FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Koga, K Cardenas, I Aldo, P Abrahams, VM Peng, B Fill, S Romero, R Mor, G AF Koga, Kaori Cardenas, Ingrid Aldo, Paulomi Abrahams, Vikki M. Peng, Bing Fill, Sara Romero, Roberto Mor, Gil TI Activation of TLR3 in the Trophoblast is Associated with Preterm Delivery SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Infection; placenta; preterm delivery; TLR3; toll-like receptors; trophoblast ID TOLL-LIKE RECEPTORS; TUMOR NECROSIS FACTOR; DOUBLE-STRANDED-RNA; X-LINKED INHIBITOR; INFLAMMATORY RESPONSE; PATHOGEN RECOGNITION; AMNIOTIC-FLUID; KAPPA-B; PREGNANCY; INFECTION AB Toll-like receptors (TLRs) recognize conserved sequences on the surface of pathogens and trigger effector cell functions. Previously, we described the expression of TLR3 by human trophoblast and their ability to respond to (Poly[I:C]). Here we evaluate the effect of Poly[I:C] on mouse pregnancy and characterize the local and systemic response. C57B/6 wild type (wt) and TLR3 knockout (TLR3KO) mice were treated with Poly[I:C] at 16.5 dpc and pregnancy outcome recorded. Morphologic changes, cytokines and chemokines levels in blood and utero-placental tissue were determined. NF-kappa B pathway was evaluated in vivo and in vitro. Poly[I:C] in C57B/6 wt mice caused preterm delivery within 24 hr (4.5 mg/kg). No effect was observed in TLR3KO mice. In addition, we observed local (placenta) and systemic (serum) response characterized by increased production of proinflammatory cytokines and chemokines. The NF-kappa B pathway was activated by Poly[I:C] in human and mice trophoblast cells. We report that Poly[I:C] induces preterm delivery via TLR3-dependent manner. Furthermore, we demonstrate that the trophoblast is able to recognize Poly[I:C] through TLR3 and respond to viral infection, modulating the immune system at the feto-maternal interface. C1 [Mor, Gil] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. [Romero, Roberto] Eunice Kennedy Natl Inst Child Hlth & Human Dev, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, 333 Cedar St,LSOG 305A, New Haven, CT 06520 USA. EM gil.mor@yale.edu OI Fill Malfertheiner, Sara/0000-0002-4274-2526 FU Perinatology Research Branch; Division of Intramural Research; NICHD; NIH; DHHS FX This study was supported in part by the Perinatology Research Branch, Division of Intramural Research, NICHD, NIH, DHHS. NR 53 TC 81 Z9 87 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAR PY 2009 VL 61 IS 3 BP 196 EP 212 DI 10.1111/j.1600-0897.2008.00682.x PG 17 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 407EH UT WOS:000263345900003 PM 19239422 ER PT J AU Ryman-Rasmussen, JP Tewksbury, EW Moss, OR Cesta, MF Wong, BA Bonner, JC AF Ryman-Rasmussen, Jessica P. Tewksbury, Earl W. Moss, Owen R. Cesta, Mark F. Wong, Brian A. Bonner, James C. TI Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE carbon nanotubes; asthma; fibrosis; lung ID INTRATRACHEAL INSTILLATION; PULMONARY TOXICITY; MICE; PARTICLES; INTERLEUKIN-13; FIBROBLASTS; DEPOSITION; RESPONSES; EXPOSURE AB Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m(3)) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and Collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-beta 1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-beta 1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-beta 1, which stimulates Collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT. C1 [Ryman-Rasmussen, Jessica P.; Cesta, Mark F.; Bonner, James C.] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. [Ryman-Rasmussen, Jessica P.; Tewksbury, Earl W.; Moss, Owen R.; Cesta, Mark F.; Wong, Brian A.; Bonner, James C.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Cesta, Mark F.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA. RP Bonner, JC (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, Box 7633, Raleigh, NC 27695 USA. EM james_bonner@ncsu.edu FU The American Chemistry Council's Long Range Research Initiative; The Intramural Research Program of the National Institutes of Health; National Institute of the Environmental Health Sciences; North Carolina State University's College of Agricultural and Life Sciences FX This study was funded by The American Chemistry Council's Long Range Research Initiative provided to The Hamner Institutes for Health Sciences, The Intramural Research Program of the National Institutes of Health, National Institute of the Environmental Health Sciences, and North Carolina State University's College of Agricultural and Life Sciences. NR 33 TC 122 Z9 123 U1 0 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 2009 VL 40 IS 3 BP 349 EP 358 DI 10.1165/rcmb.2008-0276OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 412PC UT WOS:000263735700012 PM 18787175 ER PT J AU Choyke, PL AF Choyke, Peter L. TI Commentary on "Computed Tomography in the Diagnosis of Adrenal Disease" and "Nonfunctioning Adrenal Masses: Incidental Discovery on Computed Tomography" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE adrenal disease; adrenal glands; CT; history; incidentaloma ID DELAYED ENHANCED CT; MR C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10,Room 1840, Bethesda, MD 20892 USA. EM pchoyke@nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2009 VL 192 IS 3 BP 568 EP 570 DI 10.2214/AJR.08.1718 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 416KT UT WOS:000264005700006 PM 19234249 ER PT J AU Verani, JR Seitz, A Gilman, RH LaFuente, C Galdos-Cardenas, G Kawai, V de LaFuente, E Ferrufino, L Bowman, NM Pinedo-Cancino, V Levy, MZ Steurer, F Todd, CW Kirchhoff, LV Cabrera, L Verastegui, M Bern, C AF Verani, Jennifer R. Seitz, Amy Gilman, Robert H. LaFuente, Carlos Galdos-Cardenas, Gerson Kawai, Vivian de LaFuente, Elizabeth Ferrufino, Lisbeth Bowman, Natalie M. Pinedo-Cancino, Viviana Levy, Michael Z. Steurer, Francis Todd, Charles W. Kirchhoff, Louis V. Cabrera, Lilia Verastegui, Manuela Bern, Caryn TI Geographic Variation in the Sensitivity of Recombinant Antigen-based Rapid Tests for Chronic Trypanosoma cruzi Infection SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHAGAS-DISEASE; CROSS-REACTIVITY; IMMUNOCHROMATOGRAPHIC ASSAY; CENTRAL-AMERICA; SERODIAGNOSIS; BENZNIDAZOLE; LEISHMANIA; TRANSMISSION; ANTIBODIES; DIAGNOSIS AB Chagas disease affects 8-11 million people throughout the Americas. Early detection is crucial for timely treatment and to prevent non-vectorial transmission. Recombinant antigen-based rapid tests had high sensitivity and specificity in laboratory evaluations,but no Peruvian specimens were included in previous studies. We evaluated Stat-Pak and Trypanosoma Detect rapid tests in specimens from Bolivia and Peru. Specimens positive by three conventional assays were confirmed positives; specimens negative by two or more assays were confirmed negatives. In Bolivian specimens, Stat-Pak and Trypanosoma Detect tests were 87.5% and 90.7% sensitive, respectively; both showed 100% specificity. Sensitivity in Peruvian specimens was much lower: 26.6-33.0% (Stat-Pak) and 54.3-55.2% (Trypanosoma Detect); both had specificities > 98%. Even in Bolivian specimens, these sensitivities are inadequate for stand-alone screening. The low sensitivity in Peru may be related to parasite strain differences. Chagas disease rapid tests should be field tested in each geographic site before widespread implementation for screening. C1 [Verani, Jennifer R.] Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. Emory Univ, Atlanta, GA 30322 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Asociac Benefica PRISMA, Lima, Peru. Univ Peruana Cayetano Heredia, Lima, Peru. Hosp Univ Japones, Santa Cruz, Bolivia. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Iowa, Carver Coll Med, Iowa City, IA USA. RP Verani, JR (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. EM jverani@cdc.gov FU NIH [P50 AI074285-01, 1R21 AI072093-01, K01 AI079162-01] FX This work was supported by NIH P50 AI074285-01, NIH 1R21 AI072093-01,and NIH K01 AI079162-01. NR 25 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 2009 VL 80 IS 3 BP 410 EP 415 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 417EH UT WOS:000264058800017 PM 19270291 ER PT J AU Brodine, SK Thomas, A Huang, R Harbertson, J Mehta, S Leake, J Nutman, T Moser, K Wolf, J Ramanathan, R Burbelo, P Nou, J Wilkins, P Reed, SL AF Brodine, Stephanie K. Thomas, Anne Huang, Robert Harbertson, Judith Mehta, Sanjay Leake, John Nutman, Thomas Moser, Kathleen Wolf, Jamie Ramanathan, Roshan Burbelo, Peter Nou, John Wilkins, Patricia Reed, Sharon L. TI Community Based Parasitic Screening and Treatment of Sudanese Refugees: Application and Assessment of Centers for Disease Control Guidelines SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID STRONGYLOIDES-STERCORALIS INFECTION; LOA-LOA INFECTION; PRESUMPTIVE TREATMENT; INTESTINAL PARASITES; COST-EFFECTIVENESS; AFRICAN REFUGEES; UNITED-STATES; SCHISTOSOMIASIS; DIAGNOSIS; IMMIGRANTS AB Centers for Disease Control guidelines for schistosomiasis and strongyloidiasis in Sudanese and Somali refugecs arc not widely implemented. Given limited prevalence data, we conducted a seroprevalence study of schistosomiasis, strongyloidiasis, and loiasis in Sudanese refugees across diverse ages. Sudanese refugees, ages 4-78, were recruited via community organizations. Half of the patients (86/172), were seropositive for schistosomiasis (46/171;26.9%), strongyloidiasis (56/172;33%), or both (16/171;9.4%). No Loa loa infections were detected. Infection rates were similar in adults and children except that no schistosomiasis was detected in children < 4 years of age at the time of immigration to the United States. The high prevalence of schistosomiasis and strongyloidiasis in a community-based sample of Sudanese confirms the urgency for compliance with CDC refugee health guidelines. We detected no co-infection with Loa loa using the most sensitive serologic techniques, allowing use of ivermectin, the most effective treatment of strongyloidiasis. C1 [Reed, Sharon L.] Univ Calif San Diego, Med Ctr, Dept Med, San Diego Sch Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pathol, San Diego Sch Med, San Diego, CA 92103 USA. San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. NIH, Lab Sensory Biol, Bethesda, MD 20892 USA. Cty San Diego Hlth & Human Serv Agcy, TB Control & Refugee Hlth Serv Branch, San Diego, CA USA. Ctr Dis Control, Div Parasit Dis, Atlanta, GA 30333 USA. RP Reed, SL (reprint author), Univ Calif San Diego, Med Ctr, Dept Med, San Diego Sch Med, 200 W Arbor Dr, San Diego, CA 92103 USA. EM slreed@ucsd.edu RI Burbelo, Peter/B-1027-2009 FU John and Rebecca Moores Foundation; Division of Intramural Research, NIAID FX Funding for the study was provided by the John and Rebecca Moores Foundation for New Americans and in part by the Division of Intramural Research, NIAID. NR 31 TC 10 Z9 11 U1 2 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 2009 VL 80 IS 3 BP 425 EP 430 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 417EH UT WOS:000264058800019 PM 19270293 ER PT J AU Mueller, M Kolbrich-Spargo, EA Peters, FT Huestis, MA Ricaurte, GA Maurer, HH AF Mueller, Melanie Kolbrich-Spargo, Erin A. Peters, Frank T. Huestis, Marilyn A. Ricaurte, George A. Maurer, Hans H. TI Hydrolysis of 3,4-methylenedioxymethamphetamine (MDMA) metabolite conjugates in human, squirrel monkey, and rat plasma SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE MDMA; Metabolites; LC-ESI-MS; Hydrolysis; Human; Squirrel monkey; Rat; Plasma ID BETA-GLUCURONIDASE; SPECIES-DIFFERENCES; MASS-SPECTROMETRY; HUMAN-PLACENTA; ECSTASY MDMA; ARYLSULFATASE; AMPHETAMINE; PURIFICATION; 4-HYDROXY-3-METHOXYMETHAMPHETAMINE; NEUROTOXICITY AB Characterizing the formation of metabolites of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in different species (rat, squirrel monkey, and human) may provide insight into mechanisms of MDMA neurotoxicity. Two prominent MDMA metabolites, 3,4-dihydroxymethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), are conjugated with glucuronic or sulfuric acid, but reference standards are not available; therefore, quantification is only possible after conjugate cleavage. Different concentrations of HHMA and HMMA were obtained in human, squirrel monkey, and rat plasma specimens when acid or enzymatic cleavage was performed. Our data document that these differences are due to species-specific influences on conjugate cleavage. Acidic hydrolysis should be used for analyzing free HHMA and HMMA in human or squirrel monkey plasma, while enzymatic hydrolysis with glucuronidase or sulfatase maximizes recovery of free HHMA and HMMA in rat plasma. Optimization of cleavage conditions showed that sulfate conjugates were more readily cleaved by acid hydrolysis and glucuronides by glucuronidase. C1 [Mueller, Melanie; Peters, Frank T.; Maurer, Hans H.] Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, Dept Expt & Clin Toxicol, D-66421 Homburg, Saar, Germany. [Mueller, Melanie; Ricaurte, George A.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA. [Kolbrich-Spargo, Erin A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Kolbrich-Spargo, Erin A.] SW Inst Forens Sci, Criminal Invest Lab, Dallas, TX 75235 USA. RP Maurer, HH (reprint author), Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, Dept Expt & Clin Toxicol, D-66421 Homburg, Saar, Germany. EM hans.maurer@uks.eu FU PHS [DA05707, DA017964]; National Institutes of Health; Intramural Research Program; National Institute on Drug Abuse FX The authors thank Armin A. Weber for his technical support. This work was supported by PHS Grants DA05707 and DA017964 (GAR) and National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse. NR 40 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAR PY 2009 VL 393 IS 6-7 BP 1607 EP 1617 DI 10.1007/s00216-009-2607-1 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 413XM UT WOS:000263826100009 PM 19183967 ER PT J AU Zheng, G Joo, J Yang, YN AF Zheng, Gang Joo, Jungnam Yang, Yaning TI Pearson's Test, Trend Test, and MAX Are All Trend Tests with Different Types of Scores SO ANNALS OF HUMAN GENETICS LA English DT Editorial Material DE Case-control design; genetic models; MAX; Pearson's test; robust tests; scores; trend tests ID CASE-CONTROL ASSOCIATION; GENOME-WIDE ASSOCIATION; NUISANCE PARAMETER; CORRELATED TESTS; GENETIC MODEL; SAMPLE-SIZE; CLASSIFICATIONS; STATISTICS; MAXIMUM; POWER AB Pearson's test is one of the most commonly used statistics for testing genetic association of case-control data. The trend test is another one which assumes a dose-response model between the risk of the disease and genotypes. To apply the trend test, a set of ordered scores is assigned a priori based on the underlying genetic model. Pearson's test is model-free and robust, but is less powerful for common genetic models. MAX is another robust test statistic, which takes the maximum of the trend tests over a family of scientifically plausible genetic models. We show that the three test statistics are all trend tests but with different types of scores; whether the scores are prespecified or data-driven, or whether the scores are ordered (restricted) or not ordered (unrestricted). We then provide insights into power performance of the three tests when the underlying genetic model is unknown and discuss which test to use for the analyses of case-control genetic association studies. C1 [Zheng, Gang; Joo, Jungnam] NHLBI, DPPS, Off Biostat Res, Bethesda, MD 20892 USA. [Yang, Yaning] Univ Sci & Technol, Dept Stat & Finance, Hefei, Peoples R China. RP Zheng, G (reprint author), NHLBI, DPPS, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 24 TC 25 Z9 25 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAR PY 2009 VL 73 BP 133 EP 140 DI 10.1111/j.1469-1809.2008.00500.x PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 408QC UT WOS:000263448700001 PM 19183346 ER PT J AU Troendle, JF Yu, KF Mills, JL AF Troendle, J. F. Yu, K. F. Mills, J. L. TI Testing for Genetic Association With Constrained Models Using Triads SO ANNALS OF HUMAN GENETICS LA English DT Article DE conditional distribution; genetic risk model; likelihood ratio test; power ID NEURAL-TUBE DEFECTS; DESIGN; RISK AB It has been shown that it is preferable to use a robust model that incorporated constraints on the genotype relative risk rather than rely on a model that assumes the disease operates in a recessive or dominant fashion. Previous methods are applicable to case-control studies, but not to family based studies of case children along with their parents (triads). We show here how to implement analogous constraints while analyzing triad data. The likelihood, conditional on the parents genotype, is maximized over the appropriately constrained parameter space. The asymptotic distribution for the maximized likelihood ratio statistic is found and used to estimate the null distribution of the test statistics. The properties of several methods of testing for association are compared by simulation. The constrained method provides higher power across a wide range of genetic models with little cost when compared to methods that restrict to a dominant, recessive, or multiplicative model, or make no modeling restriction. The methods are applied to two SNPs on the methylenetetrahydrofolate reductase (MTHFR) gene with neural tube defect (NTD) triads. C1 [Troendle, J. F.; Yu, K. F.; Mills, J. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA. RP Troendle, JF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bld 6100,Room 7B05, Bethesda, MD 20892 USA. EM jt3t@nih.gov FU Intramural NIH HHS [Z01 HD008812-01] NR 11 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAR PY 2009 VL 73 BP 225 EP 230 DI 10.1111/j.1469-1809.2008.00494.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 408QC UT WOS:000263448700011 PM 19178434 ER PT J AU Li, QZ Zheng, G Liang, XY Yu, K AF Li, Qizhai Zheng, Gang Liang, Xueying Yu, Kai TI Robust Tests for Single-marker Analysis in Case-Control Genetic Association Studies SO ANNALS OF HUMAN GENETICS LA English DT Article DE Association; chi(2); genetic model; MAX; power; robustness ID GENOME-WIDE ASSOCIATION; CORRELATED TESTS; SAMPLE-SIZE; RISK; CANCER AB Choosing an appropriate single-marker association test is critical to the success of case-control genetic association studies. An ideal single-marker analysis should have robust performance across a wide range of potential disease risk models. MAX was designed specifically to achieve such robustness. In this work, we derived the power calculation formula for MAX and conducted a comprehensive power comparison between MAX and two other commonly used single-marker tests, the one-degree-of-freedom (1-df) Cochran-Armitage trend test and the 2-df Pearson chi(2) test. We used a single-marker disease risk model and a two-marker haplotype risk model to explore the performances of the above three tests. We found that each test has its own "sweet" spots. Among the three tests considered, MAX appears to have the most robust performance. C1 [Li, Qizhai; Liang, Xueying; Yu, Kai] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. [Zheng, Gang] NHLBI, Off Biostat Res, Off Director, Bethesda, MD 20892 USA. RP Yu, K (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8040, Bethesda, MD 20892 USA. EM yuka@mail.nih.gov FU Intramural Program of the National Institutes of Health; Knowledge Innovation Program of the Chinese Academy of Sciences [30465W0, 30475V0] FX We would like to thank the editor and two anonymous reviewers for their insightful comments, which improved our presentation. We also thank B.J. Stone for her valuable help. K Yu, X Liang, and Q Li are supported by the Intramural Program of the National Institutes of Health. Q Li is supported in part by the Knowledge Innovation Program of the Chinese Academy of Sciences, Nos. 30465W0 and 30475V0. NR 13 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAR PY 2009 VL 73 BP 245 EP 252 DI 10.1111/j.1469-1809.2009.00506.x PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 408QC UT WOS:000263448700013 PM 19208106 ER PT J AU Yao, K Honarmand, S Espinosa, A Akhyani, N Glaser, C Jacobson, S AF Yao, Karen Honarmand, Somayeh Espinosa, Alex Akhyani, Nahid Glaser, Carol Jacobson, Steven TI Detection of Human Herpesvirus-6 in Cerebrospinal Fluid of Patients with Encephalitis SO ANNALS OF NEUROLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; MULTIPLE-SCLEROSIS; HUMAN-HERPESVIRUS-6 HHV-6; DNA; EXPRESSION; INFECTION; CHILDREN; SYSTEM; VIRUS; MENINGOENCEPHALITIS AB Objective: Virus infections are the most common causes of encephalitis, a syndrome characterized by acute inflammation of the brain. More than 150 different viruses have been implicated in the pathogenesis of encephalitis; however, because of limitations with diagnostic testing, causative factors of more than half of the cases remain unknown. Methods: To investigate whether human herpesvirus-6 (HHV-6) is a causative agent of encephalitis, we examined for evidence of virus infection by determining the presence of viral sequence using polymerase chain reaction and assessed HHV-6 antibody reactivity in the cerebrospinal fluid of encephalitis patients with unknown cause. In a cohort study, we compared virus-specific antibody levels in cerebrospinal fluid samples of patients with encephalitis, relapsing-remitting Multiple sclerosis, and other neurological diseases. Results: Our results demonstrated increased levels of HHV-6 IgG, as well as IgM levels, in a Subset of encephalitis patients compared with other neurological diseases. Moreover, cell-free viral DNA that is indicative of active infection was detected in 40% (14/35) of encephalitis patients, whereas no amplifiable viral sequence was found in either relapsing-remitting MS or other neurological diseases patients. In addition, a significant correlation between polymerase chain reaction detection and anti-HHV-6 antibody response was also demonstrated. Interpretation: Collectively, these results suggested HHV-6 as a possible pathogen in a subset of encephalitis cases. C1 [Yao, Karen; Akhyani, Nahid; Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD USA. [Yao, Karen] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Honarmand, Somayeh; Espinosa, Alex; Glaser, Carol] Viral & Rickettsial Dis Lab, Richmond, CA USA. RP Jacobson, S (reprint author), 9000 Rockville Pike,Bldg 10 Room 5N214, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov FU NIH; Centers for Disease Control and prevention Emerging Infection Program [U50/CCU915546-10] FX This research was supported by the Intramural Research Program of the NIH (National Institute of Neurological Disorders and Stroke). K.Y., N.A. and S.J. were supported by the Intramural Research Program of the NIH (National Institute of Neurological Disorders and Stroke). S.H., A.E., C.G. were Supported by Centers for Disease Control and prevention Emerging Infection Program (U50/CCU915546-10). NR 46 TC 46 Z9 47 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2009 VL 65 IS 3 BP 257 EP 267 DI 10.1002/ana.21611 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 427LA UT WOS:000264779600007 PM 19334059 ER PT J AU Dalakas, MC Rakocevic, G Salajegheh, M Dambrosia, JM Hahn, AF Raju, R McElroy, B AF Dalakas, Marincis C. Rakocevic, Goran Salajegheh, Mohammad Dambrosia, James M. Hahn, Angelika F. Raju, Raghavan McElroy, Beverly TI Placebo-Controlled Trial of Rituximab in IgM Anti-Myelin-Associated Glycoprotein Antibody Demyelinating Neuropathy SO ANNALS OF NEUROLOGY LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; RANDOMIZED CONTROLLED TRIAL; NON-HODGKINS-LYMPHOMA; B-CELL DEPLETION; INTRAVENOUS IMMUNOGLOBULIN; PERIPHERAL NEUROPATHY; RHEUMATOID-ARTHRITIS; THERAPY; GAMMOPATHY; EFFICACY AB Objective: Report a double-blind, placebo-controlled study of rituximab in patients with anti-MAG demyelinating polyneuropathy (A-MAG-DP). Methods: Twenty-six patients were randomized to four weekly infusions of 375mg/m(2) rituximab or placebo. Sample size was calculated to detect changes of >= 1 Inflammatory Neuropathy Course and Treatment (INCAT) leg disability scores at month 8. IgM levels, anti-MAG titers, B cells, antigen-presenting cells, and immunoregulatory T cells were monitored every 2 months. Results: Thirteen A-MAG-DP patients were randomized to rituximab and 13 to placebo. Randomization was balanced for age, electrophysiology, disease duration, disability scores, and baseline B cells. After 8 months, by intention to treat, 4 of 13 rituximab-treated patients improved by >= 1 INCAT score compared with 0 of 13 patients taking placebo (p = 0.096). Excluding one rituximab-randomized patient who had normal INCAT score at entry, and thus could not improve, the results were significant (p = 0.036). The time to 10m walk was significantly reduced in the rituximab group (p = 0.042) (intention to treat). Clinically, walking improved in 7 of 13 rituximab-treated patients. At month 8, IgM was reduced by 34% and anti-MAG titers by 50%. CD25(+)CD4(+)Foxp3(+) regulatory cells significantly increased by month 8. The most improved patients were those with high anti-MAG titers and most severe sensory deficits at baseline. Interpretation: Rituximab is the first drug that improves some patients with A-MAG-DP in a controlled study. The benefit may be exerted by reducing the putative pathogenic antibodies or by inducing immunoregulatory T cells. The results warrant confirmation with a larger trial. C1 [Dalakas, Marincis C.; Rakocevic, Goran; Salajegheh, Mohammad; Dambrosia, James M.; Hahn, Angelika F.; Raju, Raghavan; McElroy, Beverly] Natl Inst Neurol Disorders & Stroke, Neuromuscular Dis Sect, NIH, Bethesda, MD USA. RP Dalakas, MC (reprint author), Univ London Imperial Coll Sci Technol & Med, UK Hammersmith Hosp Campus,Burlington Danes Bldg, London W12 ONN, England. EM m.dalakas@imperial.ac.uk RI Raju, Raghavan/E-9219-2011 NR 34 TC 116 Z9 118 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2009 VL 65 IS 3 BP 286 EP 293 DI 10.1002/ana.21577 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 427LA UT WOS:000264779600010 PM 19334068 ER PT J AU Koga, F Kihara, K Neckers, L AF Koga, Fumitaka Kihara, Kazunori Neckers, Len TI Inhibition of Cancer Invasion and Metastasis by Targeting the Molecular Chaperone Heat-shock Protein 90 SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the Society-of-Biotherapeutic-Approaches CY DEC 01, 2007 CL Tokyo, JAPAN SP Soc Biotherapeut Approach DE Cancer; invasion; metastasis; molecular chaperones; heat-shock protein 90; geldanamycin; molecularly targeted therapeutics; review ID HEPATOCYTE GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; FOCAL ADHESION KINASE; CELL LUNG-CANCER; PHASE-I TRIAL; HSP90 INHIBITORS; FACTOR RECEPTOR; BLADDER-CANCER; SOLID TUMORS; ONCOGENIC TRANSFORMATION AB Heat-shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of numerous oncogenic signaling proteins that determine the hallmarks of cancer. Receptor tyrosine kinases (RTKs) and hypoxia-inducible factor-1 (HIF-1)-mediated pathways, commonly activated in aggressive cancer, potentiate each other and thus efficiently promote cancer invasion and metastasis. Hsp90 inhibitors, by interacting specifically with a single molecule, Hsp90, cause the destabilization and eventual degradation of multiple Hsp90 client proteins. These agents impede the cellular processes involved in cancer invasion and metastasis by simultaneously impairing multiple Hsp90-dependent signaling proteins including HIF-l alpha, most RTKs and their hub mediators Src, Raf-1 and Akt. Recently, a fraction of Hsp90 identified on the cell surface has been found to play a crucial role in cancer invasion and metastasis. The first-in-class Hsp90 inhibitor, 17-allylamino-17-demethoxy-geldanamycin, is currently in phase H clinical trials. The potential utility and problems of Hsp90 inhibitors in clinical settings are discussed. A fuller understanding of the roles of Hsp90 in cancer biology and accumulating clinical data oil Hsp90 inhibitors will guide us toward the goal of optimizing the use of these agents in the clinic. C1 [Koga, Fumitaka; Kihara, Kazunori] Tokyo Med & Dent Univ, Grad Sch, Dept Urol, Bunkyo Ku, Tokyo 1138519, Japan. [Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Koga, F (reprint author), Tokyo Med & Dent Univ, Grad Sch, Dept Urol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan. EM f-koga.uro@tmd.ac.jp NR 98 TC 63 Z9 65 U1 0 U2 7 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR PY 2009 VL 29 IS 3 BP 797 EP 807 PG 11 WC Oncology SC Oncology GA 430YE UT WOS:000265027700002 PM 19414312 ER PT J AU Koh, Y Das, D Leschenko, S Nakata, H Ogata-Aoki, H Amano, M Nakayama, M Ghosh, AK Mitsuya, H AF Koh, Yasuhiro Das, Debananda Leschenko, Sofiya Nakata, Hirotomo Ogata-Aoki, Hiromi Amano, Masayuki Nakayama, Maki Ghosh, Arun K. Mitsuya, Hiroaki TI GRL-02031, a Novel Nonpeptidic Protease Inhibitor (PI) Containing a Stereochemically Defined Fused Cyclopentanyltetrahydrofuran Potent against Multi-PI-Resistant Human Immunodeficiency Virus Type 1 In Vitro SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; DECREASED SENSITIVITY; 1-INFECTED PATIENTS; CROSS-RESISTANCE; HIV-1 INFECTION; VIRAL PROTEASE; GAG PROTEIN; EMERGENCE; SELECTION AB We generated a novel nonpeptidic protease inhibitor (PI), GRL-02031, by incorporating a stereochemically defined fused cyclopentanyltetrahydrofuran (Cp-THF) which exerted potent activity against a wide spectrum of human immunodeficiency virus type 1 (HIV-1) isolates, including multidrug-resistant HIV-1 variants. GRL-02031 was highly potent against laboratory HIV-1 strains and primary clinical isolates, including subtypes A, B, C, and E (50% effective concentration [EC(50)] range, 0.015 to 0.038 mu M), with minimal cytotoxicity (50% cytotoxic concentration, >100 mu M in CD(4+) MT-2 cells), although it was less active against two HIV-2 strains (HIV-2(EHO) and HIV-2(ROD)) (EC(50), similar to 0.60 mu M) than against HIV-1 strains. GRL-02031 at relatively low concentrations blocked the infection and replication of each of the HIV-1(NL4-3) variants exposed to and selected by up to 5 mu M of saquinavir, amprenavir, indinavir, nelfinavir, or ritonavir and 1 mu M of lopinavir or atazanavir (EC(50) range, 0.036 to 0.14 mu M). GRL-02031 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to the conventional antiretroviral regimens that then existed, with EC(50)s ranging from 0.014 to 0.042 mu M (changes in the EC(50)s were less than twofold the EC(50) for wild-type HIV-1). Upon selection of HIV-1NL4-3 in the presence of GRL-02031, mutants carrying L10F, L33F, M46I, I47V, Q58E, V82I, I84V, and I85V in the protease-encoding region and G62R (within p17), L363M (p24-p2 cleavage site), R409K (within p7), and I437T (p7-p1 cleavage site) in the gag-encoding region emerged. GRL-02031 was potent against a variety of HIV-1(NL4-3)-based molecular infectious clones containing a single primary mutation reported previously or a combination of such mutations, although it was slightly less active against HIV-1 variants containing consecutive amino acid substitutions: M46I and I47V or I84V and I85V. Structural modeling analysis demonstrated a distinct bimodal binding of GRL-02031 to protease, which may provide advantages to GRL-02031 in blocking the replication of a wide spectrum of HIV-1 variants resistant to PIs and in delaying the development of resistance of HIV-1 to GRL-02031. The present data warrant the further development of GRL-02031 as a potential therapeutic agent for the treatment of infections with primary and multidrug-resistant HIV-1 variants. C1 [Koh, Yasuhiro; Nakata, Hirotomo; Ogata-Aoki, Hiromi; Amano, Masayuki; Nakayama, Maki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan. [Koh, Yasuhiro; Nakata, Hirotomo; Ogata-Aoki, Hiromi; Amano, Masayuki; Nakayama, Maki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto 8608556, Japan. [Das, Debananda; Nakata, Hirotomo; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Leschenko, Sofiya; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Leschenko, Sofiya; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. RP Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med, Dept Hematol, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hmitsuya@helix.nih.gov RI Amano, Masayuki/N-7407-2016 OI Amano, Masayuki/0000-0003-0516-9502 FU Intramural Research Program of the Center for Cancer Research; National Cancer Institute; National Institutes of Health [53386]; Japan Society for the Promotion of Science [JSPS-RFTF 97L00705]; Ministry of Education, Culture, Sports, Science, and Technology (Monbu-Kagakusho) of Japan; Ministry of Health, Labor and Welfare (Kosei-Rodosho) of Japan FX This work utilized the computational resources of the Biowulf cluster at the NIH. NR 49 TC 21 Z9 22 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2009 VL 53 IS 3 BP 997 EP 1006 DI 10.1128/AAC.00689-08 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 410BY UT WOS:000263552100019 PM 18955518 ER PT J AU Haberg, SE London, SJ Stigum, H Nafstad, P Nystad, W AF Haberg, S. E. London, S. J. Stigum, H. Nafstad, P. Nystad, W. TI Folic acid supplements in pregnancy and early childhood respiratory health SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID DNA METHYLATION; DIETARY-SUPPLEMENTS; REPRODUCTIVE AGE; NORWEGIAN MOTHER; FOLATE; ASSOCIATION; COHORT; WOMEN; KNOWLEDGE; ATTITUDES AB Background: Folate supplementation is recommended for pregnant women to reduce the risk of congenital malformations. Maternal intake of folate supplements during pregnancy might also influence childhood immune phenotypes via epigenetic mechanisms. Objective: To investigate the relationship between folate supplements in pregnancy and risk of lower respiratory tract infections and wheeze in children up to 18 months of age. Methods: In the Norwegian Mother and Child Cohort Study, questionnaire data collected at several time points during pregnancy and after birth on 32 077 children born between 2000 and 2005 were used to assess the effects of folate supplements during pregnancy on respiratory outcomes up to 18 months of age, while accounting for other supplements in pregnancy and supplementation in infancy. Results: Folate supplements in the first trimester were associated with increased risk of wheeze and respiratory tract infections up to 18 months of age. Adjusting for exposure later in pregnancy and in infancy, the relative risk for wheeze for children exposed to folic acid supplements in the first trimester was 1.06 (95% CI 1.03 to 1.10), the relative risk for lower respiratory tract infections was 1.09 (95% CI 1.02 to 1.15) and the relative risk for hospitalisations for lower respiratory tract infections was 1.24 (95% CI 1.09 to 1.41). Conclusions: Folic acid supplements in pregnancy were associated with a slightly increased risk of wheeze and lower respiratory tract infections up to 18 months of age. The results suggest that methyl donors in the maternal diet during pregnancy may influence respiratory health in children consistent with epigenetic mechanisms. C1 [Haberg, S. E.; Stigum, H.; Nafstad, P.; Nystad, W.] Norwegian Inst Publ Hlth, Div Epidemiol, NO-0403 Oslo, Norway. [London, S. J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [London, S. J.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Nafstad, P.] Univ Oslo, Fac Med, Dept Community Hlth & Gen Practice, Oslo, Norway. RP Haberg, SE (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404, NO-0403 Oslo, Norway. EM siri.haberg@fhi.no OI London, Stephanie/0000-0003-4911-5290 FU Norwegian Association of Heart and Lung patients; Norwegian Foundation for Health and Rehabilitation; Norwegian Ministry of Health, NIH/NIEHS [N01-ES-85433]; NIH/NINDS [1 UO1 NS 047537-01]; Norwegian Research Council/FUGE [151918/S10] FX The study was supported by the Norwegian Association of Heart and Lung patients with EXTRA funds from the Norwegian Foundation for Health and Rehabilitation. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health, NIH/NIEHS (grant no. N01-ES-85433), NIH/NINDS (grant no. 1 UO1 NS 047537-01) and the Norwegian Research Council/FUGE (grant no. 151918/S10). The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 28 TC 140 Z9 145 U1 0 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 EI 1468-2044 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD MAR PY 2009 VL 94 IS 3 BP 180 EP 184 DI 10.1136/adc.2008.142448 PG 5 WC Pediatrics SC Pediatrics GA 410DR UT WOS:000263557600003 PM 19052032 ER PT J AU Beesdo, K Lau, JYF Guyer, AE McClure-Tone, EB Monk, CS Nelson, EE Fromm, SJ Goldwin, MA Wittchen, HU Leibenluft, E Erns, M Pine, DS AF Beesdo, Katja Lau, Jennifer Y. F. Guyer, Amanda E. McClure-Tone, Erin B. Monk, Christopher S. Nelson, Eric E. Fromm, Stephen J. Goldwin, Michelle A. Wittchen, Hans-Ulrich Leibenluft, Ellen Erns, Monique Pine, Daniel S. TI Common and Distinct Amygdala-Function Perturbations in Depressed vs Anxious Adolescents SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GENERALIZED ANXIETY DISORDER; POSTTRAUMATIC-STRESS-DISORDER; PREFRONTAL CORTEX ACTIVATION; EMOTIONAL FACIAL EXPRESSIONS; MAJOR DEPRESSION; MENTAL-DISORDERS; SOCIAL-ANXIETY; DEVELOPMENTAL EXAMINATION; ANTIDEPRESSANT TREATMENT; ATTENTIONAL BIAS AB Context: Few studies directly compare amygdala function in depressive and anxiety disorders. Data from longitudinal research emphasize the need for such studies in adolescents. Objective: To compare amygdala response to varying attention and emotion conditions among adolescents with major depressive disorder (MDD) or anxiety disorders, relative to adolescents with no psychopathology. Design: Case-control study. Setting: Government clinical research institute. Participants: Eighty-seven adolescents matched on age, sex, intelligence, and social class: 26 with MDD (14 with and 12 without anxiety disorders), 16 with anxiety disorders but no depression, and 45 without psychopathology. Main Outcome Measures: Blood oxygen level-dependent signal in the amygdala, measured by means of event-related functional magnetic resonance imaging. During imaging, participants viewed facial expressions (neutral, fearful, angry, and happy) while attention was constrained (afraid, hostility, and nose-width ratings) or unconstrained (passive viewing). Results: Left and right amygdala activation differed as a function of diagnosis, facial expression, and attention condition both when patients with comorbid MDD and anxiety were included and when they were excluded (group x emotion x attention interactions, P <= .03). Focusing on fearful face-viewing events, patients with anxiety and those with MDD both differed in amygdala responses from healthy participants and from each other during passive viewing. However, both MDD and anxiety groups, relative to healthy participants, exhibited similar signs of amygdala hyperactivation to fearful faces when subjectively experienced fear was rated. Conclusions: Adolescent MDD and anxiety disorders exhibit common and distinct functional neural correlates during face processing. Attention modulates the degree to which common or distinct amygdala perturbations manifest in these patient groups, relative to healthy peers. C1 [Beesdo, Katja; Wittchen, Hans-Ulrich] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01187 Dresden, Germany. [Lau, Jennifer Y. F.; Guyer, Amanda E.; McClure-Tone, Erin B.; Nelson, Eric E.; Goldwin, Michelle A.; Leibenluft, Ellen; Erns, Monique; Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Lau, Jennifer Y. F.; Guyer, Amanda E.; McClure-Tone, Erin B.; Nelson, Eric E.; Goldwin, Michelle A.; Leibenluft, Ellen; Erns, Monique; Pine, Daniel S.] NIMH, Sect Bipolar Spectrum Disorders, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Fromm, Stephen J.] NIMH, Mood & Anxiety Disorders Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Monk, Christopher S.] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Monk, Christopher S.] Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. [Lau, Jennifer Y. F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [McClure-Tone, Erin B.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. RP Beesdo, K (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Chemnitzer Str 46, D-01187 Dresden, Germany. EM Katja.Beesdo@tu-dresden.de RI Nelson, Eric/B-8980-2008; Beesdo-Baum, Katja/A-5793-2012; Frank, David/E-8213-2012; Wittchen, Hans-Ulrich/A-8507-2014; Monk, Christopher/J-1805-2014 OI Nelson, Eric/0000-0002-3376-2453; FU Intramural NIH HHS [ZIA MH002781-08] NR 63 TC 131 Z9 132 U1 1 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2009 VL 66 IS 3 BP 275 EP 285 PG 11 WC Psychiatry SC Psychiatry GA 413AP UT WOS:000263765600006 PM 19255377 ER PT J AU Kanaya, AM Lindquist, K Harris, TB Launer, L Rosano, C Satterfield, S Yaffe, K AF Kanaya, Alka M. Lindquist, Karla Harris, Tamara B. Launer, Lenore Rosano, Caterina Satterfield, Suzanne Yaffe, Kristine CA Hlth ABC Study TI Total and Regional Adiposity and Cognitive Change in Older Adults The Health, Aging and Body Composition (ABC) Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID MASS INDEX; RISK-FACTORS; ALZHEIMER-DISEASE; CENTRAL OBESITY; ELDERLY-WOMEN; FOLLOW-UP; DEMENTIA; HYPERTENSION; POPULATION; MEN AB Objectives: To investigate whether total and/or regional adiposity measured by anthropometry and radiographic studies influences cognitive decline in older adults and whether this association is explained by hormones and inflammatory factors known to be secreted by adipose tissue. Design: Prospective cohort study. Setting: Two clinical centers. Participants: Three thousand fifty-four elderly individuals enrolled in the Health ABC Study. Adiposity measures included body mass index, waist circumference, sagittal diameter, total fat mass by dual-energy x-ray absorptiometry, and subcutaneous and visceral fat by abdominal computed tomography. We examined the association between baseline body fat measures and change in Modified Mini-Mental State Examination (3MS) score, sequentially adjusting for confounding and mediating variables, including comorbid diseases, adipocytokines, and sex hormones. Main Outcome Measure: Scores from the 3MS, administered at the first, third, fifth, and eighth annual clinical examinations. Results: All baseline adiposity measures varied significantly by sex. In mixed-effects models, the association between total and regional adiposity and change in 3MS score varied significantly by sex, with the highest adiposity tertile being associated with greater cognitive declines in men (for each adiposity measure, P < .05) but not in women (for interaction, P < .05). Total fat mass was significantly associated with greater change in 3MS scores among men (lowest tertile, -1.6; middle tertile, -2.2; highest tertile, -2.7; P = .006), even after adjusting for mediators. Conclusions: Higher levels of all adiposity measures were associated with worsening cognitive function in men after controlling for metabolic disorders, adipocytokines, and sex hormone levels. Conversely, there was no association between adiposity and cognitive change in women. C1 [Kanaya, Alka M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Kanaya, Alka M.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94115 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat & Neurol, San Francisco, CA 94115 USA. [Harris, Tamara B.; Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Satterfield, Suzanne] Univ Tennessee Memphis, Dept Prevent Med, Memphis, TN USA. RP Kanaya, AM (reprint author), Univ Calif San Francisco, Dept Med, Box 1793,1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. EM alka.kanaya@ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU National Institutes of Health [K23HL080026, R21-DK068608]; National Institute on Aging [N01-AG-6-2101, N01AG-6-2103, N01-AG-6-2106]; National Institute on Aging FX Dr Kanaya was funded by grants K23HL080026 and R21- DK068608 from the National Institutes of Health. Dr Yaffe was supported in part by grant R01- AG021918 from the National Institutes of Health. The Health ABC Study was funded through contracts with the National Institute on Aging (N01-AG-6-2101, N01AG-6-2103, and N01-AG-6-2106). This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, and included substantial involvement of National Institute on Aging staff in data collection, analysis, interpretation, review, and approval of the manuscript. NR 30 TC 46 Z9 46 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2009 VL 66 IS 3 BP 329 EP 335 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 416EY UT WOS:000263989600008 PM 19273751 ER PT J AU Yeh, S Lew, JC Wong, WT Nussenblatt, RB AF Yeh, Steven Lew, Julie C. Wong, Wai T. Nussenblatt, Robert B. TI Relentless Placoid Chorioretinitis Associated With Central Nervous System Lesions Treated With Mycophenolate Mofetil SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID PIGMENT EPITHELIOPATHY C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, Bldg 10,10D45,10 Ctr Dr, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Intramural NIH HHS NR 4 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2009 VL 127 IS 3 BP 341 EP 343 PG 4 WC Ophthalmology SC Ophthalmology GA 416FA UT WOS:000263989800022 PM 19273806 ER PT J AU Jessup, JM Compton, CC Washington, MK AF Jessup, J. Milburn Compton, Carolyn C. Washington, Mary Kay TI For the Sake of Clarity About pT4 Category of Colorectal Cancer Reply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter ID COLON C1 [Jessup, J. Milburn; Compton, Carolyn C.; Washington, Mary Kay] NCI, Diagnost Evaluat Branch, Canc Diagnosis Program, Rockville, MD 20852 USA. [Compton, Carolyn C.] Off Director Natl Canc Inst, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. RP Jessup, JM (reprint author), NCI, Diagnost Evaluat Branch, Canc Diagnosis Program, Rockville, MD 20852 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2009 VL 133 IS 3 BP 340 EP 341 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 415PQ UT WOS:000263946900002 ER PT J AU Brenner, RA Taneja, GS Haynie, DL Trumble, AC Qian, C Klinger, RM Klebanoff, MA AF Brenner, Ruth A. Taneja, Gitanjali Saluja Haynie, Denise L. Trumble, Ann C. Qian, Cong Klinger, Ron M. Klebanoff, Mark A. TI Association Between Swimming Lessons and Drowning in Childhood A Case-Control Study SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID INJURY BEHAVIOR CHECKLIST; CHILDREN; PREVENTION; POOLS; TEMPERAMENT; ADOLESCENTS; INFANTS; RISK AB Objective: To estimate the association between swimming lessons and the risk of drowning among children aged 1 to 19 years. Design: Case-control study. Setting: Cases were identified from medical examiners'/coroners' offices between mid-2003 and mid-2005. Jurisdictions included the states of Maryland and North Carolina, 14 districts (33 counties) in Florida, 3 counties in California, 1 county in Texas, and 1 county in New York. Participants: Cases were children and adolescents aged 1 to 19 years who died of unintentional drowning. Interviews were conducted with 88 families of children who drowned and 213 matched controls. Main Exposure: Swimming lessons. Main Outcome Measure: Death due to unintentional drowning. Drownings that were intentional, of undetermined intent, or that occurred under conditions in which swimming ability was unlikely to impact risk (eg, in ice water or bathtubs) were excluded. Results: Of the 61 cases in the 1- to 4-year age group, 2 (3%) had participated in formal swimming lessons vs 35 of 134 matched controls (26%) (adjusted odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97). Among the 27 cases aged 5 to 19 years, 7 (27%) had ever taken formal swimming lessons vs 42 of 79 matched controls (53%) (adjusted OR, 0.36; 95% CI, 0.09-1.51). In adjusted analyses, there was no statistically significant association between informal instruction and drowning risk. Conclusions: Participation in formal swimming lessons was associated with an 88% reduction in the risk of drowning in the 1-to 4-year-old children, although our estimates were imprecise and 95% CIs included risk reductions ranging from 3% to 99%. C1 [Brenner, Ruth A.; Taneja, Gitanjali Saluja; Haynie, Denise L.; Trumble, Ann C.; Klebanoff, Mark A.] NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Taneja, Gitanjali Saluja; Klinger, Ron M.] Westat Corp, Rockville, MD USA. [Qian, Cong] Allied Technol Grp Inc, Rockville, MD USA. RP Brenner, RA (reprint author), NICHHD, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,Room 3A01, Bethesda, MD 20892 USA. EM brennerr@mail.nih.gov OI Haynie, Denise/0000-0002-8270-6079 FU Intramural NIH HHS [Z01 HD008743-06]; NICHD NIH HHS [N01-HD-2-3341] NR 28 TC 52 Z9 54 U1 1 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2009 VL 163 IS 3 BP 203 EP 210 PG 8 WC Pediatrics SC Pediatrics GA 413AH UT WOS:000263764800002 PM 19255386 ER PT J AU Relyea-Chew, A Hollingworth, W Chan, L Comstock, BA Overstreet, KA Jarvik, JG AF Relyea-Chew, Annemarie Hollingworth, William Chan, Leighton Comstock, Bryan A. Overstreet, Karen A. Jarvik, Jeffrey G. TI Personal Bankruptcy After Traumatic Brain or Spinal Cord Injury: The Role of Medical Debt SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Health care costs; Insurance, health; Rehabilitation; Spinal cord injuries ID HEALTH PLAN; INSURANCE; DECISION; COVERAGE; RISK AB Objective: To estimate the prevalence of medical debt among traumatic brain injury (TBI) and spinal cord injury (SCI) patients who discharged their debts through bankruptcy. Design: A cross-sectional comparison of bankruptcy filings of injured versus randomly selected bankruptcy petitioners. Setting: Patients hospitalized with SCI or TBI (1996-2002) and personal bankruptcy petitioners (2001-2004) in western Washington State. Participants: Subjects (N = 186) who filed for bankruptcy, comprised of 93 patients with previous SCI or TBI and 93 randomly selected bankruptcy petitioners. Interventions: Not applicable. Main Outcome Measures: Medical and nonmedical debt, assets, income, expenses, and employment recorded in the bankruptcy petition. Results: Five percent of randomly selected petitioners and 26% of petitioners with TBI or SCI had substantial medical debt (debt that accounted for more than 20% of all unsecured debts). SCI and TB I petitioners had fewer assets and were more likely to be receiving government income assistance at the time of bankruptcy than controls. SCI and TBI patients with a higher blood alcohol content at injury were more likely to have substantial medical debts (odds ratio=2.70; 95% confidence interval, 1.04-7.00). Conclusions: Medical debt plays an important role in some bankruptcies after TBI or SCI. We discuss policy options for reducing financial distress after serious injury. C1 [Hollingworth, William] Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. [Relyea-Chew, Annemarie; Jarvik, Jeffrey G.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Comstock, Bryan A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Jarvik, Jeffrey G.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Jarvik, Jeffrey G.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Comstock, Bryan A.; Jarvik, Jeffrey G.] Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. [Relyea-Chew, Annemarie] Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98195 USA. [Chan, Leighton] NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. [Overstreet, Karen A.] Western Dist Washington, US Bankruptey Court, Seattle, WA USA. RP Hollingworth, W (reprint author), Univ Bristol, Dept Social Med, Canynge Hall, Bristol BS8 2PR, Avon, England. EM william.hollingworth@bristol.ac.uk OI Hollingworth, William/0000-0002-0840-6254 FU Royalty Research Fund of the University of Washington; intramural research program of the National Institutes of Health FX Supported by the Royalty Research Fund of the University of Washington and the intramural research program of the National Institutes of Health. NR 31 TC 11 Z9 11 U1 3 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2009 VL 90 IS 3 BP 413 EP 419 DI 10.1016/j.apmr.2008.07.031 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 421YW UT WOS:000264395200007 PM 19254605 ER PT J AU Wingert, JR Burton, H Sinclair, RJ Brunstrom, JE Damiano, DL AF Wingert, Jason R. Burton, Harold Sinclair, Robert J. Brunstrom, Janice E. Damiano, Diane L. TI Joint-Position Sense and Kinesthesia in Cerebral Palsy SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Academy-for-Cerebral-Palsy-and-Developmental-Medicine CT Annual Conference of the Australian-Physiotherapy-Association CY SEP 13-16, 2006 CY MAY 15-18, 2004 CL Boston, MA CL Adelaide, AUSTRALIA SP Amer Acad Cerebral Palsy & Dev Med SP Australian Physiotherapy Assoc, Barwon Hlth, Dept Human Serv DE Cerebral palsy; Proprioception; Rehabilitation; Sensation ID SPASTIC HEMIPLEGIA; CHILDREN; PROPRIOCEPTION; RELIABILITY; VALIDITY; ABILITY; HANDS AB Objectives: To examine Joint-position sense and kinesthesia in all extremities in participants with diplegic or hemiplegic cerebral palsy (CP). Design: Survey of joint-position sense and kinesthesia differences between aged-matched controls and 2 groups with CP. Setting: University movement assessment laboratory. Participants: Population-based sample of participants with CP, diplegia (n=21), hemiplegia (n=17), and age-matched volunteers (n=21) without neurologic disease. Interventions: Not applicable. Main Outcome Measures: Joint-position sense and kinesthesia were measured in the transverse plane (forearm pronation/supination and hip internal/external rotation) using a custom-built device. For joint-position sense, participants actively rotated the tested limb to align the distal end with 10 target positions first with the limb and targets visible to assess their ability to perform the task motorically. The task was then repeated with vision of the limb occluded, with targets remaining visible. Joint-position sense error was determined by the magnitude and direction of the rotation errors for each limb in the vision and no vision conditions. Kinesthesia was evaluated by the ability to detect passive limb rotation without vision. Results: No group differences were detected in the vision condition. Indicative of joint-position sense deficits, a significant increase in errors was found in the no vision condition in all limbs except the dominant upper limb for both groups with CP. Joint-position sense errors were systematically biased toward the direction of internal rotation. Kinesthesia deficits were evident on the nondominant upper limb in diplegia and hemiplegia, and bilaterally in the lower limbs in hemiplegia. In herniplegia, joint-position sense and kinesthesia deficits were noted on the dominant limbs, but were significantly worse on the nondominant limbs. Conclusions: These results indicate that people with CP have proprioception deficits in all limbs. C1 [Wingert, Jason R.] Univ N Carolina, Dept Hlth & Wellness, Asheville, NC 28804 USA. [Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Anat, St Louis, MO USA. [Burton, Harold; Sinclair, Robert J.] Washington Univ, Sch Med, Dept Neurobiol, St Louis, MO USA. [Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Damiano, Diane L.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Wingert, JR (reprint author), Univ N Carolina, Dept Hlth & Wellness, WHC CPO 2730,1 Univ Hts, Asheville, NC 28804 USA. EM jwingert@unca.edu RI Damiano, Diane/B-3338-2010; Wingert, Jason/B-1528-2012 OI Damiano, Diane/0000-0002-2770-5356; FU NINDS NIH HHS [F31 NS054413, NS054413, NS31005, R01 NS031005, R01 NS031005-34] NR 28 TC 43 Z9 45 U1 0 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2009 VL 90 IS 3 BP 447 EP 453 DI 10.1016/j.apmr.2008.08.217 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 421YW UT WOS:000264395200012 PM 19254610 ER PT J AU Sack, MN Murphy, E Schulz, R AF Sack, Michael N. Murphy, Elizabeth Schulz, Rainer TI The regulation and control of mitochondrial homeostasis in changing cardiac tolerance to ischemia-reperfusion injury: a focused issue SO BASIC RESEARCH IN CARDIOLOGY LA English DT Editorial Material ID DYNAMICS; HEART C1 [Schulz, Rainer] Univ Klinikum Essen, Inst Pathophysiol, Essen, Germany. [Sack, Michael N.; Murphy, Elizabeth] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Schulz, R (reprint author), Univ Klinikum Essen, Inst Pathophysiol, Essen, Germany. EM sackm@nhlbi.nih.gov; murphy1@nhlbi.nih.gov; rainer.schulz@uk-essen.de NR 18 TC 2 Z9 2 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD MAR PY 2009 VL 104 IS 2 BP 111 EP 112 DI 10.1007/s00395-009-0005-7 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 416BS UT WOS:000263980800001 PM 19259761 ER PT J AU Steenbergen, C Das, S Su, J Wong, R Murphy, E AF Steenbergen, Charles Das, Samarjit Su, Jason Wong, Renee Murphy, Elizabeth TI Cardioprotection and altered mitochondrial adenine nucleotide transport SO BASIC RESEARCH IN CARDIOLOGY LA English DT Review ID PERMEABILITY TRANSITION PORE; DEPENDENT ANION CHANNEL; GLYCOGEN-SYNTHASE KINASE-3-BETA; OPIOID-INDUCED CARDIOPROTECTION; HEXOKINASE-II; ISCHEMIC-MYOCARDIUM; ENERGY-METABOLISM; CARDIAC MYOCYTES; PROTEIN-KINASE; RAT-HEART AB It is becoming increasingly clear that mitochondrial dysfunction is critically important in myocardial ischemic injury, and that cardioprotective mechanisms must ultimately prevent or attenuate mitochondrial damage. Mitochondria are also essential for energy production, and therefore prevention of mitochondrial injury must not compromise oxidative phosphorylation during reperfusion. This review will focus on one mitochondrial mechanism of cardioprotection involving inhibition of adenine nucleotide transport across the outer mitochondria membrane under de-energized conditions. This slows ATP hydrolysis by the mitochondria, and would be expected to lower mitochondrial membrane potential during ischemia, to inhibit calcium uptake during ischemia, and potentially to reduce free radical generation during early reperfusion. Two interventions that similarly inhibit mitochondrial adenine nucleotide transport are Bcl-2 overexpression and GSK inhibition. A possible final common mechanism shared by both of these interventions is discussed. C1 [Steenbergen, Charles; Das, Samarjit; Su, Jason] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. [Wong, Renee; Murphy, Elizabeth] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. RP Steenbergen, C (reprint author), Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. EM csteenb1@jhmi.edu FU Intramural NIH HHS [ZIA HL002066-04, ZIA HL006059-02, ZIA HL002065-04]; NHLBI NIH HHS [R01 HL039752] NR 45 TC 20 Z9 21 U1 1 U2 4 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD MAR PY 2009 VL 104 IS 2 BP 149 EP 156 DI 10.1007/s00395-009-0002-x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 416BS UT WOS:000263980800006 PM 19242642 ER PT J AU Brigman, JL Mathur, P Lu, L Williams, RW Holmes, A AF Brigman, Jonathan L. Mathur, Poonam Lu, Lu Williams, Robert W. Holmes, Andrew TI Genetic relationship between anxiety-related and fear-related behaviors in BXD recombinant inbred mice SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE gene; genetics; learning; mouse; open field; plus-maze; quantitative trait locus; rotarod; startle ID QUANTITATIVE TRAIT LOCI; DEPRESSION-RELATED BEHAVIOR; SEROTONIN TRANSPORTER GENE; ELEVATED PLUS-MAZE; MOUSE STRAINS; ANIMAL-MODELS; EMOTIONALITY; ENVIRONMENT; SELECTION; C57BL/6J AB Mood and anxiety disorders, and rodent phenotypic measures modeling these disorders, have a strong genetic component. Various assays are used to study the neurobiological basis of fear-related and anxiety-related behaviors, phenotype genetically modified mice, and elucidate pharmacological modulation of these behaviors for medication development. Earlier work, however, suggests that different trait measures are mediated by partly overlapping but ultimately distinct genetic factors. In this study, we assessed a novel panel of 23 C57BL/6J x DBA/2J (BXD) recombinant inbred strains on various trait measures of Pavlovian fear conditioning and anxiety-like behavior (novel open field, elevated plus-maze), as well as sensory (acoustic startle, prepulse inhibition of startle) and motor (baseline coordination and learning on accelerating rotarod) function. Results showed that traits were continuously distributed across strains and had modest to strong R(2) values. Principal components analysis resolved the data into five factors: factor 1 loaded fear-related traits, factor 2 loaded elevated plus-maze measures as well as context fear, factor 3 loaded novel open field measures and plus-maze closed arm entries, factor 4 loaded rotarod motor function, and factor 5 loaded acoustic startle and prepulse inhibition. These data add to evidence that murine measures of fear-like and anxiety-like traits reflect distinct constructs mediated by dissociable gene variants. Behavioural Pharmacology 20:204-209 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Brigman, Jonathan L.; Mathur, Poonam; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Lu, Lu; Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN USA. RP Brigman, JL (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM brigmanj@mail.nih.gov RI Brigman, Jonathan/O-4978-2016; OI Williams, Robert/0000-0001-8924-4447 FU NIAAA [Z01-AA000411]; NIDA; NIMH; NIAAA HPG [P20-DA 21131]; NCRR [U24 RR021760]; NIAM [U01AA13499, U24AA13513] FX The authors are grateful to Khyobeni Mozhui for Genenetwork.org data management. Research supported by the NIAAA (Z01-AA000411) intramural research program, and by NIDA, NIMH, and NIAAA HPG Grant P20-DA 21131, NCRR BIRN Grant U24 RR021760 (BIRN), and NIAM INIA Grants U01AA13499 and U24AA13513. NR 41 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD MAR PY 2009 VL 20 IS 2 BP 204 EP 209 DI 10.1097/FBP.0b013e32830c368c PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 438NB UT WOS:000265561000009 PM 18830130 ER PT J AU Shi, Z Tiwari, AK Shukla, S Robey, RW Kim, IW Parmar, S Bates, SE Si, QS Goldblatt, CS Abraham, I Fu, LW Ambudkar, SV Chen, ZS AF Shi, Zhi Tiwari, Amit K. Shukla, Suneet Robey, Robert W. Kim, In-Wha Parmar, Smitaben Bates, Susan E. Si, Qiu-Sheng Goldblatt, Curtis S. Abraham, Ioana Fu, Li-Wu Ambudkar, Suresh V. Chen, Zhe-Sheng TI Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE EGFR tyrosine kinase inhibitor; Multidrug resistance; ABCB1; ABCG2 ID GROWTH-FACTOR-RECEPTOR; HUMAN P-GLYCOPROTEIN; RESISTANT CANCER-CELLS; SUBFAMILY-B MEMBER-1; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; ACQUIRED MUTATIONS; CATALYTIC CYCLE; ATP HYDROLYSIS; HIGHLY POTENT AB The tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) is a potent and specific EGFR tyrosine kinase inhibitor (TKI); its promising pre-clinical results have led to clinical trials. Overexpression of ATP-binding cassette (ABC) transporters such as ABCB1, ABCC1 and ABCG2 is one of the main causes of multidrug resistance (MDR) and usually results in the failure of cancer chemotherapy. However, the interaction of AG1478 with these ABC transporters is still unclear. In the present study, we have investigated this interaction and found that AG1478 has differential effects on these transporters. In ABCB1-overexpressing cells, non-toxic doses of AG1478 were found to partially inhibit resistance to ABCB1 substrate anticancer drugs as well as increase intracellular accumulation of [(3)H]-paclitaxel. Similarly, in ABCG2-overexpressing cells, AG1478 significantly reversed resistance to ABCG2 substrate anticancer drugs and increased intracellular accumulation of [(3)H]-mitoxantrone as well as fluorescent compound BODIPY-prazosin. AG1478 also profoundly inhibited the transport of [(3)H]-E(2)17 beta G and [(3)H]-methotrexate by ABCG2. We also found that AG1478 slightly stimulated ABCB1 ATPase activity and significantly stimulated ABCG2 ATPase activity. Interestingly, AG1478 did not inhibit the photolabeling of ABCB1 or ABCG2 with [(125)I]-iodoarylazidoprazosin. Additionally, AG1478 did not alter the sensitivity of parental, ABCB1- or ABCG2-overexpressing cells to non-ABCB1 and non-ABCG2 substrate drug and had no effect on the function of ABCC1. Overall, we conclude that AG1478 is able to inhibit the function of ABCB1 and ABCG2, with a more pronounced effect on ABCG2. Our findings provide valuable contributions to the development of safer and more effective EGFR TKIs for use as anticancer agents in the clinic. (C) 2008 Elsevier Inc. All rights reserved. C1 [Shi, Zhi; Fu, Li-Wu] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510060, Guangdong, Peoples R China. [Shi, Zhi; Tiwari, Amit K.; Parmar, Smitaben; Abraham, Ioana; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. [Shukla, Suneet; Kim, In-Wha; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD USA. [Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Si, Qiu-Sheng; Goldblatt, Curtis S.] Conemaugh Mem Med Ctr, Dept Pathol, Johnstown, PA 15905 USA. RP Fu, LW (reprint author), Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510060, Guangdong, Peoples R China. EM rulw@mail.sysu.edu.cn; Chenz@stjohns.edu RI Tiwari, Amit/A-3667-2012; shukla, suneet/B-4626-2012 OI Tiwari, Amit/0000-0002-7427-7155; FU St. John's University Tenure Track Faculty Start-Up Funding [C-0531]; Ministry of Education Doctor Foundation [20050558062]; Guangdong Provincial Key Sciences Foundation [20041330101005]; Intramural Research Program, Center for Cancer Research, National Cancer Institute, NIH. FX We thank Drs. Michael M. Gottesman (NCI, NIH, Bethesda, MD) for KB-3-1 cells, Shin-ichi Akiyama (Kagoshima University, Japan) for KB-C2 and KB-CV60 cell lines, Gary D. Kruh (Cancer Center, University of Illinois, Chicago, IL) for antibodies for ABCC subfamily members, Dong-Hua Yang (Robert Wood Johnson Medical School, New Jersey) for technical support of immunocytochemistry, Yangmin (Mimi) Chen (Montgomery High School, New Jersey) and Tong Shen (St. John's University, New York) for the editorial assistance. We thank Novartis Pharmaceuticals (East Hanover, New Jersey) for valspodar (PSC833). This work was supported by funds from St. John's University Tenure Track Faculty Start-Up Funding (No. C-0531, ZS. Chen), the Chinese Ministry of Education Doctor Foundation (No. 20050558062, L.W. Fu), and the Guangdong Provincial Key Sciences Foundation (No. 20041330101005, L.W. Fu). I.W. Kim, S. Shukla, R.W. Robey, SE Bates and SV Ambudkar were supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, NIH. Z. Shi is a recipient of Kaisi fellowship for overseas study at St. John's University from Sun Yat-Sen University. NR 42 TC 43 Z9 44 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 1 PY 2009 VL 77 IS 5 BP 781 EP 793 DI 10.1016/j.bcp.2008.11.007 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 413SH UT WOS:000263812300003 PM 19059384 ER PT J AU Pasek, M Ramakrishnan, B Boeggeman, E Manzoni, M Waybright, TJ Qasba, PK AF Pasek, Marta Ramakrishnan, Boopathy Boeggeman, Elizabeth Manzoni, Maria Waybright, Timothy J. Qasba, Pradman K. TI Bioconjugation and Detection of Lactosamine Moiety using alpha 1,3-Galactosyltransferase Mutants That Transfer C2-Modified Galactose with a Chemical Handle SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BLOOD-GROUP-A; GROUP-B GLYCOSYLTRANSFERASES; TO-CARBOHYDRATE INTERACTION; CONFORMATIONAL-CHANGES; MASS-SPECTROMETRY; DONOR SPECIFICITY; CELL RECOGNITION; STRUCTURAL BASIS; SUBSTRATE; GLYCOSYLATION AB Studies on wild-type and mutant glycosyltransferases have shown that they can transfer modified sugars with a versatile chemical handle, such as keto or azido group, that can be used for conjugation chemistry and detection of glycan residues on glycoconjugates. To detect the most prevalent glycan epitope, N-acetyllactosamine (LacNAc (Gal beta 1-4GalNAc beta)), we have mutated a bovine alpha 1,3-galactosyltransferse (alpha 3Gal-T) enzyme which normally transfers Gal from UDP-Gal to the LacNAc acceptor, to transfer GalNAc or C2-modified galactose from their UDP derivatives. The alpha 3Gal-T enzyme belongs to the alpha 3Gal/GalNAc-T family that includes human blood group A and B glycosyltransferases, which transfer GalNAc and Gal, respectively, to the Gal moiety of the trisaccharide Fuc alpha 1-2Gal beta 1-4GlcNAc. On the basis of the sequence and structure comparison of these enzymes, we have carried out rational mutation studies on the sugar donor-binding residues in bovine alpha 3Gal-T at positions 280 to 282. A mutation of His280 to Leu/Thr/Ser/Ala or Gly and Ala281 and Ala282 to Gly resulted in the GalNAc transferase activity by the mutant alpha 3Gal-T enzymes to 5-19% of their original Gal-T activity. We show that the mutants (280)SGG(282) and (280)AGG(212) with the highest GalNAc-T activity can also transfer modified sugars such as 2-keto-galactose or GalNAz from their respective UDP-sugar derivatives to LacNAc moiety present at the nonreducing end of glycans of asialofetuin, thus enabling the detection of LacNAc moiety of glycoproteins and glycolipids by a chemiluminescence method. C1 [Pasek, Marta; Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Manzoni, Maria; Qasba, Pradman K.] NCI, Struct Glycobiol Sect, Nanobiol Program, CCR, Frederick, MD 21702 USA. [Ramakrishnan, Boopathy; Boeggeman, Elizabeth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21702 USA. [Waybright, Timothy J.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, Nanobiol Program, CCR, Bldg 469,Room 221, Frederick, MD 21702 USA. EM qasba@helix.nih.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX We thank Dr. Linda Hsieh-Wilson, Caffech, for helping Dr. Maria Manzoni during the synthesis of UDP-2-keto galactose and Dr. Natalia Mercer for the critical reading of the manuscript. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 37 TC 10 Z9 10 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR PY 2009 VL 20 IS 3 BP 608 EP 618 DI 10.1021/bc800534r PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 421WU UT WOS:000264389800026 PM 19245254 ER PT J AU Yamaguchi, Y Hearing, VJ AF Yamaguchi, Yuji Hearing, Vincent J. TI Physiological factors that regulate skin pigmentation SO BIOFACTORS LA English DT Article DE melanin; melanosome; pigmentation; regulation; skin ID MESENCHYMAL-EPITHELIAL INTERACTIONS; MATRIX PROTEIN PMEL17/GP100; LYSOSOME-RELATED ORGANELLES; EXPOSING BONE-MARROW; INTRACELLULAR TRAFFICKING; PALMOPLANTAR FIBROBLASTS; MELANOSOME BIOGENESIS; TYROSINASE ACTIVITY; MELANOCYTE FUNCTION; TRANSPORT AB More than 150 genes have been identified that affect skin color either directly or indirectly, and we review current understanding of physiological factors that regulate skin pigmentation. We focus on melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes, and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells, and nerves. Enzymatic components of melanosomes include tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase, which depend on the functions of OA1, P, MATP, ATP7A, and BLOC-1 to synthesize eumelanins and pheomelanins. The main structural component of melanosomes is Pmel17/gp100/Silv, whose sorting involves adaptor protein 1A (AP1A), AP1B, AP2, and spectrin, as well as a chaperone-like component, MART-1. During their maturation, melanosomes move from the perinuclear area toward the plasma membrane. Microtubules, dynein, kinesin, actin filaments, Rab27a, melanophilin, myosin Va, and Slp2-a are involved in melanosome transport. Foxn1 and p53 up-regulate skin pigmentation via bFGF and POMC derivatives including alpha-MSH and ACTH, respectively. Other critical factors that affect skin pigmentation include MC1R, CREB, ASP, MITF, PAX3, SOX9/10, LEF-1/TCF, PAR-2, DKK1, SCF, HGF, GM-CSF, endothelin-1, prostaglandins, leukotrienes, thromboxanes, neurotrophins, and neuropeptides. UV radiation up-regulates most factors that increase melanogenesis. Further studies will elucidate the currently unknown functions of many other pigment genes/proteins. (C) 2009 International Union of Biochemistry and Molecular Biology, Inc. Volume 35, Number 2, March/April 2009, Pages 193-199 . E-mail: yujin@med.nagoya-cu.ac.jp C1 [Yamaguchi, Yuji] Nagoya City Univ, Grad Sch Med Sci, Dept Geriatr & Environm Dermatol, Mizuho Ku, Nagoya, Aichi 4678601, Japan. [Yamaguchi, Yuji; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yamaguchi, Y (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Geriatr & Environm Dermatol, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan. EM yujin@med.nagoya-cu.ac.jp FU Ministry of Education, Culture, Sports, and Technology [18689028]; NIH; Cosmetology Foundation; Aichi Cancer Research Foundation FX This work was supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, and Technology (Japan; no. 18689028), by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, by a grant from the Cosmetology Foundation, and by a grant from the Aichi Cancer Research Foundation. We would like to thank Prof. Dr. Akimichi Morita, MD, Phl), Chairman of Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, for the critical review of this work. NR 59 TC 186 Z9 197 U1 9 U2 28 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PD MAR-APR PY 2009 VL 35 IS 2 BP 193 EP 199 DI 10.1002/biof.29 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 453ST UT WOS:000266632900012 PM 19449448 ER PT J AU Alon, S Eisenberg, E Jacob-Hirsch, J Rechavi, G Vatine, G Toyama, R Coon, SL Klein, DC Gothilf, Y AF Alon, Shahar Eisenberg, Eli Jacob-Hirsch, Jasmine Rechavi, Gideon Vatine, Gad Toyama, Reiko Coon, Steven L. Klein, David C. Gothilf, Yoav TI A new cis-acting regulatory element driving gene expression in the zebrafish pineal gland SO BIOINFORMATICS LA English DT Article ID PHOTORECEPTOR CONSERVED ELEMENTS; COMPUTATIONAL IDENTIFICATION; DNA-SEQUENCE; E-BOX; PROTEIN; MOTIFS; VALIDATION; DISCOVERY; MODULES; SITES AB Motivation: The identification of functional cis-acting DNA regulatory elements is a crucial step towards understanding gene regulation. Ab initio motif detection algorithms have been extensively used in search of regulatory elements. Yet, their success in providing experimentally validated regulatory elements in vertebrates has been limited. Results: Here we report in silico identification and in vivo validation of regulatory elements that determine enhanced gene expression in the pineal gland of zebrafish. Microarray data enabled detection of genes that exhibit high expression in the pineal gland. The promoter regions of these genes were computationally analyzed in order to identify overrepresented motifs. The highest ranking motif identified is a CRX/OTX binding site, known to govern expression in the pineal gland and retina. The second highest ranking motif was not reported before; we experimentally validated its function in vivo by mutational analysis. The methodology presented here may be applicable as a general scheme for finding regulatory elements that contribute to tissue-specific gene expression. C1 [Alon, Shahar; Vatine, Gad; Gothilf, Yoav] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. [Eisenberg, Eli] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-69978 Tel Aviv, Israel. [Jacob-Hirsch, Jasmine; Rechavi, Gideon] Tel Aviv Univ, Tel Hashomer & Sackler Sch Med, Chaim Sheba Med Ctr, Canc Res Ctr, IL-69978 Tel Aviv, Israel. [Toyama, Reiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Coon, Steven L.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Alon, S (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. EM elieis@post.tau.ac.il; yoavg@tauex.tau.ac.il RI Eisenberg, Eli/D-2587-2009 OI Eisenberg, Eli/0000-0001-8681-3202 NR 24 TC 10 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 1 PY 2009 VL 25 IS 5 BP 559 EP 562 DI 10.1093/bioinformatics/btp031 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 413ZV UT WOS:000263834600001 PM 19147662 ER PT J AU Taher, L Ovcharenko, I AF Taher, Leila Ovcharenko, Ivan TI Variable locus length in the human genome leads to ascertainment bias in functional inference for non-coding elements SO BIOINFORMATICS LA English DT Article ID ONLINE MENDELIAN INHERITANCE; GENE ONTOLOGY TERMS; MAN OMIM; MOUSE; KNOWLEDGEBASE; DISORDERS; SEQUENCES; TOOL; INTEGRATION; ANNOTATION AB Motivation: Several functional gene annotation databases have been developed in the recent years, and are widely used to infer the biological function of gene sets, by scrutinizing the attributes that appear over- and underrepresented. However, this strategy is not directly applicable to the study of non-coding DNA, as the non-coding sequence span varies greatly among different gene loci in the human genome and longer loci have a higher likelihood of being selected purely by chance. Therefore, conclusions involving the function of non-coding elements that are drawn based on the annotation of neighboring genes are often biased. We assessed the systematic bias in several particular Gene Ontology (GO) categories using the standard hypergeometric test, by randomly sampling non-coding elements from the human genome and inferring their function based on the functional annotation of the closest genes. While no category is expected to occur significantly over- or underrepresented for a random selection of elements, categories such as 'cell adhesion', 'nervous system development' and 'transcription factor activities' appeared to be systematically overrepresented, while others such as 'olfactory receptor activity'-underrepresented. Results: Our results suggest that functional inference for non-coding elements using gene annotation databases requires a special correction. We introduce a set of correction coefficients for the probabilities of the GO categories that accounts for the variability in the length of the non-coding DNA across different loci and effectively eliminates the ascertainment bias from the functional characterization of non-coding elements. Our approach can be easily generalized to any other gene annotation database. C1 [Taher, Leila; Ovcharenko, Ivan] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Ovcharenko, I (reprint author), Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM ovcharei@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health; National Library of Medicine FX Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 38 TC 17 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 1 PY 2009 VL 25 IS 5 BP 578 EP 584 DI 10.1093/bioinformatics/btp043 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 413ZV UT WOS:000263834600004 PM 19168912 ER PT J AU McDermott, JM Perez-Edgar, K Henderson, HA Chronis-Tuscano, A Pine, DS Fox, NA AF McDermott, Jennifer M. Perez-Edgar, Koraly Henderson, Heather A. Chronis-Tuscano, Andrea Pine, Daniel S. Fox, Nathan A. TI A History of Childhood Behavioral Inhibition and Enhanced Response Monitoring in Adolescence Are Linked to Clinical Anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anxiety; attention; behavioral inhibition; ERP; flanker; response monitoring ID DISORDERS; CHILDREN; ASSOCIATION; TASK; ERP AB Background: Behaviorally inhibited (BI) children who also exhibit enhanced response monitoring might be at particularly high risk for anxiety disorders. The current study tests the hypothesis that response monitoring, as manifest in the error-related negativity (ERN), moderates the association between BI and anxiety. Methods: Participants (n = 113; 73 male) assessed for early-childhood BI were re-assessed as adolescents with a clinical interview and a flanker paradigm that generated behavioral data and event-related potentials (ERPs). Risk for anxiety disorders in adolescents was examined as a function of childhood-BI status and adolescent performance on the flanker paradigm. Results: Adolescents with childhood BI displayed ERP evidence of enhanced response monitoring, manifest as large ERNs. The ERN moderated the relationship between early BI and later clinically significant disorders. Conclusions: Physiological measures of response monitoring might moderate associations between early-childhood BI and risk for psychopathology. The subset of children with BI and enhanced response monitoring might face greater risk for later-life clinical anxiety than children with either BI or enhanced response monitoring alone. C1 [McDermott, Jennifer M.] Univ Wisconsin, Waisman Ctr, Child Emot Res Lab, Madison, WI 53705 USA. [Perez-Edgar, Koraly] George Mason Univ, Fairfax, VA 22030 USA. [Henderson, Heather A.] Univ Miami, Coral Gables, FL 33124 USA. [Chronis-Tuscano, Andrea; Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA. [Pine, Daniel S.] NIH, Bethesda, MD 20892 USA. RP McDermott, JM (reprint author), Univ Wisconsin, Waisman Ctr, Child Emot Res Lab, 1500 Highland Ave, Madison, WI 53705 USA. EM mcdermott@waisman.wisc.edu OI Perez-Edgar, Koraly/0000-0003-4051-9563 FU National Institutes of Health [MH074454, HD17899] FX Supplementary material cited in thiss article is available online. NR 19 TC 86 Z9 86 U1 1 U2 12 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 MAR 1 PY 2009 VL 65 IS 5 BP 445 EP 448 DI 10.1016/j.biopsych.2008.10.043 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 408SM UT WOS:000263455300014 PM 19108817 ER PT J AU Peranteau, WH Heaton, TE Gu, YC Volk, SW Bauer, TR Alcorn, K Tuschong, LM Johnson, MP Hickstein, DD Flake, AW AF Peranteau, William H. Heaton, Todd E. Gu, Yu-Chen Volk, Susan W. Bauer, Thomas R. Alcorn, Keith Tuschong, Laura M. Johnson, Mark P. Hickstein, Dennis D. Flake, Alan W. TI Haploidentical In Utero Hematopoietic Cell Transplantation Improves Phenotype and Can Induce Tolerance for Postnatal Same-Donor Transplants in the Canine Leukocyte Adhesion Deficiency Model SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE In utero transplantation; Fetus; Canine; Leukocyte adhesion deficiency; Minimal conditioning transplantation ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; SEVERE COMBINED IMMUNODEFICIENCY; LEVEL ALLOGENEIC CHIMERISM; LINKED MUSCULAR-DYSTROPHY; PARTURITION DATE; T-CELLS; P150,95 GLYCOPROTEINS; DOGS; ENGRAFTMENT AB In the murine model, in utero hematopoietic cell transplantation (IUHCT) has been shown to achieve low levels of allogeneic chimerism and associated donor-specific tolerance permitting minimal conditioning postnatal hematopoietic stem cell transplantation (HSCT). In this pilot study, we investigated IUHCT in the canine leukocyte adhesion deficiency (CLAD) model. Haploidentical IUHCT resulted in stable low-level donor cell chimerism in all dogs that could be analyzed by sensitive detection methodology (4 of 10) through 18 months of follow-up. In the 2 CLAD recipients, low-level chimerism resulted in amelioration and complete reversal of the CLAD phenotype, respectively. Six recipients of IUHCT (5 carriers and I CLAD) subsequently received postnatal HSCT from the same haploidentical prenatal donor after minimal conditioning with busulfan 10 mg/kg. Chimerism in 2 of 5 CLAD carriers that underwent HSCT increased from < I pre-HSCT to sustained levels of 35% to 45%. Control animals undergoing postnatal haploidentical HSCT without IUHCT had no detectable donor chimerism. These results demonstrate that haploidentical IUHCT in the CLAD model can result in low-level donor chimerism that can prevent the lethal phenotype in CLAD dogs, and can result in donor-specific tolerance that can facilitate postnatal minimal conditioning HSCT. C1 [Flake, Alan W.] Childrens Hosp Philadelphia, Dept Surg, Ctr Fetal Res, Philadelphia, PA 19104 USA. [Gu, Yu-Chen; Bauer, Thomas R.; Tuschong, Laura M.; Hickstein, Dennis D.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Flake, AW (reprint author), Childrens Hosp Philadelphia, Dept Surg, Ctr Fetal Res, Abramson Res Bldg,Room 11 16B,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM flake@email.chop.edu RI Heaton, Todd/E-5197-2016 OI Heaton, Todd/0000-0003-3515-0028 FU National Institutes of Health [RO1 HL64715, U54 HL070596-01]; Pennsylvania State Health Research Formula Award; Greenfield Foundation; Ruth and Tristram C. Colket Jr Chair of Pediatric Surgery; Center for Cancer Research, National Cancer Institute; [T32 HD046402] FX This work was supported by National Institutes of Health Grants RO1 HL64715 and U54 HL070596-01 (to A.F.), a Pennsylvania State Health Research Formula Award (CHOP allocation), and the Greenfield Foundation. W.Y. and T.H. were supported by T32 HD046402. A.F. also was supported by funds from the Ruth and Tristram C. Colket Jr Chair of Pediatric Surgery. Y.G., T.B., L.T., and D.H. were supported by the Center for Cancer Research, National Cancer Institute. NR 48 TC 22 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2009 VL 15 IS 3 BP 293 EP 305 DI 10.1016/j.bbmt.2008.11.034 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 410ZQ UT WOS:000263617200002 PM 19203720 ER PT J AU Davies, SM Wang, D Wang, T Arora, M Ringden, O Anasetti, C Pavletic, S Casper, J MacMillan, ML Sanders, J Wall, D Kernan, NA AF Davies, Stella M. Wang, Dan Wang, Tao Arora, Muhkta Ringden, Olle Anasetti, Claudio Pavletic, Steven Casper, James MacMillan, Margaret L. Sanders, Jean Wall, Donna Kernan, Nancy A. TI Recent Decrease in Acute Graft-versus-Host Disease in Children with Leukemia Receiving Unrelated Donor Bone Marrow Transplants SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE GVHD; Unrelated donor transplantation; Children; Leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; RISK-FACTORS; FAILURE PROBABILITIES; MYELOID-LEUKEMIA; COMPETING RISKS; INCOMPATIBILITY; THERAPY; IMPACT; BLOOD AB Unrelated donor (URD) bone marrow transplantation (BMT) is an effective treatment for leukemia in children, but its success is threatened by graft-versus-host disease (GVHD) and relapse. In this report, we describe the incidence of and risk factors for GVHD over time in children receiving URD BMT We analyzed outcomes of 638 myeloablative URD BMTs performed between 1990 and 2003 to treat acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia, or myelodysplastic syndrome MDS, using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. All recipients were under age 18 years and had available high-resolution HLA typing for HLA-A, -B, -C, and -DRBI. Overall, 27% of the recipients developed acute GVHD (aGVHD) grade III-IV; the risk was significantly higher in children receiving T cell-replete grafts compared with those receiving T cell-depleted grafts (odds ratio [OR] = 3.12; 95% confidence interval [CI] = 2.02 to 4.83; P < .0001). Acute GVHD significantly reduced the risk of relapse in children with ALL (OR = 0.34; 95% CI = 0.13 to 0.86; P = .0052), but not in those with AML (OR = 0.58; 95% CI = 0.22 to 2.98; P = .26). The risk of aGVHD was higher in children undergoing transplantation in 1990-1998 (n = 365) compared with those doing so in 1999-2003 (OR = 1.93; 95% CI = 1.27 to 2.91; P = .002). We conclude that outcomes have changed significantly over time, with a reduced risk of aGVHD associated with the more recent transplantations. C1 [Davies, Stella M.] Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH 45230 USA. [Davies, Stella M.] Med Ctr, Cincinnati, OH USA. [Wang, Dan; Arora, Muhkta] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Wang, Tao] Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA. [Ringden, Olle] Karolinska Univ Hosp, Dept Lab Med, Huddinge, Sweden. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Pavletic, Steven] NIH, Expt Transplant & Immunol Branch, Bethesda, MD 20892 USA. [Casper, James] Childrens Hosp, Dept Pediat, Milwaukee, WI USA. [Casper, James] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [MacMillan, Margaret L.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Sanders, Jean] Fred Hutchinson Canc Res Ctr, Dept Pediat, Seattle, WA 98104 USA. [Wall, Donna] Texas Transplant Inst, San Antonio, TX USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Davies, SM (reprint author), Cincinnati Childrens Hosp, Dept Pediat, ML 7015,3333 Barnet Ave, Cincinnati, OH 45230 USA. EM stella.davies@cchmc.org OI Kernan, Nancy/0000-0003-1417-1823 FU NCI NIH HHS [U24 CA076518] NR 36 TC 22 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2009 VL 15 IS 3 BP 360 EP 366 DI 10.1016/j.bbmt.2008.12.495 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 410ZQ UT WOS:000263617200009 PM 19203727 ER PT J AU Patel, AR Turner, ML Baird, K Gea-Banacloche, J Mitchell, S Pavletic, SZ Wise, B Cowen, EW AF Patel, Asha R. Turner, Maria L. Baird, Kristin Gea-Banacloche, Juan Mitchell, Sandra Pavletic, Steven Z. Wise, Barbara Cowen, Edward W. TI Voriconazole-Induced Phototoxicity Masquerading as Chronic Graft-versus-Host Disease of the Skin in Allogeneic Hematopoietic Cell Transplant Recipients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Graft-versus-host disease; Voriconazole; Phototoxicity; Fungal infection ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; INVASIVE ASPERGILLOSIS; ANTIFUNGAL AGENTS; CLINICAL-TRIALS; PSEUDOPORPHYRIA; CHILDREN; THERAPY; DRUG; PHOTOSENSITIVITY AB Systemic fungal infections pose a significant risk to patients following allogeneic hematopoietic cell transplantation (alloHCT). Voriconazole (Vfend (R), Pfizer) is an oral second-generation triazole antifungal agent that offers a broad spectrum of coverage against fungal species and is frequently utilized in the post-HCT setting. Herein, we describe 5 patients who were initially believed to be experiencing a flare of cutaneous chronic graft-versus-host disease (cGVHD), but who were actually exhibiting phototoxicity caused by voriconazole. A high index of suspicion for this adverse reaction in the post-alloHCT setting will prevent misdiagnosis and avoid inappropriate therapy for cGVHD. C1 [Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Baird, Kristin; Wise, Barbara] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Gea-Banacloche, Juan; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Mitchell, Sandra] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, NIH, 10 Ctr Dr,MSC 1908,Bldg 10,Rm 12N238, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU NIH, Center for Cancer Research, National Cancer Institute; Clinical Research Training Program; Pfizer Inc FX This research was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. Ms. Patel was supported by the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). NR 36 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2009 VL 15 IS 3 BP 370 EP 376 DI 10.1016/j.bbmt.2008.12.491 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 410ZQ UT WOS:000263617200011 PM 19203729 ER PT J AU Savani, BN Koklanaris, EK Le, Q Shenoy, A Goodman, S Barrett, AJ AF Savani, Bipin N. Koklanaris, Eleftheria K. Le, Quan Shenoy, Aarthi Goodman, Stacey Barrett, A. J. TI Prolonged Chronic Graft-versus-Host Disease is a Risk Factor for Thyroid Failure in Long-Term Survivors After Matched Sibling Donor Stem Cell Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hypothyroidism; Thyroid antibodies; Graft-versus-host disease; Long term survivor; Stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; FOLLOW-UP; DYSFUNCTION; CHILDHOOD; LEUKEMIA; CHILDREN; GVHD AB We studied thyroid function in 81 long-term survivors of allogeneic stem cell transplantation (allo-SCT), with a median follow-up of 84 months (range, 45 to 166 months). Median age at transplantation was 35 years (range, 6 to 66). Seventy-two of the patients received a total body irradiation (TBI)-containing conditioning regimen (n = 23, 12 Gy; n = 49, 13 Gy). Twenty-one of the patients (25.9%) had subclinical hypothyroidism, and 9 (11.1%) developed overt hypothyroidism at a median of 28 months (range, 3 to 78 months) after allo-SCT Multivariate logistic regression analysis demonstrated that prolonged immunosuppressive therapy (IST) was significantly associated with subclinical hypothyroidism (odds ratio [OR] = 3.8) and overt hypothyroidism (OR = 2.6). Antithyroglobulin and thyroid peroxidase antibody were detected in 12 of 60 patients tested (20%). No correlation was found between the occurrence of thyroid antibodies and hypothyroidism (P = .13) or chronic graft-versus-host disease (cGVHD) (P = .55). In conclusion, thyroid dysfunction is relatively common after allo-SCT and is more likely to occur in patients receiving prolonged IST for cGVHD; however, thyroid dysfunction does not appear to be related to an antibody-mediated autoimmune process. C1 [Savani, Bipin N.; Koklanaris, Eleftheria K.; Le, Quan; Shenoy, Aarthi; Barrett, A. J.] NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Savani, Bipin N.; Goodman, Stacey] Vanderbilt Univ, Vet Affairs Med Ctr, Nashville, TN USA. [Savani, Bipin N.; Goodman, Stacey] Vanderbilt Univ, Div Hematol Oncol, Nashville, TN USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5330,10 Ctr Dr,MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute FX This work was supported by the National Heart, Lung, and Blood Institute's intramural research program. NR 24 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2009 VL 15 IS 3 BP 377 EP 381 DI 10.1016/j.bbmt.2008.11.032 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 410ZQ UT WOS:000263617200012 PM 19203730 ER PT J AU Jefferson, WN Padilla-Banks, E Goulding, EH Lao, SPC Newbold, RR Williams, CJ AF Jefferson, Wendy N. Padilla-Banks, Elizabeth Goulding, Eugenia H. Lao, Shin-Ping C. Newbold, Retha R. Williams, Carmen J. TI Neonatal Exposure to Genistein Disrupts Ability of Female Mouse Reproductive Tract to Support Preimplantation Embryo Development and Implantation SO BIOLOGY OF REPRODUCTION LA English DT Article DE development; early development; embryo; endocrine disruptor; environment; estrogens; female reproductive tract; ovary; oviduct; phytoestrogens; soy ID OOCYTE NEST BREAKDOWN; PHYTOESTROGEN GENISTEIN; INFANT FORMULA; IN-VITRO; SYSTEM; MICE; EXPRESSION; FOLLICLES; OVARY; RAT AB Female mice treated neonatally with the phytoestrogen genistein (50 mg/kg/day) have multioocyte follicles, lack regular estrous cyclicity, and are infertile even after superovulation. To determine the cause of their infertility, we examined oocyte developmental competence and timing of embryo loss. Eggs obtained by superovulation of genistein-treated or control females were equally capable of being fertilized in vitro and cultured to the blastocyst stage. However, if eggs were fertilized in vivo, retrieved at the pronucleus stage, and cultured, there was a significant reduction in the percentage of embryos from genistein-treated females reaching the blastocyst stage. When these blastocysts were transferred to pseudopregnant recipients, the number of live pups produced was similar to that in controls. Preimplantation embryo development in vivo was examined by flushing embryos from the oviduct and/or uterus. Similar numbers of one-cell and two-cell embryos were obtained from genistein-treated and control females. However, significantly fewer embryos (<50%) were obtained from genistein-treated females on postcoital Days 3 and 4. To determine if neonatal genistein treatment altered the ability of the uterus to support implantation, blastocysts from control donors were transferred to control and genistein-treated pseudopregnant recipients. These experiments demonstrated that genistein-treated females are not capable of supporting normal implantation of control embryos. Taken together, these results suggest that oocytes from mice treated neonatally with genistein are developmentally competent; however, the oviductal environment and the uterus have abnormalities that contribute to the observed reproductive failure. C1 [Jefferson, Wendy N.; Padilla-Banks, Elizabeth; Lao, Shin-Ping C.; Williams, Carmen J.] Natl Inst Environm Hlth Sci, Reprod Med Grp, Mol Toxicol Lab, Natl Inst Hlth, Res Triangle Pk, NC USA. [Goulding, Eugenia H.] Natl Inst Environm Hlth Sci, Gamete Biol Sect, Mol Toxicol Lab, Natl Inst Hlth, Res Triangle Pk, NC USA. [Jefferson, Wendy N.; Padilla-Banks, Elizabeth; Newbold, Retha R.] Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, Mol Toxicol Lab, Natl Inst Hlth, Res Triangle Pk, NC USA. [Jefferson, Wendy N.; Padilla-Banks, Elizabeth; Newbold, Retha R.] Natl Inst Environm Hlth Sci, Dev Endocrinol & Endocrine Disruptor Sect, Mol Toxicol Lab, Natl Inst Hlth, Res Triangle Pk, NC USA. RP Williams, CJ (reprint author), NIEHS NIH DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM williamsc5@niehs.nih.gov RI Williams, Carmen/E-2170-2013 OI Williams, Carmen/0000-0001-6440-7086 FU Intramural NIH HHS [Z99 ES999999] NR 37 TC 46 Z9 51 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 2009 VL 80 IS 3 BP 425 EP 431 DI 10.1095/biolreprod.108.073171 PG 7 WC Reproductive Biology SC Reproductive Biology GA 410TZ UT WOS:000263602500005 PM 19005167 ER PT J AU Shalini, M Yogeeswari, P Sriram, D Stables, JP AF Shalini, M. Yogeeswari, P. Sriram, D. Stables, J. P. TI Cyclization of the semicarbazone template of aryl semicarbazones: synthesis and anticonvulsant activity of 4,5-diphenyl-2H-1,2,4-triazol-3(4H)-one SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Anticonvulsant; 1,2,4-Triazoles; Semicarbazones; Neurotoxicity ID ANTIEPILEPTIC DRUG DEVELOPMENT; DERIVATIVES; SEIZURES; DESIGN AB A new series of 4,5-diphenyl-2H- 1,2,4-triazol-3(4H)-one were synthesized to study the effect of cyclization of the semicarbazone moiety of aryl semicarbazones on the anticonvulsant activity. Structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis. All compounds were evaluated for their anticonvulsant activity in four animal models of seizures, viz. maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY), and subcutaneous picrotoxin (scPIC)-induced seizure threshold tests, The compounds were also evaluated for neurotoxicity. Compounds 4, 9, 14-19 exhibited anticonvulsant activity in all the four animal models of seizure. C1 [Shalini, M.; Yogeeswari, P.; Sriram, D.] Birla Inst Technol & Sci, Med Chem Res Lab, Pharm Grp, Pilani 333031, Rajasthan, India. [Stables, J. P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Yogeeswari, P (reprint author), Birla Inst Technol & Sci, Med Chem Res Lab, Pharm Grp, Pilani 333031, Rajasthan, India. EM pyogee@bits-pilani.ac.in NR 29 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD MAR PY 2009 VL 63 IS 3 BP 187 EP 193 DI 10.1016/j.biopha.2006.04.002 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 421JA UT WOS:000264354000003 PM 19422088 ER PT J AU Proschan, MA Nason, M AF Proschan, Michael A. Nason, Martha TI Conditioning in 2 x 2 Tables SO BIOMETRICS LA English DT Article DE Adaptive sample size; Conditional inference; Contingency table; Fisher's exact test; Nuisance parameter; Test of proportions ID CLINICAL-TRIALS AB Two-by-two tables arise in a number of diverse settings in biomedical research, including analysis of data from a clinical trial with a binary outcome and gating methods in flow cytometry to separate antigen-specific immune responses from general immune responses. These applications offer interesting challenges concerning what we should really be conditioning on-the total number of events, the number of events in the control condition, etc. We give several biostatistics examples to illustrate the complexities of analyzing what appear to be simple data. C1 [Proschan, Michael A.; Nason, Martha] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA. EM ProschaM@niaid.nih.gov; mnason@niaid.nih.gov NR 8 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2009 VL 65 IS 1 BP 316 EP 322 DI 10.1111/j.1541-0420.2008.01053.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 420RS UT WOS:000264307500035 PM 18505423 ER PT J AU Cao, HP Lin, R AF Cao, Heping Lin, Rui TI Quantitative Evaluation of His-Tag Purification and Immunoprecipitation of Tristetraprolin and its Mutant Proteins from Transfected Human Cells SO BIOTECHNOLOGY PROGRESS LA English DT Article DE His-tag purification; immunoprecipitation; in vivo radiolabeling; phosphorylation site; site-directed mutagenesis; tristetraprolin; zinc finger protein ID NECROSIS-FACTOR-ALPHA; MESSENGER-RNA DECAY; MOUSE 3T3-L1 ADIPOCYTES; ZINC-FINGER PROTEINS; GENE-EXPRESSION; RECOMBINANT TRISTETRAPROLIN; BINDING PROPERTIES; TNF-ALPHA; ELEMENT; SITE AB Histidine (His)-tag is widely used for affinity purification of recombinant proteins, but the yield and purity of expressed proteins are quite different. Little information is available about quantitative evaluation of this procedure. The objective of this study was to evaluate His-tag procedure quantitatively and to compare it with immunoprecipitation using radiolabeled tristetraprolin (TTP), a zinc finger protein with anti-inflammatory property. Human embryonic kidney 293 cells were transfected with wild-type and nine mutant plasmids with single or multiple phosphorylation site mutation(s) in His-TTP. These proteins were expressed and mainly localized in the cytosol of transfected cells by immunocytochemistry and confocal microscopy. His-TTP proteins were purified by Ni-NTA beads with imidazole elution, or precipitated by TTP antibodies from transfected cells after being labeled with [(32)P]-orthophosphate. The results showed that (1) His-tag purification was more effective than immunoprecipitation for TTP purification; (2) mutations in TTP increased the yield of His-TTP by both purification procedures; and (3) mutations in TTP increased the binding affinity of mutant proteins for Ni-NTA beads. These findings suggest that bioengineering phosphorylation sites in proteins can increase the production of recombinant proteins. (C) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 25: 461-467, 2009 C1 [Cao, Heping] ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. [Cao, Heping; Lin, Rui] Natl Inst Environm Hlth Sci, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Cao, HP (reprint author), ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, 10300 Baltimore Ave, Beltsville, MD 20705 USA. EM peacetd2003@yahoo.com; ruilin@peacetd.com FU NIH; National Institute of Environmental Health Sciences; USDA-ARS Human Nutrition Research Program FX This work was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and USDA-ARS Human Nutrition Research Program. The authors thank Dr. Perry J. Blackshear (NIEHS/NIH) for his generous support, Dr. Wi S. Lai for the wild-type and S197A mutant TTP plasmids, Ms. Elizabeth A. Kennington (NIH/NIEHS) for her assistance on radiolabelling, and Dr. Joseph F. Urban Jr. (USDA/ARS) for his helpful comments on the manuscript. NR 43 TC 5 Z9 6 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAR-APR PY 2009 VL 25 IS 2 BP 461 EP 467 DI 10.1021/bp.121 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 438RI UT WOS:000265572700020 PM 19330843 ER PT J AU Nery, FG Chen, HH Hatch, JP Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Keshavan, MS Soares, JC AF Nery, Fabiano G. Chen, Hua-Hsuan Hatch, John P. Nicoletti, Mark A. Brambilla, Paolo Sassi, Roberto B. Mallinger, Alan G. Keshavan, Matcheri S. Soares, Jair C. TI Orbitofrontal cortex gray matter volumes in bipolar disorder patients: a region-of-interest MRI study SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; magnetic resonance imaging; neuronal plasticity; prefrontal cortex; region-of-interest; stress ID VOXEL-BASED MORPHOMETRY; VENTRAL PREFRONTAL CORTEX; MAJOR DEPRESSION; ANATOMICAL MRI; ANTERIOR CINGULATE; DECISION-MAKING; ABNORMALITIES; SCHIZOPHRENIA; MANIA; HIPPOCAMPUS AB Objectives: Functional and postmortem studies suggest that the orbitofrontal cortex (OFC) is involved in the pathophysiology of bipolar disorder (BD). This anatomical magnetic resonance imaging (MRI) study examined whether BD patients have smaller OFC gray matter volumes compared to healthy comparison subjects (HC). Methods: Twenty-eight BD patients were compared to 28 age- and gender-matched HC. Subjects underwent a 1.5T MRI with 3D spoiled gradient recalled acquisition. Total OFC and medial and lateral subdivisions were manually traced by a blinded examiner. Images were segmented and gray matter volumes were calculated using an automated method. Results: Analysis of covariance, with intracranial volume as covariate, showed that BD patients and HC did not differ in gray matter volumes of total OFC or its subdivisions. However, total OFC gray matter volume was significantly smaller in depressed patients (n = 10) compared to euthymic patients (n = 18). Moreover, total OFC gray matter volumes were inversely correlated with depressive symptom intensity, as assessed by the Hamilton Depression Rating Scale. OFC gray matter volumes were not related to lithium treatment, age at disease onset, number of episodes, or family history of mood disorders. Conclusions: Our results suggest that abnormal OFC gray matter volumes are not a pervasive characteristic of BD, but may be associated with specific clinical features of the disorder. C1 [Nery, Fabiano G.; Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Nery, Fabiano G.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Chen, Hua-Hsuan] Univ Cincinnati, Dept Radiol, Cincinnati, OH USA. [Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. [Nicoletti, Mark A.; Soares, Jair C.] Univ N Carolina, Sch Med, Dept Psychiat, CERT BD, Chapel Hill, NC USA. [Brambilla, Paolo] Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. [Brambilla, Paolo] Sci Inst IRCCS E Medea, Udine, Italy. [Sassi, Roberto B.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Mallinger, Alan G.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Keshavan, Matcheri S.] Wayne State Sch Med, Dept Psychiat & Behav Sci, Detroit, MI USA. [Nery, Fabiano G.] Univ Sao Paulo, Sch Med, Bipolar Disorder Res Grp, Inst Psychiat,Dept Psychiat, BR-04503010 Sao Paulo, Brazil. RP Nery, FG (reprint author), Univ Sao Paulo, Sch Med, Bipolar Disorder Res Grp, Inst Psychiat,Dept Psychiat, Rua Dr Ovidio Pires Campos, BR-04503010 Sao Paulo, Brazil. EM fabiano_nery@hotmail.com RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NARSAD; Veterans Affairs; Krus Endowed Chair in Psychiatry; [MH 68766]; [MH 068662]; [RR 20571] FX This research was partly supported by MH 68766, MH 068662, RR 20571, NARSAD, Veterans Affairs (Merit Review), and the Krus Endowed Chair in Psychiatry. The views expressed in this paper do not necessarily reflect those of the NIH or the federal government. NR 53 TC 28 Z9 28 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2009 VL 11 IS 2 BP 145 EP 153 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 433DT UT WOS:000265185200004 PM 19267697 ER PT J AU Roiser, JP Cannon, DM Gandhi, SK Tavares, JT Erickson, K Wood, S Klaver, JM Clark, L Zarate, CA Sahakian, BJ Drevets, WC AF Roiser, Jonathan P. Cannon, Dara M. Gandhi, Shilpa K. Tavares, Joana Taylor Erickson, Kristine Wood, Suzanne Klaver, Jacqueline M. Clark, Luke Zarate, Carlos A., Jr. Sahakian, Barbara J. Drevets, Wayne C. TI Hot and cold cognition in unmedicated depressed subjects with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; depression; hot cognition; neuropsychology; unmedicated ID SUSTAINED ATTENTION-DEFICIT; SPATIAL WORKING-MEMORY; UNIPOLAR DEPRESSION; EUTHYMIC PATIENTS; DECISION-MAKING; NEUROCOGNITIVE FUNCTION; PARKINSONS-DISEASE; NEGATIVE FEEDBACK; ABNORMAL RESPONSE; TASK-PERFORMANCE AB Objectives: Neuropsychological studies in subjects with bipolar disorder (BD) have reported deficits on a variety of cognitive measures. However, because the majority of subjects were medicated at the time of testing in previous studies, it is currently unclear whether the pattern of deficits reported is related to BD itself or to psychotropic medication. We addressed this issue by examining cognitive performance in a group of unmedicated, currently depressed subjects with BD. Methods: Forty-nine unmedicated subjects who met DSM-IV criteria for BD, depressed phase, and 55 control subjects participated in this study. Most patients were diagnosed with bipolar II disorder. Performance on emotion-dependent, or 'hot', and emotion-independent, or 'cold', cognitive tasks was assessed using tests from the Cambridge Neuropsychological Test Automated Battery. Results: The groups were well matched with respect to general intelligence and demographic variables. Deficits in the unmedicated depressed BD group were apparent on tests tapping 'hot' cognitive processing, for example the Cambridge Gamble task and the Probabilistic Reversal Learning task. However, other than a deficit on the Spatial Span test in the depressed BD subjects, the groups performed equivalently on most measures of 'cold' cognitive processing, for example visual memory, attention, and working memory. Conclusions: These data suggest that deficits on tests involving reward processing, short-term spatial memory storage, and sensitivity to negative feedback in depressed BD subjects represent an effect of the illness itself and not mood-stabilizing medication. C1 [Cannon, Dara M.; Erickson, Kristine; Wood, Suzanne; Klaver, Jacqueline M.; Zarate, Carlos A., Jr.; Drevets, Wayne C.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Roiser, Jonathan P.] UCL, Inst Cognit Neurosci, London, England. [Cannon, Dara M.] Natl Univ Ireland, Inst Clin Sci, Dept Psychiat, Galway, Ireland. [Gandhi, Shilpa K.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Tavares, Joana Taylor; Clark, Luke] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 1TN, England. [Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. RP Drevets, WC (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Bldg 15K,Room 203, Bethesda, MD 20892 USA. EM drevetsw@mail.nih.gov RI Cannon, Dara/C-1323-2009; Roiser, Jonathan/A-1791-2010 OI Cannon, Dara/0000-0001-7378-3411; FU NIMH FX This research was supported by the Intramural Research Program of the NIMH. JPR and JTT were supported by the NIH- Cambridge Health Science Scholars Program. NR 59 TC 45 Z9 46 U1 5 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2009 VL 11 IS 2 BP 178 EP 189 PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 433DT UT WOS:000265185200007 PM 19267700 ER PT J AU Lee, TL Pang, ALY Rennert, OM Chan, WY AF Lee, Tin-Lap Pang, Alan Lap-Yin Rennert, Owen M. Chan, Wai-Yee TI Genomic Landscape of Developing Male Germ Cells SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS LA English DT Review DE Transcriptome; alternative splicing; anti-sense; ncRNA; retrogene ID NATURAL ANTISENSE TRANSCRIPTS; LONG NONCODING RNAS; DIFFERENTIALLY EXPRESSED GENES; MAMMALIAN SPERMATOGENIC CELLS; SEX-CHROMOSOME INACTIVATION; TISSUE-SPECIFIC EXPRESSION; STAGE-SPECIFIC EXPRESSION; NITRIC-OXIDE SYNTHASE; MOUSE X-CHROMOSOME; MESSENGER-RNA AB Spermatogenesis is a highly orchestrated developmental process by which spermatogonia develop into mature spermatozoa. This process involves many testis-or male germ cell-specific gene products whose expressions are strictly regulated. In the past decade the advent of high-throughput gene expression analytical techniques has made functional genomic studies of this process, particularly in model animals such as mice and rats, feasible and practical. These studies have just begun to reveal the complexity of the genomic landscape of the developing male germ cells. Over 50% of the mouse and rat genome are expressed during testicular development. Among transcripts present in germ cells, 40% - 60% are uncharacterized. A number of genes, and consequently their associated biological pathways, are differentially expressed at different stages of spermatogenesis. Developing male germ cells present a rich repertoire of genetic processes. Tissue-specific as well as spermatogenesis stage-specific alternative splicing of genes exemplifies the complexity of genome expression. In addition to this layer of control, discoveries of abundant presence of antisense transcripts, expressed psuedogenes, non-coding RNAs (ncRNA) including long ncRNAs, microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), and retrogenes all point to the presence of multiple layers of expression and functional regulation in male germ cells. It is anticipated that application of systems biology approaches will further our understanding of the regulatory mechanism of spermatogenesis. Birth Defects Research (Part C) 87:43-63, 2009. Published by Wiley-Liss, Inc.(dagger) C1 [Lee, Tin-Lap; Pang, Alan Lap-Yin; Rennert, Owen M.; Chan, Wai-Yee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genom, Lab Clin Genom, NIH, Bethesda, MD USA. [Chan, Wai-Yee] Georgetown Univ, Dept Pediat, Coll Med, Washington, DC 20057 USA. RP Chan, WY (reprint author), NICHD, Sect Dev Genom, NIH, 49 Convent Dr,MSC 4429,Bldg 49,Room 2A08, Bethesda, MD 20892 USA. EM chanwy@mail.nih.gov RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 FU NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Grant sponsor: NIH (Intramural Research Program), Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 222 TC 24 Z9 24 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-975X J9 BIRTH DEFECTS RES C JI Birth Defects Res. Part C-Embryo Today-Rev. PD MAR PY 2009 VL 87 IS 1 BP 43 EP 63 DI 10.1002/bdrc.20147 PG 21 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 469IX UT WOS:000267891800004 PM 19306351 ER PT J AU Rahimi, Z Muniz, A Akramipour, R Tofieghzadeh, F Mozafari, H Vaisi-Raygani, A Parsian, A AF Rahimi, Zohreh Muniz, Adriana Akramipour, Reza Tofieghzadeh, Fareidon Mozafari, Hadi Vaisi-Raygani, Asad Parsian, Abbas TI Haplotype analysis of beta thalassemia patients in Western Iran SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Haplotype; beta-thalassemia; Mutation; XmnI site; Western Iran ID GLOBIN GENE; MUTATIONS; ORIGIN; POPULATION; HISTORY AB beta-thalassemia (beta-thal) is the most common single gene disorder in Iran. To determine the chromosomal background of beta thalassemia mutations in Western Iran we studied beta-globin gene cluster haplotypes in 314 beta-thal and 70 beta(A) chromosomes with a Kurd ethnic background from the province of Kermanshah, Iran using PCR-RFLP beta-thal mutations were analyzed using PCR-ARMS, RFLP and direct genomic sequencing. Haplotypes were constructed by analyzing the pattern of seven restriction sites through the beta-globin gene cluster. Haplotype I was the most prevalent haplotype (35.7%) among beta-thal chromosomes followed by haplotype III (28.6%). beta(A) chromosomes similar to beta-thal chromosomes were linked to diverse haplotypes but predominantly with haplotype I (42.9%). The predominant IVSII-1 (G -> A) mutation in this population (33%) was strongly linked to haplotype III (66.1%) but was also found on chromosomes with haplotypes I, II, V, X and atypical. The second prevalent mutation was CD8/9 +G (13.5%) and showed a strong association with haplotype I (96.4%) and a weak association with haplotype V (3.6%). Haplotype background for Kurdish mutations among our studied population was similar to those among Kurdish Jews and people of Kurdistan of Iran. Identification of the most common mutations on different haplotype backgrounds can be explained by a variety of gene conversion and recombination events. (c) 2008 Elsevier Inc. All rights reserved. C1 [Rahimi, Zohreh; Mozafari, Hadi] Kermanshah Univ Med Sci, Med Biol Res Ctr, Sch Med, Kermanshah, Iran. [Rahimi, Zohreh; Vaisi-Raygani, Asad] Kermanshah Univ Med Sci, Sch Med, Dept Biochem, Kermanshah, Iran. [Rahimi, Zohreh] Kurdistan Univ Med Sci, Sch Med, Dept Biochem, Kurdistan, Iran. [Muniz, Adriana] Albert Einstein Coll Med, Div Hematol, Dept Med, Bronx, NY 10467 USA. [Akramipour, Reza; Tofieghzadeh, Fareidon] Kermanshah Univ Med Sci, Sch Med, Dept Pediat, Kermanshah, Iran. [Parsian, Abbas] NIH, Div Neurosci & Behav, Rockville, MD USA. RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Med Biol Res Ctr, Sch Med, Daneshgah Ave, Kermanshah, Iran. EM rahimizus@yahoo.com OI Rahimi, Zohreh/0000-0001-7589-3307; Vaisi-Raygani, Asad/0000-0002-3042-2832 NR 23 TC 12 Z9 12 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2009 VL 42 IS 2 BP 140 EP 143 DI 10.1016/j.bcmd.2008.12.001 PG 4 WC Hematology SC Hematology GA 409KJ UT WOS:000263504300010 PM 19141369 ER PT J AU Wang, XJ Leiendecker-Foster, C Acton, RT Barton, JC McLaren, CE McLaren, GD Gordeuk, VR Eckfeldt, JH AF Wang, XinJing Leiendecker-Foster, Catherine Acton, Ronald T. Barton, James C. McLaren, Christine E. McLaren, Gordon D. Gordeuk, Victor R. Eckfeldt, John H. TI Heme carrier protein 1 (HCP1) genetic variants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study participants SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE HCP1; PCTF; HEIRS; Hemochromatosis; Mutation ID HEREDITARY FOLATE MALABSORPTION; TRANSFERRIN SATURATION VALUES; SERUM FERRITIN CONCENTRATIONS; HFE GENOTYPES; TRANSPORTER; MUTATIONS; IDENTIFICATION; AMERICANS; WHITES; ADULTS AB Heme carrier protein 1 (HCP1) has been identified as a possible heme carrier by in vitro analysis. To determine the association of mutations within the HCP1 gene with iron phenotypes, we examined the entire coding region of the HCP1 gene in 788 US and Canadian participants selected from the Hemochromatosis and Iron Overload Screening (HEIRS) Study using denaturing high-performance liquid chromatography. We sequenced the exon and flanking intronic regions if variants were detected. We tested 298 non-C282Y homozygotes from four racial/ethnic backgrounds (White, Black, Asian, and Hispanic) selected because they had high serum ferritin (SF) and transferrin saturations (TS). As controls, we chose 300 other random participants of the same racial/ethnic backgrounds from the same geographic locations. From the 333 HEIRS Study C282Y homozygotes, we selected 75 based on high SF and TS, 75 based on low SF and TS; and 75 were selected randomly as controls. Thirty-five of the randomly selected C282Y homozygotes were also included in the high and the low SF and TS groups due to numerical limitations. We identified eight different HCP1 genetic variants; each occurred in a heterozygous state. Except one, each was found in a single HEIRS Study participant. Thus, HCP1 variants are infrequent in the populations that we tested. Five HEIRS Study participants had non-synonymous, coding region HCP1 variants. Each of these five had TS above the 84th gender- and ethnic/racial group-specific percentile (TS percentiles: 84.7, 91.3, 97.9, 99.5, and 99.9). (c) Published by Elsevier Inc. C1 [Wang, XinJing; Leiendecker-Foster, Catherine; Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Acton, Ronald T.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Barton, James C.] So Iron Disorders Ctr, Birmingham, AL 35209 USA. [Barton, James C.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [McLaren, Christine E.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92617 USA. [McLaren, Gordon D.] Dept Vet Affairs Long Beach Healthcare Syst, Long Beach, CA 90822 USA. [McLaren, Gordon D.] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92617 USA. [Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. RP Wang, XJ (reprint author), NEI, DNA Diagnost Lab, 10 Ctr Dr,10N226, Bethesda, MD 20892 USA. EM wangx6@mail.nih.gov FU National Heart, Lung, and Blood Institute [UH1-HL03679-05]; National Human Genome Research Institute; University of Minnesota [N01-HC05185]; Minority CCOP (Howard University); [N01-HC05186, N01-CM-07003-74]; University of Alabama at Birmingham [N01-HC05188]; Kaiser Permanente Center for Health Research [N01-C05189]; University of California, Irvine [N01-HC05190]; London Health Sciences Centre [N01-HC05191]; Wake Forest University [N01-C05192]; University of Alabama at Birmingham General Clinical Research Center (GCRC) [M01-RR00032]; Howard University GCRC [M01-RR10284]; University of California, Irvine UCSD/UCI Satellite GCRC [M01-RR00827]; National Center for Research Resources; National Institutes of Health; Office of Research on Minority Health (VRG); Southern Iron Disorders Center (JCB, RTA) FX The HEIRS Study was initiated and funded by the National Heart, Lung, and Blood Institute, in conjunction with the National Human Genome Research Institute. The study is supported by contracts N01-HC05185 (University of Minnesota); N01-HC05186, N01-CM-07003-74, and Minority CCOP (Howard University); N01-HC05188 (University of Alabama at Birmingham); N01-C05189 (Kaiser Permanente Center for Health Research); N01-HC05190 (University of California, Irvine); N01-HC05191 (London Health Sciences Centre); and N01-C05192 (Wake Forest University). Additional Support was provided by the University of Alabama at Birmingham General Clinical Research Center (GCRC) grant M01-RR00032, Howard University GCRC grant M01-RR10284, and the University of California, Irvine UCSD/UCI Satellite GCRC grant M01-RR00827, sponsored by the National Center for Research Resources, National Institutes of Health; Howard University Research Scientist Award UH1-HL03679-05 from the National Heart, Lung and Blood Institute and the Office of Research on Minority Health (VRG); and Southern Iron Disorders Center (JCB, RTA). NR 17 TC 4 Z9 4 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2009 VL 42 IS 2 BP 150 EP 154 DI 10.1016/j.bcmd.2008.11.003 PG 5 WC Hematology SC Hematology GA 409KJ UT WOS:000263504300012 PM 19176287 ER PT J AU Goldstein, JA Blaisdell, JA Limdi, NA AF Goldstein, J. A. Blaisdell, J. A. Limdi, N. A. TI A potentially deleterious new CYP2C9 polymorphism identified in an African American patient with major hemorrhage on warfarin therapy SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Letter ID FUNCTIONAL-CHARACTERIZATION; EUROPEAN-AMERICANS; VARIANT; GENE C1 [Limdi, N. A.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Goldstein, J. A.; Blaisdell, J. A.] Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Limdi, NA (reprint author), Univ Alabama, Dept Neurol, 1719 6th Ave S,CIRC-312, Birmingham, AL 35294 USA. EM nlimdi@uab.edu RI Goldstein, Joyce/A-6681-2012 FU Intramural NIH HHS [ZIA ES021024-28]; NINDS NIH HHS [K23 NS045598-05, K23 NS045598] NR 13 TC 7 Z9 7 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2009 VL 42 IS 2 BP 155 EP 158 DI 10.1016/j.bcmd.2008.10.011 PG 4 WC Hematology SC Hematology GA 409KJ UT WOS:000263504300013 PM 19083245 ER PT J AU Barrett, J Smith, M McIver, Z Hensel, N Melenhorst, J AF Barrett, J. Smith, M. McIver, Z. Hensel, N. Melenhorst, J. TI Both naive and memory lymphocyte subsets participate in alloresponses to HLA mismatched stimulators implications for selective depletion of GVHD reactivity SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation CY MAR 29-APR 01, 2009 CL Goteborg, SWEDEN SP European Grp Blood & Marrow Transplantat, European Grp Blood & Marrow Transplantat, Nurses Grp, European Grp Blood & Marrow Transplantat, Data Management Grp C1 [Barrett, J.; Smith, M.; McIver, Z.; Hensel, N.; Melenhorst, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2009 VL 43 BP S304 EP S304 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 424DO UT WOS:000264545900780 ER PT J AU Saccardi, R Di Gioia, M Bosi, A Donnini, I Maggi, P Sormani, M Gualandi, F Di Bartolomeo, P La Nasa, G Donelli, A Lanza, F Papineschi, F Mancardi, GL AF Saccardi, R. Di Gioia, M. Bosi, A. Donnini, I. Maggi, P. Sormani, M. Gualandi, F. Di Bartolomeo, P. La Nasa, G. Donelli, A. Lanza, F. Papineschi, F. Mancardi, G. L. TI High incidence of improvement after autotologous HSCT in relapsing-remitting phase of multiple sclerosis SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation CY MAR 29-APR 01, 2009 CL Goteborg, SWEDEN SP European Grp Blood & Marrow Transplantat, European Grp Blood & Marrow Transplantat, Nurses Grp, European Grp Blood & Marrow Transplantat, Data Management Grp C1 [Saccardi, R.; Di Gioia, M.; Bosi, A.; Donnini, I.; Maggi, P.] Careggi Hosp, Florence, Italy. [Sormani, M.] Natl Canc Inst, Unit Clin Epidemiol & Trials, Genoa, Italy. [Di Bartolomeo, P.] Osped Civile, Pescara, Italy. [Gualandi, F.] San Martinos Hosp, Genoa, Italy. [Di Bartolomeo, P.] Osped Civile, Pescara, Italy. [Donelli, A.] Univ Modena, I-41100 Modena, Italy. [Lanza, F.] St Anna Hosp Univ, Ferrara, Italy. [Papineschi, F.] Univ Pisa, Pisa, Italy. [Mancardi, G. L.] Univ Genoa, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2009 VL 43 SU 1 BP S54 EP S54 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 424DO UT WOS:000264545900133 ER PT J AU Sundin, M Barrett, J Ringden, O Uzunel, M Lonnies, H Dackland, A Christensson, B Le Blanc, K AF Sundin, M. Barrett, J. Ringden, O. Uzunel, M. Lonnies, H. Dackland, A. Christensson, B. Le Blanc, K. TI SCT recipients have specific tolerance to MSC but not to the MSC donor SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation CY MAR 29-APR 01, 2009 CL Goteborg, SWEDEN SP European Grp Blood & Marrow Transplantat, European Grp Blood & Marrow Transplantat, Nurses Grp, European Grp Blood & Marrow Transplantat, Data Management Grp C1 [Sundin, M.; Ringden, O.; Uzunel, M.; Lonnies, H.; Dackland, A.; Christensson, B.; Le Blanc, K.] Karolinska Inst, Stockholm, Sweden. [Barrett, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2009 VL 43 BP S188 EP S188 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 424DO UT WOS:000264545900479 ER PT J AU Zahn, R Moll, J Iyengar, V Huey, ED Tierney, M Krueger, F Grafman, J AF Zahn, Roland Moll, Jorge Iyengar, Vijeth Huey, Edward D. Tierney, Michael Krueger, Frank Grafman, Jordan TI Social conceptual impairments in frontotemporal lobar degeneration with right anterior temporal hypometabolism SO BRAIN LA English DT Article DE frontotemporal dementia; semantics; social cognition; anterior temporal lobe; social behaviour ID VOXEL-BASED MORPHOMETRY; CLINICAL DIAGNOSTIC-CRITERIA; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY-PROGRESSIVE-APHASIA; BOSTON NAMING TEST; SEMANTIC DEMENTIA; CORTICOBASAL DEGENERATION; ALZHEIMERS-DISEASE; PARKINSONIAN DISORDERS; BEHAVIORAL-DISORDERS AB Inappropriate social behaviours are early and distinctive symptoms of the temporal and frontal variants of frontotemporal lobar degeneration (FTLD). Knowledge of social behaviour is essential for appropriate social conduct. It is unknown, however, in what way this knowledge is degraded in FTLD. In a recent functional MRI study, we have identified a right-lateralized superior anterior temporal lobe (aTL) region showing selective activation for social concepts (i.e. concepts describing social behaviour: e.g. polite, stingy) as compared with concepts describing less socially relevant animal behaviour (animal function concepts: e.g. trainable, nutritious). In a further fMRI study, superior aTL activation was independent of the context of actions and feelings associated with these social concepts. Here, we investigated whether the right superior sector of the aTL is necessary for context-independent knowledge of social concepts. We assessed neuronal glucose uptake using 18-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) and a novel semantic discrimination task which probed knowledge of social and animal function concepts in patients with FTLD (n 29) and corticobasal syndrome (n 18). FTLD and corticobasal syndrome groups performed equally poorly on animal function concepts but FTLD patients showed more pronounced impairments on social concepts than corticobasal syndrome patients. FTLD patients with right superior aTL hypometabolism, as determined on individual ROI analyses, were significantly more impaired on social concepts than on animal function concepts. FTLD patients with selective impairments for social concepts, as determined on individual neuropsychological profiles, showed higher levels of inappropriate social behaviours (disinhibition) and demonstrated more pronounced hypometabolism in the right superior aTL, the left temporal pole and the right lateral orbitofrontal and dorsomedial prefrontal cortex as compared with FTLD patients showing selective impairments of animal function concepts. Combining both FTLD subgroup analyses, based on anatomical and neuropsychological criteria, by using inclusive masks, revealed the right superior aTL as associated with selective impairments of social concepts in both analyses. These results corroborate the hypothesis that the right aTL is necessary for representing conceptual social knowledge. Further, we provide first evidence for the potential importance of conceptual social knowledge impairments as contributing to behavioural symptoms of FTLD. C1 [Zahn, Roland; Moll, Jorge; Iyengar, Vijeth; Huey, Edward D.; Tierney, Michael; Krueger, Frank; Grafman, Jordan] NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. [Zahn, Roland] Univ Manchester, Neurosci & Aphasia Res Unit, Sch Psychol Sci, Manchester, Lancs, England. [Moll, Jorge] LABS DOr Hosp Network, Cognit & Behav Neurosci Unit, Rio De Janeiro, Brazil. [Huey, Edward D.] Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis & Memo, Manhasset, NY USA. RP Grafman, J (reprint author), NINDS, NIH, Cognit Neurosci Sect, 10 Ctr Dr,Room 7D43, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zahn, Roland/C-4665-2008; Moll, Jorge/B-2654-2013; Neurociencia, Inct/I-1011-2013; OI Zahn, Roland/0000-0002-8447-1453; Grafman, Jordan H./0000-0001-8645-4457 FU NINDS intramural funding; Federal Ministry of Education and Research [BMBF-LPD9901/8-122]; Faculty of Medical and Human Sciences, The University of Manchester; LABS-D'Or Hospital Network, Rio de Janeiro, Brazil FX This study was supported by NINDS intramural funding to J. G. and a German Academy of Natural Scientists Leopoldina Fellowship funded by the Federal Ministry of Education and Research (BMBF-LPD9901/8-122) to R. Z. Further R. Z. was supported in part by a Stepping Stones Fellowship award (Faculty of Medical and Human Sciences, The University of Manchester). J. M. was supported in part by the LABS-D'Or Hospital Network, Rio de Janeiro, Brazil. NR 73 TC 76 Z9 77 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2009 VL 132 BP 604 EP 616 DI 10.1093/brain/awn343 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 428YW UT WOS:000264889000006 PM 19153155 ER PT J AU Olsen, RK Kippenhan, JS Japee, S Kohn, P Mervis, CB Saad, ZS Morris, CA Meyer-Lindenberg, A Berman, KF AF Olsen, Rosanna K. Kippenhan, J. Shane Japee, Shruti Kohn, Philip Mervis, Carolyn B. Saad, Ziad S. Morris, Colleen A. Meyer-Lindenberg, Andreas Berman, Karen Faith TI Retinotopically defined primary visual cortex in Williams syndrome SO BRAIN LA English DT Article DE Williams syndrome; retinotopy; V1; primary visual cortex; visuospatial construction ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; HORIZONTAL CONNECTIONS; ATTENTIONAL MODULATION; COORDINATE SYSTEM; CEREBRAL-CORTEX; DORSAL-STREAM; BRAIN; AREAS; COGNITION AB Williams syndrome, caused by a hemizygous microdeletion on chromosome 7q11.23, is characterized by severe impairment in visuospatial construction. To examine potential contributions of early visual processing to this cognitive problem, we functionally mapped the size and neuroanatomical variability of primary visual cortex (V1) in high-functioning adults with Williams syndrome and age- and IQ-matched control participants from the general population by using fMRI-based retinotopic mapping and cortical surface models generated from high-resolution structural MRI. Visual stimulation, consisting of rotating hemicircles and expanding rings, was used to retinotopically define early visual processing areas. V1 boundaries based on computed phase and field sign maps were used to calculate the functional area of V1. Neuroanatomical variability was assessed by computing overlap maps of V1 location for each group on standardized cortical surfaces, and non-parametric permutation test methods were used for statistical inference. V1 did not differ in size between groups, although its anatomical boundaries were more variable in the group with Williams syndrome. V1 overlap maps showed that the average centres of gravity for the two groups were similarly located near the fundus of the calcarine fissure, 25 mm away from the most posterior aspect of the occipital lobe. In summary, our functional definition of V1 size and location indicates that recruitment of primary visual cortex is grossly normal in Williams syndrome, consistent with the notion that neural abnormalities underlying visuospatial construction arise at later stages in the visual processing hierarchy. C1 [Olsen, Rosanna K.; Kippenhan, J. Shane; Japee, Shruti; Kohn, Philip; Meyer-Lindenberg, Andreas; Berman, Karen Faith] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Mervis, Carolyn B.] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. [Saad, Ziad S.] NIMH, Bethesda, MD 20892 USA. [Morris, Colleen A.] Univ Nevada, Sch Med, Dept Paediat, Las Vegas, NV 89154 USA. RP Berman, KF (reprint author), 10 Ctr Dr,Rm 4C101, Bethesda, MD 20892 USA. EM karen.berman@nih.gov RI Meyer-Lindenberg, Andreas/H-1076-2011; OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Olsen, Rosanna/0000-0002-2918-4152 FU DHHS/NIH/NIMH/IRP; NINDS [NS35012] FX DHHS/NIH/NIMH/IRP and NINDS (NS35012 to C. B. M., PI). NR 59 TC 7 Z9 7 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2009 VL 132 BP 635 EP 644 DI 10.1093/brain/awn362 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 428YW UT WOS:000264889000009 PM 19255058 ER PT J AU Tamura, Y Ueki, Y Lin, P Vorbach, S Mima, T Kakigi, R Hallett, M AF Tamura, Yohei Ueki, Yoshino Lin, Peter Vorbach, Sherry Mima, Tatsuya Kakigi, Ryusuke Hallett, Mark TI Disordered plasticity in the primary somatosensory cortex in focal hand dystonia SO BRAIN LA English DT Article DE associative plasticity; paired associative stimulation; focal hand dystonia; somatosensory-evoked potential ID HUMAN MOTOR CORTEX; PAIRED ASSOCIATIVE STIMULATION; TIMING-DEPENDENT PLASTICITY; WRITERS CRAMP; SPATIAL DISCRIMINATION; THALAMIC AFFERENTS; MUSICIANS DYSTONIA; INHIBITION; REORGANIZATION; ABNORMALITIES AB Interventional paired associative stimulation (PAS) can induce plasticity in the cortex, and this plasticity was previously shown to be disordered in the primary motor cortex in focal hand dystonia (FHD). This study aimed to test whether associative plasticity is abnormal in the primary somatosensory cortex (S1) in FHD and whether PAS modulates excitatory or inhibitory interneurons within the cortex. Ten FHD patients and 10 healthy volunteers were studied. We investigated the changes in single- and double-pulse somatosensory-evoked potentials before and after PAS, which consisted of peripheral electrical nerve stimulation and subsequent transcranial magnetic stimulation over S1. Four sessions of somatosensory-evoked potentials recordings were performed: before PAS, and immediately, 15 and 30 min after PAS. We compared the time course of the somatosensory-evoked potentials between the FHD and healthy groups. In the single-pulse condition, the P27 amplitudes were significantly higher in FHD immediately after PAS than before PAS, while no changes were observed in healthy subjects. In the double-pulse condition, significant differences in the suppression ratio of P27 were found immediately after and 15 min after PAS, while there were no significant differences in healthy subjects. The P27 suppression tended to normalize toward the level of the healthy volunteer group. In FHD, PAS transiently induced an abnormal increase in excitability in S1. In addition, intracortical inhibition in S1 was found to increase as well. This abnormal plasticity of the intracortical neurons in S1 may contribute to the pathophysiology of dystonia. C1 [Tamura, Yohei; Ueki, Yoshino; Lin, Peter; Vorbach, Sherry; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Tamura, Yohei] Jikei Univ, Dept Neurol, Sch Med, Tokyo, Japan. [Mima, Tatsuya] Kyoto Univ, Human Brain Res Ctr, Grad Sch Med, Kyoto, Japan. [Kakigi, Ryusuke] Natl Inst Physiol Sci, Dept Integrat Physiol, Okazaki, Aichi 444, Japan. RP Hallett, M (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 7D37,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov OI Mima, Tatsuya/0000-0001-7787-4855 FU Intramural Research Programme of NINDS; Japanese Society for the Promotion of Science; Uehara Memorial Foundation Postdoctoral Fellowship; Pfizer Health Research Foundation; JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at National Institutes of Health FX Intramural Research Programme of NINDS; Japan-US Cooperative Research Project 'Cooperative Brain Research' by the Japanese Society for the Promotion of Science; Uehara Memorial Foundation Postdoctoral Fellowship; Grant for researching abroad by the Pfizer Health Research Foundation; JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at National Institutes of Health. NR 41 TC 42 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD MAR PY 2009 VL 132 BP 749 EP 755 DI 10.1093/brain/awn348 PN 3 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 428YW UT WOS:000264889000018 PM 19151081 ER PT J AU Mochel, F Sedel, F Vanderver, A Engelke, UFH Barritault, J Yang, BZ Kulkarni, B Adams, DR Clot, F Ding, JH Kaneski, CR Verheijen, FW Smits, BW Seguin, F Brice, A Vanier, MT Huizing, M Schiffmann, R Durr, A Wevers, RA AF Mochel, F. Sedel, F. Vanderver, A. Engelke, U. F. H. Barritault, J. Yang, B. Z. Kulkarni, B. Adams, D. R. Clot, F. Ding, J. H. Kaneski, C. R. Verheijen, F. W. Smits, B. W. Seguin, F. Brice, A. Vanier, M. T. Huizing, M. Schiffmann, R. Durr, A. Wevers, R. A. TI Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA) SO BRAIN LA English DT Article DE cerebellar ataxia; free sialic acid; cerebrospinal fluid; neurometabolic disorder; nuclear magnetic resonance spectroscopy ID ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYLNEURAMINIC ACID; INBORN-ERRORS; STORAGE DISEASE; NMR-SPECTROSCOPY; BODY-FLUIDS; METABOLISM; MUTATIONS; GENE AB In order to identify new metabolic abnormalities in patients with complex neurodegenerative disorders of unknown aetiology, we performed high resolution in vitro proton nuclear magnetic resonance spectroscopy on patient cerebrospinal fluid (CSF) samples. We identified five adult patients, including two sisters, with significantly elevated free sialic acid in the CSF compared to both the cohort of patients with diseases of unknown aetiology (n 144; P 0.001) and a control group of patients with well-defined diseases (n 91; P 0.001). All five patients displayed cerebellar ataxia, with peripheral neuropathy and cognitive decline or noteworthy behavioural changes. Cerebral MRI showed mild to moderate cerebellar atrophy (5/5) as well as white matter abnormalities in the cerebellum including the peridentate region (4/5), and at the periventricular level (3/5). Two-dimensional gel analyses revealed significant hyposialylation of transferrin in CSF of all patients compared to age-matched controls (P 0.001)a finding not present in the CSF of patients with Salla disease, the most common free sialic acid storage disorder. Free sialic acid content was normal in patients urine and cultured fibroblasts as were plasma glycosylation patterns of transferrin. Analysis of the ganglioside profile in peripheral nerve biopsies of two out of five patients was also normal. Sequencing of four candidate genes in the free sialic acid biosynthetic pathway did not reveal any mutation. We therefore identified a new free sialic acid syndrome in which cerebellar ataxia is the leading symptom. The term CAFSA is suggested (cerebellar ataxia with free sialic acid). C1 [Mochel, F.; Clot, F.; Brice, A.; Durr, A.] Hop La Pitie Salpetriere, INSERM, UMR S679, F-75013 Paris, France. [Mochel, F.; Yang, B. Z.; Ding, J. H.; Kaneski, C. R.; Schiffmann, R.] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. [Sedel, F.] Hop La Pitie Salpetriere, Federat Malad Syst Nerveux, F-75013 Paris, France. [Vanderver, A.; Kulkarni, B.] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Genet Med, Washington, DC 20010 USA. [Sedel, F.] Hop La Pitie Salpetriere, Ref Ctr Lysosomal Dis, F-75013 Paris, France. [Engelke, U. F. H.; Wevers, R. A.] Radboud Univ Nijmegen, Lab Pediat & Neurol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Barritault, J.; Seguin, F.] Univ Poitiers, INSERM, U927, Hop Mil, Poitiers, France. [Adams, D. R.; Huizing, M.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Verheijen, F. W.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Smits, B. W.] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6525 ED Nijmegen, Netherlands. [Brice, A.; Durr, A.] Hop La Pitie Salpetriere, Dept Genet & Cytogenet, F-75013 Paris, France. [Vanier, M. T.] Fac Med Lyon RTH Laennec, INSERM, U820, Lyon, France. RP Mochel, F (reprint author), Hop La Pitie Salpetriere, INSERM, UMR S679, 47 Bld Hop,Batiment Nouvelle Pharm 4Eme Etage, F-75013 Paris, France. EM fanny.mochel@upmc.fr RI Wevers, Ron/H-8116-2014; Engelke, U.F.H./L-4293-2015; OI Wevers, Ron/0000-0003-2278-9746; Kaneski, Christine/0000-0003-1453-2502 FU Assistance Publique des Hopitaux de Paris [CRC 05169]; Intramural Program of the National Institute of Neurological Disorders and Stroke; National Human Genome Research Institute; National Institute of Health; Baylor Research Foundation; Integrated Molecular Core for Rehabilitation Medicine; NIH IDDRC [P30HD40677]; NIH NCMRR/NINDS [5R24 HD050846] FX Assistance Publique des Hopitaux de Paris (CRC 05169); Intramural Program of the National Institute of Neurological Disorders and Stroke; National Human Genome Research Institute; National Institute of Health; Baylor Research Foundation. Integrated Molecular Core for Rehabilitation Medicine (NIH IDDRC P30HD40677, NIH NCMRR/NINDS 5R24 HD050846). NR 29 TC 15 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2009 VL 132 BP 801 EP 809 DI 10.1093/brain/awn355 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 428YW UT WOS:000264889000023 PM 19153153 ER PT J AU Kuchinke, L van der Meer, E Krueger, F AF Kuchinke, Lars van der Meer, Elke Krueger, Frank TI Differences in processing of taxonomic and sequential relations in semantic memory: An fMRI investigation SO BRAIN AND COGNITION LA English DT Article DE Prefrontal cortex; Concept; Script; Event; Object ID POSITRON-EMISSION-TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; FRONTAL-LOBE LESIONS; TEMPORAL CORTEX; BRAIN ACTIVATION; RETRIEVAL; ORDER; REPRESENTATIONS; COMPREHENSION; IMAGEABILITY AB Conceptual knowledge of our world is represented in semantic memory in terms of concepts and semantic relations between concepts. We used functional magnetic resonance imaging (fMRI) to examine the cortical regions underlying the processing of sequential and taxonomic relations. Participants were presented verbal cues and performed three tasks: (I) a sequential relation judgement task judging the sequential relation between two script events, (2) a taxonomic relation judgement task judging the taxonomic relation between two objects, and (3) a grammatical judgement task (control condition) judging whether a presented word was a verb or a noun. We hypothesized that the processing of sequential and taxonomic relations were supported by dissociable cortical regions. The results showed that both semantic relation types activated large-scale neural networks including the left inferior and middle frontal gyrus. The activation in left inferior frontal gyrus correlated with higher processing demands during the sequential relation condition. The processing of sequential relations additionally activated left medial and middle frontal gyrus, whereas the processing of taxonomic relations activated the left superior temporal gyrus and posterior cingulate. (C) 2008 Elsevier Inc. All rights reserved. C1 [Kuchinke, Lars] Free Univ Berlin, Dept Psychol, AB, AB Allgemeine Psychol, D-14195 Berlin, Germany. [van der Meer, Elke] Humboldt Univ, Dept Psychol, D-1086 Berlin, Germany. [Krueger, Frank] NIH, Cognit Neurosci Sect, NINDS, Bethesda, MD 20892 USA. RP Kuchinke, L (reprint author), Free Univ Berlin, Dept Psychol, AB, AB Allgemeine Psychol, Habelschwerdter Alle 45, D-14195 Berlin, Germany. EM kuchinke@zedat.fu-berlin.de; krugerf@ninds.-nih.gov RI Kuchinke, Lars/E-7641-2010 NR 52 TC 8 Z9 8 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD MAR PY 2009 VL 69 IS 2 BP 245 EP 251 DI 10.1016/j.bandc.2008.07.014 PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 410MP UT WOS:000263581900003 PM 18796346 ER PT J AU Okun, E Griffioen, KJ Lathia, JD Tang, SC Mattson, MP Arumugam, TV AF Okun, Eitan Griffioen, Kathleen J. Lathia, Justin D. Tang, Sung-Chun Mattson, Mark P. Arumugam, Thiruma V. TI Toll-like receptors in neurodegeneration SO BRAIN RESEARCH REVIEWS LA English DT Review DE Toll-like receptor; Neurodegeneration; Alzheimer's disease; Stroke; Multiple sclerosis ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; NF-KAPPA-B; FOCAL CEREBRAL-ISCHEMIA; INNATE IMMUNE-RESPONSES; DOUBLE-STRANDED-RNA; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; HUMAN ASTROCYTES AB The key roles of toll-like receptors (TLRs) as mediators of the detection and responses of immune cells to invading pathogens are well known. There are at least 13 mammalian TLRs which are integral membrane proteins with a leucine-rich extracellular domain and a cytoplasmic domain similar to that of the interleukin-1 receptor which initiates downstream signaling through kinases to activate transcription factors such as AP-1 and NF kappa B. TLRs are activated in glial cells (microglia, astrocytes and oligodendrocytes) and lymphocytes that infiltrate the nervous system in response to inflammation caused by infectious agents, tissue injury or autoimmune conditions. By inducing the production of pro-inflammatory cytokines and cell adhesion molecules in immune cells, TLRs may indirectly damage neurons in conditions such as ischemic stroke and multiple sclerosis. Recent findings suggest that neurons also express a subset of TLRs and that their activation promotes neuronal degeneration in experimental models of stroke and Alzheimer's disease. TLRs may also play roles in regulating the processes of neurogenesis and neurite outgrowth, suggesting roles in neuronal plasticity. A better understanding of the molecular and cellular biology of TLRs in the normal and diseased nervous system, may lead to novel approaches for preventing neuronal degeneration and promoting recovery of function in an array of neurodegenerative conditions. Published by Elsevier B.V. C1 [Okun, Eitan; Griffioen, Kathleen J.; Lathia, Justin D.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Lathia, Justin D.] Duke Univ, Med Ctr, Dept Neurooncol, Durham, NC 27710 USA. [Tang, Sung-Chun] Natl Taiwan Univ Hosp, Dept Neurol, Yunlin 640, Taiwan. [Arumugam, Thiruma V.] Texas Tech Univ Hlth Sci Ctr, Dept Pharmaceut Sci, Sch Pharm, Amarillo, TX 79106 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; OI Tang, Sung-Chun/0000-0003-3731-5973 FU Intramural NIH HHS [Z01 AG000317-07, Z01 AG000312-07, Z01 AG000313-07, Z01 AG000314-07] NR 127 TC 181 Z9 190 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAR PY 2009 VL 59 IS 2 BP 278 EP 292 DI 10.1016/j.brainresrev.2008.09.001 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 424NS UT WOS:000264574000002 PM 18822314 ER PT J AU Maalouf, M Rho, JM Mattson, MP AF Maalouf, Marwan Rho, Jong M. Mattson, Mark P. TI The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies SO BRAIN RESEARCH REVIEWS LA English DT Review DE Neuroprotection; Calorie restriction; Ketogenic diet; Ketone bodies; Oxidative stress; Mitochondria; Brain ID ACTIVATED-RECEPTOR-GAMMA; NF-KAPPA-B; PROTEIN PHOSPHATASE 2A; AMYOTROPHIC-LATERAL-SCLEROSIS; LIFE-SPAN EXTENSION; POLYUNSATURATED FATTY-ACIDS; D-BETA-HYDROXYBUTYRATE; OXYGEN SPECIES PRODUCTION; LONG-TERM POTENTIATION; TRANSGENIC MOUSE MODEL AB Both calorie restriction and the ketogenic diet possess broad therapeutic potential in various clinical settings and in various animal models of neurological disease. Following calorie restriction or consumption of a ketogenic diet, there is notable improvement in mitochondrial function, a decrease in the expression of apoptotic and inflammatory mediators and an increase in the activity of neurotrophic factors. However, despite these intriguing observations, it is not yet clear which of these mechanisms account for the observed neuroprotective effects. Furthermore, limited compliance and concern for adverse effects hamper efforts at broader clinical application. Recent research aimed at identifying compounds that can reproduce, at least partially, the neuroprotective effects of the diets with less demanding changes to food intake suggests that ketone bodies might represent an appropriate candidate. Ketone bodies protect neurons against multiple types of neuronal injury and are associated with mitochondrial effects similar to those described during calorie restriction or ketogenic diet treatment. The present review summarizes the neuroprotective effects of calorie restriction, of the ketogenic diet and of ketone bodies, and compares their putative mechanisms of action. (C) 2008 Elsevier B.V. All rights reserved. C1 [Maalouf, Marwan] Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rho, Jong M.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Rho, Jong M.] St Josephs Hosp, Phoenix, AZ USA. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Maalouf, M (reprint author), Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, 63-323 CHS,Box 951763, Los Angeles, CA 90095 USA. EM marwan.maalouf@ucla.edu RI Mattson, Mark/F-6038-2012 FU NIH [NS 044846]; Barrow Neurological Foundation; Intramural Research Program of the National Institute on Aging FX This work was supported in part by NIH grant NS 044846 (JMR), the Barrow Neurological Foundation (JMR) and the Intramural Research Program of the National Institute on Aging (MPM). NR 376 TC 157 Z9 162 U1 6 U2 51 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 EI 1872-6321 J9 BRAIN RES REV JI Brain Res. Rev. PD MAR PY 2009 VL 59 IS 2 BP 293 EP 315 DI 10.1016/j.brainresrev.2008.09.002 PG 23 WC Neurosciences SC Neurosciences & Neurology GA 424NS UT WOS:000264574000003 PM 18845187 ER PT J AU Brody, LC AF Brody, L. C. TI Current knowledge on genetic predispositions for breast cancer SO BREAST LA English DT Meeting Abstract C1 [Brody, L. C.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 0960-9776 J9 BREAST JI Breast PD MAR PY 2009 VL 18 BP S4 EP S4 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 446VJ UT WOS:000266149200010 ER PT J AU Pierce, BL Neuhouser, ML Wener, MH Bernstein, L Baumgartner, RN Ballard-Barbash, R Gilliland, FD Baumgartner, KB Sorensen, B McTiernan, A Ulrich, CM AF Pierce, Brandon L. Neuhouser, Marian L. Wener, Mark H. Bernstein, Leslie Baumgartner, Richard N. Ballard-Barbash, Rachel Gilliland, Frank D. Baumgartner, Kathy B. Sorensen, Bess McTiernan, Anne Ulrich, Cornelia M. TI Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Body mass index; Breast cancer; C-reactive protein; Inflammation; Serum amyloid A ID SYSTEMIC INFLAMMATORY RESPONSE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PREVENT COLORECTAL ADENOMAS; PHYSICAL-ACTIVITY LEVELS; CORONARY-HEART-DISEASE; ACUTE-PHASE RESPONSE; RANDOMIZED-TRIAL; WEIGHT-LOSS; CURATIVE RESECTION; ALPHA-TOCOPHEROL AB Introduction Inflammatory status may be an important prognostic factor for breast cancer. Correlates of markers of inflammation in breast cancer survivors have not been thoroughly evaluated. Methods Using data from, the Health, Eating, Activity, and Lifestyle (HEAL) Study (a population-based, multiethnic prospective cohort study of female breast cancer patients) we evaluated the associations between circulating markers of inflammation (C-reactive protein [CRP] and serum amyloid A [SAA], measured similar to 31 months after diagnosis) and several demographic, lifestyle, and clinical characteristics in 741 disease-free breast cancer survivors. Analysis of variance and regression methods were used for statistical analyses of log-transformed values of CRP and SAA. Results After adjusting for age, BMI, ethnicity, and study site, higher concentrations of CRP were associated with increasing concentration of SAA (P-trend < 0.0001), increasing age (P-trend < 0.0001), increasing BMI (P-trend < 0.0001), increasing waist circumference (P-trend < 0.0001), positive history of heart failure (P = 0.0007), decreasing physical activity (P-trend = 0.005), Hispanic ethnicity (P = 0.05 vs. non-Hispanic white), and current smoking (P = 0.03 vs. never smoking). Vitamin E supplementation (P = 0.0005), tamoxifen use (P = 0.008), and radiation treatment (compared to no chemotherapy or radiation; P = 0.04) were associated with reduced CRP. Associations of CRP with clinical characteristics were not significant in the adjusted models. In a multivariate analysis, CRP showed significant associations with waist circumference, BMI, age, history of heart failure, tamoxifen use, and vitamin E supplementation (R(2) = 0.35). Similar, yet fewer, associations were observed for SAA (R(2) = 0.19). Conclusions This study highlights important correlates of inflammatory status in breast cancer patients. Our results are consistent with those from similar studies of healthy women. C1 [Pierce, Brandon L.; Neuhouser, Marian L.; Sorensen, Bess; McTiernan, Anne; Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Pierce, Brandon L.] Fred Hutchinson Canc Res Ctr, Epidemiol Res Program, Seattle, WA 98109 USA. [Pierce, Brandon L.] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA. [Wener, Mark H.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA. [Baumgartner, Richard N.; Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA. [Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Gilliland, Frank D.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [McTiernan, Anne; Ulrich, Cornelia M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ulrich, CM (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM nulrich@fhcrc.org OI Pierce, Brandon/0000-0002-7829-952X FU National Cancer Institute [N01-CN-75036-20, NO1-CN05228, NO1-PC-67010, U54-CA116847, R25CA94880]; National Institutes of Health [M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997] FX The Authors would like to thank Dr. Peter Campbell and Dr. Kristen Campbell for their helpful comments related to this manuscript, and the HEAL participants for their ongoing dedication to this study. This study was supported through National Cancer Institute contracts N01-CN-75036-20, NO1-CN05228, NO1-PC-67010, U54-CA116847 and training grant R25CA94880. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by the National Institutes of Health grant M01-RR-00037, and University of New Mexico grant, NCRR M01-RR-0997. Data collection for the Women's CARE Study at the University of Southern California NR 71 TC 58 Z9 62 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2009 VL 114 IS 1 BP 155 EP 167 DI 10.1007/s10549-008-9985-5 PG 13 WC Oncology SC Oncology GA 403GG UT WOS:000263070500018 PM 18401703 ER PT J AU Nieves-Alicea, R Colburn, NH Simeone, AM Tari, AM AF Nieves-Alicea, Rene Colburn, Nancy H. Simeone, Ann-Marie Tari, Ana M. TI Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer invasion; Interleukin-8; Programmed Cell Death 4; Prostaglandin E(2); Tissue Inhibitor of Metalloproteinase-2 ID COLON-CARCINOMA CELLS; SUPPRESSOR PDCD4; TRANSFORMATION SUPPRESSOR; PROGNOSTIC-FACTOR; PROTEIN; CYCLOOXYGENASE-2; TUMORIGENESIS; TRANSLATION; COX-2; PROGRAMMED-CELL-DEATH-4 AB High levels of the cyclooxygenase-2 (COX-2) protein have been associated with invasion and metastasis of breast tumors. Both prostaglandin E(2) (PGE(2)) and interleukin-8 (IL-8) have been shown to mediate the invasive activity of COX-2 in breast cancer cells. Here we expand these studies to determine how COX-2 uses PGE(2) and IL-8 to induce breast cancer cell invasion. We demonstrated that PGE(2) and IL-8 decreased the expression of the tumor suppressor protein Programmed Cell Death 4 (PDCD4). We hypothesized that suppression of PDCD4 expression is vital to the invasive activity of PGE(2) and IL-8. In MCF-7 cells overexpressing PDCD4 (MCF-7/PDCD4), PGE(2) and IL-8 failed to induce invasion, in contrast to the parental MCF-7 cells, thus indicating that PDCD4 blocks breast cancer cell invasion. MCF-7/PDCD4 cells produced higher levels of the Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) than the parental cells. Silencing TIMP-2 mRNA in MCF-7/PDCD4 cells reversed the anti-invasive effects of PDCD4, allowing PGE(2) and IL-8 to induce the invasion of these cells. Here we report the novel findings that suppression of PDCD4 expression is vital for the invasive activity of COX-2 mediated by PGE(2) and IL-8, and that PDCD4 increases TIMP-2 expression to inhibit breast cancer cell invasion. C1 [Nieves-Alicea, Rene; Simeone, Ann-Marie; Tari, Ana M.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Unit 422, Houston, TX 77030 USA. [Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21702 USA. RP Tari, AM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Unit 422, Houston, TX 77030 USA. EM atari@mdanderson.org FU Intramural NIH HHS [Z01 BC010026-12]; NCI NIH HHS [CA16672, P30 CA016672] NR 34 TC 48 Z9 51 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2009 VL 114 IS 2 BP 203 EP 209 DI 10.1007/s10549-008-9993-5 PG 7 WC Oncology SC Oncology GA 403GH UT WOS:000263070600002 PM 18386173 ER PT J AU Shen, D Tuo, J Patel, M Herzlich, AA Ding, X Chew, EY Chan, CC AF Shen, D. Tuo, J. Patel, M. Herzlich, A. A. Ding, X. Chew, E. Y. Chan, C-C TI Chlamydia pneumoniae infection, complement factor H variants and age-related macular degeneration SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NEOVASCULAR MEMBRANES; MULTIPLE-SCLEROSIS; POLYMORPHISM; ASSOCIATION; EXPOSURE; RISK; IDENTIFICATION; METAANALYSIS; PROGRESSION; GENE AB Background/aims: Impaired inhibition of the alternative complement pathway by complement factor H (CFH) is linked to age-related macular degeneration (AMD) based on the strong association between CFH variant and AMD. Chlamydia pneumoniae (C pneumoniae) infection can trigger the alternative pathway, but the evidence for an association between C pneumoniae and AMD is contradictory. This study investigated whether C pneumoniae infection is associated with AMD and whether the presence of C pneumonia modulates AMD risk conferred by CFH variants. Methods: Genomic DNA extracted from peripheral blood of 148 advanced AMD patients and 162 controls was subjected to Taqman and PCR-RFLP for the CFH polymorphism and PCR for the C pneumoniae gene. Genomic DNA was also examined from microdissected macular cells from 59 AMD and 16 age-matched non-AMD archived slides. chi(2) testing was performed for case-control analysis. Results: C pneumoniae infection was associated with increased risk of AMD (OR = 2.17, p < 0.017). A CFH variant was also linked to increased risk of AMD (OR = 1.98, p < 0.0001). However, no relationship was found between risk-conferring CFH variant and C pneumoniae (OR = 1.81, p = 0.08). Conclusion: There is a possible association between AMD and C pneumoniae infection, although CFH may not be directly involved in the pathogenesis of C pneumoniae infection-mediated AMD. C1 [Chan, C-C] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Patel, M.] NIH, Howard Hughes Med Inst, Res Scholars Program, Chevy Chase, MD USA. [Chew, E. Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU National Eye Institute Intramural Research Program FX The study is funded by the National Eye Institute Intramural Research Program. NR 38 TC 13 Z9 14 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAR PY 2009 VL 93 IS 3 BP 405 EP 408 DI 10.1136/bjo.2008.145383 PG 4 WC Ophthalmology SC Ophthalmology GA 411NH UT WOS:000263655800029 PM 18996904 ER PT J AU Savitz, J van der Merwe, L Stein, DJ Solms, M Ramesar, R AF Savitz, Jonathan van der Merwe, Lize Stein, Dan J. Solms, Mark Ramesar, Rajkumar TI Neuropsychological status of bipolar I disorder: impact of psychosis SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID SCHIZOTYPAL PERSONALITY-DISORDER; WORKING-MEMORY; SCHIZOPHRENIC-PATIENTS; CHILDHOOD TRAUMA; NEUROCOGNITIVE FUNCTION; COGNITIVE IMPAIRMENT; ADULT RELATIVES; FAMILY-HISTORY; ILLNESS; RISK AB Background The presence of schizotypal personality traits in some people with bipolar disorder, together with reports of greater cognitive dysfunction in patients with a history of psychotic features compared with patients without such a history, raises questions about the nosological relationship between bipolar disorder with psychotic features and bipolar disorder without psychotic features. Aims To test the impact of a history of DSM-IV-defined psychosis on the neuropsychological status of participants with bipolar disorder while statistically controlling for confounding factors such as mood, medication, alcohol misuse/dependence and childhood abuse, and to evaluate the impact of schizotypal personality traits (and thus potential vulnerability to psychotic illness) on the cognitive performance of people with bipolar disorder and their healthy relatives. Method Neuropsychological data were obtained for 25 participants with type I bipolar disorder and a history of psychosis, 24 with type I bipolar disorder but no history of psychosis and 61 unaffected relatives. Schizotypal traits were measured with the Schizotypal Personality Scale (STA). Childhood trauma was measured with the Childhood Trauma Questionnaire. Results The group with a history of psychosis performed significantly worse than the healthy relatives on measures of verbal working memory, cognitive flexibility and declarative memory. Nevertheless, the two bipolar disorder groups did not differ significantly from each other on any cognitive measure. Scores on the STA were negatively associated with verbal working and declarative memory, but positively associated with visual recall memory. Conclusions 'Psychotic' and 'non-psychotic' subtypes of bipolar disorder may lie on a nosological continuum that is most clearly defined by verbal memory impairment. C1 [Savitz, Jonathan] Univ Cape Town, Div Human Genet, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7700 Rondebosch, South Africa. [Solms, Mark] Univ Cape Town, Dept Psychol, ZA-7700 Rondebosch, South Africa. [Solms, Mark] Univ Cape Town, Dept Neurol, ZA-7700 Rondebosch, South Africa. [Ramesar, Rajkumar] Univ Cape Town, Div Human Genet, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa. RP Savitz, J (reprint author), NIH, Roorn 200,315K N Dr, Bethesda, MD 20892 USA. EM savitzj@mail.nih.gov RI Savitz, Jonathan/C-3088-2009; Ramesar, Raj/I-6941-2015; Stein, Dan/A-1752-2008 OI Savitz, Jonathan/0000-0001-8143-182X; Ramesar, Raj/0000-0001-5688-1634; Stein, Dan/0000-0001-7218-7810 NR 63 TC 27 Z9 29 U1 2 U2 6 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAR PY 2009 VL 194 IS 3 BP 243 EP 251 DI 10.1192/bjp.bp.108.052001 PG 9 WC Psychiatry SC Psychiatry GA 421VT UT WOS:000264387100009 PM 19252155 ER PT J AU Cox, D Federico, C Daniel, S Robert, H Gilles, T Rudolf, K AF Cox, David Federico, Canzian Daniel, Stram Robert, Hoover Gilles, Thomas Rudolf, Kaaks TI Polymorphisms in genes related to Insulin Like Growth Factor-I (IGF-I) and breast cancer risk in the Breast and Prostate Cancer Cohort Consortium SO BULLETIN DU CANCER LA English DT Meeting Abstract C1 INSERM, U590, F-75654 Paris 13, France. DKFZ Heidelberg, Heidelberg, Germany. Univ So Calif, Los Angeles, CA 90089 USA. NCI, Bethesda, MD 20892 USA. EM cox@lyon.fnclcc.fr RI Cox, David/A-2023-2009 OI Cox, David/0000-0002-2152-9259 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0007-4551 EI 1769-6917 J9 B CANCER JI Bull. Cancer PD MAR PY 2009 VL 96 SI SI MA 38 BP S33 EP S33 PG 1 WC Oncology SC Oncology GA V30JN UT WOS:000208812400040 ER PT J AU Finstad, SE Emaus, A Potischman, N Barrett, E Furberg, AS Ellison, PT Jasienska, G Thune, I AF Finstad, Sissi Espetvedt Emaus, Aina Potischman, Nancy Barrett, Emily Furberg, Anne-Sofie Ellison, Peter T. Jasienska, Grazyna Thune, Inger TI Influence of birth weight and adult body composition on 17 beta-estradiol levels in young women SO CANCER CAUSES & CONTROL LA English DT Article DE Birth weight; Adult body composition; Energy balance; 17 beta-estradiol ID BREAST-CANCER RISK; INSULIN-RESISTANCE; PREMENOPAUSAL WOMEN; HORMONAL PROFILES; LIVING-CONDITIONS; ESTRADIOL LEVELS; IN-UTERO; LIFE; SIZE; MENARCHE AB Background Estrogens induce cellular proliferation and are associated with an increased risk of breast cancer. Birth weight and adult body weight have independently been associated with both estrogen levels and breast cancer risk. Thus, we hypothesize that low birth weight, in combination with adult overweight, may influence premenopausal 17 beta-estradiol over an entire menstrual cycle of possible importance for breast cancer. Methods Among 204 healthy women, aged 25-35 years, who participated in the Norwegian EBBA-I Study, birth weight and age at menarche were assessed. Levels of 17 beta-estradiol were measured in daily saliva samples over one menstrual cycle using radioimmunoassay (RIA). Measurements of body composition; waist circumference (cm), body mass index (BMI, kg/m(2)), and total fat percentage (DEXA, %) were assessed. Fasting blood samples were drawn, and serum concentrations of lipids and hormones were determined. Results The participating women had mean birth weight of 3,389 g and age at menarche 13.1 years. Women within the highest tertile of birth weight had the lowest 17 beta-estradiol throughout the menstrual cycle (p = 0.03), and they tended to have a later age at menarche (p = 0.06). When we looked into birth weight in combination with adult-attained weight, we found that women with lower birth weights, combined with excess weight during adulthood, had higher levels of free 17 beta-estradiol over an entire menstrual cycle compared with women with high birth weights and adult overweight. Women with birth weights < 3,530 g, who later developed excess body weight (waist C 84 cm), showed 33% higher 17 beta-estradiol concentrations over a menstrual cycle compared with women with higher birth weights (>= 3,530 g) and adult excess body weight (p = 0.03). The association was even more pronounced in women with birth weights <3,220 g, early age at menarche (<12 years), and adult overweight. Conclusion Our findings support variation of premenopausal levels of 17 beta-estradiol in response to birth weight and energy status in adult life, suggesting that women with low birth weight in combination with adult overweight are put at risk for higher estradiol levels throughout menstrual cycles, which is of possible importance for breast cancer risk. C1 [Finstad, Sissi Espetvedt; Emaus, Aina; Thune, Inger] Ullevaal Univ Hosp, Dept Oncol, N-0407 Oslo, Norway. [Potischman, Nancy] NCI, Bethesda, MD 20892 USA. [Barrett, Emily] Univ Calif Los Angeles, Ctr Healthier Children Families & Communities, Los Angeles, CA 90024 USA. [Furberg, Anne-Sofie] Univ Tromso, Fac Med, Inst Community Med, N-9037 Tromso, Norway. [Furberg, Anne-Sofie] Univ Hosp N Norway, Dept Microbiol & Infect Control, N-9038 Tromso, Norway. [Ellison, Peter T.] Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. [Jasienska, Grazyna] Jagiellonian Univ, Dept Epidemiol & Populat Studies, Coll Med, Krakow, Poland. [Thune, Inger] Res Council Norway, N-0131 Oslo, Norway. RP Finstad, SE (reprint author), Ullevaal Univ Hosp, Dept Oncol, N-0407 Oslo, Norway. EM sissi.espetvedt@medisin.uio.no FU Norwegian Cancer Society [49258, 05087]; Foundation for the Norwegian Health and Rehabilitation Organizations [59010-2000/2001/2002]; Aakre Foundation [5695-2000, 57542002]; Health Region East FX We acknowledge each woman who participated in the Norwegian EBBA-I study, our nurse Gunn Knudsen, Anna Kirsti Jenssen and Sissel Andersen. The study was supported by a grant from the Norwegian Cancer Society (49 258, 05087); Foundation for the Norwegian Health and Rehabilitation Organizations (59010-2000/2001/2002); Aakre Foundation (5695-2000, 57542002), and Health Region East. NR 50 TC 14 Z9 14 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2009 VL 20 IS 2 BP 233 EP 242 DI 10.1007/s10552-008-9238-2 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 413IM UT WOS:000263786800012 PM 18853264 ER PT J AU Faupel-Badger, JM Hoover, RN Potischman, N Roberts, JM Troisi, R AF Faupel-Badger, Jessica M. Hoover, Robert N. Potischman, Nancy Roberts, James M. Troisi, Rebecca TI Pregnancy weight gain is not associated with maternal or mixed umbilical cord estrogen and androgen concentrations SO CANCER CAUSES & CONTROL LA English DT Article DE Pregnancy; Breast cancer; Estrogens; Androgens ID BREAST-CANCER RISK; WOMEN; PREECLAMPSIA; ADIPOSITY AB The association of maternal weight gain with serum hormone concentrations was explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol, estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate concentrations were measured both in maternal and mixed umbilical cord serum to assess hormone levels in both the maternal and fetal circulation at delivery. Our data show no association of maternal or cord steroid hormone concentrations with pregnancy weight gain. Increased exposure to steroid hormones, especially estrogens, during pregnancy has been hypothesized to play a role in subsequent breast cancer risk for both mother and female offspring. Our results are not consistent with an effect of pregnancy weight gain being mediated by this pathway as reflected by hormone concentrations at the end of pregnancy. C1 [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Div Canc Prevent & Mammary Biol, Ctr Canc Res,Natl Inst Hlth,EPS, Bethesda, MD 20892 USA. [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Tumorigenesis Lab, Ctr Canc Res,Natl Inst Hlth,EPS, Bethesda, MD 20892 USA. [Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Potischman, Nancy] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Roberts, James M.] Magee Womens Res Inst, Pittsburgh, PA 15213 USA. [Roberts, James M.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Roberts, James M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Troisi, Rebecca] Dartmouth Med Sch, Hanover, NH 03755 USA. RP Faupel-Badger, JM (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent & Mammary Biol, Ctr Canc Res,Natl Inst Hlth,EPS, T-41,MSC 7105, Bethesda, MD 20892 USA. EM badgerje@mail.nih.gov FU Cancer Prevention Fellowship Program; Center for Cancer Research; Division of Cancer Epidemiology and Genetics; NIH FX This research was supported by the Cancer Prevention Fellowship Program, the Division of Cancer Prevention, the Intramural Research Program of the Center for Cancer Research, and the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. NR 25 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2009 VL 20 IS 2 BP 263 EP 267 DI 10.1007/s10552-008-9235-5 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 413IM UT WOS:000263786800015 PM 18830676 ER PT J AU Mbeunkui, F Johann, DJ AF Mbeunkui, Flaubert Johann, Donald J., Jr. TI Cancer and the tumor microenvironment: a review of an essential relationship SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Review DE Tumor; Microenvironment; Secreted proteins; Extracellular matrix; Molecular targets; Therapy ID ENDOTHELIAL GROWTH-FACTOR; FIBROBLAST ACTIVATION PROTEIN; MAMMARY EPITHELIAL-CELLS; CODED AFFINITY TAGS; BREAST-CANCER; PROTEOMIC ANALYSIS; EXTRACELLULAR-MATRIX; SECRETED BIOMARKERS; COLORECTAL-CANCER; DRUG-RESISTANCE AB Purpose The role of the microenvironment during the initiation and progression of carcinogenesis is now realized to be of critical importance, both for enhanced understanding of fundamental cancer biology, as well as exploiting this source of relatively new knowledge for improved molecular diagnostics and therapeutics. Methods This review focuses on: (1) the approaches of preparing and analyzing secreted proteins, (2) the contribution of tumor microenvironment elements in cancer, and (3) the potential molecular targets for cancer therapy. Results The microenvironment of a tumor is an integral part of its physiology, structure, and function. It is an essential aspect of the tumor proper, since it supplies a nurturing environment for the malignant process. A fundamental deranged relationship between tumor and stromal cells is essential for tumor cell growth, progression, and development of life threatening metastasis. Improved understanding of this interaction may provide new and valuable clinical targets for cancer management, as well as risk assessment and prevention. Non-malignant cells and secreted proteins from tumor and stromal cells are active participants in cancer progression. Conclusions Monitoring the change in the tumor microenvironment via molecular and cellular profiles as tumor progresses would be vital for identifying cell or protein targets for cancer prevention and therapy. C1 [Mbeunkui, Flaubert] N Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA. [Johann, Donald J., Jr.] NCI, Ctr Canc Res, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Mbeunkui, F (reprint author), N Carolina State Univ, Dept Mol & Struct Biochem, 128 Polk Hall,Campus Box 7622, Raleigh, NC 27695 USA. EM fmbeunk@ncsu.edu; johannd@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 100 TC 138 Z9 153 U1 6 U2 55 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2009 VL 63 IS 4 BP 571 EP 582 DI 10.1007/s00280-008-0881-9 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 417YL UT WOS:000264114300001 PM 19083000 ER PT J AU Wacholder, S Rotunno, M AF Wacholder, Sholom Rotunno, Melissa TI Control Selection Options for Genome-Wide Association Studies in Cohorts SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID BIASED SELECTION; DESIGN; DISEASE; EPIDEMIOLOGY; CANCER; RISK AB Investigators planning studies within cohorts have many options for choosing-an efficient sampling design for genome-wide association and other molecular epidemiology studies. Consideration of person-year and proportional hazards analyses of full cohorts may add further insight into ramifications of different designs. Empirical evidence from genome-wide association studies can supplement intuition and simulations in comparing properties of various case-control designs within cohorts. Additional theoretical and empirical work, justification of sampling choice in publications,, and consideration of context and scientific aims can improve designs and, thereby, increase the scientific value and cost effectiveness of future studies. (Cancer Epidemiol Biomarkers Prev 2009;18(3):695-7) C1 [Wacholder, Sholom; Rotunno, Melissa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, NIH, EPS 8046,6120 Execut Blvd, Rockville, MD 20892 USA. EM sholom_wacholder@nih.gov FU Intramural NIH HHS [Z01 CP010181-05] NR 13 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 695 EP 697 DI 10.1158/1055-9965.EPI-08-1114 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100001 PM 19258469 ER PT J AU Kapetanovic, IM AF Kapetanovic, Izet M. TI Rapid Access to Preventive Intervention Development Program in the Division of Cancer Prevention of the US National Cancer Institute: an Overview SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CHEMOPREVENTIVE AGENTS; DEHYDROEPIANDROSTERONE; CARCINOGENESIS; RETINOIDS; EFFICACY; ANALOGS C1 NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, 6130 Execut Blvd,Room 2116, Bethesda, MD 20892 USA. EM kapetani@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 13 TC 4 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 698 EP 700 DI 10.1158/1055-9965.EPI-08-1007 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100002 PM 19240231 ER PT J AU Grubb, RL Black, A Izmirlian, G Hickey, TP Pinsky, PF Mabie, JE Riley, TL Ragard, LR Prorok, PC Berg, CD Crawford, ED Church, TR Andriole, GL AF Grubb, Robert L., III Black, Amanda Izmirlian, Grant Hickey, Thomas P. Pinsky, Paul F. Mabie, Jerome E. Riley, Thomas L. Ragard, Lawrence R. Prorok, Philip C. Berg, Christine D. Crawford, E. David Church, Timothy R. Andriole, Gerald L., Jr. CA PLCO Project Team TI Serum Prostate-Specific Antigen Hemodilution Among Obese Men Undergoing Screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; UNITED-STATES; PSA LEVELS; US ADULTS; OVERWEIGHT; MORTALITY; HEIGHT; COHORT; SIZE AB Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and body mass index (BMI). It has been recently proposed that this relationship may be explained by the larger plasma volume of obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening, 28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline. Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration, plasma volume, PSA mass, and BMI. Results: PSA concentration significantly decreased with increasing BMI (P < 0.001); mean PSA values were 1.27, 1.25,1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese (BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 mu g across the four BMI categories (P = 0.10). Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained by a hemodilution effect. These findings could have implications for prostate cancer screening in large men. (Cancer Epidemiol Biomarkers Prev 2009;18(3):748-51) C1 [Grubb, Robert L., III; Andriole, Gerald L., Jr.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Church, Timothy R.] Univ Minnesota, Minneapolis, MN USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Black, Amanda] NCI, Canc Prevent Div, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Black, Amanda] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Izmirlian, Grant; Prorok, Philip C.] NCI, Biometry Res Grp, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Black, Amanda; Pinsky, Paul F.; Berg, Christine D.] NCI, Early Detect Res Grp, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Ragard, Lawrence R.] Westat Corp, Rockville, MD USA. [Hickey, Thomas P.; Mabie, Jerome E.; Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA. RP Andriole, GL (reprint author), Washington Univ, Sch Med, Div Urol Surg, 4960 Childrens Pl,Campus Box 8242, St Louis, MO 63110 USA. EM andrioleg@wudosis.wustl.edu OI Church, Timothy R./0000-0003-3292-5035 NR 24 TC 78 Z9 79 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 748 EP 751 DI 10.1158/1055-9965.EPI-08-0938 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100010 PM 19258472 ER PT J AU Genkinger, JM Spiegelman, D Anderson, KE Bergkvist, L Bernstein, L van den Brandt, PA English, DR Freudenheim, JL Fuchs, CS Giles, GG Giovannucci, E Hankinson, SE Horn-Ross, PL Leitzmann, M Mannisto, S Marshall, JR McCullough, ML Miller, AB Reding, DJ Robien, K Rohan, TE Schatzkin, A Stevens, VL Stolzenberg-Solomon, RZ Verhage, BAJ Wolk, A Ziegler, RG Smith-Warner, SA AF Genkinger, Jeanine M. Spiegelman, Donna Anderson, Kristin E. Bergkvist, Leif Bernstein, Leslie van den Brandt, Piet A. English, Dallas R. Freudenheim, Jo L. Fuchs, Charles S. Giles, Graham G. Giovannucci, Edward Hankinson, Susan E. Horn-Ross, Pamela L. Leitzmann, Michael Mannisto, Satu Marshall, James R. McCullough, Marjorie L. Miller, Anthony B. Reding, Douglas J. Robien, Kim Rohan, Thomas E. Schatzkin, Arthur Stevens, Victoria L. Stolzenberg-Solomon, Rachael Z. Verhage, Bas A. J. Wolk, Alicja Ziegler, Regina G. Smith-Warner, Stephanie A. TI Alcohol Intake and Pancreatic Cancer Risk: A Pooled Analysis of Fourteen Cohort Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID FOOD FREQUENCY QUESTIONNAIRE; DIETARY-FOLATE CONSUMPTION; BREAST-CANCER; COFFEE CONSUMPTION; UNITED-STATES; REGRESSION-MODELS; DIABETES-MELLITUS; EXOCRINE PANCREAS; MEASUREMENT ERROR; BEVERAGE CONSUMPTION AB Background: Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk. Methods: We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks and 95% confidence intervals were calculated using Cox proportional hazards models and then pooled using a random effects model. Results: A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate relative risk, 1.22; 95% confidence interval, 1.03-1.45 comparing >= 30 to 0 grams/day of alcohol; P value, test for between-studies heterogeneity = 0.80). For this comparison, the positive association was only statistically significant among women although the difference in the results by gender was not statistically significant (P value, test for interaction = 0.19). Slightly stronger results for alcohol intake were observed when we limited the analysis to cases with adenocarcinomas of the pancreas. No statistically significant associations were observed for alcohol from wine, beer, and spirits comparing intakes of >= 5 to 0 grams/day. A stronger positive association between alcohol consumption and pancreatic cancer risk was observed among normal weight individuals compared with overweight and obese individuals (P value, test for interaction = 0.01). Discussion: Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day. (Cancer Epidemiol Biomarkers Prev 2009;18(3):765-76) C1 [Genkinger, Jeanine M.] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Div Canc Genet & Epidemiol,Dept Oncol, Washington, DC 20007 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward; Hankinson, Susan E.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Spiegelman, Donna; Giovannucci, Edward; Hankinson, Susan E.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Freudenheim, Jo L.; Marshall, James R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Reding, Douglas J.] Marshfield Clin Fdn Med Res & Educ, Dept Hematol Oncol, Marshfield, WI USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [van den Brandt, Piet A.; Verhage, Bas A. J.] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Epidemiol, Maastricht, Netherlands. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [McCullough, Marjorie L.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Div Canc Etiol, Duarte, CA 91010 USA. [Bergkvist, Leif] Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden. [Bergkvist, Leif] Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden. [Mannisto, Satu] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Horn-Ross, Pamela L.] No Calif Canc Ctr, Fremont, CA USA. [Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Leitzmann, Michael; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Smith-Warner, SA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM pooling@hsphsun2.harvard.edu OI Mannisto, Satu/0000-0002-8668-3046; Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU NIH [CA098566, CA55075] FX NIH, # CA098566 and # CA55075. NR 106 TC 60 Z9 64 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 765 EP 776 DI 10.1158/1055-9965.EPI-08-0880 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100013 PM 19258474 ER PT J AU Enewold, L Zhu, KM Ron, E Marrogi, AJ Stojadinovic, A Peoples, GE Devesa, SS AF Enewold, Lindsey Zhu, Kangmin Ron, Elaine Marrogi, Aizen J. Stojadinovic, Alexander Peoples, George E. Devesa, Susan S. TI Rising Thyroid Cancer Incidence in the United States by Demographic and Tumor Characteristics, 1980-2005 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INCREASING INCIDENCE; REPRODUCTIVE FACTORS; POOLED ANALYSIS; TIME TRENDS; CARCINOMA; PAPILLARY; EXPOSURE; RISK; RADIATION; EPIDEMIC AB Thyroid cancer incidence has been rising in the United States, and this trend has often been attributed to heightened medical surveillance and the use of improved diagnostics. Thyroid cancer incidence varies by sex and race/ethnicity, and these factors also influence access to and utilization of healthcare. We therefore examined thyroid cancer incidence rates by demographic and tumor characteristics based on 48,403 thyroid cancer patients diagnosed during 1980-2005 from the Surveillance, Epidemiology and End Results program of the National Cancer Institute. The rates varied by histologic type, sex, and race/ethnicity. Papillary carcinoma was the only histologic type for which incidence rates increased consistently among all racial/ethnic groups. Subsequent analyses focused on the 39,706 papillary thyroid cancers diagnosed during this period. Papillary carcinoma rates increased most rapidly among females. Between 1992-1995 and 2003-2005, they increased nearly 100% among White non-Hispanics and Black females but only 20% to 50% among White Hispanics, Asian/Pacific Islanders, and Black males. The increases were most rapid for localized stage and small tumors; however, rates also increased for large tumors and tumors of regional and distant stage. Since 1992-1995, half the overall increase in papillary carcinoma rates was due to increasing rates of very small (<= 1.0 cm) cancers, 30% to cancers 1.1 to 2 cm, and 20% to cancers >2 cm. Among White females, the rate of increase for cancers >5 cm almost equaled that for the smallest cancers. Medical surveillance and more sensitive diagnostic procedures cannot completely explain the observed increases in papillary thyroid cancer rates. Thus, other possible explanations should be explored. (Cancer Epidemiol Biomarkers Prev 2009;18(3):784-91) C1 [Ron, Elaine; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Peoples, George E.] Brooke Army Med Ctr, Dept Surg, Houston, TX USA. [Stojadinovic, Alexander] Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, Washington, DC 20307 USA. [Marrogi, Aizen J.] Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. [Marrogi, Aizen J.] Walter Reed Army Med Ctr, Area Lab Serv, Washington, DC 20307 USA. [Enewold, Lindsey; Zhu, Kangmin; Marrogi, Aizen J.; Stojadinovic, Alexander; Peoples, George E.] Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA. RP Enewold, L (reprint author), Armed Forces Inst Pathol, US Mil Canc Inst, Room N1512,Bldg 54,6825 16th St NW, Washington, DC 20306 USA. EM Lindsey.Enewold@us.army.mil FU Division of Cancer Epidemiology and Genetics Intramural Research Program; National Cancer Institute; NIH; Department of Health and Human Services; United States Military Cancer Institute FX Division of Cancer Epidemiology and Genetics Intramural Research Program, National Cancer Institute, NIH, Department of Health and Human Services and the United States Military Cancer Institute via the Uniformed Services University of the Health Sciences under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine. The information or content and conclusions do not necessarily represent the official position or policy of, nor should any official endorsement be inferred by, the Uniformed Services University of the Health Sciences, the United States Military Cancer Institute, the Department of Defense, or the U.S. Government. NR 44 TC 326 Z9 353 U1 2 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 784 EP 791 DI 10.1158/1055-9965.EPI-08-0960 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100015 PM 19240234 ER PT J AU Reimers, LL Anderson, WF Rosenberg, PS Henson, DE Castle, PE AF Reimers, Laura L. Anderson, William F. Rosenberg, Philip S. Henson, Donald E. Castle, Philip E. TI Etiologic Heterogeneity for Cervical Carcinoma by Histopathologic Type, Using Comparative Age-Period-Cohort Models SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; 13 EUROPEAN COUNTRIES; UTERINE CERVIX; UNITED-STATES; RISK-FACTORS; PROMOTER HYPERMETHYLATION; CHLAMYDIA-TRACHOMATIS; TEMPORAL VARIATION; INCIDENCE TRENDS; CANCER INCIDENCE AB Background: Cervical carcinomas comprise two main histopathologic types, squamous cell carcinomas and adenocarcinomas. Human papillomavirus (HPV) infections are causative for both types but the respective tumors may have different carcinogenic pathways. Methods: To assess potential etiologic heterogeneity of cervical cancer by histopathologic type, we examined invasive squamous cell carcinomas and adenocarcinoma cervical cancer incidence rates in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. We complemented standard descriptive epidemiology with comparative age-period-cohort (APC) models fitted to each histopathologic type. Results: Squamous cell tumors (n = 25,219) were nearly 5-fold more common than adenocarcinomas (n = 5,451). Age-adjusted incidence trends decreased for squamous cell carcinomas but increased for adenocarcinomas. Cross-sectional age-specific incidence rates increased more rapidly for squamous cell carcinomas than adenocarcinomas in adolescents and young adults then leveled off for both types. APC models confirmed that secular trends and age-specific rates differed for the two types (P = 0 for the null hypothesis of no difference). For squamous cell carcinoma, the APC "fitted" age-at-onset rate curve peaked before age 40 years then declined; for adenocarcinoma, the fitted curve increased rapidly until age 40 years then rose more slowly. Conclusions: Despite the necessary role of HPV infection in both squamous cell carcinomas and adenocarcinomas of the cervix, secular trends and age-related natural histories differed for the two tumor types, consistent with etiologic heterogeneity. Future analytic and clinical studies should consider the interaction (effect modification) of HPV infection and other cervical carcinoma risk factors by histopathologic type, time, and age. (Cancer Epidemiol Biomarkers Prev 2009;18(3):792-800) C1 [Castle, Philip E.] NCI, Hormone Reprod & Epidemiol Branch, DHSS NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Anderson, William F.] NCI, Biostat Branch, DHSS NIH, Div Canc Epidemiol & Genet DCEG,EPS, Bethesda, MD 20892 USA. [Reimers, Laura L.] George Washington Univ, Sch Publ Hlth & Human Serv, Washington, DC USA. [Henson, Donald E.] George Washington Univ, Ctr Canc, Dept Pathol, Washington, DC USA. RP Anderson, WF (reprint author), NCI, Biostat Branch, DHSS NIH, Div Canc Epidemiol & Genet DCEG,EPS, Room 8036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM wanderso@mail.nih.gov FU Intramural Research Program of the NIH; National Cancer Institute FX Intramural Research Program of the NIH, National Cancer Institute. The authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 52 TC 30 Z9 31 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 792 EP 800 DI 10.1158/1055-9965.EPI-08-0965 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100016 PM 19258470 ER PT J AU Kim, SM Parks, CG Deroo, LA Chen, HL Taylor, JA Cawthon, RM Sandler, DP AF Kim, Sangmi Parks, Christine G. DeRoo, Lisa A. Chen, Honglei Taylor, Jack A. Cawthon, Richard M. Sandler, Dale P. TI Obesity and Weight Gain in Adulthood and Telomere Length SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID OXIDATIVE STRESS; INSULIN-RESISTANCE; BREAST-CANCER; PERCEIVED STRESS; WOMEN; RISK; DISEASE; HEALTH; CELLS; AGE AB Obesity and weight gain in adulthood are associated with an increased risk of several cancers. Telomeres play a critical role in maintaining genomic integrity and may be involved in carcinogenesis. Using data from 647 women ages 35 to 74 years in the United States and Puerto Rico (2003-2004), we examined the association between current and past anthropometric characteristics and telomere length in blood. In a multivariate linear regression model, higher current body mass index (BMI) and hip circumference were inversely associated with telomere length. Higher BMI in the 30s was associated with shorter telomere length among women ages >= 40 years (P(trend) < 0.01). Weight gain since the age 30s (P(trend) = 0.07) and weight cycling (P(trend) = 0.04) were also inversely associated with telomere length. When current BMI and BMI at ages 30 to 39 years were considered together, the most marked decrease in telomere length was found for women who had overweight or obese BMI at both time points (mean telomere repeat copy number to single-copy gene copy number ratio = 1.26; 95% confidence interval, 1.21-1.30) compared with women who had normal BMI at both times (mean telomere repeat copy number to single-copy gene copy number ratio = 1.33; 95% confidence interval, 1.30-1.36). These findings support the hypothesis that obesity may accelerate aging, and highlight the importance of maintaining a desirable weight in adulthood. (Cancer Epidemiol Biomarkers Prev 2009;18(3):816-20) C1 [Kim, Sangmi; Parks, Christine G.; DeRoo, Lisa A.; Chen, Honglei; Taylor, Jack A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Cawthon, Richard M.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. RP Sandler, DP (reprint author), NIEHS, Epidemiol Branch, NIH, POB 12233,MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sandler@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398; Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018; Chen, Honglei/0000-0003-3446-7779 FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences [Z01 ES04400509]; National Center on Minority Health and Health Disparities; Department of Defense Breast Cancer Research Concept Award [BC045286] FX Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES04400509), National Center on Minority Health and Health Disparities, and Department of Defense Breast Cancer Research Concept Award BC045286. NR 26 TC 77 Z9 78 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 816 EP 820 DI 10.1158/1055-9965.EPI-08-0935 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100019 PM 19273484 ER PT J AU Porras, C Rodriguez, AC Hildesheim, A Herrero, R Gonzalez, P Wacholder, S Burk, RD Schiffman, M AF Porras, Carolina Rodriguez, Ana Cecilia Hildesheim, Allan Herrero, Rolando Gonzalez, Paula Wacholder, Sholom Burk, Robert D. Schiffman, Mark TI Human Papillomavirus Types by Age in Cervical Cancer Precursors: Predominance of Human Papillomavirus 16 in Young Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COSTA-RICA; ABSOLUTE RISK; GUANACASTE; INFECTION; LESIONS; ADENOCARCINOMA; ABNORMALITIES; NEOPLASIA; PRECANCER; HPV AB In a population-based study conducted in Guanacaste, Costa Rica, we investigated the human papillomavirus (HPV) types detected in 233 cases of cervical intraepithelial neoplasia (CIN) 2/3 and cancer by age. CIN2+ and CIN3+ in young women were significantly more likely to be associated with HPV 16 than the same lesions in older women (80% of CIN3+ were associated with HPV 16 among women ages 18-26 years compared with only 32% among women older than 55 years; P(trend) = 0.018). There were no differences by age in HPV 18 positivity. Lesions in older women were mainly caused by other carcinogenic types. This association was present for both prevalent and incident lesions and supports the notion that HPV 16 is a stronger carcinogen than other HPV types. It also has implications for prevention, including the need to vaccinate young women before exposure to HPV vaccine-containing types (HPV 16 and HPV 18) to prevent the majority of cervical cancer precursors. (Cancer Epidemiol Biomarkers Prev 2009;18(3):863-5) C1 [Porras, Carolina; Rodriguez, Ana Cecilia; Herrero, Rolando; Gonzalez, Paula] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. [Hildesheim, Allan; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Porras, C (reprint author), Fdn INCIENSA, Proyecto Epidemiol Guanacaste, Torre La Sabana,300 Oeste ICE,Piso 7, San Jose, Costa Rica. EM cporras@proyectoguanacaste.org RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU NIH [NO1-CP-21081, NO1-CP-33061, NO1-CP-40542, NO1-CP-50535, NO1-CP-81023, CA78527]; NIH; National Cancer Institute; Division of Cancer Epidemiology and Genetics FX The Guanacaste cohort was supported by NIH (contracts numbers NO1-CP-21081, NO1-CP-33061, NO1-CP-40542, NO1-CP-50535, NO1-CP-81023, and CA78527; R.D. Burk). This research was supported in part by the Intramural Research program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 21 TC 35 Z9 36 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 863 EP 865 DI 10.1158/1055-9965.EPI-08-0951 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100025 PM 19273486 ER PT J AU D'Aloisio, AA Schroeder, JC North, KE Poole, C West, SL Travlos, GS Baird, DD AF D'Aloisio, Aimee A. Schroeder, Jane C. North, Kari E. Poole, Charles West, Suzanne L. Travlos, Gregory S. Baird, Donna D. TI IGF-I and IGFBP-3 Polymorphisms in Relation to Circulating Levels among African American and Caucasian Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; BREAST-CANCER RISK; FACTOR BINDING-PROTEIN-3 CONCENTRATIONS; SINGLE NUCLEOTIDE POLYMORPHISM; FACTOR (IGF)-I; SERUM-LEVELS; LIFE-STYLE; POPULATION STRATIFICATION; INTERINDIVIDUAL VARIATION AB Circulating insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNP) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala(32)Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians, 631 ng/mL; 95% confidence interval, 398-864; African Americans, 897 ng/mL; 95% confidence interval, 656-1,138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than reference diplotypes with the CG genotype, whereas IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (-202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with >= 5% differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with >= 10% differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians but provides less evidence that IGF-I SNPs affect plasma IGF-I levels. (Cancer Epidemiol Biomarkers Prev 2009;18(3):954-66) C1 [D'Aloisio, Aimee A.; Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Travlos, Gregory S.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [West, Suzanne L.] RTI Int, Hlth Social & Econ Res, Res Triangle Pk, NC USA. [Schroeder, Jane C.; North, Kari E.; Poole, Charles] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP D'Aloisio, AA (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drp A3-05,Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM daloisio@niehs.nih.gov RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU NIH; NIEHS [P30ES10126]; NIH Office of Research on Minority Health FX Intramural Research Program of the NIH, NIEHS and NIH Office of Research on Minority Health; NIEHS grant P30ES10126 (C. Poole). Genotyping was supported by the University of North Carolina-GlaxoSmithKline Center of Excellence in Pharmacoepiderniology and Public Health. NR 65 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 954 EP 966 DI 10.1158/1055-9965.EPI-08-0856 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100036 PM 19240240 ER PT J AU Bapat, B Lindor, NM Baron, J Siegmund, K Li, L Zheng, YY Haile, R Gallinger, S Jass, JR Young, JP Cotterchio, M Jenkins, M Grove, J Casey, G Thibodeau, SN Bishop, DT Hopper, JL Ahnen, D Newcomb, PA Le Marchand, L Potter, JD Seminara, D AF Bapat, Bharati Lindor, Noralane M. Baron, John Siegmund, Kim Li, Lin Zheng, Yingye Haile, Robert Gallinger, Steve Jass, Jeremy R. Young, Joanne P. Cotterchio, Michelle Jenkins, Mark Grove, John Casey, Graham Thibodeau, Stephen N. Bishop, D. Timothy Hopper, John L. Ahnen, Dennis Newcomb, Polly A. Le Marchand, Loic Potter, John D. Seminara, Daniela CA Colon Cancer Family Registr TI The Association of Tumor Microsatellite Instability Phenotype with Family History of Colorectal Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLON-CANCER; LYNCH-SYNDROME; BETHESDA GUIDELINES; LARGE BOWEL; RISK; CARCINOMA; HNPCC; FREQUENCY; RELATIVES; CRITERIA AB Family history is a strong predictor of colorectal cancer risk; however, a diagnosis of colorectal cancer among first-degree relatives has not been systematically investigated as a function of the colorectal cancer molecular subtypes related to tumor microsatellite instability (MSI) status. We investigated whether the observable familial colorectal cancer risks differed according to tumor MSI subtypes, stratified as MSI-High (>30% instability), MSI-Low (<30% instability), and MSS (no instability). Data from 3,143 population-based colorectal cancer cases from five institutions were assessed for family history according to the Amsterdam criteria and the Bethesda guidelines, age at diagnosis, sex, tumor location, and MST status. The distribution of patient characteristics by MST status was compared using polytomous logistic regression. Overall, 2.8% colorectal cancer cases met the Amsterdam criteria and 37% met the Bethesda guidelines. There were 14% MST-High, 13% MSI-Low, and 73% MSS colorectal cancers. MST-High (P < 0.0001) and MSI-Low tumors (P = 0.01) were more proximally located than MSS tumors. MSI-High tumors were more common among females (P < 0.001). The highest proportion of MSI-High tumors occurred in cases <40 years of age whereas the age-dependent distribution of MSI-Low tumors was unchanged. MSI-High tumors showed a statistically significant association with increasing numbers of first-degree relatives with colorectal cancer (P = 0.002); this association disappeared, however, when MSI-High cases meeting Amsterdam criteria were removed from the analysis. MSI-Low tumors did not show a similar association with family history of colorectal cancer. Familial risk associated with MSI-High tumors is primarily driven by the Amsterdam-criteria patients. MSI-Low tumors may represent a distinct subtype of colorectal cancer with respect to certain epidemiologic variables studied here. (Cancer Epidemiol Biomarkers Prev 2009;18(3): 967-75) C1 [Bapat, Bharati] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Pathol & Lab Med, Toronto, ON M5T 3L9, Canada. [Gallinger, Steve] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Surg, Toronto, ON M5T 3L9, Canada. [Cotterchio, Michelle] Canc Care Ontario, Toronto, ON, Canada. [Lindor, Noralane M.; Thibodeau, Stephen N.] Mayo Clin, Div Gastroenterol, Dept Med Genet, Lab Med & Pathol, Rochester, MN USA. [Baron, John] Dartmouth Med Sch, Hanover, NH USA. [Siegmund, Kim; Haile, Robert; Casey, Graham] Univ So Calif, Los Angeles, CA USA. [Li, Lin; Zheng, Yingye; Newcomb, Polly A.; Potter, John D.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Jass, Jeremy R.] Univ London Imperial Coll Sci Technol & Med, Dept Pathol, London, England. [Young, Joanne P.] Royal Brisbane Hosp, Conjoint Gastroenterol Lab, Brisbane, Qld 4029, Australia. [Jenkins, Mark; Hopper, John L.] Univ Melbourne, Dept Gen Practice & Publ Hlth, Melbourne, Vic 3010, Australia. [Grove, John; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Bishop, D. Timothy] Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England. [Ahnen, Dennis] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Ahnen, Dennis] Dept Vet Affairs Med Ctr, Denver, CO USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Clin & Genet Epidemiol Res Branch, NIH, Bethesda, MD 20892 USA. RP Bapat, B (reprint author), Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Pathol & Lab Med, 60 Murray St,Box 30, Toronto, ON M5T 3L9, Canada. EM bapat@lunenfeld.ca RI Gallinger, Steven/E-4575-2013; Bapat, Bharati/B-5839-2014; Jenkins, Mark/P-7803-2015; OI Potter, John/0000-0001-5439-1500; Jenkins, Mark/0000-0002-8964-6160; Bishop, Tim/0000-0002-8752-8785 FU National Cancer Institute [RFA CA-95-011]; Australian Colorectal Cancer Family Registry [UO1 CA097735]; USC Familial Colorectal Neoplasm Collaborative Group [UO1 CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [UO1 CA074800]; Ontario Registry for Studies of Familial Colorectal Cancer [UO1 CA074783]; Seattle Colorectal Cancer Family Registry [UO1 CA074794]; University of Hawaii Colorectal Cancer Family Registry [UO1 CA074806]; University of California; Irvine Informatics Center [UO1 CA078296] FX National Cancer Institute (RFA CA-95-011) and through cooperative agreements with members of the colon family registry and principal investigators from Australian Colorectal Cancer Family Registry (UO1 CA097735), USC Familial Colorectal Neoplasm Collaborative Group (UO1 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (UO1 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (UO1 CA074783), Seattle Colorectal Cancer Family Registry (UO1 CA074794), University of Hawaii Colorectal Cancer Family Registry (UO1 CA074806), and University of California, Irvine Informatics Center (UO1 CA078296). NR 45 TC 16 Z9 17 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 967 EP 975 DI 10.1158/1055-9965.EPI-08-0878 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100037 PM 19258475 ER PT J AU Shrubsole, MJ Yang, G Gao, YT Chow, WH Shu, XO Cai, QY Rothman, N Gao, J Wagner, C Zheng, W AF Shrubsole, Martha J. Yang, Gong Gao, Yu-Tang Chow, Wang Ho Shu, Xiao Ou Cai, Qiuyin Rothman, Nathaniel Gao, Jin Wagner, Conrad Zheng, Wei TI Dietary B Vitamin and Methionine Intakes and Plasma Folate Are Not Associated with Colorectal Cancer Risk in Chinese Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NESTED CASE-CONTROL; METHYLENETETRAHYDROFOLATE REDUCTASE; FOLIC-ACID; MICROBIOLOGICAL ASSAY; LACTOBACILLUS-CASEI; POLYMORPHISMS; HEALTH; JAPAN AB Dietary factors involved in one-carbon metabolism may play a role in colorectal carcinogenesis (1). We evaluated whether dietary intakes of folate, methionine, and associated B vitamins were related to colorectal cancer risk using data from a large prospective cohort study of women in Shanghai, China. We further evaluated the relationship between baseline plasma folate levels and subsequent colorectal cancer risk in a nested case-control study from the same study population. C1 [Shrubsole, Martha J.; Yang, Gong; Shu, Xiao Ou; Cai, Qiuyin; Zheng, Wei] Vanderbilt Univ, Div Gen Internal Med & Publ Hlth, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. [Wagner, Conrad] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. [Gao, Yu-Tang; Gao, Jin] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Chow, Wang Ho; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Shrubsole, MJ (reprint author), Vanderbilt Univ, Div Gen Internal Med & Publ Hlth, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, 8th Floor,Suite 800,2525 W End Ave, Nashville, TN 37203 USA. EM martha.stirubsole@vanderbilt.edu RI Shrubsole, Martha/K-5052-2015 OI Shrubsole, Martha/0000-0002-5591-7575 FU National Cancer Institute [R01CA70867]; NIH FX Grant R01CA70867 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the NIH. NR 27 TC 18 Z9 18 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2009 VL 18 IS 3 BP 1003 EP 1006 DI 10.1158/1055-9965.EPI-08-1200 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 419NK UT WOS:000264226100042 PM 19240230 ER PT J AU Wargo, JA Robbins, PF Li, Y Zhao, YB El-Gamil, M Caragacianu, D Zheng, ZL Hong, J Downey, S Schrump, D Rosenberg, S Morgan, R AF Wargo, Jennifer A. Robbins, Paul F. Li, Yong Zhao, Yangbing El-Gamil, Mona Caragacianu, Diana Zheng, Zhili Hong, Julie A. Downey, Stephanie Schrump, David S. Rosenberg, Steven A. Morgan, Richard A. TI Recognition of NY-ESO-1+tumor cells by engineered lymphocytes is enhanced by improved vector design and epigenetic modulation of tumor antigen expression SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE NY-ESO-1; TCR; Retroviral vector; Gene therapy; Epigenetics ID BLOOD MONONUCLEAR-CELLS; GENE-EXPRESSION; T-LYMPHOCYTES; CANCER-IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; RETROVIRAL VECTOR; IN-VIVO; TCR; ANTIBODY; MELANOMA AB The therapeutic use of T cell receptor (TCR)-transduced peripheral blood lymphocytes (PBL) targeting tumor-associated antigens is emerging as a promising investigational treatment for patients with cancer. Initial response rates to therapy were low, suggesting the need to improve the function of TCR-transduced PBL. We constructed standard bicistronic retroviral vectors using an internal promoter or internal ribosomal entry site element as well as vectors incorporating coding sequences for 2A linker peptides between coding sequences for alpha and beta chains targeting the cancer-testis (CT) antigen, NY-ESO-1. Incorporation of coding sequences for 2A linker peptides in the bicistronic TCR expression cassette resulted in up to a fourfold increase in TCR expression and a significant improvement in effector function as measured by interferon-gamma release following co-culture with peptide-pulsed targets and NY-ESO-1+ tumors. We also sought to enhance reactivity of TCR-transduced PBL against tumor targets by modulation of tumor antigen expression on target cells. Induction of NY-ESO-1 expression on tumor targets using the demethylating agent 5-aza-2'-deoxycytidine (alone or in combination with the histone deacetylase inhibitor depsipeptide) resulted in enhanced interferon-gamma secretion by the TCR-transduced PBL on culture with treated targets. Taken together, these results indicate that design of TCR-based vectors incorporating 2A linker peptides improves TCR expression and effector function of transduced PBL. Furthermore, induction of CT antigen expression through treatment of tumor targets with chromatin-remodeling agents may augment TCR-based immunotherapy targeting these antigens. These results have relevance for TCR-based gene therapies targeting common epithelial malignancies. C1 [Wargo, Jennifer A.; Robbins, Paul F.; Li, Yong; Zhao, Yangbing; El-Gamil, Mona; Caragacianu, Diana; Zheng, Zhili; Hong, Julie A.; Downey, Stephanie; Schrump, David S.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Morgan, R (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 3-5940, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We thank FACS lab and TIL lab in Surgery Branch for providing technical support and maintenance of tumor cells from patients. This work is supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 39 TC 42 Z9 43 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAR PY 2009 VL 58 IS 3 BP 383 EP 394 DI 10.1007/s00262-008-0562-x PG 12 WC Oncology; Immunology SC Oncology; Immunology GA 392CH UT WOS:000262280000007 PM 18677478 ER PT J AU Bluming, AZ Tavris, C AF Bluming, Avrum Z. Tavris, Carol TI Hormone Replacement Therapy: Real Concerns and False Alarms SO CANCER JOURNAL LA English DT Review DE hormone replacement therapy (HRT); estrogen; breast cancer; women's health initiative (WHI); risk assessment ID BREAST-CANCER RISK; ESTROGEN PLUS PROGESTIN; ORAL-CONTRACEPTIVE USE; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGENS; BILATERAL PROPHYLACTIC OOPHORECTOMY; NATIONALLY REPRESENTATIVE COHORT; HEALTHY POSTMENOPAUSAL WOMEN; MILD COGNITIVE IMPAIRMENT; FEMALE FLIGHT ATTENDANTS AB From 2002 to 2008, reports from the Women's Health Initiative (WHI) claimed that hormone replacement therapy (HRT) significantly increased the risks of breast cancer development, cardiac events, Alzheimer disease, and stroke. These claims alarmed the public and health professionals alike, causing an almost immediate and sharp decline in the numbers of women receiving HRT. However, the actual data in file published WHI articles reveal that the findings reported in press releases and interviews of the principal investigators were often distorted, oversimplified, or wrong. This review highlights the history of research on HRT, including a timeline of studies that have or have not found a link between HRT and breast cancer; discusses how to distinguish important, robust findings from those that are trivial; closely examines the WHI findings on HRT and breast cancer, most of which are weak or statistically insignificant; reviews the cut-rent thinking about possible links of HRT with cardiovascular disease and cognitive functioning; and reports research on the benefits of HRT, notably relief of menopausal symptoms, that affect a woman's quality of life. On these complicated matters, physicians and the public must be cautious about accepting "findings by press release" in determining whether to prescribe or take HRT. C1 Univ So Calif, Los Angeles, CA 90089 USA. [Bluming, Avrum Z.] NCI, Bethesda, MD 20892 USA. RP Bluming, AZ (reprint author), 16133 Ventura Blvd,Suite 470, Encino, CA 91436 USA. EM av@lafn.org NR 209 TC 19 Z9 19 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2009 VL 15 IS 2 BP 93 EP 104 PG 12 WC Oncology SC Oncology GA 436NC UT WOS:000265419800001 PM 19390302 ER PT J AU Longo, DL AF Longo, Dan L. TI Hodgkin's Lymphoma: An Overview SO CANCER JOURNAL LA English DT Editorial Material C1 NIA, NIH, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, NIH, 251 Bayview Blvd,Suite 100,Room 04C224, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2009 VL 15 IS 2 BP 114 EP 116 PG 3 WC Oncology SC Oncology GA 436NC UT WOS:000265419800004 PM 19390305 ER PT J AU Caporaso, NE Goldin, LR Anderson, WF Landgren, O AF Caporaso, Neil E. Goldin, Lynn R. Anderson, William F. Landgren, Ola TI Current Insight on Trends, Causes, and Mechanisms of Hodgkin's Lymphoma SO CANCER JOURNAL LA English DT Review DE epidemiology; Hodgkin's lymphoma; etiology ID EPSTEIN-BARR-VIRUS; REED-STERNBERG CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; REGISTRY-BASED ANALYSIS; BREAST-CANCER RISK; CENTER B-CELL; RHEUMATOID-ARTHRITIS; 1ST-DEGREE RELATIVES; GENE REARRANGEMENTS; AUTOIMMUNE-DISEASES AB Hodgkin's lymphoma (HL) has a unique and distinct history, epidemiology, treatment, and biology. A viral agent or infectious agent has long been considered as the etiologic agent and Epstein-Barr virus is the main candidate for the infectious agent causing HL; however, Epstein-Barr virus genome is found within the tumor in only about 20% to 40% of HL cases with a prior diagnosis of infectious mononucleosis. Recently, autoimmune and related conditions have drawn attention to a potential role for immune-related and inflammatory conditions in the etiology and pathogenesis of the malignancy. Evidence from multiply-affected families, a twin study, a case-control Study, and population-based registry studies implicate genetic factors. Data from Eastern Asia and among Chinese immigrants in North America indicate increasing incidence trends for HL being associated with westernization. These results emphasize an interaction between environmental and genetic risk factors in HL. C1 [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Caporaso, NE (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Bldg EPS Room 7002, Bethesda, MD 20892 USA. EM caporaso@mail.nih.gov FU National Institutes of Health; National Cancer Institute FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 120 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2009 VL 15 IS 2 BP 117 EP 123 PG 7 WC Oncology SC Oncology GA 436NC UT WOS:000265419800005 PM 19390306 ER PT J AU Eberle, FC Mani, H Jaffe, ES AF Eberle, Franziska C. Mani, Haresh Jaffe, Elaine S. TI Histopathology of Hodgkin's Lymphoma SO CANCER JOURNAL LA English DT Review DE classical Hodgkin's lymphoma; nodular lymphocyte predominant Hodgkin's lymphoma; primary mediastinal large B-cell lymphoma; gray zone lymphomas; Epstein-Barr virus; epidemiology; pathology; immunophenotyping; epidemiology ID REED-STERNBERG CELLS; EPSTEIN-BARR-VIRUS; EUROPEAN TASK-FORCE; REGULATORY T-CELLS; B-CELL; PROGNOSTIC-SIGNIFICANCE; GENE REARRANGEMENTS; NODULAR SCLEROSIS; IMMUNOGLOBULIN TRANSCRIPTION; CLINICOPATHOLOGICAL ENTITY AB In the last few years, there has been a greater understanding of the Spectrum and biology of Hodgkin's lymphoma. In standard texts, Hodgkin's lymphoma is classified as 2 distinct entities, namely nodular lymphocyte predominant Hodgkin's lymphoma and classical Hodgkin's lymphoma. However, recent evidence suggests that classical Hodgkin's lymphoma is not a single disease. Although the mixed cellularity and lymphocyte-depleted subtypes may be part of a biologic continuum, the nodular sclerosis subtype has a distinct epidemiology, clinical presentation, and histology. Nodular sclerosis Hodgkin's lymphoma, particularly those cases presenting with mediastinal disease, also seems related to primary mediastinal B-cell lymphoma. As Hodgkin's lymphoma is a B-cell neoplasm, there is also a better appreciation today of cases that may be borderline with conventional B-cell lymphomas. We present an update on the histopathological features of Hodgkin's lymphoma and the immunohistochemical tools available for diagnosis in the clinical setting. C1 [Eberle, Franziska C.; Mani, Haresh; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov NR 118 TC 20 Z9 21 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2009 VL 15 IS 2 BP 129 EP 137 PG 9 WC Oncology SC Oncology GA 436NC UT WOS:000265419800007 PM 19390308 ER PT J AU Seam, P Janik, JE Longo, DL DeVita, VT AF Seam, Pamela Janik, John E. Longo, Dan L. DeVita, Vincent T., Jr. TI Role of Chemotherapy in Hodgkin's Lymphoma SO CANCER JOURNAL LA English DT Article DE Hodgkin's lymphoma; antineoplastic agents; combined modality therapy; positron emission tomography ID NATIONAL-CANCER-INSTITUTE; CLINICAL-TRIALS GROUP; COMBINATION CHEMOTHERAPY; RADIATION-THERAPY; INTERGROUP TRIAL; RANDOMIZED-TRIAL; MOPP/ABV HYBRID; STANFORD-V; ADJUVANT RADIOTHERAPY; PROGNOSTIC SCORE AB The development of curative chemotherapy regimens for the treatment of Hodgkin's lymphoma (HL) is one of the true success stories in oncology. Most patients diagnosed with HL today can be cured. The major task remaining before us is curing as many patients as possible with their initial therapeutic approach while minimizing the acute toxicities and limiting the lifetime risks of important secondary events such as cardiovascular complications and secondary malignancies. In the 40 years since DeVita et al. developed the mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy regimen, we have learned a great deal about risk stratification to minimize treatment-related toxicity. Positron emission tomography may further assist us in reducing radiation treatment without compromising cures. This review will discuss the development of the chemotherapy regimens used in the management of early and advanced stage HL and the advantages and disadvantages of their use in combination with radiation therapy. C1 [Seam, Pamela; Janik, John E.] NCI, Clin Trials Team, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Longo, Dan L.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [DeVita, Vincent T., Jr.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. RP Janik, JE (reprint author), Bldg 10CRC,Room 4-5330,9000 Rockville Pike, Bethesda, MD 20892 USA. EM janikj@mail.nih.gov FU National Cancer Institute; National Institutes of Health FX Supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 42 TC 12 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD MAR-APR PY 2009 VL 15 IS 2 BP 150 EP 154 PG 5 WC Oncology SC Oncology GA 436NC UT WOS:000265419800010 PM 19390311 ER PT J AU Kim, YS Young, MR Bobe, G Colburn, NH Milner, JA AF Kim, Young S. Young, Matthew R. Bobe, Gerd Colburn, Nancy H. Milner, John A. TI Bioactive Food Components, Inflammatory Targets, and Cancer Prevention SO CANCER PREVENTION RESEARCH LA English DT Review ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; CONJUGATED LINOLEIC-ACID; ACTIVATED-RECEPTOR-GAMMA; HISTONE DEACETYLASE INHIBITORS; COLON-CANCER; BREAST-CANCER; FACTOR-ALPHA; 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE; COLORECTAL-CANCER AB Various dietary components may modify chronic inflammatory processes at the stage of cytokine production, amplification of nuclear factor-kappa B-mediated inflammatory gene expression, and the release of anti-inflammatory cytokine, transforming growth factor-beta. This review provides a synopsis of the strengths and weaknesses of the evidence that specific bioactive food components influence inflammation-related targets linked to cancer. A target repeatedly surfacing as a site of action for several dietary components is transforming growth factor beta. Whereas the use of dietary intervention strategies offers intriguing possibilities for maintaining normal cell function by modifying a process that is essential for cancer development and progression, more information is needed to characterize the minimum quantity of the bioactive food components required to bring about a change in inflammation-mediated cancer, the ideal time for intervention, and the importance of genetics in determining the response. Unquestionably, the societal benefits of using foods and their components to prevent chronic inflammation and associated complications, including cancer, are enormous. C1 [Kim, Young S.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. [Young, Matthew R.; Bobe, Gerd; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA. RP Kim, YS (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Room 3156, Bethesda, MD 20892 USA. EM yk47s@nih.gov FU Intramural NIH HHS [ZIA BC011159-03] NR 96 TC 49 Z9 49 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAR PY 2009 VL 2 IS 3 BP 200 EP 208 DI 10.1158/1940-6207.CAPR-08-0141 PG 9 WC Oncology SC Oncology GA 420MT UT WOS:000264294600004 PM 19258539 ER PT J AU Mancino, M Esposito, C Watanabe, K Nagaoka, T Gonzales, M Bianco, C Normanno, N Salomon, DS Strizzi, L AF Mancino, Mario Esposito, Claudia Watanabe, Kazuhide Nagaoka, Tadahiro Gonzales, Monica Bianco, Caterina Normanno, Nicola Salomon, David S. Strizzi, Luigi TI Neuronal Guidance Protein Netrin-1 Induces Differentiation in Human Embryonal Carcinoma Cells SO CANCER RESEARCH LA English DT Article ID MAMMARY-GLAND; SELF-RENEWAL; STEM-CELLS; TERATOCARCINOMA; EXPRESSION; CRIPTO-1; FAMILY; MORPHOGENESIS; GROWTH; TUMORS AB Pluripotent cells within embryonal carcinoma (EC) can differentiate in vivo or in vitro on treatment with specific agents. Differentiating EC cells express lower levels of stem cell-related genes, such as Cripto-1. We show that migration of human EC cells (NTERA/2 and NCCIT) can be reduced following treatment with the guidance molecule Netrin-1. Moreover, Netrin-1 treatment increased the levels of beta-III tubulin, glial filament acidic protein, Nestin, and gamma-ammobutyric acid and reduced the expressions of Cripto-1, Nanog, and Oct4 in EC cells. These Netrin-l-induced effects in the EC cells were mediated via binding of Netrin-l to the Neogemn receptor and activation of SHP-2, resulting in increased levels of inactive phosphorylated c-sre((Y527)). These results suggest that Netrin-1 can induce neuroectodermal-like differentiation of human EC cells by affecting c-src signaling via SHP-2 activation and regulation of Nanog, Oct4, and Cripto-1 expressions. [Cancer Res 2009;69(5):1717-21] C1 [Mancino, Mario; Watanabe, Kazuhide; Nagaoka, Tadahiro; Gonzales, Monica; Bianco, Caterina; Salomon, David S.; Strizzi, Luigi] NCI, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. [Esposito, Claudia; Normanno, Nicola] CROM Ist Nazl Tumori Pascale Napoli, Mercogliano, AV, Italy. [Normanno, Nicola] Ist Nazl Tumori Fdn Pascale, Cell Biol & Proclin Models Unit, Naples, Italy. RP Mancino, M (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, 37 Convent Dr,Room 1112, Bethesda, MD 20892 USA. EM mario.mancino@cro-m.eu OI Normanno, Nicola/0000-0002-7158-2605; Nagaoka, Tadahiro/0000-0002-9391-0243 FU Intramural NIH HHS [Z99 CA999999] NR 20 TC 11 Z9 12 U1 0 U2 2 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 MAR 1 PY 2009 VL 69 IS 5 BP 1717 EP 1721 DI 10.1158/0008-5472.CAN-08-2985 PG 5 WC Oncology SC Oncology GA 415ML UT WOS:000263937800005 PM 19223540 ER PT J AU Shen, HCJ He, M Powell, A Adem, A Lorang, D Heller, C Grover, AC Ylaya, K Hewitt, SM Marx, SJ Spiegel, AM Libutti, SK AF Shen, H. -C. Jennifer He, Mei Powell, Anathea Adem, Asha Lorang, Dominique Heller, Charles Grover, Amelia C. Ylaya, Kris Hewitt, Stephen M. Marx, Stephen J. Spiegel, Allen M. Libutti, Steven K. TI Recapitulation of Pancreatic Neuroendocrine Tumors in Human Multiple Endocrine Neoplasia Type I Syndrome via Pdx1-Directed Inactivation of Men1 SO CANCER RESEARCH LA English DT Article ID HISTONE METHYLTRANSFERASE COMPLEX; ENDOTHELIAL GROWTH-FACTOR; HOX GENE-EXPRESSION; MOUSE MODEL; KINASE INHIBITORS; MURINE HOMOLOG; VEGF-A; MICE; MUTATION; IDENTIFICATION AB Multiple endocrine neoplasia type 1 (MEN1) is an autosomal syndrome caused by mutations in the MEN1 tumor suppressor gene. Whereas the protein product of MEN1, MEN1, is ubiquitously expressed, somatic loss of the remaining wildtype MEN1 allele results in tumors primarily in parathyroid, pituitary, and endocrine pancreas. To understand the endocrine specificity of the MEN1 syndrome, we evaluated biallelic loss of Men1 by inactivating Men1 in pancreatic progenitor cells using the Cre-lox system. Men1 deletion in progenitor cells that differentiate into exocrine and endocrine pancreas did not affect normal pancreas morphogenesis and development. However, mice having homozygous inactivation of the Men1 in pancreas developed endocrine tumors with no exocrine tumor manifestation, recapitulating phenotypes seen in the MEN1 patients. In the absence of MEN1n, the endocrine pancreas showed increase in cell proliferation, vascularity, and abnormal vascular structures; such changes were lacking in exocrine pancreas. Further analysis revealed that these endocrine manifestations were associated with up-regulation in vascular endothelial growth factor expression in both human and mouse MEN1 pancreatic endocrine tumors. Together, these data suggest the presence of cell-specific factors for MEN1n and a permissive endocrine environment for MEN1 tumorigenesis in endocrine pancreas. Based on our analysis, we propose that menin's ability to maintain cellular and microenvironment integrity might explain the endocrine-restrictive nature of the MEN1 syndrome. [Cancer Res 2009;69(5):1858-66] C1 [Shen, H. -C. Jennifer; He, Mei; Powell, Anathea; Adem, Asha; Lorang, Dominique; Heller, Charles; Grover, Amelia C.; Libutti, Steven K.] NCI, Tumor Angiogenesis Sect, Surg Branch, Bethesda, MD 20892 USA. [Ylaya, Kris; Hewitt, Stephen M.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Marx, Stephen J.] NIDDK, Metab Dis Branch, Bethesda, MD USA. [Spiegel, Allen M.] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Libutti, SK (reprint author), NCI, Tumor Angiogenesis Sect, Surg Branch, Bldg 10,Room 4W-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM Steven_Libutti@nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS [Z01 SC010368-08] NR 49 TC 27 Z9 27 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 MAR 1 PY 2009 VL 69 IS 5 BP 1858 EP 1866 DI 10.1158/0008-5472.CAN-08-3662 PG 9 WC Oncology SC Oncology GA 415ML UT WOS:000263937800024 PM 19208834 ER PT J AU Castellone, MD De Falco, V Rao, DM Bellelli, R Muthu, M Basolo, F Fusco, A Gutkind, S Santoro, M AF Castellone, Maria Domenica De Falco, Valentina Rao, Deva Magendra Bellelli, Roberto Muthu, Magesh Basolo, Fulvio Fusco, Alfredo Gutkind, Silvio Santoro, Massimo TI The beta-Catenin Axis Integrates Multiple Signals Downstream from RET/Papillary Thyroid Carcinoma Leading to Cell Proliferation SO CANCER RESEARCH LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; CANCER CELLS; ACTIVATION; RET; PATHWAY; BINDING; RAS AB RET/papillary thyroid carcinoma (RET/PTC) oncoproteins result from the in-frame fusion of the RET receptor tyrosine kinase domain with protein dimerization motifs encoded by heterologous genes. Here, we show that RET/PTC stimulates the beta-catenin pathway. By stimulating PI3K/AKT and Ras/extracellular signal-regulated kinase (ERK), RFT/PTC promotes glycogen synthase kinase 3 beta (GSK3 beta) phosphorylation, thereby reducing GSK3 beta-mediated NH(2)-terminal beta-catenin (Ser33/Ser37/Thr41) phosphorylation. In addition, RET/PTC physically interacts with beta-catenin and increases its phosphotyrosine content. The increased free pool of S/T(nonphospho)/Y(phospho)beta-catenin is stabilized as a result of the reduced binding affinity for the Axin/GSK3 beta complex and activates the transcription factor T-cell factor/lymphoid enhancer factor. Moreover, through the ERK pathway, RET/PTC stimulates cyclic AMP-responsive element binding protein (CREB) phosphorylation and promotes the formation of a beta-catenin-CREB-CREB-binding protein/p300 transcriptional complex. Transcriptional complexes containing beta-catenin are recruited to the cyclin D1 promoter and a cyclin D1 gene promoter reporter is active in RET/PTC-expressing cells. Silencing of beta-catenin by small interfering RNA inhibits proliferation of RET/PTC-transformed PC Cl3 thyrocytes, whereas a constitutively active form of beta-catenin stimulates autonomous proliferation of thyroid cells. Thus, multiple signaling events downstream from RET/PTC converge on beta-catenin to stimulate cell proliferation. [Cancer Res 2009;69(5):1867-76] C1 [Castellone, Maria Domenica; De Falco, Valentina; Rao, Deva Magendra; Bellelli, Roberto; Muthu, Magesh; Fusco, Alfredo; Santoro, Massimo] Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol L Calif, CNR, Inst Endocrinol & Oncol Sperimentale G Salvatore, I-80131 Naples, Italy. [Rao, Deva Magendra] Univ Madras, Inst Basic Mol Sci, Dept Genet, Madras, Tamil Nadu, India. [Basolo, Fulvio] Univ Pisa, Dept Surg, Div Pathol, Pisa, Italy. [Gutkind, Silvio] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Santoro, M (reprint author), Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol L Calif, CNR, Inst Endocrinol & Oncol Sperimentale G Salvatore, Via Pansini 5, I-80131 Naples, Italy. EM masantor@unina.it RI DE FALCO, VALENTINA/C-2061-2015; OI DE FALCO, VALENTINA/0000-0002-8972-7921; CASTELLONE, MARIADOMENICA/0000-0003-0507-8037; Fusco, Alfredo/0000-0003-3332-5197; BASOLO, FULVIO/0000-0003-1657-5020 FU Intramural NIH HHS [Z01 DE000551-16]; Associazione Italiana per la Ricerca sul Cancro NR 46 TC 47 Z9 48 U1 0 U2 0 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 MAR 1 PY 2009 VL 69 IS 5 BP 1867 EP 1876 DI 10.1158/0008-5472.CAN-08-1982 PG 10 WC Oncology SC Oncology GA 415ML UT WOS:000263937800025 PM 19223551 ER PT J AU Koutros, S Berndt, SI Sinha, R Ma, XM Chatterjee, N Alavanja, MCR Zheng, TZ Huang, WY Hayes, RB Cross, AJ AF Koutros, Stella Berndt, Sonja I. Sinha, Rashmi Ma, Xiaomei Chatterjee, Nilanjan Alavanja, Mchael C. R. Zheng, Tongzhang Huang, Wen-Yi Hayes, Richard B. Cross, Amanda J. TI Xenobiotic Metabolizing Gene Variants, Dietary Heterocyclic Amine Intake, and Risk of Prostate Cancer SO CANCER RESEARCH LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; FOOD FREQUENCY QUESTIONNAIRE; PHIP-DNA ADDUCTS; INTRAEPITHELIAL NEOPLASIA; MEAT CONSUMPTION; COOKED MEAT; GSTP1 GENE; POLYMORPHISMS; EXPRESSION; ASSOCIATION AB We recently reported that heterocyclic amines (HCA) are associated with prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We now use extensive genetic data from this resource to determine iris associated with dietary HCAs {2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx); and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)} from cooked meat are modified by single nucleotide polymorphisms (SNP) in genes involved in HCA metabolism (CYP1A1, CYP1A2, CYP1B1, GSTA1, GSTM1, GSTM3, GSTP1, NAT1, NAT2, SULT1A1, SULT1A2, and UGT1A locus). We conducted a nested case-control study that included 1,126 prostate cancer cases and 1,127 controls selected for a genome-wide association study for prostate cancer. Unconditional logistic regression was used to estimate odds ratios (OR), 95% confidence intervals (95% CI), and P values for the interaction between SNPs, HCA intake, and risk of prostate cancer. The strongest evidence for an interaction was noted between DRMeIQx and MeIQx and the polymorphism rs11102001 downstream of the GSTM3 locus (P(interaction) = 0.001 for both HCAs; statistically significant after correction for multiple testing). Among men carrying the A variant, the risk of prostate cancer associated with high DiMeIQx intake was 2-fold greater than that with low intake (OR, 2.3; 95% CI, 1.2-4.7). The SNP rs11102001, which encodes a nonsynonymous amino acid change P356S in EPS8L3, is a potential candidate modifier of the effect of HCAs on prostate cancer risk. The observed effect provides evidence to support the hypothesis that HCAs may act as promoters of malignant transformation by altering mitogenic signaling. [Cancer Res 2009;69(5):1877-84] C1 [Koutros, Stella] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Ma, Xiaomei; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8111,MSC 7240, Rockville, MD 20852 USA. EM KoutrosS@mail.nih.gov RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Hayes, Richard/0000-0002-0918-661X FU NIH (National Cancer Institute, Division of Cancer Epidemiology and Genetics); National Cancer Institute [CA105666] FX The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 47 TC 25 Z9 26 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 MAR 1 PY 2009 VL 69 IS 5 BP 1877 EP 1884 DI 10.1158/0008-5472.CAN-08-2447 PG 8 WC Oncology SC Oncology GA 415ML UT WOS:000263937800026 PM 19223546 ER PT J AU McGlynn, KA Quraishi, SM Graubard, BI Weber, JP Rubertone, MV Erickson, RL AF McGlynn, Katherine A. Quraishi, Sabah M. Graubard, Barry I. Weber, Jean-Philippe Rubertone, Mark V. Erickson, Ralph L. TI Polychlorinated Biphenyls and Risk of Testicular Germ Cell Tumors SO CANCER RESEARCH LA English DT Article ID MALE REPRODUCTIVE FUNCTION; ORGANOCHLORINE COMPOUNDS; EXPOSURE; P,P'-DDE; FERTILITY; CANCER; POPULATION; CONGENERS; TOXICITY; MARKERS AB Exposure to endocrine-disrupting chemicals, such as polychlorinated biphenyls (PCB), may alter hormonal balance and thereby increase risk of testicular germ cell tumors (TGCT). To study the relationship of PCBs to TGCT, prediagnostic serum samples from 736 cases and 913 controls in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Adjusted odds ratios and 95% confidence intervals were estimated using logistic regression. PCB levels were examined in association with all TGCT and, separately, with each histologic type (seminoma and nonseminoma). Risks associated with seven functional groupings of PCBs, as well as sum of PCBs, were also examined. There were significantly decreased risks of TGCT in association with eight PCBs (PCB-118, PCB-138, PCB-153, PCB-156, PCB-163, PCB-170, PCB-180, and PCB-187) and no association Pith the remaining three (PCB-99, PCB-101, and PCB-183). The same eight congeners were significantly associated with decreased risk of nonseminoma, whereas five (PCB-138, PCB-153, PCB-156, PCB-163, and PCB-170) were associated with decreased risk of seminoma. All functional groupings of PCBs were also associated with decreased risk of TGCT and of nonseminoma, whereas six of the seven functional groups were associated with decreased risk of seminoma. Sum of PCBs was significantly associated with decreased risk of TGCT (P(trend) = 0.006), nonseminoma (P(trend) = 0.007), and seminoma (P(trend) = 0.05). Overall, these data do not support the hypothesis that PCB exposure increases the risk of TGCT. [Cancer Res 2009;69(5):1901.-9] C1 [McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Weber, Jean-Philippe] Inst Natl Sante Publ Quebec, Toxicol Ctr, Quebec City, PQ, Canada. [Erickson, Ralph L.] Walter Reed Army Inst Res, Silver Spring, MD USA. RP McGlynn, KA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, EPS Suite 550,6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov FU National Cancer Institute; NIH Department of Health and Human Services FX The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting the views of the U.S. Department of the Army or the U.S. Department of Defense. NR 36 TC 27 Z9 28 U1 1 U2 7 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 MAR 1 PY 2009 VL 69 IS 5 BP 1901 EP 1909 DI 10.1158/0008-5472.CAN-08-3935 PG 9 WC Oncology SC Oncology GA 415ML UT WOS:000263937800029 PM 19223531 ER PT J AU Li, A Walling, J Ahn, S Kotliarov, Y Su, Q Quezado, M Oberholtzer, JC Park, J Zenklusen, JC Fine, HA AF Li, Aiguo Walling, Jennifer Ahn, Susie Kotliarov, Yuri Su, Qin Quezado, Martha Oberholtzer, J. Carl Park, John Zenklusen, Jean C. Fine, Howard A. TI Unsupervised Analysis of Transcriptomic Profiles Reveals Six Glioma Subtypes SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; MOLECULAR SUBTYPES; GLIOBLASTOMA; CLASSIFICATION; DISCOVERY; SURVIVAL; PATTERN; CANCER AB Gliomas are the most common type of primary brain tumors in adults and a significant cause of cancer-related mortality. Defining glioma subtypes based on objective genetic and molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications based on gene expression data have been attempted in the past with varying success and with only some concordance between studies, possibly due to inherent bias that can be introduced through the use of analytic methodologies that make a priori selection of genes before classification. To overcome this potential source of bias, we have applied two unsupervised machine learning methods to genome-wide gene expression profiles of 159 gliomas, thereby establishing a robust glioma classification model relying only on the molecular data. The model predicts for two major groups of gliomas (oligodendroglioma-rich and glioblastoma-rich groups) separable into six hierarchically nested subtypes. We then identified six sets of classifiers that can be used to assign any given glioma to the corresponding subtype and validated these classifiers using both internal (189 additional independent samples) and two external data sets (341 patients). Application of the classification system to the external glioma data sets allowed us to identify previously unrecognized prognostic groups within previously published data and within The Cancer Genome Atlas glioblastoma samples and the different biological pathways associated with the different glioma subtypes offering a potential clue to the pathogenesis and possibly therapeutic targets for tumors within each subtype. [Cancer Res 2009;69(5):2091-9] C1 [Li, Aiguo; Walling, Jennifer; Ahn, Susie; Kotliarov, Yuri; Su, Qin; Zenklusen, Jean C.; Fine, Howard A.] Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, NIH, Bethesda, MD USA. [Quezado, Martha; Oberholtzer, J. Carl] Natl Inst Neurol Disorders & Stroke, Pathol Lab, NCI, NIH, Bethesda, MD USA. [Fine, Howard A.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. RP Fine, HA (reprint author), 9030 Old Georgetown Rd,Room 225, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Kotliarov, Yuri/B-6938-2017 FU NIH National Cancer Institute Center for Cancer Research FX Received 6/3/2008; revised 12/19/2008; accepted 12/22/2008.; Grant support: Intramural Research Program of NIH National Cancer Institute Center for Cancer Research.; The costs of publication of this article were defrayed in part by the payment of page Charges. This article must. therefore be hereby marked advertisement in accordance with IS U.S.C. Section 1734 solely to indicate this fact. NR 25 TC 128 Z9 131 U1 1 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 MAR 1 PY 2009 VL 69 IS 5 BP 2091 EP 2099 DI 10.1158/0008-5472.CAN-08-2100 PG 9 WC Oncology SC Oncology GA 415ML UT WOS:000263937800052 PM 19244127 ER PT J AU Qu, W Liu, J Dill, AL Saavedra, JE Keefer, LK Waalkes, MP AF Qu, Wei Liu, Jie Dill, Anna L. Saavedra, Joseph E. Keefer, Larry K. Waalkes, Michael P. TI V-PROLI/NO, a nitric oxide donor prodrug, protects liver cells from arsenic-induced toxicity SO CANCER SCIENCE LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; INDUCED HEPATOTOXICITY; CADMIUM TOXICITY; TRIOXIDE AS2O3; METALLOTHIONEIN; APOPTOSIS; PYRRO/NO; MICE; ACTIVATION; KINASES AB Inorganic arsenic shows great promise in human cancer chemotherapy, although hepatotoxicity is a major limiting side-effect. O(2)-Vinyl 1-[2-(Carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (V-PROLI/NO) [Correction added after publication 19 December 2008: 1-[2-(Carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (V-PROLI/NO) was corrected to O(2)-Vinyl 1-[2-(Carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (V-PROLI/NO)] is a nitric oxide (NO) donor prodrug that is metabolized by liver cytochromes P450 to release NO. Other NO-releasing agents have been shown to mitigate arsenic toxicity. Thus, the effects of V-PROLI/NO pretreatment on the toxicity of inorganic arsenic (as NaAsO(2)) were studied in vitro in a human liver (HepG2) cell line. HepG2 cells acted upon the prodrug to release NO, as assessed by nitrite levels, in a dose- and time-dependent fashion to maximal levels of 57-fold above control levels. In cells pretreated with V-PROLI/NO (200 mu M, 24 h) then exposed to arsenic for an additional 24 h, arsenic was much less toxic (LC(50) = 151.9 +/- 5.9 mu M) than in control cells (LC(50) = 90.5 +/- 6.5 mu M) and the reduced cytolethality was directly related to the level of NO produced. V-PROLI/NO also increased CYP2E1 transcriptional expression in a dose-dependent manner and CYP2E1 expression was directly related to the level of NO produced and the reduction in arsenic cytotoxicity. V-PROLI/NO pretreatment markedly reduced arsenic-induced apoptosis as measured by DNA fragmentation. Pretreatment with V-PROLI/NO suppressed phosphorylation of JNK1/2 after arsenic exposure. Arsenic increased metallothionein, a metal-binding protein important in arsenic tolerance, and V-PROLI/NO pretreatment caused additional increases in metallothionein levels. Thus, the prodrug, V-PROLI/NO, protects against arsenic toxicity in cultured human liver cells, reducing cytolethality, apoptosis and dysregulation of mitogen-activated protein kinases, through generation of NO formed after metabolism by liver cell enzymes, possibly including CYP2E1. (Cancer Sci 2009; 100: 382-388). C1 [Qu, Wei; Liu, Jie; Dill, Anna L.; Waalkes, Michael P.] NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk, NC 27709 USA. [Saavedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. RP Waalkes, MP (reprint author), NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NIH; National Cancer Institute; Center for Cancer Research; NCI [NO1-C012400] FX The authors thank Drs Erik Tokar and Chikara Kojima for critical review of this manuscript and Mr Matthew Bell for the great assistance in preparation of the graphics. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by NCI contract NO1-C012400 with SAIC Frederick. NR 38 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD MAR PY 2009 VL 100 IS 3 BP 382 EP 388 DI 10.1111/j.1349-7006.2008.01050.x PG 7 WC Oncology SC Oncology GA 408QR UT WOS:000263450200004 PM 19154403 ER PT J AU Devoogdt, N Rasool, N Hoskins, E Simpkins, F Tchabo, N Kohn, EC AF Devoogdt, Nick Rasool, Nabila Hoskins, Ebony Simpkins, Fiona Tchabo, Nana Kohn, Elise C. TI Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo SO CANCER SCIENCE LA English DT Article ID GRANULIN-EPITHELIN PRECURSOR; LYSOPHOSPHATIDIC ACID; GROWTH-FACTOR; SURVIVAL; CELLS; PROLIFERATION; METASTASIS; SUPPRESSES; EXPRESSION; ACROGRANIN AB The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions (P <= 0.02), in soft agar colony number and size (P <= 0.05), and in anoikis resistance (P <= 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining (P <= 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination. (Cancer Sci 2009; 100: 434-440). C1 [Devoogdt, Nick; Rasool, Nabila; Hoskins, Ebony; Simpkins, Fiona; Tchabo, Nana; Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Devoogdt, Nick] Vrije Univ Brussels, Unit Cellular & Mol Immunol, VIB, Dept Mol & Cellular Interact, B-1050 Brussels, Belgium. RP Kohn, EC (reprint author), NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr MSC 1906, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov RI Devoogdt, Nick/H-5156-2013 OI Devoogdt, Nick/0000-0001-9220-4833 FU National Cancer Institute; Center for Cancer Research; Fonds voor Wetenschappelijk Onderzoek Vlaanderen FX This research was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. N.D. was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen. NR 29 TC 17 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD MAR PY 2009 VL 100 IS 3 BP 434 EP 440 DI 10.1111/j.1349-7006.2009.01076.x PG 7 WC Oncology SC Oncology GA 408QR UT WOS:000263450200011 PM 19154415 ER PT J AU Koh, KK Oh, PC Quon, MJ AF Koh, Kwang Kon Oh, Pyung Chun Quon, Michael J. TI Does reversal of oxidative stress and inflammation provide vascular protection? SO CARDIOVASCULAR RESEARCH LA English DT Review DE Inflammation; Oxidative stress; Atherosclerosis; Insulin resistance; Combination therapy ID RANDOMIZED CONTROLLED-TRIAL; ACTIVATED-RECEPTOR-ALPHA; TYPE-2 DIABETES-MELLITUS; SMOOTH-MUSCLE CELLS; NF-KAPPA-B; IMPROVE ENDOTHELIAL DYSFUNCTION; LOW-DENSITY-LIPOPROTEIN; CHOLESTEROL-FED RABBITS; FAMILY NADPH OXIDASES; ANGIOTENSIN-II AB Chronic inflammation is a pathogenic feature of atherosclerosis and cardiovascular disease mediated by substances including angiotensin II, proinflammatory cytokines, and free fatty acids. This promotes generation of reactive oxygen species in vascular endothelial cells and smooth muscle cells, which mediate injury through several mechanisms. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidaemia and the renin-angiotensin-aldosterone system (RAAS) at multiple levels contribute importantly to a variety of risk factors. Therefore, combination therapy that simultaneously addresses multiple mechanisms for the pathogenesis of atherosclerosis is an attractive emerging concept for slowing progression of atherosclerosis. Combined therapy with statins, peroxisome proliferator-activated receptors, and RAAS blockade demonstrates additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors due to both distinct and interrelated mechanisms. These additive beneficial effects of combined therapies are consistent with laboratory and recent clinical studies. Thus, combination therapy may be an important paradigm for treating and slowing progression of atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. C1 [Koh, Kwang Kon; Oh, Pyung Chun] Gachon Univ, Div Cardiol, Vasc Med & Atherosclerosis Unit, Gil Med Ctr, Inchon 405760, South Korea. [Quon, Michael J.] NCCAM, Diabet Unit, Clin Invest Lab, NIH, Bethesda, MD USA. RP Koh, KK (reprint author), Gachon Univ, Div Cardiol, Vasc Med & Atherosclerosis Unit, Gil Med Ctr, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU established investigator award (2007-1), Gil Medical Center, Gachon University, Incheon, Korea [(2007-1)] FX This study was partly supported by grants from established investigator award (2007-1), Gil Medical Center, Gachon University, Incheon, Korea. NR 118 TC 56 Z9 57 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR 1 PY 2009 VL 81 IS 4 BP 649 EP 659 DI 10.1093/cvr/cvn354 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 408BJ UT WOS:000263407900006 PM 19098298 ER PT J AU Wyatt, MD Wilson, DM AF Wyatt, M. D. Wilson, D. M., III TI Participation of DNA repair in the response to 5-fluorouracil SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Colorectal cancer; chemotherapy; DNA damage; base excision repair; mismatch repair; homologous recombination ID BASE EXCISION-REPAIR; HUMAN-TUMOR-CELLS; ACCUMULATE DEOXYURIDINE TRIPHOSPHATE; THYMIDYLATE SYNTHASE INHIBITION; MOUSE FM3A CELLS; MISMATCH REPAIR; MICROSATELLITE-INSTABILITY; COLORECTAL-CANCER; STRAND BREAKS; 5-FLUORO-2'-DEOXYURIDINE INCORPORATION AB The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anticancer treatments. C1 [Wyatt, M. D.] Univ S Carolina, Dept Pharmaceut & Biomed Sci, S Carolina Coll Pharm, Columbia, SC 29208 USA. [Wilson, D. M., III] NIA, Lab Mol Gerontol, Biomed Res Ctr, IRP,NIH, Baltimore, MD 21224 USA. RP Wyatt, MD (reprint author), Univ S Carolina, Dept Pharmaceut & Biomed Sci, S Carolina Coll Pharm, 715 Sumter St, Columbia, SC 29208 USA. EM wyatt@sccp.sc.edu OI Wyatt, Michael/0000-0003-1815-9565 FU NIH, National Institute on Aging; NIH [1 R01 CA100450] FX This article was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (DMW), and by NIH grant 1 R01 CA100450 (MDW). The authors would like to extend special thanks to their family members, "Coach" and "Grandpa" Parks. NR 99 TC 89 Z9 92 U1 0 U2 16 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2009 VL 66 IS 5 BP 788 EP 799 DI 10.1007/s00018-008-8557-5 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 413XP UT WOS:000263826400004 PM 18979208 ER PT J AU Chao, D Balboni, G Lazarus, LH Salvadori, S Xia, Y AF Chao, D. Balboni, G. Lazarus, L. H. Salvadori, S. Xia, Y. TI Na+ mechanism of delta-opioid receptor induced protection from anoxic K+ leakage in the cortex SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE Anoxia; cortex; delta-opioid receptor; K+ homeostasis; Na+ channels; ionotropic glutamate receptor channels ID OXYGEN-GLUCOSE-DEPRIVATION; RAT HIPPOCAMPAL SLICES; NEURONS IN-VITRO; SENSITIVE SODIUM-CHANNELS; NULL MUTANT MOUSE; PROTEIN-KINASE-C; INTRACELLULAR SODIUM; GLUTAMATE RECEPTORS; NEOCORTICAL NEURONS; CORTICAL-NEURONS AB Activation of delta-opioid receptors (DOR) attenuates anoxic K+ leakage and protects cortical neurons from anoxic insults by inhibiting Na+ influx. It is unknown, however, which pathway(s) that mediates the Na+ influx is the target of DOR signal. In the present work, we found that, in the cortex, (1) DOR protection was largely dependent on the inhibition of anoxic Na+ influxes mediated by voltage-gated Na+ channels; (2) DOR activation inhibited Na+ influx mediated by ionotropic glutamate N-methyl-D-aspartate (NMDA) receptors, but not that by non-NMDA receptors, although both played a role in anoxic K+ derangement; and (3) DOR activation had little effect on Na+/Ca2+ exchanger-based response to anoxia. We conclude that DOR activation attenuates anoxic K+ derangement by restricting Na+ influx mediated by Na+ channels and NMDA receptors, and that non-NMDA receptors and Na+/Ca2+ exchangers, although involved in anoxic K+ derangement in certain degrees, are less likely the targets of DOR signal. C1 [Chao, D.; Xia, Y.] Yale Univ, Dept Pediat, Sch Med, New Haven, CT 06520 USA. [Balboni, G.] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. [Balboni, G.; Lazarus, L. H.] NIEHS, Pharmacol Lab, Med Chem Grp, Res Triangle Pk, NC 27709 USA. [Salvadori, S.] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. [Salvadori, S.] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. RP Xia, Y (reprint author), Yale Univ, Dept Pediat, Sch Med, New Haven, CT 06520 USA. EM ying.xia@yale.edu FU National Institutes of Health [HD-34852]; American Heart Association [0755993T]; NIEHS; NIH FX This work was supported by grants from National Institutes of Health (HD-34852) and American Heart Association (0755993T), and in part by the Division of Intramural Research of NIEHS and NIH. NR 53 TC 18 Z9 19 U1 0 U2 1 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2009 VL 66 IS 6 BP 1105 EP 1115 DI 10.1007/s00018-009-8759-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 418UL UT WOS:000264174800012 PM 19189047 ER PT J AU Kruit, MC Launer, LJ Overbosch, J van Buchem, MA Ferrari, MD AF Kruit, M. C. Launer, L. J. Overbosch, J. van Buchem, M. A. Ferrari, M. D. TI Iron accumulation in deep brain nuclei in migraine: a population-based magnetic resonance imaging study SO CEPHALALGIA LA English DT Article DE Migraine; magnetic resonance imaging; iron accumulation; pain processing ID STEM ACTIVATION; MULTIPLE-SCLEROSIS; GRAY-MATTER; HEADACHE; MRI; DISEASE; RISK; LESIONS; PET; AGE AB A small magnetic resonance imaging (MRI) study showed increased iron depositions in the periaqueductal grey matter in migraineurs, suggestive of a disturbed central antinociceptive neuronal network. With 1.5-T MRI, we assessed iron concentrations in seven deep brain nuclei in a large population-based cohort. We compared T2 values between migraineurs (n = 138) and controls (n = 75), with multivariate regression analysis. Analyses were conducted in age strata (< 50, n = 112; >= 50) because iron measures are increasingly influenced by non-iron-related factors in the older group. Overall, migraineurs and controls did not differ, nor did migraineurs with vs. without aura. In the younger migraineurs compared with controls, T2 values were lower in the putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Similarly, in these younger migraineurs, controlling for age, those with longer migraine history had lower T2 values in the putamen (P = 0.01), caudate (P = 0.04) and red nucleus (P = 0.001). Repeated migraine attacks are associated with increased iron concentration/accumulation in multiple deep nuclei that are involved in central pain processing and migraine pathophysiology. It remains unclear whether iron accumulation in the antinociceptive network has a causative role in the development of (chronic) migraine headache. C1 [Kruit, M. C.; Overbosch, J.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. [Ferrari, M. D.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. [Launer, L. J.] Natl Inst Publ Hlth & Environm, Dept Chron Dis & Environm Epidemiol, NL-3720 BA Bilthoven, Netherlands. [Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Kruit, MC (reprint author), Leiden Univ, Med Ctr, Dept Radiol, POB 9600, NL-2300 RC Leiden, Netherlands. EM m.c.kruit@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X FU Netherlands Heart Foundation [97.108] FX This study was supported by a grant from the Netherlands Heart Foundation (Grant 97.108). The GEM study was conducted by the National Institute of Public Health and the Environment, Department of Chronic Disease and Environmental Epidemiology, Bilthoven, the Netherlands. NR 39 TC 66 Z9 72 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAR PY 2009 VL 29 IS 3 BP 351 EP 359 DI 10.1111/j.1468-2982.2008.01723.x PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 401OK UT WOS:000262950400010 PM 19025553 ER PT J AU Fisahn, A Neddens, J Yan, LQ Buonanno, A AF Fisahn, Andre Neddens, Joerg Yan, Leqin Buonanno, Andres TI Neuregulin-1 Modulates Hippocampal Gamma Oscillations: Implications for Schizophrenia SO CEREBRAL CORTEX LA English DT Article DE ErbB4; hippocampus; interneuron; mouse; parvalbumin; rat ID NITRIC-OXIDE SYNTHASE; NETWORK OSCILLATIONS; NERVOUS-SYSTEM; RECEPTOR ERBB4; GABAERGIC NEURONS; PREFRONTAL CORTEX; NEURAL SYNCHRONY; BEHAVING RAT; EXPRESSION; INTERNEURONS AB Alterations in gamma-frequency oscillations are implicated in psychiatric disorders, and polymorphisms in NRG-1 and ERBB4, genes encoding Neuregulin-1 (NRG-1) and one of its receptors, designated ErbB4, are associated with schizophrenia. Here we show that NRG-1 selectively increases the power of kainate-induced, but not carbachol-induced, gamma oscillations in acute hippocampal slices. NRG-1 beta is more effective than NRG-1 alpha, a splice variant with lower affinity for ErbB receptors, and neither isoform affects the network activity without prior induction of gamma oscillations. NRG-1 beta dramatically increases gamma oscillation power in hippocampal slices from both rats (2062 +/- 496%) and mice (710 +/- 299%). These effects of NRG-1 beta are blocked by PD158780, a pan-specific antagonist of ErbB receptors, and are mediated specifically via ErbB4 receptors, because mice harboring a targeted mutation of ErbB4 do not respond to NRG-1. Moreover, we demonstrate that 50% of gamma-amino butyric acidergic parvalbumin (PV)-positive interneurons, which heavily contribute to the generation of gamma oscillations, express ErbB4 receptors. Importantly, both the number of PV-immunoreactive interneurons (-31%) and the power of kainate-induced gamma oscillations (-60%) are reduced in ErbB4 knockout mice. This study provides the first plausible link between NRG-1/ErbB4 signaling and rhythmic network activity that may be altered in persons with schizophrenia. C1 [Neddens, Joerg; Yan, Leqin; Buonanno, Andres] NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20814 USA. [Fisahn, Andre] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden. RP Buonanno, A (reprint author), NIH, Mol Neurobiol Sect, Bldg 35,Room 2C-1000,35 Lincoln Dr, Bethesda, MD 20892 USA. EM buonanno@mail.nih.gov FU Research Council of Sweden; National Institute of Child Health and Human Development; IRP; National Institutes of Health FX Research Council of Sweden to A. F.; National Institute of Child Health and Human Development, IRP, National Institutes of Health to A. B., J. N., L. Y. NR 55 TC 92 Z9 92 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2009 VL 19 IS 3 BP 612 EP 618 DI 10.1093/cercor/bhn107 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 404OL UT WOS:000263162600011 PM 18632742 ER PT J AU Montani, G Tonelli, S Sanghez, V Ferrari, PF Palanza, P Ryba, N Tirindelli, R AF Montani, Giorgia Tonelli, Simone Sanghez, Valentina Ferrari, Pier Francesco Palanza, Paola Ryba, Nicholas Tirindelli, Roberto TI The G-Protein gamma-Subunit, G gamma 8, in the Transduction of the Pheromonal Signal SO CHEMICAL SENSES LA English DT Meeting Abstract CT 18th Congress of the European-Chemoreception-Research-Organization CY SEP 03-07, 2008 CL Univ Lyubljana, Bernardin, SLOVENIA SP European Chemorecep Res Org, Slovenian Physiol Soc HO Univ Lyubljana C1 [Montani, Giorgia; Tonelli, Simone; Tirindelli, Roberto] Univ Parma, Dept Neurosci, I-43100 Parma, Italy. [Ryba, Nicholas] Univ Parma, Dipartimento Biol Evolutiva, I-43100 Parma, Italy. [Sanghez, Valentina; Ferrari, Pier Francesco; Palanza, Paola] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD MAR PY 2009 VL 34 IS 3 BP E63 EP E63 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 408BN UT WOS:000263408400202 ER PT J AU Raman, B Joseph, J Tang, J Stopfer, M AF Raman, Baranidharan Joseph, Joby Tang, Jeff Stopfer, Mark TI Olfactory Receptor Neurons and Odor Coding SO CHEMICAL SENSES LA English DT Meeting Abstract CT 18th Congress of the European-Chemoreception-Research-Organization CY SEP 03-07, 2008 CL Univ Lyubljana, Bernardin, SLOVENIA SP European Chemorecep Res Org, Slovenian Physiol Soc HO Univ Lyubljana C1 [Raman, Baranidharan; Joseph, Joby; Tang, Jeff; Stopfer, Mark] NICHD, NIH, Bethesda, MD USA. [Raman, Baranidharan] NIST, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD MAR PY 2009 VL 34 IS 3 BP E1 EP E1 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 408BN UT WOS:000263408400010 ER PT J AU Tanaka, NK Ito, K Stopfer, M AF Tanaka, Nobuaki K. Ito, Kei Stopfer, Mark TI Odor Elicited Oscillations in Drosophila SO CHEMICAL SENSES LA English DT Meeting Abstract CT 18th Congress of the European-Chemoreception-Research-Organization CY SEP 03-07, 2008 CL Univ Lyubljana, Bernardin, SLOVENIA SP European Chemorecep Res Org, Slovenian Physiol Soc HO Univ Lyubljana C1 [Ito, Kei] Univ Tokyo, Tokyo 1138654, Japan. [Tanaka, Nobuaki K.; Stopfer, Mark] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD MAR PY 2009 VL 34 IS 3 BP E7 EP E8 PG 2 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 408BN UT WOS:000263408400030 ER PT J AU Fan, YG Hu, P Jiang, Y Chang, RS Yao, SX Wang, W He, J Prorok, P Qiao, YL AF Fan, Ya-Guang Hu, Ping Jiang, Yong Chang, Run-Sheng Yao, Shu-Xiang Wang, Wendy He, Jie Prorok, Philip Qiao, You-Lin TI Association Between Sputum Atypia and Lung Cancer Risk in an Occupational Cohort in Yunnan, China SO CHEST LA English DT Article DE atypia; lung cancer; sputum; Yunnan; China ID AIR-FLOW OBSTRUCTION; TIN MINERS; SOCIOECONOMIC-STATUS; SOUTHERN CHINA; TOBACCO USE; FOLLOW-UP; EXPOSURE; RADON; PREVALENCE; DYSPLASIA AB Background: Individuals with cytologic atypia in sputum may be at high risk for the development of lung cancer. Methods: A prospective cohort study was conducted among occupational tin miners in Yunnan China based on an annual lung cancer screening program. Sputum samples were collected prospectively at baseline and the following seven annual screenings. The associations between risk factors and sputum cytology were analyzed by univariate and multivariate logistic regression. A proportional hazard model was used to analyze the association between the baseline sputum results and the incidence of lung cancer. The effect of consecutive sputum cytology on the increase of lung cancer risk was analyzed by logistic regression. Results: Sputum cytologic atypia was associated with age, smoking, occupational radon and arsenic exposure, and asthma. Sputum cytologic atypia was an independent risk factor for lung cancer with an adjusted hazard ratio (HR) of 3.82 (95% confidence interval [CI], 2.82 to 5.18) in comparing normal to moderate or worse atypia. Compared to the lung cancer risk associated with normal sputum, the risk was significantly higher according to the degree of atypia for squamous carcinomas, small cell lung cancer and central lung cancer, with adjusted HRs of 5.70 (95% CI, 3.78 to 8.59), 3.32 (95% CI, 1.31 to 8.45), and 4.93 (95% CI, 3.51 to 6.92), respectively. Conclusions: Sputum atypia is associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may play an important role in the early detection of lung cancer or in the selection of the optimal target population for more intensive lung cancer screening among this occupational cohort or similar population. Trial registration: Clinicaltrials.gov Identifier: NCT00340405. (CHEST 2009, 135:778-785) C1 [Hu, Ping; Prorok, Philip] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Fan, Ya-Guang] Chinese Acad Med Sci, Inst Radiat Med, Dept Biol, Tianjin, Peoples R China. [Jiang, Yong; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100021, Peoples R China. [Chang, Run-Sheng] Third Peoples Hosp Honghe Autonomous Dist, Gejiu, Yunnan Province, Peoples R China. [Yao, Shu-Xiang] Kunming Med Coll, Dept Epidemiol, Kunming, Yunnan Province, Peoples R China. [Wang, Wendy] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD USA. [He, Jie] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP Hu, P (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, NIH, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM ph107y@nih.gov RI Qiao, You-Lin/B-4139-2012; Jiang, Yong/B-4103-2012 OI Qiao, You-Lin/0000-0001-6380-0871; Jiang, Yong/0000-0002-1892-1196 FU National Cancer Institute/National Institutes of Health [263-MQ-511694] FX This study Was supported by the National Cancer Institute/National Institutes of Health, grant No. 263-MQ-511694. This article describes,in ancillary study for the National Cancer Institute project "The Study of Early Markers of Lung Cancer Among Tin Miners in Yunnan China," a federally funded registered clinical trial. NR 32 TC 10 Z9 10 U1 0 U2 7 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2009 VL 135 IS 3 BP 778 EP 785 DI 10.1378/chest.08-1469 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 420SW UT WOS:000264310500027 PM 19265088 ER PT J AU Scrimin, S Haynes, M Altoe, G Bornstein, MH Axia, G AF Scrimin, S. Haynes, M. Altoe, G. Bornstein, M. H. Axia, G. TI Anxiety and stress in mothers and fathers in the 24 h after their child's surgery SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE paediatric surgery; parental anxiety and acute stress symptoms; parent-physician communication ID PEDIATRIC-PATIENTS; CANCER-PATIENTS; PARENTS; STRATEGIES; SYMPTOMS; FAMILIES; DISORDER AB Surgery in a paediatric setting stresses children and their parents. Previous studies have focused on children and the preoperative period; however, the 24 h after child surgery are highly stressful for parents as their child is still physically recovering and physician-parent communication is vital. The aims of this study are to investigate the impact of three levels of severity of paediatric surgery on mothers' and fathers' anxiety and stress and to identify factors that contribute to parental anxiety and acute stress symptoms in the first 24 h after child surgery. A total of 154 parents (91 mothers, 63 fathers) of children who had just undergone elective surgery for a major intervention (n = 41), minor intervention (n = 64) or day surgery (n = 49) completed questionnaires aimed at assessing levels of state anxiety and acute stress symptoms. Social network, socio-economic status and parental health locus of control were evaluated as contributors. Parents reported high levels of state anxiety (26% had scores on the state scale 2 standard deviations above the norm) and acute stress symptoms (28% in at least one of the four acute stress disorder symptom categories). Child's type of surgery is related to parental anxiety [F(2,134) = 38.12, P = 0.0001, eta(2) = 0.175] and acute stress symptoms [F(2,133) = 31.21, P = 0.0001, eta(2) = 0.133]. Parental state anxiety was predicted by parent's gender, trait anxiety and health external locus of control. Parent's number of acute stress symptoms was predicted by parental trait anxiety, health external locus of control, parent's level of education and the number of social contacts. There is a need to take into consideration parental anxiety and distress in the 24 h after child surgery. Parental well-being is related to several characteristics including the severity of child surgery; these aspects should be taken into consideration when interacting with parents in the aftermath of their child's surgery. C1 [Scrimin, S.; Altoe, G.; Axia, G.] Univ Padua, Dept Dev & Social Psychol, I-35131 Padua, Italy. [Haynes, M.; Bornstein, M. H.] NICHHD, Bethesda, MD 20892 USA. RP Scrimin, S (reprint author), Univ Padua, Dept Dev Psychol, Via Venezia 8, I-35131 Padua, Italy. EM sara.scrimin@unipd.it RI Boerm, Emma/A-9475-2012 FU Intramural NIH HHS [ZIA HD001119-24] NR 18 TC 16 Z9 18 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1862 J9 CHILD CARE HLTH DEV JI Child Care Health Dev. PD MAR PY 2009 VL 35 IS 2 BP 227 EP 233 DI 10.1111/j.1365-2214.2008.00920.x PG 7 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA 402TJ UT WOS:000263035700012 PM 19228156 ER PT J AU Mannon, PJ Leon, F Fuss, IJ Walter, BA Begnami, M Quezado, M Yang, Z Yi, C Groden, C Friend, J Hornung, RL Brown, M Gurprasad, S Kelsall, B Strober, W AF Mannon, P. J. Leon, F. Fuss, I. J. Walter, B. A. Begnami, M. Quezado, M. Yang, Z. Yi, C. Groden, C. Friend, J. Hornung, R. L. Brown, M. Gurprasad, S. Kelsall, B. Strober, W. TI Successful granulocyte-colony stimulating factor treatment of Crohn's disease is associated with the appearance of circulating interleukin-10-producing T cells and increased lamina propria plasmacytoid dendritic cells SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE cytokines; FoxP3; plasmacytoid dendritic cells; regulatory T cells; Th1 inflammation ID INFLAMMATORY-BOWEL-DISEASE; VERSUS-HOST-DISEASE; G-CSF; ULCERATIVE-COLITIS; REGULATORY-CELLS; FACTOR MOBILIZES; IFN-ALPHA; SUBSETS; TRANSPLANTATION; GENERATION AB Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful therapy for some patients with Crohn's disease. Given the known ability of G-CSF to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting regulatory T cells, we studied whether clinical benefit from G-CSF therapy in active Crohn's disease was associated with decreased inflammatory cytokine production and/or increased regulatory responses. Crohn's patients were treated with G-CSF (5 mu g/kg/day subcutaneously) for 4 weeks and changes in cell phenotype, cytokine production and dendritic cell subsets were measured in the peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a clinical response or remission based on the decrease in the Crohn's disease activity index differed from non-responding patients in several important ways: at the end of treatment, responding patients had significantly more CD4(+) memory T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced CD123(+) plasmacytoid dendritic cell infiltration of the lamina propria. Interferon-gamma production capacity was not changed significantly except in non-responders, where it increased. These data show that clinical benefit from G-CSF treatment in Crohn's disease is accompanied by significant induction of IL-10 secreting T cells as well as increases in plasmacytoid dendritic cells in the lamina propria of the inflamed gut mucosa. C1 [Mannon, P. J.; Fuss, I. J.; Yang, Z.; Yi, C.; Groden, C.; Friend, J.; Strober, W.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Leon, F.; Kelsall, B.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Walter, B. A.; Begnami, M.; Quezado, M.] NCI, Surg Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Brown, M.; Gurprasad, S.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Hornung, R. L.] NCI, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Mannon, PJ (reprint author), Univ Alabama, Div Gastroenterol & Hepatol, 1825 Univ Blvd,SHEL 613, Birmingham, AL 35294 USA. EM pmannon@uab.edu RI Begnami, Maria/D-9663-2012 OI Begnami, Maria/0000-0003-0848-7813 FU Division of Intramural Research, NIAID; NIH Clinical Center; National Cancer Institute [N01-CO-12400] FX The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This project has been funded by the Division of Intramural Research, NIAID, the NIH Clinical Center and the National Cancer Institute under contract N01-CO-12400. The authors thank C. Y. Huang for helpful discussions about the manuscript. NR 35 TC 20 Z9 20 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAR PY 2009 VL 155 IS 3 BP 447 EP 456 DI 10.1111/j.1365-2249.2008.03799.x PG 10 WC Immunology SC Immunology GA 401OI UT WOS:000262950100010 PM 19094118 ER PT J AU Burbelo, PD Hoshino, Y Leahy, H Krogmann, T Hornung, RL Iadarola, MJ Cohen, JI AF Burbelo, Peter D. Hoshino, Yo Leahy, Hannah Krogmann, Tammy Hornung, Ronald L. Iadarola, Michael J. Cohen, Jeffrey I. TI Serological Diagnosis of Human Herpes Simplex Virus Type 1 and 2 Infections by Luciferase Immunoprecipitation System Assay SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID GENITAL HERPES; RECOMBINANT GLYCOPROTEIN; DETECTING ANTIBODIES; ENZYME IMMUNOASSAYS; HSV-2 INFECTION; UNITED-STATES; VACCINE; RESPONSES; AUTOANTIBODIES; ACQUISITION AB Highly quantitative and high-throughput serological tests for evaluation of humoral responses to herpes simplex virus 1 (HSV-1) and HSV-2 are not available. The efficacy of luciferase immunoprecipitation system (LIPS) assays for antibody profiling and serologic diagnosis of HSV-1 and HSV-2 infection was investigated using a panel of five recombinant HSV antigens. Plasma samples from subjects seropositive for HSV-1 and/or HSV-2 or seronegative for HSV-1 and HSV-2 that had previously been analyzed by Western blotting and the Focus Plexus immunoassay were evaluated. The LIPS test measuring anti-gG1 antibody titers was 96% sensitive and 96% specific for detecting HSV-1 infection, compared with the Focus immunoassay, and was 92% sensitive and 96% specific, compared with Western blotting. The results for the anti-gG2 LIPS test for HSV-2 precisely matched those for Western blotting, with 100% sensitivity and 100% specificity, and showed robust antibody titers in all the HSV-2-infected samples that were over 1,000 times higher than those in HSV-2-negative or HSV-1-positive samples. Antibodies to three additional HSV-2 proteins, gB, gD, and ICP8, were detected in many of the HSV-1- and/or HSV-2-infected plasma samples and showed preferentially higher immunoreactivity in HSV-2-infected plasma. The titers of antibodies to these three HSV-2 antigens also significantly correlated with each other (R = 0.75 to 0.81; P < 0.0001). These studies indicate that the robust anti-gG1 and anti-gG2 antibody responses detected by LIPS assays are useful for HSV-1 and HSV-2 detection and suggest that profiling of antibody responses to a panel of HSV proteins may be useful for characterizing individual humoral responses to infection and for monitoring responses to vaccines. C1 [Burbelo, Peter D.; Leahy, Hannah; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Hoshino, Yo; Krogmann, Tammy; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hornung, Ronald L.] NCI, Clin Serv Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. RP Cohen, JI (reprint author), Bldg 10,Room 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Cancer Institute, National Institutes of Health [N01-CO-12400] FX The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 38 TC 24 Z9 24 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAR PY 2009 VL 16 IS 3 BP 366 EP 371 DI 10.1128/CVI.00350-08 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 414HJ UT WOS:000263854200011 PM 19129469 ER PT J AU Tang, SX Moayeri, M Chen, ZC Harma, H Zhao, JQ Hu, HJ Purcell, RH Leppla, SH Hewlett, IK AF Tang, Shixing Moayeri, Mahtab Chen, Zhaochun Harma, Harri Zhao, Jiangqin Hu, Haijing Purcell, Robert H. Leppla, Stephen H. Hewlett, Indira K. TI Detection of Anthrax Toxin by an Ultrasensitive Immunoassay Using Europium Nanoparticles SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; IMMUNOGLOBULIN-G ANTIBODIES; LINKED-IMMUNOSORBENT-ASSAY; TIME-RESOLVED FLUORESCENCE; PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODIES; LABEL TECHNOLOGY; LETHAL FACTOR; RECEPTOR AB We developed a europium nanoparticle-based immunoassay (ENIA) for the sensitive detection of anthrax protective antigen (PA). The ENIA exhibited a linear dose-dependent pattern within the detection range of 0.01 to 100 ng/ml and was approximately 100-fold more sensitive than enzyme-linked immunosorbent assay (ELISA). False-positive results were not observed with serum samples from healthy adults, mouse plasma without PA, or plasma samples collected from mice injected with anthrax lethal factor or edema factor alone. For the detection of plasma samples spiked with PA, the detection sensitivities for ENIA and ELISA were 100% (11/11 samples) and 36.4% (4/11 samples), respectively. The assay exhibited a linear but qualitative correlation between the PA injected and the PA detected in murine blood (r = 0.97731; P < 0.0001). Anthrax PA was also detected in the circulation of mice infected with spores from a toxigenic Sterne-like strain of Bacillus anthracis, but only in the later stages of infection. These results indicate that the universal labeling technology based on europium nanoparticles and its application may provide a rapid and sensitive testing platform for clinical diagnosis and laboratory research. C1 [Tang, Shixing; Zhao, Jiangqin; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Moayeri, Mahtab; Hu, Haijing; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. [Chen, Zhaochun; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Harma, Harri] Univ Turku, Biophys Lab, FIN-20520 Turku, Finland. RP Tang, SX (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Shixing.tang@fda.hhs.gov; Indira.hewlett@fda.hhs.gov FU Biodefense Advanced Research and Development Agency, DHHS; DIR, NIAID, NIH FX The findings and conclusions in this article have not been formally disseminated by the FDA and should not be construed to represent any agency determination or policy. NR 32 TC 62 Z9 68 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAR PY 2009 VL 16 IS 3 BP 408 EP 413 DI 10.1128/CVI.00412-08 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 414HJ UT WOS:000263854200017 PM 19129473 ER PT J AU Fleisher, TA Oliveira, JB AF Fleisher, Thomas A. Oliveira, Joao B. TI Functional Flow Cytometry Testing: An Emerging Approach for the Evaluation of Genetic Disease SO CLINICAL CHEMISTRY LA English DT Editorial Material ID SINGLE-CELL C1 [Fleisher, Thomas A.; Oliveira, Joao B.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Ctr Clin, Dept Lab Med, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM tfleishe@mail.nih.gov OI Oliveira, Joao/0000-0001-9388-8173 FU Intramural NIH HHS NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2009 VL 55 IS 3 BP 389 EP 390 DI 10.1373/clinchem.2008.119248 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 413DG UT WOS:000263772500002 PM 19147728 ER PT J AU Brock, TK Gentile, NL Louie, RF Tran, NK Kitano, T Kost, GJ AF Brock, T. Keith Gentile, Nicole L. Louie, Richard F. Tran, Nam K. Kitano, Tyler Kost, Gerald J. TI Assessing Thrombin Generation at the Point of Care SO CLINICAL CHEMISTRY LA English DT Editorial Material ID MANAGEMENT C1 [Brock, T. Keith; Gentile, Nicole L.; Louie, Richard F.; Tran, Nam K.; Kitano, Tyler; Kost, Gerald J.] Univ Calif Davis, POCT CTR, Pathol & Lab Med, Sch Med,LLNL Point Care Technol Ctr,NIBIB,NIH, Davis, CA 95616 USA. RP Brock, TK (reprint author), Univ Calif Davis, POCT CTR, Pathol & Lab Med, Sch Med,LLNL Point Care Technol Ctr,NIBIB,NIH, 3455 Tupper Hall, Davis, CA 95616 USA. EM tkbrock@ucdavis.edu FU NIBIB NIH HHS [U54 EB007959-02] NR 14 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2009 VL 55 IS 3 BP 398 EP 399 DI 10.1373/clinchem.2008.122747 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 413DG UT WOS:000263772500005 PM 19168548 ER PT J AU Contois, JH McConnel, JP Sethi, AA Csako, G Devaraj, S Hoefner, DM Warnick, R AF Contois, John H. McConnel, Joseph P. Sethi, Amar A. Csako, Gyorgy Devaraj, Sridevi Hoefner, Daniel M. Warnick, Russell TI Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices SO CLINICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; ISCHEMIC-HEART-DISEASE; MAGNETIC-RESONANCE-SPECTROSCOPY; CHEMISTRY STANDARDIZATION PROJECT; TRIGLYCERIDE TRANSFER PROTEIN; NON-HDL CHOLESTEROL; 5-YEAR FOLLOW-UP; A-I; APO-B AB BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) has been the cornerstone Measurement for assessing cardiovascular risk for nearly 20 years. CONTENT: Recent data demonstrate that apolipoprotein B (apo B) is a better measure of circulating LDL particle number (LDL-P) concentration and is a more reliable indicator of risk than LDL-C, and there is growing support for the idea that addition of apo B measurement to the routine lipid panel for assessing and monitoring patients at risk for cardiovascular disease (CVD) would enhance patient management. In this report, we review the studies of apo B and LDL-P reported to date, discuss potential advantages of their measurement over that of LDL-C, and present information related to standardization. CONCLUSIONS: In line with recently adopted Canadian guidelines, the addition of apo B represents a logical next step to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) and other guidelines in the US. Considering that it has taken years to educate physicians and patients regarding the use of LDL-C, changing perceptions and practices will not be easy. Thus, it appears prudent to consider using apo B along with LDL-C to assess LDL-related risk for an interim period until the superiority of apo B is generally recognized. (C) 2008 American Association for Clinical Chemistry C1 [Contois, John H.] Maine Stand Co LLC, Windham, ME 04062 USA. [McConnel, Joseph P.] Mayo Clin, Rochester, MN USA. [Sethi, Amar A.; Csako, Gyorgy] NIH, Bethesda, MD 20892 USA. [Devaraj, Sridevi] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Hoefner, Daniel M.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Warnick, Russell] Berkeley HeartLab Inc, Alameda, CA USA. RP Contois, JH (reprint author), Maine Stand Co LLC, 765 Roosevelt Trail, Windham, ME 04062 USA. EM jcontois@mainestandards.com FU Intramural NIH HHS NR 91 TC 129 Z9 133 U1 0 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2009 VL 55 IS 3 BP 407 EP 419 DI 10.1373/clinchem.2008.118356 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 413DG UT WOS:000263772500009 PM 19168552 ER PT J AU Barnes, AJ De Martinis, BS Gorelick, DA Goodwin, RS Kolbrich, EA Huestis, MA AF Barnes, Allan J. De Martinis, Bruno S. Gorelick, David A. Goodwin, Robert S. Kolbrich, Erin A. Huestis, Marilyn A. TI Disposition of MDMA and Metabolites in Human Sweat Following Controlled MDMA Administration SO CLINICAL CHEMISTRY LA English DT Article ID GAS-CHROMATOGRAPHY; HUMAN PHARMACOLOGY; ECSTASY MDMA; EXCRETION; DELTA(9)-TETRAHYDROCANNABINOL; PHARMACOKINETICS; METHAMPHETAMINE; AMPHETAMINE; VOLUNTEERS; FATALITIES AB BACKGROUND: Understanding the excretion of 3,4-methylenedioxymethamphetamine (MDMA) and metabolites in sweat is vital for interpretation of sweat tests in drug treatment, criminal justice, and workplace programs. METHODS: Placebo, low (1.0 mg/kg), and high (1.6 mg/kg) doses of oral MDMA were given double-blind in random order to healthy volunteers (n = 15) with histories of MDMA use. Participants resided on the closed clinical research unit for up to 7 days after each dose. Volunteers wore PharmChek (R) sweat patches (n = 640) before, during, and after controlled dosing. Patches were analyzed by solid phase extraction and GC-MS for MDMA, methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA), and 4hydroxy-3-methoxymethamphetamine (HMMA). Limits of quantification (LOQ) were 2.5 ng/patch for MDMA and 5 ng/patch for HMA, HMMA, and MDA. RESULTS: MDMA was the primary analyte detected in 382 patches (59.7%), with concentrations up to 3007 ng/patch. MDA was detected in 188 patches (29.4%) at <172 ng/patch, whereas no HMMA or HMA was detected; 224 patches (35.0%) and 60 patches (9.4%) were positive for MDMA and MDA, respectively, at the 25-ng/patch threshold proposed by the Substance Abuse and Mental Health Services Administration. CONCLUSIONS: Sweat testing was shown to be an effective and reliable method for monitoring MDMA use in this controlled MDMA administration study. However, variability in sweat excretion suggests that results should be interpreted qualitatively rather than quantitatively. These data provide a scientific database for interpretation of MDMA sweat test results. (C) 2008 American Association for Clinical Chemistry C1 [Barnes, Allan J.; Gorelick, David A.; Goodwin, Robert S.; Kolbrich, Erin A.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. [De Martinis, Bruno S.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pathol, Ctr Legal Med, Ribeirao Preto, Brazil. [Kolbrich, Erin A.] Inst Forens Sci, Med Examiners Off, Crime Invest Lab, Dallas, TX USA. RP Huestis, MA (reprint author), Biomed Res Ctr, 251 Bayview Blvd,Suite 200 Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov RI De Martinis, Bruno/I-5388-2012 OI De Martinis, Bruno/0000-0002-2702-5190 FU Intramural NIH HHS [Z01 DA000468-04] NR 34 TC 16 Z9 17 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2009 VL 55 IS 3 BP 454 EP 462 DI 10.1373/clinchem.2008.117093 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 413DG UT WOS:000263772500015 PM 19168553 ER PT J AU Maholmes, V Prinz, R AF Maholmes, Valerie Prinz, Ronald J. TI Children's Exposure to Violence SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW LA English DT Editorial Material ID RESEARCH DIRECTIONS; DOMESTIC VIOLENCE C1 [Prinz, Ronald J.] Univ S Carolina, Columbia, SC 29208 USA. [Maholmes, Valerie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Prinz, R (reprint author), Univ S Carolina, Columbia, SC 29208 USA. EM maholmev@mail.nih.gov; PRINZ@mailbox.sc.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1096-4037 J9 CLIN CHILD FAM PSYCH JI Clin. Child Fam. Psychol. Rev. PD MAR PY 2009 VL 12 IS 1 BP 1 EP 2 DI 10.1007/s10567-009-0045-4 PG 2 WC Psychology, Clinical SC Psychology GA 420AU UT WOS:000264261600001 PM 19277864 ER PT J AU Martiniova, L Lai, EW Elkahloun, AG Abu-Asab, M Wickremasinghe, A Solis, DC Perera, SM Huynh, TT Lubensky, IA Tischler, AS Kvetnansky, R Alesci, S Morris, JC Pacak, K AF Martiniova, Lucia Lai, Edwin W. Elkahloun, Abdel G. Abu-Asab, Mones Wickremasinghe, Andrea Solis, Daniel C. Perera, Shiromi M. Huynh, Thanh-Truc Lubensky, Irina A. Tischler, Arthur S. Kvetnansky, Richard Alesci, Salvatore Morris, John C. Pacak, Karel TI Characterization of an animal model of aggressive metastatic pheochromocytoma linked to a specific gene signature SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Animal model; Cell line; Pheochromocytoma; Magnetic resonance imaging; Microarray; Quantitative real-time PCR ID MALIGNANT PHEOCHROMOCYTOMA; CELLS AB Pheochromocytomas are chromaffin cell-derived neuroendocrine tumors. There is presently no cure for metastatic pheochromocytoma and no reliable way to distinguish malignant from benign tumors before the development of metastases. In order to successfully manage pheochromocytoma, it is necessary to better understand the biological determinants of tumor behavior. For this purpose, we have recently established a mouse model of metastatic pheochromocytoma using tail vein injection of mouse pheochromocytoma (MPC) cells. We optimized this model modifying the number of cells injected, length of trypsin pre-treatment, and incubation temperature and duration for the MPC cells before injection, and by serial passage and re-selection of tumors exhibiting the metastatic phenotype. We evaluated the effect of these modifications on tumor growth using serial in vivo Magnetic Resonance Imaging studies. These results show that number of cells injected, the pre-injection incubation temperature, and duration of trypsin treatment are important factors to produce faster growing, more aggressive tumors that yielded secondary metastatic lesions. Serial harvest, culture and re-selection of metastatic liver lesions produced even more aggressive pheochromocytoma cells that retained their biochemical phenotype. Microarray gene expression comparison and quantitative real-time PCR of these more aggressive cells to the MPC-parental cell line identified genes that may be important for the metastatic process. C1 [Martiniova, Lucia; Lai, Edwin W.; Wickremasinghe, Andrea; Solis, Daniel C.; Perera, Shiromi M.; Huynh, Thanh-Truc; Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program,NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Martiniova, Lucia; Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. [Elkahloun, Abdel G.] NHGRI, Bethesda, MD 20892 USA. [Abu-Asab, Mones] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Lubensky, Irina A.] NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Tischler, Arthur S.] Tufts Univ, Dept Pathol, Tufts Med Ctr, Sch Med, Boston, MA 02111 USA. [Alesci, Salvatore] NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. [Morris, John C.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program,NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bldg 10 Room 1E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Wickremasinghe, Andrea/J-7580-2013 OI Abu-Asab, Mones/0000-0002-4047-1232; Wickremasinghe, Andrea/0000-0002-4228-9055 FU Intramural NIH HHS [ZIC HG200365-01, ZIC HG200365-02, ZIC HG200365-03]; NINDS NIH HHS [NS 37685, R01 NS037685] NR 16 TC 34 Z9 34 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAR PY 2009 VL 26 IS 3 BP 239 EP 250 DI 10.1007/s10585-009-9236-0 PG 12 WC Oncology SC Oncology GA 413JD UT WOS:000263788500008 PM 19169894 ER PT J AU Choi, BY Ahmed, ZM Riazuddin, S Bhinder, MA Shahzad, M Husnain, T Riazuddin, S Griffith, AJ Friedman, TB AF Choi, B. Y. Ahmed, Z. M. Riazuddin, S. Bhinder, M. A. Shahzad, M. Husnain, T. Riazuddin, S. Griffith, A. J. Friedman, T. B. TI Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan SO CLINICAL GENETICS LA English DT Article DE DFNB9; hearing; OTOF; otoferlin ID RECESSIVE AUDITORY NEUROPATHY; HEARING-LOSS; ENCODING OTOFERLIN; HAIR-CELLS; FORM; IMPAIRMENT; PREVALENCE; EXOCYTOSIS; EXPRESSION; FAMILIES AB Choi BY, Ahmed ZM, Riazuddin S, Bhinder MA, Shahzad M, Husnain T, Riazuddin S, Griffith AJ, Friedman TB. Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan.Clin Genet 2009: 75: 237-243. (C) Blackwell Munksgaard, 2008 Mutations in OTOF, encoding otoferlin, cause non-syndromic recessive hearing loss. The goal of our study was to define the identities and frequencies of OTOF mutations in a model population. We screened a cohort of 557 large consanguineous Pakistani families segregating recessive, severe-to-profound, prelingual-onset deafness for linkage to DFNB9. There were 13 families segregating deafness consistent with linkage to markers for DFNB9. We analyzed the genomic nucleotide sequence of OTOF and detected probable pathogenic sequence variants among all 13 families. These include the previously reported nonsense mutation p.R708X and 10 novel variants: 3 nonsense mutations (p.R425X, p.W536X, and p.Y1603X), 1 frameshift (c.1103_1104delinsC), 1 single amino acid deletion (p.E766del) and 5 missense substitutions of conserved residues (p.L573R, p.A1090E, p.E1733K, p.R1856Q and p.R1939W). OTOF mutations thus account for deafness in 13 (2.3%) of 557 Pakistani families. This overall prevalence is similar, but the mutation spectrum is different from those for Western populations. In addition, we demonstrate the existence of an alternative splice isoform of OTOF expressed in the human cochlea. This isoform must be required for human hearing because it encodes a unique alternative C-terminus affected by some DFNB9 mutations. C1 [Choi, B. Y.; Ahmed, Z. M.; Riazuddin, S.; Friedman, T. B.] NIDCD, Mol Genet Lab, NIH, Rockville, MD 20850 USA. [Bhinder, M. A.; Shahzad, M.; Husnain, T.; Riazuddin, S.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Griffith, A. J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD USA. RP Friedman, TB (reprint author), NIDCD, Mol Genet Lab, NIH, 5 Res Court,Room 2A-19, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov RI Husnain, Tayyab/G-3805-2015 FU National Institute on Deafness and Other Communication Disorders [Z01-DC00039-10, Z01-DC00060-07]; Higher Education Commission (HEC), Islamabad, Pakistan; Ministry of Science and Technology (MoST), Islamabad, Pakistan FX Human cochlear cDNA was a gift from the laboratory of Cynthia C. Morton. This study was supported by National Institute on Deafness and Other Communication Disorders intramural research funds Z01-DC00039-10 and Z01-DC00060-07 and also by the Higher Education Commission (HEC), Islamabad, Pakistan; Ministry of Science and Technology (MoST), Islamabad, Pakistan. We thank Rob Morell, Julie M. Schultz, Dennis Drayna, Doris Wu, and Karen Friderici for comments and critical review of the manuscript. NR 23 TC 29 Z9 31 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAR PY 2009 VL 75 IS 3 BP 237 EP 243 DI 10.1111/j.1399-0004.2008.01128.x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 408QV UT WOS:000263450600007 PM 19250381 ER PT J AU Tegay, DH Chan, KK Leung, L Wang, C Burkett, S Stone, G Stanyon, R Toriello, HV Hatchwell, E AF Tegay, D. H. Chan, K. K. Leung, L. Wang, C. Burkett, S. Stone, G. Stanyon, R. Toriello, H. V. Hatchwell, E. TI Toriello-Carey syndrome in a patient with a de novo balanced translocation [46,XY,t(2;14)(q33;q22)] interrupting SATB2 SO CLINICAL GENETICS LA English DT Article DE balanced translocation; candidate gene; chromosome 2q33; chromosome 14q22; SATB2; Toriello-Carey syndrome ID CLEFT-PALATE; BINDING PROTEIN; EXPRESSION; ANOMALIES; 2Q32-Q33; MANNER; GENE AB Tegay DH, Chan KK, Leung L, Wang C, Burkett S, Stone G, Stanyon R, Toriello HV, Hatchwell E. Toriello-Carey syndrome in a patient with a de novo balanced translocation [46,XY,t(2;14)(q33;q22)] interrupting SATB2.Clin Genet 2009: 75: 259-264. (C) Blackwell Munksgaard, 2008 Toriello-Carey syndrome (TCS; OMIM 217980) is a multiple congenital anomaly syndrome characterized by the common manifestations of corpus callosum agenesis, cardiac defects, cleft palate/Robin sequence, hypotonia, mental retardation, postnatal growth retardation and distinctive facial dysmorphology (including micrognathia, telecanthus, small nose and full cheeks). Both autosomal recessive and X-linked inheritance have been proposed, but chromosomal abnormalities involving disparate loci have also been detected in a small number of cases. We report a patient with classical features of TCS and an apparently balanced de novo translocation between chromosomes 2 and 14 [46,XY,t(2;14)(q33;q22)]. Molecular characterization revealed direct interruption of the special AT-rich sequence-binding protein-2 (SATB2) gene at the 2q33.1 translocation breakpoint, while the 14q22.3 breakpoint was not intragenic. SATB2 mutation or deletion has been associated with both isolated and syndromic facial clefting; however, an association with TCS has not been reported. SATB2 functions broadly as a transcription regulator, and its expression patterns suggest an important role in craniofacial and central nervous system development, making it a plausible candidate gene for TCS. C1 [Tegay, D. H.] New York Coll Osteopath Med NYIT, Dept Med & Med Genet, Old Westbury, NY 11568 USA. [Tegay, D. H.] SUNY Stony Brook, Dept Pediat, Med Ctr, Stony Brook, NY 11794 USA. [Chan, K. K.; Leung, L.] Kwong Wah Hosp, Dept Pediat, Hong Kong, Hong Kong, Peoples R China. [Wang, C.] Cold Spring Harbor Lab, Genome Res Ctr, Cold Spring Harbor, NY 11724 USA. [Burkett, S.; Stone, G.; Stanyon, R.] NCI, Frederick, MD 21701 USA. [Stanyon, R.] Univ Florence, Dept Evolutionary Biol, Florence, Italy. [Toriello, H. V.] Spectrum Hlth, Grand Rapids, MI USA. [Hatchwell, E.] SUNY Stony Brook, Dept Pathol, Med Ctr, Stony Brook, NY 11794 USA. RP Tegay, DH (reprint author), New York Coll Osteopath Med NYIT, Dept Med & Med Genet, No Blvd,POB 8000, Old Westbury, NY 11568 USA. EM dtegay@nyit.edu OI Tegay, David/0000-0002-1573-9954; Stanyon, Roscoe/0000-0002-7229-1092 NR 18 TC 17 Z9 19 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAR PY 2009 VL 75 IS 3 BP 259 EP 264 DI 10.1111/j.1399-0004.2008.01145.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 408QV UT WOS:000263450600010 PM 19170718 ER PT J AU Yoshida, A Isomoto, H Hisatsune, J Nakayama, M Nakashima, Y Matsushima, K Mizuta, Y Hayashi, T Yamaoka, Y Azuma, T Moss, J Hirayama, T Kohno, S AF Yoshida, Akira Isomoto, Hajime Hisatsune, Junzo Nakayama, Masaaki Nakashima, Yujiro Matsushima, Kayoko Mizuta, Yohei Hayashi, Tomayoshi Yamaoka, Yoshio Azuma, Takeshi Moss, Joel Hirayama, Toshiya Kohno, Shigeru TI Enhanced expression of CCL20 in human Helicobacter pylori-associated gastritis SO CLINICAL IMMUNOLOGY LA English DT Article DE CC chemokine ligand 20; CC chemokine receptor 6; H. pylori; Dendritic cells; cag pathogenicity island ID INFLAMMATORY-BOWEL-DISEASE; MATURE DENDRITIC CELLS; EPITHELIAL-CELLS; CHEMOKINES; RECRUITMENT; INFECTION; MIP-3-BETA; ACTIVATION; CCL19 AB CC chemokine ligand 20 (CCL20) attracts CC chemokine receptor 6 (CCR6)-expressing cells. Using endoscopic biopsies taken from the gastric antrum of 42 subjects infected with H. pylori and 42 uninfected subjects, mucosal CCL20 mRNA and protein levels were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. CCL19 mRNA and protein levels, as well as CCL21 mRNA levels, were also measured. The CCL20 mRNA and protein levels were significantly elevated in H. pylori-positive patients and substantially decreased after successful eradication. CCL19 and CCL21 expression levels were comparable in the H. pylori-infected and the uninfected groups. The CCL20 concentrations correlated with the degree of chronic gastritis. Immunohistochemistry and the in vitro infection assay showed that CCL20 was principally produced by the gastric epithelium. CCR6-expressing cells, including CD45RO(+) memory T lymphocytes and fascin(+)-CD1a(+) immature dendritic cells, infiltrated close to the CCL20-expressing epithelial cells. The CCL20/CCR6 interaction may be involved in the development of H. pylori-associated gastritis. (C) 2008 Elsevier Inc. All rights reserved. C1 [Yoshida, Akira; Isomoto, Hajime; Nakashima, Yujiro; Matsushima, Kayoko; Mizuta, Yohei; Kohno, Shigeru] Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 8528501, Japan. [Hisatsune, Junzo; Nakayama, Masaaki; Hirayama, Toshiya] Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528501, Japan. [Hayashi, Tomayoshi] Nagasaki Univ, Sch Med, Dept Pathol, Nagasaki 8528501, Japan. [Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX USA. [Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. [Azuma, Takeshi] Kobe Univ, Sch Med, Dept Gastroenterol, Kobe, Hyogo 650, Japan. [Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Isomoto, H (reprint author), Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 8528501, Japan. EM hajimei2002@yahoo.co.jp FU intramural research program; NIH; NHLBI FX J Moss was supported by the intramural research program, NIH, NHLBI. NR 25 TC 16 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2009 VL 130 IS 3 BP 290 EP 297 DI 10.1016/j.clim.2008.09.016 PG 8 WC Immunology SC Immunology GA 409UD UT WOS:000263530400008 PM 19006683 ER PT J AU Pappas, PG Kauffman, CA Andes, D Benjamin, DK Calandra, TF Edwards, JE Filler, SG Fisher, JF Kullberg, BJ Ostrosky-Zeichner, L Reboli, AC Rex, JH Walsh, TJ Sobel, JD AF Pappas, Peter G. Kauffman, Carol A. Andes, David Benjamin, Daniel K., Jr. Calandra, Thierry F. Edwards, John E., Jr. Filler, Scott G. Fisher, John F. Kullberg, Bart-Jan Ostrosky-Zeichner, Luis Reboli, Annette C. Rex, John H. Walsh, Thomas J. Sobel, Jack D. TI Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID LIPOSOMAL AMPHOTERICIN-B; INVASIVE FUNGAL-INFECTIONS; PROSTHETIC VALVE ENDOCARDITIS; EMPIRICAL ANTIFUNGAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER-TRANSPLANT RECIPIENTS; ILL SURGICAL-PATIENTS; INTENSIVE-CARE-UNIT; ITRACONAZOLE ORAL SOLUTION; VULVO-VAGINAL CANDIDIASIS AB Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document. C1 [Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Ann Arbor Vet Adm Hlth Care Syst, Ann Arbor, MI USA. [Sobel, Jack D.] Wayne State Univ, Detroit, MI USA. [Andes, David] Univ Wisconsin, Madison, WI USA. [Benjamin, Daniel K., Jr.] Duke Univ, Med Ctr, Durham, NC USA. [Edwards, John E., Jr.; Filler, Scott G.] Harbor Univ Calif Los Angeles, Med Ctr, Torrance, CA USA. [Fisher, John F.] Med Coll Georgia, Augusta, GA 30912 USA. [Ostrosky-Zeichner, Luis] Univ Texas Houston, Houston, TX USA. [Reboli, Annette C.] Univ Med & Dent New Jersey, Cooper Hosp, Camden, NJ 08103 USA. [Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA. [Calandra, Thierry F.] CHU Vaudois, CH-1011 Lausanne, Switzerland. [Kullberg, Bart-Jan] Univ Nijmegen, Ctr Infect Dis, Nijmegen, Netherlands. [Rex, John H.] Astra Zeneca Pharmaceut, Manchester, Lancs, England. RP Pappas, PG (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 1900 Univ Blvd,THT 229, Birmingham, AL 35294 USA. EM pappas@uab.edu RI Kullberg, Bart Jan/C-8520-2013; Calandra, Thierry/D-9017-2015 OI Calandra, Thierry/0000-0003-3051-1285 FU Infectious Diseases Society of America; Pfizer Pharmaceuticals; Merck; Astellas Pharma; National Institutes of Health; Biosynexus; Associates of Cape Cod; Pfizer; Rockeby; National Institute of Child Health and Human Development; AstraZeneca International; Johnson and Johnson, Medicines Company; MedImmune; Novartis; Schering Plough; Roche Diagnostics; Amgen; Columbia University; Centers for Disease Control and Prevention; Romark Laboratories; MSD; Schering-lough; Gilead; Basilea Pharmaceutica; Viracor; Schering; Enzon; Cubist Pharmaceuticals; KV Pharmaceuticals; Vicuron FX Potential conflicts of interest. P. G. P. has received honoraria and research grants and has served as a consultant to Schering-Plough, Astellas Pharma, Merck, Novartis, Basilea, and Pfizer Pharmaceuticals. D. A. has served as an advisor and received honoraria from Pfizer Pharmaceuticals, Merck, and Astellas Pharma and has received research grants from Astellas Pharma, Pfizer Pharmaceuticals, and the National Institutes of Health. D. K. B. has received research funding from Astellas Pharma, Biosynexus, Associates of Cape Cod, Pfizer, Rockeby, National Institute of Child Health and Human Development, and Thrasher Research Fund and has received organizational grants from AstraZeneca International, Johnson and Johnson, Medicines Company, MedImmune, and Pfizer. T. C. has served as a consultant to Pfizer Pharmaceuticals, Merck, and Novartis and has received honoraria from Pfizer Pharmaceuticals, Merck, Novartis, Schering Plough, and Roche Diagnostics. S. G. F. has received research grants from Pfizer, Amgen, and Merck; has received research funding from the National Institutes of Health and Columbia University; has served as a consultant for Theravance, Forest Pharmaceuticals, and Semorex; and holds stock in NovaDigm Therapeutics. J. F. F. has received honoraria from Pfizer Pharmaceuticals, Merck, and Wyeth. C. A. K. receives royalties from UpToDate and Springer Publisher and has received funding from Merck, the Centers for Disease Control and Prevention, Astellas Pharma, and Romark Laboratories. B.- J. K. has served as a consultant or advisor to Basilea Pharmaceutica, Novartis, Pfizer Pharmaceuticals, and Schering-Plough and has received honoraria from MSD, Pfizer Pharmaceuticals, and Schering-lough. L. O.- Z. has served as a consultant for Astellas Pharma, Merck, Pfizer Pharmaceuticals, and Viracor; has received honoraria from Gilead, Merck, Pfizer, and Astellas Pharma; and has received research grants from Merck, Pfizer Pharmaceuticals, Astellas Pharma, Basilea Pharmaceutica, Associates of Cape Cod, and Viracor. A. C. R. has served as a consultant or advisor for Pfizer Pharmaceuticals, Astellas Pharma, and Merck; has received honoraria from Pfizer Pharmaceuticals; and has received research grants from Pfizer Pharmaceuticals and Merck. J. E. E. has received research funding from Schering-Plough, Schering, Enzon, Merck, Basilea Pharmaceutica, Pfizer Pharmaceuticals, Astellas Pharma, and Cubist Pharmaceuticals; has been on the scientific advisory boards of Merck, Pfizer, Gilead, Enzon, Cerexa, and Calixia; and is a founder of NovaDigm Therapeutics. J. D. S. has received honoraria from Pfizer Pharmaceuticals, Merck, and KV Pharmaceuticals; has received research funding from Pfizer Pharmaceuticals, Merck, and Astellas Pharma; and has served as a consultant for Merck, Pfizer, and Embil. T. J. W. has received research funding from Astellas Pharma and Vicuron through the Cooperative Research and Development Agreement. J. F. R. is an employee of Astra Zeneca. NR 297 TC 1495 Z9 1632 U1 15 U2 89 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 MAR 1 PY 2009 VL 48 IS 5 BP 503 EP 535 DI 10.1086/596757 PG 33 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 403DE UT WOS:000263061700001 PM 19191635 ER PT J AU Brooks, JT Kaplan, JE Holmes, KK Benson, C Pau, A Masur, H AF Brooks, John T. Kaplan, Jonathan E. Holmes, King K. Benson, Constance Pau, Alice Masur, Henry TI HIV-Associated Opportunistic Infections-Going, Going, But Not Gone: The Continued Need for Prevention and Treatment Guidelines SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID LATE DIAGNOSIS; HAART ERA; CARE; TRENDS; HOSPITALIZATIONS; SEROCONVERSION; STATES; DEATH; AIDS C1 [Brooks, John T.; Kaplan, Jonathan E.] Ctr Dis Control & Prevent, Natl Ctr HIV Hepatitis TB & STD Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. [Holmes, King K.] Univ Washington, Seattle, WA 98195 USA. [Benson, Constance] Univ Calif San Diego, San Diego, CA 92103 USA. [Pau, Alice; Masur, Henry] NIH, Bethesda, MD 20892 USA. RP Brooks, JT (reprint author), Ctr Dis Control & Prevent, Natl Ctr HIV Hepatitis TB & STD Prevent, Div HIV AIDS Prevent, 1600 Clifton Rd NE,Mailstop E-45, Atlanta, GA 30333 USA. EM zud4@cdc.gov NR 25 TC 33 Z9 34 U1 0 U2 1 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 MAR 1 PY 2009 VL 48 IS 5 BP 609 EP 611 DI 10.1086/596756 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 403DE UT WOS:000263061700014 PM 19191648 ER PT J AU Tsibris, AMN Paredes, R Chadburn, A Su, ZH Henrich, TJ Krambrink, A Hughes, MD Aberg, JA Currier, JS Tashima, K Godfrey, C Greaves, W Flexner, C Skolnik, PR Wilkin, TJ Gulick, RM Kuritzkes, DR AF Tsibris, Athe M. N. Paredes, Roger Chadburn, Amy Su, Zhaohui Henrich, Timothy J. Krambrink, Amy Hughes, Michael D. Aberg, Judith A. Currier, Judith S. Tashima, Karen Godfrey, Catherine Greaves, Wayne Flexner, Charles Skolnik, Paul R. Wilkin, Timothy J. Gulick, Roy M. Kuritzkes, Daniel R. TI Lymphoma Diagnosis and Plasma Epstein-Barr Virus Load during Vicriviroc Therapy: Results of the AIDS Clinical Trials Group A5211 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; UNFRACTIONATED WHOLE-BLOOD; NON-HODGKIN-LYMPHOMA; DNA LOAD; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE; KAPOSIS-SARCOMA; RISK AB Background. Lack of functional CCR5 increases the severity of certain viral infections, including West Nile virus and tickborne encephalitis. In a phase II trial of the investigational CCR5 antagonist vicriviroc (AIDS Clinical Trials Group protocol A5211), 4 lymphomas occurred in study patients who received vicriviroc. Because of the known association between unregulated Epstein-Barr virus (EBV) replication and lymphoma in immunocompromised patients, we evaluated whether vicriviroc exposure was associated with lymphoma EBV antigen positivity and/or had an effect on plasma levels of EBV DNA. Methods. Clinical findings for all 4 patients enrolled in the A5211 study who developed lymphoma (2 Hodgkin and 2 non-Hodgkin) were reviewed, and tumor specimens were assessed for evidence of ongoing EBV replication. Longitudinal plasma samples from 116 patients in the A5211 study were analyzed, and EBV DNA was quantified by real-time polymerase chain reaction. Results. Plasma EBV DNA was not detected in the 2 patients with non-Hodgkin lymphoma; both patients with Hodgkin lymphoma who had samples tested had EBV DNA levels <3200 copies/mL. One patient with Hodgkin lymphoma had a lymph node core biopsy specimen that was strongly positive for EBV; the other 3 lymphomas were histochemically EBV negative. None of the 116 patients with available samples experienced sustained increases in plasma EBV levels. Conclusions. CCR5 antagonism by vicriviroc treatment in treatment-experienced patients was not associated with reactivation of EBV infection. C1 [Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Cambridge, MA 02139 USA. [Tsibris, Athe M. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tsibris, Athe M. N.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. [Su, Zhaohui; Krambrink, Amy; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Skolnik, Paul R.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Chadburn, Amy; Wilkin, Timothy J.; Gulick, Roy M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Aberg, Judith A.] NYU, Sch Med, Bellevue Hosp, New York, NY USA. [Currier, Judith S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Tashima, Karen] Miriam Hosp, Providence, RI 02906 USA. [Godfrey, Catherine] NIAID, Div Aids, NIH, Baltimore, MD USA. [Flexner, Charles] Johns Hopkins Univ, Baltimore, MD USA. [Greaves, Wayne] Schering Plough Corp, Kenilworth, NJ USA. [Paredes, Roger] Fdn irsiCaixa & Lluita SIDA, Badalona, Spain. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Rm 449, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org FU Clinical Investigator Training Program; Harvard Massachusetts Institute of Technology Health Sciences and Technology; Beth Israel Deaconess Medical Center, in collaboration with Pfizer and Merck; "La Caixa"; National Institute of Allergy and Infectious Diseases; National Institutes of Health [AI068636, AI068634, AI069419, AI069472, AI055038, AI051966, AI060354]; National Center for Research Resources [RR024996, RR02635, RR016482 `]; Schering-Plough, Merck; Merck; Tibotec; Theratechnologies; Bristol-Myers Squibb; Gilead; GlaxoSmithKline; Pfizer; Schering-Plough; Monogram; Roche-Trimeris; Abbott; Bayer; Monogram Biosciences FX Potential conflicts of interest. M. D. H. has served as a paid member of data and safety monitoring boards for Boehringer-Ingelheim and Tibotec and as a consultant to Bristol-Myers Squibb. J. A. A. has served as a research investigator and/or advisory board member for Pfizer, Gilead, Tibotec, GlaxoSmithKline, Merck, Abbott, Bristol-Myers Squibb, and Boehringer-Ingelheim. J. S. C. has consulted or served on an advisory board for Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Pfizer, Tiobtec, and Merck; has served on Data Safety Monitoring Boards for Koronnis and Achillion; and her institution has received research grants from Schering-Plough, Merck, Tibotec, and Theratechnologies. W. L. G. is an employee of Schering-Plough Research Institute. C. F. served on a scientific advisory board for Schering-Plough. P. R. S. receives research grant support from Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, Pfizer, Schering-Plough, and Tibotec. T. J. W. has received honoraria from Merck and Tibotec and receives research support from Tibotec. R. M. G. receives research grant support from Pfizer and Schering-Plough and has served as an ad-hoc consultant to Abbott, GlaxoSmithKline, Monogram, Pfizer, Roche-Trimeris, and Schering-Plough. D. R. K. has served as a consultant to and has received honoraria and/or research grant support from Abbott, Bayer, Monogram Biosciences, Pfizer, and Schering-Plough. All other authors: no conflicts. NR 44 TC 13 Z9 14 U1 0 U2 0 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 MAR 1 PY 2009 VL 48 IS 5 BP 642 EP 649 DI 10.1086/597007 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 403DE UT WOS:000263061700021 PM 19191652 ER PT J AU Kutner, NG Johansen, KL Kaysen, GA Pederson, S Chen, SC Agodoa, LY Eggers, PW Chertow, GM AF Kutner, Nancy G. Johansen, Kirsten L. Kaysen, George A. Pederson, Sarah Chen, Shu-Cheng Agodoa, Lawrence Y. Eggers, Paul W. Chertow, Glenn M. TI The Comprehensive Dialysis Study (CDS): A USRDS Special Study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEALTH; DISEASE; ADULTS AB Background and objectives: The Comprehensive Dialysis Study (CDS) aimed to understand factors contributing to physical, functional, and nutritional health status among patients starting dialysis. Design, setting, participants, & measurements: A phone interview survey was conducted with patients from a geographically stratified national random sample of dialysis units, and quarterly serum samples were obtained for patients at a preidentified subset of units. The phone survey collected standardized measures of physical activity, employment and disability status, perceived health and well-being, and dietary intake. Serum samples were obtained to measure prealbumin, albumin, creatinine, normalized protein catabolic rate, and C-reactive protein. To comply with restrictions required under the Health Insurance Portability and Accountability Act (HIPAA), dialysis unit personnel could not participate in any research-related activities. Results: Overall participation rate was 18.5%. One thousand six hundred forty-six patients affiliated with 295 dialysis units completed the phone survey; 361 patients affiliated with 68 dialysis units also completed a dietary intake survey, with 269 providing serum samples. Despite challenges in the design and implementation of CDS, the population was diverse and results should be generalizable. Conclusions: Constraints within the dialysis industry and HIPAA requirements render the assembly of nationally representative cohorts extremely difficult. Nevertheless, the CDS represents the largest cohort of incident dialysis patients containing detailed information on self-reported physical activity and dietary intake and is one of few cohorts simultaneously measuring laboratory proxies of nutrition and inflammatory status. Data from CDS can be used to inform the design of interventions addressing several conditions that affect longevity and health status in ESRD. C1 [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Kutner, Nancy G.] Emory Univ, USRDS, Rehabil Qual Life Special Studies Ctr, Atlanta, GA 30322 USA. [Johansen, Kirsten L.; Kaysen, George A.; Chertow, Glenn M.] Emory Univ, USRDS, Nutr Special Studies Ctr, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kaysen, George A.] Univ Calif Davis, Davis, CA 95616 USA. [Pederson, Sarah; Chen, Shu-Cheng] Univ Minnesota, USRDS, Coordinating Ctr, Minneapolis, MN USA. [Agodoa, Lawrence Y.; Eggers, Paul W.] NIDDK, NIH, Bethesda, MD USA. RP Chertow, GM (reprint author), Stanford Univ, Sch Med, Div Nephrol, 780 Welch Rd,Suite 106, Palo Alto, CA 94304 USA. EM gchertow@stanford.edu NR 15 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2009 VL 4 IS 3 BP 645 EP 650 DI 10.2215/CJN.05721108 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 417GM UT WOS:000264064500020 PM 19261814 ER PT J AU McMaster, ML Kristinsson, SY Turesson, I Bjorkholm, M Landgren, O AF McMaster, Mary L. Kristinsson, Sigurdur Y. Turesson, Ingemar Bjorkholm, Magnus Landgren, Ola TI Novel Aspects Pertaining to the Relationship of Waldenstrom's Macroglobulinemia, IgM Monoclonal Gammopathy of Undetermined Significance, Polyclonal Gammopathy, and Hypoglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article CT 5th International Workshop on Waldenstroms Macroglobulinemia CY OCT 15-19, 2008 CL Stockholm, SWEDEN DE Genetic susceptibility; Hypergammaglobulinemia; IgM; Precursor disease ID NON-HODGKIN-LYMPHOMA; LONG-TERM; ADULT-POPULATION; RISK; PREVALENCE; DISORDERS; FAMILIES; EVOLUTION AB Waldenstrom's macroglobulinemia (WM) is associated with a precursor condition, monoclonal gammopathy of undetermined significance (MGUS) of immunoglobulin-M (IgM) type. The etiology of these conditions is unknown. Recent studies at the population level have provided new data regarding familial aggregation of these disorders and other B-cell malignancies. Studies of familial clusters of WM have demonstrated an increased frequency of IgM MGUS compared with the general population and have provided new data suggesting that the phenotypic spectrum might also include polyclonal gammopathy and hypoglobulinemia. While the preponderance of immunoglobulin abnormalities in relatives of WM cases involves IgM, other immunoglobulin types (IgG and IgA) might also be affected. Large collaborative studies are needed to confirm these findings, which present an opportunity to define the earliest lesion(s) in the WM oncogenic pathway. C1 [McMaster, Mary L.; Landgren, Ola] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp Solna, Div Hematol, Dept Med, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden. [Turesson, Ingemar] Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP McMaster, ML (reprint author), 6120 Execut Blvd,Rm 7010, Bethesda, MD 20892 USA. EM mcmastem@mail.nih.gov RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU Intramural NIH HHS [Z99 CA999999] NR 25 TC 5 Z9 5 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD MAR PY 2009 VL 9 IS 1 BP 19 EP 22 DI 10.3816/CLM.2009.n.003 PG 4 WC Oncology SC Oncology GA 425HS UT WOS:000264628200003 PM 19362963 ER PT J AU Kristinsson, SY Koshiol, J Goldin, LR Bjorkholm, M Turesson, I Gridley, G McMaster, ML Landgren, O AF Kristinsson, Sigurdur Y. Koshiol, Jill Goldin, Lynn R. Bjorkholm, Magnus Turesson, Ingemar Gridley, Gloria McMaster, Mary L. Landgren, Ola TI Genetics- and Immune-Related Factors in the Pathogenesis of Lymphoplasmacytic Lymphoma/Waldenstrom's Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article CT 5th International Workshop on Waldenstroms Macroglobulinemia CY OCT 15-19, 2008 CL Stockholm, SWEDEN DE Autoimmune disease; Familial aggregation; Hepatitis C virus; Lymphoproliferative malignancy; Rheumatoid arthritis; Susceptibility ID CHRONIC LYMPHOCYTIC-LEUKEMIA; POPULATION-BASED SAMPLES; NON-HODGKIN-LYMPHOMA; WALDENSTROMS MACROGLOBULINEMIA; RHEUMATOID-ARTHRITIS; LYMPHOPROLIFERATIVE DISORDERS; FAMILIAL AGGREGATION; RISK; DISEASE; ANTICIPATION AB There are emerging data to support a role for genetic and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia. In this article, we review our recently published, large, population-based studies using data from Sweden and from United States veterans and propose mechanisms and pathways underlying our observations. We also discuss future directions for new studies designed to increase our current knowledge and to define underlying biologic mechanisms of our findings. Finally, based on novel insights on this topic, we discuss clinical implications and provide perspective on the relevance of these data for patient counseling and clinical follow-up. C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden. [Koshiol, Jill; Goldin, Lynn R.; Gridley, Gloria; McMaster, Mary L.; Landgren, Ola] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Turesson, Ingemar] Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden. EM sigurdur.kristinsson@karolinska.se RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU Intramural NIH HHS [Z01 CP004410-31] NR 41 TC 5 Z9 5 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD MAR PY 2009 VL 9 IS 1 BP 23 EP 26 DI 10.3816/CLM.2009.n.004 PG 4 WC Oncology SC Oncology GA 425HS UT WOS:000264628200004 PM 19362964 ER PT J AU Chen, C Kouroukis, CT White, D Voralia, M Stadtmauer, E Stewart, AK Wright, JJ Powers, J Walsh, W Eisenhauer, E AF Chen, Christine Kouroukis, C. Tom White, Darrell Voralia, Michael Stadtmauer, Edward Stewart, A. Keith Wright, John J. Powers, Jean Walsh, Wendy Eisenhauer, Elizabeth TI Bortezomib in Relapsed or Refractory Waldenstrom's Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article CT 5th International Workshop on Waldenstroms Macroglobulinemia CY OCT 15-19, 2008 CL Stockholm, SWEDEN DE Hyperviscosity; Neuropathy; Neutropenia; Second-line treatment; Thrombocytopenia ID PROTEASOME INHIBITOR BORTEZOMIB; MULTIPLE-MYELOMA CELLS; NON-HODGKINS-LYMPHOMA; PHASE-II AB Bortezomib is a proteasome inhibitor that induces apoptosis in primary Waldenstrom's macroglobulinemia (WM) cells and WM cell lines. To date, 3 clinical trials of single-agent bortezomib in WM have been published. Of the 64 patients pooled from these studies (most with relapsed/refractory disease), a 25% or greater reduction of IgM was achieved in 78%-85%. Responses were rapid in onset, suggesting a role for bortezomib in the management of hyperviscosity or other settings where rapid IgM reduction is indicated. Neuropathy appears more severe and frequent in WM than in myeloma or other indolent lymphomas treated with bortezomib. Bortezomib-based combination therapies, with consideration for attenuated or intermittent dosing of bortezomib to minimize neuropathy, are under investigation. C1 [Chen, Christine] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. [Kouroukis, C. Tom] Juravinski Canc Ctr, Hamilton, ON, Canada. [White, Darrell] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Voralia, Michael] Saskatoon Canc Ctr, Saskatoon, SK, Canada. [Stadtmauer, Edward] Eastern Cooperat Oncol Grp, Philadelphia, PA USA. [Stewart, A. Keith] Mayo Clin, Scottsdale, AZ USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Powers, Jean; Walsh, Wendy; Eisenhauer, Elizabeth] Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. RP Chen, C (reprint author), Princess Margaret Hosp, 610 Univ Ave,Ste 5-220, Toronto, ON M5G 2M9, Canada. EM christine.chen@uhn.on.ca NR 11 TC 12 Z9 13 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD MAR PY 2009 VL 9 IS 1 BP 74 EP 76 DI 10.3816/CLM.2009.n.019 PG 3 WC Oncology SC Oncology GA 425HS UT WOS:000264628200019 PM 19362979 ER PT J AU Whiteley, GR Colantonio, S Sacconi, A Saul, RG AF Whiteley, Gordon R. Colantonio, Simona Sacconi, Andrea Saul, Richard G. TI Analytical Considerations for Mass Spectrometry Profiling in Serum Biomarker Discovery SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Biomarkers; Proteomic patterns; MALDI; Bioinformatics; Reproducibility; Immune Capture; Carrier proteins; Low molecular weight proteome ID OVARIAN-CANCER PATIENTS; SELDI-TOF-MS; PROTEOMIC PATTERNS; PROSTATE-CANCER; PANCREATIC-CANCER; PLASMA PROTEOME; REPRODUCIBILITY; DIAGNOSIS; IDENTIFICATION; VALIDATION AB The potential of using mass spectrometry profiling as a diagnostic tool has been demonstrated for a wide variety of diseases. Various cancers and cancer-related diseases have been the focus of much of this work because of both the paucity of good diagnostic markers and the knowledge that early diagnosis is the most powerful weapon in treating cancer. The implementation of mass spectrometry as a routine diagnostic tool has proved to be difficult, however, primarily because of the stringent controls that are required for the method to be reproducible. The method is evolving as a powerful guide to the discovery of biomarkers that could, in turn, be used either individually or in an array or panel of tests for early disease detection. Using proteomic patterns to guide biomarker discovery and the possibility of deployment in the clinical laboratory environment on current instrumentation or in a hybrid technology has the possibility of being the early diagnosis tool that is needed. C1 [Whiteley, Gordon R.; Colantonio, Simona; Sacconi, Andrea; Saul, Richard G.] NCI, Clin Prote Reference Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. [Colantonio, Simona; Sacconi, Andrea] Regina Elena Inst Canc Res, Dept Mol Med, I-00144 Rome, Italy. RP Whiteley, GR (reprint author), NCI, Clin Prote Reference Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. EM WhiteleyG@ncifcrf.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12,400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number N01-CO-12,400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NR 46 TC 3 Z9 3 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2009 VL 29 IS 1 BP 57 EP + DI 10.1016/j.cll.2009.01.003 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 450DD UT WOS:000266380300006 PM 19389551 ER PT J AU Blonder, J Veenstra, TD AF Blonder, Josip Veenstra, Timothy D. TI Clinical Proteomic Applications of Formalin-Fixed Paraffin-Embedded Tissues SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Clinical specimens; Mass spectrometry; Proteomics; Formalin-fixed tissues; Biomarker discovery ID ANTIGEN RETRIEVAL; SHOTGUN PROTEOMICS; MICROARRAYS; IMMUNOFLUORESCENCE; IDENTIFICATION; TECHNOLOGY; BIOMARKERS; SECTIONS; GENOME AB Although proteomic technology has proved to be extremely powerful in basic research, its impact has not been as great in the clinical laboratory. The future, however, looks extremely positive because technologies, such as mass spectrometry and tissue microarrays, have continued to improve over the past several years. One of the most exciting developments, particularly in the area of mass spectrometry, is the ability to examine formalin-fixed paraffin-embedded tissue using these technologies. The almost inexhaustible supply of these tissues will enable proteomic laboratories access to clinically important specimens that will undoubtedly lead to a number of important discoveries in the near future. C1 [Blonder, Josip; Veenstra, Timothy D.] Natl Canc Inst, Lab Prote & Analyt Technol, SAIC Frederick, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), Natl Canc Inst, Lab Prote & Analyt Technol, SAIC Frederick, 1050 Boyles St, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the United States Government. NR 29 TC 18 Z9 18 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2009 VL 29 IS 1 BP 101 EP + DI 10.1016/j.cll.2009.01.006 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 450DD UT WOS:000266380300009 PM 19389554 ER PT J AU Alegria, AA Petry, NM Hasin, DS Liu, SM Grant, BF Blanco, C AF Alegria, Analucia A. Petry, Nancy M. Hasin, Deborah S. Liu, Shang-Min Grant, Bridget F. Blanco, Carlos TI Disordered Gambling Among Racial and Ethnic Groups in the US: Results From the National Epidemiologic Survey on Alcohol and Related Conditions SO CNS SPECTRUMS LA English DT Article ID DSM-IV ALCOHOL; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; NORTHERN PLAINS RESERVATION; UNITED-STATES; DRUG-USE; MEXICAN-AMERICANS; PATHOLOGICAL GAMBLERS; PERSONALITY-DISORDERS AB Introduction: Prior research suggests that racial minority groups in the United States are more vulnerable to develop a gambling disorder than whites. However, no national survey on gambling disorders exists that has focused on ethnic differences. Methods: Analyses of this study were based on the National Epidemiologic Survey on Alcohol and Related Conditions, a large (N = 43,093) nationally representative survey of the adult (>= 18 years of age) population residing in households during 2001-2002 period. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision diagnoses of pathological gambling, mood, anxiety, drug use, and personality disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IVVersion. Results: Prevalence rates of disordered gambling among blacks (2.2%) and Native/Asian. Americans (2.3%) were higher than that of whites (1.2%). Demographic characteristics and psychiatric comorbidity differed among Hispanic, black, and white disordered gamblers. However, all racial and ethnic group, evidenced similarities with respect to symptom patterns, time course, and treatment seeking for pathological gambling. Conclusion: The prevalence of disordered gambling, but not its or set or course of symptoms, varies by racial a id ethnic group. These varying prevalence rates may reflect, at least in part, cultural differences in gambling and its acceptability and accessibility. These data may inform the need for targeted prevention strategies for high-risk racial a id ethnic groups. C1 [Blanco, Carlos] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA. [Alegria, Analucia A.] Columbia Univ, New York State Psychiat Inst, Columbia Gambling Disorders Clin, New York, NY 10032 USA. [Petry, Nancy M.] Univ Connecticut, Sch Med, Dept Psychiat, Mental Hlth Ctr, Farmington, CT USA. [Hasin, Deborah S.] Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Blanco, C (reprint author), Columbia Univ, Dept Psychiat, Coll Phys & Surg, 1051 Riverside Dr,Box 69, New York, NY 10032 USA. EM cb255@columbia.edu RI Blanco, Carlos/I-4906-2013; OI Blanco, Carlos/0000-0001-6187-3057; Alegria, Analucia /0000-0001-6044-3311 FU National Institute on Alcohol Abuse and Alcoholism; National Institutes of Health [DA019606, DA020783, DA023200, MH076051, AA014223]; American Foundation for Suicide Prevention; New York State Psychiatric Institute FX This research was also supported by National Institutes of Health grants DA019606, DA020783, DA023200, and MH076051 (Dr. Blanco), AA014223 (Dr. Hasin), a grant from the American Foundation for Suicide Prevention (Dr. Blanco) and the New York State Psychiatric Institute (Drs. Blanco and Hasin). NR 99 TC 47 Z9 48 U1 1 U2 14 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAR PY 2009 VL 14 IS 3 BP 132 EP 142 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 430CS UT WOS:000264967000006 PM 19407710 ER PT J AU Kent, ML Feist, SW Harper, C Hoogstraten-Miller, S Mac Law, J Sanchez-Morgado, JM Tanguay, RL Sanders, GE Spitsbergen, JM Whipps, CM AF Kent, Michael L. Feist, Stephen W. Harper, Claudia Hoogstraten-Miller, Shelley Mac Law, J. Sanchez-Morgado, Jose M. Tanguay, Robert L. Sanders, George E. Spitsbergen, Jan M. Whipps, Christopher M. TI Recommendations for control of pathogens and infectious diseases in fish research facilities SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th Conference on Aquatic Animal Models of Human Disease CY JAN 31-FEB 03, 2008 CL Duke Univ, Durham, NC SP Nicholas Sch Environm HO Duke Univ DE Fish; Pathogen; Research; Zebrafish; Medaka; Mycobacteria ID ZEBRAFISH DANIO-RERIO; BRACHYDANIO-RERIO; ORNAMENTAL FISH; HIGH MORTALITY; LABORATORY ZEBRAFISH; MYCOBACTERIUM SPP.; UV INACTIVATION; CHINOOK SALMON; RAINBOW-TROUT; ANIMAL-MODEL AB Concerns about infectious diseases in fish used for research have risen along with the dramatic increase in the use of fish as models in biomedical research. In addition to acute diseases causing severe morbidity and mortality, underlying chronic conditions that cause low-grade or subclinical infections may confound research results. Here we present recommendations and strategies to avoid or minimize the impacts of infectious agents in fishes maintained in the research setting. There are distinct differences in strategies for control of pathogens in fish used for research compared to fishes reared as pets or in aquaculture. Also, much can be learned from strategies and protocols for control of diseases in rodents used in research, but there are differences. This is due, in part, the unique aquatic environment that is modified by the source and quality of the water provided and the design of facilities. The process of control of pathogens and infectious diseases in fish research facilities is relatively new, and will be an evolving process over time. Nevertheless, the goal of documenting, detecting, and excluding pathogens in fish is just as important as in mammalian research models. (C) 2008 Published by Elsevier Inc. C1 [Kent, Michael L.; Spitsbergen, Jan M.] Oregon State Univ, Dept Microbiol, Ctr Fish Dis Res, Corvallis, OR 97331 USA. [Feist, Stephen W.] Ctr Environm Fisheries & Aquaculrure Sci, Weymouth DT4 8UB, Dorset, England. [Harper, Claudia] Amgen Inc, Cambridge, MA 02139 USA. [Hoogstraten-Miller, Shelley] Natl Inst HealthBldg, Anim Program, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. [Mac Law, J.] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27606 USA. [Sanchez-Morgado, Jose M.] CNIC, Inst Salud Carlos III, Madrid 28029, Spain. [Tanguay, Robert L.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Sanders, George E.] Univ Washington, Sch Med, Dept Comparat Med T 160, Hlth Sci Ctr, Seattle, WA 98195 USA. [Sanders, George E.] USGS Western Fisheries Res Ctr, Seattle, WA USA. [Whipps, Christopher M.] SUNY Coll Environm Sci & Forestry, Syracuse, NY 13210 USA. RP Kent, ML (reprint author), Oregon State Univ, Dept Microbiol, Ctr Fish Dis Res, 220 Nash Hall, Corvallis, OR 97331 USA. EM Michael.Kent@oregonstate.edu OI Whipps, Christopher/0000-0001-6139-0426 FU NIEHS NIH HHS [P30 ES000210, P30 ES000210-38] NR 103 TC 42 Z9 42 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1532-0456 EI 1878-1659 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Toxicol. Pharmacol. PD MAR PY 2009 VL 149 IS 2 SI SI BP 240 EP 248 DI 10.1016/j.cbpc.2008.08.001 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA 419NG UT WOS:000264225700016 PM 18755294 ER PT J AU Resnik, DB AF Resnik, David B. TI Do informed consent documents matter? SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Informed consent; Ethics; Law; Documentation ID FORMS AB This commentary argues that. despite extensive critiques of informed consent documents. there are several ethical and legal reasons for investigators and IRB members to take these documents seriously. Published by Elsevier Inc. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU NIEHS/NIH FX This research was supported by the intramural program of the NIEHS/NIH. It does not represent the views of the NIEHS or NIH. I wish to thank Jerry Menikoff for helpful ideas and discussions. NR 8 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAR PY 2009 VL 30 IS 2 BP 114 EP 115 DI 10.1016/j.cct.2008.10.004 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 422YV UT WOS:000264464500003 PM 18977313 ER PT J AU Barbera, MD Brubaker, L Menefee, S Norton, P Borello-France, D Varner, E Schaffer, J Weidner, A Xu, X Spino, C Weber, A AF Barbera, Matthew D. Brubaker, Linda Menefee, Shawn Norton, Peggy Borello-France, Diane Varner, Edward Schaffer, Joseph Weidner, Alison Xu, Xiao Spino, Cathie Weber, Anne CA Pelvic Floor Disorders Network TI Operations and pelvic muscle training in the management of apical support loss (OPTIMAL) trial: Design and methods SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Pelvic organ prolapse; Vaginal prolapse; Uterine prolapse; Stress urinary incontinence; Randomized surgical trial; Factorial design; Pelvic floor muscle training; Behavioral therapy; Sacrospinous ligament fixation; Uterosacral ligament suspension ID VAGINAL VAULT PROLAPSE; SACROSPINOUS LIGAMENT SUSPENSION; STRESS URINARY-INCONTINENCE; RANDOMIZED CLINICAL-TRIALS; FASCIA DEFECT REPAIR; QUALITY-OF-LIFE; ORGAN PROLAPSE; UNITED-STATES; CONSERVATIVE TREATMENT; FLOOR DYSFUNCTION AB The primary aims of this trial are: 1) to compare surgical outcomes following sacrospinous ligament fixation to uterosacral vaginal vault suspension in women undergoing vaginal surgery for apical or uterine pelvic organ prolapse and stress urinary incontinence and 2) to examine the effects of a structured perioperative program consisting of behavioral techniques and pelvic floor muscle training compared to usual care. This trial is performed through the Pelvic Floor Disorders Network (PFDN), which is funded by National Institute of Child Health and Human Development. Subjects will be enrolled from hospitals associated with seven PFDN clinical centers across the United States. A centralized biostatistical coordinating center will oversee data collection and analysis. Two approaches will be investigated simultaneously using a 2 x 2 randomized factorial design: a surgical intervention (sacrospinous ligament fixation versus uterosacral vaginal vault suspension) and a perioperative behavioral intervention (behavioral and pelvic floor muscle training versus usual care). Surgeons have standardized essential components of each surgical procedure and have met specific standards of expertise. Providers of the behavioral intervention have undergone standardized training. Anatomic. functional, and health-related quality of life outcomes will be assessed using validated measures by researchers blinded to all randomization assignments. Cost-effectiveness analysis will be performed using prospectively collected data on health care costs and resource utilization. The primary surgical endpoint is a composite outcome defined by anatomic recurrence, recurrence of bothersome vaginal prolapse symptoms and/or retreatment and will be assessed 2 years after the index surgery. Endpoints for the behavioral intervention include both short-term (6-month) improvement in urinary symptoms and long-term (2-year) improvement in anatomic outcomes and prolapse symptoms. This article describes the rationale and design of this randomized trial, focusing on several key design features of potential interest to researchers in the field of female pelvic floor disorders and others conducting randomized surgical trials. (C) 2008 Elsevier Inc. All rights reserved. C1 [Barbera, Matthew D.] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44195 USA. [Brubaker, Linda] Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Brubaker, Linda] Loyola Univ, Dept Urol, Chicago, IL 60611 USA. [Menefee, Shawn] Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA. [Norton, Peggy] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Borello-France, Diane] Duquesne Univ, Dept Phys Therapy, Pittsburgh, PA 15219 USA. [Varner, Edward] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Schaffer, Joseph] Univ Texas SW, Dept Obstet & Gynecol, Dallas, TX USA. [Weidner, Alison] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA. [Xu, Xiao; Spino, Cathie] Univ Michigan, Data Coordinating Ctr, Ann Arbor, MI 48109 USA. [Weber, Anne] NICHHD, Bethesda, MD 20892 USA. RP Barbera, MD (reprint author), Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, 9500 Euclid Ave,A81, Cleveland, OH 44195 USA. EM barberm2@ccf.org FU National institute of Child Health and Human Development; NIH Office of Research on Women's Health [U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, U10 HD54241] FX Grant support: supported by grants from the National institute of Child Health and Human Development and the NIH Office of Research on Women's Health (U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, and U10 HD54241). NR 74 TC 15 Z9 15 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAR PY 2009 VL 30 IS 2 BP 178 EP 189 DI 10.1016/j.cct.2008.12.001 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 422YV UT WOS:000264464500013 PM 19130903 ER PT J AU Cao, XF Plasencia, C Kanzaki, A Yang, A Burke, TR Neamati, N AF Cao, Xuefei Plasencia, Carmen Kanzaki, Atsuko Yang, Austin Burke, Terrence R., Jr. Neamati, Nouri TI Elucidation of the Molecular Mechanisms of a Salicylhydrazide Class of Compounds by Proteomic Analysis SO CURRENT CANCER DRUG TARGETS LA English DT Review ID NERVE GROWTH-FACTOR; PROTEIN-KINASE-A; HIV-1 INTEGRASE; CELL-LINES; CONTAINING INHIBITORS; SIGNALING PATHWAY; ANTICANCER DRUGS; APOPTOSIS; CANCER; ACTIVATION AB Previously, we described a series of salicylhydrazide compounds with potent anti-cancer activities against a panel of human cancer cell lines derived from different origins. Preclinical evaluation showing efficacy both in vitro and in vivo in human cancer models indicated that these agents may represent a promising class of anticancer drugs. In the present study, we performed an in-depth investigation on the underlying molecular mechanisms of the most potent compounds, SC21 and SC23, using a proteomic method and bioinformatics tools. We demonstrated that SC23 induced apoptosis through multiple signaling pathways. In particular, SC23 regulated the expression of Bcl-2, p21, acetylated histone H3 and beta-tubulin and the combined modulation of these proteins may result in the induction of apoptosis. We also examined the effect of SC21 and SC23 on cell cycle progression and found that both compounds arrested cells in S-phase in most cell lines tested. To better understand the signaling networks involved, we analyzed the SC21- and SC23-treated cell lysates by the Kinexus (TM) 628 antibody microarray. The results were interpreted with the aid of Ingenuity Pathway Analysis (IPA) software. It was found that SC21 interfered with JAK/STAT signaling and elicited apoptosis through Fas and caspases pathways. Unlike SC21, SC23 induced RAR activation and caused cell cycle arrest. The signaling networks identified by this work may provide the basis for future mechanistic studies. The validation of the proposed pathways and the elucidation of the signaling cross-talk are currently under way. C1 [Cao, Xuefei; Plasencia, Carmen; Kanzaki, Atsuko; Neamati, Nouri] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA. [Yang, Austin] Univ Maryland, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Burke, Terrence R., Jr.] NIH, Med Chem Lab, Ctr Canc Res, Frederick, MD USA. RP Neamati, N (reprint author), Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. EM neamati@usc.edu RI Burke, Terrence/N-2601-2014 FU Susan G. Komen Breast Cancer Foundation; American Lung Association to NN; Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick FX This work was supported by funds from the Susan G. Komen Breast Cancer Foundation and the American Lung Association to NN and the work in TRB's laboratory was supported by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick. NR 55 TC 6 Z9 6 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD MAR PY 2009 VL 9 IS 2 BP 189 EP 201 PG 13 WC Oncology SC Oncology GA 431WZ UT WOS:000265096800007 PM 19275759 ER PT J AU Zecavati, N Spence, SJ AF Zecavati, Nassim Spence, Sarah J. TI Neurometabolic disorders and dysfunction in autism spectrum disorders SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review ID SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; DEVELOPMENTAL REGRESSION; BIOTINIDASE DEFICIENCY; LIPID-PEROXIDATION; FOLATE-DEFICIENCY; CHILDREN; DISEASE; ABNORMALITIES AB The cause of autism remains largely unknown because it is likely multifactorial, arising from the interaction of biologic, genetic, and environmental factors. The specific role of metabolic abnormalities also is largely unknown, but current research may provide insight into the pathophysiologic underpinnings of autism, at least in some patients. We review a number of known neurometabolic disorders identified as having an autistic phenotype. We also discuss the possible involvement of mitochondrial disorders and dysfunction as well as a theory regarding an increased vulnerability to oxidative stress, by which various environmental toxins produce metabolic alterations that impair normal cellular function. Finally, we review various strategies for metabolic work-up and treatment. Accurate diagnosis of neurometabolic disorders and a broader understanding of underlying metabolic disturbance even in the absence of known disease have important implications both for individual patients and for research into the etiology of autism. C1 [Zecavati, Nassim; Spence, Sarah J.] NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Spence, SJ (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, 10 Ctr Dr,MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM spences2@mail.nih.gov NR 42 TC 51 Z9 52 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD MAR PY 2009 VL 9 IS 2 BP 129 EP 136 DI 10.1007/s11910-009-0021-x PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 416YO UT WOS:000264041600005 PM 19268036 ER PT J AU Gills, JJ Dennis, PA AF Gills, Joell J. Dennis, Phillip A. TI Perifosine: Update on a Novel Akt Inhibitor SO CURRENT ONCOLOGY REPORTS LA English DT Article ID PHASE-II TRIAL; MYELOGENOUS LEUKEMIA-CELLS; JNK-DEPENDENT MECHANISM; MULTIPLE-MYELOMA CELLS; PROSTATE-CANCER CELLS; SOFT-TISSUE SARCOMA; LIPID RAFTS; ALKYLPHOSPHOLIPID PERIFOSINE; ANTICANCER ALKYLPHOSPHOLIPIDS; COMBINATION TREATMENT AB The PI3K/Akt/mTOR pathway is aberrantly active in most human cancers and contributes to cell growth, proliferation, and survival. Akt is a nodal regulator of cellular survival pathways and an attractive target in cancer therapy. Many inhibitors of Akt are being developed. Perifosine is an oral Akt inhibitor currently being tested in phase 2 clinical trials. Unlike most kinase inhibitors, which target the adenosine triphosphate-binding region, perifosine targets the pleckstrin homology domain of Akt, thereby preventing its translocation to the plasma membrane. Single-agent activity with perifosine has been observed in sarcoma and Waldenstrom macroglobulinemia patients. However, the disappointing response rates of common solid tumors to perifosine as a single agent have diminished expectations and prompted further investigation into its mechanism of action. Perifosine exerts Akt-dependent and Akt-independent effects, and although many preclinical studies have documented Akt inhibition by perifosine, clinical validation of these findings is lacking. In this article, we review the clinical history of perifosine and discuss its many biologic activities. C1 [Dennis, Phillip A.] Natl Canc Inst, Med Oncol Branch, NNMC, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), Natl Canc Inst, Med Oncol Branch, NNMC, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 62 TC 133 Z9 141 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD MAR PY 2009 VL 11 IS 2 BP 102 EP 110 PG 9 WC Oncology SC Oncology GA V16BB UT WOS:000207844000004 PM 19216841 ER PT J AU Chen, WZ Dimitrov, DS AF Chen, Weizao Dimitrov, Dimiter S. TI Human monoclonal antibodies and engineered antibody domains as HIV-1 entry inhibitors SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE domain antibody; HIV-1; human; monoclonal antibody; neutralization AB Purpose of review To summarize the in-vivo efficacy of neutralizing human monoclonal antibodies against HIV-1, to discuss the recent finding that an engineered human antibody V(H) domain, domain antibody (dAb), exhibits exceptionally potent and broadly cross-reactive neutralizing activity against HIV-1 primary isolates by targeting a hidden conserved epitope that is not accessible by larger antibodies and to suggest the possibility of developing a novel class of potent HIV-1 inhibitors based on human dAbs. Recent findings HIV-1 has evolved a number of strategies to evade humoral immunity, including protecting highly conserved and important structures from the access of antibodies generated by the immune system. We have recently demonstrated that a human dAb (size similar to 15 kDa), m36, targets a highly protected structure on the HIV-1 envelope glycoprotein (Env), gp120, and exhibits exceptionally potent neutralizing activity against HIV-1 primary isolates, with potency on average higher than those of the broadly cross-reactive neutralizing human monoclonal antibody, scFv m9, and the inhibitory peptide, C34. Summary The efficacy of the anti-HIV-1 therapy is significantly compromised by resistance to the currently used US Food and Drug Administration-approved antiretroviral drugs, which suggests an urgent need to develop novel classes of potent inhibitors. Several broadly cross-reactive neutralizing human monoclonal antibodies are highly effective against HIV-1 infection in vitro, but their administration to HIV-1-infected humans has only resulted in modest antiviral effects. Engineered human antibody fragments, dAbs, could be more potent because of their small size (about 10-fold smaller than that of an IgG), which allows targeting of highly conserved structures on the HIV-1 envelope glycoprotein that are not accessible by full-size antibodies and relatively efficient penetration into the densely packed lymphoid environment in which HIV-1 mostly replicates and spreads. C1 [Chen, Weizao; Dimitrov, Dimiter S.] NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. RP Chen, WZ (reprint author), NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 469,Room 144, Frederick, MD 21702 USA. EM chenw@ncifcrf.gov FU National Institute of Health (NIH); NIH, National Cancer Institute, Center for Cancer Research; Gates Foundation FX We thank Dr Zhongyu Zhu in our group for helpful discussion and John Owens for technical assistance. This research was supported by the Intramural AIDS Targeted Antiviral Program of the National Institute of Health (NIH), by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by the Gates Foundation (Dimiter S. Dimitrov). NR 45 TC 17 Z9 19 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAR PY 2009 VL 4 IS 2 BP 112 EP 117 DI 10.1097/COH.0b013e328322f95e PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V19OZ UT WOS:000208083000006 PM 19339949 ER PT J AU Wu, XS Lee, VC Chevalier, E Hwang, ST AF Wu, Xuesong Lee, Vivian C. Chevalier, Eric Hwang, Sam T. TI Chemokine Receptors as Targets for Cancer Therapy SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID LYMPH-NODE METASTASIS; CELL LUNG-CANCER; CHRONIC LYMPHOCYTIC-LEUKEMIA; LIGAND BIOLOGICAL AXIS; HUMAN BREAST-CANCER; REGULATORY T-CELLS; B16 TUMOR-CELLS; IN-VIVO; DENDRITIC CELLS; STROMAL FIBROBLASTS AB Chemokines and their receptors play critical roles in leukocyte trafficking during inflammatory processes. Although the role of chemokine receptors (CKRs) in cancer biology is a relatively new field of study, a growing body of data suggest that a number of CKRs, including CXCR4, CCR4, CCR7, and CCR10, may play diverse of roles in cancer growth, cancer metastasis, cancer angiogenesis, or the composition of the cancer microenvironment. Preclinical models of cancer indicate that cancer antagonists, most notably those for CXCR4, can block cancer growth either directly or by altering the cancer stroma. Highthroughput screening methods to identify effective CKR antagonists have been developed, but specificity, potency, and drug-delivery of validated candidate compounds remain issues that result in the clinical failure of many initially promising candidates. The recent approval of a CCR5 receptor antagonist in HIV suggests that safe, effective small molecular antagonists for other CKRs may not be far away. There is still a clear need to extend our understanding of the signalling pathways by which CKRs facilitate cancer processes. Because of the role of CKRs in cancer cell survival, the combination of CKR antagonists with traditional chemotoxic agents or with immunotherapy is an alluring strategy since this increases the specificity of treatment to the cancer and potentially limits additional systemic side effects. C1 [Wu, Xuesong; Lee, Vivian C.; Hwang, Sam T.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. [Chevalier, Eric] Polyphor Ltd, CH-4123 Allschwil, Switzerland. RP Hwang, ST (reprint author), Med Coll Wisconsin, Dept Dermatol, Froedtert Clin, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM sthwang@mcw.edu NR 143 TC 58 Z9 60 U1 3 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAR PY 2009 VL 15 IS 7 BP 742 EP 757 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 415VI UT WOS:000263963800003 PM 19275640 ER PT J AU Rizzo, K Stetler-Stevenson, M Wilson, W Yuan, CM AF Rizzo, Kathryn Stetler-Stevenson, Maryalice Wilson, Wyndham Yuan, Constance M. TI Novel CD19 Expression in a Peripheral T Cell Lymphoma: A Flow Cytometry Case Report with Morphologic Correlation SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE CD19; peripheral T-cell lymphoma; immunophenotyping; PTCL-NOS; aberrant expression; flow cytometry ID RARE EXPRESSION; LEUKEMIA; MARKERS; CD79A; PAX5 AB Background: Peripheral T-cell lymphomas are uncommon lymphomas that show T-cell antigenic loss and clonal T-cell receptor (TCR) gene rearrangement. Rare cases of T-cell lymphomas with aberrant expression of CD20 have been described. However, CD19 coexpression in a mature T-cell neoplasm has not been reported. Methods: Histology, immunohistochemistry (IHC), and PCR for TCR gene rearrangement were performed on an excised lymph node specimen and a subsequent fine needle aspiration (FNA) of an additional lymph node. Flow cytometry (FC) was performed on FNA and peripheral blood specimen. Results: The lymph node's architecture was effaced by a diffuse atypical lymphoid proliferation that, by IHC, was positive for CD3, CD2, and CD43 and negative for CD4, CD5, CD8, TdT, CD1a, and B-cell-associated antigens PAX-5, CD20, and CD79a. A clonal TCR gene rearrangement was detected. FIG was performed on a subsequent FNA, and peripheral blood specimen demonstrated an aberrant T-cell population with expression of CD2, CD3, CD27, TCR alpha/beta, CD52, CD38, CD45, and CD26 (partial expression) and negative for CD4, CD5, CD7, CD8, CD10, CD30, and CD56. The aberrant T-cell population also expressed bright CD19. Conclusions: Using FC, we describe the first case of peripheral T-cell lymphoma with aberrant coexpression of CD19. Published 2008 Wiley-Liss, Inc. C1 [Rizzo, Kathryn; Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Flow Cytometry Unit, Pathol Lab, NIH, Bethesda, MD USA. [Wilson, Wyndham] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD USA. RP Yuan, CM (reprint author), 10 Ctr Dr,Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yuanc@mail.nih.gov FU NIH, National Cancer (Institute Intramural Research Program) FX Grant sponsor: NIH, National Cancer (Institute Intramural Research Program). NR 13 TC 7 Z9 7 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAR PY 2009 VL 76B IS 2 BP 142 EP 149 DI 10.1002/cyto.b.20442 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 412WP UT WOS:000263755200010 PM 18671252 ER PT J AU Hivert, MF Manning, AK McAteer, JB Dupuis, J Fox, CS Cupples, LA Meigs, JB Florez, JC AF Hivert, Marie-France Manning, Alisa K. McAteer, Jarred B. Dupuis, Josee Fox, Caroline S. Cupples, L. Adrienne Meigs, James B. Florez, Jose C. TI Association of Variants in RETN With Plasma Resistin Levels and Diabetes-Related Traits in the Framingham Offspring Study SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; ADIPOSE-TISSUE; SERUM RESISTIN; METABOLIC SYNDROME; GENE POLYMORPHISM; MESSENGER-RNA; G/G GENOTYPE; TYPE-2; OBESITY; PROMOTER AB OBJECTIVE-The RETN gene encodes the adipokine resistin. Associations of RETN with plasma resistin levels, type 2 diabetes, and related metabolic traits have been inconsistent. Using comprehensive linkage disequilibrium mapping, we genotyped tag single nucleotide polymorphisms (SNPs) in RETN and tested associations with plasma resistin levels, risk of diabetes, and glycemic traits. RESEARCH DESIGN AND METHODS-We examined 2,531 Framingham Offspring Study participants for resistin levels, glycemic phenotypes, and incident diabetes over 28 years of follow-up. We genotyped 21 tag SNPs that capture common (minor allele frequency >0.05) or previously reported SNPS at r(2) > 0.8 across RETN and its flanking regions. We used sex- and age-adjusted linear mixed-effects models (with/without BMI adjustment) to test additive associations of SNPs with traits, adjusted Cox proportional hazards models accounting for relatedness for incident diabetes, and generated empirical P values (P(e) to control for type I error. RESULTS-Four tag SNPs (rs1477341, rs4804765, rs1423096, and rs10401670) on the 3' side of RETN were strongly associated with resistin levels (all minor alleles associated with higher levels, P(e)<0.05 after multiple testing correction). rs10401670 was also associated with fasting plasma glucose (P(e) = 0.02, BMI adjusted) and mean glucose over follow-up (P(e) = 0.01; BMI adjusted). No significant association was observed for adiposity traits. On meta-analysis, the previously reported association of SNP -420C/G (rs1862513) with resistin levels remained significant (P = 0.0009) but with high heterogeneity across studies (P < 0.0001). CONCLUSIONS-SNPs in the 3' region of RETN are associated with resistin levels, and one of them is also associated with glucose levels, although replication is needed. Diabetes 58: 750-756, 2009 C1 [Hivert, Marie-France; Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Manning, Alisa K.; Dupuis, Josee; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Dept Med, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [McAteer, Jarred B.; Florez, Jose C.] MIT, Cambridge, MA 02139 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Florez, JC (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM jcflorez@partners.org OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC25195]; National Institutes of Health (NIH); National Center for Research Resources (NCRR); General Clinical Research Centers Program [M01-RR-01066]; American Diabetes Association Career Development Award; sanofi-aventis; Boston University; Centre de Recherche Medicale de I'Universite de Sherbrooke (CRMUS); Canadian Institute of Health Research (CHIR); National Institute of Diabetes and Digestive and Kidney Disease [K24 DKO80140]; [ISlORRI63736-01A1]; [K23 DK65978-05] FX Supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC25195); the National Institutes of Health (NIH), National Center for Research Resources (NCRR), General Clinical Research Centers Program (grant no. M01-RR-01066); an American Diabetes Association Career Development Award (to J.B.Me.); a research grant from sanofi-aventis (to J.B.Me.); and the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the NIH NCRR Shared Instrumentation Grant (ISlORRI63736-01A1). M.-F.H. is supported by the Centre de Recherche Medicale de I'Universite de Sherbrooke (CRMUS) and a Canadian Institute of Health Research (CHIR) Fellowships Health Professional Award. J.B.Me. is also supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant K24 DKO80140. J.C.F. is supported by NIH Research Career Award K23 DK65978-05. NR 40 TC 38 Z9 40 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2009 VL 58 IS 3 BP 750 EP 756 DI 10.2337/db08-1339 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 414FE UT WOS:000263848500032 PM 19074981 ER PT J AU Pou, KM Massaro, JM Hoffmann, U Lieb, K Vasan, RS O'Donnell, CJ Fox, CS AF Pou, Karia M. Massaro, Joseph M. Hoffmann, Udo Lieb, Kathrin Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Patterns of Abdominal Fat Distribution The Framingham Heart Study SO DIABETES CARE LA English DT Article ID VISCERAL ADIPOSE-TISSUE; BODY-FAT; WAIST CIRCUMFERENCE; METABOLIC RISK; US ADULTS; WOMEN; OBESITY; MEN; ASSOCIATION; PROFILE AB OBJECTIVE - The prevalence of abdominal obesity exceeds that of general obesity. We sought to determine the prevalence of abdominal subcutaneous and visceral obesity and to characterize the different patterns of fat distribution in a community-based sample. RESEARCH DESIGN AND METHODS - Participants from the Framingham Heart Study (n = 3,348, 48% women, mean age 52 years) underwent multidetector computed tomography; Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were assessed. Sex-specific high SAT and VAT definitions were based on 90th percentile cut points from a healthy referent sample. Metabolic risk factors were examined in subgroups with elevated SAT and VAT. RESULTS - The prevalence of high SAT was 30% (women) and 31% (men) and that for high VAT was 44% (women) and 42% (men). Overall, 27.8% of the sample was discordant for high SAT and high VAT: 19.9% had SAT less than but VAT equal to or greater than the 90th percentile, and 7.9% had SAT greater than but VAT less than the 90th percentile. The prevalence of metabolic syndrome was higher among women and men with SAT less than the 90th percentile and high VAT than in those with high SAT but VAT less than the 90th percentile, despite lower BMI and waist circumference. Findings were similar for hypertension, elevated triglycerides, and low HDL cholesterol. CONCLUSIONS - Nearly one-third of our sample has abdominal subcutaneous obesity, and >40% have visceral obesity. Clinical measures of BMI and waist circumference may misclassify individuals in terms of VAT and metabolic risk. C1 [Pou, Karia M.; Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Pou, Karia M.; Hoffmann, Udo; O'Donnell, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Massaro, Joseph M.] Sch Publ Hlth, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lieb, Kathrin; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framington Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Fox, CS (reprint author), Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, 75 Francis St, Boston, MA 02115 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195]; NHLBI/National Institutes of Health [2K24HL04334] FX No potential conflicts of interest relevant to this article were reported. NR 19 TC 75 Z9 86 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2009 VL 32 IS 3 BP 481 EP 485 DI 10.2337/dc08-1359 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 417EX UT WOS:000264060400022 PM 19074995 ER PT J AU Molenaar, EA Massaro, JM Jacques, PF Pou, KM Ellison, RC Hoffmann, U Pencina, K Shadwick, SD Vasan, RS O'Donnell, CJ Fox, CS AF Molenaar, Esther A. Massaro, Joseph M. Jacques, Paul F. Pou, Karia M. Ellison, R. Curtis Hoffmann, Udo Pencina, Karol Shadwick, Steven D. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Association of Lifestyle Factors With Abdominal Subcutaneous and Visceral Adiposity SO DIABETES CARE LA English DT Article ID CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; BODY-FAT; WAIST CIRCUMFERENCE; ALCOHOL-CONSUMPTION; CONTROLLED-TRIAL; WOMEN; MEN; FRAMINGHAM; RISK AB OBJECTIVE - The purpose of this study was to assess the relationship between lifestyle factors and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in a community-based setting. RESEARCH DESIGN AND METHODS - Cross-sectional associations between lifestyle factors (dietary quality, physical activity, smoking, and alcohol consumption) and SAT and VAT volumes were examined in 2,920 Framingham Heart Study participants (48.6% women, aged 50 +/- 10 years). RESULTS - Diets consistent wit lithe 200 5 Dietary Guidelines Adherence Index and greater physical activity were inversely associated with SAT and VAT (P < 0.0001-0.002). In men, former smoking was associated with higher SAT (2,743 +/- 56 cm(3)) compared with current smokers (2,629 +/- 88 cm(3)) or those who never smoked (2,538 +/- 44 cm(3); P = 0.02). Both former and current smoking was associated with higher VAT (P = 0.03 [women]; P = 0.005 [men]). Women with high amounts of alcohol intake (>7 drinks/week) had lower SAT (2,869 +/- 106 cm(3)) than those who consumed less alcohol (3,184 +/- 44 cm(3), P = 0.006); significant differences in VAT were not observed (P = 0.18). In men, high amounts of alcohol intake (>14 drinks/week) were associated with higher VAT (2,272 +/- 59 cm(3)) compared with intake of <= 14 drinks/week (2,139 +/- 25 cm(3), P = 0.04), wlicicas SAT did not differ (P = 0.91). An increasing number of healthy lifestyle factors were associated with lower SAT and VAT volumes (all P < 0.003). CONCLUSIONS - Adherence to recommended dietary guidelines and physical activity ire associated with lower SAT and VAT volumes. However, both smoking and high alcohol intake arc differentially associated with VAT volumes. Further research to uncover the putative mechanisms is warranted. C1 [Pou, Karia M.; Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Pou, Karia M.; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Molenaar, Esther A.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Molenaar, Esther A.] Municipal Hlth Serv Utrecht, Utrecht, Netherlands. [Massaro, Joseph M.; Pencina, Karol] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Jacques, Paul F.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Cardiol & Prevent Med, Boston, MA 02215 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac Magnet Resonace Positron Tomog Comp Tomog, Boston, MA 02114 USA. [Shadwick, Steven D.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Bramingham Heart Study, Bramingham, MA USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Fox, CS (reprint author), Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, 75 Francis St, Boston, MA 02115 USA. EM loxca@nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute (NHLBI) [(N01-HC-25195), 2K24 HL 04334]; Netherlands Organization for Scientific Research; Dutch Heart Foundation FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (NHLBI) (N01-HC-25195). E.A.M. is supported by the Netherlands Organization for Scientific Research and the Dutch Heart Foundation. R.S.V. is supported in part by 2K24 HL 04334 (NHLBI). NR 25 TC 48 Z9 50 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2009 VL 32 IS 3 BP 505 EP 510 DI 10.2337/dc08-1382 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 417EX UT WOS:000264060400026 PM 19074991 ER PT J AU Bell, RA Mayer-Davis, EJ Beyer, JW D'Agostino, RB Lawrence, JM Linder, B Liu, LL Marcovina, SM Rodriguez, BL Williams, D Dabelea, D AF Bell, Ronny A. Mayer-Davis, Elizabeth J. Beyer, Jennifer W. D'Agostino, Ralph B., Jr. Lawrence, Jean M. Linder, Barbara Liu, Lenna L. Marcovina, Santica M. Rodriguez, Beatriz L. Williams, Desmond Dabelea, Dana CA SEARCH Diabet Youth Study Grp TI Diabetes in Non-Hispanic White Youth Prevalence, incidence, and clinical characteristics: the SEARCH for Diabetes in Youth Study SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR-DISEASE RISK; CHILDHOOD TYPE-1; AMERICAN CHILDREN; YOUNG-ADULTS; MELLITUS; ADOLESCENTS; WORLDWIDE; TRENDS; UK; EPIDEMIOLOGY AB OBJECTIVE - To investigate the incidence, prevalence, and clinical characteristics of diabetes among U.S. non-Hispanic white (NHW) youth. RESEARCH DESIGN AND METHODS - Data from the SEARCH for Diabetes in Youth Study (SEARCH study), a multicenter study of diabetes among youth aged 0-19 years, were examined. Incidence rates were calculated per 100,000 person-years across 4 incident years (2002-2005), and prevalence in 2001 was calculated per 1,000 youths. Information obtained by questionnaire, physical examination, and blood and urine Collection was analyzed to describe the characteristics of youth who completed an in-person visit. RESULTS - The prevalence of type 1 diabetes (at ages 0-19 years) was 2.00/1,000, which was similar for male (2.02/1,000) and female (1.97/1,000) Subjects. The incidence of type I diabetes was 23.6/100,000, slightly higher for male compared with female subjects (24.5 vs. 22.7 per 100,000, respectively, P = 0.04). Incidence rates of type I diabetes among youth aged 0-14 years in the SEARCH study are higher than all previously reported U.S. Studies and many European studies. Few cases Of type 2 diabetes in youth aged <10 years were found. The prevalence of type 2 diabetes (at ages 10-19 years) was 0.18/1,000, which is significantly higher for female compared with male subjects (0.22 vs. 0.15 per 1,000, P = 0.01). Incidence of type 2 diabetes was 3.7/100,000, With similar rates for female and male subjects (3.9 vs. 3.4 per 1,000, respectively, P = 0.3). High levels of abnormal cardiometabolic and behavioral risk factor profiles were common among youth With both type I and type 2 diabetes. For example, within each of four age-groups for youth With type 1 diabetes and two age-groups for youth with type 2 diabetes, >40% had elevated LDL cholesterol, and <3% of youth aged >10 years met current recommendations for intake of saturated fat. Among youth aged >= 15 years, 1.8% with type I and 26% with type 2 diabetes were current smokers. CONCLUSIONS - The SEARCH study is one of the most comprehensive studies of diabetes in NHW youth. The incidence of type I diabetes in NHW youth in the U.S. is one of the highest in the world. While type 2 diabetes is still relatively rare, rates are several-fold higher than those reported by European countries. We believe efforts directed at improving the cardiometabolic and behavioral risk factor profiles in this population are warranted. Diabetes Care 32 (Suppl. 2):S102-S111, 2009 C1 [Bell, Ronny A.; Beyer, Jennifer W.; D'Agostino, Ralph B., Jr.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Mayer-Davis, Elizabeth J.] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. [Mayer-Davis, Elizabeth J.] Univ S Carolina, Ctr Res Nutr & Hlth Dispar, Columbia, SC 29208 USA. [Mayer-Davis, Elizabeth J.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Linder, Barbara] NIDDK, NIH, Bethesda, MD USA. [Liu, Lenna L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Marcovina, Santica M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Rodriguez, Beatriz L.] Pacific Hlth Res Inst, Honolulu, HI USA. [Williams, Desmond] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Dabelea, Dana] Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. RP Bell, RA (reprint author), Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. EM rbell@wfubmc.edu RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU Centers for Disease Control and Prevention [00097, DP-05-069]; National Institute of Diabetes and Digestive and Kidney Diseases; Kaiser Permanente Southern California [U01 DP000246]; University of Colorado Health Sciences Center [U01 DP000247]; Pacific Health Research Institute [U01 DP000245]; Children's Hospital Medical Center (Cincinnati) [U01 DP000248]; University of North Carolina [U01 DP000254]; University of Washington School of Medicine [U01 DP000244, M01RR00037, M01RR001271]; Wake Forest University School of Medicine [U01 DP000250]; Medical University of South Carolina [M01 RR01070]; Cincinnati Children's Hospital [M01 RR08084]; Children's Hospital and Regional Medical Center; Colorado Pediatric General Clinical Research Center [M01 RR00069] FX The SEARCH for Diabetes in Youth Study is funded by the Centers for Disease Control and Prevention (PA no. 00097 and DP-05-069) and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Site contract numbers are as follows: Kaiser Permanente Southern California (U01 DP000246), the University of Colorado Health Sciences Center (U01 DP000247), the Pacific Health Research Institute (U01 DP000245), the Children's Hospital Medical Center (Cincinnati) (U01 DP000248), the University of North Carolina (U01 DP000254), the University of Washington School of Medicine (U01 DP000244), and the Wake Forest University School of Medicine (U01 DP000250). The authors acknowledge the involvement of general clinical research centers at the following institutions in the SEARCH for Diabetes in Youth Study: the Medical University of South Carolina (grant no. M01 RR01070), Cincinnati Children's Hospital (grat no. M01 RR08084),Children's Hospital and Regional Medical Center and the University of Washington School of Medicine (grant nos. M01RR00037 and M01RR001271), and the Colorado Pediatric General Clinical Research Center (grant no. M01 RR00069).; No potential conflicts of interest relevant to this article were reported.; The SEARCH study is indebted to the many youth and their families and their health care providers, whose participation made this study possible. NR 52 TC 87 Z9 92 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2009 VL 32 SU 2 BP S102 EP S111 DI 10.2337/dc09-S202 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 417EZ UT WOS:000264060600002 PM 19246575 ER PT J AU Koska, J Ortega, E Bunt, JC Gasser, A Impson, J Hanson, RL Forbes, J de Courten, B Krakoff, J AF Koska, J. Ortega, E. Bunt, J. C. Gasser, A. Impson, J. Hanson, R. L. Forbes, J. de Courten, B. Krakoff, J. TI The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study SO DIABETOLOGIA LA English DT Article DE Clinical science; Cytokines; Human; Insulin sensitivity and resistance; Prediction and prevention of type 2 diabetes ID NF-KAPPA-B; DIABETES-MELLITUS; PIMA-INDIANS; IKK-BETA; ACETYLSALICYLIC-ACID; PLASMA-GLUCOSE; IMMUNE-SYSTEM; IN-VIVO; RESISTANCE; SALICYLATE AB Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI a parts per thousand yenaEuro parts per thousand 30 kg/m(2). The intervention was salsalate (3 g/day, n = 28) or identical placebo (n = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal (R (d)) by euglycaemic-hyperinsulinaemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) and glucose tolerance by 75 g OGTT. The study was completed by 47 participants, of which 40 were analysed (salsalate n = 22, placebo n = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p = 0.001) and glucose AUC during the OGTT (p = 0.01), and in increased R (d) (20 [8] vs 18 [6] A mu mol [kg estimated metabolic body size](-1) min(-1), p = 0.002), while there was no significant change in these variables with placebo (p > 0.3 for all). The effect of salsalate on R (d) disappeared (p = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p < 0.0001) measured during the clamp. No side effects of salsalate were observed during the study. The glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes. Trial registration: ClinicalTrials.gov NCT 00339833. Funding: Intramural research programme of the NIDDK/NIH/DHHS. C1 [Koska, J.; Ortega, E.; Bunt, J. C.; Impson, J.; Hanson, R. L.; de Courten, B.; Krakoff, J.] NIDDK, Obes & Diabet Clin Res Sect, NIH, DHHS, Phoenix, AZ USA. [Gasser, A.; Forbes, J.; de Courten, B.] Baker Heart Res Inst, Melbourne, Vic, Australia. [Gasser, A.; Forbes, J.; de Courten, B.] Int Diabet Inst, Melbourne, Vic, Australia. RP Koska, J (reprint author), NIDDK, Obes & Diabet Clin Res Sect, NIH, DHHS, 4212 N 16th St, Phoenix, AZ USA. EM koskaj@mail.nih.gov RI Forbes, Josephine/A-4569-2012; Hanson, Robert/O-3238-2015; OI Forbes, Josephine/0000-0002-5595-8174; Hanson, Robert/0000-0002-4252-7068; de Courten, Barbora/0000-0001-8760-2511 FU National Institute of Diabetes and Digestive and Kidney Diseases FX We acknowledge P. A. Tataranni for an important contribution to study design and initiation, T. Brookshire and the nursing and dietary staffs for the care of the volunteers, and B. Anthony, S. Parrington and E. Spencer for excellent laboratory assistance. We also thank our study participants and members of the Gila River Indian Community. The study was funded by intramural programme of The National Institute of Diabetes and Digestive and Kidney Diseases. NR 37 TC 66 Z9 67 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2009 VL 52 IS 3 BP 385 EP 393 DI 10.1007/s00125-008-1239-x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 403HB UT WOS:000263072600002 PM 19104769 ER PT J AU Archer, KJ Mas, VR O'Brien, TR Pfeiffer, R Lum, NL Fisher, RA AF Archer, Kellie J. Mas, Valeria R. O'Brien, Thomas R. Pfeiffer, Ruth Lum, Nicole L. Fisher, Robert A. TI Quality Assessment of Microarray Data in a Multicenter Study SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE microarray; multicenter study; gene expression; Affymetrix GeneChip; quality ID GENE-EXPRESSION ANALYSIS; PROBE LEVEL DATA; CDNA MICROARRAY; RNA QUALITY; IMPACT; BIOINFORMATICS; NORMALIZATION; DEGRADATION; PLATFORMS; SUMMARIES AB Issues implicit in a multicenter microarray study are protocol standardization and monitoring center adherence to established protocols. This study explored the effects of submitting center and sample preservation method on the quality of isolated RNA. In addition, the effects of sample preservation method and laboratory on microarray quality were also examined. Herein we evaluated the contribution of specific technical factors [center, laboratory, and preservation method (frozen/RNAlater)] on quality of isolated RNA, cRNA synthesis products, and reproducibility of gene expression microarray data for independent biologic samples collected in a multicenter microarray study. The Kruskal-Wallis test was used to test for differences owing to Submitting center on isolated RNA quality. Mixed effects analysis of variance was used in assessing the impact of laboratory and preservation method on gene expression values for the 12 samples hybridized at 2 independent laboratories (24 GeneChips). One center was found to be in violation of the tissue handling protocol. No significant effect was noted owing to preservation method, which ensured that our tissue handling protocols are working properly. There wits a significant laboratory effect with respect to cRNA yield, though this effect did not impact sample quality. We conclude that use of consistent protocols for sample collection, RNA extraction, cDNA/cRNA synthesis, labeling, hybridization, platform, image acquisition, normalization, and expression summaries can yield consistent expression values. Moreover, evaluation of sample quality at various steps in the data acquisition process is an important component of it multicenter study to ensure all participating centers adhere to established protocols. C1 [Archer, Kellie J.; Mas, Valeria R.; Fisher, Robert A.] Virginia Commonwealth Univ, Richmond, VA 23298 USA. [O'Brien, Thomas R.; Pfeiffer, Ruth] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lum, Nicole L.] NCI, Lab Mol Technol, Frederick, MD 21701 USA. RP Archer, KJ (reprint author), Virginia Commonwealth Univ, 730 E Broad St,Theater Row 3-022, Richmond, VA 23298 USA. EM kjarcher@vcu.edu RI Pfeiffer, Ruth /F-4748-2011 FU National Institute of Diabetes and Digestive and Kidney Diseases [IROI-DK069859]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases IROI-DK069859 its well its by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 35 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD MAR PY 2009 VL 18 IS 1 BP 34 EP 43 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 413GN UT WOS:000263781000005 PM 19214110 ER PT J AU Dib, A Glebov, OK Shou, YP Singer, RH Kuehl, WM AF Dib, Amel Glebov, Oleg K. Shou, Yaping Singer, Robert H. Kuehl, W. Michael TI A der(8)t(8;11) chromosome in the Karpas-620 myeloma cell line expresses only Cyclin D1: Yet both Cyclin D1 and MYC are repositioned in close proximity to the 3 ' IGH enhancer SO DNA REPAIR LA English DT Article DE Multiple myeloma; Karpas-620; Translocations; Cyclin D1; MYC; IgH enhancer ID CIRCULAR BINARY SEGMENTATION; ARRAY CGH DATA; MULTIPLE-MYELOMA; TRANSLOCATIONS; IMMUNOGLOBULIN; GENES AB The Karpas-620 human myeloma cell line (HMCL) expresses high levels of Cyclin D1 (CCND1), but has a der(8)t(8;11) and a der(14)t(8;14), and not a conventional t(11;14). Fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) studies suggest that der(14)t(11;14) from a primary translocation underwent a secondary translocation with chromosome 8 to generate der(8)t(8;[14];11) and der(14)t(8;[11];14). Both secondary derivatives share extensive identical sequences from chromosomes 8, 11, and 14, including MYC and the 3' IgH enhancers. Der(14), with MYC located similar to 700 kb telomeric to the 3' IGH enhancer, expresses MYC By contrast, der(8), with both CCND1 and MYC repositioned near a 3' IGH enhancer, expresses CCND1, which is telomeric of the enhancer, but not MYC, which is centromeric to the enhancer. The secondary translocation that dysregulated MYC resulted in extensive regions from both donor chromosomes being transmitted to both derivative chromosomes, suggesting a defect in DNA recombination or repair in the myeloma tumor cell. (C) 2008 Elsevier B.V. All rights reserved. C1 [Dib, Amel; Glebov, Oleg K.; Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, NIH,Bethesda Naval Hosp, Bethesda, MD 20889 USA. [Shou, Yaping] Novartis Inst BioMed Res, Cambridge, MA 02139 USA. [Singer, Robert H.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Albert Einstein Canc Ctr, Bronx, NY 10461 USA. RP Kuehl, WM (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH,Bethesda Naval Hosp, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM wmk@helix.nih.gov FU NIH [CA83208, EB2060]; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research: and NIH grants CA83208 and EB2060 (R.H.S.). The authors would like to acknowledge Leslie Brents for technical contributions, Ana Gabrea for help in preparation of the manuscript, and also Keith Caldecott, James Haber, and Richard Kolodner for helpful discussions. NR 25 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD MAR 1 PY 2009 VL 8 IS 3 BP 330 EP 335 DI 10.1016/j.dnarep.2008.11.010 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 415LC UT WOS:000263934300005 PM 19064000 ER PT J AU Vidal, AE Woodgate, R AF Vidal, Antonio E. Woodgate, Roger TI Insights into the cellular role of enigmatic DNA polymerase iota SO DNA REPAIR LA English DT Article DE Translesion DNA synthesis; Mutagenesis; DNA repair; Oxidative damage; UV-light; Y-family DNA polymerase ID BASE EXCISION-REPAIR; XERODERMA-PIGMENTOSUM; REV1 PROTEIN; IN-VITRO; POL-IOTA; ETA; BYPASS; CELLS; REPLICATION; XRCC1 AB It has been a decade since the discovery of human DNA polymerase iota (pol iota). Since that time, the enzyme has been characterized extensively at the biochemical level, but the cellular function Of pol iota remains enigmatic. Recent studies on pol iota have, however, provided much needed insights into its biological role(s) and suggest that the enzyme plays important functions in protecting humans from the deleterious consequences of exposure to both oxidative- and ultraviolet light-induced DNA damage. Published by Elsevier B.V. C1 [Vidal, Antonio E.] Inst Parasitol & Biomed Lopez Neyra, Consejo Super Invest Cient, Granada 18100, Spain. [Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), 9800 Med Ctr Dr,Bldg C,Room 320, Bethesda, MD 20892 USA. EM woodgate@nih.gov FU NICHD/NIH; Ministerio de Ciencia e Innovacion FX This work is supported in part by funds from the NICHD/NIH Intramural Research Program (RW) and the Programa Ramon y Cajal (Ministerio de Ciencia e Innovacion) (AV). NR 39 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAR 1 PY 2009 VL 8 IS 3 BP 420 EP 423 DI 10.1016/j.dnarep.2008.12.007 PG 4 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 415LC UT WOS:000263934300015 PM 19162565 ER PT J AU Compton, WM Saha, TD Conway, KP Grant, BF AF Compton, Wilson M. Saha, Tulshi D. Conway, Kevin P. Grant, Bridget F. TI The role of cannabis use within a dimensional approach to cannabis use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cannabis use disorders; IRT analysis; Cannabis use ID ITEM RESPONSE THEORY; NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE DISORDER; MARGINAL MAXIMUM-LIKELIHOOD; DSM-IV ALCOHOL; AUDADIS-ADR; EM ALGORITHM; DRUG MODULES; CRITERIA; RELIABILITY AB Context: Cannabis consumption is central to diagnosis of cannabis use disorders; yet, most research on cannabis disorders has focused just on diagnosis or criteria. The present study examines the ability of a frequency and quantity measure of cannabis use as well as cannabis abuse and dependence criteria to discriminate between individuals across the cannabis use disorder continuum. Method: A representative sample of USA adults in 2001-2002 (N=43,093) were queried about the past year frequency of cannabis use and each Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) cannabis abuse and dependence criterion. Factor analysis and item response theory (IRT) models were used to define the relationship between observed responses and the underlying unobserved latent trait (cannabis use disorder severity) among past year cannabis users (n = 1603). Results: Factor analyses demonstrated a good fit fora one-factor model both with and without the cannabis use criterion and no differential criterion functioning was demonstrated across sex. The IRT model including the cannabis use criterion had discriminatory power comparable to the model without the cannabis use criterion and exceeded the informational value of the model without the cannabis use criterion in mild and moderate ranges of the severity continuum. Discussion: Factor and IRT analyses disprove the validity of the DSM-IV abuse and dependence distinction: A single dimension represented the criteria rather than the two implied by the separate abuse/dependence categories. IRT models identified some dependence criteria to be among the mildest and some abuse criteria to be among the most severe-results inconsistent with the interpretation of DSM-IV cannabis abuse as a milder disorder or prodrome of cannabis dependence. The consumption criterion defined the mild end of the cannabis use disorder continuum and its excellent psychometric properties supported its consideration for inclusion in the next edition of DSM as a criterion for cannabis use disorders. Additional work is needed to identify candidate consumption criteria across all drugs that apply to the milder end of the severity Continuum while also improving overall model performance and clinical diagnostic utility. (C) 2008 Published by Elsevier Ireland Ltd. C1 [Compton, Wilson M.; Conway, Kevin P.] Natl Inst Drug Abuse, Div Epidemiol, Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. [Saha, Tulshi D.; Grant, Bridget F.] NIAAA, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Compton, WM (reprint author), Natl Inst Drug Abuse, Div Epidemiol, Serv & Prevent Res, NIH, 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA. EM wcompton@nida.nih.gov OI Conway, Kevin/0000-0002-7638-339X FU Intramural NIH HHS [Z99 DA999999] NR 38 TC 51 Z9 51 U1 4 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2009 VL 100 IS 3 BP 221 EP 227 DI 10.1016/j.drugalcdep.2008.10.009 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 404HA UT WOS:000263140900005 PM 19062204 ER PT J AU Wellman, PJ Davis, KW Clifford, PS Rothman, RB Blough, BE AF Wellman, Paul J. Davis, Kristina W. Clifford, P. Shane Rothman, Richard B. Blough, Bruce E. TI Changes in feeding and locomotion induced by amphetamine analogs in rats SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Body weight; Cumulative food intake; Monoamine; Amphetamine ID CONDITIONED PLACE PREFERENCE; INDUCED HYPOPHAGIA; FOOD-DEPRIVATION; MOTOR-ACTIVITY; DRUG REWARD; COCAINE; BEHAVIOR; MECHANISMS; ANOREXIA; ABUSE AB Studies of the biobehavioral actions of psychostimulants commonly focus on locomotion and less commonly on feeding, and only rarely are these measures considered in conjunction within the same animal. The present study compared the impact of (+)-amphetamine and three amphetamine analogs, PAL-287, PAL-313, and PAL-353, on eating and locomotion assessed concurrently using an automated activity/feeding chamber during a daily 45 min session. Each analog is a potent releaser of norepinephrine and of dopamine, but exerts differential serotonin-releasing activity (PAL-287 > PAL-313 > amphetamine > PAL-353). Rats were tested with each of five doses of drug (0, 2, 4, 8, or 16 mu mol/kg, i.p.), given in equimolar concentrations and in random dose order. PAL-353, an analog with minimal serotonin-releasing capacity, markedly stimulated forward locomotion at 2,4,8 and 16 mu mol/kg, as did amphetamine, whereas PAL-287 and PAL-313 did not. In contrast to the locomotor findings, all four amphetamine-like drugs exerted similar effects on the suppression of food intake. These results suggest that the capacity of an amphetamine analog (i.e. amphetamine and PAL-353) to stimulate serotonin release can diminish its psychostimulant action on locomotion, but does not reliably augment drug-induced hypophagia. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Wellman, Paul J.; Davis, Kristina W.; Clifford, P. Shane] Texas A&M Univ, Dept Psychol, Behav Neurosci Program, College Stn, TX 77843 USA. [Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Blough, Bruce E.] RTI Int, Sci & Engn Grp, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA. RP Wellman, PJ (reprint author), Texas A&M Univ, Dept Psychol, Behav Neurosci Program, Rm 248 Psyc, College Stn, TX 77843 USA. EM PJW@PSYC.TAMU.EDU FU NIDA [R21 DA017230-01, R01 DA012970]; Intramural Research Program; National Institute on Drug Abuse; NIH; DHHS FX Role of the funding source: The present Study was supported by NIDA R21 DA017230-01 (P.J.W.), by NIDA R01 DA012970 (B.E.B.) and in part by the Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS (R.R.). NIH had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 44 TC 23 Z9 23 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2009 VL 100 IS 3 BP 234 EP 239 DI 10.1016/j.drugalcdep.2008.10.005 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 404HA UT WOS:000263140900007 PM 19062203 ER PT J AU Diaz, T Pencina, MJ Benjamin, EJ Aragam, J Fuller, DL Pencina, KM Levy, D Vasan, RS AF Diaz, Tulio Pencina, Michael J. Benjamin, Emelia J. Aragam, Jayashri Fuller, Deborah L. Pencina, Karol M. Levy, Daniel Vasan, Ramachandran S. TI Prevalence, Clinical Correlates, and Prognosis of Discrete Upper Septal Thickening on Echocardiography: The Framingham Heart Study SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE echocardiography; ventricular septum; epidemiology; prognosis ID LEFT-VENTRICULAR HYPERTROPHY; SYSTEMIC HYPERTENSION; CARDIOMYOPATHY; PATTERNS; DISEASE; AGE AB The upper interventricular septum may be prominent in elderly individuals, a finding referred to as discrete upper septal thickening (DUST). We examined the prevalence, clinical and echocardiographic correlates, and prognostic significance of DUST in a community-based sample. We evaluated Framingham Study participants who underwent routine echocardiography. In 3562 Framingham Study participants (mean age 58 years, 57% women), DUST was observed in 52 participants. The clinical correlates of DUST were increasing age (odds ratio [OR] per 10 year increment 2.59, 95% confidence intervals [CI] 1.64-4.08) and systolic blood pressure (OR per SD increment 1.55, 95% CI 1.15-2.09). DUST was positively associated with left ventricular (LV) fractional shortening and mitral annular calcification but inversely with LV diastolic dimensions (P < 0.02 for all). On follow-up (mean 15 years), 732 individuals died (33 with DUST) and 560 experienced a cardiovascular disease (CVD) event (18 with DUST). Adjusting for cardiovascular risk factors, DUST was not associated with CVD or mortality risk (P > 0.30 for both). The follow-up component of our study suggests that DUST is not independently associated with adverse prognosis. (ECHOCARDIOGRAPHY, Volume 26, March 2009) C1 [Diaz, Tulio; Pencina, Michael J.; Benjamin, Emelia J.; Aragam, Jayashri; Fuller, Deborah L.; Levy, Daniel; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Diaz, Tulio] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Diaz, Tulio] Harvard Univ, Sch Med, Boston, MA USA. [Pencina, Michael J.; Pencina, Karol M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol & Prevent Med Sect, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Epidemiol Sect, Boston, MA 02215 USA. [Aragam, Jayashri] Vet Adm Hosp, Boston, MA USA. [Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NIH/NHLBI [NO1-HC-25195, HL080124, K24-HL-04334] FX This work was supported by NIH/NHLBI NO1-HC-25195, HL080124 (to RSV), and K24-HL-04334 (to Dr. Vasan). NR 20 TC 12 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD MAR PY 2009 VL 26 IS 3 BP 247 EP 253 DI 10.1111/j.1540-8175.2008.00806.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428VQ UT WOS:000264879900002 PM 19175779 ER PT J AU Shoham, S Han, G Granek, T Walsh, T Magee, MF AF Shoham, Shmuel Han, Grace Granek, Tal Walsh, Thomas Magee, Michelle F. TI ASSOCIATION BETWEEN BLOOD GLUCOSE LEVELS AND DEVELOPMENT OF CANDIDEMIA IN HOSPITALIZED PATIENTS SO ENDOCRINE PRACTICE LA English DT Article ID INTENSIVE INSULIN THERAPY; IMPAIRED GRANULOCYTE-ADHERENCE; DIABETES-MELLITUS; POLYMORPHONUCLEAR LEUKOCYTES; ACTIVE SURVEILLANCE; GLYCEMIC CONTROL; TRAUMA PATIENTS; INCREASED RISK; UNITED-STATES; HOST DEFENSE AB Objective: To examine the relationship between blood glucose levels in hospitalized patients and the risk of occurrence of candidemia. Methods: We undertook a retrospective review of medical records and hospital computerized database information to compare blood glucose levels in 48 patients with nosocomial candidemia and 144 contemporaneous matched control subjects without candidemia at a tertiary teaching hospital. Results: The proportions of days (for patients with candidemia versus control subjects without candidemia) with blood glucose levels >= 100 mg/dL (293 of 325 [90%] versus 849 of 1.007 [84%]; P = .009), >= 140 mg/dL ( 184 of 325 [57%] versus 507 of 1,007 [50%] P = .049), and 200 mg/dL (80 of 325 [25%] versus 163 of 1,007 [16%]; P = .001) were significantly higher during the 7 days preceding the diagnosis of candidemia than during a 7-day period of hospitalization of control subjects. Blood glucose levels exceeding 200 mg/dL for 4 or more days of the week preceding the diagnosis of candidemia were significantly associated with its development (P = .04; odds ratio, 2.44 and 95% confidence interval, 1.01 to 5.94). Conclusion: Inpatient hyperglycemia is ail important-and potentially modifiable-risk factor for development of nosocomial candidemia. These findings have implications for innovative infection control strategies that focus Oil glycemic control. (Endocr Pract. 2009;15:111-115) C1 [Shoham, Shmuel] Washington Hosp Ctr, Infect Dis Sect, Washington, DC 20010 USA. [Han, Grace; Granek, Tal; Magee, Michelle F.] Washington Hosp Ctr, Dept Med, Washington, DC 20010 USA. [Shoham, Shmuel; Walsh, Thomas] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Granek, Tal] Coll William & Mary, Williamsburg, VA USA. [Magee, Michelle F.] MedStar Diabet & Res Inst, Washington, DC USA. RP Shoham, S (reprint author), Washington Hosp Ctr, Infect Dis Sect, 110 Irving St NW, Washington, DC 20010 USA. NR 34 TC 5 Z9 6 U1 0 U2 0 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAR PY 2009 VL 15 IS 2 BP 111 EP 115 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440IE UT WOS:000265693200003 PM 19289320 ER PT J AU Ghayee, HK Havekes, B Corssmit, EPM Eisenhofer, G Hammes, SR Ahmad, Z Tessnow, A Lazurova, I Adams, KT Fojo, AT Pacak, K Auchus, RJ AF Ghayee, Hans K. Havekes, Bas Corssmit, Eleonora P. M. Eisenhofer, Graeme Hammes, Stephen R. Ahmad, Zahid Tessnow, Alexander Lazurova, Ivica Adams, Karen T. Fojo, Antonio T. Pacak, Karel Auchus, Richard J. TI Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior SO ENDOCRINE-RELATED CANCER LA English DT Article ID MALIGNANT PARAGANGLIOMAS; MIDDLE MEDIASTINUM; PHEOCHROMOCYTOMA; SDHB; MANAGEMENT; ANTERIOR AB Extra-adrenal pheochromocytomas, otherwise known as paragangliomas (PGLs), account for about 20% of catecholamine-producing tumors. Catecholamine excess and mutations in the genes encoding succinate dehydrogenase subunits (SDHx) are frequently found in patients with PGLs. Only 2% of PGLs are found in the mediastinum, and little is known about genetic alterations in patients with mediastinal PGLs, catecholamine production by these tumors, or their clinical behavior. We hypothesized that most mediastinal PGLs are associated with germ line SDHx mutations, norepinephrine and/or dopamine excess, and aggressive behavior. The objective of this study was to characterize genetic, biochemical, and clinical data in a series of ten patients with mediastinal PGLs. All ten primary mediastinal PGL patients had germ line SDHx mutations, six in SDHB, and four in SDHD genes. Chest or back pain were the most common presenting symptoms (five patients), and catecholamines and/or their metabolites were elevated in seven patients. Additional tumors included head and neck PGLs in four patients, pheochromocytoma in one patient, and bladder PGL in another. Metastatic disease was documented in six patients (60%), and a concurrent abdominal mass was found in one patient. We conclude that mediastinal PGLs are strongly associated with SDHB and SDHD gene mutations, noradrenergic phenotype, and aggressive behavior. The present data suggest that all patients with mediastinal PGLs should be screened for SDHx gene mutations, regardless of age. C1 [Ghayee, Hans K.; Hammes, Stephen R.; Ahmad, Zahid; Tessnow, Alexander; Auchus, Richard J.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Endocrinol, Dallas, TX 75390 USA. [Havekes, Bas; Adams, Karen T.; Pacak, Karel] NICHHD, Reprod Biol & Med Program, NIH, Bethesda, MD 20892 USA. [Havekes, Bas; Corssmit, Eleonora P. M.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab, Leiden, Netherlands. [Eisenhofer, Graeme] Univ Hosp, Inst Clin Chem & Lab Med, Dresden, Germany. [Eisenhofer, Graeme] Univ Hosp, Dept Med, Dresden, Germany. [Lazurova, Ivica] Safarik Univ, Fac Med, Dept Med, Kosice, Slovakia. [Fojo, Antonio T.] NCI, Med Oncol Branch, NIH, Bethesda, MD USA. RP Auchus, RJ (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Endocrinol, 5323 Harry Hines Blvd,Suite Y-5-318, Dallas, TX 75390 USA. EM richard.auchus@utsouthwestern.edu FU NIH/NICHD; Burroughs Wellcome Fund [1005954] FX This research was supported (in part) by the Intramural Research Program of the NIH/NICHD as well as the Clinical Scientist Award in Translational Research (#1005954) from the Burroughs Wellcome Fund (to R J Auchus). NR 29 TC 19 Z9 19 U1 1 U2 1 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2009 VL 16 IS 1 BP 291 EP 299 DI 10.1677/ERC-08-0214 PG 9 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 436MP UT WOS:000265418500023 PM 19075037 ER PT J AU Xie, Y Kole, S Precht, P Pazin, MJ Bernier, M AF Xie, Yi Kole, Sutapa Precht, Patricia Pazin, Michael J. Bernier, Michel TI S-Glutathionylation Impairs Signal Transducer and Activator of Transcription 3 Activation and Signaling SO ENDOCRINOLOGY LA English DT Article ID NF-KAPPA-B; HEPATOCELLULAR-CARCINOMA CELLS; ACUTE-PHASE RESPONSE; OXIDATIVE STRESS; DNA-BINDING; TYROSINE PHOSPHORYLATION; STAT3 ACTIVATION; EPITHELIAL-CELLS; REDOX REGULATION; GLUTAREDOXIN AB S-glutathionylation is a physiological, reversible protein modification of cysteine residues with glutathione in response to mild oxidative stress. Because the key cell growth regulator signal transducer and activator of transcription ( STAT) 3 is particularly susceptible to redox regulation, we hypothesized that oxidative modification of cysteine residues of STAT3 by S-glutathionylation may occur. Herein, we show that the cysteine residues of STAT3 are modified by a thiol-alkylating agent and are the targets of S-glutathionylation. STAT3 protein thiol reactivity was reversibly attenuated with concomitant increase in the S-glutathionylation of STAT3 upon treatment of human HepG2 hepatoma cells with pyrrolidine dithiocarbamate, glutathione disulfide, or diamide. Under these conditions there was a marked reduction in IL-6-dependent STAT3 signaling, including decreased STAT3 tyrosine phosphorylation, loss in nuclear accumulation of STAT3, and impaired expression of target genes, such as fibrinogen-gamma. In a cell-free system, diamide induced glutathionylation of STAT3, which was decreased upon addition of glutaredoxin (GRX)-1, a deglutathionylation enzyme, or the reducing agent, dithiothreitol. Glutathionylated STAT3 was a poor Janus protein tyrosine kinase 2 substrate in vitro, and it exhibited low DNA-binding activity. Cellular GRX-1 activity was inhibited by diamide and pyrrolidine dithiocarbamate treatment; however, ectopic expression of GRX-1 was accompanied by a modest increase in phosphorylation, nuclear translocation, and DNA-binding ability of STAT3 in response to IL-6. These results are the first to show S-glutathionylation of STAT3, a modification that may exert regulatory function in STAT3 signaling. ( Endocrinology 150: 1122-1131, 2009) C1 [Bernier, Michel] NIA, Clin Invest Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Precht, Patricia; Pazin, Michael J.] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Kole, Sutapa] MedStar Res Inst, Hyattsville, MD 20783 USA. RP Bernier, M (reprint author), NIA, Clin Invest Lab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM Bernierm@mail.nih.gov OI Bernier, Michel/0000-0002-5948-368X; Pazin, Michael/0000-0002-7561-3640 FU National Institutes of Health; National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. A portion of that support was through a Research and Development contract with MedStar Research Institute. NR 58 TC 57 Z9 57 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2009 VL 150 IS 3 BP 1122 EP 1131 DI 10.1210/en.2008-1241 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 410YC UT WOS:000263613200009 PM 18988672 ER PT J AU Constantin, S Caligioni, CS Stojilkovic, S Wray, S AF Constantin, Stephanie Caligioni, Claudia Simone Stojilkovic, Stanko Wray, Susan TI Kisspeptin-10 Facilitates a Plasma Membrane-Driven Calcium Oscillator in Gonadotropin-Releasing Hormone-1 Neurons SO ENDOCRINOLOGY LA English DT Article ID EMBRYONIC OLFACTORY PLACODE; PROTEIN-COUPLED RECEPTOR; PRIMARY-CELL CULTURE; LHRH NEURONS; HYPOTHALAMIC NEURONS; EXPLANT CULTURES; RHESUS-MONKEY; RAT HYPOTHALAMUS; GNRH SECRETION; MESSENGER-RNA AB Kisspeptins, the natural ligands of the G-protein-coupled receptor (GPR)-54, are the most potent stimulators of GnRH-1 secretion and as such are critical to reproductive function. However, the mechanism by which kisspeptins enhance calcium-regulated neuropeptide secretion is not clear. In the present study, we used GnRH-1 neurons maintained in mice nasal explants to examine the expression and signaling of GPR54. Under basal conditions, GnRH-1 cells exhibited spontaneous baseline oscillations in intracellular calcium concentration ([Ca(2+)](i)), which were critically dependent on the operation of voltage-gated, tetrodotoxin (TTX)-sensitive sodium channels and were not coupled to calcium release from intracellular pools. Activation of native GPR54 by kisspeptin-10 initiated [Ca(2+)](i) oscillations in quiescent GnRH-1 cells, increased the frequency of calcium spiking in oscillating cells that led to summation of individual spikes into plateau-bursting type of calcium signals in a subset of active cells. These changes predominantly reflected the stimulatory effect of GPR54 activation on the plasma membrane oscillator activity via coupling of this receptor to phospholipase C signaling pathways. Both components of this pathway, inositol 1,3,4-trisphosphate and protein kinase C, contributed to the receptor-mediated modulation of baseline [Ca(2+)](i) oscillations. TTX and 2-aminoethyl diphenylborinate together abolished agonist-induced elevation in [Ca(2+)](i) in almost all cells, whereas flufenamic acid was less effective. Together these results indicate that a plasma membrane calcium oscillator is spontaneously operative in the majority of prenatal GnRH-1 neurons and is facilitated by kisspeptin-10 through phosphatidyl inositol diphosphate hydrolysis and depolarization of neurons by activating TTX-sensitive sodium channels and nonselective cationic channels. (Endocrinology 150: 1400-1412, 2009) C1 [Constantin, Stephanie; Caligioni, Claudia Simone; Wray, Susan] Natl Inst Neurol Disorder & Stroke, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Stojilkovic, Stanko] NICHHD, Sect Celular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Constantin, Stephanie] Univ Otago, Sch Med Sci, Dept Physiol, Ctr Neuroendocrinol, Dunedin 9054, New Zealand. RP Wray, S (reprint author), Natl Inst Neurol Disorder & Stroke, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov RI Constantin, Stephanie/C-5264-2009; OI Constantin, Stephanie/0000-0003-0596-9737; wray, susan/0000-0001-7670-3915 FU National Institutes of Health; National Institute of Neurological Disorder and Stroke FX Disclosure Statement: The authors have nothing to disclose. NR 59 TC 57 Z9 57 U1 1 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2009 VL 150 IS 3 BP 1400 EP 1412 DI 10.1210/en.2008-0979 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 410YC UT WOS:000263613200038 PM 18948403 ER PT J AU Lu, AL Ng, L Ma, M Kefas, B Davies, TF Hernandez, A Chan, CC Forrest, D AF Lu, Ailing Ng, Lily Ma, Michelle Kefas, Benjamin Davies, Terry F. Hernandez, Arturo Chan, Chi-Chao Forrest, Douglas TI Retarded Developmental Expression and Patterning of Retinal Cone Opsins in Hypothyroid Mice SO ENDOCRINOLOGY LA English DT Article ID THYROID-HORMONE RECEPTOR; DEVELOPING MOUSE RETINA; CONGENITAL HYPOTHYROIDISM; GENE-EXPRESSION; COLOR-VISION; RAT RETINA; PHOTORECEPTORS; RESISTANCE; CELLS; DIFFERENTIATION AB Color vision is mediated by cone photoreceptors that express opsin photopigments with sensitivities to different light wavelengths. Most mammals, including mice, differentially express M and S opsins for response to medium-long and short wavelengths, respectively. Previous studies demonstrated that a thyroid hormone receptor (TR beta 2) is critical for opsin patterning: in TR beta 2-deficient mice, Mopsin is lost and all cones instead express S opsin. Here, to investigate the requirement for thyroid hormone in cone development, we studied Tshr(-/-) mice as a model of congenital hypothyroidism. The onset of M opsin expression in Tshr(-/-) mice was severely delayed until after postnatal d 17(P17), and M opsin expression failed to attain normal levels at older adult ages. S opsin showed a subtler change with an extended distribution pattern over the superior-inferior axis of the retina. Similar opsin abnormalities were detected in wild-type C57BL/6J mice made hypothyroid by methimazole treatment. In Tshr(-/-) mice, T3 treatment from P8 recovered significant M opsin expression at P17. Tshr(-/-) mice produced normal numbers of cones, indicating that the major requirement for thyroid hormone is in opsin patterning rather than in cone generation. The phenotype is similar to, although milder than, that caused by loss of TR beta 2 and indicates the necessity for thyroid hormone for cone maturation. (Endocrinology 150: 1536-1544, 2009) C1 [Forrest, Douglas] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA. [Davies, Terry F.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Hernandez, Arturo] Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03766 USA. RP Forrest, D (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM forrestd@niddk.nih.gov FU Intramural Research Program at the NIH/National Institute of Diabetes and Digestive and Kidney Diseases; NIH/NEI; Hirschl Trust Award; NIH [DK52464, DK069713, DK054716]; Veterans Affairs Merit Award Program FX This work was supported by the Intramural Research Program at the NIH/National Institute of Diabetes and Digestive and Kidney Diseases ( D. F.), and NIH/NEI (C.-C. C.), a Hirschl Trust Award ( D. F.), NIH Grants DK52464 and DK069713 ( T. F. D.) and the Veterans Affairs Merit Award Program ( T. F. D.) and NIH Grant DK054716 ( A. H.). NR 45 TC 31 Z9 32 U1 2 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2009 VL 150 IS 3 BP 1536 EP 1544 DI 10.1210/en.2008-1092 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 410YC UT WOS:000263613200053 PM 18974269 ER PT J AU Keshava, C Divi, RL Einem, TL Richardson, DL Leonard, SL Keshova, N Poirier, MC Weston, A AF Keshava, Channa Divi, Rao L. Einem, Tracey L. Richardson, Diana L. Leonard, Sarah L. Keshova, Nagalakshmi Poirier, Miriam C. Weston, Ainsley TI Chlorophyllin Significantly Reduces Benzo[a]pyrene-DNA Adduct Formation and Alters Cytochrome P450 1A1 and 1B1 expression and EROD Activity in Normal Human Mammary Epithelial Cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE polycyclic aromatic hydrocarbons; microarray; chemoprevention; chlorophyllin; NQO1; chemiluminescence immunoassay; interferon ID POLYCYCLIC AROMATIC-HYDROCARBONS; MOLECULAR-COMPLEX FORMATION; DNA-ADDUCTS; RAINBOW-TROUT; AFLATOXIN B-1; COVALENT BINDING; GENE-EXPRESSION; LUNG-CANCER; MOUSE SKIN; METABOLIC-ACTIVATION AB We hypothesized that chlorophyllin (CHLN) would reduce benzo[a]pyrene-DNA (BP-DNA) adduct levels. Using normal human mammary epithelial cells (NHMECs) exposed to 4 mu M BP for 24 hr in the presence or absence of 5 mu M CHLN, we measured BP-DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the following experimental groups: BP alone, BP given simultaneously with CHLN (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN, postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN, postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87% inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we monitored expression by Affymetrix microarray (U133A), and found BP-induced up-regulation of CYP1A1 and CYP1B1 expression, as well as upregulation of groups of interferon-inducible, inflammation and signal transduction genes. Incubation of cells with CHLN and BP in any combination decreased expression of many of these genes. Using reverse transcription real time PCR (RT-PCR) the maximal inhibition of BP-induced gene expression, >85% for CYP1A1 and >70% for CYP1B1, was observed in the preCHLN, postBP + CHLN group. To explore the relationship between transcription and enzyme activity, the ethoxyresorufin-O-deethylase (EROD) assay was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused the EROD levels to double, when compared with the unexposed controls, The CHLN-exposed groups all showed EROD levels similar to the unexposed controls. Therefore, the addition of CHLN to BP-exposed cells reduced BPdG formation and CYP1A1 and CYP1B1 expression, but EROD activity was not significantly reduced. Environ. Mal. Mutagen. 50:134-144, 2009. Published 2009 Wiley-Liss, Inc.(+) C1 [Divi, Rao L.; Einem, Tracey L.; Leonard, Sarah L.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Keshava, Channa; Richardson, Diana L.; Weston, Ainsley] NIOSH, Mol Carcinogenesis Team, Toxicol & Mol Biol Branch, Hlth Effects Lab Div,Ctr Dis Control & Prevent, Morgantown, WV USA. [Keshava, Channa; Keshova, Nagalakshmi] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. [Weston, Ainsley] NIOSH, Div Resp Dis Studies, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, Ctr Canc Res, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov FU US Centers, for Disease Control (CDC); National Institute for Occupational Safety and Health (NIOSH); US National Institutes of Health (NIH) National Cancer Institute (NCI) Center for Cancer Research FX Grant sponsors: Intramural Research Programs of the US Centers, for Disease Control (CDC), National Institute for Occupational Safety and Health (NIOSH), US National Institutes of Health (NIH) National Cancer Institute (NCI) Center for Cancer Research. NR 58 TC 12 Z9 12 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD MAR PY 2009 VL 50 IS 2 BP 134 EP 144 DI 10.1002/em.20449 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 408SS UT WOS:000263455900010 PM 19152381 ER PT J AU Salo, PW Jaramillo, R Cohn, RD London, SJ Zeldin, DC AF Salo, Paeivi W. Jaramillo, Renee Cohn, Richard D. London, Stephanie J. Zeldin, Darryl C. TI Exposure to Mouse Allergen in US Homes Associated with Asthma Symptoms SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergy; asthma; exposure; indoor; mouse allergen ID INNER-CITY CHILDREN; NUTRITION EXAMINATION SURVEY; SKIN-TEST SENSITIVITY; 3RD NATIONAL-HEALTH; ENVIRONMENTAL INTERVENTION; SUBURBAN HOMES; PREVALENCE; SENSITIZATION; POPULATION; MORBIDITY AB BACKGROUND: Most studies investigating the role of residential mouse allergen exposures in asthma have focused on inner-city populations. OBJECTIVE: We examined whether elevated mouse allergen levels were associated with occupants' asthma status in a nationally representative sample of U.S. households. METHODS: Data for this study were collected as part of the National Survey of Lead and Allergens in Housing. This cross-sectional study surveyed 831 housing units inhabited by 2,456 individuals in 75 different locations throughout the United States. The survey obtained information on demographics, household characteristics, and occupants' health status by questionnaire and environmental observations. We used a polyclonall immunoassay to assess concentrations of mouse urinary protein (M UP) in vacuumed dust collected from various indoor sites. RESULTS: Of the surveyed homes, 82% had detectable levels of MUP, and in 35% of the homes, MUP concentrations exceeded 1.6 mu g/g, a level that has been associated with increased mouse allergen sensitization rates. Current asthma, defined as having doctor-diagnosed asthma and asthma symptoms in the preceding 12 months, was positively associated with increased MUP levels. The observed association was modified by atopic status; in allergic individuals, elevated MUP levels (> 1.6 mu g/g) increased the odds of having asthma symptoms [adjusted OR = 1.93; 95% confidence interval (CI), 1.14-3.27], but we found no association in those who did not report allergies (adjusted OR = 0.69; 95% CI, 0.33-1.44). CONCLUSIONS: In allergic asthma, residential mouse allergen exposure is an important risk factor for asthma morbidity. C1 [Salo, Paeivi W.; London, Stephanie J.; Zeldin, Darryl C.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Jaramillo, Renee; Cohn, Richard D.] Constella Grp LLC, Durham, NC USA. RP Zeldin, DC (reprint author), NIEHS, NIH, US Dept HHS, 111 Alexander Dr,Mail Drop D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health, National Institute of Environmental Health Sciences; U.S. Department of Housing and Urban Development FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, and by the U.S. Department of Housing and Urban Development. NR 34 TC 28 Z9 29 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2009 VL 117 IS 3 BP 387 EP 391 DI 10.1289/ehp.11847 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 415KV UT WOS:000263933600026 PM 19337513 ER PT J AU Pan, IJ Daniels, JL Goldman, BD Herring, AH Siega-Riz, AM Rogan, WJ AF Pan, I-Jen Daniels, Julie L. Goldman, Barbara D. Herring, Amy H. Siega-Riz, Anna Maria Rogan, Walter J. TI Lactational Exposure to Polychlorinated Biphenyls, Dichlorodiphenyltrichloroethane, and Dichlorodiphenyldichloroethylene and Infant Neurodevelopment: An Analysis of the Pregnancy, Infection, and Nutrition Babies Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE breast milk; DDE; DDT; lactation; MacArthur-Bates Communicative Development Indices; Mullen Scales of Early Learning; PCBs ID POLYBROMINATED DIPHENYL ETHERS; FATTY-ACID REQUIREMENTS; PRENATAL EXPOSURE; HUMAN-MILK; ENVIRONMENTAL CHEMICALS; MOTOR DEVELOPMENT; BREAST-MILK; BRAIN; HEALTH; PCBS AB BACKGROUND: Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) are persistent, bioaccumulative, and toxic pollutants that were broadly used in the United States until the 1970s. Common exposure to PCBs, DDT, and dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of DDT, may influence children's neurodevelopment, but study results are not consistent. OBJECTIVES: We examined the associations between lactational exposure to PCBs, DDT, and DDE and infant development at 12 months, using data from the Pregnancy, Infection, and Nutrition Babies Study, 2004-2006. METHODS: We measured PCBs, DDT, and DDE in breast milk at the third month postpartum. Lactational exposure of these chemicals was estimated by the product of chemical concentrations and the duration of breast-feeding. Infant development at 12 months of age was measured by the Mullen Scales of Early Learning (n = 231) and the Short Form: Level I (infant) of the MacArthur-Bates Communicative Development Indices (n = 218). RESULTS: No consistent associations were observed between lactational exposure to PCBs, DDT, and DDE through the first 12 months and the measures of infant development. However, DDE was associated with scoring below average on the gross motor scale of the Mullen among males only (adjusted odds ratio = 1.9; 95% confidence interval, 1.1-3.3). CONCLUSION: Infant neurodevelopment at 12 months of age was not impaired by PCBs, DDT, and DDE at the concentrations measured here, in combination with benefits from long duration of breast-feeding in this population. C1 [Pan, I-Jen; Daniels, Julie L.; Siega-Riz, Anna Maria] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Daniels, Julie L.] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC 27599 USA. [Goldman, Barbara D.] Univ N Carolina, Frank Porter Graham Child Dev Inst, Chapel Hill, NC 27599 USA. [Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Herring, Amy H.; Siega-Riz, Anna Maria] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA. [Siega-Riz, Anna Maria] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Rogan, Walter J.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Daniels, JL (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. EM julie_daniels@unc.edu RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU U.S. Environmental Protection Agency [RD832736]; NIEHS [P30ES10126]; NIEHS, NIH FX This research was supported by grants from the U.S. Environmental Protection Agency (RD832736) and the NIEHS (P30ES10126). The work of W.J.R. on this project was supported by the Intramural Research Program, NIEHS, NIH. NR 42 TC 21 Z9 21 U1 1 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2009 VL 117 IS 3 BP 488 EP 494 DI 10.1289/ehp.0800063 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 415KV UT WOS:000263933600040 PM 19337527 ER PT J AU Bucher, JR AF Bucher, John R. TI Bisphenol A: Where to Now? SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, NTP, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NIEHS, NTP, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM bucher@niehs.nih.gov NR 12 TC 10 Z9 10 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2009 VL 117 IS 3 BP A96 EP A97 DI 10.1289/ehp.12492 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 415KV UT WOS:000263933600001 PM 19337497 ER PT J AU Jacobs, MP Leblanc, GG Brooks-Kayal, A Jensen, FE Lowenstein, DH Noebels, JL Spencer, DD Swann, JW AF Jacobs, Margaret P. Leblanc, Gabrielle G. Brooks-Kayal, Amy Jensen, Frances E. Lowenstein, Dan H. Noebels, Jeffrey L. Spencer, Dennis D. Swann, John W. TI Curing epilepsy: Progress and future directions SO EPILEPSY & BEHAVIOR LA English DT Review DE Genetics; Epileptogenesis; Co-morbidities; Therapeutics ID TEMPORAL-LOBE EPILEPSY; TUBEROUS SCLEROSIS COMPLEX; HIGH-FREQUENCY OSCILLATIONS; SEVERE MYOCLONIC EPILEPSY; HUMAN CEREBRAL-CORTEX; ANTIEPILEPTIC DRUGS; MOUSE MODEL; RECURRENT SEIZURES; RAT MODEL; PERIVENTRICULAR HETEROTOPIA AB During the past decade, substantial progress has been made in delineating clinical features of the epilepsies and the basic mechanisms responsible for these disorders. Eleven human epilepsy genes have been identified and many more are now known from animal models. Candidate targets for cures are now based upon newly identified cellular and molecular mechanisms that underlie epileptogenesis. However, epilepsy is increasingly recognized as a group of heterogeneous syndromes characterized by other conditions that co-exist with seizures. Cognitive. emotional and behavioral co-morbidities are common and offer fruitful areas for study. These advances in understanding mechanisms are being matched by the rapid development of new diagnostic methods and therapeutic approaches. This article reviews these areas of progress and suggests specific goals that once accomplished promise to lead to cures for epilepsy. (C) 2009 Elsevier Inc. All rights reserved. C1 [Jacobs, Margaret P.; Leblanc, Gabrielle G.] Natl Inst Neurol Disorders & Stroke, NIH, Rockville, MD USA. [Brooks-Kayal, Amy] Univ Penn, Philadelphia, PA 19104 USA. [Jensen, Frances E.] Harvard Univ, Childrens Hosp, Boston, MA 02115 USA. [Lowenstein, Dan H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Noebels, Jeffrey L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Spencer, Dennis D.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Swann, John W.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Leblanc, GG (reprint author), 3020 Tilden St NW 503, Washington, DC 20008 USA. EM QHRTS21@gmail.com OI Noebels, Jeffrey /0000-0002-2887-0839 FU National Institute of Neurological Disorders and Stroke; American Epilepsy Society; Centers for Disease Control and Prevention; Epilepsy Foundation; Epilepsy Therapy Project; Milken Family Foundation; National Association of Epilepsy Centers; Parents Against Childhood Epilepsy, Inc., FX This review is based in part on presentations and discussions at the Curing Epilepsy 2007 meeting, which took place oil March 29-30 in Bethesda, MD, and was sponsored by the National Institute of Neurological Disorders and Stroke in collaborations with the American Epilepsy Society, Centers for Disease Control and Prevention, Citizens United for Research in Epilepsy, Epilepsy Foundation, Epilepsy Therapy Project, Finding a Cure for Epilepsy and Seizures, International League Against Epilepsy, Milken Family Foundation, National Association of Epilepsy Centers, Parents Against Childhood Epilepsy, Inc., and Tuberous Sclerosis Alliance. The conference agenda, participant list, research recommendations, and videocasts of the meeting can be found at this website: http://www.ninds.nih.gov/research/epilepsyweb/curingepilepsy/index.htm. NR 144 TC 56 Z9 57 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAR PY 2009 VL 14 IS 3 BP 438 EP 445 DI 10.1016/j.yebeh.2009.02.036 PG 8 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 431CZ UT WOS:000265040200003 PM 19341977 ER PT J AU Pugsley, D Norris, KC Garcia-Garcia, G Agodoa, L AF Pugsley, David Norris, Keith C. Garcia-Garcia, Guillermo Agodoa, Lawrence TI GLOBAL APPROACHES FOR UNDERSTANDING THE DISPROPORTIONATE BURDEN OF CHRONIC KIDNEY DISEASE FOREWORD SO ETHNICITY & DISEASE LA English DT Editorial Material ID ETHNIC DISPARITIES; UNITED-STATES; SURVIVAL; RACE C1 [Pugsley, David] Univ Adelaide, Adelaide, SA 5005, Australia. [Norris, Keith C.] Charles Drew Univ Med & Sci, Los Angeles, CA USA. [Garcia-Garcia, Guillermo] Hosp Civil Guadalajara, Jalisco Dialysis & Transplant Registry, Guadalajara, Jalisco, Mexico. [Agodoa, Lawrence] NIDDK, Off Minor Hlth Res Coordinat, Natl Inst Hlth, Bethesda, MD USA. RP Norris, KC (reprint author), Charles Drew Univ Med & Sci, 11705 Deputy Yamamoto Pl,Suite B, Lynwood, CA 90262 USA. EM keithnorris@cdrewu.edu NR 12 TC 19 Z9 19 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SPR PY 2009 VL 19 IS 1 SU 1 BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 437XA UT WOS:000265519000001 ER PT J AU Lea, JP Greene, EL Nicholas, SB Agodoa, L Norris, KC AF Lea, Janice P. Greene, Eddie L. Nicholas, Susanne B. Agodoa, Lawrence Norris, Keith C. TI CARDIORENAL METABOLIC SYNDROME IN THE AFRICAN DIASPORA: RATIONALE FOR INCLUDING CHRONIC KIDNEY DISEASE IN THE METABOLIC SYNDROME DEFINITION SO ETHNICITY & DISEASE LA English DT Article; Proceedings Paper CT Global Summit on Cardio Renal Metabolic Syndrome in People of the African Diaspora CY DEC 02, 2007 CL Columbus, OH DE Metabolic Syndrome; Cardiovascular Disease; Chronic Kidney Disease; Ethnic ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; RENAL-DISEASE; US ADULTS; RISK; PREVALENCE; MICROALBUMINURIA; PROTEINURIA; ASSOCIATION; REDUCTION AB Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markersmicroalburninuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome." (Ethn Dis.2009;19[Suppl 2]:S2-11-S2-14) C1 [Lea, Janice P.] Emory Univ, Dept Med, Div Renal, Atlanta, GA 30308 USA. [Greene, Eddie L.] Mayo Clin, Rochester, NY USA. [Nicholas, Susanne B.; Norris, Keith C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Norris, Keith C.] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. [Agodoa, Lawrence] NIH, Bethesda, MD 20892 USA. RP Lea, JP (reprint author), Emory Univ, Dept Med, Div Renal, 550 Peachtree St,8th Floor, Atlanta, GA 30308 USA. EM jlea@emory.edu NR 19 TC 0 Z9 1 U1 0 U2 1 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SPR PY 2009 VL 19 IS 2 BP S11 EP S14 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 455OB UT WOS:000266769300023 ER PT J AU Kummar, S Doroshow, JH Tomaszewski, JE Calvert, AH Lobbezoo, M Giaccone, G AF Kummar, Shivaani Doroshow, James H. Tomaszewski, Joseph E. Calvert, A. Hilary Lobbezoo, Marinus Giaccone, Giuseppe CA Task Force MDICT TI Phase 0 clinical trials: Recommendations from the task force on methodology for the development of innovative cancer therapies SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Clinical trials; Phase 0; Drug development; Oncology; MDICT ID TARGETED ANTICANCER THERAPY; I ONCOLOGY TRIALS; DRUG DEVELOPMENT; BIOMARKERS; DESIGN; MDICT AB The Methodology for the Development of Innovative Cancer Therapies (MDICT) task force has been established as an expert forum to develop practical guidance on the development of innovative anticancer agents, in particular targeted agents. The task force recently addressed the utility, design and application of Phase 0 clinical trials in anticancer drug development. It was concluded that the role of non-therapeutic Phase 0 trials is controversial for several reasons, including the lack of clinical benefit for participating patients. However, it was recognised that Phase 0 trials provide an opportunity to generate essential human pharmacokinetic and pharmacodynamic data earlier in the drug development process, which could be a major advantage in the design and decision making concerning further clinical development of an agent. Construction of a 'decision chart' was highly recommended to assist investigators and sponsors in determining whether an agent is suitable for evaluation in a Phase 0 trial. Published by Elsevier Ltd. C1 [Giaccone, Giuseppe] NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Kummar, Shivaani; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Doroshow, James H.; Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Calvert, A. Hilary] No Inst Canc Res, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England. [Lobbezoo, Marinus] NDDO Res Fdn, Amsterdam, Netherlands. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, CCR, NIH, Bldg 10,Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU NDDO Research Foundation (Amsterdam, The Netherlands) FX We wish to thank Ms. Gina Uhlenbrauck, Dr. Yvonne A. Evrard and Dr. Melanie Simpson, SAIC-Frederick, Inc., for editorial assistance in the preparation of this manuscript. NR 25 TC 24 Z9 26 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2009 VL 45 IS 5 BP 741 EP 746 DI 10.1016/j.ejca.2008.10.024 PG 6 WC Oncology SC Oncology GA 447QH UT WOS:000266205900012 PM 19091546 ER PT J AU Bottomley, A Quinten, C Coens, C Martinelli, F Mauer, M Maringwa, J Cleeland, CS Flechtner, H Gotay, C Greimel, E King, M Osoba, D Taphoorn, MJB Reeve, BB Ringash, J Koch, JSV Weis, J AF Bottomley, Andrew Quinten, Chantal Coens, Corneel Martinelli, Francesca Mauer, Murielle Maringwa, John Cleeland, Charles S. Flechtner, Henning Gotay, Carolyn Greimel, Eva King, Madeleine Osoba, David Taphoorn, Martin J. B. Reeve, Bryce B. Ringash, Jolie Koch, Joseph Schmucker-Von Weis, Joachim TI Making better use of existing cancer data: Patient Reported Outcomes and Behavioural Evidence: a new international initiative SO EUROPEAN JOURNAL OF CANCER CARE LA English DT Editorial Material DE cancer; quality of life; patient reported outcomes ID QUALITY-OF-LIFE C1 [Bottomley, Andrew; Quinten, Chantal; Coens, Corneel; Martinelli, Francesca; Mauer, Murielle; Maringwa, John] EORTC Headquarters, Brussels, Belgium. [Cleeland, Charles S.] UTMD Anderson Canc Ctr, Houston, TX USA. [Flechtner, Henning] Otto von Guericke Univ Magdeburg, Fac Med, City Hosp Magdeburg, Magdeburg, Germany. [Gotay, Carolyn] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Greimel, Eva] Med Univ Graz, Graz, Austria. [King, Madeleine] Univ Sydney, Sydney, NSW 2006, Australia. [Osoba, David] Qual Life Consulting, W Vancouver, BC, Canada. [Taphoorn, Martin J. B.] Hague & VU Univ, Med Ctr, Med Ctr Haaglanden, Amsterdam, Netherlands. [Reeve, Bryce B.] NCI, NIH, Bethesda, MD 20892 USA. [Ringash, Jolie] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Koch, Joseph Schmucker-Von] Univ Regensburg, Regensburg, Germany. [Weis, Joachim] Univ Freiburg, Freiburg, Germany. RP Bottomley, A (reprint author), EORTC, AISBL IVZW, Qual Life Dept, Ave E Mounierlaan 83-11, B-1200 Brussels, Belgium. EM andrew.bottomley@eortc.be NR 6 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0961-5423 J9 EUR J CANCER CARE JI Eur. J. Cancer Care PD MAR PY 2009 VL 18 IS 2 BP 105 EP 107 DI 10.1111/j.1365-2354.2009.01092.x PG 3 WC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation SC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation GA 436ZR UT WOS:000265455500001 PM 19267723 ER PT J AU Aleksandrowicz, P Feldmann, H Schnittler, HJ AF Aleksandrowicz, P. Feldmann, H. Schnittler, H. J. TI Entry of Ebola virus-like particles into host cells follows a non-caveolae-mediated mechanism SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the German-Society-for-Cell-Biology CY MAR 24-27, 2009 CL Konstanz, GERMANY SP German Soc Cell Biol C1 [Aleksandrowicz, P.; Schnittler, H. J.] Tech Univ Dresden, Inst Physiol, Dresden, Germany. [Feldmann, H.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. EM p.aleksandrowicz@gmail.com NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2009 VL 88 BP 19 EP 19 PG 1 WC Cell Biology SC Cell Biology GA 428RB UT WOS:000264865700030 ER PT J AU Stroeve, JHM Brufau, G Stellaard, F Gonzalez, FJ Staels, B Kuipers, F AF Stroeve, J. H. M. Brufau, G. Stellaard, F. Gonzalez, F. J. Staels, B. Kuipers, F. TI The intestinal FXR-mediated Fgf-115 pathway contributes to the diurnal control of hepatic bile acid synthesis and bile formation in chow fed mice but its contribution is overruled during bile acid feeding and bile acid sequestration SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Meeting Abstract C1 [Stroeve, J. H. M.; Brufau, G.; Stellaard, F.; Kuipers, F.] Univ Groningen, Univ Med Ctr Groningen, Ctr Liver Digest & Metab Dis, Pediat Lab, NL-9713 AV Groningen, Netherlands. [Gonzalez, F. J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Staels, B.] Inst Pasteur, Dept Atherosclerose, Lille, France. RI Staels, Bart/N-9497-2016 OI Staels, Bart/0000-0002-3784-1503 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 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD MAR PY 2009 VL 21 IS 3 BP A10 EP A10 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 421MG UT WOS:000264362400035 ER PT J AU van den Broek, FJC Dekker, E de Graaf, EJR Bemelman, WA Fockens, P Reitsma, JB AF van den Broek, F. J. C. Dekker, E. de Graaf, E. J. R. Bemelman, W. A. Fockens, P. Reitsma, J. B. TI Piecemeal endoscopic mucosal resection appears equally effective as, but associated with less morbidity than transanal endoscopic microsurgery for the treatment of large rectal adenomas SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIDDK, 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 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD MAR PY 2009 VL 21 IS 3 BP A54 EP A55 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 421MG UT WOS:000264362400142 ER PT J AU Nakajima, M Yamada, M Yamaguchi, K Sakiyama, Y Oda, A Nelson, DL Yawaka, Y Ariga, T AF Nakajima, Masaru Yamada, Masafumi Yamaguchi, Koji Sakiyama, Yukio Oda, Atsushi Nelson, David L. Yawaka, Yasutaka Ariga, Tadashi TI Possible application of flow cytometry for evaluation of the structure and functional status of WASP in peripheral blood mononuclear cells SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE Wiskott-Aldrich syndrome protein; flow cytometry; Wiskott-Aldrich syndrome; peripheral blood mononuclear cells ID WISKOTT-ALDRICH-SYNDROME; SYNDROME PROTEIN; ACTIN POLYMERIZATION; CARRIER STATUS; T-CELLS; EXPRESSION; MUTATIONS; LYMPHOCYTES; ACTIVATION; PATIENT AB The Wiskott-Aldrich syndrome protein (WASP), which is defective in Wiskott-Aldrich syndrome (WAS) patients, is an intracellular protein expressed in non-erythroid hematopoietic cells. Previously, we have established methods to detect intracellular WASP expression in peripheral blood mononuclear cells (PBMNCs) using flow cytometric analysis (FCM-WASP) and have revealed that WAS patients showed absent or very low level intracellular WASP expression in lymphocytes and monocytes, while a significant amount of WASP was detected in those of normal individuals. We applied these methods for diagnostic screening of WAS patients and WAS carriers, as well as to the evaluation of mixed chimera in WAS patients who had previously undergone hematopoietic stem cell transplantation. During these procedures, we have noticed that lymphocytes from normal control individuals showed dual positive peaks, while their monocytes invariably showed a single sharp WASP-positive peak. To investigate the basis of the dual positive peaks (WASP(low-bright) and WASP(high-bright)), we characterized the constituent linage lymphocytes of these two WASP-positive populations. As a result, we found each WASP(low/high) population comprised different linage PBMNCs. Furthermore, we propose that the difference between the two WASP-positive peaks did not result from any difference in WASP expression in the cells, but rather from a difference in the structural and functional status of the WASP protein in the cells. It has been shown that WASP may exist in two forms; an activated or inactivated form. Thus, the structural and functional WASP status or configuration could be evaluated by flow cytometric analysis. C1 [Yamada, Masafumi; Ariga, Tadashi] Hokkaido Univ, Grad Sch Med, Dept Pediat, Sapporo, Hokkaido 060, Japan. [Nakajima, Masaru; Yawaka, Yasutaka] Hokkaido Univ, Div Oral Funct Sci, Dept Dent Children & Disabled Person, Grad Sch Dent Med, Sapporo, Hokkaido 060, Japan. [Nakajima, Masaru; Yamaguchi, Koji; Sakiyama, Yukio] Hokkaido Univ, Res Grp Human Gene Therapy, Grad Sch Med, Sapporo, Hokkaido 060, Japan. [Oda, Atsushi] Hokkaido Univ, Dept Prevent Med, Sch Med, Sapporo, Hokkaido 060, Japan. [Nelson, David L.] NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. RP Ariga, T (reprint author), Hokkaido Univ, Grad Sch Med, Dept Pediat, Sapporo, Hokkaido 060, Japan. EM tada-ari@med.hokudai.ac.jp RI Ariga, Tadashi/A-4252-2012 FU Japanese Ministry of Health, Labor and Welfare [2542002917, 15COE011-02, H19-Child-General-003] FX This study was supported by Grant-in-aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare (2542002917, 15COE011-02 and H19-Child-General-003). NR 28 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD MAR PY 2009 VL 82 IS 3 BP 223 EP 230 DI 10.1111/j.1600-0609.2008.01180.x PG 8 WC Hematology SC Hematology GA 399VK UT WOS:000262827200009 PM 19018864 ER PT J AU Spolski, R Leonard, WJ AF Spolski, Rosanne Leonard, Warren J. TI Cytokine mediators of Th17 function SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4(+) T cells; Cell differentiation; Cytokines; Th cells ID FOLLICULAR-HELPER-CELLS; GROWTH-FACTOR-BETA; ROR-GAMMA-T; CUTTING EDGE; AUTOIMMUNE ENCEPHALOMYELITIS; HOST-DEFENSE; DIFFERENTIATION; IL-21; INFLAMMATION; RECEPTOR AB Th17 cells were identified as an independent lineage of CD4(+) T cells that secrete a distinctive set of immunoregulatory cytokines, including IL-17A, IL-17F, IL-22, and IL-21. These cytokines collectively play roles in inflammation and autoimmunity and in response to extracellular pathogens. The expression of the lineage-specific transcription factor retinoic acid receptor-related orphan receptor (ROR)gamma t leads to Th17 lineage commitment; however, it has become increasingly clear that the population of cells designated as Th17 cells is not homogeneous. Although these cells collectively produce characteristic Th17 cytokines, not all are produced by each individual cell in the population. The cytokines produced by individual cells are presumably affected in part by the specific local cytokine milieu. In this review, we discuss the current understanding of the specific functional characteristics and regulation of Th17 cytokines and clarify how they mediate the actions of Th17 cells. C1 [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 43 TC 37 Z9 40 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2009 VL 39 IS 3 BP 658 EP 661 DI 10.1002/eji.200839066 PG 4 WC Immunology SC Immunology GA 426BW UT WOS:000264683500011 PM 19283717 ER PT J AU Blum, A AF Blum, Amon TI The possible role of red blood cell microvesicles in atherosclerosis SO EUROPEAN JOURNAL OF INTERNAL MEDICINE LA English DT Review DE Red blood cells' microvesicles; Atherosclerosis; Endothelial function; Sickle cell disease ID C-REACTIVE PROTEIN; TRANSLUMINAL CORONARY ANGIOPLASTY; INTERCELLULAR-ADHESION MOLECULE-1; NITRIC-OXIDE ACTIVITY; E-SELECTIN; SICKLE ERYTHROCYTES; ENDOTHELIAL-CELLS; UNSTABLE ANGINA; HEART-DISEASE; MYOCARDIAL-INFARCTION AB The tendency of sickle cells to adhere to the endothelium reflects the surface features not only of the red cells but also of the endothelial cells. Sickle cell disease is a prototype of a condition where the erythrocyte is under stress, ischemic, oxidative, or shear stress, that causes changes in the erythrocyte morphology. This change leads eventually to enhanced erythrocyte-endothelial cell adhesion. Reactive oxygen species generated by cytokine-activated inflammatory cells oxidize lipoproteins such as LDL and lipoprotein(a) within the vessel wall, facilitating uptake of these particles by activated macrophages and smooth muscle cells, with conversion into lipid-laden foam cells. Notably, the membranes of sickle RBCs have undergone excessive cytoskeletal protein thiol oxidation, and sickle RBCs are abnormally prone to vesiculation during mechanical stress in vitro and apparently in vivo. This abnormality was successfully reproduced in normal RBCs by causing stress conditions using PMS-induced stimulation of intracellular superoxide generation, a process similar to that occurring in sickle RBCs. It could be that the generation of reactive oxygen species in atherosclerosis activates red blood cells, and microvesicles of red blood cells are formed, enhancing the activation of the vascular endothelium and leading to vascular inflammation and atherogenesis. (C) 2008 European Federation of Internal Medicine. Published by Elsevier B.V All rights reserved. C1 [Blum, Amon] NHLBI, Cardiovasc Dept, Translat Branch, NIH, Bethesda, MD USA. [Blum, Amon] Baruch Padeh Poriya Med Ctr, Dept Internal Med, IL-15208 Lower Galilee, Israel. RP Blum, A (reprint author), NHLBI, Cardiovasc Dept, Translat Branch, NIH, Bethesda, MD USA. EM navablum@hotmail.com NR 62 TC 11 Z9 11 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0953-6205 J9 EUR J INTERN MED JI Eur. J. Intern. Med. PD MAR PY 2009 VL 20 IS 2 BP 101 EP 105 DI 10.1016/j.ejim.2008.06.001 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 438ZF UT WOS:000265594900001 PM 19327596 ER PT J AU Gupta, A Mishra, P Pandeya, SN Kashaw, SK Kashaw, V Stables, JP AF Gupta, Arun Mishra, Pradeep Pandeya, S. N. Kashaw, Sushil K. Kashaw, Varsha Stables, James P. TI Synthesis and anticonvulsant activity of some substituted 1.2,4-thiadiazoles SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE 1,2,4-Thiadiazole; Anticonvulsant activity; Maximal electroshock-induced seizures; Subcutaneous pentylenetetrazole-induced seizure; Neurotoxicity ID ANTIEPILEPTIC DRUG DEVELOPMENT; EPILEPSY AB A series of new substituted 1,2,4-thiadiazoles were synthesized by appropriate route and screened for anticonvulsant, neurotoxic and sedative-hypnotic activity. The structures of the synthesized compounds were confirmed by IR spectroscopy, (13)C NMR and elemental (nitrogen and sulphur) analysis. After i.p. injection of the compounds to mice or rate at doses of 30, 100, and 300 mg/kg, body weights were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models after 0.5 and 4 h. Rotorod method and phenobarbitone-induced hypnosis potentiation study were employed to examine neurotoxicity and sedative-hypnotic activity, respectively. All the compounds except 4g showed protection against MES screen after 0.5 h. Compounds 3a-c, 4a-c were active at 100 mg/kg dose i.p., whereas remaining compounds showed activity at 300 mg/kg. All 14 compounds except 3 g showed neurotoxicity at 100 and 300 mg/kg after 0.5 h. Compounds 3b and 4b showed NT after 4 h. Two compounds 3b and 4g showed significant (p < 0.05) percentage increase in sleeping time i.e. 67% and 59%, respectively. It may be concluded that the synthesized compounds were potent against MES-induced seizures than ScPTZ induced and showed low potency as sedative-hypnotic agent which is advantageous. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [Gupta, Arun; Mishra, Pradeep; Kashaw, Sushil K.; Kashaw, Varsha] Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar, India. [Pandeya, S. N.] VBS Purvanchal Univ, Inst Pharm, Jaunpur, Uttar Pradesh, India. [Stables, James P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Kashaw, SK (reprint author), Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar, India. EM sushilkashaw@gmail.com NR 10 TC 26 Z9 27 U1 0 U2 3 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD MAR PY 2009 VL 44 IS 3 BP 1100 EP 1105 DI 10.1016/j.ejmech.2008.06.015 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 424HU UT WOS:000264558600019 PM 18672318 ER PT J AU Staff, AC Harsem, NK Braekke, K Hyer, M Hoover, RN Troisi, R AF Staff, Anne Cathrine Harsem, Nina Kittelsen Braekke, Kristin Hyer, Marianne Hoover, Robert N. Troisi, Rebecca TI Maternal, gestational and neonatal characteristics and maternal angiogenic factors in normotensive pregnancies SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE Angiogenic factors; Pregnancy; Preeclampsia; Antiangiogenic profile; Breast cancer ID SOLUBLE ENDOGLIN; PREECLAMPSIA; SFLT1; FETAL; SERUM AB Objective: Alterations in maternal circulating angiogenic factors are proposed to result in hypertension and proteinuria and development of preeclampsia. The aim of this study was to explore whether preeclampsia risk factors are associated with maternal angiogenic profile in normotensive pregnancies. Study design: Associations of pregnancy characteristics and maternal serum concentrations at delivery of proangiogenic placental growth factor (PIGF), antiangiogenic soluble fms-like tyrosine kinase receptor (sFlt1) and soluble endoglin (sEng), as well as the antiangiogenic ratios sFlt1/P1GF and (sFlt1 + sEng)/P1GF were analyzed in 43 normotensive and 44 preeclamptic pregnancies. Results: In normotensive pregnancies, increasing maternal age was associated with a more antiangiogenic profile, including lower PIGF concentrations and a higher (sFlt1 + sEng)/P1GF ratio (P < 0.05). In preeclampsia, shorter length of gestation and lower birth weight percentile were associated with a more antiangiogenic profile. Conclusion: A greater antiangiogenic profile with older maternal age may suggest a biological mechanism which mediates this preeclampsia risk factor. In preeclampsia, the antiangiogenic state was more pronounced with clinical characteristics indicative of greater disease severity. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Staff, Anne Cathrine; Harsem, Nina Kittelsen] Ullevaal Univ Hosp, Dept Obstet & Gynaecol, N-0407 Oslo, Norway. [Staff, Anne Cathrine] Univ Oslo, Fac Med, Oslo, Norway. [Braekke, Kristin] Ullevaal Univ Hosp, Dept Paediat, N-0407 Oslo, Norway. [Hyer, Marianne] Informat Management Serv Inc, Rockville, MD USA. [Hoover, Robert N.; Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Troisi, Rebecca] Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA. RP Staff, AC (reprint author), Ullevaal Univ Hosp, Dept Obstet & Gynaecol, Kirkeveien 166, N-0407 Oslo, Norway. EM annetine.staff@uus.no FU VIRUUS (Vitenskapsradet Ulleval universitetssykehus); Woman and Chilas Division, Ulleval University Hospital FX Financial support: The work was supported by grants from VIRUUS (Vitenskapsradet Ulleval universitetssykehus) and the Woman and Chilas Division, Ulleval University Hospital. The Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services also provided funding for this work. NR 17 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD MAR PY 2009 VL 143 IS 1 BP 29 EP 33 DI 10.1016/j.ejogrb.2008.11.003 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 427RI UT WOS:000264796000007 PM 19135290 ER PT J AU Sutin, AR Costa, PT Miech, R Eaton, WW AF Sutin, Angelina R. Costa, Paul T., Jr. Miech, Richard Eaton, William W. TI Personality and Career Success: Concurrent and Longitudinal Relations SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article DE personality; five-factor model; occupations; income; job satisfaction ID CORE SELF-EVALUATIONS; WORK EXPERIENCES; 5-FACTOR MODEL; UNITED-STATES; FOLLOW-UP; METAANALYSIS; TRAITS; TRAJECTORIES; DIMENSIONS; PREDICTORS AB The present research addresses the transaction between extrinsic (occupational prestige, income) and intrinsic (job satisfaction) career success and the Five-Factor Model (FFM) of personality. Participants (N = 7.31) completed a comprehensive measure of personality and reported their job title, annual income and job sati.ffiction; a subset of these participants (n = 302) provided the same information approximately 10 years letter: Measured concurrently , emotionally v stable and conscientious participants reported higher incomes and job satisfaction. Longitudinal analyses revealed that, among younger participants, higher income at baseline predicted decreases in Neuroticism and baseline Extraversion predicted increases in income across the 10 years. Results suggest that the mutual influence of career success and personality is limited to income and occures early in the career. Copyright (c) 2009 John Wiley & Sons, Ltd. C1 [Sutin, Angelina R.; Costa, Paul T., Jr.] NIA, NIH, Biomed Res Ctr, DHHS, Baltimore, MD 21224 USA. [Miech, Richard] Univ Colorado, Denver, CO 80202 USA. [Eaton, William W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Sutin, AR (reprint author), NIA, NIH, Biomed Res Ctr, DHHS, IRP 251 Bayview Blvd,Suite 100,Room 04B323, Baltimore, MD 21224 USA. EM sutina@mail.nih.gov RI Miech, Richard/B-3170-2016; OI Miech, Richard/0000-0002-2722-3277; Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [Z99 AG999999]; NIMH NIH HHS [K23 MH064543, R01 MH047447, R01 MH047447-15, R01 MH050616] NR 43 TC 47 Z9 49 U1 9 U2 36 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD MAR PY 2009 VL 23 IS 2 BP 71 EP 84 DI 10.1002/per.704 PG 14 WC Psychology, Social SC Psychology GA 421MZ UT WOS:000264364300001 PM 19774106 ER PT J AU Talani, G Lovinger, DM AF Talani, G. Lovinger, D. M. TI Interaction between ethanol and the cannabinoid system at GABAergic synapses on basolateral amygdala principal neurons SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT European-College-of-Neuropsychopharmacology Workshop on Neuropsychopharmacology for Young Scientists in Europe CY MAR 05-08, 2009 CL Nice, FRANCE SP European Coll Neuropsychopharmacol C1 [Talani, G.] Univ Cagliari, Dept Exp Biol, Cagliari, Italy. [Lovinger, D. M.] NIH, Sect Synapt Pharmacol, Lab Integrat Neurosci, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2009 VL 19 BP S93 EP S94 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 425NJ UT WOS:000264644100107 ER PT J AU Rojo, DG Michaud, DS Villanueva, C Serra, C Rothman, N Malats, N Dosemeci, M Kogevinas, M Tardon, A Carrato, A Garcia-Closas, R Bielsa, O Saladie, JM Prera, A Malet, JM Lopez, FG Abad, C Guate, JL Herrero, A Abascal, R Diaz, M Cespedes, M Mateos, A Muntanola, P Huergo, F Mosquera, J Prats, J Mas, AG Silverman, DT Real, FX AF Garcia Rojo, D. Michaud, D. S. Villanueva, C. Serra, C. Rothman, N. Malats, N. Dosemeci, M. Kogevinas, M. Tardon, A. Carrato, A. Garcia-Closas, R. Bielsa, O. Saladie, J. M. Prera, A. Malet, J. M. Garcia Lopez, F. Abad, C. Guate, J. L. Herrero, A. Abascal, R. Diaz, M. Cespedes, M. Mateos, A. Muntanola, P. Huergo, F. Mosquera, J. Prats, J. Gelabert Mas, A. Silverman, D. T. Real, F. X. CA EPICURO Grp TI TOTAL FLUID AND WATER CONSUMPTION AND THE JOINT EFFECT OF EXPOSURE TO DISINFECTION BY-PRODUCTS ON RISK OF BLADDER CANCER SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 [Garcia Rojo, D.; Prera, A.; Abad, C.; Prats, J.] Hosp Sabadell, Dept Urol, Sabadell, Spain. [Michaud, D. S.; Rothman, N.; Dosemeci, M.; Silverman, D. T.] NCI, Dept Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Villanueva, C.; Malats, N.; Kogevinas, M.; Real, F. X.] Imim, Ctr Res Environm Epidemiol, Barcelona, Spain. [Serra, C.] Hosp Sabadell, Dept Epidemiol, Sabadell, Spain. [Tardon, A.] Univ Oviedo, Dept Epidemiol, Oviedo, Spain. [Carrato, A.] Hosp Elche, Dept Oncol, Elche, Spain. [Garcia-Closas, R.] Hosp Univ De Canarias, Unidad Invest, San Cristobal la Laguna, Spain. [Bielsa, O.] Hosp del Mar, Dept Urol, Barcelona, Spain. [Saladie, J. M.] Hosp Badalona Germans Trias & Pujol, Dept Urol, Badalona, Spain. [Malet, J. M.] Hosp Manresa, Dept Urol, Manresa, Spain. [Garcia Lopez, F.] Hosp Elche, Dept Urol, Elche, Spain. [Guate, J. L.] Hosp San Agustin, Dept Urol, Aviles, Spain. [Herrero, A.] Hosp Cent Covadonga, Dept Urol, Oviedo, Spain. [Abascal, R.] Hosp Cent Gen, Dept Urol, Oviedo, Spain. [Diaz, M.] Hosp Cabueries, Dept Urol, Gijon, Spain. [Cespedes, M.] Hosp De Sant Boi, Dept Urol, St Boi De Llobregat, Spain. [Mateos, A.] Hosp Cruz Roja, Dept Urol, Gijon, Spain. [Muntanola, P.] Hosp Alvarez Buylla, Dept Urol, Mieres, Spain. [Huergo, F.] Hosp Jarrio, Dept Urol, Caona, Spain. [Mosquera, J.] Hosp Carmen & Severo Ochoa, Dept Urol, Cangas, Spain. [Gelabert Mas, A.] Univ Autonoma Barcelona, Dept Urol, E-08193 Barcelona, Spain. RI Serra, C/E-6879-2014; Michaud, Dominique/I-5231-2014; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD MAR PY 2009 VL 8 IS 4 BP 288 EP 288 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 453CF UT WOS:000266587100657 ER PT J AU Moser, GJ Foley, J Burnett, M Goldsworthy, TL Maronpot, R AF Moser, Glenda J. Foley, Julie Burnett, Merrie Goldsworthy, Thomas L. Maronpot, Robert TI Furan-induced dose-response relationships for liver cytotoxicity, cell proliferation, and tumorigenicity (furan-induced liver tumorigenicity) SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE Furan; Mouse liver carcinogenesis; Cytotoxic; Proliferation; Inflammation ID INCREASED CARCINOGENICITY; FISCHER-344 RATS; B6C3F(1) MICE; HEPATOCYTE; APOPTOSIS; TESTS; HEPATOCARCINOGENESIS; EXPRESSION; REGRESSION; GROWTH AB Rodent studies of furan are associated with liver cell necrosis, release or liver-associated enzymes, increased hepatocyte proliferation, and hepatocarcinogenesis. For carcinogens whose proposed mode of action is cytolethality, it is hypothesized that the dose-response curve for tumor development would parallel the dose-response curve for cell death with compensatory proliferation in the target organ. To prospectively test this hypothesis, female B6C3F(1), mice were exposed to furan at carcinogenic doses and lower for 3 weeks or 2 years. At 3 weeks and in the 2-year study, there were dose-dependent and significant increases in hepatic cytotoxicity at 1.0, 2.0, 4.0, and 8.0 mg furan/kg. For cell proliferation as measured by 5-bromo-2'-deoxyuridine (BrdU) labeling index (LI), there was a statistically significant trend with increasing dose levels of furan and increased LI at 8.0 mg/kg. There was an increased incidence of foci of altered hepatocytes, hepatocellular adenomas, and adenomas or carcinomas at 4.0 and 8.0 mg/kg and carcinomas at 8.0 mg/kg. The multiplicity of microscopic tumors was increased and latency was decreased in mice exposed to 8.0 mg/kg. Prevalence of hepatic nodules at necropsy was increased in mice exposed to 4.0 and 8.0 mg/kg. Data demonstrate an association among furan-induced hepatic cytotoxicity, compensatory cell replication, and liver tumor formation in mice; at high doses >= 4.0 mg/kg, furan induced hepatotoxicity, compensatory cell replication and tumorigenesis in a dose-related manner, while furan did not produce tumors at cytotoxic doses of 1.0 and 2.0 mg/kg. (C) 2008 Published by Elsevier GmbH. C1 [Moser, Glenda J.; Burnett, Merrie; Goldsworthy, Thomas L.] Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. [Foley, Julie; Maronpot, Robert] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Moser, GJ (reprint author), Integrated Lab Syst Inc, POB 13501, Res Triangle Pk, NC 27709 USA. EM gmoser@ils-inc.com FU NIH, NIEHS [N01-ES-95434] FX We thank Grace Kissling for statistical support, Clinical Pathology Laboratory at NIEHS for enzyme analyses, Greg Kedderis for initial study design considerations, and the ILS animal care and toxicology and histology staff. This research was supported by the Intramural Research Program of the NIH, NIEHS, and contract no. N01-ES-95434. NR 39 TC 45 Z9 46 U1 1 U2 12 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD MAR PY 2009 VL 61 IS 2 BP 101 EP 111 DI 10.1016/j.etp.2008.06.006 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 423CL UT WOS:000264473900002 PM 18809303 ER PT J AU Lonsdorf, AS Hedrick, MN Shirakawa, A Lee, CR Singh, SP Hwang, ST Farber, JM AF Lonsdorf, A. S. Hedrick, M. N. Shirakawa, A. Lee, C. R. Singh, S. P. Hwang, S. T. Farber, J. M. TI Murine psoriasis-like inflammation induced by IL-23 is dependent on CC-chemokine receptor 6 (CCR6) expression on skin homing T-cells and non Tcells as a source of IL-22 SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY MAR 05-07, 2009 CL Heidelberg, GERMANY SP Arbeits Gemeinsch Dermatol Forsch C1 [Lonsdorf, A. S.; Hwang, S. T.] NCI, NIH, Dept Dermatol, Bethesda, MD 20892 USA. [Hedrick, M. N.; Shirakawa, A.; Singh, S. P.; Farber, J. M.] NIAID, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. [Lee, C. R.] NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. [Lonsdorf, A. S.] Univ Heidelberg Hosp, Dept Dermatol, D-69115 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2009 VL 18 IS 3 BP 287 EP 287 PG 1 WC Dermatology SC Dermatology GA 409QF UT WOS:000263520200090 ER PT J AU Guenova, E Ghoreschi, K Hotzenecker, W Mailhammer, R Weindl, G Sauer, K Schakel, K Schaller, M Rocken, M Biedermann, T AF Guenova, E. Ghoreschi, K. Hoetzenecker, W. Mailhammer, R. Weindl, G. Sauer, K. Schaekel, K. Schaller, M. Roecken, M. Biedermann, T. TI Systemic IL-4 therapy abrogates IL-23 secretion and Th17 responses in psoriasis SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY MAR 05-07, 2009 CL Heidelberg, GERMANY SP Arbeits Gemeinsch Dermatol Forsch C1 [Guenova, E.; Hoetzenecker, W.; Sauer, K.; Schaller, M.; Roecken, M.; Biedermann, T.] Univ Hautklin, Univ Tubingen, D-72076 Tubingen, Germany. [Ghoreschi, K.] NIH, Bethesda, MD 20892 USA. [Weindl, G.] Free Univ Berlin, Inst Pharm Pharmacol & Toxicol, D-14195 Berlin, Germany. [Schaekel, K.] Tech Univ Dresden, Inst Immunol, D-01307 Dresden, Germany. [Mailhammer, R.] Univ Munich, Klin & Poliklin Dermatol & Allergol, D-80337 Munich, Germany. RI Weindl, Gunther/B-6161-2011; Guenova, Emmanuella/A-4656-2015 OI Weindl, Gunther/0000-0002-4493-7597; NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2009 VL 18 IS 3 BP 293 EP 293 PG 1 WC Dermatology SC Dermatology GA 409QF UT WOS:000263520200127 ER PT J AU Wolf, R Dong, H Winston, J Mascia, F Cataisson, C Chavakis, T Howard, ZO Yuspa, SH AF Wolf, R. Dong, H. Winston, J. Mascia, F. Cataisson, C. Chavakis, T. Howard, Z. O. Yuspa, S. H. TI Functional link for a psoriasis candidate gene: S100A7 mediates leukocyte chemotaxis directly through the pattern recognition receptor RAGE SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY MAR 05-07, 2009 CL Heidelberg, GERMANY SP Arbeits Gemeinsch Dermatol Forsch C1 [Wolf, R.; Dong, H.; Winston, J.; Mascia, F.; Cataisson, C.; Yuspa, S. H.] NCI, NIH, CCR, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Dong, H.] NCI, NIH, SAIC Frederick, Div Basic Sci & Cellular Immunol, Frederick, MD 21701 USA. [Chavakis, T.] NCI, NIH, CCR, Expt Immunol Branch, Bethesda, MD 20892 USA. [Howard, Z. O.] NCI, NIH, CCR, Lab Mol Immunoregulat, Frederick, MD 21701 USA. [Wolf, R.] Ludwig Maximilians Univ Munchen, Dept Dermatol, D-80337 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2009 VL 18 IS 3 BP 293 EP 293 PG 1 WC Dermatology SC Dermatology GA 409QF UT WOS:000263520200122 ER PT J AU Kostka, SL Hurst, J Demircik, F von Landenberg, P Udey, MC Waisman, A von Stebut, E AF Kostka, S. Lopez Hurst, J. Demircik, F. von Landenberg, P. Udey, M. C. Waisman, A. von Stebut, E. TI Anti-phospholipid antibodies opsonise L. major parasites to promote dendriticcell (DC) phagocytosis and induction of protective immunity SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY MAR 05-07, 2009 CL Heidelberg, GERMANY SP Arbeits Gemeinsch Dermatol Forsch C1 [Hurst, J.; von Landenberg, P.] Johannes Gutenberg Univ Mainz, Inst Clin Chem & Lab Med, Mainz, Germany. [Demircik, F.; Waisman, A.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Udey, M. C.] NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. RI Waisman, Ari/C-7383-2015 OI Waisman, Ari/0000-0003-4304-8234 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2009 VL 18 IS 3 BP 303 EP 303 PG 1 WC Dermatology SC Dermatology GA 409QF UT WOS:000263520200187 ER PT J AU Prabakaran, P Zhu, ZY Xiao, XD Biragyn, A Dimitrov, AS Broder, CC Dimitrov, DS AF Prabakaran, Ponraj Zhu, Zhongyu Xiao, Xiaodong Biragyn, Arya Dimitrov, Antony S. Broder, Christopher C. Dimitrov, Dimiter S. TI Potent human monoclonal antibodies against SARS CoV, Nipah and Hendra viruses SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE antibody; Hendra virus; Nipah virus; SARS CoV; therapeutics; vaccines ID ACUTE RESPIRATORY SYNDROME; CORONAVIRUS SPIKE PROTEIN; RECEPTOR-BINDING DOMAIN; ANGIOTENSIN-CONVERTING ENZYME-2; EMERGENT DEADLY PARAMYXOVIRUS; CROSS-REACTIVE NEUTRALIZATION; HUMAN-IMMUNODEFICIENCY-VIRUS; RED-CELL APLASIA; INTRAVENOUS IMMUNOGLOBULIN; S-GLYCOPROTEIN AB Background: Recently, several potent human monoclonal antibodies (hmAbs) targeting the severe acute respiratory syndrome-associated coronavirus (SARS CoV) S glycoproteins, as well as the first fully human mAbs against two other paramyxoviruses, Hendra virus (HeV) and Nipah virus (NiV) have been discovered. Objective: To examine, compare and contrast the functional characteristics of hmAbs with potential for prophylaxis and treatment of diseases caused by SARS CoV, HeV and NiV. Methods: A review of relevant literature. Results/conclusions: Structural analyses have provided insights into the molecular mechanisms of receptor recognition and antibody neutralization, and suggested that these antibodies alone or in combination could fight the viruses' heterogeneity and mutability, which is a major problem in the development of effective therapeutic agents against viruses, including therapeutic antibodies. C1 [Prabakaran, Ponraj; Zhu, Zhongyu; Xiao, Xiaodong; Dimitrov, Dimiter S.] NCI Frederick, Protein Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. [Prabakaran, Ponraj] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Zhu, Zhongyu] SAIC Frederick Inc, BRP, NCI Frederick, Frederick, MD 21702 USA. [Biragyn, Arya] NIA, Immunotherapeut Unit, Baltimore, MD 21224 USA. [Dimitrov, Antony S.] Profectus BioSci Inc, Baltimore, MD 21224 USA. [Dimitrov, Antony S.; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Prabakaran, P (reprint author), NCI Frederick, Protein Interact Grp, CCRNP, CCR,NIH, Bldg 469,150B,POB B,Miller Dr, Frederick, MD 21702 USA. EM prabakaran.ponraj@duke.edu RI Ponraj, Prabakaran/D-6325-2011 FU National Institutes of Health (NIH); Middle Atlantic Regional Center of Excellence (MARCE) [AI057168]; Uniformed Services University of the Health Sciences (USUHS) [R0731L]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; National Institutes of Health [NOI-CO-12400] FX This study was supported by the National Institutes of Health (NIH) biodefense program (D.S.D.), and by the Middle Atlantic Regional Center of Excellence (MARCE) for Biodefense and Emerging Infectious Disease Research, NIH AI057168 and Uniformed Services University of the Health Sciences (USUHS) R0731L grants (C.C.B.). This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract NOI-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 117 TC 9 Z9 10 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD MAR PY 2009 VL 9 IS 3 BP 355 EP 368 DI 10.1517/14712590902763755 PG 14 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 418AW UT WOS:000264120600008 PM 19216624 ER PT J AU Otto, M AF Otto, Michael TI Understanding the epidemic of community-associated MRSA and finding a cure: are we asking the right questions? SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Editorial Material ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN; VIRULENCE DETERMINANTS; PNEUMONIA; INFECTIONS; DISEASE; USA300; CLONE; GENE C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS [Z99 AI999999, ZIA AI000904-08] NR 20 TC 3 Z9 3 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD MAR PY 2009 VL 7 IS 2 BP 141 EP 143 DI 10.1586/14787210.7.2.141 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 418AS UT WOS:000264120200001 PM 19254161 ER PT J AU Stoll-Keller, F Barth, H Fafi-Kremer, S Zeisel, MB Baumert, TF AF Stoll-Keller, Francois Barth, Heidi Fafi-Kremer, Samira Zeisel, Mirjam B. Baumert, Thomas F. TI Development of hepatitis C virus vaccines: challenges and progress SO EXPERT REVIEW OF VACCINES LA English DT Review DE antibody; chimpanzee model; HCV; prophylactic vaccine; therapeutic vaccine ID CD8(+) T-CELLS; SCAVENGER RECEPTOR-BI; HUMAN MONOCLONAL-ANTIBODIES; CELLULAR IMMUNE-RESPONSES; INTERFERON-BASED THERAPY; IN-VITRO PROLIFERATION; HUMAN DENDRITIC CELLS; NEUTRALIZING ANTIBODIES; HCV INFECTION; ENVELOPE PROTEIN AB Development of an effective vaccine against the hepatitis C virus (HCV) has long been defined as a difficult challenge due to the considerable variability of this RNA virus and the observation that convalescent humans and chimpanzees could be re-infected after re-exposure. On the other hand, progress in the understanding of antiviral immune responses in patients with viral clearance has elucidated key mechanisms playing a role in the control of viral infection. Studies investigating prophylactic vaccine approaches in chimpanzees have confirmed that the induction and maintenance of strong helper and cytotoxic T-cell immune responses against multiple viral epitopes is necessary for protection against viral clearance and chronic infection. A multispecific B-cell response, resulting in rapid induction of cross-neutralizing antibodies may assist cellular responses. Therapeutic vaccine formulations currently being evaluated in clinical trials are facing the fact that the immune system of chronic carriers is impaired and needs the restoration of T-cell functions to enhance their efficacy. C1 [Stoll-Keller, Francois; Baumert, Thomas F.] Univ Strasbourg, Hop Univ Strasbourg, Serv Hepatogastroenterol, INSERM,U748, F-67000 Strasbourg, France. [Stoll-Keller, Francois; Fafi-Kremer, Samira] Hop Univ Strasbourg, Virol Lab, F-67000 Strasbourg, France. [Barth, Heidi] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RP Stoll-Keller, F (reprint author), Univ Strasbourg, Hop Univ Strasbourg, Serv Hepatogastroenterol, INSERM,U748, 3 Rue Koeberle, F-67000 Strasbourg, France. EM francoise.stoll@viro-ulp.u-strasbg.fr RI Zeisel, Mirjam/E-9205-2016 OI Zeisel, Mirjam/0000-0003-1606-0131 FU Inserm, France; Universite Louis Pasteur de Strasbourg (CONECTUS), France; Hopitaux Universitaires de Strasbourg, France; European Union [LSHM-CT-2004-503359]; Agence Nationale de la Recherche, France [ANR-05-CEXC-008]; Agence Nationale de la Recherche sur lee SIDA et les Hepatites Vitrales, France [ANRS-06221]; Else-Kroner-Fresmius Foundation, Bad Homburg, Germany [P17/07//A83/06]; Deutsche Forschungsgemeinschaft, Bonn, Germany FX This work was supported by Inserm, France, Universite Louis Pasteur de Strasbourg (CONECTUS), France, Hopitaux Universitaires de Strasbourg, France, the European Union (LSHM-CT-2004-503359),the chair of excellence program of the Agence Nationale de la Recherche (ANR-05-CEXC-008), France, the Agence Nationale de la Recherche sur lee SIDA et les Hepatites Vitrales (ANRS-06221), France, the Else-Kroner-Fresmius Foundation, Bad Homburg (P17/07//A83/06), Germany and the Deutsche Forschungsgemeinschaft (Ba3643/1-1; Ba1417/11-2), Bonn, Germany, The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 121 TC 53 Z9 61 U1 1 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD MAR PY 2009 VL 8 IS 3 BP 333 EP 345 DI 10.1586/14760584.8.3.333 PG 13 WC Immunology SC Immunology GA 423AT UT WOS:000264469500014 PM 19249975 ER PT J AU Hall, J Gray, S A'Hern, R Shanley, S Watson, M Kash, K Croyle, R Eeles, R AF Hall, Julia Gray, Susan A'Hern, Roger Shanley, Susan Watson, Maggie Kash, Kathryn Croyle, Robert Eeles, Rosalind TI Genetic testing for BRCA1: effects of a randomised study of knowledge provision on interest in testing and long term test uptake; implications for the NICE guidelines SO FAMILIAL CANCER LA English DT Article DE BRCA1; Genetic testing; Interest; Knowledge; NICE guidelines ID BREAST-CANCER SUSCEPTIBILITY; CONTROLLED-TRIAL; OVARIAN-CANCER; PSYCHOLOGICAL IMPACT; HEREDITARY BREAST; DECISION-MAKING; INCREASED RISK; WOMEN; FAMILIES; ATTITUDES AB Introduction Interest in searching for mutations in BRCA1 and BRCA2 is high. Knowledge regarding these genes and the advantages and limitations of genetic testing is limited. It is unknown whether increasing knowledge about breast cancer genetic testing alters interest in testing. Methods Three hundred and seventy nine women (260 with a family history of breast cancer; 119 with breast cancer) from The Royal Marsden NHS Foundation Trust were randomised to receive or not receive written educational information on cancer genetics. A questionnaire was completed assessing interest in BRCA1 testing and knowledge on breast cancer genetics and screening. Actual uptake of BRCA1 testing is reported with a six year follow-up. Results Eighty nine percent of women at risk of breast cancer and 76% of women with breast cancer were interested in BRCA1 testing (P < 0.0001). Provision of educational information did not affect level of interest. Knowledge about breast cancer susceptibility genes was poor. According to the NICE guidelines regarding eligibility for BRCA1 and BRCA2 testing, the families of 66% of the at risk group and 13% of the women with breast cancer would be eligible for testing (probability of BRCA1 mutation a parts per thousand yen20%). Within six years of randomisation, genetic testing was actually undertaken on 12 women, only 10 of whom would now be eligible, on the NICE guidelines. Conclusions There is strong interest in BRCA1 testing. Despite considerable ignorance of factors affecting the inheritance of breast cancer, education neither reduced nor increased interest to undergo testing. The NICE guidelines successfully triage those with a high breast cancer risk to be managed in cancer genetics clinics. C1 [A'Hern, Roger; Eeles, Rosalind] Inst Canc Res, Sutton SM2 5PT, Surrey, England. [A'Hern, Roger; Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England. [Hall, Julia; Gray, Susan; Shanley, Susan; Watson, Maggie] Royal Marsden NHS Fdn Trust, London, England. [Kash, Kathryn] Thomas Jefferson Univ, Jefferson Med Coll, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. [Croyle, Robert] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Eeles, R (reprint author), Inst Canc Res, Downs Rd, Sutton SM2 5PT, Surrey, England. EM rosalind.eeles@icr.ac.uk OI Eeles, Rosalind/0000-0002-3698-6241 FU The Corinne Burton Trust and Dr Eeles' research fund; The Institute of Cancer Research; The Royal Marsden NHS Foundation Trust FX The Corinne Burton Trust and Dr Eeles' research fund provided funding for the study. We also acknowledge funding from The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Sue Gray is a Corinne Burton Trust nurse. We should like to thank Professor John Yarnold for entering patients into this study. We should like to thank the Clinical Trials Unit (Professor J Bliss and colleagues) at the Institute of Cancer Research for performing the randomisation. Funding The funding bodies played no part in study design, analysis or report writing. NR 34 TC 4 Z9 4 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9600 J9 FAM CANCER JI Fam. Cancer PD MAR PY 2009 VL 8 IS 1 BP 5 EP 13 DI 10.1007/s10689-008-9201-0 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 403CI UT WOS:000263059200002 PM 18679829 ER PT J AU Yakar, S Rosen, CJ Bouxsein, ML Sun, H Mejia, W Kawashima, Y Wu, YJ Emerton, K Williams, V Jepsen, K Schaffler, MB Majeska, RJ Gavrilova, O Gutierrez, M Hwang, D Pennisi, P Frystyk, J Boisclair, Y Pintar, J Jasper, H Domene, H Cohen, P Clemmons, D LeRoith, D AF Yakar, Shoshana Rosen, Clifford J. Bouxsein, Mary L. Sun, Hui Mejia, Wilson Kawashima, Yuki Wu, Yingjie Emerton, Kelly Williams, Valerie Jepsen, Karl Schaffler, Mitchell B. Majeska, Robert J. Gavrilova, Oksana Gutierrez, Mariana Hwang, David Pennisi, Patricia Frystyk, Jan Boisclair, Yves Pintar, John Jasper, Hector Domene, Horacio Cohen, Pinchas Clemmons, David LeRoith, Derek TI Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism SO FASEB JOURNAL LA English DT Article DE cortical bone; trabecular bone; osteoblast; osteoclast; ternary complex; binary complex ID ACID-LABILE SUBUNIT; FACTOR-BINDING PROTEIN-5; TYPE-1 IGF RECEPTOR; BONE-MINERAL DENSITY; BREAST-CANCER CELLS; TRANSGENIC MICE; SECRETING CELLS; FACTOR SYSTEM; GENE; HORMONE AB Serum insulin-like growth factor (IGF)-1 is secreted mainly by the liver and circulates bound to IGF-binding proteins (IGFBPs), either as binary complexes or ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS). The purpose of this study was to genetically dissect the role of IGF-1 circulatory complexes in somatic growth, skeletal integrity, and metabolism. Phenotypic comparisons of controls and four mouse lines with genetic IGF-1 deficits liver-specific IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout, and a triply deficient LID/ALSKO/BP3 line-produced several novel findings. 1) All deficient strains had decreased serum IGF-1 levels, but this neither predicted growth potential or skeletal integrity nor defined growth hormone secretion or metabolic abnormalities. 2) IGF-1 deficiency affected development of both cortical and trabecular bone differently, effects apparently dependent on the presence of different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted in increased linear growth. In summary, each IGF-1 complex constituent appears to play a distinct role in determining skeletal phenotype, with different effects on cortical and trabecular bone compartments.-Yakar, S., Rosen, C. J., Bouxsein, M. L., Sun, H., Mejia, W., Kawashima, Y., Wu, Y., Emerton, K., Williams, V., Jepsen, K., Schaffler, M. B., Majeska, R. J., Gavrilova, O., Gutierrez, M., Hwang, D., Pennisi, P., Frystyk, J., Boisclair, Y., Pintar, J., Jasper, H., Domene, H., Cohen, P., Clemmons, D., LeRoith, D. Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism. FASEB J. 23, 709-719 (2009) C1 [Yakar, Shoshana; Sun, Hui; Mejia, Wilson; Kawashima, Yuki; Wu, Yingjie; Emerton, Kelly; Williams, Valerie; Jepsen, Karl; Schaffler, Mitchell B.; Majeska, Robert J.; LeRoith, Derek] Mt Sinai Sch Med, Div Endocrine, New York, NY 10029 USA. [Yakar, Shoshana; Sun, Hui; Mejia, Wilson; Kawashima, Yuki; Wu, Yingjie; Emerton, Kelly; Williams, Valerie; Jepsen, Karl; Schaffler, Mitchell B.; Majeska, Robert J.; LeRoith, Derek] Mt Sinai Sch Med, Orthoped Div, New York, NY 10029 USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA. [Bouxsein, Mary L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Orthoped Biomech Lab, Boston, MA 02215 USA. [Gavrilova, Oksana; Pennisi, Patricia] NIDDK, NIH, Bethesda, MD USA. [Gutierrez, Mariana; Jasper, Hector; Domene, Horacio] R Gutierrez Childrens Hosp, Div Endocrinol, Endocrinol Res Ctr, Buenos Aires, DF, Argentina. [Hwang, David; Cohen, Pinchas] Mattel Hosp Children, David Geffen Sch Med, Div Pediat Endocrinol, Los Angeles, CA USA. [Frystyk, Jan] Aarhus Univ Hosp, Inst Clin, Med Res Labs, DK-8000 Aarhus, Denmark. [Frystyk, Jan] Aarhus Univ Hosp, Med Dept M Diabet & Endocrinol, DK-8000 Aarhus, Denmark. [Boisclair, Yves] Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. [Pintar, John] Univ Med & Dent New Jersey, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. [Clemmons, David] Univ N Carolina, Div Endocrinol, Chapel Hill, NC USA. RP Yakar, S (reprint author), Mt Sinai Sch Med, Div Endocrine, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. EM shoshana.yakar@mssm.edu FU NCRR NIH HHS [S10 RR017868]; NIAMS NIH HHS [1R01AR055141-01, AR054919-01A, AR45433, R01 AR041210, R01 AR045433, R01 AR054919, R01 AR055141] NR 64 TC 47 Z9 48 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2009 VL 23 IS 3 BP 709 EP 719 DI 10.1096/fj.08-118976 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 437SD UT WOS:000265506300007 PM 18952711 ER PT J AU Izzotti, A Calin, GA Arrigo, P Steele, VE Croce, CM De Flora, S AF Izzotti, Alberto Calin, George A. Arrigo, Patrizio Steele, Vernon E. Croce, Carlo M. De Flora, Silvio TI Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke SO FASEB JOURNAL LA English DT Article DE mirnome; transcriptome; proteome; microarrays ID GENE-EXPRESSION; CANCER; CHEMOPREVENTION; POLYMORPHISM; CARCINOGENS; INHIBITION; MODULATION; APOPTOSIS; PROFILES; GENOME AB Although microRNAs have been investigated extensively in cancer research, little is known regarding their response to noxious agents in apparently healthy tissues. We analyzed the expression of 484 miRNAs in the lungs of rats exposed to environmental cigarette smoke (ECS) for 28 days. ECS down-regulated 126 miRNAs (26.0%) at least 2-fold and 24 miRNAs more than 3-fold. We previously demonstrated that 107 of 4858 genes (2.9%) and 50 of 518 proteins (9.7%) were up-regulated by ECS in the same tissue, which is consistent with the role of microRNAs as negative regulators of gene expression. The most remarkably down-regulated microRNAs belonged to the families of let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223, which regulate stress response, apoptosis, proliferation, angiogenesis, and expression of genes. In contrast, miR-294, an inhibitor of transcriptional repressor genes, was up-regulated by ECS. There was a strong parallelism in dysregulation of rodent microRNAs and their human homologues, which are often transcribed from genes localized in fragile sites deleted in lung cancer. Five ECS-down-regulated microRNAs are known to be affected by single nucleotide polymorphisms. Thus, changes in microRNA expression are an early event following exposure to cigarette smoke.-Izzotti, A., Calin, G. A., Arrigo, P., Steele, V. E., Croce, C. M., De Flora, S. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 23, 806-812 (2009) C1 [Izzotti, Alberto; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Calin, George A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Arrigo, Patrizio] CNR, Inst Study Macromol, Genoa, Italy. [Steele, Vernon E.] NCI, Rockville, MD USA. [Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU U.S. National Cancer Institute [N01-CN 53301] FX This study was supported by the U.S. National Cancer Institute (contract N01-CN 53301). NR 43 TC 231 Z9 244 U1 4 U2 32 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAR PY 2009 VL 23 IS 3 BP 806 EP 812 DI 10.1096/fj.08-121384 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 437SD UT WOS:000265506300016 PM 18952709 ER PT J AU Randhawa, M Huff, T Valencia, JC Younossi, Z Chandhoke, V Hearing, VJ Baranova, A AF Randhawa, Manpreet Huff, Tom Valencia, Julio C. Younossi, Zobair Chandhoke, Vikas Hearing, Vincent J. Baranova, Ancha TI Evidence for the ectopic synthesis of melanin in human adipose tissue SO FASEB JOURNAL LA English DT Article DE obesity; metabolic syndrome; inflammation; alpha-MSH; pigmentation ID EUMELANIN; SKIN; PATHOGENESIS; MELANOCYTES; MELANOSOMES; EXPRESSION; RADICALS AB Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes, in retinal pigment epithelium (RPE) cells, in the inner ear, and in the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes. In the current study, we confirmed the expression of melanogenesis-related mRNAs and proteins in human adipose tissue using real-time polymerase chain reaction and immunohistochemical staining. TYR mRNA signals were also detected by in situ hybridization in visceral adipocytes. The presence of melanin in human adipose tissue was revealed both by Fontana-Masson staining and by permanganate degradation of melanin coupled with liquid chromatography/ultraviolet/mass spectrometry determination of the pyrrole-2,3,5-tricarboxylic acid ( PTCA) derivative of melanin. We also compared melanogenic activities in adipose tissues and in other human tissues using the L-[U-(14)C] tyrosine assay. A marked heterogeneity in the melanogenic activities of individual adipose tissue extracts was noted. We hypothesize that the ectopic synthesis of melanin in obese adipose may serve as a compensatory mechanism that uses its anti-inflammatory and its oxidative damage-absorbing properties. In conclusion, our study demonstrates for the first time that the melanin biosynthesis pathway is functional in adipose tissue.-Randhawa, M., Huff, T., Valencia, J. C., Younossi, Z., Chandhoke, V., Hearing, V. J., Baranova, A. Evidence for the ectopic synthesis of melanin in human adipose tissue. FASEB J. 23, 835-843 (2009) C1 [Randhawa, Manpreet; Chandhoke, Vikas; Baranova, Ancha] George Mason Univ, Mol & Microbiol Dept, Manassas, VA USA. [Randhawa, Manpreet; Chandhoke, Vikas; Baranova, Ancha] George Mason Univ, Ctr Study Genom Liver Dis, Manassas, VA USA. [Huff, Tom] George Mason Univ, Coll Sci, Shared Instrumentat Res Facil, Manassas, VA USA. [Valencia, Julio C.; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Younossi, Zobair; Baranova, Ancha] INOVA Fairfax Hosp, Ctr Liver Dis, Fairfax, VA USA. RP Baranova, A (reprint author), George Mason Univ, David King Hall,MSN 3E1, Fairfax, VA 22030 USA. EM abaranov@gmu.edu RI Baranova, Ancha/B-4608-2012 OI Baranova, Ancha/0000-0001-6810-5982 FU Thomas F. Jeffress and Kate Miller Jeffress Memorial Trust; U.S. National Institutes of Health FX This research has been supported by a grant from the Thomas F. Jeffress and Kate Miller Jeffress Memorial Trust and by the Intramural Research Program of the National Cancer Institute at the U.S. National Institutes of Health. A. B. and M. R. are grateful to Shobha M. Gowder and Jenefir Ibister for initial technical assistance with the project, V. Espina for cryoslicing of adipose, and F. Otaizo for the help with the first round of RT-PCR experiments. NR 22 TC 20 Z9 21 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2009 VL 23 IS 3 BP 835 EP 843 DI 10.1096/fj.08-116327 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 437SD UT WOS:000265506300019 PM 18971261 ER PT J AU Cerritelli, SM Crouch, RJ AF Cerritelli, Susana M. Crouch, Robert J. TI Ribonuclease H: the enzymes in eukaryotes SO FEBS JOURNAL LA English DT Review DE Aicardi-Goutieres Syndrome (AGS); DNA repair; DNA replication; DNA replication errors; hybrid binding domain (HBD); mitochondrial DNA (mtDNA); PCNA-interacting peptide (PIP); proliferating cell nuclear antigen (PCNA); reverse transcriptases; RNA/DNA hybrid ID AICARDI-GOUTIERES-SYNDROME; DNA-RNA HYBRIDS; SACCHAROMYCES-CEREVISIAE; SUBSTRATE-SPECIFICITY; RNA/DNA HYBRID; HUMAN RNASE-H1; HETERODUPLEX SUBSTRATE; MITOCHONDRIAL-DNA; HII; CATALYSIS AB Ribonucleases H are enzymes that cleave the RNA of RNA/DNA hybrids that form during replication and repair and which could lead to DNA instability if they were not processed. There are two main types of RNase H, and at least one of them is present in most organisms. Eukaryotic RNases H are larger and more complex than their prokaryotic counterparts. Eukaryotic RNase H1 has acquired a hybrid binding domain that confers processivity and affinity for the substrate, whereas eukaryotic RNase H2 is composed of three different proteins: the catalytic subunit (2A), similar to the monomeric prokaryotic RNase HII, and two other subunits (2B and 2C) that have no prokaryotic counterparts and as yet unknown functions, but that are necessary for catalysis. In this minireview, we discuss some of the most recent findings on eukaryotic RNases H1 and H2, focusing on the structural data on complexes between human RNase H1 and RNA/DNA hybrids that had provided great detail of how the hybrid binding- and RNase H-domains recognize and cleave the RNA strand of the hybrid substrates. We also describe the progress made in understanding the in vivo function of eukaryotic RNases H. Although prokayotes and some single-cell eukaryotes do not require RNases H for viability, in higher eukaryotes RNases H are essential. Rnaseh1 null mice arrest development around E8.5 because RNase H1 is necessary during embryogenesis for mitochondrial DNA replication. Mutations in any of the three subunits of human RNase H2 cause Aicardi-Goutieres syndrome, a human neurological disorder with devastating consequences. C1 [Cerritelli, Susana M.; Crouch, Robert J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Crouch, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM robert_crouch@nih.gov FU National Institutes of Health, NICHD FX This work was supported by the intramural program of the National Institutes of Health, NICHD. We thank Marcin Nowotny and Hyongi Chon for help with figures. NR 49 TC 198 Z9 200 U1 7 U2 29 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD MAR PY 2009 VL 276 IS 6 BP 1494 EP 1505 DI 10.1111/j.1742-4658.2009.06908.x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 430LU UT WOS:000264991400003 PM 19228196 ER PT J AU Armstrong, AY DeCherney, A Leppert, P Rebar, R Maddox, YT AF Armstrong, Alicia Y. DeCherney, Alan Leppert, Phyllis Rebar, Robert Maddox, Yvonne T. TI Keeping clinicians in clinical research: the Clinical Research/Reproductive Scientist Training Program SO FERTILITY AND STERILITY LA English DT Editorial Material DE Physician-scientist; clinical research ID PHYSICIAN-SCIENTIST AB In recent years the need for translational and clinical research has increased, whereas the number of physicians involved in clinical research has diminished. There is clearly a need for formalized academic training in the quantitative and methodologic principles of clinical research in reproductive medicine. The Clinical Research/Reproductive Scientist Training Program (CREST), a program supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the Clinical Research Training Program (CRTP) at Duke University, and the American Society for Reproductive Medicine (ASRM), meets this existing need. In addition, this program is specifically designed for physicians in private or academic clinical practice in reproductive medicine. Innovative programs such as CREST encourage the practicing physician to engage in clinical research while maintaining an active role in clinical practice. Participants in the program receive didactic on-line training from the CRTP and attend intensive weekend seminars at the National Institutes of Health (NIH) as well as CREST seminars at the annual meeting of the ASRM. Successful participants in the program receive a Certificate in Clinical Research from the CRTP. The program's goal is to provide practicing physicians with the tools and research credentials that will facilitate collaborations with investigators involved in large clinical trials. (Fertil Steril (R) 2009;91:664-6. (C) 2009 by American Society for Reproductive Medicine.) C1 [Armstrong, Alicia Y.; DeCherney, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA. [Leppert, Phyllis] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Rebar, Robert] Amer Soc Reprod Med, Birmingham, AL USA. RP Armstrong, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, 10 Ctr Dr, Bethesda, MD 20892 USA. EM aa257w@nih.gov FU Intramural NIH HHS [ZIA HD008737-09, Z99 HD999999] NR 12 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2009 VL 91 IS 3 BP 664 EP 666 DI 10.1016/j.fertnstert.2008.10.029 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 418JC UT WOS:000264143500002 PM 19144332 ER PT J AU Arlen, PM Mohebtash, M Madan, RA Gulley, JL AF Arlen, Philip M. Mohebtash, Mahsa Madan, Ravi A. Gulley, James L. TI Promising novel immunotherapies and combinations for prostate cancer SO FUTURE ONCOLOGY LA English DT Review DE clinical trials; dendritic cells; immunology; poxviral vector; prostate cancer; vaccines ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; ANDROGEN-DEPRIVATION THERAPY; IMMUNE-RESPONSES; PHASE-I; COSTIMULATORY MOLECULES; IMMUNOLOGICAL RESPONSE; ANTITUMOR IMMUNITY; RADIATION-THERAPY; CTLA-4 BLOCKADE AB The field of therapeutic cancer vaccines is currently in a state of active preclinical and clinical investigation, and certain novel therapies involving tumor immunotherapy have recently come to the forefront of prostate cancer research, While no therapeutic cancer vaccine has yet been approved by the US FDA, recent findings have demonstrated that new paradigms of combination therapies involving vaccines, employed in clinical trials with appropriate design and end points, may ultimately lead to cancer vaccines being used to treat various malignancies. Several characteristics of prostate cancer make it an ideal target for immunotherapy. Its relative indolence allows sufficient time to generate immune responses, which usually take weeks or months to mount. In addition, prostate cancer-associated antigens direct the immune response to prostate cancer cells, thus sparing normal tissue. This review focuses on the future of promising new vaccines and novel perspectives in the treatment of prostate cancer. C1 [Arlen, Philip M.; Mohebtash, Mahsa; Madan, Ravi A.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [Z99 CA999999] NR 69 TC 9 Z9 11 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD MAR PY 2009 VL 5 IS 2 BP 187 EP 196 DI 10.2217/14796694.5.2.187 PG 10 WC Oncology SC Oncology GA 423AW UT WOS:000264469800012 PM 19284377 ER PT J AU Everhart, JE Ruhl, CE AF Everhart, James E. Ruhl, Constance E. TI Burden of Digestive Diseases in the United States Part II: Lower Gastrointestinal Diseases SO GASTROENTEROLOGY LA English DT Review C1 [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. Social & Sci Syst, Silver Spring, MD USA. RP Everhart, JE (reprint author), NIDDK, Div Digest Dis & Nutr, 2 Democracy Plaza,Room 655,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM JE17G@nih.gov FU HHS [N267200612918C, N267200700001G] FX Supported by HHS contracts N267200612918C and N267200700001G. NR 8 TC 108 Z9 109 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2009 VL 136 IS 3 BP 741 EP 754 DI 10.1053/j.gastro.2009.01.015 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 412VD UT WOS:000263751400005 PM 19166855 ER PT J AU Martinez, ME Baron, JA Lieberman, DA Schatzkin, A Lanza, E Winawer, SJ Zauber, AG Jiang, RY Ahnen, DJ Bond, JH Church, TR Robertson, DJ Smith-Warner, SA Jacobs, ET Alberts, DS Greenberg, ER AF Martinez, Maria Elena Baron, John A. Lieberman, David A. Schatzkin, Arthur Lanza, Elaine Winawer, Sidney J. Zauber, Ann G. Jiang, Ruiyun Ahnen, Dennis J. Bond, John H. Church, Timothy R. Robertson, Douglas J. Smith-Warner, Stephanie A. Jacobs, Elizabeth T. Alberts, David S. Greenberg, E. Robert TI A Pooled Analysis of Advanced Colorectal Neoplasia Diagnoses After Colonoscopic Polypectomy SO GASTROENTEROLOGY LA English DT Article ID AMERICAN-CANCER-SOCIETY; ADENOMA CHARACTERISTICS; TASK-FORCE; SURVEILLANCE COLONOSCOPY; SCREENING COLONOSCOPY; ANTIOXIDANT VITAMINS; RECURRENCE; RISK; PREDICTORS; PREVENTION AB Background & Aims: Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk. Methods: We pooled individual data from 8 prospective studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance. Results: During a median follow-up period of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; standard error, 2.2) and those with an adenoma 20 mm in size or greater (19.3%; standard error, 1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age (P < .0001 for trend) and male sex (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.19-1.65) were associated significantly with an increased risk for metachronous advanced neoplasia, as were the number and size of prior adenomas (P < .0001 for trend), the presence of villous features (OR, 1.28; 95% Cl, 1.07-1.52), and proximal location (OR, 1.68; 95% CI, 1.43-1.98). High-grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics. Conclusions: Occurrence of advanced colorectal neoplasia is common after polypectomy. Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas. C1 [Martinez, Maria Elena; Jiang, Ruiyun; Jacobs, Elizabeth T.; Alberts, David S.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. [Martinez, Maria Elena; Jiang, Ruiyun; Jacobs, Elizabeth T.; Alberts, David S.] Univ Arizona, Mel & Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ 85724 USA. [Alberts, David S.] Univ Arizona, Dept Med, Tucson, AZ 85724 USA. [Baron, John A.; Greenberg, E. Robert] Dartmouth Med Sch, Dept Med, Lebanon, NH USA. [Baron, John A.; Greenberg, E. Robert] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. [Lieberman, David A.] Dept Vet Affairs Med Ctr, Portland, OR USA. [Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Lanza, Elaine] NCI, Ctr Canc Res, NIH, Rockville, MD USA. [Winawer, Sidney J.] Mem Sloan Kettering Canc Ctr, Dept Gastroenterol & Nutr Sci, New York, NY 10021 USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Ahnen, Dennis J.] Dept Vet Affairs Med Ctr, Denver, CO USA. [Bond, John H.] Minneapolis Vet Affairs Med Ctr, Dept Med, Minneapolis, MN USA. [Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA. [Robertson, Douglas J.] Dept Vet Affairs Med Ctr, White River Jct, VT USA. [Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Greenberg, E. Robert] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Martinez, ME (reprint author), Univ Arizona, Arizona Canc Ctr, POB 245024, Tucson, AZ 85724 USA. EM emartinez@azcc.arizona.edu OI Church, Timothy R./0000-0003-3292-5035 FU National Cancer Institute [CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, CA26852, CA106269]; Cooperative Studies Program, Department of Veterans Affairs FX The authors disclose the following: this work was supported by Public Health Service grants CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, and CA26852 from the National Cancer Institute. Dr Jacobs is supported by a K07 Career Development Award (CA106269) from the National Cancer Institute. Funding for the Veteran's Affairs Study was supported by the Cooperative Studies Program, Department of Veterans Affairs. NR 41 TC 211 Z9 221 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2009 VL 136 IS 3 BP 832 EP 841 DI 10.1053/j.gastro.2008.12.007 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 412VD UT WOS:000263751400021 PM 19171141 ER PT J AU Yamashita, T Ji, JF Budhu, A Forgues, M Yang, W Wang, HY Jia, HL Ye, QH Qin, LX Wauthier, E Reid, LM Minato, H Honda, M Kaneko, S Tang, ZY Wang, XW AF Yamashita, Taro Ji, Junfang Budhu, Anuradha Forgues, Marshonna Yang, Wen Wang, Hong-Yang Jia, Huliang Ye, Qinghai Qin, Lun-Xiu Wauthier, Elaine Reid, Lola M. Minato, Hiroshi Honda, Masao Kaneko, Shuichi Tang, Zhao-You Wang, Xin Wei TI EpCAM-Positive Hepatocellular Carcinoma Cells Are Tumor-Initiating Cells With Stem/Progenitor Cell Features SO GASTROENTEROLOGY LA English DT Article ID CANCER STEM-CELLS; PROGENITOR CELLS; MATURATION ARREST; LIVER-CANCER; EXPRESSION; ANTIGEN; IDENTIFICATION; ORIGIN; MARKER; ACTIVATION AB Background & Aims: Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC), in part, may be owing to the presence of hepatic cancer cells with stem/progenitor features. Methods: Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from 2 recently identified HCC subtypes (EpCAM(+) alpha -fetoprotein [AFP(+)] HCC and EpCAM(-) AFP(-) HCC). These subtypes differed in their expression of AFP, a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting was used to isolate EpCAM(+) HCC cells, which were tested for hepatic stem/progenitor cell properties. Results: Gene expression and pathway analyses revealed that the EpCAM(+) AFP(+) HCC subtype had features of hepatic stem/progenitor cells. Indeed, the fluorescence-activated cell sorting-isolated EpCAM(+) HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in nonobese diabetic, severe combined immunodeficient mice. Activation of Wnt/beta-catenin signaling enriched the EpCAM(+) cell population, whereas RNA interference-based blockage of EpCAM, a Wnt/beta-catenin signaling target, attenuated the activities of these cells. Conclusions: Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM(+) cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/beta-catenin signaling components such as EpCAM. C1 [Yamashita, Taro; Ji, Junfang; Budhu, Anuradha; Forgues, Marshonna; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Yang, Wen; Wang, Hong-Yang] Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai, Peoples R China. [Jia, Huliang; Ye, Qinghai; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. [Jia, Huliang; Ye, Qinghai; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Wauthier, Elaine; Reid, Lola M.] Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC USA. [Minato, Hiroshi; Honda, Masao; Kaneko, Shuichi] Liver Dis Ctr, Kanazawa, Ishikawa, Japan. [Minato, Hiroshi; Honda, Masao; Kaneko, Shuichi] Kanazawa Univ Hosp, Kanazawa, Ishikawa, Japan. RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 3044A,MSC 4258, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009; Wang, Hongyang/B-1340-2010; OI Minato, Hiroshi/0000-0003-2166-2874 FU Intramural NIH HHS [Z01 BC010876-01]; NIAAA NIH HHS [R01 AA014243]; NIDDK NIH HHS [R01 IP30-DK065933] NR 51 TC 487 Z9 539 U1 14 U2 89 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2009 VL 136 IS 3 BP 1012 EP 1024 DI 10.1053/j.gastro.2008.12.004 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 412VD UT WOS:000263751400039 PM 19150350 ER PT J AU Kamangar, F Chow, WH Abnet, CC Dawsey, SM AF Kamangar, Farin Chow, Wong-Ho Abnet, Christian C. Dawsey, Sanford M. TI Environmental Causes of Esophageal Cancer SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review DE Esophageal cancer; Risk factor; Tobacco; Alcohol; Socioeconomic status; Obesity; Acid reflux; Helicobacter pylori ID SQUAMOUS-CELL CARCINOMA; POLYCYCLIC AROMATIC-HYDROCARBONS; HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL-REFLUX DISEASE; N-NITROSO COMPOUNDS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; POLYMERASE-CHAIN-REACTION; HIGH-RISK REGION; BODY-MASS INDEX; PAPILLOMAVIRUS TYPE-16 INFECTION AB This article reviews the environmental risk factors and predisposing conditions for the two main histologic types of esophageal cancer. Tobacco smoking, excessive alcohol consumption, drinking mate, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of esophageal squamous cell carcinoma. Results of investigations on other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and, probably, absence of H pylori in the stomach increase the risk of esophageal adenocarcinoma. Results of studies investigating other factors are also discussed. C1 [Kamangar, Farin; Chow, Wong-Ho; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 3034, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU National Cancer Institute, National Institutes of Health FX Writing this review article was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 261 TC 159 Z9 162 U1 7 U2 25 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 EI 1558-1942 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2009 VL 38 IS 1 BP 27 EP + DI 10.1016/j.gtc.2009.01.004 PG 32 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 435UZ UT WOS:000265370100005 PM 19327566 ER PT J AU Diebold, SS Schulz, O Alexopoulou, L Leitner, WW Flavell, RA Sousa, CRE AF Diebold, S. S. Schulz, O. Alexopoulou, L. Leitner, W. W. Flavell, R. A. Reis e Sousa, C. TI Role of TLR3 in the immunogenicity of replicon plasmid-based vaccines SO GENE THERAPY LA English DT Article DE dendritic cells; Toll-like receptors; double-stranded RNA; replicon vaccines ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; TRANSFECTED DENDRITIC CELLS; DNA VACCINES; IN-VIVO; ANTIGEN PRESENTATION; IMMUNE-RESPONSES; RIG-I; INNATE; RECOGNITION AB Replicon plasmids encoding an alphavirus RNA replicase constitute an alternative to conventional DNA plasmids with promise for DNA vaccination in humans. Replicase activity amplifies the levels of transgene mRNA through a copying process involving double-stranded (ds) RNA intermediates, which contribute to vaccine immunogenicity by activating innate antiviral responses. Toll-like receptor 3 (TLR3) is a dsRNA innate immune receptor expressed by antigen-presenting dendritic cells (DCs). Here, we test the hypothesis that TLR3 is necessary for the immunogenicity of replicon plasmid-based DNA vaccines. We show that mouse CD8 alpha(+) DC phagocytose dying replicon plasmid-transfected cells in vitro and are activated in a TLR3-dependent manner by dsRNA present within those cells. However, we find that cytotoxic T-cell responses to a replicon plasmid intramuscular vaccine are not diminished in the absence of TLR3 in vivo. Our results underscore the potential role of TLR3 in mediating immune activation by dsRNA-bearing replicon plasmid-transfected cells and indicate that other innate sensing pathways can compensate for TLR3 absence in vivo. C1 [Diebold, S. S.; Schulz, O.; Reis e Sousa, C.] London Res Inst, Canc Res UK, Immunobiol Lab, London, England. [Alexopoulou, L.] Univ Aix Marseille 2, INSERM, CNRS, Ctr Immunol Marseille Luminy, Marseille, France. [Leitner, W. W.] NCI, NIH, Bethesda, MD 20892 USA. [Flavell, R. A.] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. [Flavell, R. A.] Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Diebold, SS (reprint author), Guys Hosp, Kings Coll London, Dept Immunobiol, 2nd Floor Borough Wing, London SE1 9RT, England. EM sandra.diebold@kcl.ac.uk RI Leitner, Wolfgang/F-5741-2011; Alexopoulou, Lena/A-5041-2017 OI Leitner, Wolfgang/0000-0003-3125-5922; Alexopoulou, Lena/0000-0003-4619-697X FU CRUK Career Development Award FX We thank Vincenzo Cerundolo and Michael Palmowski for their kind advice on DNA vaccination and members of the Immunobiology Laboratory, CRUK, for support and useful discussions. SSD is currently funded by a CRUK Career Development Award. NR 36 TC 18 Z9 18 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 2009 VL 16 IS 3 BP 359 EP 366 DI 10.1038/gt.2008.164 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 417ZB UT WOS:000264115900007 PM 19052633 ER PT J AU Moy, SS Nadler, JJ Young, NB Nonneman, RJ Grossman, AW Murphy, DL D'Ercole, AJ Crawley, JN Magnuson, TR Lauder, JM AF Moy, S. S. Nadler, J. J. Young, N. B. Nonneman, R. J. Grossman, A. W. Murphy, D. L. D'Ercole, A. J. Crawley, J. N. Magnuson, T. R. Lauder, J. M. TI Social approach in genetically engineered mouse lines relevant to autism SO GENES BRAIN AND BEHAVIOR LA English DT Review DE Autism spectrum disorders; endophenotype; engrailed; Fmr1; fragile X; Sert; Slc6a4; sociability ID FRAGILE-X-SYNDROME; TRANSPORTER KNOCKOUT MICE; LEMLI-OPITZ-SYNDROME; HOMEOBOX-TRANSCRIPTION-FACTOR; ANXIETY-RELATED BEHAVIOR; LONG-TERM DEPRESSION; SEROTONIN TRANSPORTER; SPECTRUM-DISORDER; MENTAL-RETARDATION; HEAD CIRCUMFERENCE AB Profound impairment in social interaction is a core symptom of autism, a severe neurodevelopmental disorder. Deficits can include a lack of interest in social contact and low levels of approach and proximity to other children. In this study, a three-chambered choice task was used to evaluate sociability and social novelty preference in five lines of mice with mutations in genes implicated in autism spectrum disorders. Fmr1(tm1Cgr/Y) (Fmr1(-/y)) mice represent a model for fragile X, a mental retardation syndrome that is partially comorbid with autism. We tested Fmr1(-/y) mice on two genetic backgrounds, C57BL/6J and FVB/N-129/OlaHsd (FVB/129). Targeted disruption of Fmr1 resulted in low sociability on one measure, but only when the mutation was expressed on FVB/129. Autism has been associated with altered serotonin levels and polymorphisms in SLC6A4 (SERT), the serotonin transporter gene. Male mice with targeted disruption of Slc6a4 displayed significantly less sociability than wild-type controls. Mice with conditional overexpression of Igf-1 (insulin-like growth factor-1) offered a model for brain overgrowth associated with autism. Igf-1 transgenic mice engaged in levels of social approach similar to wild-type controls. Targeted disruption in other genes of interest, En2 (engrailed-2) and Dhcr7, was carried on genetic backgrounds that showed low levels of exploration in the choice task, precluding meaningful interpretations of social behavior scores. Overall, results show that loss of Fmr1 or Slc6a4 gene function can lead to deficits in sociability. Findings from the fragile X model suggest that the FVB/129 background confers enhanced susceptibility to consequences of Fmr1 mutation on social approach. C1 [Moy, S. S.; Nadler, J. J.; Young, N. B.; Nonneman, R. J.; D'Ercole, A. J.; Crawley, J. N.; Magnuson, T. R.; Lauder, J. M.] Univ N Carolina, Neurodev Disorders Res Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Moy, S. S.; Crawley, J. N.] Univ N Carolina, Dept Psychiat, Sch Med, Chapel Hill, NC 27599 USA. [Nadler, J. J.; Magnuson, T. R.] Univ N Carolina, Dept Genet, Sch Med, Chapel Hill, NC 27599 USA. [Grossman, A. W.] Univ Illinois, Beckman Inst, Grad Program Neurosci, Urbana, IL 61801 USA. [Murphy, D. L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA. [D'Ercole, A. J.] Univ N Carolina, Dept Pediat, Sch Med, Chapel Hill, NC 27599 USA. [Crawley, J. N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. [Lauder, J. M.] Univ N Carolina, Dept Cell & Dev Biol, Sch Med, Chapel Hill, NC 27599 USA. RP Moy, SS (reprint author), Univ N Carolina, Neurodev Disorders Res Ctr, Sch Med, CB 7146, Chapel Hill, NC 27599 USA. EM ssmoy@med.unc.edu FU Fragile X Research Foundation; National Institutes of Health STAART [U54 MH66418 (]; National Institute of Child Health and Human Development (NICHD) [P30 HD03110, HD008299]; National Institute of Mental Health (NIMH) [MH035321] FX This work was supported by the Fragile X Research Foundation (FRAXA; PI: Dr J.M.L.), National Institutes of Health STAART grant U54 MH66418 (project principal investigator: Dr T.R.M.), National Institute of Child Health and Human Development (NICHD) grants P30 HD03110 (to Dr Joseph Piven) and HD008299 (to Dr A.J.D.), National Institute of Mental Health (NIMH) grant MH035321 (to Dr William Greenough) and by the NIMH Intramural Research Program (Drs J.N.C. and D.L.M.). We thank Dr William Greenough for providing Fmr1 mice, Dr Karl Herrup and Dr Barbara Kuemerle for providing En2 breeding pairs, Dr Kathleen Sulik and Dr Heather Baudet for providing Dhcr7 breeding pairs and Dr Ping Ye for providing Igf-1 mice for these studies. NR 104 TC 117 Z9 117 U1 2 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD MAR PY 2009 VL 8 IS 2 BP 129 EP 142 DI 10.1111/j.1601-183X.2008.00452.x PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 412WY UT WOS:000263756100001 PM 19016890 ER PT J AU Yan, JZ Yang, X Mortin, MA Shahabuddin, M AF Yan, Jizhou Yang, Xiang Mortin, Mark A. Shahabuddin, Mohammed TI Malaria Sporozoite Antigen-Directed Genome-Wide Response in Transgenic Drosophila SO GENESIS LA English DT Article DE Drosophila melanogaster; immunity; malaria; microarray; mosquito; Plasmodium falciparum ID PARASITE PLASMODIUM-FALCIPARUM; CIRCUMSPOROZOITE PROTEIN; IMMUNE-RESPONSE; SURFACE PROTEIN-2; ANOPHELES-GAMBIAE; BLOOD STAGES; INVASION; SEQUENCE; GENE; THROMBOSPONDIN AB Malaria kills a million people annually. Understanding the relationship between a causative parasite, Plasmodium falciparum, and the mosquito vector might suggest novel prevention approaches. We created and transformed into Drosophila two genes encoding, thrombospondin-related adhesive protein (TRAP) and circumsporozoite protein (CSP), found on the cell surface of Plasmodium sporozoites. To understand a model insect's response, we induced these proteins separately and together, performing whole genome microarray analysis measuring gene expression changes. Gene ontology classification of responding genes reveals that TRAP and CSP strongly and differentially influence Drosophila genes involved with cell motility and gene regulation, respectively; however, the most striking effects are on the immune system. While immune-related genes are but modestly elevated compared with responses to sepsis, there is a marked repression of the Toll pathway. This suggests: (1) how Plasmodium infection of the mosquito might use TRAP and CSP to modulate the host insect's physiology to promote sporozoite survival and transmission to man and (2) that approaches to elevate expression of the mosquito's Toll pathway might lead to novel methods of malaria prevention. genesis 47:196203, 2009. (c) 2009 Wiley-Liss, Inc. C1 [Mortin, Mark A.] Eunice Kennedy Shriver NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Yan, Jizhou; Shahabuddin, Mohammed] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Yan, Jizhou] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Yang, Xiang; Mortin, Mark A.] NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Mortin, MA (reprint author), Eunice Kennedy Shriver NICHHD, Mol Genet Lab, NIH, 6 Ctr Dr,Bldg 6B,Room 3B331, Bethesda, MD 20892 USA. EM jyan2@mail.med.upenn.edu; mortinm@mail.nih.gov RI Mortin, Mark/B-4251-2008 FU Intramural NIH HHS NR 23 TC 3 Z9 3 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD MAR PY 2009 VL 47 IS 3 BP 196 EP 203 DI 10.1002/dvg.20483 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 425RT UT WOS:000264655500008 PM 19241390 ER PT J AU Edskes, HK McCann, LM Hebert, AM Wickner, RB AF Edskes, Herman K. McCann, Lindsay M. Hebert, Andrea M. Wickner, Reed B. TI Prion Variants and Species Barriers Among Saccharomyces Ure2 Proteins SO GENETICS LA English DT Article ID BETA-SHEET STRUCTURE; POLAR ZIPPERS; SUP35 PROTEIN; SCRAPIE PRION; YEAST; CEREVISIAE; STRAINS; DOMAIN; CONSERVATION; FIBRILS AB As hamster scrapie cannot infect mice, due to sequence differences in their PrP proteins, we find "species barriers" to transmission of the [URE3] prion in Saccharomyces cerevisiae among Ure2 proteins of S. cerevisiae, paradoxus, bayanus, cariocanus, and mikatae on the basis of differences among their Ure2p prion domain sequences. The rapid variation of the N-terminal Ure2p prion domains results in protection against the detrimental effects of infection by a prion, just as the PrP residue 129 Met/Val polymorphism may have arisen to protect humans from the effects of cannibalism. Just as spread of bovine spongiform encephalopathy prion variant is less impaired by species barriers than is sheep scrapie, we find that some [URE3] prion variants are infectious to another yeast species while other variants (with the identical amino acid sequence) are not. The species barrier is thus prion variant dependent as in mammals. [URE3] prion variant characteristics are maintained even on passage through the Ure2p of another species. Ure2p of Saccharomyces castelli has an N-terminal Q/N-rich "prion domain" but does not form prions (in S. cerevisiae) and is not infected with [URE3] from Ure2p of other Saccharomyces. This implies that conservation of its prion domain is not for the purpose of forming prions. Indeed the Ure2p prion domain has been shown to be important, though not essential, for the nitrogen catabolism regulatory role of the protein. C1 [Edskes, Herman K.; McCann, Lindsay M.; Hebert, Andrea M.; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, Natl Inst Hlth, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov FU Intramural NIH HHS NR 64 TC 40 Z9 42 U1 0 U2 2 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 2009 VL 181 IS 3 BP 1159 EP 1167 DI 10.1534/genetics.108.099929 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 499IU UT WOS:000270213500031 PM 19124570 ER PT J AU Havrilesky, LJ Maxwell, GL Chan, JK Myers, ER AF Havrilesky, Laura J. Maxwell, G. Larry Chan, John K. Myers, Evan R. TI Cost effectiveness of a test to detect metastases for endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Lymph node metastasis; Diagnostic test; Cost effectiveness; Gynecologic Oncologist ID GYNECOLOGIC-ONCOLOGY-GROUP; LYMPH-NODE METASTASIS; CORPUS CANCER; CARCINOMA; SURVIVAL; RESECTION; DETERMINANTS; RADIOTHERAPY AB Objective. To estimate the potential cost-effectiveness of a hypothetical test to screen for lymph node metastases in women with newly diagnosed, apparent early stage endometrial cancer. Methods. A decision model was constructed to inform a choice between the following strategies: (I) Usual care, in which the probability of undergoing full surgical staging (29%) is based on literature review; (2) Noninvasive diagnostic testing for metastasis (Testing), in which patients with abnormal test results undergo full surgical staging; (3) 100% referral, in which all patients are referred for full surgical staging. Survival was modeled using Surveillance Epidemiology and End Results (SEER) database. Base case diagnostic test characteristic estimates (sensitivity 0.90, specificity 0.90) were varied for sensitivity analysis. Cost of the diagnostic test was set at $500 and varied; costs of treatment for endometrial cancer (surgery, adjuvant therapies, diagnosis of recurrence, salvage therapies and palliative care) were incorporated. Results. Usual care was the least expensive strategy, while Testing was more expensive and more effective, with an incremental cost-effectiveness ratio (ICER) of $18,785 per year of life saved (YLS) compared to Usual care. 100% referral was the most expensive and most effective strategy, with an ICER of $35,358 per YLS compared to Testing. Results are relatively sensitive to variation in test characteristics and the cost of the diagnostic test but insensitive to cost of treatment and probability of adjuvant therapies. Testing remains cost-effective compared to Usual care unless the usual rate of referral to a Gynecologic Oncologist for full staging exceeds 90%. Conclusions. Given the current low rates of full surgical staging and/or referral to a Gynecologic Oncologist, a diagnostic test to detect nodal metastasis for endometrial cancer has potential to be costeffective when compared to usual care. Testing is also potentially cost-effective compared to 100% referral at very high test sensitivities and at the lower range of test costs. (C) 2008 Elsevier Inc. All rights reserved. C1 [Havrilesky, Laura J.] Duke Univ, Med Ctr, Div Gynecol Oncol, Durham, NC 27710 USA. [Myers, Evan R.] Duke Univ, Med Ctr, Div Clin & Epidemiol Res, Durham, NC 27710 USA. [Havrilesky, Laura J.; Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Havrilesky, Laura J.; Myers, Evan R.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. [Maxwell, G. Larry] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Maxwell, G. Larry] United States Mil Canc Inst, Washington, DC USA. [Maxwell, G. Larry] NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. [Chan, John K.] Univ Calif San Francisco, Div Gynecol Oncol, San Francisco, CA 94143 USA. [Chan, John K.] Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA. [Chan, John K.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Havrilesky, LJ (reprint author), Box 3079 DUMC, Durham, NC 27710 USA. EM havri001@mc.duke.edu FU American Board of Obstetrics and Gynecology; American Association of Obstetricians and Gynecologists Foundation. FX LH is supported by a grant from the American Board of Obstetrics and Gynecology/American Association of Obstetricians and Gynecologists Foundation. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2009 VL 112 IS 3 BP 526 EP 530 DI 10.1016/j.ygyno.2008.11.017 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 418QH UT WOS:000264162800018 PM 19100608 ER PT J AU Minniti, CR Sable, C Campbel, A Rana, S Ensing, G Dham, N Onyekwere, O Nouraie, M Kato, GJ Gladwin, MT Castro, OL Gordeuk, VR AF Minniti, Caterina R. Sable, Craig Campbel, Andrew Rana, Sohail Ensing, Gregory Dham, Niti Onyekwere, Onyinye Nouraie, Mehdi Kato, Gregory J. Gladwin, Mark T. Castro, Oswaldo L. Gordeuk, Victor R. TI Elevated tricuspid regurgitant jet velocity in children and adolescents with sickle cell disease: association with hemolysis and hemoglobin oxygen desaturation SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE sickle cell disease; pulmonary hypertension; hemolysis; oxygen saturation; tricuspid regurgitant jet velocity; children ID 6-MINUTE WALK TEST; SOCIETY-OF-ECHOCARDIOGRAPHY; PULMONARY-HYPERTENSION; RISK-FACTOR; VASOOCCLUSIVE PAIN; PULSE OXIMETRY; TASK-FORCE; ANEMIA; DEATH; GUIDELINES AB Background Elevation of echocardiography-determined tricuspid regurgitant jet velocity predicts high systolic pulmonary artery pressure and early mortality in adults with sickle cell disease. The definition, prevalence and clinical correlates of elevated jet velocity have not been established in pediatric patients. The present study tested the hypotheses that elevated jet velocity affects 10% of pediatric patients, is associated with both hemolysis and hypoxia, and has clinical correlates with acute chest syndrome, stroke, transfusion requirement and abnormal 6-minute walk test results. Design and Methods A prospective multicenter study of 310 patients aged 3-20 years old with sickle cell disease under basal conditions and 54 matched controls was conducted. A hemolytic index was generated by principal component analysis of the levels of lactate dehydrogenase, aspartate aminotransferase and bilirubin and reticulocyte count. Results Elevated jet velocity (defined as >= 2.60 m/sec based on the mean +/- 2 SD in controls) occurred in 32 patients (11.0%) including one child of 3 years old. After adjustment for hemoglobin concentration, systolic blood pressure and left ventricular diastolic function, a 2 SD increase in the hemolytic index was associated with a 4.5-fold increase in the odds of elevated jet velocity (p=0.009) and oxygen saturation <= 98% with a 3.2-fold increase (p=0.028). Two or more episodes of acute chest syndrome had occurred in 28% of children with elevated jet velocity compared to in 13% of other children (P=0.012), more than ten units of blood had been transfused in 39% versus 18% (p=0.017) and stroke had occurred in 19% versus 11% (p=0.2). The distance walked in 6-minute walk tests did not differ significantly, but oxygen saturation declined during the tests in 68% of children with elevated jet velocity compared to in 32% of other children (p=0.0002). Conclusions According to a pediatric-specific definition the prevalence of elevated jet velocity in this population of young patients with sickle cell disease was 11%. The study provides evidence for independent associations of elevated jet velocity with hemolysis and oxygen desaturation. Further investigations should address whether elevated jet velocity may indicate future complications and whether early intervention is beneficial. C1 [Rana, Sohail; Onyekwere, Onyinye; Nouraie, Mehdi; Castro, Oswaldo L.; Gordeuk, Victor R.] Howard Univ, Washington, DC 20060 USA. [Minniti, Caterina R.; Sable, Craig; Dham, Niti] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Campbel, Andrew; Ensing, Gregory] Univ Michigan, Ann Arbor, MI 48109 USA. [Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Kato, Gregory J.; Gladwin, Mark T.] Natl Inst Hlth, Dept Crit Care Med, Ctr Clin, Bethesda, MD USA. RP Gordeuk, VR (reprint author), Howard Univ, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM vgordeuk@howard.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU NHLBI [2 R25 HL003679-08, 1 R01 HL079912-02]; Howard University GCRC [2MOl RR10284-10]; NCRR; NIH, Bethesda, MD,; National Institutes of Health (USA) FX supported in part by grant nos. 2 R25 HL003679-08 and 1 R01 HL079912-02 from NHLBI, by Howard University GCRC grant no 2MOl RR10284-10 from NCRR, NIH, Bethesda, MD, and by the intramural research program of the National Institutes of Health (USA). NR 36 TC 84 Z9 86 U1 0 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAR PY 2009 VL 94 IS 3 BP 340 EP 347 DI 10.3324/haematol.13812 PG 8 WC Hematology SC Hematology GA 415GP UT WOS:000263922600007 PM 19211639 ER PT J AU Scheinberg, P Wu, CO Nunez, O Scheinberg, P Boss, C Sloand, EM Young, NS AF Scheinberg, Phillip Wu, Colin O. Nunez, Olga Scheinberg, Priscila Boss, Carol Sloand, Elaine M. Young, Neal S. TI Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE aplastic anemia; antithymocyte globulin; cyclosporine; sirolimus; immunosuppression; pancytopenia ID COLONY-STIMULATING FACTOR; ANTI-THYMOCYTE GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; AUTOIMMUNE UVEORETINITIS; ANTILYMPHOCYTE GLOBULIN; PHASE-III; FOLLOW-UP; RAPAMYCIN; TRANSPLANTATION; SURVIVAL AB Background We hypothesized that the addition of sirolimus to standard horse antithymocyte globulin (h-ATG) and cyclosporine (CsA) would improve response rates in severe aplastic anemia, due to its complementary and synergistic properties to cyclosporine A. Design and Methods To test this hypothesis, we conducted a prospective randomized study comparing hATG/CsA/sirolimus to standard h-ATG/CsA. A total of 77 patients were treated from June 2003 to November 2005; 35 received h-ATG/CsA/sirolimus and 42 h-ATG/CsA. The two groups were well matched demographically and in blood counts prior to therapy. The primary end-point was hematologic response rate at 3 months. defined as no longer meeting the criteria for severe aplastic anemia. The study was powered to show a superior hematologic response rate of h-ATG/CsA/sirolimus compared to standard h-ATG/CsA. Results The overall response rate at 3 months was 37% for h-ATG/CsA/sirolimus and 50% for h-ATG/CsA and at 6 months 51% for h-ATG/CsA/sirolimus and 62% for h-ATG/CsA. After a planned interim analysis of 30 evaluable patients in each arm, accrual to the hATG/CsA/sirolimus arm was closed, as the conditional power for rejecting the null hypothesis was less than 1%. The rate of relapse, clonal evolution, and survival (secondary outcomes) did not differ significantly between patients treated with the two different regimens. Conclusions Despite a theoretical rationale for its use, sirolimus did not improve the response rate in patients with severe aplastic anemia when compared to standard h-ATG/CsA (ClinicalTrials.gov Identifier: NCT00061360). C1 [Scheinberg, Phillip] NHLBI, Hematol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, Natl Inst Hlth, 10 Ctr Dr,Bldg 10 CRC,Room 3-5140,MSC 1202, Bethesda, MD 20892 USA. EM scheinbp@mail.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 FU NIH; National Heart, Lung and Blood Institute FX this research was supported by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. NR 31 TC 62 Z9 75 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAR PY 2009 VL 94 IS 3 BP 348 EP 354 DI 10.3324/haematol.13829 PG 7 WC Hematology SC Hematology GA 415GP UT WOS:000263922600008 PM 19181786 ER PT J AU Lozier, J Menashe, I Kroner, B Goedert, J Rosenberg, P AF Lozier, Jay Menashe, Idan Kroner, Barbara Goedert, James Rosenberg, Philip TI Immunogenetics of factor VIII inhibitor development SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Lozier, Jay; Menashe, Idan; Kroner, Barbara; Goedert, James; Rosenberg, Philip] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAR PY 2009 VL 15 IS 2 BP 634 EP 634 PG 1 WC Hematology SC Hematology GA 424DY UT WOS:000264546900089 ER PT J AU Miller, FG AF Miller, Franklin G. TI A Planned Death in the Family SO HASTINGS CENTER REPORT LA English DT Article C1 NIH, Dept Bioeth, Bethesda, MD USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bethesda, MD USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAR-APR PY 2009 VL 39 IS 2 BP 28 EP 30 PG 3 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 425QL UT WOS:000264652100015 PM 19388383 ER PT J AU Han, PKJ Lehman, TC Massett, H Lee, SJC Klein, WMP Freedman, AN AF Han, Paul K. J. Lehman, Thomas C. Massett, Holly Lee, Simon J. C. Klein, William M. P. Freedman, Andrew N. TI Conceptual problems in laypersons' understanding of individualized cancer risk: a qualitative study SO HEALTH EXPECTATIONS LA English DT Article DE cancer; numeracy; risk; risk perception ID I CLINICAL-TRIALS; BREAST-CANCER; NUMERACY SCALE; HEALTH; COMMUNICATION; EXPECTATIONS; PROBABILITY; INFORMATION; PERCEPTION; CONFIDENCE AB To explore laypersons' understanding of individualized cancer risk estimates, and to identify conceptual problems that may limit this understanding. Risk prediction models are increasingly used to provide people with information about their individual risk of cancer and other diseases. However, laypersons may have difficulty understanding individualized risk information, because of conceptual as well as computational problems. A qualitative study was conducted using focus groups. Semi-structured interviews explored participants' understandings of the concept of risk, and their interpretations of a hypothetical individualized colorectal cancer risk estimate. Eight focus groups were conducted with 48 adults aged 50-74 years residing in two major US metropolitan areas. Participants had high school or greater education, some familiarity with information technology, and no personal or family history of cancer. Several important conceptual problems were identified. Most participants thought of risk not as a neutral statistical concept, but as signifying danger and emotional threat, and viewed cancer risk in terms of concrete risk factors rather than mathematical probabilities. Participants had difficulty acknowledging uncertainty implicit to the concept of risk, and judging the numerical significance of individualized risk estimates. The most challenging conceptual problems related to conflict between subjective and objective understandings of risk, and difficulties translating aggregate-level objective risk estimates to the individual level. Several conceptual problems limit laypersons' understanding of individualized cancer risk information. These problems have implications for future research on health numeracy, and for the application of risk prediction models in clinical and public health settings. C1 [Han, Paul K. J.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. [Lehman, Thomas C.] Acad Educ Dev, Washington, DC USA. [Massett, Holly] NCI, Off Market Res & Evaluat, Bethesda, MD 20892 USA. [Lee, Simon J. C.] UT SW Med Ctr Dalls, Div Eth & Hlth Policy, Dallas, TX USA. [Klein, William M. P.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Han, PKJ (reprint author), NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4091,MSC 7344, Rockville, MD 20892 USA. EM hanp@mail.nih.gov RI Lee, Simon/B-2443-2008; OI Han, Paul/0000-0003-0165-1940; Lee, Simon J. Craddock/0000-0001-6345-1237 FU Intramural NIH HHS [Z99 HG999999] NR 75 TC 21 Z9 21 U1 4 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD MAR PY 2009 VL 12 IS 1 BP 4 EP 17 DI 10.1111/j.1369-7625.2008.00524.x PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 412XF UT WOS:000263756800002 PM 19250148 ER PT J AU Waters, EA Weinstein, ND Colditz, GA Emmons, K AF Waters, Erika A. Weinstein, Neil D. Colditz, Graham A. Emmons, Karen TI Explanations for Side Effect Aversion in Preventive Medical Treatment Decisions SO HEALTH PSYCHOLOGY LA English DT Article DE decision making; risk perception; risk communication; informed consent; side effects ID AFFECTIVE PSYCHOLOGY; RISK COMMUNICATION; BREAST-CANCER; FORMATS; TAMOXIFEN; PREFERENCES; FREQUENCY; JUDGMENT; MODELS AB Objective: Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such "side effect aversion." One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design: Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions, the net absolute risk reduction associated with the treatment was 15% Main Outcome Measures: Participants indicated their willingness to accept treatment and their perceptions of the treatment's effects on their overall cancer risk. Results: Data were consistent only with the "mere presence" explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion: Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. C1 [Waters, Erika A.] NCI, HCIRB, BRP, DCCPS, Bethesda, MD 20892 USA. [Waters, Erika A.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Weinstein, Neil D.] Univ Arizona, Coll Med, Dept Family & Community Med, Tucson, AZ USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Alvin J Siteman Canc Ctr, St Louis, MO USA. [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Waters, EA (reprint author), NCI, HCIRB, BRP, DCCPS, Execut Plaza N,6130 Execut Blvd MSC 7365, Bethesda, MD 20892 USA. EM erika.a.waters@gmail.com RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Waters, Erika/0000-0001-7402-0133 FU Intramural NIH HHS [NIH0011143336] NR 29 TC 22 Z9 22 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAR PY 2009 VL 28 IS 2 BP 201 EP 209 DI 10.1037/a0013608 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 420YY UT WOS:000264326300008 PM 19290712 ER PT J AU Brunt, EM Kleiner, DE Wilson, LA Unalp, A Behling, CE Lavine, JF Neuschwander-Tetri, BA AF Brunt, Elizabeth M. Kleiner, David E. Wilson, Laura A. Unalp, Aynur Behling, Cynthia E. Lavine, Joel F. Neuschwander-Tetri, Brent A. CA NASH Clinical Res Network TI Portal Chronic Inflammation in Nonalcoholic Fatty Liver Disease (NAFLD): A Histologic Marker of Advanced NAFLD-Clinicopathologic Correlations from the Nonalcoholic Steatohepatitis Clinical Research Network SO HEPATOLOGY LA English DT Article ID HEPATITIS-C; METABOLIC SYNDROME; DUCTULAR REACTION; FIBROSIS; FEATURES; CIRRHOSIS; LESIONS AB Adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in children, portal CI may be predominant. This study correlated clinical features with portal CI. Centrally graded biopsies and temporally-related clinical parameters from 728 adults and 205 children. From the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) were evaluated. Mild, more than mild and no portal CI were found in 60%, 23% and 16% of adult biopsies and 76%, 14% and 10% of pediatric biopsies. Autoantibodies, and elevated alanine aminotransferase were not associated with portal CI. Clinical features associated with "more than mild" in adults were older age (P < 0.0001.), female gender (P = 0.001), higher body mass index (P < 0.0001), elevated insulin levels (P = 0.001), higher homeostasis model assessment of insulin resistance score (HOMA-IR) (P < 0.0001), and medications used for NAFLD (P = 0.0004), diabetes (P < 0.0001.),and hypertension (P < 0.0001). "More than mild" in the pediatric biopsies correlated with younger age (P = 0.01), but not with body mass index, insulin or HOMA-IR. In both groups, lobular and portal inflammation scores had no association, but there was an association with definite steatohepatitis (P < 0.0001). Features associated in the adult biopsies with "more than mild" were steatosis amount (P = 0.01) and location (P < 0.0001), ballooning (P < 0.0001), and advanced fibrosis (P < 0.0001). In the pediatric biopsies, "more than mild" was associated with steatosis location (P = 0.0008) and fibrosis score (P < 0.0001), specifically, the portal/periportal fibrosis or greater fibrosis) (P < 0.01). Conclusion: Increased portal CI is associated with many clinical and pathologic features of progressive NAFLD in both adults and children, but not with ALT, autoantibodies, or lobular inflammation. More than mild portal CI in liver biopsies of untreated NAFLD may be considered a marker of advanced disease. (HEPATOLOGY 2009;49:809-820.) C1 [Brunt, Elizabeth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Wilson, Laura A.; Unalp, Aynur] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Behling, Cynthia E.; Lavine, Joel F.] Univ Calif San Diego, San Diego, CA 92103 USA. [Neuschwander-Tetri, Brent A.] St Louis Univ, Sch Med, St Louis, MO USA. RP Brunt, EM (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA. EM ebrunt@wustl.edu OI Sirlin, Claude/0000-0002-6639-9072; Kleiner, David/0000-0003-3442-4453 FU National Institute of Diabetes and Digestive and kidney Diseases [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Institute of Child Health and Human Development FX The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and kidney Diseases (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713), and the National Institute of Child Health and Human Development. NR 30 TC 124 Z9 130 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2009 VL 49 IS 3 BP 809 EP 820 DI 10.1002/hep.22724 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 413UC UT WOS:000263817000014 PM 19142989 ER PT J AU Zhang, XC Chen, XC Yu, YQ Sun, DL Ma, N He, S Hu, XP Zhang, DR AF Zhang, Xiaochu Chen, Xiangchuan Yu, Yongqiang Sun, Delin Ma, Ning He, Sheng Hu, Xiaoping Zhang, Daren TI Masked Smoking-Related Images Modulate Brain Activity in Smokers SO HUMAN BRAIN MAPPING LA English DT Article DE unawareness; smoking-related cue; functional magnetic resonance imaging (fMRI); amygdala; addiction ID EVENT-RELATED FMRI; FUNCTIONAL CONNECTIVITY; NICOTINE DEPENDENCE; DRUG-ADDICTION; HUMAN AMYGDALA; FAGERSTROM TEST; CUE-REACTIVITY; ACTIVATION; RESPONSES; FEAR AB The questions of whether and how indiscriminate drug-related stimuli could influence drug-users are important to our understanding of addictive behavior, but the answers are still inconclusive. In the present preliminary functional magnetic resonance imaging study using a backward masking paradigm, the effect of indiscriminate smoking-related stimuli on 10 smokers and 10 nonsmokers was examined. The BOLD response showed a significant reduction (P = 0.001) in the right amygdala of smokers when they viewed but did not perceive masked smoking-related stimuli, while no significant differences were found in the nonsmoker group. More voxels in anterior cingulate cortex were negatively correlated with the amygdala during the masked smoking-related picture condition in smokers but not in nonsmokers, whereas more positively correlated voxels were observed during the masked neutral condition. The BOLD response in drug-users indicates the amygdala responds to drug-related stimuli that are below the perceptual threshold. The functional connectivity data suggest a functional interaction between the amygdala and the anterior cingulate cortex when drug users view 33ms back-masked drug-related stimuli. This observation suggests that the amygdala plays an important role in the indiscriminate drug-related cue process. Hum Brain Mapp 30:896-907, 2009. (c) 2008 Wiley-Liss, Inc. C1 [Zhang, Xiaochu; Chen, Xiangchuan; Sun, Delin; Ma, Ning; Zhang, Daren] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China. [Zhang, Xiaochu; Chen, Xiangchuan; Sun, Delin; Ma, Ning; Zhang, Daren] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China. [Zhang, Xiaochu] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. [Yu, Yongqiang] Anhui Med Univ, Affiliated Hosp 1, Hefei 230027, Anhui, Peoples R China. [He, Sheng] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Hu, Xiaoping] Emory Univ, Dept Biomed Engn, Atlanta, GA 30322 USA. [Hu, Xiaoping] Georgia Tech, Atlanta, GA 30322 USA. RP Zhang, DR (reprint author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China. EM drzhang@ustc.edu.cn RI Chen, Xiangchuan/E-5699-2010; Zhang, Xiaochu/O-9592-2014; Sun, Delin/A-4154-2010 OI Zhang, Xiaochu/0000-0002-7541-0130; Sun, Delin/0000-0003-3283-423X FU National Nature Science Foundation of China [30770713, 30328017, 30470572]; Ministry of Science and Technology of China [2006CB500705]; NIH [RO1 EB002009]; James S. McDonnell Foundation FX Contract grant sponsor: National Nature Science Foundation of China; Contract grant numbers: 30770713, 30328017, 30470572; Contract grant sponsor: Ministry of Science and Technology of China; Contract grant number: 2006CB500705; Contract grant sponsor: NIH; Contract grant number: RO1 EB002009; Contract grant sponsor: James S. McDonnell Foundation. NR 86 TC 10 Z9 10 U1 6 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAR PY 2009 VL 30 IS 3 BP 896 EP 907 DI 10.1002/hbm.20552 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 416OR UT WOS:000264015900017 PM 18344177 ER PT J AU Marrelec, G Kim, J Doyon, J Horwitz, B AF Marrelec, G. Kim, J. Doyon, J. Horwitz, B. TI Large-Scale Neural Model Validation of Partial Correlation Analysis for Effective Connectivity Investigation in Functional MRI SO HUMAN BRAIN MAPPING LA English DT Article DE functional MRI; brain functional interactions; effective connectivity; structural equation modeling; partial correlation; large-scale neural model ID INDEPENDENT COMPONENT ANALYSIS; NETWORK ANALYSIS; VISUAL PATHWAYS; BRAIN NETWORKS; TIME-SERIES; FMRI; INTERACTIVITY; SIGNALS; CORTEX; TASK AB Recent Studies of functional connectivity based upon blood oxygen level dependent functional magnetic resonance imaging have shown that this technique allows one to investigate large-scale functional brain networks. In a previous study, we advocated that data-driven measures of effective connectivity should be developed to bridge the gap between functional and effective connectivity. To attain this goal, we proposed a novel approach based on the partial correlation matrix. In this study, we further validate the use of partial correlation analysis by employing a large-scale, neurobiologically realistic neural network model to generate simulated data that we analyze with both structural equation modeling (SEM) and the partial correlation approach. Unlike real experimental data, where the interregional anatomical links are not necessarily known, the links between the nodes of the network model are fully specified, and thus provide a standard against which to judge the results of SEM and partial correlation analyses. Our results show that partial correlation analysis from the data alone exhibits patterns of effective connectivity that are similar to those found using SEM, and both are in agreement with respect to the underlying neuroarchitecture. Our findings thus provide a strong validation for the partial correlation method. Hunt Brain Mapp 30:941-950, 2009. (c) 2008 Wiley-Liss, Inc. C1 [Marrelec, G.] Univ Paris 06, INSERM, U678, F-75013 Paris, France. [Marrelec, G.] Univ Paris 06, Fac Med Pitie Salpetriere, F-75013 Paris, France. [Marrelec, G.; Doyon, J.] Univ Montreal, Unite Neuroimagerie Fonct, Montreal, PQ H3W 1W5, Canada. [Kim, J.; Horwitz, B.] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. RP Marrelec, G (reprint author), CHU Pitie Salpetriere, INSERM, U678, 91 Blvd Hop, F-75634 Paris 13, France. EM marrelec@imed.jussieu.fr NR 51 TC 24 Z9 24 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAR PY 2009 VL 30 IS 3 BP 941 EP 950 DI 10.1002/hbm.20555 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 416OR UT WOS:000264015900021 PM 18344176 ER PT J AU Olivier, M Petitjean, A Teague, J Forbes, S Dunnick, JK den Dunnen, JT Langerod, A Wilkinson, JM Vihinen, M Cotton, RGH Hainaut, P AF Olivier, M. Petitjean, A. Teague, J. Forbes, S. Dunnick, J. K. den Dunnen, J. T. Langerod, A. Wilkinson, J. M. Vihinen, M. Cotton, R. G. H. Hainaut, P. TI Somatic Mutation Databases as Tools for Molecular Epidemiology and Molecular Pathology of Cancer: Proposed Guidelines for Improving Data Collection, Distribution, and Integration SO HUMAN MUTATION LA English DT Article DE somatic mutation; database; standards ID RECOMMENDATIONS AB There are currently less than 40 locus-specific databases (LSDBs) and one large general database that curate data on somatic mutations in human cancer genes. These databases have different scope and use different annotation standards and database systems, resulting in duplicated efforts in data curation, and making it difficult for users to find clear and consistent information. As data related to somatic mutations are generated at an increasing pace it is urgent to create a framework for improving the collecting of this information and making it more accessible to clinicians, scientists, and epidemiologists to facilitate research on biomarkers. Here we propose a data flow for improving the connectivity between existing databases and we provide practical guidelines for data reporting, database contents, and annotation standards. These proposals are based on common standards recommended by the Human Genome Variation Society (HGVS) with additions related to specific requirements of somatic mutations in cancer. Indeed, somatic mutations may be used in molecular pathology and clinical studies to characterize tumor types, help treatment choice, predict response to treatment and patient outcome, or in epidemiological studies as markers for tumor etiology or exposure assessment. Thus, specific annotations are required to cover these diverse research topics. This initiative is meant to promote collaboration and discussion on these issues and the development of adequate resources that would avoid the loss of extremely valuable information generated by years of basic and clinical research. Hum Mutat 30, 275-282, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Olivier, M.; Petitjean, A.; Hainaut, P.] IARC, Grp Mol Carcinogenesis & Biomarkers, World Hlth Org, F-69372 Lyon, France. [Teague, J.; Forbes, S.] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England. [Dunnick, J. K.] Natl Inst Environm Hlth Sci, Toxicol Operat Branch, Res Triangle Pk, NC USA. [den Dunnen, J. T.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Langerod, A.] Univ Oslo, Rikshosp, Radiumhosp Med Ctr, Dept Genet,Inst Canc Res, N-0027 Oslo, Norway. [Wilkinson, J. M.] NCRI, Canc Informat Initiat, London, England. [Vihinen, M.] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. [Cotton, R. G. H.] Tampere Univ Hosp, Tampere, Finland. [Vihinen, M.] St Vincents Hosp, Genom Disorders Res Ctr, Melbourne, Vic, Australia. RP Olivier, M (reprint author), IARC, Grp Mol Carcinogenesis & Biomarkers, World Hlth Org, 150 Cours Albert Thomas, F-69372 Lyon, France. EM molivier@iarc.fr RI Vihinen, Mauno/A-8452-2012; Hainaut, Pierre /B-6018-2012; Olivier, Magali/G-3728-2010 OI Vihinen, Mauno/0000-0002-9614-7976; Hainaut, Pierre /0000-0002-1303-1610; Olivier, Magali/0000-0002-8202-342X FU IARC; EC FX These recommendations were prepared during a working group session of a training workshop on mutation databases that was held at IARC in Lyon in July 2007. The workshop was funded by IARC and by EC FP6. This publication reflects the author's views and not necessarily those of the European Community (EC). The Community is not liable for any use that may be made of the information contained herein. NR 15 TC 11 Z9 13 U1 1 U2 1 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 MAR PY 2009 VL 30 IS 3 BP 275 EP 282 DI 10.1002/humu.20832 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 416NB UT WOS:000264011700001 PM 19006239 ER PT J AU Ma, D Feitosa, MF Wilk, JB Laramie, JM Yu, K Leiendecker-Foster, C Myers, RH Province, MA Borecki, IB AF Ma, Duanduan Feitosa, Mary F. Wilk, Jemma B. Laramie, Jason M. Yu, Kai Leiendecker-Foster, Catherine Myers, Richard H. Province, Michael A. Borecki, Ingrid B. TI Leptin Is Associated With Blood Pressure and Hypertension in Women From the National Heart, Lung, and Blood Institute Family Heart Study SO HYPERTENSION LA English DT Article DE leptin; blood pressure; hypertension; association; gender ID CENTRAL NEURAL-NETWORKS; BODY-MASS INDEX; GENDER-DIFFERENCES; TRANSMISSION/DISEQUILIBRIUM TEST; QUANTITATIVE TRAITS; INSULIN-RESISTANCE; ARTERIAL-PRESSURE; GENE; OBESITY; ANGIOTENSINOGEN AB Leptin is a key neuroendocrine hormone regulating food intake, metabolism, and fat accumulation, and it may also affect blood pressure and contribute to hypertension through sympathetic activation in the vasculature or at the renal level. Although previous studies have shown that the distribution of leptin is significantly different between males and females, as is the risk of hypertension between males and females, results regarding the role of leptin in the gender-specific regulation of blood pressure are controversial. Thus, we performed family-based association analyses in the National Heart, Lung, and Blood Institute Family Heart Study to test the hypothesis that LEPTIN gene variants and the plasma leptin level influence variability in blood pressure and the risk of hypertension differently by gender. We identified significant associations between LEPTIN single nucleotide polymorphisms with blood pressure and hypertension, but in postmenopausal women only. We also identified significant associations between plasma leptin levels and both blood pressure and hypertension in women. The current study supports a role for LEPTIN and plasma leptin levels in blood pressure regulation in women. It also provides insight into the gender differences in hypertension, as well as the differential distribution and activity of leptin in men and women. (Hypertension. 2009;53:473-479.) C1 [Ma, Duanduan; Feitosa, Mary F.; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO 63108 USA. [Wilk, Jemma B.; Laramie, Jason M.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Yu, Kai] NCI, Div Canc Biol & Genet, Bethesda, MD 20892 USA. [Leiendecker-Foster, Catherine] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Borecki, IB (reprint author), Washington Univ, Sch Med, Div Stat Genom, 4444 Forest Pk Blvd,Campus Box 8506, St Louis, MO 63108 USA. EM iborecki@wustl.edu RI Feitosa, Mary/K-8044-2012; OI Feitosa, Mary/0000-0002-0933-2410; Myers, Richard/0000-0002-8365-2674 FU National Institutes of Health [5RO-1 DK068336-03, RO-1 HL068891-06] FX This study is supported by National Institutes of Health grants 5RO-1 DK068336-03 (adiposity quantitative trait loci in the NHLBI-FHS) and RO-1 HL068891-06 (epidemiological and genetic studies of BMI in the Family Heart Study). NR 43 TC 28 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD MAR PY 2009 VL 53 IS 3 BP 473 EP 479 DI 10.1161/HYPERTENSIONAHA.108.118133 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 421EG UT WOS:000264341200011 PM 19204185 ER PT J AU Cutler, JA Sorlie, PD AF Cutler, Jeffrey A. Sorlie, Paul D. TI Response to Upward Hypertension Trends: Changes in Blood Pressure or in Antihypertensive Treatment? SO HYPERTENSION LA English DT Letter C1 [Cutler, Jeffrey A.; Sorlie, Paul D.] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Cutler, JA (reprint author), NHLBI, NIH, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2009 VL 53 IS 3 DI 10.1161/HYPERTENSIONAHA.108.127183 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 421EG UT WOS:000264341200026 ER PT J AU Kuslak, SL Van Dyke, T AF Kuslak, Sheri L. Van Dyke, Terry TI Advances in Prostate Cancer Research - AACR Special Conference in Cancer Research SO IDRUGS LA English DT Editorial Material C1 [Kuslak, Sheri L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Van Dyke Lab, Chapel Hill, NC 27599 USA. [Van Dyke, Terry] NCI, Frederick, MD 21702 USA. RP Kuslak, SL (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Van Dyke Lab, Chapel Hill, NC 27599 USA. EM kuslak@email.unc.edu; vandyket@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD MAR PY 2009 VL 12 IS 3 BP 159 EP 162 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 419PB UT WOS:000264230500008 PM 19333894 ER PT J AU White, RJ Peng, GCY Demir, SS AF White, Ronald J. Peng, Grace C. Y. Demir, Semahat S. TI Multiscale Modeling of Biomedical, Biological, and Behavioral Systems (Part 1) SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Editorial Material C1 [Peng, Grace C. Y.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. [White, Ronald J.] NASA, Human Res Program, Washington, DC USA. [White, Ronald J.] Baylor Coll Med, Houston, TX 77030 USA. [White, Ronald J.] NASA, Div Life Sci, Washington, DC USA. [White, Ronald J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [White, Ronald J.] Univ Louisiana Lafayette, Lafayette, LA USA. RP Peng, GCY (reprint author), Natl Inst Biomed Imaging & Bioengn, 6707 Democracy Blvd,Suite 200,MSC 5469, Bethesda, MD 20892 USA. EM penggr@mail.nih.gov NR 0 TC 9 Z9 9 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAR-APR PY 2009 VL 28 IS 2 BP 12 EP 13 DI 10.1109/MEMB.2009.932388 PG 2 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 431UV UT WOS:000265090600004 PM 19349247 ER PT J AU Park, S Badano, A Gallas, BD Myers, KJ AF Park, Subok Badano, Aldo Gallas, Brandon D. Myers, Kyle J. TI Incorporating Human Contrast Sensitivity in Model Observers for Detection Tasks SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Anthropomorphic observer; channelized-Hotelling observer; human contrast sensitivity; lumpy backgrounds; signal detection ID HOTELLING OBSERVER; VISUAL-SYSTEM; PERFORMANCE; NOISE; SIGNAL; DISPLAYS; DISCRIMINATION; DETECTABILITY; BACKGROUNDS; COMPUTATION AB Contrast sensitivity of the human visual system is a characteristic that can adversely affect human performance in detection tasks. In this paper, we propose a method for incorporating human contrast sensitivity in anthropomorphic model observers. In our method, we model human contrast sensitivity using the Barten model with the mean luminance of a region of interest centered at the signal location. In addition, one free parameter is varied to control the effect of the contrast sensitivity on the model observer's performance. We investigate our model of human contrast sensitivity in a channelized-Hotelling observer (CHO) with difference-of-Gaussian channels. We call the CHO incorporating the contrast sensitivity a contrast-sensitive CHO (CS-CHO). The human data from a psychophysical study by Park et al. [1] are used for comparing the performance of the CS-CHO to human performance. That study used Gaussian signals with six different signal intensities in non-Gaussian lumpy backgrounds. A value of the free parameter is chosen to match the performance of the CS-CHO to the mean human performance only at the strongest signal. Results show that the CS-CHO with the chosen value of the free parameter predicts the mean human performance at the five lower signal intensities. Our results show that the CS-CHO predicts human performance well as a function of signal intensity. C1 [Park, Subok; Badano, Aldo; Gallas, Brandon D.; Myers, Kyle J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. RP Park, S (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. EM subok.park@fda.hhs.gov RI Bouwman, Ramona/B-7215-2013; OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 FU National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health FX This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health. NR 30 TC 19 Z9 19 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2009 VL 28 IS 3 BP 339 EP 347 DI 10.1109/TMI.2008.929096 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 415FU UT WOS:000263920500003 PM 19244006 ER PT J AU Greenspan, H Gordon, S Zimmerman, G Lotenberg, S Jeronimo, J Antani, S Long, R AF Greenspan, Hayit Gordon, Shiri Zimmerman, Gali Lotenberg, Shelly Jeronimo, Jose Antani, Sameer Long, Rodney TI Automatic Detection of Anatomical Landmarks in Uterine Cervix Images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Cervical cancer; curvature features; image segmentation; landmark extraction; medical image analysis ID HUMAN-PAPILLOMAVIRUS; SEGMENTATION; NEOPLASIA; REGIONS AB The work focuses on a unique medical repository of digital cervicographic images ("Cervigrams") collected by the National Cancer Institute (NCI) in longitudinal multiyear studies. NCI, together with the National Library of Medicine (NLM), is developing a unique web-accessible database of the digitized cervix images to study the evolution of lesions related to cervical cancer. Tools are needed for automated analysis of the cervigram content to support cancer research. We present a multistage scheme for segmenting and labeling regions of anatomical interest within the cervigrams. In particular, we focus on the extraction of the cervix region and fine detection of the cervix boundary; specular reflection is eliminated as an important preprocessing step; in addition, the entrance to the endocervical canal (the "os"), is detected. Segmentation results are evaluated on three image sets of cervigrams that were manually labeled by NCI experts. C1 [Greenspan, Hayit] Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Ramat Aviv, Israel. [Jeronimo, Jose] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Antani, Sameer; Long, Rodney] NIH, Commun Engn Branch, Natl Lib Med, Bethesda, MD 20894 USA. RP Greenspan, H (reprint author), Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Ramat Aviv, Israel. EM hayit@eng.tau.ac.il; shiri@superfish.com; zimer@post.tau.ac.il; shelly.lotenberg@mobileye.com; jjeronimo@path.org; santani@mail.nih.gov; rlong@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 FU National Institutes of Health (NIH); National Library of Medicine (NLM); Lister Hill National Center for Biomedical Communications (LHNCBC) FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM), and Lister Hill National Center for Biomedical Communications (LHNCBC) NR 33 TC 14 Z9 14 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2009 VL 28 IS 3 BP 454 EP 468 DI 10.1109/TMI.2008.2007823 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 415FU UT WOS:000263920500014 PM 19244017 ER PT J AU Coligan, JE AF Coligan, John E. TI National Institutes of Health/NIAID special issue Introduction SO IMMUNOLOGIC RESEARCH LA English DT Editorial Material C1 NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Twinbrook 2,Room 205,MS 8180 12441,Parklawn Dr, Rockville, MD 20852 USA. EM JCOLIGAN@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 1 EP 7 DI 10.1007/s12026-008-8077-2 PG 7 WC Immunology SC Immunology GA 424VW UT WOS:000264597400001 ER PT J AU Prabhakar, M Lenardo, MJ AF Prabhakar, Madhavi Lenardo, Michael J. TI Human genetic approaches to diseases of lymphocyte activation SO IMMUNOLOGIC RESEARCH LA English DT Article DE Autoimmunity; Apoptosis; T lymphocyte; Human Immunodeficiency Virus; NF-kappa B; Caspase-8; Autophagy ID AUTOIMMUNE-LYMPHOPROLIFERATIVE-SYNDROME; DOMINANT INHIBITION; MEDIATED APOPTOSIS; RECEPTORS; DOMAIN; CYTOPATHICITY; CASPASE-8; DEATH AB Our laboratory focuses on the study of the molecular regulation of T lymphocyte homeostasis, particularly as it relates to immunological tolerance, apoptosis, and autoimmune diseases. Through intense molecular research on the regulation of lymphocyte fate, the Fas receptor and other tumor necrosis factor receptors as well as their ligands have emerged as key regulators of T lymphocyte apoptosis. We are studying genetic abnormalities of this death pathway, particularly in the context of autoimmune lymphoproliferative syndrome (ALPS) and other non-ALPS conditions affecting lymphocyte homeostasis. These studies have led to further investigations of the regulation of the NF-kappa B signaling pathway, the molecular basis for programed cell death and viral cytopathicity, mechanisms of autoimmunity, and the regulation of mature T-cell tolerance. Our investigations promise to provide insight into the molecular mechanisms behind the regulation of immune response and contribute to the development of novel diagnostic and treatment methods for autoimmune diseases. C1 [Prabhakar, Madhavi; Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM lenardo@NIH.gov FU Intramural NIH HHS [ZIA AI000718-15] NR 14 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 8 EP 14 DI 10.1007/s12026-008-8045-x PG 7 WC Immunology SC Immunology GA 424VW UT WOS:000264597400002 PM 18795237 ER PT J AU Gilfillan, AM Peavy, RD Metcalfe, DD AF Gilfillan, Alasdair M. Peavy, Richard D. Metcalfe, Dean D. TI Amplification mechanisms for the enhancement of antigen-mediated mast cell activation SO IMMUNOLOGIC RESEARCH LA English DT Article DE Mast cells; Fc epsilon RI; KIT; Antigen; IgE; SCF; Signaling ID C-KIT LIGAND; INFLAMMATORY CYTOKINES; RI; RELEASE; RECEPTORS; PHOSPHORYLATION; DEGRANULATION; APOPTOSIS; RESPONSES; SIGNALS AB Activation of mast cells in the allergic inflammatory response occurs via the high affinity receptor for IgE (Fc epsilon RI) following receptor aggregation induced by antigen-mediated cross-linking of IgE-occupied Fc epsilon RI. Recent observations suggest this response is profoundly influenced by other factors that reduce the threshold for, and increase the extent of, mast cell activation. For example, under experimental conditions, cell surface receptors such as KIT and specific G protein-coupled receptors synergistically enhance Fc epsilon RI-mediated mast cell degranulation and cytokine production. Activating mutations in critical signaling molecules may also contribute to such responses. In this review, we describe our research exploring the mechanisms regulating these synergistic interactions and, furthermore, discuss the relevance of our observations in the context of clinical considerations. C1 [Gilfillan, Alasdair M.; Peavy, Richard D.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 43 TC 20 Z9 21 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 15 EP 24 DI 10.1007/s12026-008-8046-9 PG 10 WC Immunology SC Immunology GA 424VW UT WOS:000264597400003 PM 18827981 ER PT J AU Kennedy, AD Deleo, FR AF Kennedy, Adam D. Deleo, Frank R. TI Neutrophil apoptosis and the resolution of infection SO IMMUNOLOGIC RESEARCH LA English DT Review DE Neutrophil; Cell death; Apoptosis; Phagocytosis; Pyroptosis; Autophagy; Macrophage; Inflammation; Pathogen; Innate immunity ID TUMOR-NECROSIS-FACTOR; PROGRAMMED CELL-DEATH; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; MYCOBACTERIUM-TUBERCULOSIS INFECTION; CHRONIC GRANULOMATOUS-DISEASE; MONOCYTE-DERIVED MACROPHAGES; ADENYLATE CYCLASE-HEMOLYSIN; COLONY-STIMULATING FACTOR; HUMAN BONE-MARROW; RESISTANT STAPHYLOCOCCUS-AUREUS AB Polymorphonuclear leukocytes (PMNs) are the most abundant white cell in humans and an essential component of the innate immune system. PMNs are typically the first type of leukocyte recruited to sites of infection or areas of inflammation. Ingestion of microorganisms triggers production of reactive oxygen species and fusion of cytoplasmic granules with forming phagosomes, leading to effective killing of ingested microbes. Phagocytosis of bacteria typically accelerates neutrophil apoptosis, which ultimately promotes the resolution of infection. However, some bacterial pathogens alter PMN apoptosis to survive and thereby cause disease. Herein, we review PMN apoptosis and the ability of microorganisms to alter this important process. C1 [Kennedy, Adam D.; Deleo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Deleo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 364 TC 152 Z9 156 U1 6 U2 22 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 25 EP 61 DI 10.1007/s12026-008-8049-6 PG 37 WC Immunology SC Immunology GA 424VW UT WOS:000264597400004 PM 19066741 ER PT J AU Druey, KM AF Druey, Kirk M. TI Regulation of G-protein-coupled signaling pathways in allergic inflammation SO IMMUNOLOGIC RESEARCH LA English DT Article DE G proteins; RGS proteins; Signal transduction; Allergy; Asthma; Inflammation; Mast cells; Lymphocytes; Bronchial smooth muscle ID AIRWAY SMOOTH-MUSCLE; FOLLICULAR-HELPER-CELLS; MAST-CELLS; T-CELLS; LYMPHOCYTE MIGRATION; CHEMOKINE RECEPTORS; RGS PROTEINS; B-CELLS; ACTIVATION; EXPRESSION AB Allergic diseases such as asthma are elicited by maladaptive activation of immune cells such as mast cells and lymphocytes by otherwise innocuous allergens. The numerous mediators secreted by such cells promote both acute inflammation and, in many instances, chronic tissue remodeling. Most of these compounds exert their effects on end-organ targets such as epithelial and endothelial cells and airway smooth muscle by activating G-protein-coupled receptors (GPCRs), which are by far the most abundant type of cell surface receptor. Since GPCRs are also the most common target of allergy therapeutics, a better understanding of their intracellular signaling mechanisms is vital to improve the efficacy of such drugs or to develop new targets. In this review, we focus on some of the new regulatory elements that control the duration and amplitude of GPCR signal transduction pathways in immune effector cells and end-organ structural cells affected by allergic inflammation. C1 NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 10 Ctr Dr Room 11N242, Bethesda, MD 20892 USA. EM kdruey@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX The author thanks Dr. Zhihui Xie, our generous collaborators, and members of the Laboratory of Allergic Diseases for invaluable input and discussion. This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 72 TC 25 Z9 25 U1 2 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 62 EP 76 DI 10.1007/s12026-008-8050-0 PG 15 WC Immunology SC Immunology GA 424VW UT WOS:000264597400005 PM 18810336 ER PT J AU Kang, EM Malech, HL AF Kang, Elizabeth M. Malech, Harry L. TI Advances in treatment for chronic granulomatous disease SO IMMUNOLOGIC RESEARCH LA English DT Article DE Chronic granulomatous disease; Gene therapy; Allogeneic transplantation; Autoimmune complications; Antibiotic prophylaxis; Interferon gamma ID BONE-MARROW-TRANSPLANTATION; SEVERE COMBINED IMMUNODEFICIENCY; CORD BLOOD TRANSPLANTATION; STEM-CELL TRANSPLANTATION; INTERFERON-GAMMA THERAPY; GENE-THERAPY; HEMATOPOIETIC ALLOGRAFT; LUPUS-ERYTHEMATOSUS; OXIDASE DEFECT; CD34(+) CELLS AB Chronic granulomatous disease (CGD) is a rare congenital disorder resulting from a failure of neutrophils to produce oxidases. Patients are therefore prone to recurrent infections from various organisms including fungi and atypical bacteria. The mortality in patients with the X-linked form of CGD, the most common type, ranges from 3% to 5% per year and although management of infections has improved with advances in antimicrobial therapies, better methods are needed to be able to cure these patients. Peripheral blood stem cell or bone marrow transplantation, while curative, is not widely used due to the episodic nature of the infections and the belief by many that conservative management is preferable to the risks of transplantation. Still, as will be discussed, improvements in the Weld are making allogenic transplantation more desirable and tilting the risk benefit ratio in favor of this modality. Additionally, gene therapy, which has been a long touted method to cure CGD, has within the last 5-10 years become more and more of a reality and may be realized by the end of this decade. C1 [Kang, Elizabeth M.; Malech, Harry L.] NIH, Bethesda, MD 20892 USA. RP Kang, EM (reprint author), NIH, Bldg 10 Room 6-3752,10 Ctr Dr, Bethesda, MD 20892 USA. EM Ekang@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 NR 44 TC 27 Z9 29 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 77 EP 84 DI 10.1007/s12026-008-8051-z PG 8 WC Immunology SC Immunology GA 424VW UT WOS:000264597400006 PM 18806936 ER PT J AU Pierce, SK AF Pierce, Susan K. TI Understanding B cell activation: from single molecule tracking, through Tolls, to stalking memory in malaria SO IMMUNOLOGIC RESEARCH LA English DT Article DE B cells; B cell receptors; Signaling; Malaria; Immunological memory ID RESONANCE ENERGY-TRANSFER; IG-ALPHA/IG-BETA; ANTIGEN RECEPTOR; LIVING CELLS; LIPID RAFTS; LYMPH-NODE; DISEASE PROGRESSION; SUBCAPSULAR SINUS; SYNAPSE FORMATION; IMMUNE SYNAPSE AB B lymphocyte activation is initiated by the binding of antigens to the clonally expressed B cell receptors (BCRs) triggering signaling cascades that lead to the transcription of a variety of genes associated with B cell activation. Provided with the appropriate T cell help and the microenvironment of germinal centers antigen drives B cells to proliferate and differentiate into long-lived plasma cells and memory B cells that together constitute immunological memory. Here I describe efforts in my laboratory to gain an understanding of the cellular and molecular mechanisms that underlie three processes central to B cell biology namely, the initiation of BCR signaling, the interactions of the BCR with the innate immune system Toll-like receptors, and the generation and maintenance of B cell memory. Such knowledge is likely to aid research efforts in two areas of high public health priority, namely, the development of new therapeutics to control B cell responses in autoimmune disease and the design of effective vaccines to control infectious diseases. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 200B,MSC 8180, Rockville, MD 20852 USA. EM spierce@nih.gov FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 48 TC 14 Z9 14 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 85 EP 97 DI 10.1007/s12026-008-8052-y PG 13 WC Immunology SC Immunology GA 424VW UT WOS:000264597400007 PM 18810335 ER PT J AU Xiao, T AF Xiao, Tsan TI Innate immune recognition of nucleic acids SO IMMUNOLOGIC RESEARCH LA English DT Article DE Innate immune response; Pattern recognition receptors; Nucleic acids; Signal transduction; Antiviral defense; Autoimmunity; Vaccine adjuvants ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; Z-DNA-BINDING; COLD AUTOINFLAMMATORY SYNDROME; PLASMACYTOID DENDRITIC CELLS; NF-KAPPA-B; RIG-I; CRYSTAL-STRUCTURE; NALP3 INFLAMMASOME; ANTIVIRAL RESPONSES AB The innate immune system employs a number of pattern recognition receptor families in response to DNAs and RNAs, either from invading microbes or within the hosts. These include the Toll-like receptors (TLRs), the retinoic acid inducible gene I (RIG-I) like receptors (RLRs), and the nucleotide-binding domain leucine-rich repeat/NOD-like receptor (NLRs), among other potential sensors in the cytoplasm. These receptors are composed of modular domain architecture, with ligand binding/sensing domains and signaling domains regulated either through dimerization/oligomerization, or conformational changes directed by enzymatic activities. Signaling pathways from different families of receptors converge on their respective common adapter proteins and lead to activation of transcription factors or caspases. Many of these receptors induce orchestrated responses to similar ligands from different cell types, resulting in redundant and complementary immunity to infections. This highly efficient defense system is a double-edged sword: inappropriate reaction to host ligands leads to compromised innate tolerance and autoimmune diseases. Structural studies of innate immune receptors and their signaling pathways are essential in our understanding of pattern recognition mechanisms and design of more efficient vaccine adjuvants. C1 NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Xiao, T (reprint author), NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, 4 Mem Dr,Bldg 4,Room 138, Bethesda, MD 20892 USA. EM Xiaot@niaid.nih.gov RI Xiao, Tsan/A-8590-2010; Xiao, Tsan/I-7616-2013 OI Xiao, Tsan/0000-0001-9688-475X FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX The author is supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 86 TC 12 Z9 13 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 98 EP 108 DI 10.1007/s12026-008-8053-x PG 11 WC Immunology SC Immunology GA 424VW UT WOS:000264597400008 PM 18810334 ER PT J AU Wang, HS Morse, HC AF Wang, Hongsheng Morse, Herbert C., III TI IRF8 regulates myeloid and B lymphoid lineage diversification SO IMMUNOLOGIC RESEARCH LA English DT Article DE Hematopoietic stem cell; Common lymphoid progenitor; IRF8; PU.1; EBF; PAX5; E2A; Pre-pro-B; Lineage; B cell ID SEQUENCE-BINDING-PROTEIN; TRANSCRIPTION FACTOR PU.1; LEUKEMIA-LIKE SYNDROME; CELL-DEVELOPMENT; INTERLEUKIN-12 EXPRESSION; HEMATOPOIETIC STEM; PROGENITOR CELLS; FACTOR FAMILY; TARGET GENES; ELEMENT AB Interferon regulatory factor 8 (IRF8) is a member of the IRF family of transcription factors whose members play critical roles in interferon (IFN) signaling pathways governing the establishment of innate immune responses by myeloid and dendritic cells. IRF8 is also expressed in lymphoid cells and recent studies have documented its involvement in B cell lineage specification, immunoglobulin light chain gene rearrangement, the distribution of mature B cells into the marginal zone and follicular B cell compartment, and the transcriptional regulation of critical elements of the germinal center reaction. Here we review the contributions of IRF8 to B cell development from hematopoietic stem cells in the bone marrow and its place in the hierarchical regulatory network governing specification and commitment to the B cell fate. C1 [Wang, Hongsheng; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. RP Wang, HS (reprint author), NIAID, Immunopathol Lab, NIH, Twinbrook 1,Rm 1518,5640 Fishers Lane, Rockville, MD 20852 USA. EM wanghongs@niaid.nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU NIH; National Institute of Allergy and Infectious Diseases FX The authors thank Drs. Keiko Ozato and Prafullakumar Tailor, NICHD, for providing BXH2 mice, and members of LIP and the Ozato laboratory for many helpful discussions. This study was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 46 TC 72 Z9 72 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 109 EP 117 DI 10.1007/s12026-008-8055-8 PG 9 WC Immunology SC Immunology GA 424VW UT WOS:000264597400009 PM 18806934 ER PT J AU Jin, T Xu, XH Fang, J Isik, N Yan, JS Brzostowski, JA Hereld, D AF Jin, Tian Xu, Xuehua Fang, Jun Isik, Nilgun Yan, Jianshe Brzostowski, Joseph A. Hereld, Dale TI How human leukocytes track down and destroy pathogens: lessons learned from the model organism Dictyostelium discoideum SO IMMUNOLOGIC RESEARCH LA English DT Article DE Innate immunity; Chemotaxis; Chemokines; GPCR; Phagocytosis; Phagosome maturation; Dictyostelium discoideum ID LEADING-EDGE; PHAGOSOME MATURATION; CHEMOKINE RECEPTORS; SIGNALING EVENTS; LIVING CELLS; CHEMOTAXIS; PHAGOCYTOSIS; POLARIZATION; MECHANISMS; ENGULFMENT AB Human leukocytes, including macrophages and neutrophils, are phagocytic immune cells that capture and engulf pathogens and subsequently destroy them in intracellular vesicles. To accomplish this vital task, these leukocytes utilize two basic cell behaviors-chemotaxis for chasing down infectious pathogens and phagocytosis for destroying them. The molecular mechanisms controlling these behaviors are not well understood for immune cells. Interestingly, a soil amoeba, Dictyostelium discoideum, uses these same behaviors to pursue and injest its bacterial food source and to organize its multi-cellular development. Consequently, studies of this model system have provided and will continue to provide us with mechanistic insights into the chemotaxis and phagocytosis of immune cells. Here, we review recent research in these areas that have been conducted in the Chemotaxis Signal Section of NIAID's Laboratory of Immunogenetics. C1 [Jin, Tian; Isik, Nilgun; Yan, Jianshe] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Xu, Xuehua] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Fang, Jun] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Brzostowski, Joseph A.] NIAID, Lab Immunogenet Light Imaging Facil, NIH, Rockville, MD 20852 USA. [Hereld, Dale] NIAAA, Div Metab & Hlth Effects, NIH, Rockville, MD 20852 USA. RP Jin, T (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Twinbrook 2 Facil,12331 Parklawn Dr, Rockville, MD 20852 USA. EM tjin@niaid.nih.gov OI xu, xuehua/0000-0002-3863-9593 FU NIAID/NIH FX We thank other members of the Jin Laboratory for their help. The Chemotaxis Signal Section is supported by NIAID/NIH intramural funds. NR 38 TC 28 Z9 28 U1 5 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 118 EP 127 DI 10.1007/s12026-008-8056-7 PG 10 WC Immunology SC Immunology GA 424VW UT WOS:000264597400010 PM 18827980 ER PT J AU Rosenberg, HF Dyer, KD Domachowske, JB AF Rosenberg, Helene F. Dyer, Kimberly D. Domachowske, Joseph B. TI Eosinophils and their interactions with respiratory virus pathogens SO IMMUNOLOGIC RESEARCH LA English DT Article DE Eosinophils; Inflammation; Virus; Ribonuclease; Cytokine ID SYNCYTIAL VIRUS; PNEUMOVIRUS INFECTION; PNEUMONIA VIRUS; HOST-DEFENSE; RIBONUCLEASE GENES; ASTHMA; MICE; EVOLUTION; FAMILY; BRONCHIOLITIS AB Eosinophils are implicated in the pathophysiology of respiratory virus infection, most typically in negative roles, such as promoting wheezing and bronchoconstriction in conjunction with virus-induced exacerbations of reactive airways disease and in association with aberrant hypersensitivity responses to viral vaccines. However, experiments carried out in vitro and in vivo suggest positive roles for eosinophils, as they have been shown to reduce virus infectivity in tissue culture and promote clearance of the human pathogen, respiratory syncytial virus in a mouse challenge model. The related natural rodent pathogen, pneumonia virus of mice (PVM), is highly virulent in mice, and is not readily cleared by eosinophils in vivo. Interestingly, PVM replicates in eosinophils and promotes cytokine release. The molecular basis of virus infection in eosinophils and its relationship to disease outcome is currently under study. C1 [Rosenberg, Helene F.; Dyer, Kimberly D.] NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA. RP Rosenberg, HF (reprint author), NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU NIAID FX Ongoing studies in the Eosinophil Biology Section of the Laboratory of Allergic Diseases, NIAID, are supported by funding from the NIAID Division of Intramural Research. NR 38 TC 8 Z9 8 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 128 EP 137 DI 10.1007/s12026-008-8058-5 PG 10 WC Immunology SC Immunology GA 424VW UT WOS:000264597400011 PM 18818885 ER PT J AU Shannon, JG Heinzen, RA AF Shannon, Jeffrey G. Heinzen, Robert A. TI Adaptive immunity to the obligate intracellular pathogen Coxiella burnetii SO IMMUNOLOGIC RESEARCH LA English DT Article DE Adaptive immunity; Coxiella burnetii; Cell-mediated immunity; Antibody-mediated immunity; Dendritic cell; Vaccine ID TUMOR-NECROSIS-FACTOR; Q-FEVER ENDOCARDITIS; INFECTED GUINEA PIGS; PHASE-I; DENDRITIC CELLS; VACCINE PROPHYLAXIS; PROTECTIVE IMMUNITY; CELLULAR-IMMUNITY; DAIRY-CATTLE; WHITE MICE AB Coxiella burnetii is an obligate intracellular bacterial pathogen that causes the zoonosis Q fever. While an effective whole-cell vaccine (WCV) against Q fever exists, the vaccine has limitations in being highly reactogenic in sensitized individuals. Thus, a safe and effective vaccine based on recombinant protein antigen (Ag) is desirable. To achieve this goal, a better understanding of the host response to primary infection and the precise mechanisms involved in protective immunity to C. burnetii are needed. This review summarizes our current understanding of adaptive immunity to C. burnetii with a focus on recent developments in the Weld. C1 [Shannon, Jeffrey G.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX We thank Shelly Robertson for critical review of the manuscript, Dave Dorward for scanning electron microscopy, and Anita Mora for graphic illustrations. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 68 TC 22 Z9 24 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 138 EP 148 DI 10.1007/s12026-008-8059-4 PG 11 WC Immunology SC Immunology GA 424VW UT WOS:000264597400012 PM 18813881 ER PT J AU Peterson, KE Du, M AF Peterson, Karin E. Du, Min TI Innate immunity in the pathogenesis of polytropic retrovirus infection in the central nervous system SO IMMUNOLOGIC RESEARCH LA English DT Article DE Retrovirus; Brain; Mouse; Cytokines; Microglia; Astrocytes ID MURINE LEUKEMIA-VIRUS; SIMIAN IMMUNODEFICIENCY VIRUS; NECROSIS-FACTOR-ALPHA; NEUROLOGIC DISEASE; ENVELOPE PROTEIN; PROINFLAMMATORY CYTOKINES; CHEMOATTRACTANT PROTEIN-1; MOUSE GAMMARETROVIRUSES; CELLULAR-LOCALIZATION; INCREASED EXPRESSION AB Neuroinflammation, including astrogliosis, microgliosis, and the production of proinflammatory cytokines and chemokines is a common response in the central nervous system (CNS) to virus infection, including retrovirus infection. However, the contribution of this innate immune response in disease pathogenesis remains unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus infection in the mouse has provided insight into the potential contribution of the innate immune response to retrovirus-induced neurologic disease. In this model, retroviral pathogenesis correlates with the induction of neuroinflammatory responses including the activation of astrocytes and microglia, as well as the production of proinflammatory cytokines and chemokines. Studies of the neurovirulent determinants of the polytropic envelope protein as well as studies with knockout mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism of disease pathogenesis. Analysis of the activation of the innate immune response to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is a contributing factor to retrovirus-induced neuroinflammation, but that other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease. C1 [Peterson, Karin E.; Du, Min] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Peterson, KE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM petersonka@niaid.nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU NIH FX This research was supported in part by the Intramural Research Program of the NIH. NR 59 TC 13 Z9 13 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 149 EP 159 DI 10.1007/s12026-008-8060-y PG 11 WC Immunology SC Immunology GA 424VW UT WOS:000264597400013 PM 18818884 ER PT J AU Myers, L Hasenkrug, KJ AF Myers, Lara Hasenkrug, Kim J. TI Retroviral immunology: lessons from a mouse model SO IMMUNOLOGIC RESEARCH LA English DT Article DE Regulatory T cells; Suppression; Retrovirus; Immunotherapy; CD8+T cells; Chronic viral infection; Friend virus ID REGULATORY T-CELLS; VIRUS-INDUCED ERYTHROLEUKEMIA; FRIEND MURINE RETROVIRUS; GAMMA-INTERFERON; CUTTING EDGE; IN-VIVO; INDUCED IMMUNOSUPPRESSION; SPONTANEOUS-RECOVERY; RESISTANCE GENE; SELF-TOLERANCE AB Friend virus (FV) is a murine retrovirus that causes acute disease leading to lethal erythroleukemia in most strains of mice. Strains of mice that mount strong and rapid immune responses can recover from acute infection, but nevertheless develop life-long chronic infections. The study of this infection has revealed the types of immune responses required for both recovery from the acute phase and the control of the chronic phase of infection. This knowledge has led to vaccines and therapeutics to prevent and treat infections and associated disease states. The FV model has provided insights into immunological mechanisms found to be relevant to human infections with retroviruses such as HIV-1 and HTLV-1. C1 [Myers, Lara; Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This research was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 49 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X EI 1559-0755 J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 160 EP 166 DI 10.1007/s12026-008-8061-x PG 7 WC Immunology SC Immunology GA 424VW UT WOS:000264597400014 PM 18830572 ER PT J AU Su, HC AF Su, Helen C. TI The technological transformation of patient-driven human immunology research SO IMMUNOLOGIC RESEARCH LA English DT Article DE Autoimmune lymphoproliferative syndrome (ALPS); Caspase-8 deficiency state (CEDS); NRAS; Small interfering RNA (siRNA); Next generation sequencing ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; FAS GENE-MUTATIONS; APOPTOSIS; LYMPHOCYTE; CASPASE-8; IMMUNODEFICIENCY; ACTIVATION; DEFECTS; DISEASE AB New scientific technologies applied to patients with rare diseases are facilitating discoveries about how the human immune system is regulated at the molecular level. Studies of patients with autoimmune lymphoproliferative syndrome (ALPS) or caspase-8 deficiency state (CEDS) demonstrated the ability of gene expression microarray analyses and small interfering RNAs ( siRNA) to establish the physiologically important roles of NRAS, caspase-10, and caspase-8 for normal lymphocyte apoptosis and activation. The advent of genomics technologies such as next generation sequencing will complement these and more traditional approaches. These advances are anticipated to accelerate the pace of new discoveries in patients with immunological disorders. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Su, HC (reprint author), NIAID, NIH, Bldg 10CRC,Room 5W3940,10CRC Ctr Dr,MSC 1456, Bethesda, MD 20892 USA. EM hsu@niaid.nih.gov RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 FU NIH; National Institute for Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the NIH, the National Institute for Allergy and Infectious Diseases. NR 16 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 167 EP 171 DI 10.1007/s12026-008-8062-9 PG 5 WC Immunology SC Immunology GA 424VW UT WOS:000264597400015 PM 18818883 ER PT J AU Robertson, SJ Mitzel, DN Taylor, RT Best, SM Bloom, ME AF Robertson, Shelly J. Mitzel, Dana N. Taylor, R. Travis Best, Sonja M. Bloom, Marshall E. TI Tick-borne flaviviruses: dissecting host immune responses and virus countermeasures SO IMMUNOLOGIC RESEARCH LA English DT Article DE Tick-borne flavivirus; Ixodes tick vector; Interferon antagonism; Dendritic cells ID HUMAN DENDRITIC CELLS; IXODES-SCAPULARIS LARVAE; DOUBLE-STRANDED-RNA; REGULATORY T-CELLS; DENGUE VIRUS; I-INTERFERON; ALPHA-INTERFERON; VIRAL-INFECTION; ADAPTIVE IMMUNITY; IFN-ALPHA AB The tick-borne encephalitis (TBE) serocomplex of viruses, genus Flavivirus, includes a number of important human pathogens that cause serious neurological illnesses and hemorrhagic fevers. These viruses pose a significant public health problem due to high rates of morbidity and mortality, their emergence to new geographic areas, and the recent rise in the incidence of human infections. The most notable member of the TBE serocomplex is tick-borne encephalitis virus (TBEV), a neurotropic flavivirus that causes debilitating and sometimes fatal encephalitis. Although effective prophylactic anti-TBEV vaccines have been developed, there is currently no specific treatment for infection. To identify new targets for therapeutical intervention, it is imperative to understand interactions between TBEV and the host immune response to infection. Interferon (IFN) has a critical role in controlling flavivirus replication. Dendritic cells (DCs) represent an early target of TBEV infection and are major producers of IFN. Thus, interactions between DCs, IFN responses, and the virus are likely to substantially influence the outcome of infection. Early IFN and DC responses are modulated not only by the virus, but also by the tick vector and immunomodulatory compounds of tick saliva inoculated with virus into the skin. Our laboratory is examining interactions between the triad of virus, tick vector, and mammalian host that contribute to the pathogenesis of tick-borne flaviviruses. This work will provide a more detailed understanding of early events in virus infection and their impact on flavivirus pathogenesis. C1 [Robertson, Shelly J.; Mitzel, Dana N.; Taylor, R. Travis; Best, Sonja M.; Bloom, Marshall E.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Bloom, ME (reprint author), NIAID, Virol Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM mbloom@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; NIH FX The authors thank A. Mora for graphical assistance and Drs. H. Feldmann, R. A. Heinzen, and B. Rockx for critical review of the manuscript. The authors' research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. NR 71 TC 28 Z9 28 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 172 EP 186 DI 10.1007/s12026-008-8065-6 PG 15 WC Immunology SC Immunology GA 424VW UT WOS:000264597400016 PM 18841330 ER PT J AU Davis, MD Kehrl, JH AF Davis, Michael D. Kehrl, John H. TI The influence of sphingosine-1-phosphate receptor signaling on lymphocyte trafficking: How a bioactive lipid mediator grew up from an "immature" vascular maturation factor to a "mature" mediator of lymphocyte behavior and function SO IMMUNOLOGIC RESEARCH LA English DT Review DE Lymphocyte; Trafficking; Sphingosine-1-phosphate; S1P ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; CANINE KIDNEY-TRANSPLANTATION; ISCHEMIA-REPERFUSION INJURY; PROTEIN-COUPLED RECEPTOR; LONG-TERM SURVIVAL; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNOMODULATORY DRUG FTY720; COMPLETE RENAL ISCHEMIA; ALLOGRAFT SURVIVAL; IMMUNOSUPPRESSANT FTY720 AB Since the initial observations that highlighted the importance of lymphocyte trafficking for immune responses, the pathways utilized by B and T lymphocytes to recirculate and properly position themselves have been intensely studied. Most of the chemoattractants along with their cognate receptors that affect lymphocyte trafficking have been identified. Some of their functions are promotion of lymphocyte ingress into immune organs, localization of cells to specific regions within those organs, maintenance of lymphocyte basal motility in immune organs, facilitation of lymphocyte egress from these organs, and control of migration and homing of lymphocytes in the periphery. Since the seminal discovery that agonism of sphingosine-1-phosphate receptors evokes changes in lymphocyte homing and trafficking, considerable effort has been undertaken to characterize the mechanism utilized by these receptors to influence lymphocyte behavior. This review will focus on the influence of sphingosine-1-phosphate signaling system on lymphocyte localization, egress from lymph organs, and its effects on the lymphatic vasculature. C1 [Davis, Michael D.; Kehrl, John H.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11N214,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 110 TC 6 Z9 6 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 187 EP 197 DI 10.1007/s12026-008-8066-5 PG 11 WC Immunology SC Immunology GA 424VW UT WOS:000264597400017 PM 18854957 ER PT J AU Rada, B Leto, TL AF Rada, Balazs Leto, Thomas L. TI Redox warfare between airway epithelial cells and Pseudomonas: dual oxidase versus pyocyanin SO IMMUNOLOGIC RESEARCH LA English DT Article DE NADPH oxidase; Nox; Dual oxidase; Pyocyanin; Pseudomonas aeruginosa; Cystic fibrosis; Airway epithelium; Hydrogen peroxide; Oxidative stress ID AERUGINOSA PHENAZINE PIGMENTS; PEROXIDE-THIOCYANATE SYSTEM; FAMILY NADPH OXIDASES; SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; HYDROGEN-PEROXIDE; CYSTIC-FIBROSIS; HOST-DEFENSE; REACTIVE OXYGEN; LACTOPEROXIDASE-THIOCYANATE AB The importance of reactive oxygen species-dependent microbial killing by the phagocytic cell NADPH oxidase has been appreciated for some time, although only recently has an appreciation developed for the partnership of lactoperoxidase with related dual oxidases (Duox) within secretions of the airway surface layer. This system produces mild oxidants designed for extracellular killing that are effective against several airway pathogens, including Staphylococcus aureus, Burkholderia cepacia, and Pseudomonas aeruginosa. Establishment of chronic pseudomonas infections involves adaptations to resist oxidant-dependent killing by expression of a redox-active virulence factor, pyocyanin, that competitively inhibits epithelial Duox activity by consuming intracellular NADPH and producing superoxide, thereby inflicting oxidative stress on the host. C1 [Rada, Balazs; Leto, Thomas L.] NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA. RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM tleto@nih.gov FU Intramural NIH HHS [ZIA AI000614-19] NR 94 TC 21 Z9 21 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 198 EP 209 DI 10.1007/s12026-008-8071-8 PG 12 WC Immunology SC Immunology GA 424VW UT WOS:000264597400018 PM 18979077 ER PT J AU Peruzzi, G Masilamani, M Borrego, F Coligan, JE AF Peruzzi, Giovanna Masilamani, Madhan Borrego, Francisco Coligan, John E. TI Endocytosis as a mechanism of regulating natural killer cell function: unique endocytic and trafficking pathway for CD94/NKG2A SO IMMUNOLOGIC RESEARCH LA English DT Article DE NK cells; Inhibitory/activating receptors; Endocytosis; Trafficking; CD94/NKG2A ID CLATHRIN-INDEPENDENT ENDOCYTOSIS; MEMBRANE DOMAINS; NK CELLS; PLASMA-MEMBRANE; LIPID RAFTS; INHIBITORY RECEPTOR; RECYCLING PATHWAY; PINOCYTIC PATHWAY; ENDOSOMES; DYNAMIN AB Natural killer (NK) cells are lymphocytes generally recognized as sentinels of the innate immune system due to their inherent capacity to deal with diseased ( stressed) cells, including malignant and infected. This ability to recognize many potentially pathogenic situations is due to the expression of a diverse panel of activation receptors. Because NK cell activation triggers an aggressive inflammatory response, it is important to have a means of throttling this response. Hence, NK cells also express a panel of inhibitory receptors that recognize ligands expressed by "normal" cells. Little or nothing is known about the endocytosis and trafficking of NK cell receptors, which are of great relevance to understanding how NK cells maintain the appropriate balance of activating and inhibitory receptors on their cell surface. In this review, we focus on the ITIM-containing inhibitory receptor CD94/NKG2A showing that it is endocytosed by a previously undescribed macropinocytic-like process that may be related to the maintenance of its surface expression. C1 [Peruzzi, Giovanna; Borrego, Francisco; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Masilamani, Madhan] Mt Sinai Sch Med, Dept Pediat, Div Pediat Allergy & Immunol, New York, NY 10029 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Twinbrook 2,Room 205,MS 8180 12441 Parklawn Dr, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov OI Peruzzi, Giovanna/0000-0002-6517-9107; Masilamani, Madhan/0000-0001-8181-8848 FU NIAID/NIH FX This work was supported by the intramural program of the NIAID/NIH. NR 89 TC 3 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 210 EP 222 DI 10.1007/s12026-008-8072-7 PG 13 WC Immunology SC Immunology GA 424VW UT WOS:000264597400019 PM 18979076 ER PT J AU De Ravin, SS Malech, HL AF De Ravin, Suk See Malech, Harry L. TI Partially corrected X-linked severe combined immunodeficiency: long-term problems and treatment options SO IMMUNOLOGIC RESEARCH LA English DT Review DE Severe combined immunodeficiency; Hematopoietic stem cell transplant; Gene therapy; Haploidentical; T cell recombination excision circles; T cell receptor Vbeta spectratype ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; COMBINED IMMUNE-DEFICIENCY; RECEPTOR-GAMMA-CHAIN; LYMPHOPENIC IMMUNOLOGICAL DEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; RETROVIRAL VECTOR DESIGN; VIVO GENE DELIVERY; INFLUENZA-A VIRUS; INSERTIONAL MUTAGENESIS AB Rapid progress has been made from the identification of the molecular defects causing X-linked severe combined immune deficiency (X-SCID) to the development of cutting-edge therapeutic approaches such as hematopoietic stem cell transplant and gene therapy for XSCID. Successful treatment of XSCID has created a new population of patients, many of whom are now adolescents and young adults and are facing a variety of chronic problems secondary to partial correction of their underlying disease. This review focuses on the clinical challenges facing these patients (and their caregivers) and provides an overview of some of the treatment options available, including gene therapy. C1 [De Ravin, Suk See; Malech, Harry L.] NIH, Host Def Lab, Bethesda, MD 20892 USA. RP De Ravin, SS (reprint author), NIH, Host Def Lab, Bldg 10,Room 5-3816,5 W Labs CRC,10 Ctr Dr MSC145, Bethesda, MD 20892 USA. EM sderavin@nih.gov OI Malech, Harry/0000-0001-5874-5775 FU NIH; National Institute of Allergy and Infectious Diseases FX This project was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. We thank Dr Kol Zarember for his critical review of the manuscript and apologize to the authors of many excellent publications that we were not able to present adequately in this review. NR 110 TC 8 Z9 8 U1 1 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 223 EP 242 DI 10.1007/s12026-008-8073-6 PG 20 WC Immunology SC Immunology GA 424VW UT WOS:000264597400020 PM 18979075 ER PT J AU Leung, WH Tarasenko, T Bolland, S AF Leung, Wai-Hang Tarasenko, Tatyana Bolland, Silvia TI Differential roles for the inositol phosphatase SHIP in the regulation of macrophages and lymphocytes SO IMMUNOLOGIC RESEARCH LA English DT Article DE SHIP; Lymphocytes; Macrophages; T-bet; Conditional knockout ID FC-GAMMA-RIIB; POLYPHOSPHATE 5-PHOSPHATASE SHIP; AFFINITY IGE RECEPTOR; T-CELL DEVELOPMENT; ZONE B-CELLS; MARGINAL ZONE; 5'-PHOSPHATASE SHIP; NEGATIVE REGULATOR; MYELOID CELLS; MICE AB The SH2 domain-containing inositol 50-phosphatase (SHIP) negatively regulates antigen, cytokine, and Fc receptor signaling pathways in immune cells. Our knowledge of the function of SHIP largely derives from in vitro studies that utilized SHIP-deficient cell lines and immune cells isolated from SHIP null mice. To avoid the pleiotropic effects observed in mice with germline deletion of SHIP, we have used the Cre-lox system to generate SHIP conditional knockout mice with deletion in specific immune cell populations. In this review we summarize our observations from mice with deletion of SHIP in lymphocyte and macrophage lineages and contrast them with earlier data gathered by the analysis of SHIP null mice. C1 [Leung, Wai-Hang; Tarasenko, Tatyana; Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr,Twinbrook 2,Room 217, Rockville, MD 20852 USA. EM sbolland@niaid.nih.gov FU NIH FX This work was funded by the NIH intramural research. NR 53 TC 28 Z9 30 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 243 EP 251 DI 10.1007/s12026-008-8078-1 PG 9 WC Immunology SC Immunology GA 424VW UT WOS:000264597400021 PM 18989630 ER PT J AU Venugopal, PG Nutman, TB Semnani, RT AF Venugopal, Priyanka Goel Nutman, Thomas B. Semnani, Roshanak Tolouei TI Activation and regulation of Toll-Like Receptors (TLRs) by helminth parasites SO IMMUNOLOGIC RESEARCH LA English DT Article DE APC; Lymphatic filariasis; Schistosomiasis; Dendritic cells ID HUMAN DENDRITIC CELLS; NF-KAPPA-B; INFLUENCES EOSINOPHIL RECRUITMENT; ENDOSYMBIOTIC WOLBACHIA BACTERIA; SCHISTOSOMA-MANSONI EGGS; INNATE IMMUNE-RESPONSES; BRUGIA-MALAYI; LYMPHATIC FILARIASIS; GRANULOMA-FORMATION; SURFACE PROTEIN AB Helminth (worm) infections are major public health problems that have important socioeconomic consequences for the more than 2 billion infected individuals. Chronicity (their hallmark) can lead to anemia (in hookworm infection), river blindness (onchcerciasis), cirrhosis (schistosomiasis), and elephantiasis (lymphatic filariasis). Although there have been many studies examining innate immune responses (including TLR expression and function) in response to intracellular pathogens, fewer have examined the interaction of the multicellular helminth parasites and the innate immune system. This review will focus on two "systemic'' helminth parasitic infections (lymphatic filariasis and schistosomiasis) and the regulation of TLRs that may contribute to infection outcome. C1 [Venugopal, Priyanka Goel; Nutman, Thomas B.; Semnani, Roshanak Tolouei] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Semnani, RT (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,4 Ctr Dr,Room 105, Bethesda, MD 20892 USA. EM rsemnani@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Healt FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank NIAID intramural editor Brenda Rae Marshall for assistance. NR 81 TC 38 Z9 43 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 252 EP 263 DI 10.1007/s12026-008-8079-0 PG 12 WC Immunology SC Immunology GA 424VW UT WOS:000264597400022 PM 18982454 ER PT J AU Mans, J Zhi, L Revilleza, MJR Smith, L Redwood, A Natarajan, K Margulies, DH AF Mans, Janet Zhi, Li Revilleza, Maria Jamela R. Smith, Lee Redwood, Alec Natarajan, Kannan Margulies, David H. TI Structure and function of murine cytomegalovirus MHC-I-like molecules: how the virus turned the host defense to its advantage SO IMMUNOLOGIC RESEARCH LA English DT Review DE MHC recognition; NK cells; T cells; Immunoevasins; X-ray crystallography; MHC-Iv molecules; Cytomegalovirus ID COMPLETE DNA-SEQUENCE; NATURAL-KILLER-CELLS; ANTIGEN PRESENTATION; IMMUNE-SYSTEM; CRYSTAL-STRUCTURE; VIRAL MODULATION; NKG2D LIGANDS; HOMOLOG M144; T-CELLS; COMPLEX AB The mouse cytomegalovirus (CMV), a beta-herpesvirus, exploits its large (similar to 230 kb) double-stranded DNA genome for both essential and non-essential functions. Among the non-essential functions are those that offer the virus a selective advantage in eluding both the innate and adaptive immune responses of the host. Several non-essential genes of MCMV are thought to encode MHC-I-like genes and to function as immunoevasins. To understand further the evolution and function of these viral MHC-I (MHC-Iv) molecules, X-ray structures of several of them have been determined, not only confirming the overall MHC-I-like structure, but also elucidating features unique to this family. Future efforts promise to clarify the nature of the molecular ligands of these molecules, their evolution in the context of the adapting immune response of the murine host, and by analogy the evolution of the host response to human CMV as well. C1 [Mans, Janet; Zhi, Li; Revilleza, Maria Jamela R.; Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Smith, Lee; Redwood, Alec] Univ Western Australia, Discipline Microbiol & Immunol, Sch Biomed Biomol & Chem Sci, Crawley, WA 6009, Australia. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, Bldg 10 Room 11N311,10 Ctr Dr, Bethesda, MD 20892 USA. EM dhm@nih.gov RI Redwood, Alec/A-6138-2008; Smith, Lee/A-6087-2008; Margulies, David/H-7089-2013; OI Redwood, Alec/0000-0001-8601-8292; Mans, Janet/0000-0001-6721-1177; Margulies, David/0000-0001-8530-7375 FU National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 55 TC 10 Z9 10 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2009 VL 43 IS 1-3 BP 264 EP 279 DI 10.1007/s12026-008-8081-6 PG 16 WC Immunology SC Immunology GA 424VW UT WOS:000264597400023 PM 19011767 ER PT J AU Readinger, JA Mueller, KL Venegas, AM Horai, R Schwartzberg, PL AF Readinger, Julie A. Mueller, Kristen L. Venegas, Ana M. Horai, Reiko Schwartzberg, Pamela L. TI Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk SO IMMUNOLOGICAL REVIEWS LA English DT Review DE T cells; Th1; Th2; Th17 cells; asthma; thymus; protein kinases; phosphatases ID BRUTONS TYROSINE KINASE; NKT CELL-DEVELOPMENT; LINKED LYMPHOPROLIFERATIVE SYNDROME; STABLE MICROTUBULE FORMATION; PLECKSTRIN HOMOLOGY DOMAIN; NF-KAPPA-B; FAMILY KINASES; POSITIVE SELECTION; HUMORAL IMMUNITY; CUTTING EDGE AB The Tec (tyrosine kinase expressed in hepatocellular carcinoma) family of non-receptor tyrosine kinases consists of five members: Tec, Bruton's tyrosine kinase (Btk), inducible T-cell kinase (Itk), resting lymphocyte kinase (Rlk/Txk), and bone marrow-expressed kinase (Bmx/Etk). Although their functions are probably best understood in antigen receptor signaling, where they participate in the phosphorylation and regulation of phospholipase C-gamma (PLC-gamma), it is now appreciated that these kinases contribute to signaling from many receptors and that they participate in multiple downstream pathways, including regulation of the actin cytoskeleton. In T cells, three Tec kinases are expressed, Itk, Rlk/Txk, and Tec. Itk is expressed at highest amounts and plays the major role in regulating signaling from the T-cell receptor. Recent studies provide evidence that these kinases contribute to multiple aspects of T-cell biology and have unique roles in T-cell development that have revealed new insight into the regulation of conventional and innate T-cell development. We review new findings on the Tec kinases with a focus on their roles in T-cell development and mature T-cell differentiation. C1 [Readinger, Julie A.; Mueller, Kristen L.; Venegas, Ana M.; Horai, Reiko; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bldg 49,Room 4A38,49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA. EM pams@nhgri.nih.gov FU Intramural NIH HHS [Z01 HG000123-10] NR 163 TC 61 Z9 64 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAR PY 2009 VL 228 BP 93 EP 114 DI 10.1111/j.1600-065X.2008.00757.x PG 22 WC Immunology SC Immunology GA 415WD UT WOS:000263966200006 PM 19290923 ER PT J AU Gilfillan, AM Rivera, J AF Gilfillan, Alasdair M. Rivera, Juan TI The tyrosine kinase network regulating mast cell activation SO IMMUNOLOGICAL REVIEWS LA English DT Review DE mast cells; Fc epsilon RI; KIT; Bruton's tyrosine kinase; Lyn; Fyn ID FC-EPSILON-RI; AFFINITY IGE RECEPTOR; SRC FAMILY KINASES; N-TERMINAL KINASE; C-KIT RECEPTOR; PROTEIN-TYROSINE; FYN KINASE; T-CELL; PHOSPHOINOSITIDE 3-KINASE; CYTOKINE PRODUCTION AB Mast cell mediator release represents a pivotal event in the initiation of inflammatory reactions associated with allergic disorders. These responses follow antigen-mediated aggregation of immunoglobulin E (IgE)-occupied high-affinity receptors for IgE (Fc epsilon RI) on the mast cell surface, a response which can be further enhanced following stem cell factor-induced ligation of the mast cell growth factor receptor KIT (CD117). Activation of tyrosine kinases is central to the ability of both Fc epsilon RI and KIT to transmit downstream signaling events required for the regulation of mast cell activation. Whereas KIT possesses inherent tyrosine kinase activity, Fc epsilon RI requires the recruitment of Src family tyrosine kinases and Syk to control the early receptor-proximal signaling events. The signaling pathways propagated by these tyrosine kinases can be further upregulated by the Tec kinase Bruton's tyrosine kinase and downregulated by the actions of the tyrosine Src homology 2 domain-containing phosphatase 1 (SHP-1) and SHP-2. In this review, we discuss the regulation and role of specific members of this tyrosine kinase network in KIT and Fc epsilon RI-mediated mast cell activation. C1 [Rivera, Juan] NIAMSD, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA. [Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMSD, Lab Immune Cell Signaling, NIH, Bldg 10,Room 13C103,MSC 1930,10 Ctr Dr, Bethesda, MD 20892 USA. EM juan-rivera@nih.gov FU NIAMS; NIAID FX Research in the authors' laboratory is supported by the NIAMS (J. R.) NIAID (A. M. G.) Intramural Programs within the National Institutes of Health, USA. NR 174 TC 194 Z9 196 U1 1 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAR PY 2009 VL 228 BP 149 EP 169 DI 10.1111/j.1600-065X.2008.00742.x PG 21 WC Immunology SC Immunology GA 415WD UT WOS:000263966200008 PM 19290926 ER PT J AU Ghoreschi, K Laurence, A O'Shea, JJ AF Ghoreschi, Kamran Laurence, Arian O'Shea, John J. TI Janus kinases in immune cell signaling SO IMMUNOLOGICAL REVIEWS LA English DT Review DE cytokines; immunoregulation; immunosuppression; Janus kinases; leukemia; signal transduction ID PROTEIN-TYROSINE KINASE; HYPER-IGE SYNDROME; CHRONIC MYELOID-LEUKEMIA; RECEPTOR-GAMMA-CHAIN; MICE LACKING JAK3; SEVERE COMBINED IMMUNODEFICIENCY; BCR-JAK2 FUSION GENE; POLYCYTHEMIA-VERA; MYELOPROLIFERATIVE DISORDERS; LYMPHOID DEVELOPMENT AB The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non-receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jaks in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical disorders, which are also evident in mouse models. A striking phenotype associated with inactivating Jak3 mutations is severe combined immunodeficiency syndrome, whereas mutation of Tyk2 results in another primary immunodeficiency termed autosomal recessive hyperimmunoglobulin E syndrome. By contrast, complete deletion of Jak1 or Jak2 in the mouse are not compatible with life and, unsurprisingly, do not have counterparts in human disease. However, activating mutations of each of the Jaks are found in association with malignant transformation, the most common being gain-of-function mutations of Jak2 in polycythemia vera and other myeloproliferative disorders. Our existing knowledge on Jak signaling pathways and fundamental work on their biochemical structure and intracellular interactions allow us to develop new strategies for controlling autoimmune diseases or malignancies by developing selective Jak inhibitors, which are now coming into clinical use. Despite the fact that Jaks were discovered only a little more than a decade ago, at the time of writing there are 20 clinical trials underway testing the safety and efficacy of Jak inhibitors. C1 [Ghoreschi, Kamran; Laurence, Arian; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Ghoreschi, K (reprint author), Bldg 10 13C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM ghoreschik@mail.nih.gov RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 FU Intramural NIH HHS [Z01 AR041106-14] NR 146 TC 359 Z9 381 U1 3 U2 34 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAR PY 2009 VL 228 BP 273 EP 287 DI 10.1111/j.1600-065X.2008.00754.x PG 15 WC Immunology SC Immunology GA 415WD UT WOS:000263966200016 PM 19290934 ER PT J AU Casellas, R Yamane, A Kovalchuk, AL Potter, M AF Casellas, Rafael Yamane, Arito Kovalchuk, Alexander L. Potter, Michael TI Restricting activation-induced cytidine deaminase tumorigenic activity in B lymphocytes SO IMMUNOLOGY LA English DT Review DE activation-induced cytidine deaminase; chromosomal translocations; class switch recombination; somatic hypermutation; tumorigenesis ID CLASS SWITCH RECOMBINATION; C-MYC ONCOGENE; SINGLE-STRANDED-DNA; ANTIBODY DIVERSIFICATION ENZYME; INTERLEUKIN-6 TRANSGENIC MICE; PLASMA-CELL DIFFERENTIATION; SOMATIC HYPERMUTATION; CHROMOSOMAL TRANSLOCATIONS; POLYMERASE-ETA; BURKITT-LYMPHOMA AB DNA breaks play an essential role in germinal centre B cells as intermediates to immunoglobulin class switching, a recombination process initiated by activation-induced cytidine deaminase (AID). Immunoglobulin gene hypermutation is likewise catalysed by AID but is believed to occur via single-strand DNA breaks. When improperly repaired, AID-mediated lesions can promote chromosomal translocations (CTs) that juxtapose the immunoglobulin loci to heterologous genomic sites, including oncogenes. Two of the most studied translocations are the t(8;14) and T(12;15), which deregulate cMyc in human Burkitt's lymphomas and mouse plasmacytomas, respectively. While a complete understanding of the aetiology of such translocations is lacking, recent studies using diverse mouse models have shed light on two important issues: (1) the extent to which non-specific or AID-mediated DNA lesions promote CTs, and (2) the safeguard mechanisms that B cells employ to prevent AID tumorigenic activity. Here we review these advances and discuss the usage of pristane-induced mouse plasmacytomas as a tool to investigate the origin of Igh-cMyc translocations and B-cell tumorigenesis. C1 [Casellas, Rafael; Yamane, Arito] NIAMS, NIH, Bethesda, MD 20892 USA. [Kovalchuk, Alexander L.; Potter, Michael] NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Casellas, R (reprint author), NIAMS, NIH, Bethesda, MD 20892 USA. EM casellar@mail.nih.gov RI Yamane, Arito/A-2959-2013 FU Intramural Research Program of NIAMS; NCI of the National Institutes of Health FX The authors thank Susan Lim and Kristien Zaal for providing the AID-GFP micrograph, Konrad Huppi for sharing unpublished data, and Michel Nussenzweig, Javier DiNoia and Siegfried Janz for critically reading the manuscript. The writing of this review was supported (in part) by the Intramural Research Program of NIAMS and NCI of the National Institutes of Health. NR 124 TC 16 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2009 VL 126 IS 3 BP 316 EP 328 DI 10.1111/j.1365-2567.2008.03050.x PG 13 WC Immunology SC Immunology GA 402UN UT WOS:000263038700003 PM 19302140 ER PT J AU Elmore, E Redpath, JL Steele, VE AF Elmore, Eugene Redpath, J. Leslie Steele, Vernon E. TI Using Gene Expression and Pathway Analysis for Efficacy and Toxicity Assessment SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Elmore, Eugene; Redpath, J. Leslie] Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. [Elmore, Eugene; Redpath, J. Leslie] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA 92697 USA. [Steele, Vernon E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. EM eelmore@uci.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2009 VL 45 BP S10 EP S11 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 481ZS UT WOS:000268853400027 ER PT J AU Sebbane, F Jarrett, C Gardner, D Long, D Hinnebusch, BJ AF Sebbane, Florent Jarrett, Clayton Gardner, Donald Long, Daniel Hinnebusch, B. Joseph TI The Yersinia pestis caf1M1A1 Fimbrial Capsule Operon Promotes Transmission by Flea Bite in a Mouse Model of Bubonic Plague SO INFECTION AND IMMUNITY LA English DT Article ID EARLY-PHASE TRANSMISSION; MURINE PERITONEAL-MACROPHAGES; POLYMERASE-CHAIN-REACTION; DETECT YERSINIA-PESTIS; REAL-TIME PCR; PASTEURELLA-PESTIS; PNEUMONIC PLAGUE; Y-PESTIS; IN-VITRO; HUMAN INTERLEUKIN-1-BETA AB Plague is a zoonosis transmitted by fleas and caused by the gram-negative bacterium Yersinia pestis. During infection, the plasmidic caf1M1A1 operon that encodes the Y. pestis F1 protein capsule is highly expressed, and anti-F1 antibodies are protective. Surprisingly, the capsule is not required for virulence after injection of cultured bacteria, even though it is an antiphagocytic factor and capsule-deficient Y. pestis strains are rarely isolated. We found that a caf-negative Y. pestis mutant was not impaired in either flea colonization or virulence in mice after intradermal inoculation of cultured bacteria. In contrast, absence of the caf operon decreased bubonic plague incidence after a flea bite. Successful development of plague in mice infected by flea bite with the caf-negative mutant required a higher number of infective bites per challenge. In addition, the mutant displayed a highly autoaggregative phenotype in infected liver and spleen. The results suggest that acquisition of the caf locus via horizontal transfer by an ancestral Y. pestis strain increased transmissibility and the potential for epidemic spread. In addition, our data support a model in which atypical caf-negative strains could emerge during climatic conditions that favor a high flea burden. Human infection with such strains would not be diagnosed by the standard clinical tests that detect F1 antibody or antigen, suggesting that more comprehensive surveillance for atypical Y. pestis strains in plague foci may be necessary. The results also highlight the importance of studying Y. pestis pathogenesis in the natural context of arthropod-borne transmission. C1 [Sebbane, Florent] Univ Lille 2, Inst Pasteur, INSERM, U801, F-59021 Lille, France. [Jarrett, Clayton; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA. [Gardner, Donald; Long, Daniel] NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Sebbane, F (reprint author), Univ Lille 2, Inst Pasteur, INSERM, U801, 1 Rue Professeur Calmette, F-59021 Lille, France. EM florent.sebbane@ibl.fr RI Sebbane, Florent/D-4213-2009 FU Division of Intramural Research, NIAID, NIH; Ellison Medical Foundation; INSERM FX This work was supported by the Division of Intramural Research, NIAID, NIH; the Ellison Medical Foundation (New Scholars Award in Global Infectious Diseases to B. J. H.); and INSERM. NR 73 TC 40 Z9 41 U1 0 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 MAR PY 2009 VL 77 IS 3 BP 1222 EP 1229 DI 10.1128/IAI.00950-08 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 408DZ UT WOS:000263416700034 PM 19103769 ER PT J AU Deleo, FR Diep, BA Otto, M AF DeLeo, Frank R. Diep, Binh An Otto, Michael TI Host Defense and Pathogenesis in Staphylococcus aureus Infections SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Staphylococcus; Neutrophil; Innate immunity; Virulence ID PANTON-VALENTINE LEUKOCIDIN; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; COMMUNITY-ASSOCIATED MRSA; CATABOLIC MOBILE ELEMENT; PEPTIDE-SENSING SYSTEM; SOFT-TISSUE INFECTIONS; TOXIC-SHOCK-SYNDROME; METHICILLIN-RESISTANT; HUMAN-NEUTROPHILS; IMMUNE EVASION AB Staphylococcus aureus is the most abundant cause of bacterial infections in the United States. As such, the pathogen has devised means to circumvent destruction by the innate immune system. Neutrophils are a critical component of innate immunity and the primary cellular defense against S aureus infections. This article reviews human neutrophil function in the context of S aureus virulence mechanisms and provides an overview of community-associated methicillin-resistant S aureus pathogenicity. C1 [DeLeo, Frank R.; Otto, Michael] NIAID, NIH, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, Hamilton, MT 59840 USA. [Diep, Binh An] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94110 USA. RP Deleo, FR (reprint author), NIAID, NIH, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, 903 South 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 FU Intramural Program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by the Intramural Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 100 TC 93 Z9 97 U1 4 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2009 VL 23 IS 1 BP 17 EP + DI 10.1016/j.idc.2008.10.003 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 406TC UT WOS:000263316800003 PM 19135914 ER PT J AU Engels, EA Shen, M Chapman, RS Pfeiffer, RM Yu, YY He, XZ Lan, Q AF Engels, Eric A. Shen, Min Chapman, Robert S. Pfeiffer, Ruth M. Yu, Ying-Ying He, Xingzhou Lan, Qing TI Tuberculosis and subsequent risk of lung cancer in Xuanwei, China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lung cancer; tuberculosis; inflammation; pulmonary fibrosis; epidemiology; cohort study ID NONSMOKING WOMEN; UNITED-STATES; DISEASE; INFLAMMATION; IMPROVEMENT; EXPOSURE; TOBACCO; STOVES AB Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2,459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1,000 person-years). The association was especially pronounced in the first 5 years after tuberculosis diagnosis (hazard ratios [HRs] ranging 6.7-13) but remained strong 5-9.9 years (HR 3.4, 95% CI 1.3-9.1) and 10+ years (HR 3.0, 95% CI 1.3-7.3) after tuberculosis. These associations were similar among men and women and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis. Published 2008 Wiley-Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America. C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok, Thailand. [He, Xingzhou] Chinese Acad Prevent Med, Inst Environm Hlth & Engn, Beijing, Peoples R China. RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7076, Rockville, MD 20852 USA. EM engelse@exchange.nih.gov FU Intramural Research Program of the National Cancer Institute FX Grant sponsor: Intramural Research Program of the National Cancer Institute. NR 24 TC 36 Z9 38 U1 0 U2 8 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 MAR 1 PY 2009 VL 124 IS 5 BP 1183 EP 1187 DI 10.1002/ijc.24042 PG 5 WC Oncology SC Oncology GA 403JC UT WOS:000263077900023 PM 19058197 ER PT J AU Koutros, S Lynch, CF Ma, XM Lee, WJ Hoppin, JA Christensen, CH Andreotti, G Freeman, LB Rusiecki, JA Hou, LF Sandler, DP Alavanja, MCR AF Koutros, Stella Lynch, Charles F. Ma, Xiaomei Lee, Won Jin Hoppin, Jane A. Christensen, Carol H. Andreotti, Gabriella Freeman, Laura Beane Rusiecki, Jennifer A. Hou, Lifang Sandler, Dale P. Alavanja, Michael C. R. TI Heterocyclic aromatic amine pesticide use and human cancer risk: Results from the US Agricultural Health Study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE pesticides; bladder; colon; occupational exposures ID COLORECTAL-CANCER; BLADDER-CANCER; UNITED-STATES; COLON-CANCER; PHENOXY HERBICIDES; MEAT INTAKE; LIFE-STYLE; MORTALITY; WORKERS; EXPOSURE AB Imazethapyr, a heterocyclic aromatic amine, is a widely used crop herbicide first registered for use in the United States in 1989. We evaluated cancer incidence among imazethapyr-exposed pesticide applicators enrolled in the Agricultural Health Study (AHS). The AHS is a prospective cohort of 57,311 licensed pesticide applicators in the U.S., enrolled from 1993-1997. Among the 49,398 licensed pesticide applicators eligible for analysis, 20,646 applicators reported use of imazethapyr and 2,907 incident cancers developed through 2004. Imazethapyr exposure was classified by intensity-weighted lifetime exposure days calculated as [years of use X days per year X intensity level]. Poisson regression analysis was used to evaluate the relationship between imazethapyr exposure and cancer incidence. We found significant trends in risk with increasing lifetime exposure for bladder cancer (p for trend 0.01) and colon cancer (p for trend 0.02). Rate ratios (RRs) were increased by 137% for bladder cancer and 78% for colon cancer when the highest exposed were compared to the nonexposed. The excess risk for colon cancer was limited to proximal cancers, (RR = 2.73, 95% confidence intervals 1.42, 5.25, p for trend 0.001). No association was observed for prostate, lung, rectum, kidney, oral, pancreas, lymphohematopoietic cancers or melanoma. These findings provide new evidence that exposure to aromatic amine pesticides may be an overlooked exposure in the etiology of bladder and colon cancer. The use of imazethapyr and other imidazolinone compounds should continue to be evaluated for potential risk to humans. Published 2008 Wiley-Liss, Inc. C1 [Koutros, Stella; Andreotti, Gabriella; Freeman, Laura Beane; Alavanja, Michael C. R.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Ma, Xiaomei] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Environm Hlth, New Haven, CT 06510 USA. [Lee, Won Jin] Korea Univ, Coll Med, Dept Prevent Med, Seoul 136705, South Korea. [Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Christensen, Carol H.] US EPA, Toxicol & Epidemiol Branch, Div Hlth Effects, Off Pesticide Programs, Washington, DC 20460 USA. [Christensen, Carol H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Rusiecki, Jennifer A.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8000,MSC 7240, Rockville, MD 20852 USA. EM KoutrosS@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS [Z01 CP010119-12]; NCI NIH HHS [TU2 CA105666, TU2 CA105666-05] NR 36 TC 44 Z9 48 U1 0 U2 11 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 MAR 1 PY 2009 VL 124 IS 5 BP 1206 EP 1212 DI 10.1002/ijc.24020 PG 7 WC Oncology SC Oncology GA 403JC UT WOS:000263077900027 PM 19058219 ER PT J AU Friedman, ES Thase, ME Wisniewski, SR Trivedi, MH Biggs, MM Fava, M Warden, D Niederehe, G Luther, JF Rush, AJ AF Friedman, Edward S. Thase, Michael E. Wisniewski, Stephen R. Trivedi, Madhukar H. Biggs, Melanie M. Fava, Maurizio Warden, Diane Niederehe, George Luther, James F. Rush, A. John TI Cognitive Therapy Augmentation versus CT Switch Treatment: A STAR*D Report SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; BEHAVIORAL-ANALYSIS SYSTEM; MAJOR DEPRESSIVE DISORDER; ILLNESS RATING-SCALE; REPORT QIDS-SR; QUICK INVENTORY; MOOD DISORDERS; CHRONIC FORMS; PSYCHOMETRIC EVALUATION; PSYCHOTHERAPY AB Objective: This report compares the effectiveness of cognitive therapy (CT) as an augmentation to citalopram vs. CT as a switch from citalopram as a second-step treatment for outpatients with non-psychotic major depressive disorder (MDD) who had received unsatisfactory benefit from an initial trial of citalopram. Methods: 1 Participants who experienced intolerance to or who did not reach remission with an optimal trial of citalopram, and who accepted randomization only to one of the two CT options were randomized to a second-step treatment of either CT switch or CT augmentation of citalopram. Treatment outcomes, side effects, and serious adverse events were compared between the two groups. Results: As a second-step treatment following an optimal trial of citalopram) discontinuing medication and switching to CT (n=32) was as effective as augmenting citalopram with CT (n=26)). Unlike the CT switch subjects, most individuals in the CT augmentation group endorsed mild-to-marked levels of side effect frequency, intensity, and burden. Conclusions: This is the first study to compare CT as a switch or augmentation strategy following unsatisfactory benefit or intolerance to an SSRI antidepressant medication. In these individuals with highly recurrent and chronic depression, there was no apparent benefit to continuing the citalopram and augmenting with CT vs. switching to CT in terms of acute phase treatment features and outcomes, or probability of relapse over one year. Implications for clinical practice arc discussed. C1 [Trivedi, Madhukar H.; Biggs, Melanie M.; Warden, Diane; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15213 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Friedman, Edward S.; Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. [Niederehe, George] NIMH, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Friedman, ES (reprint author), Univ Pittsburgh, Med Ctr, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. EM friedmane@upmc.edu NR 63 TC 1 Z9 1 U1 1 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 EI 1937-1217 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD MAR PY 2009 VL 2 IS 1 BP 66 EP 87 PG 22 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 483ZF UT WOS:000269011500006 ER PT J AU Wang, HB Chen, RY Ding, GW Ma, YL Ma, JG Jiao, JH Wo, ZL Sharp, GB Wang, N AF Wang, Haibo Chen, Ray Y. Ding, Guowei Ma, Yanling Ma, Jianguo Jiao, Jin Hua Wo, Zhenglai Sharp, Gerald B. Wang, Ning TI Prevalence and predictors of HIV infection among female sex workers in Kaiyuan City, Yunnan Province, China SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Female sex workers; Sex work venues; HIV; Injection drug users; Condom; Sexually transmitted infections; China ID SEXUALLY-TRANSMITTED-DISEASES; HERPES-SIMPLEX-VIRUS; INTRAVAGINAL PRACTICES; TRANSMISSION; RISK; ACQUISITION; REDUCTION; INCREASES; HIV/AIDS; SYPHILIS AB Background: Sexual transmission is the fastest growing route of HIV transmission in China. We undertook this study to describe the risk factors for HIV infection in female sex workers (FSWs), and to determine the commercial sex venues where FSWs are most at risk of being infected with or infecting others with HIV. Methods: This was a cross-sectional study of 737 FSWs in Kaiyuan City, Yunnan Province in southern China, which took place from March to May 2006. Results: The overall HIV prevalence was 10.3%, but prevalence varied with sex venue with 25.8% of FSWs working on the streets being HIV-positive and none of the FSWs working in nightclubs. Adjusted odds ratios (OR) of HIV infection were 9.1 (95% confidence interval (CI) 4.67-17.55) for injection drug use, 3.3 (95% CI 1.46-7.37) for non-injection illegal drug use, 2.7 (95% CI 1.25-5.93) for duration of sex work >= 5 years, 2.2 (95% CI 1.05-4.70) for infection with herpes simplex virus type 2, and 2.0 (95% CI 1.12-3.47) for working at a higher risk entertainment venue. Although condom use was not a significant risk factor in the overall model, FSWs in tower risk venues who reported consistent use with clients had a 70% reduction in HIV infections (OR 0.30, 95% CI 0.12-0.90). Conclusions: Illegal drug use, particularly with injection drugs, is the single greatest risk factor for HIV infection among FSWs in Kaiyuan City, China. FSWs working on the street or in temporary sublets, beauty salons, or saunas are at particularly high risk for transmitting and being infected with HIV. HIV prevention efforts among FSWs should target illegal drug users and these other subgroups. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Wang, Haibo; Ding, Guowei; Wo, Zhenglai; Wang, Ning] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Prevent & Control, Beijing 100050, Peoples R China. [Chen, Ray Y.; Sharp, Gerald B.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Ma, Yanling] Yunnan Ctr Dis Control & Prevent, Dept AIDS, Yunnan, Peoples R China. [Ma, Jianguo] Kaiyuan Ctr Dis Control & Prevent, Kaiyuan, Yunnan, Peoples R China. [Jiao, Jin Hua] Westat Corp, Rockville, MD USA. RP Wang, N (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Prevent & Control, 27 Nanwei Rd, Beijing 100050, Peoples R China. EM wangnbj@163.com OI Chen, Ray/0000-0001-6344-1442 FU National Institute of Allergy and Infectious Diseases, US National Institutes of Health [U19 AI51915-05] FX This study was funded by a grant from the National Institute of Allergy and Infectious Diseases, US National Institutes of Health (U19 AI51915-05). NR 28 TC 76 Z9 82 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD MAR PY 2009 VL 13 IS 2 BP 162 EP 169 DI 10.1016/j.ijid.2008.05.1229 PG 8 WC Infectious Diseases SC Infectious Diseases GA 426KM UT WOS:000264707200008 PM 18718801 ER PT J AU Luo, XL Li, ZM Yan, Q Li, XL Tao, DD Wang, J Leng, Y Gardner, K Judge, SIV Li, QDQ Hu, JB Gong, J AF Luo, Xuelai Li, Zhaoming Yan, Qun Li, Xiaolan Tao, Deding Wang, Jing Leng, Yan Gardner, Kevin Judge, Susan I. V. Li, Qingdi Q. Hu, Junbo Gong, Jianping TI The human WW45 protein enhances MST1-mediated apoptosis in vivo SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE hWW45; mammalian sterile 20-like kinase 1; apoptosis ID PROMOTES APOPTOSIS; CELL-PROLIFERATION; CASPASE CLEAVAGE; MST1 KINASE; ACTIVATION; PHOSPHORYLATION; DOMAIN; HIPPO; IRRADIATION; DROSOPHILA AB Mammalian sterile 20-like kinase 1 (MST1) is a serine/threonine protein kinase that is activated in response to a variety of apoptotic stimuli and causes apoptosis when over-expressed in mammalian cells. The physiological regulation and cellular targets of MST1 are not well understood. Using a yeast two-hybrid system, we identified human WW45 (hWW45, also called hSav1) as an MST1-binding protein. The association between the two proteins was confirmed by immunofluorescence and co-immunoprecipitation, and hWW45 was present in both the cytoplasm and nucleus. When hWW45 alone was over-expressed, it weakly induced apoptosis. However, hWW45 augmented MST1-induced apoptosis when the two were co-expressed. Conversely, RNA interference-mediated depletion of endogenous hWW45 suppressed MST1-induced apoptosis. These results indicate that hWW45 is required to enhance MST1-mediated apoptosis in vivo and thus is a critical player in an MST1-driven cell death signaling pathway. C1 [Hu, Junbo] Cent China Univ Sci & Technol, Dept Surg, Tongji Hosp, Tongji Med Sch, Wuhan 430030, Peoples R China. [Luo, Xuelai; Li, Zhaoming; Yan, Qun; Li, Xiaolan; Tao, Deding; Leng, Yan; Hu, Junbo; Gong, Jianping] Cent China Univ Sci & Technol, Inst Canc Res, Tongji Hosp, Wuhan 430030, Peoples R China. [Wang, Jing] Cent China Univ Sci & Technol, Dept Immunol, Tongji Med Coll, Wuhan 430030, Peoples R China. [Gardner, Kevin; Li, Qingdi Q.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Judge, Susan I. V.] Univ Maryland, Sch Med, MS Ctr Excellence E, VA Maryland Hlth Care Syst, Baltimore, MD 21201 USA. [Judge, Susan I. V.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Hu, JB (reprint author), Cent China Univ Sci & Technol, Dept Surg, Tongji Hosp, Tongji Med Sch, Wuhan 430030, Peoples R China. EM liquenti@mail.nih.gov; jbhu@tjh.tjmu.edu.cn; jpgong@tjh.tjmu.edu.cn FU Program for New Century Excellent Talents in Universities [04-0699]; National Natural Science Foundation of China [30872472, 30800569]; National Basic Research Program of China [2009CB521802] FX This work was partly supported by grants from the Program for New Century Excellent Talents in Universities (NCET: No. 04-0699), the National Natural Science Foundation of China (NSFC: Nos. 30872472 and 30800569), and the National Basic Research Program of China (973: No. 2009CB521802). NR 26 TC 10 Z9 13 U1 0 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 2009 VL 23 IS 3 BP 357 EP 362 DI 10.3892/ijmm_00000139 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 410JK UT WOS:000263573100008 PM 19212654 ER PT J AU Fiorentino, M Fu, LZ Shi, YB AF Fiorentino, Maria Fu, Liezhen Shi, Yun-Bo TI Mutational analysis of the cleavage of the cancer-associated laminin receptor by stromelysin-3 reveals the contribution of flanking sequences to site recognition and cleavage efficiency SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE stromelysin-3; laminin receptor; matrix metalloproteinase; Xenopus laevis; tumor invasion; extracellular matrix ID MATRIX-METALLOPROTEINASE STROMELYSIN-3; XENOPUS-LAEVIS; BREAST-CARCINOMA; MESSENGER-RNA; PROGNOSTIC-SIGNIFICANCE; MOUSE STROMELYSIN-3; FROG METAMORPHOSIS; BINDING PROTEIN; EXPRESSION; METASTASIS AB The matrix metalloproteinase stromelysin-3 (ST3) has long been implicated to play an important role in cell fate determination during normal and pathological processes. Using the thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we have previously shown that ST3 is required for apoptosis during intestinal remodeling and that laminin receptor (LR) is an in vivo substrate of ST3 during this process. ST3 cleaves LR at two distinct sites that are conserved in mammalian LR. Human ST3 and LR are both associated with tumor development and cancer progression and human LR can also be cleaved by ST3, implicating a role of LR cleavage by ST3 in human cancers. Here, we carried out a series of mutational analyses on the two cleavage sites in LR. Our findings revealed that in addition to primary sequence at the cleavage site (positions P3-P3', with the cleavage occurring between P1-P1'), flanking sequences/conformation also influenced the cleavage of LR by ST3. Furthermore, alanine substitution studies led to a surprising finding that surrounding sequence and/or conformation dictated the site of cleavage in LR by ST3. These results thus have important implications in our understanding of substrate recognition and cleavage by ST3 and argue for the importance of studying ST3 cleavage in the context of full-length substrates. Furthermore, the LR cleavage mutants generated here will also be valuable tools for future studies on the role of LR cleavage by ST3 in vertebrate development and cancer progression. C1 [Fiorentino, Maria; Fu, Liezhen; Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov OI Fiorentino, Maria R/0000-0001-5318-7313 FU Intramural Research Program of NICHD; NIH FX We thank Dr L. Notari and Dr A. Antignani for suggestions on protein purification. This research was supported by the Intramural Research Program of NICHD, NIH. NR 52 TC 9 Z9 9 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 2009 VL 23 IS 3 BP 389 EP 397 DI 10.3892/ijmm_00000143 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 410JK UT WOS:000263573100012 PM 19212658 ER PT J AU Olivares, D Huang, XD Branden, L Greig, NH Rogers, JT AF Olivares, David Huang, Xudong Branden, Lars Greig, Nigel H. Rogers, Jack T. TI Physiological and Pathological Role of Alpha-synuclein in Parkinson's Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE PD: Parkinson's disease; AD: Alzheimer's disease; alpha-syn: alpha-synuclein; PLD2: phospholipase D2; CNS: central nervous system; ER: endoplasmatic reticulum; PM: plasmatic membrane; LBs: Lewy bodies; LNs: Lewy neurites; GCIs: glial cytoplasmic inclusions; DLB: dementia with Lewy Bodies; DA: dopamine; DAT: dopamine transporter; NAC: non-amyloidogenic component; 5-UTR: 5 '-untranslated region; IRE: iron responsive element; IRPs: interacting binding proteins; wt: wild-type; ROS: reactive oxygen species; GSH: reduced gluthatione; 6-OHDA: 6-hydroxydopamine; MPTP: 1-methyl 4-phenyl 1, 2, 3, 6 tetrapyridine; TfR: transferrin receptor; TH: tyrosine hydroxylase; nt: nucleotide(s); aa: amino acid(s). ID MITOCHONDRIAL COMPLEX-I; A-BETA COMPONENT; ALZHEIMERS-DISEASE; MESSENGER-RNA; LEWY BODIES; SUBSTANTIA-NIGRA; NEURODEGENERATIVE DISEASES; FIBRIL FORMATION; 5'-UNTRANSLATED REGION; PRECURSOR PROTEIN AB Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer's disease (AD) and represents a large health burden to society. Genetic and oxidative risk factors have been proposed as possible causes, but their relative contribution remains unclear. Dysfunction of alpha-synuclein (alpha-syn) has been associated with PD due to its increased presence, together with iron, in Lewy bodies. Brain oxidative damage caused by iron may be partly mediated by alpha- syn oligomerization during PD pathology. Also, alpha-syn gene dosage can cause familial PD and inhibition of its gene expression by blocking translation via a newly identified Iron Responsive Element-like RNA sequence in its 5'-untranslated region may provide a new PD drug target. C1 [Olivares, David; Huang, Xudong; Rogers, Jack T.] Harvard Univ, Neurochem Lab, Dept Psychiat Neurosci, Massachusetts Gen Hosp E,Med Sch, Charlestown, MA 02129 USA. [Branden, Lars] Yale Univ, Sch Med, Lab High Throughput Biol, West Haven, CT 06516 USA. [Greig, Nigel H.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Olivares, D (reprint author), Harvard Univ, Neurochem Lab, Dept Psychiat Neurosci, Massachusetts Gen Hosp E,Med Sch, CNY2,Bldg 149, Charlestown, MA 02129 USA. EM david2177@hotmail.com; jrogers@partners.org OI Branden, Lars/0000-0002-1904-0470 FU Harvard Medical School, Yale University School of Medicine; Intramural Research Program, National Institute on Aging FX This work was supported in part by Harvard Medical School, Yale University School of Medicine, and the Intramural Research Program, National Institute on Aging. NR 198 TC 40 Z9 43 U1 0 U2 9 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD MAR PY 2009 VL 10 IS 3 BP 1226 EP 1260 DI 10.3390/ijms10031226 PG 35 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 424KJ UT WOS:000264565300029 PM 19399246 ER PT J AU Tobin, S Newman, AH Quinn, T Shalev, U AF Tobin, Stephanie Newman, Amy H. Quinn, Tammie Shalev, Uri TI A role for dopamine D-1-like receptors in acute food deprivation-induced reinstatement of heroin seeking in rats SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Dopamine receptors; food deprivation; relapse; reinstatement; stress ID CORTICOTROPIN-RELEASING-FACTOR; STRESS-INDUCED RELAPSE; COCAINE-INDUCED REINSTATEMENT; DRUG-SEEKING; PREFRONTAL CORTEX; D-3 RECEPTORS; BEHAVIOR; ANTAGONISTS; NGB-2904; LEPTIN AB Dopan-Line has a critical role in drug reinforcement and the reinstatement of drug seeking due to priming or exposure to drug-associated cues. In contrast, the role of dopamine in stress-induced reinstatement is not clear. We have previously demonstrated that acute food deprivation, a clinically relevant stressor, reinstates heroin seeking in rats via a leptin-dependent mechanism. Recent reports have suggested a modulating role for leptin on dopamine transmission and drug-related behaviours. Thus, here we investigated the role of dopamine in acute food deprivation-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin (0.05 mg/kg per infusion) for 10 d. Following training, heroin seeking was extinguished and rats were tested for 48-h food deprivation-induced reinstatement while pretreated with the dopamine D-1-, D-2-, or D-3-like receptor antagonists: SCH 23390 (0.0, 5.0 or 10.0 mu g/kg), raclopride (0.0, 50.0 or 100.0 mu g/kg) or NGB 2904 (0.0, 0.1 or 5.0 mg/kg), respectively. The dopamine D-1-like receptor antagonist, SCH 23390, but neither of the other antagonists, showed a dose-dependent attenuation of food deprivation-induced reinstatement. Our results suggest that acute food deprivation-induced reinstatement may be mediated, at least in part, by activation of the dopamine D-1-like receptor. C1 [Tobin, Stephanie; Quinn, Tammie; Shalev, Uri] Concordia Univ, Dept Psychol, Ctr Studies Behav Neurobiol, Montreal, PQ H4B 1R6, Canada. [Newman, Amy H.] NIDA, Med Chem Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, Baltimore, MD USA. RP Shalev, U (reprint author), Concordia Univ, Dept Psychol, Ctr Studies Behav Neurobiol, 7141 Sherbrooke St W, Montreal, PQ H4B 1R6, Canada. EM uri.shaiev@concordia.ca FU Natural Science and Engineering Council of Canada (NSERC); Canada Research Chair (CRC) FX This research was supported by a Discovery grant from the Natural Science and Engineering Council of Canada (NSERC), and funds from the Canada Research Chair (CRC) program to U.S., and in part by the NIDA-IRP, National Institute of Health. We thank J. Cao (Medicinal Chemistry Section, Medications Discovery Research Branch, Intramural Research Program, NIDA-NIH) for synthesizing the NGB 2904 used in this study, and Dr Jane Stewart for helpful comments. NR 47 TC 14 Z9 14 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD MAR PY 2009 VL 12 IS 2 BP 217 EP 226 DI 10.1017/S1461145708008778 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 419JZ UT WOS:000264216900007 PM 18405418 ER PT J AU Neznanova, O Bjork, K Rimondini, R Hansson, AC Hyytia, P Heilig, M Sommer, WH AF Neznanova, Olga Bjoerk, Karl Rimondini, Roberto Hansson, Anita C. Hyytia, Petri Heilig, Markus Sommer, Wolfgang H. TI Acute ethanol challenge inhibits glycogen synthase kinase-3 beta in the rat prefrontal cortex SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Alcohol use disorder; animal model; reinforcement; Western blotting ID ALCOHOL-PREFERRING AA; AVOIDING ANA RATS; PROTEIN-KINASE-B; BRAIN; LITHIUM; PHOSPHORYLATION; EXPRESSION; DEPENDENCE; ADDICTION; HISTORY AB Intracellular signalling pathways emerge as key mediators of the molecular and behavioural effects of addictive drugs including ethanol. Previously, we demonstrated that the innate high ethanol preference in AA rats is driven by dysfunctional endocannabinoid signalling in the medial prefrontal cortex (mPFC). Here, we report that acute ethanol challenge, at a dose commonly regarded as reinforcing, strongly phosphorylates glycogen synthase kinase-3 beta (GSK-3 beta) in this region with corresponding increased phosphorylation of AKT, a major regulator of GSK-3 beta. In the non-preferring counterpart ANA line we found a weaker, AKT-independent phosphorylation of GSK-3 beta by ethanol. Furthermore, AA rats showed rapid and transient dephosphorylation of ERK1/2 upon acute ethanol challenge in the medial prefrontal cortex (mPFC) and to a lesser degree in the nucleus accumbens; ANA rats were completely non-responsive for this mechanism. Together, these results identify candidate pathways for mediating high ethanol preference and emphasize the importance of the mPFC in controlling this behaviour. C1 [Neznanova, Olga; Bjoerk, Karl; Hansson, Anita C.; Heilig, Markus; Sommer, Wolfgang H.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Neznanova, Olga] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Rimondini, Roberto] Univ Bologna, Dept Pharmacol, Bologna, Italy. [Hyytia, Petri] Natl Publ Hlth Inst, Helsinki, Finland. RP Sommer, WH (reprint author), Cent Inst Mental Hlth Mol Pharmacol, D-68159 Mannheim, Germany. EM wolfgang.sommer@zi-mannheim.de RI Rimondini, Roberto/B-2500-2010; OI Rimondini, Roberto/0000-0003-4099-513X; Heilig, Markus/0000-0003-2706-2482; Hyytia, Petri/0000-0002-0284-1298 FU NIAAA; Karolinska Institute FX This study was supported by intramural funding from NIAAA and Karolinska Institute. The manuscript has been edited for language by San Francisco Edit. NR 28 TC 14 Z9 14 U1 0 U2 4 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 MAR PY 2009 VL 12 IS 2 BP 275 EP 280 DI 10.1017/S1461145708009620 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 419JZ UT WOS:000264216900012 PM 19007447 ER PT J AU Yan, X Hai, B Shan, ZC Zheng, CY Zhang, CM Wang, SL AF Yan, Xing Hai, Bo Shan, Zhao-chen Zheng, Chang-yu Zhang, Chun-mei Wang, Song-lin TI Effect of Same-dose Single or Dual Field Irradiation on Damage to Miniature Pig Parotid Glands SO INTERNATIONAL JOURNAL OF ORAL SCIENCE LA English DT Article DE irradiation damage; miniature pig; parotid gland ID INTENSITY-MODULATED RADIOTHERAPY; MINIPIG SALIVARY-GLANDS; NECK-CANCER PATIENTS; RADIATION-THERAPY; FRACTIONATED-IRRADIATION; ANIMAL-MODEL; FLOW-RATES; HEAD; XEROSTOMIA; SECRETION AB Aim To evaluate the effect of single or dual field irradiation (IR) with the same dose on damage to miniature pig parotid glands. Methodology Sixteen miniature pigs were divided into two IR groups (n=6) and a control group (n=4). The irradiation groups were subjected to 20 Gy X-radiation to one parotid gland using single-field or dual-field modality by linear accelerator. The dose-volume distributions between two IR groups were compared. Saliva from parotid glands and blood were collected at 0, 4, 8 and 16 weeks after irradiation. Parotid glands were removed at 16 weeks to evaluate tissue morphology. Results The irradiation dose volume distributions were significantly different between single and dual field irradiation groups (t=4.177, P=0.002), although dose volume histogramin (DVH) indicated the equal maximal dose in parotid glands. Saliva flow rates from IR side decreased dramatically at all time points in IR groups, especially in dual field irradiation group. The radiation caused changes of white blood cell count in blood, lactate dehydrogenase and amylase in serum, calcium, potassium and amylase in saliva. Morphologically, more severe radiation damage was found in irradiated parotid glands from dual field irradiation group than that from single field irradiation group. Conclusion Data from this large animal model demonstrated that the radiation damage from the dual field irradiation was more severe than that of the single field irradiation at the same dose, suggesting that dose-volume distribution is an important factor in evaluation of the radiobiology of parotid glands. C1 [Yan, Xing; Shan, Zhao-chen; Zhang, Chun-mei; Wang, Song-lin] Capital Med Univ, Salivary Gland Dis Ctr, Sch Stomatol, Beijing 100050, Peoples R China. [Yan, Xing; Shan, Zhao-chen; Zhang, Chun-mei; Wang, Song-lin] Capital Med Univ, Mol Lab Gene Therapy, Sch Stomatol, Beijing 100050, Peoples R China. [Yan, Xing; Hai, Bo] Capital Med Univ, Beijing Friendship Hosp, Beijing, Peoples R China. [Zheng, Chang-yu] Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. [Wang, Song-lin] Capital Med Univ, Dept Biochem & Mol Biol, Beijing, Peoples R China. RP Wang, SL (reprint author), Capital Med Univ, Salivary Gland Dis Ctr, Sch Stomatol, Tian Tan Xi Li 4, Beijing 100050, Peoples R China. EM slwang@ccmu.edu.cn FU National Natural Science Foundation of China [30430690]; Beijing Major Scientific Program Grants [D09 06007000091] FX This study was supported by the National Natural Science Foundation of China (Grant 30430690) and Beijing Major Scientific Program Grants (D09 06007000091). NR 33 TC 4 Z9 4 U1 0 U2 2 PU SICHUAN UNIV PI CHENGDU PA SICHUAN UNIV, CHENGDU, SICHUAN, 610064 00000, PEOPLES R CHINA SN 1674-2818 J9 INT J ORAL SCI JI Int. J. Oral Sci. PD MAR PY 2009 VL 1 IS 1 BP 16 EP 25 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 617LD UT WOS:000279281300005 PM 20690500 ER PT J AU Economopoulou, M Hammer, J Wang, F Fariss, R Maminishkis, A Miller, SS AF Economopoulou, Matina Hammer, Jeffrey Wang, Fei Fariss, Robert Maminishkis, Arvydas Miller, Sheldon S. TI Expression, Localization, and Function of Junctional Adhesion Molecule-C (JAM-C) in Human Retinal Pigment Epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DENSE DEPOSIT DISEASE; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; TIGHT JUNCTIONS; CELL POLARITY; GROWTH-FACTOR; INTERENDOTHELIAL JUNCTIONS; LEUKOCYTE TRANSMIGRATION; FAMILY-MEMBERS; COMPLEMENT AB PURPOSE. To determine the localization of JAM-C in human RPE and characterize its functions. METHODS. Immunofluorescence, Western blot, and PCR was used to identify the localization and expression of JAM-C, ZO-1, N-cadherin, and ezrin in cultures of human fetal RPE (hfRPE) with or without si-RNA mediated JAM-C knockdown and in adult native RPE wholemounts. A transepithelial migration assay was used to study the migration of leukocytes through the hfRPE monolayer. RESULTS. JAM-C localized at the tight junctions of cultured hfRPE cells and adult native RPE. During initial junction formation JAM-C was recruited to the primordial cell-cell contacts and after JAM-C knockdown, the organization of N-cadherin and ZO-1 at those contacts was disrupted. JAM-C knockdown caused a delay in the hfRPE cell polarization, as shown by reduced apical staining of ezrin. JAM-C inhibition significantly decreased the chemokine-induced transmigration of granulocytes but not monocytes through the hfRPE monolayer. CONCLUSIONS. JAM-C localizes specifically in the tight junctions of hfRPE and adult native RPE. It is important for tight junction formation in hfRPE, possibly by regulating the recruitment of N-cadherin and ZO-1 at the cell-cell contacts, and has a role in the polarization of hfRPE cells. Finally, JAM-C promotes the basal-to-apical transmigration of granulocytes but not monocytes through the hfRPE monolayer. (Invest Ophthalmol Vis Sci. 2009; 50: 1454-1463) DOI:10.1167/iovs.08-2129 C1 [Economopoulou, Matina; Hammer, Jeffrey; Wang, Fei; Fariss, Robert; Maminishkis, Arvydas; Miller, Sheldon S.] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA. RP Miller, SS (reprint author), NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, 31 Ctr Dr MSC 2510, Bethesda, MD 20892 USA. EM millers@nei.nih.gov FU National Eye Institute FX Supported by the Intramural Research Program of the National Eye Institute. NR 64 TC 20 Z9 21 U1 0 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2009 VL 50 IS 3 BP 1454 EP 1463 DI 10.1167/iovs.08-2129 PG 10 WC Ophthalmology SC Ophthalmology GA 411QO UT WOS:000263665000063 PM 19060272 ER PT J AU Ratnayaka, K Raman, VK Faranesh, AZ Sonmez, M Kim, JH Gutierrez, LF Ozturk, C McVeigh, ER Slack, MC Lederman, RJ AF Ratnayaka, Kanishka Raman, Venkatesh K. Faranesh, Anthony Z. Sonmez, Merdim Kim, June-Hong Gutierrez, Luis F. Ozturk, Cengizhan McVeigh, Elliot R. Slack, Michael C. Lederman, Robert J. TI Antegrade Percutaneous Closure of Membranous Ventricular Septal Defect Using X-Ray Fused With Magnetic Resonance Imaging SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE image-guided intervention; interventional magnetic resonance imaging; congenital heart disease; multimodality image fusion; heart septal defects; ventricular ID TRANSCATHETER CLOSURE; DEVICE CLOSURE; OCCLUDER; CHILDREN; REGISTRY AB Objectives We hypothesized that X-ray fused with magnetic resonance imaging (XFM) roadmaps might permit direct antegrade crossing and delivery of a ventricular septal defect (VSD) closure device and thereby reduce procedure time and radiation exposure. Background Percutaneous device closure of membranous VSD is cumbersome and time-consuming. The procedure requires crossing the defect retrograde, snaring and exteriorizing a guidewire to form an arteriovenous loop, then delivering antegrade a sheath and closure device. Methods Magnetic resonance imaging roadmaps of cardiac structures were obtained from miniature swine with spontaneous VSD and registered with live X-ray using external fiducial markers. We compared antegrade XFM-guided VSD crossing with conventional retrograde X-ray-guided crossing for repair. Results Antegrade XFM crossing was successful in all animals. Compared with retrograde X-ray, antegrade XFM was associated with shorter time to crossing (167 +/- 103 s vs. 284 +/- 61 s; p = 0.025), shorter time to sheath delivery (71 +/- 32 s vs. 366 +/- 145 s; p = 0.001), shorter fluoroscopy time (158 +/- 95 s vs. 390 +/- 137 s; p = 0.003), and reduced radiation dose-area product (2,394 +/- 1,522 mG.m(2) vs. 4,865 +/- 1,759 mG.m(2); p = 0.016). Conclusions XFM facilitates antegrade access to membranous VSD from the right ventricle in swine. The simplified procedure is faster and reduces radiation exposure compared with the conventional retrograde approach. (J Am Coll Cardiol Intv 2009;2:224-30) (C) 2009 by the American College of Cardiology Foundation C1 [Ratnayaka, Kanishka; Raman, Venkatesh K.; Faranesh, Anthony Z.; Sonmez, Merdim; Kim, June-Hong; Gutierrez, Luis F.; Ozturk, Cengizhan; McVeigh, Elliot R.; Slack, Michael C.; Lederman, Robert J.] NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Ratnayaka, Kanishka; Slack, Michael C.] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA. [Sonmez, Merdim] Siemens Corp Res, Princeton, NJ USA. [Sonmez, Merdim; Ozturk, Cengizhan] Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey. RP Lederman, RJ (reprint author), NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713,MSC1538, Bethesda, MD 20892 USA. EM ledermar@nhlbi.nih.gov RI Ozturk, Cengizhan/A-6177-2016; OI Ozturk, Cengizhan/0000-0002-6966-0774; lederman, robert/0000-0003-1202-6673 FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health [Z01-HL005062-04 CVB] FX This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health (grant Z01-HL005062-04 CVB). NR 18 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAR PY 2009 VL 2 IS 3 BP 224 EP 230 DI 10.1016/j.jcin.2008.09.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 613HR UT WOS:000278970500010 PM 19463430 ER PT J AU Chang, LVW Alamo, S Guma, S Christopher, J Suntoke, T Omasete, R Montis, JP Quinn, TC Juncker, M Reynolds, SJ AF Chang, Larry W. Alamo, Stella Guma, Samuel Christopher, Jason Suntoke, Tara Omasete, Richard Montis, Jennifer P. Quinn, Thomas C. Juncker, Margrethe Reynolds, Steven J. TI Two-Year Virologic Outcomes of an Alternative AIDS Care Model: Evaluation of a Peer Health Worker and Nurse-Staffed Community-Based Program in Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; Africa; antiretroviral treatment; community health services; nurses; program evaluation ID SUB-SAHARAN AFRICA; ACTIVE ANTIRETROVIRAL THERAPY; RAPID SCALE-UP; HIV PREVENTION; ADHERENCE; PERFORMANCE; CHALLENGES; SETTINGS; LESSONS; HAITI AB Background: There is growing concerti about the human resources needed to care for increasing numbers of patients receiving antiretroviral therapy in resource-limited settings. We evaluated all alternative model, community-based, comprehensive antiretroviral program staffed primarily by peer health workers and nurses. Methods: We conducted a retrospective cohort study of patients receiving antiretroviral therapy during the first 10 months of program enrollment beginning in late 2003. Virologic, immunologic, clinical, and adherence data were collected. Results: Of 360 patients started on treatment, 258 (72%) were active and on therapy approximately 2 years later. Viral load testing demonstrated that 86% of active patients (211/246 tested) had a viral load < 400 copies per milliliter. The median CD4 increase for active patients was 197 cells per cubic millimeter (interquartile range, 108346). Patients with either a history of antiretroviral use or lack of CD4 response were more likely to experience virologic failure. Survival was 84% at 1 year and 82% at 2 years. World Health Organization stage 4 was predictive of both not sustaining therapy and increased mortality. Conclusions: A community-based antiretroviral treatment program in a resource-limited setting can provide excellent AIDS care over at, least a 2-year period. A comprehensive program based upon peer health workers and nurses provides an effective alternative model for AIDS care. C1 [Chang, Larry W.; Quinn, Thomas C.; Reynolds, Steven J.] Johns Hopkins Med Inst, Div Infect Dis, Baltimore, MD 21287 USA. [Alamo, Stella; Guma, Samuel; Christopher, Jason; Omasete, Richard; Montis, Jennifer P.; Juncker, Margrethe] Reach Out Mbuya Parish HIV AIDS Initiat, Kampala, Uganda. [Suntoke, Tara; Quinn, Thomas C.; Reynolds, Steven J.] NIAID, NIH, Bethesda, MD 20892 USA. RP Chang, LVW (reprint author), Johns Hopkins Med Inst, Div Infect Dis, 1830 E Monument St,Room 401, Baltimore, MD 21287 USA. EM lchang8@jhmi.edu FU Division of Intramural Research; National Institute for Allergy and Infectious Diseases; National Institutes of Health FX Supported by the Division of Intramural Research, the National Institute for Allergy and Infectious Diseases, and the National Institutes of Health. NR 26 TC 40 Z9 40 U1 0 U2 4 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 MAR 1 PY 2009 VL 50 IS 3 BP 276 EP 282 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 415FX UT WOS:000263920800005 PM 19194316 ER PT J AU Haas, DW Koletar, SL Laughlin, L Kendall, MA Suckow, C Gerber, JG Zolopa, AR Bertz, R Child, MJ Hosey, L Alston-Smith, B Acosta, EP AF Haas, David W. Koletar, Susan L. Laughlin, Laura Kendall, Michelle A. Suckow, Carol Gerber, John G. Zolopa, Andrew R. Bertz, Richard Child, Michael J. Hosey, Lara Alston-Smith, Beverly Acosta, Edward P. CA A5213 Study Team TI Hepatotoxicity and Gastrointestinal Intolerance When Healthy Volunteers Taking Rifampin Add Twice-Daily Atazanavir and Ritonavir SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 15th Conference on Retroviruses and Opportunistic Infections CY FEB 03-06, 2008 CL Boston, MA DE atazanavir; hepatotoxicity; rifampin; ritonavir; tuberculosis ID PHARMACOKINETICS; LOPINAVIR/RITONAVIR AB Background: Rifampin is the cornerstone of antituberculosis therapy, but induction of hepatic cytochrome P4503A by rifampin markedly lowers HIV protease inhibitor plasma concentrations. Methods: This phase 1, open-label, one-arm study was designed to assess pharmacokinetic interactions and safety of atazanavir, ritonavir, and rifampin among 14 evaluable HIV-seronegative volunteers. The study included 3 sequential periods of study drug dosing, with plasma sampling for pharmacokinetic analyses to occur on the last day of each period. During period 1, participants received rifampin 600 mg every 24 hours for 8 days. During period 2, participants continued rifampin 600 mg every 24 hours, and added atazanavir 300 mg and ritonavir 100 mg every 12 hours, to continue for at least 11 days. During period 3, atazanavir was to be increased to 400 mg every 12 hours. Results: Upon adding atazanavir and ritonavir, the first 3 subjects developed vomiting and transaminase elevations resulting in study drug discontinuation. The study was therefore terminated. Conclusions: Coadministration of rifampin with HIV protease inhibitors may not be a viable treatment option if rifampin administration precedes protease inhibitor initiation. Future studies, which explore concomitant HIV protease inhibitors with rifampin must carefully consider the sequence in which drugs are initiated. C1 [Haas, David W.] Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, Nashville, TN 37203 USA. [Koletar, Susan L.; Laughlin, Laura] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Kendall, Michelle A.] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Suckow, Carol] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Gerber, John G.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Zolopa, Andrew R.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Bertz, Richard; Child, Michael J.] Bristol Myers Squibb Co, Princeton, NJ USA. [Hosey, Lara] Social & Sci Syst Inc, Silver Spring, MD USA. [Alston-Smith, Beverly] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Acosta, Edward P.] Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL USA. RP Haas, DW (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, 345 24th Ave N,Suite 105, Nashville, TN 37203 USA. EM david.w.haas@vanderbilt.edu RI Kendall, Michelle/B-7665-2016 OI Kendall, Michelle/0000-0001-9160-4544 FU NCRR NIH HHS [UL1 RR024975-01, UL1 RR024975, KL2 RR024977, UL1 RR024975-017782, TL1 RR024978, RR024975]; NIAID NIH HHS [UM1 AI069452, U01 AI068636, U01 AI069452-03, U01 AI069439, U01 AI032775, U01 AI068634, U01 AI069556, U01 AI068634-03, UM1 AI068634, U01 AI069452, AI32775, U01 AI069450, U01 AI069450-03, UM1 AI069439, U01 AI069474-03, UM1 AI068636, AI069556, AI068634, U01 AI069439-03, U01 AI068636-03, U01 AI032775-10, AI068636, U01 AI069474, U01 AI069556-03, AI069439, AI694742, AI69452, UM1 AI069556] NR 12 TC 34 Z9 35 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 MAR 1 PY 2009 VL 50 IS 3 BP 290 EP 293 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 415FX UT WOS:000263920800007 PM 19194314 ER PT J AU Wang, GJ Volkow, ND Thanos, PK Fowler, JS AF Wang, Gene-Jack Volkow, Nora D. Thanos, Panayotis K. Fowler, Joanna S. TI Imaging of Brain Dopamine Pathways Implications for Understanding Obesity SO JOURNAL OF ADDICTION MEDICINE LA English DT Review DE brain dopamine; obesity; positron emission tomography ID HIGH-FAT DIET; POSITRON-EMISSION-TOMOGRAPHY; INCREASES ACCUMBENS DOPAMINE; RANDOMIZED CONTROLLED-TRIAL; COCAINE-SEEKING BEHAVIOR; CHRONIC FOOD RESTRICTION; WEIGHT-LOSS; NUCLEUS-ACCUMBENS; DORSAL STRIATUM; IN-VIVO AB Obesity is typically associated with abnormal eating behaviors. Brain imaging studies in humans implicate the involvement of dopamine (DA)-modulated circuits in pathologic eating behavior(s). Food cues increase striatal extracellular DA, providing evidence for the involvement of DA in the nonhedonic motivational properties of food. Food cues also increase metabolism in the orbitofrontal cortex indicating the association of this region with the motivation for food consumption. Similar to drug-addicted subjects, striatal DA D2 receptor availability is reduced in obese subjects, which may predispose obese subjects to seek food as a means to temporarily compensate for understimulated reward circuits. Decreased DA D2 receptors in the obese subjects are also associated with decreased metabolism in prefrontal regions involved in inhibitory control, which may underlie their inability to control food intake. Gastric stimulation in obese subjects activates cortical and limbic regions involved with self-control, motivation, and memory. These brain regions are also activated during drug craving in drug-addicted subjects. Obese subjects have increased metabolism in the somatosensory cortex, which suggests an enhanced sensitivity to the sensory properties of food. The reduction in DA D2 receptors in obese subjects coupled with the enhanced sensitivity to food palatability could make food their most salient reinforcer putting them at risk for compulsive eating and obesity. The results from these studies suggest that multiple but similar brain circuits are disrupted in obesity and drug addiction and suggest that strategies aimed at improving DA function might be beneficial in the treatment and prevention of obesity. C1 [Wang, Gene-Jack; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Wang, Gene-Jack; Fowler, Joanna S.] Mt Sinai Sch Med, New York, NY USA. [Volkow, Nora D.; Thanos, Panayotis K.] NIAAA, Natl Inst Drug Abuse, Bethesda, MD USA. RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. EM gjwang@bnl.gov FU scientific and technical staffs at the Brookhaven Center; U.S. Department of Energy OBER [DE-ACO2-76CH00016]; National Institute on Drug Abuse [5RO1DA006891-14, 5RO1DA6278-16, 5821, DA018457-2]; National Institute on Alcohol Abuse and Alcoholism [RO1AA9481-11, Y1AA3009]; General Clinical Research Center at Stony Brook University Hospital [NIH MOIRR 10710] FX The authors also thank the scientific and technical staffs at the Brookhaven Center for Translational Neuroimaging, for their support of these research studies as well as the individuals who volunteered for these studies.; Supported in part by grants from the U.S. Department of Energy OBER (DE-ACO2-76CH00016), the National Institute on Drug Abuse (5RO1DA006891-14, 5RO1DA6278-16, 5821, DA018457-2), the National Institute on Alcohol Abuse and Alcoholism (RO1AA9481-11 & Y1AA3009), and by the General Clinical Research Center at Stony Brook University Hospital (NIH MOIRR 10710). NR 155 TC 79 Z9 81 U1 6 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD MAR PY 2009 VL 3 IS 1 BP 8 EP 18 PG 11 WC Substance Abuse SC Substance Abuse GA 416WD UT WOS:000264035300002 PM 21603099 ER PT J AU Meyer, SE Carlson, GA Youngstrom, E Ronsaville, DS Martinez, PE Gold, PW Hakak, R Radke-Yarrow, M AF Meyer, Stephanie E. Carlson, Gabrielle A. Youngstrom, Eric Ronsaville, Donna S. Martinez, Pedro E. Gold, Philip W. Hakak, Rashelle Radke-Yarrow, Marian TI Long-term outcomes of youth who manifested the CBCL-Pediatric Bipolar Disorder phenotype during childhood and/or adolescence SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Childhood; High risk; Longitudinal; CBCL ID BEHAVIOR CHECKLIST; MANIC SYMPTOMS; HIGH-RISK; CHILDREN; PREVALENCE; INTERVIEW; PARENT; ADHD; PSYCHOPATHOLOGY; ASSOCIATION AB Objective: Recent Studies have identified a Child Behavior Checklist (CBCL) profile that characterizes children with severe aggression, inattention, and mood instability. This profile has been coined the CBCL-Pediatric Bipolar Disorder (PBD) phenotype, because it is commonly seen among children with bipolar disorder. However, mounting evidence suggests that the CBCL-PBD may be a better tool for identifying children with severe functional impairment and broad-ranging psychiatric comorbidities rather than bipolar disorder itself. No studies have followed individuals with the CBCL-PBD profile through adulthood, so its long-term implications remain unclear. The present author,,; examined diagnostic and functional trajectories of individuals with the CBCL-PBD profile from early childhood through young adulthood using data from a longitudinal high-risk study. Method: Participants (n=101) are part of a 23-year study of youth at risk for major mood disorder who have completed diagnostic and functional assessments at regular intervals. Results: Across development, participants with the CBCL-PBD phenotype exhibited marked psychosocial impairment, increased rates of suicidal thoughts and behaviors and heightened risk for comorbid anxiety, bipolar disorder. cluster B personality disorders and ADHD in young adulthood, compared to participants without this presentation. However, diagnostic accuracy for any one particular disorder was found to be low. Conclusions: Children with the CBCL-PBD profile are at risk for ongoing, severe, psychiatric symptomatology including behavior and emotional comorbidities in general, and bipolar disorder, anxiety, ADHD, Cluster B personality disorders in particular. However, the value of this profile may be in predicting ongoing comorbidity and impairment, rather than any one specific DSM-IV diagnosis. (C) 2008 Elsevier B.V All rights reserved. C1 [Meyer, Stephanie E.; Hakak, Rashelle] Cedars Sinai Med Ctr, Div Child & Adolescent Psychiat, Los Angeles, CA 90048 USA. [Carlson, Gabrielle A.] SUNY Stony Brook, Sch Med, Div Child & Adolescent Psychiat, Stony Brook, NY USA. [Youngstrom, Eric] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Ronsaville, Donna S.; Gold, Philip W.] NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. [Martinez, Pedro E.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Meyer, SE (reprint author), Cedars Sinai Med Ctr, Div Child & Adolescent Psychiat, 8730 Alden Dr,Thalians W101, Los Angeles, CA 90048 USA. EM Stephanie.Meyer@cshs.org FU Intramural NIH HHS NR 31 TC 65 Z9 65 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2009 VL 113 IS 3 BP 227 EP 235 DI 10.1016/j.jad.2008.05.024 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 407UZ UT WOS:000263391100003 PM 18632161 ER PT J AU Metcalfe, DD Schwartz, LB AF Metcalfe, Dean D. Schwartz, Lawrence B. TI Assessing anaphylactic risk? Consider mast cell clonality SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE Anaphylaxis; tryptase; mast cells; KIT; venom ID SYSTEMIC MASTOCYTOSIS; HUMAN TRYPTASE; KIT; BLOOD C1 [Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C-207A,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov; lbschwar@vcu.edu FU Intramural NIH HHS [Z01 AI000249-27] NR 20 TC 34 Z9 35 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 MAR PY 2009 VL 123 IS 3 BP 687 EP 688 DI 10.1016/j.jaci.2009.02.003 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 426TQ UT WOS:000264731200031 PM 19281912 ER PT J AU Choo, E Hsu, A Holland, S Kirkpatrick, C AF Choo, E. Hsu, A. Holland, S. Kirkpatrick, C. TI A Novel Mutation of STAT3 Produces a Unique Phenotype of the Hyperimmunoglobulin E Syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Choo, E.; Kirkpatrick, C.] Univ Colorado, Denver, CO 80202 USA. [Hsu, A.; Holland, S.] NIAID, LCID, 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 MAR PY 2009 VL 123 IS 3 MA LB31 BP 731 EP 731 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 426TQ UT WOS:000264731200075 ER PT J AU Foster, PMD AF Foster, Paul M. D. TI MODEL SYSTEMS FOR STUDYING ENDOCRINE DISRUPTORS: EFFECTS OF ANTIANDROGENS ON MALE RAT REPRODUCTIVE DEVELOPMENT SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 9th International Congress of Andrology CY MAR 07-10, 2009 CL Barcelona, SPAIN SP Int Soc Androl C1 [Foster, Paul M. D.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2009 VL 30 BP 24 EP 24 PG 1 WC Andrology SC Endocrinology & Metabolism GA 414FO UT WOS:000263849500052 ER PT J AU Badalyan, R Darbinyan, A Nalbandyan, N Gasparyan, A Sarkissian, T AF Badalyan, Rafael Darbinyan, Artak Nalbandyan, Nora Gasparyan, Armen Sarkissian, Tamara TI ACCURATE PCR ANALYSIS FOR STD DIAGNOSTICS IN MALE PATIENTS: WHICH SUBSTANCES SHOULD BE EVALUATED? SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 9th International Congress of Andrology CY MAR 07-10, 2009 CL Barcelona, SPAIN SP Int Soc Androl C1 [Badalyan, Rafael; Darbinyan, Artak; Gasparyan, Armen] Natl Inst Hlth, Dept Urol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2009 VL 30 BP 125 EP 126 PG 2 WC Andrology SC Endocrinology & Metabolism GA 414FO UT WOS:000263849500343 ER PT J AU Jahromi, LB Kasari, CL McCracken, JT Lee, LSY Aman, MG McDougle, CJ Scahill, L Tierney, E Arnold, LE Vitiello, B Ritz, L Witwer, A Kustan, E Ghuman, J Posey, DJ AF Jahromi, Laudan B. Kasari, Connie L. McCracken, James T. Lee, Lisa S-Y. Aman, Michael G. McDougle, Christopher J. Scahill, Lawrence Tierney, Elaine Arnold, L. Eugene Vitiello, Benedetto Ritz, Louise Witwer, Andrea Kustan, Erin Ghuman, Jaswinder Posey, David J. TI Positive Effects of Methylphenidate on Social Communication and Self-Regulation in Children with Pervasive Developmental Disorders and Hyperactivity SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Methylphenidate; Pervasive developmental disorders; Hyperactivity; Autism spectrum disorder ID ABERRANT BEHAVIOR CHECKLIST; JOINT ATTENTION; EMOTION REGULATION; INDIVIDUAL-DIFFERENCES; AUTISTIC DISORDER; STRATEGIES; INFANT; INTERVENTIONS; PRESCHOOLERS; ASSOCIATIONS AB This report examined the effect of methylphenidate on social communication and self-regulation in children with pervasive developmental disorders and hyperactivity in a secondary analysis of RUPP Autism Network data. Participants were 33 children (29 boys) between the ages of 5 and 13 years who participated in a four-week crossover trial of placebo and increasing doses of methylphenidate given in random order each for one week. Observational measures of certain aspects of children's social communication, self-regulation, and affective behavior were obtained each week. A significant positive effect of methylphenidate was seen on children's use of joint attention initiations, response to bids for joint attention, self-regulation, and regulated affective state. The results go beyond the recent literature and suggest that methylphenidate may have positive effects on social behaviors in children with PDD and hyperactivity. C1 [Jahromi, Laudan B.] Arizona State Univ, Sch Social & Family Dynam, Tempe, AZ 85287 USA. [Kasari, Connie L.; McCracken, James T.; Lee, Lisa S-Y.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aman, Michael G.; Arnold, L. Eugene; Witwer, Andrea] Ohio State Univ, Columbus, OH 43210 USA. [McDougle, Christopher J.; Posey, David J.] Indiana Univ, Bloomington, IN USA. [Scahill, Lawrence; Kustan, Erin] Yale Univ, New Haven, CT USA. [Tierney, Elaine; Ghuman, Jaswinder] Kennedy Krieger Inst, Baltimore, MD USA. [Vitiello, Benedetto; Ritz, Louise] NIMH, Bethesda, MD 20892 USA. RP Jahromi, LB (reprint author), Arizona State Univ, Sch Social & Family Dynam, Box 873701, Tempe, AZ 85287 USA. EM Laudan.Jahromi@asu.edu OI Witwer, Andrea/0000-0002-1268-4222; Scahill, Lawrence/0000-0001-5073-1707 FU NCRR NIH HHS [M01 RR-00052, M01 RR000034, M01 RR006022, M01 RR000052, M01 RR-06022, M01 RR-00750, M01 RR000750, M01 RR-00034]; NIDA NIH HHS [N01MH80011]; NIMH NIH HHS [N01 MH-70009, K23 MH001883-05, 5 T32 MH18372, N01 MH-70001, K24 MH001805, MH-01805, K23 MH068627, U01 MH070009, T32 MH018372, MH-68627, N01 MH 80011, N01 MH-70070] NR 39 TC 44 Z9 45 U1 1 U2 18 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAR PY 2009 VL 39 IS 3 BP 395 EP 404 DI 10.1007/s10803-008-0636-9 PG 10 WC Psychology, Developmental SC Psychology GA 404IA UT WOS:000263143800001 PM 18752063 ER PT J AU Nikolov, RN Bearss, KE Lettinga, J Erickson, C Rodowski, M Aman, MG McCracken, JT McDougle, CJ Tierney, E Vitiello, B Arnold, LE Shah, B Posey, DJ Ritz, L Scahill, L AF Nikolov, Roumen N. Bearss, Karen E. Lettinga, Jelle Erickson, Craig Rodowski, Maria Aman, Michael G. McCracken, James T. McDougle, Christopher J. Tierney, Elaine Vitiello, Benedetto Arnold, L. Eugene Shah, Bhavik Posey, David J. Ritz, Louise Scahill, Lawrence TI Gastrointestinal Symptoms in a Sample of Children with Pervasive Developmental Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Chronic gastrointestinal problems; Pervasive developmental disorders ID AUTISTIC SPECTRUM DISORDERS; ABERRANT BEHAVIOR CHECKLIST; DIAGNOSTIC INTERVIEW; DISEASE; ASSOCIATION; RISPERIDONE; PREVALENCE; COMMUNITY; MEASLES; MUMPS AB Objective To evaluate gastrointestinal (GI) problems in a large, well-characterized sample of children with pervasive developmental disorders (PDDs). Methods One hundred seventy two children entering one of two trials conducted by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were assessed comprehensively prior to starting treatment and classified with regard to GI symptoms. Results Thirty nine (22.7%) were positive for GI problems, primarily constipation and diarrhea. Those with GI problems were no different from subjects without GI problems in demographic characteristics, measures of adaptive functioning, or autism symptom severity. Compared to children without GI problems, those with GI problems showed greater symptom severity on measures of irritability, anxiety, and social withdrawal. Those with GI problems were also less likely to respond to treatment. C1 [Nikolov, Roumen N.; Bearss, Karen E.; Scahill, Lawrence] Yale Univ, Yale Child Study Ctr, New Haven, CT 06520 USA. [Lettinga, Jelle] Univ Groningen, Groningen, Netherlands. [Erickson, Craig; McDougle, Christopher J.; Posey, David J.] Indiana Univ, Indianapolis, IN 46204 USA. [Rodowski, Maria; Tierney, Elaine] Kennedy Krieger Inst, Baltimore, MD USA. [Aman, Michael G.; Arnold, L. Eugene] Ohio State Univ, Columbus, OH 43210 USA. [McCracken, James T.; Shah, Bhavik] Univ Calif Los Angeles, Los Angeles, CA USA. [Vitiello, Benedetto; Ritz, Louise] NIMH, Bethesda, MD 20892 USA. RP Scahill, L (reprint author), Yale Univ, Yale Child Study Ctr, POB 207900, New Haven, CT 06520 USA. EM roumen.nikolov@yale.edu; lawrence.scahill@yale.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU NIMH NIH HHS [N0MH70009, N01MH70001, N01MH80011, N01MH70010] NR 44 TC 62 Z9 65 U1 1 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAR PY 2009 VL 39 IS 3 BP 405 EP 413 DI 10.1007/s10803-008-0637-8 PG 9 WC Psychology, Developmental SC Psychology GA 404IA UT WOS:000263143800002 PM 18791817 ER PT J AU Beare, PA Howe, D Cockrell, DC Omsland, A Hansen, B Heinzen, RA AF Beare, Paul A. Howe, Dale Cockrell, Diane C. Omsland, Anders Hansen, Bryan Heinzen, Robert A. TI Characterization of a Coxiella burnetii ftsZ Mutant Generated by Himar1 Transposon Mutagenesis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; RICKETTSIA-PROWAZEKII; ESCHERICHIA-COLI; Q-FEVER; CHLAMYDIA-TRACHOMATIS; TRANSFORMATION; EXPRESSION; RESISTANCE; CLONING; GENE AB Coxiella burnetii is a gram-negative obligate intracellular bacterium and the causative agent of human Q fever. The lack of methods to genetically manipulate C. burnetii significantly impedes the study of this organism. We describe here the cloning and characterization of a C. burnetii ftsZ mutant generated by mariner-based Himar1 transposon (Tn) mutagenesis. C. burnetii was coelectroporated with a plasmid encoding the Himar1 C9 transposase variant and a plasmid containing a Himar1 transposon encoding chloramphenicol acetyltransferase, mCherry fluorescent protein, and a ColE1 origin of replication. Vero cells were infected with electroporated C. burnetii and transformants scored as organisms replicating in the presence of chloramphenicol and expressing mCherry. Southern blot analysis revealed multiple transpositions in the C. burnetii genome and rescue cloning identified 30 and 5 insertions in coding and noncoding regions, respectively. Using micromanipulation, a C. burnetii clone was isolated containing a Tn insertion within the C terminus of the cell division gene ftsZ. The ftsZ mutant had a significantly lower growth rate than wild-type bacteria and frequently appeared as filamentous forms displaying incomplete cell division septa. The latter phenotype correlated with a deficiency in generating infectious foci on a per-genome basis compared to wild-type organisms. The mutant FtsZ protein was also unable to bind the essential cell division protein FtsA. This is the first description of C. burnetii harboring a defined gene mutation generated by genetic transformation. C1 [Beare, Paul A.; Howe, Dale; Cockrell, Diane C.; Omsland, Anders; Heinzen, Robert A.] NIAID, Rocky Mt Labs, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Hamilton, MT 59840 USA. [Hansen, Bryan] NIAID, Rocky Mt Labs, Electron Microscopy Facil, Res Technol Branch, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 44 TC 63 Z9 63 U1 0 U2 6 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 MAR PY 2009 VL 191 IS 5 BP 1369 EP 1381 DI 10.1128/JB.01580-08 PG 13 WC Microbiology SC Microbiology GA 409KC UT WOS:000263503600002 PM 19114492 ER PT J AU Yao, LS Ying, JF Bax, A AF Yao, Lishan Ying, Jinfa Bax, Ad TI Improved accuracy of N-15-H-1 scalar and residual dipolar couplings from gradient-enhanced IPAP-HSQC experiments on protonated proteins SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE Cross-correlated relaxation; GB3; IPAP; Liquid crystal; Magnetic susceptibility anisotropy ID CROSS-CORRELATED RELAXATION; MAGNETIC-FIELD DEPENDENCE; 2-DIMENSIONAL NMR-SPECTRA; MODEL-FREE ANALYSIS; HUMAN UBIQUITIN; CONSERVATIVE MUTAGENESIS; ORIENTED MACROMOLECULES; DYNAMIC INTERPRETATION; SENSITIVITY; SPECTROSCOPY AB The presence of dipole-dipole cross-correlated relaxation as well as unresolved E.COSY effects adversely impacts the accuracy of (1) J (NH) splittings measured from gradient-enhanced IPAP-HSQC spectra. For isotropic samples, the size of the systematic errors caused by these effects depends on the values of (2) J (NH alpha) , (3) J (NH beta) and (3) J (HNH alpha) . Insertion of band-selective H-1 decoupling pulses in the IPAP-HSQC experiment eliminates these systematic errors and for the protein GB3 yields (1) J (NH) splittings that agree to within a root-mean-square difference of 0.04 Hz with values measured for perdeuterated GB3. Accuracy of the method is also highlighted by a good fit to the GB3 structure of the H-1-N-15 RDCs extracted from the minute differences in (1)J(NH) splitting measured at 500 and 750 MHz H-1 frequencies, resulting from magnetic susceptibility anisotropy. A nearly complete set of (2) J (NH alpha) couplings was measured in GB3 in order to evaluate whether the impact of cross-correlated relaxation is dominated by the N-15-H-1 (alpha) or N-15-H-1 (beta) dipolar interaction. As expected, we find that (2) J (NH alpha) a parts per thousand currency sign 2 Hz, with values in the alpha-helix (0.86 +/- A 0.52 Hz) slightly larger than in beta-sheet (0.66 +/- A 0.26 Hz). Results indicate that under isotropic conditions, N-H-N/N-H (beta) cross-correlated relaxation often dominates. Unresolved E.COSY effects under isotropic conditions involve (3) J (HNH alpha) and J (NH alpha) , but when weakly aligned any aliphatic proton proximate to both N and H-N can contribute. C1 [Yao, Lishan; Ying, Jinfa; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI Yao, Lishan /C-6961-2009; yao, lishan/H-3662-2012 OI yao, lishan/0000-0003-1797-922X FU Intramural Research Program of the NIDDK; NIH FX This work was supported in part by the Intramural Research Program of the NIDDK, NIH, and by the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH. NR 45 TC 38 Z9 38 U1 1 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAR PY 2009 VL 43 IS 3 BP 161 EP 170 DI 10.1007/s10858-009-9299-x PG 10 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 411TJ UT WOS:000263673200004 PM 19205898 ER PT J AU Yi, F Zhu, PJ Southall, N Inglese, J Austin, CP Zheng, W Regan, L AF Yi, Fang Zhu, Pingjun Southall, Noel Inglese, James Austin, Christopher P. Zheng, Wei Regan, Lynne TI An AlphaScreen (TM)-Based High-Throughput Screen to Identify Inhibitors of Hsp90-Cochaperone Interaction SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE heat shock protein 90 (Hsp90); Hsp organizing protein (HOP); tetratricopeptide repeat (TPR); AlphaScreen (TM); high-throughput screening (HTS) ID CO-CHAPERONE; PHASE-I; CANCER; COMPLEXES; MECHANISM; BINDING; DOMAIN AB Hsp90 has emerged as an important anticancer drug target because of its essential role in promoting the folding and maturation of many oncogenic proteins. The authors describe the development of the first high-throughput screen, based on AlphaScreen (TM) technology, to identify a novel type of Hsp90 inhibitors that interrupt its interaction with the cochaperone HOP. The assay used the 20-mer C-terminal peptide of Hsp90 and the TPR2A domain of HOP. Assay specificity was demonstrated by measuring different interactions using synthetic peptides, with measured IC(50)s in good agreement with reported values. The assay was stable over 12 h and tolerated DMSO up to 5%. The authors first validated the assay by screening against 20,000 compounds in a 384-well format. After further optimization into a 1536-well format, it was screened against an NIH Chemical Genomics Center library of 76,134 compounds, with a signal-to-background ratio of 78 and Z' factor of 0.77. The present assay can be used for discovery of novel small-molecule Hsp90 inhibitors that can be used as chemical probes to investigate the role of cochaperones in Hsp90 function. Such molecules have the potential to be developed into novel anticancer drugs, for use alone or in combination with other Hsp90 inhibitors. (Journal of Biomolecular Screening 2009:273-281) C1 [Zhu, Pingjun; Southall, Noel; Inglese, James; Austin, Christopher P.; Zheng, Wei] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Yi, Fang; Regan, Lynne] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. [Regan, Lynne] Yale Univ, Dept Chem, New Haven, CT USA. RP Zheng, W (reprint author), NHGRI, Chem Genom Ctr, NIH, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU NIH [5R01CA113677]; Breast Cancer Alliance (LR); Anna Fuller Postdoctoral Fellowship foundation; NIH Molecular Libraries Screening Centers Network [XO1-MH077625-01]; Department of Defense, Breast Cancer Research Program [W91ZSQ7167N696]; Molecular Libraries Initiative of the NIH Roadmap for Medical Research; Intramural Research Program of the National Human Genome Research Institute FX We thank Dr. Paul Fletcher for his invaluable suggestions and help with the early assay development and screening at the Yale Chemical Genomics Screening Facility. This work was supported by an NIH grant (5R01CA113677) and Breast Cancer Alliance (LR); Anna Fuller Postdoctoral Fellowship foundation, NIH Molecular Libraries Screening Centers Network (XO1-MH077625-01), Concept Award, Department of Defense, Breast Cancer Research Program (W91ZSQ7167N696) (FY); and Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute, National Institute of Health (PZ, NS, JI, CPA, WZ). NR 22 TC 25 Z9 25 U1 1 U2 4 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 MAR PY 2009 VL 14 IS 3 BP 273 EP 281 DI 10.1177/1087057108330114 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 428VC UT WOS:000264878500007 PM 19211782 ER PT J AU Ix, JH Wassel, CL Bauer, DC Toroian, D Tylavsky, FA Cauley, JA Harris, TB Price, PA Cummings, SR Shlipak, MG AF Ix, Joachim H. Wassel, Christina L. Bauer, Douglas C. Toroian, Damon Tylavsky, Frances A. Cauley, Jane A. Harris, Tamara B. Price, Paul A. Cummings, Steven R. Shlipak, Michael G. CA Hlth ABC Study TI Fetuin-A and BMD in Older Persons: The Health Aging and Body Composition (Health ABC) Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fetuin-A; BMD; elderly ID ALPHA-2 HS-GLYCOPROTEIN; VASCULAR CALCIFICATION; HUMAN-BONE; SERUM; DISEASE; PROTEIN; MINERALIZATION; ASSOCIATION; INHIBITION; MATRIX AB Fetuin-A is a hepatic secretory protein that promotes bone mineralization in vitro. Whether fetuin-A levels are associated with BMD in humans is unknown. The Health Aging and Body Composition study enrolled 3075 well-functioning black and white persons 70-79 yr of age and measured BMD. This cross-sectional study measured serum fetuin-A using ELISA among a random sample of 508 participants within sex and race strata. Multivariate linear regression analysis evaluated the associations of fetuin-A with BMD. Among women (n = 257), higher fetuin-A levels were significantly associated with higher total hip (p = 0.02), lumbar spine (p = 0.03), and whole body BMD (p = 0.01) in models adjusted for age, race, diabetes, alcohol and tobacco use, physical activity, body mass index, C-reactive protein levels, calcium supplement, and estrogen use. For example, each SD (0.38 g/liter) higher level of fetuin-A was associated with 0.0.16 g/cm(2) higher total hip area] BMD. The association was of similar magnitude and direction for femoral neck BMD but did not reach statistical significance (p = 0.11). In contrast, among men (n = 251), fetuin-A had no significant associations with total hip (p = 0.79), lumbar spine (p = 0.35), whole body (p = 0.46), or femoral neck BMD (p = 0.54) in multivariable models. We conclude that higher fetuin-A levels are independently associated with higher BMD among well-functioning community-dwelling older women but not older men. Future studies should evaluate whether fetuin-A may refine fracture risk assessment in older women. C1 [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Wassel, Christina L.] Univ Minnesota, Dept Epidemiol & Community Hlth, Minneapolis, MN USA. [Wassel, Christina L.; Bauer, Douglas C.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med & Epidemiol & Biostat, San Francisco, CA 94143 USA. [Toroian, Damon; Price, Paul A.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92161 USA. [Tylavsky, Frances A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Dept Med, San Francisco, CA USA. [Cummings, Steven R.] San Francisco Coordinating Ctr, San Francisco, CA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Med Sect, San Francisco, CA USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU American Diabetes Association (ADA); Atlantic Philanthropies; John A. Hartford Foundation; ASP; American Heart Association Fellow to Faculty Transition Award (JHI) [N01-AG-6-2101, N01-AG-6-2103, N01-AG6-2106]; Intramural Research Program from the National Institutes on Aging (NIA) FX The authors thank the other investigators, the staff, and the participants of the Health ABC stud), for valuable contributions and Dr Elsa Strotmeyer for her critical review of the manuscript. This Study was supported by an American Diabetes Association (ADA)-ASP Young Investigator Innovation Award in Geriatric Endocrinology sponsored by the Atlantic Philanthropies, ADA, the John A. Hartford Foundation, and ASP, an American Heart Association Fellow to Faculty Transition Award (JHI), and Contracts N01-AG-6-2101. N01-AG-6-2103, and N01-AG6-2106 and an Intramural Research Program from the National Institutes on Aging (NIA). The funding sources NR 41 TC 21 Z9 21 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2009 VL 24 IS 3 BP 514 EP 521 DI 10.1359/JBMR.081017 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 410JA UT WOS:000263572100015 PM 19016589 ER PT J AU Vogiatzi, MG Macklin, EA Fung, EB Cheung, AM Vichinsky, E Olivieri, N Kirby, M Kwiatkowski, JL Cunningham, M Holm, IA Lane, J Schneider, R Fleisher, M Grady, RW Peterson, CC Giardina, PJ AF Vogiatzi, Maria G. Macklin, Eric A. Fung, Ellen B. Cheung, Angela M. Vichinsky, Elliot Olivieri, Nancy Kirby, Melanie Kwiatkowski, Janet L. Cunningham, Melody Holm, Ingrid A. Lane, Joseph Schneider, Robert Fleisher, Martin Grady, Robert W. Peterson, Charles C. Giardina, Patricia J. CA Thalassemia Clinical Res Network TI Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE DXA; BMD; fractures; vertebral morphometry; thalassemia ID BETA-THALASSEMIA; MINERAL DENSITY; REPLACEMENT THERAPY; OSTEOPOROSIS; CHILDREN; ADOLESCENTS; METABOLISM; FRACTURES; ADULTS; HYPOGONADISM AB Adults with P thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, >= 6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1-75 yr), were studied. Spine and femur BMD Z-scores < -2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was Suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures. C1 [Vogiatzi, Maria G.; Grady, Robert W.; Giardina, Patricia J.] Weill Cornell Med Coll, Dept Pediat, New York, NY USA. [Macklin, Eric A.] New England Res Inst, Watertown, MA 02172 USA. [Fung, Ellen B.; Vichinsky, Elliot] Childrens Hosp Oakland, Oakland, CA USA. [Cheung, Angela M.; Olivieri, Nancy] Univ Hlth Network, Dept Med, Toronto, ON, Canada. [Cheung, Angela M.; Olivieri, Nancy] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Kirby, Melanie] Toronto Hosp Sick Children, Toronto, ON, Canada. [Kwiatkowski, Janet L.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. [Kwiatkowski, Janet L.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Cunningham, Melody; Holm, Ingrid A.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Lane, Joseph; Schneider, Robert] Hosp Special Surg, New York, NY 10021 USA. [Fleisher, Martin] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Peterson, Charles C.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Vogiatzi, MG (reprint author), Cornell Univ, Weill Med Coll, New York Presblyterian Hosp, Div Pediat Endocrinol, 525 E 68th St,Box 103, New York, NY 10065 USA. EM mvogiatz@med.cornell.edu RI Vichinsky, Elliott/F-8541-2011; Macklin, Eric/E-2955-2013; OI Vichinsky, Elliott/0000-0002-0500-9579; Macklin, Eric/0000-0003-1618-3502; Quinn, Charles/0000-0002-2372-2175; Schneider, Robert/0000-0001-5807-5564 FU National Heart, Lung, and Blood Institute; National Institutes of Health [U01-HL-65232, U01-HL-65233, U01-HL-65239, U01-HL-65244, U01-HL-65260, U01-HL-65238, 5K24HL004184-08]; Weill Medical College of Cornell University [K08 HL088231]; NIH-NCRR [UL1-RR024134]; Children's Hospital Boston by NIH-NCRR [M01-RR02172] FX This work was supported by a cooperative agreement with the National Heart, Lung, and Blood Institute, National Institutes of Health (U01-HL-65232 to Children's Hospital of Philadelphia, U01-HL-65233 to University Health Network Toronto General Hospital, U01-HL-65239 to Children's Hospital and Research Center at Oakland, U01-HL-65244 to Weill Medical College of Cornell University, U01-HL-65260 to Children's Hospital Boston, and U01-HL-65238 to New England Research Institutes). The study was also supported, in part, at Weill Medical College of Cornell University by Grant K08 HL088231 awarded to MGV, at Children's Hospital of Philadelphia by NIH-NCRR Grant UL1-RR024134, and by Children's Hospital Boston by NIH-NCRR Grant M01-RR02172 and NIH Grant 5K24HL004184-08 to EN. NR 38 TC 78 Z9 79 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2009 VL 24 IS 3 BP 543 EP 557 DI 10.1359/JBMR.080505 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 410JA UT WOS:000263572100018 PM 18505376 ER PT J AU Hava, D Forster, U Matsuda, M Cui, S Link, BA Eichhorst, J Wiesner, B Chitnis, A Abdelilah-Seyfried, S AF Hava, David Forster, Ulrike Matsuda, Miho Cui, Shuang Link, Brian A. Eichhorst, Jenny Wiesner, Burkhard Chitnis, Ajay Abdelilah-Seyfried, Salim TI Apical membrane maturation and cellular rosette formation during morphogenesis of the zebrafish lateral line SO JOURNAL OF CELL SCIENCE LA English DT Article DE Lethal giant larvae 2; Cell polarity; Lateral line organ; Protein kinase C iota; Heart and soul; Adhesion ID CADHERIN-2 FUNCTION; TISSUE MIGRATION; REVEALS MULTIPLE; CRANIAL GANGLIA; GIANT LARVAE; EXPRESSION; POLARITY; GENE; COMPLEX; HEART AB Tissue morphogenesis and cell sorting are major forces during organ development. Here, we characterize the process of tissue morphogenesis within the zebrafish lateral line primordium, a migratory sheet of cells that gives rise to the neuromasts of the posterior lateral line organ. We find that cells within this epithelial tissue constrict actin-rich membranes and enrich apical junction proteins at apical focal points. The coordinated apical membrane constriction in single Delta D-positive hair cell progenitors and in their neighbouring prospective support cells generates cellular rosettes. Live imaging reveals that cellular rosettes subsequently separate from each other and give rise to individual neuromasts. Genetic analysis uncovers an involvement of Lethal giant larvae proteins in the maturation of apical junction belts during cellular rosette formation. Our findings suggest that apical constriction of cell membranes spatially confines regions of strong cell-cell adhesion and restricts the number of tightly interconnected cells into cellular rosettes, which ensures the correct deposition of neuromasts during morphogenesis of the posterior lateral line organ. C1 [Hava, David; Forster, Ulrike; Abdelilah-Seyfried, Salim] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. [Eichhorst, Jenny; Wiesner, Burkhard] Leibniz Inst Mol Pharmacol FMP, D-13125 Berlin, Germany. [Cui, Shuang; Link, Brian A.] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA. [Matsuda, Miho; Chitnis, Ajay] NICHD, Unit Vertebrate Neural Dev, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Abdelilah-Seyfried, S (reprint author), Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. EM salim@mdc-berlin.de RI Matsuda, Miho/G-1616-2011 FU Helmholtz society FX We thank C. Birchmeier-Kohler, C. Dahm and members of the Abdelilah- Seyfried laboratory for their critical comments on the manuscript. We are indebted to W. Birchmeier, R. Kster, C. Petit and S. Sokol for sharing reagents and tools. R. Fechner was an excellent help in the maintenance and technical assistance of our fish facility. We apologize to colleagues whose work may not have been mentioned in this study. This work was supported by a presidential grant of the Helmholtz society towards the Berlin Institute for Heart Research (BIHR) to D. H. and from the Volkswagen Stiftung to S.A.-S. NR 43 TC 30 Z9 30 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR 1 PY 2009 VL 122 IS 5 BP 687 EP 695 DI 10.1242/jcs.032102 PG 9 WC Cell Biology SC Cell Biology GA 409OT UT WOS:000263516400012 PM 19208766 ER PT J AU Fazakerley, DJ Lawrence, SP Lizunov, VA Cushman, SW Holman, GD AF Fazakerley, Daniel J. Lawrence, Scott P. Lizunov, Vladimir A. Cushman, Samuel W. Holman, Geoffrey D. TI A common trafficking route for GLUT4 in cardiomyocytes in response to insulin, contraction and energy-status signalling SO JOURNAL OF CELL SCIENCE LA English DT Article DE GLUT4 trafficking; Insulin; AMPK signalling; Cardiomyocytes; Sarcolemma; Transverse tubules ID GTPASE-ACTIVATING PROTEIN; GLUCOSE-TRANSPORTER GLUT4; CHRONIC HEART-FAILURE; RAT ADIPOSE-CELLS; SKELETAL-MUSCLE; CARDIAC MYOCYTES; LIVING MICE; GLUCOSE-TRANSPORTER-4 GLUT4; VESICLE POPULATIONS; T-TUBULES AB A new mouse model has been developed to study the localisation and trafficking of the glucose transporter GLUT4 in muscle. The mouse line has specific expression of a GFP and HA-epitope-tagged version of GLUT4 under the control of a muscle-specific promoter. The exofacial HA-tag has enabled fluorescent labelling of only the GLUT4 exposed at the external surface. A distinction between sarcolemma labelling and transverse-tubule labelling has also been possible because the former compartment is much more accessible to intact anti-HA antibody. By contrast, the Fab fragment of the anti-HA antibody could readily detect GLUT4 at the surface of both the sarcolemma and transverse tubules. Here, we have used this mouse model to examine the route taken by cardiomyocyte GLUT4 as it moves to the limiting external membrane surface of sarcolemma and transverse-tubules in response to insulin, contraction or activators of energy-status signalling, including hypoxia. HA-GLUT4-GFP is largely excluded from the sarcolemma and transverse-tubule membrane of cardiomyocytes under basal conditions, but is similarly trafficked to these membrane surfaces after stimulation with insulin, contraction or hypoxia. Internalisation of sarcolemma GLUT4 has been investigated by pulse-labelling surface GLUT4 with intact anti-HA antibody. At early stages of internalisation, HA-tagged GLUT4 colocalises with clathrin at puncta at the sarcolemma, indicating that in cells returning to a basal state, GLUT4 is removed from external membranes by a clathrin-mediated route. We also observed colocalisation of GLUT4 with clathrin under basal conditions. At later stages of internalisation and at steady state, anti-HA antibody labeled-GLUT4 originating from the sarcolemma was predominantly detected in a peri-nuclear compartment, indistinguishable among the specific initial stimuli. These results taken together imply a common pathway for internalisation of GLUT4, independent of the initial stimulus. C1 [Fazakerley, Daniel J.; Lawrence, Scott P.; Holman, Geoffrey D.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. [Lizunov, Vladimir A.; Cushman, Samuel W.] NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Holman, GD (reprint author), Univ Bath, Dept Biol & Biochem, Claverton Down, Bath BA2 7AY, Avon, England. EM g.d.holman@bath.ac.uk RI Lizunov, Vladimir/B-5468-2009; OI Holman, Geoffrey/0000-0001-7045-1358 FU MRC (UK); Wellcome Trust; British Heart Foundation; AstraZeneca; CASE FX We are grateful to the MRC (UK), the Wellcome Trust and the British Heart Foundation for grant support. This work was supported in part by AstraZeneca through an industrial CASE studentship to D. J. F. Deposited in PMC for release after 6 months. NR 43 TC 25 Z9 25 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR 1 PY 2009 VL 122 IS 5 BP 727 EP 734 DI 10.1242/jcs.041178 PG 8 WC Cell Biology SC Cell Biology GA 409OT UT WOS:000263516400016 PM 19208760 ER PT J AU Shirakawa, H Rochman, M Furusawa, T Kuehn, MR Horigome, S Haketa, K Sugita, Y Inada, T Komai, M Bustin, M AF Shirakawa, Hitoshi Rochman, Mark Furusawa, Takashi Kuehn, Michael R. Horigome, Satoru Haketa, Keiichi Sugita, Yumi Inada, Tomoyuki Komai, Michio Bustin, Michael TI The Nucleosomal Binding Protein NSBP1 Is Highly Expressed in the Placenta and Modulates the Expression of Differentiation Markers in Placental Rcho-1 Cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE CHROMOSOMAL PROTEINS; PLACENTA; GENE REGULATION; TROPHOBLAST; NSBP1 ID CHROMOSOMAL-PROTEINS; HMGA AB We report that NSBP1, a nucleosome binding protein that affects the structure of chromatin, is highly expressed in mouse placenta, In Rcho-1 cells, which recapitulate the differentiation of trophoblast giant cells of living placenta, NSBP1 expression is linked to differentiation. Disregulation of NSBP1 protein levels, by either siRNA treatment or by overexpression, alters the expression of several members of the prolactin gene family without affecting the levels of several transcription factors involved in placental differentiation. Our studies identify NSBP1 as a nucleosome binding protein that modulates the expression of prolactin gene Family members, most likely by inducing changes in chromatin structure. J. Cell. Biochem. 106: 651-658, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rochman, Mark; Furusawa, Takashi; Bustin, Michael] NIH, Prot Sect, Lab Metab, Bethesda, MD 20892 USA. [Shirakawa, Hitoshi; Horigome, Satoru; Haketa, Keiichi; Sugita, Yumi; Inada, Tomoyuki; Komai, Michio] Tohoku Univ, Grad Sch Agr Sci, Lab Nutr, Sendai, Miyagi 980, Japan. RP Bustin, M (reprint author), Bldg 37,Room 3122, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Shirakawa, Hitoshi/D-1406-2009; Kuehn, Michael/A-4573-2014; Bustin, Michael/G-6155-2015 OI Kuehn, Michael/0000-0002-7703-9160; FU Japan Society for the Promotion of Science; National Cancer Institute, NIH FX This work was partially supported by Japan Society for the Promotion of Science (The US-Japan cooperative cancer research program) to HS and by the intramural research program of the National Cancer Institute, NIH. We thank Dr. M.J. Soares, Institute of Maternal-Fetal Biology, University of Kansas Medical Center, Kansas City, for I gift of Rcho-1 cells. NR 13 TC 8 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 1 PY 2009 VL 106 IS 4 BP 651 EP 658 DI 10.1002/jcb.22046 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 422VR UT WOS:000264456300018 PM 19160411 ER PT J AU Ishibashi, S Maric, D Mou, Y Ohtani, R Ruetzler, C Hallenbeck, JM AF Ishibashi, Satoru Maric, Dragan Mou, Yongshan Ohtani, Ryo Ruetzler, Christl Hallenbeck, John M. TI Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain ischemia; Foxp3; functional recovery; neurognesis; Treg; vascular niche ID FOCAL CEREBRAL-ISCHEMIA; TUMOR-NECROSIS-FACTOR; SUBVENTRICULAR ZONE; PROGENITOR PROLIFERATION; IMMUNOLOGICAL-TOLERANCE; ADHESION MOLECULES; BRAIN-INJURY; ADULT BRAIN; NEUROGENESIS; NEURONS AB Neuroblasts in the subventricular zone (SVZ) proliferate markedly after brain ischemia, and migrate to the site of injury along with blood vessels. However, a large fraction of stroke-generated neuroblasts die shortly after being born, in part, because of local inflammation. In spontaneously hypertensive rats (SHRs) subjected to permanent middle cerebral artery occlusion, we primed E-selectin-specific regulatory T cells (Tregs) by repetitive intranasal administration of recombinant E-selectin to target local secretion of immunomodulating, antiinflammatory cytokines to activating blood vessel segments. E-selectin-tolerized SHRs had decreased infarction volumes, and increased numbers of Tregs in the cervical lymph nodes and ischemic brain. The brain Tregs were distributed primarily in periinfarct regions. E-selectin tolerization did not alter cellular proliferation in the ipsilateral SVZ after stroke, but the expression of tumor necrosis factor on vascular niche blood vessels was suppressed and both doublecortin protein levels and the number of newly generated neuroblasts or neurons were increased in the brain. This enhanced survival of neural progenitor cells and neurons was paralleled by improved functional performance. These studies suggest that E-selectin-specific Tregs can modulate the efficacy of neurogenesis after ischemia and promote repair after brain injury. C1 [Ishibashi, Satoru; Mou, Yongshan; Ohtani, Ryo; Ruetzler, Christl; Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Ishibashi, Satoru] Tokyo Med & Dent Univ, Grad Sch Med, Dept Neurol & Neurol Sci, Bunkyo Ku, Tokyo, Japan. [Maric, Dragan] NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. [Ohtani, Ryo] Natl Hosp Org, Dept Neurol, Kyoto Med Ctr, Fushimi Ku, Kyoto, Japan. RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, Bldg 49,Rm2A10,MSC 4476,49 Convent Dr, Bethesda, MD 20892 USA. EM hallenbj@ninds.nih.gov FU Intramural Research Program of the NINDS/NIH FX This research was supported by the Intramural Research Program of the NINDS/NIH. NR 40 TC 30 Z9 31 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2009 VL 29 IS 3 BP 606 EP 620 DI 10.1038/jcbfm.2008.153 PG 15 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 412KD UT WOS:000263722800016 PM 19107136 ER PT J AU Chang, L Rapoport, SI Nguyen, HN Greenstein, D Chen, M Basselin, M AF Chang, Lisa Rapoport, Stanley I. Nguyen, Henry N. Greenstein, Dede Chen, Mei Basselin, Mireille TI Acute nicotine reduces brain arachidonic acid signaling in unanesthetized rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE arachidonic acid; imaging; mecamylamine; nicotine; phospholipase A(2); receptors ID CEREBRAL GLUCOSE-UTILIZATION; PHOSPHOLIPASE A(2) ACTIVATION; ACETYLCHOLINE-RECEPTORS; STIMULATES PHOSPHOLIPASE-A2; CIGARETTE SMOKERS; TURNOVER; NMDA; HIPPOCAMPUS; METABOLISM; SUBTYPES AB Nicotine exerts its central effects by activating pre- and postsynaptic nicotinic acetylcholine receptors (nAChRs). Presynaptic nAChRs modulate the release of many neurotransmitters that bind to postsynaptic receptors. These may be coupled to the activation of cytosolic phospholipase A(2) (cPLA(2)), which hydrolyzes arachidonic acid (AA) from membrane phospholipids. We hypothesized that nicotine would modify brain signaling involving AA by binding to nAChRs. Nicotine (0.1 mg/kg, subcutaneously) or saline was injected 2 or 10 mins before infusing [1-(14)C] AA in unanesthetized rats. The AA incorporation coefficient k* (a marker of the AA signal) was measured in 80 brain regions by quantitative autoradiography. Nicotine, compared to saline, when administrated 2 mins before [1-(14)C] AA infusion, significantly decreased k* for AA in 26 regions, including cerebral cortex, thalamus, and habenula-interpeduncular regions, by 13% to 45%. These decreases could be entirely prevented by pretreatment with mecamylamine (1.0 mg/kg, subcutaneously). When administered 10 mins before [1-(14)C] AA infusion, nicotine did not alter any value of k*. In summary, nicotine given to unanesthetized rats rapidly reduces signaling involving AA in brain regions containing nAChRs, likely by modulating the presynaptic release of neurotransmitters. The effect shows rapid desensitization and is produced at a nicotine dose equivalent to smoking one cigarette in humans. C1 [Chang, Lisa; Rapoport, Stanley I.; Nguyen, Henry N.; Chen, Mei; Basselin, Mireille] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Greenstein, Dede] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126,9 Mem Dr, Bethesda, MD 20892 USA. EM mirvasln@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 42 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2009 VL 29 IS 3 BP 648 EP 658 DI 10.1038/jcbfm.2008.159 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 412KD UT WOS:000263722800020 PM 19142197 ER PT J AU Filippov, IV Nicklaus, MC AF Filippov, Igor V. Nicklaus, Marc C. TI Optical Structure Recognition Software To Recover Chemical Information: OSRA, An Open Source Solution SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article AB Until recently most scientific and patent documents dealing with chemistry have described molecular structures either with systematic names or with graphical images of Kekule structures. The latter method poses inherent problems in the automated processing that is needed when the number of documents ranges in the hundreds of thousands or even millions since graphical representations cannot be directly interpreted by a computer. To recover this structural information, which is otherwise all but lost, we have built an optical structure recognition application based on modern advances in image processing implemented in open source tools, OSRA. OSRA can read documents in over 90 graphical formats including GIF, JPEG, PNG, TIFF, PDF, and PS, automatically recognizes and extracts the graphical information representing chemical structures in such documents, and generates the SMILES or SD representation of the encountered molecular structure images. C1 [Filippov, Igor V.] SAIC Frederick Inc, Med Chem Lab, NCI Frederick, Frederick, MD 21702 USA. [Nicklaus, Marc C.] NCI, NIH, DHHS, Med Chem Lab, Frederick, MD 21702 USA. RP Filippov, IV (reprint author), SAIC Frederick Inc, Med Chem Lab, NCI Frederick, Frederick, MD 21702 USA. EM igorf@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 18 TC 36 Z9 36 U1 1 U2 6 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 MAR PY 2009 VL 49 IS 3 BP 740 EP 743 DI 10.1021/ci800067r PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 423YT UT WOS:000264533400022 PM 19434905 ER PT J AU Baroni, A Lunsford, JR Luckenbaugh, DA Towbin, KE Leibenluft, E AF Baroni, Argelinda Lunsford, Jessica R. Luckenbaugh, David A. Towbin, Kenneth E. Leibenluft, Ellen TI Practitioner Review: The assessment of bipolar disorder in children and adolescents SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Bipolar disorder; severe mood dysregulation; mania; diagnosis; assessment ID SEVERE MOOD DYSREGULATION; MAJOR DEPRESSIVE DISORDER; I-DISORDER; PREPUBERTAL CHILDREN; UNIPOLAR DEPRESSION; SPECTRUM DISORDERS; BEHAVIOR CHECKLIST; NATURAL-HISTORY; JUVENILE MANIA; FOLLOW-UP AB An increasing number of youth are being diagnosed with, and treated for, bipolar disorder (BD). Controversy exists about whether youth with non-episodic irritability and symptoms of attention deficit hyperactivity disorder (ADHD) should be considered to have a developmental presentation of mania. A selective review of the literature related to this question, along with recommendations to guide clinical assessment. Data indicate differences between youth with episodic mania and those with non-episodic irritability in longitudinal diagnostic associations, family history, and pathophysiology. In youth with episodic mania, elation and irritability are both common during manic episodes. In diagnosing mania in youth, clinicians should focus on the presence of episodes that consist of a distinct change in mood accompanied by concurrent changes in cognition and behavior. BD should not be diagnosed in the absence of such episodes. In youth with ADHD, symptoms such as distractibility and agitation should be counted as manic symptoms only if they are markedly increased over the youth's baseline symptoms at the same time that there is a distinct change in mood and the occurrence of other associated symptoms of mania. Although different techniques for diagnosing comorbid illnesses have not been compared systematically, it appears most rational to diagnose co-occurring illnesses such as ADHD only if the symptoms of the co-occurring illness are present when the youth is euthymic. C1 [Baroni, Argelinda; Lunsford, Jessica R.; Towbin, Kenneth E.; Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Luckenbaugh, David A.] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,Dept Hlth & Human Serv, Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov OI Baroni, Argelinda/0000-0002-3296-9153 FU Intramural NIH HHS [Z01 MH002778-08] NR 68 TC 25 Z9 25 U1 2 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAR PY 2009 VL 50 IS 3 BP 203 EP 215 DI 10.1111/j.1469-7610.2008.01953.x PG 13 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 417JY UT WOS:000264073500003 PM 19309325 ER PT J AU Hatch, M Brenner, A Bogdanova, T Derevyanko, A Kuptsova, N Likhtarev, I Bouville, A Tereshchenko, V Kovgan, L Shpak, V Ostroumova, E Greenebaum, E Zablotska, L Ron, E Tronko, M AF Hatch, M. Brenner, A. Bogdanova, T. Derevyanko, A. Kuptsova, N. Likhtarev, I. Bouville, A. Tereshchenko, V. Kovgan, L. Shpak, V. Ostroumova, E. Greenebaum, E. Zablotska, L. Ron, E. Tronko, M. TI A Screening Study of Thyroid Cancer and Other Thyroid Diseases among Individuals Exposed in Utero to Iodine-131 from Chernobyl Fallout SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NEEDLE-ASPIRATION-CYTOLOGY; RADIATION-EXPOSURE; RADIOIODINE UPTAKE; ACCIDENT; UKRAINE; COHORT; CELLS; RISK; CHILDHOOD; DOSIMETRY AB Background: Like stable iodine, radioiodines concentrate in the thyroid gland, increasing thyroid cancer risk in exposed children. Data on exposure to the embryonic/fetal thyroid are rare, raising questions about use of iodine 131 (I-131) in pregnant women. We present here estimated risks of thyroid disease from exposure in utero to I-131 fallout from the Chernobyl nuclear accident. Methods: We conducted a cross-sectional thyroid screening study (palpation, ultrasound, thyroid hormones, and, if indicated, fine needle aspiration) from 2003 to 2006. Participants were 2582 mother-child pairs from Ukraine in which the mother had been pregnant at the time of the accident on April 26, 1986, or 2 months after the time during which I-131 fallout was still present (1494 from contaminated areas, 1088 in the comparison group). Individual cumulative in utero thyroid dose estimates were derived from estimated I-131 activity in the mother's thyroid (mean 72 mGy; range 0-3230 mGy). Results: There were seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm identified as a result of the screening. Whereas the estimated excess odds ratio per gray for thyroid carcinoma was elevated (excess odds ratio per gray 11.66), it was not statistically significant (P = 0.12). No radiation risks were identified for other thyroid diseases. Conclusion: Our results suggest that in utero exposure to radioiodines may have increased the risk of thyroid carcinoma approximately 20 yr after the Chernobyl accident, supporting a conservative approach to medical uses of I-131 during pregnancy. (J Clin Endocrinol Metab 94: 899-906, 2009) C1 [Hatch, M.] NCI, Chernobyl Res Unit, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, Rockville, MD 20852 USA. [Bogdanova, T.; Derevyanko, A.; Kuptsova, N.; Tereshchenko, V.; Shpak, V.; Tronko, M.] Inst Endocrinol & Metab, UA-04114 Kiev, Ukraine. [Likhtarev, I.; Kovgan, L.] Res Ctr Radiat Med, UA-04050 Kiev, Ukraine. [Ostroumova, E.] Urals Res Ctr Radiat Med, Chelyabinsk 454076, Russia. [Greenebaum, E.; Zablotska, L.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. RP Hatch, M (reprint author), NCI, Chernobyl Res Unit, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, 6120 Execut Blvd,EPS 7098, Rockville, MD 20852 USA. EM hatchm@mail.nih.gov FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The Nuclear Regulatory Commission provided the initial funds for purchase of equipment. The study team is grateful to the Louise Hamilton Kyiv Data Management Center of the University of Illinois at Chicago, supported in part by the National Institutes of Health Fogarty International Center, and to its head, Oleksandr Zvinchuk, and his assistant, Tatiana Odnolko, for database support and management. NR 34 TC 23 Z9 26 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 MAR PY 2009 VL 94 IS 3 BP 899 EP 906 DI 10.1210/jc.2008-2049 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 416QN UT WOS:000264020700029 PM 19106267 ER PT J AU Hewitt, CE Torgerson, DJ Berger, VW AF Hewitt, Catherine E. Torgerson, David J. Berger, Vance W. TI Potential for technical errors and subverted allocation can be reduced if certain guidelines are followed: Examples from a web-based survey SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Randomization; Subversion; Technical errors; Manipulation; Bias; Online survey ID RANDOMIZED-TRIALS; MINIMIZATION; CONCEALMENT; QUALITY; BIAS AB Objective: To elicit researchers' experiences and knowledge of how the randomization process can be undermined. Study Design and Setting: Web-based survey conducted in February 2006 using a convenience sample of individuals who are, or have been, involved in some aspect of randomized controlled trials. Results: Thirty responses were received that described incidences of manipulation. Seven reasons were identified for manipulation: interest of participants, demonstrating treatment efficacy, treatment preference, lack of knowledge, pressure from participants, pressure from trial workers, and practical or technical concerns. In many cases when manipulation was discovered, it was rarely mentioned in the trial publication. Twenty-three responses that described technical errors were received. Technical errors were reported for both the generation and implementation stages of the randomization process. Conclusions: This study provides further evidence on trial subversion and highlighted that the potential for technical errors can be reduced, and in most cases eliminated, if certain guidelines are followed. Recommendations are as follows: use simple randomization where possible, use third party allocation, test computer randomization programs prior to participant recruitment and ensure that individuals are aware of the procedures needed to be performed if the treatment allocations cannot be accessed using the intended methods. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hewitt, Catherine E.; Torgerson, David J.] Univ York, Dept Hlth Sci, York Trials Unit, York YO10 5DD, N Yorkshire, England. [Berger, Vance W.] NCI, Bethesda, MD 20892 USA. [Berger, Vance W.] Univ Maryland Baltimore Cty, Biometry Res Grp, Bethesda, MD 20892 USA. RP Hewitt, CE (reprint author), Univ York, Dept Hlth Sci, York Trials Unit, 1st Floor Area 2,Seebohm Rowntree Bldg, York YO10 5DD, N Yorkshire, England. EM ceh121@york.ac.uk NR 22 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAR PY 2009 VL 62 IS 3 BP 261 EP 269 DI 10.1016/j.jclinepi.2008.06.005 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 408IA UT WOS:000263427500005 PM 18823755 ER PT J AU Kang, BH Plescia, J Song, HY Meli, M Colombo, G Beebe, K Scroggins, B Neckers, L Altieri, DC AF Kang, Byoung Heon Plescia, Janet Song, Ho Young Meli, Massimiliano Colombo, Giorgio Beebe, Kristin Scroggins, Bradley Neckers, Len Altieri, Dario C. TI Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELL-DEATH; PERMEABILITY TRANSITION; CYCLOPHILIN-D; HUMAN BREAST; HEAT-SHOCK-PROTEIN-90 INHIBITOR; COLORECTAL CANCERS; MYELOID-LEUKEMIA; APOPTOSIS; PROTEIN; DISCOVERY AB Although therapeutically targeting a single signaling pathway that drives tumor development and/or progression has been effective for a number of cancers, in many cases this approach has not been successful. Targeting networks of signaling pathways, instead of isolated pathways, may overcome this problem, which is probably due to the extreme heterogeneity of human tumors. However, the possibility that such networks may be spatially arranged in specialized subcellular compartments is not often considered in pathway-oriented drug discovery and may influence the design of new agents. Hsp90 is a chaperone protein that controls the folding of proteins in multiple signaling networks that drive tumor development and progression. Here, we report the synthesis and properties of Gamitrinibs, a class of small molecules designed to selectively target Hsp90 in human tumor mitochondria. Gamitrinibs were shown to accumulate in the mitochondria of human tumor cell fines and to inhibit Hsp90 activity by acting as ATPase antagonists. Unlike Hsp90 antagonists not targeted to mitochondria, Gamitrinibs exhibited a "mitochondriotoxic" mechanism of action, causing rapid tumor cell death and inhibiting the growth of xenografted human tumor cell lines in mice. Importantly, Gamitrinibs were not toxic to normal cells or tissues and did not affect Hsp90 homeostasis in cellular compartments other than mitochondria. Therefore, combinatorial drug design, whereby inhibitors of signaling networks are targeted to specific subcellular compartments, may generate effective anticancer drugs with novel mechanisms of action. C1 [Altieri, Dario C.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. [Song, Ho Young] LegoChem Biosci Inc, Taejon, South Korea. [Meli, Massimiliano; Colombo, Giorgio] Ist Chim Riconoscimento Mol, Milan, Italy. [Beebe, Kristin; Scroggins, Bradley; Neckers, Len] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Altieri, DC (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, LRB428,364 Plantat St, Worcester, MA 01605 USA. EM dario.altieri@umassmed.edu RI Kang, Byoung Heon/E-6165-2010; Colombo, Giorgio/A-2730-2012 OI Kang, Byoung Heon/0000-0001-5902-0549; Colombo, Giorgio/0000-0002-1318-668X FU National Institutes of Health [CA78810, CA90917, HLS4131]; Research Prograrn of the National Cancer Institute, National Institutes of Health FX We thank Kris Depew and Nafeeza Ifafeez (Infinity Pharmaceitticals Inc.) for technical assistance, M. DeFeUdis for generous support, and D. Garlick for histologic evaluation. This work was supported by National Institutes of Health grants CA78810, CA90917, and HLS4131 (D.C. Altieri) and by funding from the intramural Research Prograrn of the National Cancer Institute, National Institutes of Health (K. Beebe, 13. Scroggins, and L Neckers). NR 56 TC 88 Z9 91 U1 2 U2 14 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 MAR PY 2009 VL 119 IS 3 BP 454 EP 464 DI 10.1172/JCI37613 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 415NP UT WOS:000263941000009 PM 19229106 ER PT J AU Aravamuthan, BR McNab, JA Miller, KL Rushworth, M Jenkinson, N Stein, JF Aziz, TZ AF Aravamuthan, Bhooma R. McNab, Jennifer A. Miller, Karla L. Rushworth, Matthew Jenkinson, Ned Stein, John F. Aziz, Tipu Z. TI Cortical and subcortical connections within the pedunculopontine nucleus of the primate Macaca mulatta determined using probabilistic diffusion tractography SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article ID MESENCEPHALIC LOCOMOTOR REGION; DEEP BRAIN-STIMULATION; CENTRAL-NERVOUS-SYSTEM; TEGMENTAL NUCLEUS; SQUIRREL-MONKEY; EXPERIMENTAL PARKINSONISM; MESOPONTINE TEGMENTUM; HUMAN THALAMUS; BASAL-GANGLIA; PROJECTIONS AB The anatomical connections of the pedunculopontine nucleus (PPN), a brainstem structure associated with locomotion, have been determined recently in healthy humans using probabilistic diffusion tractography (PDT). In order to compare these with histologically demonstrated connections of the PPN in monkeys, and thus to Support the use of PDT in humans, we have carried out PDT in a fixed rhesus monkey (Macaca mulatta) brain. Probabilistic diffusion tractography was carried out in a fixed post-mortem rhesus monkey brain using diffusion data acquired at 3T MRI (60 directions x 5 averages, b = 3000 s/mm(2), matrix size = 104 x 132 x 96, 720 x 720 x 720 mu m voxels). We identified the major connections of the PPN from single seed voxels that could be confidently located within the nucleus on the diffusion images. The organisation of these connections within a 3 x 3 x 3 voxel (similar to 10 mm(3)) region surrounding the initial seed voxel was then examined. PDT confirmed that the rhesus monkey PPN connections with the basal ganglia and motor cortical areas matched those previously demonstrated using conventional anatomical tracing techniques. Furthermore, although the Organisation Of subcortical connections within the PPN has not been extensively demonstrated in animals, we show here in a rhesus monkey that there are clearly separated connections of the PPN with the thalamus, substantia nigra, and subthalamic nucleus. Thus, in addition to increasing confidence in the accuracy of PDT for tracing PPN connections and determining the Organisation of these connections within the PPN in vivo, our observations suggest that diffusion tractography will be a useful new technique to rapidly identify connections in animal brains pre-mortem and post-mortem. Published by Elsevier Ltd. C1 [Aravamuthan, Bhooma R.; Jenkinson, Ned; Stein, John F.; Aziz, Tipu Z.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England. [Aravamuthan, Bhooma R.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [McNab, Jennifer A.; Miller, Karla L.] John Radcliffe Hosp, Oxford Ctr Funct MRI Brain, Oxford OX3 9DU, England. [Rushworth, Matthew] Univ Oxford, Dept Expt Psychol, Oxford OX1 3PT, England. [Aziz, Tipu Z.] John Radcliffe Hosp, Dept Neurosurg, Oxford OX3 9DU, England. RP Aravamuthan, BR (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Parks Rd, Oxford OX1 3PT, England. EM bhooma.aravamuthan@dpag.ox.ac.uk RI Jenkinson, Ned/B-1718-2009; OI Jenkinson, Ned/0000-0002-6803-486X; Miller, Karla/0000-0002-2511-3189 FU Medical Research Council [G0200561] NR 50 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD MAR PY 2009 VL 16 IS 3 BP 413 EP 420 DI 10.1016/j.jocn.2008.03.018 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 412ZI UT WOS:000263762300011 PM 19167229 ER PT J AU Lima, JE Reid, MS Smith, JL Zhang, YL Jiang, HP Rotrosen, J Nunes, E AF Lima, Jennifer E. Reid, Malcolm S. Smith, Jennifer L. Zhang, Yulei Jiang, Huiping Rotrosen, John Nunes, Edward TI MEDICAL AND MENTAL HEALTH STATUS AMONG DRUG DEPENDENT PATIENTS PARTICIPATING IN A SMOKING CESSATION TREATMENT STUDY SO JOURNAL OF DRUG ISSUES LA English DT Article ID ABUSE REHABILITATION PROGRAMS; ADDICTION SEVERITY INDEX; PSYCHIATRIC-DISORDERS; ALCOHOL DEPENDENCE; CONTROLLED-TRIAL; UNITED-STATES; PRIMARY-CARE; INTERVENTION; DEPRESSION; SMOKERS AB Substance abusers have a large number of medical and psychiatric problems, and 70-90% are smokers. The aim of this analysis was to examine the prevalence and correlates of medical and psychiatric problems in this sample of drug dependent patients who were participants in a multi-site study of smoking cessation interventions while engaged in substance abuse treatment. Descriptive analyses showed 72.8% of participants had at least one medical problem at baseline and 64.1% had at least one psychiatric diagnosis. Medical problems correlated strongly with age, smoking severity, and pack-years; psychiatric problems correlated with gender and ethnicity. Smoking cessation treatment was associated with a moderate reduction in the ASI Medical composite score. More research is needed on the possible effects of combined treatment of substance abuse and concurrent medical and psychiatric problems. Offering smoking cessation in conjunction with primary care may be a way to address the health needs of this population. C1 [Lima, Jennifer E.; Jiang, Huiping] New York State Psychiat Inst & Hosp, Div Biostat, New York, NY 10032 USA. [Lima, Jennifer E.; Rotrosen, John; Nunes, Edward] Natl Inst Drug Abuse, Clin Trials Network, Bethesda, MD 20892 USA. [Reid, Malcolm S.; Rotrosen, John] NYU, Sch Med, Dept Psychiat, New York, NY 10003 USA. [Zhang, Yulei; Jiang, Huiping] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10027 USA. [Nunes, Edward] Columbia Univ, Coll Phys & Surg, Dept Biostat, New York, NY 10027 USA. RP Lima, JE (reprint author), New York State Psychiat Inst & Hosp, Div Biostat, New York, NY 10032 USA. FU NIDA NIH HHS [U10 DA013035-07, U10 DA013045-09, U10 DA013046, U10 DA013720-09, U10 DA013727, U10 DA013727-08, U10 DA013727-09, U10 DA013710-05, U10 DA013710, U10 DA013046-09, U10 DA013035, K24 DA022412-03, K24 DA022412, U10 DA013727-10, U10 DA013720, U10 DA013711-05, U10 DA013711, U10 DA013045] NR 43 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0426 EI 1945-1369 J9 J DRUG ISSUES JI J. Drug Issues PD SPR PY 2009 VL 39 IS 2 BP 293 EP 311 PG 19 WC Substance Abuse SC Substance Abuse GA 478RM UT WOS:000268605900004 PM 20628556 ER PT J AU Koepsell, D Arp, R Fostel, J Smith, B AF Koepsell, David Arp, Robert Fostel, Jennifer Smith, Barry TI CREATING A CONTROLLED VOCABULARY FOR THE ETHICS OF HUMAN RESEARCH: TOWARDS A BIOMEDICAL ETHICS ONTOLOGY SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE ontology; taxonomy; ethics committee review; automation; semantics AB ONTOLOGIES DESCRIBE REALITY IN SPECIFIC domains in ways that can bridge various disciplines and languages. They allow easier access and integration of information that is collected by different groups. Ontologies are currently used in the biomedical sciences, geography, and law. A Biomedical Ethics Ontology (BMEO) would benefit members of ethics committees who deal with protocols and consent forms spanning numerous fields of inquiry. There already exists the Ontology for Biomedical Investigations (OBI); the proposed BMEO would interoperate with OBI, creating a powerful information tool. We define a domain ontology and begin to construct a BMEO, focused on the process of evaluating human research protocols. Finally, we show how our BMEO can have practical applications for ethics committees. This paper describes ongoing research and a strategy for its broader continuation and cooperation. C1 [Koepsell, David] Delft Univ Technol, Dept Philosophy, Fac Technol Policy & Management, NL-2600 GA Delft, Netherlands. [Arp, Robert; Smith, Barry] SUNY Buffalo, Natl Ctr Biomed Ontol, Buffalo, NY 14260 USA. [Fostel, Jennifer] NIEHS, CEBS, NIH, Res Triangle Pk, NC 27709 USA. [Koepsell, David] Delft Univ Technol, Sect Philosophy, Dept Technol Policy & Management, NL-2600 GA Delft, Netherlands. RP Koepsell, D (reprint author), Delft Univ Technol, Dept Philosophy, Fac Technol Policy & Management, POB 5015, NL-2600 GA Delft, Netherlands. EM drkoepsell@yahoo.com RI Smith, Barry/A-9525-2011 OI Smith, Barry/0000-0003-1384-116X FU Division of Intramural Research of the National Institute of Environmental Health Science [HHSN273200700046U]; National Institutes of Health through the NIH Roadmap for Medical Research [1 U 54 HG004028] FX This work was supported in part by the National Center for Ontological Research and the State University of New York at Buffalo. The contribution of Jennifer Fostel to this work was supported by the Division of Intramural Research of the National Institute of Environmental Health Science, under contract HHSN273200700046U. This work was funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant 1 U 54 HG004028 (National Center for Biomedical Ontology). NR 18 TC 4 Z9 4 U1 0 U2 3 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS & DIGITAL PUBLISHING DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD MAR PY 2009 VL 4 IS 1 BP 43 EP 58 DI 10.1525/jer.2009.4.1.43 PG 16 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 436GP UT WOS:000265401000006 PM 19374479 ER PT J AU Wheeler, DC Waller, LA AF Wheeler, David C. Waller, Lance A. TI Comparing spatially varying coefficient models: a case study examining violent crime rates and their relationships to alcohol outlets and illegal drug arrests SO JOURNAL OF GEOGRAPHICAL SYSTEMS LA English DT Article DE GWR; Bayesian regression; Collinearity; Penalization methods ID GEOGRAPHICALLY WEIGHTED REGRESSION; AVAILABILITY; DYNAMICS AB In this paper, we compare and contrast a Bayesian spatially varying coefficient process (SVCP) model with a geographically weighted regression (GWR) model for the estimation of the potentially spatially varying regression effects of alcohol outlets and illegal drug activity on violent crime in Houston, Texas. In addition, we focus on the inherent coefficient shrinkage properties of the Bayesian SVCP model as a way to address increased coefficient variance that follows from collinearity in GWR models. We outline the advantages of the Bayesian model in terms of reducing inflated coefficient variance, enhanced model flexibility, and more formal measuring of model uncertainty for prediction. We find spatially varying effects for alcohol outlets and drug violations, but the amount of variation depends on the type of model used. For the Bayesian model, this variation is controllable through the amount of prior influence placed on the variance of the coefficients. For example, the spatial pattern of coefficients is similar for the GWR and Bayesian models when a relatively large prior variance is used in the Bayesian model. C1 [Wheeler, David C.] Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA. [Wheeler, David C.] NCI, Rockville, MD 20852 USA. [Waller, Lance A.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. RP Wheeler, DC (reprint author), Harvard Univ, Harvard Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dwheeler@hsph.harvard.edu NR 24 TC 25 Z9 26 U1 1 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1435-5930 EI 1435-5949 J9 J GEOGR SYST JI J. Geogr. Syst. PD MAR PY 2009 VL 11 IS 1 BP 1 EP 22 DI 10.1007/s10109-008-0073-5 PG 22 WC Geography SC Geography GA 409IL UT WOS:000263499300001 ER PT J AU Hilgert, N Monahan, K Kurima, K Li, C Friedman, RA Griffith, AJ Van Camp, G AF Hilgert, Nele Monahan, Kelly Kurima, Kiyoto Li, Cindy Friedman, Rick A. Griffith, Andrew J. Van Camp, Guy TI Amino acid 572 in TMC1: hot spot or critical functional residue for dominant mutations causing hearing impairment SO JOURNAL OF HUMAN GENETICS LA English DT Article DE D527N; DFNA36; hereditary hearing loss; hot spot; TMC1 ID MOUSE MODEL; LOSS DFNA36; GENE; CONNEXIN-26; BEETHOVEN; FOUNDER; CELLS AB Two different missense mutations, p. D572N and p. D572H, affecting the same nucleotide and codon of the TMC1 gene were earlier reported to cause autosomal dominant hearing impairment at locus DFNA36 in two North American families. No other dominant mutations of human TMC1 have been published. We ascertained a third North American family segregating autosomal dominant nonsyndromic hearing impairment at the DFNA36 locus. We identified the p. D572N mutation of TMC1 co-segregating with hearing loss in our study family. A comparative haplotype analysis of linked single nucleotide polymorphisms and short tandem repeats in the two families segregating p. D572N was not consistent with a founder effect. These findings can be explained in two ways. Either nucleotide 1714 is a hot spot for mutations or, alternatively, missense mutations at this site confer a specific pathogenic gain-of-function or dominant-negative effect. C1 [Hilgert, Nele; Van Camp, Guy] Univ Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium. [Monahan, Kelly; Kurima, Kiyoto; Griffith, Andrew J.] NIDCD, Otolaryngol Branch, NIH, Rockville, MD USA. [Li, Cindy; Friedman, Rick A.] House Ear Res Inst, Sect Hereditary Disorders Ear, Los Angeles, CA USA. RP Van Camp, G (reprint author), Univ Antwerp, Dept Med Genet, Univ Pl 1, B-2610 Antwerp, Belgium. EM guy.vancamp@ua.ac.be RI Van Camp, Guy/F-3386-2013 OI Van Camp, Guy/0000-0001-5105-9000 FU EUROHEAR [LSHG-CT-2005-4512063]; Fund for Scientific Research Flanders [0138.07]; NIH [Z01-DC-000060-07] FX This study was supported by grants from EUROHEAR (LSHG-CT-2005-4512063), the Fund for Scientific Research Flanders (FWO-F, Grant G. 0138.07), and the NIH intramural research fund Z01-DC-000060-07. Nele Hilgert is a fellow of the Fund for Scientific Research Flanders (FWO-F). NR 14 TC 10 Z9 11 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD MAR PY 2009 VL 54 IS 3 BP 188 EP 190 DI 10.1038/jhg.2009.1 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 435PP UT WOS:000265356100009 PM 19180119 ER PT J AU Wang, KL Cheng, HM Chuang, SY Spurgeon, HA Ting, CT Lakatta, EG Yin, FCP Chou, P Chen, CH AF Wang, Kang-Ling Cheng, Hao-Min Chuang, Shao-Yuan Spurgeon, Harold A. Ting, Chih-Tai Lakatta, Edward G. Yin, Frank C. P. Chou, Pesus Chen, Chen-Huan TI Central or peripheral systolic or pulse pressure: which best relates to target organs and future mortality? SO JOURNAL OF HYPERTENSION LA English DT Article DE central blood pressure; glomerular filtration rate; mortality; pulse pressure ID DIASTOLIC BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE RISK; GLOMERULAR-FILTRATION-RATE; CAROTID-ARTERY TONOMETRY; CORONARY-HEART-DISEASE; CHRONIC KIDNEY-DISEASE; LEFT-VENTRICULAR MASS; WAVE REFLECTION; AORTIC PRESSURE; 2007 GUIDELINES AB Objective To examine the relationship between brachial and central carotid pressures and target organ indices at baseline and their association with future mortality. Methods We examined, cross-sectionally and longitudinally, the relations of baseline systolic and pulse pressures in central (calibrated tonometric carotid pulse) and peripheral (brachial, mercury sphygmomanometer) arteries to baseline left ventricular mass, carotid intima-media thickness, estimated glomerular filtration rate, and 10-year all-cause and cardiovascular mortality in 1272 participants (47% women aged 30-79 years) from a community of homogeneous Chinese. Results Left ventricular mass was more strongly related to central and peripheral systolic pressures than pulse pressures. Intima-media thickness and glomerular filtration rate were more strongly related to central pressures than peripheral pressures. A total of 130 participants died, 37 from cardiovascular causes. In univariate analysis, all four blood pressure variables significantly predicted all-cause and cardiovascular mortality. Each blood pressure variable was entered into the multivariate models, both individually and jointly with another blood pressure variable. After adjustment for age, sex, heart rate, BMI, current smoking, glucose, ratio of total cholesterol to high-density lipoprotein cholesterol, carotid-femoral pulse wave velocity, left ventricular mass, intima-media thickness, and glomerular filtration rate, only central systolic pressure consistently and independently predicted cardiovascular mortality (hazards ratio, 1.30 per 10 mmHg). No significant sex interactions were observed in all analyses. Conclusion Systolic and pulse pressures relate differently to different target organs. Central systolic pressure is more valuable than other blood pressure variables in predicting cardiovascular mortality. J Hypertens 27:461-467 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Chen, Chen-Huan] Taipei Vet Gen Hosp, Div Cardiol, Dept Res & Educ, Taipei, Taiwan. [Wang, Kang-Ling] Taipei Vet Gen Hosp, Dept Med, Taipei, Taiwan. [Chuang, Shao-Yuan] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Spurgeon, Harold A.] NIA, Lab Cardiovascular Sci, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Ting, Chih-Tai] Taichung Vet Gen Hosp, Ctr Cardiovasc, Taichung, Taiwan. [Yin, Frank C. P.] Washington Univ, Dept Biomed Engn, St Louis, MO USA. [Chen, Chen-Huan] Natl Yang Ming Univ, Cardiovasc Res Ctr, Taipei 112, Taiwan. [Chou, Pesus; Chen, Chen-Huan] Natl Yang Ming Univ, Dept Publ Hlth, Taipei 112, Taiwan. [Chen, Chen-Huan] Natl Yang Ming Univ, I Lan Univ Hosp, Taipei 112, Taiwan. RP Chen, CH (reprint author), Taipei Vet Gen Hosp, Div Cardiol, Dept Res & Educ, 201 Sec,2 Shih Pai rd, Taipei, Taiwan. EM chench@vghtpe.gov.tw RI Chuang, Shao-Yuan/B-3478-2011 FU Taipei Veterans General Hospital [V95CI-052]; Research Foundation of Cardiovascular Medicine [91-02-032, 93-02-014]; Talpei, Taiwan, Research and Development [IAG-1-2118]; National Institute on Aging; National Institutes of Health FX This work was supported in part by the intramural grants from the Taipei Veterans General Hospital (grant no. V95CI-052), grants in aid from the Research Foundation of Cardiovascular Medicine (91-02-032, 93-02-014), Talpei, Taiwan, Research and Development contract no. IAG-1-2118 and the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 37 TC 180 Z9 188 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD MAR PY 2009 VL 27 IS 3 BP 461 EP 467 DI 10.1097/HJH.0b013e3283220ea4 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 432QM UT WOS:000265149200005 PM 19330899 ER PT J AU Kastenmuller, W Gasteiger, G Stross, L Busch, DH Drexler, I AF Kastenmuller, Wolfgang Gasteiger, Georg Stross, Leon Busch, Dirk H. Drexler, Ingo TI Cutting Edge: Mucosal Application of a Lyophilized Viral Vector Vaccine Confers Systemic and Protective Immunity toward Intracellular Pathogens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; SELECTIVE EXPRESSION; MEMORY; IMMUNIZATION; RECEPTOR; VIRUSES; DESIGN; MVA AB A major problem of current vaccines is storage stability, often requiring strict maintenance of cold chains. In the course of the eradication of smallpox, a freeze-dried vaccinia virus (Dryvax), which proved to be very stable, was used to overcome this limitation. However, Dryvax needs to be reconstituted before usage and is administered using a bifurcated needle, procedures that pose a number of additional health risks. We report in this study that a stable, lyophilized, modified vaccinia virus Ankara (MVA) vaccine can be directly applied to the nostrils of mice without previous reconstitution. This direct mucosal application induced systemic Ab and T cell responses comparable to those achieved by i.m. administration. Importantly, mucosal application of lyophilized MVA induced long-lasting protective immunity against lethal bacterial and viral challenges. These data clearly demonstrate the potency of a simple needle-free vaccination, combining the advantages of mucosal application with the stability and efficiency of lyophilized MVA. The Journal of Immunology, 2009, 182: 2573-2577. C1 [Stross, Leon; Drexler, Ingo] Helmholtz Ctr Munich, Inst Virol, Munich, Germany. [Kastenmuller, Wolfgang; Gasteiger, Georg; Stross, Leon; Drexler, Ingo] Tech Univ Munich, Inst Virol, Munich, Germany. [Busch, Dirk H.] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, Munich, Germany. [Kastenmuller, Wolfgang; Gasteiger, Georg; Busch, Dirk H.; Drexler, Ingo] Helmholtz Ctr Munich, Antigen Specif Immunotherapy & Immune Monitoring, Clin Cooperat Grp, Munich, Germany. [Kastenmuller, Wolfgang; Gasteiger, Georg; Busch, Dirk H.; Drexler, Ingo] German Res Ctr Environm Hlth, Munich, Germany. RP Kastenmuller, W (reprint author), NIAID, Lymphocyte Biol Sect, NIH, Bethesda, MD 20982 USA. EM kastenmullerw@niaid.nih.gov; drexler@helmholtz-muenchen.de OI Gasteiger, Georg/0000-0001-6986-127X NR 22 TC 7 Z9 7 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 MAR 1 PY 2009 VL 182 IS 5 BP 2573 EP 2577 DI 10.4049/jimmunol.0803871 PG 5 WC Immunology SC Immunology GA 411MG UT WOS:000263653100005 PM 19234150 ER PT J AU Spolski, R Kim, HP Zhu, W Levy, DE Leonard, WJ AF Spolski, Rosanne Kim, Hyoung-Pyo Zhu, Wei Levy, David E. Leonard, Warren J. TI IL-21 Mediates Suppressive Effects via Its Induction of IL-10 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOLLICULAR-HELPER-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COMMON GAMMA-CHAIN; T-CELLS; B-CELLS; CUTTING EDGE; PLASMA-CELLS; IFN-GAMMA; DIFFERENTIATION; INTERLEUKIN-21 AB IL-21 is a pleiotropic cytokine that is required for normal Ig production. We previously showed that IL-21 was elevated in BXSB-Yaa mice with systemic lupus erythematosus. These mice also had elevated 11,40 levels, and we now show that IL-21 induces IL-10 mRNA and protein, suggesting unexpected immunosuppressive activities for IL-21. Indeed, Th1 priming with IL-21 leads to accumulation of cells with immunosuppressive activity, and IL-21 overexpression decreases specific Ab production after immunization in an IL-10-dependent fashion. Moreover, we show that IL-21 signaling is required for maximal induction of IL-10 by IL-6 or IL-27. Overall, our data indicate that IL-21 regulates immune responses at least in part by inducing IL-10 and reveal unanticipated immunosuppressive actions for this cytokine. The Journal of Immunology, 2009, 182: 2859-2867. C1 [Spolski, Rosanne; Kim, Hyoung-Pyo; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Spolski, Rosanne; Kim, Hyoung-Pyo; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA. [Zhu, Wei; Levy, David E.] NYU, Dept Pathol, New York, NY 10016 USA. [Zhu, Wei; Levy, David E.] NYU, Dept Microbiol, New York, NY 10016 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov OI Levy, David/0000-0002-7320-7788 FU Intramural Research Program; National Heart, Lung, and Blood Institute, National Institutes of Health; National Institutes of Health [AI28900] FX This research was supported by the Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health (to W.J.L-) and National Institutes of Health Grant AI28900 (to D.E.L.). NR 56 TC 96 Z9 97 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2009 VL 182 IS 5 BP 2859 EP 2867 DI 10.4049/jimmunol.0802978 PG 9 WC Immunology SC Immunology GA 411MG UT WOS:000263653100036 PM 19234181 ER PT J AU Tran, DQ Class, DD Uzel, G Darnell, DA Spalding, C Holland, SM Shevach, EA AF Tran, Dat Q. Class, Deborah D. Uzel, Gulbu Darnell, Dirk A. Spalding, Christine Holland, Steven M. Shevach, Ethan A. TI Analysis of Adhesion Molecules, Target Cells, and Role of IL-2 in Human FOXP3(+) Regulatory T Cell Suppressor Function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DENDRITIC CELLS; TGF-BETA; IN-VITRO; AUTOIMMUNE-DISEASE; CUTTING EDGE; COSTIMULATORY MOLECULES; MEDIATED SUPPRESSION; SPECIES-SPECIFICITY; SELF-TOLERANCE; VIVO AB FOXP3(+) regulatory T cells (Tregs) are central to the maintenance of self-tolerance and immune homeostasis. The mechanisms of action and cellular targets for Treg-mediated suppression remain controversial. The critical adhesion molecules utilized by Tregs for the interaction with their target cells have not been well characterized. We show that human CD4+FOXP3(+) CD25(high) cells (hTregs) suppress the activation or mouse responders as efficiently its mouse Tregs. LFA-1 (CD11a/CD18) on the hTregs is critical for their suppressor function, since suppression can be reversed with blocking anti-hCD11a or anti-hCD18 mAb. Tregs from patients with LFA-1 deficiency fail to suppress human and mouse responders. Mouse CD4(+) T cells deficient in ICAM-I can be suppressed by hTregs, indicating that the hTregs target mouse dendritic cells (DCs) through the binding of human LFA-1 to mouse ICAM-1. Coculture of mouse DCs with hTregs, but not hTregs from LFA-1-deficient patients, prevented the up-regulation of CD80/CD86 on the DCs and their capacity to activate responder T cells. Lastly, IL-2 is not required for hTreg suppressor function under optimal stimulatory condition and IL-2 consumption plays no role in hTreg-mediated suppression. Taken together, one of the mechanisms of Treg-mediated suppression functions across species and mediates an LFA-1/ICAM-1-dependent interaction between Tregs and DCs. The Journal of Immunology, 2009, 182: 2929-2938. C1 [Tran, Dat Q.; Class, Deborah D.; Shevach, Ethan A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Uzel, Gulbu; Darnell, Dirk A.; Spalding, Christine; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Shevach, EA (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This work was funded by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 45 TC 57 Z9 60 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2009 VL 182 IS 5 BP 2929 EP 2938 DI 10.4049/jimmunol.0803827 PG 10 WC Immunology SC Immunology GA 411MG UT WOS:000263653100043 PM 19234188 ER PT J AU Kostka, SL Dinges, S Griewank, K Iwakura, Y Udey, MC von Stebut, E AF Kostka, Susanna Lopez Dinges, Stephanie Griewank, Klaus Iwakura, Yoichiro Udey, Mark C. von Stebut, Esther TI IL-17 Promotes Progression of Cutaneous Leishmaniasis in Susceptible Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IL-17-PRODUCING T-CELLS; DENDRITIC CELLS; MAJOR INFECTION; AUTOIMMUNE ENCEPHALOMYELITIS; RECEPTOR ANTAGONIST; BALB/C MICE; TGF-BETA; NEUTROPHILS; IL-23; ACTIVATION AB Resistance to leishmaniasis in C57BL/6 mice depends on Th1/Te1 cells. BALB/c mice preferentially develop Th2 immunity and succumb to infection. We now assessed the role of IL-17 in cutaneous leishmaniasis. During the course of Leishmania major infection, BALB/c CD4 cells and neutrophils produced increased amounts or IL-17 as compared with cells from C57BL/6 mice. This increase was associated with significantly increased IL-23 release from L. major-infected BALB/c dendritic cells (DC), whereas IL-6 and TGF-beta 1 production by BALB/c and C57BL/6 DC were comparable. Interestingly, lesion sizes in infected IL-17-deficient BALB/c mice were dramatically smaller and railed to progress as compared with those in control mice. Similar amounts of IL-4, IL-10, and IFN-gamma were produced by T cells from IL-17-deficient mice and control mice consistent with development of Th2-predominant immunity in all animals. Improved disease outcome was associated with decreased CXCL2-accumulation in lesion sites and decreased neutrophil immigration into lesions of infected IL-17-deficient mice confirming prior observations that enhanced neutrophil recruitment contributes to disease susceptibility in BALB/c mice. This study excludes an important facilitating role for IL-17 in Th1/Th2 development in L. major-infected BALB/c mice, and suggests that IL-23 production by L. major-infected DC maintains IL-17(+) cells that influence disease progression via regulation of neutrophil recruitment. The Journal of Immunology, 2009, 182: 3039-3046. C1 [Kostka, Susanna Lopez; Dinges, Stephanie; Griewank, Klaus; von Stebut, Esther] Johannes Gutenberg Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1138654, Japan. [Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP von Stebut, E (reprint author), Johannes Gutenberg Univ Mainz, Dept Dermatol, Langenbeckstr 1, D-55131 Mainz, Germany. EM vonstebut@mail.uni-mainz.de RI Iwakura, Yoichiro/E-5457-2011; Griewank, Klaus/A-9097-2017 OI Iwakura, Yoichiro/0000-0002-9934-5775; FU Deutsche Forschungsgemeinschaft [S H 490, SFB 548]; Intramural Program of the National Cancer Institute; Center for Cancel Research; National Institutes of Health FX This work was supported by Grants S H 490 and SFB 548 from the Deutsche Forschungsgemeinschaft and the Berliner Stiftung for Dermatologic (to E.v.S.). M.C.U, is supported by the Intramural Program of the National Cancer Institute, Center for Cancel Research, National Institutes of Health. NR 40 TC 63 Z9 65 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 MAR 1 PY 2009 VL 182 IS 5 BP 3039 EP 3046 DI 10.4049/jimmunol.0713598 PG 8 WC Immunology SC Immunology GA 411MG UT WOS:000263653100055 ER PT J AU Poon, LLM Leung, YHC Nicholls, JA Perera, PY Lichy, JH Yamamoto, M Waldmann, TA Peiris, JSM Perera, LP AF Poon, Leo L. M. Leung, Y. H. Connie Nicholls, John A. Perera, Pin-Yu Lichy, Jack H. Yamamoto, Masafumi Waldmann, Thomas A. Peiris, J. S. Malik Perera, Liyanage P. TI Vaccinia Virus-Based Multivalent H5N1 Avian Influenza Vaccines Adjuvanted with IL-15 Confer Sterile Cross-Clade Protection in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID A VIRUSES; IMMUNITY; RECOMBINANT; CELLS; LIVE; INTERLEUKIN-15; IMMUNIZATION; INFECTION; VECTORS; FERRETS AB The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment or the highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people, We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune stimulatory cytokine IL-15. The pentavalent Wyethl/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from the H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and NI neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing Abs and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with the H5N1 virus or a different clade. In addition to having potential as a universal influenza vaccine, in the event of an impending pandemic the Wyeth/IL-15/5Flu is also readily amenable to bulk production to cover the global population. For those individuals for whom the use or the Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago. The Journal of Immunology, 2009, 182: 3063-3071. C1 [Waldmann, Thomas A.; Perera, Liyanage P.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Poon, Leo L. M.; Leung, Y. H. Connie; Nicholls, John A.; Peiris, J. S. Malik] Univ Hong Kong, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China. [Perera, Pin-Yu; Lichy, Jack H.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Yamamoto, Masafumi] Nihon Univ, Sch Dent Matsudo, Dept Microbiol & Immunol, Chiba, Japan. RP Perera, LP (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Room 4B40, Bethesda, MD 20892 USA. EM malik@hkucc.hku.hk; perera1@mail.nih.gov FU National Cancel Institute; Center for Cancer Research; National Institutes of Health (NIH) [HHSN206200700005C]; National Institute of Allergy and Infections Diseases; Area of Excellence Scheme of the University Grants Committee Hong Kong [AoE/M-12/06] FX This work was supported by the Intramural Research Program of the National Cancel Institute, Center for Cancer Research, National Institutes of Health (NIH), National Institute of Allergy and Infections Diseases, NIH Contract HHSN206200700005C, and Area of Excellence Scheme of the University Grants Committee Hong Kong Grant AoE/M-12/06. NR 27 TC 33 Z9 38 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2009 VL 182 IS 5 BP 3063 EP 3071 DI 10.4049/jimmunol.0803467 PG 9 WC Immunology SC Immunology GA 411MG UT WOS:000263653100058 PM 19234203 ER PT J AU O'Connor, JC Lawson, MA Andre, C Briley, EM Szegedi, SS Lestage, J Castanon, N Herkenham, M Dantzer, R Kelley, KW AF O'Connor, Jason C. Lawson, Marcus A. Andre, Caroline Briley, Eileen M. Szegedi, Sandra S. Lestage, Jacques Castanon, Nathalie Herkenham, Miles Dantzer, Robert Kelley, Keith W. TI Induction of IDO by Bacille Calmette-Guerin Is Responsible for Development of Murine Depressive-Like Behavior SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MYCOBACTERIUM-TUBERCULOSIS INFECTION; INTRACELLULAR BACTERIAL-INFECTIONS; PLASMACYTOID DENDRITIC CELLS; DECREASED SERUM TRYPTOPHAN; RAT-BRAIN SLICES; INDOLEAMINE 2,3-DIOXYGENASE; T-CELL; IFN-GAMMA; IMMUNE ACTIVATION AB Chronic inflammation activates the tryptophan-degrading enzyme EDO, which is well known to impair T cell proliferation. We have previously established that bacille Calmette-Guerin (BCG), an attenuated form of Mycobacterium bovis, is associated with persistent activation of IDO in the brain and chronic depressive-like behavior, but a causative role has not been established. In these experiments we used both pharmacologic and genetic approaches to test the hypothesis that IDO activation is responsible for the development of chronic depression that follows BCG infection. BCG induced TNF-alpha, IFN-gamma, and IDO mRNA steady-state transcripts in the brain as well as the enzyme 3-hydroxyanthranilic acid oxygenase (3-HAO) that lies downstream of IDO and generates the neuroactive metabolite, quinolinic acid. Behaviors characteristic of depression were apparent 1 wk after BCG infection. Pretreatment with the competitive IDO inhibitor I-methyltryptophan fully blocked BCG-induced depressive-like behaviors. Importantly, EDO-deficient mice were completely resistant to BCG-induced depressive-like behavior but responded normally to BCG induction of proinflammatory cytokines. These results are the first to prove that the BCG-induced persistent activation of IDO is accompanied by the induction of 3-hydroxyanthranilic acid oxygenase and that IDO is required as an initial step for the subsequent development of chronic depressive-like behavior. The Journal of Immunology, 2009, 182: 3202-3212. C1 [O'Connor, Jason C.; Lawson, Marcus A.; Andre, Caroline; Szegedi, Sandra S.; Dantzer, Robert; Kelley, Keith W.] Univ Illinois, Coll Agr Consumer & Environm Sci, Integrat Immunol & Behav Program, Dept Anim Sci, Urbana, IL 61801 USA. [Dantzer, Robert; Kelley, Keith W.] Univ Illinois, Coll Med, Dept Pathol, Urbana, IL 61801 USA. [Briley, Eileen M.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. [Lestage, Jacques; Castanon, Nathalie] Univ Victor Segalen Bordeaux II, CNRS, INRA, Bordeaux, France. RP Kelley, KW (reprint author), Univ Illinois, Coll Agr Consumer & Environm Sci, Integrat Immunol & Behav Program, Dept Anim Sci, 227 Edward R Madigan Lab,1201 W Gregory Dr, Urbana, IL 61801 USA. EM kwkelley@illinois.edu OI Kelley, Keith W./0000-0002-6837-8793; Herkenham, Miles/0000-0003-2228-4238; Dantzer, Robert/0000-0001-9399-6107 FU National Institutes of Health [R01 AG 029573, R01 MH 71349, R01 MH 079829] FX This work was supported by National Institutes of Health Grants R01 AG 029573 (to K.W.K.), R01 MH 71349 (to R.D.), and R01 MH 079829 (to R.D.). NR 80 TC 136 Z9 144 U1 2 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2009 VL 182 IS 5 BP 3202 EP 3212 DI 10.4049/jimmunol.0802722 PG 11 WC Immunology SC Immunology GA 411MG UT WOS:000263653100073 PM 19234218 ER PT J AU Crompton, PD Mircetic, M Weiss, G Baughman, A Huang, CY Topham, DJ Treanor, JJ Sanz, I Lee, FEH Durbin, AP Miura, K Narum, DL Ellis, RD Malkin, E Mullen, GED Miller, LH Martin, LB Pierce, SK AF Crompton, Peter D. Mircetic, Marko Weiss, Greta Baughman, Amy Huang, Chiung-Yu Topham, David J. Treanor, John J. Sanz, Inaki Lee, F. Eun-Hyung Durbin, Anna P. Miura, Kazutoyo Narum, David L. Ellis, Ruth D. Malkin, Elissa Mullen, Gregory E. D. Miller, Louis H. Martin, Laura B. Pierce, Susan K. TI The TLR9 Ligand CpG Promotes the Acquisition of Plasmodium falciparum-Specific Memory B Cells in Malaria-Naive Individuals SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOSTIMULATORY PHOSPHOROTHIOATE OLIGONUCLEOTIDE; MONOCLONAL-ANTIBODY THERAPY; TOLL-LIKE RECEPTORS; SMALLPOX VACCINATION; ANTIGEN; IMMUNITY; SAFETY; VIRUS; IMMUNOGENICITY; PERSISTENCE AB Despite the central role of memory B cells (MBC) in protective immune responses, little is understood about how they are acquired in naive individuals in response to Ag exposure, and how this process is influenced by concurrent activation of the innate immune system's TLR. In this longitudinal study of malaria-naive individuals, we examined the MBC response to two candidate malaria vaccines administered with or without CpG, a TLR9 ligand. We show that the acquisition of MBC is a dynamic process in which the vaccine-specific MBC pool rapidly expands and then contracts, and that CpG enhances the kinetics, magnitude, and longevity of this response. We observed that the percentage of vaccine-specific MBC present at the time of reimmunization predicts vaccine-specific Ab levels 14 days later; and that at steady-state, there is a positive correlation between vaccine-specific MBC and Ab levels. An examination of the total circulating MBC and plasma cell pools also suggests that MBC differentiate into plasma cells through polyclonal activation, independent of Ag specificity. These results provide important insights into the human MBC response, which can inform the development of vaccines against malaria and other pathogens that disrupt immunological memory. The Journal of Immunology, 2009, 182: 3318-3326. C1 [Crompton, Peter D.; Mircetic, Marko; Weiss, Greta; Baughman, Amy; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20852 USA. [Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Topham, David J.; Treanor, John J.; Sanz, Inaki; Lee, F. Eun-Hyung] Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Miura, Kazutoyo; Narum, David L.; Ellis, Ruth D.; Malkin, Elissa; Mullen, Gregory E. D.; Miller, Louis H.; Martin, Laura B.] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20852 USA. RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2 Bldg,Room 200F,12441 Parklawn Dr, Rockville, MD 20852 USA. EM perompton@niaid.nih.gov RI Martin, Laura/N-1789-2013; Crompton, Peter/N-1130-2016 OI Martin, Laura/0000-0002-4431-4381; FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases; National Institutes of Health; National Institutes of Health [N01-AI-25460]; National Center for Research Resources [ULI RR024160] FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases. National Institutes of Health; by contract N01-AI-25460 from the National Institutes of Health (to D.J.T. and J.J.T.); and by ULI RR024160 from the National Center for Research Resources (to U.R.M.C.). NR 33 TC 52 Z9 53 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 MAR 1 PY 2009 VL 182 IS 5 BP 3318 EP 3326 DI 10.4049/jimmunol.0803596 PG 9 WC Immunology SC Immunology GA 411MG UT WOS:000263653100086 PM 19234231 ER PT J AU Aramayo, CF Gil, JF Cruz, MC Poma, HR Last, MS Rajal, VB AF Aramayo, Cristian F. Gil, Jose F. Cruz, Mercedes C. Poma, Hugo R. Last, Michael S. Rajal, Veronica B. TI Diarrhea and parasitosis in Salta, Argentina SO JOURNAL OF INFECTION IN DEVELOPING COUNTRIES LA English DT Article DE Diarrhea; parasitosis; Geographical Information Systems; Argentina AB Background: Salta city is the capital of the province with the same name located in the northwest of Argentina. Its great growth over the last decade was not organized and the population expanded to occupy places where water and sanitation were not yet available. Although the Arenales River, crossing the city, receives the impact of point and non-point source pollution, the water is used for many purposes, including domestic in the poorest areas, industrial, and recreational with children as the main users. According to the World Health Organization, an estimated 24% of the global disease burden and 23% of all deaths can be attributed to environmental factors. In particular, an estimated 94% of the diarrheal burden of disease is attributable to environment, and is associated with risk factors such as unsafe drinking water and poor sanitation and hygiene. Chronic diarrhea can be caused by an infection or other etiologies; however, most of the times the etiological agent is not identified. Methodology: All the cases of diarrhea and parasitosis reported during 2005 in four public health centers of the city of Salta were classified by gender and age, analyzed, and represented geographically to show areas of higher morbidity rates, which were probably related to environmental factors. Results: Water, poor sanitation, and pollution are candidate risk factors. Diarrhea cases showed seasonality, with the highest incidence during late spring and summer, while parasitosis was persistent throughout the year. Conclusion: Our spatial analysis permitted us to detect the regions of higher incidence of diarrhea and parasitosis during 2005 in the area of study. C1 [Aramayo, Cristian F.; Gil, Jose F.; Cruz, Mercedes C.; Poma, Hugo R.; Rajal, Veronica B.] UNSa, CONICET, INIQUI, Inst Invest Ind Quim, RA-4400 Salta, Argentina. [Last, Michael S.; Rajal, Veronica B.] UC Davis, NIH, FIC, Davis, CA USA. [Rajal, Veronica B.] Univ Nacl Salta, Fac Ingn, Buenos Aires, DF, Argentina. RP Rajal, VB (reprint author), UNSa, CONICET, INIQUI, Inst Invest Ind Quim, Buenos Aires 177, RA-4400 Salta, Argentina. EM vbrajal@gmail.com OI Gil, Jose/0000-0003-3994-1265 FU Fogarty International Center at the University of California in Davis (USA); Nivel Primario de Atencion FX The authors would like to thank Andres Perez for his invaluable help. This work was funded by the Fogarty International Center at the University of California in Davis (USA). It was performed based on the epidemiological information obtained through a collaboration with Dr. Alberto Gentile at the Epidemiology Coordination Agency of Salta Province. The authors also want to thank the Nivel Primario de Atencion and the Health Centers studied for their support. The worthy help from the Direccion Provincial de Estadisticas y Censos through its director Lic. Mauro Rosas, and directly from Gladis Romero from the Cartography section, is especially appreciated. NR 14 TC 7 Z9 7 U1 0 U2 3 PU J INFECTION DEVELOPING COUNTRIES PI TRAMANIGLIO PA JIDC CENT OFF PORTO CONTE RICERCHE RES CTR, S P 55, PORTO CONTE CAPO CACCIA KM 8.400 LOC, TRAMANIGLIO, 07041, ITALY SN 1972-2680 J9 J INFECT DEV COUNTR JI J. Infect. Dev. Ctries. PD MAR PY 2009 VL 3 IS 2 BP 105 EP 111 PG 7 WC Infectious Diseases SC Infectious Diseases GA V22BK UT WOS:000208250500006 PM 19755739 ER PT J AU Karron, RA Callahan, K Luke, C Thumar, B McAuliffe, J Schappell, E Joseph, T Coelingh, K Jin, H Kemble, G Murphy, BR Subbarao, K AF Karron, Ruth A. Callahan, Karen Luke, Catherine Thumar, Bhagvanji McAuliffe, Josephine Schappell, Elizabeth Joseph, Tomy Coelingh, Kathleen Jin, Hong Kemble, George Murphy, Brian R. Subbarao, Kanta TI A Live Attenuated H9N2 Influenza Vaccine Is Well Tolerated and Immunogenic in Healthy Adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CANDIDATE VACCINES; PANDEMIC INFLUENZA; DOSE-RESPONSE; H5N1 VIRUS; VOLUNTEERS; REASSORTANT; INFECTION; ANTIBODY; SAFETY AB Development of live attenuated influenza vaccines (LAIV) against avian strains with pandemic potential is an important public-health strategy. Either 1 or 2 10(7)-TCID(50) doses of H9N2 LAIV A/chicken/Hong Kong/G9/97 were administered intra-nasally to 50 adults in isolation; 41 participants were H9N2 seronegative, 24 of whom received 2 doses. The vaccine was well tolerated; vaccine shedding was minimal. After 2 doses, 92% of H9-seronegative participants had >= 4-fold increases in hemagglutination-inhibition antibody, and 79% had >= 4-fold increases in neutralizing antibody; 100% had responses detected by at least 1 assay. Although replication of the H9N2 LAIV was restricted, 2 doses were immunogenic in H9N2-seronegative adults. Trial registration. ClinicalTrials.gov identifier: NCT00110279. C1 [Karron, Ruth A.; Callahan, Karen; Thumar, Bhagvanji; Schappell, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. [Luke, Catherine; McAuliffe, Josephine; Joseph, Tomy; Murphy, Brian R.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Coelingh, Kathleen; Jin, Hong; Kemble, George] MedImmune, Gaithersburg, MD USA. RP Karron, RA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Hampton House 217,624 N Broadway, Baltimore, MD 21205 USA. EM rkarron@jhsph.edu OI Schappell, Elizaeth/0000-0003-2142-5318 FU National Institutes of Health [N01-AI-15444]; MedImmune; National Institute of Allergy and Infectious Diseases Intramural Program FX Financial support: National Institutes of Health (contract N01-AI-15444 to X. X. X.); MedImmune; National Institute of Allergy and Infectious Diseases Intramural Program. NR 15 TC 45 Z9 47 U1 0 U2 2 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 MAR 1 PY 2009 VL 199 IS 5 BP 711 EP 716 DI 10.1086/596558 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 406ND UT WOS:000263301300016 PM 19210163 ER PT J AU Grady, C AF Grady, Christine TI Vulnerability in Research: Individuals with Limited Financial and/or Social Resources SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID RESEARCH PARTICIPANTS; CLINICAL-RESEARCH; INFORMED-CONSENT; AFRICAN-AMERICANS; TRIALS; POPULATIONS; PROTECTION; QUALITY; SUBJECT; CANCER AB Individuals with limited resources are often presumed to be vulnerable in research. Concerns include the possibility of impaired decision making, susceptibility to undue inducement, and risk of exploitation. Although each of these concerns should be considered by investigators and IRBs, none justifies categorical exclusion of individuals with limited resources. C1 NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. NR 36 TC 13 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2009 VL 37 IS 1 BP 19 EP + PG 10 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 418EX UT WOS:000264131400004 PM 19245599 ER PT J AU Menikoff, J AF Menikoff, Jerry TI The Vulnerability of the Very Sick SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID CONSENT AB When seriously ill patients for whom existing treatments are inadequate are invited to participate in clinical trials that offer a new treatment, should those persons be considered "vulnerable"? And if so, what additional protections should they he accorded? This article attempts to provide some answers. C1 NIH, Off Human Subjects Res, Bethesda, MD 20892 USA. RP Menikoff, J (reprint author), NIH, Off Human Subjects Res, Bethesda, MD 20892 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2009 VL 37 IS 1 BP 51 EP + PG 9 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 418EX UT WOS:000264131400007 PM 19245602 ER PT J AU Chen, K Tjandra, N AF Chen, Kang Tjandra, Nico TI Direct measurements of protein backbone N-15 spin relaxation rates from peak line-width using a fully-relaxed Accordion 3D HNCO experiment SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Relaxation; HNCO; Accordion; Line width; Protein ID NUCLEAR-MAGNETIC-RESONANCE; GLUTAMINE-BINDING PROTEIN; NMR-SPECTROSCOPY; RATE CONSTANTS; SPECTRA; SELECTION; DYNAMICS; MOTIONS AB Protein backbone N-15 spin relaxation rates measured by Solution NMR provide useful dynamic information with a site-specific resolution. The conventional method is to record a series of 2D H-1-N-15 HSQC spectra with varied relaxation delays, and derive relaxation rate from the following Curve fitting on the resonance intensities. Proteins with poorly resolved spectra often require several 3D HNCO spectra to be collected on a N-15/C-13 double labeled protein sample. In order to reduce the relaxation dimension Carr et al. (P.A. Carr, D.A. Fearing, A.G. Palmer, 3D accordion spectroscopy for measuring N-15 and (CO)-Carbon-13 relaxation rates in poorly resolved NMR spectra, J. Magn. Reson. 132 (1998) 25-33) employed an Accordion type HNCO pulse sequence to obtain N-15 or C-13 T-1 relaxation rates by numerical fitting of the relaxation interfered free induction decay (FID) data. To avoid intensive analysis of the time domain data, we propose a modified protocol to measure N-15 T-1 and T-2 relaxation rates from easily obtained line-widths in an Accordion HNCO spectrum. Both T-1 and T-2 relaxation Could be simultaneously Convoluted into the constant-time evolution periods of C-13' and N-15, respectively. The relaxation delay was allowed to reach at least 3 x T-1 or 3 x T-2 so that the signal was substantially decayed by the end of the FID, and the resulting peak full-width at half height (FWHH) could be directly used to calculate relaxation rate. When applied to the 76-residue Ubiquitin and the 226-residue glutamine-binding protein (GlnBP), this method yielded T-1 and T-2 values deviating on average by 4-6% and 5-7%, respectively, from the Measurements based on the conventional 2D method. In comparison, the conventional methods possessed intrinsic error ranges of 2-4% for T-1 and 3-6% for T-2. In addition to comparable accuracy, the fully-relaxed Accordion HNCO method presented here allowed measurements of relaxation rates for resonances unresolved in 2D spectra, thus providing a more complete dynamic picture of the protein. Published by Elsevier Inc. C1 [Chen, Kang; Tjandra, Nico] NHLBI, NIH, Lab Mol Biophys, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, NIH, Lab Mol Biophys, 50 Ctr Dr,Bld 50,Room 3513, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov FU NIH, National Heart, Lung, and Blood Institute FX We thank James Gruschus for careful reading of the manuscript. This work was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute. NR 26 TC 5 Z9 5 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 2009 VL 197 IS 1 BP 71 EP 76 DI 10.1016/j.jmr.2008.12.001 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 416EE UT WOS:000263987500011 PM 19114314 ER PT J AU Martiniova, L Kotys, MS Thomasson, D Schimel, D Lai, EW Bernardo, M Merino, MJ Powers, JF Ruzicka, J Kvetnansky, R Choyke, PL Pacak, K AF Martiniova, Lucia Kotys, Melanie S. Thomasson, David Schimel, Daniel Lai, Edwin W. Bernardo, Marcelino Merino, Maria J. Powers, James F. Ruzicka, Jan Kvetnansky, Richard Choyke, Peter L. Pacak, Karel TI Noninvasive Monitoring of a Murine Model of Metastatic Pheochromocytoma: A Comparison of Contrast-Enhanced MicroCT and Nonenhanced MRI SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE pheochromocytoma; anatomical imaging; microCT; MRI; animal model ID EXPERIMENTAL LIVER-TUMORS; COMPUTED-TOMOGRAPHY; ANIMAL-MODELS; AGENTS; TRIGLYCERIDE; EXPERIENCE; DOPAMINE; CELLS; MICE AB Purpose: To compare contrast-enhanced micro-computed tomography (microCT and nonenhanced respiratory-triggered magnetic resonance imaging (MRI) in an animal model of metastatic pheochromocytoma. Animal models are becoming important in the study of cancer treatment and imaging is useful in minimizing the number of animals needed and reducing costs associated with autopsies. However, the choice of imaging modality is still evolving. Materials and Methods: Adult female nude mice were injected by tail vein with a mouse pheochromocytoma (MPC) cell line (MPC 4/30PRR) to create a metastatic model. After optimizing imaging techniques, eight mice were imaged with both respiratory triggered MRI and microCT and the findings were verified histologically. Results: MicroCT and MRI were approximately equal in their ability to detect hepatic metastases at a size threshold of 350 mu m. In the lungs, MRI was more sensitive than microCT, detecting lesions 0.6 mm in diameter versus I mm for microCT. Additionally, MRI was more sensitive for lesions in the kidneys, bone, ovaries, and adrenal glands. MRI demonstrated a higher contrast-to-noise ratio (CNR) than microCT. Conclusion: In addition to the advantage of not exposing the animal to ionizing radiation, MRI provided a more complete assessment of the extent of metastases in this model compared to microCT. C1 [Martiniova, Lucia; Lai, Edwin W.; Pacak, Karel] NICHHD, Reprod & Adult Endocrinol Program, Bethesda, MD 20892 USA. [Kotys, Melanie S.] NHLBI, Bethesda, MD 20892 USA. [Thomasson, David] NIH, Warren Grant Magnuson Clin Ctr, Lab Diagnost Radiol, Bethesda, MD 20892 USA. [Schimel, Daniel] Natl Inst Neurol Disorders & Stroke, Mouse Imaging Facil, Charles River Labs, Bethesda, MD USA. [Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Bernardo, Marcelino] NCI Frederick, SAIC Frederick, Lab Anim Sci Program, Frederick, MD USA. [Merino, Maria J.] NCI, Pathol Lab, Frederick, MD 21701 USA. [Powers, James F.] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. [Powers, James F.] Tufts Univ New England Med Ctr, Boston, MA 02111 USA. [Ruzicka, Jan] Comenius Univ, Dept Nucl Sub Nucl Phys, Bratislava, Slovakia. [Martiniova, Lucia; Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia. RP Pacak, K (reprint author), NICHD, NIH, Bldg 10,Rm 1E-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400]; NINDS NIH HHS [NS37685, R01 NS037685-05, R01 NS037685] NR 24 TC 24 Z9 25 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAR PY 2009 VL 29 IS 3 BP 685 EP 691 DI 10.1002/jmri.21654 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 415GT UT WOS:000263923000026 PM 19243052 ER PT J AU Dean, M AF Dean, Michael TI ABC Transporters, Drug Resistance, and Cancer Stem Cells SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE ATP-binding cassette transporters; Cancer stem cell; Multidrug resistance; Estrogen; Aromatase; EGF receptor; Transport inhibitors ID BINDING CASSETTE TRANSPORTER; SIDE POPULATION CELLS; P-GLYCOPROTEIN GENE; BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE; IN-VIVO; BACTERIAL TRANSPORT; HEMATOPOIETIC-CELLS; IMATINIB MESYLATE; ESTROGEN-RECEPTOR AB The protection of the body's stem cells from damage or death due to toxins is a critical function of an organism, as the stem cells need to remain intact for the entire life of the organism. One of the principal mechanisms for protecting stem cells is through the expression of multifunctional efflux transporters from the ATP-binding cassette (ABC) gene family. These same transporters have been known for over 25 years to also play a role in multidrug resistance of tumor cells. An exciting outcome of the concept of the cancer stem cell is that the tumor initiating cell may be innately resistant to many standard therapies. This provides one mechanism in which cancer stem cells could survive cytotoxic or targeted therapies and lead to tumor regrowth or relapse. Gaining a better insight into the mechanisms of stem cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anti-cancer strategies. C1 NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. EM dean@ncifcrf.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 59 TC 180 Z9 193 U1 7 U2 28 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD MAR PY 2009 VL 14 IS 1 BP 3 EP 9 DI 10.1007/s10911-009-9109-9 PG 7 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 417TY UT WOS:000264102600002 PM 19224345 ER PT J AU Manoukis, NC Diabate, A Abdoulaye, A Diallo, M Dao, A Yaro, AS Ribeiro, JMC Lehmann, T AF Manoukis, Nicholas C. Diabate, Abdoulaye Abdoulaye, Adamou Diallo, Moussa Dao, Adama Yaro, Alpha S. Ribeiro, Jose M. C. Lehmann, Tovi TI Structure and Dynamics of Male Swarms of Anopheles gambiae SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Anopheles gambiae; swarm; mate recognition; three-dimensional localization; stereoscopic image analysis ID MOLECULAR-FORMS; MATING-BEHAVIOR; MOSQUITO; DIPTERA; CULICIDAE; SPECIATION; VILLAGE; AREA; S.S.; SL AB Mosquito swarms are poorly Understood mating aggregations. In the malaria vector Anopheles gambiae Giles, they are known to depend on environmental conditions, such as the presence of a marker on the ground, and they may be highly relevant to reproductive isolation. We present quantitative measurements of individual Art. gambiae positions within swarms from Doneguebougou, Mali, estimated by stereoscopic video image analysis. Results indicate that swarms in this species are approximately spherical, with all unexpectedly high density of individuals close to the swarm centroid. This high density may be the result of individual males maximizing their probability of encountering a female or a product of mosquito orientation through cues within the swarm. Our analysis also suggests a difference in swarm organization between putative incipient species of An. gambiae with increasing numbers of males. This may be related to a difference in marker use between these groups, supporting the hypothesis that swarming behavior is a mechanism of mate recognition and ultimately reproductive isolation, C1 [Manoukis, Nicholas C.; Diabate, Abdoulaye; Ribeiro, Jose M. C.; Lehmann, Tovi] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Abdoulaye, Adamou; Diallo, Moussa; Dao, Adama; Yaro, Alpha S.] Univ Mali, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali. RP Manoukis, NC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-28,Twinbrook 3 Bldg,, Bethesda, MD 20892 USA. EM manoukisn@niaid.nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU Bioinformatics and Scientific Information Technology Program (BSIP); Intramural Research Program of the NIH, NIAID FX We thank the residents of Doneguebougou for their kind permission to conduct the filming in their village; S. Doumbia, S. F. Traore, and R. Sakai of the Malaria Research and Training Center (MRTC), University of Bamako, for invaluable logistical assistance and discussion of this work; M. B. Toure and the GIS team at MRTC for the weather data from Banambani; R. Gwadz and F. Tokumasu of the Laboratory of Malaria and Vector Research, NIAID, for assistance with planning, support, and discussion; C. Reynolds for discussions on a visual approach to these data; C. Struchiner of the Fundacao Oswaldo Cruz and P. McQueen of the NIH for statistical advice; and C. Taylor and D. Earl of UCLA for valuable discussions. We acknowledge the support of the Bioinformatics and Scientific Information Technology Program (BSIP), NIAID OTIS for hosting materials related to this work. This research was Supported by the Intramural Research Program of the NIH, NIAID. NR 30 TC 23 Z9 23 U1 0 U2 10 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD MAR PY 2009 VL 46 IS 2 BP 227 EP 235 DI 10.1603/033.046.0207 PG 9 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 418QZ UT WOS:000264164800007 PM 19351073 ER PT J AU Rezgui, D Williams, C Savage, SA Prince, SN Zaccheo, OJ Jones, EY Crump, MP Hassan, AB AF Rezgui, Dellel Williams, Christopher Savage, Sharon A. Prince, Stuart N. Zaccheo, Oliver J. Jones, E. Yvonne Crump, Matthew P. Hassan, A. Bassim TI Structure and function of the human Gly1619Arg polymorphism of M6P/IGF2R domain 11 implicated in IGF2 dependent growth SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID II/MANNOSE 6-PHOSPHATE RECEPTOR; FACTOR-II RECEPTOR; LIGAND-BINDING; IGF-II/MANNOSE-6-PHOSPHATE RECEPTOR; CARBOHYDRATE-RECOGNITION; BETA-GALACTOSIDASE; MISSENSE MUTATIONS; COLORECTAL-CANCER; GENETIC-VARIATION; INSULIN AB The mannose 6-phosphate/IGF 2 receptor (IGF2R) is comprised of 15 extra-cellular domains that bind IGF2 and man nose 6-phosphate ligands. IGF2R transports ligands from the Golgi to the pre-lysosomal compartment and thereafter to and from the cell surface. IGF2R regulates growth, placental development, tumour suppression and signalling. The ligand IGF2 is implicated in the growth phenotype, where IGF2R normally limits bioavailability, such that loss and gain of IGF2R results in increased and reduced growth respectively. The IGF2R exon 34 (5002A>G) polymorphism (rs629849) of the IGF2 specific binding domain has been correlated with impaired childhood growth (A/A homozygotes). We evaluated the function of the Gly1619Arg non-synonymous amino acid modification of domain 11. NMR and X-ray crystallography structures located 1619 remote from the ligand binding region of domain 11. Arg1619 was located close to the fibronectin type 11 (FnII) domain of domain 13, previously implicated as a modifier of IGF2 ligand binding through indirect interaction with the AB loop of the binding cleft. However, comparison of binding kinetics of IGF2R, Gly1619 and Arg1619 to either IGF2 or mannose 6-phosphate revealed no differences in 'on' and 'off' rates. Quantitative PCR, (35)S pulse chase and flow cytometry failed to demonstrate altered gene expression, protein half-life and cell membrane distribution, suggesting the polymorphism had no direct effect on receptor function. Intronic polymorphisms were identified which may be in linkage disequilibrium with rs629849 in certain populations. Other potential IGF2R polymorphisms may account for the correlation with childhood growth, warranting further functional evaluation. Journal of Molecular Endocrinology (2009) 42, 341-356 C1 [Rezgui, Dellel; Prince, Stuart N.; Zaccheo, Oliver J.; Hassan, A. Bassim] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Tumor Growth Control Grp, Oxford OX3 9DS, England. [Williams, Christopher; Crump, Matthew P.] Univ Bristol, Sch Chem, Dept Organ & Biol Chem, Bristol BS8 1TS, Avon, England. [Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Jones, E. Yvonne] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Canc Res UK Receptor Struct Res Grp, Oxford OX3 7BN, England. RP Hassan, AB (reprint author), Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Tumor Growth Control Grp, Oxford OX3 9DS, England. EM bass.hassan@imm.ox.ac.uk RI Wiliams, Christopher/P-4904-2015; Savage, Sharon/B-9747-2015; Jones, Yvonne/J-2293-2016; OI Wiliams, Christopher/0000-0001-5806-9842; Savage, Sharon/0000-0001-6006-0740; Jones, Yvonne/0000-0002-3834-1893; Crump, Matthew/0000-0002-7868-5818 FU Cancer Research UK [C429, C375]; Wellcome Trust; NIH FX Supported by Cancer Research UK (C429, C375), Wellcome Trust and NIH. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 49 TC 13 Z9 13 U1 0 U2 4 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD MAR-APR PY 2009 VL 42 IS 3-4 BP 341 EP 356 DI 10.1677/JME-08-0154 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 530ZA UT WOS:000272630300015 PM 19208780 ER PT J AU Gunatilaka, AAL Bolzani, VD Newman, DJ AF Gunatilaka, A. A. Leslie Bolzani, Vanderlan da S. Newman, David J. TI Special Issue in Honor of Professor David G. I. Kingston SO JOURNAL OF NATURAL PRODUCTS LA English DT Biographical-Item C1 [Gunatilaka, A. A. Leslie] Univ Arizona, Tucson, AZ 85721 USA. [Bolzani, Vanderlan da S.] Sao Paulo State Univ, Araraquara, Brazil. [Newman, David J.] NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Gunatilaka, AAL (reprint author), Univ Arizona, Tucson, AZ 85721 USA. RI Bolzani, Vanderlan/C-2111-2012 OI Bolzani, Vanderlan/0000-0001-7019-5825 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2009 VL 72 IS 3 BP 325 EP 326 DI 10.1021/np900052p PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 425HM UT WOS:000264627600001 PM 19243191 ER PT J AU Meragelman, TL Scudiero, DA Davis, RE Staudt, LM McCloud, TG Cardellina, JH Shoemaker, RH AF Meragelman, Tamara L. Scudiero, Dominic A. Davis, R. Eric Staudt, Louis M. McCloud, Thomas G. Cardellina, John H., II Shoemaker, Robert H. TI Inhibitors of the NF-kappa B Activation Pathway from Cryptocarya rugulosa SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CYTOTOXIC FLAVONOIDS; STEREOCHEMISTRY; LAURACEAE AB The nuclear factor-kappa B (NF-kappa B) signaling pathway is constitutively active in many types of cancers and is a potential therapeutic target. Using a cell-based assay for stability of inhibitor of kappa B (I kappa B), a critical regulator of NF-kappa B activity, we found that an organic solvent extract of the plant Cryptocarya rugulosa inhibited constitutive NF-kappa B activity in human lymphoma cell lines. The active components were identified as rugulactone, a new alpha-pyrone (1), and the known cryptocaryone (2). Rugulactone was the more active compound, exhibiting up to 5-fold induction of I kappa B at 25 mu g/mL; maximal activity was observed with 10 h exposure of test cells to 1 or 2. C1 [Meragelman, Tamara L.; Cardellina, John H., II; Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. [Scudiero, Dominic A.] SAIC Frederick Inc, Mol Target Screening Lab, Frederick, MD USA. [Davis, R. Eric; Staudt, Louis M.] NCI, Metab Branch, Clin Res Ctr, Bethesda, MD 20892 USA. [McCloud, Thomas G.] SAIC Frederick Inc, Nat Prod Support Grp, Frederick, MD USA. RP Cardellina, JH (reprint author), ReevesGroup, 9374 Highlander Blvd, Walkersville, MD 21793 USA. EM jhcardellina@aol.com FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX We thank S. S. Kurian for recording the CD spectrum, L. Cartner for the IR spectrum, N. Whittaker for the HRMS, J. Klose for the NMR spectra, and M. Selby for assistance with the assays. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. N01-CO-12400. This research was supported [in part] by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 19 TC 36 Z9 36 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2009 VL 72 IS 3 BP 336 EP 339 DI 10.1021/np800350x PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 425HM UT WOS:000264627600003 PM 19093800 ER PT J AU O'Donnell, G Poeschl, R Zimhony, O Gunaratnam, M Moreira, JBC Neidle, S Evangelopoulos, D Bhakta, S Malkinson, JP Boshoff, HI Lenaerts, A Gibbons, S AF O'Donnell, Gemma Poeschl, Rosemarie Zimhony, Oren Gunaratnam, Mekala Moreira, Joao B. C. Neidle, Stephen Evangelopoulos, Dimitrios Bhakta, Sanjib Malkinson, John P. Boshoff, Helena I. Lenaerts, Anne Gibbons, Simon TI Bioactive Pyridine-N-oxide Disulfides from Allium stipitatum SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; MYCOBACTERIUM-TUBERCULOSIS; ANTIMYCOBACTERIAL ACTIVITY; ANTIBACTERIAL PRINCIPLE; FATTY-ACID; IDENTIFICATION; BACTEREMIA; INHIBITORS; ALKALOIDS; ALLICIN AB From Allium stipitatum, three pyridine-N-oxide alkaloids (1-3) possessing disulfide functional groups were isolated. The structures of these natural products were elucidated by spectroscopic means as 2-(methyldithio)pyridine-N-oxide (1), 2-[(methylthiomethyl)dithio]pyridine-N-oxide (2), and 2,2'-dithio-bis-pyridine-N-oxide (3). The proposed structure of 1 was confirmed by synthetic S-methylthiolation of commercial 2-thiopyridine-N-oxide. Compounds 1 and 2 are new natural products, and 3 is reported for the first time from an Allium species. All compounds were evaluated for activity against fast-growing species of Mycobacterium, methicillin-resistant Staphylococcus aureus, and a multidrug-resistant (MDR) variants of S. aureus. Compounds 1 and 2 exhibited minimum inhibitory concentrations (MICs) of 0.5-8 mu g/mL against these strains. A small series of analogues of 1 were synthesized in an attempt to optimize antibacterial activity, although the natural product had the most potent in vitro activity. In a whole-cell assay at 30 mu g/mL, 1 was shown to give complete inhibition of the incorporation of (14)C-labeled acetate into soluble fatty acids, indicating that it is potentially an inhibitor of fatty acid biosynthesis. In a human cancer cell line antiproliferative assay, 1 and 2 displayed IC(50) values ranging from 0.3 to 1.8 mu M with a selectivity index of 2.3 when compared to a human somatic cell line. Compound 1 was evaluated in a microarray analysis that indicated a similar mode of action to menadione and 8-quinolinol by interfering with the thioredoxin system and up-regulating the production of various heat shock proteins. This compound was also assessed in a mouse model for in vivo toxicity. C1 [O'Donnell, Gemma; Poeschl, Rosemarie; Gibbons, Simon] Univ London, Sch Pharm, Ctr Pharmacognosy & Phytotherapy, London WC1N 1AX, England. [Zimhony, Oren] Hebrew Univ, Div Infect Dis, Kaplan Med Ctr, Rehovot, Israel. [Gunaratnam, Mekala; Moreira, Joao B. C.; Neidle, Stephen] Univ London, CRUK Biomol Struct Grp, Sch Pharm, London WC1N 1AX, England. [Evangelopoulos, Dimitrios; Bhakta, Sanjib] Univ London, Birkbeck Coll, Sch Biol & Chem Sci, London WC1E 7HX, England. [Malkinson, John P.] Univ London, Sch Pharm, Dept Pharmaceut & Biol Chem, London WC1N 1AX, England. [Boshoff, Helena I.] NIAID, TB Res Sect, Immunogenet Lab, Rockville, MD 20852 USA. [Lenaerts, Anne] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Gibbons, S (reprint author), Univ London, Sch Pharm, Ctr Pharmacognosy & Phytotherapy, 29-39 Brunswick Sq, London WC1N 1AX, England. EM simon.gibbons@pharmacy.ac.uk RI Evangelopoulos, Dimitrios/F-8251-2013 OI Evangelopoulos, Dimitrios/0000-0003-0472-7576 FU Engineering and Physical Sciences Research Council; NIH; NIAID FX We thank the Engineering and Physical Sciences Research Council for the award of a doctoral scholarship to G.O. CRUK is thanked for support to M.G. and S.N. This work was funded, in part, by the Division of Intramural Research of NIH, NIAID. NR 31 TC 42 Z9 42 U1 1 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2009 VL 72 IS 3 BP 360 EP 365 DI 10.1021/np800572r PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 425HM UT WOS:000264627600007 PM 19093848 ER PT J AU Godecke, T Lankin, DC Nikolic, D Chen, SN van Breemen, RB Farnsworth, NR Pauli, GF AF Godecke, Tanja Lankin, David C. Nikolic, Dejan Chen, Shao-Nong van Breemen, Richard B. Farnsworth, Norman R. Pauli, Guido F. TI Guanidine Alkaloids and Pictet-Spengler Adducts from Black Cohosh (Cimicifuga racemosa) SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID TETRAHYDRO-BETA-CARBOLINE; OLIVE OIL; BIOSYNTHESIS; MECHANISM; ARGININE; HYDROXYTYROSOL; (-)-TRYPARGINE; CONSTITUENTS; METABOLISM; DEPRESSION AB As an extension of work on the recently discovered nitrogenous metabolites from Cimicifuga/Actaea species, three new guanidine alkaloids have been isolated and characterized from C. racemosa (syn. A. racemosa) roots. Of these, cyclo-cimipronidine (1) and cimipronidine methyl ester (2) are congeners of cimipronidine (3), whereas dopargine (5) is a derivative of dopamine. By employing NMR- and MS-guided chemodiversity profiling of a polar serotonergic (5-HT(gamma)) fraction, the guanidine alkaloids were initially detected in a clinical extract of black cohosh and were isolated along with a congener of salsolinol 4, 5, and 3-hydroxytyrosol 3-O-glucoside (7). The structures of 1, 2, and 5 were confirmed by 1D and 2D NMR spectroscopy as well as LC-MS and HRMS spectroscopy. A plausible biosynthetic relationship may be inferred between the homoproline-analogue cimipronidines and the dopamine-derived Cimicifuga alkaloids. These strongly basic and frequently zwitterionic nitrogenous metabolites contribute considerable chemical diversity to the polar serotonergic fraction of black cohosh. C1 [Pauli, Guido F.] Univ Illinois, UIC, NIH, Ctr Botan Dietary Supplements Res,Coll Pharm, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. RP Pauli, GF (reprint author), Univ Illinois, UIC, NIH, Ctr Botan Dietary Supplements Res,Coll Pharm, Chicago, IL 60612 USA. EM gfp@uic.edu OI Pauli, Guido/0000-0003-1022-4326; Godecke, Tanja/0000-0001-9188-1613 FU NIH [P50AT00155]; National Center for Complementary and Alternative Medicine (NCCAM) FX This study was supported by NIH grant P50AT00155 from the Office of Dietary Supplements (ODS) and the National Center for Complementary and Alternative Medicine (NCCAM). We gratefully acknowledge the assistance of Dr. C. M. Ireland, University.of Utah, who provided both the spectroscopic data (NMR and MS) and an authentic reference sample of the alkaloid, trypargine, for direct LC-MS comparison. Thanks are also due to Mr. A. Kotadia, University of Illinois at Chicago, for committed technical assistance with the online pH metering setup. ne contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Complementary and Alternative Medicine, the Office of Dietary Supplements, or the National Institutes of Health. NR 53 TC 14 Z9 14 U1 1 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2009 VL 72 IS 3 SI SI BP 433 EP 437 DI 10.1021/np8006952 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 425HM UT WOS:000264627600018 PM 19220011 ER PT J AU Beutler, JA Kang, MI Robert, F Clement, JA Pelletier, J Colburn, NH Mckee, TC Goncharova, E McMahon, JB Henrich, CJ AF Beutler, John A. Kang, Moon-Il Robert, Francis Clement, Jason A. Pelletier, Jerry Colburn, Nancy H. McKee, Tawnya C. Goncharova, Ekaterina McMahon, James B. Henrich, Curtis J. TI Quassinoid Inhibition of AP-1 Function Does Not Correlate with Cytotoxicity or Protein Synthesis Inhibition SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID NF-KAPPA-B; ANTI-CANCER AGENTS; CONSTITUENTS; BRUCEANTIN; SIMAROUBACEAE; ACTIVATION; PROMOTION; TARGETS; MODE AB Several quassinoids were identified in a high-throughput screening assay as inhibitors of the transcription factor AP-1. Further biological characterization revealed that while their effect was not specific to AP-1, protein synthesis inhibition and cell growth assays were inconsistent with a mechanism of simple protein synthesis inhibition. Numerous plant extracts from the plant family Simaroubaceae were also identified in the same screen; bioassay-guided fractionation of one extract (Ailanthus triphylla) yielded two known quassinoids, ailanthinone (3) and glaucarubinone (4), which were also identified in the pure compound screening procedure. C1 [Beutler, John A.; Clement, Jason A.; McKee, Tawnya C.; Goncharova, Ekaterina; McMahon, James B.; Henrich, Curtis J.] Natl Canc Inst, Mol Targets Dev Program, Frederick, MD 21702 USA. [Kang, Moon-Il; Colburn, Nancy H.] Natl Canc Inst, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. [Robert, Francis; Pelletier, Jerry] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. [Goncharova, Ekaterina] Data Management Serv Inc, Frederick, MD 21702 USA. [Henrich, Curtis J.] SAIC Frederick Inc, Basic Res Program, NCI Frederick, Frederick, MD 21702 USA. RP Beutler, JA (reprint author), Natl Canc Inst, Mol Targets Dev Program, Frederick, MD 21702 USA. EM beutlerj@mail.nih.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU National Cancer Institute, National Institutes of Health [NOI-CO-12400] FX We would like to thank D. D. Soejarto for identification of the Ailanthus specimen, T. McCloud for plant extract preparation, D. Newman for plant collection contracting, D. Covell for COMPARE analyses, and the Drug Synthesis & Chemistry Branch, DTP, NCI, for repository samples of quassinoids. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and funded in part by the Division of Cancer Treatment and Diagnosis, National Cancer Institute. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract NOI-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 36 TC 16 Z9 16 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2009 VL 72 IS 3 BP 503 EP 506 DI 10.1021/np800732n PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 425HM UT WOS:000264627600033 PM 19199792 ER PT J AU Wilberg, T Karterud, S Pedersen, G Urnes, O Costa, PT AF Wilberg, Theresa Karterud, Sigmund Pedersen, Geir Urnes, Oyvind Costa, Paul T. TI Nineteen-Month Stability of Revised NEO Personality Inventory Domain and Facet Scores in Patients With Personality Disorders SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Personality disorders; personality; five-factor model; NEO-PI-R; stability ID 5-FACTOR MODEL; TEMPORAL STABILITY; SELF-REPORTS; AGE-CHANGES; OLD-AGE; PI-R; TRAITS; PSYCHOTHERAPY; BORDERLINE; PSYCHOPATHOLOGY AB We lack knowledge of the temporal stability of major personality dimensions in patients with personality disorders (PDs). The Revised NEO Personality Inventory (NEO-PI-R) is a self-report instrument that operationalizes the Five-Factor Model of personality. This study investigated the relative stability, mean level stability, and individual level stability of the NEO-PI-R scores in patients with PDs (n = 393) and patients with symptom disorders only (n = 131). The NEO-PI-R was administered at admission to short-term day treatment and after an average of 19 months. The results showed a moderate to high degree of stability of NEO-PI-R scale scores with no substantial difference in stability between patients with and without PD. Changes in NEO-PI-R scores were associated with changes in symptom distress. Neuroticism was the least stable domain. The study indicates that the Five-Factor Model of personality dimensions and traits are fairly stable in patients with PDs. The lower stability of Neuroticism may partly be explained by its inherent state aspects. C1 [Wilberg, Theresa] Ullevaal Univ Hosp, Div Psychiat, Dept Res & Educ, N-0407 Oslo, Norway. [Karterud, Sigmund] Univ Oslo, Inst Psychiat, Oslo, Norway. [Karterud, Sigmund; Pedersen, Geir; Urnes, Oyvind] Ullevaal Univ Hosp, Div Psychiat, Dept Personal Psychiat, N-0407 Oslo, Norway. [Costa, Paul T.] NIA, Intramural Res Program, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Wilberg, T (reprint author), Ullevaal Univ Hosp, Div Psychiat, Dept Res & Educ, N-0407 Oslo, Norway. EM theresa.wilberg@medisin.uio.no OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS NR 46 TC 9 Z9 9 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 2009 VL 197 IS 3 BP 187 EP 195 DI 10.1097/NMD.0b013e3181923fa0 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 420BL UT WOS:000264263300008 PM 19282686 ER PT J AU Yang, J Shen, J AF Yang, Jehoon Shen, Jun TI Elevated endogenous GABA concentration attenuates glutamate-glutamine cycling between neurons and astroglia SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE GABA; Vigabatrin; Glutamate; Magnetic resonance spectroscopy ID GAMMA-AMINOBUTYRIC-ACID; MAGNETIC-RESONANCE-SPECTROSCOPY; ANTIDEPRESSANT/ANTIPANIC DRUG PHENELZINE; VIVO C-13 NMR; IN-VIVO; VINYL-GABA; AMINO-ACIDS; HUMAN BRAIN; RAT-BRAIN; MAJOR DEPRESSION AB In this study, the relationship between endogenous brain GABA concentration and glutamate-glutamine cycling flux (V (cyc)) was investigated using in vivo (1)H and (1)H{(13)C} magnetic resonance spectroscopy techniques. Graded elevations of brain GABA levels were induced in rat brain after administration of the highly specific GABA-transaminase inhibitor vigabatrin (gamma-vinyl-GABA). The glial-specific substrate [2-(13)C]acetate and (1)H{(13)C} magnetic resonance spectroscopy were used to measure V (cyc) at different GABA levels. Significantly reduced V (cyc) was found in rats pretreated with vigabatrin. The reduction in group mean V (cyc) over the range of GABA concentrations investigated in this study (1.0 +/- A 0.3-5.1 +/- A 0.5 mu mol/g) was found to be nonlinear: Delta V (cyc)/V (cyc) = [GABA (mu mol/g)](-0.35) - 1.0 (r (2) = 0.98). The results demonstrate that V (cyc) is modulated by endogenous GABA levels, and that glutamatergic and GABAergic interactions can be studied in vivo using noninvasive magnetic resonance spectroscopy techniques. C1 [Shen, Jun] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Yang, Jehoon] Samsung Biomed Res Inst, Seoul, South Korea. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Hlth Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU NIH; NIMH FX The authors are grateful to Mr. Christopher Johnson, Drs. Steve Li, Steve Fox and Su Xu for valuable help and Ms. Ioline Henter for editing the manuscript. This work was supported by the Intramural Research Program of the NIH, NIMH. NR 43 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD MAR PY 2009 VL 116 IS 3 BP 291 EP 300 DI 10.1007/s00702-009-0186-0 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 414XG UT WOS:000263897900004 PM 19184333 ER PT J AU Kreisl, TN Lassman, AB Mischel, PS Rosen, N Scher, HI Teruya-Feldstein, J Shaffer, D Lis, E Abrey, LE AF Kreisl, Teri N. Lassman, Andrew B. Mischel, Paul S. Rosen, Neal Scher, Howard I. Teruya-Feldstein, Julie Shaffer, David Lis, Eric Abrey, Lauren E. TI A pilot study of everolimus and gefitinib in the treatment of recurrent glioblastoma (GBM) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; mTOR; EGFR; PTEN ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; MALIGNANT GLIOMA; MAMMALIAN TARGET; MULTIFORME; RAPAMYCIN; INHIBITION; PATHWAY; TEMOZOLOMIDE; COMBINATION AB Twenty-two patients with recurrent glioblastoma (GBM) were prospectively treated with everolimus and gefitinib, designed to test the combined inhibition of mammalian target of rapamycin (mTOR) and epidermal growth factor receptor (EGFR) as part of a larger clinical trial. The primary endpoint was radiographic response rate. Secondary endpoints included progression-free survival and correlation of molecular profiles with treatment response. 36% of patients had stable disease and 14% a partial response; however, responses were not durable and only one patient was progression-free at six months. Radiographic changes were not well characterized by conventional response criteria, and implied differential effects of therapy within the tumor and/or antiangiogenic effects. EGFR and PTEN status did not clearly predict response to treatment. C1 [Lassman, Andrew B.; Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Kreisl, Teri N.] NCI, Neurooncol Branch, Bethesda, MD 20892 USA. [Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rosen, Neal; Scher, Howard I.; Shaffer, David] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Lis, Eric] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. RP Abrey, LE (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA. EM Abreyl@mskcc.org FU Novartis FX This study was supported in part by Novartis ( drug supply and funding) and Astra Zeneca ( drug supply). NR 26 TC 95 Z9 96 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAR PY 2009 VL 92 IS 1 BP 99 EP 105 DI 10.1007/s11060-008-9741-z PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 413LH UT WOS:000263794100014 PM 19018475 ER PT J AU Mezey, E Leker, RR Shahar, T Pastorino, S Szalayova, I Asemenew, B Key, S Parmelee, A Mayer, B Nemeth, K Bratincsak, A Toth, EZ AF Mezey, E. Leker, R. R. Shahar, T. Pastorino, S. Szalayova, I. Asemenew, B. Key, S. Parmelee, A. Mayer, B. Nemeth, K. Bratincsak, A. Toth, E. Z. TI CONTRIBUTION OF CIRCULATING TRANSPLANTED BONE MARROW CELLS TO RECOVERY AFTER STROKE IN MICE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Mezey, E.; Leker, R. R.; Shahar, T.; Pastorino, S.; Szalayova, I.; Asemenew, B.; Key, S.; Parmelee, A.; Mayer, B.; Nemeth, K.; Bratincsak, A.; Toth, E. Z.] NIH, Bethesda, MD 20892 USA. [Toth, E. Z.] SOTE, Budapest, Hungary. [Leker, R. R.] Hebrew Univ Jerusalem, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 25 EP 25 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800050 ER PT J AU Saha, RN Dudek, SM Pahan, K AF Saha, R. N. Dudek, S. M. Pahan, K. TI TNF-ALPHA PRECONDITIONING PROTECTS NEURONS VIA NEURON-SPECIFIC UPREGULATION OF CREB-BINDING PROTEIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Saha, R. N.; Pahan, K.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Dudek, S. M.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 67 EP 67 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800141 ER PT J AU Choi, SH Bosetti, F AF Choi, S. H. Bosetti, F. TI CYCLOOXYGENASE-1 AND-2 HAVE OPPOSITE ROLES IN MODULATING LPS-INDUCED LEUKOCYTE RECRUITMENT AND INFLAMMATORY RESPONSE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Choi, S. H.; Bosetti, F.] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 76 EP 76 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800159 ER PT J AU Harry, GJ Funk, J Kraft, A AF Harry, G. J. Funk, J. Kraft, A. TI CONTRIBUTION OF IL-6 IN EXERCISE INDUCED NEUROPROTECTION SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Harry, G. J.; Funk, J.; Kraft, A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Funk, J.] Univ S Carolina, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 93 EP 93 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800205 ER PT J AU Szuchet, S Nielsen, JA Lovas, G De Velasco, JM Maric, D Hudson, LD AF Szuchet, S. Nielsen, J. A. Lovas, G. De Velasco, Martinez J. Maric, D. Hudson, L. D. TI THE GENETIC SIGNATURE OF PERINEURONAL OLIGODENDROCYTES REVEALS THEIR UNIQUE PHENOTYPE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Szuchet, S.] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Nielsen, J. A.; De Velasco, Martinez J.; Hudson, L. D.] NINDS, NIH, Sect Dev Genet, Bethesda, MD 20892 USA. [Lovas, G.] Sammelweis Univ, Dept Neurol, Budapest, Hungary. [Maric, D.] NINDS, NIH, Neurophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 110 EP 111 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800249 ER PT J AU Kraft, AD Turmel, GJ Bolton, M Lo, DC Harry, GJ AF Kraft, A. D. Turmel, G. J. Bolton, M. Lo, D. C. Harry, G. J. TI PROLIFERATIVE MICROGLIA LOCALIZE TO NEURITES OF STRIATAL NEURONS EXPRESSING MUTANT HUNTINGTIN AND CONTRIBUTE TO DEGENERATION SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Kraft, A. D.; Harry, G. J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Turmel, G. J.; Bolton, M.; Lo, D. C.] Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 120 EP 120 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800273 ER PT J AU McPherson, CA Aoyama, M Grissom, SF Gohlke, J Harry, GJ AF McPherson, C. A. Aoyama, M. Grissom, S. F. Gohlke, J. Harry, G. J. TI DIFFERENTIAL INFLAMMATORY GENE EXPRESSION IN YOUNG AND MIDDLE AGED MICE DURING INJURY-INDUCED HIPPOCAMPAL NEUROGENESIS. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Aoyama, M.] Nagoya City Univ, Nagoya, Aichi, Japan. [McPherson, C. A.] Univ N Carlolina Chapel Hill, Curriculum Toxicol, Chapel Hill, NC USA. [McPherson, C. A.; Grissom, S. F.; Gohlke, J.; Harry, G. J.] NIEHS, NIH, DHHS, Res Triangle Pk, NC USA. OI Gohlke, Julia/0000-0002-6984-2893 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 122 EP 122 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800279 ER PT J AU Aid, S Silva, AC Candelario-Jalil, E Rosenberg, GA Bosetti, F AF Aid, S. Silva, A. C. Candelario-Jalil, E. Rosenberg, G. A. Bosetti, F. TI CYCLOOXYGENASE-2 NULL MICE SHOW INCREASED BLOOD-BRAIN BARRIER DISRUPTION DURING LIPOPOLYSACCHARIDE-INDUCED NEUROINFLAMMATION SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Aid, S.; Bosetti, F.] NIA, BPMS, NIH, Bethesda, MD 20892 USA. [Silva, A. C.] NINDS, LFMI, NIH, Bethesda, MD 20892 USA. [Candelario-Jalil, E.; Rosenberg, G. A.] Univ New Mexico, Albuquerque, NM 87131 USA. RI Silva, Afonso/A-7129-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 129 EP 129 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800294 ER PT J AU Bosetti, F Palumbo, S Toscano, CD AF Bosetti, F. Palumbo, S. Toscano, C. D. TI CUPRIZONE INDUCED-DEMYELINATION IN MICE ALTERS BRAIN EXPRESSION OF GENES INVOLVED IN ARACHIDONIC ACID METABOLISM SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Bosetti, F.; Palumbo, S.; Toscano, C. D.] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RI palumbo, sara/B-1603-2013 OI palumbo, sara/0000-0002-3809-6058 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 142 EP 142 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800328 ER PT J AU Gomes, CARV Simoes, PF Canas, PM Quiroz, C Sebastiao, AM Ferre, S Cunha, RA Ribeiro, JA AF Gomes, Catarina A. R. V. Simoes, Patricia F. Canas, Paula M. Quiroz, Cesar Sebastiao, Ana M. Ferre, Sergi Cunha, Rodrigo A. Ribeiro, Joaquim A. TI GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A(2A) receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE A(2A) receptor; adenosine; cortico-striatal pathway; glial cell line-derived neurotrophic factor; glutamate; rearranged during transfection; GDNF family receptor alpha 1 ID HIPPOCAMPAL SYNAPTIC-TRANSMISSION; LONG-TERM POTENTIATION; HUNTINGTONS-DISEASE; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; BRAIN; NEURONS; RAT; HETEROMERS; ANTAGONIST AB Glial cell line-derived neurotrophic factor (GDNF) affords neuroprotection in Parkinson's disease in accordance with its ability to bolster nigrostriatal innervation. We previously found that GDNF facilitates dopamine release in a manner dependent on adenosine A(2A) receptor activation. As motor dysfunction also involves modifications of striatal glutamatergic innervation, we now tested if GDNF and its receptor system, Ret (rearranged during transfection) and GDNF family receptor alpha 1 controlled the cortico-striatal glutamatergic pathway in an A(2A) receptor-dependent manner. GDNF (10 ng/mL) enhanced (by approximate to 13%) glutamate release from rat striatal nerve endings, an effect potentiated (up to approximate to 30%) by the A(2A) receptor agonist CGS 21680 (10 nM) and prevented by the A(2A) receptor antagonist, SCH 58261 (50 nM). Triple immunocytochemical studies revealed that Ret and GDNF family receptor alpha 1 were located in 50% of rat striatal glutamatergic terminals (immunopositive for vesicular glutamate transporters-1/2), where they were found to be co-located with A(2A) receptors. Activation of the glutamatergic system upon in vivo electrical stimulation of the rat cortico-striatal input induced striatal Ret phosphorylation that was prevented by pre-treatment with the A(2A) receptor antagonist, MSX-3 (3 mg/kg). The results provide the first functional and morphological evidence that GDNF controls cortico-striatal glutamatergic pathways in a manner largely dependent on the co-activation of adenosine A(2A) receptors. C1 [Gomes, Catarina A. R. V.; Sebastiao, Ana M.; Ribeiro, Joaquim A.] Univ Lisbon, Inst Pharmacol & Neurosci, Fac Med, P-1649028 Lisbon, Portugal. [Gomes, Catarina A. R. V.; Sebastiao, Ana M.; Ribeiro, Joaquim A.] Univ Lisbon, Inst Mol Med, Unit Neurosci, P-1649028 Lisbon, Portugal. [Simoes, Patricia F.; Canas, Paula M.; Cunha, Rodrigo A.] Univ Coimbra, Inst Biochem, Fac Med, Ctr Neurosci, Coimbra, Portugal. [Quiroz, Cesar; Ferre, Sergi] NIDA, Intramural Res Program, Dept Hlth & Human Serv, NIH, Baltimore, MD USA. RP Sebastiao, AM (reprint author), Univ Lisbon, Inst Pharmacol & Neurosci, Fac Med, P-1649028 Lisbon, Portugal. EM anaseb@fm.ul.pt RI Ferre, Sergi/K-6115-2014; Canas, Paula/Q-2101-2015; Cunha, Rodrigo/E-7475-2015; Gomes, Catarina/K-6218-2015; OI Ferre, Sergi/0000-0002-1747-1779; Canas, Paula/0000-0002-4091-6406; Cunha, Rodrigo/0000-0003-2550-6422; Gomes, Catarina/0000-0001-9415-2109; Ribeiro, Joaquim/0000-0002-9330-3507; Simoes, Ana Patricia/0000-0003-2937-7015; Sebastiao, Ana M/0000-0001-9030-6115 FU Fundacao para a Ciencia e para a Tecnologia, Portugal; Intramural Research funds of the National Institute on Drug Abuse; NIH, USA; Faculdade de Medicina, Universidade de Lisboa, Portugal FX This study was supported by Fundacao para a Ciencia e para a Tecnologia, Portugal (work at Lisboa and Coimbra) and by the Intramural Research funds of the National Institute on Drug Abuse, NIH, USA and Faculdade de Medicina, Universidade de Lisboa, Portugal. NR 42 TC 22 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 IS 5 BP 1208 EP 1219 DI 10.1111/j.1471-4159.2009.05876.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 402WW UT WOS:000263044800011 PM 19141075 ER PT J AU Insel, TR AF Insel, Thomas R. TI Foreword for inaugural issue of Journal of Neurodevelopmental Disorders SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Editorial Material ID X MENTAL-RETARDATION; MICE C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 13 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1866-1947 J9 J NEURODEV DISORD JI J. Neurodev. Disord. PD MAR PY 2009 VL 1 IS 1 BP 2 EP 3 DI 10.1007/s11689-009-9005-z PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 558FR UT WOS:000274727000001 PM 21547619 ER PT J AU Bachis, A Biggio, F Major, E Mocchetti, I AF Bachis, Alessia Biggio, Francesca Major, Eugene O. Mocchetti, Italo TI M- and T-tropic HIVs Promote Apoptosis in Rat Neurons SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Article DE acquired immune deficiency syndrome-associated dementia complex; gp120; neuronal apoptosis; CXCR4; CCR5; AMD3100; DAPTA ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTOR CXCR4; LASER CAPTURE MICRODISSECTION; CEREBELLAR GRANULE CELLS; AIDS DEMENTIA COMPLEX; NECROSIS-FACTOR-ALPHA; NEUROTROPHIC FACTOR; HUMAN BRAIN; NMDA RECEPTOR AB Neuronal loss, reactive astrocytes, and other abnormalities are seen in the brain of individuals with acquired immune deficiency syndrome-associated Dementia Complex (ADC). Human immunodeficiency virus-1 (HIV-1) is believed to be the main agent causing ADC. However, little is known about the molecular and cellular mechanisms of HIV-1 neurotoxicity considering that HIV-1 does not infect post-mitotic neurons and that viral load does not necessarily correlate with ADC. Various viral proteins, such as the envelope protein gp120 and the transcription activator Tat, have been shown to induce neuronal apoptosis through direct and indirect mechanisms both in vitro and in vivo. Progeny HIV-1 virions can also cause neuronal death. However, it has not been fully established yet whether HIV-1 promotes neuronal apoptosis by a direct mechanism. To explore the neurotoxic effect of HIV-1, we exposed rat cerebellar granule cells and cortical neurons in culture to two different strains of HIV-1, IIIB and BaL, T- and M-tropic strains that utilize CXCR4 and CCR5 coreceptors, respectively, to infect cells. We observed that both viruses elicit a time-dependent apoptotic cell death in these cultures without inducing a productive infection as determined by the absence of the core protein of HIV-1, p24, in cell lysates. Instead, neurons were gp120 positive, suggesting that the envelope protein is shed by the virus and then subsequently internalized by neurons. The CXCR4 receptor antagonist AMD3100 or the CCR5 receptor inhibitor d-Ala-peptide T-amide blocked HIV IIIB and HIV Bal neurotoxicity, respectively. In contrast, the N-methyl-d-aspartate receptor blocker MK801 failed to protect neurons from HIV-mediated apoptosis, suggesting that HIV-1 neurotoxicity can be initiated by the viral protein gp120 binding to neuronal chemokine receptors. C1 [Bachis, Alessia; Biggio, Francesca; Mocchetti, Italo] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20814 USA. RP Mocchetti, I (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, Res Bldg,Room EP04,Box 571464, Washington, DC 20057 USA. EM moccheti@georgetown.edu FU Intramural NIH HHS [Z01 NS002851-16]; NINDS NIH HHS [NS 040670, R01 NS040670] NR 71 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD MAR PY 2009 VL 4 IS 1 BP 150 EP 160 DI 10.1007/s11481-008-9141-3 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 409JU UT WOS:000263502800017 PM 19034668 ER PT J AU Damiano, DL DeJong, SL AF Damiano, Diane L. DeJong, Stacey L. TI A Systematic Review of the Effectiveness of Treadmill Training and Body Weight Support in Pediatric Rehabilitation SO JOURNAL OF NEUROLOGIC PHYSICAL THERAPY LA English DT Review DE cerebral palsy; spinal cord injury; Down syndrome; gait; walking; therapy AB Background and Purpose: Given the extensive literature on body weight-supported treadmill training (BWSTT) in adult rehabilitation, a systematic review was undertaken to explore the strength, quality, and conclusiveness of evidence supporting use of treadmill training and body weight support in those with pediatric motor disabilities. A secondary goal was to ascertain whether protocol guidelines for BWSTT are available to guide pediatric physical therapy practice. Methods: The database search included MEDLINE, EMBASE, CINAHL Plus, PEDro, Cochrane Library databases, and ERIC from January 1, 1980 to May 31, 2008 for articles that included treadmill training and body weight support for individuals under 21 years of age, with or at risk for a motor disability. We identified 277 unique articles from which 29 met all inclusion criteria. Results: Efficacy of treadmill training in accelerating walking development in Down syndrome has been well demonstrated. Evidence supporting efficacy or effectiveness of BWSTT in pediatric practice for improving gait impairments and level of activity and participation in those with cerebral palsy, spinal cord injury, and other central nervous system disorders remains insufficient, although many studies noted positive effects. Discussion and Conclusion: The original evidence demonstrates efficacy of BWSTT in children with Down syndrome, but largescale controlled trials are needed to support the use of BWSTT in other pediatric subgroups. Increased use of randomized designs, studies with treadmill training-only groups, and dosage studies are needed before practice guidelines can be formulated. Neural changes in response to training warrant exploration, especially given the capacity for change in developing nervous systems. C1 [Damiano, Diane L.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [DeJong, Stacey L.] Washington Univ, Sch Med, Movement Sci Program, Program Phys Therapy, St Louis, MO USA. RP Damiano, DL (reprint author), NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. EM damianod@cc.nih.gov RI Damiano, Diane/B-3338-2010 OI Damiano, Diane/0000-0002-2770-5356 FU NIH [T32HD007434]; Foundation for Physical Therapy, Inc FX Supported, in part, by NIH T32HD007434 and by a scholarship from the Foundation for Physical Therapy, Inc (to S.L.D.). NR 47 TC 69 Z9 70 U1 6 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1557-0576 J9 J NEUROL PHYS THER JI J. Neurol. Phys. Ther. PD MAR PY 2009 VL 33 IS 1 BP 27 EP 44 DI 10.1097/NPT.0b013e31819800e2 PG 18 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA V23BM UT WOS:000208318300004 PM 19265768 ER PT J AU Schulz, JB Di Prospero, NA Fischbeck, K AF Schulz, Jorg B. Di Prospero, Nicholas A. Fischbeck, Kenneth TI Clinical experience with high-dose idebenone in Friedreich ataxia SO JOURNAL OF NEUROLOGY LA English DT Article DE Friedreich ataxia; idebenone; rare disorders; clinical trials; cardiomyopathy; neurologic; ICARS; FARS; oxidative stress ID PLACEBO-CONTROLLED TRIAL; TERM-FOLLOW-UP; HYPERTROPHY; DEFICIT AB Several reports in the literature describe the effects of low-dose (5 mg/kg/day) idebenone in significantly reducing cardiac hypertrophy in patients with Friedreich ataxia. However, the effects of idebenone on neurological function have not been reliably determined in these studies; when neurological parameters were reported, results were often inconclusive, usually because of subject heterogeneity and lack of adequate statistical power. In two of these studies, some patients showed beneficial effects of idebenone on their cardiomyopathy only when the dose was increased, prompting the systematic investigation of higher doses of idebenone. Following a phase 1 dose escalation study, a phase 2 tolerability and efficacy trial with low, intermediate, and high doses of idebenone was conducted. The results suggested that treatment with intermediate- and high-dose idebenone had beneficial effects on neurological symptoms. On the basis of these results, two phase 3 trials have been initiated, one in the United States with young ambulatory patients and one in Europe without limits on age and disease severity. C1 [Schulz, Jorg B.] Rhein Westfal TH Aachen, Univ Med Ctr, Dept Neurol, D-52074 Aachen, Germany. [Di Prospero, Nicholas A.] Johnson & Johnson Pharmaceut, Res & Dev, Raritan, NJ USA. [Fischbeck, Kenneth] NINDS, Neurogenet Branch, NIH, Bethesda, MD USA. RP Schulz, JB (reprint author), Rhein Westfal TH Aachen, Univ Med Ctr, Dept Neurol, Pauwelsstr 30, D-52074 Aachen, Germany. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU Intramural NIH HHS [ZIA NS003037-03] NR 19 TC 25 Z9 27 U1 0 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAR PY 2009 VL 256 BP 42 EP 45 DI 10.1007/s00415-009-1008-x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 418VH UT WOS:000264177000008 PM 19283350 ER PT J AU Hattori, N Shibasaki, H Wheaton, L Wu, T Matsuhashi, M Hallett, M AF Hattori, Noriaki Shibasaki, Hiroshi Wheaton, Lewis Wu, Tao Matsuhashi, Masao Hallett, Mark TI Discrete Parieto-Frontal Functional Connectivity Related to Grasping SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; INTRAPARIETAL SULCUS; MENTAL ROTATION; IDEOMOTOR APRAXIA; MACAQUE MONKEY; RHESUS-MONKEY; BRAIN-AREAS; CORTEX; MOTOR; FMRI AB Hattori N, Shibasaki H, Wheaton L, Wu T, Matsuhashi M, Hallett M. Discrete parieto-frontal functional connectivity related to grasping. J Neurophysiol 101: 1267-1282, 2009. First published December 24, 2008; doi:10.1152/jn.90249.2008. The human inferior parietal lobule (IPL) is known to have neuronal connections with the frontal lobe, and these connections have been shown to be associated with sensorimotor integration to perform various types of movement such as grasping. The function of these anatomical connections has not been fully investigated. We studied the judgment of graspability of objects in an event-related functional MRI study in healthy subjects, and found activation in two different regions within IPL: one in the left dorsal IPL extending to the intraparietal sulcus and the other in the left ventral IPL. The former region was activated only in the judgment of graspable objects, whereas the latter was activated in the judgment of both graspable and nongraspable objects although the activation was greater for the graspable objects. Psychophysiological interaction analysis showed that these regions had similar but discrete functional connectivity to the lateral and medial frontal cortices. In relation to this particular task, the left dorsal IPL had functional connectivity to the left ventral premotor cortex, supplementary motor area (SMA) and right cerebellar cortex, whereas the left ventral IPL had functional connectivity to the left dorsolateral prefrontal cortex and pre-SMA. These findings suggest that the connection from the left dorsal IPL is associated specifically with automatic flow of information about grasping behavior. By contrast, the connection from the left ventral IPL might be related to motor imagination or enhanced external attention to the presented stimuli. C1 [Hattori, Noriaki; Shibasaki, Hiroshi; Wheaton, Lewis; Wu, Tao; Matsuhashi, Masao; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Shibasaki, H (reprint author), Takeda Gen Hosp, Fushimi Ku, Kyoto 6011495, Japan. EM shib@kuhp.kyoto-u.ac.jp RI Wheaton, Lewis /B-4482-2009 OI Wheaton, Lewis /0000-0003-0771-0294 FU Intramural Research Program of National Institute of Neurological Disorders and Stroke FX The study was supported by the Intramural Research Program of National Institute of Neurological Disorders and Stroke. NR 63 TC 19 Z9 19 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2009 VL 101 IS 3 BP 1267 EP 1282 DI 10.1152/jn.90249.2008 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 412SW UT WOS:000263745500014 PM 19109459 ER PT J AU Alipanah, N Varadhan, R Sun, K Ferrucci, L Fried, LP Semba, RD AF Alipanah, N. Varadhan, R. Sun, K. Ferrucci, L. Fried, L. P. Semba, R. D. TI LOW SERUM CAROTENOIDS ARE ASSOCIATED WITH A DECLINE IN WALKING SPEED IN OLDER WOMEN SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE Aging; carotenoids; disability; walking speed; women ID HUMAN SKELETAL-MUSCLE; PLASMA SELENIUM CONCENTRATIONS; COMMUNITY-DWELLING ADULTS; MEDITERRANEAN-STYLE DIET; GROWTH-FACTOR-I; CARDIOVASCULAR-DISEASE; PHYSICAL PERFORMANCE; FOLLOW-UP; ENDOTHELIAL DYSFUNCTION; ATHEROSCLEROSIS RISK AB Background and Objectives: Walking speed is an important measure of physical performance that is predictive of disability and mortality. The relationship of dietary factors to changes in physical performance has not been well characterized in older adults. The aim was to determine whether total serum carotenoid concentrations, a marker for fruit and vegetable intake, and serum selenium are related to changes in walking speed in older women. Subjects and Methods: The relationship between total serum carotenoids and selenium measured at baseline, 12, and 24 months follow-up and walking speed assessed at baseline and every six months for 36 months was examined in 687 moderately to severely disabled women, 65 years or older, living in the community. Results: Mean total serum carotenoids were associated with mean walking speed over three years of follow-up (P = 0.0003) and rate of change of walking speed (P = 0.007) in multivariate linear regression models adjusting for age, body mass index, and chronic diseases. Mean serum selenium was associated with mean walking speed over three years of follow-up (P = 0.0003) but not with the rate of change of walking speed (P = 0.26). Conclusions: These findings suggest that a higher fruit and vegetable intake, as indicated by higher total serum carotenoid concentrations, may be protective against a decline in walking speed in older women. C1 [Alipanah, N.; Varadhan, R.; Sun, K.; Fried, L. P.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Ferrucci, L.; Semba, R. D.] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu FU National Institute on Aging [R01 AG027012, AG11703-01A1]; NIH-NCRR; OPD-GCRC [RR00722]; NIA [N01-AG12112] FX This work was supported by National Institute on Aging Grant R01 AG027012, AG11703-01A1, NIH-NCRR, OPD-GCRC grant RR00722, NIA Contract N01-AG12112, and the Intramural Research Program, National Institute on Aging, NIH. NR 46 TC 29 Z9 29 U1 0 U2 5 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD MAR PY 2009 VL 13 IS 3 BP 170 EP 175 PG 6 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 443WJ UT WOS:000265941200002 PM 19262947 ER PT J AU Moon, HS Lee, HG Seo, JH Chung, CS Kim, TG Choi, YJ Cho, CS AF Moon, Hyun-Seuk Lee, Hong-Gu Seo, Ji-Hye Chung, Chung-Soo Kim, Tae-Gyu Choi, Yun-Jaie Cho, Chong-Su TI Antiobesity effect of PEGylated conjugated linoleic acid on high-fat diet-induced obese C57BL/6J (ob/ob) mice: attenuation of insulin resistance and enhancement of antioxidant defenses SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE PEGylated conjugated linoleic acid; C57BL/6J (ob/ob) mouse; Lipid reduction; Insulin resistance; Anti-oxidant defense ID BODY-COMPOSITION; HEPATIC STEATOSIS; ADIPOCYTE DIFFERENTIATION; PEROXISOME PROLIFERATOR; LIPID-ACCUMULATION; ENERGY-METABOLISM; GENE-EXPRESSION; CALCIUM SALTS; LIVER-INJURY; MILK-FAT AB This study was designed to test that dietary conjugated linoleic acids (CLA) used in a mixture of cis-9,trans-11 and trans-10, cis-12 isomers (40% each in weight) coupled to poly(ethylene glycol) (PEG) as PEGylated CLA (PCLA) act as mediators inducing or inhibiting specific metabolic pathways in high-fat (HF)-fed obese C57BL/6J (ob/ob) mice. After an acclimatization period of 7 days, animals were given a normal (control) or HF diet, the latter being added either alone (HF) or with CLA, PEG or PCLA for 6 weeks. Although the food intakes were not different among the dietary groups, final body weights were significantly lower in the HF-PCLA group than in the HF group. Also the HF-PCLA diet strongly prevented the dramatic increase in blood low-density lipoprotein cholesterol observed with the HF diet, with no difference in high-density lipoprotein cholesterol between control, HF and HF-PCLA treatments. Furthermore, homeostasis model assessment levels showed a marked decrease in HF-PCLA-fed mice, preventing the increase found in mice fed the HF diet, and suggesting that PCLA lowered insulin resistance in HF-mice. The liver steatosis observed in mice fed the HF diet was also prevented by PCLA. Interestingly, the activity of mitochondrial glutathione peroxidase was increased by PCLA, which may enhance antioxidant defenses. Overall, PCLA exerted its beneficial effects through reduction of lipid accumulation and attenuation of insulin resistance induced by the HF diet in obese C57BL/6J (ob/ob) mice, which might confer to these products antiobesity properties in other species. (C) 2009 Elsevier Inc. All rights reserved. C1 [Moon, Hyun-Seuk; Lee, Hong-Gu; Seo, Ji-Hye; Choi, Yun-Jaie; Cho, Chong-Su] Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151921, South Korea. [Moon, Hyun-Seuk] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA. [Chung, Chung-Soo] Chungbuk Natl Univ, Coll Agr Life & Environm Sci, Cheongju 361763, South Korea. [Kim, Tae-Gyu] Agribrands Purina Korea Inc, Seoul 463808, South Korea. RP Cho, CS (reprint author), Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151921, South Korea. EM chocs@plaza.snu.ac.kr RI Choi, Yunjaie /B-4697-2014; Moon, Hyun-Seuk/G-8576-2015 OI Moon, Hyun-Seuk/0000-0002-5216-2090 FU Agricultural R&D Promotion Center [2006-0053]; Brain Korea 21 [BK21] FX This work was supported by the Agricultural R&D Promotion Center (2006-0053). We thank the National Instrumentation Center for Environmental Management for providing 1H NMR measurement and Research Institute of Pharmaceutical Sciences (RIPS) for providing SOD, GSH and GPX measurement. Ji-Hye Seo was supported by Brain Korea 21 (BK21) grant. NR 47 TC 14 Z9 16 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD MAR PY 2009 VL 20 IS 3 BP 187 EP 194 DI 10.1016/j.jnutbio.2008.02.001 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 408AW UT WOS:000263406400006 PM 18602810 ER PT J AU O'Mara, AM Germain, DS Ferrell, B Bornemann, T AF O'Mara, Ann M. Germain, Diane St. Ferrell, Betty Bornemann, Tami TI Challenges to and Lessons Learned from Conducting Palliative Care Research SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; symptom management; end of life; research AB In response to a 2005 solicitation from the U.S. National Institutes of Health, 16 investigators received funding to test interventions that would reduce the barriers that prevent Cancer Patients from receiving adequate and appropriate symptom management therapies. Since the awards have been issued, the investigators have met two times and have identified a number of challenges to implementing their re respective studies. A survey was conducted that focused oil. their experiences with hiring and retaining study personnel, gaining Institutional Review Board approval, incurring unexpected costs, challenges to accruing participants, and a listin of standard measures used in hte study. The survey was complted online by the Principal Investigator for each project in late 2006 and the initioal results were confirmed one year later by resending the initial survey and by a follow-up telephone call. All but one Principal investgator completed the survey. Obaining Institutional Review Board approval, hiring and recruiting research personnel, establishing subcontracts, adn accruing research subjects were the primary challenges experienced by the investigators. This palliative care solicitation achieved more than its original intent of stimulating research in overcoming barriers to delivering cancer symptom management, palliative care and end-of-life care. From a surevy o the challenges and issues that emerged from their projects, grantees were able to identify specific hurdles and their unique solutions that may help other ivestigators as they plan their program of research. J Pain Symptom Manage 2009; 37 : 387-394. (C) 2009 U.S. Cancer Pain Relief Committee. Published Elsever Inc. All rights reserved. C1 [O'Mara, Ann M.] NCI, Community Oncol & Prevent Trials Res Grp, Bethesda, MD 20892 USA. [Ferrell, Betty; Bornemann, Tami] City Hope Comprehens Canc Ctr, Duarte, CA USA. RP O'Mara, AM (reprint author), NCI, Community Oncol & Prevent Trials Res Grp, 6130 Execut Blvd,EPN 2010, Bethesda, MD 20892 USA. EM omaraa@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 14 TC 18 Z9 18 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 2009 VL 37 IS 3 BP 387 EP 394 DI 10.1016/j.jpainsymman.2008.03.014 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 414VP UT WOS:000263893600013 PM 18715749 ER PT J AU Rodrigue, JR Balistreri, W Haber, B Jonas, MM Mohan, P Molleston, JP Murray, KF Narkewicz, MR Rosenthal, P Smith, LJ Schwarz, KB Robuck, P Barton, B Gonzalez-Peralta, RP AF Rodrigue, James R. Balistreri, William Haber, Barbara Jonas, Maureen M. Mohan, Parvathi Molleston, Jean P. Murray, Karen F. Narkewicz, Michael R. Rosenthal, Philip Smith, Lesley J. Schwarz, Kathleen B. Robuck, Patricia Barton, Bruce Gonzalez-Peralta, Regino P. TI Impact of Hepatitis C Virus Infection on Children and Their Caregivers: Quality of Life, Cognitive, and Emotional Outcomes SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE clinical trial; HCV; parents; quality of life ID PREVALENCE; DEPRESSION; INTERFERON; RIBAVIRIN AB Objective: Hepatitis C virus (HCV) infection is associated with decreased quality of life (QOL) and neurocognitive dysfunction in adults, but little is known about its impact on children and their caregivers. Patients and Methods: We Studied the QOL, behavioral, emotional, and cognitive functioning of 114 treatment-naive children with HCV enrolled in a placebo-con trolled, randomized, multisite clinical trial evaluating peginterferon alpha-2a alone or with ribavirin. Baseline assessment included measures of children's QOL, cognitive functioning, behavioral adaptation, and depression. Caregivers' QOL also was assessed. Results: Relative to published normative data, caregivers were more likely to believe that their children's health was poor and would likely worsen (t = 3.93; P < 0.0001), and reported higher concern about their children's health status (t = 6.63; P < 0.0001) and that this concern limited family activities (t = 2.45; P < 0.01); they also viewed their children as having more internalizing behavioral problems (t = 1.98; P < 0.05). Only 2 (2%) children had a score in the clinically depressed range. Children with HCV had worse cognitive functioning than the normative sample but significantly better functioning than children with attention-deficit/hyperactivity disorder. Caregivers' QOL scores did not differ significantly from the normative sample, but infected mothers had lower QOL than noninfected caregivers. Caregivers were highly distressed about their children's medical circumstances. Conclusions: Although HCV infection, in its early stages, does not lead to global impairment in QOL, cognitive, behavioral, or emotional functioning in children, it is associated with higher caregiver stress and strain on the family system, and it may be associated with some cognitive changes in children. JPGN 48:341-347, 2009. C1 [Rodrigue, James R.] Beth Israel Deaconess Med Ctr, Transplant Ctr, Boston, MA 02115 USA. [Balistreri, William] Childrens Hosp Med Ctr, Cincinnati, OH USA. [Haber, Barbara] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Jonas, Maureen M.] Childrens Hosp Boston, Boston, MA USA. [Mohan, Parvathi] George Washington Univ, Washington, DC USA. [Molleston, Jean P.] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. [Murray, Karen F.] Childrens Hosp & Reg Med Ctr, Seattle, WA USA. [Narkewicz, Michael R.] Childrens Hosp, Denver, CO 80218 USA. [Rosenthal, Philip] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Smith, Lesley J.] Columbia Univ, New York, NY USA. [Schwarz, Kathleen B.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Robuck, Patricia] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Barton, Bruce] Maryland Med Res Inst, Baltimore, MD USA. [Gonzalez-Peralta, Regino P.] Univ Florida, Gainesville, FL USA. RP Rodrigue, JR (reprint author), Beth Israel Deaconess Med Ctr, Transplant Ctr, 110 Francis St,7th Floor, Boston, MA 02115 USA. EM jrrodrig@bidmc.harvard.edu OI Barton, Bruce/0000-0001-7878-8895 FU National Institute of Diabetes and Digestive and Kidney Diseases; Food and Drug Administration [IUOIDKO67767-01]; Hoffman-La Roche FX Supported by a cooperative agreement between the National Institute of Diabetes and Digestive and Kidney Diseases and the Food and Drug Administration, contract number IUOIDKO67767-01, and by Hoffman-La Roche (Study medications and central laboratory costs). NR 34 TC 27 Z9 30 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAR PY 2009 VL 48 IS 3 BP 341 EP 347 PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 414SP UT WOS:000263885800019 PM 19242286 ER PT J AU Cao, Y Rao, SD Phillips, TM Umbach, DM Bernbaum, JC Archer, JI Rogan, WJ AF Cao, Yang Rao, Sanmati D. Phillips, Terry M. Umbach, David M. Bernbaum, Judy C. Archer, Janet I. Rogan, Walter J. TI Are Breast-fed Infants More Resilient? Feeding Method and Cortisol in Infants SO JOURNAL OF PEDIATRICS LA English DT Article AB The effect of feeding method on stress hormone levels in infants is unknown. We studied infants from birth to I year and found salivary cortisol 40% higher in breast-fed infants compared with formula-fed infants. The higher cortisol levels among breast-fed children may be involved in the analgesic effect of breastfeeding. (J Pediatr 2009;154:452-4) C1 [Cao, Yang; Rogan, Walter J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Umbach, David M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Rao, Sanmati D.] Emory Univ, Sch Med, Atlanta, GA USA. [Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. [Bernbaum, Judy C.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Archer, Janet I.] Social & Sci Syst Inc, Survey & Epidemiol Serv Div, Durham, NC USA. [Archer, Janet I.] Coda Inc, Res Triangle Pk, NC USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,FedEx UPS 111 TW Alexan, Res Triangle Pk, NC 27709 USA. EM rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU Intramural NIH HHS [Z01 ES044006-07, Z01 ES044006-08]; NICHD NIH HHS [2 T32 HD 007446] NR 12 TC 8 Z9 8 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2009 VL 154 IS 3 BP 452 EP 454 DI 10.1016/j.jpeds.2008.09.025 PG 3 WC Pediatrics SC Pediatrics GA 418RM UT WOS:000264166100031 PM 19874763 ER PT J AU Gellar, L Nansel, TR AF Gellar, Lauren Nansel, Tonja R. TI High and Low Glycemic Index Mixed Meals and Blood Glucose in Youth with Type 2 Diabetes or Impaired Glucose Tolerance SO JOURNAL OF PEDIATRICS LA English DT Article ID INSULIN-RESISTANCE; OBESITY; DIET AB This cross-over pilot study tested blood glucose response to low and high glycemic index meals in 12 obese youth with type 2 diabetes or impaired glucose tolerance. Participants demonstrated significantly lower mean daytime blood glucose and it trend toward lower variability, suggesting a clinically relevant impact of reducing glycemic index. (J Pediatr 2009;154:455-8) C1 [Gellar, Lauren; Nansel, Tonja R.] Eurice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Nansel, TR (reprint author), 6100 Execut Blvd,Room 7B 13R,MSC 7500, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS [Z01 HD008805-01] NR 12 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2009 VL 154 IS 3 BP 455 EP 458 DI 10.1016/j.jpeds.2008.09.040 PG 4 WC Pediatrics SC Pediatrics GA 418RM UT WOS:000264166100032 PM 19874764 ER PT J AU Halloran, DR McClure, E Chakraborty, H Chomba, E Wright, LL Carlo, WA AF Halloran, D. R. McClure, E. Chakraborty, H. Chomba, E. Wright, L. L. Carlo, W. A. TI Birth asphyxia survivors in a developing country SO JOURNAL OF PERINATOLOGY LA English DT Article DE asphyxia neonatorum; child development; neurologic manifestations; developing countries; Zambia; infant ID NEONATAL ENCEPHALOPATHY; CHILDREN; TERM; RELIABILITY; DIFFICULTY; NEWBORN; INFANTS; DEATHS; DIFFER AB Objective: Determine the baseline incidence of birth asphyxia in neonatal intensive care unit (NICU) survivors in a developing country and the early neurodevelopmental outcomes of such infants. Study Design: This cross-sectional, prospective study collected diagnostic and examination findings on all infants seen in the University of Zambia NICU follow-up clinic over a 4-week period. Result: Of the 182 infants, 42 (23%) had a clinical diagnosis of birth asphyxia. Of 42 infants with birth asphyxia, 13 (31%) had an abnormal neurologic examination during the clinic visit; in contrast, 13 of 141 infants without birth asphyxia (9%) had an abnormal examination (odds ratio 4.4, 95% confidence interval: 1.8, 10.4). Conclusion: Birth asphyxia survivors account for almost a quarter of NICU survivors in a developing country and half of those with an abnormal neurologic examination. Studies are necessary to determine the percent of birth asphyxia survivors who have permanent motor and cognitive disabilities. C1 [Halloran, D. R.] St Louis Univ, Dept Pediat, St Louis, MO 63104 USA. [McClure, E.; Chakraborty, H.] RTI Int, Dept Stat & Epidemiol, Res Triangle Pk, NC USA. [Chomba, E.] Univ Teaching Hosp, Lusaka, Zambia. [Wright, L. L.] NICHHD, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. [Carlo, W. A.] Univ Alabama, Dept Pediat, Birmingham, AL USA. RP Halloran, DR (reprint author), St Louis Univ, Dept Pediat, 1465 S Grand Blvd, St Louis, MO 63104 USA. EM dhallor2@slu.edu FU Global Network for Women's and Children's Health Research [HD 434646-03]; National Institute of Health; The Bill and Melinda Gates Foundation; BRAIN Planning Grant for the Developing World [TW006703-02]; National Institute of Child Health and Development; UAB [KL2 RR024994-ICTS] FX This study was supported by Global Network for Women's and Children's Health Research ( HD 434646-03) - National Institute of Health, The Bill and Melinda Gates Foundation; BRAIN Planning Grant for the Developing World ( TW006703-02) - National Institute of Child Health and Development; UAB Perinatal Health and Human Development Pilot Grant; KL2 RR024994-ICTS Multidisciplinary Clinical Research Career Development Program. NR 32 TC 14 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD MAR PY 2009 VL 29 IS 3 BP 243 EP 249 DI 10.1038/jp.2008.192 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 414VO UT WOS:000263893500012 PM 19037228 ER PT J AU Pan, H Mukhopadhyay, P Rajesh, M Patel, V Mukhopadhyay, B Gao, B Hasko, G Pacher, P AF Pan, Hao Mukhopadhyay, Partha Rajesh, Mohanraj Patel, Vivek Mukhopadhyay, Bani Bin Gao Hasko, Gyoergy Pacher, Pal TI Cannabidiol Attenuates Cisplatin-Induced Nephrotoxicity by Decreasing Oxidative/Nitrosative Stress, Inflammation, and Cell Death SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RECEPTOR-INDEPENDENT MECHANISM; INDUCED RENAL INJURY; ANTITUMOR-ACTIVITY; NITRIC-OXIDE; PEROXYNITRITE; CANNABINOIDS; CONSTITUENT; EXPRESSION; PROTECTS; KIDNEY AB The platinum compound cisplatin is one of the most potent chemotherapy agents available to treat various malignancies. Nephrotoxicity is a common complication of cisplatin chemotherapy, which involves increased oxidative and nitrosative stress, limiting its clinical use. In this study, we have investigated the effects of a nonpsychoactive cannabinoid cannabidiol, which was reported to exert antioxidant effects and has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in patients in a mouse model of cisplatin-induced nephropathy. Cisplatin induced increased expression of superoxide-generating enzymes RENOX (NOX4) and NOX1, enhanced reactive oxygen species generation, inducible nitric-oxide synthase expression, nitrotyrosine formation, apoptosis (caspase-3/7 activity, DNA fragmentation, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining), poly(ADP-ribose) polymerase activity, and inflammation (tumor necrosis factor-alpha and interleukin-1 beta) in the kidneys of mice, associated with marked histopathological damage and impaired renal function (elevated serum blood urea nitrogen and creatinine levels) 72 h after the administration of the drug. Treatment of mice with cannabidiol markedly attenuated the cisplatin-induced oxidative/nitrosative stress, inflammation, and cell death in the kidney, and it improved renal function. Thus, our results suggest that cannabidiol may represent a promising new protective strategy against cisplatin-induced nephrotoxicity. C1 [Pan, Hao] Zhejiang Univ, Coll Med, Dept Urol, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China. [Pan, Hao; Mukhopadhyay, Partha; Rajesh, Mohanraj; Patel, Vivek; Mukhopadhyay, Bani; Bin Gao; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Pan, Hao; Mukhopadhyay, Partha; Rajesh, Mohanraj; Patel, Vivek; Mukhopadhyay, Bani; Bin Gao; Pacher, Pal] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU National Institutes of Health National Institute on Alcohol Abuse and Alcoholism FX This study was supported by the Intramural Research Program of National Institutes of Health National Institute on Alcohol Abuse and Alcoholism. NR 40 TC 84 Z9 86 U1 0 U2 9 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 MAR PY 2009 VL 328 IS 3 BP 708 EP 714 DI 10.1124/jpet.108.147181 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 410DL UT WOS:000263556900004 PM 19074681 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-4-Methylphenyl)-2-Aminopropane in Rhesus Monkeys: Antagonism and Apparent pA(2) Analyses SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HALLUCINOGENIC DRUGS; 5-HT1A RECEPTORS; RATS; AGONISTS; DOM; NALTREXONE; MORPHINE; VALUES AB Discriminative stimulus effects of the serotonin (5-HT) receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) have been studied in rats and, more recently, in rhesus monkeys. This study examined DOM, 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and dipropyltryptamine hydrochloride (DPT) alone and in combination with three antagonists, MDL100907 [(+/-) 2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol]], ketanserin [3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-1H-quinazoline-2,4-dione], and ritanserin [6-[2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl] ethyl]-7-methyl-[1,3] thiazolo[2,3-b]pyrimidin-5-one], to identify the 5-HT receptor subtype(s) that mediates the discriminative stimulus effects of these 5-HT receptor agonists. Four adult rhesus monkeys discriminated between 0.32 mg/kg s. c. DOM and vehicle while responding under a fixed ratio 5 schedule of stimulus shock termination. DOM, 2C-T-7, and DPT dose-dependently increased responding on the DOM-associated lever. MDL100907 (0.001-0.01 mg/kg), ketanserin (0.01-0.1 mg/kg), and ritanserin (0.01-0.1 mg/kg) each shifted the dose-response curves of DOM, 2C-T-7, and DPT rightward in a parallel manner. Schild analysis of each drug combination was consistent with a simple, competitive, and reversible interaction. Similar apparent affinity (pA(2)) values were obtained for MDL100907 in combination with DOM (8.61), 2C-T-7 (8.58), or DPT (8.50), for ketanserin with DOM (7.67), 2C-T-7 (7.75), or DPT (7.71), and for ritanserin with DOM (7.65), 2C-T-7 (7.75), or DPT (7.65). Potency of antagonists in this study was correlated with binding affinity at 5-HT2A receptors and not at 5-HT2C or alpha(1) adrenergic receptors. This study used Schild analysis to examine receptor mechanisms mediating the discriminative stimulus effects of hallucinogenic drugs acting at 5-HT receptors; results provide quantitative evidence for the predominant, if not exclusive, role of 5-HT2A receptors in the discriminative stimulus effects of DOM, 2C-T-7, and DPT in rhesus monkeys. 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.] NIDA, Chem Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu RI Li, Jun-Xu/K-9192-2013 FU National Institutes of Health [DA17918] FX This work was supported in part by the Intramural Research program of the National Institutes of Health National Institute on Drug Abuse and National of Institutes of Health National Institute on Alcohol Abuse and Alcoholism; and by National Institutes of Health National Institute on Drug Abuse [Grant DA17918]. NR 27 TC 6 Z9 6 U1 0 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 MAR PY 2009 VL 328 IS 3 BP 976 EP 981 DI 10.1124/jpet.108.145458 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 410DL UT WOS:000263556900034 PM 19098164 ER PT J AU Kuo, J Schmitz, KH Evenson, KR McKenzie, TL Jobe, JB Rung, AL Gittelsohn, J Pate, RR AF Kuo, JoAnn Schmitz, Kathryn H. Evenson, Kelly R. McKenzie, Thomas L. Jobe, Jared B. Rung, Ariane L. Gittelsohn, Joel Pate, Russell R. TI Physical and Social Contexts of Physical Activities Among Adolescent Girls SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE environment; 3-day physical activity recall; out-of-school ID HEALTH PROMOTION; AFRICAN-AMERICAN; CAUCASIAN GIRLS; YOUTH; ENVIRONMENT; PROGRAMS; AGE AB Background: With limited opportunities for physical activity during school hours, it is important to understand the contexts of physical activities done outside of school time. Given the importance of physical and social aspects of environments, the purpose of this study was to describe where and with whom girls participate in physical activities outside of school. Methods: Participants were 1925 sixth-grade girls in the Trial of Activity for Adolescent Girls (TAAG). At baseline, they completed a 3-day physical activity recall (3DPAR), reporting the main activity performed during 30-minute intervals and the physical and social contexts of physical activities. Results: The most frequently reported physical activities done outside of school time were house chores, walking (for transportation or exercise), dance, basketball, playing with younger children, and running or jogging. The most common location for these activities was at home or in the neighborhood. With the exception of household chores, these activities were typically done with at least one other person. Conclusions: Interventions that pro-mote physical activities that can be done at or around home or developing supportive social networks for physical activity would be consistent with the current physical activity contexts of adolescent girls. C1 [Kuo, JoAnn] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. [Schmitz, Kathryn H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Evenson, Kelly R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA. [McKenzie, Thomas L.] San Diego State Univ, Sch Exercise & Nutr Sci, San Diego, CA 92182 USA. [Jobe, Jared B.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Rung, Ariane L.] Louisiana State Univ, Sch Publ Hlth, Program Epidemiol, New Orleans, LA 70112 USA. [Gittelsohn, Joel] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. [Pate, Russell R.] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. RP Kuo, J (reprint author), Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. RI Schmitz, Kathryn/B-7154-2011; Loureiro, Nuno/I-6400-2012 OI Loureiro, Nuno/0000-0002-1166-3219 FU NHLBI NIH HHS [U01 HL066845, HL-66852, HL-66853, HL-66855, HL-66856, HL-66857, HL-66858, U01 HL066852, U01 HL066853, U01 HL066855, U01 HL066856, U01 HL066857, U01 HL066858, U01HL-66845] NR 26 TC 16 Z9 16 U1 1 U2 11 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAR PY 2009 VL 6 IS 2 BP 144 EP 152 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 625XR UT WOS:000279930600002 PM 19420391 ER PT J AU Shen, JX Tu, B Yakel, JL AF Shen, Jian-xin Tu, Bin Yakel, Jerrel L. TI Inhibition of alpha 7-containing nicotinic ACh receptors by muscarinic M-1 ACh receptors in rat hippocampal CA1 interneurones in slices SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID STRATUM-ORIENS INTERNEURONS; ACETYLCHOLINE-RECEPTORS; CA2+ PERMEABILITY; CHOLINERGIC INNERVATION; PARASYMPATHETIC NEURONS; SYMPATHETIC NEURONS; SYNAPTIC PLASTICITY; MYENTERIC NEURONS; MODULATION; ACTIVATION AB Cys-loop ligand-gated nicotinic ACh receptors (nAChRs) and G protein-coupled muscarinic ACh receptors (mAChRs) are expressed on rat hippocampal interneurones where they can regulate excitability, synaptic communication and cognitive function. Even though both nAChRs and mAChRs appear to co-localize to the same interneurones, it is not clear whether there is crosstalk between them. We utilized patch-clamp techniques to investigate this issue in rat hippocampal CA1 interneurones in slices under conditions where synaptic transmission was blocked. The alpha 7 nAChR-mediated currents were activated by choline, and when the activation of this receptor was preceded by the activation of the M-1 mAChR subtype, the amplitude of alpha 7 responses was significantly reduced in a rapidly reversible and voltage-independent manner, without any change in the kinetics of responses. This M-1 mAChR-mediated inhibition of alpha 7 nAChRs was through a PLC-, calcium- and PKC-dependent signal transduction cascade. These data show that M-1 mAChRs and alpha 7 nAChRs are functionally co-localized on individual rat hippocampal interneurones where the activation of these particular mAChRs inhibits alpha 7 nAChR function. This information will help to understand how these cholinergic receptor systems might be regulating neuronal excitability in the hippocampus in a manner that has relevance for synaptic plasticity and cognition. C1 [Shen, Jian-xin; Tu, Bin; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU NIH FX We would like to thank C. Erxleben and S. Gentile for advice in preparing the manuscript. Research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 46 TC 10 Z9 10 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 1 PY 2009 VL 587 IS 5 BP 1033 EP 1042 DI 10.1113/jphysiol.2008.167593 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 412YJ UT WOS:000263759800008 PM 19124535 ER PT J AU Andersen, JF Pham, VM Meng, ZJ Champagne, DE Ribeiro, JMC AF Andersen, John F. Pham, Van M. Meng, Zhaojing Champagne, Donald E. Ribeiro, Jos M. C. TI Insight into the Sialome of the Black Fly, Simulium vittatum SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE Simulium vittatum; black fly; sialotranscriptomes; salivary gland transcriptome; sialome; proteome; hematophagy; onchocerciasis ID ADULT FEMALE MOSQUITO; SALIVARY-GLAND TRANSCRIPTS; RICH SECRETORY PROTEINS; O-GLYCOSYLATION SITES; VIRUS NEW-JERSEY; SAND FLY; LUTZOMYIA-LONGIPALPIS; AEDES-AEGYPTI; IXODES-SCAPULARIS; ANOPHELES-GAMBIAE AB Adaptation to vertebrate blood feeding includes development of a salivary "magic potion" that can disarm host hemostasis and inflammatory reactions. Within the lower Diptera, a vertebrate blood-sucking mode evolved in the Psychodidae (sand flies), Culicidae (mosquitoes), Ceratopogonidae (biting midges), Simuliidae (black flies), and the frog-feeding Corethrellidae. Sialotranscriptome analyses from several species of mosquitoes and sand flies and from one biting midge indicate divergence in the evolution of the blood-sucking salivary potion, manifested in the finding of many unique proteins within each insect family, and even genus. Gene duplication and divergence events are highly prevalent, possibly driven by vertebrate host immune pressure. Within this framework, we describe the sialome (from Greek sialo, saliva) of the black fly Simulium vittatum and discuss the findings within the context of the protein families found in other blood-sucking Diptera. Sequences and results of Blast searches against several protein family databases are given in Supplemental Tables S1 and S2, which can be obtained from http://exon.niaid.nih.gov/transcriptome/S_vittatum/T1/SV-tb1.zip and http://exon.niaid.nih.gov/transcriptome/S_vittatum/T2/SV-tb2.zip. C1 [Andersen, John F.; Pham, Van M.; Ribeiro, Jos M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Meng, Zhaojing] Natl Canc Inst, SAIC Frederick Inc, Lab Prote & Analyt Technol, NIH, Frederick, MD USA. [Champagne, Donald E.] Univ Georgia, Dept Entomol, Athens, GA 30602 USA. RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E32, Rockville, MD 20852 USA. EM jribeiro@nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU National Institutes of Health [NO1-CO-12400] FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the government of the United States of America. We are grateful to Elmer Gray and Dr. Ray Noblet, University of Georgia, for allowing generous access to the black fly colony, and to NIAID intramural editor Brenda Rae Marshall for assistance. NR 106 TC 29 Z9 30 U1 1 U2 4 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 MAR PY 2009 VL 8 IS 3 BP 1474 EP 1488 DI 10.1021/pr8008429 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 416WA UT WOS:000264035000036 PM 19166301 ER PT J AU Zwang, NA Hoffert, JD Pisitkun, T Moeller, HB Fenton, RA Knepper, MA AF Zwang, Nicholas A. Hoffert, Jason D. Pisitkun, Tratrak Moeller, Hanne B. Fenton, Robert A. Knepper, Mark A. TI Identification of Phosphorylation-Dependent Binding Partners of Aquaporin-2 Using Protein Mass Spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE tandem mass spectrometry; phosphoproteomics; chaperone; affinity chromatography ID MEDULLARY COLLECTING DUCT; WATER CHANNEL AQUAPORIN-2; LONG-TERM REGULATION; SURFACE EXPRESSION; PROTEOMIC ANALYSIS; AQP2 TRAFFICKING; EPITHELIAL-CELLS; VASOPRESSIN; COMPLEX; KIDNEY AB Vasopressin-mediated control of water permeability in the renal collecting duct occurs in part through regulation of the distribution of aquaporin-2 (AQP2) between the apical plasma membrane and intracellular membrane compartments. Phosphorylation of Ser-256 at AQP2's cytoplasmic COOH-terminus is well-accepted as a critical step for translocation. The aim of this study was to identify binding partners to phosphorylated versus nonphosphorylated forms of the AQP2 COOH-terminus via a targeted comparative proteomic approach. Cytosol from inner medullary collecting ducts isolated from rat kidneys was incubated with "bait" peptides, representing the COOH-terminal AQP2 tail in its nonphosphorylated and phosphorylated forms, to capture differentially bound proteins prior to LC-MS/MS analysis. Mass spectrometric results were confirmed by immunoblotting. Immunoprecipitation was performed using an AQP2 COOH-terminal antibody combined with immunblotting against the proposed binding partners to demonstrate interactions with native AQP2. Our studies confirmed previously identified interactions between AQP2 and hsc70, hsp70-1 and -2, as well as annexin II. These proteins were found to bind less to the Ser-256-phosphorylated AQP2 than to the nonphosphorylated form. In contrast, another heat shock protein, hsp70-5 (BiP/grp78), bound to phosphorylated AQP2 more avidly than to nonphosphorylated AQP2. Immunogold EM studies demonstrated that BiP is present not only in the ER but also in the cytoplasm and apical plasma membrane of rat collecting duct cells. Furthermore, confocal immunofluorescence studies showed partial colocalization of BiP with AQP2 in non-ER compartments. These results suggest that phosphorylation of AQP2 at Ser-256 may regulate AQP2 trafficking in part by mediating differential binding of hsp70 family proteins to the COOH-terminal tail. C1 [Zwang, Nicholas A.; Hoffert, Jason D.; Pisitkun, Tratrak; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Moeller, Hanne B.; Fenton, Robert A.] Univ Aarhus, Water & Salt Ctr, Aarhus, Denmark. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Room 6N260, Bethesda, MD 20892 USA. EM knepperm@nhlbi.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU Marie Curie Intra-European Fellowship; EU 7th Framework; Novo Nordisk Foundation; Danish Medical Research Foundation; Danish National Research Foundation (Danmarks Grandforskriingsfond); National Heart, Lung, and Blood Institute [Z01-HL-01285-KE] FX We are grateful to Grzegorz Piszczek, of the National Heart, Lung, and Blood Institute Laboratory of Biochemistry, for his assistance with CD spectrometry. Protein mass spectrometry was carried out in the Proteomics Core Facility of the NHLBI Division of Intramural Research. We thank Inger-Merete Paulsen and Else-Merete Locke for expert technical assistance in immunolabeling experiments. Nicholas Zwang is supported by Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program. Robert A. Fenton is supported by a Marie Curie Intra-European Fellowship, The EU 7th Framework, The Novo Nordisk Foundation, and the Danish Medical Research Foundation. The Water and Salt Research Center at the University of Aarhus was established and supported by the Danish National Research Foundation (Danmarks Grandforskriingsfond). This work was also supported in part by the intramural budget of the National Heart, Lung, and Blood Institute (Z01-HL-01285-KE). NR 56 TC 28 Z9 29 U1 0 U2 1 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 MAR PY 2009 VL 8 IS 3 BP 1540 EP 1554 DI 10.1021/pr800894p PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 416WA UT WOS:000264035000041 PM 19209902 ER PT J AU Preskorn, SH Drevets, WC AF Preskorn, Sheldon H. Drevets, Wayne C. TI Neuroscience Basis of Clinical Depression: Implications for Future Antidepressant Drug Development SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE clinical depression; neuroscience; antidepressant drug development; brain imaging; hippocampus; amygdala; genetics ID D-ASPARTATE ANTAGONIST; MAJOR DEPRESSION; HIPPOCAMPAL NEUROGENESIS; PAROXETINE TREATMENT; GLUCOSE-METABOLISM; BED NUCLEUS; RECEPTOR; STRESS; NEUROBIOLOGY; SEROTONIN AB This column reviews progress in our understanding of the neuroanatomy, pathophysiology, and genetics underlying clinical depression. Such understanding is fundamental to the ability to rationally identify the neural regulatory processes involved and develop drugs specifically targeted to those processes. The goal of the column is to help clinicians better conceptualize the nature of depressive illness and its treatment and educate their patients about these issues. (Journal of Psychiatric Practice 2009;15:125-132) C1 [Preskorn, Sheldon H.] Univ Kansas, Sch Med Wichita, Dept Psychiat, Lawrence, KS 66045 USA. [Preskorn, Sheldon H.] Clin Res Inst, Wichita, KS USA. [Drevets, Wayne C.] NIH, Sect Neuroimaging Mood & Anxiety Disorders, Div Intramural Res Programs, Bethesda, MD 20892 USA. RP Preskorn, SH (reprint author), Univ Kansas, Sch Med Wichita, Dept Psychiat, Lawrence, KS 66045 USA. RI Preskorn, Sheldon/L-9839-2016 NR 48 TC 7 Z9 9 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAR PY 2009 VL 15 IS 2 BP 125 EP 132 PG 8 WC Psychiatry SC Psychiatry GA 426PZ UT WOS:000264721500006 PM 19339846 ER PT J AU Zhang, H Chen, HF Li, ZH AF Zhang, Hong Chen, Hanfeng Li, Zhaohai TI Large sample interval mapping method for genetic trait loci in finite regression mixture models SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Backcross design; Binomial mixture; Generalized linear regression mixture; Identifiability; Intercross design; Likelihood ratio test; Logistic regression mixture; Normal mixture; Poisson mixture ID LIKELIHOOD RATIO TEST; HOMOGENEITY AB This article investigates the large sample interval mapping method for genetic trait loci (GTL) in a finite non-linear regression mixture model. The general model includes most commonly used kernel functions, such as exponential family mixture, logistic regression mixture and generalized linear mixture models, as special cases. The populations derived from either the backcross or intercross design are considered. In particular, unlike all existing results in the literature in the finite mixture models, the large sample results presented in this paper do not require the boundness condition on the parametric space. Therefore, the large sample theory presented in this article possesses general applicability to the interval mapping method of GTL in genetic research. The limiting null distribution of the likelihood ratio test statistics can be utilized easily to determine the threshold values or p-values required in the interval mapping. The limiting distribution is proved to be free of the parameter values of null model and free of the choice of a kernel function. Extension to the multiple marker interval GTL detection is also discussed. Simulation study results show favorable performance of the asymptotic procedure when sample sizes are moderate. (c) 2008 Elsevier B.V. All rights reserved. C1 [Chen, Hanfeng] Bowling Green State Univ, Dept Math & Stat, Bowling Green, OH 43403 USA. [Zhang, Hong] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Li, Zhaohai] NCI, NIH, Biostat Branch, Div Canc Epidemiol & Genet,DHHS,EPS, Bethesda, MD 20892 USA. RP Chen, HF (reprint author), Bowling Green State Univ, Dept Math & Stat, Bowling Green, OH 43403 USA. EM hchen@bgsu.edu NR 23 TC 0 Z9 0 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 MAR 1 PY 2009 VL 139 IS 3 BP 764 EP 779 DI 10.1016/j.jspi.2008.03.041 PG 16 WC Statistics & Probability SC Mathematics GA 389AE UT WOS:000262061300007 ER PT J AU Sheng, Y Tsai-Morris, CH Li, J Dufau, ML AF Sheng, Yi Tsai-Morris, Chon-Hwa Li, Jie Dufau, Maria L. TI Lessons from the gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS) null mouse model: A role in steroidogenesis, but not result in X-ALD phenotype SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 18th International Symposium of the Journal of Steroid Biochemistry and Molecular Biology CY SEP 18-21, 2008 CL Seefeld, AUSTRIA DE GR-LACS (gonadotropin-regulated long chain acyl-CoA synthetase); X-ALD (X-linked adrenoleukodystrophy); Lipidosin; Bubblegum; Fatty acids; Testosterone; Leydig cell; Gonadotropin desensitization; Aging ID DESENSITIZED LEYDIG-CELLS; ACID TRANSPORT PROTEIN-4; LINKED ADRENOLEUKODYSTROPHY; FATTY-ACIDS; MICE; GENE; BUBBLEGUM; INACTIVATION; DISRUPTION; EXPRESSION AB Gonadotropin-regulated long chain fatty acid Acyl-CoA synthetase (GR-LACS), is a member of the LACS family that is regulated by gonadotropin in the rat Leydig cell (LC). Its mouse/human homologs, lipidosin/bubblegum, have been suggested to participate in X-linked adrenoleukodystrophy (X-ALD), an adreno/neurodegenerative disorder with accumulation of very long chain fatty acids (VLCFA) in tissues and plasma. To further gain insights into its regulatory function, a GR-LACS/lipidosin null mouse was generated. No apparent phenotypic abnormalities were observed in the X-ALD target tissues (brain, testis, adrenal). Nuclear inclusions seen in mice >15 month-old, were present in LC of 9 month-old GR-LACS(-/-) mice. LC of the null mice showed refractoriness to the gonadotropin-induced desensitization of testosterone production that is observed in adult animals. LCFAs were moderately increased in the testis, ovary and brain, but not in the adrenal gland of GR-LACS(-/-) mice, with no major changes in VLCFA. No change in LACS activity was observed in these tissues, suggesting a compensatory mechanism exhibited by other LACS members. The GR-LACS(-/-) model did not support its association with X-ALD. These studies revealed a role of GR-LACS in reducing the aging process of the LC, and its participation in gonadotropin-induced testicular desensitization of testosterone production. Published by Elsevier Ltd. C1 [Sheng, Yi; Tsai-Morris, Chon-Hwa; Li, Jie; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHD, Sect Mol Endocrinol, ERRB, PDEGEN,NIH, Bldg 49,Room 6A28,49 Convent Dr, Bethesda, MD 20892 USA. EM dufaum@mail.nh.gov NR 38 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD MAR PY 2009 VL 114 IS 1-2 BP 44 EP 56 DI 10.1016/j.jsbmb.2008.12.011 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 437DH UT WOS:000265465900007 PM 19167491 ER PT J AU Asarnow, JR Emslie, G Clarke, G Wagner, KD Spirito, A Vitiello, B Iyengar, S Shamseddeen, W Ritz, L Birmaher, B Ryan, N Kennard, B Mayes, T DeBar, L McCracken, J Strober, M Suddath, R Leonard, H Porta, G Keller, M Brent, D AF Asarnow, Joan Rosenbaum Emslie, Graham Clarke, Greg Wagner, Karen Dineen Spirito, Anthony Vitiello, Benedetto Iyengar, Satish Shamseddeen, Wael Ritz, Louise Birmaher, Boris Ryan, Neal Kennard, Betsy Mayes, Taryn DeBar, Lynn McCracken, James Strober, Michael Suddath, Robert Leonard, Henrietta Porta, Giovanna Keller, Martin Brent, David TI Treatment of Selective Serotonin Reuptake Inhibitor-Resistant Depression in Adolescents: Predictors and Moderators of Treatment Response SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE depression; adolescents; treatment-resistant; cognitive-behavioral therapy ID RANDOMIZED CONTROLLED-TRIAL; COLLABORATIVE RESEARCH-PROGRAM; MAJOR DEPRESSION; CLINICAL-TRIALS; PSYCHOTHERAPY; CHILDREN; SCALE; PHARMACOTHERAPY; INTERVENTIONS; RELIABILITY AB Objective: To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we conducted a randomized controlled trial evaluating alternative treatment strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with medication change was associated with higher rates of positive response to short-term (12-week) treatment than medication alone. This study examines predictors and moderators of treatment response, with the goal of informing efforts to match youths to optimal treatment strategies. Method: Youths who had not improved during an adequate SSRI trial (N = 334) were randomized to an alternative SSRI, an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses examined predictors and moderators of treatment response. Results: Less severe depression, less family conflict, and absence of nonsuicidal self-injurious behavior predicted better treatment response status. Significant moderators of response to CBT + medication (combined) treatment were number of comorbid disorders and abuse history; hopelessness was marginally significant. The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders (particularly attention-deficit/hyperactivity disorder and anxiety disorders), no abuse history, and lower hopelessness. Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer prestudy pharmacotherapy. Conclusions: Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders. Given the additional costs of adding CBT to medication, consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(3):330-339. C1 [Asarnow, Joan Rosenbaum] Univ Calif Los Angeles, Semel Inst, Dept Psychiat, Los Angeles, CA 90024 USA. [Iyengar, Satish; Shamseddeen, Wael; Birmaher, Boris; Ryan, Neal; Porta, Giovanna; Brent, David] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Emslie, Graham; Kennard, Betsy; Mayes, Taryn] Univ Texas SW Med Ctr Dallas, Dallas, TX USA. [Clarke, Greg; DeBar, Lynn] Kaiser Permanente Ctr Hlth Sci, Oakland, CA USA. [Wagner, Karen Dineen] Univ Texas Med Branch, Galveston, TX USA. [Spirito, Anthony; Keller, Martin] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. [Vitiello, Benedetto; Ritz, Louise] NIMH, Bethesda, MD USA. RP Asarnow, JR (reprint author), Univ Calif Los Angeles, Semel Inst, Dept Psychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM jasarnow@mednet.ucla.edu RI Espinosa, Daniel/B-7285-2012 FU NIMH [MH61835, MH161856, MH61864, MH61869, MH61958, MH62014, MH66371] FX This study was supported by NIMH grants MH61835 (Pittsburgh), MH161856 (Galveston), MH61864 (UCLA), MH61869 (Portland), MH61958 (Dallas), and MH62014 (Brown) and the Advanced Center for Early-Onset Mood and Anxiety Disorders (MH66371, PI: D. B.). NR 41 TC 86 Z9 87 U1 2 U2 32 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2009 VL 48 IS 3 BP 330 EP 339 DI 10.1097/CHI.0b013e3181977476 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 412RO UT WOS:000263742100012 PM 19182688 ER PT J AU Guchereau, M Jourkiv, O Zametkin, A AF Guchereau, Michelle Jourkiv, Oxana Zametkin, Alan TI MENTAL DISORDERS AMONG ADOLESCENTS IN JUVENILE DETENTION AND CORRECTIONAL FACILITIES: POSTTRAUMATIC STRESS DISORDER IS OVERLOOKED SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 [Guchereau, Michelle; Jourkiv, Oxana] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Zametkin, Alan] NIMH, Bethesda, MD 20892 USA. RP Guchereau, M (reprint author), Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2009 VL 48 IS 3 BP 340 EP 340 DI 10.1097/CHI.0b013e3181949004 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 412RO UT WOS:000263742100013 PM 19242294 ER PT J AU Bradford, P Goldstein, A Tucker, M McMaster, M AF Bradford, Porcia Goldstein, Alisa Tucker, Margaret McMaster, Mary TI Acral lentiginous, melanoma: Incidence and survival patterns in the United States, 1986-2004 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Bradford, Porcia; Goldstein, Alisa; Tucker, Margaret; McMaster, Mary] NIH, Rockville, MD USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB132 EP AB132 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100524 ER PT J AU Constantinescu, M Yee, C Vogel, J AF Constantinescu, Monica Yee, Carole Vogel, Jonathan TI Altering dermal vascularity in order to assess vascular effects on keratinocyte biology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Constantinescu, Monica; Yee, Carole; Vogel, Jonathan] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAR PY 2009 VL 60 IS 3 BP AB185 EP AB185 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100728 ER PT J AU Farasat, S Toro, J Fleckman, P Bale, S AF Farasat, Sharifeh Toro, Jorge Fleckman, Philip Bale, Sherri TI Tratisglutaminase-1 mutations and genotype-phenotype investigations in 104 North American patients with autosomal recessive congenital ichthyosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Farasat, Sharifeh; Toro, Jorge] Natl Inst Hlth, Rockville, MD USA. [Fleckman, Philip] Univ Washington, Seattle, WA 98195 USA. [Bale, Sherri] GeneDx, Gaithersburg, 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB5 EP AB5 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100018 ER PT J AU Mahindra, P Tamura, D DiGiovanna, J Kraemer, K Faghri, S AF Mahindra, Priya Tamura, Deborah DiGiovanna, John Kraemer, Kenneth Faghri, Salma TI Trichothiodystrophy: A ram multisystem genetic disease with marked phenotypic diversity SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Mahindra, Priya] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Tamura, Deborah; Kraemer, Kenneth] Natl Inst Hlth, Bethesda, MD USA. [DiGiovanna, John; Faghri, Salma] Brown Med Sch, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB99 EP AB99 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100393 ER PT J AU Unutzer, J Schoenbaum, M Katon, WJ Fan, MY Pincus, HA Hogan, D Taylor, J AF Unutzer, Jurgen Schoenbaum, Michael Katon, Wayne J. Fan, Ming-Yu Pincus, Harold A. Hogan, Diane Taylor, Jennifer TI Healthcare Costs Associated with Depression in Medically Ill Fee-for-Service Medicare Participants SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression; medical costs ID LATE-LIFE DEPRESSION; OLDER-ADULTS; SYMPTOMS; POPULATION; PREDICTORS; DISORDERS; ADHERENCE; OUTCOMES; ILLNESS; TRIAL AB To examine the association between depression and healthcare costs in medically ill fee-for-service (FFS) Medicare recipients. Observational analysis of Medicare claims data. Medicare Health Support (MHS) program at Green Ribbon Health. Fourteen thousand nine hundred two participants with diabetes mellitus, congestive heart failure (CHF), or both. This study examined participant data for a 12-month period before MHS enrollment (collected between November 2004 and August 2006). Twelve-month healthcare costs (based on Medicare claims) in 2,108 participants with International Classification of Diseases, Ninth Revision, claims diagnoses of depression, 1,081 participants with possible depression (positive depression screen on the two-item Patient Health Questionnaire or self reported antidepressant use), and 11,713 participants without depression were compared. Gamma regression models were used to adjust for demographic and clinical differences and nonnormal distribution of cost data. Participants with depression had significantly higher total healthcare costs than those without ($20,046 vs $11,956; P <.01). Higher costs were observed in participants with depression in every cost category except specialty mental health care, which accounted for less than 1% of total healthcare costs. Participants with depression had higher costs in each quartile of increasing medical severity (measured using the Charlson Comorbidity Index). These differences remained statistically significant after adjusting for demographic and other clinical differences. Depression is associated with significantly higher healthcare costs in FFS Medicare recipients with diabetes mellitus and CHF. Only a small proportion of the increased costs are spent on mental health specialty care. C1 [Unutzer, Jurgen; Katon, Wayne J.; Fan, Ming-Yu] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Schoenbaum, Michael] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Pincus, Harold A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Hogan, Diane; Taylor, Jennifer] Green Ribbon Hlth, Tampa, FL USA. RP Unutzer, J (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Box 356560,1959 NE Pacific St, Seattle, WA 98195 USA. EM unutzer@u.washington.edu FU National Institute of Mental Health [R01 MH0751590-03] FX Conflict of Interest: Jurgen Unutzer: Grant: National Institute of Mental Health (R01 MH0751590-03; Unutzer). Wayne Katon: Consultant: Lilly. Honoraria: Lilly, Forrest, Wyeth, and Pfizer. Harold Pincus: Consultant for: Bristol Myers Squibb, Cisco Systems, Community Care Behavioral Health Organization/UPMC Health Plan, Magellan Health Care, and Urban Institute. Speaker fees from: Bimark Medical Education, Comprehensive NeuroScience Inc., Medical Information Technologies, Cardinal Health Inc., Health Partners, and American Medical Association. NR 31 TC 84 Z9 84 U1 4 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 IS 3 BP 506 EP 510 DI 10.1111/j.1532-5415.2008.02134.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 414JL UT WOS:000263859600017 PM 19175438 ER PT J AU Cholitkul, S Launer, L Cholitkul, S Bell, C Chen, R Abbott, R Petrovitch, H Ross, W Blanchette, P White, L Masaki, K AF Cholitkul, S. Launer, L. Cholitkul, S. Bell, C. Chen, R. Abbott, R. Petrovitch, H. Ross, W. Blanchette, P. White, L. Masaki, K. TI Endogenous Serum Testosterone and Estradiol and All-Cause Mortality in Older Men: The Honolulu-Asia Aging Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Cholitkul, S.; Cholitkul, S.; Bell, C.; Abbott, R.; Petrovitch, H.; Ross, W.; Blanchette, P.; White, L.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [Chen, R.; Abbott, R.; Petrovitch, H.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [White, L.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, W.] Dept Vet Affairs, Honolulu, HI USA. [Launer, L.] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S13 EP S13 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900035 ER PT J AU Dickerson, E Venkatraman, V Guralnik, J Pahor, M Aizenstein, H Rosano, C AF Dickerson, E. Venkatraman, V. Guralnik, J. Pahor, M. Aizenstein, H. Rosano, C. TI White matter hyperintensities and eye-hand coordination in the oldest old: Exploratory study using an automated white matter hyperintensity labeling pathway SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Dickerson, E.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Dickerson, E.; Venkatraman, V.; Aizenstein, H.; Rosano, C.] Univ Pittsburgh, Pittsburgh, PA USA. [Guralnik, J.] NIA, Bethesda, MD 20892 USA. [Pahor, M.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S102 EP S103 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900290 ER PT J AU Gray, S Boudreau, R Newman, A Studenski, S Shorr, R Bauer, D Simonsick, E Hanlon, J AF Gray, S. Boudreau, R. Newman, A. Studenski, S. Shorr, R. Bauer, D. Simonsick, E. Hanlon, J. TI Angiotensin-converting Enzyme Inhibitor (ACEI) Medication Use and Persistent Lower Extremity Limitation (PLL) in Community Elderly: The Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Gray, S.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Boudreau, R.; Newman, A.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Newman, A.; Studenski, S.; Hanlon, J.] Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA USA. [Studenski, S.; Hanlon, J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Studenski, S.; Hanlon, J.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Shorr, R.] N Florida S Georgia Vet Hlth Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. [Bauer, D.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Simonsick, E.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S176 EP S176 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900505 ER PT J AU Hanlon, JT Boudreau, RM Studenski, SA Newman, AB Simonsick, EM Shorr, RI Bauer, DC Gray, SL AF Hanlon, J. T. Boudreau, R. M. Studenski, S. A. Newman, A. B. Simonsick, E. M. Shorr, R. I. Bauer, D. C. Gray, S. L. TI HMG-CoA Reductase Inhibitor Medication Use and Persistent Lower Extremity Limitation in Community Elders. The Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Hanlon, J. T.; Studenski, S. A.; Newman, A. B.] UPITT, Pittsburgh, PA USA. [Hanlon, J. T.; Studenski, S. A.] Pittsburgh VAHS, CHERP GRECC, Pittsburgh, PA USA. [Simonsick, E. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Shorr, R. I.] N Florida S Georgia Vet Hlth Syst, GRECC, Gainesville, FL USA. [Bauer, D. C.] UCSF, Gen IM, San Francisco, CA USA. [Gray, S. L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Boudreau, R. M.; Newman, A. B.] UPITT, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S174 EP S174 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900500 ER PT J AU Hernandez, J Yazdanyar, A Sutton-Tyrrell, K Satterfield, S Harris, TB Strotmeyer, ES Newman, AB AF Hernandez, J. Yazdanyar, A. Sutton-Tyrrell, K. Satterfield, S. Harris, T. B. Strotmeyer, E. S. Newman, A. B. TI Subclinical peripheral arterial disease and lower leg strength in older adults: the role of nerve function SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Hernandez, J.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Yazdanyar, A.; Sutton-Tyrrell, K.; Strotmeyer, E. S.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Satterfield, S.] Univ Tennessee, Memphis, TN USA. [Harris, T. B.] NIA, Bethesda, MD 20892 USA. RI Strotmeyer, Elsa/F-3015-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S73 EP S73 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900208 ER PT J AU Mangieri, DA Williamson, J Lovato, J Fitzpatrick, A Atkinson, H Saxton, J Rapp, S Carlson, M DeKosky, S Nahin, R Sink, K AF Mangieri, D. A. Williamson, J. Lovato, J. Fitzpatrick, A. Atkinson, H. Saxton, J. Rapp, S. Carlson, M. DeKosky, S. Nahin, R. Sink, K. TI Moderate Alcohol Intake Is Associated with Lower Dementia Incidence: Results from the Ginkgo Evaluation of Memory Study (GEMS). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Mangieri, D. A.; Williamson, J.; Lovato, J.; Atkinson, H.; Rapp, S.; Sink, K.] Wake Forest U, Winston Salem, NC USA. [Fitzpatrick, A.] U Washington, Seattle, WA USA. [Saxton, J.; DeKosky, S.] U Pittsburgh, Pittsburgh, PA USA. [Carlson, M.] Johns Hopkins U, Baltimore, MD USA. [Nahin, R.] NCCAM, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S69 EP S70 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900199 ER PT J AU Ochner, M Abbott, R Chen, R Bell, C White, L Petrovitch, H Ross, G Launer, L Blanchette, P Masaki, K AF Ochner, M. Abbott, R. Chen, R. Bell, C. White, L. Petrovitch, H. Ross, G. Launer, L. Blanchette, P. Masaki, K. TI Impaired Olfaction Predicts Incident Dementia in Elderly Men: The Honolulu-Asia Aging Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Ochner, M.; Abbott, R.; Bell, C.; White, L.; Petrovitch, H.; Ross, G.; Blanchette, P.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [Abbott, R.; Chen, R.; Petrovitch, H.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [White, L.] Kuakini Med Ctr, Honolulu, HI USA. [Launer, L.] NIA, Bethesda, MD USA. [Ross, G.] Dept Vet Affairs, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S104 EP S104 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900294 ER PT J AU Rianon, NJ Lang, T Sigurdsson, G Siggeirsdottir, K Eiriksdottir, G Sigurdsson, S Garcia, M Yu, B Pajala, S Koster, A Gudnason, V Harris, TB AF Rianon, N. J. Lang, T. Sigurdsson, G. Siggeirsdottir, K. Eiriksdottir, G. Sigurdsson, S. Garcia, M. Yu, B. Pajala, S. Koster, A. Gudnason, V. Harris, T. B. TI Lifelong physical activity and bone health in elderly men and women: AGES-Reykjavik Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Rianon, N. J.] Baylor Coll Med, Houston, TX 77030 USA. [Lang, T.] UCSF, San Francisco, CA USA. [Sigurdsson, G.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland. [Siggeirsdottir, K.; Eiriksdottir, G.; Sigurdsson, S.] Iceland Heart Assoc, Kopavogur, Iceland. [Garcia, M.; Yu, B.; Pajala, S.; Koster, A.; Harris, T. B.] NIA, LEDB, IRP, Bethesda, MD USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S74 EP S75 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900212 ER PT J AU Romelus, AM Champion, H Najjar, S Shetty, V Zieman, S AF Romelus, A. M. Champion, H. Najjar, S. Shetty, V. Zieman, S. TI Pulmonary Artery Systolic Pressure Increases with Advancing Age in Healthy Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Romelus, A. M.] Univ Florida, Gainesville, FL USA. [Romelus, A. M.; Champion, H.; Zieman, S.] Johns Hopkins Univ, Baltimore, MD USA. [Najjar, S.; Shetty, V.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S78 EP S78 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900222 ER PT J AU Spangler, E Watson, N Venkitachalam, L Sutton-Tyrrell, K Newman, A Brach, J Mackey, RH Boudreau, R Simonsick, E Najjar, S Windham, BG Bauer, D Rodondi, N Johnson, K AF Spangler, E. Watson, N. Venkitachalam, L. Sutton-Tyrrell, K. Newman, A. Brach, J. Mackey, R. H. Boudreau, R. Simonsick, E. Najjar, S. Windham, B. G. Bauer, D. Rodondi, N. Johnson, K. TI Ankle Arm Index and Walking Endurance in Community-Dwelling Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Spangler, E.; Watson, N.; Venkitachalam, L.; Sutton-Tyrrell, K.; Newman, A.; Brach, J.; Mackey, R. H.; Boudreau, R.] Univ Pittsburgh, Hlth ABC study, Pittsburgh, PA USA. [Simonsick, E.; Najjar, S.; Windham, B. G.] Natl Inst Aging, NIH, Baltimore, MD USA. [Bauer, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rodondi, N.] Univ Lausanne, Lausanne, Switzerland. [Johnson, K.] Univ Tennessee, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S173 EP S173 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900496 ER PT J AU Tao, C White, L Bell, C Chen, R Abbott, R Petrovitch, H Launer, L Ross, G Blanchette, P Schatz, I Masaki, K AF Tao, C. White, L. Bell, C. Chen, R. Abbott, R. Petrovitch, H. Launer, L. Ross, G. Blanchette, P. Schatz, I. Masaki, K. TI Atrial Fibrillation and Cognitive Decline: The Honolulu-Asia Aging Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Tao, C.; White, L.; Bell, C.; Abbott, R.; Petrovitch, H.; Ross, G.; Blanchette, P.; Schatz, I.; Masaki, K.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [White, L.; Chen, R.; Abbott, R.; Petrovitch, H.; Masaki, K.] Pacific Hlth Res Inst, Honolulu, HI USA. [Ross, G.] Dept Vet Affairs, Honolulu, HI USA. [Launer, L.] Natl Inst Aging, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S193 EP S194 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900554 ER PT J AU Chen, YH Chatterjee, N Carroll, RJ AF Chen, Yi-Hau Chatterjee, Nilanjan Carroll, Raymond J. TI Shrinkage Estimators for Robust and Efficient Inference in Haplotype-Based Case-Control Studies SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Empirical Bayes; Genetic epidemiology; LASSO (Least Absolute Shrinkage and Selection Operator); Model averaging; Model robustness; Model selection ID GENE-ENVIRONMENT INDEPENDENCE; REGRESSION-MODEL; LINKAGE PHASE; GENOTYPE DATA; LIKELIHOOD; SELECTION; ASSOCIATIONS; TRAITS; TESTS; RISK AB Case-control association studies often aim to investigate the role of genes and gene-environment interactions in terms of the underlying haplotypes (i.e., the combinations of alleles at multiple genetic loci along chromosomal regions). The goal of this article is to develop robust but efficient approaches to the estimation of disease odds-ratio parameters associated with haplotypes and haplotype-environment interactions. We consider "shrinkage" estimation techniques that can adaptively relax the model assumptions of Hardy-Weinberg-Equilibrium and gene-environment independence required by recently proposed efficient "retrospective" methods. Our proposal involves first development of a novel retrospective approach to the analysis of case-control data, one that is robust to the nature of the gene-environment distribution in the underlying population. Next, it involves shrinkage of the robust retrospective estimator toward a more precise, but model-dependent, retrospective estimator using novel empirical Bayes and penalized regression techniques. Methods for variance estimation are proposed based on asymptotic theories. Simulations and two data examples illustrate both the robustness and efficiency of the proposed methods. C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. EM yhchen@stat.sinica.edu.tw; chattern@mail.nih.gov; carroll@stat.tamu.edu FU National Science Council of ROC [95-2118-M-001-022-MY3]; National Heart Lung and Blood Institute [RO1HL091172-01]; National Cancer Institute [CA57030, CA104620]; King Abdullah University of Science and Technology (KAUST) [KUS-CI-016-04] FX Chen's research was supported by the National Science Council of ROC (NSC 95-2118-M-001-022-MY3). Chatterjee's research was supported by a gene-environment initiative grant from the National Heart Lung and Blood Institute (RO1HL091172-01) and by the Intramural Research Program of the National Cancer Institute. Carroll's research was supported by grants from the National Cancer Institute (CA57030, CA104620) and by Award Number KUS-CI-016-04, made by King Abdullah University of Science and Technology (KAUST). The authors thank the editor, associate editor, and referees for their helpful comments. NR 26 TC 34 Z9 34 U1 0 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2009 VL 104 IS 485 BP 220 EP 233 DI 10.1198/jasa.2009.0104 PG 14 WC Statistics & Probability SC Mathematics GA 425PI UT WOS:000264649200023 PM 19430598 ER PT J AU Rueda, C Fernandez, MA Das Peddada, S AF Rueda, Cristina Fernandez, Miguel A. Das Peddada, Shyamal TI Estimation of Parameters Subject to Order Restrictions on a Circle With Application to Estimation of Phase Angles of Cell Cycle Genes SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Circular isotonic regression; Order restrictions on circle; Phase angles; Pool adjacent violator algorithm; Restricted maximum likelihood estimators; von Mises distribution ID FISSION YEAST; EXPRESSION; IDENTIFICATION; MODEL AB Motivated by a problem encountered in the analysis of cell cycle gene expression data. this article deals with the estimation of parameters subject to order restrictions on a unit circle. A normal eukaryotic cell cycle has four major phases, during cell division, and a cell cycle gene has its peak expression (phase angle) during the phase that may correspond to its biological function. Because the phases are ordered along a circle, the phase angles of cell cycle genes are ordered unknown parameters on a unit circle. The problem of interest is to estimate the phase angles using the information regarding the order among them. We address this problem by developing a circular version of the well-known isotonic regression for Euclidean data. Because of the underlying geometry, the standard pool adjacent violator algorithm (PAVA) cannot be used for deriving the circular isotonic regression estimator (CIRE). However, PAVA can be modified to obtain a computationally efficient algorithm for deriving the CIRE. We illustrate the CIRE by estimating the phase angles of some of well-known cell cycle genes using the unrestricted estimators obtained in the literature. C1 [Rueda, Cristina; Fernandez, Miguel A.] Univ Valladolid, Dept Stat & Operat Res, Valladolid, Spain. [Das Peddada, Shyamal] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Rueda, C (reprint author), Univ Valladolid, Dept Stat & Operat Res, Valladolid, Spain. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012; Fernandez, Miguel/I-2874-2015 OI Fernandez, Miguel/0000-0002-1272-8950 FU Spanish DGES [MTM2004-07740]; PAPIJCL [VA047A05]; National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES101744-04] FX Cristina Rueda is with the Department of Statistics and Operations Research, University of Valladolid, Valladolid, Spain. Miguel A. Fernandez is with the Department of Statistics and Operations Research, University of Valladolid. Valladolid. Spain. Shyamal Das Peddada is with the Biostatistical Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (E-mail: peddada@niehs.nih.gov). Research of Rueda and Fernandez was supported in part by Spanish DGES (grant MTM2004-07740) and by PAPIJCL (grant VA047A05); and Peddada's research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES101744-04]. The authors thank Drs. Dunson, Umbach. Weinberg, and Guo; two referees; the associate editor; and the editor for numerous suggestions that improved the presentation of the manuscript. They specifically thank Drs. Umbach and Weinberg for suggesting that they extend their methodology to rotation-invariant simple order around the circle, a biologically important order restriction. The authors also thank Dr. Gauthier. Technical University of Denmark, for the permission to use the figure from wwwcyclebase.org, and for providing the duration of phases in Whitfield's data. NR 20 TC 17 Z9 17 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2009 VL 104 IS 485 BP 338 EP 347 DI 10.1198/jasa.2009.0120 PG 10 WC Statistics & Probability SC Mathematics GA 425PI UT WOS:000264649200032 PM 19750145 ER PT J AU Pop-Busui, R Lu, J Lopes, N Jones, TLZ AF Pop-Busui, Rodica Lu, Jiang Lopes, Neuza Jones, Teresa L. Z. CA BARI 2D Investigators TI Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Article DE coronary artery disease; diabetic peripheral neuropathy; glycemic control therapy; Michigan Neuropathy Screening Instrument; type 2 diabetes ID SENSITIVE POTASSIUM CHANNEL; BLOOD-GLUCOSE CONTROL; OXIDATIVE STRESS; COMPLICATIONS TRIAL; GAMMA-LIGAND; RISK-FACTORS; CELL-DEATH; INSULIN; METFORMIN; NEUROPROTECTION AB We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score > 2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15-2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN. C1 [Pop-Busui, Rodica] Univ Michigan, Div Endocrinol Diabet & Metab, Dept Internal Med, Ann Arbor, MI 48109 USA. [Lu, Jiang] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Lopes, Neuza] Univ Sao Paulo, Heart Inst InCor, Sao Paulo, Brazil. [Jones, Teresa L. Z.] NIDDK, NIH, Bethesda, MD USA. RP Pop-Busui, R (reprint author), Univ Michigan, Div Endocrinol Diabet & Metab, Dept Internal Med, 5570D MSRB 2,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM rpbusui@umich.edu RI Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 FU National Heart, Lung and Blood Institute (NHLBI) [U01 HL061746, U01 HL061748, U01 HL063804]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01 HL061744]; GlaxoSmithKline; Bristol-Myers Squibb Medical Imaging, Inc.; Astellas Pharma US, Inc.; Merck Co., Inc.; Abbott Laboratories, Inc.; Pfizer, Inc.; Abbott Laboratories Ltd.; MediSense Products; Bayer Diagnostics; Beckton, Dickinson and Company; J.R. Carlson Laboratories, Inc.; Centocor, Inc.; Eli Lilly and Company; LipoScience, Inc.; Merck Sante; Novartis Pharmaceuticals Corporation; Novo Nordisk, Inc. FX Clinical Trial Registration No: NCT00006305 clinicaltrials.gov. These studies were supported by National Heart, Lung and Blood Institute (NHLBI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): NHLBI Nos. U01 HL061746, U01 HL061748, and U01 HL063804. NIDDK No. U01 HL061744. The BARI 2D trial is sponsored by the NHLBI and receives substantial funding from the NIDDK. The BARI 2D trial is coordinated by the Epidemiology Data Center at the University of Pittsburgh, Graduate School of Public Health. BARI 2D receives significant supplemental funding from GlaxoSmithKline; Bristol-Myers Squibb Medical Imaging, Inc.; Astellas Pharma US, Inc.; Merck & Co., Inc.; Abbott Laboratories, Inc.; and Pfizer, Inc. BARI 2D also receives generous support from Abbott Laboratories Ltd.; MediSense Products; Bayer Diagnostics; Beckton, Dickinson and Company; J.R. Carlson Laboratories, Inc.; Centocor, Inc.; Eli Lilly and Company; LipoScience, Inc.; Merck Sante; Novartis Pharmaceuticals Corporation; and Novo Nordisk, Inc. NR 32 TC 30 Z9 36 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1085-9489 EI 1529-8027 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD MAR PY 2009 VL 14 IS 1 BP 1 EP 13 DI 10.1111/j.1529-8027.2009.00200.x PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 425KO UT WOS:000264635600001 PM 19335534 ER PT J AU Vaisbuch, E Romero, R Kusanovic, JP Erez, O Mazaki-Tovi, S Gotsch, F Kim, CJ Kim, JS Yeo, L Hassan, SS AF Vaisbuch, Edi Romero, Roberto Kusanovic, Juan Pedro Erez, Offer Mazaki-Tovi, Shali Gotsch, Francesca Kim, Chong Jai Kim, Jung-Sun Yeo, Lami Hassan, Sonia S. TI Three-Dimensional Sonography of Placental Mesenchymal Dysplasia and Its Differential Diagnosis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE chorioangioma; complete hydatidiform mole and coexistent fetus; Doppler sonography; mesenchymal hyperplasia; pseudo partial mole; sonography ID BECKWITH-WIEDEMANN-SYNDROME; STEM VILLOUS HYPERPLASIA; VASCULAR MALFORMATION; PRENATAL-DIAGNOSIS; GROWTH RESTRICTION; HYDATIDIFORM MOLE; MATERNAL SERUM; TWIN PREGNANCY; CHORIOANGIOMA; HYDROPS AB Objective. Placental mesenchymal dysplasia (PMD) is an uncommon vascular anomaly of the placenta characterized by mesenchymal stem villous hyperplasia. its main sonographic feature is a thickened placenta with hypoechoic areas, and an accurate sonographic diagnosis is challenging. The aim of this study was to report 2 cases of PMD and discuss the differential diagnosis of its sonographic features. Methods. Cases of placental masses were studied by 2-dimensional (2D), 3-dimensional (3D), and color Doppler imaging. Results. In case 1, a thick placenta with multiple hypoechoic areas was noted at 13 weeks' gestation. At 19 weeks, the multicystic area, clearly demarcated from a normal-looking placenta, measured 6.5 x 8.5 cm and enlarged gradually. The patient gave birth to a 625-g female neonate after spontaneous labor at almost 26 weeks' gestation, In case 2, a first sonographic examination at 25 weeks' gestation revealed a thickened placenta with hypoechoic areas and a fetus with a single umbilical artery and a ventricular septal defect. At 27 weeks, the abnormal area of the placenta measured 14.5 x 7.5 cm. At 32 weeks' gestation, a caesarean delivery was performed because of a nonreassuring fetal heart tracing, and a 1415-g female neonate was delivered. Both cases were evaluated by 2D, 3D, and color Doppler imaging, and the pathologic features of both placentas were consistent with PMD. Conclusions. Placental mesenchymal dysplasia should be considered in the differential diagnosis of every placental mass, especially in cases of multicystic placental lesion with lack of high-velocity signals inside the lesion, and a normal karyotype. C1 [Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Mazaki-Tovi, Shali; Gotsch, Francesca; Kim, Chong Jai; Kim, Jung-Sun; Yeo, Lami; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Mazaki-Tovi, Shali; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA. [Kim, Chong Jai; Kim, Jung-Sun] Wayne State Univ, Dept Pathol, Sch Med, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 36 TC 17 Z9 17 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2009 VL 28 IS 3 BP 359 EP 368 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 452QH UT WOS:000266555800012 PM 19244073 ER PT J AU Mullins, C Kaplan, SA AF Mullins, Chris Kaplan, Steven A. TI A New Vision for the Study of Benign Prostate Disease: The NIDDK Prostate Research Strategic Plan SO JOURNAL OF UROLOGY LA English DT Article DE National Institutes of Health (US); prostate; epidemiology; research ID SYMPTOMS; HYPERPLASIA; PREVALENCE; HEALTH AB Purpose: The American population continues to enjoy a steady increase in life expectancy. A major goal for this population is to maintain and improve quality of life as it ages. For men a major source of age related health burden is benign disorders of the prostate which, despite much research, remain poorly defined and require greater advancement in prevention and treatment. Thus, there is a substantial need to develop a long-range vision to focus and promote efforts to better understand and manage benign prostate disease. In response the National Institute of Diabetes and Digestive and Kidney Diseases convened a panel of key opinion leaders including basic researchers, translational scientists, epidemiologists, and clinicians and clinical researchers to develop a comprehensive strategic plan to advance research in benign prostate disease. Materials and Methods: The overall mission statement of this effort is "To discuss, evaluate, and propose research needs and a long-range research agenda (ie a strategic plan) for NIDDK grant portfolios related to research into benign prostate disease." Implementation and practical application of this strategic plan will require a partnership of the scientific community, the Federal Government, and other public and private organizations and institutions. Results: This focused group of research and thought leaders identified 4 major areas of key significance for future investigation: basic science, epidemiology/population based studies, translational opportunities and clinical sciences. Great opportunities are identified within these 4 areas to develop new insights, and translate findings for benign prostate diseases and related syndromes between the research laboratory and the clinical setting. Conclusions: The product of these efforts, the National Institute of Diabetes and Digestive and Kidney Diseases Prostate Research Strategic Plan, represents a blueprint that researchers and Federal Government can use to review where the field has been, define where the field is and, most importantly, identify where and how future research efforts should be directed. To accomplish this goal many priorities must be addressed, including the need to create more effective lines of communication among scientific disciplines to improve translation of research findings and ultimately advance patient treatment. The overall goals and missions of the National Institute of Diabetes and Digestive and Kidney Diseases Prostate Research Strategic Plan, along with key scientific recommendations and priorities for the major areas of focus, are summarized. C1 [Kaplan, Steven A.] Weill Cornell Med Coll, Dept Urol, New York, NY 10065 USA. NIDDK, NIH, Bethesda, MD USA. RP Kaplan, SA (reprint author), Weill Cornell Med Coll, Dept Urol, F9-W,Box 261,525 E 68th St, New York, NY 10065 USA. EM kaplans@med.cornell.edu NR 18 TC 3 Z9 3 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 MAR PY 2009 VL 181 IS 3 BP 963 EP 971 DI 10.1016/j.juro.2008.11.033 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 406VA UT WOS:000263321800008 PM 19150562 ER PT J AU Figg, WD Hussain, MH Gulley, JL Arlen, PM Aragon-Ching, JB Petrylak, DP Higano, CS Steinberg, SM Chatta, GS Parnes, H Wright, JJ Sartor, O Dahut, WL AF Figg, William D. Hussain, Maha H. Gulley, James L. Arlen, Philip M. Aragon-Ching, Jeanny B. Petrylak, Daniel P. Higano, Celestia S. Steinberg, Seth M. Chatta, Gurkamal S. Parnes, Howard Wright, John J. Sartor, Oliver Dahut, William L. TI A Double-Blind Randomized Crossover Study of Oral Thalidomide Versus Placebo for Androgen Dependent Prostate Cancer Treated With Intermittent Androgen Ablation SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; hormones; thalidomide; disease-free survival; angiogenesis inhibitors ID PHASE-II TRIAL; RADICAL PROSTATECTOMY; DEPRIVATION THERAPY; BIOCHEMICAL RECURRENCE; TUMOR ANGIOGENESIS; NATURAL-HISTORY; SURVIVAL; NORMALIZATION; METASTASIS; CARCINOMA AB Purpose: We determined whether thalidomide can prolong progression-free survival in men with biochemically recurrent prostate cancer treated with limited androgen deprivation therapy. Materials and Methods: A total of 159 patients were enrolled in a double-blind randomized trial to determine if thalidomide can improve the efficacy of a gonadotropin-releasing hormone agonist in hormone responsive patients with an increasing prostate specific antigen after primary definitive therapy for prostate cancer. Patients were randomized to 6 months of gonadotropin-releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo (oral phase A). At the time of prostate specific antigen progression gonadotropin-releasing hormone agonist was restarted for 6 additional months. Patients were then crossed over to the opposite drug and were treated until prostate specific antigen progression (oral phase B). Testosterone and dihydroxytestosterone were likewise monitored throughout the study. Results: During oral phase A the median time to prostate specific antigen progression was 15 months for the thalidomide group compared to 9.6 months on placebo (p = 0.21). The median time to prostate specific antigen progression during oral phase B for the thalidomide group was 17.1 vs 6.6 months on placebo (p = 0.0002). No differences in time to serum testosterone normalization between the thalidomide and placebo arms were documented during oral phase A and oral phase B. Thalidomide was tolerable although dose reductions occurred in 47% (58 of 124) of patients. Conclusions: Despite thalidomide having no effect on testosterone normalization, there was a clear effect on prostate specific antigen progression during oral phase B. This is the first study to our knowledge to demonstrate the effects of thalidomide using intermittent hormonal therapy. C1 [Figg, William D.; Aragon-Ching, Jeanny B.; Dahut, William L.] NCI, Med Oncol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Figg, William D.] NCI, NIH, Mol Pharmacol Sect, Bethesda, MD USA. [Gulley, James L.; Arlen, Philip M.] NCI, NIH, Tumor Immunol & Biol Lab, Bethesda, MD USA. [Steinberg, Seth M.] NCI, NIH, Biostat & Data Management Sect, Bethesda, MD USA. [Parnes, Howard] NCI, NIH, Canc Prevent Div, Bethesda, MD USA. [Wright, John J.] NCI, NIH, Canc Therapy Evaluat Program, Bethesda, MD USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Urol, Ann Arbor, MI USA. [Hussain, Maha H.] Wayne State Univ, Dept Med Oncol, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Petrylak, Daniel P.] Columbia Univ, Dept Med, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Higano, Celestia S.] Univ Washington, Dept Med, Seattle, WA USA. [Higano, Celestia S.] Univ Washington, Dept Urol, Seattle, WA USA. [Chatta, Gurkamal S.] Univ Pittsburgh, Dept Med, Inst Canc, Pittsburgh, PA USA. [Sartor, Oliver] Tulane Med Sch, New Orleans, LA USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, NIH, Ctr Canc Res, Bldg 10-Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016; OI Gulley, James/0000-0002-6569-2912; Aragon-Ching, Jeanny/0000-0002-6714-141X FU Intramural NIH HHS [Z01 BC010547-05] NR 20 TC 24 Z9 26 U1 1 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 MAR PY 2009 VL 181 IS 3 BP 1104 EP 1113 DI 10.1016/j.juro.2008.11.026 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 406VA UT WOS:000263321800062 PM 19167733 ER PT J AU Sarma, AV Kanaya, AM Nyberg, LM Kusek, JW Vittinghoff, E Rutledge, B Cleary, PA Gatcomb, P Brown, JS AF Sarma, Aruna V. Kanaya, Alka M. Nyberg, Leroy M. Kusek, John W. Vittinghoff, Eric Rutledge, Brandy Cleary, Patricia A. Gatcomb, Patricia Brown, Jeanette S. CA Diabetes Interventions Complicatio TI Urinary Incontinence Among Women With Type 1 Diabetes-How Common is it? SO JOURNAL OF UROLOGY LA English DT Article DE women; urinary incontinence; diabetes mellitus, type 1; prevalence ID EPIDEMIOLOGIC SURVEY; AUTONOMIC NEUROPATHY; RISK-FACTORS; COMPLICATIONS; IMPLEMENTATION; CYSTOPATHY; PREVALENCE; MELLITUS AB Purpose: We compared the prevalence, level of bother and effect on daily activities of urinary incontinence among women with type 1 diabetes enrolled in the Epidemiology of Diabetes Interventions and Complications study to a population based sample of women with normal glucose. Materials and Methods: We performed a cross-sectional analysis of women with type I diabetes and normal glucose tolerance using 2 study populations. The Diabetes Control and Complications Trial cohort followup, Epidemiology of Diabetes Interventions and Complications, began in 1994. In 2004 women participants (550) completed a self-administered questionnaire on urinary incontinence. Our primary outcome was weekly or greater incontinence, overall and by type. Prevalence of urinary incontinence was compared to a subgroup of women with normal glucose in the 2001 to 2002 National Health and Nutrition Examination Survey (NHANES). Results: Overall 65% of women with type 1 diabetes reported any urinary incontinence (17% reported weekly incontinence). Nearly 40% of these women were greatly bothered by their incontinence and 9% believed it affected their day-today activities. Women with type 1 diabetes had a nearly 2-fold greater prevalence of weekly urge incontinence compared to those without diabetes in the NHANES cohort (8.8% vs 4.5%, p = 0.01). Conclusions: Urinary incontinence is common in women with type 1 diabetes and the prevalence of weekly urge incontinence is far greater compared to that in women with normal glucose levels. Moreover, the prevalence of urinary incontinence in women with type I diabetes was greater than that of neuropathy, retinopathy and nephropathy. These findings highlight the importance of screening for urinary incontinence among women with type 1 diabetes. Studies examining factors associated with urinary incontinence in women with type I diabetes are warranted. C1 [Sarma, Aruna V.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Kanaya, Alka M.; Vittinghoff, Eric; Brown, Jeanette S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nyberg, Leroy M.; Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Rutledge, Brandy; Cleary, Patricia A.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Gatcomb, Patricia] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. RP Sarma, AV (reprint author), Univ Michigan, Dept Urol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM asarma@umich.edu FU Division of Diabetes, Endocrinology; Metabolic Disease of die National Institute of Diabetes; Digestive and Kidney Diseases; General Clinical Research Center Program; National Center for Research Resources FX Supported by contracts with the Division of Diabetes, Endocrinology and Metabolic Disease of die National Institute of Diabetes and Digestive and Kidney Diseases, and the General Clinical Research Center Program, National Center for Research Resources. NR 20 TC 18 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD MAR PY 2009 VL 181 IS 3 BP 1224 EP 1230 DI 10.1016/j.juro.2008.11.024 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 406VA UT WOS:000263321800121 PM 19152930 ER PT J AU Buss, DD Atchison, ML Corps, KN Falkowski, LB Fox, JG Hendricks, JC Mexas, AM Rosol, TJ Stromberg, BF AF Buss, Daryl D. Atchison, Michael L. Corps, Kara N. Falkowski, Lauren B. Fox, James G. Hendricks, Joan C. Mexas, Angela M. Rosol, Thomas J. Stromberg, Bert F. TI Veterinarians in Biomedical Research: Building National Capacity SO JOURNAL OF VETERINARY MEDICAL EDUCATION LA English DT Article DE veterinarians; veterinary medicine; biomedical research; research; careers AB This Executive Summary provides the conclusions from the presentations and discussions at the conference Veterinarians in Biomedical Research-Building National Capacity, a meeting coordinated by the AAVMC and held at the National institutes of Health (NIH), Bethesda, MD, August 1-4, 2007. C1 [Buss, Daryl D.] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. [Atchison, Michael L.] Univ Penn, NIH, Merck Summer Res Program, Sch Vet Med, Philadelphia, PA 19104 USA. [Corps, Kara N.] Michigan State Univ, DVM Program, Coll Vet Med, E Lansing, MI 48824 USA. [Falkowski, Lauren B.] Colorado State Univ, Coll Vet Med & Biomed Sci, DVM Program, Ft Collins, CO 80523 USA. [Fox, James G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Hendricks, Joan C.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. [Rosol, Thomas J.] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA. [Stromberg, Bert F.] Univ Minnesota, Coll Vet Med, Res & Grad Programs, St Paul, MN 55108 USA. RP Buss, DD (reprint author), Univ Wisconsin, Sch Vet Med, 2015 Linden Dr, Madison, WI 53706 USA. RI Rosol, Thomas/G-9585-2011 OI Rosol, Thomas/0000-0003-3737-1190 NR 4 TC 4 Z9 4 U1 0 U2 1 PU UNIV TORONTO PRESS INC PI TORONTO PA JOURNALS DIVISION, 5201 DUFFERIN ST, DOWNSVIEW, TORONTO, ON M3H 5T8, CANADA SN 0748-321X J9 J VET MED EDUC JI J. Vet. Med. Educ. PD SPR PY 2009 VL 36 IS 1 BP 62 EP 69 DI 10.3138/jvme.36.1.62 PG 8 WC Education, Scientific Disciplines; Veterinary Sciences SC Education & Educational Research; Veterinary Sciences GA 443GU UT WOS:000265899000009 PM 19435991 ER PT J AU Johnson, KM Kines, RC Roberts, JN Lowy, DR Schiller, JT Day, PM AF Johnson, Katherine M. Kines, Rhonda C. Roberts, Jeffrey N. Lowy, Douglas R. Schiller, John T. Day, Patricia M. TI Role of Heparan Sulfate in Attachment to and Infection of the Murine Female Genital Tract by Human Papillomavirus SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN KERATINOCYTES; BINDING; PROTEIN; GLYCOSAMINOGLYCANS; NEUTRALIZATION; INHIBITION; RECEPTOR; DISTINCT; CAPSIDS; FURIN AB The host factors required for in vivo infection have not been investigated for any papillomavirus. Using a recently developed murine cervicovaginal challenge model, we evaluated the importance of heparan sulfate proteoglycans (HSPGs) in human papillomavirus (HPV) infection of the murine female genital tract. We examined HPV type 16 (HPV16) as well as HPV31 and HPV5, for which some evidence suggests that they may differ from HPV16 in their utilization of HSPGs as their primary attachment factor in vitro. Luciferase-expressing pseudovirus of all three types infected the mouse genital tract, although HPV5, which normally infects nongenital epidermis, was less efficient. Heparinase III treatment of the genital tract significantly inhibited infection of all three types by greater than 90% and clearly inhibited virion attachment to the basement membrane and cell surfaces, establishing that HSPGs are the primary attachment factors for these three viruses in vivo. However, the pseudoviruses differed in their responses to treatment with various forms of heparin, a soluble analog of heparan sulfate. HPV16 and HPV31 infections were effectively inhibited by a highly sulfated form of heparin, but HPV5 was not, although it bound the compound. In contrast, a N-desulfated and N-acylated variant preferentially inhibited HPV5. Inhibition of infection paralleled the relative ability of the variants to inhibit basement membrane and cell surface binding. We speculate that cutaneous HPVs, such as HPV5, and genital mucosal HPVs, such as HPV16 and -31, may have evolved to recognize different forms of HSPGs to enable them to preferentially infect keratinocytes at different anatomical sites. C1 [Johnson, Katherine M.; Kines, Rhonda C.; Roberts, Jeffrey N.; Lowy, Douglas R.; Schiller, John T.; Day, Patricia M.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Day, PM (reprint author), NCI, Cellular Oncol Lab, NIH, 37 Convent Dr,Room 4112,MSC 4263, Bethesda, MD 20892 USA. EM pmd@nih.gov FU Intramural Research Program of the National Institutes of Health; National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 24 TC 110 Z9 114 U1 0 U2 4 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 MAR 1 PY 2009 VL 83 IS 5 BP 2067 EP 2074 DI 10.1128/JVI.02190-08 PG 8 WC Virology SC Virology GA 405GB UT WOS:000263209900002 PM 19073722 ER PT J AU Sakakibara, S Pise-Masison, CA Brady, JN Tosato, G AF Sakakibara, Shuhei Pise-Masison, Cynthia A. Brady, John N. Tosato, Giovanna TI Gene Regulation and Functional Alterations Induced by Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORFK13/vFLIP in Endothelial Cells SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; THYMIDINE PHOSPHORYLASE; GROWTH-FACTOR; KINASE COMPLEX; TNF-ALPHA; IN-VIVO; ACTIVATION; VFLIP; EXPRESSION; VIRUS AB Kaposi's sarcoma (KS) is an angioproliferative inflammatory disorder induced by endothelial cell infection with the KS-associated herpesvirus (KSHV). ORFK13/vFLIP, one of the KSHV genes expressed in KS, encodes a 188-amino-acid protein which binds to the I kappa b kinase (IKK) complex to activate NF-kappa B. We examined ORFK13/vFLIP contribution to KS phenotype and potential for therapeutic targeting. Retroviral transduction of ORFK13/vFLIP into primary human endothelial cells induces the spindle morphology distinctive of KS cells and promotes the formation of abnormal vascular networks typical of KS vasculature; upregulates the expression of proinflammatory cytokines, chemokines, and interferon-responsive genes; and stimulates the adhesion of inflammatory cells characteristic of KS lesions. Thymidine phosphorylase, a cellular enzyme markedly induced by ORFK13/vFLIP, can metabolize the prodrug 5-fluoro-5-deoxyuridine (5-dFUrd) to 5-fluouridine (5-FU), a potent thymidine synthase inhibitor, which blocks DNA and RNA synthesis. When tested for cytotoxicity, 5-dFUrd (0.1 to 1 mu M) selectively killed ORFK13/vFLIP-expressing endothelial cells while sparing control cells. These results demonstrate that ORFK13/vFLIP directly and indirectly contributes to the inflammatory and vascular phenotype of KS and identify 5-dFUrd as a potential new drug that targets KSHV latency for the treatment of KS and other KSHV-associated malignancies. C1 [Sakakibara, Shuhei; Pise-Masison, Cynthia A.; Brady, John N.; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Sakakibara, S (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 4134, Bethesda, MD 20892 USA. EM sakakibs@mail.nih.gov FU National Institute of Health, National Cancer Institute, Center for Cancer Research FX This study was supported by the intramural research program of the National Institute of Health, National Cancer Institute, Center for Cancer Research. NR 49 TC 24 Z9 24 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 MAR 1 PY 2009 VL 83 IS 5 BP 2140 EP 2153 DI 10.1128/JVI.01871-08 PG 14 WC Virology SC Virology GA 405GB UT WOS:000263209900009 PM 19091861 ER PT J AU Kong, WP Wu, L Wallstrom, TC Fischer, W Yang, ZY Ko, SY Letvin, NL Haynes, BF Hahn, BH Korber, B Nabel, GJ AF Kong, Wing-Pui Wu, Lan Wallstrom, Timothy C. Fischer, Will Yang, Zhi-Yong Ko, Sung-Youl Letvin, Norman L. Haynes, Barton F. Hahn, Beatrice H. Korber, Bette Nabel, Gary J. TI Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHOCYTE-BASED CONTROL; SUBTYPE-B ENVELOPE; IMMUNE-RESPONSES; HIV-1 INFECTION; RHESUS-MONKEYS; IMMUNOGENICITY; REPLICATION; GLYCOPROTEIN; VACCINES; AIDS AB An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV-1 Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential T-cell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. One-, two-, and three-mosaic sets that increased theoretical epitope coverage were developed. The breadth and magnitude of T-cell immunity stimulated by these vaccines were compared to those for natural strain Envs; additional comparisons were performed on mutant Envs, including gp160 or gp145 with or without V regions and gp41 deletions. Among them, the two-or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs. Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based HIV-1 vaccines. C1 [Kong, Wing-Pui; Wu, Lan; Yang, Zhi-Yong; Ko, Sung-Youl; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Wallstrom, Timothy C.; Fischer, Will; Korber, Bette] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Letvin, Norman L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02115 USA. [Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Hahn, Beatrice H.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Korber, Bette] Santa Fe Inst, Santa Fe, NM 87501 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov RI Fischer, Will/B-1323-2013; OI Fischer, Will/0000-0003-4579-4062; Wallstrom, Timothy/0000-0002-9295-2441; Korber, Bette/0000-0002-2026-5757 FU Intramural Research Program of the National Institutes of Health, Vaccine Research Center, National Institute of Allergy and Infectious Disease; Los Alamos National Laboratory FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, Vaccine Research Center, National Institute of Allergy and Infectious Disease, and by Los Alamos National Laboratory directed research funding. NR 38 TC 43 Z9 44 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 MAR 1 PY 2009 VL 83 IS 5 BP 2201 EP 2215 DI 10.1128/JVI.02256-08 PG 15 WC Virology SC Virology GA 405GB UT WOS:000263209900014 PM 19109395 ER PT J AU Crist, RM Datta, SAK Stephen, AG Soheilian, F Mirro, J Fisher, RJ Nagashima, K Rein, A AF Crist, Rachael M. Datta, Siddhartha A. K. Stephen, Andrew G. Soheilian, Ferri Mirro, Jane Fisher, Robert J. Nagashima, Kunio Rein, Alan TI Assembly Properties of Human Immunodeficiency Virus Type 1 Gag-Leucine Zipper Chimeras: Implications for Retrovirus Assembly SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA-VIRUS; HIV-1 MATRIX PROTEIN; NUCLEIC-ACID BINDING; SINGLE-STRANDED-DNA; IN-VITRO; NUCLEOCAPSID PROTEIN; COILED-COIL; PARTICLE FORMATION; VIRAL-RNA AB Expression of the retroviral Gag protein leads to formation of virus-like particles in mammalian cells. In vitro and in vivo experiments show that nucleic acid is also required for particle assembly. However, several studies have demonstrated that chimeric proteins in which the nucleocapsid domain of Gag is replaced by a leucine zipper motif can also assemble efficiently in mammalian cells. We have now analyzed assembly by chimeric proteins in which nucleocapsid of human immunodeficiency virus type 1 (HIV-1) Gag is replaced by either a dimerizing or a trimerizing zipper. Both proteins assemble well in human 293T cells; the released particles lack detectable RNA. The proteins can coassemble into particles together with full-length, wild-type Gag. We purified these proteins from bacterial lysates. These recombinant "Gag-Zipper" proteins are oligomeric in solution and do not assemble unless cofactors are added; either nucleic acid or inositol phosphates (IPs) can promote particle assembly. When mixed with one equivalent of IPs (which do not support assembly of wild-type Gag), the "dimerizing" Gag-Zipper protein misassembles into very small particles, while the "trimerizing" protein assembles correctly. However, addition of both IPs and nucleic acid leads to correct assembly of all three proteins; the "dimerizing" Gag-Zipper protein also assembles correctly if inositol hexakisphosphate is supplemented with other polyanions. We suggest that correct assembly requires both oligomeric association at the C terminus of Gag and neutralization of positive charges near its N terminus. C1 [Crist, Rachael M.; Datta, Siddhartha A. K.; Mirro, Jane; Rein, Alan] Natl Canc Inst Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Stephen, Andrew G.; Fisher, Robert J.] SAIC Frederick Inc, Prot Chem Lab, Frederick, MD 21702 USA. [Soheilian, Ferri; Nagashima, Kunio] SAIC Frederick Inc, Image Anal Lab, Frederick, MD 21702 USA. RP Rein, A (reprint author), Natl Canc Inst Frederick, HIV Drug Resistance Program, POB B, Frederick, MD 21702 USA. EM rein@ncifcrf.gov RI Fisher, Robert/B-1431-2009; Crist, Rachael/K-7603-2012; OI Datta, Siddhartha/0000-0002-4098-7490 FU Intramural Research Program of the NIH; National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [NO1-CO-12400] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. NO1-CO-12400. NR 59 TC 55 Z9 55 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 MAR 1 PY 2009 VL 83 IS 5 BP 2216 EP 2225 DI 10.1128/JVI.02031-08 PG 10 WC Virology SC Virology GA 405GB UT WOS:000263209900015 PM 19073719 ER PT J AU Springer, DA Phillippi-Falkenstein, K Smith, G AF Springer, Danielle A. Phillippi-Falkenstein, Kathrine Smith, Gary TI RETROSPECTIVE ANALYSIS OF WOUND CHARACTERISTICS AND TETANUS DEVELOPMENT IN CAPTIVE MACAQUES SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Review DE Matched case-control study; macaque; nonhuman primate; tetanus; wound ID DELAYED-TYPE HYPERSENSITIVITY; HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; MONKEYS MACACA-MULATTA; CELL-MEDIATED-IMMUNITY; DISEASE PROGRESSION; CONTINUING PROBLEM; INFECTION; COLONY; VACCINE AB Traumatic wounds and access to outdoor enclosures containing soil contribute to development of tetanus in nonhuman primates. A retrospective, matched case-control study was conducted at a primate center to evaluate these factors by analysis of medical records of animals sustaining traumatic injuries during a 3-yr study period. Thirty-one macaques with traumatic injuries and a clinical diagnosis of tetanus were selected as cases, and 62 macaques with traumatic injuries and no diagnosis of tetanus were selected as controls. For an animal with injuries to the digits, the odds of developing tetanus were 9.6 times those of a similar animal without injuries to the digits (Odds Ratio [OR] = 9.55. 95% CI = 1.56-58.59): with injuries to the tail, the odds of developing tetanus were 8.0 times those of a similar animal without injuries to the tail (OR = 7.95, 95% CI = 0.82-77.04); and with injuries in more than one location, the odds of developing tetanus were 8.5 times those for a similar animal with injuries in just one location (OR = 8.45, 95% Cl = 1.01-70.46). A nonhuman primate with injuries to the leg was less likely to develop tetanus than a similar nonhuman primate without injuries to the leg (OR = 0.19, 95% CI = 0.03-1.2). Results indicated that wound location is associated with development of tetanus infection in rhesus macaques. Identification of high-risk trauma cases will allow better allocation of wound management and tetanus prophylaxis in institutions, especially in those housing nonhuman primates outdoors. C1 [Springer, Danielle A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Phillippi-Falkenstein, Kathrine] Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. [Smith, Gary] Univ Penn, Sch Vet Med, Sect Epidemiol & Publ Hlth, New Bolton Ctr, Kennett Sq, PA 19348 USA. RP Springer, DA (reprint author), NHLBI, NIH, 9000 Rockville Pike,Bldg 14E,Room 107A, Bethesda, MD 20892 USA. EM ds628k@nih.gov FU National Center for Research Resources (NCRR) [5P51-RR00164, U24-RR18111, U42-RR016026] FX This research was funded by a National Center for Research Resources (NCRR) base grant (5P51-RR00164) and additional NCRR grants (U24-RR18111, U42-RR016026). The authors thank Dr. Rudolf Bohm for supporting this study and Dr. Erin Ribka and Dr. Marion Ratterree for clinical support. NR 39 TC 4 Z9 4 U1 0 U2 6 PU AMER ASSOC ZOO VETERINARIANS PI YULEE PA 581705 WHITE OAK ROAD, YULEE, FL 32097 USA SN 1042-7260 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD MAR PY 2009 VL 40 IS 1 BP 95 EP 102 DI 10.1638/2008-0055.1 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 427JO UT WOS:000264775800013 PM 19368246 ER PT J AU Cesari, M Pahor, M Lauretani, F Zamboni, V Bandinelli, S Bernabei, R Guralnik, JM Ferrucci, L AF Cesari, Matteo Pahor, Marco Lauretani, Fulvio Zamboni, Valentina Bandinelli, Stefania Bernabei, Roberto Guralnik, Jack M. Ferrucci, Luigi TI Skeletal Muscle and Mortality Results From the InCHIANTI Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Skeletal muscle; Body composition; Fat mass; Walking speed; Obesity; Sarcopenia; Mortality; InCHIANTI ID BODY-MASS INDEX; LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; OLDER PERSONS; FUNCTIONAL DECLINE; ELDERLY PERSONS; GAIT SPEED; SARCOPENIA; STRENGTH; WOMEN AB Sarcopenia, the age-related loss of muscle mass, may not be an isolated process but is associated with an increase in fat mass. The aim of this study was to estimate the mortality risk of sarcopenia in the presence or absence of obesity. Data are from 934 participants aged 65 years or older, enrolled in the "Invecchiare in Chianti" study, and followed for 6 years. At baseline, a peripheral quantitative computerized tomography (pQCT) scan was performed on all participants to evaluate the muscle density, and the muscular and fat cross-sectional areas of the calf. Walking speed was measured on a 7-m track. Cox proportional hazard models were performed to estimate the association of pQCT measures (per 1 standard deviation increase) with mortality. Unadjusted analyses showed significant associations of muscle density (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.69-0.88), muscle area (HR 0.75, 95% CI 0.66-0.86), and fat area (HR 0.82, 95% CI 0.73-0.92) with mortality. After adjustment for potential confounders, no body composition parameter was significantly associated with mortality. Walking speed (used as a reference measure to verify whether the negative results were due to peculiarities of the study sample) confirmed its well-established association with mortality risk (HR 0.73, 95% CI 0.60-0.88). These results did not change after the analyses were stratified according to sarcopenia and body mass index groups, and restricted to participants with frailty or a high inflammatory profile. Calf skeletal muscle and fat mass are not significant risk factors for mortality in community-dwelling older adults. Walking speed confirmed to be a powerful predictor of health-related events. C1 [Cesari, Matteo; Pahor, Marco] Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL 32611 USA. [Cesari, Matteo; Zamboni, Valentina; Bernabei, Roberto] Univ Cattolica Sacro Cuore, Dept Gerontol Geriatr & Physiatry, I-00168 Rome, Italy. [Lauretani, Fulvio] Tuscany Hlth Reg Agcy, Florence, Italy. [Bandinelli, Stefania] Hlth Agcy Florence, Geriatr Rehabil Unit, Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Cesari, M (reprint author), Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, POB 112610, Gainesville, FL 32611 USA. EM macesari@gmail.com RI Cesari, Matteo/A-4649-2008; Lauretani, Fulvio/K-5115-2016 OI Cesari, Matteo/0000-0002-0348-3664; Lauretani, Fulvio/0000-0002-5287-9972 FU Italian Ministry of Health [110.1/RS97.71]; U.S. National Institute on Aging [N01-AG-916413, N01-AG-5-0002, N01-AG-821336, R01-AG-027012]; Intramural Research Program, National Institute on Aging, National Institutes of Health FX The InCHIANTI study was supported as a "targeted project" (ICS 110.1/RS97.71) by the Italian Ministry of Health and by the U.S. National Institute on Aging ( contracts N01-AG-916413, N01-AG-5-0002, and N01-AG-821336, and grant R01-AG-027012). This research was supported in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health. We thank Hazel Lees for editing the manuscript. NR 46 TC 118 Z9 121 U1 3 U2 9 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 MAR PY 2009 VL 64 IS 3 BP 377 EP 384 DI 10.1093/gerona/gln031 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 419AC UT WOS:000264190500007 PM 19181709 ER PT J AU Neuwelt, EA Hamilton, BE Varallyay, CG Rooney, WR Edelman, RD Jacobs, PM Watnick, SG AF Neuwelt, Edward A. Hamilton, Bronwyn E. Varallyay, Csanad G. Rooney, William R. Edelman, Robert D. Jacobs, Paula M. Watnick, Suzanne G. TI Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)? SO KIDNEY INTERNATIONAL LA English DT Article DE nephrogenic systemic fibrosis; magnetic resonance imaging; ferumoxytol; i.v. iron ID CENTRAL-NERVOUS-SYSTEM; BRAIN-TUMORS; IN-VITRO; GADOLINIUM; FERUMOXTRAN-10; FERUMOXYTOL; ANGIOGRAPHY; NANOPARTICLES; FERUMOXIDES; PARTICLES AB Gadolinium (Gd) based contrast agents (GBCAs) in magnetic resonance imaging (MRI) are used in daily clinical practice and appear safe in most patients; however, nephrogenic systemic fibrosis (NSF) is a recently recognized severe complication associated with GBCAs. It affects primarily patients with renal disease, such as stage 4 or 5 chronic kidney disease (CKD; glomerular filtration rate < 30 ml/min per 1.73 m(2)), acute kidney injury, or kidney and liver transplant recipients with kidney dysfunction. Contrast-enhanced MRI and computed tomography (CT) scans provide important clinical information and influence patient management. An alternative contrast agent is needed to obtain adequate imaging results while avoiding the risk of NSF in this vulnerable patient group. One potential alternative is ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, which provide enhancement characteristics similar to GBCAs. We review our experience in approximately 150 patients on the potential benefits of the USPIOs ferumoxtran-10 and ferumoxytol. We focus on central nervous system (CNS) MRI but also review imaging of other vascular beds. Safety studies, including USPIO administration (ferumoxytol) as iron supplement therapy in CKD patients on and not on dialysis, suggest that decreased kidney function does not alter the safety profile. We conclude that for both CNS MR imaging and MR angiography, USPIO agents like ferumoxytol are a viable option for patients at risk for NSF. C1 [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol & Neurosurg, Portland, OR 97239 USA. [Neuwelt, Edward A.; Watnick, Suzanne G.] Portland VA Med Ctr, Portland, OR USA. [Hamilton, Bronwyn E.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Varallyay, Csanad G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Rooney, William R.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Edelman, Robert D.] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Jacobs, Paula M.] NCI Frederick, SAIC Frederick Inc, Natl Canc Inst, Canc Imaging Program, Frederick, MD USA. [Watnick, Suzanne G.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol & Neurosurg, 3181 SW Sam Jackson Pk Rd,Mailcode L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU NIH [NS33618, NS34608, NS44687]; National Institute of Neurological Disorders and Stroke [NIB1B EB007258] FX This research was supported by a Veteran's Administration Merit Review Grant and NIH grants NS33618, NS34608, and NS44687 from the National Institute of Neurological Disorders and Stroke to EAN and NIB1B EB007258 to WDR. AMAG Pharmaceuticals Inc. donated ferumoxtran-10 and ferumoxytol. NR 28 TC 109 Z9 113 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2009 VL 75 IS 5 BP 465 EP 474 DI 10.1038/ki.2008.496 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 406UJ UT WOS:000263320100010 PM 18843256 ER PT J AU Stevens, LA Schmid, CH Greene, T Li, L Beck, GJ Joffe, MM Froissart, M Kusek, JW Zhang, YP Coresh, J Levey, AS AF Stevens, Lesley A. Schmid, Christopher H. Greene, Tom Li, Liang Beck, Gerald J. Joffe, Marshall M. Froissart, Marc Kusek, John W. (Lucy) Zhang, Yaping Coresh, Josef Levey, Andrew S. TI Factors other than glomerular filtration rate affect serum cystatin C levels SO KIDNEY INTERNATIONAL LA English DT Article DE creatinine; cystatin; glomerular filtration rate generation ID CHRONIC KIDNEY-DISEASE; RENAL-DISEASE; CREATININE VALUES; ELDERLY PERSONS; UNITED-STATES; EQUATION; RISK; DIET; PERFORMANCE; PROGRESSION AB Cystatin C is an endogenous glomerular filtration marker hence its serum level is affected by the glomerular filtration rate (GFR). To study what other factors might affect it blood level we performed a cross-sectional analysis of 3418 patients which included a pooled dataset of clinical trial participants and a clinical population with chronic kidney disease. The serum cystatin C and creatinine levels were related to clinical and biochemical parameters and errors-in-variables models were used to account for errors in GFR measurements. The GFR was measured as the urinary clearance of (125)I-iothalamate and (51)Cr-EDTA. Cystatin C was determined at a single laboratory while creatinine was standardized to reference methods and these were 2.1+/-1.1 mg/dL and 1.8+/-0.8 mg/L, respectively. After adjustment for GFR, cystatin C was 4.3% lower for every 20 years of age, 9.2% lower for female gender but only 1.9% lower in blacks. Diabetes was associated with 8.5% higher levels of cystatin C and 3.9% lower levels of creatinine. Higher C-reactive protein and white blood cell count and lower serum albumin were associated with higher levels of cystatin C and lower levels of creatinine. Adjustment for age, gender and race had a greater effect on the association of factors with creatinine than cystatin C. Hence, we found that cystatin C is affected by factors other than GFR which should be considered when the GFR is estimated using serum levels of cystatin C. C1 [Stevens, Lesley A.; Schmid, Christopher H.; (Lucy) Zhang, Yaping; Levey, Andrew S.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. [Li, Liang; Beck, Gerald J.] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Joffe, Marshall M.] Univ Penn, Ctr Clin Epidemiol & Biostatist, Philadelphia, PA 19104 USA. [Froissart, Marc] Paris Descartes Univ, Dept Physiol & Biophys, Paris, France. [Kusek, John W.] NIDDKD, Bethesda, MD 20892 USA. [Coresh, Josef] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Stevens, LA (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA. EM lstevens1@tuftsmedicalcenter.org OI Froissart, Marc/0000-0002-4010-3173; Schmid, Christopher/0000-0002-0855-5313 FU [UO1 DK 053869]; [UO1 DK 067651]; [UO1 DK 35073] FX This study was supported by grants UO1 DK 053869, UO1 DK 067651, and UO1 DK 35073. Additional investigators and research staff of CKD-EPI include-Tufts Medical Center: Robert D. Bruce III; Cleveland Clinic: Frederick Van Lente; Johns Hopkins University: Jane Manzi, Brad Astor, Elizabeth Selvin; University of Pennsylvania: Harold I. Feldman, J. Richard Landis; National Institute of Diabetes and Digestive and Kidney Diseases: Paul W. Eggers and Robert Star. We acknowledge Michael Dowd for his contributions in development of the initial analytical approach described here. The results of this research were presented in abstract form at the Annual Meeting of the American Society of Nephrology in San Francisco, CA, 3 November 2007. NR 33 TC 239 Z9 261 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2009 VL 75 IS 6 BP 652 EP 660 DI 10.1038/ki.2008.638 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 412KH UT WOS:000263723200013 PM 19119287 ER PT J AU Whitlock, G Lewington, S Sherliker, P Clarke, R Emberson, J Halsey, J Qizilbash, N Collins, R Peto, R Lewington, S MacMahon, S Peto, R Aromaa, A Baigent, C Carstensen, J Chen, Z Clarke, R Collins, R Duffy, S Kromhout, D Neaton, J Qizilbash, N Rodgers, A Tominaga, S Tornberg, S Tunstall-Pedoe, H Whitlock, G Chambless, L De Backer, G De Bacquer, D Kornitzer, M Whincup, P Wannamethee, SG Morris, R Wald, N Morris, J Law, M Knuiman, M Bartholomew, H Smith, GD Sweetnam, P Elwood, P Yarnell, J Kronmal, R Kromhout, D Sutherland, S Keil, J Jensen, G Schnohr, P Hames, C Tyroler, A Aromaa, A Knekt, P Reunanen, A Tuomilehto, J Jousilahti, P VArtiainen, E Puska, P Kuznetsova, T Richart, T Staessen, J Thijs, L Jorgensen, T Thomsen, T Sharp, D Curb, JD Qizilbash, N Iso, H Sato, S Kitamura, A Naito, Y Benetos, A Guize, L Goldbourt, U Tomita, M Nishimoto, Y Murayama, T Criqui, M Davis, C Hart, C Smith, GD Hole, D Gillis, C Jacobs, D Blackburn, H Luepker, R Neaton, J Eberly, L Cox, C Levy, D D'Agostino, R Silbershatz, H Tverdal, A Selmer, R Meade, T Garrow, K Cooper, J Speizer, F Stampfer, M Menotti, A Spagnolo, A Tsuji, I Imai, Y Ohkubo, T Hisamichi, S Haheim, L Holme, I Hjermann, I Leren, P Ducimetiere, P Empana, J Jamrozik, K Broadhurst, R Assmann, G Schulte, H Bengtsson, C Bjorkelund, C Lissner, L Sorlie, P Garcia-Palmieri, M Barrett-Conner, E Criqui, M Langer, R Hart, C Smith, GD Hole, D Nakachi, K Imai, K Fang, X Li, S Buzina, R Nissinen, A Aravanis, C Dontas, A Kafatos, A Menotti, A Adachi, H Toshima, H Imaizumi, T Kromhout, D Nedeljkovic, S Ostojic, M Chen, Z Tunstall-Pedoe, H Nakayama, T Yoshiike, N Yokoyama, T Date, C Tanaka, H Keller, J Bonaa, K Arnesen, E Tunstall-Pedoe, H Rimm, E Gaziano, M Buring, JE Hennekens, C Tornberg, S Carstensen, J Shipley, M Leon, D Marmot, M Clarke, R Collins, R Emberson, J Halsey, J Lewington, S Palmer, A Parish, S Peto, R Sherliker, P Whitlock, G AF Whitlock, Gary Lewington, Sarah Sherliker, Paul Clarke, Robert Emberson, Jonathan Halsey, Jim Qizilbash, Nawab Collins, Rory Peto, Richard Lewington, S. MacMahon, S. Peto, R. Aromaa, A. Baigent, C. Carstensen, J. Chen, Z. Clarke, R. Collins, R. Duffy, S. Kromhout, D. Neaton, J. Qizilbash, N. Rodgers, A. Tominaga, S. Toernberg, S. Tunstall-Pedoe, H. Whitlock, G. Chambless, L. De Backer, G. De Bacquer, D. Kornitzer, M. Whincup, P. Wannamethee, S. G. Morris, R. Wald, N. Morris, J. Law, M. Knuiman, M. Bartholomew, H. Smith, G. Davey Sweetnam, P. Elwood, P. Yarnell, J. Kronmal, R. Kromhout, D. Sutherland, S. Keil, J. Jensen, G. Schnohr, P. Hames, C. Tyroler, A. Aromaa, A. Knekt, P. Reunanen, A. Tuomilehto, J. Jousilahti, P. VArtiainen, E. Puska, P. Kuznetsova, T. Richart, T. Staessen, J. Thijs, L. Jorgensen, T. Thomsen, T. Sharp, D. Curb, J. D. Qizilbash, N. Iso, H. Sato, S. Kitamura, A. Naito, Y. Benetos, A. Guize, L. Goldbourt, U. Tomita, M. Nishimoto, Y. Murayama, T. Criqui, M. Davis, C. Hart, C. Smith, G. Davey Hole, D. Gillis, C. Jacobs, D. Blackburn, H. Luepker, R. Neaton, J. Eberly, L. Cox, C. Levy, D. D'Agostino, R. Silbershatz, H. Tverdal, A. Selmer, R. Meade, T. Garrow, K. Cooper, J. Speizer, F. Stampfer, M. Menotti, A. Spagnolo, A. Tsuji, I. Imai, Y. Ohkubo, T. Hisamichi, S. Haheim, L. Holme, I. Hjermann, I. Leren, P. Ducimetiere, P. Empana, J. Jamrozik, K. Broadhurst, R. Assmann, G. Schulte, H. Bengtsson, C. Bjoerkelund, C. Lissner, L. Sorlie, P. Garcia-Palmieri, M. Barrett-Conner, E. Criqui, M. Langer, R. Hart, C. Smith, G. Davey Hole, D. Nakachi, K. Imai, K. Fang, X. Li, S. Buzina, R. Nissinen, A. Aravanis, C. Dontas, A. Kafatos, A. Menotti, A. Adachi, H. Toshima, H. Imaizumi, T. Kromhout, D. Nedeljkovic, S. Ostojic, M. CHen, Z. Tunstall-Pedoe, H. Nakayama, T. Yoshiike, N. Yokoyama, T. Date, C. Tanaka, H. Keller, J. Bonaa, K. Arnesen, E. Tunstall-Pedoe, H. Rimm, E. Gaziano, M. Buring, J. E. Hennekens, C. Tornberg, S. Carstensen, J. Shipley, M. Leon, D. Marmot, M. Clarke, R. Collins, R. Emberson, J. Halsey, J. Lewington, S. Palmer, A. Parish, S. Peto, R. Sherliker, P. Whitlock, G. CA PSC Collaborator ARIC TI Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies SO LANCET LA English DT Article ID CORONARY-HEART-DISEASE; BLOOD-PRESSURE; ABDOMINAL ADIPOSITY; VASCULAR MORTALITY; RANDOMIZED-TRIALS; INDIVIDUAL DATA; UNITED-STATES; KOREAN MEN; RISK; OBESITY AB Background The main associations of body-mass index (BMI) with overall and-cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies. Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894576 participants, mostly in western Europe and North America (61% [n=541452] male, mean recruitment age 46 [SD 11] years, median recruitment year 1,979 [IQR 1975-85], mean BMI 25 [SD 4] kg/m(2)). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the first 5 years of follow up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070 diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other. Findings In both sexes, mortality was lowest at about 22.5-25 kg/m(2). Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m2 higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m(2) [HR] 1.29 [95% CI 1.27-1.32]): 40% for vascular mortality (HR 1.41 [1.37-1.45]); 60-120% for diabetic, renal, and hepatic mortality (HRs 2.16 [1.89-2.46], 1.59 [1.27-1.99], and 1.82 [1.59-2.09], respectively); 10% for neoplastic mortality (HR 1.10 [1.06-1.15]); and 20% for respiratory and for all other mortality (HRs 1.20 [1.07-1.34] and 1.20 [1.16-1.25], respectively). Below the range 22.5-25 kg/m(2), BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer. These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI. Interpretation Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22.5-25 kg/m(2). The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal. At 30 35 kg/m(2), median survival is reduced by 2-4 years; at 40-45 kg/m(2), it is reduced by 8-10 years (which is comparable with the effects of smoking). The definite excess mortality below 22.5 kg/m(2) is due mainly to smoking-related diseases, and is not fully explained. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, EU BIOMED programme, US National Institute on Aging, and Clinical Trial Service Unit (Oxford, UK). C1 [Whitlock, Gary] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England. [Jensen, G.; Schnohr, P.] Copenhagen City Heart Study, Copenhagen, Denmark. [Sharp, D.; Curb, J. D.] Honolulu Heart Program, Honolulu, HI USA. [Iso, H.; Sato, S.; Kitamura, A.; Naito, Y.] Ikawa Noichi & Kyowa, Kyowa, Hokkaido, Japan. [Benetos, A.; Guize, L.] Ctr Invest Prevent & Clin IPC, Paris, France. [Levy, D.; D'Agostino, R.; Silbershatz, H.] NHLBI Framingham Heart Study, Framingham, MA USA. [Menotti, A.; Spagnolo, A.] Occupat Grp, Rome, Italy. [Ducimetiere, P.; Empana, J.] Paris Prospect Study, Paris, France. [Bengtsson, C.; Bjoerkelund, C.; Lissner, L.] Prospect Study Women, Gothenburg, Sweden. [Nakachi, K.; Imai, K.] Saitama Cohort Study, Saitama, Japan. RP Whitlock, G (reprint author), Univ Oxford, Clin Trial Serv Unit, Richard Doll Bldg, Oxford OX3 7LF, England. EM psc@ctsu.ox.ac.uk RI Leon, David/G-2195-2010; Mavoa, Suzanne/B-5372-2010; Kromhout, Daan/A-8566-2014; Knuiman, Matthew/I-5549-2013; Staessen, Jan/A-1065-2011; OI Marmot, Michael/0000-0002-2431-6419; Leon, David/0000-0001-9747-1762; Staessen, Jan/0000-0002-3026-1637; Eberly, Lynn/0000-0003-4763-330X; Carstensen, John/0000-0003-2256-8089; Jorgensen, Torben/0000-0001-9453-2830 FU UK Medical Research Council; British Heart Foundation; Cancer Research UK; EU BIOMED; NIA [P01 AG17625-01]; CTSU; Girdlers' Health Research Council of New Zealand Fellowship; Sarah Lewington had a British Heart Foundation Fellowship FX The Prospective Studies Collaboration has been supported by the UK Medical Research Council, British Heart Foundation, Cancer Research UK, EU BIOMED programme, NIA grant P01 AG17625-01, and CTSU overheads. Merck (F Walker) helped support the 1996 meeting of collaborators. Gary Whitlock was supported by a Girdlers' Health Research Council of New Zealand Fellowship, Sarah Lewington had a British Heart Foundation Fellowship to coordinate the project. Sarah Parish supplied unpublished analyses of BMI and cotinine (webappendix). NR 38 TC 1413 Z9 1457 U1 13 U2 131 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR-APR PY 2009 VL 373 IS 9669 BP 1083 EP 1096 DI 10.1016/S0140-6736(09)60318-4 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 427IS UT WOS:000264773600029 ER PT J AU Nash, TE Garcia, HH AF Nash, Theodore E. Garcia, Hector H. TI Perilesional brain oedema and seizure activity: cause or effect? Reply SO LANCET NEUROLOGY LA English DT Letter ID STATUS EPILEPTICUS; NEUROCYSTICERCOSIS C1 [Nash, Theodore E.; Garcia, Hector H.] NIAID, NIH, Bethesda, MD 20892 USA. RP Nash, TE (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM tnash@niaid.nih.gov NR 8 TC 0 Z9 0 U1 1 U2 1 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 MAR PY 2009 VL 8 IS 3 BP 225 EP 226 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 412FZ UT WOS:000263711200007 ER PT J AU Cohen, EEW Davis, DW Karrison, TG Seiwert, TY Wong, SJ Nattam, S Kozloff, MF Clark, JI Yan, DH Liu, W Pierce, C Dancey, JE Stenson, K Blair, E Dekker, A Vokes, EE AF Cohen, Ezra E. W. Davis, Darren W. Karrison, Theodore G. Seiwert, Tanguy Y. Wong, Stuart J. Nattam, Sreenivasa Kozloff, Mark F. Clark, Joseph I. Yan, Duen-Hwa Liu, Wen Pierce, Carolyn Dancey, Janet E. Stenson, Kerstin Blair, Elizabeth Dekker, Allison Vokes, Everett E. TI Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study SO LANCET ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; BREAST-CANCER CELLS; II TRIAL; ACQUIRED-RESISTANCE; ANTITUMOR-ACTIVITY; CETUXIMAB; THERAPY; CHEMOTHERAPY; EGFR AB Background Epidermal growth factor receptor (EGFR) is a validated target in squamous-cell carcinoma of the head and neck, but in patients with recurrent or metastatic disease, EGFR targeting agents have displayed modest efficacy. Vascular endothelial growth factor (VEGF)-mediated angiogenesis has been implicated as a mechanism of resistance to anti-EGFR therapy. In this multi-institutional phase I/II study we combined an EGFR inhibitor, erlotinib, with an anti-VEGF antibody, bevacizumab. Methods Between April 15, 2003, and Jan 27, 2005, patients with recurrent or metastatic squamous-cell carcinoma of the head and neck were enrolled from seven centres in the USA and were given erlotinib (150 mg daily) and bevacizumab in escalating dose cohorts. The primary objectives in the phase I and II sections, respectively, were to establish the maximum tolerated dose and dose-limiting toxicity of bevacizumab when administered with erlotinib and to establish the proportion of objective responses and time to disease progression. Pretreatment serum and tissues were collected and analysed by enzyme-linked immunosorbent assay and immunofluorescence quantitative laser analysis, respectively. This study was registered with ClinicalTrials.gov, number NCT00055913. Findings In the phase I section of the trial, ten patients were enrolled in three successive cohorts with no dose-limiting toxic effects noted. 46 patients were enrolled in the phase II section of the trial (including three patients from the phase I section) on the highest dose of bevacizumab (15 mg/kg every 3 weeks). Two additional patients were accrued beyond the protocol-stipulated 46, leaving a total of 48 patients for the phase II assessment. The most common toxic effects of any grade were rash and diarrhoea (41 and 16 of 48 patients, respectively). Three patients had serious bleeding events of grade 3 or higher. Seven patients had a response, with four showing a complete response allowing rejection of the null hypothesis. Median time of overall survival and progression-free survival (PFS) were 7.1 months (95% CI 5.7-9.0) and 4.1 months (2.8-4.4), respectively. Higher ratios of tumour-cell phosphorylated VEGF receptor-2 (pVEGFR2) over total VEGFR2 and endothelial-cell pEGFR over total EGFR in pretreatment biopsies were associated with complete response (0.704 vs 0.386, p=0.036 and 0.949 vs 0.332, p=0.036, respectively) and tumour shrinkage (p=0.007 and p=0.008, respectively) in a subset of 11 patients with available tissue. Interpretation The combination of erlotinib and bevacizumab is well tolerated in recurrent or metastatic squamous-cell carcinoma of the head and neck. A few patients seem to derive a sustained benefit and complete responses were associated with expression of putative targets in pretreatment tumour tissue. C1 [Cohen, Ezra E. W.; Seiwert, Tanguy Y.; Pierce, Carolyn; Dekker, Allison; Vokes, Everett E.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Karrison, Theodore G.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Stenson, Kerstin; Blair, Elizabeth] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Vokes, Everett E.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. [Cohen, Ezra E. W.; Seiwert, Tanguy Y.; Vokes, Everett E.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. [Davis, Darren W.; Yan, Duen-Hwa; Liu, Wen] ApoCell Inc, Houston, TX USA. [Wong, Stuart J.] Med Coll Wisconsin, Dept Med, Div Neoplast Dis, Milwaukee, WI 53226 USA. [Nattam, Sreenivasa] Ft Wayne Med Oncol Hematol, Ft Wayne, IN USA. [Kozloff, Mark F.] Ingalls Hosp, Harvey, IL USA. [Clark, Joseph I.] Loyola Univ Chicago, Maywood, IL USA. [Dancey, Janet E.] Natl Canc Inst, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA. RP Cohen, EEW (reprint author), 5841 S Maryland Ave,MC2115, Chicago, IL 60637 USA. EM ecohen@medicine.bsd.uchicago.edu FU National Cancer Institute, National Institutes of Health, Bethesda, MD, USA [N01-CM-17102]; University of Chicago Cancer Research Center, Chicago, IL, USA [P30 CA14599] FX Funding National Cancer Institute, National Institutes of Health, Bethesda, MD, USA (grant number N01-CM-17102) and the University of Chicago Cancer Research Center, Chicago, IL, USA (grant number P30 CA14599). NR 38 TC 152 Z9 155 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2009 VL 10 IS 3 BP 247 EP 257 DI 10.1016/S1470-2045(09)70002-6 PG 11 WC Oncology SC Oncology GA 421BF UT WOS:000264332200019 PM 19201650 ER PT J AU Ito, W Pan, BX Yang, C Thakur, S Morozov, A AF Ito, Wataru Pan, Bing-Xing Yang, Chao Thakur, Siddarth Morozov, Alexei TI Enhanced generalization of auditory conditioned fear in juvenile mice SO LEARNING & MEMORY LA English DT Article ID LONG-TERM POTENTIATION; STIMULUS-GENERALIZATION; BEHAVIORAL EXPRESSION; LEARNED FEAR; RATS; ADOLESCENCE; AMYGDALA; CONTEXT; CORTEX; MEMORY AB Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4-5-wk-old mice (juveniles) than in their 9-10-wk-old counterparts (adults), whereas nonassociative sensitization induced by foot shock (US) and the ability to discriminate CS+ from an explicitly unpaired stimulus (CS-) are not dependent on age. These results suggest that aversive associations are less precise in juvenile mice and can more easily produce conditional responses to stimuli different from CS+. Yet, through the explicit unpairing of CS- from US during training, juveniles are able to overcome this greater fear generalization and learn that CS- is not associated with foot shock. C1 [Ito, Wataru; Pan, Bing-Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei] NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Morozov, A (reprint author), NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. EM morozova@mail.nih.gov RI PAN, BINGXING/C-7870-2011 FU NIMH Intramural Research Program FX This research was supported by NIMH Intramural Research Program. We thank Jacqueline N. Crawley (NIMH), Gleb Shumyatsky (Rutgers University), and Gael Malleret (Faculte de Medecine Laennec, Lyon) for comments on the manuscript. NR 34 TC 23 Z9 23 U1 3 U2 14 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD MAR PY 2009 VL 16 IS 3 BP 187 EP 192 DI 10.1101/lm.1190809 PG 6 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 410TV UT WOS:000263602100004 PM 19228588 ER PT J AU Wang, SS Maurer, MJ Morton, LM Habermann, TM Davis, S Cozen, W Lynch, CF Severson, RK Rothman, N Chanock, SJ Hartge, P Cerhan, JR AF Wang, S. S. Maurer, M. J. Morton, L. M. Habermann, T. M. Davis, S. Cozen, W. Lynch, C. F. Severson, R. K. Rothman, N. Chanock, S. J. Hartge, P. Cerhan, J. R. TI Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma SO LEUKEMIA LA English DT Letter ID NON-HODGKIN-LYMPHOMA; RISK C1 [Wang, S. S.; Morton, L. M.; Rothman, N.; Chanock, S. J.; Hartge, P.] NCI, Div Canc Epidemiol, Rockville, MD USA. [Maurer, M. J.; Habermann, T. M.; Cerhan, J. R.] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN USA. [Davis, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cozen, W.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Lynch, C. F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Severson, R. K.] Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Severson, R. K.] Karmanos Canc Inst, Detroit, MI USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol, Rockville, MD USA. EM wangso@mail.nih.gov RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS; NCI NIH HHS [N01 PC067010, N01 PC065064, N01 PC067008, N01 PC067009, P50 CA097274, P50-CA97274, R01 CA096704, R01 CA096704-01, R01-CA96704] NR 8 TC 17 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2009 VL 23 IS 3 BP 596 EP 602 DI 10.1038/leu.2008.240 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 416VC UT WOS:000264032600024 PM 18830263 ER PT J AU Beaulieu, SE Mullineaux, LS Adams, DK Mills, SW AF Beaulieu, Stace E. Mullineaux, Lauren S. Adams, Diane K. Mills, Susan W. TI Comparison of a sediment trap and plankton pump for time-series sampling of larvae near deep-sea hydrothermal vents SO LIMNOLOGY AND OCEANOGRAPHY-METHODS LA English DT Article ID MID-ATLANTIC RIDGE; INVERTEBRATE LARVAE; PARTICLE-FLUX; IN-SITU; DISPERSAL; BOTTOM; BEHAVIOR; IDENTIFICATION; SETTLEMENT; EFFICIENCY AB Studies of larval dispersal and supply are critical to understanding benthic population and community dynamics. A major limitation to these studies in the deep sea has been the restriction of larval sampling to infrequent research cruises. In this study, we investigated the utility of a sediment trap for autonomous, time-series sampling of larvae near deep-sea hydrothermal vents. We conducted simultaneous deployments of a time-series sediment trap and a large-volume plankton pump in close proximity on the East Pacific Rise (2510-m depth). Grouped and species-specific downward fluxes of larvae into the sediment trap were not correlated to larval abundances in pump samples, mean horizontal flow speeds, or mean horizontal larval fluxes. The sediment trap collected a higher ratio of gastropod to polychaete larvae, a lower diversity of gastropod species, and over- or undercollected some gastropod species relative to frequencies in pump sampling. These differences between the two sampling methods indicate that larval concentrations in the plankton are not well predicted by fluxes of larvae into the sediment trap. Future studies of deep-sea larvae should choose a sampling device based on specific research goals. Limited by battery power, a plankton pump in combination with a current meter is useful for estimating horizontal advective fluxes in short-term (days to weeks) studies of larval dispersal. A sediment trap, selecting for larvae with downward trajectories, is more appropriate for studies of larval supply to the benthos. For some species, a time-series sediment trap can collect sequential larval samples for long-term studies (months to years) for correlation to larval settlement and recruitment patterns. C1 [Beaulieu, Stace E.; Mullineaux, Lauren S.; Mills, Susan W.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [Adams, Diane K.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Beaulieu, SE (reprint author), Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. EM stace@whoi.edu RI Beaulieu, Stace/C-8526-2013; Adams, Diane/E-7831-2015 OI Beaulieu, Stace/0000-0002-2609-5453; Adams, Diane/0000-0001-6638-5781 FU Woods Hole Oceanographic Institution Deep Ocean Exploration Institute; NSF [OCE-0424953]; National Defense Science and Engineering Grant Fellowship FX We thank S. Manganini, A. Fleer, S. Worrilow, J. Kemp, and R. Trask for providing, respectively, a sediment trap, plankton pump, current meter, acoustic releases, and floats for our moorings. We also thank Chief Scientist M. Lilley, the crew of R/V Atlantis, the shipboard scientific support group, and the Alvin group during Cruise AT11-20. We thank V. Starczak for help with statistics, and S. Bayer, I. Garcia Berdeal, N. Reyns, C. Strasser, D. Thistle, and three anonymous reviewers for comments on the manuscript. Funding for this study was provided by a Woods Hole Oceanographic Institution Deep Ocean Exploration Institute grant to L. S. M. and S. E. B., NSF grant OCE-0424953 to L. S. M., and a National Defense Science and Engineering Grant Fellowship to D. K. A. NR 41 TC 13 Z9 13 U1 0 U2 10 PU AMER SOC LIMNOLOGY OCEANOGRAPHY PI WACO PA 5400 BOSQUE BLVD, STE 680, WACO, TX 76710-4446 USA SN 1541-5856 J9 LIMNOL OCEANOGR-METH JI Limnol. Oceanogr. Meth. PD MAR PY 2009 VL 7 BP 235 EP 248 PG 14 WC Limnology; Oceanography SC Marine & Freshwater Biology; Oceanography GA 432YX UT WOS:000265171400004 ER PT J AU Bonner, MR Shen, M Liu, CS DiVita, M He, XZ Lan, Q AF Bonner, Matthew R. Shen, Min Liu, Chin-San DiVita, Margaret He, Xingzhou Lan, Qing TI Mitochondrial DNA content and lung cancer risk in Xuan Wei, China SO LUNG CANCER LA English DT Article DE Lung Cancer; Mitochondrial DNA copy number; Mitochondrial DNA content; Case-control study; Polycyclic aromatic hydrocarbons; Smoky coal ID HUMAN HEPATOCELLULAR-CARCINOMA; COAL COMBUSTION EMISSIONS; RENAL-CELL CARCINOMA; OXIDATIVE STRESS; COPY NUMBER; CURRENT PROGRESS; MUTATIONS; INCREASE; APOPTOSIS; DEPLETION AB Smoky coal contains polycyclic aromatic hydrocarbons (PAHs) and has been strongly implicated in etiology of lung cancer in Xuan Wei, China. While PAHs form bulky adducts in nuclear DNA, they have a 40-90-fold greater affinity for mitochondrial DNA (mtDNA). mtDNA content may increase to compensate for mtDNA damage. We conducted a population-based case-control study of lung cancer in Xuan Wei, China hypothesizing that mtDNA content is positively associated with lung cancer risk. Cases (n=122) and controls (n=121) were individually matched on age (+/- 2 years), sex, village of residence, and current fuel type. Lifetime smoky coal use and potential confounders were determined with questionnaires. mtDNA was extracted from sputum and mtDNA content was determined with quantitative PCR. ORs and 95% Cls were calculated with unconditional logistic regression. mtDNA content >157 copies per cell was associated with lung cancer risk (OR=1.8; 95% CI=1.0-3.2) compared with those with <= 157 copies. In summary, mtDNA content was positively associated with lung cancer risk. Furthermore, mtDNA content was more strongly associated with lung cancer risk among older individuals. However, due to the small sample size, additional studies are needed to evaluate this potential association. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Bonner, Matthew R.; DiVita, Margaret] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14214 USA. [Shen, Min; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Liu, Chin-San] Changhua Christian Hosp, Changhua, Taiwan. [He, Xingzhou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. RP Bonner, MR (reprint author), SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, 270 Farber Hall, Buffalo, NY 14214 USA. EM mrbonner@buffalo.edu OI DiVita, Margaret/0000-0002-4878-2959 FU National Cancer Institute FX This manuscript was supported by intramural funds from the National Cancer Institute. NR 40 TC 26 Z9 28 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD MAR PY 2009 VL 63 IS 3 BP 331 EP 334 DI 10.1016/j.lungcan.2008.06.012 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 417PO UT WOS:000264088700004 PM 18691788 ER PT J AU Isenberg, JS Qin, Y Maxhimer, JB Sipes, JM Despres, D Schnermann, J Frazier, WA Roberts, DD AF Isenberg, Jeff S. Qin, Yan Maxhimer, Justin B. Sipes, John M. Despres, Daryl Schnermann, Jurgen Frazier, William A. Roberts, David D. TI Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress SO MATRIX BIOLOGY LA English DT Article DE Thrombospondin-1; CD47; Nitric oxide; Blood pressure; Cardiac output ID MUSCLE-CELL RESPONSES; NITRIC-OXIDE; MYOCARDIAL-INFARCTION; PLASMA THROMBOSPONDIN; GENERAL-ANESTHESIA; ISCHEMIC TISSUE; CGMP; INHIBITION; ARTERY; PHOSPHODIESTERASES AB Nitric oxide (NO) locally regulates vascular resistance and blood pressure by modulating blood vessel tone. Thrombospondin-1 signaling via its receptor CD47 locally limits the ability of NO to relax vascular smooth muscle cells and increase regional blood flow in ischemic tissues. To determine whether thrombospondin-1 plays a broader role in central cardiovascular physiology, we examined vasoactive stress responses in mice lacking thrombospondin-1 or CD47. Mice lacking thrombospondin-1 exhibit activity-associated increases in heart rate, central diastolic and mean arterial blood pressure and a constant decrease in pulse pressure. CD47-deficient mice have normal central pulse pressure but elevated resting peripheral blood pressure. Both null mice show exaggerated decreases in peripheral blood pressure and increased cardiac output and ejection fraction in response to NO. Autonomic blockade also induces exaggerated hypotensive responses in awake thrombospondin-1 null and CD47 null mice. Both null mice exhibit a greater hypotensive response to isoflurane, and autonomic blockage under isoflurane anesthesia leads to premature death of thrombospondin-1 null mice. Conversely, the hypertensive response to epinephrine is attenuated in thrombospondin-1 null mice. Thus, the matricellular protein thrombospondin-1 and its receptor CD47 serve as acute physiological regulators of blood pressure and exert a vasopressor activity to maintain global hemodynamics under stress. Published by Elsevier B.V. C1 [Roberts, David D.] NCI, NIH, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Qin, Yan; Schnermann, Jurgen] NIDDKD, Kidney Dis Branch, Bethesda, MD 20892 USA. [Despres, Daryl] NIH, Mouse Imaging Facil, Bethesda, MD 20892 USA. [Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Roberts, DD (reprint author), NCI, NIH, Pathol Lab, Ctr Canc Res, Bldg 10 Room 2A33, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NIH [HL54390, GM57573]; National Cancer Institute; Center for Cancer Research; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Dr. Larry Keefer for providing reagents and Kevin Kaltenbronn and Dr. Ken Blumer for performing the carotid pressure measurements. This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (D.D.R.), National Institute of Diabetes and Digestive and Kidney Diseases (J.S.) and NIH grants HL54390 and GM57573 (W.A.F.). NR 48 TC 41 Z9 41 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD MAR PY 2009 VL 28 IS 2 BP 110 EP 119 DI 10.1016/j.matbio.2009.01.002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 437YI UT WOS:000265522400007 PM 19284971 ER PT J AU Qu, T Walston, JD Yang, H Fedarko, NS Xue, QL Beamer, BA Ferrucci, L Rose, NR Leng, SX AF Qu, Tao Walston, Jeremy D. Yang, Huanle Fedarko, Neal S. Xue, Qian-Li Beamer, Brock A. Ferrucci, Luigi Rose, Noel R. Leng, Sean X. TI Upregulated ex vivo expression of stress-responsive inflammatory pathway genes by LPS-challenged CD14(+) monocytes in frail older adults SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Frailty; Monocyte-mediated inflammatory pathways; Gene expression; Stress-responsive genes; Geriatrics; Aging ID GROWTH-FACTOR-I; SERUM INTERLEUKIN-6; GERIATRIC SYNDROME; WOMENS-HEALTH; ACTIVATION; DISEASE; PROTEIN; CHEMOKINES; RECEPTOR; DIFFERENTIATION AB Frailty has been increasingly recognized as an important clinical syndrome in old age. The frailty syndrome is characterized by chronic inflammation, decreased functional and physiologic reserve, and increased vulnerability to stressors, leading to disability and mortality. However, molecular mechanisms that contribute to inflammation activation and regulation in frail older adults have not been investigated. To begin to address this, we conducted a pathway-specific gene array analysis of 367 inflammatory pathway genes by lipopolysaccharide (LPS)-challenged CD14(+) monocytes from 32 community-dwelling frail and age-, race-, and sex-paired nonfrail older adults (mean age 83 years, range 72-94). The results showed that ex vivo LPS-challenge induced average 2.0-fold or higher upregulated expression of 116 genes in frail participants and 85 genes in paired nonfrail controls. In addition, frail participants had 2-fold or higher upregulation in LPS-incluced expression of 7 stress-responsive genes than nonfrail controls with validation by quantitative real time RT-PCR. These findings suggest upregulated expression of specific stress-responsive genes in monocyte-mediated inflammatory pathway in the syndrome of frailty with potential mechanistic and interventional implications. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Qu, Tao; Walston, Jeremy D.; Yang, Huanle; Fedarko, Neal S.; Xue, Qian-Li; Beamer, Brock A.; Leng, Sean X.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol,Biol Frailty Program, Baltimore, MD 21224 USA. [Rose, Noel R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21224 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Leng, SX (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol,Biol Frailty Program, John R Burton Pavil,5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM sleng1@jhmi.edu OI Fedarko, Neal/0000-0001-6055-6279 FU National Institutes of Health, National Institute on Aging [R21 AG024235]; [K23 AG028963] FX Financial disclosure: There is no conflict of financial interest, relationships or affiliations other than those listed on the title page.; Grant support: This work was supported in part by the National Institutes of Health, National Institute on Aging, R21 AG024235 (Dr. Leng). Dr. Leng is a current recipient of the Paul Beeson career development award in aging research, K23 AG028963.; Sponsor's role: None. NR 41 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD MAR PY 2009 VL 130 IS 3 BP 161 EP 166 DI 10.1016/j.mad.2008.10.005 PG 6 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 414OC UT WOS:000263873000005 PM 19027777 ER PT J AU Senay, I Kaphingst, KA AF Senay, Ibrahim Kaphingst, Kimberly A. TI Anchoring-and-Adjustment Bias in Communication of Disease Risk SO MEDICAL DECISION MAKING LA English DT Article DE risk communication; information processing; genetic counseling; anchoring and adjustment heuristic; health-protective behavior ID BREAST-CANCER RISK; SELECTIVE ACCESSIBILITY; PERSPECTIVE-TAKING; FAMILY-HISTORY; PERCEIVED RISK; WOMEN; IMPACT; PERCEPTIONS; HEALTH; SUSCEPTIBILITY AB Over the next decade, advances in genomics will make it increasingly possible to provide patients with personalized, genetic-based risks of common diseases, allowing them the opportunity to take preventive steps through behavioral changes. However, previous research indicates that people may insufficiently adjust their subjective risk to the objective risk value communicated to them by a healthcare provider, a phenomenon called anchoring-and-adjustment bias. In this narrative review, we analyze existing research on how patients process disease-risk information, and the processing biases that may occur, to show that the bias observed in disease-risk communication is potentially malleable to change. We recommend that, to reduce this bias and change patients' misperceptions of disease risk in clinical settings, future studies investigate the effects of forewarning patients about the bias, tailoring risk information to their numeracy level, emphasizing social roles, increasing motivation to form accurate risk perception, and reducing social stigmatization, disease worry and information overload. C1 [Senay, Ibrahim; Kaphingst, Kimberly A.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Senay, I (reprint author), Univ Illinois, Dept Psychol, 603 E Daniel St, Champaign, IL 61820 USA. EM senay@illinois.edu FU Intramural NIH HHS [Z01 HG200321-03] NR 46 TC 33 Z9 33 U1 7 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAR PY 2009 VL 29 IS 2 BP 193 EP 201 DI 10.1177/0272989X08327395 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 432CB UT WOS:000265110000005 PM 19279297 ER PT J AU Caldicott, CV Danis, M AF Caldicott, Catherine V. Danis, Marion TI Medical ethics contributes to clinical management: teaching medical students to engage patients as moral agents SO MEDICAL EDUCATION LA English DT Article DE clinical medicine; *education; ethics; clinical; *education; teaching; *methods; physician-patient relations; *ethics; *education; medical; undergraduate; *morals ID EDUCATION AB In order to teach medical students to engage more fully with patients, we offer ethics education as a tool to assist in the management of patient health issues. We propose that many dilemmas in clinical medicine would benefit by having the doctor embark on an iterative reasoning process with the patient. Such a process acknowledges and engages the patient as a moral agent. We recommend employing Kant's ethic of respect and a more inclusive definition of patient autonomy drawn from philosophy and clinical medicine, rather than simply presenting dichotomous choices to patients, which represents a common, but often suboptimal, means of approaching both medical and moral concerns. We describe how more nuanced teaching about the ethics of the doctor-patient relationship might fit into the medical curriculum and offer practical suggestions for implementing a more respectful, morally engaged relationship with patients that should assist them to achieve meaningful health goals. C1 [Caldicott, Catherine V.] SUNY Upstate Med Univ, Ctr Bioeth & Humanities, Syracuse, NY 13210 USA. [Danis, Marion] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Caldicott, CV (reprint author), SUNY Upstate Med Univ, Ctr Bioeth & Humanities, 725 Irving Ave,Suite 406, Syracuse, NY 13210 USA. EM caldicoc@upstate.edu FU Intramural NIH HHS [Z99 CL999999] NR 12 TC 6 Z9 8 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0308-0110 J9 MED EDUC JI Med. Educ. PD MAR PY 2009 VL 43 IS 3 BP 283 EP 289 DI 10.1111/j.1365-2923.2008.03277.x PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 408WM UT WOS:000263466200014 PM 19250356 ER PT J AU Thein, M Ershler, WB Artz, AS Tecson, J Robinson, BF Rothstein, G Liede, A Gylys-Colwell, I Lu, ZJ Robbins, S AF Thein, Mya Ershler, William B. Artz, Andrew S. Tecson, Josephine Robinson, Bruce F. Rothstein, Gerald Liede, Alexander Gylys-Colwell, Ina Lu, Z. John Robbins, Sean TI Diminished Quality of Life and Physical Function in Community-Dwelling Elderly With Anemia SO MEDICINE LA English DT Article ID HEALTH SURVEY SF-36; NURSING-HOME; HEMOGLOBIN CONCENTRATION; OLDER WOMEN; STEM-CELLS; UNEXPLAINED ANEMIA; IRON-METABOLISM; UNITED-STATES; OUTCOMES; CANCER AB The occurrence of anemia in older adults has been associated with adverse outcomes including functional decline, disability, morbidity. and mortality. It is not clear to what extent these outcomes are the result of the anemia or concurrent illness. We performed a cross-sectional, observational study to determine whether lower hemoglobin concentrations in older adults are associated with reduced health-related quality of life, functional status. depression, disability, and physical strength, independent of chronic disease. Three sites participated in this research:,in academic geriatric practice, it hospital-based geriatric outpatient unit, and a community-based multispecialty internal medicine group. Health-related quality of life and functional status were measured using the Short Form-36 Health Survey (SF-36) and the Functional Assessment of Chronic Illness Therapy-Anemia (FACIT-An). Disability and depression were assessed using the Instrumental Activities of Daily Living (IADL) and the Geriatric Depression Scale (GDS) questionnaires, respectively. Handgrip strength wits used as it physical per Forti lance measure. Anemia was defined as hemoglobin <13 g/dL for men or <12 g/dL. for women, The mean SF-36 physical health component summary scores were 38.9 (with anemia) and 44.1 (without anemia) (p < 0.001), Anemia was associated with greater fatigue (p < 0.001), lower handgrip strength (p = 0.014), increased number of disabilities (p = 0.005), and more depressive symptoms (p = 0.002). Multivariate regression analysis, adjusted for demographic and clinical characteristics, demonstrated strong associations for reduced hemoglobin, even within the "normal" range, and poorer health-related quality of life across Multiple domains. Thus. anemia was independently associated with clinically significant impairments in multiple domains of health-related quality of life, especially in measures of functional limitation. Mildly low hemoglobin levels, even when above tire World health Organization (WHO) anemia threshold, were associated with significant declines in quality of life among the elderly. C1 [Ershler, William B.] Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD 21225 USA. [Thein, Mya; Ershler, William B.; Artz, Andrew S.; Tecson, Josephine] Inst Adv Studies Aging & geriatr Med, Washington, DC USA. [Artz, Andrew S.] Univ Chicago Hosp, Chicago, IL 60637 USA. [Robinson, Bruce F.] Univ S Florida, Sarasota Hosp, Sarasota, FL USA. [Rothstein, Gerald] Univ Utah, Sch Med, Salt Lake City, UT USA. [Liede, Alexander; Gylys-Colwell, Ina; Lu, Z. John; Robbins, Sean] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Ershler, WB (reprint author), Harbor Hosp, NIA, Clin Res Branch, NM545, Baltimore, MD 21225 USA. EM ershlerwi@mail.nih.gov FU Amgen Inc.; Intramural Research Program; National Institute on Aging; Val A. Browning Foundation FX This work was supported in part by it grant front Amgen Inc. WBE was supported by the Intramural Research Program, National Institute on Aging. GR received support from the Val A. Browning Foundation. A L, IGC, ZJL, and SR were employees and stock holders of Amgen Inc. at the time of the study. They were involved as statistical consultants; final data analysis the responsibility of WBE and ASA. NR 57 TC 35 Z9 37 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 2009 VL 88 IS 2 BP 107 EP 114 DI 10.1097/MD.0b013e31819d89d5 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 420FB UT WOS:000264273200005 PM 19282701 ER PT J AU Charles, C Yuskavage, J Carlson, O John, M Tagalicud, AS Maggio, M Muller, DC Egan, J Basaria, S AF Charles, Cornelia Yuskavage, Julia Carlson, Olga John, Majnu Tagalicud, Arlene S. Maggio, Marcello Muller, Denis C. Egan, Josephine Basaria, Shehzad TI Effects of high-dose isoflavones on metabolic and inflammatory markers in healthy postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Adipokines; Cytokines; Insulin resistance ID ESTROGEN PLUS PROGESTIN; INSULIN SENSITIVITY; SOY; GLUCOSE; ADIPONECTIN; TRANSITION; MENOPAUSE; GHRELIN; PHYTOESTROGENS; REPLACEMENT AB Objective: After menopause, women experience changes in body composition, especially all increase in fat mass. In addition, advancing age, decreased physical activity, and increased inflammation may predispose them to develop type 2 diabetes. Isoflavones have been shown to improve metabolic parameters in postmenopausal women. However, the effect of isoflavones on adipokines/cytokines remains unclear. The Purpose of this study was to evaluate the effect of high-dose isoflavones on inflammatory and metabolic markers in postmenopausal women. Methods: We measured glucose, insulin, and adipokines/cytokines in 75 healthy postmenopausal women who were randomized to receive 20 g of soy protein with 160 mg of total isoflavones (64 mg genistein, 63 mg daidzein, and 34 mg glycitein) or 20 g of soy protein placebo for 12 weeks. Women taking estrogen discontinued therapy at least 3 months before the study. The supplements were given in a powder form and consumed once daily with milk or other beverages. Results: Mean ages in the placebo and active groups were similar (P = 0.4). Average time since menopause was 9 years, and two thirds of the women underwent natural menopause. There was no significant difference in body mass index at baseline between the groups (placebo, 25.1 kg/m(2); active, 26 kg/m(2)) and it did not change significantly during the study. At baseline, the placebo group had significantly higher levels of tumor necrosis factor a (P < 0.0001); otherwise, there was no difference in any other parameter. After 12 weeks of treatment, there were significant positive changes in tumor necrosis factor a levels within the placebo group (P < 0.0001) and adiponectin levels within the isoflavone group (P = 0.03). Comparison of pre-post change between the groups showed a small but significant increase in serum adiponectin levels in the isoflavone group (P = 0.03) compared with the placebo group. No significant changes were seen in any other parameter between the two groups. Conclusions: Healthy, normal-weight postmenopausal women may not experience improvement in metabolic parameters when given high-dose isoflavones despite an increase in serum adiponectin levels. The role of isoflavones in obese and insulin-resistant postmenopausal women needs exploration. C1 [Basaria, Shehzad] Johns Hopkins Univ, Sch Med, Dept Internal Med, Div Endocrinol & Metab,Bayview Med Ctr, Baltimore, MD 21224 USA. [Charles, Cornelia; Yuskavage, Julia; Carlson, Olga; Tagalicud, Arlene S.; Maggio, Marcello; Muller, Denis C.; Egan, Josephine] NIA, Clin Invest Lab, Diabet Sect, Baltimore, MD 21224 USA. RP Basaria, S (reprint author), Johns Hopkins Univ, Sch Med, Dept Internal Med, Div Endocrinol & Metab,Bayview Med Ctr, Suite 4300,Ctr Tower,Mason F Lord Bldg,5200 Easte, Baltimore, MD 21224 USA. EM sbasari1@jhmi.edu FU Intramural NIH HHS [Z01 AG000906-11] NR 29 TC 35 Z9 37 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR-APR PY 2009 VL 16 IS 2 BP 395 EP 400 DI 10.1097/gme.0b013e3181857979 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 417GI UT WOS:000264064100026 PM 18981951 ER PT J AU Maes, M Yirmiya, R Noraberg, J Brene, S Hibbeln, J Perini, G Kubera, M Bob, P Lerer, B Maj, M AF Maes, Michael Yirmiya, Raz Noraberg, Jens Brene, Stefan Hibbeln, Joe Perini, Giulia Kubera, Marta Bob, Petr Lerer, Bernard Maj, Mario TI The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression SO METABOLIC BRAIN DISEASE LA English DT Review DE Depression; Inflammation; Cytokines; Neurodegeneration; Oxidative stress; Nitrosative stress; Tryptophan; Serotonin; IDO ID ADULT HIPPOCAMPAL NEUROGENESIS; CHRONIC-FATIGUE-SYNDROME; NECROSIS-FACTOR-ALPHA; TREATMENT-RESISTANT DEPRESSION; KYNURENINE PATHWAY METABOLISM; POLYUNSATURATED FATTY-ACIDS; GENERAL MEDICAL CONDITION; CELL-ADHESION MOLECULES; PITUITARY-ADRENAL AXIS; ACUTE-PHASE PROTEINS AB Despite extensive research, the current theories on serotonergic dysfunctions and cortisol hypersecretion do not provide sufficient explanations for the nature of depression. Rational treatments aimed at causal factors of depression are not available yet. With the currently available antidepressant drugs, which mainly target serotonin, less than two thirds of depressed patients achieve remission. There is now evidence that inflammatory and neurodegenerative (I&ND) processes play an important role in depression and that enhanced neurodegeneration in depression may-at least partly-be caused by inflammatory processes. Multiple inflammatory-cytokines, oxygen radical damage, tryptophan catabolites-and neurodegenerative biomarkers have been established in patients with depression and these findings are corroborated by animal models of depression. A number of vulnerability factors may predispose towards depression by enhancing inflammatory reactions, e.g. lower peptidase activities (dipeptidyl-peptidase IV, DPP IV), lower omega-3 polyunsaturated levels and an increased gut permeability (leaky gut). The cytokine hypothesis considers that external, e.g. psychosocial stressors, and internal stressors, e.g. organic inflammatory disorders or conditions, such as the postpartum period, may trigger depression via inflammatory processes. Most if not all antidepressants have specific anti-inflammatory effects, while restoration of decreased neurogenesis, which may be induced by inflammatory processes, may be related to the therapeutic efficacy of antidepressant treatments. Future research to disentangle the complex etiology of depression calls for a powerful paradigm shift, i.e. by means of a high throughput-high quality screening, including functional genetics and genotyping microarrays; established and novel animal and ex vivo-in vitro models for depression, such as new transgenic mouse models and endophenotype-based animal models, specific cell lines, in vivo and ex vivo electroporation, and organotypic brain slice culture models. This screening will allow to: 1) discover new I&ND biomarkers, both at the level of gene expression and the phenotype; and elucidate the underlying molecular I&ND pathways causing depression; and 2) identify new therapeutic targets in the I&ND pathways; develop new anti-I&ND drugs for these targets; select existing anti-I&ND drugs or substances that could augment the efficacy of antidepressants; and predict therapeutic response by genetic I&ND profiles. C1 [Maes, Michael] Clin Res Ctr Mental Hlth, B-2610 Antwerp, Belgium. [Yirmiya, Raz] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. [Noraberg, Jens] Univ So Denmark, Ctr Med Biotechnol, Mol Neurobiol Lab, Odense, Denmark. [Noraberg, Jens] Univ So Denmark, Dept Anat & Neurobiol, Odense, Denmark. [Brene, Stefan] Karolinska Univ Hosp, MR Ctr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Hibbeln, Joe] NIAAA, Sect Nutr Neurochem, LMBB, DICBR,NIH, Washington, DC USA. [Perini, Giulia] Univ Padua, Dept Psychiat, Padua, Italy. [Kubera, Marta] Polish Acad Sci, Inst Pharmacol, Krakow, Poland. [Bob, Petr] Charles Univ Prague, Fac Med 1, Dept Psychiat, Prague, Czech Republic. [Lerer, Bernard] Hadassah Hebrew Univ, Hadassah Biol Psychiat Lab, Jerusalem, Israel. [Maj, Mario] Univ Naples Federico 2, SUN, Dept Psychiat, Naples, Italy. RP Maes, M (reprint author), Clin Res Ctr Mental Hlth, Olmenlaan 9, B-2610 Antwerp, Belgium. EM neutrim@telenet.be RI Bob, Petr /E-3414-2012; Yirmiya, Raz/D-1090-2014; OI Maes, Michael/0000-0002-2012-871X; PERINI, GIULIA/0000-0003-3261-1984 NR 201 TC 357 Z9 374 U1 16 U2 105 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD MAR PY 2009 VL 24 IS 1 BP 27 EP 53 DI 10.1007/s11011-008-9118-1 PG 27 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 407RE UT WOS:000263381200004 PM 19085093 ER PT J AU Le, DSNT Brookshire, T Krakoff, J Bunt, JC AF Le, Duc Son N. T. Brookshire, Thomas Krakoff, Jonathan Bunt, Joy C. TI Repeatability and reproducibility of the hyperinsulinemic-euglycemic clamp and the tracer dilution technique in a controlled inpatient setting SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INSULIN-INDUCED HYPOGLYCEMIA; DEPENDENT DIABETES-MELLITUS; PHYSICAL-ACTIVITY; PORCINE INSULIN; GLUCOSE CLAMP; PIMA-INDIANS; CLINICAL MEASUREMENT; HEALTHY-SUBJECTS; RESISTANCE; AGREEMENT AB The objective of the study was to evaluate the reproducibility and repeatability of the combined use of the hyperinsulinemic-euglycemic (H-E) clamp and tracer dilution techniques. Ten nondiabetic men under-went a low-dose (40 mU/[m(2) min]) H-E clamp that was repeated within 3 to 4 days using porcine or human insulin in a double-blinded, randomized, crossover design. Coefficients of variation (CVs) for intraindividual differences and repeatability coefficient were calculated to evaluate reproducibility and repeatability. The Bland and Altman method was used to quantify repeatability. The CVs for intraindividual differences were 5.7% +/- 3.5% for steady-state (SS) insulin; 6.7% +/- 6.2% and 54.2 +/- 38.3% for basal and SS endogenous glucose product (EGP), respectively; and 10.3% +/- 8.5% for total insulin-stimulated glucose disposal (M) values. Basal EGP, SS EGP, and SS glucose and insulin concentrations were similar for the 2 clamps;, but glucose infusion rate (P = .02) and M (borderline significant, P = .06) were higher in the first clamp than the second clamp. No significant correlations between mean of differences and average of basal and SS EGP, SS insulin concentration, and M between the 2 clamps were observed. We also found that the different values were less than the repeatability coefficients of these parameters and that the 95% limits of agreement and the interval of repeatability coefficient of these parameters were similar. There were no differences in metabolic responses between clamps when compared by the type of insulin (porcine vs human) infused. Our findings indicate that, although SS EGP has a high CV, the clamp, which measures insulin action (ie, SS insulin, M), and the tracer dilution technique for assessing basal EGP are repeatable and reproducible. Decreased glucose infusion rate and M over a short period in the second clamp may reflect an accumulative effect of continued physical inactivity. (C) 2009 Elsevier Inc. All rights reserved. C1 [Le, Duc Son N. T.; Brookshire, Thomas; Krakoff, Jonathan; Bunt, Joy C.] NIDDKD, Obes & Diabet Clin Res Sect, Natl Inst Hlth, Phoenix, AZ 85016 USA. RP Le, DSNT (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, Natl Inst Hlth, Phoenix, AZ 85016 USA. EM leds@ttdinhduong.org FU Intramural Research Program of the NIH, NIDDK FX This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 36 TC 2 Z9 2 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 2009 VL 58 IS 3 BP 304 EP 310 DI 10.1016/j.metabol.2008.09.029 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 414RH UT WOS:000263882400006 PM 19217443 ER PT J AU Lundqvist, A Kubler-Kielb, J Teneberg, S Ahlman, K Lagergard, T AF Lundqvist, Annika Kubler-Kielb, Joanna Teneberg, Susann Ahlman, Karin Lagergard, Teresa TI Immunogenic and adjuvant properties of Haemophilus ducreyi lipooligosaccharides SO MICROBES AND INFECTION LA English DT Article DE Haemophilus ducreyi; Lipooligosaccharide; Lipid A; IgG subclasses; Immunogenicity; Adjuvant ID NEISSERIA-MENINGITIDIS; MONOCLONAL-ANTIBODIES; T-CELLS; LIPID-A; BIOSYNTHESIS; ENDOTOXIN; LIPOPOLYSACCHARIDE; RECOGNITION; GLYCOFORMS; PROTEINS AB Haemophilus ducreyi, the chancroid-causing bacterium, produces lipooligosaccharides (HdLOS) that comprise 5-11 partially sialylated monosaccharides. Subcutaneous immunisation of mice with 5 mu g of HdLOS purified from H. ducreyi strains 4438 and 7470 induced high levels of anti-HdLOS IgG. The antibody responses displayed T-cell-independent features, and were dependent upon Toll-like receptor 4/MyD88 signalling pathways as demonstrated using knockout mice. The immunogenicity of HdLOS was found to require the intact lipid A moiety. The specificity studies of the anti-HdLOS antibodies, as revealed by absorption studies, antibody detection in ELISA, and immune thin-layer chromatography, indicated that the majority of the anti-LOS antibodies were specific for the inner core of the HdLOS. Antibodies to HdLOS failed to inhibit LOS induction of TNF-alpha release from human mononuclear cells. The adjuvanticity of HdLOS7470 was assessed in BALB/c mice that were immunised with bovine serum albumin (BSA) with or without the addition of HdLOS. The addition of 5 mu g HdLOS resulted in a 10-fold increase in the total anti-BSA IgG antibody level as estimated by ELISA. The highest increase was noted for IgG2b, which contrasted with the predominantly IgG1 subclass response to immunisation with BSA alone, indicating an immunomodulatory activity of the HdLOS. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [Lundqvist, Annika; Ahlman, Karin; Lagergard, Teresa] Gothenburg Univ, Sahlgrenska Acad, Inst Biomed, Dept Microbiol & Immunol, S-40530 Gothenburg, Sweden. [Lundqvist, Annika; Ahlman, Karin; Lagergard, Teresa] Gothenburg Univ, MIVAC, S-40530 Gothenburg, Sweden. [Kubler-Kielb, Joanna] NICHHD, Natl Inst Hlth, Bethesda, MD 20892 USA. [Teneberg, Susann] Gothenburg Univ, Dept Med Biochem & Cell Biol, Inst Biomed, S-40530 Gothenburg, Sweden. RP Lagergard, T (reprint author), Gothenburg Univ, Sahlgrenska Acad, Inst Biomed, Dept Microbiol & Immunol, POB 435, S-40530 Gothenburg, Sweden. EM teresa.lagergard@microbio.gu.se FU Swedish Agency for Research Cooperation with Developing Countries (Sida/SAREQ, the Swedish Research Council [K2007-58X-2036501-3, K2007-66X-12628]; Swedish Cancer Foundation FX This study was supported by the Swedish Agency for Research Cooperation with Developing Countries (Sida/SAREQ, the Swedish Research Council (K2007-58X-2036501-3, T.L.), K2007-66X-12628, S.T.) and the Swedish Cancer Foundation. NR 33 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAR PY 2009 VL 11 IS 3 BP 352 EP 360 DI 10.1016/j.micinf.2008.12.014 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 436HA UT WOS:000265402100005 PM 19397884 ER PT J AU Qian, F Aebig, JA Reiter, K Barnafo, E Zhang, YL Shimp, RL Rausch, KM Jones, DS Zhu, DM Lambert, L Mullen, GED Narum, DL Miller, LH Wu, YM AF Qian, Feng Aebig, Joan A. Reiter, Karine Barnafo, Emma Zhang, Yanling Shimp, Richard L., Jr. Rausch, Kelly M. Jones, David S. Zhu, Daming Lambert, Lynn Mullen, Gregory E. D. Narum, David L. Miller, Louis H. Wu, Yimin TI Enhanced antibody responses to Plasmodium falciparum Pfs28 induced in mice by conjugation to ExoProtein A of Pseudomonas aeruginosa with an improved procedure SO MICROBES AND INFECTION LA English DT Article DE Conjugation; Pfs28; rEPA; Malaria; Transmission blocking vaccine ID TRANSMISSION-BLOCKING VACCINES; MALARIA VACCINE; PROTEIN; CANDIDATE; STAGE AB In this paper we report our efforts to enhance the immunogenicity of Pfs28, a transmission blocking vaccine candidate of Plasmodium falciparum, using a strategy of chemical conjugation. With an improved procedure, Pfs28 was covalently coupled to the mutant and non-toxic ExoProtein A of Pseudomonas aeruginosa by the reaction between thiolated antigen and maleimide modified carrier protein. The optimized process resulted in a higher antigen-carrier conjugation ratio, and the conjugation product could be purified using single-step size-exclusion chromatography. A significant increase in immunogenicity measured by ELISA was observed in mice immunized with conjugated Pfs28 as compared to unconjugated Pfs28. Published by Elsevier Masson SAS. C1 [Qian, Feng; Aebig, Joan A.; Reiter, Karine; Barnafo, Emma; Zhang, Yanling; Shimp, Richard L., Jr.; Rausch, Kelly M.; Jones, David S.; Zhu, Daming; Lambert, Lynn; Mullen, Gregory E. D.; Narum, David L.; Miller, Louis H.; Wu, Yimin] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Qian, F (reprint author), Second Mil Med Univ, Dept Pathogen Biol, 800 Xiang Yin Rd, Shanghai 200433, Peoples R China. EM fqian-cn@hotmail.com; yiwu@niaid.nih.gov FU NIH, NIAID FX This research was supported by the Intramural Research Program of the NIH, NIAID. NR 12 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD MAR PY 2009 VL 11 IS 3 BP 408 EP 412 DI 10.1016/j.micinf.2008.12.009 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 436HA UT WOS:000265402100012 PM 19146977 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Microbial genomics as pursuit of happiness SO MICROBIAL BIOTECHNOLOGY LA English DT Editorial Material C1 NIH, NCBI, NLM, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, NCBI, NLM, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 6 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-7907 J9 MICROB BIOTECHNOL JI Microb. Biotechnol. PD MAR PY 2009 VL 2 IS 2 SI SI BP 135 EP 136 DI 10.1111/j.1751-7915.2009.00090_6.x PG 2 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA V16XX UT WOS:000207903400007 PM 21261894 ER PT J AU Amyot, F Small, A Boukari, H Camphausen, K Gandjbakhche, A AF Amyot, Franck Small, Alex Boukari, Hacene Camphausen, Kevin Gandjbakhche, Amir TI Topology of the heterogeneous nature of the extracellular matrix on stochastic modeling of tumor-induced angiogenesis SO MICROVASCULAR RESEARCH LA English DT Article DE Angiogenesis; Chemotaxis; Apoptosis; Extracellular matrix; Percolation; Endothelial cell ID ENDOTHELIAL-CELLS; GROWTH-FACTOR; BASEMENT-MEMBRANE; MIGRATION; PERCOLATION; ADHESION; BINDING; NEOVASCULARIZATION; PROLIFERATION; MORPHOGENESIS AB We have modeled tumor-induced angiogenesis; our model includes the phenomena of the migratory response of endothelial cells (ECs) to tumor angiogenic factors, and the interaction of ECs with the extracellular matrix (ECM). ECs switch between growth, differentiation, motility, or apoptotic behavior in response to the local topology and composition of the ECM. Assuming the ECM medium as a statistically inhomogeneous medium (some area support sprout growth, some not), we show that the ECM can be a natural barrier to angiogenesis. We study vascular network formation for several ECM distributions and topologies, and we find an analogy with percolation. A threshold exists, under which sprouts cannot reach the tumor. During the growth of the vascular network, a competition exists between the attraction exerted by tumor and the preferred path created by the ECM. We also examined the influence of branching on the tumor vascularization. Branching is a natural phenomenon which helps the tumor become vascularized. By increasing the number of sprouts, the vascular network increases the probability of reaching the tumor, as it can explore more pathways. Our simulations show after two branching events, the vascular network is very likely to reach the tumor. Published by Elsevier Inc. C1 [Amyot, Franck; Small, Alex; Boukari, Hacene; Gandjbakhche, Amir] NICHHD, Lab Integrat & Med Biophys, Sect Biomed Stochast Phys, NIH, Bethesda, MD 20892 USA. [Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Amyot, F (reprint author), NICHHD, Lab Integrat & Med Biophys, Sect Biomed Stochast Phys, NIH, 9 S Dr, Bethesda, MD 20892 USA. EM amyotf@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 37 TC 5 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 2009 VL 77 IS 2 BP 87 EP 95 DI 10.1016/j.mvr.2007.11.001 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 423CV UT WOS:000264474900003 PM 19013623 ER PT J AU Talbot, LA Weinstein, AA Fleg, JL AF Talbot, Laura A. Weinstein, Ali A. Fleg, Jerome L. TI Army Physical Fitness Test Scores Predict Coronary Heart Disease Risk in Army National Guard Soldiers SO MILITARY MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE; INTENSITY; MEN AB An increased rate of cardiac symptoms at combat theater hospitals brings concerns about the predeployment health of Army National Guard (ARNG) soldiers on the basis of older age, lower fitness level, and sedentary lifestyle than active duty troops. The purpose of this study was to examine the association of physical fitness, reported physical activity (PA), and coronary risk factors to calculated 10-year hard coronary heart disease (CHD) risk in 136 ARNG soldiers, aged 18-53 years, who failed the 2-mile run of the Army Physical Fitness Test (APFT). The APFT score, derived from a composite of 2-mile run time, sit-ups, and push-ups, related inversely to 10-year CHD risk (r = -0.23, p < 0.01) but no relationship with CHD risk was observed for PA. APFT scores were positively associated with high-density lipoprotein (HDL) cholesterol and inversely with triglycerides, total cholesterol:HDL ratio, diastolic blood pressure, and body mass index (BMI). No relationship existed between PA and any of the CHD risk factors. We conclude that a higher APFT score is associated with a healthier CHD risk factor profile and is a predictor of better predeployment cardiovascular health. C1 [Talbot, Laura A.] Univ N Carolina, Sch Nursing, Charlotte, NC 28223 USA. [Weinstein, Ali A.] George Mason Univ, Ctr Study Chron Illness & Disabil, Fairfax, VA 22030 USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Dis, Bethesda, MD 20892 USA. RP Talbot, LA (reprint author), Univ N Carolina, Sch Nursing, 9201 Univ City Blvd, Charlotte, NC 28223 USA. RI Weinstein, Ali/D-3919-2012 FU TriService Nursing Research Program; Uniformed Services University of the Health Sciences; Department of Health and Human Services, National Institutes of Health, National Center for Research Resources [5 M01 RR0279]; Johns Hopkins Bayview General Clinical Research Center FX The authors express their appreciation to the Army National Guard volunteers in the Fitness for Life Study. This research was sponsored by the TriService Nursing Research Program, Uniformed Services University of the Health Sciences. We also acknowledge the core laboratory and data management support and equipment provided by Johns Hopkins Bayview General Clinical Research Center, (which is funded by Department of Health and Human Services, National Institutes of Health, National Center for Research Resources, no. 5 M01 RR0279). NR 17 TC 7 Z9 7 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAR PY 2009 VL 174 IS 3 BP 245 EP 252 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 601KZ UT WOS:000278059400006 PM 19354087 ER PT J AU Tsai, CW Duggan, PF Jin, AJ MacDonald, NJ Kotova, S Lebowitz, J Hurt, DE Shimp, RL Lambert, L Miller, LH Long, CA Saul, A Narum, DL AF Tsai, Chiawei W. Duggan, Peter F. Jin, Albert J. MacDonald, Nicholas J. Kotova, Svetlana Lebowitz, Jacob Hurt, Darrell E. Shimp, Richard L., Jr. Lambert, Lynn Miller, Louis H. Long, Carole A. Saul, Allan Narum, David L. TI Characterization of a protective Escherichia coli-expressed Plasmodium falciparum merozoite surface protein 3 indicates a non-linear, multi-domain structure SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Malaria; Plasmodium falciparum; MSP3; Vaccine; Aotus; Escherichia coli ID ATOMIC-FORCE MICROSCOPY; MALARIA VACCINE; COILED-COILS; PICHIA-PASTORIS; HEPTAD REPEAT; PREDICTION; ANTIBODIES; ANTIGEN; ULTRACENTRIFUGATION; SECONDARY AB Immunization with a recombinant yeast-expressed Plasmodium falciparum merozoite surface protein 3 (MSP3) protected Aotus nancymai monkeys against a virulent challenge infection. Unfortunately. the production process for this yeast-expressed material was not optimal for human trials. In an effort to produce a recombinant MSP3 protein in a scaleable manner, we expressed and purified near-full-length MSP3 in Escherichia coli (EcMSP3). Purified EcMSP3 formed non-globular dimers as determined by analytical size-exclusion HPLC with in-line multi-angle light scatter and quasi-elastic light scatter detection and velocity sedimentation (R(h) 7.6 +/- 0.2 nm and 6.9 nm, respectively). Evaluation by high-resolution atomic force microscopy revealed non-linear asymmetric structures, with beaded domains and flexible loops that were recognized predominantly as dimers, although monomers and larger multimers; were observed. The beaded substructure corresponds to predicted structural domains, which explains the velocity sedimentation results and improves the conceptual model of the protein. Vaccination with EcMSP3 in Freund's adjuvant-induced antibodies that recognized native MSP3 in parasitized erythrocytes by an immunofluorescence assay and gave delayed time to treatment in a group of Aotus monkeys in a virulent challenge infection with the FVO strain of P. falciparum. Three of the seven monkeys vaccinated with EcMSP3 had low peak parasitemias. EcMSP3, which likely mimics the native MSP3 structure located on the merozoite surface, is a viable candidate for inclusion in a multi-component malaria vaccine. Published by Elsevier B.V. C1 [Tsai, Chiawei W.; Duggan, Peter F.; MacDonald, Nicholas J.; Shimp, Richard L., Jr.; Lambert, Lynn; Miller, Louis H.; Long, Carole A.; Saul, Allan; Narum, David L.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. [Jin, Albert J.; Kotova, Svetlana; Lebowitz, Jacob] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. [Hurt, Darrell E.] NIAID, Bioinformat & Sci IT Program, Off Technol Informat Syst, NIH, Bethesda, MD 20892 USA. RP Narum, DL (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane,Twinbrook 1, Rockville, MD 20852 USA. RI Hurt, Darrell/B-5076-2013; Saul, Allan/I-6968-2013; OI Hurt, Darrell/0000-0002-9829-8567; Saul, Allan/0000-0003-0665-4091; Jin, Albert/0000-0003-3826-1081 FU NIAID/NIH FX We are grateful to Drs. David Garboczi and Brandt Burgess (Structural Biology Section, Laboratory of Immunogenetics, NIAID/NIH) for discussions on the design and expression of MSP3 constructs in E coff; to Jacqueline Glen, Vu Nguyen, and Dr. Yanling Zhang for assistance with production of recombinant EcMSP3-, to Karine Reiter for assistance with characterization and to Olga Muratova for performing the ELISAs. We thank Dr. Paul Smith of NIBIB/NIH for encouragement and support. Part of this work was carried out by using the resources of the Computational Biology Service Unit from Cornell University, which is partially funded by Microsoft Corporation. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov), This research is supported by intramural funding of NIAID/NIH. NR 34 TC 14 Z9 14 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAR PY 2009 VL 164 IS 1 BP 45 EP 56 DI 10.1016/j.molbiopara.2008.11.006 PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 408RD UT WOS:000263451500005 PM 19073223 ER PT J AU Burnett, BG Munoz, E Tandon, A Kwon, DY Sumner, CJ Fischbeck, KH AF Burnett, Barrington G. Munoz, Eric Tandon, Animesh Kwon, Deborah Y. Sumner, Charlotte J. Fischbeck, Kenneth H. TI Regulation of SMN Protein Stability SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; MOTOR-NEURONS PROTEIN; SINGLE NUCLEOTIDE; DETERMINING GENE; MUSCLE STRENGTH; SNRNP PROTEINS; CYCLIC-AMP; SURVIVAL; COMPLEX; EXPRESSION AB Spinal muscular atrophy (SMA) is caused by mutations of the survival of motor neuron (SMN1) gene and deficiency of full-length SMN protein (FL-SMN). All SMA patients retain one or more copies of the SMN2 gene, but the principal protein product of SMN2 lacks exon 7 (SMN Delta 7) and is unable to compensate for a deficiency of FL-SMN. SMN is known to oligomerize and form a multimeric protein complex; however, the mechanisms regulating stability and degradation of FL-SMN and SMN Delta 7 proteins have been largely unexplored. Using pulse-chase analysis, we characterized SMN protein turnover and confirmed that SMN was ubiquitinated and degraded by the ubiquitin proteasome system (UPS). The SMN Delta 7 protein had a twofold shorter half-life than FL-SMN in cells despite similar intrinsic rates of turnover by the UPS in a cell-free assay. Mutations that inhibited SMN oligomerization and complex formation reduced the FL-SMN half-life. Furthermore, recruitment of SMN into large macromolecular complexes as well as increased association with several Gemin proteins was regulated in part by protein kinase A. Together, our data indicate that SMN protein stability is modulated by complex formation. Promotion of the SMN complex formation may be an important novel therapeutic strategy for SMA. C1 [Burnett, Barrington G.; Munoz, Eric; Tandon, Animesh; Kwon, Deborah Y.; Fischbeck, Kenneth H.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Sumner, Charlotte J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Burnett, BG (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bldg 35,Rm 2A1008, Bethesda, MD 20892 USA. EM burnettb@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke (NINDS); NINDS Competitive Postdoctoral Fellowship; NINDS Career Transition Award [K22-NS0048199-01] FX This study was supported by intramural National Institute of Neurological Disorders and Stroke (NINDS) funds. This study was also supported by a NINDS Competitive Postdoctoral Fellowship (to B.G.B.), a NINDS Career Transition Award (K22-NS0048199-01), and Families of Spinal Muscular Atrophy (to C.J.S.). NR 45 TC 109 Z9 110 U1 0 U2 11 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 MAR 1 PY 2009 VL 29 IS 5 BP 1107 EP 1115 DI 10.1128/MCB.01262-08 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 406KI UT WOS:000263293500001 PM 19103745 ER PT J AU Ma, WJ Panduri, V Sterling, JF Van Houten, B Gordenin, DA Resnick, MA AF Ma, Wenjian Panduri, Vijayalakshmi Sterling, Joan F. Van Houten, Bennett Gordenin, Dmitry A. Resnick, Michael A. TI The Transition of Closely Opposed Lesions to Double-Strand Breaks during Long-Patch Base Excision Repair Is Prevented by the Coordinated Action of DNA Polymerase delta and Rad27/Fen1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; LIGASE I; BIOLOGICAL CONSEQUENCES; OKAZAKI FRAGMENTS; REPLICATION FORK; ABASIC SITES; DAMAGE; POL32; RADIATION AB DNA double-strand breaks can result from closely opposed breaks induced directly in complementary strands. Alternatively, double-strand breaks could be generated during repair of clustered damage, where the repair of closely opposed lesions has to be well coordinated. Using single and multiple mutants of Saccharomyces cerevisiae ( budding yeast) that impede the interaction of DNA polymerase delta and the 5'-flap endonuclease Rad27/Fen1 with the PCNA sliding clamp, we show that the lack of coordination between these components during long-patch base excision repair of alkylation damage can result in many double-strand breaks within the chromosomes of nondividing haploid cells. This contrasts with the efficient repair of nonclustered methyl methanesulfonate-induced lesions, as measured by quantitative PCR and S1 nuclease cleavage of single-strand break sites. We conclude that closely opposed single-strand lesions are a unique threat to the genome and that repair of closely opposed strand damage requires greater spatial and temporal coordination between the participating proteins than does widely spaced damage in order to prevent the development of double-strand breaks. C1 [Gordenin, Dmitry A.] Natl Inst Environm Hlth Sci, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Van Houten, Bennett] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Inst Canc, Pittsburgh, PA 15213 USA. RP Gordenin, DA (reprint author), Natl Inst Environm Hlth Sci, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM gordenin@niehs.nih.gov; resnick@niehs.nih.gov RI Ma, Wenjian/C-1071-2012 FU Intramural Research Program of the NIEHS [1 Z01 ES065073, 2 Z01 ES61062] FX This work was supported by the Intramural Research Program of the NIEHS (NIH, DHHS) under projects 1 Z01 ES065073 (M.A.R.) and 2 Z01 ES61062 (B.V.H.). NR 61 TC 21 Z9 22 U1 3 U2 4 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 MAR 1 PY 2009 VL 29 IS 5 BP 1212 EP 1221 DI 10.1128/MCB.01499-08 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 406KI UT WOS:000263293500011 PM 19075004 ER PT J AU Huang, B Yang, XD Zhou, MM Ozato, K Chen, LF AF Huang, Bo Yang, Xiao-Dong Zhou, Ming-Ming Ozato, Keiko Chen, Lin-Feng TI Brd4 Coactivates Transcriptional Activation of NF-kappa B via Specific Binding to Acetylated RelA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BROMODOMAIN PROTEIN BRD4; RNA-POLYMERASE-II; P-TEFB; DEPENDENT TRANSCRIPTION; PCAF BROMODOMAIN; ELONGATION; PHOSPHORYLATION; RECOGNITION; RECRUITMENT; HISTONE AB Acetylation of the RelA subunit of NF-kappa B, especially at lysine-310, is critical for the transcriptional activation of NF-kappa B and the expression of inflammatory genes. In this study, we demonstrate that bromodomains of Brd4 bind to acetylated lysine-310. Brd4 enhances transcriptional activation of NF-kappa B and the expression of a subset of NF-kappa B-responsive inflammatory genes in an acetylated lysine-310-dependent manner. Bromodomains of Brd4 and acetylated lysine-310 of RelA are both required for the mutual interaction and coactivation function of Brd4. Finally, we demonstrate that Brd4 further recruits CDK9 to phosphorylate C-terminal domain of RNA polymerase II and facilitate the transcription of NF-kappa B-dependent inflammatory genes. Our results identify Brd4 as a novel coactivator of NF-kappa B through specifically binding to acetylated lysine-310 of RelA. In addition, these studies reveal a mechanism by which acetylated RelA stimulates the transcriptional activity of NF-kappa B and the NF-kappa B-dependent inflammatory response. C1 [Huang, Bo; Yang, Xiao-Dong; Chen, Lin-Feng] Univ Illinois, Coll Med, Dept Biochem, Urbana, IL 61801 USA. [Zhou, Ming-Ming] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA. [Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Chen, LF (reprint author), Univ Illinois, Coll Med, Dept Biochem, MC-714, Urbana, IL 61801 USA. EM lfchen@life.uiuc.edu RI Yang, Xiao-Dong/A-3768-2009; Huang, Bo/D-5220-2009 FU American Lung Association; Arthritis Foundation Investigator Award FX This study was supported in part by ICR provided by the University of Illinois at Urbana-Champaign and Biomedical Research Grant from American Lung Association. L.-F.C. is the recipient of an Arthritis Foundation Investigator Award. NR 51 TC 178 Z9 187 U1 1 U2 11 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 MAR 1 PY 2009 VL 29 IS 5 BP 1375 EP 1387 DI 10.1128/MCB.01365-08 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 406KI UT WOS:000263293500023 PM 19103749 ER PT J AU Kang, MI Henrich, CJ Bokesch, HR Gustafson, KR McMahon, JB Baker, AR Young, MR Colburn, NH AF Kang, Moon-Il Henrich, Curtis J. Bokesch, Heidi R. Gustafson, Kirk R. McMahon, James B. Baker, Alyson R. Young, Matthew R. Colburn, Nancy H. TI A selective small-molecule nuclear factor-kappa B inhibitor from a high-throughput cell-based assay for "activator protein-1 hits" SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NEGATIVE C-JUN; IKK-ALPHA; TRANSCRIPTIONAL REGULATION; INDUCED TRANSFORMATION; HUMAN KERATINOCYTES; GENE-EXPRESSION; TUMOR PROMOTION; AP-1 ACTIVITY; TARGET GENES; P65 SUBUNIT AB NSC 676914 has been identified as a selective nuclear factor-kappa B (NF-kappa B) inhibitor that does not inhibit cell proliferation. This compound was originally identified in a high-throughput cell-based assay for activator protein-1 (AP-1) inhibitors using synthetic compound libraries and the National Cancer Institute natural product repository. NSC 676914 shows activity against NF-kappa B in luciferase reporter assays at concentrations much less than the IC(50) for AP-1. A serum response element reporter used as a specificity control and indicator of cell proliferation was relatively insensitive to the compound. Pretreatment with NSC 676914 is here shown to repress 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced I kappa B-alpha phosphorylation and translocation of p65/50 to the nucleus but not the processing of p52 from p100, suggesting the inhibition of NF-kappa B regulator IKK beta rather than IKK alpha. Inhibition of NF-kappa B activation occurred as a consequence of blocking phosphorylation of IKK. Induction of I kappa B-alpha phosphorylation by TPA was diminished by pretreatment of NSC 676914 even at 1.1 mu mol/L. In contrast, kinases c-Jun-NH(2)-kinase and extracellular signal-regulated kinases 1 and 2, important for AP-1 activation, showed no significant repression by this compound. Furthermore, a Matrigel invasion assay with breast cancer cell lines and a transformation assay in mouse JB6 cells revealed that TPA-induced invasion and transformation responses were completely repressed by this compound. These results suggest that NSC 676914 could be a novel inhibitor having potential therapeutic activity to target NF-kappa B for cancer treatment or prevention. [Mol Cancer Ther 2009;8(3):571 - 81] C1 [Kang, Moon-Il; Baker, Alyson R.; Young, Matthew R.; Colburn, Nancy H.] Natl Canc Inst Frederick, Lab Canc Prevent, Gene Regulat Sect, Ft Detrick, MD 21702 USA. [Henrich, Curtis J.; Bokesch, Heidi R.; Gustafson, Kirk R.; McMahon, James B.] Natl Canc Inst Frederick, Mol Targets Dev Program, Ft Detrick, MD 21702 USA. [Henrich, Curtis J.; Bokesch, Heidi R.] Natl Canc Inst Frederick, Sci Applicat Int Corp Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. RP Kang, MI (reprint author), Natl Canc Inst Frederick, Lab Canc Prevent, Gene Regulat Sect, Room 187,Bldg 567, Ft Detrick, MD 21702 USA. EM kangm@ncifcrf.gov FU NIH [N01-C0-12400]; National Cancer Institute; Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, and Center for Cancer Research. This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under contract N01-C0-12400. NR 44 TC 14 Z9 14 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2009 VL 8 IS 3 BP 571 EP 581 DI 10.1158/1535-7163.MCT-08-0811 PG 11 WC Oncology SC Oncology GA 423CZ UT WOS:000264475300010 PM 19258426 ER PT J AU Xie, H Valera, VA Merino, MJ Amato, AM Signoretti, S Linehan, WM Sukhatme, VP Seth, P AF Xie, Han Valera, Vladimir A. Merino, Maria J. Amato, Angela M. Signoretti, Sabina Linehan, William M. Sukhatme, Vikas P. Seth, Pankaj TI LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID INDUCIBLE FACTOR 1-ALPHA; DEHYDROGENASE M-SUBUNIT; FUMARATE-HYDRATASE; TUMOR-SUPPRESSOR; EXPRESSION PROFILE; AEROBIC GLYCOLYSIS; UTERINE FIBROIDS; HYPOXIA; GENE; CARCINOMA AB The genetic basis for the hereditary leiomyomatosis and renal cell cancer syndrome is germ-line inactivating mutation in the gene for the Krebs/tricarboxylic acid cycle enzyme, fumarate hydratase (FH), the enzyme that converts fumarate to malate. These individuals are predisposed to development of leiomyomas of the skin and uterus as well as highly aggressive kidney cancers. Inhibition of FH should result in significant decrease in oxidative phosphorylation necessitating that glycolysis followed by fermentation of pyruvate to lactate will be required to provide adequate ATP as well as to regenerate NAD(+). Moreover, FH deficiency is known to up-regulate expression of hypoxia-inducible factor (HIF)-1 alpha by enhancing the stability of HIF transcript. This leads to activation of various HIF-regulated genes including vascular endothelial growth factor and glucose transporter GLUT1 and increased expression of several glycolytic enzymes. Because lactate dehydrogenase-A (LDH-A), also a HIF-1 alpha target, promotes fermentative glycolysis (conversion of pyruvate to lactate), a step essential for regenerating NAD(+), we asked whether FH-deficient cells would be exquisitely sensitive to LDH-A blockade. Here, we report that hereditary leiomyomatosis and renal cell cancer tumors indeed overexpress LDH-A, that LDH-A inhibition results in increased apoptosis in a cell with FH deficiency and that this effect is reactive oxygen species mediated, and that LDH-A knockdown in the background of FH knockdown results in significant reduction in tumor growth in a xenograft mouse model. [Mol Cancer Ther 2009;8(3):626 - 35] C1 [Xie, Han; Sukhatme, Vikas P.; Seth, Pankaj] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol,Dept Med, Boston, MA 02215 USA. [Amato, Angela M.; Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Valera, Vladimir A.; Linehan, William M.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Seth, P (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol,Dept Med, Dana 5 RW 561,330 Brookline Ave, Boston, MA 02215 USA. EM pseth@bidmc.harvard.edu FU National Cancer Institute Temin [K01 CA104700]; Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence; NIH [N01-C0-12400] FX National Cancer Institute Temin award K01 CA104700 (P. Seth), Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence (P. Seth, H. Xie, A.M. Amato, S. Signoretti, and V.P. Sukhatme), and National Cancer Institute, NIH contract N01-C0-12400 (V.A. Valera, M.J. Merino, and W.M. Linehan). NR 43 TC 122 Z9 130 U1 2 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2009 VL 8 IS 3 BP 626 EP 635 DI 10.1158/1535-7163.MCT-08-1049 PG 10 WC Oncology SC Oncology GA 423CZ UT WOS:000264475300015 PM 19276158 ER PT J AU Loisel-Meyer, S Felizardo, T Mariotti, J Mossoba, ME Foley, JE Kammerer, R Mizue, N Keefe, R McCart, JA Zimmermann, W Dropulic, B Fowler, DH Medin, JA AF Loisel-Meyer, Severine Felizardo, Tania Mariotti, Jacopo Mossoba, Miriam E. Foley, Jason E. Kammerer, Robert Mizue, Nobuo Keefe, Robert McCart, J. Andrea Zimmermann, Wolfgang Dropulic, Boro Fowler, Daniel H. Medin, Jeffrey A. TI Potent induction of B- and T-cell immunity against human carcinoembryonic antigen-expressing tumors in human carcinoembryonic antigen transgenic mice mediated by direct lentivector injection SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID THERAPEUTIC ANTITUMOR IMMUNITY; TRANSDUCED DENDRITIC CELLS; HUMAN COLORECTAL-CANCER; IN-VIVO; LENTIVIRAL VECTORS; PHASE-I; SUPPRESSOR-CELLS; CLINICAL-TRIALS; GENE-THERAPY; RESPONSES AB The applicability of immunotherapy would be dramatically broadened to a greater number of recipients if direct "off-the-shelf" products could be engineered to engender functionally potent immune responses against true "self"-tumor antigens. This would obviate the need for ex vivo culture of dendritic cells or T cells on a patient-by-patient basis, for example. The carcinoembryonic antigen (CEA) is a glycoprotein expressed in normal gut epithelium that is up-regulated in the majority of colon cancers, non-small cell lung cancers, and half of all breast cancers. Such properties make CEA an excellent and important target for cancer immunotherapy. In this study, we show stabilization of 14-day established s.c. mGC4CEA tumors in human CEA (huCEA) transgenic mice following two direct low-dose injections of 0.15 x 10(6) transducing units of a lentiviral vector (LV) that directs expression of huCEA (LV-huCEA). This stabilization result was reproducible and detailed analyses including antibody assays, multiplex cytokine analyses on unstimulated splenocytes, lymph node cell characterizations, tetramer staining, and immunofluorescence staining of tumor sections showed that this outcome correlated with both a cellular and humoral immune response. Similar tumor outcomes were not seen when mice were vaccinated with a control LV that engineered expression of enGFP only. The long-term potency of this vaccination strategy was also studied and revealed the requirement for maintenance of tumor antigen-specific immunity for efficient tumor control. These data support the use of direct injections of low doses of LV-huCEA for enhancement of tumor immunotherapy directed against CEA. [Mol Cancer Ther 2009;8(3):692 - 702] C1 [Loisel-Meyer, Severine; Felizardo, Tania; Mizue, Nobuo; Medin, Jeffrey A.] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M1, Canada. [McCart, J. Andrea; Medin, Jeffrey A.] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON M5G 2M1, Canada. [Medin, Jeffrey A.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [McCart, J. Andrea; Medin, Jeffrey A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Mariotti, Jacopo; Mossoba, Miriam E.; Foley, Jason E.; Fowler, Daniel H.] Natl Canc Inst, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD USA. [Mariotti, Jacopo; Mossoba, Miriam E.; Foley, Jason E.; Fowler, Daniel H.] Natl Canc Inst, Med Oncol Branch, NIH, Bethesda, MD USA. [Kammerer, Robert; Zimmermann, Wolfgang] Univ Munich, Tumor Immunol Lab, LIFE Ctr, Klinikum Grosshadern, Munich, Germany. [Kammerer, Robert] Friedrich Loeffler Inst, Inst Immunol, Tubingen, Germany. [Keefe, Robert; Dropulic, Boro] Lentigen Corp, Baltimore, MD USA. RP Medin, JA (reprint author), Univ Hlth Network, Ontario Canc Inst, 67 Coll St, Toronto, ON M5G 2M1, Canada. EM jmedin@uhnres.utoronto.ca RI Zimmermann, Wolfgang/L-9277-2013 FU Colorectal Cancer Campaign in Canada FX Colorectal Cancer Campaign in Canada. NR 35 TC 9 Z9 9 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2009 VL 8 IS 3 BP 692 EP 702 DI 10.1158/1535-7163.MCT-08-0769 PG 11 WC Oncology SC Oncology GA 423CZ UT WOS:000264475300022 PM 19276164 ER PT J AU Vijayachandra, K Higgins, W Lee, J Glick, A AF Vijayachandra, Kinnimulki Higgins, William Lee, Jessica Glick, Adam TI Induction of p16(ink4a) and P19(ARF) by TGF beta 1 Contributes to Growth Arrest and Senescence Response in Mouse Keratinocytes SO MOLECULAR CARCINOGENESIS LA English DT Article DE senescence; TGF beta 1; mouse; tumor suppressor; keratinocyte ID CELL-CYCLE ARREST; TGF-BETA; RAS; INK4A/ARF; TRANSFORMATION; PROLIFERATION; TUMORIGENESIS; INHIBITION; DISRUPTION; P15(INK4B) AB TGF beta 1 acts as a potent negative regulator of the cell cycle and tumor suppressor in part through induction of cyclin dependent kinase inhibitors p15(ink4b), p21, and p57. We previously showed that primary mouse epidermal keratinocytes (MEK) expressing a v-ras(Ha) oncogene undergo hyperproliferation followed by growth arrest and senescence that was dependent on TGF beta 1 signaling and associated with increased levels of p16(ink4a) and p19(ARF). Here we show that the induction of both p16(ink4a), and p19(ARF) in v-ras(Ha) expressing keratinocytes is dependent on TGF beta 1 signaling, as TGF beta 1 treatment or Smad3 overexpression induces both p16(ink4a) and p19(ARF) protein and mRNA, while Smad3 depletion or Smad7 overexpression blocks induction. Genetic ablation of the cdkn2a (ink4alaf) locus reduced sensitivity to TGF beta 1 mediated cell cycle arrest and induction of senescence suggesting that alteration of TGF beta 1 responses may be an additional pathway impacted by the inactivation of cdkn2a locus during tumor development. (C) 2008 Wilev-Liss, Inc C1 [Higgins, William; Glick, Adam] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16801 USA. [Vijayachandra, Kinnimulki; Lee, Jessica] NCI, Lab Can Biol & Genet, Bethesda, MD 20892 USA. RP Glick, A (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, 201 Life Sci Bld, University Pk, PA 16801 USA. FU NIH [RO1 CA122109] FX The authors would like to acknowledge Stuart Yuspa for his Support in the early stages of this work, and Dr. Beverly Mock, NCI for the p16-luciferase prornoter constructs. This work was carried out with NIH intramural grant Support and RO1 CA122109 (to A.G.). NR 24 TC 27 Z9 28 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 2009 VL 48 IS 3 BP 181 EP 186 DI 10.1002/mc.20472 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 415OI UT WOS:000263943000001 PM 18655107 ER PT J AU Araki, O Ying, H Zhu, XG Willingham, MC Cheng, SY AF Araki, O. Ying, H. Zhu, X. G. Willingham, M. C. Cheng, S. Y. TI Distinct Dysregulation of Lipid Metabolism by Unliganded Thyroid Hormone Receptor Isoforms SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DOMINANT-NEGATIVE ACTIVITY; FATTY-ACID OXIDATION; TRANSGENIC MICE; LIGAND-BINDING; BETA-RECEPTOR; GENE; TEMPERATURE; RESISTANCE; MUTATION; GROWTH AB Thyroid hormone receptors (TRs) play critical roles in energy homeostasis. To understand the role of TRs in lipid homeostasis in vivo, we adopted the loss-of-function approach by creating knock-in mutant mice with targeted mutation in the TR alpha gene (TR alpha 1PV mouse) or TR alpha gene (TR beta PV mouse). The PV mutation, identified in a patient with resistance to thyroid hormone, exhibits potent dominant-negative activity. Here we show that in contrast to TR alpha 1PV mouse, TR beta PV mice exhibited no significant reduction in WAT but had significant increases in serum free fatty acids and total triglycerides. Moreover, the liver of TR beta PV mice was markedly increased (33%) with excess lipid accumulation, but the liver mass of TR alpha 1PV mouse was decreased (23%) with paucity of lipids. These results indicate that apo-TR beta and apo-TR alpha 1 exerted distinct abnormalities in lipid metabolism. Further biochemical analyses indicate that increased lipogenic enzyme expression, activated peroxisome proliferator-activated receptor gamma(Ppar gamma) signaling, and decreased fatty acid beta-oxidation activity contributed to the adipogenic steatosis and lipid accumulation in the liver of TR beta PV mice. In contrast, the expression of lipogenic enzymes and Ppar gamma was decreased in the liver of TR alpha 1PV mice. These results suggest that the regulation of genes critical for lipid metabolism by TRs in the liver is isoform dependent. These results indicate that apo-TR beta and apo-TR alpha 1 had different effects on lipid metabolism and that both TR isoforms contribute to the pathogenesis of lipid metabolism in hypothyroidism. (Molecular Endocrinology 23: 308-315, 2009) C1 [Araki, O.; Ying, H.; Zhu, X. G.; Cheng, S. Y.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Willingham, M. C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural Research Program of Center for Cancer Research; National Cancer Institute; National Institutes of Health FX We thank Dr. Valentina Factor for her assistance in the preparation of mouse primary hepatocytes.; Address all correspondence and requests for reprints to: S. Y. Cheng, Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Drive, Room 5128, Bethesda, Maryland 20892-4264. E-mail: chengs@mail.nih.gov.; The present research was supported by the Intramural Research Program of Center for Cancer Research, National Cancer Institute, National Institutes of Health.; Disclosure Statement: The authors have nothing to disclose. NR 36 TC 28 Z9 29 U1 0 U2 4 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 MAR PY 2009 VL 23 IS 3 BP 308 EP 315 DI 10.1210/me.2008-0311 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 411RQ UT WOS:000263668100003 PM 19131509 ER PT J AU Pascau, J Gispert, JD Michaelides, M Thanos, P Volkow, N Vaquero, JJ Soto-Montenegro, ML Desco, M AF Pascau, Javier Gispert, Juan Domingo Michaelides, Michael Thanos, Panayotis K. Volkow, Nora D. Vaquero, Juan Jose Soto-Montenegro, Maria Luisa Desco, Manuel TI Automated Method for Small-Animal PET Image Registration with Intrinsic Validation SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Image registration; Positron emission tomography (PET); Validation; Algorithm; Rats ID MUTUAL-INFORMATION; RAT-BRAIN; INTERPOLATION ARTIFACTS; PROBABILISTIC ATLASES; MICROPET; MRI; MAXIMIZATION AB We propose and compare different registration approaches to align small-animal PET studies and a procedure to validate the results by means of objective registration consistency measurements. Procedures: We have applied a registration algorithm based on information theory, using different approaches to mask the reference image. The registration consistency allows for the detection of incorrect registrations. This methodology has been evaluated on a test dataset (FDG-PET rat brain images). Results: The results show that a multiresolution two-step registration approach based on the use of the whole image at the low resolution step, while masking the brain at the high resolution step, provides the best robustness (87.5% registration success) and highest accuracy (0.67-mm average). Conclusions: The major advantages of our approach are minimal user interaction and automatic assessment of the registration error, avoiding visual inspection of the results, thus facilitating the accurate, objective, and rapid analysis of large groups of rodent PET images. C1 [Pascau, Javier; Vaquero, Juan Jose; Soto-Montenegro, Maria Luisa; Desco, Manuel] Hosp Gen Gregorio Maranon, Unidad Med & Cirugia Expt, Madrid 28007, Spain. [Gispert, Juan Domingo] CRC Corp Sanitaria, Inst Alta Tecnol, Barcelona 08003, Spain. [Michaelides, Michael; Thanos, Panayotis K.] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Dept Med, Upton, NY 11973 USA. [Michaelides, Michael; Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Michaelides, Michael] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Thanos, Panayotis K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Thanos, Panayotis K.] SUNY Stony Brook, Dept Neurosci & Biomed Engn, Stony Brook, NY 11794 USA. RP Pascau, J (reprint author), Hosp Gen Gregorio Maranon, Unidad Med & Cirugia Expt, C Doctor Esquerdo 46, Madrid 28007, Spain. EM jpascau@mce.hggm.es RI Pascau, Javier/B-5734-2013; Michaelides, Michael/K-4736-2013; Vaquero, Juan Jose/D-3033-2009; Desco, Manuel/D-2822-2009; OI Pascau, Javier/0000-0003-1484-731X; Michaelides, Michael/0000-0003-0398-4917; Vaquero, Juan Jose/0000-0001-9200-361X; Desco, Manuel/0000-0003-0989-3231; Gispert, Juan Domingo/0000-0002-6155-0642 FU CIBER [CB06/01/0079]; CDTEAM (CENIT program, Ministerio de Industria); NIAAA Intramural Research Program [AA 11034, AA07574, AA07611]; US Department of Energy [DE-AC02-98CH10886] FX This work was supported by projects CIBER CB06/01/0079 (Ministerio de Sanidad y Consumo) and CDTEAM (CENIT program, Ministerio de Industria). Further support came from NIAAA Intramural Research Program (AA 11034 and AA07574, AA07611) and the US Department of Energy (DE-AC02-98CH10886). NR 27 TC 14 Z9 14 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD MAR PY 2009 VL 11 IS 2 BP 107 EP 113 DI 10.1007/s11307-008-0166-z PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 403XW UT WOS:000263116300008 PM 18670824 ER PT J AU Hunter, MJ Iodice, MW Pathak, AK Street, MA Helm, BA AF Hunter, Michael J. Iodice, Marco W. Pathak, Ashutosh K. Street, Mark A. Helm, Birgit A. TI Characterization of an early signaling defect following Fc epsilon RI activation in the canine mastocytoma cell line, C2 SO MOLECULAR IMMUNOLOGY LA English DT Article DE Canine IgE high-affinity receptor; IgE receptor signaling; Allergy ID AFFINITY IGE RECEPTOR; MAST-CELL; BASOPHILIC LEUKEMIA; CONTINUOUS-CULTURE; RAT AB A comparison of IgE recognition by cognate receptors expressed on the C2 canine mastocytoma cell line with analogous events in a rat basophilic leukemia cell line transfected with the alpha-chain subunit of the canine high-affinity IgE receptor using flow cytometry show that canine IgE recognizes the alpha-chain of its cognate receptor on both cell lines. Our study confirms the expression of functional IgE receptors in both cell lines, but receptor-mediated signaling in the C2 line only supports the early stages of downstream signaling as shown by the phosphorylation of the gamma-chain and the failure to effect the phosphorylation of Syk. In contrast RBL-2H3 cells respond to sensitization with IgE and challenge with cognate antigen with tyrosine phosphorylation of the gamma-subunits of the receptor complex followed by downstream phosphorylation of Syk and Ca(2+) mobilization, culminating in beta-hexosaminidase release. We propose that the identification of the precise signaling defect in C2 cells will yield useful information regarding the pathway leading to mast cell exocytosis and facilitate the restoration of the complete signaling cascade through complementation of the missing/defective signal transducer since signaling events downstream of Ca(2+) mobilization are intact as demonstrated by beta-hexosaminidase release following non-immunologic stimulation with the calcium ionophore, A23187. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Hunter, Michael J.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hunter, Michael J.; Iodice, Marco W.; Pathak, Ashutosh K.; Street, Mark A.; Helm, Birgit A.] Univ Sheffield, Dept Mol Biol & Biotechnol, Krebs Inst Biomol Res, Sheffield S10 2TN, S Yorkshire, England. [Iodice, Marco W.] Abcam Plc, Cambridge CB4 0GZ, England. [Pathak, Ashutosh K.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. RP Hunter, MJ (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr,MSC1203,Bldg 10-CRC,Room 3-3264, Bethesda, MD 20892 USA. EM huntermj@mail.nih.gov FU BBSRC [BBSQ/Q/2005/06706] FX C2 canine mastocytoma cell line was a gift of Dr. T. Gueck, University of Leipzig, Germany. Part of this work was supported by BBSRC Case award (BBSQ/Q/2005/06706) to MAS. NR 14 TC 2 Z9 2 U1 0 U2 1 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 MAR PY 2009 VL 46 IS 6 BP 1260 EP 1265 DI 10.1016/j.molimm.2008.10.036 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 426FK UT WOS:000264693200029 PM 19135724 ER PT J AU Ogawa, M Kosaka, N Longmire, MR Urano, Y Choyke, PL Kobayashi, H AF Ogawa, Mikako Kosaka, Nobuyuki Longmire, Michelle R. Urano, Yasuteru Choyke, Peter L. Kobayashi, Hisataka TI Fluorophore-Quencher Based Activatable Targeted Optical Probes for Detecting in Vivo Cancer Metastases SO MOLECULAR PHARMACEUTICS LA English DT Article DE Molecular imaging; FRET; photoquencher; activatable; cancer ID RESONANCE ENERGY-TRANSFER; FLUORESCENCE PROBE; CELLS; FRET; BIOSENSORS; CONJUGATE; HERCEPTIN; PROTEINS; AVIDIN; TUMORS AB In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a fluorophore-quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the fluorophore-quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the fluorophore-quencher pair. We selected the TAMRA (fluorophore)-QSY7 (quencher) pair and conjugated it to either avidin (targeting the D-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA-QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-TM-07) were synthesized. Both demonstrated better than similar self-quenching probes. In vitro fluorescence microscopic studies of SHIN3 and NIH/3T3/HER2+ cells demonstrated that Av-TM-Q7 and Traz-TM-Q7 produced high intracellular fluorescent signal. In vivo imaging with Av-TM-Q7 and Traz-TM-07 in mice enabled the detection of small tumors. This molecular imaging probe, based on a fluorophore-quencher pair conjugated to a targeting ligand, successfully detected tumors in vivo due to its high activation ratio and low background signal. Thus, these activatable probes, based on the fluorophore-quencher system, hold promise clinically for "see and treat" strategies of cancer management. C1 [Ogawa, Mikako; Kosaka, Nobuyuki; Longmire, Michelle R.; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Urano, Yasuteru] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Canc Res Ctr, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 36 TC 61 Z9 62 U1 4 U2 39 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAR-APR PY 2009 VL 6 IS 2 BP 386 EP 395 DI 10.1021/mp800115t PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430ME UT WOS:000264992400006 PM 19718793 ER PT J AU Sahu, A Tyeryar, KR Vongtau, HO Sibley, DR Undieh, AS AF Sahu, Asha Tyeryar, Kimberly R. Vongtau, Habiba O. Sibley, David R. Undieh, Ashiwel S. TI D-5 Dopamine Receptors are Required for Dopaminergic Activation of Phospholipase C SO MOLECULAR PHARMACOLOGY LA English DT Article ID INOSITOL PHOSPHATE FORMATION; RAT-BRAIN; ADENYLATE-CYCLASE; PHOSPHOINOSITIDE HYDROLYSIS; INTRACELLULAR CALCIUM; MONKEY BRAIN; D1; STIMULATION; NEURONS; MICE AB Dopamine activates phospholipase C in discrete regions of the mammalian brain, and this action is believed to be mediated through a D-1-like receptor. Although multiple lines of evidence exclude a role for the D-1 subtype of D-1-like receptors in the phosphoinositide response, the D-5 subtype has not been similarly examined. Here, mice lacking D-5 dopamine receptors were tested for dopamine agonist-induced phosphoinositide signaling both in vitro and in vivo. The results show that hippocampal, cortical, and striatal tissues of D-5 receptor knockout mice significantly or completely lost the ability to produce inositol phosphate or diacylglycerol messengers after stimulation with dopamine or several selective D-1-like receptor agonists. Moreover, endogenous inositol-1,4,5-trisphosphate stimulation by the phospholipase C-selective D-1-like agonist 3-methyl-6chloro- 7,8-dihydroxy-1-[3methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) was robust in wild-type animals but undetectable in the D-5 receptor mutants. Hence, D-5 receptors are required for dopamine and selective D-1-like agonists to induce phospholipase C-mediated phosphoinositide signaling in the mammalian brain. C1 [Undieh, Ashiwel S.] Thomas Jefferson Univ, Dept Pharmaceut Sci, Lab Integrat Neuropharmacol, Sch Pharm, Philadelphia, PA 19107 USA. [Sibley, David R.] NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. [Sahu, Asha; Tyeryar, Kimberly R.; Vongtau, Habiba O.] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Undieh, AS (reprint author), Thomas Jefferson Univ, Dept Pharmaceut Sci, Lab Integrat Neuropharmacol, Sch Pharm, 130 S 9th St,Suite 1540, Philadelphia, PA 19107 USA. EM ashiwel.undieh@jefferson.edu OI Undieh, Ashiwel/0000-0003-1823-5230 FU Intramural NIH HHS; NIDA NIH HHS [R01-DA017614, R01 DA017614-04, R01 DA017614] NR 40 TC 49 Z9 51 U1 0 U2 1 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 MAR PY 2009 VL 75 IS 3 BP 447 EP 453 DI 10.1124/mol.108.053017 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 410EE UT WOS:000263559500003 PM 19047479 ER PT J AU Willour, VL Chen, H Toolan, J Belmonte, P Cutler, DJ Goes, FS Zandi, PP Lee, RS MacKinnon, DF Mondimore, FM Schweizer, B DePaulo, JR Gershon, ES McMahon, FJ Potash, JB AF Willour, V. L. Chen, H. Toolan, J. Belmonte, P. Cutler, D. J. Goes, F. S. Zandi, P. P. Lee, R. S. MacKinnon, D. F. Mondimore, F. M. Schweizer, B. DePaulo, J. R., Jr. Gershon, E. S. McMahon, F. J. Potash, J. B. CA Bipolar Disorder Phenome Grp NIMH Genetics Initiative Bipolar D TI Family-based association of FKBP5 in bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE HPA axis; mood disorder; linkage disequilibrium ID GLUCOCORTICOID-RECEPTOR GENE; GENOME-WIDE ASSOCIATION; DIAGNOSTIC INTERVIEW; ENDOCRINE FUNCTIONS; MAJOR DEPRESSION; THYROID-HORMONES; BLOOD-LEVELS; CRH TEST; POLYMORPHISMS; ILLNESS AB The FKBP5 gene product forms part of a complex with the glucocorticoid receptor and can modulate cortisol-binding affinity. Variations in the gene have been associated with increased recurrence of depression and with rapid response to antidepressant treatment. We sought to determine whether common FKBP5 variants confer risk for bipolar disorder. We genotyped seven tag single-nucleotide polymorphisms (SNPs) in FKBP5, plus two SNPs previously associated with illness, in 317 families with 554 bipolar offspring, derived primarily from two studies. Single marker and haplotypic analyses were carried out with FBAT and EATDT employing the standard bipolar phenotype. Association analyses were also conducted using 11 disease-related variables as covariates. Under an additive genetic model, rs4713902 showed significant overtransmission of the major allele (P=0.0001), which was consistent across the two sample sets (P=0.004 and 0.006). rs7757037 showed evidence of association that was strongest under the dominant model (P=0.001). This result was consistent across the two datasets (P=0.017 and 0.019). The dominant model yielded modest evidence for association (P<0.05) for three additional markers. Covariate-based analyses suggested that genetic variation within FKBP5 may influence attempted suicide and number of depressive episodes in bipolar subjects. Our results are consistent with the well-established relationship between the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the stress response through regulation of cortisol, and mood disorders. Ongoing whole-genome association studies in bipolar disorder and major depression should further clarify the role of FKBP5 and other HPA genes in these illnesses. C1 [Willour, V. L.; Toolan, J.; Belmonte, P.; Goes, F. S.; Lee, R. S.; MacKinnon, D. F.; Mondimore, F. M.; Schweizer, B.; DePaulo, J. R., Jr.; Potash, J. B.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. [Chen, H.] Univ Michigan, Dept Psychiat, Sch Med, Ann Arbor, MI 48109 USA. [Cutler, D. J.] Johns Hopkins Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Zandi, P. P.] Johns Hopkins Bloomberg Sch Pub Hlth, Dept Mental Hlth, Baltimore, MD USA. [Gershon, E. S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [McMahon, F. J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Willour, VL (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Meyer 4-143,600 N Wolfe St, Baltimore, MD 21287 USA. EM willour@jhmi.edu RI Meyer, Eric/C-1029-2011; OI Meyer, Eric/0000-0002-1998-7162; Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690 FU National Institute of Mental Health [R01 MH-042243, R01 MH-061613]; Charles A Dana Foundation Consortium on the Genetic Basis of Manic Depressive Illness; National Alliance for Research on Schizophrenia and Depression,; Alex Brown Foundation and the Stanley Medical Research Institute; Margaret Ann Price Investigatorships; NIMH; Genetic Basis of Mood and Anxiety Disorders Unit; Mood and Anxiety Program; National Institutes of Health, Bethesda; Department of Psychiatry; School of Medicine; Department of Mental Health; School of Public Health; Division of Genetic Epidemiology in Psychiatry; Central Institute of Mental Health; Ruprecht-Karls-University of Heidelberg, Mannheim, Germany; Howard University Hospital; University of Colorado at Denver, Denver, CO FX Some of the data and biomaterials were collected in four projects that participated in the NIMH Bipolar Disorder Genetics Initiative from 1991-1998. The Principal Investigators and Co-Investigators were Indiana University, Indianapolis, IN, U01 MH46282, John Nurnberger, MD, PhD, Marvin Miller, MD and Elizabeth Bowman, MD; Washington University, St Louis, MO, U01 MH46280, Theodore Reich, MD, Allison Goate, PhD and John Rice, PhD; Johns Hopkins University, Baltimore, MD U01 MH46274, J Raymond DePaulo, Jr, MD, Sylvia Simpson, MD, MPH and Colin Stine, PhD; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD, Elliot Gershon, MD, Diane Kazuba, BA and Elizabeth Maxwell, MSW. Other data and biomaterials were collected in 10 NIMH Bipolar Disorder Genetics Initiative projects from 1999-2003. The Principal Investigators and Co-Investigators were Indiana University, Indianapolis, IN, R01 MH59545, John Nurnberger, MD, PhD, Marvin J Miller, MD, Elizabeth S Bowman, MD, N Leela Rau, MD, P Ryan Moe, MD, Nalini Samavedy, MD, Rif El-Mallakh, MD (at University of Louisville), Husseini Manji, MD (at Wayne State University), Debra A Glitz, MD (atWayne State University), Eric T Meyer, MS, Carrie Smiley, RN, Tatiana Foroud, PhD, Leah Flury, MS, Danielle M Dick, PhD, Howard Edenberg, PhD; Washington University, St Louis, MO, R01 MH059534, John Rice, PhD, Theodore Reich, MD, Allison Goate, PhD, Laura Bierut, MD; Johns Hopkins University, Baltimore, MD, R01 MH59533, Melvin McInnis MD, J. Raymond DePaulo, Jr, MD, Dean F MacKinnon, MD, Francis M Mondimore, MD, James B Potash, MD, Peter P Zandi, PhD, Dimitrios Avramopoulos, PhD and Jennifer Payne, MD; University of Pennsylvania, PA, R01 MH59553, Wade Berrettini MD, PhD; University of California at Irvine, CA, R01 MH60068, William Byerley MD and Mark Vawter MD; University of Iowa, IA, R01 MH059548, William Coryell MD and Raymond Crowe MD; University of Chicago, IL, R01 MH59535, Elliot Gershon, MD, Judith Badner PhD, Francis McMahon MD, Chunyu Liu PhD, Alan Sanders MD, Maria Caserta, Steven Dinwiddie MD, Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567, John Kelsoe, MD, Rebecca McKinney, BA; Rush University, IL, R01 MH059556, William Scheftner MD, Howard M Kravitz, DO, MPH, Diana Marta, BS, Annette Vaughn- Brown, MSN, RN and Laurie Bederow, MA; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810- 01, Francis J McMahon, MD, Layla Kassem, PsyD, Sevilla Detera- Wadleigh, PhD, Lisa Austin, PhD, Dennis L Murphy, MD. NR 42 TC 74 Z9 77 U1 0 U2 6 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 MAR PY 2009 VL 14 IS 3 BP 261 EP 268 DI 10.1038/sj.mp.4002141 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 410DF UT WOS:000263556000006 PM 18180755 ER PT J AU Lan, MJ McLoughlin, GA Griffin, JL Tsang, TM Huang, JTJ Yuan, P Manji, H Holmes, E Bahn, S AF Lan, M. J. McLoughlin, G. A. Griffin, J. L. Tsang, T. M. Huang, J. T. J. Yuan, P. Manji, H. Holmes, E. Bahn, S. TI Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar disorder; lithium; valproic acid; glutamic acid; creatine; gamma-aminobutyric acid ID MAGNETIC-RESONANCE-SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX; HISTONE DEACETYLASE INHIBITION; CHRONIC LITHIUM; RAT-BRAIN; MITOCHONDRIAL DYSFUNCTION; VALPROIC ACID; METABOLIC CHARACTERIZATION; ARACHIDONIC-ACID; SODIUM VALPROATE AB Bipolar affective disorder is a severe and debilitating psychiatric condition characterized by the alternating mood states of mania and depression. Both the molecular pathophysiology of the disorder and the mechanism of action of the mainstays of its treatment remain largely unknown. Here, (1)H NMR spectroscopy-based metabonomic analysis was performed to identify molecular changes in post-mortem brain tissue (dorsolateral prefrontal cortex) of patients with a history of bipolar disorder. The observed changes were then compared to metabolic alterations identified in rat brain following chronic oral treatment with either lithium or valproate. This is the first study to use (1)H NMR spectroscopy to study post-mortem bipolar human brain tissue, and it is the first to compare changes in disease brain with changes induced in rat brain following mood stabilizer treatment. Several metabolites were found to be concordantly altered in both the animal and human tissues. Glutamate levels were increased in post-mortem bipolar brain, while the glutamate/glutamine ratio was decreased following valproate treatment, and gamma-aminobutyric acid levels were increased after lithium treatment, suggesting that the balance of excitatory/inhibitory neurotransmission is central to the disorder. Both creatine and myo-inositol were increased in the post-mortem brain but depleted with the medications. Lastly, the level of N-acetyl aspartate, a clinically important metabolic marker of neuronal viability, was found to be unchanged following chronic mood stabilizer treatment. These findings promise to provide new insight into the pathophysiology of bipolar disorder and may be used to direct research into novel therapeutic strategies. C1 [Lan, M. J.; Bahn, S.] Univ Cambridge, Inst Biotechnol, Cambridge CB2 1QT, England. [Lan, M. J.; Yuan, P.; Manji, H.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [McLoughlin, G. A.; Tsang, T. M.; Holmes, E.] Univ London Imperial Coll Sci Technol & Med, Dept Biomol Med, Div Surg Oncol Reproduct Biol & Anesthet, Fac Med, London, England. [Griffin, J. L.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QT, England. RP Bahn, S (reprint author), Univ Cambridge, Inst Biotechnol, Tennis Court Rd, Cambridge CB2 1QT, England. EM sb209@cam.ac.uk FU Stanley Medical Research Institute; Stanley brain collection courtesy; NIH-Cambridge health scholarship; AstraZeneca and Unilever; NARSAD Essel Independent Investigator Fellowship FX This research was supported by the Stanley Medical Research Institute and the donations of the Stanley brain collection courtesy of Drs Michael B Knable, E Fuller Torrey and Robert H Yolken. Special thanks to Dr Maree Webster for providing post-mortem brain samples. Thanks to all members of the Bahn Laboratory for discussions, help and encouragement. Most of all, thanks to all patients and healthy volunteers for their selfless donation of samples used in this study. MJL is the recipient of an NIH-Cambridge health scholarship and GAMcL is funded by the METAGRAD project (supported by AstraZeneca and Unilever). SB holds a NARSAD Essel Independent Investigator Fellowship. NR 77 TC 66 Z9 68 U1 3 U2 12 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 MAR PY 2009 VL 14 IS 3 BP 269 EP 279 DI 10.1038/sj.mp.4002130 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 410DF UT WOS:000263556000007 PM 18256615 ER PT J AU Wilson, MS Wynn, TA AF Wilson, M. S. Wynn, T. A. TI Pulmonary fibrosis: pathogenesis, etiology and regulation SO MUCOSAL IMMUNOLOGY LA English DT Review ID TRANSFORMING-GROWTH-FACTOR; BRONCHOALVEOLAR LAVAGE FLUID; HUMAN LUNG FIBROBLASTS; USUAL INTERSTITIAL PNEUMONIA; MESSENGER-RNA EXPRESSION; FACTOR-BETA 1; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; UNILATERAL URETERAL OBSTRUCTION; EXTRINSIC ALLERGIC ALVEOLITIS AB Pulmonary fibrosis and architectural remodeling of tissues can severely disrupt lung function, often with fatal consequences. The etiology of pulmonary fibrotic diseases is varied, with an array of triggers including allergens, chemicals, radiation and environmental particles. However, the cause of one of the most common pulmonary fibrotic conditions, idiopathic pulmonary fibrosis (IPF), is still unclear. This review examines common mechanisms of pulmonary wound-healing responses following lung injury, and highlights the pathogenesis of some of the most widespread pulmonary fibrotic diseases. A three phase model of wound repair is reviewed that includes; (1) injury; (2) inflammation; and (3) repair. In most pulmonary fibrotic conditions dysregulation at one or more of these phases has been reported. Chronic inflammation can lead to an imbalance in the production of chemokines, cytokines, growth factors, and disrupt cellular recruitment. These changes coupled with excessive pro-fibrotic IL-13 and/or TGF beta 1 production can turn a well-controlled healing response into a pathogenic fibrotic response. Endogenous regulatory mechanisms are discussed including novel areas of therapeutic intervention. Restoring homeostasis to these dysregulated healing responses, or simply neutralizing the key pro-fibrotic mediators may prevent or slow the progression of pulmonary fibrosis. C1 [Wilson, M. S.; Wynn, T. A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Wilson, MS (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonmar@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 FU Intramural Research Program at the NIH/NIAID FX This review was improved by peer-review and funded by the Intramural Research Program at the NIH/NIAID. Owing to space and word limitations, we apologize to the many researchers whose work we have not mentioned in this review, but who have significantly contributed to our current understanding of pulmonary fibrosis. We also thank Dr Allen Cheever for helpful comments. NR 378 TC 226 Z9 242 U1 6 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAR PY 2009 VL 2 IS 2 BP 103 EP 121 DI 10.1038/mi.2008.85 PG 19 WC Immunology SC Immunology GA 406XI UT WOS:000263327800003 PM 19129758 ER PT J AU Johnson, D Sung, GH Hywel-Jones, NL Luangsa-Ard, JJ Bischoff, JF Kepler, RM Spatafora, JW AF Johnson, Desiree Sung, Gi-Ho Hywel-Jones, Nigel L. Luangsa-Ard, J. Jennifer Bischoff, Joseph F. Kepler, Ryan M. Spatafora, Joseph W. TI Systematics and evolution of the genus Torrubiella (Hypocyeales, Ascomycota) SO MYCOLOGICAL RESEARCH LA English DT Article DE Conoideocrella; Gibellula; Orbiocrella; Phylogeny; Scale insect pathogens; Spider; Torrubiella ID SCALE INSECTS; MIXED MODELS; CORDYCEPS; THAILAND; LECANICILLIUM; ASSOCIATION; REVISION; PATHOGEN; COMPLEX; FUNGI AB Torrubiella is a genus of arthropod-pathogenic fungi that primarily attacks spiders and scale insects. Based on the morphology of the perithecia, asci, and ascospores, it is classified in Clavicipitaceae s. lat. (Hypocreales), and is considered a close relative of Cordyceps s. 1., which was recently reclassified into three families (Clavicipitaceae s. str., Cordycipitaceae, Ophiocordycipitaceae) and four genera (Cordyceps s. str, Elaphocordyceps, Metacordyceps, and Ophiocordyceps). Torrubiella is distinguished morphologically from Cordyceps s. lat. mainly by the production of superficial perithecia and the absence of a well-developed stipitate stroma. To test and refine evolutionary hypotheses regarding the placement of Torrubiella and its relationship to Cordyceps s. lat., a multi-gene phylogeny was constructed by conducting ML and Bayesian analyses. The monophyly of Torrubiella was rejected by these analyses with species of the genus present in Clavicipitaceae, Cordycipitaceae, and ophiocordycipitaceae, and often intermixed among species of Cordyceps s. lat. The morphological characters traditionally used to define the genus are, therefore, not phylogenetically informative, with the stipitate stromata being gained and/or lost several times among clavicipitaceous fungi. Two new genera (Conoideocrella, Orbiocrella) are proposed to accommodate two separate lineages of torrubielloid fungi in the Clavicipitaceae s. str. In addition, one species is reclassified in Cordyceps s. str. and three are reclassified in Ophiocordyceps. The phylogenetic importance of anamorphic genera, host affiliation, and stipitate stromata is discussed. (c) 2008 The British Mycological Society. Published by Elsevier Ltd. All rights reserved. C1 [Johnson, Desiree; Sung, Gi-Ho; Kepler, Ryan M.; Spatafora, Joseph W.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Hywel-Jones, Nigel L.] Natl Ctr Genet Engn & Biotechnol, Mycol Lab, Pathum Thani, Thailand. [Luangsa-Ard, J. Jennifer] Natl Ctr Genet Engn & Biotechnol, Phylogenet Lab, Pathum Thani, Thailand. [Bischoff, Joseph F.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Sung, GH (reprint author), Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. EM sungg@science.oregonstate.edu FU National Science Foundation [DEB-0129212, DEB-0-297-2] FX We thank Walter Gams for assistance with Latin diagnoses and for his constructive comments to this manuscript. This research was supported by grants from the National Science Foundation (DEB-0129212 and DEB-0-297-2 to JW.S.). NR 39 TC 31 Z9 38 U1 3 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0953-7562 J9 MYCOL RES JI Mycol. Res. PD MAR PY 2009 VL 113 BP 279 EP 289 DI 10.1016/j.mycres.2008.09.008 PN 3 PG 11 WC Mycology SC Mycology GA 426FP UT WOS:000264693700001 PM 18938242 ER PT J AU Buch, I Brooks, BR Wolfson, HJ Nussinov, R AF Buch, Idit Brooks, Bernard R. Wolfson, Haim J. Nussinov, Ruth TI Computational Validation of Protein Nanotubes SO NANO LETTERS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; SURFACTANT-LIKE PEPTIDES; SELF-ASSEMBLY PATHWAYS; HIV-1 CAPSID PROTEIN; NANOSTRUCTURE DESIGN; BUILDING-BLOCKS; CYCLIC-PEPTIDES; MONTE-CARLO; NANOSCALE; DOMAIN AB We present a novel generic computational method to assess protein nanotubes with variable diameter sizes at the atomic level given their low resolution protomeric structures. The method is based on the symmetrical assembly of a repeating protein subunit into a nanotube. Given the protein unit-cell, and the tube diameter and helicity, we carry out all-atom molecular dynamics simulations, combined with a unique mathematical transformation. This allows us to mimic nanotubes of even huge sizes without end or edge effects. All our simulation setups attempt to explicitly adhere to the conditions under which the experiments were conducted. Thus, we are able to obtain high resolution atomic-scale structures at reasonable computational costs. We expect that our approach would prove useful in assessing protein nanotubes, as well as in silico constructions of novel nanobiomaterials. C1 [Buch, Idit; Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sch Comp Sci,Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Nussinov, Ruth] NCI, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Fac Med, Sch Comp Sci,Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. EM ruthn@ncifcrf.gov RI Wolfson, Haim/A-1837-2011 FU National Cancer Institute; NIH [NO1-CO-12400]; National Heart, Lung and Blood Institute FX We thank Barbie K. Ganser-Pornillos for providing the atomic model of the HIV-1 CA hexamer. We also thank Chung-Jung Tsai, Dan Fishelovitch, Nurit Haspel, Tim Miller, Richard Venable, Ehud Gazit, and Ruth Arav for fruitful discussions and support. This project has been funded in part with Federal funds from the National Cancer Institute, NIH, under contract number NO1-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the National Heart, Lung and Heart Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 43 TC 3 Z9 3 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD MAR PY 2009 VL 9 IS 3 BP 1096 EP 1102 DI 10.1021/nl803521j PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 418IO UT WOS:000264142100032 PM 19199488 ER PT J AU Keng, VW Villanueva, A Chiang, DY Dupuy, AJ Ryan, BJ Matise, I Silverstein, KAT Sarver, A Starr, TK Akagi, K Tessarollo, L Collier, LS Powers, S Lowe, SW Jenkins, NA Copeland, NG Llovet, JM Largaespada, DA AF Keng, Vincent W. Villanueva, Augusto Chiang, Derek Y. Dupuy, Adam J. Ryan, Barbara J. Matise, Ilze Silverstein, Kevin A. T. Sarver, Aaron Starr, Timothy K. Akagi, Keiko Tessarollo, Lino Collier, Lara S. Powers, Scott Lowe, Scott W. Jenkins, Nancy A. Copeland, Neal G. Llovet, Josep M. Largaespada, David A. TI A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma SO NATURE BIOTECHNOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; NF-KAPPA-B; SLEEPING-BEAUTY; IN-VITRO; LIVER-CANCER; EXPRESSION; KINASE; TUMOR; ACTIVATION; PATHWAY AB We describe a system that permits conditional mobilization of a Sleeping Beauty (SB) transposase allele by Cre recombinase to induce cancer specifically in a tissue of interest. To demonstrate its potential for developing tissue-specific models of cancer in mice, we limit SB transposition to the liver by placing Cre expression under the control of an albumin enhancer/promoter sequence and screen for hepatocellular carcinoma (HCC)-associated genes. From 8,060 nonredundant insertions cloned from 68 tumor nodules and comparative analysis with data from human HCC samples, we identify 19 loci strongly implicated in causing HCC. These encode genes, such as EGFR and MET, previously associated with HCC and others, such as UBE2H, that are potential new targets for treating this neoplasm. Our system, which could be modified to drive transposon-based insertional mutagenesis wherever tissue-specific Cre expression is possible, promises to enhance understanding of cancer genomes and identify new targets for therapeutic development. C1 [Keng, Vincent W.; Ryan, Barbara J.; Matise, Ilze; Silverstein, Kevin A. T.; Sarver, Aaron; Starr, Timothy K.; Largaespada, David A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. [Keng, Vincent W.; Ryan, Barbara J.; Starr, Timothy K.; Largaespada, David A.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Villanueva, Augusto; Llovet, Josep M.] Hosp Clin Barcelona, CIBERehd, IDIBAPS, HCC Translat Res Lab,BCLC Grp Liver Unit, E-08036 Barcelona, Spain. [Chiang, Derek Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chiang, Derek Y.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chiang, Derek Y.] Broad Inst Harvard, Canc Program, Cambridge, MA 02142 USA. [Chiang, Derek Y.] MIT, Cambridge, MA 02142 USA. [Dupuy, Adam J.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Akagi, Keiko; Tessarollo, Lino] NCI, Frederick, MD 21702 USA. [Collier, Lara S.] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USA. [Powers, Scott; Lowe, Scott W.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Jenkins, Nancy A.; Copeland, Neal G.] Inst Mol & Cellular Biol, Singapore 138673, Singapore. [Llovet, Josep M.] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, New York, NY 10029 USA. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Spain. RP Largaespada, DA (reprint author), Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. EM larga002@umn.edu RI Augusto, Villanueva/F-9378-2012; Largaespada, David/C-9832-2014; Llovet, Josep M /D-4340-2014; OI Augusto, Villanueva/0000-0003-3585-3727; Llovet, Josep M /0000-0003-0547-2667; Chiang, Derek/0000-0002-1131-6065; Keng, Vincent/0000-0003-3473-0653; Starr, Timothy/0000-0002-6308-3451 FU European Association for the Study of the Liver; National Cancer Institute [1K01CA122183-01, U01 CA84221, R01 CA113636]; Department of Health and Human Services; National Institutes of Health; US National Institute of Diabetes; Digestive and Kidney Diseases [1R01DK076986-01]; Spanish National Institute of Health [SAF-200761898]; Samuel Waxman Cancer Research Foundation FX The authors wish to thank Christine E. Nelson, Stefanie S. Breitbarth, Michelle K. Gleason and Geoff Hart for their excellent technical support; Jason B. Bell for performing the hydrodynamic injections; and Heidi Gruelich, Dana Farber Cancer Institute, for her kind gift pBabe-Puro-LTR-EGFR. We are also grateful to the Minnesota Supercomputing Institute for providing extensive computational resources (hardware and systems administration support) used to carry out the sequence analysis. A.V. is supported by a Sheila Sherlock fellowship from the European Association for the Study of the Liver. L.S.C. is supported by a 1K01CA122183-01 grant from the National Cancer Institute. N.G.C., N.A.J. and L.T. are supported by the Department of Health and Human Services, National Institutes of Health and the National Cancer Institute. J.M.L. is supported by the US National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01), Spanish National Institute of Health (SAF-200761898) and Samuel Waxman Cancer Research Foundation. D.A.L. is supported by U01 CA84221 and R01 CA113636 grants from the National Cancer Institute. NR 52 TC 118 Z9 125 U1 2 U2 9 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 MAR PY 2009 VL 27 IS 3 BP 264 EP 274 DI 10.1038/nbt.1526 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 416UJ UT WOS:000264030700020 PM 19234449 ER PT J AU Gillette, JM Larochelle, A Dunbar, CE Lippincott-Schwartz, J AF Gillette, Jennifer M. Larochelle, Andre Dunbar, Cynthia E. Lippincott-Schwartz, Jennifer TI Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche SO NATURE CELL BIOLOGY LA English DT Article ID HEMATOPOIETIC-STEM-CELL; PROGENITOR CELLS; SURFACE PROTEINS; STROMAL CELLS; INTERNALIZATION; OSTEOBLASTS; MIGRATION; MEMBRANE; PATHWAYS; ADHESION AB Haematopoietic stem-progenitor cells (HSPCs) reside in the bone marrow niche, where interactions with osteoblasts provide essential cues for their proliferation and survival. Here, we use live-cell imaging to characterize both the site of contact between osteoblasts and haematopoietic progenitor cells (HPCs) and events at this site that result in downstream signalling responses important for niche maintenance. HPCs made prolonged contact with the osteoblast surface through a specialized membrane domain enriched in prominin 1, CD63 and rhodamine PE. At the contact site, portions of the specialized domain containing these molecules were taken up by the osteoblast and internalized into SARA-positive signalling endosomes. This caused osteoblasts to downregulate Smad signalling and increase production of stromal-derived factor-1 (SDF-1), a chemokine responsible for HSPC homing to bone marrow. These findings identify a mechanism involving intercellular transfer to signalling endosomes for targeted regulation of signalling and remodelling events within an ex vivo osteoblastic niche. C1 [Gillette, Jennifer M.; Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Larochelle, Andre; Dunbar, Cynthia E.] NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lippincj@mail.nih.gov FU Intramural Research Program of the US National Institute of Child Health and Human Development; National Institutes of Health FX We are grateful to Victoria Cogger ( University of Sydney, ANZAC Research Institute, Australia) for assistance with scanning electron microscopy. We would also like to thank Denis Corbeil ( University of Dresden, Germany) for providing the prominin 1 - GFP construct, and Suliana Manley and George Patterson ( NIH) for critical reading of the manuscript. This project was supported by the Intramural Research Program of the US National Institute of Child Health and Human Development, National Institutes of Health. NR 32 TC 59 Z9 60 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2009 VL 11 IS 3 BP 303 EP U168 DI 10.1038/ncb1838 PG 10 WC Cell Biology SC Cell Biology GA 413FI UT WOS:000263777900014 PM 19198600 ER PT J AU Ferre, S Baler, R Bouvier, M Caron, MG Devi, LA Durroux, T Fuxe, K George, SR Javitch, JA Lohse, MJ Mackie, K Milligan, G Pfleger, KDG Pin, JP Volkow, ND Waldhoer, M Woods, AS Franco, R AF Ferre, Sergi Baler, Ruben Bouvier, Michel Caron, Marc G. Devi, Lakshmi A. Durroux, Thierry Fuxe, Kjell George, Susan R. Javitch, Jonathan A. Lohse, Martin J. Mackie, Ken Milligan, Graeme Pfleger, Kevin D. G. Pin, Jean-Philippe Volkow, Nora D. Waldhoer, Maria Woods, Amina S. Franco, Rafael TI Building a new conceptual framework for receptor heteromers SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; INTERNATIONAL UNION; PHARMACOLOGY; RELEVANCE; HETERODIMERIZATION; CLASSIFICATION; IDENTIFICATION; NOMENCLATURE; MODULATION; STRIATUM AB Receptor heteromers constitute a new area of research that is reshaping our thinking about biochemistry, cell biology, pharmacology and drug discovery. In this commentary, we recommend clear definitions that should facilitate both information exchange and research on this growing class of transmembrane signal transduction units and their complex properties. We also consider research questions underlying the proposed nomenclature, with recommendations for receptor heteromer identification in native tissues and their use as targets for drug development. C1 [Ferre, Sergi] NIH, Natl Inst Drug Abuse, IRP, DHHS, Baltimore, MD 21224 USA. [Baler, Ruben] NIH, Natl Inst Drug Abuse, DHHS, Bethesda, MD 20892 USA. [Bouvier, Michel] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada. [Caron, Marc G.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [Devi, Lakshmi A.] Mt Sinai Sch Med, New York, NY 10029 USA. [Durroux, Thierry] Univ Montpellier, INSERM, CNRS, Inst Genom Fonct, F-34000 Montpellier, France. [Fuxe, Kjell] Karolinska Inst, S-17177 Stockholm, Sweden. [George, Susan R.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M5S 1A8, Canada. [Javitch, Jonathan A.] Columbia Univ, Ctr Mol Recognit, Coll Phys & Surg, New York, NY 10032 USA. [Lohse, Martin J.] Univ Wurzburg, Rudolf Virchow Ctr, D-97078 Wurzburg, Germany. [Mackie, Ken] Indiana Univ, Bloomington, IN 47405 USA. [Milligan, Graeme] Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland. [Pfleger, Kevin D. G.] Univ Western Australia, Western Australian Inst Med Res, Nedlands, WA 6009, Australia. [Pfleger, Kevin D. G.] Univ Western Australia, Med Res Ctr, Nedlands, WA 6009, Australia. [Pin, Jean-Philippe] Univ Montpellier, INSERM, CNRS, Inst Genom Fonct, F-34000 Montpellier, France. [Volkow, Nora D.] NIH, Natl Inst Drug Abuse, DHHS, Bethesda, MD 20892 USA. [Waldhoer, Maria] Med Univ Graz, A-8010 Graz, Austria. [Woods, Amina S.] NIH, Natl Inst Drug Abuse, IRP, DHHS, Baltimore, MD 21224 USA. [Franco, Rafael] Univ Barcelona, IDIBAPS Fac Biol, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona 08028, Spain. [Franco, Rafael] Univ Navarra, CIMA, Pamplona 31008, Spain. RP Ferre, S (reprint author), NIH, Natl Inst Drug Abuse, IRP, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Mackie, Kenneth/B-7358-2011; Lohse, Martin/A-7160-2012; Milligan, Graeme/F-9426-2011; Mackie, Ken/E-3715-2013; Bouvier, Michel/H-2758-2014; Pfleger, Kevin/H-5629-2014; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; OI Lohse, Martin/0000-0002-0599-3510; Milligan, Graeme/0000-0002-6946-3519; Mackie, Ken/0000-0001-8501-6199; Bouvier, Michel/0000-0003-1128-0100; Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Fuxe, Kjell/0000-0001-8491-4288 FU Intramural NIH HHS [Z99 DA999999]; Medical Research Council [G9811527]; NIDA NIH HHS [K05 DA022413, R01 DA007223]; NIMH NIH HHS [R01 MH054137] NR 30 TC 191 Z9 193 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAR PY 2009 VL 5 IS 3 BP 131 EP 134 DI 10.1038/nchembio0309-131 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 410DG UT WOS:000263556100004 PM 19219011 ER PT J AU Erdmann, J Grosshennig, A Braund, PS Konig, IR Hengstenberg, C Hall, AS Linsel-Nitschke, P Kathiresan, S Wright, B Tregouet, DA Cambien, F Bruse, P Aherrahrou, Z Wagner, AK Stark, K Schwartz, SM Salomaa, V Elosua, R Melander, O Voight, BF O'Donnell, CJ Peltonen, L Siscovick, DS Altshuler, D Merlini, PA Peyvandi, F Bernardinelli, L Ardissino, D Schillert, A Blankenberg, S Zeller, T Wild, P Schwarz, DF Tiret, L Perret, C Schreiber, S El Mokhtari, NE Schafer, A Marz, W Renner, W Bugert, P Kluter, H Schrezenmeir, J Rubin, D Ball, SG Balmforth, AJ Wichmann, HE Meitinger, T Fischer, M Meisinger, C Baumert, J Peters, A Ouwehand, WH Deloukas, P Thompson, JR Ziegler, A Samani, NJ Schunkert, H AF Erdmann, Jeanette Grosshennig, Anika Braund, Peter S. Koenig, Inke R. Hengstenberg, Christian Hall, Alistair S. Linsel-Nitschke, Patrick Kathiresan, Sekar Wright, Ben Tregouet, David-Alexandre Cambien, Francois Bruse, Petra Aherrahrou, Zouhair Wagner, Arnika K. Stark, Klaus Schwartz, Stephen M. Salomaa, Veikko Elosua, Roberto Melander, Olle Voight, Benjamin F. O'Donnell, Christopher J. Peltonen, Leena Siscovick, David S. Altshuler, David Merlini, Piera Angelica Peyvandi, Flora Bernardinelli, Luisa Ardissino, Diego Schillert, Arne Blankenberg, Stefan Zeller, Tanja Wild, Philipp Schwarz, Daniel F. Tiret, Laurence Perret, Claire Schreiber, Stefan El Mokhtari, Nour Eddine Schaefer, Arne Maerz, Winfried Renner, Wilfried Bugert, Peter Klueter, Harald Schrezenmeir, Juergen Rubin, Diana Ball, Stephen G. Balmforth, Anthony J. Wichmann, H-Erich Meitinger, Thomas Fischer, Marcus Meisinger, Christa Baumert, Jens Peters, Annette Ouwehand, Willem H. Deloukas, Panos Thompson, John R. Ziegler, Andreas Samani, Nilesh J. Schunkert, Heribert CA Italian Atherosclerosis Thrombosis Myocardial Infarction Genetics Con Wellcome Trust Case Control Consor Cardiogenics Consortium TI New susceptibility locus for coronary artery disease on chromosome 3q22.3 SO NATURE GENETICS LA English DT Article ID ASSOCIATION; GENOME AB We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in similar to 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11). C1 [Erdmann, Jeanette; Grosshennig, Anika; Linsel-Nitschke, Patrick; Bruse, Petra; Aherrahrou, Zouhair; Wagner, Arnika K.; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. [Grosshennig, Anika; Koenig, Inke R.; Schillert, Arne; Schwarz, Daniel F.; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Ctr, Glenfield Hosp, Leicester LE3 9QP, Leics, England. [Hengstenberg, Christian; Stark, Klaus; Fischer, Marcus] Univ Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany. [Hall, Alistair S.; Ball, Stephen G.; Balmforth, Anthony J.] Univ Leeds, LIGHT, Leeds LS1 3EX, W Yorkshire, England. [Kathiresan, Sekar] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wright, Ben; Thompson, John R.] Univ Leicester, Dept Hlth Sci & Genet, Leicester LE1 7RH, Leics, England. [Tregouet, David-Alexandre; Cambien, Francois; Tiret, Laurence; Perret, Claire] Univ Paris 06, INSERM, UMR S 525, Paris, France. [Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98109 USA. [Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Gen Med, Seattle, WA 98109 USA. [Salomaa, Veikko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Chron Dis Epidemiol Unit, FI-00271 Helsinki, Finland. [Elosua, Roberto] Inst Municipal Invest Med, Cardiovasc Epidemiol & Genet Grp, Barcelona 08036, Spain. [Elosua, Roberto] Ciber Epidemiol & Salud Publ, CIBERESP, Barcelona, Spain. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, SE-20502 Malmo, Sweden. [Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [O'Donnell, Christopher J.] NHLBI, NIH, Bethesda, MD 20824 USA. [Peltonen, Leena; Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02115 USA. [Altshuler, David] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Merlini, Piera Angelica] Azienda Osped Niguarda Ca Granda, Div Cardiol, I-20162 Milan, Italy. [Peyvandi, Flora] Univ Milan, Osped Maggiore Mangiagalli & Regina Elena, Fdn Ist Ricovera & Cura Carattere Sci, Dept Internal Med & Med Special, I-20162 Milan, Italy. [Bernardinelli, Luisa] Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy. [Bernardinelli, Luisa] MRC, Biostat Unit, Cambridge CB2 0SR, England. [Ardissino, Diego] Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy. [Blankenberg, Stefan; Zeller, Tanja; Wild, Philipp] Johannes Gutenberg Univ Mainz, Dept Med 2, D-55099 Mainz, Germany. [Schreiber, Stefan; El Mokhtari, Nour Eddine; Schaefer, Arne] Univ Kiel, Inst Klin Mol Biol, D-24118 Kiel, Germany. [Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, D-69037 Heidelberg, Germany. [Renner, Wilfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria. [Maerz, Winfried] Univ Heidelberg, Dept Publ Hlth Social & Prevent Med, D-69117 Heidelberg, Germany. [Bugert, Peter; Klueter, Harald] Univ Heidelberg, Inst Transfus Med & Immunol, D-69117 Heidelberg, Germany. [Bugert, Peter; Klueter, Harald] Med Fac Mannheim, D-68131 Mannheim, Germany. [Schrezenmeir, Juergen; Rubin, Diana] Inst Physiol & Biochem Ernahrung, Bundesforsch Sanstalt Ernahrung & Lebensmittel, D-24118 Kiel, Germany. [Wichmann, H-Erich; Meisinger, Christa; Baumert, Jens; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany. [Wichmann, H-Erich] LMU, Inst Med Informat Sci Biometry & Epidemiol, D-80539 Munich, Germany. [Meitinger, Thomas] Deutsch Forschungszentrum Umwelt & Gesundheit, Helmholtz Zentrum Munchen, Inst Humangenet, D-85764 Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Humangenet, D-80333 Munich, Germany. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 2PT, England. RP Erdmann, J (reprint author), Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. EM j.erdmann@cardiogenics.eu RI Erdmann, Jeanette/A-4417-2009; Schreiber, Stefan/B-6748-2008; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; Stark, Klaus/D-3813-2009; Deloukas, Panos/B-2922-2013; Meisinger, Christine/B-5358-2014; Peters, Annette/A-6117-2011; Meitinger, Thomas/O-1318-2015; Ziegler, Andreas/G-4246-2012; Tregouet, David-Alexandre/E-3961-2016; Konig, Inke/A-4544-2009; Erdmann, Jeanette/P-7513-2014; OI Schreiber, Stefan/0000-0003-2254-7771; Altshuler, David/0000-0002-7250-4107; Stark, Klaus/0000-0002-7832-1942; Deloukas, Panos/0000-0001-9251-070X; ELOSUA, ROBERTO/0000-0001-8235-0095; Ziegler, Andreas/0000-0002-8386-5397; Erdmann, Jeanette/0000-0002-4486-6231; Peyvandi, Flora/0000-0001-7423-9864; Wagner, Arnika/0000-0002-0339-8259; Meisinger, Christa/0000-0002-9026-6544 FU British Heart Foundation; Medical Research Council; NCRR NIH HHS [U54 RR020278, U54RR020278]; NHLBI NIH HHS [R01 HL087676, R01 HL056931, R01 HL056931-02, R01 HL056931-03, R01 HL056931-04, R01HL087676]; Wellcome Trust [, 076113, 077011, 089061] NR 14 TC 274 Z9 280 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2009 VL 41 IS 3 BP 280 EP 282 DI 10.1038/ng.307 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200006 PM 19198612 ER PT J AU Kathiresan, S Altschuler, D Anand, S Ardissino, D Asselta, R Ball, SG Balmforth, AJ Berger, K Berglund, G Bernardi, F Bernardinelli, L Berzuini, C Braund, PS Burnett, MS Burtt, N Cambien, F Casari, G Celli, P Chen, Z Corrocher, R Daly, MJ Deloukas, P Devaney, J Do, R Duga, S Elosua, R Engert, JC Epstein, SE Erdmann, J Ferrario, M Fetiveau, R Fischer, M Friedlander, Y Gabriel, SB Galli, M Gianniny, L Girelli, D Grosshennig, A Guiducci, C Hakonarson, HH Hall, AS Havulinna, AS Hengstenberg, C Hirschhorn, JN Holm, H Huge, A Kent, KM Konig, IR Korn, JM Li, M Lieb, W Lindsay, JM Linsel-Nitschke, P Lucas, G MacRae, CA Mannucci, PM Marrugat, J Martinelli, N Marziliano, N Matthai, W McCarroll, SA McKeown, PP Meigs, JB Melander, O Merlini, PA Mirel, D Morgan, T Musunuru, K Nathan, DM Nemesh, J O'Donnell, CJ Olivieri, O Ouwehand, W Parkin, M Patterson, CC Peltonen, L Peyvandi, F Piazza, A Pichard, AD Preuss, M Purcell, S Qasim, A Rader, DJ Ramos, R Reilly, MP Ribichini, F Rossi, M Sala, J Salomaa, V Samani, NJ Satler, L Scheffold, T Scholz, M Schreiber, S Schunkert, H Schwartz, SM Siscovick, DS Spertus, JA Spreafico, M Stark, K Stefansson, K Stoll, M Subirana, I Surti, A Thompson, JR Thorleifsson, G Thorsteinsdottir, U Tubaro, M Voight, BF Waksman, R Wichmann, HE Wilensky, R Williams, G Wright, BJ Xie, C Yee, J Ziegler, A Zonzin, P AF Kathiresan, Sekar Altschuler, David Anand, Sonia Ardissino, Diego Asselta, Rosanna Ball, Stephen G. Balmforth, Anthony J. Berger, Klaus Berglund, Goran Bernardi, Francesco Bernardinelli, Luisa Berzuini, Carlo Braund, Peter S. Burnett, Mary-Susan Burtt, Noel Cambien, Francois Casari, Giorgio Celli, Patrizia Chen, Zhen Corrocher, Roberto Daly, Mark J. Deloukas, Panos Devaney, Joe Do, Ron Duga, Stefano Elosua, Roberto Engert, James C. Epstein, Stephen E. Erdmann, Jeanette Ferrario, Maurizio Fetiveau, Raffaela Fischer, Marcus Friedlander, Yechiel Gabriel, Stacey B. Galli, Michele Gianniny, Lauren Girelli, Domenico Grosshennig, Anika Guiducci, Candace Hakonarson, Hakon H. Hall, Alistair S. Havulinna, Aki S. Hengstenberg, Christian Hirschhorn, Joel N. Holm, Hilma Huge, Andreas Kent, Kenneth M. Konig, Inke R. Korn, Joshua M. Li, Mingyao Lieb, Wolfgang Lindsay, Joseph M. Linsel-Nitschke, Patrick Lucas, Gavin MacRae, Calum A. Mannucci, Pier M. Marrugat, Jaume Martinelli, Nicola Marziliano, Nicola Matthai, William McCarroll, Steven A. McKeown, Pascal P. Meigs, James B. Melander, Olle Merlini, Pier Angelica Mirel, Daniel Morgan, Thomas Musunuru, Kiran Nathan, David M. Nemesh, James O'Donnell, Christopher J. Olivieri, Oliviero Ouwehand, Willem Parkin, Melissa Patterson, Chris C. Peltonen, Leena Peyvandi, Flora Piazza, Alberto Pichard, Augusto D. Preuss, Michael Purcell, Shaun Qasim, Atif Rader, Daniel J. Ramos, Rafael Reilly, Muredach P. Ribichini, Flavio Rossi, Marco Sala, Joan Salomaa, Veikko Samani, Nilesh J. Satler, Lowell Scheffold, Thomas Scholz, Michael Schreiber, Stefan Schunkert, Heribert Schwartz, Stephen M. Siscovick, David S. Spertus, John A. Spreafico, Marta Stark, Klaus Stefansson, Kari Stoll, Monika Subirana, Isaac Surti, Aarti Thompson, John R. Thorleifsson, Gudmar Thorsteinsdottir, Unnur Tubaro, Marco Voight, Benjamin F. Waksman, Ron Wichmann, H-Erich Wilensky, Robert Williams, Gordon Wright, Benjamin J. Xie, Changchun Yee, Jean Ziegler, Andreas Zonzin, Pietro CA Myocardial Infarction Genetics Consortium TI Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants SO NATURE GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; LDL-RECEPTOR GENE; HEART-DISEASE; CARDIOVASCULAR-DISEASE; COMMON VARIANTS; RISK; CHOLESTEROL; LOCI; PCSK9; HYPERCHOLESTEROLEMIA AB We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases ad 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations(1-4) (9p21, 1p13 near CERSL2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (> 1% allele frequency) and none met the pre-specified threshold for replication (P < 10(-3)). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Hum Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Div, Boston, MA 02114 USA. Broad Inst MIT & Harvard, Prgm Med Populat Genet, Cambridge, MA 02142 USA. Harvard Med Sch, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. Univ Parma, Azienda Osped, I-43100 Parma, Italy. Univ Milan, Dept Intern Med & Med Specialities, Fdn Ist Ricov & Cura Carattere Sci, Osped Maggiore Mangiagalle & Regina Elena, I-20122 Milan, Italy. Univ Milan, Dept Biol Genet Med Sci, I-20133 Milan, Italy. McMaster Univ, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON L8L 2X2, Canada. McMaster Univ, Hamilton Hlth Sci, Dept Med, Hamilton, ON L8L 2X2, Canada. McMaster Univ, Hamilton Hlth Sci, Dept Clin Epidemiol, Hamilton, ON L8L 2X2, Canada. McMaster Univ, Hamilton Hlth Sci, Dept Biostatist, Hamilton, ON L8L 2X2, Canada. McGill Univ, Dept Med, Quebec City, PQ H3A 1A1, Canada. McGill Univ, Dept Human Genet, Quebec City, PQ H3A 1A1, Canada. Azienda Osped Niguarda Ca Granda, Div Cardiol, I-20162 Milan, Italy. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Cardiovasc Endocrinol Sect, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. Univ Kiel, Inst Klin Molekularbiol, D-24105 Kiel, Germany. CIBER Epidemiol & Salud Publ, Barcelona 08003, Spain. Ctr Mathemat Sci, Stat Lab, Cambridge CB3 0WA, England. deCODE Genet Inc, IS-101 Reykjavik, Iceland. Framingham Heart Study &, Natl Heart Lung Blood Inst, Framingham, MA 01702 USA. Hebrew Univ Hadassah Sch Publ Hlth, Epidemiol, IL-91120 Jerusalem, Israel. Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany. Hosp Girona Josep Trueta, Cardiol, Coronar, Girona 17007, Spain. Inst Catala Salut, IDIAP Jordi Gol, Barcelona 08007, Spain. Inst Invest Biomed Girona, Girona 17007, Spain. Inst Municip Invest Med, Cardiovasc Epidemiol & Genet, Barcelona 08003, Spain. Ist Clin Humanitas, Fdn Ist Ricov & Cura Carrattere Sci, Div Cardiol, I-20089 Milan, Italy. Ludwig Maximilians Univ Munchen, Inst Med Inform Sci Biometr & Epidemiol, D-81377 Munich, Germany. Lund Univ, Univ Hosp Malmo, Dept Clin Sci Hypertens & Cardiovasc Dis, S-20502 Malmo, Sweden. Lund Univ, Univ Hosp Malmo, Dept Clin Sci, Int Med, S-20502 Malmo, Sweden. MRC, Biostat Unit, Cambridge, England. Mid America Heart Inst & Univ Missouri, Kansas City, MO 64111 USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki 00300, Finland. Osped Livorno, Div Cardiol, I-57100 Livorno, Italy. Osped San Camillo, Div Cardiol, I-00151 Rome, Italy. Osped San Filippo Neri, Div Cardiol, I-00135 Rome, Italy. Policlin San Matteo, Fdn Ist Ricov & Cura Carrattere Sci, I-27100 Pavia, Italy. Queens Univ Belfast, Ctr Publ Hlth, Inst Clin Sci, Belfast BT12 6BJ, North Ireland. Ist Sci San Raffaele, Milan, Italy. San Raffaele Univ, Vita Salute, I-20132 Milan, Italy. Trium Anal Online GmbH, D-81677 Munich, Germany. Univ Cambridge, Dept Hematol, Cambridge CB2 2PT, England. Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy. Univ Helsinki, Inst Mol Med, Helsinki 00029, Finland. Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds LS1 3EX, England. Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, England. Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, England. Univ Lubeck, Med Klinik 2, D-23538 Lubeck, Germany. Univ Lubeck, Inst Med Biometr & Stat, D-23538 Lubeck, Germany. Univ Munster, Liebniz Inst Arterioscler Res, D-48149 Munster, Germany. Univ Munster, Inst Epidemiol & Social Med, D-48149 Munster, Germany. Univ Paris 06, INSERM UMR S 525, F-75634 Paris, France. Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy. Univ Pennsylvania, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. Univ Pennsylvania, Cardiovasc Inst, Philadelphia, PA 19104 USA. Univ Pennsylvania, Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Regensburg, Klin & Poliklin Innere Med 2, D-93042 Regensburg, Germany. Osped Rovigo, Div Cardiol, I-45100 Rovigo, Italy. Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy. Univ Verona, Dept Clin & Expt Med, I-37134 Verona, Italy. Univ Verona, Osped Borgo Trento, Div Cardiol, I-37126 Verona, Italy. Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Witten Herdecke, Inst Heart & Circulat Res, D-44227 Dortmund, Germany. Vanderbilt Univ Sch Med, Dept Pediat, Nashville, TN 37232 USA. Washington Hosp Ctr, MedStar Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM skathiresan1@partners.org RI Erdmann, Jeanette/A-4417-2009; Erdmann, Jeanette/P-7513-2014; Mannucci, Pier/C-3102-2014; Duga, Stefano/F-8173-2014; Altshuler, David/A-4476-2009; Ziegler, Andreas/G-4246-2012; Ramos , Rafel/D-9627-2016; Martinelli, Nicola/J-5622-2016; Schreiber, Stefan/B-6748-2008; Voight, Benjamin/F-1775-2011; Stark, Klaus/D-3813-2009; Morgan, Tom/C-3478-2012; Lieb, Wolfgang/C-1990-2012; Lucas, Gavin/D-4346-2012; Deloukas, Panos/B-2922-2013; Konig, Inke/A-4544-2009; OI Piazza, Alberto/0000-0002-2355-4183; Asselta, Rosanna/0000-0001-5351-0619; Ramos , Rafel/0000-0001-7970-5537; ELOSUA, ROBERTO/0000-0001-8235-0095; CASARI, Giorgio/0000-0002-0115-8980; Erdmann, Jeanette/0000-0002-4486-6231; Peyvandi, Flora/0000-0001-7423-9864; Altshuler, David/0000-0002-7250-4107; Ziegler, Andreas/0000-0002-8386-5397; Ramos , Rafel/0000-0001-8146-5288; Martinelli, Nicola/0000-0001-6465-5119; Schreiber, Stefan/0000-0003-2254-7771; Stark, Klaus/0000-0002-7832-1942; Deloukas, Panos/0000-0001-9251-070X; Duga, Stefano/0000-0003-3457-1410; Marrugat, Jaume/0000-0003-3320-554X FU Canada Graduate Scholarship Doctoral Award from the Canadian Institutes for Health Research; May Cohen Eli Lilly Endowed Chair in Womens Health Research, McMaster University; Michael G. DeGroote and Heart and Stroke Foundation of Ontario Chair in Population Health; Cardiovascular Institute of the University of Pennsylvania; UK Medical Research Council; European Union [LSHM-CT- 2006-037593]; Canadian Institutes for Health Research; German Federal Ministry of Education and Research; Deutsche Forschungsgemeinschaft; Heart Trust Fund (Royal Victoria Hospital); Northern Ireland Chest, Heart and Stroke Association; Royal Victoria Hospital Research Fellowship; Northern Ireland Research and Development Office; Cariverona Foundation, Verona, Italy; Veneto Region; Italian Ministry of University and Research; MedStar Research Institute; GlaxoSmithKline; British Heart Foundation; Wellcome Trust; Finnish Foundation for Cardiovascular Research; Nordic Center of Excellence in Disease Genetics; Center of Excellence in Complex Disease Genetics of the Academy of Finland; Sigrid Juselius Foundation; National Center for Research Resources [U54 RR020278]; The Broad Institute Center for Genotyping and Analysis; Department of Medicine and Cardiovascular Research Center at Massachusetts General Hospital; Donovan Family Foundation; Fannie E. Rippel Foundation; Doris Duke Charitable Foundation Clinical Scientist Development Award; National Heart, Lung, and Blood Institute; AGAUR Generalitat de Catalunya; FIS de Catalunya; CIBER Epidemiologia y Salud Publica; Ministerio de Sanidad y Consumo Instituto de Salud Carlos III [Red HERACLES RD06/0009]; US National Institutes of Health [K24 DK080140, N01HD013107, P30ES007033, R01HL056931] FX The HARPS study was supported by the grants (R01HL056931, P30ES007033) and a contract (N01HD013107) from US National Institutes of Health.; The REGICOR study was partially funded by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Red HERACLES RD06/0009), the CIBER Epidemiologia y Salud Publica, the FIS and AGAUR Generalitat de Catalunya.; Massachusetts General Hospital. The MIGen study was funded by the US National Institutes of Health (NIH) and National Heart, Lung, and Blood Institutes STAMPEED genomics research program through a grant to D.A. S.K. is supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award, a charitable gift from the Fannie E. Rippel Foundation, the Donovan Family Foundation, a career development award from the NIH and the Department of Medicine and Cardiovascular Research Center at Massachusetts General Hospital. J.B.M. is supported by grant K24 DK080140 from the NIH.; Broad Institute. Genotyping was partially funded by The Broad Institute Center for Genotyping and Analysis, which is supported by grant U54 RR020278 from the National Center for Research Resources.; FINRISK. V.S. was supported by the Sigrid Juselius Foundation. L.P. was supported by the Center of Excellence in Complex Disease Genetics of the Academy of Finland, the Nordic Center of Excellence in Disease Genetics and the Finnish Foundation for Cardiovascular Research.; WTCCC Study. The study was funded by the Wellcome Trust. Recruitment of cases for the WTCCC Study was carried out by the British Heart Foundation (BHF) Family Heart Study Research Group and supported by the BHF and the UK Medical Research Council. N.J.S. and S.G.B. hold chairs funded by the BHF.; PennCATH/MedStar. Recruitment of the PennCATH cohort was supported by the Cardiovascular Institute of the University of Pennsylvania. Recruitment of the MedStar cohort was supported by a research grant from GlaxoSmithKline and from the MedStar Research Institute. Genotyping was done at the Center for Applied Genomics at the Childrens Hospital of Philadelphia and supported by GlaxoSmithKline through an Alternate Drug Discovery Initiative research alliance award (to M.P.R. and D.J.R.) with the University of Pennsylvania School of Medicine. D.J.R. was supported by a Doris Duke Charitable Foundation Distinguished Clinical Scientist Award.; Verona Heart Study. The study was supported by a grant from the Italian Ministry of University and Research and grants from the Veneto Region and the Cariverona Foundation, Verona, Italy; Mid-America Heart Institute. T.M. is supported by a career development grant from the NIH.; Irish Family Study. We thank the clinical staff members for their valuable contribution to the collection of families for this study. The research was supported by the Northern Ireland Research and Development Office, a Royal Victoria Hospital Research Fellowship, the Northern Ireland Chest, Heart and Stroke Association, and the Heart Trust Fund (Royal Victoria Hospital).; GerMIFS I and II. The German Study was supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research in the context of the German National Genome Research Network. Cardiogenics. Cardiogenics is an EU-funded integrated project (LSHM-CT- 2006-037593).; INTERHEART. S.A. holds the Michael G. DeGroote and Heart and Stroke Foundation of Ontario Chair in Population Health and the May Cohen Eli Lilly Endowed Chair in Womens Health Research, McMaster University. We acknowledge the contribution of S. Yusuf who initiated and, together with the Steering Committee, supervised the conduct of the INTERHEART study. We thank members of the Project Office, S. Rangarajan (study coordinator) and K. Hall (laboratory manager), for their assistance in coordinating the genetics component of the INTERHEART project. R.D. is a recipient of a Canada Graduate Scholarship Doctoral Award from the Canadian Institutes for Health Research. NR 30 TC 538 Z9 548 U1 5 U2 62 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 MAR PY 2009 VL 41 IS 3 BP 334 EP 341 DI 10.1038/ng.327 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200023 ER PT J AU Newton-Cheh, C Larson, MG Vasan, RS Levy, D Bloch, KD Surti, A Guiducci, C Kathiresan, S Benjamin, EJ Struck, J Morgenthaler, NG Bergmann, A Blankenberg, S Kee, F Nilsson, P Yin, XY Peltonen, L Vartiainen, E Salomaa, V Hirschhorn, JN Melander, O Wang, TJ AF Newton-Cheh, Christopher Larson, Martin G. Vasan, Ramachandran S. Levy, Daniel Bloch, Kenneth D. Surti, Aarti Guiducci, Candace Kathiresan, Sekar Benjamin, Emelia J. Struck, Joachim Morgenthaler, Nils G. Bergmann, Andreas Blankenberg, Stefan Kee, Frank Nilsson, Peter Yin, Xiaoyan Peltonen, Leena Vartiainen, Erkki Salomaa, Veikko Hirschhorn, Joel N. Melander, Olle Wang, Thomas J. TI Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; HYPERTENSION; PLASMA; RISK; PROJECT; IMPACT; CONTRIBUTE; MUTATIONS; MORTALITY AB We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension. C1 [Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Bloch, Kenneth D.; Kathiresan, Sekar; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Surti, Aarti; Guiducci, Candace; Kathiresan, Sekar; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Newton-Cheh, Christopher; Larson, Martin G.; Vasan, Ramachandran S.; Levy, Daniel; Kathiresan, Sekar; Benjamin, Emelia J.; Yin, Xiaoyan; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Larson, Martin G.] Boston Univ, Sch Med, Dept Math, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Struck, Joachim; Morgenthaler, Nils G.; Bergmann, Andreas] BRAHMS AG, Dept Res, D-16761 Hennigsdorf, Germany. [Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Dept Med 2, D-55131 Mainz, Germany. [Kee, Frank] Royal Victoria Hosp, Ctr Excellence Publ Hlth NI, A UKCRC, Belfast BT12 6BJ, Antrim, North Ireland. [Nilsson, Peter; Melander, Olle] Malmo Univ Hosp, CRC, SE-20502 Malmo, Sweden. [Peltonen, Leena; Vartiainen, Erkki; Salomaa, Veikko] KTL Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FI-00300 Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Peltonen, Leena] Inst Mol Med Finland FIMM, Biomedicum Helsinki, FI-00290 Helsinki, Finland. [Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 55 Fruit St, Boston, MA 02114 USA. EM cnewtoncheh@chgr.mgh.harvard.edu; tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Medical Research Council [G0601463: 80983]; NHLBI NIH HHS [HL66582, K23 HL074077, K23 HL074077-05, K23 HL080025, K23 HL080025-04, K23-HL-074077, K23-HL-080025, K24 HL004334, K24-HL-04334, N01-HC-25195, N01HC25195, R01 HL070896, R01 HL083197, R01 HL086875, R01 HL093328, R01-HL-070896, R01-HL-083197, R01-HL-086875, U01 HL066582]; NIDDK NIH HHS [R01 DK081572, R01-DK-081572]; Wellcome Trust [089061] NR 30 TC 183 Z9 193 U1 1 U2 2 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 MAR PY 2009 VL 41 IS 3 BP 348 EP 353 DI 10.1038/ng.328 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200017 PM 19219041 ER PT J AU McGeachy, MJ Chen, Y Tato, CM Laurence, A Joyce-Shaikh, B Blumenschein, WM McClanahan, TK O'Shea, JJ Cua, DJ AF McGeachy, Mandy J. Chen, Yi Tato, Cristina M. Laurence, Arian Joyce-Shaikh, Barbara Blumenschein, Wendy M. McClanahan, Terrill K. O'Shea, John J. Cua, Daniel J. TI The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo SO NATURE IMMUNOLOGY LA English DT Article ID AUTOIMMUNE INFLAMMATION; MEMORY CELLS; TH17 CELLS; ROR-GAMMA; TGF-BETA; CYTOKINE; IL-23; GENERATION; LINEAGE; DISTINCT AB Interleukin 23 (IL-23) is required for autoimmune inflammation mediated by IL-17-producing helper T cells (T(H)-17 cells) and has been linked to many human immune disorders. Here we restricted deficiency in the IL-23 receptor to defined cell populations in vivo to investigate the requirement for IL-23 signaling in the development and function of T(H)-17 cells in autoimmunity, inflammation and infection. In the absence of IL-23, T(H)-17 development was stalled at the early activation stage. T(H)-17 cells failed to downregulate IL-2 and also failed to maintain IL-17 production or upregulate expression of the IL-7 receptor alpha-chain. These defects were associated with less proliferation; consequently, fewer effector T(H)-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues. C1 [McGeachy, Mandy J.; Chen, Yi; Tato, Cristina M.; Joyce-Shaikh, Barbara; Blumenschein, Wendy M.; McClanahan, Terrill K.; Cua, Daniel J.] Schering Plough Biopharma, Palo Alto, CA 94304 USA. [Laurence, Arian; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Cua, DJ (reprint author), Schering Plough Biopharma, Palo Alto, CA 94304 USA. EM daniel.cua@spcorp.com RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 FU Intramural NIH HHS [Z99 AR999999] NR 48 TC 464 Z9 488 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2009 VL 10 IS 3 BP 314 EP 324 DI 10.1038/ni.1698 PG 11 WC Immunology SC Immunology GA 408SY UT WOS:000263456500016 PM 19182808 ER PT J AU Franchini, G AF Franchini, Genoveffa TI Choosing the right memory T cell for HIV SO NATURE MEDICINE LA English DT Editorial Material ID VACCINE; MACAQUES; INFANT; AIDS; SIV AB An experimental simian immunodeficiency virus vaccine boosts production of memory T cells at the site where the virus first contacts the body-in the mucosa (293-299). The approach has the potential to result in more effective HIV vaccines than those currently under development. C1 US Natl Canc Inst, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), US Natl Canc Inst, Anim Models & Retroviral Vaccines Sect, Bldg 41,Room D-804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov FU Intramural NIH HHS [Z01 BC005645-18] NR 9 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2009 VL 15 IS 3 BP 244 EP 246 DI 10.1038/nm0309-244 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 415DH UT WOS:000263914000018 PM 19265821 ER PT J AU Hansen, SG Vieville, C Whizin, N Coyne-Johnson, L Siess, DC Drummond, DD Legasse, AW Axthelm, MK Oswald, K Trubey, CM Piatak, M Lifson, JD Nelson, JA Jarvis, MA Picker, LJ AF Hansen, Scott G. Vieville, Cassandra Whizin, Nathan Coyne-Johnson, Lia Siess, Don C. Drummond, Derek D. Legasse, Alfred W. Axthelm, Michael K. Oswald, Kelli Trubey, Charles M. Piatak, Michael, Jr. Lifson, Jeffrey D. Nelson, Jay A. Jarvis, Michael A. Picker, Louis J. TI Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge SO NATURE MEDICINE LA English DT Article ID CYTOMEGALOVIRUS-SPECIFIC CD4(+); HIV-1 INFECTION; HUMAN CMV; SIV; REPLICATION; MACAQUES; AIDS; INDUCTION; VACCINES; MODEL AB The rapid onset of massive, systemic viral replication during primary HIV or simian immunodeficiency virus (SIV) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector T cell expansion and differentiation(1-5). We hypothesized that vaccines designed to maintain differentiated effector memory T cell (T(EM) cell) responses(5,6) at viral entry sites might improve efficacy by impairing viral replication at its earliest stage(2), and we have therefore developed SIV protein-encoding vectors based on rhesus cytomegalovirus (RhCMV), the prototypical inducer of life-long TEM cell responses(7-9). RhCMV vectors expressing SIV Gag, Rev-Tat-Nef and Env persistently infected rhesus macaques, regardless of preexisting RhCMV immunity, and primed and maintained robust, SIV-specific CD4(+) and CD8(+) TEM cell responses (characterized by coordinate tumor necrosis factor, interferon-c and macrophage inflammatory protein-1 beta expression, cytotoxic degranulation and accumulation at extralymphoid sites) in the absence of neutralizing antibodies. Compared to control rhesus macaques, these vaccinated rhesus macaques showed increased resistance to acquisition of progressive SIVmac239 infection upon repeated limiting-dose intrarectal challenge, including four macaques who controlled rectal mucosal infection without progressive systemic dissemination. These data suggest a new paradigm for AIDS vaccine development-vaccines capable of generating and maintaining HIV-specific TEM cells might decrease the incidence of HIV acquisition after sexual exposure. C1 [Hansen, Scott G.; Vieville, Cassandra; Whizin, Nathan; Coyne-Johnson, Lia; Siess, Don C.; Drummond, Derek D.; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol, Beaverton, OR 97006 USA. [Hansen, Scott G.; Vieville, Cassandra; Whizin, Nathan; Coyne-Johnson, Lia; Siess, Don C.; Drummond, Derek D.; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Immunol, Beaverton, OR 97006 USA. [Hansen, Scott G.; Vieville, Cassandra; Whizin, Nathan; Coyne-Johnson, Lia; Siess, Don C.; Drummond, Derek D.; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. [Hansen, Scott G.; Vieville, Cassandra; Whizin, Nathan; Coyne-Johnson, Lia; Siess, Don C.; Drummond, Derek D.; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. [Oswald, Kelli; Trubey, Charles M.; Piatak, Michael, Jr.; Lifson, Jeffrey D.] Sci Applicat Int Corp, AIDS & Canc Virus Program, Natl Canc Inst Frederick, Frederick, MD 21702 USA. RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol, 505 NW 185th Ave, Beaverton, OR 97006 USA. EM pickerl@ohsu.edu FU US National Institute of Allergy and Infectious Diseases; International AIDS Vaccine Initiative; Bill & Melinda Gates Foundation; AIDS Vaccine Discovery; US National Center for Research Resources; US National Cancer Institute FX This work was supported by the US National Institute of Allergy and Infectious Diseases, the International AIDS Vaccine Initiative, the Bill & Melinda Gates Foundation-supported Collaboration for AIDS Vaccine Discovery, the US National Center for Research Resources and the US National Cancer Institute. We thank J. Edgar, A. Keech, J. Ford, J. Cook, M. Rohankhedkar, T. Ha, A. Sylwester and J. Dewane for technical assistance; P. Barry (University of California-Davis) for the RhCMV bacterial artificial chromosome, G. Pavlakis (National Cancer Institute) for the SIV Gag and Env constructs, G. Franchini (National Cancer Institute) for the SIV Retanef construct, R. Seder (Vaccine Research Center, National Institutes of Health) for the Gag protein immunogens, C. Miller (University of California-Davis) for the pathogenic SIVmac239 challenge stock, K. Reimann and Centocor for the cM-T807 antibody, M. Mori and J. O'Malley for statistical assistance and K. Frueh and S. Wong for helpful discussion and advice. NR 40 TC 407 Z9 413 U1 4 U2 33 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2009 VL 15 IS 3 BP 293 EP 299 DI 10.1038/nm.1935 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 415DH UT WOS:000263914000029 PM 19219024 ER PT J AU Malinin, NL Zhang, L Choi, J Ciocea, A Razorenova, O Ma, YQ Podrez, EA Tosi, M Lennon, DP Caplan, AI Shurin, SB Plow, EF Byzova, TV AF Malinin, Nikolay L. Zhang, Li Choi, Jeongsuk Ciocea, Alieta Razorenova, Olga Ma, Yan-Qing Podrez, Eugene A. Tosi, Michael Lennon, Donald P. Caplan, Arnold I. Shurin, Susan B. Plow, Edward F. Byzova, Tatiana V. TI A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans SO NATURE MEDICINE LA English DT Article ID CELL-MATRIX ADHESION; LAD-III; PLATELET-AGGREGATION; LOCALIZATION; GLYCOPROTEIN; DEFICIENCY; COMPONENT; MEMBRANE; UNC-112; GENE AB Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteopetrosis at an early age. These symptoms are consistent with but more severe than those reported for people with leukocyte adhesion deficiency III (LAD-III). Mechanistically, these symptoms arose from an inability to activate the integrins expressed on hematopoietic cells, including platelets and leukocytes. Immortalized lymphocyte cell lines isolated from the two individuals showed integrin activation defects. Several proteins previously implicated in integrin activation, including Ras-associated protein-1 (RAP1)(1) and calcium and diacylglycerol-regulated guanine nucleotide exchange factor-1 (CALDAG-GEF1)(2), were present and functional in these cell lines. The genetic basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene(3). When wild-type KINDLIN-3 was expressed in the immortalized lymphocytes, their integrins became responsive to activation signals. These results identify a genetic disease that severely compromises the health of the affected individuals and establish an essential role of KINDLIN-3 in integrin activation in humans. Furthermore, allogeneic bone marrow transplantation was shown to alleviate the symptoms of the disease. C1 [Malinin, Nikolay L.; Choi, Jeongsuk; Ciocea, Alieta; Razorenova, Olga; Ma, Yan-Qing; Podrez, Eugene A.; Plow, Edward F.; Byzova, Tatiana V.] Cleveland Clin, Dept Mol Cardiol, Joseph J Jacobs Ctr Thrombosis & Vasc Biol, Cleveland, OH 44195 USA. [Zhang, Li] Univ Maryland, Ctr Vasc & Inflammatory Dis, Dept Physiol, Sch Med, Baltimore, MD 21201 USA. [Tosi, Michael] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Lennon, Donald P.; Caplan, Arnold I.] Case Western Reserve Univ, Skeletal Res Ctr, Dept Biol, Cleveland, OH 44106 USA. [Shurin, Susan B.] NHLBI, Bethesda, MD 20892 USA. RP Byzova, TV (reprint author), Cleveland Clin, Dept Mol Cardiol, Joseph J Jacobs Ctr Thrombosis & Vasc Biol, NB50,9500 Euclid Ave, Cleveland, OH 44195 USA. EM byzovat@ccf.org RI Malinin, Nikolay/J-4271-2012; Razorenova, Olga/A-6400-2014; OI Malinin, Nikolay/0000-0002-2654-1783 FU US National Institutes of Health [HL073311, HL071625] FX We thank Roswell Park Cancer Institute Proteomics Resources, Lerner Research Institute Proteomics and Imaging Cores (J. Drazba) and Stranad Fellows I. Byzov and R. Swaninger for help with the project, A. Graybiel (Massachusetts Institute of Technology) for providing antibodies to CALDAG-GEF1 and L. Parise (University of North Carolina) for providing the GST-RALGDS fusion cDNA construct. This study was supported by HL073311 and HL071625 US National Institutes of Health grants. NR 27 TC 168 Z9 173 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2009 VL 15 IS 3 BP 313 EP 318 DI 10.1038/nm.1917 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 415DH UT WOS:000263914000032 PM 19234460 ER PT J AU Yin, HH Mulcare, SP Hilario, MRF Clouse, E Holloway, T Davis, MI Hansson, AC Lovinger, DM Costa, RM AF Yin, Henry H. Mulcare, Shweta Prasad Hilario, Monica R. F. Clouse, Emily Holloway, Terrell Davis, Margaret I. Hansson, Anita C. Lovinger, David M. Costa, Rui M. TI Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill SO NATURE NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; TERM SYNAPTIC DEPRESSION; PRIMARY MOTOR CORTEX; PARKINSONS-DISEASE; DORSAL STRIATUM; STRIATOPALLIDAL NEURONS; RAT NEOSTRIATUM; HABIT FORMATION; PLASTICITY; RECEPTORS AB The learning of new skills is characterized by an initial phase of rapid improvement in performance and a phase of more gradual improvements as skills are automatized and performance asymptotes. Using in vivo striatal recordings, we observed region-specific changes in neural activity during the different phases of skill learning, with the associative or dorsomedial striatum being preferentially engaged early in training and the sensorimotor or dorsolateral striatum being engaged later in training. Ex vivo recordings from medium spiny striatal neurons in brain slices of trained mice revealed that the changes observed in vivo corresponded to regional- and training-specific changes in excitatory synaptic transmission in the striatum. Furthermore, the potentiation of glutamatergic transmission observed in dorsolateral striatum after extensive training was preferentially expressed in striatopallidal neurons, rather than striatonigral neurons. These findings demonstrate that region- and pathway-specific plasticity sculpts the circuits involved in the performance of the skill as it becomes automatized. C1 [Yin, Henry H.; Mulcare, Shweta Prasad; Hilario, Monica R. F.; Clouse, Emily; Holloway, Terrell; Davis, Margaret I.; Lovinger, David M.; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, US Natl Inst Hlth, Rockville, MD 20852 USA. [Yin, Henry H.] Duke Univ, Ctr Cognit Neurosci, Dept Psychol & Neurosci, Durham, NC 27708 USA. [Hansson, Anita C.] NIAAA, Lab Clin & Translat Studies, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Costa, RM (reprint author), NIAAA, Lab Integrat Neurosci, US Natl Inst Hlth, 5625 Fishers Lane,MSC 9411, Rockville, MD 20852 USA. EM costarui@mail.nih.gov RI Davis, Margaret/F-4165-2010; OI Davis, Margaret/0000-0002-0489-8351; Costa, Rui/0000-0003-0495-8374 FU Intramural NIH HHS [Z01 AA000407-06] NR 50 TC 256 Z9 258 U1 1 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAR PY 2009 VL 12 IS 3 BP 333 EP 341 DI 10.1038/nn.2261 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 410LF UT WOS:000263577900019 PM 19198605 ER PT J AU Isenberg, JS Martin-Manso, G Maxhimer, JB Roberts, DD AF Isenberg, Jeff S. Martin-Manso, Gema Maxhimer, Justin B. Roberts, David D. TI Regulation of nitric oxide signalling by thrombospondin 1: implications for anti-angiogenic therapies SO NATURE REVIEWS CANCER LA English DT Review ID ENDOTHELIAL-GROWTH-FACTOR; C-TERMINAL DOMAIN; COLORECTAL LIVER METASTASES; INTEGRIN-ASSOCIATED PROTEIN; ISCHEMIC TISSUE SURVIVAL; SQUAMOUS-CELL CARCINOMA; TUMOR BLOOD-FLOW; IN-VITRO; HEPATOCELLULAR-CARCINOMA; PLASMA THROMBOSPONDIN AB In addition to long-term regulation of angiogenesis, angiogenic growth factor signalling through nitric oxide (NO) acutely controls blood flow and haemostasis. Inhibition of this pathway may account for the hypertensive and pro-thrombotic side effects of the vascular endothelial growth factor antagonists that are currently used for cancer treatment. The first identified endogenous angiogenesis inhibitor, thrombospondin 1, also controls tissue perfusion, haemostasis and radiosensitivity by antagonizing NO signalling. We examine the role of these and other emerging activities of thrombospondin 1 in cancer. Clarifying how endogenous and therapeutic angiogenesis inhibitors regulate vascular NO signalling could facilitate development of more selective inhibitors. C1 [Isenberg, Jeff S.; Martin-Manso, Gema; Maxhimer, Justin B.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Martin Manso, Maria Gema/D-4612-2013 OI Roberts, David/0000-0002-2481-2981; FU Intramural Research Program of the National Institutes of Health; National Cancer Institute, Center for Cancer Research; BEFI from Instituto de Salud Carlos III (Spanish Ministry of Heath) FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (D. D. R.). Gema Martin-Manso is recipient of a grant BEFI from Instituto de Salud Carlos III (Spanish Ministry of Heath). NR 185 TC 126 Z9 128 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAR PY 2009 VL 9 IS 3 BP 182 EP 194 DI 10.1038/nrc2561 PG 13 WC Oncology SC Oncology GA 410LM UT WOS:000263578700011 PM 19194382 ER PT J AU Koonin, EV Wolf, YI Nagasaki, K Dolja, VV AF Koonin, Eugene V. Wolf, Yuri I. Nagasaki, Keizo Dolja, Valerian V. TI The complexity of the virus world SO NATURE REVIEWS MICROBIOLOGY LA English DT Letter ID EVOLUTION; RNA C1 [Koonin, Eugene V.; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Nagasaki, Keizo] Natl Res Inst Fisheries & Environm Inland Sea, Hiroshima 7390452, Japan. [Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Dolja, Valerian V.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov; doljav@science.oregonstate.edu NR 11 TC 14 Z9 14 U1 0 U2 3 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 MAR PY 2009 VL 7 IS 3 DI 10.1038/nrmicro2030-c2 PG 2 WC Microbiology SC Microbiology GA 407KC UT WOS:000263361000021 ER PT J AU Neckers, L Tsutsumi, S Mollapour, M AF Neckers, Len Tsutsumi, Shinji Mollapour, Mehdi TI Visualizing the twists and turns of a molecular chaperone SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID ESCHERICHIA-COLI HSP90; CONFORMATIONAL DYNAMICS; TUMOR SELECTIVITY; CLIENT PROTEIN; ATPASE CYCLE; INHIBITORS; MACHINERY; COMPLEX; STATES AB Intermediate conformations of the Hsp90 ATPase cycle have been identified in solution by fluorescence resonance energy transfer, and the impact of nucleotides and of modulatory cochaperones has been visualized in real time. (c) 2009 Nature America, Inc. All rights reserved. C1 [Neckers, Len; Tsutsumi, Shinji; Mollapour, Mehdi] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM len@helix.nih.gov NR 19 TC 12 Z9 12 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAR PY 2009 VL 16 IS 3 BP 235 EP 236 DI 10.1038/nsmb0309-235 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 415AF UT WOS:000263906000004 PM 19259122 ER PT J AU Young, MR Ileva, LV Bernardo, M Riffle, LA Jones, YL Kim, YS Colburn, NH Choyke, PL AF Young, Matthew R. Ileva, Lilia V. Bernardo, Marcelino Riffle, Lisa A. Jones, Yava L. Kim, Young S. Colburn, Nancy H. Choyke, Peter L. TI Monitoring of Tumor Promotion and Progression in a Mouse Model of Inflammation-Induced Colon Cancer with Magnetic Resonance Colonography SO NEOPLASIA LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; PARTIAL LIQUID VENTILATION; LUMEN MR-COLONOGRAPHY; CONVENTIONAL COLONOSCOPY; COLORECTAL-CANCER; CARCINOGENESIS; ACCURACY; MICE AB Early detection of precancerous tissue has significantly improved survival of most cancers including colorectal cancer (CRC). Animal models designed to study the early stages of cancer are valuable for identifying molecular events and response indicators that correlate with the onset of disease. The goal of this work was to investigate magnetic resonance (MR) colonography in a mouse model of CRC on a clinical MR imager. Mice treated with azoxy-methane and dextran sulfate sodium were imaged by serial MR colonography (MRC) from initiation to euthanasia. Magnetic resonance colonography was obtained with both T1- and T2-weighted images after administration of a Fluorinert enema to remove residual luminal signal and intravenous contrast to enhance the colon wall. Individual tumor volumes were calculated and validated ex vivo. The Fluorinert enema provided a clear differentiation of the lumen of the colon from the mucosal lining. Inflammation was detected 3 days after dextran sulfate sodium exposure and subsided during the next week. Tumors as small as 1.2 mm(3) were detected and as early as 29 days after initiation. Individual tumor growths were followed over time, and tumor volumes were measured by MR imaging correlated with volumes measured ex vivo. The use of a Fluorinert enema during MRC in mice is critical for differentiating mural processes from intraluminal debris. Magnetic resonance colonography with Fluorinert enema and intravenous contrast enhancement will be useful in the study of the initial stages of colon cancer and will reduce the number of animals needed for preclinical trials of prevention or intervention. C1 [Young, Matthew R.] NCI, Frederick, MD 21702 USA. RP Young, MR (reprint author), NCI, B576, Frederick, MD 21702 USA. EM youngm@ncifcrf.gov NR 21 TC 25 Z9 25 U1 1 U2 5 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAR PY 2009 VL 11 IS 3 BP 237 EP U30 DI 10.1593/neo.81326 PG 11 WC Oncology SC Oncology GA 424FR UT WOS:000264551400003 PM 19242605 ER PT J AU Momeni, P Pittman, A Lashley, T Vandrovcova, J Malzer, E Luk, C Hulette, C Lees, A Revesz, T Hardy, J de Silva, R AF Momeni, Parastoo Pittman, Alan Lashley, Tammaryn Vandrovcova, Jana Malzer, Elke Luk, Connie Hulette, Christine Lees, Andrew Revesz, Tamas Hardy, John de Silva, Rohan TI Clinical and pathological features of an Alzheimer's disease patient with the MAPT Delta K280 mutation SO NEUROBIOLOGY OF AGING LA English DT Article DE Tau; Alzheimer; Tauopathy; Exon 10 ID PAIRED HELICAL FILAMENTS; FRONTOTEMPORAL DEMENTIA; TAU GENE; BETA-STRUCTURE; AGGREGATION; MISSENSE; ASSOCIATION; ANTIBODIES; DIAGNOSIS; PROTEINS AB We identified a case of Alzheimer's disease with a deletion of the lysine residue at codon 280 (Delta K280) in exon 10-encoded microtubule-binding repeat domain of the tau gene (MAPT). This mutation was originally identified in a sporadic case of frontotemporal dementia (FTD) with a family history of Parkinson's disease. In the original report, the authors were careful in their assessment of the pathogenicity and suggested one could not be sure whether the mutation was pathogenic or not. The mutation has always presented a conundrum because it is the only known mutation, of assumed pathogenicity, which increases the proportion of 3-repeat tau mRNA in in vitro assays. Here we present the clinical and pathological features of a new case with this mutation and discuss whether the mutation is indeed pathogenic. (C) 2007 Elsevier Inc. All rights reserved. C1 [Momeni, Parastoo; Hardy, John] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79430 USA. [Hulette, Christine] Duke Univ, Med Ctr, Dept Neurol, Durham, NC 27710 USA. [Hulette, Christine] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Hulette, Christine] Duke Univ, Med Ctr, Dept Neuropathol & Med, Durham, NC 27710 USA. [Pittman, Alan; Vandrovcova, Jana; Malzer, Elke; Luk, Connie; Lees, Andrew; Hardy, John; de Silva, Rohan] UCL Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1N 3BG, England. [Pittman, Alan; Lashley, Tammaryn; Vandrovcova, Jana; Malzer, Elke; Luk, Connie; Revesz, Tamas; Hardy, John; de Silva, Rohan] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 1PJ, England. RP de Silva, R (reprint author), Reta Lila Weston Inst Neurol Studies, 1 Wakefield St, London WC1N 1PJ, England. EM rsilva@ion.ucl.ac.uk RI Lashley, Tammaryn/D-2583-2009; Luk, Connie/A-7252-2011; Hardy, John/C-2451-2009; Pittman, Alan/D-6231-2012; Lees, Andrew/A-6605-2009; Revesz, Tamas/A-8732-2010 OI Revesz, Tamas/0000-0003-2501-0259 FU NIH; NIA; PHS [P50 AG05128]; Reta Lila Weston Trust for Medical Research; MRC [G0501560] FX This work was supported in part by the NIH, NIA intramural program, PHS P50 AG05128 and by the Reta Lila Weston Trust for Medical Research. RdS is funded by a grant front the MRC (G0501560). NR 22 TC 26 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2009 VL 30 IS 3 BP 388 EP 393 DI 10.1016/j.neurobiolaging.2007.07.013 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 404LV UT WOS:000263154700005 PM 17723255 ER PT J AU Chang, YYC Rapoport, SI Rao, JS AF Chang, Yunyoung C. Rapoport, Stanley I. Rao, Jagadeesh S. TI Chronic Administration of Mood Stabilizers Upregulates BDNF and Bcl-2 Expression Levels in Rat Frontal Cortex SO NEUROCHEMICAL RESEARCH LA English DT Article DE BDNF; Bcl-2; Lithium; Valproate; Carbamazepine; Lamotrigine; Brain; Bipolar; Disorder; Rat ID CYTOSOLIC PHOSPHOLIPASE A(2); FATTY-ACID DEPRIVATION; DNA-BINDING ACTIVITY; BIPOLAR DISORDER; ARACHIDONIC-ACID; PROTEIN EXPRESSION; TEMPORAL CORTEX; BRAIN; LITHIUM; SCHIZOPHRENIA AB Brain-derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2) proteins are neuroprotective factors involved in neuronal signaling, survival and plasticity. Both can be regulated by cyclic AMP response element binding (CREB) protein. Decreased levels of BDNF and Bcl-2 are implicated in the pathogenesis of bipolar disorder. The present study investigated whether chronically administered mood stabilizers would increase BDNF and/or Bcl-2 levels in rat brain. Real time RT-PCR, sandwich ELISA and Western blotting were used to measure BDNF and Bcl-2 mRNA and protein levels in the frontal cortex of rats chronically administered carbamazepine (CBZ) or lamotrigine (LTG) to produce plasma concentrations therapeutically relevant to bipolar disorder. Chronic CBZ and LTG significantly increased BDNF and Bcl-2 mRNA and protein levels in the frontal cortex. A common mechanism of action of mood stabilizers in the treatment of bipolar disorder may involve neuroprotection mediated by upregulation of brain BDNF and Bcl-2 expression. C1 [Chang, Yunyoung C.; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,IS-126, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov RI Rao, Jagadeesh/C-1250-2009 FU National Institute on Aging, National Institutes of Health FX This work was entirely supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. We thank the National Cancer Institute (NCI), Center for Cancer Research (CCR) Fellows Editorial Board, for proofreading the manuscript. NR 46 TC 53 Z9 57 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAR PY 2009 VL 34 IS 3 BP 536 EP 541 DI 10.1007/s11064-008-9817-3 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 404JQ UT WOS:000263148200018 PM 18719996 ER PT J AU Honea, R Verchinski, BA Pezawas, L Kolachana, BS Callicott, JH Mattay, VS Weinberger, DR Meyer-Lindenberg, A AF Honea, Robyn Verchinski, Beth A. Pezawas, Lukas Kolachana, Bhaskar S. Callicott, Joseph H. Mattay, Venkata S. Weinberger, Daniel R. Meyer-Lindenberg, Andreas TI Impact of interacting functional variants in COMT on regional gray matter volume in human brain SO NEUROIMAGE LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; VOXEL-BASED MORPHOMETRY; DORSOLATERAL PREFRONTAL CORTEX; VAL(108/158) MET GENOTYPE; 22Q11.2 DELETION SYNDROME; MESSENGER-RNA EXPRESSION; CARDIO-FACIAL SYNDROME; CHRONIC-SCHIZOPHRENIA; VAL(158)MET GENOTYPE; MOLECULAR-GENETICS AB Background: Functional variants in the catechol-O-methyltransferase (COMT) gene have been shown to impact cognitive function, cortical physiology and risk for schizophrenia. A recent study showed that previously reported effects of the functional val158met SNP (rs4680) on brain function are modified by other functional SNPs and haplotypes in the gene, though it was unknown if these effects are also seen in brain structure. Methods: We used voxel-based morphometry to investigate the impact of multiple functional variants in COMT on gray matter volume in a large group of 151 healthy volunteers from the CBDB/NIMH Genetic Study of Schizophrenia. Results: We found that the previously described rs4680 val risk variant affects hippocampal and dorsolateral prefrontal (DLPFC) gray matter volume. In addition, we found that this SNP interacts with a variant in the P2 promoter region (rs2097603) in predicting changes in hippocampal gray matter volume consistent with a nonlinear effect of extracellular dopamine. Conclusions: We report evidence that interacting functional variants in COMT affect gray matter regional volume in hippocampus and DLPFC, providing further in vivo validation of the biological impact of complex genetic variation in COMT on neural systems relevant for the pathophysiology of schizophrenia and extending observations of nonlinear dependence of prefrontal neurons on extracellular dopamine to the domain of human brain structure. (C) 2008 Elsevier Inc. All rights reserved. C1 [Honea, Robyn; Verchinski, Beth A.; Pezawas, Lukas; Kolachana, Bhaskar S.; Callicott, Joseph H.; Mattay, Venkata S.; Weinberger, Daniel R.; Meyer-Lindenberg, Andreas] NIMH, Genes Cognit & Psychosis Program, Div Intramural Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-68159 Mannheim, Germany. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Div Intramural Res, NIH,Dept Hlth & Human Serv, Rm 4S-235, Bethesda, MD 20892 USA. EM weinberger@mail.nih.gov RI Callicott, Joseph/C-9102-2009; Meyer-Lindenberg, Andreas/H-1076-2011; OI Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Pezawas, Lukas/0000-0002-1329-6352 FU NIMH/IRP; NIAAA; ORD FX This study was supported by the NIMH/IRP and by a bench-to-bedside award by NIMH, NIAAA and ORD to A. M. L. We thank Katherine Hobbs and Aaron Goldman for their assistance in data preprocessing and Joshua Buckholtz for his advice in the process of manuscript preparation. NR 77 TC 77 Z9 82 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2009 VL 45 IS 1 BP 44 EP 51 DI 10.1016/j.neuroimage.2008.10.064 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KR UT WOS:000263862900006 PM 19071221 ER PT J AU McLaren, DG Kosmatka, KJ Oakes, TR Kroenke, CD Kohama, SG Matochik, JA Ingram, DK Johnson, SC AF McLaren, Donald G. Kosmatka, Kristopher J. Oakes, Terrance R. Kroenke, Christopher D. Kohama, Steven G. Matochik, John A. Ingram, Don K. Johnson, Sterling C. TI A population-average MRI-based atlas collection of the rhesus macaque SO NEUROIMAGE LA English DT Article DE Rhesus macaque; MRI; Atlas; Macaca mulatta; Priors; Brain mapping; Probabilistic ID AUTOMATED IMAGE REGISTRATION; HUMAN PARIETAL OPERCULUM; PRIMATE CEREBRAL-CORTEX; SURFACE-BASED ATLASES; NONHUMAN PRIMATE; TEMPLATE IMAGES; HUMAN BRAIN; PROBABILISTIC ATLAS; MONKEY BRAIN; BABOON AB Magnetic resonance imaging (MRI) studies of non-human primates are becoming increasingly common; however, the well-developed voxel-based methodologies used in human studies are not readily applied to non-human primates. In the present study, we create a population-average MRI-based atlas collection for the rhesus macaque (Macaca mulatta) that can be used with common brain mapping packages such as SPM or FSL. In addition to creating a publicly available T1-weighted atlas (http://www.brainmap.wisc.edu/monkey. html), probabilistic tissue classification maps and T2-weighted atlases were also created. Theses atlases are aligned to the MRI volume from the Saleem, K. S. and Logothetis, N. K. (2006) atlas providing an explicit link to histological sections. Additionally, we have created a transform to integrate these atlases with the F99 surface-based atlas in CARET. It is anticipated that these tools will help facilitate voxel-based imaging methodologies in non-human primate species, which in turn may increase our understanding of brain function, development, and evolution. Published by Elsevier Inc. C1 [McLaren, Donald G.; Kosmatka, Kristopher J.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [McLaren, Donald G.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [McLaren, Donald G.; Kosmatka, Kristopher J.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Kroenke, Christopher D.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Kroenke, Christopher D.; Kohama, Steven G.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. [Matochik, John A.] Natl Inst Drug Abuse, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD 21224 USA. [Ingram, Don K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. [Oakes, Terrance R.] Univ Wisconsin, Waisman Ctr Brain Imaging Lab, Madison, WI 53705 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu RI McLaren, Donald/G-9906-2011; OI Johnson, Sterling/0000-0002-8501-545X FU National Institutes of Health [RR000167, AG11915, AG20013, GM007507, RR00163, AG029612]; National Institute on Aging FX This study was supported in part by the National Institutes of Health RR000167 (UW), AG11915 (UW), AG20013 (UW), GM007507 (UW), RR00163 (ONPRC), AG029612 (OHSU) and the Intramural Research Program of the National Institute on Aging. This study was also supported with resources and use of facilities at the William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. John Matochik is now at the National Institute on Alcohol Abuse and Alcoholism. The assistance of Erik K. Kastman, Brent W. Thiel, Michele E. Fitzgerald, Ron Fisher, Scott T. Baum, Josh Smith, Ricki J. Colman, Ph. D., Andy. A. Alexander, Ph. D., Barbara B. Bendlin, Ph. D. and the Waisman Center for Brain Imaging was greatly appreciated. We would especially like to thank Drs. Kadharbatcha S. Saleem and Nikos K. Logothetis for providing a digital copy of the D99-SL atlas. GRECC Manuscript Number: 2008-31. NR 66 TC 103 Z9 104 U1 3 U2 14 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 MAR PY 2009 VL 45 IS 1 BP 52 EP 59 DI 10.1016/j.neuroimage.2008.10.058 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KR UT WOS:000263862900007 PM 19059346 ER PT J AU Bianciardi, M Fukunaga, M van Gelderen, P Horovitz, SG de Zwart, JA Duyn, JH AF Bianciardi, Marta Fukunaga, Masaki van Gelderen, Peter Horovitz, Silvina G. de Zwart, Jacco A. Duyn, Jeff H. TI Modulation of spontaneous fMRI activity in human visual cortex by behavioral state SO NEUROIMAGE LA English DT Article DE 7 T BOLD fMRI; Evoked activity; Eyes open/closed; Spontaneous activity; Visual cortex ID FUNCTIONAL CONNECTIVITY; ALPHA-RHYTHM; BOLD SIGNAL; DEFAULT-MODE; HUMAN BRAIN; SPONTANEOUS FLUCTUATIONS; SIMULTANEOUS EEG; RESTING BRAIN; VARIABILITY; NETWORKS AB The phenomenon of spontaneous fMRI activity is increasingly being exploited to investigate the connectivity of functional networks in human brain with high spatial-resolution. Although mounting evidence points towards a neuronal contribution to this activity, its functional role and dependence on behavioral state remain unclear. In this work, we used BOLD fMRI at 7 T to study the modulation of spontaneous activity in occipital areas by various behavioral conditions, including resting with eyes closed, eyes open with visual fixation, and eyes open with fixation and focal visual stimulation. Spontaneous activity was separated from evoked activity and from signal fluctuations related to cardiac and respiratory cycles. We found that spontaneous activity in visual areas was substantially reduced (amplitude (44%) and coherence (25%)) with the fixation conditions relative to the eyes-closed condition. No significant further modulation was observed when the visual stimulus was added. The observed dependence on behavioral condition suggests that part of spontaneous fMRI signal fluctuations represents neuronal activity. Possible mechanisms for the modulation of spontaneous activity by behavioral state are discussed. The observed linear superposition of spontaneous fMRI activity with focal evoked activity related to visual processing has important implications for fMRI studies, which ideally should take into account the effect of spontaneous activity to properly define brain activations during task conditions. Published by Elsevier Inc. C1 [Bianciardi, Marta; Fukunaga, Masaki; van Gelderen, Peter; Horovitz, Silvina G.; de Zwart, Jacco A.; Duyn, Jeff H.] NINDS, Lab Funct & Mol Imaging, Adv MRI Sect, NIH, Bethesda, MD 20892 USA. RP Bianciardi, M (reprint author), NINDS, Lab Funct & Mol Imaging, Adv MRI Sect, NIH, Bldg 10,Rm B1D-723A-MSC 1065, Bethesda, MD 20892 USA. EM bianciardim@mail.nih.gov RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 FU National Institutes of Health; National Institutes of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institutes of Neurological Disorders and Stroke. NR 50 TC 84 Z9 85 U1 1 U2 10 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 MAR PY 2009 VL 45 IS 1 BP 160 EP 168 DI 10.1016/j.neuroimage.2008.10.034 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KR UT WOS:000263862900019 PM 19028588 ER PT J AU Mueller, SC Swainson, R Jackson, GM AF Mueller, S. C. Swainson, R. Jackson, G. M. TI ERP indices of persisting and current inhibitory control: A study of saccadic task switching SO NEUROIMAGE LA English DT Article DE Antisaccade; ERP; Cognitive control; Task switching; N2 ID DYNAMIC COGNITIVE CONTROL; SUPPLEMENTARY EYE FIELD; MEDIAL FRONTAL-CORTEX; INTENTIONAL SET; SELECTION; INFORMATION; COMPONENTS; MOVEMENTS; CONFLICT; TRIAL AB Previous studies have found that inhibition of a biologically dominant prepotent response tendency is required during the execution of a less familiar, non-prepotent response. However, the lasting impact of this inhibition and the cognitive mechanisms to flexibly switch between prepotent and non-prepotent responses are poorly understood. We examined the neurophysiological (ERP) correlates of switching between prosaccade and antisaccade responses in 22 healthy volunteers. The behavioural data showed significant switch costs in terms of response latency for the prosaccade task only. These costs occurred exclusively in trials when preparation for the switch was limited to 300 ms, suggesting that inhibition of the prepotent prosaccade task either passively dissipated or was actively overcome during the longer 1000 ms preparation interval. In the neurophysiological data, a late frontal negativity (LFN) was visible during preparation for a switch to the prosaccade task that was absent when switching to the antisaccade task, which may reflect the overcoming of persisting inhibition. During task implementation both saccade types were associated with a late parietal positivity (LPP) for switch relative to repetition trials, possibly indicating attentional reorienting to the switched-to task, and visible only with short preparation intervals. When the prosaccade and antisaccade task were contrasted directly during task implementation, the antisaccade task exhibited increased stimulus-locked N2 and decreased P3 amplitudes indicative of active inhibition. The present findings indicate that neurophysiological markers of persisting and current inhibition can be revealed using a prosaccade/antisaccade-switching task. Published by Elsevier Inc. C1 [Mueller, S. C.] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England. [Swainson, R.] Univ Aberdeen, Sch Psychol, Aberdeen AB9 1FX, Scotland. [Jackson, G. M.] Univ Nottingham, Div Psychiat, Nottingham NG7 2RD, England. RP Mueller, SC (reprint author), NIMH, SDAN, MAP, NIH, 15K N Dr, Bethesda, MD 20892 USA. EM msven@mail.nih.gov NR 37 TC 21 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2009 VL 45 IS 1 BP 191 EP 197 DI 10.1016/j.neuroimage.2008.11.019 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KR UT WOS:000263862900022 PM 19100841 ER PT J AU Knight, DC Waters, NS Bandettini, PA AF Knight, David C. Waters, Najah S. Bandettini, Peter A. TI Neural substrates of explicit and implicit fear memory SO NEUROIMAGE LA English DT Article ID UNILATERAL TEMPORAL LOBECTOMY; SKIN-CONDUCTANCE RESPONSES; HUMAN AMYGDALA; CONTINGENCY AWARENESS; CONDITIONAL FEAR; FUNCTIONAL MRI; BRAIN SYSTEMS; STIMULI; TRACE; ACQUISITION AB Distinct aspects of our fearful experiences appear to be mediated by separate explicit and implicit memory processes. To identify brain regions that support these separate memory processes, we measured contingency awareness, conditional fear expression, and functional magnetic resonance imaging signal during a Pavlovian fear conditioning procedure in which tones that predicted an aversive event were presented at supra and sub-threshold volumes. Contingency awareness developed in conjunction with learning-related hippocampal and parahippocampal activity on perceived conditioning trials only. In contrast, conditional fear and differential amygdala activity developed on both perceived and unperceived trials, regardless of whether contingency awareness was expressed. These findings demonstrate the distinct roles of these brain regions in explicit and implicit fear memory processes. Published by Elsevier Inc. C1 [Knight, David C.; Waters, Najah S.; Bandettini, Peter A.] Natl Inst Mental Hlth, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Knight, DC (reprint author), CIRC 235H,1530 3RD AVE S, Birmingham, AL 35294 USA. EM knightdc@uab.edu FU NIH; National Institute of Mental Health FX This research was supported by the Intramural Research Program of the NIH, National Institute of Mental Health. NR 56 TC 55 Z9 56 U1 1 U2 9 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 MAR PY 2009 VL 45 IS 1 BP 208 EP 214 DI 10.1016/j.neuroimage.2008.11.015 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KR UT WOS:000263862900024 PM 19100329 ER PT J AU Luo, XZJ Kennedy, DN Cohen, Z AF Luo, Xiao-zhong James Kennedy, David N. Cohen, Zohara TI Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) Resource Announcement SO NEUROINFORMATICS LA English DT Editorial Material C1 [Luo, Xiao-zhong James; Cohen, Zohara] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Kennedy, David N.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Kennedy, David N.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Luo, XZJ (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. EM luoja@mail.nih.gov; zcohen@mail.nih.gov RI Kennedy, David/H-3627-2012 NR 3 TC 18 Z9 20 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD MAR PY 2009 VL 7 IS 1 BP 55 EP 56 DI 10.1007/s12021-008-9036-8 PG 2 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 407SK UT WOS:000263384400005 PM 19184562 ER PT J AU Jiang, XY Zhou, J Mash, DC Marini, AM Lipsky, RH AF Jiang, Xueying Zhou, Jian Mash, Deborah C. Marini, Ann M. Lipsky, Robert H. TI Human BDNF Isoforms are Differentially Expressed in Cocaine Addicts and are Sorted to the Regulated Secretory Pathway Independent of the Met66 Substitution SO NEUROMOLECULAR MEDICINE LA English DT Article DE Brain-derived neurotrophic factor; Signal peptide; Isoform; Polymorphism; Trafficking; Regulated secretion; mRNA; Cocaine ID ACTIVITY-DEPENDENT SECRETION; NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR; CORTICAL-NEURONS; MESSENGER-RNA; ENDOPLASMIC-RETICULUM; HIPPOCAMPAL-NEURONS; CARBOXYPEPTIDASE-E; MEMBRANE-PROTEINS; BRAIN AB Differential BDNF gene (BDNF) promoter use leads to protein isoforms differing by 8 or 15 N-terminal residues (BDNF1 and BDNF2) whose regulation and function are not completely understood versus the well-known 247-aa BDNF "short" form. To describe how BDNF isoform levels were regulated by chronic drug use, we measured BDNF isoform-specific mRNA levels in different human brain regions from cocaine addicts relative to age, race, and gender-matched controls. The cocaine group had threefold higher levels of exon 4-specific (BDNF Short) mRNAs in cerebellum versus controls (P < 0.01). In cortex, exon 4 and exon 1-specific BDNF mRNA levels (BDNF1) were significantly reduced in the cocaine group relative to controls (40%, P < 0.01). We also tested the hypothesis that the signal peptides of isoforms BDNF1 and BDNF2 confer different functional properties and determined if the functional Val66Met polymorphism influenced these functions. In contrast to transfected AtT-20 cells producing BDNF Short, regulated secretion of BDNF1 or BDNF2 was not affected by the Met66 substitution. Hippocampal neurons producing BDNF1 or BDNF2 on either the Val66 or Met66 background were similarly distributed in dendrites and had similar colocalization patterns with the secretory granule marker Sec II. This pattern differed from neurons producing BDNF Short Met66, which had impaired trafficking. Together, these findings support a mechanism by which variant BDNF proteins can overcome the functional defect of the Met66 substitution and suggest how functional differences in BDNF may impact brain responses in disease. C1 [Jiang, Xueying; Zhou, Jian; Lipsky, Robert H.] NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Mash, Deborah C.] Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. [Marini, Ann M.] Uniformed Serv Univ Hlth Sci, Dept Neurol & Neurosci, Bethesda, MD 20814 USA. RP Lipsky, RH (reprint author), NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM rlipsky@mail.nih.gov OI Lipsky, Robert/0000-0001-7753-1473 FU NIH [NIAAA Z01-AA00325]; Defense Brain and Spinal Cord Injury Program [F-192EG-C1] FX This study was supported by NIH intramural grant NIAAA Z01-AA00325 (RHL) and extramural grant F-192EG-C1 from the Defense Brain and Spinal Cord Injury Program (AMM). NR 42 TC 9 Z9 10 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PD MAR PY 2009 VL 11 IS 1 BP 1 EP 12 DI 10.1007/s12017-008-8051-0 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 425HN UT WOS:000264627700001 PM 18946637 ER PT J AU Liu, D Gharavi, R Pitta, M Gleichmann, M Mattson, MP AF Liu, Dong Gharavi, Robert Pitta, Michael Gleichmann, Marc Mattson, Mark P. TI Nicotinamide Prevents NAD(+) Depletion and Protects Neurons Against Excitotoxicity and Cerebral Ischemia: NAD(+) Consumption by SIRT1 may Endanger Energetically Compromised Neurons SO NEUROMOLECULAR MEDICINE LA English DT Article DE Excitotoxicity; Glutamate; NMDA; NAD(+); NADH; SIRT1; PARP-1; PAR; Nicotinamide; MCAO; TUNEL ID LIFE-SPAN EXTENSION; OXIDATIVE STRESS; POLY(ADP-RIBOSE) POLYMERASE; BRAIN-INJURY; MITOCHONDRIAL-FUNCTION; ADENINE-DINUCLEOTIDE; CELL-DEATH; NEURODEGENERATIVE DISORDERS; CALORIE RESTRICTION; HISTONE DEACETYLASE AB Neurons require large amounts of energy to support their survival and function, and are therefore susceptible to excitotoxicity, a form of cell death involving bioenergetic stress that may occur in several neurological disorders including stroke and Alzheimer's disease. Here we studied the roles of NAD(+) bioenergetic state, and the NAD(+)-dependent enzymes SIRT1 and PARP-1, in excitotoxic neuronal death in cultured neurons and in a mouse model of focal ischemic stroke. Excitotoxic activation of NMDA receptors induced a rapid decrease of cellular NAD(P)H levels and mitochondrial membrane potential. Decreased NAD(+) levels and poly (ADP-ribose) polymer (PAR) accumulation in nuclei were relatively early events (< 4 h) that preceded the appearance of propidium iodide- and TUNEL-positive cells (markers of necrotic cell death and DNA strand breakage, respectively) which became evident by 6 h. Nicotinamide, an NAD(+) precursor and an inhibitor of SIRT1 and PARP1, inhibited SIRT1 deacetylase activity without affecting SIRT1 protein levels. NAD(+) levels were preserved and PAR accumulation and neuronal death induced by excitotoxic insults were attenuated in nicotinamide-treated cells. Treatment of neurons with the SIRT1 activator resveratrol did not protect them from glutamate/NMDA-induced NAD(+) depletion and death. In a mouse model of focal cerebral ischemic stroke, NAD(+) levels were decreased in both the contralateral and ipsilateral cortex 6 h after the onset of ischemia. Stroke resulted in dynamic changes of SIRT1 protein and activity levels which varied among brain regions. Administration of nicotinamide (200 mg/kg, i.p.) up to 1 h after the onset of ischemia elevated brain NAD(+) levels and reduced ischemic infarct size. Our findings demonstrate that the NAD(+) bioenergetic state is critical in determining whether neurons live or die in excitotoxic and ischemic conditions, and suggest a potential therapeutic benefit in stroke of agents that preserve cellular NAD(+) levels. Our data further suggest that, SIRT1 is linked to bioenergetic state and stress responses in neurons, and that under conditions of reduced cellular energy levels SIRT1 enzyme activity may consume sufficient NAD(+) to nullify any cell survival-promoting effects of its deacetylase action on protein substrates. C1 [Liu, Dong; Gharavi, Robert; Pitta, Michael; Gleichmann, Marc; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM liudo@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institute on Aging FX We would like to thank Graeme I. Bell for providing us the mouse GLUT3 cDNA clone used for riboprobe preparation and in situ hybridization. This research was supported by the Intramural Research Program of the National Institute on Aging. NR 74 TC 123 Z9 128 U1 0 U2 13 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PD MAR PY 2009 VL 11 IS 1 BP 28 EP 42 DI 10.1007/s12017-009-8058-1 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 425HN UT WOS:000264627700004 PM 19288225 ER PT J AU Li, YC Hu, XM Liu, YX Bao, YM An, LJ AF Li, Yachen Hu, Xiaoming Liu, Yuxin Bao, Yongming An, Lijia TI Nimodipine protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation SO NEUROPHARMACOLOGY LA English DT Article DE Nimodipine; Microglia; Neuroinflammation; LPS; Neurodegeneration; NADPH oxidase ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; NEURODEGENERATIVE DISEASES; NADPH OXIDASE; PARKINSONS-DISEASE; NITRIC-OXIDE; RAT-BRAIN; CALCIUM; ASTROCYTES AB Nimodipine, a calcium channel blocker, has been used mainly in the therapy of cardiovascular diseases. Recently, its indications have been extended experimentally to a wider range of disorders especially some central nervous system (CNS) disorders. In this study, we investigated whether nimodipine is neuroprotective to inflammation-mediated neurodegenerative diseases. Pretreatment with nimodipine reduced the degeneration of dopaminergic (DA) neurons induced by LPS in mesencephalic neuron-glia cultures in a dose-dependent manner. The neuroprotective effect of nimodipine was attributed to the inhibition of microglial activation, since nimodipine significantly inhibited the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E(2) (PGE(2)) from LPS-stimulated microglia. Moreover, nimodipine was not neuroprotective to 1-methyi-4-phenylpyridinium (MPP(+))-induced DA neurotoxicity in the absence of microglia. Mechanistic study showed that nimodipine failed to protect the degeneration of neurons in neuron-glia cultures from mice lacking functional NADPH oxidase (PHOX), a key enzyme for extracellular superoxide production in immune cells. Taken together these results suggest that nimodipine is protective to DA neurodegeneration via inhibiting the microglial-mediated oxidative stress and inflammatory response. Thus, nimodipine may be a potential therapeutic agent for the treatment of inflammation-related neurodegenerative disorders such as Parkinson's disease. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Li, Yachen; Bao, Yongming; An, Lijia] Dalian Univ Technol, Sch Environm & Biol Sci & Technol, Dalian 116024, Liaoning, Peoples R China. [Li, Yachen; Hu, Xiaoming; Liu, Yuxin] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP An, LJ (reprint author), Dalian Univ Technol, Sch Environm & Biol Sci & Technol, 2 Linggong Rd, Dalian 116024, Liaoning, Peoples R China. EM lijiaan97@yahoo.com NR 51 TC 36 Z9 38 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAR PY 2009 VL 56 IS 3 BP 580 EP 589 DI 10.1016/j.neuropharm.2008.10.016 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 412UC UT WOS:000263748700002 PM 19049811 ER PT J AU Peng, XQ Ashby, CR Spiller, K Li, X Li, J Thomasson, N Millan, MJ Mocaer, E Munoz, C Gardner, EL Xi, ZX AF Peng, Xiao-Qing Ashby, Charles R., Jr. Spiller, Krista Li, Xia Li, Jie Thomasson, Nitza Millan, Mark J. Mocaer, Elisabeth Munoz, Carmen Gardner, Eliot L. Xi, Zheng-Xiong TI The preferential dopamine D-3 receptor antagonist S33138 inhibits cocaine reward and cocaine-triggered relapse to drug-seeking behavior in rats SO NEUROPHARMACOLOGY LA English DT Article DE S33138; Cocaine; Dopamine; Self-administration; Brain reward; Reinstatement ID POTENTIAL ANTIPSYCHOTIC AGENT; ENHANCED BRAIN REWARD; INDUCED REINSTATEMENT; MEDICATION DEVELOPMENT; LOCOMOTOR-ACTIVITY; PROGRESSIVE-RATIO; SELF-STIMULATION; ANIMAL-MODELS; SB-277011A; REINFORCEMENT AB We have previously reported that selective dopamine (DA) D-3 receptor antagonists are effective in a number of animal models of drug addiction, but not in intravenous drug self-ad ministration, suggesting a limited ability to modify drug reward. In the present study, we evaluated the actions of S33138, a novel partially selective D-3 receptor antagonist, in animal models relevant to drug addiction. S33138, at doses of 0.156 or 0.625 mg/kg (i.p.), attenuated cocaine-enhanced brain-stimulation reward (BSR), and the highest dose tested (2.5 mg/kg) produced a significant aversive-like rightward shift, in BSR rate-frequency reward functions. Further, 533138 produced biphasic effects on cocaine self-administration, i.e., a moderate dose (2.5 mg/kg, p.o.) increased, while a higher dose (5 mg/kg, p.o.) inhibited, cocaine self-ad ministration. The increase in cocaine self-administration likely reflects a compensatory response to a partial reduction in drug reward after S33138. In addition, S33138 (0.156-2.5 mg/kg, p.o.) also dose-dependently inhibited cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-enhanced BSR and cocaine-triggered reinstatement produced by lower effective doses (e.g., 0.156 or 0.625 mg/kg) of S33138 is unlikely due to impaired locomotion, as lower effective doses of S33138 decreased neither Y-max levels in the BSR paradigm, rotarod performance, nor locomotion. However, the higher doses (2.5 or 5 mg/kg) of S33138 also significantly inhibited sucrose self-administration and rotarod performance, suggesting non-D-3 receptor-mediated effects on non-drug reward and locomotion. These data suggest that lower doses of S33138 interacting essentially with D-3 receptors have pharmacotherapeutic potential in treatment of cocaine addiction, while higher doses occupying D-2 receptors may influence locomotion and non-drug reward. Published by Elsevier Ltd. C1 [Peng, Xiao-Qing; Spiller, Krista; Li, Xia; Li, Jie; Gardner, Eliot L.; Xi, Zheng-Xiong] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. [Ashby, Charles R., Jr.] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA. [Thomasson, Nitza; Mocaer, Elisabeth; Munoz, Carmen] Inst Rech Int Servier, Dept Neuropsychiat, F-92615 Courbevoie, France. [Millan, Mark J.] Inst Rech Servier, Dept Psychopharmacol, F-78290 Croissy Sur Seine, France. RP Xi, ZX (reprint author), Natl Inst Drug Abuse, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov OI PENG, XIAOQING/0000-0002-7272-5428 FU National Institute on Drug Abuse; National Institutes of Health (NIH), USA; Les Laboratoires Servier, France FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health (NIH), USA and Les Laboratoires Servier, France. NR 43 TC 27 Z9 29 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAR PY 2009 VL 56 IS 4 BP 752 EP 760 DI 10.1016/j.neuropharm.2008.12.007 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 423TQ UT WOS:000264519000004 PM 19136017 ER PT J AU Chefer, VI Shippenberg, TS AF Chefer, V. I. Shippenberg, T. S. TI Augmentation of Morphine-Induced Sensitization but Reduction in Morphine Tolerance and Reward in Delta-Opioid Receptor Knockout Mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE delta-opioid receptor; morphine; sensitization; tolerance; reward ID CONDITIONED PLACE PREFERENCE; MU-AGONIST/DELTA-ANTAGONIST; PHYSICAL-DEPENDENCE; BEHAVIORAL SENSITIZATION; INDUCED ANALGESIA; OUT MICE; ADDICTION; PREVENTS; COCAINE; MECHANISMS AB Studies in experimental animals have shown that individuals exhibiting enhanced sensitivity to the locomotor-activating and rewarding properties of drugs of abuse are at increased risk for the development of compulsive drug-seeking behavior. The purpose of the present study was to assess the effect of constitutive deletion of delta-opioid receptors (DOPr) on the rewarding properties of morphine as well as on the development of sensitization and tolerance to the locomotor-activating effects of morphine. Locomotor activity testing revealed that mice lacking DOPr exhibit an augmentation of context-dependent sensitization following repeated, alternate injections of morphine (20 mg/kg; s.c.; 5 days). In contrast, the development of tolerance to the locomotor-activating effects of morphine following chronic morphine administration (morphine pellet: 25 mg: 3 days) is reduced relative to WT mice. The conditioned rewarding effects of morphine were reduced significantly in DOPrKO mice as compared to WT controls. Similar findings were obtained in response to pharmacological inactivation of DOPr in WT mice, indicating that observed effects are not due to developmental adaptations that occur as a consequence of constitutive deletion of DOPr. Together, these findings indicate that the endogenous DOPr system is recruited in response to both repeated and chronic morphine administration and that this recruitment serves an essential function in the development of tolerance, behavioral sensitization, and the conditioning of opiate reward. Importantly, they demonstrate that DOPr has a distinct role in the development of each of these drug-induced adaptations. The anti-rewarding and tolerance-reducing properties of DOPr antagonists may offer new opportunities for the treatment and prevention of opioid dependence as well as for the development of effective analgesics with reduced abuse liability. C1 [Chefer, V. I.] NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, IRP,NIH, Baltimore, MD 21224 USA. RP Chefer, VI (reprint author), NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, IRP,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM vchefer@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000504-01, Z99 DA999999] NR 57 TC 40 Z9 42 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2009 VL 34 IS 4 BP 887 EP 898 DI 10.1038/npp.2008.128 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 405YG UT WOS:000263259500008 PM 18704097 ER PT J AU Negus, SS Rice, KC AF Negus, S. Stevens Rice, Kenner C. TI Mechanisms of Withdrawal-Associated Increases in Heroin Self-Administration: Pharmacologic Modulation of Heroin vs Food Choice in Heroin-Dependent Rhesus Monkeys SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE heroin; dependence; withdrawal; self-administration; choice; corticotropin-releasing factor 1 receptors ID CORTICOTROPIN-RELEASING-FACTOR; PRECIPITATED MORPHINE-WITHDRAWAL; OPIATE WITHDRAWAL; DISCRIMINATIVE STIMULUS; NUCLEUS-ACCUMBENS; OPIOID WITHDRAWAL; RATS; COCAINE; CLONIDINE; NALOXONE AB Opioid withdrawal can produce a constellation of physiological and behavioral signs, including an increase in opioid self-administration. Different mechanisms mediate different withdrawal signs, and the present study used pharmacologic tools to assess mechanisms underlying withdrawal-associated increases in opioid reinforcement. Five rhesus monkeys were rendered heroin dependent via daily 21-h heroin self-administration sessions. One hour after each heroin self-administration session, monkeys chose between heroin (0-0.1 mg/kg per injection) and food (1 g pellets) during 2-h choice sessions. Under these conditions, heroin maintained a dose-dependent increase in heroin choice, such that monkeys responded primarily for food when low heroin doses were available (0-0.01 mg/kg per injection) and primarily for heroin when higher heroin doses were available (0.032-0.1 mg/kg per injection). Periods of spontaneous withdrawal were intermittently introduced by omitting one 21-h heroin self- administration session, and test drugs were administered during these withdrawal periods. Untreated withdrawal robustly increased heroin choice during choice sessions. Withdrawal-associated increases in heroin choice were completely suppressed by the mu opioid agonist morphine (0.032-0.32 mg/kg/h,i.v.), but not by the alpha-2 noradrenergic agonist clonidine (0.01-0.1 mg/kg/h, i.v.), the dopamine/norepinephrine releaser amphetamine (0.032-0.1 mg/kg/h, i.v.), or the kappa-opioid antagonist 5'-guanidinonaltrindole (1.0 mg/kg,i.m.). The corticotropin-releasing factor 1 antagonist antalarmin (1.0-10 mg/kg per day, i.m.) produced a morphine-like suppression of withdrawal-associated increases in heroin choice in one of three monkeys. These results suggest that mechanisms of withdrawal-associated increases in the relative reinforcing efficacy of opioid agonists may be different from mechanisms of many other somatic, mood-related, and motivational signs of opioid withdrawal. C1 [Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Negus, S. Stevens] Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. [Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St, Richmond, VA 23298 USA. EM ssnegus@vcu.edu FU NIDA NIH HHS [P01 DA014528, R01 DA002519-22, P01 DA014528-050001, R01 DA002519] NR 64 TC 25 Z9 26 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2009 VL 34 IS 4 BP 899 EP 911 DI 10.1038/npp.2008.127 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 405YG UT WOS:000263259500009 PM 18704098 ER PT J AU Grillon, C Chavis, C Covington, MF Pine, DS AF Grillon, Christian Chavis, Chanen Covington, Matthew F. Pine, Daniel S. TI Two-Week Treatment With the Selective Serotonin Reuptake Inhibitor Citalopram Reduces Contextual Anxiety but Not Cued Fear in Healthy Volunteers: A Fear-Potentiated Startle Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fear; anxiety; SSRI; citalopram; startle reflex; predictability ID STRIA TERMINALIS; BED NUCLEUS; TRYPTOPHAN DEPLETION; BEHAVIORAL ASSAYS; MICE LACKING; RESPONSES; FLUOXETINE; RECEPTOR; STIMULI; HUMANS AB Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) alleviates both anxiety symptoms and associated physiologic disturbances in anxious patients. However, limited research considers the degree to which chronic SSRI treatment influences anxiety in healthy individuals. This study examined the effect of 2-week citalopram treatment on two threat responses: short-and long-duration-potentiated startle. Prior work suggests that these two responses provide neurally and functionally distinct models of fear and anxiety, respectively, in rodents. Healthy volunteers (n=53) received either placebo or citalopram (20 mg per day) for 2 weeks under double-blind conditions. They were each tested twice, before and after treatment. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Aversive states were indexed by acoustic startle. Phasic fear-potentiated startle to the threat cue, as well as sustained startle potentiation to the experimental context in the predictable and unpredictable conditions, were investigated. Citalopram affected neither baseline startle nor short-duration fear-potentiated startle to discrete threat cues. However, citalopram reduced long-duration startle potentiation in the predictable conditions. These results are consistent with the hypothesis that short-and long-duration aversive states are mediated by distinct neural systems. They suggest that citalopram alleviates symptoms of anticipatory anxiety, not fear, by acting on mechanisms underlying long-duration aversive states. C1 [Grillon, Christian; Chavis, Chanen; Covington, Matthew F.; Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K North Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM Christian.grillon@nih.gov FU National Institute of Mental Health FX This research was supported by the Intramural Research Program of the National Institute of Mental Health. NR 35 TC 26 Z9 26 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2009 VL 34 IS 4 BP 964 EP 971 DI 10.1038/npp.2008.141 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 405YG UT WOS:000263259500015 PM 18800069 ER PT J AU Azdad, K Gall, D Woods, AS Ledent, C Ferre, S Schiffmann, SN AF Azdad, Karima Gall, David Woods, Amina S. Ledent, Catherine Ferre, Sergi Schiffmann, Serge N. TI Dopamine D-2 and Adenosine A(2A) Receptors Regulate NMDA-Mediated Excitation in Accumbens Neurons Through A(2A)-D-2 Receptor Heteromerization SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE basal ganglia; G-protein-coupled receptor; heteromerization; membrane potential oscillation; calcium channel ID MEDIUM SPINY NEURONS; SYNTHETIC PEPTIDE SUBSTRATE; DEPENDENT PROTEIN-KINASE; CEREBELLAR GRANULE CELLS; RAT NEOSTRIATAL NEURONS; NUCLEUS-ACCUMBENS; IN-VIVO; GENE-EXPRESSION; BASAL GANGLIA; D-2 RECEPTORS AB Bursting activity of striatal medium spiny neurons results from membrane potential oscillations between a down- and an upstate that could be regulated by G-protein-coupled receptors. Among these, dopamine D-2 and adenosine A(2A) receptors are highly enriched in striatal neurons and exhibit strong interactions whose physiological significance and molecular mechanisms remain partially unclear. More particularly, respective involvements of common intracellular signaling cascades and A(2A)-D-2 receptor heteromerization remain unknown. Here we show, by performing perforated-patch-clamp recordings on brain slices and loading competitive peptides, that D-2 and A(2A) receptors regulate the induction by N-methyl-D-aspartate of a depolarized membrane potential plateau through mechanisms relying upon specific protein-protein interactions. Indeed, D-2 receptor activation abolished transitions between a hyperpolarized resting potential and a depolarized plateau potential by regulating the Ca(V)1.3a calcium channel activity through interactions with scaffold proteins Shank1/3. Noticeably, A(2A) receptor activation had no effect per se but fully reversed the effects of D-2 receptor activation through a mechanism in which A(2A)-D-2 receptors heteromerization is strictly mandatory, demonstrating therefore a first direct physiological relevance of these heteromers. Our results show that membrane potential transitions and firing patterns in striatal neurons are tightly controlled by D-2 and A(2A) receptors through specific protein-protein interactions including A(2A)-D-2 receptors heteromerization. C1 [Azdad, Karima; Gall, David; Schiffmann, Serge N.] Univ Libre Bruxelles, Neurophysiol Lab, B-1070 Brussels, Belgium. [Azdad, Karima; Gall, David; Schiffmann, Serge N.] European Grad Sch Neurosci EURON, Brussels, Belgium. [Woods, Amina S.; Ferre, Sergi] NIDA, Intramural Res Program, Behav Neurosci Branch, NIH, Bethesda, MD USA. [Ledent, Catherine] Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium. RP Azdad, K (reprint author), Univ Libre Bruxelles, Neurophysiol Lab, CP601,Campus Erasme,Route Lennik 808, B-1070 Brussels, Belgium. EM kazdad@ulb.ac.be; sschiffm@ulb.ac.be RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU FMRE (Belgium); FNRS (Belgium); Van Buuren Foundation; CFWB; EC [QLG3-20001-01056]; NIDA FX This work was supported by FMRE (Belgium), FNRS (Belgium), Van Buuren Foundation, FER from ULB, Action de Recherche Concertee (2002-2007) from the CFWB, EC (QLG3-20001-01056), and the intramural funds of NIDA. DG was supported by FNRS. NR 62 TC 88 Z9 88 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2009 VL 34 IS 4 BP 972 EP 986 DI 10.1038/npp.2008.144 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 405YG UT WOS:000263259500016 PM 18800071 ER PT J AU Ernst, M Fudge, JL AF Ernst, Monique Fudge, Julie L. TI A developmental neurobiological model of motivated behavior: Anatomy, connectivity and ontogeny of the triadic nodes SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Amygdala; Striatum; Medial prefrontal cortex; Adolescence; Development; Connectivity; Motivated behavior; Functional anatomy; Approach; Avoidance; Regulatory system; Triadic Model ID MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS SHELL; SURPRISE-INDUCED ENHANCEMENT; NEONATAL AMYGDALA LESIONS; MACAQUE MONKEY AMYGDALA; CAUDAL VENTRAL STRIATUM; PITUITARY-ADRENAL AXIS; ORBITAL FRONTAL-CORTEX; EVENT-RELATED FMRI; RHESUS-MONKEY AB Adolescence is the transition period that prepares individuals for fulfilling their role as adults. Most conspicuous in this transition period is the peak level of risk-taking behaviors that characterize adolescent motivated behavior. Significant neural remodeling contributes to this change. This review focuses on the functional neuroanatomy underlying motivated behavior, and how ontogenic changes can explain the typical behavioral patterns in adolescence. To help model these changes and provide testable hypotheses, a neural systems-based theory is presented. In short, the Triadic Model proposes that motivated behavior is governed by a carefully orchestrated articulation among three systems, approach, avoidance and regulatory. These three systems map to distinct, but overlapping, neural circuits, whose representatives are the striatum, the amygdala and the medial prefrontal cortex. Each of these system-representatives will be described from a functional anatomy perspective that includes a review of their connectivity and what is known of their ontogenic changes. Published by Elsevier Ltd. C1 [Ernst, Monique] Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Fudge, Julie L.] Univ Rochester, Dept Psychiat & Neurobiol & Anat, Med Ctr, Rochester, NY 14642 USA. RP Ernst, M (reprint author), Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 231 TC 186 Z9 187 U1 5 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD MAR PY 2009 VL 33 IS 3 BP 367 EP 382 DI 10.1016/j.neubiorev.2008.10.009 PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 417RM UT WOS:000264094400013 PM 19028521 ER PT J AU Hoshi, M Saito, K Murakami, Y Taguchi, A Fujigaki, H Tanaka, R Takemura, M Ito, H Hara, A Seishima, M AF Hoshi, Masato Saito, Kuniaki Murakami, Yuki Taguchi, Ayako Fujigaki, Hidetsugu Tanaka, Ryo Takemura, Masao Ito, Hiroyasu Hara, Akira Seishima, Mitsuru TI Marked increases in hippocampal neuron indoleamine 2, 3-dioxygenase via IFN-gamma-independent pathway following transient global ischemia in mouse SO NEUROSCIENCE RESEARCH LA English DT Article DE Indoleamine 2; 3-Dioxygenase; IFN-gamma KO mouse; Immunohistochemistry ID FOCAL CEREBRAL-ISCHEMIA; QUINOLINIC ACID FORMATION; TRYPTOPHAN DEGRADATION; FOREBRAIN ISCHEMIA; INTERFERON-GAMMA; KAPPA-B; 2,3-DIOXYGENASE; MECHANISM; CELL; ACTIVATION AB Indoleamine 2,3-dioxygenase (IDO), which catabolizes L-tryptophan (L-TRP) to L-kynurenine (L-KYN), is an immunoregulatory factor that is up-regulated via an interferon-gamma (IFN-gamma)-dependent and/or independent mechanism. In this study, we investigated the localization of IDO and whether induction of IDO expression is an IFN-gamma-dependent and/or -independent mechanism in the CNS after cerebral ischemia. The expressions of IDO protein and mRNA were investigated at different time points following cerebral ischemia using immunohistochemistry, immunofluorescence and RT-PCR. Hippocampal neuron IDO mRNA and immunohistochemical staining were significantly up-regulated 72 h after transient global ischemia. Although IFN-gamma is a dominant inducer of IDO, hippocampal neuron IDO was clearly up-regulated in IFN-gamma KO mice. In summary, this is the first finding that up-regulation of IDO in hippocampal neurons after transient global ischemia occurs via INF-gamma-independent mechanisms. (C) 2009 Published by Elsevier Ireland Ltd and the Japan Neuroscience Society. C1 [Hoshi, Masato; Saito, Kuniaki; Fujigaki, Hidetsugu; Tanaka, Ryo; Takemura, Masao; Ito, Hiroyasu; Seishima, Mitsuru] Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 5011194, Japan. [Taguchi, Ayako; Hara, Akira] Gifu Univ, Grad Sch Med, Dept Tumor Pathol, Gifu 5011194, Japan. [Murakami, Yuki] NIMH, NIH, Pharmacol Sect, Bethesda, MD 20892 USA. [Saito, Kuniaki] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Saito, Kuniaki] Kyoto Univ, Fac Med, Kyoto, Japan. RP Saito, K (reprint author), Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 5011194, Japan. EM saito@gifu-u.ac.jp NR 21 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD MAR PY 2009 VL 63 IS 3 BP 194 EP 198 DI 10.1016/j.neures.2008.12.003 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 420YV UT WOS:000264326000006 PM 19121343 ER PT J AU Piknova, B Keszler, A Hogg, N Schechter, AN AF Piknova, Barbora Keszler, Agnes Hogg, Neil Schechter, Alan N. TI The reaction of cell-free oxyhemoglobin with nitrite under physiologically relevant conditions: Implications for nitrite-based therapies SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE Oxyhemoglobin; Nitrite; Ferrylhemoglobin; Nitric oxide; Reactive nitrogen species; Ascorbic acid; Uric acid; Haptoglobin; Cell-free hemoglobin ID LOW-DENSITY-LIPOPROTEIN; HAPTOGLOBIN-HEMOGLOBIN COMPLEX; MEDIATED OXIDATIVE STRESS; ISCHEMIA-REPERFUSION; IN-VIVO; AUTOCATALYTIC OXIDATION; HUMAN-PLASMA; OXIDE; MECHANISM; DEOXYHEMOGLOBIN AB Nitric oxide (NO(center dot)) participates in the regulation of a wide array of biological processes and its deficit contributes to the severity of many diseases. Recently, a role of NO deficiency that occurs as a result of intravascular hemolysis and increases in levels of cell-free hemoglobin in the pathway of chronic anemic pathologies has been suggested. Experimental evidence for deoxyhemoglobin-catalyzed reduction of nitrite to NO(center dot) leads to the possibility of nitrite infusion-based therapies to correct NO(center dot) deficits. However, the presence of plasma hemoglobin also raises the possibility of deleterious free radical-mediated oxidative damage from the reaction between nitrite and oxyhemoglobin in the vasculature. We show that the conditions required for the reaction between nitrite and oxyhemoglobin to exhibit free radical-mediated autocatalytic kinetics are highly unlikely to occur in the plasma compartment, even during extensive hemolysis and with pharmacological nitrite doses. Although the presence of haptoglobin enhances the rate of the reaction between nitrite and oxyhemoglobin, common plasma antioxidants-ascorbate and urate, as well as catalase-prevent autocatalysis. Our findings suggest that pharmacological doses of nitrite are unlikely to cause free radical or ferrylhemoglobin formation in plasma originating from the reaction of nitrite with cell-free oxyhemoglobin in vivo. (C) 2008 Elsevier Inc. All rights reserved. C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, NIH, Mol Med Branch, Bethesda, MD 20892 USA. [Keszler, Agnes; Hogg, Neil] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. [Keszler, Agnes; Hogg, Neil] Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. RP Schechter, AN (reprint author), NIDDK, NIH, Mol Med Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM aschecht@helix.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 FU Intramural NIH HHS; NIBIB NIH HHS [P41 EB001980, P41 EB001980-30, P41 EB001980-31, P41 EB001980-32, P41 EB001980-29, EB001980, P41 EB001980-28]; NIGMS NIH HHS [R01 GM055792-08, R01 GM055792-07, R01 GM055792-10A2, R01 GM055792-11, R01 GM055792, R01 GM055792-09, R29 GM055792, GM55792] NR 49 TC 11 Z9 11 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 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAR 1 PY 2009 VL 20 IS 2 BP 88 EP 94 DI 10.1016/j.niox.2008.10.005 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 408AP UT WOS:000263405700003 PM 19010434 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI Darwinian evolution in the light of genomics SO NUCLEIC ACIDS RESEARCH LA English DT Review ID HORIZONTAL GENE-TRANSFER; UNIVERSAL COMMON ANCESTOR; OVERDISPERSED MOLECULAR CLOCK; PROTEIN-SEQUENCE EVOLUTION; AMINO-ACID REPLACEMENTS; HIGHLY EXPRESSED GENES; EUKARYOTIC EVOLUTION; NONCODING DNA; ULTRACONSERVED ELEMENTS; MICROBIAL OCEANOGRAPHY AB Comparative genomics and systems biology offer unprecedented opportunities for testing central tenets of evolutionary biology formulated by Darwin in the Origin of Species in 1859 and expanded in the Modern Synthesis 100 years later. Evolutionary-genomic studies show that natural selection is only one of the forces that shape genome evolution and is not quantitatively dominant, whereas non-adaptive processes are much more prominent than previously suspected. Major contributions of horizontal gene transfer and diverse selfish genetic elements to genome evolution undermine the Tree of Life concept. An adequate depiction of evolution requires the more complex concept of a network or forest of life. There is no consistent tendency of evolution towards increased genomic complexity, and when complexity increases, this appears to be a non-adaptive consequence of evolution under weak purifying selection rather than an adaptation. Several universals of genome evolution were discovered including the invariant distributions of evolutionary rates among orthologous genes from diverse genomes and of paralogous gene family sizes, and the negative correlation between gene expression level and sequence evolution rate. Simple, non-adaptive models of evolution explain some of these universals, suggesting that a new synthesis of evolutionary biology might become feasible in a not so remote future. C1 [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov FU DHHS FX DHHS (NIH, National Library of Medicine) intramural funds. Funding for open access charge: DHHS (NIH, National Library of Medicine) intramural funds. NR 276 TC 124 Z9 128 U1 6 U2 60 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 MAR PY 2009 VL 37 IS 4 BP 1011 EP 1034 DI 10.1093/nar/gkp089 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 415VA UT WOS:000263962600010 PM 19213802 ER PT J AU Grady, PA AF Grady, Patricia A. TI The NINR Research Centers Program SO NURSING OUTLOOK LA English DT Editorial Material C1 NINR, Off Sci Policy & Publ Liaison, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, Off Sci Policy & Publ Liaison, Bldg 31,Room 5B-10,31 Ctr Dr,MSC 2178, Bethesda, MD 20892 USA. EM binghamr@mail.nih.gov FU Intramural NIH HHS [Z99 NR999999] NR 2 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD MAR-APR PY 2009 VL 57 IS 2 BP 113 EP 115 DI 10.1016/j.outlook.2009.01.008 PG 3 WC Nursing SC Nursing GA 427NT UT WOS:000264786700009 PM 19318164 ER PT J AU Castle, PE Fetterman, B Poitras, N Lorey, Y Shaber, R Kinney, W AF Castle, Philip E. Fetterman, Barbara Poitras, Nanty Lorey, Yhomas Shaber, Ruth Kinney, Walter TI Five-Year Experience of Human Papillomavirus DNA and Papanicolaou Test Cotesting SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ATYPICAL SQUAMOUS-CELLS; UNDETERMINED SIGNIFICANCE; CYTOLOGY INTERPRETATIONS; CONSENSUS GUIDELINES; CLINICAL-PRACTICE; RANDOMIZED-TRIAL; SCREENING-TESTS; UNITED-STATES; FOLLOW-UP AB OBJECTIVE: To estimate the 5-year age group-specific test positives for Pap tests and human papillomavirus (HPV) testing in a large, general screening population of women 30 and older. METHODS: Using data from Kaiser Permanente Northern California, a large health maintenance organization that introduced cotesting in 2003, we evaluated the cotesting results overall and by 5-year age groups. Women (n=580,289) who opted for and underwent cotesting (n cotests=812,598) between January 2003 and April 2008 were included in the analysis. Pap tests interpreted as atypical squamous cells of undetermined significance (ASC-US) or more severe were considered to be positive. Women were tested for carcinogenic HPV using an assay approved by the U.S. Food and Drug Administration. Binomial exact 95% confidence intervals (CIs) were calculated. RESULTS: Overall, 6.27% (950% Cl 6.21-6.32%) of cotests were carcinogenic HPV positive, and only 3.99% (95% CI 3.94-4.03%) cotests had normal cytology and were carcinogenic HPV positive. By comparison, 5.18% (95% Cl 5.13-5.23%) of cotests had ASC-US or more severe cytology, and 2.87% (95% CI 2.84-2.91%) of cotests had ASC-US or more severe cytology and were carcinogenic HPV negative. CONCLUSION: In a general screening population, concerns about excessive HPV test positives among women aged 30 years and older are not borne out. C1 Natl Inst Hlth, Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD USA. Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA. Kaiser Permanente Med Care Program, Womens Hlth Res Inst, Oakland, CA USA. Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. RP Kinney, W (reprint author), Kaiser Permanente Med Grp, Div Gynecol Oncol, Oakland, CA 95815 USA. EM Walter.Kinney@kp.org FU Intramural NIH HHS [Z99 CA999999, Z01 CP010124-12] NR 33 TC 69 Z9 71 U1 0 U2 0 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 MAR PY 2009 VL 113 IS 3 BP 595 EP 600 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 412UP UT WOS:000263750000004 PM 19300322 ER PT J AU Laughlin, SK Baird, DD Savitz, DA Herring, AH Hartmann, KE AF Laughlin, Shannon K. Baird, Donna D. Savitz, David A. Herring, Amy H. Hartmann, Katherine E. TI Prevalence of Uterine Leiomyomas in the First Trimester of Pregnancy An Ultrasound-Screening Study SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; FOLLOW-UP; COMPLICATIONS; MYOMAS; FIBROIDS; OUTCOMES; DIAGNOSIS; DELIVERY; MODELS; WOMEN AB OBJECTIVE: To estimate the proportion of pregnant women with one or more leiomyomas detected by research-quality ultrasound screening in the first trimester, to describe the size and location of leiomyomas identified, and to report variation in prevalence by race/ethnicity. METHODS: Within an ongoing prospective cohort, we conducted 4,271 first-trimester or postmiscarriage ultrasound examinations. Sonographers measured each leiomyoma three separate times, recording the maximum diameter in three perpendicular planes each time. Sonographers and investigators classified type and location. RESULTS: Among 458 women with one or more leiomyomas (prevalence 10.7%), we identified a total of 687 leiomyomas. The mean size of the largest leiomyoma was 2.3 cm (95% confidence interval [CI] 1.8-2.8). Mean gestational age at ultrasonography was 61 +/- 13 days from last menstrual period. Prevalence varied by race/ethnicity: 18% in African-American women (95% CI 13-25), 8% in white women (95% Cl 7-11), and 10% in Hispanic women (95% CI 5-19). The proportion of women with leiomyomas increased with age much more steeply for African-American women than for white women. CONCLUSION: Leiomyomas are common in pregnancy and occur more often among African-American women. Given the limited research on effects of leiomyomas on reproductive outcomes, the degree to which race/ethnic disparities in prevalence of leiomyomas may contribute to disparities in events such as miscarriage and preterm birth warrants investigation. C1 Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. Mt Sinai Sch Med, New York, NY USA. Univ N Carolina, Sch Publ Hlth, Biostat & Carolina Populat Ctr, Chapel Hill, NC USA. Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth, Nashville, TN 37232 USA. RP Hartmann, KE (reprint author), Vanderbilt Univ, Inst Med & Publ Hlth, 2525 W End Ave,Suite 600,6th Floor, Nashville, TN 37203 USA. EM katherine.hartmann@vanderbilt.edu RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU NICHD [RO1 HDO43883-04] FX Conducted as part of the Right from theStartstudy. Supported by the American Water Works Association Research Foundation under contract #2579 (Savitz); the Environmental Protection Agency Cooperative Agreement R-82845507 (Savitz); Pfizer Scholars Grants for Faculty Development in Clinical Epidemiology (Hartmann), NICHD RO1 HDO43883-04: "Consequences and Course of Uterine Fibroids in Pregnancy" (Hartmann and Herring); and the National Institutes of Health (NIH) Women's Health Fellowships in Intramural Women's Health Research (Laughlin). Also supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 26 TC 84 Z9 86 U1 1 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 MAR PY 2009 VL 113 IS 3 BP 630 EP 635 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 412UP UT WOS:000263750000009 PM 19300327 ER PT J AU Tita, ATN Rouse, DJ Blackwell, S Saade, GR Spong, CY Andrews, WW AF Tita, Alan T. N. Rouse, Dwight J. Blackwell, Sean Saade, George R. Spong, Catherine Y. Andrews, William W. TI Emerging Concepts in Antibiotic Prophylaxis for Cesarean Delivery A Systematic Review SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID EARLY POSTPARTUM ENDOMETRITIS; RANDOMIZED CLINICAL-TRIAL; SURGICAL SITE INFECTIONS; POSTCESAREAN ENDOMETRITIS; UREAPLASMA-UREALYTICUM; CHLAMYDIA-TRACHOMATIS; GENITAL MYCOPLASMAS; INTACT MEMBRANES; UNITED-STATES; SECTION AB OBJECTIVE: To review the current status of antibiotic prophylaxis for cesarean delivery, emerging strategies to enhance the effectiveness of antibiotic prophylaxis in reducing postcesarean infection, and the implications of the emerging practices. DATA SOURCES: We conducted a full PubMed (January 1966 to July 2008) search using the key words "cesarean" and "antibiotic prophylaxis." A total of 277 articles were identified and supplemented by a bibliographic search. METHODS OF STUDY SELECTION: We selected a total Of 15) Studies, which included all published clinical trials, meta-analyses of clinical trials, and observational studies evaluating either the timing of antibiotics or the use of extended-spectrum prophylaxis. We also reviewed nine reports involving national recommendations or technical reviews supporting current standards for antibiotic prophylaxis. TABULATION, INTEGRATION, AND RESULTS: We conducted an analytic review and tabulation of selected studies without further meta-analysis. Although current guidelines for antibiotic prophylaxis recommend the administration of narrow-spectrum antibiotics (cefazolin) after clamping of the umbilical cord, the data suggest that antibiotic administration before Surgical incision or the use of extended-spectrum regimens (involving azithromycin or metronidazole) after cord clamp may reduce postcesarean maternal infection by up to 50%. However, these two strategies have not been compared with each other. In addition, their effect on neonatal infection or infection with resistant organisms warrants further study. CONCLUSION: The use of either cefazolin alone before surgical incision or an extended-spectrum regimen after cord clamp seems to be associated with a reduction in postcesarean maternal infection. Confirmatory studies focusing additionally on neonatal outcomes and the effect on resistant organisms, as well as studies comparing both strategies, are needed. C1 [Tita, Alan T. N.] Univ Alabama, Div Maternal Fetal Med, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Univ Texas Med Branch, Galveston, TX USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Tita, ATN (reprint author), Univ Alabama, Div Maternal Fetal Med, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. EM alan.tita@obgyn.uab.edu FU NICHD NIH HHS [K12 HD001258-09] NR 60 TC 48 Z9 59 U1 0 U2 2 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 MAR PY 2009 VL 113 IS 3 BP 675 EP 682 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 412UP UT WOS:000263750000016 PM 19300334 ER PT J AU Signore, C Freeman, RK Spong, CY AF Signore, Caroline Freeman, Roger K. Spong, Catherine Y. TI Antenatal Testing-A Reevaluation Executive Summary of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID FETAL BIOPHYSICAL PROFILE; AMNIOTIC-FLUID VOLUME; CONTRACTION STRESS TEST; HIGH-RISK PREGNANCIES; INTRAUTERINE GROWTH RESTRICTION; UMBILICAL-ARTERY VELOCIMETRY; PRETERM PREMATURE RUPTURE; FLOW VELOCITY WAVEFORMS; NONSTRESS TEST; ANTEPARTUM SURVEILLANCE AB August 2007, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health Office of Rare Diseases, the American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics cosponsored a 2-day workshop to reassess the body of evidence supporting antepartum assessment of fetal well-being, identify key gaps in the evidence, and formulate recommendations for further research. Participants included experts in obstetrics and fetal physiology and representatives from relevant stakeholder groups and organizations. This article is a summary of the discussions at the workshop, including synopses of oral presentations on the epidemiology of stillbirth and fetal neurological injury, fetal physiology, techniques for antenatal monitoring, and maternal and fetal indications for monitoring. Finally, a synthesis of recommendations for further research compiled from three breakout workgroups is presented. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, US Dept HHS, Bethesda, MD USA. Pediat Med Grp, Ft Lauderdale, FL USA. Univ Calif Irvine, Womens Hosp, Mem Med Ctr, Dept Obstet & Gynecol, Long Beach, CA USA. RP Signore, C (reprint author), NICHD, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA. EM signoret@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 128 TC 25 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2009 VL 113 IS 3 BP 687 EP 701 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 412UP UT WOS:000263750000018 PM 19300336 ER PT J AU Yang, XY Guan, M Vigil, D Der, CJ Lowy, DR Popescu, NC AF Yang, X-Y Guan, M. Vigil, D. Der, C. J. Lowy, D. R. Popescu, N. C. TI p120Ras-GAP binds the DLC1 Rho-GAP tumor suppressor protein and inhibits its RhoA GTPase and growth-suppressing activities SO ONCOGENE LA English DT Article DE deleted in liver cancer; Ras-GAP; protein interaction; modulation of tumor cell proliferation; Rho-GAP; SH3 ID HUMAN HEPATOCELLULAR-CARCINOMA; ACTIVATING PROTEIN; SH3 DOMAIN; CELL-PROLIFERATION; SIGNALING PATHWAYS; GENE-EXPRESSION; RAS; CANCER; TRANSFORMATION; MORPHOLOGY AB DLC1 (deleted in liver cancer 1), which encodes a Rho GTPase-activating protein (Rho-GAP), is a potent tumor suppressor gene that is frequently inactivated in several human cancers. DLC1 is a multidomain protein that has been shown previously to bind members of the tensin gene family. Here we show that p120Ras-GAP (Ras-GAP; also known as RASA1) interacts and extensively colocalizes with DLC1 in focal adhesions. The binding was mapped to the SH3 domain located in the N terminus of Ras-GAP and to the Rho-GAP catalytic domain located in the C terminus of the DLC1. In vitro analyses with purified proteins determined that the isolated Ras-GAP SH3 domain inhibits DLC1 Rho-GAP activity, suggesting that Ras-GAP is a negative regulator of DLC1 Rho-GAP activity. Consistent with this possibility, we found that ectopic overexpression of Ras-GAP in a Ras-GAP-insensitive tumor line impaired the growth-suppressing activity of DLC1 and increased RhoA activity in vivo. Our observations expand the complexity of proteins that regulate DLC1 function and define a novel mechanism of the cross talk between Ras and Rho GTPases. C1 [Yang, X-Y; Guan, M.; Popescu, N. C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Vigil, D.; Der, C. J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Lowy, D. R.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 4128,37 Convent Dr,MSC4262, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI yang, xuyu/D-1414-2012 FU NIH [1R01CA129610]; American Cancer Society FX The Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH supported this work. CJD is also supported by an NIH grant (1R01CA129610), and DV was supported by a fellowship from the American Cancer Society. NR 48 TC 33 Z9 36 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2009 VL 28 IS 11 BP 1401 EP 1409 DI 10.1038/onc.2008.498 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 421JE UT WOS:000264354400001 PM 19151751 ER PT J AU Vikram, B Coleman, CN Deye, JA AF Vikram, Bhadrasain Coleman, C. Norman Deye, James A. TI Current Status and Future Potential of Advanced Technologies in Radiation Oncology Part 1. Challenges and Resources SO ONCOLOGY-NEW YORK LA English DT Article AB In 2006, the Radiation Research Program of the Division of Cancer Treatment and Diagnosis of the National Cancer Institute hosted a workshop intended to address current issues related to advanced radiation therapy technologies, with an eye toward (1) defining the specific toxicities that have limited the success of "conventional" radiation therapy, (2) examining the evidence from phase III studies for the improvements attributed to the advanced technologies in the treatment of several cancers commonly treated with radiation therapy, and (3) determining the opportunities and priorities for further technologic development and clinical trials. The new technologies offer substantial theoretical advantage in radiation dose distributions that, if realized in clinical practice, may help many cancer patients live longer and/or better. The precision of the advanced technologies may allow us to reduce the volume of normal tissue irradiated in the vicinity of the clinical target volume. Part 1 of this two-part article will provide a general overview of the workshop discussion, focusing on the challenges posed by the new technologies and resources available or in development for meeting those challenges. Part 2, which will appear in next month's issue of ONCOLOGY, will address the state of the science for each disease site. C1 [Vikram, Bhadrasain] NCI, Clin Radiat Oncol Branch, Radiat Res Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. RP Vikram, B (reprint author), NCI, Clin Radiat Oncol Branch, Radiat Res Program, Div Canc Treatment & Diag, 6130 Execut Blvd, Rockville, MD 20852 USA. EM vikramb@mail.nih.gov NR 11 TC 13 Z9 13 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2009 VL 23 IS 3 BP 279 EP 283 PG 5 WC Oncology SC Oncology GA V18PM UT WOS:000208016700007 PM 19418829 ER PT J AU Ko, C Citrin, D AF Ko, C. Citrin, D. TI Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck SO ORAL DISEASES LA English DT Review DE head and neck cancer; radiation treatment; chemotherapy ID INTENSITY-MODULATED RADIOTHERAPY; EPIDERMAL-GROWTH-FACTOR; QUALITY-OF-LIFE; PHASE-III TRIAL; RADIATION-INDUCED FIBROSIS; ADVANCED LARYNGEAL-CANCER; SALIVARY-GLAND FUNCTION; RANDOMIZED-TRIAL; OROPHARYNGEAL CARCINOMA; INDUCTION CHEMOTHERAPY AB Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35 000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical. Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described. Postoperative chemoradiation is used in patients with high-risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity-modulated radiation treatment have proven to decrease some debilitating side effects from radiation treatment. Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long-term side effects can be minimized with the use of newer technologies and with careful treatment planning. C1 [Ko, C.; Citrin, D.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, Bldg 10,CRC B2-3500, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov FU Intramural NIH HHS [Z01 BC010850-01] NR 101 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD MAR PY 2009 VL 15 IS 2 BP 121 EP 132 DI 10.1111/j.1601-0825.2008.01495.x PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 404GB UT WOS:000263138000001 PM 19036056 ER PT J AU Chen, J Sorensen, KP Gupta, T Kilts, T Young, M Wadhwa, S AF Chen, J. Sorensen, K. P. Gupta, T. Kilts, T. Young, M. Wadhwa, S. TI Altered functional loading causes differential effects in the subchondral bone and condylar cartilage in the temporomandibular joint from young mice SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Temporomandibular joint; Mouse model; Mechanical loading; Fibrocartilage; Subchondral bone ID MANDIBULAR CONDYLE; CHONDROCYTE MATURATION; RAT; GROWTH; PTHRP; OSTEOCLASTOGENESIS; EXPRESSION; DISORDERS; FORCES; RANKL AB Objective: Altered loading is an important etiological factor for temporomandibular joint (TMJ) disorders. Studies examining altered loading of the TMJ have been done in rats but the response of the TMJ to altered loading in mice is largely unknown. Therefore, due to the potential usefulness of genetically engineered mice, the goal of this study was to develop a mouse TMJ altered functional loading model. Methods: One hundred and thirty four, 21-day-old CD-1 female mice were divided into two groups: (1) normal loading (hard pellet diet) for 2-6 weeks and (2) altered functional loading (incisor trimming every other day and soft dough diet) for 2-6 weeks. The mandibular condylar cartilage was evaluated by histology, the subchondral bone was evaluated by microcomputed tomography (micro-CT) analysis and gene expression was evaluated by real time polymerase chain reaction (PCR) analysis. Results: Altered functional loading for 2-6 weeks caused significant reduction in the thickness of the condylar cartilage whereas, only at 4 weeks was there a significant decrease in the bone volume fraction and trabecular thickness of the subchondral bone. Gene expression analysis showed that altered functional loading for 4 weeks caused a significant reduction in the expression of SRY-box containing gene 9 (Sox9), Collagen type X (Col X), Indian hedgehog (Ihh), Collagen type 11 (Col II) and Vascular endothelial growth factor (Vegf) and altered loading for 6 weeks caused a significant decrease in the expression of Sox9, Col II, Vegf and Receptor activator of NF-kappa B ligand (Rankl compared to the normal loading group. Conclusion: Altered functional TMJ loading in mice for 2-6 weeks leads to a loss of the condylar cartilage and a transient loss in the density of the mandibular condylar subchondral bone. (c) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Chen, J.; Sorensen, K. P.; Gupta, T.; Wadhwa, S.] Univ Connecticut, Ctr Hlth, Sch Dent Med, Dept Craniofacial Sci,Div Orthodont, Farmington, CT 06030 USA. [Kilts, T.; Young, M.] NIDCR, Mol Biol Bones & Teeth Sect, Craniofacial & Skeletal Dis Branch, NIH,DHHS Bethesda, Bethesda, MD 20892 USA. RP Wadhwa, S (reprint author), Univ Connecticut, Ctr Hlth, Sch Dent Med, Dept Craniofacial Sci,Div Orthodont, Farmington, CT 06030 USA. EM wadhwa@uchc.edu FU NIDCR [K-22 DE017193] FX This work was supported by NIDCR K-22 DE017193 grant (SW), an American Association of Orthodontists Foundation Faculty Development Award (SW) and by the DIR, NIDCR, of the 1RP, NIH, DHHS (TK, MFY). NR 23 TC 39 Z9 43 U1 5 U2 11 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD MAR PY 2009 VL 17 IS 3 BP 354 EP 361 DI 10.1016/j.joca.2008.05.021 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 419SJ UT WOS:000264239700011 PM 18789726 ER PT J AU Zhu, JL Basso, O Obel, C Hvidtjorn, D Olsen, J AF Zhu, Jin Liang Basso, Olga Obel, Carsten Hvidtjorn, Dorte Olsen, Jorn TI Infertility, infertility treatment and psychomotor development: the Danish National Birth Cohort SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE child development; infertility; assisted reproduction; time to pregnancy ID INTRACYTOPLASMIC SPERM INJECTION; IN-VITRO FERTILIZATION; CHILDREN BORN; FOLLOW-UP; PRETERM DELIVERY; INCREASED RISK; TERM INFANTS; OUTCOMES; ICSI; WEIGHT AB Babies born of infertile couples, regardless of treatment, have a higher risk of preterm birth and low birthweight, conditions associated with delayed development. We examined developmental milestones in singletons as a function of parental infertility [time to pregnancy (TTP) > 12 months] and infertility treatment. From the Danish National Birth Cohort (1997-2003), we identified 37 897 singletons born of fertile couples (TTP <= 12 months), 4351 born of infertile couples conceiving naturally (TTP > 12 months), and 3309 born after infertility treatment. When the children were about 18 months old, mothers reported 12 developmental milestones by responding to structured questions. We defined a failure to achieve the assessed milestone or the minimal numbers of milestones in a summary (motor, or cognitive/language skills) as delay. Naturally conceived children born of infertile couples had a pattern of psychomotor development similar to that of children born of fertile couples, but increasing TTP correlated with a modest delay. When the analysis was restricted to infertile couples (treated and untreated), children born after treatment showed a slight delay in cognitive/language development (odds ratio 1.24, [95% confidence interval 1.01, 1.53]) for not meeting at least three out of six cognitive/language milestones); children born after intracytoplasmic sperm injection (ICSI) had the highest estimated relative risk of delay for most milestones, especially motor milestones. These results suggest that a long TTP may be associated with a modest developmental delay. Infertility treatment, especially ICSI, may be associated with a slight delay for some of these early milestones. C1 [Zhu, Jin Liang; Obel, Carsten] Univ Aarhus, Danish Epidemiol Sci Ctr, Inst Publ Hlth, DK-8000 Aarhus C, Denmark. [Hvidtjorn, Dorte] Univ Aarhus, NANEA, Inst Publ Hlth, Dept Epidemiol, DK-8000 Aarhus, Denmark. [Obel, Carsten] Aarhus Univ Hosp, Perinatal Epidemiol Res Unit, Dept Obstet & Gynaecol, Skejby, Denmark. [Basso, Olga] NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. [Olsen, Jorn] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. RP Zhu, JL (reprint author), Univ Aarhus, Danish Epidemiol Sci Ctr, Inst Publ Hlth, Vennelyst Blvd 6, DK-8000 Aarhus C, Denmark. EM zjl@soci.au.dk RI Basso, Olga/E-5384-2010; Olsen, Jorn/F-8801-2015 OI Basso, Olga/0000-0001-9298-4921; Olsen, Jorn/0000-0001-7462-5140 FU Danish Medical Research Council [271-05-0115]; NIH; National Institute of Environmental Health Sciences; Pharmacy Foundation; Egmont Foundation; March of Dimes Birth Defects Foundation; Augustinus Foundation; Health Foundation FX This work was supported by a grant from the Danish Medical Research Council (No. 271-05-0115) and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the DNBC. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the DNBC is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Foundation. NR 33 TC 31 Z9 32 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAR PY 2009 VL 23 IS 2 BP 98 EP 106 DI 10.1111/j.1365-3016.2008.00989.x PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 397EQ UT WOS:000262645600001 PM 19159396 ER PT J AU Grewal, J Carmichael, SL Song, J Shaw, GM AF Grewal, Jagteshwar Carmichael, Suzan L. Song, Jun Shaw, Gary M. TI Neural tube defects: an analysis of neighbourhood- and individual-level socio-economic characteristics SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE neighbourhood characteristics; neural tube defects; congenital malformations; maternal education; socio-economic status ID SPINA-BIFIDA; RISK-FACTORS; AREA DIFFERENCES; SOCIAL-CLASS; PREVALENCE; BIRTH; ANENCEPHALUS; POPULATION; PROVINCE; OUTCOMES AB Several studies have reported that neural tube defects (NTD) occur more frequently among children born to women of lower socio-economic status (SES). This study investigated the relationship between individual- and neighbourhood-level SES and the risk of an NTD-affected pregnancy. Data were drawn from a population-based case-control study of fetuses and infants among a cohort of California births between July 1999 and June 2003. Information on individual SES was obtained via telephone interviews with mothers of 337 (76% of eligible) cases and 626 (79% of eligible) non-malformed liveborn controls. Respondents' addresses were linked to the 2000 US Census to characterise six measures of neighbourhood SES (education, poverty, unemployment, occupation, crowding and rental occupancy). The analyses indicated that relative to women with a high school education, those with less than a high school education had a 1.7-fold increased risk of delivering infants with NTDs [95% CI 1.2, 2.6]. Twofold elevated risks for NTDs were observed for women with less than a high school education who lived in neighbourhoods where a majority of residents had not graduated from high school [95% CI 1.3, 3.1]. No consistent risk gradients were observed between NTD-affected pregnancies and indicators of lower neighbourhood SES. Results for phenotype subgroups were similar to those for all cases. Low maternal education was associated with an elevated risk of NTD in offspring. This risk varied by the education profile of the neighbourhood: women who did not graduate from high school and lived in less educated neighbourhoods exhibited a higher risk. C1 [Carmichael, Suzan L.; Song, Jun; Shaw, Gary M.] Childrens Hosp, Oakland Res Inst, March Dimes Calif Res Div, Oakland, CA 94609 USA. [Grewal, Jagteshwar] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Carmichael, SL (reprint author), Childrens Hosp, Oakland Res Inst, March Dimes Calif Res Div, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. EM scarmichael@marchofdimes.com OI Grewal, Jagteshwar/0000-0002-0141-4876 FU NIH [R01 HD 42538-03]; Centers for Disease Control and Prevention, Centers of Excellence Award [U50/CCU913241] FX This research was supported by NIH grant number R01 HD 42538-03 and a cooperative agreement from the Centers for Disease Control and Prevention, Centers of Excellence Award No. U50/CCU913241. NR 25 TC 22 Z9 22 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAR PY 2009 VL 23 IS 2 BP 116 EP 124 DI 10.1111/j.1365-3016.2008.00992.x PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 397EQ UT WOS:000262645600003 PM 19159398 ER PT J AU Wactawski-Wende, J Schisterman, EF Hovey, KM Howards, PP Browne, RW Hediger, M Liu, A Trevisan, M AF Wactawski-Wende, Jean Schisterman, Enrique F. Hovey, Kathleen M. Howards, Penelope P. Browne, Richard W. Hediger, Mary Liu, Aiyi Trevisan, Maurizio CA BioCycle Study Grp TI BioCycle study: design of the longitudinal study of the oxidative stress and hormone variation during the menstrual cycle SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE menstrual cycle; sex hormones; antioxidants; BioCycle study; study design; oxidative stress ID LIPID-PEROXIDATION; ENDOMETRIOSIS; POPULATIONS; BIOMARKERS; MARKERS; DISEASE; PHASE; WOMEN; SERUM AB Studies in both human and animal species have suggested that oxidative stress may be associated with health outcomes, including the risk of infertility in both males and females. Sex hormones have been shown to have antioxidant properties. The difficulty in studying the role of oxidative stress in females is partly due to fluctuation in these endogenous sex hormones across the menstrual cycle. The aim of this study was to determine the association of oxidative stress levels with endogenous reproductive hormone levels and antioxidants, including vitamin levels, across the menstrual cycle in a prospective cohort of premenopausal women. The goal was to enrol 250 healthy, regularly menstruating premenopausal women for two menstrual cycles. Participants visited the clinic up to 8 times per cycle, at which time blood and urine were collected. The visits occurred at key hormonally defined phases of the menstrual cycle, with the help of an algorithm based on cycle length and data from a fertility monitor. In addition, participants were administered standardised questionnaires, had various physical measures taken, and had other pertinent data collected. A total of 259 women were enrolled in this study, with 250 completing two cycles, despite a demanding study protocol which participants were required to follow. This report describes the study design, baseline characteristics and visit completion rate for the BioCycle study. C1 [Wactawski-Wende, Jean; Hovey, Kathleen M.; Trevisan, Maurizio] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Gynecol & Obstet, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. [Browne, Richard W.] SUNY Buffalo, Dept Clin Sci Lab, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. [Schisterman, Enrique F.; Howards, Penelope P.; Hediger, Mary; Liu, Aiyi] NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Wactawski-Wende, J (reprint author), SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, 270 Farber Hall, Buffalo, NY 14214 USA. EM jww@buffalo.edu OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X FU NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HHSN275200403394C] FX This investigation was supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) contract #HHSN275200403394C to the University at Buffalo. We are indebted to all the investigators and staff at the University at Buffalo and NICHD for their respective roles in the study, their dedication and effort; to Jennifer Reschke, Andrea Hughes and Christopher Bole for assistance in preparing tables for this manuscript; to Karen Falkner, Michael Bloom, Alan Wu and Leila Jackson for their assistance in study implementation; to Myron Gross for guidance on measures of oxidative stress and completion of the isoprostane samples; and to the BioCycle participants for their extraordinary commitment to the study. NR 25 TC 75 Z9 75 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAR PY 2009 VL 23 IS 2 BP 171 EP 184 DI 10.1111/j.1365-3016.2008.00985.x PG 14 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 397EQ UT WOS:000262645600008 PM 19159403 ER PT J AU Mulla, CM Geras-Raaka, E Raaka, BM Gershengorn, MC AF Mulla, Christopher M. Geras-Raaka, Elizabeth Raaka, Bruce M. Gershengorn, Marvin C. TI High Levels of Thyrotropin-Releasing Hormone Receptors Activate Programmed Cell Death in Human Pancreatic Precursors SO PANCREAS LA English DT Article DE thyrotropin-releasing hormone; thyrotropin-releasing hormone receptor; programmed cell death; embryonic development ID TO-MESENCHYMAL TRANSITION; IN-VITRO; MESSENGER-RNA; PROLINE AMIDE; RAT PANCREAS; BETA-CELLS; INSULIN; ISLETS; EXPRESSION; TRH AB Objectives: Thyrotropin-releasing hormone (TRH) is expressed in rodent and human adult pancreata and in mouse pancreas during embryonic development. However, expression of TRH receptors (TRHRs) in the pancreas is controversial. We sought to provide evidence that the TRH/TRHR system might play a role in fetal development. Methods: We used quantitative reverse transcription-polymerase chain reaction to measure TRH and TRHR messenger RNA (mRNA). To study the effects of TRHR expression in a pancreatic progenitor population, we expressed TRHRs in human islet-derived precursor cells (hIPCs) by infection with adenoviral vector AdCMVmTRHR. Thyrotropin-releasing hormone receptor signaling was measured as inositol phosphate production and intracellular calcium transients. Thyrotropinreleasing hormone receptor expression was measured by [(3)H]methylTRH binding. Apoptosis was monitored by release of cytochrome c from mitochondria. Results: We show that TRH mRNA is expressed in human fetal and adult pancreata, and that TRHR mRNA is expressed in fetal human pancreas but not in adult human pancreas. Thyrotropin-releasing hormone receptors expressed in hIPCs were shown to signal normally. Most importantly, TRH treatment for several days stimulated apoptosis in hIPCs expressing approximately 400,000 TRHRs per cell. Conclusions: These findings suggest a possible role for TRH/TRHR signaling in pancreatic precursors to promote programmed cell death, a normal constituent of morphogenesis during embryonic development in humans. C1 [Mulla, Christopher M.; Geras-Raaka, Elizabeth; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov FU Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX This work was supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 30 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2009 VL 38 IS 2 BP 197 EP 202 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 415AC UT WOS:000263905700015 PM 18948837 ER PT J AU Oliveira, F Jochim, RC Valenzuela, JG Kamhawi, S AF Oliveira, Fabiano Jochim, Ryan C. Valenzuela, Jesus G. Kamhawi, Shaden TI Sand flies, Leishmania, and transcriptome-borne solutions SO PARASITOLOGY INTERNATIONAL LA English DT Review DE Saliva; Midgut; Vector-based vaccine; Transmission-blocking vaccine; Salivary gland ID FLY LUTZOMYIA-LONGIPALPIS; DELAYED-TYPE HYPERSENSITIVITY; PHLEBOTOMUS-PAPATASI; VISCERAL LEISHMANIASIS; ARTHROPOD SALIVA; IMMUNE-RESPONSE; IMMUNOMODULATORY FACTORS; CUTANEOUS LEISHMANIASIS; VECTOR SALIVA; IN-VITRO AB Sand fly-parasite and sand fly-host interactions play an important role in the transmission of leishmaniasis. Vector Molecules relevant for such interactions include midgut and salivary proteins. These potential targets for interruption of propagation of Leishmania parasites have been poorly characterized. Transcriptomic analysis has proven to be an effective tool for identification of new sand fly molecules, providing exciting new insights into vector-based control strategies against leishmaniasis. Published by Elsevier Ireland Ltd. C1 [Oliveira, Fabiano; Jochim, Ryan C.; Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Kamhawi, S (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-22, Rockville, MD 20852 USA. EM skamhawi@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; Jochim, Ryan/C-6756-2013 OI Oliveira, Fabiano/0000-0002-7924-8038; FU Intramural Research Program of the Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank MAID intramural editor Brenda Rae Marshall for assistance. NR 48 TC 33 Z9 34 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1383-5769 J9 PARASITOL INT JI Parasitol. Int. PD MAR PY 2009 VL 58 IS 1 BP 1 EP 5 DI 10.1016/j.parint.2008.07.004 PG 5 WC Parasitology SC Parasitology GA 413FA UT WOS:000263777100001 PM 18768167 ER PT J AU Street, RL Makoul, G Arora, NK Epstein, RM AF Street, Richard L., Jr. Makoul, Gregory Arora, Neeraj K. Epstein, Ronald M. TI How does communication heal? Pathways linking clinician-patient communication to health outcomes SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Physician-patient communication; Health outcomes; Disease management ID QUALITY-OF-LIFE; SHARED DECISION-MAKING; CANCER-PATIENTS; BREAST-CANCER; PHYSICIAN COMMUNICATION; SELF-MANAGEMENT; SOCIAL SUPPORT; PATIENTS PERCEPTIONS; PRIMARY-CARE; BAD-NEWS AB Objective: Although prior research indicates that features of clinician-patient communication can predict health outcomes weeks and months after the consultation, the mechanisms accounting for these findings are poorly understood. While talk itself can be therapeutic (e.g., lessening the patient's anxiety, providing comfort), more often clinician-patient communication influences health outcomes via a more indirect route. Proximal outcomes of the interaction include patient understanding, trust, and clinician-patient agreement. These affect intermediate outcomes (e.g., increased adherence, better self-care skills) which, in turn, affect health and well-being. Seven pathways through which communication can lead to better health include increased access to care, greater patient knowledge and shared understanding, higher quality medical decisions, enhanced therapeutic alliances, increased social support, patient agency and empowerment, and better management of emotions. Conclusion: Future research should hypothesize pathways connecting communication to health outcomes and select measures specific to that pathway. Practice implications: Clinicians and patients should maximize the therapeutic effects of communication by explicitly orienting communication to achieve intermediate outcomes (e.g., trust, mutual understanding. adherence, social support, self-efficacy) associated with improved health. (C) 2008 Elsevier Ireland Ltd All rights reserved. C1 [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX 77843 USA. [Street, Richard L., Jr.] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Street, Richard L., Jr.] Baylor Coll Med, Houston, TX 77030 USA. [Makoul, Gregory] St Francis Hosp & Med Ctr, Hartford, CT USA. [Arora, Neeraj K.] NCI, Outcomes Res Branch, ARP, DCCPS, Bethesda, MD 20892 USA. [Epstein, Ronald M.] Univ Rochester, Sch Med & Dent, Dept Family Med Psychiat & Oncol, Rochester, NY USA. RP Street, RL (reprint author), Texas A&M Univ, Dept Commun, College Stn, TX 77843 USA. EM r-street@tamu.edu FU Division of Cancer Control and Population Sciences; National Cancer Institute, NIH [HFP90-020] FX This work was in part supported by a contract to the senior and lead authors from the Outcomes Research Branch of the Applied Research Program in the Division of Cancer Control and Population Sciences, National Cancer Institute, NIH and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). NR 96 TC 414 Z9 420 U1 29 U2 109 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAR PY 2009 VL 74 IS 3 BP 295 EP 301 DI 10.1016/j.pec.2008.11.015 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 420UZ UT WOS:000264316000004 PM 19150199 ER PT J AU Khademian, Z Speller-Brown, B Nouraie, SM Minniti, CP AF Khademian, Zarir Speller-Brown, Barbara Nouraie, Seyed-Medhi Minniti, Caterina P. TI Reversible Posterior Leuko-Encephalopathy in Children With Sickle Cell Disease SO PEDIATRIC BLOOD & CANCER LA English DT Article DE hemoglobinopathies; neurology and sickle cell; sickle cell disease ID LEUKOENCEPHALOPATHY SYNDROME; RELATIVE HYPERTENSION; RISK FACTOR; STROKE; ANEMIA AB Children with sickle cell disease (SCD) have high risk of neurologic morbidity and mortality, such as strokes, silent infarcts, and IIA's. A retrospective review of magnetic resonance imaging and magnetic resonance angiography identified eight children with radiological and clinical characteristics of reversible posterior em ephalopathy (RPLS). These patients had no evidence of previous cerebral infarcts or vasculopathy. Three have died during the 5-year follow up; one developed a stroke and one a conditional TCD. RPLS needs to be considered in the differential diagnosis of children with SCD that present with acute neurological changes, especially if they are already been hospitalized. Pediatr Blood Cancer 2009;52:373-375. (C) 2008 Wiley-Liss, Inc. C1 [Minniti, Caterina P.] NHLBI, NIH, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Khademian, Zarir] George Washington Univ, Childrens Natl Med Ctr, Dept Radiol, Washington, DC USA. [Speller-Brown, Barbara] Ctr Canc & Blood Disorders, Childrens Natl Med Ctr, Washington, DC USA. [Nouraie, Seyed-Medhi] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. RP Minniti, CP (reprint author), NHLBI, NIH, Pulm & Vasc Med Branch, Bldg 10 CRC,Room 5-5140,10 Ctr Dr,MSC 1476, Bethesda, MD 20892 USA. EM minnitic@mail.nih.gov NR 15 TC 13 Z9 15 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 MAR PY 2009 VL 52 IS 3 BP 373 EP 375 DI 10.1002/pbc.21812 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 396PP UT WOS:000262603900016 PM 19003906 ER PT J AU Nansel, TR Anderson, BJ Laffel, LMB Simons-Morton, BG Weissberg-Benchell, J Wysocki, T Iannotti, RJ Holmbeck, GN Hood, KK Lochrie, AS AF Nansel, Tonja R. Anderson, Barbara J. Laffel, Lori M. B. Simons-Morton, Bruce G. Weissberg-Benchell, Jill Wysocki, Tim Iannotti, Ronald J. Holmbeck, Grayson N. Hood, Korey K. Lochrie, Amanda S. TI A multisite trial of a clinic-integrated intervention for promoting family management of pediatric type 1 diabetes: feasibility and design SO PEDIATRIC DIABETES LA English DT Article DE adolescent; child; clinical trial; family; type 1 diabetes mellitus ID PEER-GROUP INTERVENTION; QUALITY-OF-LIFE; GLYCEMIC CONTROL; METABOLIC-CONTROL; SELF-MANAGEMENT; BEHAVIOR-THERAPY; ADOLESCENTS; ADHERENCE; CHILDREN; MELLITUS AB Nansel TR, Anderson BJ, Laffel LMB, Simons-Morton BG, Weissberg-Benchell J, Wysocki T, Iannotti RJ, Holmbeck GN, Hood KK, Lochrie AS. A multisite trial of a clinic-integrated intervention for promoting family management of pediatric type 1 diabetes: feasibility and design.Pediatric Diabetes 2009: 10: 105-115. The feasibility of a family-based clinic-integrated behavioral intervention to improve family management of type 1 diabetes was evaluated. In each of four clinical sites, 30-32 families (a total of 122) were randomized to intervention or usual care comparison groups. The WE*CAN intervention, based on family problem-solving methods, was delivered during three routine clinic visits by trained 'Health Advisors'. Of eligible families across the four sites, 83% agreed to participate, of whom 96% completed the baseline, mid-term, and postintervention assessments. Families participated in an average of 2.85 intervention sessions over an 8-month period. The intervention was integrated into the clinic setting without impairing clinic flow and was implemented with fidelity and consistency across sites by trained non-professionals. The findings provide evidence of the feasibility of conducting a multisite trial to evaluate the effects of a clinic-integrated problem-solving intervention to improve family management. Many lessons were learned that provide guidance for recruitment, measurement, and intervention for the larger clinical trial. C1 [Nansel, Tonja R.; Simons-Morton, Bruce G.] NIH, Div Epidemiol Stat & Prevent Res, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, DHHS, Bethesda, MD 20892 USA. [Anderson, Barbara J.; Iannotti, Ronald J.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Laffel, Lori M. B.; Hood, Korey K.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Weissberg-Benchell, Jill] Childrens Mem Hosp, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. [Holmbeck, Grayson N.] Loyola Univ Chicago, Dept Psychol, Chicago, IL USA. [Wysocki, Tim; Lochrie, Amanda S.] Nemours Childrens Clin, Dept Biomed Res, Jacksonville, FL USA. RP Nansel, TR (reprint author), 6100 Execut Blvd,Room 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Simons-Morton, Bruce/0000-0003-1099-6617 FU National Institutes of Health; National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The following institutions and investigators comprised the steering committee of the Family Management of Diabetes multisite trial. Eunice Kennedy Shriver National Institute of Child Health and Human Development: T. R. N., B. G. S.-M., R. J. I. Joslin Diabetes Center: L. M. B. L., K. K. H., Contract N01-HD-4-3364. Nemours Children's Clinic: T. W., A. S. L., Contract N01-HD-4-3361. Texas Children's Hospital, Houston, TX: B. J. A., Contract N01-HD-4-3362. Children's Memorial Hospital: J. W.-B., G. N. H., Contract N01-HD-4-3363. James Bell Associates, Arlington, VA: Cheryl McDonnell, PhD, MaryAnn D'Elio, Contract N01-HD-3-3360. NR 34 TC 25 Z9 27 U1 5 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAR PY 2009 VL 10 IS 2 BP 105 EP 115 DI 10.1111/j.1399-5448.2008.00448.x PG 11 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 412DQ UT WOS:000263704100004 PM 18721167 ER PT J AU Howitz, MF Simonsen, J Krause, TG Robbins, JB Schneerson, R Molbak, K Miller, MA AF Howitz, Michael F. Simonsen, Jacob Krause, Tyra Grove Robbins, John B. Schneerson, Rachel Molbak, Kare Miller, Mark A. TI Risk of Adverse Birth Outcome After Group B Meningococcal Disease Results From A Danish National Cohort SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE meningococcal disease; Neisseria meningitidis; birth defects; congenital malformations; PSA; NCAM; epidemiology; Denmark ID CELL-ADHESION MOLECULES; ESCHERICHIA-COLI K1; NEISSERIA-MENINGITIDIS; CONGENITAL-MALFORMATIONS; CAPSULAR POLYSACCHARIDE; MONOCLONAL-ANTIBODY; POLYSIALIC ACID; FOLLOW-UP; DENMARK; REGISTRATION AB Background: Group B meningococcal (GBM) disease induces antibodies that react in vitro with neural cell adhesion molecules in fetal brain tissue. Because IgG antibodies to GBM cross the placenta, the authors investigated whether women with a previous GBM disease had an increased risk of giving birth to preterm or to stillborn infants and whether the live-born children had an increased risk of birth defects. Methods: Data were obtained from 4 national registries in the per 0 1974-2005 to form 2 cohorts: (1) 1422 women with confirmed GBM disease, and (2) their 502 firstborn children. Results: Overall, there was no increased risk of preterm or stillbirths among the first cohort. Among the children, there was no increased risk of being born small for the gestational age, having birth defects (OR: 1.00; 95% Cl: 0.53-1.90), diseases of the nervous system (HR: 0.38; 95% Cl: 0.08-1.74), or any diseases within the first 3 years of life (HR: 1.06; 95% Cl: 0.78-1.45) compared to births from a reference population with prior group C meningococcal disease. Conclusions: The results do not support the proposal that GBM is associated with immunoreactive disease that may affect the health of the offspring and are consistent with previous findings that GBM disease is not associated with an increased risk of autoimmune disease. C1 [Howitz, Michael F.; Krause, Tyra Grove; Molbak, Kare] Statens Serum Inst, Dept Epidemiol, DK-2300 Copenhagen, Denmark. [Simonsen, Jacob] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Miller, Mark A.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Howitz, MF (reprint author), Artillerivej 5, DK-2300 Copenhagen S, Denmark. EM how@ssi.dk OI Molbak, Kare/0000-0002-3100-4990 FU Fogarty International Center; National Institute of Child Health; Human Development of the National Institutes of Health; Graduate Research School in International Health, University of Copenhagen FX Supported by The Fogarty International Center, the National Institute of Child Health and Human Development of the National Institutes of Health, and The Graduate Research School in International Health, University of Copenhagen. NR 37 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 2009 VL 28 IS 3 BP 199 EP 203 DI 10.1097/INF.0b013e31818c9049 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 416LL UT WOS:000264007500007 PM 19165135 ER PT J AU Chadwick, EG Pinto, J Yogev, R Alvero, CG Hughes, MD Palumbo, P Robbins, B Hazra, R Browning, L Heckman, BE Purdue, L Browning, R Luzuriaga, K Rodman, J Capparelli, E AF Chadwick, Ellen Gould Pinto, Jorge Yogev, Ram Alvero, Carmelita G. Hughes, Michael D. Palumbo, Paul Robbins, Brian Hazra, Rohan Browning, Leslie Heckman, Barbara E. Purdue, Lynette Browning, Renee Luzuriaga, Katherine Rodman, John Capparelli, Edmund CA Int Maternal Pediat Adolescent Cli TI Early Initiation of Lopinavir/Ritonavir in Infants Less Than 6 Weeks of Age Pharmacokinetics and 24-Week Safety and Efficacy SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article ID ANTIRETROVIRAL THERAPY; INFECTED CHILDREN; PHARMACOKINETICS; MORTALITY C1 [Chadwick, Ellen Gould] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60614 USA. [Pinto, Jorge] Univ Fed Minas Gerais, Sch Med, Belo Horizonte, MG, Brazil. [Alvero, Carmelita G.; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Palumbo, Paul] Dartmouth Med Sch, Div Infect Dis & Int Hlth, Lebanon, NH USA. [Robbins, Brian; Rodman, John] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Hazra, Rohan; Browning, Leslie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA. [Heckman, Barbara E.] Frontier Sci & Technol Res Fdn Inc, Div Pediat, Amherst, NY USA. [Purdue, Lynette; Browning, Renee] NIAID, Henry M Jackson Fdn, Div Aids, NIH, Bethesda, MD 20892 USA. [Luzuriaga, Katherine] Univ Massachusetts, Sch Med, Worcester, MA USA. [Capparelli, Edmund] Univ Calif San Diego, Dept Pediat, Sch Med, San Diego, CA 92103 USA. [Capparelli, Edmund] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Sch Med, San Diego, CA 92103 USA. RP Chadwick, EG (reprint author), Northwestern Univ, Dept Pediat, Feinberg Sch Med, Div Infect Dis, 2300 Childrens Plaza,Box 20, Chicago, IL 60614 USA. EM egchadwick@childrensmemorial.org FU National Institute of Allergy and Infectious Diseases [U01AI068632, 1 U01 AI068616]; National Institute of Allergy and Infectious Diseases, National Institutes of Health; Department of Health and Human Service [HHSN272200800014C]; Abbott Laboratories FX Supported by Grants U01AI068632 and 1 U01 AI068616 from the National Institute of Allergy and Infectious Diseases. This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health and Department of Health and Human Services, under contract no. HHSN272200800014C. This study was also supported by Abbott Laboratories. NR 18 TC 29 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 2009 VL 28 IS 3 BP 215 EP 219 DI 10.1097/INF.0b013e31818cc053 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 416LL UT WOS:000264007500010 PM 19209098 ER PT J AU Robbins, JB Schneerson, R Keith, JM Miller, MA Kubler-Kielb, J Trollfors, B AF Robbins, John B. Schneerson, Rachel Keith, Jerry M. Miller, Mark A. Kubler-Kielb, Joanna Trollfors, Birger TI Pertussis Vaccine A Critique SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Editorial Material DE pertussis toxin; genetically-inactivated; monovalent; FHA; pertactin ID BORDETELLA-PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; WHOOPING-COUGH; TOXOID VACCINE; CONTROLLED-TRIAL; SERUM ANTIBODIES; UNITED-STATES; ACELLULAR VACCINES; PRETERM INFANTS; TOXIN AB A critical level of serum IgG pertussis toxin antibody is both essential and sufficient to confer individual and herd immunity to pertussis. Monocomponent pertussis toxoid conferred such immunity in Sweden and in Denmark. We refute the notion that filamentous hemagglutinin, pertactin, and fimbriae add to the immunity conferred by pertussis toxoid and describe the artifact created when efficacy is estimated for multicomponent pertussis vaccines. Lastly, the genetically-inactivated mutant pertussis toxoid is safer, more immunogenic, and should be more effective than the current chemically-inactivated pertussis toxin. C1 [Robbins, John B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, Bethesda, MD 20892 USA. [Miller, Mark A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Trollfors, Birger] Univ Gothenburg, Gothenburg, Sweden. RP Robbins, JB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, 31 Ctr Dr,Rm 2A25, Bethesda, MD 20892 USA. EM robbinsJo@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 66 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 2009 VL 28 IS 3 BP 237 EP 241 DI 10.1097/INF.0b013e31818a8958 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 416LL UT WOS:000264007500014 PM 19165133 ER PT J AU Fine, R Friedman, A Gassman, J Greene, T Gipson, D Hogg, R Kaskel, F Moxey-Mims, M Radeva, M Trachtman, H Watkins, S Siegel, N AF Fine, Richard Friedman, Aaron Gassman, Jennifer Greene, Tom Gipson, Debra Hogg, Ron Kaskel, Frederick Moxey-Mims, Marva Radeva, Melina Trachtman, Howard Watkins, Sandra Siegel, Norm CA FSGS Steering Comm TI TITLE OF STUDY: THE FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN CHILDREN AND YOUNG ADULTS CLINICAL TRIAL (FSGS-CT) SO PEDIATRIC NEPHROLOGY LA English DT Meeting Abstract C1 [Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD MAR PY 2009 VL 24 IS 3 BP 636 EP 637 PG 2 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 403DZ UT WOS:000263064400051 ER PT J AU Molloy, AM Kirke, PN Troendle, JF Burke, H Sutton, M Brody, LC Scott, JM Mills, JL AF Molloy, Anne M. Kirke, Peadar N. Troendle, James F. Burke, Helen Sutton, Marie Brody, Lawrence C. Scott, John M. Mills, James L. TI Maternal Vitamin B-12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification SO PEDIATRICS LA English DT Article DE vitamin B-12; cobalamin; neural tube defects; folic acid fortification; folate ID ELEVATED PLASMA HOMOCYSTEINE; AMNIOTIC-FLUID; SPINA-BIFIDA; FOOD FORTIFICATION; COBALAMIN STATUS; EARLY-PREGNANCY; UNITED-STATES; FOLATE LEVELS; WOMEN; PREVENTION AB OBJECTIVE. Folic acid fortification has reduced neural tube defect prevalence by 50% to 70%. It is unlikely that fortification levels will be increased to reduce neural tube defect prevalence further. Therefore, it is important to identify other modifiable risk factors. Vitamin B-12 is metabolically related to folate; moreover, previous studies have found low B-12 status in mothers of children affected by neural tube defect. Our objective was to quantify the effect of low B-12 status on neural tube defect risk in a high-prevalence, unfortified population. METHODS. We assessed pregnancy vitamin B-12 status concentrations in blood samples taken at an average of 15 weeks' gestation from 3 independent nested case-control groups of Irish women within population-based cohorts, at a time when vitamin supplementation or food fortification was rare. Group 1 blood samples were from 95 women during a neural tube defect-affected pregnancy and 265 control subjects. Group 2 included blood samples from 107 women who had a previous neural tube defect birth but whose current pregnancy was not affected and 414 control subjects. Group 3 samples were from 76 women during an affected pregnancy and 222 control subjects. RESULTS. Mothers of children affected by neural tube defect had significantly lower B-12 status. In all 3 groups those in the lowest B-12 quartiles, compared with the highest, had between two and threefold higher adjusted odds ratios for being the mother of a child affected by neural tube defect. Pregnancy blood B-12 concentrations of < 250 ng/L were associated with the highest risks. CONCLUSIONS. Deficient or inadequate maternal vitamin B-12 status is associated with a significantly increased risk for neural tube defects. We suggest that women have vitamin B-12 levels of > 300 ng/L (221 pmol/L) before becoming pregnant. Improving B-12 status beyond this level may afford a further reduction in risk, but this is uncertain. Pediatrics 2009;123: 917-923 C1 [Molloy, Anne M.] Univ Dublin Trinity Coll, Sch Med, Dublin 2, Ireland. [Scott, John M.] Univ Dublin Trinity Coll, Sch Immunol & Biochem & Immunol, Dublin 2, Ireland. [Kirke, Peadar N.; Burke, Helen; Sutton, Marie] Hlth Res Board, Child Hlth Epidemiol Unit, Dublin, Ireland. [Troendle, James F.; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA. RP Molloy, AM (reprint author), Univ Dublin Trinity Coll, Sch Med, Dublin 2, Ireland. EM amolloy@tcd.ie OI Molloy, Anne/0000-0002-1688-9049 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Health Research Board (Ireland) FX This work was supported by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and the Health Research Board (Ireland).; We gratefully acknowledge the cooperation of the masters and nursing staff of the Dublin Maternity hospitals who enabled the 1986-1990 blood collections. We also thank the director and staff of the Virus Reference Laboratory, Department of Medical Microbiology (University College Dublin), who made the Irish National Rubella Screening Program samples available during 1983-1986. NR 51 TC 92 Z9 99 U1 3 U2 21 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 MAR PY 2009 VL 123 IS 3 BP 917 EP 923 DI 10.1542/peds.2008-1173 PG 7 WC Pediatrics SC Pediatrics GA 413XH UT WOS:000263825500026 PM 19255021 ER PT J AU Schwartz, DA AF Schwartz, David A. TI Gene-Environment Interactions and Airway Disease in Children SO PEDIATRICS LA English DT Article; Proceedings Paper CT Conference on the State of Childhood Asthma and Future Directions CY DEC, 2006 CL Washington, DC SP Merck Childhood Asthma Network DE genetic susceptibility; environmental exposure; bronchial diseases ID LOWER RESPIRATORY-TRACT; NITROGEN-DIOXIDE EXPOSURE; INDUCED LUNG INFLAMMATION; DUST-INDUCED INFLAMMATION; SERUM IMMUNOGLOBULIN-E; EMERGENCY ROOM VISITS; INNER-CITY CHILDREN; GENOME-WIDE SEARCH; GRAIN DUST; FAMILIAL AGGREGATION AB Asthma is the most common chronic disease of childhood in the United States, affecting nearly 6.5 million children. The prevalence and severity of childhood asthma have continued to increase over the past 2 decades, despite major advances in the recognition and treatment of this condition. Representing a heterogeneous collection of airway diseases, asthma has multiple pathologic processes resulting from the interactions of genetic susceptibility and environmental exposures. Preventing and treating airway disease in children will require new research approaches to understanding these complex interactions. Pediatrics 2009; 123:S151-S159 C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov FU Intramural NIH HHS NR 105 TC 13 Z9 13 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 MAR PY 2009 VL 123 BP S151 EP S159 DI 10.1542/peds.2008-2233E PG 9 WC Pediatrics SC Pediatrics GA 413XL UT WOS:000263826000004 PM 19221158 ER PT J AU Aklin, WM Tull, MT Kahler, CW Lejuez, CW AF Aklin, Will M. Tull, Matthew T. Kahler, Christopher W. Lejuez, C. W. TI Risk-taking propensity changes throughout the course of residential substance abuse treatment SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Risk-taking behaviors; Assessment; Substance abuse; Treatment; Trait-disinhibition ID TASK BART; DEPENDENCE; BEHAVIOR; ADULTS; AGE AB High rates of relapse following treatment have compelled researchers to elucidate the individual difference factors that change among those who receive substance abuse treatment. Previous research has suggested that trait-disinhibition variables may be of particular relevance. Given that these variables are primarily considered to be trait-level factors, the extent to which they are malleable by treatment is an important consideration. Thus, the purpose of this study was to examine the effect of a residential substance abuse treatment program on specific trait-disinhibition variables (e.g., risk-taking and impulsivity). A sample of 81 inner-city substance users was assessed on self-report and behavioral indicators of trait-disinhibition over a 30-day course of treatment. Risk-taking propensity was found to significantly decrease from pre- to post-treatment. Results are discussed with respect to implications for better understanding the factors that may operate as mechanisms of change during treatment, thereby having the potential to inform substance abuse prevention and treatment programs. Published by Elsevier Ltd. C1 [Aklin, Will M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. [Tull, Matthew T.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Kahler, Christopher W.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Lejuez, C. W.] Univ Maryland, Ctr Addict Personal & Emot Res, College Pk, MD 20742 USA. [Lejuez, C. W.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Aklin, WM (reprint author), NIDA, Behav & Integrat Treatment Branch, Div Clin Neurosci & Behav Res, NIH, 6001 Execut Blvd,Rm 3150,MSC 9593, Bethesda, MD 20892 USA. EM aklinwm@mail.nih.gov FU NIDA NIH HHS [R01 DA019405, R01 DA019405-02] NR 16 TC 11 Z9 11 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD MAR PY 2009 VL 46 IS 4 BP 454 EP 459 DI 10.1016/j.paid.2008.11.018 PG 6 WC Psychology, Social SC Psychology GA 409OJ UT WOS:000263515200013 PM 20161264 ER PT J AU Mishra, PJ AF Mishra, Prasun J. TI MicroRNA polymorphisms: a giant leap towards personalized medicine SO PERSONALIZED MEDICINE LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PAPILLARY THYROID-CARCINOMA; SPASTIC PARAPLEGIA TYPE-31; BINDING-SITE POLYMORPHISM; REDUCTASE GENE LEADS; BREAST-CANCER; METHOTREXATE RESISTANCE; CAENORHABDITIS-ELEGANS; TARGET SITE; EXPRESSION C1 NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Mishra, PJ (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. EM mishrapj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 51 TC 12 Z9 13 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAR PY 2009 VL 6 IS 2 BP 119 EP 125 DI 10.2217/17410541.6.2.119 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 423UV UT WOS:000264522100001 PM 20428464 ER PT J AU Schechter, AN Perlman, RL AF Schechter, Alan N. Perlman, Robert L. TI EVIDENCE-BASED MEDICINE AGAIN SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Editorial Material C1 [Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Perlman, Robert L.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. RP Schechter, AN (reprint author), NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM aschecht@helix.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD SPR PY 2009 VL 52 IS 2 BP 161 EP 163 PG 3 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA 438WR UT WOS:000265587200001 PM 19395816 ER PT J AU Cabanero, M Laje, G Detera-Wadleigh, S McMahon, FJ AF Cabanero, Michael Laje, Gonzalo Detera-Wadleigh, Sevilla McMahon, Francis J. TI Association study of phosphodiesterase genes in the Sequenced Treatment Alternatives to Relieve Depression sample SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE citalopram; depression; PDE; pharmacogenetics; phosphodiesterase; Sequenced Treatment Alternatives to Relieve Depression; SSRI; STAR*D ID STAR-ASTERISK-D; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; ANTIDEPRESSANT TREATMENT; MOLECULAR-CLONING; MAJOR DEPRESSION; CITALOPRAM; INHIBITORS; DESIGN; FAMILY; PDE11A AB A recent study has reported a significant association of variants in phosphodiesterase (PDE) genes with antidepressant treatment outcome in a Mexican American sample. We set out to investigate these findings in a large sample of patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. STAR*D is a longitudinal study of antidepressant outcome in depressed outpatients. We genotyped three single nucleotide polymorphisms (SNPs) in PDE11A (rs1880916), PDE1A (rs1549870), and PDE9A (rs729861) for replication and we also report three additional SNPs in PDE11A (rs3770016, rs4893975, rs6433687) that had been genotyped for a previous study. Single marker analysis of remission within the Hispanic subsamples (n=268) revealed no significant evidence of association with markers in PDE11A, PDE9A, or PDE1A. Additional analyses of remission within the total STAR*D sample (n=1914) were also largely negative, as were analyses utilizing a narrower definition of remission. Haplotype analyses were carried out with the four PDE11A SNIPS we genotyped; these also failed to show significant evidence of association in the STAR*D sample. In conclusion, we could not reproduce the reported association between PDE genes and antidepressant outcome in a sample of participants comparable to that reported previously. We conclude that PDE11A, PDE9A, and PDE1A are unlikely to play an important role in antidepressant outcome in this sample. Pharmacogenetics and Genomics 19:235-238 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Cabanero, Michael; Laje, Gonzalo; Detera-Wadleigh, Sevilla; McMahon, Francis J.] NIMH, NIH, Bethesda, MD 20892 USA. RP Laje, G (reprint author), NIMH, NIH, 35 Convent Dr,Room 1A207, Bethesda, MD 20892 USA. EM gonzalo.laje@nih.gov RI Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [N01MH90003] NR 23 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD MAR PY 2009 VL 19 IS 3 BP 235 EP 238 DI 10.1097/FPC.0b013e328320a3e2 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 418SQ UT WOS:000264169500006 PM 19214142 ER PT J AU Mishra, PJ Bertino, JR AF Mishra, Prasun J. Bertino, Joseph R. TI MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine SO PHARMACOGENOMICS LA English DT Article DE classification; diagnosis; disease; drug resistance; epidemiology; epigenetics; microRNA; miRSNP; mutations; pharmacogenomics; polymorphism; prognosis; SNP ID SINGLE-NUCLEOTIDE POLYMORPHISM; DIHYDROFOLATE-REDUCTASE GENE; CHRONIC LYMPHOCYTIC-LEUKEMIA; PAPILLARY THYROID-CARCINOMA; SPASTIC PARAPLEGIA TYPE-31; BINDING-SITE POLYMORPHISM; TARGET MESSENGER-RNAS; HUMAN BREAST-CANCER; CAENORHABDITIS-ELEGANS; TUMOR SUPPRESSORS AB Referred to as the micromanagers of gene expression, microRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs. Polymorphisms in the miRNA pathway (miR-polymorphisms) are emerging as powerful tools to study the biology of a disease and have the potential to be used in disease prognosis and diagnosis. Detection of miR-polymorphisms holds promise in the field of miRNA pharmacogenomics, molecular epidemiology and for individualized medicine. MiRNA pharmacogenomics can be defined as the study of miRNAs and polymorphisms affecting miRNA function in order to predict drug behavior and to improve drug efficacy. Advancements in the miRNA field indicate the clear involvement of miRNAs and genetic variations within the miRNA pathway in the progression and prognosis of diseases such as cancer, neurological disorders, muscular hypertrophy, gastric mucosal atrophy, cardiovascular disease and Type 11 diabetes. Various algorithms are available to predict miRNA-target mRNA sites; however, it is advisable to use multiple algorithms to confirm the predictions. Polymorphisms that may potentially affect miRNA-mediated regulation of the cell can be present not only in the 3'-UTR of a miRNA target gene, but also in the genes involved in miRNA biogenesis and in pri-, pre- and mature-miRNA sequences. A polymorphism in processed miRNAs may affect expression of several genes and have serious consequences, whereas a polymorphism in miRNA target site, in the 3'-UTR of the target mRNA, may be more target and/or pathway specific. In this review, we for the first time suggest a classification of miRNA polymorphisms/mutations. We also describe the importance and implications of miR-polymorphisms in gene regulation, disease progression, pharmacogenomics and molecular epidemiology. C1 [Mishra, Prasun J.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Bertino, Joseph R.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Newark, NJ 07103 USA. RP Mishra, PJ (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. EM mishrapj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 96 TC 162 Z9 173 U1 2 U2 28 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD MAR PY 2009 VL 10 IS 3 BP 399 EP 416 DI 10.2217/14622416.10.3.399 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 426EM UT WOS:000264690800011 PM 19290790 ER PT J AU Maguire, JJ Parker, WAE Foord, SM Bonner, TI Neubig, RR Davenport, AP AF Maguire, Janet J. Parker, William A. E. Foord, Steven M. Bonner, Tom I. Neubig, Richard R. Davenport, Anthony P. TI International Union of Pharmacology. LXXII. Recommendations for Trace Amine Receptor Nomenclature SO PHARMACOLOGICAL REVIEWS LA English DT Review ID PROTEIN-COUPLED-RECEPTOR; CHEMOSENSORY RECEPTORS; MONOAMINE TRANSPORTERS; BETA-PHENYLETHYLAMINE; OLFACTORY EPITHELIUM; DOPAMINE TRANSPORTER; TYRAMINE; TRACE-AMINE-ASSOCIATED-RECEPTOR-1; SCHIZOPHRENIA; EXPRESSION AB Trace amines such as p-tyramine and beta-phenylethylamine are found endogenously as well as in the diet. Concomitant ingestion of these foodstuffs with monoamine oxidase inhibitors may result in the hypertensive crisis known as the "beer, wine, and cheese effect" attributed to their sympathomimetic action. Trace amines have been shown to act on one of a novel group of mammalian seven transmembrane spanning G protein-coupled receptors belonging to the rhodopsin superfamily, cloned in 2001. This receptor encoded by the human TAAR1 gene is also present in rat and mouse genomes (Taar1) and has been shown to be activated by endogenous trace amine ligands, including p-tyramine and beta-phenylethylamine. A number of drugs, most notably amphetamine and its derivatives, act as agonists at this receptor. This review proposes an official nomenclature designating TAAR1 as the trace amine 1 receptor following the convention of naming receptors after the endogenous agonist, abbreviated to TA(1) where necessary. It goes on to discuss briefly the significance of the receptor, agents acting upon it, its distribution, and currently hypothesized physiological and pathophysiological roles. In humans, a further five genes are thought to encode functional receptors (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9). TAAR3 seems to be a pseudogene in some individuals but not others. TAAR4 is a pseudogene in humans, but occurs with TAAR3 as a functional gene in rodents. Nine further genes are present in rats and mice. The endogenous ligands are not firmly established but some may respond to odorants consistent with their expression in olfactory epithelium. C1 [Maguire, Janet J.; Parker, William A. E.; Davenport, Anthony P.] Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 0QQ, England. [Foord, Steven M.] GlaxoSmithKline Res & Dev Ltd, Stevenage, Herts, England. [Bonner, Tom I.] NIMH, Genet Lab, Bethesda, MD 20892 USA. [Neubig, Richard R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP Davenport, AP (reprint author), Univ Cambridge, Addenbrookes Hosp, NC IUPHAR Emerging Pharmacol Grp, Clin Pharmacol Unit, Cambridge CB2 0QQ, England. EM apd10@medschl.cam.ac.uk OI Maguire, Janet/0000-0002-9254-7040; Davenport, Anthony Peter/0000-0002-2096-3117 FU British Heart Foundation [PS/02/001, PG/05/127/19872]; National Institutes of Health National Institute of Mental Health FX This work was supported by British Heart Foundation [Grants PS/02/001, PG/05/127/19872]; and by the Intramural Research Program of the National Institutes of Health National Institute of Mental Health. NR 72 TC 21 Z9 22 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD MAR PY 2009 VL 61 IS 1 BP 1 EP 8 DI 10.1124/pr.109.001107 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 424KC UT WOS:000264564600001 PM 19325074 ER PT J AU Bagrov, AY Shapiro, JI Fedorova, OV AF Bagrov, Alexei Y. Shapiro, Joseph I. Fedorova, Olga V. TI Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets SO PHARMACOLOGICAL REVIEWS LA English DT Review ID DIGITALIS-LIKE FACTORS; NA-K-ATPASE; OUABAIN-LIKE COMPOUND; DIGOXIN-LIKE IMMUNOREACTIVITY; BOVINE ADRENOCORTICAL-CELLS; ATRIAL-NATRIURETIC-PEPTIDE; OBSTRUCTIVE SLEEP-APNEA; SALT-SENSITIVE HYPERTENSION; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE AB Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, have been postulated to play important roles in health and disease for nearly half a century. Recent discoveries, which include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of an alternative mechanism by which CTS can signal through the Na+/K+-ATPase, have increased the interest in this field substantially. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the regulation of cell growth, differentiation, apoptosis, and fibrosis, the modulation of immunity and of carbohydrate metabolism, and the control of various central nervous functions and even behavior. This review focuses on the physiological interactions between CTS and other regulatory systems that may be important in the pathophysiology of essential hypertension, preeclampsia, endstage renal disease, congestive heart failure, and diabetes mellitus. Based on our increasing understanding of the regulation of CTS as well as the molecular mechanisms of these hormone increases, we also discuss potential therapeutic strategies. C1 [Bagrov, Alexei Y.; Fedorova, Olga V.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Shapiro, Joseph I.] Univ Toledo, Dept Med, Toledo, OH 43606 USA. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bagrova@mail.nih.gov FU National Institutes of Health National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institutes of Health National Institute on Aging. NR 411 TC 190 Z9 201 U1 1 U2 25 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD MAR PY 2009 VL 61 IS 1 BP 9 EP 38 DI 10.1124/pr.108.000711 PG 30 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 424KC UT WOS:000264564600002 PM 19325075 ER PT J AU Dopico, AM Lovinger, DM AF Dopico, Alex M. Lovinger, David M. TI Acute Alcohol Action and Desensitization of Ligand-Gated Ion Channels SO PHARMACOLOGICAL REVIEWS LA English DT Review ID NICOTINIC ACETYLCHOLINE-RECEPTORS; NCB-20 NEUROBLASTOMA-CELLS; ACTIVATED POTASSIUM CHANNELS; CEREBELLAR GRANULE CELLS; VENTRAL TEGMENTAL AREA; CENTRAL-NERVOUS-SYSTEM; LARGE-CONDUCTANCE; GENERAL-ANESTHETICS; ETHANOL INHIBITION; SINGLE-CHANNEL AB Ethanol exerts its biological actions through multiple receptors, including ion channels. Ion channels that are sensitive to pharmacologically relevant ethanol concentrations constitute a heterogeneous set, including structurally unrelated proteins solely sharing the property that their gating is regulated by a ligand(s). Receptor desensitization is almost universal among these channels, and its modulation by ethanol may be a crucial aspect of alcohol pharmacology and effects in the body. We review the evidence documenting interactions between ethanol and ionotropic receptor desensitization, and the contribution of this interaction to overall ethanol action on channel function. In some cases, such as type 3 serotonin, nicotinic acetylcholine, GABA-A, and alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionate receptors, ethanol actions on apparent desensitization play a significant role in acute drug action on receptor function. In a few cases, mutagenesis helped to identify different areas within a receptor protein that differentially sense nalcohols, resulting in differential modulation of receptor desensitization. However, desensitization of a receptor is linked to a variety of biochemical processes that may alter protein conformation, such as the lipid microenvironment, post-translational channel modification, and channel subunit composition, the relative contribution of these processes to ethanol interactions with channel desensitization remains unclear. Understanding interactions between ethanol and ionotropic receptor desensitization may help to explain different ethanol actions 1) when ethanol is evaluated in vitro on cloned channel proteins, 2) under physiological or pathological conditions or in distinct cell domains with modified ligand concentration and/or receptor conformation. Finally, receptor desensitization is likely to participate in molecular and, possibly, behavioral tolerance to ethanol, which is thought to contribute to the risk of alcoholism. C1 [Dopico, Alex M.] Univ Tennessee, HSC, Dept Pharmacol, Memphis, TN 38163 USA. [Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Bethesda, MD USA. RP Dopico, AM (reprint author), Univ Tennessee, HSC, Dept Pharmacol, 874 Union Ave, Memphis, TN 38163 USA. EM adopico@utmem.edu FU National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [AA11560] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism and by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant AA11560]. We thank Maria T. Asuncion-Chin for technical assistance. NR 196 TC 48 Z9 48 U1 0 U2 11 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD MAR PY 2009 VL 61 IS 1 BP 98 EP 114 DI 10.1124/pr.108.000430 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 424KC UT WOS:000264564600005 PM 19270242 ER PT J AU Pappu, RV Nussinov, R AF Pappu, Rohit V. Nussinov, Ruth TI Protein folding: lessons learned and new frontiers PREFACE SO PHYSICAL BIOLOGY LA English DT Editorial Material C1 [Pappu, Rohit V.] Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA. [Pappu, Rohit V.] Washington Univ, Ctr Computat Biol, St Louis, MO USA. [Nussinov, Ruth] NCI, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet, Tel Aviv, Israel. RP Pappu, RV (reprint author), Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD MAR PY 2009 VL 6 IS 1 AR 010301 DI 10.1088/1478-3967/6/1/010301 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 446VE UT WOS:000266148700001 PM 19208944 ER PT J AU Tsai, CJ Ma, BY Nussinov, R AF Tsai, Chung-Jung Ma, Buyong Nussinov, Ruth TI Intra-molecular chaperone: the role of the N-terminal in conformational selection and kinetic control SO PHYSICAL BIOLOGY LA English DT Article ID BUILDING-BLOCKS; FOLDING UNITS; MICROCIN J25; PROTEINS; BINDING; STABILITY; PATHWAY; PROPEPTIDE; DYNAMICS; DOMAIN AB The vast majority of the proteins in nature are under thermodynamic control, consistent with the universally accepted notion that proteins exist in their thermodynamically most stable state. Yet, recently a number of examples of proteins whose fold is under kinetic control have come to light. Their functions and environments vary. The first among these are some proteases, discovered in the early 1990s. There, an N-terminal proregion is self-cleaved after the protein folded, leaving the remainder of the chain in a kinetically trapped state. A related scenario was observed for microcin J25, an antibacterial peptide. This peptide presents a trapped covalently knotted conformation. The third and the most recently discovered case is the multidrug-resistant transporter protein, P-glycoprotein. There, a synonymous 'silent' mutation leads to ribosome stalling with a consequent altered kinetically trapped state. Here we argue that in all three examples, the N-terminal plays the role of an intra-molecular chaperone, that is, the N-terminal conformation selects among all competing local conformations of a downstream segment. By providing a pattern, the N-terminal chaperone segment assists the protein folding process. If the N-terminal is subsequently cleaved, the protein can be under kinetic control, since it is trapped in a thermodynamically less-stable state. C1 [Tsai, Chung-Jung; Ma, Buyong; Nussinov, Ruth] SAIC Frederick Inc, Basic Res Program, Ctr Canc Res Nanobiol Program, NCI, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Basic Res Program, Ctr Canc Res Nanobiol Program, NCI, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 55 TC 5 Z9 5 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD MAR PY 2009 VL 6 IS 1 AR 013001 DI 10.1088/1478-3975/6/1/013001 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 446VE UT WOS:000266148700002 PM 19193974 ER PT J AU Krekelberg, WP Kumar, T Mittal, J Errington, JR Truskett, TM AF Krekelberg, William P. Kumar, Tanuj Mittal, Jeetain Errington, Jeffrey R. Truskett, Thomas M. TI Anomalous structure and dynamics of the Gaussian-core fluid SO PHYSICAL REVIEW E LA English DT Article DE cooling; diffusion; entropy; liquid structure; liquid theory; molecular dynamics method; short-range order; thermal expansion ID EXCESS ENTROPY; MODEL; LIQUID; DIFFUSION; SIMULATION; PARTICLES; TRANSPORT; DENSITY; SYSTEMS; WATER AB It is known that there are thermodynamic states for which the Gaussian-core fluid displays anomalous properties such as expansion upon isobaric cooling (density anomaly) and increased single-particle mobility upon isothermal compression (self-diffusivity anomaly). Here, we investigate how temperature and density affect its short-range translational structural order, as characterized by the two-body excess entropy. We find that there is a wide range of conditions for which the short-range translational order of the Gaussian-core fluid decreases upon isothermal compression (structural order anomaly). As we show, the origin of the structural anomaly is qualitatively similar to that of other anomalous fluids (e.g., water or colloids with short-range attractions) and is connected to how compression affects static correlations at different length scales. Interestingly, we find that the self-diffusivity of the Gaussian-core fluid obeys a scaling relationship with the two-body excess entropy that is very similar to the one observed for a variety of simple liquids. One consequence of this relationship is that the state points for which structural, self-diffusivity, and density anomalies of the Gaussian-core fluid occur appear as cascading regions on the temperature-density plane; a phenomenon observed earlier for models of waterlike fluids. There are, however, key differences between the anomalies of Gaussian-core and waterlike fluids, and we discuss how those can be qualitatively understood by considering the respective interparticle potentials of these models. Finally, we note that the self-diffusivity of the Gaussian-core fluid obeys different scaling laws depending on whether the two-body or total excess entropy is considered. This finding, which deserves more comprehensive future study, appears to underscore the significance of higher-body correlations for the behavior of fluids with bounded interactions. C1 [Krekelberg, William P.; Kumar, Tanuj; Truskett, Thomas M.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Mittal, Jeetain] NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. [Errington, Jeffrey R.] SUNY Buffalo, Dept Chem & Biol Engn, Buffalo, NY 14260 USA. [Truskett, Thomas M.] Univ Texas Austin, Inst Theoret Chem, Austin, TX 78712 USA. RP Truskett, TM (reprint author), Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. EM wpkrekelberg@gmail.com; jeetain@helix.nih.gov; jerring@buffalo.edu; truskett@che.utexas.edu RI Truskett, Thomas/D-4624-2009; Errington, Jeffrey/E-8644-2011; Truskett, Thomas/C-4996-2014 OI Truskett, Thomas/0000-0002-6607-6468; Errington, Jeffrey/0000-0003-0365-0271; FU Intramural NIH HHS NR 51 TC 66 Z9 66 U1 0 U2 7 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 MAR PY 2009 VL 79 IS 3 AR 031203 DI 10.1103/PhysRevE.79.031203 PG 6 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 427GH UT WOS:000264767300051 PM 19391927 ER PT J AU Aladjem, M Chattoraj, DK AF Aladjem, Mirit Chattoraj, Dhruba K. TI EMBO Conference on Replication and Segregation of Chromosomes, Geilo, Norway, June 16-20 Replication and segregation of chromosomes in the three domains of life: EMBO conference reports common grounds SO PLASMID LA English DT Article DE Replication; Segregation; Chromosome AB A meeting of the EMBO Conference Series on Replication and Segregation of Chromosomes was held in Geilo, Norway, 16-20 June, 2008, under a scenic backdrop of high mountains. The meeting focused on the mechanistic details of replication and segregation primarily from well-characterized systems. Because the same basic principles govern chromosome maintenance in all three domains of life, participants encountering parallel processes in distantly-related organisms were stimulated to interact. Another successful aspect of the meeting was the quality of the posters, several of which were chosen for platform presentation and two for special rewards. The organizers Kirsten Skarstad and Erik Boye deserve praise for their skillful organization of the meeting, the highlights of which are discussed below. C1 [Aladjem, Mirit] NCI, Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Aladjem, M (reprint author), NCI, Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM aladjemm@mail.nih.gov; chattord@mail.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU NIH, Center for Cancer Research, National Cancer Institute FX The authors are grateful to Kirsten Skarstad, Erik Boye, David Lane and Michael Yarmolinsky for their comments and acknowledge the support of the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. 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 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2009 VL 61 IS 2 BP 89 EP 93 DI 10.1016/j.plasmid.2008.10.003 PG 5 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 410AE UT WOS:000263546400001 PM 19041668 ER PT J AU Fong, JH Shoemaker, BA Garbuzynskiy, SO Lobanov, MY Galzitskaya, OV Panchenko, AR AF Fong, Jessica H. Shoemaker, Benjamin A. Garbuzynskiy, Sergiy O. Lobanov, Michail Y. Galzitskaya, Oxana V. Panchenko, Anna R. TI Intrinsic Disorder in Protein Interactions: Insights From a Comprehensive Structural Analysis SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID NATIVELY UNFOLDED PROTEINS; AMINO-ACID-COMPOSITION; UNSTRUCTURED PROTEINS; MOLECULAR RECOGNITION; WEB SERVER; DATA-BANK; BINDING; PREDICTION; REGIONS; DYNAMICS AB We perform a large-scale study of intrinsically disordered regions in proteins and protein complexes using a non-redundant set of hundreds of different protein complexes. In accordance with the conventional view that folding and binding are coupled, in many of our cases the disorder-to-order transition occurs upon complex formation and can be localized to binding interfaces. Moreover, analysis of disorder in protein complexes depicts a significant fraction of intrinsically disordered regions, with up to one third of all residues being disordered. We find that the disorder in homodimers, especially in symmetrical homodimers, is significantly higher than in heterodimers and offer an explanation for this interesting phenomenon. We argue that the mechanisms of regulation of binding specificity through disordered regions in complexes can be as common as for unbound monomeric proteins. The fascinating diversity of roles of disordered regions in various biological processes and protein oligomeric forms shown in our study may be a subject of future endeavors in this area. C1 [Fong, Jessica H.; Shoemaker, Benjamin A.; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Garbuzynskiy, Sergiy O.; Lobanov, Michail Y.; Galzitskaya, Oxana V.] Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. RP Fong, JH (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. EM ogalzit@vega.protres.ru; panch@ncbi.nlm.nih.gov RI GALZITSKAYA, OXANA/L-2664-2015 FU Intramural Research Program of the NIH; National Library of Medicine; Russian Foundation for Basic Research [08-04-00561-a]; Science School [2791.2008.4]; INTAS [05-1000004-7747]; "Russian Science Support Foundation"; Howard Hughes Medical Institute [55005607] FX This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. OVG, SOG, MYL were supported by the program "Molecular and Cell Biology'', by the Russian Foundation for Basic Research (08-04-00561-a), by Science School (2791.2008.4), by the INTAS grant (05-1000004-7747), "Russian Science Support Foundation'' and by Howard Hughes Medical Institute (grant 55005607). NR 75 TC 59 Z9 60 U1 1 U2 9 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 MAR PY 2009 VL 5 IS 3 AR e1000316 DI 10.1371/journal.pcbi.1000316 PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 447TF UT WOS:000266214000021 PM 19282967 ER PT J AU Jo, J Gavrilova, O Pack, S Jou, W Mullen, S Sumner, AE Cushman, SW Periwal, V AF Jo, Junghyo Gavrilova, Oksana Pack, Stephanie Jou, William Mullen, Shawn Sumner, Anne E. Cushman, Samuel W. Periwal, Vipul TI Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID DIET-INDUCED OBESITY; HIGH-FAT DIET; ADIPOCYTE SIZE; INSULIN-RESISTANCE; PROGENITOR CELLS; BONE-MARROW; IN-VITRO; MICE; MOUSE; CELLULARITY AB Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity. In this study, the size distributions of epididymal adipose cells from two mouse strains, obesity-resistant FVB/N and obesity-prone C57BL/6, were measured after 2, 4, and 12 weeks under regular and high-fat feeding conditions. The total cell number in the epididymal fat pad was estimated from the fat pad mass and the normalized cell-size distribution. The cell number and volume-weighted mean cell size increase as a function of fat pad mass. To address adipose tissue growth precisely, we developed a mathematical model describing the evolution of the adipose cell-size distributions as a function of the increasing fat pad mass, instead of the increasing chronological time. Our model describes the recruitment of new adipose cells and their subsequent development in different strains, and with different diet regimens, with common mechanisms, but with diet-and genetics-dependent model parameters. Compared to the FVB/N strain, the C57BL/6 strain has greater recruitment of small adipose cells. Hyperplasia is enhanced by high-fat diet in a strain-dependent way, suggesting a synergistic interaction between genetics and diet. Moreover, high-fat feeding increases the rate of adipose cell size growth, independent of strain, reflecting the increase in calories requiring storage. Additionally, high-fat diet leads to a dramatic spreading of the size distribution of adipose cells in both strains; this implies an increase in size fluctuations of adipose cells through lipid turnover. C1 [Jo, Junghyo; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Gavrilova, Oksana; Pack, Stephanie; Jou, William] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD USA. [Mullen, Shawn] NIH, GPP OITE OIR OD, Bethesda, MD 20892 USA. [Sumner, Anne E.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. [Cushman, Samuel W.] NIDDK, Diabet Branch, NIH, Bethesda, MD USA. RP Jo, J (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM vipulp@mail.nih.gov RI Jo, Junghyo/D-4889-2011; Periwal, Vipul/I-1728-2012 FU NIH; NIDDK FX This work was supported by funding from the intramural research program of the NIH, NIDDK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 164 Z9 164 U1 3 U2 23 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 MAR PY 2009 VL 5 IS 3 AR e1000324 DI 10.1371/journal.pcbi.1000324 PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 447TF UT WOS:000266214000029 PM 19325873 ER PT J AU Dennis, MY Paracchini, S Scerri, TS Prokunina-Olsson, L Knight, JC Wade-Martins, R Coggill, P Beck, S Green, ED Monaco, AP AF Dennis, Megan Y. Paracchini, Silvia Scerri, Thomas S. Prokunina-Olsson, Ludmila Knight, Julian C. Wade-Martins, Richard Coggill, Penny Beck, Stephan Green, Eric D. Monaco, Anthony P. TI A Common Variant Associated with Dyslexia Reduces Expression of the KIAA0319 Gene SO PLOS GENETICS LA English DT Article ID READING-DISABILITY; DEVELOPMENTAL DYSLEXIA; TRANSCRIPTION FACTOR; NEURONAL MIGRATION; HUMAN GENOME; FUNCTIONAL ELEMENTS; SUSCEPTIBILITY GENE; NUCLEAR-MATRIX; DNA-SEQUENCES; LARGE-SAMPLE AB Numerous genetic association studies have implicated the KIAA0319 gene on human chromosome 6p22 in dyslexia susceptibility. The causative variant(s) remains unknown but may modulate gene expression, given that (1) a dyslexia-associated haplotype has been implicated in the reduced expression of KIAA0319, and (2) the strongest association has been found for the region spanning exon 1 of KIAA0319. Here, we test the hypothesis that variant(s) responsible for reduced KIAA0319 expression resides on the risk haplotype close to the gene's transcription start site. We identified seven single-nucleotide polymorphisms on the risk haplotype immediately upstream of KIAA0319 and determined that three of these are strongly associated with multiple reading-related traits. Using luciferase-expressing constructs containing the KIAA0319 upstream region, we characterized the minimal promoter and additional putative transcriptional regulator regions. This revealed that the minor allele of rs9461045, which shows the strongest association with dyslexia in our sample (max p-value = 0.0001), confers reduced luciferase expression in both neuronal and non-neuronal cell lines. Additionally, we found that the presence of this rs9461045 dyslexia-associated allele creates a nuclear protein-binding site, likely for the transcriptional silencer OCT-1. Knocking down OCT-1 expression in the neuronal cell line SHSY5Y using an siRNA restores KIAA0319 expression from the risk haplotype to nearly that seen from the non-risk haplotype. Our study thus pinpoints a common variant as altering the function of a dyslexia candidate gene and provides an illustrative example of the strategic approach needed to dissect the molecular basis of complex genetic traits. C1 [Dennis, Megan Y.; Paracchini, Silvia; Scerri, Thomas S.; Knight, Julian C.; Monaco, Anthony P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Dennis, Megan Y.; Green, Eric D.] NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. [Prokunina-Olsson, Ludmila] NCI, NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. [Wade-Martins, Richard] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. [Coggill, Penny] Wellcome Trust Sanger Inst, Cambridge, England. [Beck, Stephan] UCL, UCL Canc Inst, London, England. RP Dennis, MY (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM egreen@nhgri.nih.gov; anthony.monaco@well.ox.ac.uk RI Knight, Julian/C-7242-2009; Monaco, Anthony/A-4495-2010; OI Knight, Julian/0000-0002-0377-5536; Monaco, Anthony/0000-0001-7480-3197; Paracchini, Silvia/0000-0001-9934-8602; Prokunina-Olsson, Ludmila/0000-0002-9622-2091 FU Wellcome Trust; Intramural Research Programs of the National Human Genome Research Institute; National Cancer Institute (MPO); NIH/Ox-Cam Graduate Partnership Program (MYD) FX This work was supported by the Wellcome Trust (MYD, SP, TSS, JCK, RWM, PC, SB, and APM), the Intramural Research Programs of the National Human Genome Research Institute (MYD and EDG) and National Cancer Institute (MPO), and the NIH/Ox-Cam Graduate Partnership Program (MYD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 51 Z9 51 U1 1 U2 6 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 MAR PY 2009 VL 5 IS 3 AR e1000436 DI 10.1371/journal.pgen.1000436 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 449GZ UT WOS:000266320100042 PM 19325871 ER PT J AU Nalls, MA Simon-Sanchez, J Gibbs, JR Paisan-Ruiz, C Bras, JT Tanaka, T Matarin, M Scholz, S Weitz, C Harris, TB Ferrucci, L Hardy, J Singleton, AB AF Nalls, Michael A. Simon-Sanchez, Javier Gibbs, J. Raphael Paisan-Ruiz, Coro Bras, Jose Tomas Tanaka, Toshiko Matarin, Mar Scholz, Sonja Weitz, Charles Harris, Tamara B. Ferrucci, Luigi Hardy, John Singleton, Andrew B. TI Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics SO PLOS GENETICS LA English DT Article ID HOMOZYGOSITY; GENOME; SUSCEPTIBILITY; POPULATIONS; DISEASE AB This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19-99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so. C1 [Nalls, Michael A.; Simon-Sanchez, Javier; Gibbs, J. Raphael; Bras, Jose Tomas; Matarin, Mar; Scholz, Sonja; Singleton, Andrew B.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Nalls, Michael A.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Simon-Sanchez, Javier] CSIC, Inst Biomed Valencia, Unidad Genet Mol, Dept Genom & Prote, Valencia, Spain. [Gibbs, J. Raphael; Paisan-Ruiz, Coro; Scholz, Sonja; Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Gibbs, J. Raphael; Paisan-Ruiz, Coro; Scholz, Sonja; Hardy, John] Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Intramural Res Program, Bethesda, MD 20892 USA. [Weitz, Charles] Temple Univ, Dept Anthropol, Biol Anthropol Program, Philadelphia, PA 19122 USA. [Singleton, Andrew B.] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA. RP Nalls, MA (reprint author), NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Paisan-Ruiz, Coro/C-2912-2009; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Gibbs, J. Raphael/A-3984-2010; Bras, Jose/A-1428-2011; Matarin, Mar/F-1771-2016; OI Matarin, Mar/0000-0002-4717-5735; Scholz, Sonja/0000-0002-6623-0429 FU NINDS; National Institute on Aging's Baltimore Longitudinal Study of Aging; National Institute on Aging; National Institutes of Health; Department of Health Human Services [Z01 AG000949-02] FX The samples for this study are derived from the NINDS Neurogenetics repository at Coriell Cell Repositories, supported by an extramural NINDS contract and from the National Institute on Aging's Baltimore Longitudinal Study of Aging. Study design, data collection and analysis, decision to publish, and preparation of the manuscript were primarily carried out by researchers affiliated with the Intramural Program of the National Institute on Aging. This work was supported by the Intramural Program of the National Institute on Aging, National Institutes of Health, Department of Health Human Services; project Z01 AG000949-02. NR 15 TC 41 Z9 42 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2009 VL 5 IS 3 AR e1000415 DI 10.1371/journal.pgen.1000415 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 449GZ UT WOS:000266320100021 PM 19282984 ER PT J AU Van Doninck, K Mandigo, ML Hur, JH Wang, P Guglielmini, J Milinkovitch, MC Lane, WS Meselson, M AF Van Doninck, Karine Mandigo, Morgan L. Hur, Jae H. Wang, Peter Guglielmini, Julien Milinkovitch, Michel C. Lane, William S. Meselson, Matthew TI Phylogenomics of Unusual Histone H2A Variants in Bdelloid Rotifers SO PLOS GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; DEINOCOCCUS-RADIODURANS; DEGENERATE TETRAPLOIDY; PHYLOGENETIC ANALYSIS; MAXIMUM-LIKELIHOOD; IONIZING-RADIATION; TERMINAL TAIL; DNA; SEQUENCE; SELECTION AB Rotifers of Class Bdelloidea are remarkable in having evolved for millions of years, apparently without males and meiosis. In addition, they are unusually resistant to desiccation and ionizing radiation and are able to repair hundreds of radiation-induced DNA double-strand breaks per genome with little effect on viability or reproduction. Because specific histone H2A variants are involved in DSB repair and certain meiotic processes in other eukaryotes, we investigated the histone H2A genes and proteins of two bdelloid species. Genomic libraries were built and probed to identify histone H2A genes in Adineta vaga and Philodina roseola, species representing two different bdelloid families. The expressed H2A proteins were visualized on SDS-PAGE gels and identified by tandem mass spectrometry. We find that neither the core histone H2A, present in nearly all other eukaryotes, nor the H2AX variant, a ubiquitous component of the eukaryotic DSB repair machinery, are present in bdelloid rotifers. Instead, they are replaced by unusual histone H2A variants of higher mass. In contrast, a species of rotifer belonging to the facultatively sexual, desiccation-and radiation-intolerant sister class of bdelloid rotifers, the monogononts, contains a canonical core histone H2A and appears to lack the bdelloid H2A variant genes. Applying phylogenetic tools, we demonstrate that the bdelloid-specific H2A variants arose as distinct lineages from canonical H2A separate from those leading to the H2AX and H2AZ variants. The replacement of core H2A and H2AX in bdelloid rotifers by previously uncharacterized H2A variants with extended carboxy-terminal tails is further evidence for evolutionary diversity within this class of histone H2A genes and may represent adaptation to unusual features specific to bdelloid rotifers. C1 [Van Doninck, Karine] Univ Namur, Dept Biol, Namur, Belgium. [Van Doninck, Karine; Mandigo, Morgan L.; Hur, Jae H.; Wang, Peter; Meselson, Matthew] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Mandigo, Morgan L.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Guglielmini, Julien] Univ Libre Bruxelles, Lab Bacterial Physiol & Genet, Inst Mol Biol & Med, Gosselies, Belgium. [Milinkovitch, Michel C.] Univ Geneva, Lab Artificial & Nat Evolut, Dept Zool & Anim Biol, Geneva, Switzerland. [Lane, William S.] Harvard Univ, Harvard Mass Spectrometry & Prote Resource Lab, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Meselson, Matthew] Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Marine Biol Lab, Woods Hole, MA USA. RP Van Doninck, K (reprint author), Univ Namur, Dept Biol, Namur, Belgium. EM karine.vandoninck@fundp.ac.be; msm@wjh.harvard.edu RI Guglielmini, Julien/E-8029-2011 OI Guglielmini, Julien/0000-0002-8566-1726 FU Belgian American Educational Foundation; Fulbright; U.S. National Science Foundation FX KVD was supported in part by grants from the Belgian American Educational Foundation and the Fulbright. Overall research support was provided by a grant from the U.S. National Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 15 Z9 15 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2009 VL 5 IS 3 AR e1000401 DI 10.1371/journal.pgen.1000401 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 449GZ UT WOS:000266320100007 PM 19266019 ER PT J AU Wilk, JB Chen, TH Gottlieb, DJ Walter, RE Nagle, MW Brandler, BJ Myers, RH Borecki, IB Silverman, EK Weiss, ST O'Connor, GT AF Wilk, Jemma B. Chen, Ting-hsu Gottlieb, Daniel J. Walter, Robert E. Nagle, Michael W. Brandler, Brian J. Myers, Richard H. Borecki, Ingrid B. Silverman, Edwin K. Weiss, Scott T. O'Connor, George T. TI A Genome-Wide Association Study of Pulmonary Function Measures in the Framingham Heart Study SO PLOS GENETICS LA English DT Article ID NATIONAL HEART; SERPINE2 GENE; DISEASE; LUNG; OBSTRUCTION; DESIGN; SCAN; RISK AB The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC) is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV(1)/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV(1)/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09). One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV(1)/FVC (p-value = 2.0e-04). The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV(1)/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV(1) and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV(1)/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation. C1 [Wilk, Jemma B.; Nagle, Michael W.; Brandler, Brian J.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Chen, Ting-hsu; Gottlieb, Daniel J.; Walter, Robert E.; O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Chen, Ting-hsu; Gottlieb, Daniel J.; Walter, Robert E.; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Gottlieb, Daniel J.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Silverman, Edwin K.; Weiss, Scott T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Wilk, JB (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM jwilk@bu.edu OI Walter, Robert/0000-0003-4931-5049; Chen, Ting-hsu/0000-0002-1231-4600; O'Connor, George/0000-0002-6476-3926; Myers, Richard/0000-0002-8365-2674 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Flight Attendant Medical Research Institute (FAMRI); FAMRI; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center FX This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). Drs. Wilk and Walter are each supported by a Young Clinical Scientist Award from the Flight Attendant Medical Research Institute (FAMRI). Genotyping in the Family Heart Study sample was supported by Dr. Wilk's FAMRI award. A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. None of the funding agencies had a role in the analysis or interpretation of the data or in the preparation of the manuscript. NR 29 TC 144 Z9 147 U1 2 U2 15 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 MAR PY 2009 VL 5 IS 3 AR e1000429 DI 10.1371/journal.pgen.1000429 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 449GZ UT WOS:000266320100035 PM 19300500 ER PT J AU Brooks, PJ Enoch, MA Goldman, D Li, TK Yokoyama, A AF Brooks, Philip J. Enoch, Mary-Anne Goldman, David Li, Ting-Kai Yokoyama, Akira TI The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption SO PLOS MEDICINE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ALDEHYDE DEHYDROGENASE-2 GENOTYPES; JAPANESE MEN; GENETIC POLYMORPHISMS; CARCINOGENETIC IMPACT; SALIVARY ACETALDEHYDE; ALDH2; ADH1B; POPULATION; DEFICIENCY C1 [Brooks, Philip J.; Enoch, Mary-Anne; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Yokoyama, Akira] Natl Hosp Org, Kurihama Alcoholism Ctr, Clin Res Unit, Kanagawa, Japan. RP Brooks, PJ (reprint author), NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. EM pjbrooks@mail.nih.gov; a_yokoyama@kurihama1.hosp.go.jp RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS [Z01 AA000083-14] NR 36 TC 127 Z9 130 U1 2 U2 23 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAR PY 2009 VL 6 IS 3 AR e1000050 DI 10.1371/journal.pmed.1000050 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 447TM UT WOS:000266214700012 PM 19320537 ER PT J AU Beaty, BJ Prager, DJ James, AA Jacobs-Lorena, M Miller, LH Law, JH Collins, FH Kafatos, FC AF Beaty, Barry J. Prager, Denis J. James, Anthony A. Jacobs-Lorena, Marcelo Miller, Louis H. Law, John H. Collins, Frank H. Kafatos, Fotis C. TI From Tucson to Genomics and Transgenics: The Vector Biology Network and the Emergence of Modern Vector Biology SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID MOSQUITO ANOPHELES-GAMBIAE; YELLOW-FEVER MOSQUITO; POLYMERASE CHAIN-REACTION; INTEGRATED GENETIC-MAP; AEDES-AEGYPTI; MALARIA VECTOR; SINDBIS-VIRUS; GERMLINE TRANSFORMATION; ENGINEERED RESISTANCE; INNATE IMMUNITY C1 [Beaty, Barry J.; Collins, Frank H.; Kafatos, Fotis C.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Prager, Denis J.] Strateg Consulting Serv, Clyde Pk, MT USA. [James, Anthony A.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. [James, Anthony A.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. [Jacobs-Lorena, Marcelo] Johns Hopkins Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Law, John H.] Univ Arizona, Dept Biochem & Mol Biophys, Tucson, AZ USA. [Law, John H.] Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. [Law, John H.] Univ Georgia, Dept Entomol, Athens, GA 30602 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, London, England. RP Beaty, BJ (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. EM bbeaty@colostate.edu FU The MacArthur Foundation FX This work was supported by The MacArthur Foundation. NR 55 TC 17 Z9 17 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAR PY 2009 VL 3 IS 3 AR e343 DI 10.1371/journal.pntd.0000343 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 438DT UT WOS:000265536800001 PM 19333394 ER PT J AU Dussupt, V Javid, MP Abou-Jaoude, G Jadwin, JA de La Cruz, J Nagashima, K Bouamr, F AF Dussupt, Vincent Javid, Melodi P. Abou-Jaoude, Georges Jadwin, Joshua A. de La Cruz, Jason Nagashima, Kunio Bouamr, Fadila TI The Nucleocapsid Region of HIV-1 Gag Cooperates with the PTAP and LYPXnL Late Domains to Recruit the Cellular Machinery Necessary for Viral Budding SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ESCRT-III RECOGNITION; MURINE LEUKEMIA-VIRUS; LATE ASSEMBLY DOMAIN; ROUS-SARCOMA-VIRUS; YPXL LATE DOMAINS; PARTICLE-PRODUCTION; STRUCTURAL BASIS; PLASMA-MEMBRANE; SORTING COMPLEX AB HIV-1 release is mediated through two motifs in the p6 region of Gag, PTAP and LYPXnL, which recruit cellular proteins Tsg101 and Alix, respectively. The Nucleocapsid region of Gag (NC), which binds the Bro1 domain of Alix, also plays an important role in HIV-1 release, but the underlying mechanism remains unclear. Here we show that the first 202 residues of the Bro1 domain (Bro(i)) are sufficient to bind Gag. Bro(i) interferes with HIV-1 release in an NC-dependent manner and arrests viral budding at the plasma membrane. Similar interrupted budding structures are seen following over-expression of a fragment containing Bro1 with the adjacent V domain (Bro1-V). Although only Bro1-V contains binding determinants for CHMP4, both Bro(i) and Bro1-V inhibited release via both the PTAP/Tsg101 and the LYPXnL/Alix pathways, suggesting that they interfere with a key step in HIV-1 release. Remarkably, we found that over-expression of Bro1 rescued the release of HIV-1 lacking both L domains. This rescue required the N-terminal region of the NC domain in Gag and the CHMP4 binding site in Bro1. Interestingly, release defects due to mutations in NC that prevented Bro1 mediated rescue of virus egress were rescued by providing a link to the ESCRT machinery via Nedd4.2s over-expression. Our data support a model in which NC cooperates with PTAP in the recruitment of cellular proteins necessary for its L domain activity and binds the Bro1-CHMP4 complex required for LYPXnL-mediated budding. C1 [Dussupt, Vincent; Javid, Melodi P.; Abou-Jaoude, Georges; Jadwin, Joshua A.; Bouamr, Fadila] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [de La Cruz, Jason; Nagashima, Kunio] NCI Frederick, SAIC, Frederick, MD USA. RP Dussupt, V (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bouamrf@mail.nih.gov OI Javid, Melodi/0000-0002-8163-6881 FU NIH; NIAID FX This work was supported by the Intramural Research Program of the NIH, NIAID (http://www3.niaid.nih.gov/about/organization/dir/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 75 Z9 77 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAR PY 2009 VL 5 IS 3 AR e1000339 DI 10.1371/journal.ppat.1000339 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 447TZ UT WOS:000266216000019 PM 19282983 ER PT J AU Hong, YH Kim, ES Lillehoj, HS Lillehoj, EP Song, KD AF Hong, Y. H. Kim, E. -S. Lillehoj, H. S. Lillehoj, E. P. Song, K. -D. TI Association of resistance to avian coccidiosis with single nucleotide polymorphisms in the zyxin gene SO POULTRY SCIENCE LA English DT Article DE single nucleotide polymorphism; zyxin; CD4; disease resistance; coccidiosis ID QUANTITATIVE TRAIT LOCI; EXPRESSED SEQUENCE TAGS; EMBRYO CDNA LIBRARY; SALMONELLA-ENTERITIDIS; CANDIDATE GENE; YOUNG CHICKS; DISEASE RESISTANCE; EIMERIA-ACERVULINA; LESION SCORES; E-TENELLA AB Our previous genetic studies demonstrated that resistance to avian coccidiosis is linked with microsatellite markers LEI0071 and LEI0101 on chromosome 1. In this study, the associations between parameters of resistance to coccidiosis and single nucleotide polymorphisms (SNP) in 3 candidate genes located between LEI0071 and LEI0101 [zyxin, CD4, and tumor necrosis factor receptor super family 1A (TNFRSF1A)] were determined. The SNP were genotyped in 24 F(1) generation and 290 F(2) generation animals. No SNP were identified in the TNFRSF1A gene, whereas 10 were located in the zyxin gene and 4 in the CD4 gene. At various times following experimental infection of the F(2) generation with Eimeria maxima, BW, fecal oocyst shedding, and plasma levels of carotenoid, nitrite plus nitrate (NO(2)(-) NO(3)(-)), and interferon-gamma (IFN-gamma) were measured as parameters of resistance. Single marker and haplotype-based tests were applied to determine the associations between the 14 SNP and the parameters of coccidiosis resistance. None of the CD4 SNP were correlated with disease resistance. However, by single marker association, several of the zyxin SNP were significantly associated with carotenoid or NO(2)(-) + NO(3)(-) concentrations. These were the SNP at nucleotide 149 associated with carotenoid at d 3 postinfection ( PI), nucleotide 187 with carotenoid at d 6 and 9 PI, and nucleotide 159 with carotenoid between d 3 and 9 PI. In addition, the zyxin SNP at nucleotide 191 was significantly associated with increased levels of NO(2)(-) + NO(3)(-) at d 3 PI. By haplotype association, the zyxin SNP also were found to be highly associated with NO(2)(-) + NO(3)(-) at d 3 PI and increased IFN-gamma at d 6 PI. These results suggest that zyxin is a candidate gene potentially associated with increased resistance to experimental avian coccidiosis. C1 [Hong, Y. H.; Lillehoj, H. S.] USDA, Anim Parasit Dis Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. [Kim, E. -S.] Univ Wisconsin, Dept Anim Sci, Madison, WI 53706 USA. [Lillehoj, E. P.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. [Song, K. -D.] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Lillehoj, HS (reprint author), USDA, Anim Parasit Dis Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. EM Hyun.Lillehoj@ars.usda.gov FU National Research Initiative of the USDA Cooperative State Research; Education and Extension Service [2004-35204-14798] FX This project was supported, in part, by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service (NRI grant # 2004-35204-14798). NR 41 TC 7 Z9 13 U1 0 U2 2 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD MAR PY 2009 VL 88 IS 3 BP 511 EP 518 DI 10.3382/ps.2008-00344 PG 8 WC Agriculture, Dairy & Animal Science SC Agriculture GA 410FP UT WOS:000263563200008 PM 19211519 ER PT J AU Salinas, CA Koopmeiners, JS Kwon, EM FitzGerald, L Lin, DW Ostrander, EA Feng, ZD Stanford, JL AF Salinas, Claudia A. Koopmeiners, Joseph S. Kwon, Erika M. FitzGerald, Liesel Lin, Daniel W. Ostrander, Elaine A. Feng, Ziding Stanford, Janet L. TI Clinical Utility of Five Genetic Variants for Predicting Prostate Cancer Risk and Mortality SO PROSTATE LA English DT Article DE prostate cancer; 8q24; 17q12; 17q24; screen; genetic ID GENOME-WIDE ASSOCIATION; 8Q24; LOCUS AB BACKGROUND. A recent report suggests that the combination of five single-nucleotide polymorphisms (SNPs) at 8q24, 17q12, 17q24.3 and a family history of the disease may predict risk of prostate cancer. The present study tests the performance of these factors in prediction models for prostate cancer risk and prostate cancer-specific mortality. METHODS. SNP's were genotyped in population-based samples from Caucasians in King County, Washington. Incident cases (n = 1,308), aged 35-74, were compared to age-matched controls (n = 1,266) using logistic regression to estimate odds ratios (OR) associated with genotypes and family history. Cox proportional hazards models estimated hazard ratios for prostate cancer-specific mortality according to genotypes. RESULTS. The combination of SNP genotypes and family history was significantly associated with prostate cancer risk (p(trend) -1.5 x 10(20)), Men with >5 risk factors had an OR of 4.9 (95% CI 1.6-18.5) compared to men with none. However, this combination of factors did not improve the ROC curve after accounting for known risk predictors (i.e., age, serum PSA, family history). Neither the individual nor combined risk factors was associated with prostate cancer-specific mortality. CONCLUSION. Genotypes for five SNPs plus family history are associated with a significant elevation in risk for prostate cancer and may explain Lip to 45% of prostate cancer in our population. However, they do not improve prediction models for assessing who is at risk of getting or dying from the disease, once known risk or prognostic factors are taken into account. Thus, this SNP panel may have limited clinical utility. Prostate 69: 363-372, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. [Salinas, Claudia A.; Stanford, Janet L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Koopmeiners, Joseph S.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Lin, Daniel W.] Univ Washington, Med Ctr, Dept Urol, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, M4-B874 POB 19024, Seattle, WA 98109 USA. EM jstanfor@hfcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [R01 CA56679, R01 CA092579, R01 CA082664]; Pacific Northwest Cancer SPORE Program [1150 CA097186]; Department of Defense [PC061445]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX Grant sponsor National Cancer Institute; Grant numbers: R01 CA56678, R01 CA092579, R01 CA082664; Grant sponsor: Pacific Northwest Cancer SPORE Program; Grant number: 1150 CA097186; Grant sponsor: Department of Defense; Grant number: PC061445; Grant sponsor: Fred Hutchinson Cancer Research Center; Grant sponsor: National Human Genome Research Institute. NR 29 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 0270-4137 J9 PROSTATE JI Prostate PD MAR 1 PY 2009 VL 69 IS 4 BP 363 EP 372 DI 10.1002/pros.20887 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 410AC UT WOS:000263546000004 PM 19058137 ER PT J AU Zhang, D Tozser, J Waugh, DS AF Zhang, Di Tozser, Jozsef Waugh, David S. TI Molecular cloning, overproduction, purification and biochemical characterization of the p39 nsp2 protease domains encoded by three alphaviruses SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Protease; Affinity tag; Fusion protein; Maltose-binding protein; Venezuelan equine encephalitis virus; Sindbis virus; Semliki forest virus; Nonstructural protein 2 ID MALTOSE-BINDING PROTEIN; ETCH VIRUS PROTEASE; ESCHERICHIA-COLI; SINDBIS VIRUS; NONSTRUCTURAL PROTEINASE; SUBSTRATE-SPECIFICITY; CYSTEINE PROTEASE; IN-VITRO; SEMLIKI; POLYPROTEIN AB Alphaviruses cause serious diseases that pose a potential health threat to both humans and livestock. The nonstructural protein 2 (nsp2) encoded by alphaviruses is a multifunctional enzyme that is essential for viral replication and maturation. Its 39-kDa C-terminal domain (nsp2pro) is a cysteine protease that is responsible for cleaving a viral polyprotein at three sites to generate nonstructural proteins 1, 2, 3 and 4. In the present study, we evaluated nsp2pro domains from the following three sources as reagents for site-specific cleavage of fusion proteins: Venezuelan Equine Encephalitis Virus (VEEV), Semliki Forest Virus (SFV) and Sindbis Virus (SIN). All three alphavirus proteases cleaved model fusion protein substrates with high specificity but they were much less efficient enzymes than potyviral proteases from tobacco etch virus (TEV) and tobacco vein mottling virus (TVMV). Oligopeptide substrates were also cleaved with very low efficiency by the alphavirus proteases. We conclude that, in general, alphavirus nsp2pro proteases are not very useful tools for the removal of affinity tags from recombinant proteins although they do remain promising therapeutic targets for the treatment of a variety of diseases. Published by Elsevier Inc. C1 [Zhang, Di; Waugh, David S.] NCI, Ctr Canc Res, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Tozser, Jozsef] Univ Debrecen, Dept Biochem & Mol Biol, Fac Med, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. RP Waugh, DS (reprint author), NCI, Ctr Canc Res, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU NIH FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Scott Cherry for technical assistance, the SAIC-Frederick Protein Chemistry Laboratory for assistance with N-terminal amino acid sequencing and Beata Bozoki for help in peptide assays. Electrospray mass spectrometry experiments were conducted on the LC/ESMS instrument maintained by the Biophysics Resource in the Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, while amino acid analysis and MALDI MS measurements for peptides were performed in the Food Science and Quality Assurance Laboratory and Proteomics Core Facility of the Debrecen University, respectively. NR 40 TC 13 Z9 13 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 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAR PY 2009 VL 64 IS 1 BP 89 EP 97 DI 10.1016/j.pep.2008.10.013 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 399KR UT WOS:000262799300013 PM 19013248 ER PT J AU Duncan, MW Yergey, AL Patterson, SD AF Duncan, Mark W. Yergey, Alfred L. Patterson, Scott D. TI Quantifying proteins by mass spectrometry: The selectivity of SRM is only part of the problem SO PROTEOMICS LA English DT Article DE Mass spectrometry; Protein quantification; Selected reaction monitoring ID ALTERED GLYCOSYLATION; PHOSPHORYLATION; DISEASE; CANCER; GLYCOPROTEIN; EXPRESSION; FLUID AB Precise and accurate protein quantification is critical to many areas of proteomics. Antibody-based approaches are costly and time-consuming to develop, consequently, there is considerable interest in alternative quantitative methods that are versatile and can be implemented without the considerable delays associated with antibody development and characterization. Approaches based on MS have therefore attracted considerable attention and are now frequently touted as the most practical and powerful of all options. Nevertheless, there are serious limitations associated with quantifying a protein based on tandem mass analysis of one or two peptides generated by either chemical or enzymatic cleavage. In an accompanying Viewpoint article, Molloy and co-workers point out that selectivity is not necessarily guaranteed despite the power of SRM. Here we address an additional concern that can also compromise specificity. In complex mammalian systems, multiple proteins can serve as precursors of a single peptide and consequently, depending on the peptide(s) selected, protein levels may be significantly under- or overestimated. C1 [Duncan, Mark W.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Duncan, Mark W.] Biodesix Inc, Broomfield, CO USA. [Duncan, Mark W.] King Saud Univ, Obes Res Ctr, Riyadh, Saudi Arabia. [Yergey, Alfred L.] NICHHD, NIH, Bethesda, MD 20892 USA. [Patterson, Scott D.] Amgen Inc, Mol Sci, Thousand Oaks, CA 91320 USA. RP Duncan, MW (reprint author), Univ Colorado, Sch Med, Aurora, CO 80045 USA. EM mark.duncan@ucdenver.edu FU Intramural NIH HHS [ZIC HD001421-13] NR 25 TC 57 Z9 57 U1 1 U2 7 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 MAR PY 2009 VL 9 IS 5 BP 1124 EP 1127 DI 10.1002/pmic.200800739 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426GL UT WOS:000264695900002 PM 19253279 ER PT J AU Seliger, B Dressler, SP Wang, E Kellner, R Recktenwald, CV Lottspeich, F Marincola, FM Baumgartner, M Atkins, D Lichtenfels, R AF Seliger, Barbara Dressler, Sven P. Wang, Ena Kellner, Roland Recktenwald, Christian V. Lottspeich, Friedrich Marincola, Francesco M. Baumgaertner, Maja Atkins, Derek Lichtenfels, Rudolf TI Combined analysis of transcriptome and proteome data as a tool for the identification of candidate biomarkers in renal cell carcinoma SO PROTEOMICS LA English DT Article DE Biomarkers; Proteome-based technologies; RCC; Transcriptomics ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; ALPHA-ENOLASE; GENE-EXPRESSION; TUMOR CLASSIFICATION; RNA AMPLIFICATION; ANNEXIN A3; CANCER; ANTIGEN; MICROARRAY; MARKERS AB Results obtained from expression profilings of renal cell carcinoma using different "ome"-based approaches and comprehensive data analysis demonstrated that proteome-based technologies and cDNA microarray analyses complement each other during the discovery phase for disease-related candidate biomarkers. The integration of the respective data revealed the uniqueness and complementarities of the different technologies. While comparative cDNA microarray analyses though restricted to up-regulated targets largely revealed genes involved in controlling gene/protein expression (19%) and signal transduction processes (13%), proteomics/PROTEOMEX-defined candidate biomarkers include enzymes of the cellular metabolism (36%), transport proteins (12%), and cell motility/structural molecules (10%). Candidate biomarkers defined by proteomics and PROTEOMEX are frequently shared, whereas the sharing rate between cDNA microarray and proteome-based profilings is limited. Putative candidate biomarkers provide insights into their cellular (dys)function and their diagnostic/prognostic value but still warrant further validation in larger patient numbers. Based on the fact that merely three candidate biomarkers were shared by all applied technologies, namely annexin A4, tubulin alpha-1A chain, and ubiquitin carboxyl-terminal hydrolase L1, the analysis at a single hierarchical level of biological regulation seems to provide only limited results thus emphasizing the importance and benefit of performing rather combinatorial screenings which can complement the standard clinical predictors. C1 [Seliger, Barbara; Dressler, Sven P.; Recktenwald, Christian V.; Baumgaertner, Maja; Lichtenfels, Rudolf] Univ Halle Wittenberg, Inst Med Immunol, D-06112 Halle, Germany. [Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Kellner, Roland] Merck KGaA, Dept Biotechnol & Prot Chem, Darmstadt, Germany. [Lottspeich, Friedrich] Max Planck Inst Biochem, D-82152 Martinsried, Germany. [Atkins, Derek] Univ Witten Herdecke, Inst Pathol, Wuppertal, Germany. RP Seliger, B (reprint author), Univ Halle Wittenberg, Inst Med Immunol, Magdeburger Str 2, D-06112 Halle, Germany. EM barbara.seliger@medizin.uni-halle.de FU BMBF [031U101H]; NGFN [0313376]; Martin-Luther-University Halle-Wittenberg [FKZ 16130] FX We would like to thank C. Stoerr and A. Wasilewski for excellent secretarial help. This work represents part of the PhD thesis of Sven Dressler. This work was funded by the BMBF (BMBF project 031U101H (B. S.)), NGFN II EP grant 0313376 (B. S), and the Roux program of the Martin-Luther-University Halle-Wittenberg (FKZ 16130) (M. B.). NR 60 TC 25 Z9 25 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAR PY 2009 VL 9 IS 6 BP 1567 EP 1581 DI 10.1002/pmic.200700288 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 428ZK UT WOS:000264890400015 PM 19235166 ER PT J AU Riley, AW Coiro, MJ Broitman, M Colantuoni, E Hurley, KM Bandeen-Roche, K Miranda, J AF Riley, Anne W. Coiro, Mary Jo Broitman, Marina Colantuoni, Elizabeth Hurley, Kristen M. Bandeen-Roche, Karen Miranda, Jeanne TI Mental Health of Children of Low-Income Depressed Mothers: Influences of Parenting, Family Environment, and Raters SO PSYCHIATRIC SERVICES LA English DT Article ID GENERALIZED LINEAR-MODELS; MATERNAL DEPRESSION; YOUNG-CHILDREN; PSYCHOLOGICAL ADJUSTMENT; BEHAVIOR PROBLEMS; CONTROLLED-TRIAL; PRIMARY-CARE; CHILDHOOD; RISK; PSYCHOPATHOLOGY AB Objective: This study examined the association of maternal depression with the emotional and behavioral problems and adaptive skills of four-to ten-year-old children as rated by their mothers, fathers, and teachers. Methods: Eighty-four mothers had major depressive disorder, and 49 did not. They were predominantly African American or Latino and lived in low-income, urban communities. Mothers, fathers, and teachers reported on children's emotional and behavioral problems and adaptive functioning. Parenting behavior and family stress were examined as potential mediators, and generalized estimating equations were used to test mediation and to account for discrepancies in reports by different raters. Results: According to the combined reports, children of mothers with depression had significantly poorer adaptive skills than children of sociodemographically similar mothers without depression; according to the reports of mothers and fathers, these children also had more emotional and behavioral problems. The quality of mothers' parenting mediated these associations, but measured family stressors did not. Conclusions: This study contributes to the scientific literature by demonstrating the effects of raters and testing mediators of maternal depression in low-income African-American and Latino families. It demonstrated that mothers, fathers, and teachers observed worse functioning among children of mothers with depression than without depression, although reporters' perspectives varied somewhat. The impact of maternal depression over and above that of poverty suggests the importance of developing and funding services to address the needs of affected families. (Psychiatric Services 60: 329-336,2009) C1 [Riley, Anne W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA. [Colantuoni, Elizabeth; Bandeen-Roche, Karen] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Coiro, Mary Jo] Loyola Coll, Dept Psychol, Baltimore, MD 21210 USA. [Broitman, Marina] NIMH, Bethesda, MD 20892 USA. [Hurley, Kristen M.] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Miranda, Jeanne] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Riley, AW (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, 615 N Wolfe St,E4539, Baltimore, MD 21205 USA. EM ariley@jhsph.edu FU National Institute of Mental Health [MH-58384, MH-56864] FX This research was supported by grants MH-58384 to Dr. Riley and MH-56864 to Dr. Miranda from the National Institute of Mental Health. The authors thank the families and many clinic staff who participated in this project and acknowledge the analytic assistance of Maureen Keefer, Judy Robertson, and Carrie Mills. This work was not conducted as part of Dr. Broitman's official duties as a U. S. government employee.; The authors report no competing interests. NR 63 TC 37 Z9 38 U1 5 U2 14 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2009 VL 60 IS 3 BP 329 EP 336 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 412KL UT WOS:000263723600008 PM 19252045 ER PT J AU Dolbeault, S Blay, JY Eisinger, F Pivot, X Morere, J Calazel-Benque, A Cals, L Coscas, Y Namer, M Rixe, O Roussel, C Serin, D Viguier, J AF Dolbeault, S. Blay, J. Y. Eisinger, F. Pivot, X. Morere, J. F. Calazel-Benque, A. Cals, L. Coscas, Y. Namer, M. Rixe, O. Roussel, C. Serin, D. Viguier, J. TI 25(th) Congress of the SFPO "Cancers, cultures and practices of care". Paris on 28 November 2008-Brakes and motivations in the screening of breast cancer: what typological profiles? Results from the EDIFICE survey SO PSYCHO-ONCOLOGIE LA French DT Editorial Material ID WOMEN C1 [Dolbeault, S.] Inst Curie, Paris, France. [Dolbeault, S.] INSERM, U 669, Paris, France. [Dolbeault, S.] UMR S0669, Paris, France. [Blay, J. Y.] INSERM, U590, Ctr Leon Berard, UJOMM HEH & Conticanet,FP6 018806, F-69373 Lyon, France. [Eisinger, F.] Inst J Paoli I Calmettes, F-13009 Marseille, France. [Eisinger, F.] INSERM, U599, F-13009 Marseille, France. [Pivot, X.] CHU Minjoz, F-25030 Besancon, France. [Morere, J. F.] CHU Avicenne, F-93000 Bobigny, France. [Calazel-Benque, A.] Clin Parc, F-31400 Toulouse, France. [Cals, L.] Hop Font Pre, F-83100 Toulon, France. [Namer, M.] Ctr Azureen Cancerol, F-06250 Mougins, France. [Rixe, O.] NCI, Bethesda, MD 20892 USA. [Roussel, C.] Lab Roche, F-92000 Neuilly Sur Seine, France. [Serin, D.] Inst St Catherine, F-84000 Avignon, France. [Viguier, J.] CHRU Trousseau, Tours, France. [Coscas, Y.] Clin Porte St Cloud, F-92100 Boulogne, France. RP Dolbeault, S (reprint author), Inst Curie, Paris, France. EM sylvie.dolbeault@curie.net RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 14 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1778-3798 J9 PSYCHO-ONCOLOGIE JI Psycho-Oncologie PD MAR PY 2009 VL 3 IS 1 BP 60 EP 62 DI 10.1007/s11839-009-0117-1 PG 3 WC Oncology; Psychology SC Oncology; Psychology GA 433OZ UT WOS:000265216300012 ER PT J AU Fowler, KA Lilienfeld, SO Patrick, CJ AF Fowler, Katherine A. Lilienfeld, Scott O. Patrick, Christopher J. TI Detecting Psychopathy From Thin Slices of Behavior SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE thin slices; psychopathy; personality disorders; assessment ID PERSONALITY-TRAITS; PHYSICAL ATTRACTIVENESS; PRELIMINARY VALIDATION; EXPRESSIVE BEHAVIOR; NONVERBAL BEHAVIOR; ZERO-ACQUAINTANCE; VALIDITY; PERCEPTION; DISORDERS; INVENTORY AB This study is the first to demonstrate that features of psychopathy can be reliably and validly detected by lay raters from "thin slices" (i.e., small samples) of behavior. Brief excerpts (5 s, 10 s, and 20 s) from interviews with 96 maximum-security inmates were presented in video or audio form or in both modalities combined. Forty raters used these excerpts to complete assessments of overall psychopathy and its Factor 1 and Factor 2 components, various personality disorders, violence proneness, and attractiveness. Thin-slice ratings of psychopathy correlated moderately and significantly with psychopathy criterion measures, especially those related to interpersonal features of psychopathy, particularly in the 5- and 10-s excerpt conditions and in the video and combined channel conditions. These findings demonstrate that first impressions of psychopathy and related constructs, particularly those pertaining to interpersonal functioning, can be reasonably reliable and valid. They also raise intriguing questions regarding how individuals form first impressions and about the extent to which first impressions may influence the assessment of personality disorders. C1 [Fowler, Katherine A.; Lilienfeld, Scott O.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Patrick, Christopher J.] Univ Minnesota, Minneapolis, MN 55455 USA. RP Fowler, KA (reprint author), NIMH, Mood & Anxiety Program, NIH, 15 K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM fowlerka@mail.nih.gov NR 54 TC 35 Z9 35 U1 3 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 2009 VL 21 IS 1 BP 68 EP 78 DI 10.1037/a0014938 PG 11 WC Psychology, Clinical SC Psychology GA 481UR UT WOS:000268838000006 PM 19290767 ER PT J AU Levy, BR Zonderman, AB Slade, MD Ferrucci, L AF Levy, Becca R. Zonderman, Alan B. Slade, Martin D. Ferrucci, Luigi TI Age Stereotypes Held Earlier in Life Predict Cardiovascular Events in Later Life SO PSYCHOLOGICAL SCIENCE LA English DT Article ID SELF-PERCEPTIONS C1 [Levy, Becca R.; Slade, Martin D.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Zonderman, Alan B.; Ferrucci, Luigi] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Levy, BR (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM becca.levy@yale.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the National Institute on Aging; Patrick and Catherine Weldon Donaghue Medical Research Foundation Investigator Award; National Institute of Heart, Lung and Blood [R01HL089314] FX This research was supported by the Intramural Research Program of the National Institute on Aging, and by a Patrick and Catherine Weldon Donaghue Medical Research Foundation Investigator Award and a National Institute of Heart, Lung and Blood grant (R01HL089314) to the first author. NR 10 TC 77 Z9 78 U1 2 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD MAR PY 2009 VL 20 IS 3 BP 296 EP 298 DI 10.1111/j.1467-9280.2009.02298.x PG 3 WC Psychology, Multidisciplinary SC Psychology GA 415WM UT WOS:000263967200007 PM 19222809 ER PT J AU Gao, ZG Teng, B Wu, HT Joshi, BV Griffiths, GL Jacobson, KA AF Gao, Zhan-Guo Teng, Bao Wu, Haitao Joshi, Bhalchandra V. Griffiths, Gary L. Jacobson, Kenneth A. TI Synthesis and pharmacological characterization of [I-125]MRS1898, a high-affinity, selective radioligand for the rat A(3) adenosine receptor SO PURINERGIC SIGNALLING LA English DT Article; Proceedings Paper CT 8th International Symposium on Adenosine and Adenine Nucleotides CY 2006 CL Ferrara, ITALY DE Iodination; G protein-coupled receptor; Binding assay; Purine; Nucleoside; Carbocyclic ID CELL-LINES; AGONISTS; LIGANDS; NUCLEOSIDES; POTENT; DERIVATIVES; INHIBITION; TUMOR AB A known selective agonist of the A(3) adenosine receptors (AR), MRS1898 [(1'R,2'R,3'S,4'R,5'S)-4-{2-chloro-6-[(3-iodophenylmethyl)amino]purin-9-yl}-1-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2,3-diol], was synthesized in radioactive form and characterized pharmacologically. This agonist ligand series, based on nucleoside analogues containing a rigid, bicyclic ring system in place of the ribose moiety, was selected for radiolabeling due to its high A(3)AR affinity across species, with nanomolar binding at both rat and human A(3)ARs. The radioiodination of MRS1898 on its N (6)-3-iodobenzyl substituent was accomplished in 76% radiochemical yield by iododestannylation of a 3-(trimethylstannyl)benzyl precursor. [I-125]MRS1898 bound to the rat A(3)AR with a K-d value of 0.17 +/- 0.04 nM and a B-max value of 0.66 +/- 0.15 pmol/mg protein. The competition binding profiles for other agonists and antagonists obtained with this radioligand are similar to those previously obtained with other radioligands. The advantages of [I-125]MRS1898 compared with previously used radioligands are primarily its high selectivity and affinity for the rat A(3)AR and also its facile synthesis and radiochemical stability; however, a relatively high level of nonspecific binding presents a limitation. Thus, we have introduced the first selective radioligand for the rat A(3)AR. C1 [Gao, Zhan-Guo; Joshi, Bhalchandra V.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Teng, Bao; Wu, Haitao; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 21 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 J9 PURINERG SIGNAL JI Purinergic Signal. PD MAR PY 2009 VL 5 IS 1 BP 31 EP 37 DI 10.1007/s11302-008-9107-1 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407UN UT WOS:000263389900004 PM 18528782 ER PT J AU Kim, Y Klutz, AM Hechler, B Gao, ZG Gachet, C Jacobson, K AF Kim, Yoonkyung Klutz, Athena M. Hechler, Beatrice Gao, Zhan-Guo Gachet, Christian Jacobson, Kenneth A. TI Application of the functionalized congener approach to dendrimer-based signaling agents acting through A(2A) adenosine receptors SO PURINERGIC SIGNALLING LA English DT Article; Proceedings Paper CT 8th International Symposium on Adenosine and Adenine Nucleotides CY 2006 CL Ferrara, ITALY DE A(2A) adenosine receptors; Dendrimers; Functionalized congeners; G protein-coupled receptors.; Antithrombotic; Nanotechnology ID PROTEIN-COUPLED RECEPTORS; BIOMEDICAL APPLICATIONS; PAMAM DENDRIMERS; POLY(AMIDOAMINE) DENDRIMERS; POLYAMIDOAMINE DENDRIMERS; INTERNATIONAL UNION; IN-VITRO; CYTOTOXICITY; BIODISTRIBUTION; NOMENCLATURE AB As a continued effort to develop multivalent ligands to enhance the pharmacological effects of monomeric drugs, DITC-APEC, a chemically reactive nucleoside A(2A) adenosine receptor (AR) agonist, was employed to derivatize the surface of third-generation (G3) polyamidoamine (PAMAM) dendrimers. The resulting conjugates carried multiple copies of the agonist attached through a thiourea linkage and differed in the number of attachments and in the presence of a fluorophore or additional surface modification. Computer modeling studies suggested that these DITC-APEC-loaded dendrimers extended the overall diameter of the previously reported PAMAM-CGS21680 dendrimer derivatives (Kim et al., Bioconjugate Chem 2008 19:406-411) by ca. 20 A..., potentially increasing the conformational flexibility of the appended ligands to achieve optimal geometry for efficient binding at A(2A) ARs. Increased affinity and selectivity in binding in comparison to the CGS21680 conjugate were envisioned, due to the presence of an extended linker, i.e., a dithioureylenephenyl functionality. In vitro radioligand competition experiments showed effective binding of these PAMAM-DITC-APEC dendrimer conjugates at the human A(2A) and A(3) ARs with submicromolar K (i) values and selectivity in comparison to the human A(1) AR. Furthermore, these nucleoside-loaded dendrimers exhibited an A(2A) AR-mediated inhibitory effect on ADP-induced aggregation of human platelets. The present study demonstrates the potential of applying the functionalized congener concept to engineer dendrimer-based multivalent ligands for G protein-coupled receptors. C1 [Kim, Yoonkyung; Klutz, Athena M.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Hechler, Beatrice; Gachet, Christian] INSERM, U 311, Strasbourg, France. [Hechler, Beatrice; Gachet, Christian] EFS Alsace, Strasbourg, France. [Hechler, Beatrice; Gachet, Christian] Univ Strasbourg, Strasbourg, France. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Hechler, Beatrice/D-4227-2017; Gachet, Christian/H-9156-2016 OI Jacobson, Kenneth/0000-0001-8104-1493; NR 36 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD MAR PY 2009 VL 5 IS 1 BP 39 EP 50 DI 10.1007/s11302-008-9113-3 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407UN UT WOS:000263389900005 PM 18600474 ER PT J AU Jacobson, KA Ivanov, AA de Castro, S Harden, TK Ko, HJ AF Jacobson, Kenneth A. Ivanov, Andrei A. de Castro, Sonia Harden, T. Kendall Ko, Hyojin TI Development of selective agonists and antagonists of P2Y receptors SO PURINERGIC SIGNALLING LA English DT Article CT 8th International Symposium on Adenosine and Adenine Nucleotides CY 2006 CL Ferrara, ITALY DE Nucleotide; Purine; Pyrimidine; G protein-coupled receptor; Structure activity relationship ID P2Y(11) PURINERGIC RECEPTOR; NUCLEOTIDE RECEPTORS; PHARMACOLOGICAL CHARACTERIZATION; BIOLOGICAL-ACTIVITY; PHOSPHOLIPASE-C; HUMAN PLATELETS; P-2Y-PURINOCEPTOR AGONISTS; ADENINE-NUCLEOTIDES; POTENT ANTAGONISTS; CYSTIC-FIBROSIS AB Although elucidation of the medicinal chemistry of agonists and antagonists of the P2Y receptors has lagged behind that of many other members of group A G protein-coupled receptors, detailed qualitative and quantitative structure-activity relationships (SARs) were recently constructed for several of the subtypes. Agonists selective for P2Y(1), P2Y(2), and P2Y(6) receptors and nucleotide antagonists selective for P2Y(1) and P2Y(12) receptors are now known. Selective nonnucleotide antagonists were reported for P2Y(1), P2Y(2), P2Y(6), P2Y(11), P2Y(12), and P2Y(13) receptors. At the P2Y(1) and P2Y(12) receptors, nucleotide agonists (5'-diphosphate derivatives) were converted into antagonists of nanomolar affinity by altering the phosphate moieties, with a focus particularly on the ribose conformation and substitution pattern. Nucleotide analogues with conformationally constrained ribose-like rings were introduced as selective receptor probes for P2Y(1) and P2Y(6) receptors. Screening chemically diverse compound libraries has begun to yield new lead compounds for the development of P2Y receptor antagonists, such as competitive P2Y(12) receptor antagonists with antithrombotic activity. Selective agonists for the P2Y(4), P2Y(11), and P2Y(13) receptors and selective antagonists for P2Y(4) and P2Y(14) receptors have not yet been identified. The P2Y(14) receptor appears to be the most restrictive of the class with respect to modification of the nucleobase, ribose, and phosphate moieties. The continuing process of ligand design for the P2Y receptors will aid in the identification of new clinical targets. C1 [Jacobson, Kenneth A.; Ivanov, Andrei A.; de Castro, Sonia; Ko, Hyojin] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. [Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD USA. EM kajacobs@helix.nih.gov RI de castro, sonia/E-7303-2012; Jacobson, Kenneth/A-1530-2009 OI de castro, sonia/0000-0002-3838-6856; Jacobson, Kenneth/0000-0001-8104-1493 NR 89 TC 52 Z9 54 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 J9 PURINERG SIGNAL JI Purinergic Signal. PD MAR PY 2009 VL 5 IS 1 BP 75 EP 89 DI 10.1007/s11302-008-9106-2 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407UN UT WOS:000263389900008 PM 18600475 ER PT J AU Clark, EAS AF Clark, Erin A. S. TI Association of Repeated Dose Antenatal Steroids and IL6-174 Genotype with Neurodevelopemental Outcomes at Age 2. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Clark, Erin A. S.] MF MU Network, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 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 MAR PY 2009 VL 16 IS 3 MA 19 BP 74A EP 74A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609800020 ER PT J AU Gyamfi, C Shriver, EK AF Gyamfi, Cynthia Shriver, Eunice K. TI The Rate of Recurrent Preterm Birth Analyzed by Indication for Prior Spontaneous Preterm Birth SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Gyamfi, Cynthia; Shriver, Eunice K.] NICHD, MFMU 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 MAR PY 2009 VL 16 IS 3 MA 54 BP 84A EP 84A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609800055 ER PT J AU Caritis, SN Sharma, S Zhang, S Miodovnik, M Hankins, GDV Hebert, M Mattison, DR Venkataramanan, R AF Caritis, Steve N. Sharma, Shringi Zhang, Shimin Miodovnik, Menachem Hankins, Gary D. V. Hebert, Mary Mattison, Donald R. Venkataramanan, Raman TI Pharmacokinetics (PK) of 17-Hydroxyprogesterone Caproate (17-OHPC) in Singleton Gestation SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Caritis, Steve N.; Sharma, Shringi; Zhang, Shimin; Venkataramanan, Raman] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Miodovnik, Menachem] Washington Hosp Ctr, Washington, DC 20010 USA. [Miodovnik, Menachem] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Hankins, Gary D. V.] Univ Texas Med Branch, Galveston, TX USA. [Hebert, Mary] Univ Washington, Seattle, WA 98195 USA. [Mattison, Donald R.] Obstetr Fetal Pharmacol Res Units Network, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 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 MAR PY 2009 VL 16 IS 3 MA 58 BP 85A EP 85A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609800059 ER EF