomaviruses; SV40; VP1; plaque phenotype; vacuolization; ganglioside ID MAJOR HISTOCOMPATIBILITY PROTEINS; MURINE POLYOMAVIRUS; VIRUS; SIMIAN-VIRUS-40; RESOLUTION; GANGLIOSIDES; MUTANTS; REVEALS; BINDING; COMPLEX AB A plaque variant of SV40 that was first isolated in the 1960s, designated SV40-LP(KT), was molecularly cloned and subjected to sequence analysis. The genome of SV40-LP(KT) was found to be nearly identical to the previously described isolate known as 777. However, SV40-LP (KT) contained a mutation in the VP1 coding region resulting in a change of histidine 136 to tyrosine. This VP1 mutation was identified as a genetic determinant influencing a number of phenotypes associated with SV40-LP(KT) such as plaque morphology, intracellular vacuole formation, and ganglioside receptor usage. Published by Elsevier Inc. C1 [Murata, Haruhiko; Lewis, Andrew M., Jr.] US FDA, Lab DNA Viruses, Div Viral Products, CBER, Bethesda, MD 20892 USA. [Murata, Haruhiko] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Div Canc Prevent,NIH, Bethesda, MD 20892 USA. [Murata, Haruhiko; Peden, Keith] US FDA, Lab Retrovirus Res, Div Viral Products, CBER, Bethesda, MD 20892 USA. RP Lewis, AM (reprint author), US FDA, Lab DNA Viruses, Div Viral Products, CBER, Bldg 29A,Room 1B10,29 Lincoln Dr, Bethesda, MD 20892 USA. EM andrew.lewis@fda.hiis.gov NR 24 TC 7 Z9 7 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 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 2008 VL 370 IS 2 BP 343 EP 351 DI 10.1016/j.virol.2007.08.040 PG 9 WC Virology SC Virology GA 242BF UT WOS:000251698800013 PM 17936868 ER PT J AU Sengupta, A Carlson, BA Hoffmann, VJ Gladyshev, VN Hatfield, DL AF Sengupta, Aniruddha Carlson, Bradley A. Hoffmann, Victoria J. Gladyshev, Vadim N. Hatfield, Dolph L. TI Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE apolipoprotein E; conditional-knockout; selenocysteine tRNA; housekeeping selenoproteins; stress-related selenoproteins ID SELENOCYSTEINE TRANSFER-RNAS; VITAMIN-E; PLASMA-LIPOPROTEIN; DIETS DEFICIENT; GENE TRSP; SELENIUM; POPULATION; LACKING; RAT AB Selenium is incorporated into proteins as selenocysteine (Sec), which is dependent on its specific tRNA, designated tRNA([Ser]Sec). Targeted removal of the tRNA([Ser]Sec) gene (Trsp) in mouse hepatocytes previously demonstrated the importance of selenoproteins in liver function. Herein, analysis of plasma proteins in this Trsp knockout mouse revealed increases in apolipoprotein E (ApoE) that was accompanied by elevated plasma cholesterol levels. The expression of genes involved in cholesterol biosynthesis, metabolism and transport were also altered in knockout mice. Additionally, in two transgenic Trsp mutant mouse lines (wherein only housekeeping selenoprotein synthesis was restored), the expression of ApoE, as well as genes involved in cholesterol biosynthesis, metabolism and transport were similar to those observed in wild type mice. These data correlate with reports that selenium deficiency results in increased levels of ApoE, indicating for the first time that housekeeping selenoproteins have a role in regulating lipoprotein biosynthesis and metabolism. (c) 2007 Elsevier Inc. All rights reserved. C1 [Sengupta, Aniruddha; Carlson, Bradley A.; Hatfield, Dolph L.] Natl Inst Hlth, Natl Canc Inst, Canc Res Ctr, Mol Biol Selenium Sect Lab Canc Prevent, Bethesda, MD 20892 USA. [Hoffmann, Victoria J.] Natl Inst Hlth, Off Director Diagnost & Res Branch, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RP Hatfield, DL (reprint author), Natl Inst Hlth, Natl Canc Inst, Canc Res Ctr, Mol Biol Selenium Sect Lab Canc Prevent, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS [Z99 CA999999] NR 22 TC 23 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 18 PY 2008 VL 365 IS 3 BP 446 EP 452 DI 10.1016/j.bbrc.2007.10.189 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 241NM UT WOS:000251663100008 PM 17996733 ER PT J AU Fan, YX Wong, LL Ding, JH Spiridonov, NA Johnson, RC Johnson, GR AF Fan, Ying-Xin Wong, Lily Ding, Jinhui Spiridonov, Nikolay A. Johnson, Richard C. Johnson, Gibbes R. TI Mutational activation of ErbB2 reveals a new protein kinase autoinhibition mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; EXTRACELLULAR REGION; CRYSTAL-STRUCTURE; SIGNAL-TRANSDUCTION; CATALYTIC-ACTIVITY; LUNG-CANCER; DOMAIN; EGF; COMPLEX AB Autoinhibition plays a key role in the control of protein kinase activity. ErbB2 is a unique receptor-tyrosine kinase that does not bind ligand but possesses an extracellular domain poised to engage other ErbBs. Little is known about the molecular mechanism for ErbB2 catalytic regulation. Here we show that ErbB2 kinase is strongly autoinhibited, and a loop connecting the alpha C helix and beta 4 sheet within the kinase domain plays a major role in the control of kinase activity. Mutations of two Gly residues at positions 776 and 778 in this loop dramatically increase ErbB2 catalytic activity. Kinetic analysis demonstrates that mutational activation is due to similar to 10- and similar to 7-fold increases in ATP binding affinity and turnover number, respectively. Expression of the activated ErbB2 mutants in cells resulted in elevated ligand- independent ErbB2 autophosphorylation, ErbB3 phosphorylation, and stimulation of mitogen-activated protein kinase. Molecular modeling suggests that the ErbB2 kinase domain is stabilized in an inactive state via a hydrophobic interaction between the alpha C-beta 4 and activation loops. Importantly, many ErbB2 human cancer mutations have been identified in the alpha C-beta 4 loop, including the activating G776S mutation studied here. Our findings reveal a new kinase regulatory mechanism in which the alpha C-beta 4 loop functions as an intramolecular switch that controls ErbB2 activity and suggests that loss of alpha C-beta 4 loop-mediated autoinhibition is involved in oncogenic activation of ErbB2. C1 [Fan, Ying-Xin; Wong, Lily; Spiridonov, Nikolay A.; Johnson, Gibbes R.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. [Ding, Jinhui] NIH, NIA, Neurogenet Lab, Bioinformat Sect, Bethesda, MD 20892 USA. [Johnson, Richard C.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Fan, YX (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bldg 29A,Rm 3B-20,8800 Rockville Pike, Bethesda, MD 20892 USA. EM ying-xin.fan@fda.hhs.gov; gibbes.johnson@fda.hhs.gov RI Spiridonov, Nikolay/B-6287-2014 NR 49 TC 22 Z9 22 U1 0 U2 4 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 JAN 18 PY 2008 VL 283 IS 3 BP 1588 EP 1596 DI 10.1074/jbc.M708116200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250EL UT WOS:000252282700044 PM 18039657 ER PT J AU Burgess, SC Iizuka, K Jeoung, NH Harris, RA Kashiwaya, Y Veech, RL Kitazume, T Uyeda, K AF Burgess, Shawn C. Iizuka, Katsumi Jeoung, Nam Ho Harris, Robert A. Kashiwaya, Yoshihiro Veech, Richard L. Kitazume, Tatsuya Uyeda, Kosaku TI Carbohydrate-response element-binding protein deletion alters substrate utilization producing an energy-deficient liver SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PYRUVATE-DEHYDROGENASE COMPLEX; TRICARBOXYLIC-ACID CYCLE; TRANSCRIPTION FACTOR; RAT-LIVER; GLUCOSE; MECHANISM; KINASE; PHOSPHORYLATION; PHOSPHATASE; LIPOGENESIS AB Livers from mice lacking the carbohydrate-responsive element-binding protein (ChREBP) were compared with wild type (WT) mice to determine the effect of this transcription factor on hepatic energy metabolism. The pyruvate dehydrogenase complex was considerably more active in ChREBP(-/-) mice because of diminished pyruvate dehydrogenase kinase activity. Greater pyruvate dehydrogenase complex activity caused a stimulation of lactate and pyruvate oxidation, and it significantly impaired fatty acid oxidation in perfused livers from ChREBP(-/-) mice. This shift in mitochondrial substrate utilization led to a 3-fold reduction of the free cytosolic [NAD(+)]/[NADH] ratio, a 1.7-fold increase in the free mitochondrial [NAD(+)]/[NADH] ratio, and a 2-fold decrease in the free cytosolic [ATP]/[ADP][P-i] ratio in the ChREBP(-/-) liver compared with control. Hepatic pyruvate carboxylase flux was impaired with ChREBP deletion secondary to decreased fatty acid oxidation, increased pyruvate oxidation, and limited pyruvate availability because of reduced activity of liver pyruvate kinase and malic enzyme, which replenish pyruvate via glycolysis and pyruvate cycling. Overall, the shift from fat utilization to pyruvate and lactate utilization resulted in a decrease in the energy of ATP hydrolysis and a hypo-energetic state in the livers of ChREBP(-/-) mice. C1 [Iizuka, Katsumi; Kitazume, Tatsuya; Uyeda, Kosaku] Univ Texas SW Med Sch, Dept Biochem, Adv Imaging Res Ctr, Dallas, TX 75390 USA. [Burgess, Shawn C.] Univ Texas SW Med Sch, Dept Pharmacol, Dallas, TX 75390 USA. [Uyeda, Kosaku] Dept Vet Affairs Med Ctr, Dallas, TX 75390 USA. [Jeoung, Nam Ho; Harris, Robert A.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Kashiwaya, Yoshihiro; Veech, Richard L.] NIAAA, Lab Met Control, NIH, Bethesda, MD 20892 USA. RP Uyeda, K (reprint author), Univ Texas SW Med Sch & Vet Affairs, Dept Biochem, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM kuyeda6400@aol.com OI Jeoung, Nam Ho/0000-0002-7584-3761; Iizuka, Katsumi/0000-0002-9837-6238 FU NCRR NIH HHS [RR 02584]; NIDDK NIH HHS [DK 063948-04, DK 076169, DK 47844] NR 34 TC 27 Z9 29 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 18 PY 2008 VL 283 IS 3 BP 1670 EP 1678 DI 10.1074/jbc.M706540200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250EL UT WOS:000252282700054 PM 18042547 ER PT J AU Guo, ZH Jiang, HY Xu, XR Duan, WZ Mattson, MP AF Guo, Zhihong Jiang, Haiyang Xu, Xiangru Duan, Wenzhen Mattson, Mark P. TI Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; AMPA RECEPTOR SUBUNITS; NEUROTROPHIC FACTOR; LIPID-PEROXIDATION; NITRIC-OXIDE; PHOSPHOINOSITIDE 3-KINASE; PEROXYNITRITE PRODUCTION; REPRODUCTIVE FUNCTION; INDUCED APOPTOSIS; OXIDATIVE STRESS AB Leptin plays a pivotal role in the regulation of energy homeostasis and metabolism, primarily by acting on neurons in the hypothalamus that control food intake. However, leptin receptors are more widely expressed in the brain suggesting additional, as yet unknown, functions of leptin. Here we show that both embryonic and adult hippocampal neurons express leptin receptors coupled to activation of STAT3 and phosphatidylinositol 3-kinase-Akt signaling pathways. Leptin protects hippocampal neurons against cell death induced by neurotrophic factor withdrawal and excitotoxic and oxidative insults. The neuroprotective effect of leptin is antagonized by the JAK2-STAT3 inhibitor AG-490, STAT3 decoy DNA, and phosphatidylinositol 3-kinase/Akt inhibitors but not by an inhibitor of MAPK. Leptin induces the production of manganese superoxide dismutase and the anti-apoptotic protein Bcl-xL, and stabilizes mitochondrial membrane potential and lessens mitochondrial oxidative stress. Leptin receptor-deficient mice (db/db mice) are more vulnerable to seizure-induced hippocampal damage, and intraventricular administration of leptin protects neurons against seizures. By enhancing mitochondrial resistance to apoptosis and excitotoxicity, our findings suggest that leptin signaling serves a neurotrophic function in the developing and adult hippocampus. C1 [Guo, Zhihong; Jiang, Haiyang; Xu, Xiangru; Duan, Wenzhen; Mattson, Mark P.] NIA, Neurosci Lab, Baltimore, MD 21224 USA. [Guo, Zhihong; Jiang, Haiyang; Xu, Xiangru; Duan, Wenzhen; Mattson, Mark P.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 60 TC 99 Z9 103 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 18 PY 2008 VL 283 IS 3 BP 1754 EP 1763 DI 10.1074/jbc.M703753200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250EL UT WOS:000252282700062 PM 17993459 ER PT J AU Casanovas, J Jimenez, AI Cativiela, C Nussinov, R Aleman, C AF Casanovas, Jordi Jimenez, Ana I. Cativiela, Carlos Nussinov, Ruth Aleman, Carlos TI 1-amino-2-phenylcyclopentane-1-carboxylic acid: A conformationally restricted phenylalanine analogue SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ALPHA-AMINOISOBUTYRIC-ACID; X-RAY-DIFFRACTION; TRANS-CYCLOHEXANE ANALOGS; C-ALPHA,ALPHA-DIALKYLATED GLYCINES; STRUCTURAL VERSATILITY; LINEAR OLIGOPEPTIDES; 1-AMINOCYCLOPENTANE-1-CARBOXYLIC ACID; SIDE-CHAIN; AMINO-ACIDS; MODEL PEPTIDES AB DFT calculations at the B3LYP/6-311G(d,p) level have been used to investigate the intrinsic conformational preferences of 1-amino-2-phenylcyclopentane-1-carboxylic acid (c(5)Phe), a constrained analogue of phenylalanine in which the alpha and beta carbons are included in a cyclopentane ring. Specifically, the N'-acetyl-N'-methylamide derivatives of the cis and trans stereoisomers, where cis and trans refer to the relative position between the amino group and the phenyl ring, have been calculated. Solvent effects have been examined using a self-consistent reaction field (SCRF) method. Results indicate that the conformational space of the cis stereoisomer is much more restricted than that of the trans derivative both in the gas phase and in solution. C1 [Casanovas, Jordi] Univ Lleida, Escola Politecn Super, Dept Quim, E-25001 Lleida, Spain. [Jimenez, Ana I.; Cativiela, Carlos] Univ Zaragoza, CSIC, Dept Quim Organ, Inst Ciencia Mat Aragon, E-50009 Zaragoza, Spain. [Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. [Aleman, Carlos] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain. RP Casanovas, J (reprint author), Univ Lleida, Escola Politecn Super, Dept Quim, C Jaume II 69, E-25001 Lleida, Spain. EM jcasanovas@quimica.iedl.cat; anisjim@unizar.es; carlos.aleman@upc.edu RI Casanovas, Jordi/B-5435-2013 OI Casanovas, Jordi/0000-0002-4914-9194 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 74 TC 11 Z9 11 U1 0 U2 3 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 JAN 18 PY 2008 VL 73 IS 2 BP 644 EP 651 DI 10.1021/jo702107s PG 8 WC Chemistry, Organic SC Chemistry GA 250UA UT WOS:000252325200039 PM 18081347 ER PT J AU Sacho, EJ Kadyrov, FA Modrich, P Kunkel, TA Erie, DA AF Sacho, Elizabeth J. Kadyrov, Farid A. Modrich, Paul Kunkel, Thomas A. Erie, Dorothy A. TI Direct visualization of asymmetric adenine nucleotide-induced conformational changes in MutL alpha SO MOLECULAR CELL LA English DT Article ID DNA MISMATCH REPAIR; C-TERMINAL DOMAIN; FUNCTIONAL ANTHOLOGY; INTRINSIC DISORDER; CRYSTAL-STRUCTURE; TOPOISOMERASE-VI; HSP90 CHAPERONE; ATPASE ACTIVITY; HMUTS-ALPHA; GHL ATPASE AB MutL alpha, the heterodimeric eukaryotic MutL homolog, is required for DNA mismatch repair (MMR) in vivo. It has been suggested that conformational changes, modulated by adenine nucleotides, mediate the interactions of MutLa with other proteins in the MMR pathway, coordinating the recognition of DNA mismatches by MutS alpha and the activation of MutL alpha with the downstream events that lead to repair. Thus far, the only evidence for these conformational changes has come from X-ray crystallography of isolated domains, indirect biochemical analyses, and comparison to other members of the GHL ATPase family to which MutL alpha belongs. Using atomic force microscopy (AFM), coupled with biochemical techniques, we demonstrate that adenine nucleotides induce large asymmetric conformational changes in full-length yeast and human MutL alpha and that these changes are associated with significant increases in secondary structure. These data reveal an ATPase cycle in which sequential nucleotide binding, hydrolysis, and release modulate the conformational states of MutL alpha. C1 [Sacho, Elizabeth J.; Erie, Dorothy A.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Modrich, Paul] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. [Modrich, Paul] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Erie, DA (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. EM derie@unc.edu OI Sacho, Elizabeth/0000-0002-4499-5869 FU Intramural NIH HHS [Z01 ES065089-11]; NIGMS NIH HHS [R01 GM079480-02, R01 GM079480, R01 GM045190, GM45190] NR 58 TC 65 Z9 68 U1 2 U2 17 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 JAN 18 PY 2008 VL 29 IS 1 BP 112 EP 121 DI 10.1016/j.molcel.2007.10.030 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 253NN UT WOS:000252525000011 PM 18206974 ER PT J AU Uawithya, P Pisitkun, T Ruttenberg, BE Knepper, MA AF Uawithya, Panapat Pisitkun, Trairak Ruttenberg, Brian E. Knepper, Mark A. TI Transcriptional profiling of native inner medullary collecting duct cells from rat kidney SO PHYSIOLOGICAL GENOMICS LA English DT Review DE oligonucleotide array; vasopressin; aquaporin-2; urea transport; kinases ID EPITHELIAL SODIUM-CHANNEL; GENE-EXPRESSION PROFILES; RENAL PRINCIPAL CELLS; AQUAPORIN-2 TRAFFICKING; UREA TRANSPORTER; PLASMA-MEMBRANE; WATER CHANNEL; BINDING-PROTEIN; INTRACELLULAR VESICLES; ESSENTIAL REGULATOR AB Vasopressin acts on the inner medullary collecting duct (IMCD) in the kidney to regulate water and urea transport. To obtain a "parts list" of gene products expressed in the IMCD, we carried out mRNA profiling of freshly isolated rat IMCD cells using Affymetrix Rat 230 2.0 microarrays with similar to 31,000 features; 7,913 annotated transcripts were found to be expressed above background in the IMCD cells. We have created a new online database (the "IMCD Transcriptome Database;" http://dir.nhlbi.nih.gov/papers/lkem/imcdtr/)to make the results publicly accessible. Among the 30 transcripts with the greatest signals on the arrays were 3 water channels: aquaporin-2, aquaporin-3, and aquaporin-4, all of which have been reported to be targets for regulation by vasopressin. In addition, the transcript with the greatest signal among members of the solute carrier family of genes was the UT-A urea transporter (Slc14a2), which is also regulated by vasopressin. The V2 vasopressin receptor was strongly expressed, but the V1a and V1b vasopressin receptors did not produce signals above background. Among the 200 protein kinases expressed, the serum-glucocorticoid-regulated kinase (Sgk1) had the greatest signal intensity in the IMCD. WNK1 and WNK4 were also expressed in the IMCD with a relatively high signal intensity, as was protein kinase A (beta-catalytic subunit). In addition, a large number of transcripts corresponding to A kinase anchoring proteins and 14-3-3 proteins (phospho-S/T-binding proteins) were expressed. Altogether, the results combine with proteomics studies of the IMCD to provide a framework for modeling complex interaction networks responsible for vasopressin action in collecting duct cells. C1 [Uawithya, Panapat; Pisitkun, Trairak; Ruttenberg, Brian E.; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM Knepperm@nhlbi.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21]; NHLBI NIH HHS [Z01 HL001285] NR 102 TC 61 Z9 63 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JAN 17 PY 2008 VL 32 IS 2 BP 229 EP 253 DI 10.1152/physiolgenomics.00201.2007 PG 25 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 314NH UT WOS:000256815600008 PM 17956998 ER PT J AU Glynn, SA O'Sullivan, D Eustace, AJ Clynes, M O'Donovan, N AF Glynn, Sharon A. O'Sullivan, Dermot Eustace, Alex J. Clynes, Martin O'Donovan, Norma TI The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells SO BMC CANCER LA English DT Article ID BREAST-CANCER CELLS; COLORECTAL-CANCER; CARCINOMA CELLS; LOWERING DRUGS; IN-VITRO; STATINS; RISK; METAANALYSIS; CHOLESTEROL; APOPTOSIS AB Background: A number of recent studies have suggested that cancer incidence rates may be lower in patients receiving statin treatment for hypercholesterolemia. We examined the effects of statin drugs on in vitro proliferation, migration and invasion of melanoma cells. Methods: The ability of lovastatin, mevastatin and simvastatin to inhibit the melanoma cell proliferation was examined using cytotoxicity and apoptosis assays. Effects on cell migration and invasion were assessed using transwell invasion and migration chambers. Hypothesis testing was performed using 1-way ANOVA, and Student's t-test. Results: Lovastatin, mevastatin and simvastatin inhibited the growth, cell migration and invasion of HT144, M14 and SK-MEL-28 melanoma cells. The concentrations required to inhibit proliferation of melanoma cells (0.8-2.1 mu M) have previously been achieved in a phase I clinical trial of lovastatin in patients with solid tumours, (45 mg/kg/day resulted in peak plasma concentrations of approximately 3.9 mu M). Conclusion: Our results suggest that statin treatment is unlikely to prevent melanoma development at standard doses. However, higher doses of statins may have a role to play in adjuvant therapy by inhibiting growth and invasion of melanoma cells. C1 [Glynn, Sharon A.; O'Sullivan, Dermot; Eustace, Alex J.; Clynes, Martin; O'Donovan, Norma] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland. [Glynn, Sharon A.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Glynn, SA (reprint author), Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland. EM glynnsh@mail.nih.gov; dermot.osullivan2@mail.dcu.ie; alex.eustace@dcu.ie; martin.clynes@dcu.ie; norma.odonovan@dcu.ie RI O'Donovan, Norma/B-6710-2013; Glynn, Sharon/D-7136-2013; OI Glynn, Sharon/0000-0003-1459-2580; Eustace, Alex/0000-0002-4092-1360; O'Donovan, Norma/0000-0003-1113-3872 NR 35 TC 53 Z9 57 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JAN 16 PY 2008 VL 8 AR 9 DI 10.1186/1471-2407-8-9 PG 9 WC Oncology SC Oncology GA 268RF UT WOS:000253596400001 PM 18199328 ER PT J AU Pastor, MC Bradley, MM Low, A Versace, F Molto, J Lang, PJ AF Pastor, M. Carmen Bradley, Margaret M. Low, Andreas Versace, Francesco Molto, Javier Lang, Peter J. TI Affective picture perception: Emotion, context, and the late positive potential SO BRAIN RESEARCH LA English DT Article DE emotion; event-related potentials; pictures; attention; late positive potential ID BRAIN POTENTIALS; VISUAL-CORTEX; HABITUATION; STIMULI; AROUSAL; NOVELTY AB Event-related potentials (ERP) were measured when pleasant, neutral or unpleasant pictures were presented in the context of similarly valenced stimuli, and compared to ERPs elicited when the same pictures were viewed in an intermixed context. An early ERP component (150-300 ms) measured over occipital and fronto-central sensors was specific to viewing pleasant pictures and was not affected by presentation context. Replicating previous studies, emotional pictures prompted a larger late positive potential (LPP, 400-700 ms) and a larger positive slow wave (1-6 s) over centro-parietal sensors that also did not differ by presentation context. On the other hand, ERPs elicited when viewing neutral pictures varied as a function of context, eliciting somewhat larger LPPs when presented in blocks, and prompting smaller slow waves over occipital sensors. Taken together, the data indicate that emotional pictures prompt increased attention and orienting that is unaffected by its context of presentation, whereas neutral pictures are more vulnerable to context manipulations. (c) 2007 Elsevier B.V. All rights reserved. C1 [Pastor, M. Carmen; Molto, Javier] Jaume I Univ, Dept Psychol, Castellon de La Plana 12071, Spain. [Pastor, M. Carmen; Bradley, Margaret M.; Low, Andreas; Versace, Francesco; Lang, Peter J.] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL USA. RP Pastor, MC (reprint author), Jaume I Univ, Dept Psychol, Ave Sos Baynat S-N, Castellon de La Plana 12071, Spain. EM mpastor@psb.uji.es RI Frank, David/E-8213-2012; Pastor, M. Carmen/H-7183-2015; OI Pastor, M. Carmen/0000-0001-9909-3646; Molto, Javier/0000-0001-5539-966X FU NIDCR NIH HHS [DE 13956, R01 DE013956]; NIMH NIH HHS [P50 MH 72850, P50 MH072850, P50 MH072850-010003] NR 29 TC 69 Z9 70 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 16 PY 2008 VL 1189 BP 145 EP 151 DI 10.1016/j.brainres.2007.10.072 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 264MN UT WOS:000253291800015 PM 18068150 ER PT J AU Liu, H Etter, P Hayes, S Jones, I Nelson, B Hartman, B Forrest, D Reh, TA AF Liu, Hong Etter, Paige Hayes, Susan Jones, Iwan Nelson, Branden Hartman, Byron Forrest, Douglas Reh, Thomas A. TI NeuroD1 regulates expression of thyroid hormone receptor beta 2 and cone opsins in the developing mouse retina SO JOURNAL OF NEUROSCIENCE LA English DT Article DE TR beta 2; S-opsin; M-opsin; proneural; bHLH; photoreceptor ID PHOTORECEPTOR DEVELOPMENT; GENE-EXPRESSION; HOMEOBOX GENE; CELL FATE; DIFFERENTIATION; BETA2/NEUROD1; GRADIENT AB The correct patterning of opsin expression in cone photoreceptors is critical for normal color vision. Thyroid hormone, and one of its receptors [thyroid hormone receptor beta 2 (TR beta 2)], is an important regulator of opsin expression during cone photoreceptor development. Mice have two genes, encoding medium-wavelength (M) and short-wavelength (S) cone opsins. Targeted deletion of TR beta 2 leads to a uniform expression of S-opsin in all cone photoreceptors and a loss of M-opsin. The control of expression of TR beta 2 is therefore central to cone differentiation, yet there is little known about its regulation in the retina. Wenow report that the proneural bHLH basic helix-loop-helix) transcription factor, NeuroD1, is necessary for sustained expression of TR beta 2 in immature cone photoreceptors. Mice deficient in NeuroD1 develop an opsin phenotype virtually identical with that of TR beta 2-deficient mice: all cones express S-opsin, and none expresses M-opsin. The introduction of NeuroD1 into embryonic retinal explants from NeuroD1(-/-) mice restores TR beta 2 expression. NeuroD1 binds an E-box in the intron control region of the TR beta 2 gene that mediates cone-specific expression, suggesting that NeuroD1 is a critical contributory factor to the expression of TR beta 2 in cones. These results thus connect the proneural pathway with opsin selection to ensure correct cone patterning during retinal development. C1 [Etter, Paige; Hayes, Susan; Nelson, Branden; Hartman, Byron; Reh, Thomas A.] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. [Liu, Hong; Forrest, Douglas] Natl Inst Hlth, Clin Endocrinol Branch, NIDDK, Bethesda, MD 20892 USA. RP Reh, TA (reprint author), Univ Washington, Dept Biol Struct, Box 357420, Seattle, WA 98195 USA. EM tomreh@u.washington.edu FU Intramural NIH HHS; NICHD NIH HHS [T32 HD007183]; NIDCD NIH HHS [DC03441]; NINDS NIH HHS [NS28308] NR 26 TC 37 Z9 38 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 16 PY 2008 VL 28 IS 3 BP 749 EP 756 DI 10.1523/JNEUROSCI.4832-07.2008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 252FP UT WOS:000252432700018 PM 18199774 ER PT J AU Dreher, MR Simnick, AJ Fischer, K Smith, RJ Patel, A Schmidt, M Chilkoti, A AF Dreher, Matthew R. Simnick, Andrew J. Fischer, Karl Smith, Richard J. Patel, Anand Schmidt, Manfred Chilkoti, Ashutosh TI Temperature triggered self-assembly of polypeptides into multivalent spherical micelles SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEIN-BASED POLYMERS; ELASTIN-LIKE POLYPEPTIDES; FREE-ENERGY TRANSDUCTION; BLOCK-COPOLYMERS; DRUG-DELIVERY; REVERSIBLE HYDROGELS; LIGHT-SCATTERING; CHAIN-LENGTH; TUMOR; BIOMATERIALS AB We report herein thermally responsive elastin-like polypeptides (ELPs) in a linear AB diblock architecture with an N-terminal peptide ligand that self-assemble into spherical micelles when heated slightly above body temperature. A series of 10 ELP block copolymers (ELPBC's) with different molecular weights and hydrophilic-to-hydrophobic block ratios were genetically synthesized by recursive directional ligation. The self-assembly of these polymers from unimers into micelles was investigated by light scattering, fluorescence spectroscopy, and cryo-TEM. These ELPBC's undergo two phase transitions as a function of solution temperature: a unimer-to-spherical micelle transition at an intermediate temperature and a micelle-to-bulk aggregate transition at a higher temperature when the. hydrophilic-to-hydrophobic block ratio is between 1:2 and 2:1. The critical micelle temperature is controlled by the length of the hydrophobic block, and the size of the micelle is controlled by both the total ELPBC length and hydrophilic-to-hydrophobic block ratio. These polypeptide micelles display a critical micelle concentration in the range 4-8 mu M demonstrating the high stability of these structures. These studies have also identified a subset of ELPBC's bearing terminal peptide ligands that are capable of forming multivalent spherical micelles that present multiple copies of the ligand on their corona in the clinically relevant temperature range 37-42 degrees C and target cancer cells. These ELPBC's may be useful for drug targeting" by thermally triggered multivalency. More broadly, the design rules uncovered by this study should be applicable to the design of other thermally reversible nanoparticles for diverse applications in medicine and biology. C1 [Dreher, Matthew R.; Simnick, Andrew J.; Smith, Richard J.; Patel, Anand; Chilkoti, Ashutosh] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. [Dreher, Matthew R.] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Fischer, Karl; Schmidt, Manfred] Johannes Gutenberg Univ Mainz, Inst Phys Chem, D-6500 Mainz, Germany. RP Chilkoti, A (reprint author), Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. EM chilkoti@duke.edu FU Intramural NIH HHS; NIBIB NIH HHS [EB-000188, R01 EB000188, R01 EB000188-07] NR 55 TC 168 Z9 170 U1 23 U2 146 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 16 PY 2008 VL 130 IS 2 BP 687 EP 694 DI 10.1021/ja0764862 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 250IF UT WOS:000252292500064 PM 18085778 ER PT J AU Narazaki, M Segarra, M Tosato, G AF Narazaki, Masashi Segarra, Marta Tosato, Giovanna TI Neuropilin-2: A new molecular target for antiangiogenic and antitumor strategies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; ANTI-VEGF; CANCER; ANGIOGENESIS; SEMAPHORIN; CELLS; INHIBITION; EXPRESSION; VEGF(165); BIOLOGY C1 [Segarra, Marta; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Narazaki, Masashi] Osaka Univ, Grad Sch Med, Dept Resp Med Allergy & Rheumat Dis, Osaka, Japan. RP Tosato, G (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bldg 37,Rm 4124, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov OI narazaki, masashi/0000-0002-5613-4409 NR 31 TC 5 Z9 5 U1 0 U2 0 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 JAN 16 PY 2008 VL 100 IS 2 BP 81 EP 83 DI 10.1093/jnci/djm305 PG 3 WC Oncology SC Oncology GA 258FO UT WOS:000252854000002 PM 18182614 ER PT J AU Baba, M Furihata, M Hong, SB Tessarollo, L Haines, DC Southon, E Patel, V Igarashi, P Alvord, WG Leighty, R Yao, M Bernardo, M Ileva, L Choyke, P Warren, MB Zbar, B Linehan, WM Schmidt, LS AF Baba, Masaya Furihata, Mutsuo Hong, Seung-Beom Tessarollo, Lino Haines, Diana C. Southon, Eileen Patel, Vishal Igarashi, Peter Alvord, W. Gregory Leighty, Robert Yao, Masahiro Bernardo, Marcelino Ileva, Lilia Choyke, Peter Warren, Michelle B. Zbar, Berton Linehan, W. Marston Schmidt, Laura S. TI Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; GERMAN-SHEPHERD DOG; BHD GENE; INTERCALATED CELLS; RENAL-CARCINOMA; NODULAR DERMATOFIBROSIS; GENITOURINARY TRACT; COLLECTING DUCT; RAT MODEL; CANCER AB Background Patients with Birt-Hogg-Dube ( BHD) syndrome harbor germline mutations in the BHD tumor suppressor gene that are associated with an increased risk for kidney cancer. BHD encodes folliculin, a protein that may interact with the energy- and nutrient-sensing 5'-AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling pathways. Methods We used recombineering methods to generate mice with a conditional BHD allele and introduced the cadherin 16 ( KSP)-Cre transgene to target BHD inactivation to the kidney. Kidney cell proliferation was measured by BrdU incorporation and phospho-histone H3 staining. Kidney weight data were analyzed with Wilcoxon's rank-sum, Student's t, and Welch's t tests. Hematoxylin and eosin staining and immunoblot analysis and immunohistochemistry of cell cycle and signaling proteins were performed on mouse kidney cells and tissues. BHD knockout mice and kidney cells isolated from BHD knockout and control mice were treated with the mTOR inhibitor rapamycin. Mouse survival was evaluated by Kaplan-Meier analyses. All statistical tests were two-sided. Results BHD knockout mice developed enlarged polycystic kidneys and died from renal failure by 3 weeks of age. Targeted BHD knockout led to the activation of Raf-extracellular signal-regulated protein kinase ( Erk)1/ 2 and Akt-mTOR pathways in the kidneys and increased expression of cell cycle proteins and cell proliferation. Rapamycin-treated BHD knockout mice had smaller kidneys than buffer-treated BHD knockout mice had ( n = 4 - 6 mice per group, relative kidney/ body weight ratios, mean = 4.64% vs 12.2%, difference = 7.6%, 95% confidence interval = 5.2% to 10.0%; P <.001) and longer median survival time ( n = 4 - 5 mice per group, 41.5 vs 23 days; P =.0065). Conclusions Homozygous loss of BHD may initiate renal tumorigenesis in the mouse. The conditional BHD knockout mouse may be a useful research model for dissecting multistep kidney carcinogenesis, and rapamycin may be considered as a potential treatment for Birt-Hogg-Dube syndrome. C1 [Baba, Masaya; Hong, Seung-Beom; Warren, Michelle B.; Zbar, Berton; Linehan, W. Marston; Schmidt, Laura S.] Natl Canc Inst, Urol Oncol Branch, Ft Detrick, MD 21702 USA. [Tessarollo, Lino] Mouse Canc Genet Program, Frederick, MD USA. [Haines, Diana C.] Ctr Canc Res, Pathol Histechnol Lab, Frederick, MD USA. [Southon, Eileen; Schmidt, Laura S.] Basic Res Program, Frederick, MD USA. [Ileva, Lilia] Lab Anim Sci Program, Small Anim Imaging Program, Frederick, MD USA. [Alvord, W. Gregory; Leighty, Robert] SAIC Frederick Inc, Frederick, MD USA. [Alvord, W. Gregory; Leighty, Robert] Data Management Serv Inc, Frederick, MD USA. [Baba, Masaya; Hong, Seung-Beom; Warren, Michelle B.; Zbar, Berton; Linehan, W. Marston; Schmidt, Laura S.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD USA. [Baba, Masaya; Choyke, Peter] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Mol Imaging Program, Bethesda, MD USA. [Furihata, Mutsuo] Kochi Med Sch, Dept Pathol, Kochi, Japan. [Patel, Vishal; Igarashi, Peter] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Yao, Masahiro] Yokohama City Univ, Grad Sch Med, Dept Urol & Mol Genet, Yokohama, Kanagawa 232, Japan. RP Schmidt, LS (reprint author), Natl Canc Inst, Urol Oncol Branch, Bldg 560,Rm 12-69, Ft Detrick, MD 21702 USA. EM schmidtl@ncifcrf.gov RI Baba, Masaya/L-7490-2013; OI Baba, Masaya/0000-0002-5308-6683; Igarashi, Peter/0000-0001-8698-1185; Patel, Vishal/0000-0003-2875-4659 FU Intramural NIH HHS [Z01 SC006659-25]; NCI NIH HHS [N01 CO012400]; NIDDK NIH HHS [P30DK079328, P30 DK079328, R01 DK067565, R37 DK042921]; PHS HHS [N01 C012400] NR 43 TC 112 Z9 114 U1 0 U2 5 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 JAN 16 PY 2008 VL 100 IS 2 BP 140 EP 154 DI 10.1093/jnci/djm288 PG 15 WC Oncology SC Oncology GA 258FO UT WOS:000252854000012 PM 18182616 ER PT J AU Duan, RQ Ginsburg, E Vonderhaar, BK AF Duan, Renqin Ginsburg, Erika Vonderhaar, Barbara K. TI Estrogen stimulates transcription from the human prolactin distal promoter through AP1 and estrogen responsive elements in T47D human breast cancer cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE estrogen; prolactin; autocrine/paracrine; breast cancer; promoter; extrapituitary ID STEROID-HORMONE RECEPTORS; MAMMARY-GLAND DEVELOPMENT; ENDOTHELIAL GROWTH-FACTOR; PROGESTERONE RECEPTORS; GENE-TRANSCRIPTION; SELECTIVE LIGANDS; MESSENGER-RNA; ER-ALPHA; IN-VIVO; EXPRESSION AB Human prolactin (hPRL) is a pleiotropic and versatile hormone that exercises more than 300 biological activities through binding to its cognate receptors. Recently, multiple studies have implicated hPRL in the development of human breast cancer. As a target of hPRL, both normal and neoplastic human breast cells also synthesize and secrete hPRL, which therefore establishes an autocrine/paracrine action loop in the mammary gland. In contrast to the extensive studies of regulation of hPRL expression in the pituitary gland, regulation of hPRL in mammary tissue and human breast cancer cells has not been extensively addressed. Extrapituitary PRL expression is primarily regulated by a distal promoter located 5.8 kb upstream to the pituitary promoter. As a result of alternative promoter usage, extrapituitary PRL is regulated by different signalling pathways and different hormones, cytokines or neuropeptides compared to regulation in the pituitary. Here, we present evidence that shows estrogen directly induces hPRL gene expression in T47D human breast cancer cells. We have identified a functional, non-canonical estrogen responsive element (ERE) and an AP1 site located in the hPRL distal promoter. Gel shift and chromatin immunoprecipitation assays demonstrated that both estrogen receptor (ER)alpha and ER beta directly bind to the ERE. However, only ER alpha interacts with AP1 proteins that bind to the AP1 site in the hPRL distal promoter. Promoter-reporter gene studies demonstrate that both ERE and AP1 sites are required for full induction of the promoter activity by estradiol. Our studies suggest that the interactions between estrogens, ERs, the ERE and AP1 transcription factors in regulation of autocrine/paracrine PRL in the human breast may be critical for oncogenesis and may contribute to progression of breast cancer. Published by Elsevier Ireland Ltd. C1 [Duan, Renqin; Ginsburg, Erika; Vonderhaar, Barbara K.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. RP Vonderhaar, BK (reprint author), Natl Inst Hlth, Mol & Cellular Endocrinol Sect, Mammary Biol & Tumorigenesis Lab, Bldg 37 Room 1160A1,37 Convent Dr, Bethesda, MD 20892 USA. EM bv10w@nih.gov FU Intramural NIH HHS NR 57 TC 24 Z9 25 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 16 PY 2008 VL 281 IS 1-2 BP 9 EP 18 DI 10.1016/j.mce.2007.10.004 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 262BQ UT WOS:000253124400002 PM 18022314 ER PT J AU Neubert, JK Mannes, AJ Karai, LJ Jenkins, AC Zawatski, L Abu-Asab, M Iadarola, MJ AF Neubert, John K. Mannes, Andrew J. Karai, Laszlo J. Jenkins, Alan C. Zawatski, Lanel Abu-Asab, Mones Iadarola, Michael J. TI Perineural resiniferatoxin selectively inhibits inflammatory hyperalgesia SO MOLECULAR PAIN LA English DT Article ID VANILLOID RECEPTOR-1; CAPSAICIN RECEPTOR; PERIPHERAL-NERVE; TRP CHANNELS; IN-VIVO; PAIN; RAT; NOCICEPTION; ANTAGONIST; ANALGESIA AB Resiniferatoxin (RTX) is an ultrapotent capsaicin analog that binds to the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1). There is a large body of evidence supporting a role for TRPV1 in noxious-mediated and inflammatory hyperalgesic responses. In this study, we evaluated low, graded, doses of perineural RTX as a method for regional pain control. We hypothesized that this approach can provide long-term, but reversible, blockade of a portion of nociceptive afferent fibers within peripheral nerves when given at a site remote from the neuronal perikarya in the dorsal root ganglia. Following perineural RTX application to the sciatic nerve, we demonstrated a significant inhibition of inflammatory nociception that was dose- and time-dependent. At the same time, treated animals maintained normal proprioceptive sensations and motor control, and other nociceptive responses were largely unaffected. Using a range of mechanical and thermal algesic tests, we found that the most sensitive measure following perineural RTX administration was inhibition of inflammatory hyperalgesia. Recovery studies showed that physiologic sensory function could return as early as two weeks post-RTX treatment, however, immunohistochemical examination of the DRG revealed a partial, but significant reduction in the number of the TRPV1-positive neurons. We propose that this method could represent a beneficial treatment for a range of chronic pain problems, including neuropathic and inflammatory pain not responding to other therapies. C1 [Neubert, John K.; Jenkins, Alan C.] Univ Florida, Dept Orthodont, Coll Dent, Gainesville, FL 32611 USA. [Neubert, John K.] Univ Florida, Dept Neurosci, Coll Med, Gainesville, FL USA. [Neubert, John K.] Univ Florida, Evelyn F & William L McKnight Brain Inst, Gainesville, FL USA. [Karai, Laszlo J.; Zawatski, Lanel; Iadarola, Michael J.] Natl Inst Dent & Craniofac Res, Lab Sensory Biol, Neurobiol & Pain Therapeut Sect, Bethesda, MD USA. [Abu-Asab, Mones] Natl Canc Inst, Sect Ultrastruct Pathol, Natl Inst Hlth, Bethesda, MD USA. RP Neubert, JK (reprint author), Univ Florida, Dept Orthodont, Coll Dent, Gainesville, FL 32611 USA. EM jneubert@dental.ufl.edu; amannes@mail.nih.gov; lkarai@mail.nih.gov; ajenkins@dental.ufl.edu; lzawatski@temple.edu; amones@mail.nih.gov; miadarola@dir.nidcr.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232; Mannes, Andrew/0000-0001-5834-5667 FU NIDCR NIH HHS [1K22DE014865-01A1, K22 DE014865] NR 35 TC 23 Z9 23 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD JAN 16 PY 2008 VL 4 AR 3 DI 10.1186/1744-8069-4-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 265XE UT WOS:000253394300001 PM 18199335 ER PT J AU Li, CI Malone, KE Daling, JR Potter, JD Bernstein, L Marchbanks, PA Strom, BL Simon, MS Press, MF Ursin, G Burkman, RT Folger, SG Norman, S McDonald, JA Spirtas, R AF Li, Christopher I. Malone, Kathleen E. Daling, Janet R. Potter, John D. Bernstein, Leslie Marchbanks, Polly A. Strom, Brian L. Simon, Michael S. Press, Michael F. Ursin, Giske Burkman, Ronald T. Folger, Suzanne G. Norman, Sandra McDonald, Jill A. Spirtas, Robert TI Timing of menarche and first full-term birth in relation to breast cancer risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; histology; menarche; menopause; pregnancy; premenopause; receptors, estrogen; receptors, progesterone ID REPRODUCTIVE FACTORS; WOMEN; AGE; CARCINOMA AB Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of >= 16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had <= 5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women. C1 [Li, Christopher I.; Malone, Kathleen E.; Daling, Janet R.; Potter, John D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Bernstein, Leslie; Ursin, Giske] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA USA. [Bernstein, Leslie; Ursin, Giske] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Marchbanks, Polly A.; Folger, Suzanne G.; McDonald, Jill A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. [Strom, Brian L.; Norman, Sandra] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Strom, Brian L.; Norman, Sandra] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA USA. [Ursin, Giske] Univ Oslo, Fac Med, Dept Nutr, Oslo, Norway. [Burkman, Ronald T.] Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. [Spirtas, Robert] NICHHD, Populat Res Ctr, Bethesda, MD 20892 USA. RP Li, CI (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-C308,POB 19024, Seattle, WA 98109 USA. EM cili@fhcrc.org OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [P30 CA022453]; NICHD NIH HHS [N01 HD023166, N01 HD033174, N01 HD033175, N01 HD033176, N01-HD-2-3166, N01-HD-2-3168, N01-HD-3-3174, N01-HD-3-3175, N01-HD-3-3176, Y01 HD007022, Y01-HD-7022] NR 17 TC 52 Z9 52 U1 0 U2 3 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 JAN 15 PY 2008 VL 167 IS 2 BP 230 EP 239 DI 10.1093/aje/kwm271 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 253DF UT WOS:000252498200013 PM 17965112 ER PT J AU Goodwin, H Brooks, BP Porter, FD AF Goodwin, Halima Brooks, Brian P. Porter, Forbes D. TI Acute postnatal cataract formation in Smith-Lemh-Opitz syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Smith-Lemli-Opitz syndrome; SLOS; RSH syndrome; DHCR7; cataracts; inborn errors of cholesterol synthesis ID CHOLESTEROL-BIOSYNTHESIS AB We report on two patients with severe Smith-Lemli-Opitz syndrome who acutely developed postnatal cataracts. These postnatal cataracts appear to be due to a different pathological mechanism and have a different clinical Course than the typical congenital cataracts that occur in SLOS. The rapid development of these cataracts suggests that dysfunction or rupture of the lens capsule leading to acute osmotic shifts contributes to their formation. In addition, cataract formation in these patients was associated with conjunctival injection, fibrotic irido-lenticular adhesions, and capsular fibrosis. These findings are suggestive an inflammatory component that is consistent with impaired competence of the lens capsule. (c) 2007 Wiley-Liss, Inc. C1 [Goodwin, Halima; Porter, Forbes D.] NICHHD, Heritable Disorders Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Porter, FD (reprint author), NICHHD, Heritable Disorders Branch, NIH, DHHS, Bld 10,Rm 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov FU Intramural NIH HHS NR 10 TC 4 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN 15 PY 2008 VL 146A IS 2 BP 208 EP 211 DI 10.1002/ajmg.a.32084 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 248EJ UT WOS:000252134400010 PM 18076100 ER PT J AU Hoshino, T Young, HA Aizawa, H AF Hoshino, Tomoaki Young, Howard A. Aizawa, Hisamichi TI Cytokines in pulmonary emphysema: Can results in mice be translated to humans? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID IL-18; INFLAMMATION C1 [Hoshino, Tomoaki; Aizawa, Hisamichi] Kurume Univ, Kurume, Fukuoka 830, Japan. [Young, Howard A.] NCI, Frederick, MD 21701 USA. RP Hoshino, T (reprint author), Kurume Univ, Kurume, Fukuoka 830, Japan. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2008 VL 177 IS 2 BP 238 EP 239 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 251BJ UT WOS:000252345300022 ER PT J AU Loomba, R Ghany, M AF Loomba, Rohit Ghany, Marc TI Association between body mass index and diabetes and hepatocellular carcinoma SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID OBESITY; RISK C1 [Loomba, Rohit; Ghany, Marc] Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, Bethesda, MD 20892 USA. RP Loomba, R (reprint author), Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 2008 VL 148 IS 2 BP 166 EP 167 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 254NZ UT WOS:000252594600013 PM 18195343 ER PT J AU Zou, TT Liu, L Raot, JN Marasa, BS Chen, J Xiao, L Zhou, HP Gorospe, M Wang, JY AF Zou, Tongtong Liu, Lan Raot, Jaladanki N. Marasa, Bernard S. Chen, Jie Xiao, Lan Zhou, Huiping Gorospe, Myriam Wang, Jian-Ying TI Polyamines modulate the subcellular localization of RNA-binding protein HuR through AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha 1 SO BIOCHEMICAL JOURNAL LA English DT Article DE AMP-activated protein kinase (AMPK); growth arrest; HuR; importin alpha 1; intestinal epithelium; ornithine decarboxylase ID INTESTINAL EPITHELIAL-CELLS; PROXIMAL PROMOTER REGION; KAPPA-B ACTIVATION; MESSENGER-RNA; C-MYC; CYTOPLASMIC HUR; MUCOSAL GROWTH; ENERGY-CHARGE; IEC-6 CELLS; DEPLETION AB Polyamines are required for maintenance of intestinal epithelial integrity, and a decrease in cellular polyamines increases the cytoplasmic levels of RNA-binding protein HuR stabilizing p53 and nucleophosmin mRNAs, thus inhibiting IEC (intestinal epithelial cell) proliferation. The AMPK (AMP-activated protein kinase), an enzyme involved in responding to metabolic stress, was recently found to be implicated in regulating the nuclear import of HuR. Here, we provide evidence showing that polyamines modulate subcellular localization of HuR through AMPK-regulated phosphorylation and acetylation of Imp alpha 1 (importin alpha 1) in IECs. Decreased levels of cellular polyamines as a result of inhibiting ODC (ornithine decarboxylase) with DFMO (D,L-alpha-difluoromethylornithine) repressed AMPK activity and reduced Imp alpha 1 levels, whereas increased levels of polyamines as a result of ODC overexpression induced both AMPK and Imp alpha 1 levels. AMPK activation by overexpression of the AMPK gene increased Imp alpha 1 but reduced the cytoplasmic levels of HuR in control and polyamine-deficient cells. IECs overexpressing wild-type Imp alpha 1 exhibited a decrease in cytoplasmic HuR abundance, while cells overexpressing Imp alpha 1 proteins bearing K22R (lacking acetylation site), S105A (lacking phosphorylation site) or K22R/S105A (lacking both sites) mutations displayed increased levels of cytoplasmic HuR. Ectopic expression of these Imp alpha 1 mutants also prevented the increased levels of cytoplasmic HuR following polyamine depletion. These results indicate that polyamine-mediated AMPK activation triggers HuR nuclear import through phosphorylation and acetylation of Imp alpha 1 in IECs and that polyamine depletion increases cytoplasmic levels of HuR as a result of inactivation of the AMPK-driven Imp alpha 1 pathway. C1 [Zou, Tongtong; Liu, Lan; Raot, Jaladanki N.; Chen, Jie; Xiao, Lan; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Surg Serv, Baltimore, MD 21201 USA. [Zou, Tongtong; Liu, Lan; Raot, Jaladanki N.; Marasa, Bernard S.; Chen, Jie; Xiao, Lan; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA. [Marasa, Bernard S.; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Zhou, Huiping] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA. [Gorospe, Myriam] NIA, NIH, IRP Intramural Res Program, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Wang, JY (reprint author), Baltimore Vet Affairs Med Ctr, Surg Serv, 112,10 N Greene St, Baltimore, MD 21201 USA. EM jwang@smail.umaryland.edu FU NIAID NIH HHS [AI-68432]; NIDDK NIH HHS [DK-68491, DK-57819, DK-61972] NR 55 TC 34 Z9 37 U1 1 U2 2 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2008 VL 409 BP 389 EP 398 DI 10.1042/BJ20070860 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 259BV UT WOS:000252915000007 PM 17919121 ER PT J AU Bosedasgupta, S Das, BB Sengupta, S Ganguly, A Roy, A Tripathi, G Majumder, HK AF Bosedasgupta, Somdeb Das, Benu Brata Sengupta, Souvik Ganguly, Agneyo Roy, Annit Tripathi, Gayatri Majumder, Hemanta K. TI Amino acids 39-456 of the large subunit and 210-262 of the small subunit constitute the minimal functionally interacting fragments of the unusual heterodimeric topoisomerase IB of Leishmania SO BIOCHEMICAL JOURNAL LA English DT Article DE co-immobilization; DNA topoisomerase; far-Westem analysis; fragment complementation; Leishmania; substrate competition ID DNA TOPOISOMERASE; RNA INTERFERENCE; DONOVANI; RECONSTITUTION AB The unusual, heterodimeric topoisomerase 113 of Leishmania shows functional activity upon reconstitution of the DNA-binding large subunit (LdTOPIL; or Q and the catalytic small subunit (LdTOPIS; or S). In the present study, we generated N- and C-terminal-truncated deletion constructs of either subunit and identified proteins LdTOPIL(39-456). (lacking amino acids 1-39 and 457-635) and LdTOPIS(210-262) (lacking amino acids 1-210) as the minimal interacting fragments. The interacting region of LdTOPIL lies between residues 40-99 and 435-456, while for LdTOPIS it lies between residues 210-215 and 245-262. The heterodimerization between the two fragments is weak and therefore co-purified fragments showed reduced DNA binding, cleavage and relaxation properties compared with the wild-type enzyme. The minimal fragments could complement their respective wild-type subunits inside parasites when the respective subunits were down-regulated by transfection with conditional antisense constructs. Site-directed mutagenesis studies identify Lys(455) of LdTOPIL and ASp(261) of LdTOPIS as two residues involved in subunit interaction. Taken together, the present study provides crucial insights into the mechanistic details for understanding the unusual structure and inter-subunit co-operativity of this heterodimeric enzyme. C1 [Bosedasgupta, Somdeb; Sengupta, Souvik; Ganguly, Agneyo; Roy, Annit; Majumder, Hemanta K.] Indian Inst Chem Biol, Mol Parasitol Lab, Kolkata 700032, India. [Das, Benu Brata] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Tripathi, Gayatri] Indian Inst Chem Biol, Div Cellular Physiol, Kolkata 700032, India. RP Majumder, HK (reprint author), Indian Inst Chem Biol, Mol Parasitol Lab, 4 Raja SC Mullick Rd, Kolkata 700032, India. EM hkmajumder@iicb.res.in OI Sengupta, Souvik/0000-0001-7452-979X NR 15 TC 8 Z9 8 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2008 VL 409 BP 481 EP 489 DI 10.1042/BJ20071358 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 259BV UT WOS:000252915000016 PM 17924857 ER PT J AU Roy, A Das, BB Ganguly, A Dasgupta, SB Khalkho, NVM Pal, C Dey, S Giri, VS Jaisankar, P Dey, S Majumder, HK AF Roy, Amit Das, Benu Brata Ganguly, Agneyo Dasgupta, Somdeb Bose Khalkho, Neeta V. M. Pal, Churala Dey, Sumit Giri, Venkatachalam Sesha Jaisankar, Parasuraman Dey, Sanjit Majumder, Hemanta K. TI An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I from Leishmania donovani by 3,3 '-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzyme SO BIOCHEMICAL JOURNAL LA English DT Article DE cleavable complex; 3,3 '-di-indolylmethane (DIM); Leishmania donovani; reconstitution; topoisomerase I; topoisomerase poison ID BREAST-CANCER CELLS; CAMPTOTHECIN; APOPTOSIS; COMPLEX; 3,3'-DIINDOLYLMETHANE; CLEAVAGE; ACTIVATION; LUTEOLIN; AGENT; ALPHA AB DIM (3,3'-di-indolylmethane), an abundant dietary component of cruciferous vegetables, exhibits a wide spectrum of pharmacological properties. In the present study, we show that DIM is a potent inhibitor of Leishmania donovani topoisomerase I with an IC50 of 1.21 mu M. Equilibrium dialysis shows that DIM binds strongly to the free enzyme with a binding constant of 9.73 x 10(-9) M. The binding affinity of DIM to the small subunit is 8.6-fold more than that of the large subunit of unusual LdTOPILS (bi-subunit L. donovani topoisomerase 1). DIM stabilizes topoisomerase I-DNA cleavage complexes in vitro and also in vivo. Like CPT (camptothecin), DIM inhibits the religation step when the drug was added to preformed topoisomerase I-DNA binary complex. Hence, DIM is similar to CPT with respect to its ability to form the topoisomerase I-mediated 'cleavable complexes' in vitro and in vivo. But unlike CPT, DIM interacts with both free enzyme and substrate DNA. Therefore DIM is a non-competitive class I inhibitor of topoisomerase I. DIM also inhibits the relaxation activity of the CPT-resistant mutant enzyme LdTOPI Delta 39LS (N-terminal deletion of amino acids I 39 of LdTOP1LS). The IC50 values of DIM in simultaneous and enzyme pre-incubation relaxation assays were 3.6 and 2.9 mu M respectively, which are higher than that of wild-type topoisomerase I (LdTOP1LS), indicating that the affinity of DIM to LdTOP1 Delta 39LS is less than that for LdTOP1LS. This is the first report on DIM as an L. donovani topoisomerase I poison. Our study illuminates a new mode of action of enzyme inhibition by DIM that might be exploited for rational drug design in human leishmaniasis. C1 [Roy, Amit; Ganguly, Agneyo; Dasgupta, Somdeb Bose; Khalkho, Neeta V. M.; Majumder, Hemanta K.] Indian Inst Chem Biol, Dept Mol Parasitol, Kolkata 700032, India. [Das, Benu Brata] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Pal, Churala; Dey, Sumit; Giri, Venkatachalam Sesha; Jaisankar, Parasuraman] Indian Inst Chem Biol, Dept Med Chem, Kolkata 700032, India. [Dey, Sanjit] Univ Calcutta, Dept Physiol, Kolkata 700009, W Bengal, India. RP Majumder, HK (reprint author), Indian Inst Chem Biol, Dept Mol Parasitol, 4 Raja SC Mullick Rd, Kolkata 700032, India. EM hkmajumder@iicb.res.in NR 35 TC 20 Z9 20 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2008 VL 409 BP 611 EP 622 DI 10.1042/BJ20071286 PN 2 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 259BV UT WOS:000252915000030 PM 17922678 ER PT J AU Sommer, WH Rimondini, R Hansson, AC Hipskind, PA Gehlert, DR Barr, CS Heilig, MA AF Sommer, Wolfgang H. Rimondini, Roberto Hansson, Anita C. Hipskind, Philip A. Gehlert, Donald R. Barr, Christina S. Heilig, Markus A. TI Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala Crhr1 expression following a history of dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcoholism; animal model; conflict test; in situ hybridization; neuroaclaptation ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY-LIKE BEHAVIOR; WITHDRAWAL-INDUCED ANXIETY; ETHANOL WITHDRAWAL; RAT-BRAIN; RECEPTOR ANTAGONIST; CENTRAL NUCLEUS; ANIMAL-MODELS; CRF; INTERMITTENT AB Background: A history of alcohol dependence recruits increased voluntary alcohol intake and sensitivity to stress. Corticotropin-releasing hormone (CRH) has been implicated in this transition, but underlying molecular mechanisms remain unclear. Methods: A postdependent state was induced using intermittent alcohol exposure. Experiments were carried out following >= 3 weeks of recovery to eliminate contributions of acute withdrawal. Voluntary alcohol consumption was assessed in a two-bottle, free choice procedure. Behavioral sensitivity to stress was examined using fear suppression of behavior in a punished drinking (Vogel) conflict test. Effects of forced swim stress on voluntary alcohol intake were examined as a function of exposure history. Expression of Crh, Crhr1, and Crhr2 transcripts was analyzed by in situ hybridization histochemistry. Results: Alcohol drinking was upregulated long-term following a history of dependence. Fear suppression of behavior was selectively potentiated in postdependent animals. This persisted 3 months after alcohol exposure and was reversed by the selective CRH-R1 antagonist 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) (10 mg/kg). Forced swim stress increased alcohol intake in postdependent animals but not in control animals. Behavioral changes were paralleled by an upregulation of Crhr1 transcript expression within basolateral (BLA) and medial (MeA) amygdala and Crh messenger RNA (mRNA) in central amygdala (CeA). In contrast, Crhr2 expression was down in the BLA. Conclusions: Neuroadaptations encompassing amygdala CRH signaling contribute to the behavioral phenotype of postdependent animals. C1 [Sommer, Wolfgang H.; Hansson, Anita C.; Barr, Christina S.; Heilig, Markus A.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Rimondini, Roberto] Univ Bologna, Dept Pharmacol, Bologna, Italy. [Hipskind, Philip A.; Gehlert, Donald R.] Lilly Res Labs, Discovery Res, Indianapolis, IN USA. RP Heilig, MA (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,B 10,R 15330, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov RI Rimondini, Roberto/B-2500-2010; OI Rimondini, Roberto/0000-0003-4099-513X; Heilig, Markus/0000-0003-2706-2482; Sommer, Wolfgang/0000-0002-5903-6521 FU Intramural NIH HHS NR 56 TC 158 Z9 159 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2008 VL 63 IS 2 BP 139 EP 145 DI 10.1016/j.biopsych.2007.01.010 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 250MO UT WOS:000252304400002 PM 17585886 ER PT J AU Kakko, J von Wachenfeldt, J Svanborg, KD Lidstrom, J Barr, CS Heilig, M AF Kakko, Johan von Wachenfeldt, Joachim Svanborg, Kerstin Dybrandt Lidstrom, Jessica Barr, Christina S. Heilig, Markus TI Mood and neuroendocrine response to a chemical stressor, metyrapone, in buprenorphine-maintained heroin dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ACTH; cortisol; heroin; mood; stress ID METHADONE-MAINTENANCE TREATMENT; RECEPTOR GENE POLYMORPHISM; BETA-ENDORPHIN; CORTISOL-LEVELS; OPIATE ADDICTS; REWARD; ACTH; GLUCOCORTICOIDS; DEPRESSION; PLASTICITY AB Background: Heroin dependence is associated with a hyperactive hypothalamic-pituitary-adrenal (HPA) axis, proposed as a biological correlate of craving. Maintenance treatment with methadone normalizes HPA axis activity. Here, we examined HPA axis activity under maintenance treatment with the increasingly utilized partial opiate agonist buprenorphine. Methods: Responses to a metyrapone challenge were compared in 20 buprenorphine-maintained heroin addicts and 20 healthy volunteers (10 received a single 50 mg naltrexone dose [NTX+] and 10 received no naltrexone [NTX-]). Patients were 16 male subjects and 4 female subjects, aged 30 to 38 years, heroin-dependent and relapse-free under buprenorphine maintenance (BUP) for a minimum of 6 months. Healthy volunteers were 9 male subjects and 11 female subjects, aged 36 to 49 years, with no history of dependence. Serial measures were obtained of plasma adrenocorticotropic hormone (ACTH) and cortisol and Profile of Mood States (POMS) ratings over time. Subjects were genotyped for the OPRM1 118A/G polymorphism. Results: Buprenorphine maintenance showed a dampened HPA axis response to metyrapone, with OPRM1 118G carriers showing a significantly attenuated response compared with 118A carriers. The response of the NTX+ group was markedly increased. In contrast, negative affect was elevated in the BUP group but did not differ between NTX- and NTX+. Buprenorphine maintenance and NTX- groups did not differ in positive affect, whereas the NTX+ group was lower. Conclusions: In contrast to exaggerated HPA axis responsiveness reported in untreated heroin dependence, response to metyrapone was subnormal in heroin addicts maintained on buprenorphine. Despite this, increased measures of negative affect were seen in this group. This implies a dissociation of HPA axis responsiveness and affect in heroin dependence. C1 [Lidstrom, Jessica; Barr, Christina S.; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Kakko, Johan; von Wachenfeldt, Joachim; Svanborg, Kerstin Dybrandt; Heilig, Markus] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,10-1-5334, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482 NR 39 TC 18 Z9 18 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 JAN 15 PY 2008 VL 63 IS 2 BP 172 EP 177 DI 10.1016/j.biopsych.2007.05-001 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 250MO UT WOS:000252304400007 PM 17850768 ER PT J AU Nakae, T Uto, Y Tanaka, M Shibata, H Nakata, E Tominaga, M Maezawa, H Hashimoto, T Kirk, KL Nagasawa, H Hori, H AF Nakae, Takashi Uto, Yoshihiro Tanaka, Motoko Shibata, Haruna Nakata, Eiji Tominaga, Masahide Maezawa, Hiroshi Hashimoto, Toshihiro Kirk, Kenneth L. Nagasawa, Hideko Hori, Hitoshi TI Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID CARBOHYDRATE HYBRIDS; BIOLOGICAL-ACTIVITIES; CHEMICAL-SYNTHESIS; MOLECULAR DESIGN; TX-1877; DNA; RADIATION; NITROIMIDAZOLES; THERAPY; ANALOGS AB We have designed sugar-hybrid TX-1877 derivatives conjugated with sugar moieties including beta-glucose (beta-Glc), beta-galactose (beta-Gal), alpha-mannose (alpha-Man) and N-acetyl-beta-galactosamine (beta-GaINAc). Compound 1 (TX-1877) was glycosylated with appropriate peracetylated sugars using BF3-OEt2 to give acetylated sugar-hybrids, 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), and 10 (TX-2243). Removal of the acetyl groups afforded the sugar-hybrids having free hydroxyl groups, 11 (TX-2141), 12 (TX-2218), 13 (TX-2217) and 14 (TX-2068). We evaluated their radiosensitizing activities by an in vitro radiosensitization assay. All free hydroxyl hybrids have lower enhancement ratio (ER) values (ER <= 1.43) and lower n-octanol/water partition coefficient (P-oct) values (P-oct < 1.00 X 10(-2)) than does 1 (TX-1877, ER = 1.75, P-oct: 5.60 x 10(-2)). All acetylated hybrids have similar P-oct values (3.55 x 10(-2)-1.05 x 10(-1)) to 1 (TX-1877) and have improved ER values (ER >= 1.47) compared to the hybrids having free hydroxyl groups. Among these, 5 (TX-2244) is the most active radiosensitizer (ER = 2.30). We found a good correlation (r = 0.866) between the magnitude of P-oct (logP(oct)) and the ER value of 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), 10 (TX-2243) and I (TX-1877), suggesting that increasing the hydrophobicity is reflected in increased in vitro radiosensitizing activity. In the present study, we have Succeeded in producing sugar-hybrid hypoxic cell radiosensitizers that have an increased radiosensitizing activity that does not depend on increased hydrophobicity. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Nakae, Takashi; Uto, Yoshihiro; Tanaka, Motoko; Shibata, Haruna; Nakata, Eiji; Hori, Hitoshi] Univ Tokushima, Grad Sch, Inst Technol & Sci, Dept Life Syst, Tokushima 7708506, Japan. [Tominaga, Masahide; Maezawa, Hiroshi] Univ Tokushima, Fac Med, Tokushima 7708506, Japan. [Hashimoto, Toshihiro] Tokushima Bunri Univ, Fac Pharmaceut Sci, Tokushima 7708514, Japan. [Kirk, Kenneth L.] NIH, DHHS, NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. [Nagasawa, Hideko] Gifu Pharmaceut Univ, Lab Pharmaceut Chem, Gifu 5028585, Japan. RP Uto, Y (reprint author), Univ Tokushima, Grad Sch, Inst Technol & Sci, Dept Life Syst, Minamijosanjimacho-2, Tokushima 7708506, Japan. EM uto@bio.tokushima-u.ac.jp; hori@bio.tokushima-u.ac.jp RI Nakata, Eiji/G-5523-2013 OI Nakata, Eiji/0000-0001-9564-6805 FU Intramural NIH HHS NR 27 TC 22 Z9 24 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 15 PY 2008 VL 16 IS 2 BP 675 EP 682 DI 10.1016/j.bmc.2007.10.035 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 268LO UT WOS:000253581500007 PM 18029186 ER PT J AU Cullen, MD Sarkar, T Hamel, E Hartman, TL Watson, KM Buckheit, RW Pannecouque, C De Clercq, E Cushman, M AF Cullen, Matthew D. Sarkar, Taradas Hamel, Ernest Hartman, Tracy L. Watson, Karen M. Buckheit, Robert W., Jr. Pannecouque, Christophe De Clercq, Erik Cushman, Mark TI Inhibition of tubulin polymerization by select alkenyidiarylmethanes SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE cytotoxicity; tubulin; HIV; alkenyldiarylmethane; ADAM; antiviral; anticancer; anti-HIV ID REVERSE-TRANSCRIPTASE INHIBITORS; ANTI-HIV ACTIVITY; ALKENYLDIARYLMETHANE ADAM; BIOLOGICAL EVALUATION; FIDELITY; STABILITY; PROTEINS; SERIES; AGENTS; DRUGS AB During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were tested for inhibition of tubulin polymerization in an attempt to identify the biological target responsible for their cytotoxicity. The results indicate that, overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of tubulin assembly with IC50 values of 3.7 +/- 0.3 and 2.8 +/- 0.2 mu M, respectively, and they both inhibit the binding of colchicine to tubulin. Both compounds were investigated for anticancer activity in the National Cancer Institute's panel of 60 human cancer cell lines, and both compounds consistently displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of 0.31 +/- 0.08 and 0.47 +/- 0.09 mu M, respectively. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Cullen, Matthew D.; Cushman, Mark] Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Sarkar, Taradas; Hamel, Ernest] NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment, Frederick, MD 21702 USA. [Hartman, Tracy L.; Watson, Karen M.; Buckheit, Robert W., Jr.] ImQuest Biosci Inc, Frederick, MD 21704 USA. [Pannecouque, Christophe; De Clercq, Erik] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, Purdue Canc Ctr, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NIAID NIH HHS [R01 AI043637, R01 AI043637-06, R01-AI-43637]; PHS HHS [C06-14499] NR 23 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 15 PY 2008 VL 18 IS 2 BP 469 EP 473 DI 10.1016/j.bmel.2007.11.114 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 266CX UT WOS:000253410100003 PM 18083556 ER PT J AU Lee, GE Joshi, BV Chen, W Jeong, LS Moon, HR Jacobson, KA Kim, YC AF Lee, Ga Eun Joshi, Bhalchandra V. Chen, Wangzhong Jeong, Lak Shin Moon, Hyung Ryong Jacobson, Kenneth A. Kim, Yong-Chul TI Synthesis and structure-activity relationship studies of tyrosine-based antagonists at the human P2X(7) receptor SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE P2X(7) receptor; tyrosine-based antagonists; ethidium bromide uptake; IL-1 beta release ID POTENT ANTAGONIST; CUTTING EDGE; P2 RECEPTORS; RELEASE; CELLS; LIPOPOLYSACCHARIDE; EXPRESSION; MECHANISM; ANALOGS; KN62 AB Analogues of the P2X(7) receptor antagonist KN-62, modified at the piperazine and arylsulfonyl groups, were synthesized and assayed at the human P2X(7) receptor for inhibition of BzATP-induced effects, that is, uptake of a fluorescent dye (ethidium bromide) in stably transfected HEK293 cells and IL-1 beta release in differentiated THP-1 cells. Substitution of the arylsulfonyl, moiety with a nitro group increased antagonistic potency relative to methyl substitution, such that compound 21 was slightly more potent than KN-62. Substitution with D-tyrosine in 36 and sterically bulky tyrosyl 3,5-dimethyl groups in 9 enhanced antagonistic potency. (c) 2007 Elsevier Ltd. All rights reserved. C1 GIST, Dept Life Sci, Kwangju 500712, South Korea. NIH, Natl Inst Diab & Digest & Kidney Dis, Lab Bioorg Chem, Bethesda, MD USA. Ewha Womans Univ, Coll Pharm, Lab Med Chem, Seoul 120750, South Korea. Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea. RP Kim, YC (reprint author), GIST, Dept Life Sci, 1 Oryang dong, Buk gu, Kwangju 500712, South Korea. EM yongchul@gist.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031115-24, Z01 DK031127-01] NR 27 TC 12 Z9 13 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 15 PY 2008 VL 18 IS 2 BP 571 EP 575 DI 10.1016/j.bmcl.2007.11.077 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 266CX UT WOS:000253410100024 PM 18078749 ER PT J AU Rao, VK AF Rao, V. Koneti TI Taking ALPS down a Notch SO BLOOD LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Rao, VK (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2008 VL 111 IS 2 BP 477 EP 477 DI 10.1182/blood-2007-10-119479 PG 1 WC Hematology SC Hematology GA 252PP UT WOS:000252458700007 ER PT J AU Caspi, RR AF Caspi, Rachel R. TI Expanding Tregs with IVIg SO BLOOD LA English DT Editorial Material ID INTRAVENOUS IMMUNOGLOBULIN C1 NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2008 VL 111 IS 2 BP 481 EP 482 DI 10.1182/blood-2007-10-119495 PG 2 WC Hematology SC Hematology GA 252PP UT WOS:000252458700012 ER PT J AU Lin, JX Spolski, R Leonard, WJ AF Lin, Jian-Xin Spolski, Rosanne Leonard, Warren J. TI Critical role for Rsk2 in T-lymphocyte activation SO BLOOD LA English DT Review ID RIBOSOMAL S6 KINASE; COFFIN-LOWRY-SYNDROME; KAPPA B ALPHA; MAP-KINASE; PROTEIN-KINASES; SIGNAL-TRANSDUCTION; FAMILY CYTOKINES; CELL DEVELOPMENT; CHAIN PROMOTER; IL-2 RECEPTOR AB During T-cell activation, a number of cytokine-activated signaling cascades, including the Jak-STAT, phosphoinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinase (MAPK) pathways, play important roles in modulating the expression of target genes and mediating a cellular response. We now report that interleukin 2 (IL-2) and IL-15, but not IL-7, rapidly activate the p90 ribosomal S6 kinases, Rsk1 and Rsk2, in human T lymphocytes. Surprisingly, mouse spleen T cells transduced with either the wild-type or a dominant-negative (DN) Rsk2-expressing retrovirus could not be recovered, in contrast to the normal survival of T cells transduced with retroviruses expressing wild-type or DN mutants of Rsk1 or Rsk3. Examination of Rsk2 knockout (KO) mice revealed normal T-cell development, but these T cells had delayed cell-cycle progression and lower production of IL-2 in response to anti-CD3 and anti-CD28 stimulation in vitro. Moreover, Rsk2 KO mice had defective homeostatic T-cell expansion following sublethal irradiation in vivo, which is known to involve T-cell receptor (TCR), IL-2, and/or IL-15 signals, each of which we demonstrate can rapidly and potently activate Rsk2 in mouse T cells. These results indicate an essential nonredundant role of Rsk2 in T-cell activation. C1 [Lin, Jian-Xin; Spolski, Rosanne; Leonard, Warren J.] NHLBI, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, NIH, Lab Mol Immunol, Bldg 10,Rm 7B05,10 Ctr Dr, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 63 TC 24 Z9 25 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 JAN 15 PY 2008 VL 111 IS 2 BP 525 EP 533 DI 10.1182/blood-2007-02-072207 PG 9 WC Hematology SC Hematology GA 252PP UT WOS:000252458700020 PM 17938253 ER PT J AU Fox, E Razzouk, BI Widemann, BC Xiao, S O'Brien, M Goodspeed, W Reaman, GH Blaney, SM Murgo, AJ Balis, FM Adamson, PC AF Fox, Elizabeth Razzouk, Bassem I. Widemann, Brigitte C. Xiao, Shaun O'Brien, Michelle Goodspeed, Wendy Reaman, Gregory H. Blaney, Susan M. Murgo, Anthony J. Balis, Frank M. Adamson, Peter C. TI Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma SO BLOOD LA English DT Review ID RETINOIC ACID SYNDROME; APOPTOSIS; CELLS; REMISSION; MALIGNANCIES; PATHWAY; AS2O3 AB Arsenic trioxide (ATO) induces remission in 85% of adults with refractory acute promyelocytic leukemia (APL). We conducted a phase 1 trial of ATO in children (median age 13 y, range, 2-19) with refractory leukemia. ATO was administered intravenously over 2 hours, 5 d/wk for 20 doses/cycle. Patients with APL (n = 13) received 0.15 mg/kg per day, and patients with other types of leukemia received 0.15 mg/kg per day (n = 2) or 0.2 mg/kg per day (n = 4). Nineteen of the 24 enrolled patients were fully evaluable for toxicity. At 0.15 mg/kg per day, 2 of 15 patients experienced dose-limiting corrected QT interval (QTc) prolongation, pneumonitis, or neuropathic pain. At 0.2 mg/kg per day, 2 of 4 patients had dose-limiting QTc prolongation or pancreatitis. Non-dose-limiting toxicities included elevated serum transaminases, nausea, vomiting, abdominal pain, constipation, electrolyte imbalance, hyperglycemia, dermatitis, and headache. At 0.15 mg/kg per day, the median (range) plasma arsenic maximum concentration (C-max) was 0.28 mu M (0.11-0.37 mu M) and at 0.2 mg/kg per day5 C-max was 0.40 and 0.46 mu M; area under the concentration times time curve (AUC(0-24)) was 2.50 mu M-hr (1.28-3.85 mu M-hr) and 4.37 mu M-hr and 4.69 mu M-hr, respectively. Morphologic complete response (CR) was achieved in 85% of patients with APL; no responses were observed in non-APL patients. ATO is well-tolerated in children at the recommended dose of 0.15 mg/kg per day. The response rate in children with relapsed APL is similar to the response rate in adults. C1 [Fox, Elizabeth; Widemann, Brigitte C.; Xiao, Shaun; O'Brien, Michelle; Goodspeed, Wendy; Balis, Frank M.] NCI, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Razzouk, Bassem I.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Razzouk, Bassem I.] St Vincent Childrens Hosp, Indianapolis, IN USA. [Reaman, Gregory H.] Chidrens Oncol Grp, Arcadia, CA USA. [Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Murgo, Anthony J.] NCI, Canc Therapy & Evaluat Program, Bethesda, MD USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Fox, E (reprint author), NCI, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS; NCI NIH HHS [CA97452, U01 CA097452, UM1 CA097452] NR 24 TC 64 Z9 68 U1 0 U2 6 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 JAN 15 PY 2008 VL 111 IS 2 BP 566 EP 573 DI 10.1182/blood-2007-08-107839 PG 8 WC Hematology SC Hematology GA 252PP UT WOS:000252458700026 PM 17959855 ER PT J AU Isenberg, JS Romeo, MJ Yu, C Yu, CK Nghiem, K Monsale, J Rick, ME Wink, DA Frazier, WA Roberts, DD AF Isenberg, Jeff S. Romeo, Martin J. Yu, Christine Yu, Christine K. Nghiem, Khauh Monsale, Jude Rick, Margaret E. Wink, David A. Frazier, William A. Roberts, David D. TI Thrombospondin-1 stimulates platelet aggregation by blocking the antithrombotic activity of nitric oxide/cGMP signaling SO BLOOD LA English DT Review ID INTEGRIN-ASSOCIATED PROTEIN; VON-WILLEBRAND-FACTOR; FACTOR MULTIMER SIZE; GLYCOPROTEIN-IV; CELL RESPONSES; MONOCLONAL-ANTIBODY; TERMINAL PEPTIDE; L-ARGININE; KINASE-I; ACTIVATION AB Platelet a-granules constitute the major rapidly releasable reservoir of thrombospondin-1 in higher animals. Although some fragments and peptides derived from thrombospondin-1 stimulate or inhibit platelet aggregation, its physiologic function in platelets has remained elusive. We now show that endogenous thrombospondin-1 is necessary for platelet aggregation in vitro in the presence of physiologic levels of nitric oxide (NO). Exogenous NO or elevation of cGMP delays thrombin-induced platelet aggregation under high shear and static conditions, and exogenous thrombospondin-1 reverses this delay. Thrombosponclin-1-null murine platelets fail to aggregate in response to thrombin in the presence of exogenous NO or 8Br-cGMP. At physiologic concentrations of the NO synthase substrate arginine, thrombospondin-1-null platelets have elevated basal cGMP. Ligation of CD36 or CD47 is sufficient to block NO-induced cGMP accumulation and mimic the effect of thrombospondin-1 on aggregation. Exogenous thrombospondin-1 also re verses the suppression by NO Of alpha(llb)/beta(3) integrin-mediated platelet adhesion on immobilized fibrinogen, mediated in part by increased GTP loading of Rapl. Thrombospondin-1 also inhibits cGMP-mediated activation of cGMP-dependent protein kinase and thereby prevents phosphorylation of VASP. Thus, release of thrombospondin-1 from a-granules during activation provides positive feedback to promote efficient platelet aggregation and adhesion by overcoming the antithrombotic activity of physiologic NO. C1 [Isenberg, Jeff S.; Romeo, Martin J.; Yu, Christine; Yu, Christine K.; Roberts, David D.] NIH, NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. [Nghiem, Khauh; Monsale, Jude; Rick, Margaret E.] NIH, Ctr Canc, Hematol Serv, Bethesda, MD 20892 USA. [Wink, David A.] NIH, NCI, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. [Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO USA. RP Isenberg, JS (reprint author), NIH, NCI, Ctr Canc Res, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008; Silva, Mariana/B-9530-2012 OI Roberts, David/0000-0002-2481-2981; FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL054390, HL54390, R56 HL054390]; NIGMS NIH HHS [GM57573, R01 GM057573] NR 70 TC 92 Z9 94 U1 1 U2 10 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 JAN 15 PY 2008 VL 111 IS 2 BP 613 EP 623 DI 10.1182/blood-2007-06-098392 PG 11 WC Hematology SC Hematology GA 252PP UT WOS:000252458700032 PM 17890448 ER PT J AU Biancotto, A Iglehart, SJ Vanpouille, C Condack, CE Lisco, A Ruecker, E Hirsch, I Margolis, LB Grivel, JC AF Biancotto, Angelique Iglehart, Sarah J. Vanpouille, Christophe Condack, Cristian E. Lisco, Andrea Ruecker, Elke Hirsch, Ivan Margolis, Leonid B. Grivel, Jean-Charles TI HIV-1-induced activation of CD4(+) T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo SO BLOOD LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ANTIGEN-EXPRESSION; IMMUNE ACTIVATION; CD69 EXPRESSION; FLOW-CYTOMETRY; DEPLETION; LYMPHOCYTES; APOPTOSIS; DISEASE AB We demonstrate mechanisms by which HIV-1 appears to facilitate its own infection in ex vivo-infected human lymphoid tissue. In this system, HIV-1 readily infects various CD4(+) T cells, but productive viral infection was supported predominantly by activated T cells expressing either CD25 or HLA-DR or both (CD25/HLA-DR) but not other activation markers: There was a strong positive correlation (r = 0.64, P =.001) between virus production and the number of CD25(+)/HLA-DR+ T cells. HIV-1 infection of lymphoid tissue was associated with activation of both HIV-1-infected and uninfected (bystanders) T cells. In these tissues, apoptosis was selectively increased in T cells expressing CD25/HLA-DR and p24gag but not in cells expressing either of these markers alone. In the course of HlIV-1 infection, there was a significant increase in the number of activated (CD25+/HLA-DR+) T cells both infected and uninfected (bystander). By inducing T cells to express particular markers of activation that create new targets for infection, HIV-1 generates in ex vivo lymphoid tissues a vicious destructive circle of activation and infection. In vivo, such self-perpetuating cycle could contribute to HIV-1 disease. C1 [Biancotto, Angelique; Iglehart, Sarah J.; Vanpouille, Christophe; Condack, Cristian E.; Lisco, Andrea; Ruecker, Elke; Margolis, Leonid B.; Grivel, Jean-Charles] NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. [Hirsch, Ivan] Univ Aix Marseille 2, Inst J Paoli I Calmettes, Ctr Rech Cancerol Marseille, INSERM UMR 599, Marseille, France. RP Biancotto, A (reprint author), NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. RI Hirsch, Ivan/J-7726-2015 FU Intramural NIH HHS NR 53 TC 40 Z9 40 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 JAN 15 PY 2008 VL 111 IS 2 BP 699 EP 704 DI 10.1182/blood-2007-05-088435 PG 6 WC Hematology SC Hematology GA 252PP UT WOS:000252458700042 PM 17909079 ER PT J AU Guimond, M Leonard, WJ Spolski, R Rossi, SW Veenstra, RG Hollander, GA Mackall, CL Blazar, BR AF Guimond, Martin Leonard, Warren J. Spolski, Rosanne Rossi, Simona W. Veenstra, Rachelle G. Hollander, Georg A. Mackall, Crystal L. Blazar, Bruce R. TI Thymic stromal lymphopoietin is not necessary or sufficient to mediate the thymopoietic effects of keratinocyte growth factor SO BLOOD LA English DT Letter ID T-CELL DEVELOPMENT; EPITHELIAL-CELLS; TSLP; INFLAMMATION C1 [Mackall, Crystal L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, Bldg 10-CRC,1W-3490,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA. EM cm35c@nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA72669]; NHLBI NIH HHS [HL073794, HL55209]; PHS HHS [R01 A1057477] NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2008 VL 111 IS 2 BP 969 EP 970 DI 10.1182/blood-2007-09-113316 PG 2 WC Hematology SC Hematology GA 252PP UT WOS:000252458700080 PM 18182587 ER PT J AU Noll, KM Lapierre, P Gogarten, JP Nanavati, DM AF Noll, Kenneth M. Lapierre, Pascal Gogarten, J. Peter Nanavati, Dhaval M. TI Evolution of mal ABC transporter operons in the Thermococcales and Thermotogales SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; LATERAL GENE-TRANSFER; SP-NOV REPRESENTS; PYROCOCCUS-FURIOSUS; BINDING PROTEIN; BIOCHEMICAL-ANALYSIS; CRYSTAL-STRUCTURE; MARITIMA; LITORALIS; ARCHAEA AB Background: The mal genes that encode maltose transporters have undergone extensive lateral transfer among ancestors of the archaea Thermococcus litoralis and Pyrococcus furiosus. Bacterial hyperthermophiles of the order Thermotogales live among these archaea and so may have shared in these transfers. The genome sequence of Thermotoga maritima bears evidence of extensive acquisition of archaeal genes, so its ancestors clearly had the capacity to do so. We examined deep phylogenetic relationships among the mal genes of these hyperthermophiles and their close relatives to look for evidence of shared ancestry. Results: We demonstrate that the two maltose ATP binding cassette (ABC) transporter operons now found in Tc. litoralis and P. furiosus (termed mal and mdx genes, respectively) are not closely related to one another. The Tc. litoralis and P. furiosus mal genes are most closely related to bacterial mal genes while their respective mdx genes are archaeal. The genes of the two mal operons in Tt. maritima are not related to genes in either of these archaeal operons. They are highly similar to one another and belong to a phylogenetic lineage that includes mal genes from the enteric bacteria. A unique domain of the enteric MalF membrane spanning proteins found also in these Thermotogales MalF homologs supports their relatively close relationship with these enteric proteins. Analyses of genome sequence data from other Thermotogales species, Fervidobacterium nodosum, Thermosipho melanesiensis, Thermotoga petrophila, Thermotoga lettingae, and Thermotoga neapolitana, revealed a third apparent mal operon, absent from the published genome sequence of Tt. maritima strain MSB8. This third operon, mal3, is more closely related to the Thermococcales' bacteria- derived mal genes than are mal1 and mal2. F. nodosum, Ts. melanesiensis, and Tt. lettingae have only one of the mal1- mal2 paralogs. The mal2 operon from an unknown species of Thermotoga appears to have been horizontally acquired by a Thermotoga species that had only mal1. Conclusion: These data demonstrate that the Tc. litoralis and P. furiosus mdx maltodextrin transporter operons arose in the Archaea while their mal maltose transporter operons arose in a bacterial lineage, but not the same lineage as the two maltose transporter operons found in the published Tt. maritima genome sequence. These Tt. maritima maltose transporters are phylogenetically and structurally similar to those found in enteric bacteria and the mal2 operon was horizontally transferred within the Thermotoga lineage. Other Thermotogales species have a third mal operon that is more closely related to the bacterial Thermococcales mal operons, but the data do not support a recent horizontal sharing of that operon between these groups. C1 [Noll, Kenneth M.; Gogarten, J. Peter] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. [Lapierre, Pascal] Univ Connecticut, Biotechnol Bioserv Ctr, Storrs, CT 06269 USA. [Nanavati, Dhaval M.] NIMH, Analyt Biochem Sect, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Noll, KM (reprint author), Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. EM kenneth.noll@uconn.edu; pascal.lapierre@uconn.edu; j.p.gogarten@uconn.edu; nanavatid@mail.nih.gov OI Gogarten, Johann Peter/0000-0001-6459-6518 NR 41 TC 12 Z9 12 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD JAN 15 PY 2008 VL 8 AR 7 DI 10.1186/1471-2148-8-7 PG 15 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 267XF UT WOS:000253541800002 PM 18197971 ER PT J AU Uddin, M Opazo, JC Wildman, DE Sherwood, CC Hof, PR Goodman, M Grossman, LI AF Uddin, Monica Opazo, Juan C. Wildman, Derek E. Sherwood, Chet C. Hof, Patrick R. Goodman, Morris Grossman, Lawrence I. TI Molecular evolution of the cytochrome c oxidase subunit 5A gene in primates SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID ANTHROPOID PRIMATES; THYROID-HORMONE; POSITIVE SELECTION; ACCELERATED EVOLUTION; PHYLOGENETIC ANALYSIS; ADAPTIVE EVOLUTION; BRAIN-DEVELOPMENT; SIMIAN PRIMATES; MITOCHONDRIAL; EXPRESSION AB Background: Many electron transport chain (ETC) genes show accelerated rates of nonsynonymous nucleotide substitutions in anthropoid primate lineages, yet in non-anthropoid lineages the ETC proteins are typically highly conserved. Here, we test the hypothesis that COX5A, the ETC gene that encodes cytochrome c oxidase subunit 5A, shows a pattern of anthropoid-specific adaptive evolution, and investigate the distribution of this protein in catarrhine brains. Results: In a dataset comprising 29 vertebrate taxa, including representatives from all major groups of primates, there is nearly 100% conservation of the COX5A amino acid sequence among extant, non-anthropoid placental mammals. The most recent common ancestor of these species lived about 100 million years ( MY) ago. In contrast, anthropoid primates show markedly elevated rates of nonsynonymous evolution. In particular, branch site tests identify five positively selected codons in anthropoids, and ancestral reconstructions infer that substitutions in these codons occurred predominantly on stem lineages (anthropoid, ape and New World monkey) and on the human terminal branch. Examination of catarrhine brain samples by immunohistochemistry characterizes for the first time COX5A protein distribution in the primate neocortex, and suggests that the protein is most abundant in the mitochondria of large-size projection neurons. Real time quantitative PCR supports previous microarray results showing COX5A is expressed in cerebral cortical tissue at a higher level in human than in chimpanzee or gorilla. Conclusion: Taken together, these results suggest that both protein structural and gene regulatory changes contributed to COX5A evolution during humankind's ancestry. Furthermore, these findings are consistent with the hypothesis that adaptations in ETC genes contributed to the emergence of the energetically expensive anthropoid neocortex. C1 [Uddin, Monica; Opazo, Juan C.; Wildman, Derek E.; Goodman, Morris; Grossman, Lawrence I.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Opazo, Juan C.] Univ Austral Chile, Inst Ecol Evoluc, Valdivia, Chile. [Wildman, Derek E.] NICHHD, Natl Inst Hlth, Perinatol Res Branch, Bethesda, MD 20892 USA. [Wildman, Derek E.] Wayne State Univ, Hutzel Womens Hosp, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Sherwood, Chet C.] George Washington Univ, Dept Anthropol, Washington, DC 20052 USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Goodman, Morris] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. RP Grossman, LI (reprint author), Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. EM muddin@med.wayne.edu; jopazo2@unlnotes.unl.edu; dwildman@genetics.wayne.edu; sherwood@gwu.edu; patrick.hof@mssm.edu; mgoodwayne@aol.com; l.grossman@wayne.edu RI Opazo, Juan/A-9363-2009; OI Opazo, Juan/0000-0001-7938-4083 FU NIA NIH HHS [AG14308, P30 AG13854]; NIDDK NIH HHS [R01 DK56927] NR 53 TC 24 Z9 40 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD JAN 15 PY 2008 VL 8 AR 8 DI 10.1186/1471-2148-8-8 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 262OL UT WOS:000253157700001 PM 18197981 ER PT J AU Joannin, N Abhiman, S Sonnhammer, EL Wahlgren, M AF Joannin, Nicolas Abhiman, Saraswathi Sonnhammer, Erik L. Wahlgren, Mats TI Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family SO BMC GENOMICS LA English DT Article ID PLASMODIUM-FALCIPARUM RIFIN; VARIANT PROTEINS; GENE FAMILIES; LIFE-CYCLE; INFECTED ERYTHROCYTE; ANTIGENIC VARIATION; SEQUENCE ALIGNMENT; MALARIA; EXPRESSION; SURFACE AB Background: Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extracellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection. Results: We have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in Plasmodium falciparum. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the Plasmodium export (PEXEL) motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization. Conclusion: These results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins. C1 [Joannin, Nicolas; Wahlgren, Mats] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden. [Joannin, Nicolas; Wahlgren, Mats] Swedish Inst Infect Dis Control, SE-17182 Stockholm, Sweden. [Abhiman, Saraswathi; Sonnhammer, Erik L.] AlbaNova Univ Ctr, Stockholm Bioinformat Ctr, SE-10691 Stockholm, Sweden. [Abhiman, Saraswathi] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. RP Wahlgren, M (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden. EM nicolas.joannin@ki.se; saraswaa@ncbi.nlm.nih.gov; erik.sonnhammer@sbc.su.se; mats.wahlgren@ki.se NR 60 TC 44 Z9 44 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JAN 15 PY 2008 VL 9 AR 19 DI 10.1186/1471-2164-9-19 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 267WT UT WOS:000253540600001 PM 18197962 ER PT J AU Ford, JG Howerton, MW Lai, GY Gary, TL Mid, SB Gibbons, MC Tilburt, J Baffi, C Tanpitukpongse, TP Wilson, RF Powe, NR Bass, EB AF Ford, Jean G. Howerton, Mollie W. Lai, Gabriel Y. Gary, Tiffany L. Mid, Shari Bolen Gibbons, M. Chris Tilburt, Jon Baffi, Charles Tanpitukpongse, Teerath Peter Wilson, Renee F. Powe, Neil R. Bass, Eric B. TI Barriers to recruiting underrepresented populations to cancer clinical trials: A systematic review SO CANCER LA English DT Review DE clinical trials; recruitment; underrepresented populations; systematic review; racial/ethnic minority populations; health disparities ID COOPERATIVE-ONCOLOGY-GROUP; PATIENT-CARE SYSTEMS; AFRICAN-AMERICANS; BREAST-CANCER; MINORITY RECRUITMENT; PREVENTION TRIAL; OLDER PERSONS; PHYSICIAN PERSPECTIVES; HEALTH-PROMOTION; RANDOMIZED-TRIAL AB Racial and ethnic minorities, older adults, rural residents, and individuals of low socioeconomic status are underrepresented among participants in cancer-related trials. The authors conducted a systematic review to determine the barriers to participation of underrepresented populations in cancer-related trials. Their search included English-language publications that reported original data on the recruitment of underrepresented groups to cancer treatment or prevention trials between 1966 and December 2005 in multiple electronic databases. They also hand-searched titles in 34 journals from January 2003 to December 2005 and they examined reference lists for eligible articles. Titles and abstracts were reviewed to identify relevant studies. Data on barriers to participation were synthesized both qualitatively and based on statistically significant associations with trial enrollment. Of 5257 studies that were cited, 65 studies were eligible for inclusion in the current analysis, including 46 studies on recruitment into cancer, therapeutic trials, 15 studies on recruitment into prevention trials, and 4 studies on recruitment into both prevention and treatment trials. Numerous factors were reported as barriers to participation in cancer-related trials. However, only 20 of the studies reported statistically significant associations between hypothesized barriers and enrollment. The available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data-collection methods, potential for bias, and data analysis. The results indicate that underrepresented populations face numerous barriers to participation in cancer-related trials. The current systematic review highlighting the literature on recruitment of underrepresented populations to cancer trials and may be used as the evidence base toward developing an agenda for etiologic and intervention research to reduce the disparities in participation in cancer-related trials. C1 [Ford, Jean G.; Lai, Gabriel Y.; Gary, Tiffany L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Ford, Jean G.; Howerton, Mollie W.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Mid, Shari Bolen; Tilburt, Jon; Tanpitukpongse, Teerath Peter; Powe, Neil R.; Bass, Eric B.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Mid, Shari Bolen; Tilburt, Jon; Tanpitukpongse, Teerath Peter; Powe, Neil R.; Bass, Eric B.] Johns Hopkins Univ, Evidence Based Practice Ctr, Baltimore, MD 21205 USA. [Mid, Shari Bolen; Tilburt, Jon; Tanpitukpongse, Teerath Peter; Wilson, Renee F.; Powe, Neil R.; Bass, Eric B.] Johns Hopkins Univ, Welch Ctr Prevent Epidemol & Clin Res, Baltimore, MD 21205 USA. [Gibbons, M. Chris] Johns Hopkins Univ, Urban Hlth Inst, Baltimore, MD 21205 USA. [Baffi, Charles] NCI, Div Canc Prevent, Off Prevent Oncol, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Ford, JG (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM jford@jhsph.edu NR 88 TC 240 Z9 241 U1 6 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 2008 VL 112 IS 2 BP 228 EP 242 DI 10.1002/cncr.23157 PG 15 WC Oncology SC Oncology GA 249YH UT WOS:000252266200002 PM 18008363 ER PT J AU Yang, Y Padilla-Nash, HM Vira, MA Abu-Asab, MS Val, D Worrell, R Tsokos, M Merino, MJ Pavlovich, CP Ried, T Linehan, WM Vocke, CD AF Yang, Youfeng Padilla-Nash, Hesed M. Vira, Manish A. Abu-Asab, Mones S. Val, Daniel Worrell, Robert Tsokos, Maria Merino, Maria J. Pavlovich, Christian P. Ried, Thomas Linehan, W. Marston Vocke, Cathy D. TI The UOK 257 cell line: a novel model for studies of the human Birt-Hogg-Dube gene pathway SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID RENAL TUMORS; MUTATIONS; KIDNEY; BHD; CHROMOSOMES; NEOPLASIA AB The establishment, characterization, and tumorigenicity of a new epithelial cell line (UOK 257) derived from human renal carcinoma of an individual with Birt-Hogg-Dube (BHD) syndrome are reported. Unlike other established renal tumor cell lines from sporadic renal cell carcinoma, this is the first established renal tumor cell line of BHD, an inheritable neoplastic syndrome. The isolated tumor cells display loss of contact inhibition in vitro, and produce subcutaneous tumors in mouse xenografts. Histopathologic, ultrastructural, and cytogenetic characterizations of the established tumor cells are reported. Cytogenetic analysis using spectral karyotyping on UOK 257 cells revealed 17p loss and a near-triploid and aneuploid karyotype with multiple fluorescence in situ hybridization analysis using a locus-specific gene probe for MYC. The result demonstrates that the established tumor cells consist of two cell populations, one containing four and one containing five copies of the MYC oncogene. (C) 2008 Elsevier Inc. All rights reserved. C1 [Yang, Youfeng; Vira, Manish A.; Worrell, Robert; Pavlovich, Christian P.; Linehan, W. Marston; Vocke, Cathy D.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. [Padilla-Nash, Hesed M.; Ried, Thomas] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Genet Branch, Bethesda, MD USA. [Abu-Asab, Mones S.; Val, Daniel; Tsokos, Maria] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Pathol Lab, Bethesda, MD USA. RP Vocke, CD (reprint author), Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Urol Oncol Branch, Bldg 10,Rm 1W-5888, Bethesda, MD 20892 USA. EM vockec@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z01 SC006659-25] NR 17 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JAN 15 PY 2008 VL 180 IS 2 BP 100 EP 109 DI 10.1016/j.cancergencyto.2007.10.010 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 258AW UT WOS:000252841800002 PM 18206534 ER PT J AU Amundson, SA Do, KT Vinikoor, LC Lee, RA Koch-Paiz, CA Ahn, J Reimers, M Chen, Y Scudiero, DA Weinstein, JN Trent, JM Bittner, ML Meltzer, PS Fornace, AJ AF Amundson, Sally A. Do, Khanh T. Vinikoor, Lisa C. Lee, R. Anthony Koch-Paiz, Christine A. Ahn, Jaeyong Reimers, Mark Chen, Yidong Scudiero, Dominic A. Weinstein, John N. Trent, Jeffrey M. Bittner, Michael L. Meltzer, Paul S. Fornace, Albert J., Jr. TI Integrating global gene expression and radiation survival parameters across the 60 cell lines of the National Cancer Institute Anticancer Drug Screen SO CANCER RESEARCH LA English DT Article ID GENOTOXIC STRESS; MOLECULAR PHARMACOLOGY; PROSTATE CARCINOMA; GAMMA-IRRADIATION; CDNA MICROARRAY; WILD-TYPE; IN-VIVO; CHEMOSENSITIVITY; SENSITIVITY; RESPONSES AB The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis, and gene expression response by microarray. Although several studies have profiled relative basal gene expression in the NCI-60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. Twenty-two genes were differentially regulated in cells with low survival after 2-Gy gamma-rays; 14 genes identified lines more sensitive to 8 Gy. Unlike reported basal gene expression patterns, changes in expression in response to radiation showed little tissue-of-origin effect, except for differentiating the lymphoblastoid cell lines from other cell types. Basal expression patterns, however, discriminated well between radiosensitive and more resistant lines, possibly being more informative than radiation response signatures. The most striking patterns in the radiation data were a set of genes up-regulated preferential in the p53 wild-type lines and a set of cell cycle regulatory genes down-regulated across the entire NCI-60 panel. The response of those genes to gamma-rays seems to be unaffected by the myriad of genetic differences across this diverse cell set; it represents the most penetrant gene expression response to ionizing radiation yet observed. C1 [Amundson, Sally A.; Ahn, Jaeyong; Fornace, Albert J., Jr.] Columbia Univ, Med Ctr, Ctr Radiol Res, New York, NY 10032 USA. [Amundson, Sally A.; Do, Khanh T.; Vinikoor, Lisa C.; Lee, R. Anthony; Koch-Paiz, Christine A.] NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. [Reimers, Mark; Weinstein, John N.] NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Chen, Yidong; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Reimers, Mark] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA USA. [Scudiero, Dominic A.] NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21701 USA. [Trent, Jeffrey M.; Bittner, Michael L.] Translat Genom, Phoenix, AZ USA. [Fornace, Albert J., Jr.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Amundson, SA (reprint author), Columbia Univ, Med Ctr, Ctr Radiol Res, 630 W 168th St,VC11-215, New York, NY 10032 USA. EM saa2l08@columbia.edu RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU Intramural NIH HHS NR 44 TC 122 Z9 124 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2008 VL 68 IS 2 BP 415 EP 424 DI 10.1158/0008-5472.CAN-07-2120 PG 10 WC Oncology SC Oncology GA 253FJ UT WOS:000252503800012 PM 18199535 ER PT J AU Memmott, RM Gills, JJ Hollingshead, M Powers, MC Chen, ZP Kemp, B Kozikowski, A Dennis, PA AF Memmott, Regan M. Gills, Joell J. Hollingshead, Melinda Powers, Margaret C. Chen, Zhiping Kemp, Bruce Kozikowski, Alan Dennis, Phillip A. TI Phosphatidylinositol ether lipid analogues induce AMP-activated protein kinase-dependent death in LKB1-mutant non-small cell lung cancer cells SO CANCER RESEARCH LA English DT Article ID CYCLE CHECKPOINT PATHWAY; ATAXIA-TELANGIECTASIA; UPSTREAM KINASE; LKB1; MTOR; AKT; ENERGY; SURVIVAL; MUTATION; BETA AB Loss of function of the tumor suppressor LKB1 occurs in 30% to 50% of lung adenocarcinomas. Because LKB1 activates AMP-activated protein kinase (AMPK), which can negatively regulate mTOR, AMPK activation might be desirable for cancer therapy. However, no known compounds activate AMPK independently of LKB1 in vivo, and the usefulness of activating AMPK in LKB1-mutant cancers is unknown. Here, we show that lipid-based Akt inhibitors, phosphatidylinositol ether lipid analogues (PIA), activate AMPK independently of LKB1. PIAs activated AMPK in LKB1-mutant non-small cell lung cancer (NSCLC) cell lines with similar concentration dependence as that required to inhibit Akt. However, AMPK activation was independent of Akt inhibition. AMPK activation was a major mechanism of mTOR inhibition. To assess whether another kinase capable of activating AMPK, CaMKK beta, contributed to PIA-induced AMPK activation, we used an inhibitor of CaMKK, STO-609. STO-609 inhibited PIA-induced AMPK activation in LKB1-mutant NSCLC cells, and delayed AMPK activation in wild-type LKB1 NSCLC cells. In addition, AMPK activation was not observed in NSCLC cells with mutant CaMKK beta, suggesting that CaMKK beta contributes to PIA-induced AMPK activation in cells. AMPK activation promoted PIA-induced cytotoxicity because PIAs were less cytotoxic in AMPK alpha-/- murine embryonic fibroblasts or LKB1-mutant NSCLC cells transfected with mutant AMPK. This mechanism was also relevant in vivo. Treatment of LKB1-mutant NSCLC xenografts with PIA decreased tumor volume by similar to 50% and activated AMPK. These studies show that PIAs recapitulate the activity of two tumor suppressors (PTEN and LKB1) that converge on mTOR. Moreover, they suggest that PIAs might have utility in the treatment of LKB1-mutant lung adenocarcinomas. C1 [Memmott, Regan M.; Gills, Joell J.; Powers, Margaret C.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Hollingshead, Melinda] NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. [Chen, Zhiping; Kemp, Bruce] Univ Melbourne, St Vincents Inst, Fitzroy, Vic 3065, Australia. [Chen, Zhiping; Kemp, Bruce] Univ Melbourne, Dept Med, Fitzroy, Vic 3065, Australia. [Kozikowski, Alan] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL USA. RP Dennis, PA (reprint author), Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov RI Kemp, Bruce/L-2633-2014 OI Kemp, Bruce/0000-0001-6735-5082 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, P30 CA006973, N01-CO-12400] NR 33 TC 37 Z9 38 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2008 VL 68 IS 2 BP 580 EP 588 DI 10.1158/0008-5472.CAN-07-3091 PG 9 WC Oncology SC Oncology GA 253FJ UT WOS:000252503800032 PM 18199555 ER PT J AU Bai, RK Leal, SM Covarrubias, D Wong, LJC Liu, A AF Bai, Ren-Kui Leal, Suzanne M. Covarrubias, Daniel Wong, Lee-Jun C. Liu, Aiyi TI Is mitochondrial DNA variation associated with sporadic breast cancer risk? Response SO CANCER RESEARCH LA English DT Letter ID REGION SEQUENCES; MTDNAS C1 [Bai, Ren-Kui; Leal, Suzanne M.; Covarrubias, Daniel; Wong, Lee-Jun C.] Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA. [Covarrubias, Daniel] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Liu, Aiyi] NICHHD, Biometry & Math Stat Branch, NIH, Rockville, MD USA. RP Bai, RK (reprint author), Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2008 VL 68 IS 2 BP 624 EP 625 DI 10.1158/0008-5472.CAN-07-5706 PG 2 WC Oncology SC Oncology GA 253FJ UT WOS:000252503800038 ER PT J AU Maltsev, VA Lakatta, EG AF Maltsev, Victor A. Lakatta, Edward G. TI Dynamic interactions of an intracellular Ca(2+) clock and membrane ton channel clock underlie robust initiation and regulation of cardiac pacemaker function SO CARDIOVASCULAR RESEARCH LA English DT Review DE sinus node; SR (function); calcium (cellular); Na/Ca-exchanger; ion channels ID SINOATRIAL NODE CELLS; RETICULUM CALCIUM-RELEASE; SINO-ATRIAL NODE; SARCOPLASMIC-RETICULUM; DIASTOLIC DEPOLARIZATION; I-F; RYANODINE RECEPTOR; PROTEIN-KINASE; RABBIT HEART; BEATING RATE AB For almost half a century it has been thought that the initiation of each heartbeat is driven by surface membrane voltage-gated ion channels (M clocks) within sinoatrial nodal cells. It has also been assumed that pacemaker cell automaticity is initiated at the maximum diastolic potential (MDP). Recent experimental evidence based on confocal cell imaging and supported by numerical modelling, however, shows that initiation of cardiac impulse is a more complex phenomenon and involves yet another clock that resides under the sarcolemma. This clock is the sarcoplasmic reticulum (SR): it generates spontaneous, but precisely timed, rhythmic, submembrane, local Ca(2+) releases (LCR) that appear not at the MDP but during the late, diastolic depolarization (M). The Ca(2+) clock and M clock dynamically interact, defining a novel paradigm of robust cardiac pacemaker function and regulation. Rhythmic LCRs during the late DD activate inward Na(+)/Ca(2+) exchanger currents and ignite action potentials, which in turn induce Ca(2+) transients and SR depletions, resetting the Ca(2+) clock. Both basal and reserve protein kinase A-dependent phosphorylation of Ca(2+) cycling proteins control the speed and amplitude of SR Ca(2+) cycling to regulate the beating rate by strongly coupled Ca(2+) and M clocks. C1 [Maltsev, Victor A.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,Natl Inst Hlth, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,Natl Inst Hlth, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov FU Intramural NIH HHS NR 92 TC 76 Z9 79 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JAN 15 PY 2008 VL 77 IS 2 BP 274 EP 284 DI 10.1093/cvr/cvm058 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 266QA UT WOS:000253450100007 PM 18006441 ER PT J AU Lee, KS Park, JE Kang, YH Zimmerman, W Soung, NK Seong, YS Kwak, SJ Erikson, RL AF Lee, Kyung S. Park, Jung-Eun Kang, Young H. Zimmerman, Wendy Soung, Nak-Kyun Seong, Yeon-Sun Kwak, Sahng-June Erikson, Raymond L. TI Mechanisms of mammalian polo-like kinase 1 (Plk1) localization: Self-priming SO CELL CYCLE LA English DT Article DE polo kinase; polo-box domain; self-priming; non-self-priming ID POLO-BOX DOMAIN; CYTOKINESIS; PHOSPHORYLATION; KINASE; PROTEIN; CELLS; RECRUITMENT; DIVISION; FAILURE; REVEALS AB Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key element in regulating diverse mitotic events during M-phase progression. Plk1 is spatially regulated through the targeting activity of the conserved polo-box domain (PBD) present in the C-terminal non-catalytic region. Over the years, studies have demonstrated that the PBD forms a phospho-epitope binding module and the PBD-dependent interaction is critical for proper subcellular localization of Plk1. The current prevailing model is that the PBD binds to a phospho-epitope generated by Cdc2 or other Pro-directed kinases. Here we discuss a recent finding that Plk1 also self-promotes its localization by generating its own PBD-docking site. C1 [Lee, Kyung S.; Park, Jung-Eun; Kang, Young H.; Soung, Nak-Kyun] NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. [Zimmerman, Wendy; Erikson, Raymond L.] Harvard Univ, Biol Labs, Cambridge, MA 02138 USA. [Seong, Yeon-Sun; Kwak, Sahng-June] Dankook Univ, Coll Med, Dept Biochem, Chunan, South Korea. RP Lee, KS (reprint author), NCI, NIH, Lab Metab, 9000 Rockville Pike,Bldg 37,Rm 3118, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov NR 24 TC 29 Z9 29 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2008 VL 7 IS 2 BP 141 EP 145 PG 5 WC Cell Biology SC Cell Biology GA 266OS UT WOS:000253446300003 PM 18216497 ER PT J AU Mi, Z Rapisarda, A Taylor, L Brooks, A Creighton-Gutteridge, M Melillo, G Varesio, L AF Mi, Zenghui Rapisarda, Annamaria Taylor, Lynn Brooks, Alan Creighton-Gutteridge, Mark Melillo, Giovanni Varesio, Luigi TI Synergystic induction of HIF-1 alpha transcriptional activity by hypoxia and lipopolysaccharide in macrophages SO CELL CYCLE LA English DT Article DE HIF-1; macrophages; hypoxia; LPS; iNOS; ROS ID NITRIC-OXIDE SYNTHASE; INDUCIBLE FACTOR 1-ALPHA; TUMOR-ASSOCIATED MACROPHAGES; CREB-BINDING PROTEIN; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; INTERFERON-GAMMA; HIF-ALPHA; ANTICANCER THERAPIES; MURINE MACROPHAGES AB Hypoxia Inducible Factor-1 (HIF-1) is activated by a variety of stimuli, including inflammatory mediators. In this report we investigated the role that bacterial lipopolysaccharide (LPS) and hypoxia play in the regulation of HIF-1-dependent gene expression in macrophages. We report that murine macrophages stimulated with low concentrations of LPS (1-10ng/ml) expressed significantly higher levels of inducible nitric oxide synthase ( iNOS) mRNA when cultured under hypoxic compared to normoxic conditions. Functional studies of the iNOS promoter demonstrated that the synergistic interaction between LPS and hypoxia was mediated, at least in part, by the NF kappa B and the HIF-1 binding sites. In addition, transient transfection experiments using a Hypoxia Response Element (HRE)-containing plasmid showed that LPS and hypoxia synergistically induced HIF-1-dependent transcriptional activity. Interestingly, LPS did not significantly affect HIF-1 alpha protein levels or HIF-1 DNA binding activity relative to hypoxic induction. HIF-1 alpha, but not HIF-2 alpha, was critical for the synergistic induction of HRE-dependent transcriptional activity in macrophages, as indicated by experiments using siRNA targeting HIF-1 alpha or HIF-2 alpha. Addition of ROS-scavengers completely abrogated the synergistic induction of HIF-1 transcriptional activity by LPS and hypoxia, but neither inhibited HIF-1 transcriptional activity induced by hypoxia alone nor affected HIF-1 alpha protein levels or HIF-1 DNA binding induced by hypoxia alone or hypoxia plus LPS. Taken together, our results demonstrate that LPS and hypoxia act synergistically to induce HIF-1 alpha-transcriptional activity and they emphasize the existence of a cross talk between hypoxic and non-hypoxic signaling pathways in the regulation of macrophages gene expression. C1 [Mi, Zenghui; Creighton-Gutteridge, Mark] Natl Canc Inst, Dev Therapeut Program, Frederick, MD USA. [Rapisarda, Annamaria; Brooks, Alan; Melillo, Giovanni] Fredrick Inc, Sci Applicat Int Corp, Frederick, MD USA. [Taylor, Lynn] NCI, Inst Frederick, Canc Res Ctr, Frederick, MD USA. [Varesio, Luigi] Ist Giannina Gaslini, Mol Biol Lab, I-16148 Genoa, Italy. RP Melillo, G (reprint author), NCI, DTP Tumor Hypox Lab, Bldg 432,Rm 218, Ft Detrick, MD 21702 USA. EM luigivaresio@ospedale-gaslini.ge.it RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 FU NCI NIH HHS [N01-CO-12400] NR 59 TC 32 Z9 34 U1 3 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2008 VL 7 IS 2 BP 232 EP 241 PG 10 WC Cell Biology SC Cell Biology GA 266OS UT WOS:000253446300017 PM 18212534 ER PT J AU Horvath, A Bossis, L Giatzakis, C Levine, E Weinberg, F Meoli, E Robinson-White, A Siegel, J Soni, P Groussin, L Matyakhina, L Verma, S Remmers, E Nesterova, M Carney, JA Bertherat, J Stratakis, CA AF Horvath, Anelia Bossis, Loannis Giatzakis, Christoforos Levine, Elizabeth Weinberg, Frank Meoli, Elise Robinson-White, Audrey Siegel, Jennifer Soni, Payal Groussin, Lionel Matyakhina, Ludmila Verma, Somya Remmers, Elaine Nesterova, Maria Carney, J. Aidan Bertherat, Jerome Stratakis, Constantine A. TI Large deletions of the PRKAR1A gene in Carney complex SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-A; NODULAR ADRENOCORTICAL DISEASE; ALPHA REGULATORY SUBUNIT; ENDOCRINE OVERACTIVITY; MOLECULAR-GENETICS; RI-ALPHA; MUTATIONS; MYXOMAS; TUMORS; PIGMENTATION AB Purpose: Since the identification of PRKAR1A mutations in Carney complex, substitutions and small insertions/deletions have been found in similar to 70% of the patients. To date, no germ-line PRKAR1A deletion and/or insertion exceeded a few base pairs (up to 15). Although a few families map to chromosome 2, it is possible that current sequencing techniques do not detect larger gene changes in PRKAR1A-mutation-negative individuals with Carney complex. Experimental Design: To screen for gross alterations of the PRKAR1A gene, we applied Southern hybridization analysis on 36 unrelated Carney complex patients who did not have small intragenic mutations or large aberrations in PRKAR1A, including the probands from two kindreds mapping to chromosome 2. Results: We found large PRKAR1A deletions in the germ-line of two patients with Carney complex, both sporadic cases; no changes were identified in the remaining patients, including the two chromosome-2-mapping families. In the first patient, the deletion is expected to lead to decreased PRKAR1A mRNA levels but no other effects on the protein; the molecular phenotype is predicted to be PRKAR1A haploinsufficiency, consistent with the majority of PRKAR1A mutations causing Carney complex. In the second patient, the deletion led to in-frame elimination of exon 3 and the expression of a shorter protein, lacking the primary site for interaction with the catalytic protein kinase A subunit. In vitro transfection studies of the mutant PRKAR1A showed impaired ability to bind cyclic AMP and activation of the protein kinase A enzyme. The patient bearing this mutation had a more-severe-than-average Carney complex phenotype that included the relatively rare psammomatous melanotic schwannoma. Conclusions: Large PRKAR1A deletions may be responsible for Carney complex in patients that do not have PRKAR1A gene defects identifiable by sequencing. Preliminary data indicate that these patients may have a different phenotype especially if their defect results in an expressed, abnormal version of the PRKAR1A protein. C1 [Horvath, Anelia; Bossis, Loannis; Giatzakis, Christoforos; Levine, Elizabeth; Weinberg, Frank; Meoli, Elise; Robinson-White, Audrey; Siegel, Jennifer; Soni, Payal; Matyakhina, Ludmila; Verma, Somya; Nesterova, Maria; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Horvath, Anelia; Bossis, Loannis; Giatzakis, Christoforos; Levine, Elizabeth; Weinberg, Frank; Meoli, Elise; Robinson-White, Audrey; Siegel, Jennifer; Soni, Payal; Matyakhina, Ludmila; Verma, Somya; Nesterova, Maria; Stratakis, Constantine A.] NICHHD, Pediat Endocrinol Training Program, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Carney, J. Aidan] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD USA. [Groussin, Lionel; Bertherat, Jerome] Univ Paris 05, Hop Cochin, CNRS,UMR 8104, Inst Natl Sante Rech Med U567,Inst Cochin, Paris, France. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Bossis, Ioannis/J-6883-2012; OI Soni, Payal/0000-0001-8166-6442 FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD000642-04] NR 22 TC 48 Z9 51 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 388 EP 395 DI 10.1158/1078-0432.CCR-07-1155 PG 8 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200010 PM 18223213 ER PT J AU Baskar, S Kwong, K Hofer, T Levy, JM Kennedy, MG Lee, E Staudt, LM Wilson, WH Wiestner, A Rader, C AF Baskar, Sivasubramanian Kwong, Kayin Hofer, Thomas Levy, Jessica M. Kennedy, Michael G. Lee, Elinor Staudt, Louis M. Wilson, Wyndham H. Wiestner, Adrian Rader, Christoph TI Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY THERAPY; GENE-EXPRESSION; MOUSE DEVELOPMENT; FAMILY; FLUDARABINE; INHIBITION; PHENOTYPE; CANCER; HEART; CD52 AB Purpose: Gene expression profiling identified receptor tyrosine kinase ROR1, an embryonic protein involved in organogenesis, as a signature gene in B-cell chronic lymphocytic leukemia (B-CLL). To assess the suitability of ROR1 as a cell surface antigen for targeted therapy of B-CLL, we carried out a comprehensive analysis of ROR1 protein expression. Experimental Design: Peripheral blood mononuclear cells, sera, and other adult tissues from B-CLL patients and healthy donors were analyzed qualitatively and quantitatively for ROR1 protein expression by flow cytometry, cell surface biotinylation, Western blotting, and ELISA. Results: ROR1 protein is selectively expressed on the surface of B-CLL cells, whereas normal B cells, other normal blood cells, and normal adult tissues do not express cell surface ROR1. Moreover, cell surface expression of ROR1 is uniform and constitutive, i.e., independent of anatomic niches, independent of biological and clinical heterogeneity of B-CLL, independent of B-cell activation, and found at similar levels in all B-CLL samples tested. The antibody binding capacity of B-CLL cell surface ROR1 was determined to be in the range of 103 to 104 molecules per cell. A portion of B-CLL cell surface ROR1 was actively internalized upon antibody binding. Soluble ROR1 protein was detectable in sera of <25% of B-CLL patients and a similar fraction of healthy donors at concentrations below 200 ng/mL. Conclusions: The restricted, uniform, and constitutive cell surface expression of ROR1 protein in B-CLL provides a strong incentive for the development of targeted therapeutics such as monoclonal antibodies. C1 [Baskar, Sivasubramanian; Kwong, Kayin; Hofer, Thomas; Levy, Jessica M.; Kennedy, Michael G.; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Staudt, Louis M.; Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rader, C (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10 CRC,Room 3-3150, Bethesda, MD 20892 USA. EM raderc@mail.nih.gov FU Intramural NIH HHS NR 38 TC 89 Z9 95 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 396 EP 404 DI 10.1158/1078-0432.CCR-07-1823 PG 9 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200011 PM 18223214 ER PT J AU Hassan, S Baccarelli, A Salvucci, O Basik, M AF Hassan, Saima Baccarelli, Andrea Salvucci, Ombretta Basik, Mark TI Plasma stromal cell-derived factor-1: Host derived marker predictive of distant metastasis in breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CHEMOKINE GENE VARIANT; PERIPHERAL-BLOOD; PATHOLOGICAL FINDINGS; CIRCULATING LEVELS; COLORECTAL-CANCER; BONE-MARROW; CXCR4; EXPRESSION; SDF-1; POLYMORPHISM AB Purpose: Homing of breast cancer cells to metastatic sites may be regulated by the production of stromal cell-derived factor (SDF)-1 by specific target organs, which attracts CXCR4-expressing breast cancer cells. We investigated the value of SDF-1 as a predictive blood marker of distant metastasis in breast cancer, together with a common polymorphism of SDF-1, SDF-1-3'A. Experimental Design: Plasma samples were collected prospectively for 270 consecutive primary breast cancer patients with a median follow-up of 3.3 years. Plasma SDF-1 levels were measured using an ELISA, and the polymorphism was identified via PCR-RFLP analysis. Results: Plasma SDF-1 levels were divided into two groups, low and high, based on the median SDF-1 value of 2,661 pg/mL. Patients with low SDF-1 showed an increased risk of developing distant metastasis (relative risk, 1.94; P = 0.02) and poorer breast cancer-specific survival [adjusted hazard ratio (AHR), 3.92; P = 0.007]. Patients with both low plasma SDF-1 levels and the SDF-1-3'A polymorphism showed a poorer breast cancer-specific survival (AHR, 3.98; P = 0.001) and distant disease-free survival (AHR, 2.88; P = 0.003). In a separate cohort of 22 breast cancer patients, we found no significant difference in SDF-1 levels before and posttumor resection. Conclusion: We found that low plasma SDF-1 is an independent host-derived predictive marker of distant metastasis in breast cancer. The prognostic value of the combination of a low plasma SDF-1 level and the SDF-1-3'A polymorphism identifies a cohort of patients with an intrinsic susceptibility for poorer survival. C1 [Hassan, Saima; Basik, Mark] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst, Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Hassan, Saima; Basik, Mark] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst, Dept Surg, Montreal, PQ H3T 1E2, Canada. [Baccarelli, Andrea] Univ Milan, Ctr Mol & Genet Epidemiol, EPOCA Epidemiol Res Ctr, Milan, Italy. [Baccarelli, Andrea] IRCCS, Maggiore Policlin Hosp, Milan, Italy. [Salvucci, Ombretta] NCI, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Basik, M (reprint author), Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst, Dept Oncol, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada. EM mark.basik@mcgill.ca OI Baccarelli, Andrea/0000-0002-3436-0640 NR 35 TC 43 Z9 45 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 446 EP 454 DI 10.1158/1078-0432.CCR-07-1189 PG 9 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200017 PM 18223219 ER PT J AU Kurzrock, R Kantarjian, HM Blascovich, MA Bucher, C Verstovsek, S Wright, JJ Pilat, SR Cortes, JE Estey, EH Giles, FJ Beran, M Sebti, SM AF Kurzrock, Razelle Kantarjian, Hagop M. Blascovich, Michelle A. Bucher, Cindy Verstovsek, Srdan Wright, John J. Pilat, Susan R. Cortes, Jorge E. Estey, Elihu H. Giles, Francis J. Beran, Miloslav Sebti, Said M. TI Phase I study of alternate-week administration of tipifarnib in patients with myelodysplastic syndrome SO CLINICAL CANCER RESEARCH LA English DT Article ID FARNESYLTRANSFERASE INHIBITOR TIPIFARNIB; FARNESYL TRANSFERASE INHIBITOR; HEMATOLOGIC MALIGNANCIES; R115777; LEUKEMIA; CLASSIFICATION; EFFICACY; CANCER; TRIAL; RISK AB Purpose: To determine the safety and describe the antitumor activity of tipifarnib in patients with myelodysplastic syndrome (MDS) using an alternate-week schedule. Experimental Design: Patients with MDS were given tipifarnib, escalating from 100 mg orally twice daily until the maximum tolerated dose for 8 weeks followed by maintenance therapy (same dose/schedule) for patients with stable disease or better. Results: Sixty-three patients were treated. The most common toxicity was myelosuppression (60% of patients). Twenty percent of patients had no side effects. Nonhematologic toxicities included fatigue (20%), skin rash (9%), diarrhea (16%), increase in liver transaminases (14%) and bilirubin (11%), and nausea (11%). Dose-limiting toxicities of ataxia (n = 1), fatigue (n = 1), nausea (n = 1), and neutropenic fever (n = 2) occurred at tipifarnib doses above 1,200 mg/d. Sixteen of 61 (26%) evaluable patients responded (3 complete remissions and 13 hematologic improvements) with major platelet responses being most common (11 of 16 responders). There was no obvious dose-response relationship. Four of the 16 responders (25%; including a complete responder) were treated at the lowest dose level (100 mg twice daily). Only one responder had a Ras mutation. Giving tipifarnib resulted in potent inhibition of farnesyl transferase (usually more than 75%) in peripheral blood mononuclear cells regardless of dose. Partial farnesyl transferase inhibition persisted during the week off. Conclusions: Alternate-week tipifarnib is active and well tolerated in patients with MDS at doses up to and including 600 mg orally twice daily. The biological activity of tipifarnib is not dependent on dose. C1 [Kurzrock, Razelle; Pilat, Susan R.] Univ Texas Houston, MD Anderson Canc Ctr, Unit 422, Phase Program, Houston, TX 77230 USA. [Kantarjian, Hagop M.; Verstovsek, Srdan; Estey, Elihu H.; Giles, Francis J.; Beran, Miloslav] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77230 USA. [Blascovich, Michelle A.; Bucher, Cindy; Sebti, Said M.] Univ S Florida, H Lee Moffitt Canc Ctr, Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33682 USA. [Wright, John J.] NCI, Bethesda, MD 20892 USA. RP Kurzrock, R (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Unit 422, Phase Program, POB 301402, Houston, TX 77230 USA. EM rkurzroc@mdanderson.org FU NCI NIH HHS [1 R21 CA91518-1, 2 U01 CA062461] NR 20 TC 16 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 509 EP 514 DI 10.1158/1078-0432.CCR-07-1532 PG 6 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200025 PM 18223226 ER PT J AU Bertino, P Piccardi, F Porta, C Favoni, R Cilli, M Mutti, L Gaudino, G AF Bertino, Pietro Piccardi, Federica Porta, Camillo Favoni, Roberto Cilli, Michele Mutti, Luciano Gaudino, Giovanni TI Imatinib mesylate enhances therapeutic effects of gemcitabine in human malignant mesothelioma xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTORS; PLEURAL MESOTHELIOMA; DIFFERENTIAL EXPRESSION; ASBESTOS EXPOSURE; CELLS; SV40; INHIBITION; EPIDEMIC; PATHWAY; CANCER AB Purpose: Platelet-derived growth factor receptor beta (PDGFR beta), frequently activated in malignant mesothelioma, is a promising cancer therapeutic target. Imatinib mesylate (STI571; Glivec) is a selective inhibitor of tyrosine kinases as bcr-abl, c-kit, c-fms, and PDGFR beta and enhances tumor drug uptake by reducing the interstitial fluid pressure. We previously showed that imatinib mesylate synergizes with gemcitabine and pemetrexed in PDGFR beta-positive mesothelioma cells. Here, we aimed at investigating these combined treatments in a novel mesothelioma model. Experimental Design: REN mesothelioma cells, infected with a lentiviral vector carrying the luciferase gene, were injected in the peritoneum of severe combined immunodeficient mice. This model allowed imaging of live animals treated with pemetrexed or gemcitabine chemotherapeutics, or with imatinib mesylate alone, as well as with a combination of gemcitabine and imatinib mesylate. Results: We show here that, consistent with our previous in vitro studies, gemcitabine inhibited tumor growth, whereas pemetrexed was ineffective, even at the highest dosage tested. Compared with monotreatment, the combination of gemcitabine with imatinib mesylate led to a further tumor growth inhibition and improved mice survival, by a decrease rate of tumor cell proliferation and an increase in number of apoptotic tumor cells. Conclusions: Imatinib mesylate enhances the therapeutic response to gemcitabine, in accordance with our previous in vitro data. These in vivo results validate imatinib mesylate and gemcitabine as a combination treatment of malignant mesothelioma, also in view of its known positive effects on tumor drug uptake. These evidences provide the rationale for the currently ongoing clinical trials. C1 [Bertino, Pietro; Gaudino, Giovanni] Univ Piemonte Orientale, Dept Chem Food pharmaceut & Pharmacol Sci, I-28100 Novara, Italy. [Bertino, Pietro; Gaudino, Giovanni] Univ Piemonte Orientale, Drug & Food Biotechnol Ctr, I-28100 Novara, Italy. [Favoni, Roberto] Natl Canc Inst, Lab Expt Pharmacol, Genoa, Italy. [Porta, Camillo] San Matteo Univ Hosp, Ist Ricovero & Cura Carattere Sci, Pavia, Italy. [Mutti, Luciano] Dept Med, Local Hlth Unit 11, Piemonte, Italy. RP Gaudino, G (reprint author), Univ Piemonte Orientale, Dept Chem Food pharmaceut & Pharmacol Sci, Via Bovio 6, I-28100 Novara, Italy. EM giovanni.gaudino@unipmn.it OI Porta, Camillo/0000-0003-2412-1563 FU Associazione Italiana per la Ricerca sul Cancro NR 38 TC 42 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 541 EP 548 DI 10.1158/1078-0432.CCR-07-1388 PG 8 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200029 PM 18223230 ER PT J AU Hu, P Arias, RS Sadun, RE Nien, YC Zhang, N Sabzevari, H Lutsiak, MEC Khawli, LA Epstein, AL AF Hu, Peisheng Arias, Robyn S. Sadun, Rebecca E. Nien, Yu-Chih Zhang, Nan Sabzevari, Helen Lutsiak, M. E. Christine Khawli, Leslie A. Epstein, Alan L. TI Construction and preclinical characterization of Fc-mGITRL for the immunotherapy of cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID REGULATORY T-CELLS; INDUCED TNF RECEPTOR; IMMUNOLOGICAL SELF-TOLERANCE; EXPERIMENTAL SOLID TUMORS; CD4(+) CD25(+); FUSION PROTEIN; CUTTING EDGE; GITR; FAMILY; IMMUNITY AB Purpose: To provide proper costimulation required for effective cancerT-cell immunity, Fc-GITRL fusion proteins were generated for use in immunotherapy protocols. Experimental Design: Soluble fusion proteins consisting of the Fc fragment of immunoglobulin and the murine glucocorticoid-induced tumor necrosis factor-related receptor ligand (mGITRL) connected with different linkers were genetically engineered and tested for their potency in two BALB/c solid tumor models. Results: In vivo, construct #178-14 (-5aa, -linker) showed the best activity (> 90% tumor reduction) at doses ranging from 5 to 25 lug and was found to be intact by gel electrophoresis. Similar doses used with construct #175-2 (-linker) produced good but not as high tumor regression. Construct #5-1 (+linker), which was found to be relatively unstable by SDS gel electrophoresis, produced < 60% tumor regression and required a higher dose (100 jig) to produce optimal results. Survival curves showed that Fc-mGITRL treatment extended the life of 80% of tumor-bearing mice to > 3 months compared with controls that died by day 40. T-cell depletion studies showed that CD8(+) T cells play a major role in Fc-mGITRL immunotherapy, and tumors removed from Fc-mGITRL- and DTA-1-treated mice showed a significant influx of granzyme B+ lymphocytes compared with controls. Finally,Tregulatory (Treg) cell assays showed that, unlike other Fc fusion proteins, all three Fc-mGITRL constructs profoundly suppressed Treg activity. Conclusions: These studies suggest that a stable, intact Fc-mGITRL fusion protein can provide missing costimulation for the immunotherapy of solid tumors. In addition, Fc-mGITRL may alter Treg activity to enhance its effectiveness for tumor immunotherapy. C1 [Hu, Peisheng; Arias, Robyn S.; Sadun, Rebecca E.; Zhang, Nan; Khawli, Leslie A.; Epstein, Alan L.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Nien, Yu-Chih] Univ So Calif, Keck Sch Med, Dept Microbiol, Los Angeles, CA 90033 USA. [Sabzevari, Helen; Lutsiak, M. E. Christine] NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. RP Epstein, AL (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, 2011 Zonl Ave,HMR 205, Los Angeles, CA 90033 USA. EM aepstein@usc.edu NR 41 TC 22 Z9 22 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 579 EP 588 DI 10.1158/1078-0432.CCR-07-0940 PG 10 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200033 PM 18223234 ER PT J AU Moore, CC Jacob, ST Pinkerton, R Meya, DB Mayanja-Kizza, H Reynolds, SJ Scheld, WM AF Moore, Christopher C. Jacob, Shevin T. Pinkerton, Relana Meya, David B. Mayanja-Kizza, Harriet Reynolds, Steven J. Scheld, W. Michael TI Point-of-care lactate testing predicts mortality of severe sepsis in a predominantly HIV type 1-infected patient population in Uganda SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTENSIVE-CARE; BLOOD LACTATE; SEPTIC SHOCK; ANTIRETROVIRAL THERAPY; INFECTION; SETTINGS; ACCURACY; POOR AB Background. Prediction of mortality may improve management and outcomes of patients with sepsis in resource-limited settings. Therefore, we evaluated the ability of a hand-held portable whole-blood lactate (PWBL) analyzer to predict mortality of patients who are admitted to the hospital with severe sepsis. Methods. A prospective observational study enrolled 253 patients at a national referral hospital in Uganda. Inclusion criteria required (1) >= 2 systemic inflammatory response syndrome criteria or thermodysregulation, (2) hypotension, and (3) suspected infection. A subset of 72 patients had PWBL and standard laboratory serum lactate measured. The primary measured outcome was in-hospital mortality. Results. Fifty-nine (81.9%) of 72 evaluated patients were infected with human immunodeficiency virus type 1. The in-hospital mortality rate was 25.7% (18 of 70), and the in-and outpatient mortality at 30 days was 41.6% (30 of 72). PWBL was positively associated with in-hospital but not outpatient mortality (P < .001). The receiver operating characteristic area under the curve for PWBL was 0.81 (P < .001). The optimal PWBL concentration for predicting in-hospital mortality (sensitivity, 88.3%; specificity, 71.2%) was >= 4.0 mmol/L. Patients with a PWBL concentration >= 4.0 mmol/L died while in the hospital substantially more often (50.0%) than did those with a PWBL concentration <4.0 mmol/L (7.5%) (odds ratio, 12.3; 95% confidence interval, 3.5-48.9; P < .001. Standard laboratory serum lactate results were inconsistent and less predictive of mortality than were those of PWBL in a multiple logistic regression model. Conclusion. A PWBL concentration >= 4.0 mmol/L predicts with 81% accuracy a 7-fold higher mortality of patients with sepsis than does a PWBL concentration <4.0 mmol/L. PWBL testing would be useful in places where clinical decisions are limited by lack of laboratory infrastructure and poor reliability. C1 [Moore, Christopher C.; Jacob, Shevin T.; Pinkerton, Relana; Scheld, W. Michael] Univ Virginia Hlth Syst, Dept Internal Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. [Reynolds, Steven J.] NIH, Div Intramural Res, Bethesda, MD 20892 USA. [Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Meya, David B.; Mayanja-Kizza, Harriet] Makerere Univ, Infect Dis Inst, Fac Med, Kampala, Uganda. RP Moore, CC (reprint author), Univ Virginia Hlth Syst, Dept Internal Med, Div Infect Dis & Int Hlth, 409 Lane Rd,MR-4 Bldg,Rm 2111, Charlottesville, VA 22908 USA. EM ccm5u@virginia.edu RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Meya, David/0000-0002-4138-240X; Mayanja-Kizza, Harriet/0000-0002-9297-6208 FU Intramural NIH HHS NR 25 TC 26 Z9 27 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 15 PY 2008 VL 46 IS 2 BP 215 EP 222 DI 10.1086/524665 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 249II UT WOS:000252221100010 PM 18171253 ER PT J AU Brown, PH Schuck, P AF Brown, Patrick H. Schuck, Peter TI A new adaptive grid-size algorithm for the simulation of sedimentation velocity profiles in analytical ultracentrifugation SO COMPUTER PHYSICS COMMUNICATIONS LA English DT Article DE protein interactions; analytical ultracentrifugation; finite element methods; size distributions ID COEFFICIENT DISTRIBUTIONS C(S); PROTEIN-PROTEIN INTERACTIONS; SELF-ASSOCIATING SOLUTES; LAMM EQUATION; INTERACTING PARTICLES; GENERALIZED SYSTEMS; NUMERICAL-SOLUTIONS; DENSITY GRADIENT; MOLAR-MASS; CENTRIFUGATION AB Analytical ultracentrifugation allows one to measure in real-time the concentration gradients arising from the application of a centrifugal force to macromolecular mixtures in solution. In the last decade, the ability to efficiently solve the partial differential equation governing the ultracentrifugal sedimentation and diffusion process, the Lamm equation, has spawned significant progress in the application of sedimentation velocity analytical ultracentrifugation for the study of biological macromolecules, for example, the characterization of protein oligomeric states and the study of multi-protein complexes in solution. The present work describes a numerical algorithm that can provide an improvement in accuracy or efficiency over existing algorithms by more than one order of magnitude, and thereby greatly facilitate the practical application of sedimentation velocity analysis, in particular, for the study of multi-component macromolecular mixtures. It is implemented in the public domain software SEDFIT for the analysis of experimental data. Published by Elsevier B.V. C1 [Brown, Patrick H.; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS [Z01 OD010485-10, Z99 EB999999] NR 73 TC 29 Z9 29 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-4655 J9 COMPUT PHYS COMMUN JI Comput. Phys. Commun. PD JAN 15 PY 2008 VL 178 IS 2 BP 105 EP 120 DI 10.1016/j.cpc.2007.08.012 PG 16 WC Computer Science, Interdisciplinary Applications; Physics, Mathematical SC Computer Science; Physics GA 259DQ UT WOS:000252919700003 PM 18196178 ER PT J AU Ohsugi, M Zheng, P Baibakov, B Li, L Dean, J AF Ohsugi, Mami Zheng, Ping Baibakov, Boris Li, Lei Dean, Jurrien TI Maternally derived FILIA-MATER complex localizes asymmetrically in cleavage-stage mouse embryos SO DEVELOPMENT LA English DT Article DE preimplantation mouse development; maternal effect genes; FILIA-MATER complex; apical cytocortical polarization in blastomeres ID PLURIPOTENT STEM-CELLS; LEUCINE-RICH REPEAT; EFFECT GENE; 8-CELL BLASTOMERES; PLASMA-MEMBRANE; MESSENGER-RNAS; MICE; PROTEIN; EZRIN; OOCYTES AB Initial cell lineages that presage the inner cell mass and extra-embryonic trophectoderm are established when eight blastomeres compact to form polarized morulae in preimplantation mouse development. FILIA has been identified as a binding partner to MATER (maternal antigen that embryos require; also known as NLRP5), which is encoded by a maternal effect gene. Products of each gene are detected in growing oocytes and, although transcripts are degraded before fertilization, the cognate proteins persist in early blastocysts. The two proteins co-localize to the cytocortex of ovulated eggs, where the stability of FILIA is dependent on the presence of MATER. After fertilization, FILIA-MATER complexes become asymmetrically restricted in the apical cytocortex of two-cell embryos due to their absence in regions of cell-cell contact. This asymmetry is reversible upon disaggregation of blastomeres of the two- and four-cell embryo. Each protein persists in cells of the preimplantation embryo, but the continuous cell-cell contact of 'inner' cells of the morulae seemingly precludes formation of the subcortical FILIA-MATER complex and results in cell populations that are marked by its presence ('outer') or absence ('inner'). Thus, the FILIA-MATER complex provides a molecular marker of embryonic cell lineages, but it remains to be determined if the molecular asymmetry established after the first cell division plays a role in cell fate determinations in the early mouse embryo. C1 [Ohsugi, Mami; Zheng, Ping; Baibakov, Boris; Li, Lei; Dean, Jurrien] NIDDK, Cellular & Dev Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. OI Li, Lei/0000-0001-5478-5681 FU Intramural NIH HHS NR 67 TC 61 Z9 64 U1 0 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JAN 15 PY 2008 VL 135 IS 2 BP 259 EP 269 DI 10.1242/dev.011445 PG 11 WC Developmental Biology SC Developmental Biology GA 249UF UT WOS:000252254700007 PM 18057100 ER PT J AU Le Gall, M De Mattel, C Giniger, E AF Le Gall, Maude De Mattel, Cordell Giniger, Edward TI Molecular separation of two signaling pathways for the receptor, Notch SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Notch; signal transduction; non-canonical signalling; Ab1; Disabled; Trio; axon guidance; CSL ID ABL TYROSINE KINASE; DROSOPHILA-ABL; AXON GUIDANCE; CELL FATE; GENETIC INTERACTIONS; ABELSON; LEUKEMIA; SUPPRESSOR; SUBSTRATE; COMPLEX AB Notch is required for many aspects of cell fate specification and morphogenesis during development, including neurogenesis and axon guidance. We here provide genetic and biochemical evidence that Notch directs axon gowth and guidance in Drosophila via a "non-canonical", i.e. non-Su(H)-mediated, signaling pathway, characterized by association with the adaptor protein, Disabled, and Trio, an accessory factor of the AN tyrosine kinase. We find that forms of Notch lacking the binding sites for its canonical effector, Su(H), are nearly inactive for the cell fate function of the receptor, but largely or fully active in axon patterning. Conversely, deletion from Notch of the binding site for Disabled impairs its action in axon patterning without disturbing cell fate control. Finally, we show by co-immunoprecipitation that Notch protein is physically associated in vivo with both Disabled and Trio. Together, these data provide evidence for an alternate Notch signaling pathway that mediates a postmitotic, morphogenetic function of the receptor. (C) 2007 Elsevier Inc. All rights reserved. C1 [Le Gall, Maude; Giniger, Edward] NINDS, Natl Inst Hlth, Basic Neurosci Program, Axon Guidance & Neural Connect Unit, Bethesda, MD 20892 USA. [De Mattel, Cordell] NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Giniger, E (reprint author), NINDS, Natl Inst Hlth, Basic Neurosci Program, Axon Guidance & Neural Connect Unit, Bldg 37,Rm 1016,37 Convent Dr, Bethesda, MD 20892 USA. EM ginigere@ninds.nih.gov RI Giniger, Edward/C-1764-2015; Le Gall, Maude/C-3917-2017 OI Giniger, Edward/0000-0002-8340-6158; Le Gall, Maude/0000-0002-5372-4585 FU Intramural NIH HHS [Z01 NS003013-03]; NIGMS NIH HHS [R01 GM057830-04, GM57830, R01 GM057830-01A1, R01 GM057830-02, R01 GM057830-03, R01 GM057830-05] NR 64 TC 49 Z9 49 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2008 VL 313 IS 2 BP 556 EP 567 DI 10.1016/j.ydbio.2007.10.030 PG 12 WC Developmental Biology SC Developmental Biology GA 253UA UT WOS:000252541900007 PM 18062953 ER PT J AU Attala, H Cohen-Hillel, E Meshel, T Wang, JM Gong, W Ben-Baruch, A AF Attala, Hila Cohen-Hillel, Efrat Meshel, Tsipi Wang, Ji Ming Gong, Wanghua Ben-Baruch, Adit TI Intracellular cross-talk between the GPCR CXCR1 and CXCR2: Role of carboxyl terminus phosphorylation sites SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE CXCR1; CXCR2; CXCL8; G protein-coupled receptors; internalization; phosphorylation ID GRANULOCYTE CHEMOTACTIC PROTEIN-2; NEUTROPHIL-ACTIVATING PEPTIDE-2; CHEMOKINE RECEPTORS CXCR1; HUMAN INTERLEUKIN-8 RECEPTOR; GROWTH-STIMULATORY ACTIVITY; IL-8 RECEPTORS; COUPLED RECEPTORS; BETA-ARRESTINS; INDUCED INTERNALIZATION; LEUKOCYTE MIGRATION AB In the present study, we used the human chemokine receptors CXCR1 and CXCR2 as a model system for the study of intracellular cross-talk between two closely related G protein-coupled receptors (GPCR). In cells expressing either CXCR1 or CXCR2, exposure to the CXCL8 ligand resulted in prominent reduction in cell surface expression of the receptors. We have shown previously that the reduction in cell surface expression of CXCR1 and CXCR2, to be termed herein ''down-regulation'', is significantly lower in cells expressing both receptors together. Now we show that reduced receptor down-regulation was specific to the CXCR1 + CXCR2 pair. Also, CXCR2 carboxyl terminus phosphorylation sites were required for inducing inhibition of CXCR1 down-regulation, and vice versa. Accordingly, phosphorylation of CXCR2 carboxyl terminus domain was intact when expressed together with CXCR1. Moreover, specific carboxyl terminus phosphorylation sites on each of the wild type receptors protected them from more severe inhibition of down-regulation, induced by joint expression with the other receptor. When concomitantly expressed, CXCR1 and CXCR2 were impaired in recycling to the plasma membrane, despite their undergoing intact dephosphorylation. Overall, we show that cross-talk between two GPCR is manifested by impairment of their intracellular trafficking, primarily of ligand-induced down-regulation, via carboxyl terminus phosphorylation sites. (C) 2007 Elsevier Inc. All rights reserved. C1 [Attala, Hila; Cohen-Hillel, Efrat; Meshel, Tsipi; Ben-Baruch, Adit] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Wang, Ji Ming] NCI, SAIC Frederick, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. [Gong, Wanghua] NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Ben-Baruch, A (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. EM aditbb@tauex.tau.ac.il NR 59 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 15 PY 2008 VL 314 IS 2 BP 352 EP 365 DI 10.1016/j.yexcr.2007.09.019 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 244UR UT WOS:000251891300013 PM 17996233 ER PT J AU Cretekos, CJ Wang, Y Green, ED Martin, JF Rasweiler, JJ Behringer, RR AF Cretekos, Chris J. Wang, Ying Green, Eric D. Martin, James F. Rasweiler, John J., IV Behringer, Richard R. CA NISC Comparative Sequencing Progra TI Regulatory divergence modifies limb length between mammals SO GENES & DEVELOPMENT LA English DT Review DE Chiroptera; Carollia perspicillata; Prx1; Prrx1; limb development; evolution ID TAILED FRUIT BAT; CAROLLIA-PERSPICILLATA; GENE-EXPRESSION; STEM-CELLS; EVOLUTION; DROSOPHILA; ENHANCERS; ELEMENTS; MICE; SKELETOGENESIS AB Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation. We replaced a limb-specific transcriptional enhancer of the mouse Prx1 locus with the orthologous sequence from a bat. Prx1 expression directed by the bat enhancer results in elevated transcript levels in developing forelimb bones and forelimbs that are significantly longer than controls because of endochondral bone formation alterations. Surprisingly, deletion of the mouse Prx1 limb enhancer results in normal forelimb length and Prx1 expression, revealing regulatory redundancy. These findings suggest that mutations accumulating in pre-existing noncoding regulatory sequences within a population are a source of variation for the evolution of morphological differences between species and that cis-regulatory redundancy may facilitate accumulation of such mutations. C1 [Cretekos, Chris J.; Wang, Ying; Behringer, Richard R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. [Cretekos, Chris J.] Idaho State Univ, Dept Biol Sci, Pocatello, ID 83209 USA. [Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, Natl Inst Hlth Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Green, Eric D.; NISC Comparative Sequencing Progra] Gen Technol Branch, Bethesda, MD 20892 USA. [Martin, James F.] Texas A&M Hlth Sci Ctr, Alkek Inst Biosci & Technol, Houston, TX 77030 USA. [Rasweiler, John J., IV] Suny Downstate Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. RP Behringer, RR (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Mol Genet, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM rrb@mdanderson.org RI Phelps, Steve/H-2263-2011; Cretekos, Chris/D-8350-2013 FU Intramural NIH HHS; NCI NIH HHS [CA 09299, P30 CA016672, T32 CA009299]; NICHD NIH HHS [T32 HD007325, HD 16672]; NIDCR NIH HHS [DE 16329, R01 DE016329] NR 49 TC 103 Z9 106 U1 1 U2 28 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2008 VL 22 IS 2 BP 141 EP 151 DI 10.1101/gad.1620408 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 251TJ UT WOS:000252397700003 PM 18198333 ER PT J AU Magnus, T Carmen, J Deleon, J Xue, HP Pardo, AC Lepore, AC Mattson, MP Rao, MS Maragakis, NJ AF Magnus, Tim Carmen, Jessica Deleon, Jessica Xue, Haipeng Pardo, Andrea C. Lepore, Angelo C. Mattson, Mark P. Rao, Mahendra S. Maragakis, Nicholas J. TI Adult glial precursor proliferation in mutant SOD1(G93A) mice SO GLIA LA English DT Article DE ALS; reactive astrocyte; astrocytosis; progenitors ID AMYOTROPHIC-LATERAL-SCLEROSIS; NEUROEPITHELIAL STEM-CELLS; TRANSCRIPTION FACTOR OLIG2; REACTIVE ASTROCYTES; MOTOR-NEURONS; SPINAL-CORDS; INCREASED EXPRESSION; ALS; DIFFERENTIATION; REPAIR AB The focus of most neurodegenerative disease studies has been on neuronal death in particular subpopulations of the central nervous system. The associated response of glial populations has been ascribed the term "reactive astrocytosis." This has been defined as the proliferation of astrocytes accompanied by cellular hypertrophy and changes in gene expression following injury to the central nervous system. Yet the significance of that response to disease course is debated. In both human ALS and in the SOD1(G93A) mouse model of ALS, reactive astrocytosis is a hallmark of the disease-particularly at endstage. The brain also harbors immature progenitors which have the capacity for differentiation into both glial and neuronal lineages. We examined whether glial progenitors in the adult spinal cord of SOD1(G93A) mice become activated and contribute the astroglial response observed in this model. We found that the glial progenitor proteoglycan NG2 is increased in parallel with GFAP during the symptomatic phase of the disease and that there is a differential in vitro response of SOD1(G93A) glial progenitors to inflammatory cytokines when compared to wildtype mouse glial progenitors. This response was accompanied by the proliferation of glial progenitors but not mature GFAP. astrocytes, through the translocation of the transcription factor Olig2 from the nucleus to the cytoplasm-resulting in astrocyte differentiation. These data suggest that adult glial progenitors from SOD1(G93A) mice differentially respond to inflammatory cytokines and contribute to the observed reactive astrocytosis observed in SOD1(G93A) mouse lumbar spinal cord. (c) 2007 Wiley-Liss, Inc. C1 [Carmen, Jessica; Pardo, Andrea C.; Lepore, Angelo C.; Maragakis, Nicholas J.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Magnus, Tim; Deleon, Jessica; Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Natl Inst Hlth, Neurosci Lab, Baltimore, MD USA. [Xue, Haipeng; Rao, Mahendra S.] Corp Res Labs, Invitrogen, Carlsbad, CA USA. RP Maragakis, NJ (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, Meyer 6-119, Baltimore, MD 21287 USA. EM nmaragak@jhmi.edu RI Mattson, Mark/F-6038-2012; OI Pardo, Andrea/0000-0001-7767-8539 NR 44 TC 48 Z9 48 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-1491 J9 GLIA JI Glia PD JAN 15 PY 2008 VL 56 IS 2 BP 200 EP 208 DI 10.1002/glia.20604 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 248TN UT WOS:000252178600007 PM 18023016 ER PT J AU Galan-Moya, EM Hernandez-Losa, J Luquero, CIA de la Cruz-Morcillo, MA Ramirez-Castillejo, C Callejas-Valera, JL Arriaga, A Aranburo, AF Cajal, SRY Gutkind, JS Sanchez-Prieto, R AF Galan-Moya, Eva M. Hernandez-Losa, Javier Luquero, Clara I. Aceves de la Cruz-Morcillo, Miguel A. Ramirez-Castillejo, Carmen Callejas-Valera, Juan L. Arriaga, Angel Aranburo, Antonio Fernandez Cajal, Santiago Ramon y Gutkind, J. Silvio Sanchez-Prieto, Ricardo TI c-Abl activates p38 MAPK independently of its tyrosine kinase activity: Implications in cisplatin-based therapy SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cisplatin; c-Abl; MKK6; p38 MAPK; imatinib mesylate ID PROTEIN-KINASE; DNA-DAMAGE; APOPTOTIC RESPONSE; IONIZING-RADIATION; INDUCE APOPTOSIS; CANCER-THERAPY; IN-VIVO; PATHWAY; CELLS; STRESS AB Activation of p38 MAPK is a critical requisite for the therapeutics activity of the antitumor agent cisplatin. In this sense, a growing body of evidences supports the role of c-Abl as a major determinant of p38 MAPK activation, especially in response to genotoxic stress when triggered by cisplatin. Here, we demonstrate that p38 MAPK activation in response to cisplatin does not require the tyrosine kinase activity of c-Abl. Indeed, c-Abl can activate the p38 MAPK signaling pathway by a mechanism that is independent of its tyrosine kinase activity, but that instead involves the ability of c-Abl to increase the stability of MKK6. Similar results were obtained in chronic myeloid leukemia-derived cell lines, in which a chimeric Bcr/Abl protein mimics the effects of c-Abl overexpression on p38 MAPK activation. These findings may explain why a clinically used c-Abl inhibitor, imatinib mesylate, fails to inhibit the p38 MAPK pathway alone or in combination with cisplatin, and provide evidence of a novel signaling mechanism in which these antitumor agents act. (C) 2007 Wiley-Liss, Inc. C1 [Galan-Moya, Eva M.; Luquero, Clara I. Aceves; de la Cruz-Morcillo, Miguel A.; Ramirez-Castillejo, Carmen; Callejas-Valera, Juan L.; Arriaga, Angel; Sanchez-Prieto, Ricardo] Univ Castilla La Mancha, Oncol Mol Lab, CRIB, Fac Med, Albacete 02006, Spain. [Hernandez-Losa, Javier; Cajal, Santiago Ramon y] Hosp Univ Vall Hebron, Serv Anat Patol, Barcelona 08035, Spain. [Aranburo, Antonio Fernandez] CHUA, Serv Oncol, Albacete 02006, Spain. [Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Sanchez-Prieto, R (reprint author), Univ Castilla La Mancha, Oncol Mol Lab, CRIB, Fac Med, C Almansa 14, Albacete 02006, Spain. EM ricardo.sanchez@uclm.es RI Gutkind, J. Silvio/A-1053-2009; Espinosas, Maribel /H-8083-2012; Sanchez-Prieto, Ricardo/B-6877-2008; Ramon y Cajal, Santiago/H-4955-2016; Javier, Hernandez Losa/C-1173-2008; OI Galan-Moya, Eva M/0000-0001-5758-7592; Sanchez-Prieto, Ricardo/0000-0003-0882-9780; Ramon y Cajal, Santiago/0000-0002-3867-1390; Javier, Hernandez Losa/0000-0003-1526-3201; de la Cruz-Morcillo, Miguel Angel/0000-0002-6674-1333 NR 40 TC 19 Z9 21 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 2008 VL 122 IS 2 BP 289 EP 297 DI 10.1002/ijc.23063 PG 9 WC Oncology SC Oncology GA 242DJ UT WOS:000251704400006 PM 17893873 ER EF