FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Michelin, R Frederick, L Williams, A Lowe, H Kinyua, A Shaw, R Lobban, K Johnson, C Leitner, W Pramanik, S Bronner, Y Joubert, A Stewart, J AF Michelin, Ruel Frederick, Lafayette Williams, Arthur Lowe, Henry Kinyua, Antony Shaw, Roosevelt Lobban, Kathleen Johnson, Cynthia Leitner, Wolfgang Pramanik, Soroj Bronner, Yvonne Joubert, Ava Stewart, Juarine TI Recently identified Bacillus species producer of potent nematocidal compounds SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Morgan State Univ, Baltimore, MD 21239 USA. Howard Univ, Washington, DC 20059 USA. Univ W Indies, Kingston, Jamaica. Tech Univ, UWI, Kingston, Jamaica. Tai Sophia Sch Healing Ats, Laurel, MD USA. Natl Inst Hlth, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 1105 BP 320 EP 320 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343901540 ER PT J AU Singh, UB Bhanu, NV Suresh, VN Arora, J Rana, T Seth, P AF Singh, Urvashi B. Bhanu, N. Vijaya Suresh, V. Naga Arora, Jyoti Rana, Tanu Seth, Pradeep TI Utility of polymerase chain reaction in diagnosis of tuberculosis from samples of bone marrow aspirate SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NUCLEIC-ACID AMPLIFICATION; MYCOBACTERIUM-TUBERCULOSIS; MILIARY TUBERCULOSIS; RAPID DIAGNOSIS; UNKNOWN ORIGIN; INFECTIONS; COMPLEX; DNA; SPECIMENS; CULTURE AB Fever of unknown origin (FUO) poses a diagnostic challenge to the clinicians, with a differential diagnosis as varied as neoplastic and infectious diseases. In developing countries, the infectious causes are responsible for more cases of FUO, with tuberculosis as one of the main causes of classic FUO. Disseminated tuberculosis with negative pulmonary findings is a diagnostic problem. This study examines the diagnostic utility of the polymerase chain reaction (PCR) in samples of bone marrow aspirate in 85 patients presenting with diverse clinical symptoms. Using primers specific for Mycobacterium tuberculosis, tubercular etiology was detected in 33% of patients clinically suspected of tuberculosis while culture on Lowenstein-Jensen medium grew M. tuberculosis in only one patient (2.5%). None of these patients had been diagnosed by microscopy. Clinical improvement with ATT was observed in 85% of the patients with positive PCR. PCR demonstrated much higher sensitivity and specificity, thereby facilitating early therapeutic decisions for suspected extrapulmonary tuberculosis. C1 All India Inst Med Sci, Dept Microbiol, New Delhi 110029, India. NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. RP Singh, UB (reprint author), All India Inst Med Sci, Dept Microbiol, New Delhi 110029, India. EM urvashi00@hotmail.com; BhanuN@intra.niddk.nih.gov; vnsuresh@hotmail.com; mailjyoti09@yahoo.co.in; tanurana@gmail.com; sethpradeep@hotmail.com RI Veerapu, Naga Suresh/F-4338-2011 NR 36 TC 14 Z9 15 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 BP 960 EP 963 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 107RQ UT WOS:000242189100034 PM 17123996 ER PT J AU Griffith, DC Kelly-Hope, LA Miller, MA AF Griffith, David C. Kelly-Hope, Louise A. Miller, Mark A. TI Review of reported cholera outbreaks worldwide, 1995-2005 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Review ID EPIDEMIC CHOLERA; RISK-FACTORS; HEALTH AB The global temporal and spatial distribution of cholera is underappreciated, given the lack of surveillance in endemic areas and economic disincentives to report outbreaks. To judge the use of specific novel interventions such as vaccines or anti-secretory agents, we compiled a database and analyzed cholera reports from the Program for Monitoring Emerging Diseases from 1995 to 2005. Of the 632 reports meeting the search criteria, 66% originated in Sub-Saharan Africa, followed by 16.8% from Southeast Asia. Reported outbreaks in Africa tended to be larger in size. The most common risk factors were water source contamination, heavy rainfall and flooding, and population dislocation. While cholera reporting is sub-optimal, this review provides a detailed sub-national quantification of cholera, identifies foci of endemicity in Africa, and describes risk factors by region. We highlight the need for more extensive outbreak reporting to justify investments in new interventions. C1 NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA. RP Miller, MA (reprint author), NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, 16 Ctr Dr, Bethesda, MD 20892 USA. EM millermark@nih.gov NR 14 TC 105 Z9 110 U1 0 U2 7 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 NOV PY 2006 VL 75 IS 5 BP 973 EP 977 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 107RQ UT WOS:000242189100037 PM 17123999 ER PT J AU Bodar, EJ Van der Hilst, JC Drenth, JP Van der Meer, JW Simon, A AF Bodar, E. J. Van der Hilst, J. C. Drenth, J. P. Van der Meer, J. W. Simon, A. TI Patients with AA amyloidosis have a higher monocytic cathepsin B : D ratio SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Meeting Abstract CT 11th International Symposium on Amyloidosis CY NOV 05-09, 2006 CL Woods Hole, MA C1 Univ Nijmegen, Med Ctr, Gastroenterol Radboud, Nijmegen, Netherlands. NIH, NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. RI Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD NOV PY 2006 VL 13 SU 1 BP 20 EP 20 PG 1 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 110WL UT WOS:000242411900041 ER PT J AU Van der Hilst, JC Bodar, EJ Drenth, JP Van der Meer, JW Simon, A AF Van der Hilst, J. C. Bodar, E. J. Drenth, J. P. Van der Meer, J. W. Simon, A. TI AL amyloidosis enhances development of AA amyloidosis SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Meeting Abstract CT 11th International Symposium on Amyloidosis CY NOV 05-09, 2006 CL Woods Hole, MA C1 Dept Gen Internal Med, Nijmegen, Netherlands. Radboud Univ Nijmegen, Gastroenterol, Nijmegen Med Ctr, Nijmegen, Netherlands. NIH, Natl Inst Arthritis & Musculoskeletal & Skin Dis, Genet & Genom Branch, Bethesda, MD USA. RI Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD NOV PY 2006 VL 13 SU 1 BP 65 EP 65 PG 1 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 110WL UT WOS:000242411900171 ER PT J AU Van Gameren, II Hazenberg, BPC Bijzet, J Brouwer, E Posthumus, MD Van Rijswijk, MH AF Van Gameren, I. I. Hazenberg, B. P. C. Bijzet, J. Brouwer, E. Posthumus, M. D. Van Rijswijk, M. H. TI Semi-quantitative assessment of amyloid in Congo red-stained subcutaneous abdominal fat tissue in systemic amyloidosis and disease severity SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Meeting Abstract CT 11th International Symposium on Amyloidosis CY NOV 05-09, 2006 CL Woods Hole, MA C1 Dept Gen Internal Med, Nijmegen, Netherlands. Radboud Univ Nijmegen, Gastroenterol, Med Ctr, Nijmegen, Netherlands. NIH, Natl Inst Arthritis & Musculoskeletal & Skin Dis, Genet & Genom Branch, Bethesda, MD USA. RI Brouwer, Elisabeth/A-3198-2015; Hazenberg, Bouke/I-2866-2016 OI Hazenberg, Bouke/0000-0003-1827-0482 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD NOV PY 2006 VL 13 SU 1 BP 65 EP 66 PG 2 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 110WL UT WOS:000242411900172 ER PT J AU Datta, K Neumann, RD Winters, TA AF Datta, Kamal Neumann, Ronald D. Winters, Thomas A. TI An in vitro nonhomologous end-joining assay using linear duplex oligonucleotides SO ANALYTICAL BIOCHEMISTRY LA English DT Editorial Material ID DOUBLE-STRAND BREAK; IONIZING-RADIATION; DNA; COMPLEX; REPAIR; EXTRACTS; 3'-OVERHANGS; TERMINI; CELLS; KU C1 NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Winters, TA (reprint author), NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM twinters@mail.cc.nih.gov FU Intramural NIH HHS NR 12 TC 3 Z9 3 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 2006 VL 358 IS 1 BP 155 EP 157 DI 10.1016/j.ab.2006.06.035 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 097DW UT WOS:000241428000022 PM 16934213 ER PT J AU Law, DCG Bernstein, KT Serre, ML Schumacher, CM Leone, PA Zenilman, JM Miller, WC Rompalo, AM AF Law, Dionne C. Gesink Bernstein, Kyle T. Serre, Marc L. Schumacher, Christina M. Leone, Peter A. Zenilman, Jonathan M. Miller, William C. Rompalo, Anne M. TI Modeling a syphilis outbreak through space and time using the Bayesian maximum entropy approach SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE syphilis; disease outbreaks; spatial distribution; space-time clustering; surveillance ID SEXUALLY-TRANSMITTED-DISEASES; GEOGRAPHIC INFORMATION-SYSTEM; UNITED-STATES; GONORRHEA; BALTIMORE; EPIDEMIOLOGY; TRANSMISSION; CHLAMYDIA; MARYLAND AB PURPOSE: The aim of the study is to describe changes in the spatial distribution of syphilis before, during, and after an outbreak in Baltimore, MD, by using Bayesian maximum entropy (BME), a modern geostatistical technique for space-time analysis and mapping. METHODS: BME was used to conduct simple and composite space-time analyses of the density of syphilis infection based on primary, secondary and early latent syphilis cases reported to the Baltimore City Health Department between January 1, 1994, and December 31, 2002. RESULTS: Spatiotemporal covariance plots indicated that the distribution of the density of syphilis cases showed both spatial and temporal dependence. Temporally dependent disease maps suggested that syphilis increased within two geographic core areas of infection and spread outward. A new core area of infection was established to the northwest. As the outbreak waned, density diminished and receded in all core areas. Morbidity remained elevated in the two original central and new northwestern core areas after the outbreak. CONCLUSIONS: Density of syphilis infection was a simple informative measure easily compared across years. The BME approach was useful for quantitatively and qualitatively describing the spatial development and spread of syphilis. Our results are specific to Baltimore; however, the BME approach is generalizable to other settings and diseases. C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP Rompalo, AM (reprint author), Montana State Univ, Dept Microbiol, 109 Lewis Hall,POB 173520, Bozeman, MT 59717 USA. EM dionne.gesinklaw@montana.edu; arompalo@jhmi.edu RI Serre, Marc/C-2254-2009; Miller, William/H-4800-2014; OI Miller, William/0000-0002-1934-7827; serre, marc/0000-0003-3145-4024 NR 27 TC 22 Z9 22 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2006 VL 16 IS 11 BP 797 EP 804 DI 10.1016/j.annepidem.2006.05.003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 110NZ UT WOS:000242386900001 ER PT J AU Miller, ME Everhart, JE Hoofnagle, JH AF Miller, Megan E. Everhart, James E. Hoofnagle, Jay H. TI Epidemiologic research and the action plan for liver disease research SO ANNALS OF EPIDEMIOLOGY LA English DT Letter C1 Off Sci Program & Policy Anal, Bethesda, MD USA. Epidemiol & Clin Trials Branch, Bethesda, MD USA. NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Miller, ME (reprint author), Off Sci Program & Policy Anal, Bethesda, MD USA. NR 6 TC 2 Z9 2 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2006 VL 16 IS 11 BP 861 EP 865 DI 10.1016/j.annepidem.2006.07.005 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 110NZ UT WOS:000242386900009 PM 17067816 ER PT J AU Marroni, F Pichler, I De Grandi, A Volpato, CB Vogl, FD Pinggera, GK Bailey-Wilson, JE Pramstaller, PP AF Marroni, F. Pichler, I. De Grandi, A. Volpato, C. Beu Vogl, F. D. Pinggera, G. K. Bailey-Wilson, J. E. Pramstaller, P. P. TI Population isolates in south Tyrol and their value for genetic dissection of complex diseases SO ANNALS OF HUMAN GENETICS LA English DT Article DE linkage disequilibrium; population isolates; X chromosome ID LINKAGE DISEQUILIBRIUM; PHYLOGENETIC TREES; BIPOLAR DISORDER; DNA; DISTANCES; PATTERNS; TRAITS AB The study of genetic isolates is a promising approach for the study of complex genetic traits. The small and constant population size, lack of migration, and multiple relationships between individuals in the isolate population could reduce the genetic diversity, and lead to increased levels of linkage disequilibrium (LD). We studied the extent of LD on Xq13 in six population isolates from South Tyrol in the Eastern Italian Alps. We found different levels of LD in our study samples, probably reflecting their degrees of isolation and their demographic histories. The highest values were obtained in Val Gardena (ranking among the highest levels of LD in Europe) and in Stelvio, which qualified as a microisolate according to historical information, and biodemographic and genealogical criteria. Phylogenetic analysis revealed that the two Ladin-speaking populations are genetically distant from each other, and from their German-speaking neighbours, and are characterized by a smaller effective population size than the neighbouring valleys. These peculiar characteristics suggest that South Tyrol could be a unique resource for the study of complex diseases, showing all the characteristics of isolated populations with the advantage of including, in a fairly homogeneous environment, two genetically differentiated sub-populations. This could allow investigators to gain an insight into the contribution of genetic heterogeneity in complex diseases. C1 European Acad, Inst Med Genet, I-39100 Bolzano, Italy. Hosp Merano, Dept Gynaecol, I-39012 Merano, Italy. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. Ctr Hosp Bolzano, Dept Neurol, I-39100 Bolzano, Italy. Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Pramstaller, PP (reprint author), European Acad, Inst Med Genet, Viale Druso 1, I-39100 Bolzano, Italy. EM peter.pramstaller@eurac.edu RI Pramstaller, Peter/C-2357-2008; OI Marroni, Fabio/0000-0002-1556-5907; Bailey-Wilson, Joan/0000-0002-9153-2920 NR 41 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 2006 VL 70 BP 812 EP 821 DI 10.1111/j.1469-1809.2006.00274.x PN 6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 093TE UT WOS:000241191400013 PM 17044856 ER PT J AU Zheng, G Ghosh, K Chen, Z Li, Z AF Zheng, G. Ghosh, K. Chen, Z. Li, Z. TI Extreme rank selections for linkage analysis of quantitative trait loci using selected sib-pairs SO ANNALS OF HUMAN GENETICS LA English DT Article DE extreme rank selection (ERS); linkage; QTL; ranked set sampling (RSS); truncation selection (TS) ID DISCORDANT SIBLING PAIRS; ROBUST; TESTS; POWER AB It is well known that linkage analysis using simple random sib-pairs has relatively low power for detecting quantitative trait loci with small genetic effects. The power can be substantially increased by using samples selected based on their trait values. Usually, samples that are obtained by truncation selection consist of random samples from a truncated trait distribution. In this article we propose an alternative method using extreme ranks for linkage analysis with selected sib-pairs. This approach approximates the truncation selection. With similar screening sizes and the same sample size of selected sib-pairs, the extreme rank selection and truncation method have similar power performance, both of which are substantially more powerful than when using random sib-pairs. Simulation results on the comparison of powers between the truncation selection and the extreme rank selection and/or random selection for linkage analysis are reported. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, MSC 7938,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov FU NEI NIH HHS [EY 014478] NR 17 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 2006 VL 70 BP 857 EP 866 DI 10.1111/j.1468-1809.2006.00268.x PN 6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 093TE UT WOS:000241191400018 PM 17044861 ER PT J AU Scher, AI Terwindt, GM Verschuren, WMM Kruit, MC Blom, HJ Kowa, H Frants, RR van den Maagdenberg, AMJM van Buchem, M Ferrari, MD Launer, LJ AF Scher, Ann I. Terwindt, Gisela M. Verschuren, W. M. Monique Kruit, Mark C. Blom, Henk J. Kowa, Hisanori Frants, Rune R. van den Maagdenberg, Arn M. J. M. van Buchem, Mark Ferrari, Michel D. Launer, Lenore J. TI MTHFR C677T polymorphism and migraine with aura - Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NIA, Lab Epidemiol Demograph & Biometry, NIH, Bethesda, MD 20892 USA. Leiden Univ, Ctr Med, Dept Neurol, NL-2300 RA Leiden, Netherlands. Natl Inst Publ Hlth & Environm, Ctr Prevent & Hlth Serv Res, Bilthoven, Netherlands. Leiden Univ, Dept Radiol, NL-2300 RA Leiden, Netherlands. Radboud Univ Nijmegen Med Ctr, Nijmegen Ctr Mol Life Sci, Lab Pediat & Neurol, Nijmegen, Netherlands. Tottori Univ, Fac Med, Dept Neurol, Inst Neurol Sci, Yonago, Tottori 683, Japan. Leiden Univ, Dept Human Genet, NL-2300 RA Leiden, Netherlands. RP Scher, AI (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X NR 4 TC 0 Z9 0 U1 1 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 NOV PY 2006 VL 60 IS 5 BP 622 EP 623 DI 10.1002/ana.21014 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100027 ER PT J AU Ingeholm, JE Dold, GR Pfeffer, LE Goldstein, SR Johnson, KO Ide, D Van Boven, RW AF Ingeholm, J. E. Dold, G. R. Pfeffer, L. E. Goldstein, S. R. Johnson, K. . O. Ide, D. Van Boven, R. W. TI The helix: A multi-modal tactile stimulator for human functional neuroimaging SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 131st Annual Meeting of the American-Neurological-Association CY OCT 08-11, 2006 CL Chicago, IL SP Amer Neurol Assoc C1 NIMH, Res Serv Branch, NIH, Bethesda, MD USA. NIH, Biomed Engn & Phys Sci Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Krieger Mind Brain Inst, Baltimore, MD 21218 USA. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2006 VL 60 IS 5 BP 638 EP 638 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100065 ER PT J AU Matarin, M Brown, WM Rich, SS Brown, RD Singleton, A Meschia, JF AF Matarin, Mar Brown, W. Mark Rich, Stephen S. Brown, Robert D., Jr. Singleton, Andrew Meschia, James F. TI Robust genetic association between common variability in Itga2 and ischemic stroke SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 131st Annual Meeting of the American-Neurological-Association CY OCT 08-11, 2006 CL Chicago, IL SP Amer Neurol Assoc C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Dept Neurol, Rochester, MN USA. NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV PY 2006 VL 60 IS 5 BP 642 EP 642 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100077 ER PT J AU Reis, J Celnik, PA Swayne, O Cohen, LG AF Reis, Janine Celnik, Pablo A. Swayne, Orlando Cohen, Leonardo G. TI Lasting motor learning induced by transcranial direct current stimulation of the primary motor cortex in combination with physical training SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 131st Annual Meeting of the American-Neurological-Association CY OCT 08-11, 2006 CL Chicago, IL SP Amer Neurol Assoc C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 2006 VL 60 IS 5 BP 644 EP 644 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100081 ER PT J AU Timmons, MM Garbern, J Brady, RO Robinson, C Schiffmann, R AF Timmons, Margaret M. Garbern, James Brady, Roscoe O. Robinson, Chevalia Schiffmann, Raphael TI A familial encephalopathy with intracranial calcifications and metaphyseal dysplasia SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 131st Annual Meeting of the American-Neurological-Association CY OCT 08-11, 2006 CL Chicago, IL SP Amer Neurol Assoc C1 Wayne State Univ, Detroit, MI 48202 USA. NINDS, NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 60 IS 5 BP 644 EP 644 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100083 ER PT J AU Hassan, R Alexander, R Antman, K Boffetta, P Churg, A Coit, D Hausner, P Kennedy, R Kindler, H Metintas, M Mutti, L Onda, M Pass, H Premkumar, A Roggli, V Sterman, D Sugarbaker, P Taub, R Verschraegen, C AF Hassan, R. Alexander, R. Antman, K. Boffetta, P. Churg, A. Coit, D. Hausner, P. Kennedy, R. Kindler, H. Metintas, M. Mutti, L. Onda, M. Pass, H. Premkumar, A. Roggli, V. Sterman, D. Sugarbaker, P. Taub, R. Verschraegen, C. TI Current treatment options and biology of peritoneal mesothelioma: meeting summary of the first NIH peritoneal mesothelioma conference SO ANNALS OF ONCOLOGY LA English DT Review DE cancer; mesothelioma; peritoneal ID MALIGNANT MESOTHELIOMA; PLEURAL MESOTHELIOMA; UNITED-STATES; ASBESTOS; EXPOSURE; INTRAPERITONEAL; CHEMOTHERAPY AB Peritoneal mesothelioma is a rare cancer of the peritoneum with about 250 new cases diagnosed each year in the United States. It is the second most common site for mesothelioma development and accounts for 10-20% of all mesotheliomas diagnosed in the United States. A meeting sponsored by the NIH Office of Rare Diseases was held in Bethesda, Maryland on September 13 and 14, 2004. The objective of this meeting was to review the epidemiology, biology and current surgical and medical management of peritoneal mesothelioma. In addition, the meeting also discussed clinical and pre-clinical evaluation of novel treatments for mesothelioma as well as ongoing laboratory research to better understand this disease. This report summarizes the proceedings of the meeting as well as directions for future clinical and basic research. C1 Natl Canc Inst Hlth, Bethesda, MD USA. Int Agcy Res Canc, F-69372 Lyon, France. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Maryland, College Pk, MD 20742 USA. Texas Tech Univ, Ctr Hlth Sci, Lubbock, TX 79409 USA. Univ Chicago, Chicago, IL 60637 USA. Osmangazi Univ, Eskisehir, Turkey. Local Hlth Unit 11, Vercelli, Italy. Karmanos Canc Inst, Detroit, MI USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Penn, Philadelphia, PA 19104 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Columbia Univ, New York, NY 10027 USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov OI Antman, Karen/0000-0002-1093-8356; Sterman, Daniel/0000-0003-1249-0804 NR 22 TC 29 Z9 34 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2006 VL 17 IS 11 BP 1615 EP 1619 DI 10.1093/annonc/mdl060 PG 5 WC Oncology SC Oncology GA 102AV UT WOS:000241784000002 PM 16600983 ER PT J AU Ward, MM AF Ward, M. M. TI Outcomes in ankylosing spondylitis: what makes the assessment of treatment effects in ankylosing spondylitis different? SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article; Proceedings Paper CT 8th International Symposium on Advances in Targeted Therapies CY APR 05-09, 2006 CL Cambridge, MA ID NECROSIS-FACTOR-ALPHA; RESONANCE-IMAGING EXAMINATIONS; DISEASE-ACTIVITY; CONTROLLED-TRIAL; CORE SET; MATRIX METALLOPROTEINASES; BONE TURNOVER; SERUM-LEVELS; INFLIXIMAB; ETANERCEPT AB There are four major challenges in the assessment of outcomes in patients with ankylosing spondylitis (AS) that are particularly relevant to the evaluation of new therapies. Firstly, measures of symptoms and impairment in AS are not specific for inflammatory processes, they also capture mechanical symptoms and fixed limitations. The non-specific nature of these measures may cause them to be less responsive and therefore less useful in determining treatment efficacy. Secondly, acute phase reactants have limited value as measures of AS activity and other surrogate markers have not yet been established. Thirdly, the assessment of the disease modifying potential of new therapies is hampered by the slow rate of spinal fusion. Fourthly, work disability has not be studied as an endpoint in clinical trials in AS, despite the fact that work disability is an important outcome in patients with AS. Research into ways to overcome these challenges in outcome measurement will help identify useful therapies and define the range of outcomes that they influence. C1 NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 52 TC 6 Z9 6 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2006 VL 65 SU 3 BP 25 EP 28 DI 10.1136/ard.2006.058461 PG 4 WC Rheumatology SC Rheumatology GA 094CB UT WOS:000241215800005 ER PT J AU Lodde, BM Baum, BJ Tak, PP Illei, G AF Lodde, B. M. Baum, B. J. Tak, P. P. Illei, G. TI Experience with experimental biological treatment and local gene therapy in Sjogren's syndrome: implications for exocrine pathogenesis and treatment SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Review ID NF-KAPPA-B; VASOACTIVE-INTESTINAL-PEPTIDE; ADENOASSOCIATED VIRUS VECTORS; SYSTEMIC AUTOIMMUNE-DISEASES; MESSENGER-RNA EXPRESSION; LABIAL SALIVARY-GLANDS; NOD MOUSE MODEL; MURINE MODEL; ALPHA-FODRIN; RHEUMATOID-ARTHRITIS AB Sjogren's syndrome is an autoimmune exocrinopathy, mainly affecting the lacrimal and salivary glands, and resulting in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are largely unknown, and only palliative treatment is currently available. Data obtained from experimental animal and human studies using biological agents or gene therapeutics can offer insight into the disease process of Sjogren's syndrome. This article reviews the current literature on these approaches and assesses the lessons learnt about the pathogenesis of Sjogren's syndrome. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Illei, G (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, 10 Ctr Dr,Bldg 10,Room 1N114, Bethesda, MD 20892 USA. EM gillei@mail.nih.gov FU Intramural NIH HHS NR 85 TC 8 Z9 8 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2006 VL 65 IS 11 BP 1406 EP 1413 DI 10.1136/ard.2006.052761 PG 8 WC Rheumatology SC Rheumatology GA 094BY UT WOS:000241215500003 PM 16880196 ER PT J AU Ware, JH Zhou, ZZ Kopelovich, L Kennedy, AR AF Ware, Jeffrey H. Zhou, Zhaozong Kopelovich, Levy Kennedy, Ann R. TI Evaluation of cancer chemopreventive agents using clones derived from a human prostate cancer cell line SO ANTICANCER RESEARCH LA English DT Article DE LNCaP; prostate cancer cell clones; chemopreventive agents ID BREAST EPITHELIAL-CELLS; RETINOIC ACID; UNITED-STATES; PREVENTION; SELENOMETHIONINE; CARCINOGENESIS; TRANSFORMATION; PROLIFERATION; CARCINOMA; MODEL AB Background: The successful use of clonal selection through fluctuation analysis of human cancer cells as a means for studying tumor progression has been previously reported. Materials and Methods: Three clones derived from a parental population of human prostate cancer (LNCaP) cells were selected based on proliferation, hormone sensitivity and anchorage-independent growth. The effects of five potential cancer preventive agents were evaluated using cell proliferation, anchorage-independent growth and apoptosis as end-points. Results: Clone 21 cells, which represent a presumptive normal phenotype, were generally more sensitive than Clone 17 and Clone 6 cells, which represent a more malignant phenotype, to fluasterone, 7 beta-HF, L-selenomethionine and troglitazone in assays for proliferation and/or apoptosis. Conclusion: The results confirm the efficacy of the above agents as cancer chemopreventive agents and support our contention that clonal selection of established human cancer cells provides a model to study the efficacy of chemopreventive agents. C1 Univ Penn, Sch Med, Dept Radiat Oncol, Div Oncol Res, Philadelphia, PA 19104 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Ware, JH (reprint author), Univ Penn, Sch Med, Dept Radiat Oncol, Div Oncol Res, 195 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM jhware@mail.med.upenn.edu FU NCI NIH HHS [N01-CN-15134] NR 32 TC 3 Z9 3 U1 0 U2 0 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 NOV-DEC PY 2006 VL 26 IS 6B BP 4177 EP 4183 PG 7 WC Oncology SC Oncology GA 119UU UT WOS:000243040300012 PM 17201130 ER PT J AU Hope, WW Warn, PA Sharp, A Howard, S Kasai, M Louie, A Walsh, TJ Drusano, GL Denning, DW AF Hope, William W. Warn, Peter A. Sharp, Andrew Howard, Susan Kasai, Miki Louie, Arnold Walsh, Thomas J. Drusano, George L. Denning, David W. TI Derivation of an in vivo drug exposure breakpoint for flucytosine against Candida albicans and impact of the MIC, growth rate, and resistance genotype on the antifungal effect SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; MODEL; PHARMACOKINETICS; PHARMACODYNAMICS; SUSCEPTIBILITY; 5-FLUOROCYTOSINE; AGENTS AB Drug exposure or pharmacodynamic breakpoints refer to a magnitude of drug exposure which separates a population into groups with high and low probabilities of attaining a desired outcome. We used a pharmacodynamic model of disseminated candidiasis to define an in vivo drug exposure breakpoint for flucytosine (5FC) against Candida albicans. The results were bridged to humans by using population pharmacokinetics and Monte Carlo simulation. An in vivo drug exposure breakpoint for 5FC was apparent when serum levels were above the MIC for 45% of the dosing interval. The Monte Carlo simulations suggested that using a human dose of 100 mg/kg of body weight/day in four divided doses, 5FC resistance was defined at an MIC of 32 mg/liter. Target attainment rates following administration of 25, 50, and 100 mg/kg/day were similar, suggesting that the use of a lower dose of 5FC is possible. Using six isolates of C. albicans with MICs ranging from 0.06 to > 64 mg/liter, we also explored the influence that the MIC, the fraction of the dosing interval that the serum levels of 5FC remained above the MIC (T > MIC), the 5FC resistance genotype, and the in vivo growth rate had on the response to 5FC. The MIC and T > MIC were both critical measures affecting the generation of a drug effect but had no bearing on the magnitude of the maximal kill induced by 5FC. The in vivo growth rate was a critical additional determinant of the exposure-response relationship. There was a relationship between the 5FC resistance genotype and the exposure-response relationship. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Manchester, Sch Med, Manchester M13 9PT, Lancs, England. Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. Ordway Res Inst, Albany, NY 12208 USA. RP Hope, WW (reprint author), NCI, Pediat Oncol Branch, NIH, CRC Rm 1-5750,10 Ctr Dr,MSC 1100, Bethesda, MD 20892 USA. EM hopew@mail.nih.gov OI , /0000-0003-0340-2016; Denning, David/0000-0001-5626-2251; Hope, William/0000-0001-6187-878X NR 26 TC 18 Z9 18 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2006 VL 50 IS 11 BP 3680 EP 3688 DI 10.1128/AAC.00369-06 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 104DC UT WOS:000241935200022 PM 16954320 ER PT J AU Karginov, VA Nestorovich, EM Yohannes, A Robinson, TM Fahmi, NE Schmidtmann, F Hecht, SM Bezrukov, SM AF Karginov, Vladimir A. Nestorovich, Ekaterina M. Yohannes, Adiamseged Robinson, Tanisha M. Fahmi, Nour Eddine Schmidtmann, Frank Hecht, Sidney M. Bezrukov, Sergey M. TI Search for cyclodextrin-based inhibitors of anthrax toxins: Synthesis, structural features, and relative activities SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PROTECTIVE ANTIGEN CHANNEL; BACILLUS-ANTHRACIS; BETA-CYCLODEXTRIN; LETHAL TOXIN; DERIVATIVES; CIPROFLOXACIN; MEMBRANES; DESIGN AB Recently, using structure-inspired drug design, we demonstrated that aminoalkyl derivatives of beta-cyclodextrin inhibited anthrax lethal toxin action by blocking the transmembrane pore formed by the protective antigen (PA) subunit of the toxin. In the present study, we evaluate a series of new beta-cyclodextrin derivatives with the goal of identifying potent inhibitors of anthrax toxins. Newly synthesized hepta-6-thioaminoalkyl and hepta-6-thioguanidinoalkyl derivatives of beta-cyclodextrin with alkyl spacers of various lengths were tested for the ability to inhibit cytotoxicity of lethal toxin in cells as well as to block ion conductance through PA channels reconstituted in planar bilayer lipid membranes. Most of the tested derivatives were protective against anthrax lethal toxin action at low or submicromolar concentrations. They also blocked ion conductance through PA channels at concentrations as low as 0.1 nM. The activities of the derivatives in both cell protection and channel blocking were found to depend on the length and chemical nature of the substituent groups. One of the compounds was also shown to block the edema toxin activity. It is hoped that these results will help to identify a new class of drugs for anthrax treatment, i.e., drugs that block the pathway for toxin translocation into the cytosol, the PA channel. C1 Innovat Biol Inc, Manassas, VA 20110 USA. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20982 USA. Pinnacle Pharmaceut Inc, Emerging Technol Ctr 1, Charlottesville, VA 22911 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22901 USA. RP Karginov, VA (reprint author), Innovat Biol Inc, 10900 Univ Blvd,MSN 1A8, Manassas, VA 20110 USA. EM vak@innovbio.com FU Intramural NIH HHS; NIAID NIH HHS [2R44AI052894-02, R44 AI052894] NR 31 TC 43 Z9 44 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2006 VL 50 IS 11 BP 3740 EP 3753 DI 10.1128/AAC.00693-06 PG 14 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 104DC UT WOS:000241935200030 PM 16982795 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID-BETA-PEPTIDE; TRANSGENIC MOUSE MODEL; PERTURBED CALCIUM HOMEOSTASIS; CEREBELLAR GRANULE NEURONS; PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE AB When subjected to excessive oxidative stress, neurons may respond adaptively to overcome the stress, or they may activate a programmed cell death pathway called apoptosis. Apoptosis is characterized by alterations in mitochondria and the endoplasmic reticulum and activation of cysteine proteases called caspases. Increasing evidence suggests that apoptotic biochemical cascades are involved in the dysfunction and death of neurons in neurodegenerative disorders such as Alzheimer's, Parkinson, and Huntington's diseases. Studies of normal aging, of genetic mutations that cause disease, and of environmental factors that affect disease risk are revealing cellular and molecular alterations that may cause excessive oxidative stress and trigger neuronal apoptosis. Accumulation of self-aggregating proteins such as amyloid beta-peptide, tau, alpha-synuclein, and huntingtin may be involved in apoptosis both upstream and downstream of oxidative stress. Membrane-associated oxidative stress resulting in perturbed lipid metabolism and disruption of cellular calcium homeostasis may trigger apoptosis in several different neurodegenerative disorders. Counteracting neurodegenerative processes are an array of mechanisms including neurotrophic factor signaling, antioxidant enzymes, protein chaperones, antiapoptotic proteins, and ionostatic systems. Emerging findings suggest that the resistance of neurons to death during aging can be enhanced by modifications of diet and lifestyle. C1 NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 148 TC 119 Z9 126 U1 2 U2 18 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV-DEC PY 2006 VL 8 IS 11-12 BP 1997 EP 2006 DI 10.1089/ars.2006.8.1997 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 100BD UT WOS:000241641200006 PM 17034345 ER PT J AU Hensley, K Mhatre, M Mou, S Pye, QN Stewart, C West, M Williamson, KS AF Hensley, Kenneth Mhatre, Molina Mou, Shenyun Pye, Quentin N. Stewart, Charles West, Melinda Williamson, Kelly S. TI On the relation of oxidative stress to neuroinflammation: Lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID ZINC SUPEROXIDE-DISMUTASE; TUMOR-NECROSIS-FACTOR; MOTOR-NEURON DEGENERATION; CYTOCHROME-C RELEASE; COPPER-BINDING-SITE; TRANSGENIC MICE; GENE-EXPRESSION; CU,ZN-SUPEROXIDE DISMUTASE; ALZHEIMERS-DISEASE; SPINAL-CORDS AB The central nervous system (CNS) presents both challenges and opportunities to researchers of redox biochemistry. The CNS is sensitive to oxidative damage during aging or disease; excellent transgenic models of specific neurodegenerative diseases have been created that reproduce oxidative stress components of the corresponding human disorder. Mouse models of familial amyotrophic lateral sclerosis (ALS) based on overexpressed mutant human Cu,Zn-superoxide dismutase (SOD1) are cases in point. These animals experience predictably staged, age-dependent motor neuron degeneration with profound cellular and biochemical damage to nerve fibers and spinal cord tissue. Severe protein and lipid oxidation occurs in these animals, apparently as an indirect consequence of protein aggregation or cytopathic protein-protein interactions, as opposed to aberrant redox catalysis by the mutant enzyme. Recent studies of G93A-SOD1 mice and rats suggest that oxidative damage is part of an unmitigated neuroinflammatory reaction, possibly arising in combination from mitochondrial dysfunction plus pathophysiologic activation of both astrocytes and microglia. Lesions to redox signal-transduction pathways in mutant SOD1+ glial cells may stimulate broad-spectrum upregulation of proinflammatory genes, including arachidonic acid-metabolizing enzymes [e.g., cyclooxygenase-II (COX-II) and 5-lipoxygenase (5LOX)]; nitric oxide synthase (NOS) isoforms; cytokines (particularly tumor necrosis factor alpha, TNF-alpha); chemokines; and immunoglobulin F-c receptors (Fc gamma Rs). The integration of these processes creates a paracrine milieu inconsistent with healthy neural function. This review summarizes what has been learned to date from studies of mutant SOD1 transgenic animals and demonstrates that the G93A-SOD1 mouse in particular is a robust laboratory for the study of neuroinflammation and redox biochemistry. C1 NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Hensley, K (reprint author), Oklahoma Med Res Fdn, Free Rad Biol & Aging Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Kenneth-Hensley@omrf.ouhsc.edu FU NIA NIH HHS [AG20783]; NINDS NIH HHS [NS044154] NR 88 TC 97 Z9 98 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV-DEC PY 2006 VL 8 IS 11-12 BP 2075 EP 2087 DI 10.1089/ars.2006.8.2075 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 100BD UT WOS:000241641200012 PM 17034351 ER PT J AU Davis, DA Brown, CA Singer, KE Wang, V Kaufman, J Stahl, SJ Wingfield, P Maeda, K Harada, S Yoshimura, K Kosalaraksa, P Mitsuya, H Yarchoan, R AF Davis, David A. Brown, Cara A. Singer, Kathleen E. Wang, Victoria Kaufman, Joshua Stahl, Stephen J. Wingfield, Paul Maeda, Kenji Harada, Shigeyoshi Yoshimura, Kazuhisa Kosalaraksa, Pope Mitsuya, Hiroaki Yarchoan, Robert TI Inhibition of HIV-1 replication by a peptide dimerization inhibitor of HIV-1 protease SO ANTIVIRAL RESEARCH LA English DT Article DE HIV-1; protease; dimer; peptide; inhibitor; polyprotein ID IMMUNODEFICIENCY-VIRUS TYPE-1; MEMBRANE-PERMEABLE PEPTIDES; ARGININE-RICH PEPTIDES; REVERSE-TRANSCRIPTASE; DRUG-RESISTANCE; TRANSDUCTION DOMAIN; BASIC DOMAIN; MUTATIONS; DELIVERY; CELLS AB Peptides based on the amino (N) and carboxy (Q-terminal regions of human immunodeficiency virus type-1 (HIV-1) protease and on the C-terminus of p6(*) can inhibit HIV-1 protease activity by preventing dimerization. We developed a peptide dimerization inhibitor, P27, that included these domains and a cell permeable domain derived from HIV-1 Tat. P27 inhibited wild type (WT) and protease inhibitor (PI)-resistant HIV-1 protease (IC50: 0.23-0.32 mu M). Kinetic and biochemical assays confirmed that P27 inhibits protease dimerization. Fluorescein-labeled peptide accumulated in MT-2 cells and protected acutely infected MT-2 cells from HIV-1-induced cytotoxicity (IC50: 5.1 mu M). P27 also inhibited p24 accumulation from H9 and U937 cells chronically infected with WT or PI-resistant HIV-1. Immunoblot analysis on the supernatants and infected cells revealed a block in virus release by P27 rather than an inhibition of polyprotein processing. However, inhibition of p55 Gag processing by active-site inhibitors was enhanced when combined with P27, suggesting that P27 can affect protease function in maturing virions. Although P27 was rationally designed to block dimerization of the mature HIV-1 protease, the effects of P27 on HIV-1 replication may be related to partial inhibition of Gag-Pol processing leading to a disruption in virus release. Published by Elsevier B.V. C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bldg 10,Room 10S255, Bethesda, MD 20892 USA. EM dadavis@helix.nih.gov FU Intramural NIH HHS NR 57 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 2006 VL 72 IS 2 BP 89 EP 99 DI 10.1016/j.antiviral.2006.03.015 PG 11 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 092JN UT WOS:000241092900002 PM 16687179 ER PT J AU Reddy, GS Omdahl, JL Robinson, M Wang, GC Palmore, GTR Vicchio, D Yergey, AL Tserng, KY Uskokovic, MR AF Reddy, G. Satyanarayana Omdahl, John L. Robinson, Matthew Wang, Guochun Palmore, G. Tayhas R. Vicchio, Domenick Yergey, Alfred L. Tserng, Kou-Yi Uskokovic, Milan R. TI 23-carboxy-24,25,26,27-tetranorvitamin D-3 (calcioic acid) and 24-carboxy-25,26,27-trinorvitamin D-3 (cholacalcioic acid): End products of 25-hydroxyvitamin D-3 metabolism in rat kidney through C-24 oxidation pathway SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE 25OHD3; 24R,25(OH)2D3; rat kidney; metabolism; CYP24A1; calcioic acid; cholacalcioic acid; bile acid; vitamin D3 ID VITAMIN-D-RECEPTOR; SPECIES-BASED DIFFERENCE; CALCITROIC ACID; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ESCHERICHIA-COLI; LITHOCHOLIC ACID; 1,25-DIHYDROXYVITAMIN-D3; CYP24; 24-HYDROXYLASE; EPIDEMIOLOGY AB During the past two and half decades the elucidation of the metabolic pathways of 250HD(3) and its active metabolite 1 alpha,25(OH)(2)D-3 progressed in parallel. In spite of many advances in this area of vitamin D research, the unequivocal identification of the end products of 250HD(3) metabolism through C-24 oxidation pathway has not been achieved. It is now well established that both 250HD(3) and 1 alpha,25(OH)(2)D-3 are metabolized through the same C-24 oxidation pathway initiated by the enzyme 24-hydroxylase (CYP24A1). Based on the information that the end product of 1 alpha,25(OH)(2)D-3 metabolism through C-24 oxidation pathway is 1 alpha-OH-23- COOH-24,2 5,26,27-tetranor D-3 or calcitroic acid; the metabolism of 250HD(3) into 23-COOH-24,25,26,27-tetranor D-3 has been assumed. Furthermore, a previous study indicated 24-COOH25,26,27-trinor D-3 as a water soluble metabolite of 24R,25(OH)(2)D-3 produced in rat kidney homogenates. Therefore, 24-COOH-25,26,27-trinor D3 was also assumed as another end product of 250HD3 metabolism through C-24 oxidation pathway. We embarked on our present study to provide unequivocal proof for these assumptions. We first studied the metabolism of 250HD(3) at low substrate concentration (3 x 10(-10) M) using [1,2-H-3]250HD(3) as the substrate in the perfused rat kidneys isolated from both normal and vitamin D-3 intoxicated rats. A highly polar water soluble metabolite, labeled as metabolite X was isolated from the kidney perfusate. The amount of metabolite X produced in the kidney of a vitamin D intoxicated rat was about seven times higher than that produced in the kidney of a normal rat. We then produced metabolite X in a quantity sufficient for its structure identification by perfusing kidneys isolated from vitamin D intoxicated rats with high substrate concentration of 250HD(3) (5 x 10(-6) M). Using the techniques of electron impact and thermospray mass spectrometry, we established that the metabolite X contained both 23-COOH-24,25,26,27-tetranor D-3 and 24-COOH-25,26,27-trinor D-3 in a ratio of 4: 1. The same metabolite X containing both acids in the same ratio of 4:1 was also produced when 24R,25(OH)(2)D-3 was used as the starting substrate. Previously, the trivial name of cholacalcioic acid was assigned to 24-COOH-25,26,27-trinorvitamin D-3. Using the same guidelines, we now assign the trivial name of calcioic acid to 23-COOH-24,25,26,27-tetranor D-3. In summary, for the first time our study provides unequivocal evidence to indicate that both calcioic and cholacalcioic acids as the end products of 250HD(3) metabolism in rat kidney through C-24 oxidation pathway. (c) 2006 Elsevier Inc. All rights reserved. C1 Epimer LLC, Providence, RI 02906 USA. Brown Univ, Dept Chem, Providence, RI 02912 USA. Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. Brown Univ, Div Engn, Providence, RI 02912 USA. NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Nutr & Med, Cleveland, OH 44106 USA. Vet Adm Med Ctr, Cleveland, OH 44106 USA. Bioxell Inc, Nutley, NJ 07110 USA. RP Reddy, GS (reprint author), Epimer LLC, 4 Richmond Sq,Suite 500, Providence, RI 02906 USA. EM Satya_Reddy@Brown.edu FU Intramural NIH HHS; NIDDK NIH HHS [DK 52488] NR 30 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 2006 VL 455 IS 1 BP 18 EP 30 DI 10.1016/j.abb.2006.08.021 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 101VD UT WOS:000241768100003 PM 17027908 ER PT J AU Mukhopadhyay, I Siddique, HR Bajpai, VK Saxena, DK Chowdhuri, DK AF Mukhopadhyay, Indranil Siddique, Hifzur Rahman Bajpai, Virendra Kumar Saxena, Daya Krishna Chowdhuri, Debapratim Kar TI Synthetic pyrethroid cypermethrin induced cellular damage in reproductive tissues of Drosophila melanogaster: Hsp70 as a marker of cellular damage SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; TRANSGENIC DROSOPHILA; STRESS-PROTEINS; MOLECULAR CHAPERONES; ION CHANNELS; INDUCTION; EXPRESSION; TOXICITY; CYTOTOXICITY; CELLS AB We tested a working hypothesis of whether the synthetic pyrethroid cypermethrin, used worldwide for insecticidal purpose, causes adverse effects on reproduction in Drosophila melanogaster. Freshly eclosed first instar larvae of a transgenic strain of Drosophila melanogaster, Bg(9), transgenic for hsp70 (hsp70-lacZ), were transferred to different dietary concentrations of the test chemical (0.002, 0.02, 0.2, 0.5, and 50.0 ppm). Larval mortality was observed at the higher dosed groups (0.2, 0.5, and 50.0 ppm). Following pair mating of virgin flies emerging from the treatment groups, a significant (p < 0.05) effect on reproduction was observed in the lowest two dietary concentrations of the test chemical as compared to control. The test chemical exhibited a hazardous effect on the reproductive organs of the exposed organism as evident by Hsp70 expression and tissue damage. The impact of damage was comparatively more prominent in male flies than in females. Hsp70 expression was restricted only within the testis lobes of male, while ovary in the female fly did not exhibit any Hsp70 expression. Interestingly, the accessory glands of male flies in these treatment groups reflected intense tissue damage as evident by Trypan Blue staining. This was further corroborated by ultrastructural changes like higher vacuolization and disorganized filamentous bodies in the accessory glands of these groups. The present study indicates a profound effect on reproduction by cypermethrin and suggests the protective role of hsp70. C1 Ind Toxicol Res Ctr, Embryotoxicol Sect, Lucknow 226001, Uttar Pradesh, India. Cent Drug Res Inst, Electron Microscopy Unit, Lucknow 226001, Uttar Pradesh, India. RP Chowdhuri, DK (reprint author), NCI, Lab Clin Trials Unit, Dev Therapeut Program, NIH, Bldg 37,Rm 1052,9000 Rockville Pike, Bethesda, MD USA. EM dkchowdhuri@yahoo.com NR 57 TC 12 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD NOV PY 2006 VL 51 IS 4 BP 673 EP 680 DI 10.1007/s00244-005-0169-6 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 094TW UT WOS:000241263000025 PM 16418893 ER PT J AU Schaefer, EJ Bongard, V Beiser, AS Lamon-Fava, S Robins, SJ Au, R Tucker, KL Kyle, DJ Wilson, PWF Wolf, PA AF Schaefer, Ernst J. Bongard, Vanina Beiser, Alexa S. Lamon-Fava, Stefania Robins, Sander J. Au, Rhoda Tucker, Katherine L. Kyle, David J. Wilson, Peter W. F. Wolf, Philip A. TI Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease - The Framingham heart study SO ARCHIVES OF NEUROLOGY LA English DT Article ID N-3 FATTY-ACIDS; COGNITIVE DECLINE; APOLIPOPROTEIN-E; FISH; BRAIN; PHOSPHOLIPIDS; PERFORMANCE; CONSUMPTION; EPSILON-4; FREQUENCY AB Background: Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found mostly in fatty fish. The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia. Objective: To determine whether plasma phosphatidylcholine (PC) DHA content is associated with the risk of developing dementia. Design, Setting, and Participants: A prospective follow-up study in 899 men and women who were free of dementia at baseline, had a median age of 76.0 years, and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease. Main Outcome Measures: Plasma PC fatty acid levels were measured at baseline. Cox proportional regression analysis was used to assess relative risks of all-cause dementia and Alzheimer disease according to baseline plasma levels. Results: Ninety-nine new cases of dementia (including 71 of Alzheimer disease) occurred during the follow-up. After adjustment for age, sex, apolipoprotein E epsilon 4 allele, plasma homocysteine concentration, and education level, subjects in the upper quartile of baseline plasma PC DHA levels, compared with subjects in the lower 3 quartiles, had a relative risk of 0.53 of developing all-cause dementia (95% confidence interval, 0.29-0.97; P = .04) and 0.61 of developing Alzheimer disease (95% confidence interval, 0.31-1.18; P = .14). Subjects in the upper quartile of plasma PC, DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week (P < .001) in a subset of 488 participants. We found no other significant associations. Conclusion: The top quartile of plasma PC DHA level was associated with a significant 47% reduction in the risk of developing all-cause dementia in the Framingham Heart Study. C1 Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA. Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Dietary Assessment & Epidemiol Program, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Endocrinol Nutr & Diabet, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Market Biosci Corp, Columbia, MD USA. NHLBI, Framinham Heart Study, Framingham, MA USA. RP Schaefer, EJ (reprint author), Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Lipid Metab Lab, 711 Washington St, Boston, MA 02111 USA. EM ernst.schaefer@tufts.edu RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X FU NHLBI NIH HHS [HV-83-03, N01-HC-25195]; NIA NIH HHS [5R01-AG-08122-14] NR 25 TC 319 Z9 333 U1 4 U2 42 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 NOV PY 2006 VL 63 IS 11 BP 1545 EP 1550 DI 10.1001/archneur.63.11.1545 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 104JJ UT WOS:000241954400004 PM 17101822 ER PT J AU Akomolafe, A Beiser, A Meigs, PB Au, R Green, RC Farrer, LA Wolf, PA Seshadri, S AF Akomolafe, Abimbola Beiser, Alexa Meigs, Phdjames B. Au, Rhoda Green, Robert C. Farrer, Lindsay A. Wolf, Philip A. Seshadri, Sudha TI Diabetes mellitus and risk of developing Alzheimer disease - Results from the Framingham study SO ARCHIVES OF NEUROLOGY LA English DT Article ID INSULIN-DEGRADING ENZYME; COGNITIVE IMPAIRMENT; VASCULAR DEMENTIA; OLDER WOMEN; APOE GENE; POPULATION; DECLINE; STROKE; HYPERINSULINEMIA; PERFORMANCE AB Background: Diabetes mellitus (DM) could increase the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between DM and the development of AD remains uncertain. Objective: To compare the risk of developing AD in subjects with and without DM. Design: Prospective community-based cohort study. Participants: Framingham Study Original cohort participants who were dementia free and-attended the 16th biennial examination (n = 2210 persons, 1325 women; mean age, 70 years). Main Outcome Measures: Relative risk of incident AD (criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) associated with baseline DM (casual plasma glucose >= 200 mg/dL [>= 11.1 mmol/L] or use of insulin or a hypoglycemic drug) in overall group and within subgroups defined by apolipoprotein E genotype and plasma homocysteine levels; models were adjusted for age, sex, and cardiovascular risk factors. Results: At baseline, 202 participants (9.1%) had DM During the follow-up period (mean, 12.7 years; range, 1-20 years), 17 of 202 persons with DM (8.4%) and 220 of 2008 persons without DM (11.0%) developed AD, yielding a relative risk of 1.15 (95% confidence interval, 0.65-2.05). Among subjects without an apolipoprotein E F,4 allele or elevated plasma homocysteine levels, 44 of 684 persons (6.4%) developed AD; relative risk for AD comparing diabetic patients with nondiabetic patients was 2.98 (95% confidence interval, 1.06-8.39; P = .03). The effect was strongest in persons aged 75 years or older with a relative risk of 4.77 (95% confidence interval, 1.28-17.72; P = .02). Conclusion: Diabetes mellitus did not increase the risk of incident AD in the Framingham cohort overall; however, DM may be a risk factor for AD in the absence of other known major AD risk factors. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Med, Genet Program, Boston, MA 02118 USA. Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-608, Boston, MA 02118 USA. EM suseshad@bu.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU NHLBI NIH HHS [N01-HC-25195]; NIA NIH HHS [3R01-AG09029, 5R01-AG08122, 5R01-AG16495, P30 AG13846]; NINDS NIH HHS [5R01-NS17950] NR 42 TC 146 Z9 151 U1 6 U2 20 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 NOV PY 2006 VL 63 IS 11 BP 1551 EP 1555 DI 10.1001/archneur.63.11.1551 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 104JJ UT WOS:000241954400005 PM 17101823 ER PT J AU Chew, EY Clemons, TE AF Chew, Emily Y. Clemons, Traci E. TI Heart outcomes prevention evaluation - The ongoing outcomes study, vitamin E, and age-related macular degeneration - In reply SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID EYE DISEASE; SUPPLEMENTATION C1 NIH, Div Epidemiol & Clin Res, CRC, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NIH, Div Epidemiol & Clin Res, CRC, Bldg 10,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 124 IS 11 BP 1665 EP 1666 DI 10.1001/archopht.124.11.1665-b PG 2 WC Ophthalmology SC Ophthalmology GA 104VG UT WOS:000241987700029 ER PT J AU O'Hanlon, TP Rider, LG Mamyrova, G Targoff, IN Arnett, FC Reveille, JD Carrington, M Gao, XJ Oddis, CV Morel, PA Malley, JD Malley, K Shamim, EA Chanock, SJ Foster, CB Bunch, T Reed, AM Love, LA Miller, FW AF O'Hanlon, Terrance P. Rider, Lisa G. Mamyrova, Gulnara Targoff, Ira N. Arnett, Frank C. Reveille, John D. Carrington, Mary Gao, Xiaojiang Oddis, Chester V. Morel, Penelope A. Malley, James D. Malley, Karen Shamim, Ejaz A. Chanock, Stephen J. Foster, Charles B. Bunch, Thomas Reed, Ann M. Love, Lori A. Miller, Frederick W. TI HLA polymorphisms in African Americans with idiopathic inflammatory myopathy - Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSFER RNA-SYNTHETASES; MAJOR POPULATION GROUPS; CLASS-II ALLELES; PROTECTIVE FACTORS; DRB3 ASSOCIATIONS; UNITED-STATES; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; IMMUNOGENETIC RISK AB Objective. To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. Methods. Molecular genetic analyses of HLA-A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American. patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571). Results. In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti-jo-I autoantibodies shared the risk factor HLA-DRBI*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti-signal recognition particle (DQAI*0102) and anti-Mi-2 autoantibodies (DRBI*0302). DRB1*0302 and the European American-, anti-Mi-2-associated risk factor DRBI*0701 were found to share a 4-amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove. Conclusion. These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene-environment interactions. C1 NIEHS, NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. SAIC Frederick, Natl Canc Inst, Frederick, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Ctr Informat Technol, NIH, Bethesda, MD USA. Malley Res Programming, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Mayo Clin, Rochester, MN USA. US FDA, Rockville, MD 20857 USA. RP O'Hanlon, TP (reprint author), NIEHS, NIH, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. EM ohanlont@niehs.nih.gov OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593; Morel, Penelope/0000-0002-1743-3676 FU Intramural NIH HHS NR 51 TC 28 Z9 29 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2006 VL 54 IS 11 BP 3670 EP 3681 DI 10.1002/art.22205 PG 12 WC Rheumatology SC Rheumatology GA 104TH UT WOS:000241981800035 PM 17075818 ER PT J AU Targoff, IN Mamyrova, G Trieu, EP Perurena, O Koneru, B O'Hanlon, TP Miller, FW Rider, LG AF Targoff, Ira N. Mamyrova, Gulnara Trieu, Edward P. Perurena, Osvaldo Koneru, Bhanu O'Hanlon, Terrance P. Miller, Frederick W. Rider, Lisa G. CA Childhood Myositis Heterogeneity Int Myositis Collaborative Study G TI A novel autoantibody to a 155-kd protein is associated with dermatomyositis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHY; TRANSFER-RNA-SYNTHETASES; MYOSITIS-SPECIFIC AUTOANTIBODIES; JAPANESE PATIENTS; MUSCLE DISEASE; JUVENILE DERMATOMYOSITIS; NUCLEAR; EXPRESSION; SERA; CLASSIFICATION AB Objective. In polymyositis and dermatomyositis (DM), identified autoantibodies occur in < 50% of adult patients and in a smaller proportion of children. This study was undertaken as part of a larger effort to define novel autoantibodies that assist in the clinical evaluation of myositis. Methods. Sera from children and adults satisfying criteria for idiopathic inflammatory myopathies and from patients with other connective tissue diseases (CTDs), patients with noninflammatory myopathies, and healthy individuals were tested for autoantibodies by immunoprecipitation (IP). A previously unrecognized autoantibody that immunoprecipitated a 155-kd protein along with a weaker 140-kd protein was seen. When the presence of this anti-p155 autoantibody in test sera was suggested based on IP results, it was confirmed by immunoblotting of immunoprecipitates. Results. Sera from 51 of 244 myositis patients (21%), including 30 with juvenile DM (29%), 5 with juvenile CTD-associated myositis (33%), 8 with adult DM (21%), 6 with cancer-associated DM (75%), and 2 with adult CTD-associated myositis (15%), were found to have anti-p155 autoantibody. One of 49 patients with lupus, and none of 89 others without myositis, had anti-p155. Caucasian patients with anti-p155 had a unique HLA risk factor, DQA1*0301 (odds ratio 5.4, corrected P = 0.004). In adults with anti-p155, of several clinical features assessed only the frequency of V-sign rash was increased, but patients with this antibody were clinically distinct from those with autoantibodies to aminoacyl-transfer RNA synthetases. Conclusion. A newly recognized autoantibody, antip155, is associated with DM and cancer-associated DM, and is one of the most common autoantibodies in this condition, occurring as frequently in children as in adults. The clinical features and immunogenetics associated with anti-p155 differ from those associated with antisynthetases. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. NIEHS, NIH, Bethesda, MD USA. Texas A&M Univ, College Stn, TX USA. RP Targoff, IN (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Ira-Targoff@ouhsc.edu OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 31 TC 167 Z9 186 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2006 VL 54 IS 11 BP 3682 EP 3689 DI 10.1002/art.22164 PG 8 WC Rheumatology SC Rheumatology GA 104TH UT WOS:000241981800036 PM 17075819 ER PT J AU Valeri, CR Ragno, G Veech, RL AF Valeri, C. Robert Ragno, Gina Veech, Richard L. TI Effects of the resuscitation fluid and the hemoglobin based oxygen carrier (HBOC) excipient on the toxicity of the HBOC: Ringer's (D, L)- lactate, Ringer's (L)-lactate, and Ringer's ketone solutions SO ARTIFICIAL CELLS BLOOD SUBSTITUTES AND BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on Blood Substitutes CY JUN 12-15, 2005 CL Brown Univ, Providence, RI HO Brown Univ DE excipients for HBOC; resuscitative solutions; Ringer's D L lactate; Ringer's L lactate and Ringer's ketone solutions ID ACUTE-RENAL-FAILURE; HEMORRHAGIC-SHOCK; PULMONARY APOPTOSIS; NEUTROPHIL ACTIVATION; FREE-RADICALS; RAT MODEL; KAPPA-B; LEUKOCYTES; ADHESION; BODIES AB Hemoglobin based oxygen carriers ( HBOC) are resuspended in "excipients'' consisting of Ringer's D, L- lactate containing antioxidants to prevent methemoglobin formation during storage. Investigators have reported cardiac arrhythmias following infusion of Ringer's D, L- lactate solution. Studies have shown that D- lactate stimulates human granulocytes to generate oxygen free radicals and L- lactate inhibits glycolysis. Patients receiving HBOC in Ringer's D, L- lactate excipient are also resuscitated or hemodiluted with Ringer's lactate solution. Oxygen- free radicals generated by Ringer's D, L- lactate and HBOC may oxidize nitric oxide in endothelial cells, causing the vasoconstrictor effects reported following HBOC infusion, and activate NF-kappa b and the apoptotic cascade. The combination of Ringer's D, L- lactate and HBOC in Ringer's D, L- lactate excipient may be responsible for the severe adverse events observed in clinical studies of HBOC. Veech has recommended replacing the 27mM of lactate in Ringer's with 27mM D- betahydroxybutyrate ( BHB). BHB reduces the generation of oxygen free radicals by mitochondria and human granulocytes. C1 USN, Blood Res Lab, Boston, MA USA. NIAAA, NIH, Bethesda, MD USA. RP Valeri, CR (reprint author), USN, Blood Res Lab, 195 Bournehurst Dr, Plymouth, MA 02360 USA. EM navblood@nbrl.org NR 22 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1073-1199 J9 ARTIF CELL BLOOD SUB JI Artif. Cells Blood Substit. Biotechnol. PD NOV-DEC PY 2006 VL 34 IS 6 BP 601 EP 606 DI 10.1080/10731190600974087 PG 6 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials Science, Biomaterials SC Biotechnology & Applied Microbiology; Engineering; Materials Science GA 102NI UT WOS:000241818500007 PM 17090432 ER PT J AU Elosua, R Cupples, LA Fox, CS Polak, JF D'Agostino, RA Wolf, PA O'Donnell, CJ Ordovas, JM AF Elosua, Roberto Cupples, L. Adrienne Fox, Caroline S. Polak, Joseph F. D'Agostino, Ralph A., Sr. Wolf, Philip A. O'Donnell, Christopher J. Ordovas, Jose M. TI Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study SO ATHEROSCLEROSIS LA English DT Article DE carotid; epidemiology; genetics; lipids ID CHOLESTEROL LEVELS; LIPASE GENE; MYOCARDIAL-INFARCTION; PLASMA-LIPIDS; DISEASE RISK; POLYMORPHISM; PROTEIN; ATHEROSCLEROSIS; STROKE; MEN AB Objective: To determine the association of well-characterized lipoprotein-related genetic variants with carotid intimal medial thickness (IMT) and stenosis. Methods: 3380 men and women from the Framingham Offspring Study underwent carotid ultrasound to determine carotid IMT and stenosis >= 25%. We genotyped 12 variants in 10 lipoprotein-related genes known to be associated with significant differences in lipoprotein levels. Results: For most of the variants, there was no association with carotid IMT. In multivariable, sex-specific analyses, the rare allele of the cholesterol ester transfer protein (CETP) TaqIB variant was associated with lower ICA IMT in men. Hypertension was associated with higher ICA IMT only in male carriers of the rare allele of the APOCIII Sst-1 variant (p for the interaction=0.041). In analyses of carotid stenosis in male, carriers of the lipoprotein lipase (LPL) N291S rare variant showed a higher risk of carotid stenosis (OR = 2.59, 95% confidence interval: 1.11-6.02, p=0.028) compared to NN genotype. Conclusions: While there is no evidence for a significant association of several common lipoprotein-related genetic variants with carotid IMT, our results are consistent with the previously reported role of CETP and LPL genetic variants in cardiovascular risk and the possible modulation of the association between hypertension and carotid IMT by APOCIII Sst-1 variant. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. Inst Municipal Invest Med, E-08003 Barcelona, Spain. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM codonnell@nih.gov OI Cupples, L. Adrienne/0000-0003-0273-7965; ELOSUA, ROBERTO/0000-0001-8235-0095; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [N01-HC-25195, HL54776]; NINDS NIH HHS [5R01-NS17950-22] NR 27 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2006 VL 189 IS 1 BP 222 EP 228 DI 10.1016/j.atherosclerosis.2005.12.005 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 097SD UT WOS:000241467900028 PM 16430904 ER PT J AU Shepard, JD Schulkin, J Myers, DA AF Shepard, Jack D. Schulkin, Jay Myers, Dean A. TI Chronically elevated corticosterone in the amygdala increases corticotropin releasing factor mRNA in the dorsolateral bed nucleus of stria terminalis following duress SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE corticosterone; corticotropin releasing factor (CRF); bed nuclei of stria terminalis (BNST) ID PARAVENTRICULAR NUCLEUS; FACTOR ANTAGONIST; RAT-BRAIN; PLUS-MAZE; STRESS; RESPONSES; BEHAVIOR; FEAR; CRH; LOCALIZATION AB Elevated corticosterone in the amygdala leads to cautious avoidance behaviors on the elevated plus maze. The current study examined the effect of elevated corticosterone in the amygdala on corticotropin releasing factor (CRF) mRNA levels in the bed nuclei of stria terminalis (BNST). Exposure to the elevated plus maze increased CRF mRNA in both the dorsolateral and ventrolateral BNST. Corticosterone implants in the amygdala potentiated this effect in the dorsolateral, but not ventrolateral BNST. Corticosterone also resulted in an increased number of neurons expressing CRF in the dorsolateral BNST in response to the behavioral stimuli. (c) 2006 Elsevier B.V. All rights reserved. C1 Towson Univ, Dept Biol Sci, Towson, MD 21252 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC USA. Amer Coll Obstetricians & Gynecologists, Res Dept, Washington, DC 20024 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. RP Shepard, JD (reprint author), Towson Univ, Dept Biol Sci, Towson, MD 21252 USA. EM jshepard@towson.edu NR 28 TC 35 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 1 PY 2006 VL 174 IS 1 BP 193 EP 196 DI 10.1016/j.bbr.2006.07.019 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 097IU UT WOS:000241441500023 PM 16934343 ER PT J AU Hurley, JH Lee, S Prag, G AF Hurley, James H. Lee, Sangho Prag, Gali TI Ubiquitin-binding domains SO BIOCHEMICAL JOURNAL LA English DT Review DE endocytosis; proteasome; protein structure; ubiquitination; ubiquitin-binding domain; vesicle trafficking ID LYS48-LINKED POLYUBIQUITIN CHAIN; PROTEIN-PROTEIN INTERACTIONS; DAMAGE-INDUCIBLE PROTEINS; ZINC-FINGER DOMAIN; INTERACTING MOTIF; UBA DOMAIN; STRUCTURAL BASIS; DNA-REPAIR; GGA PROTEINS; GAT DOMAIN AB The covalent modification of proteins by ubiquitination is a major regulatory mechanism of protein degradation and quality control, endocytosis, vesicular trafficking, cell-cycle control, stress response, DNA repair, growth-factor signalling, transcription, gene silencing and other areas of biology. A class of specific ubiquitin-binding domains mediates most of the effects of protein ubiquitination. The known membership of this group has expanded rapidly and now includes at least sixteen domains: UBA, UIM, MIU, DUIM, CUE, GAT, NZF, A20 ZnF, UBP ZnF, UBZ, Ube, UEV, UBM, GLUE, Jab1/MPN and PFU. The structures of many of the complexes with mono-ubiquitin have been determined, revealing interactions with multiple surfaces on ubiquitin. Inroads into understanding polyubiquitin specificity have been made for two UBA domains, whose structures have been characterized in complex with Lys(48)-linked di-ubiquitin. Several ubiquitin-binding domains, including the UIM, CUE and A20 ZnF (zinc finger) domains, promote auto-ubiquitination, which regulates the activity of proteins that contain them. At least one of these domains, the A20 ZnF, acts as a ubiquitin ligase by recruiting a ubiquitin-ubiquitin-conjugating enzyme thiolester adduct in a process that depends on the ubiquitin-binding activity of the A20 ZnF. The affinities of the mono-ubiquitin-binding interactions of these domains span a wide range, but are most commonly weak, with K-d > 100 mu M. The weak interactions between individual domains and mono-ubiquitin are leveraged into physiologically relevant high-affinity interactions via several mechanisms: ubiquitin polymerization, modification multiplicity, oligomerization of ubiquitinated proteins and binding domain proteins, tandem-binding domains, binding domains with multiple ubiquitin-binding sites and co-operativity between ubiquitin binding and binding through other domains to phospholipids and small G-proteins. C1 NIDDK, Mol Biol Lab, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov FU Intramural NIH HHS NR 110 TC 367 Z9 373 U1 6 U2 45 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2006 VL 399 BP 361 EP 372 DI 10.1042/BJ20061138 PN 3 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 104ED UT WOS:000241938300001 PM 17034365 ER PT J AU Dasso, M AF Dasso, M. TI Ran at kinetochores SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE checkpoint; kinetochore; mitosis; nuclear pore; Ran GTPase; spindle ID NUCLEAR-PORE COMPLEX; SMALL GTPASE RAN; IMPORTIN-BETA; SOMATIC-CELLS; CHECKPOINT PROTEINS; BINDING PROTEIN-2; SPINDLE; MICROTUBULE; NUCLEOPORIN; MITOSIS AB The Ran GTPase controls many cellular functions, including nucleocytoplasmic trafficking, spindle assembly, nuclear assembly and cell-cycle progression. Considerable evidence suggests that diffusible Ran-GTP near mitotic chromatin facilitates the release of critical factors from nuclear transport receptors, thereby promoting organization of mitotic spindles with respect to chromosomes. In addition to this role of soluble Ran-GTP, Ran has two important but less understood roles at mitotic kinetochores. Namely, it is essential for regulation of the spindle assembly checkpoint and for assembly of microtubule fibres that attach kinetochores to spindle poles. Here, I will briefly summarize evidence for these kinetochore-associated functions and mention some of the issues that remain to be addressed regarding them. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD008740-06] NR 54 TC 18 Z9 18 U1 2 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 2006 VL 34 BP 711 EP 715 PN 5 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 109EE UT WOS:000242289900014 PM 17052180 ER PT J AU Zhang, FR Di, YJ Li, JJ Shi, Y Zhang, LP Wang, CY He, XH Liu, YZ Wan, DF Huo, KK Gu, JR AF Zhang, Fengrui Di, Yujun Li, Jinjun Shi, Yan Zhang, Liping Wang, Chunyan He, Xianghuo Liu, Yongzhong Wan, Dafang Huo, Keke Gu, Jianren TI Molecular cloning and characterization of human Aph2 gene, involved in AP-1 regulation by interaction with JAB1 SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE hAph2; zf-DHHC; yeast two-hybrid; JAB1; AP-1 ID ACTIVATOR PROTEIN-1; INHIBITOR P27(KIP1); INVERSE EXPRESSION; COP9 SIGNALOSOME; POOR-PROGNOSIS; DOMAIN; DEGRADATION; COMPLEX; BINDING; CANCER AB A human Aph2 gene (hAph2) was identified and cloned from a human placenta cDNA library. Bioinformatics analysis revealed hAPH2 protein shares 96% identity with mouse APH2 and contains a zf-DHHC domain (148-210aa), which is always involved in protein-protein or protein-DNA interaction. Differential expression patterns of hAph2 mRNA were observed in normal human tissues. Yeast two-hybrid screening found another hAPH2-interacting protein JAB1. The zf-DHHC domain of hAPH2 and the C-terminal of JAB1 were confirmed to be critical for the interaction. Fused with GFP and expressed in COS-7, NIH/3T3 and SMMC-7721 cell lines, hAPH2 showed predominant distribution in the cytoplasm and co-localized with JAB1 around the nucleus. Furthermore, overexpression of hAPH2 could increase apoptosis of COS-7 cells and negatively regulate JAB1-induced activation of AP-1 in a concentration dependent manner. The expression level of c-jun was also down-regulated by overexpression of hAPH2 in COS-7 cells. These data showed some basic characterization and function of hAph2 (hAPH2), dependent or independent with JAB1. (c) 2006 Elsevier B.V. All rights reserved. C1 Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst, Shanghai 200032, Peoples R China. Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China. Univ Gothenburg, Dept Cell & Mol Biol Microbiol, S-40530 Gothenburg, Sweden. Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. RP Li, JJ (reprint author), Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst, Shanghai 200032, Peoples R China. EM lijj64@yahoo.com.cn RI Zhang, Fengrui/A-1240-2012; He, Xianghuo/I-1497-2014 OI He, Xianghuo/0000-0001-8872-668X NR 42 TC 5 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD NOV-DEC PY 2006 VL 1759 IS 11-12 BP 514 EP 525 DI 10.1016/j.bbaexp.2006.10.002 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132RH UT WOS:000243959400002 PM 17123647 ER PT J AU Beghi, E Logroscino, G Chio, A Hardiman, O Mitchell, D Swingler, R Traynor, BJ AF Beghi, Ettore Logroscino, Giancarlo Chio, Adriano Hardiman, Orla Mitchell, Douglas Swingler, Robert Traynor, Bryan J. CA EURALS Consortium TI The epidemiology of ALS and the role of population-based registries SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE amyotrophic lateral sclerosis; motor neuron disease; incidence; mortality; risk factor ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; CAPTURE-RECAPTURE METHODS; EL-ESCORIAL; CIGARETTE-SMOKING; SURVIVAL PREDICTION; DIAGNOSTIC-CRITERIA; PROLONGED SURVIVAL; CLINICAL-FEATURES; PROGRESSION RATE C1 Ist Ric Farmacol Mario Negri, I-20157 Milan, Italy. Harvard Univ, HSPH, Dept Epidemiol, Boston, MA 02115 USA. Univ Turin, Dept Neurosci, I-10124 Turin, Italy. Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. Royal Coll Surgeons Ireland, Dublin 2, Ireland. Royal Preston Hosp, Preston MND Care & Res Ctr, Preston, Lancs, England. Univ Dundee, Ninewells Hosp & Med Sch, Dept Neurol, Dundee DD1 9SY, Scotland. NIMH, Sect Dev Genet Epidemiol, NIH, Bethesda, MD 20892 USA. RP Beghi, E (reprint author), Ist Ric Farmacol Mario Negri, Via Eritrea 62, I-20157 Milan, Italy. EM beghi@marionegri.it RI Traynor, Bryan/G-5690-2010; LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chio, Adriano/0000-0001-9579-5341; Hardiman, Orla/0000-0003-2610-1291 NR 71 TC 110 Z9 114 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD NOV-DEC PY 2006 VL 1762 IS 11-12 BP 1150 EP 1157 DI 10.1016/j.bbadis.2006.09.008 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 118FB UT WOS:000242926600017 PM 17071060 ER PT J AU Smyth, JT DeHaven, WI Jones, BF Mercer, JC Trebak, M Vazquez, G Putney, JW AF Smyth, Jeremy T. DeHaven, Wayne I. Jones, Bertina F. Mercer, Jason C. Trebak, Mohamed Vazquez, Guillermo Putney, James W., Jr. TI Emerging perspectives in store-operated Ca2+ entry: Roles of Orai, Stim and TRP SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article; Proceedings Paper CT 9th European Symposium on Calcium-Binding Proteins in Normal and Transformed Cells CY JUL 19-22, 2006 CL Ecole Superieure Biotechnol, Strasbourg, FRANCE HO Ecole Superieure Biotechnol DE calcium channel; TRP channel; Stim 1; Orai 1; calcium-release-activated-calcium current; store-operated channel; capacitative calcium entry; calcium oscillation ID CAPACITATIVE CALCIUM-ENTRY; INOSITOL TRISPHOSPHATE RECEPTOR; CA2+-PERMEABLE CATION CHANNEL; PROTEIN-COUPLED RECEPTOR; MOUSE TRANSIENT RECEPTOR; PANCREATIC ACINAR-CELLS; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE; 2-AMINOETHOXYDIPHENYL BORATE; XENOPUS-OOCYTES AB Depletion of intracellular Ca2+ stores induces Ca2+ influx across the plasina membrane through store-operated channels (SOCs). This store-operated Ca2+ influx is important for the replenishment of the Ca2+ stores, and is also involved in many signaling processes by virtue of the ability of intracellular Ca2+ to act as a second messenger. For many years, the molecular identities of particular SOCs, as well as the signaling mechanisms by which these channels are activated, have been elusive. Recently, however, the mammalian proteins STIM1 and Orai1 were shown to be necessary for the activation of store-operated Ca2+ entry in a variety of mammalian cells. Here we present molecular, pharmacological, and electrophysiological properties of SOCs, with particular focus on the roles that STIM1and Orai1may play in the signaling processes that regulate various pathways of store-operated entry. Published by Elsevier B.V. C1 Natl Inst Environm Hlth Serv, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), Natl Inst Environm Hlth Serv, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov RI Trebak, Mohamed/E-7405-2014 NR 163 TC 142 Z9 151 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV PY 2006 VL 1763 IS 11 SI SI BP 1147 EP 1160 DI 10.1016/j.bbamcr.2006.08.050 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 117SB UT WOS:000242892200003 PM 17034882 ER PT J AU Wilder, PT Lin, J Bair, CL Charpentier, TH Yang, D Liriano, M Varney, KM Lee, A Oppenheim, AB Adhya, S Carrier, F Weber, DJ AF Wilder, Paul T. Lin, Jing Bair, Catherine L. Charpentier, Thomas H. Yang, Dong Liriano, Melissa Varney, Kristen M. Lee, Andrew Oppenheim, Amos B. Adhya, Sankar Carrier, France Weber, David J. TI Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article; Proceedings Paper CT 9th European Symposium on Calcium-Binding Proteins in Normal and Transformed Cells CY JUL 19-22, 2006 CL Ecole Superieure Biotechnol, Strasbourg, FRANCE HO Ecole Superieure Biotechnol DE S100B; calcium-binding protein; S100 protein; p53; Hdm2; Mdm2 ID MALIGNANT-MELANOMA; KINASE-C; POSTTRANSLATIONAL MODIFICATION; S100-BETA EXPRESSION; MULTIDIMENSIONAL NMR; RAT S100B(BETA-BETA); REGULATORY DOMAIN; FAMILY; CELLS; MDM2 AB S100B is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effect by binding and affecting various target proteins. A consensus sequence for S100B target proteins was published as (K/R)(L/I)xWxxIL and matches a region in the actin capping protein CapZ (VV. Ivanenkov, G.A. Jamieson, Jr., E. Gruenstein, R.V. Dimlich, Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ, J. Biol. Chem. 270 (1995) 14651-14658). Several additional S100B targets are known including p53, a nuclear Dbf2 related (NDR) kinase, the RAGE receptor, neuromodulin, protein kinase C, and others. Examining the binding sites of such targets and new protein sequence searches provided additional potential target proteins for S100B including Hdm2 and Hdm4, which were both found to bind S100B in a calcium-dependent manner. The interaction between S100B and the Hdm2 and/or the Hdm4 proteins may be important physiologically in light of evidence that like Hdm2, S100B also contributes to lowering protein levels of the tumor suppressor protein, p53. For the S100B-p53 interaction, it was found that phosphorylation of specific serine and/or threonine residues reduces the affinity of the S10B-p53 interaction by as much as an order of magnitude, and is important for protecting p53 from S100B-dependent downregulation, a scenario that is similar to what is found for the Hdm2-p53 complex. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20879 USA. RP Weber, DJ (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, 108 N Greene St, Baltimore, MD 21201 USA. EM dweber@umaryland.edu FU Intramural NIH HHS; NCI NIH HHS [CA 107331, R01 CA107331]; NCRR NIH HHS [S10 RR 15741, S10 RR016812, S10 RR029601, S10 RR 16812, S10 RR 10441]; NIGMS NIH HHS [R01 GM058888, GM 58888] NR 91 TC 52 Z9 52 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV PY 2006 VL 1763 IS 11 SI SI BP 1284 EP 1297 DI 10.1016/j.bbamcr.2006.08.024 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 117SB UT WOS:000242892200018 PM 17010455 ER PT J AU Makarova, KS Grishin, NV Koonin, EV AF Makarova, Kira S. Grishin, Nick V. Koonin, Eugene V. TI The HicAB cassette, a putative novel, RNA-targeting toxin-antitoxin system in archaea and bacteria SO BIOINFORMATICS LA English DT Article ID CRYSTAL-STRUCTURE; DATABASE; LOCI AB Toxin-antitoxin systems (TAS) are abundant, diverse, horizontally mobile gene modules that encode powerful resistance mechanisms in prokaryotes. We use the comparative-genomic approach to predict a new TAS that consists of a two-gene cassette encoding uncharacterized HicA and HicB proteins. Numerous bacterial and archaeal genomes encode from one to eight HicAB modules which appear to be highly prone to horizontal gene transfer. The HicB protein (COG1598/COG4226) has a partially degraded RNAse H fold, whereas HicA (COG1724) contains a double-stranded RNA-binding domain. The stable combination of these two domains suggests a link to RNA metabolism, possibly, via an RNA interference-type mechanism. In most HicB proteins, the RNAse H-like domain is fused to a DNA-binding domain, either of the ribbon-helix-helix or of the helix-turn-helix class; in other TAS, proteins containing these DNA-binding domains function as antitoxins. Thus, the HicAB module is predicted to be a novel TAS whose mechanism involves RNA-binding and, possibly, cleavage. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Texas, SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 16 TC 54 Z9 56 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2006 VL 22 IS 21 BP 2581 EP 2584 DI 10.1093/bioinformatics/btl418 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 099XC UT WOS:000241629600001 PM 16895922 ER PT J AU Klimes-Dougan, B Ronsaville, D Wiggs, EA Martinez, PE AF Klimes-Dougan, Bonnie Ronsaville, Donna Wiggs, Edythe A. Martinez, Pedro E. TI Neuropsychological functioning in adolescent children of mothers with a history of bipolar or major depressive disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adolescent; attention; bipolar disorder; executive functioning; major depression; memory ID CARD SORTING TEST; COGNITIVE-DEVELOPMENT; POSTNATAL DEPRESSION; MATERNAL DEPRESSION; UNIPOLAR DEPRESSION; MEMORY PERFORMANCE; ATTENTION-DEFICIT; COMPLEX FIGURE; VERBAL MEMORY; SCHIZOPHRENIA AB Background: Growing evidence demonstrates an association of neuropsychological deficits with mood disorders, but it is not yet clear whether these deficits are risk factors or are concomitant with the symptoms. This study examines the neuropsychological functioning of a group of adolescent offspring who are at risk for a mood disorder by virtue of being raised by mothers who have been diagnosed with major depressive disorder (MDD) or bipolar disorder (BPD). Methods: Adolescent offspring of mothers with BPD (n = 43) or MDD (n = 72) and of psychiatrically well parents (n = 50) completed a battery of neuropsychological tests to assess executive functioning, memory, and attention. Results: Children of mothers with BPD showed deficits in executive functioning and selective deficits in spatial memory and attention, in comparison with children of well mothers. Deficits were not found for children of MDD mothers. Conclusions: Knowledge of these neurocognitive processes could aid ultimately in determining whether neurocognitive deficits precede BPD, whether unique profiles are associated with various types of mood disorders, and who may benefit from interventions. C1 Univ Minnesota, Sch Med, Dept Psychiat, Div Child & Adolescent Psychiat, Minneapolis, MN 55454 USA. NIMH, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Klimes-Dougan, B (reprint author), Univ Minnesota, Sch Med, Dept Psychiat, Div Child & Adolescent Psychiat, F256-2B W,2450 Riverside Ave, Minneapolis, MN 55454 USA. EM klimes@umn.edu FU Intramural NIH HHS NR 78 TC 69 Z9 73 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2006 VL 60 IS 9 BP 957 EP 965 DI 10.1016/j.biopsych.2006.03.031 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600009 PM 16934765 ER PT J AU Roberson-Nay, R McClure, EB Monk, CS Nelson, EE Guyer, AE Fromm, SJ Charney, DS Leibenluft, E Blair, J Ernst, M Pine, DS AF Roberson-Nay, Roxann McClure, Erin B. Monk, Christopher S. Nelson, Eric E. Guyer, Amanda E. Fromm, Stephen J. Charney, Dennis S. Leibenluft, Ellen Blair, James Ernst, Monique Pine, Daniel S. TI Increased amygdala activity during successful memory encoding in adolescent major depressive disorder: An fMRI study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE amygdala; anxiety; encoding; fMRI; MDD; recognition memory ID EVENT-RELATED FMRI; ANTIDEPRESSANT TREATMENT; PSYCHIATRIC-DISORDERS; EMOTIONAL FACES; MOOD DISORDERS; CHILDREN; MECHANISMS; CHILDHOOD; ANXIETY AB Background: Although major depressive disorder (MDD) represents one of the most serious psychiatric problems afflicting adolescents, efforts to understand the neural circuitry of adolescent MDD have lagged behind those of adult MDD. This study tests the hypothesis that adolescent MDD is associated with abnormal amygdala activity during evocative-face viewing. Methods: Using functional magnetic resonance imaging (fMRI), between-group differences among MDD (n = 10), anxious (n = 11), and non-psychiatric comparisons (n = 23) were examined during successful vs. unsuccessful face encoding, with encoding success measured post-scan. Results: Compared to healthy adolescents, MDD patients exhibited poorer memory for faces. fMRI analyses accounted for this performance difference through event-related methods. In an analysis comparing successful vs. unsuccessful face encoding, MDD patients exhibited greater left amygdala activation relative to healthy and anxious youth. Conclusions. Given prior findings among adults, this study suggests that adolescent and adult MDD may involve similar underlying abnormalities in amygdala functioning. C1 NIMH, Sect Dev & Affect Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. Mt Sinai Sch Med, Dept Pharmacol, New York, NY USA. Mt Sinai Sch Med, Dept Biol Chem, New York, NY USA. NIMH, Unit Affect Disorders, Pediat & Dev Neuropsychiat Branch, Intramural Res Program, Bethesda, MD 20892 USA. NIMH, Unit Affect Cognit Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. RP Roberson-Nay, R (reprint author), Virginia Commonwealth Univ, Dept Psychiat, Commonwealth Inst Child & Family Studies, Richmond, VA 23298 USA. EM rrobersonnay@vcu.edu RI Nelson, Eric/B-8980-2008; Monk, Christopher/J-1805-2014 OI Nelson, Eric/0000-0002-3376-2453; NR 35 TC 81 Z9 84 U1 2 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 NOV 1 PY 2006 VL 60 IS 9 BP 966 EP 973 DI 10.1016/j.biopsych.2006.02.018 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600010 PM 16603133 ER PT J AU Brotman, MA Schmajuk, M Rich, BA Dickstein, DP Guyer, AE Costello, EJ Egger, HL Angold, A Pine, DS Leibenluft, E AF Brotman, Melissa A. Schmajuk, Mariana Rich, Brendan A. Dickstein, Daniel P. Guyer, Amanda E. Costello, E. Jane Egger, Helen L. Angold, Adrian Pine, Daniel S. Leibenluft, Ellen TI Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY APR 16, 2005 CL Coral Gables, FL SP NIMH DE bipolar disorder; children; prevalence; depression; irritability; ADHD ID PEDIATRIC BIPOLAR DISORDER; PSYCHIATRIC-ASSESSMENT CAPA; GREAT SMOKY MOUNTAINS; ANXIETY DISORDERS; JUVENILE MANIA; ADOLESCENTS; YOUTH; COMORBIDITY; SYMPTOMS; ASSOCIATIONS AB Background: Controversy concerning the diagnosis of pediatric bipolar disorder (BD) has focused attention on children with chronic irritability and hyperarousal. This syndrome has been called the "broad BD phenotype" or severe mood dysregulation (SMD). This study examines prevalence, concurrent Axis 1 diagnoses, and longitudinal outcome of SMD in an epidemiologic sample. Methods: Data were drawn from the Great Smoky Mountains Study, a longitudinal epidemiological study. Items from the Child and Adolescent Psychiatric Assessment were used to generate SMD criteria. Results. Among 1420 children, the lifetime prevalence of SMD in children ages 9-19 was 3.3%. Most (67.7%) SMD youth bad an Axis 1 diagnosis, most commonly attention-deficit/hyperactivity disorder (26.9%), conduct disorder (25.9%), and/or oppositional defiant disorder (24.5%). In young adulthood (mean age 18.3 +/- 2.1 years), youth who met criteria for SMD in the first wave (mean age 10.6 +/- 1.4 years) were significantly more likely to be diagnosed with a depressive disorder (odds ratio 7.2, confidence interval 1.3-38.8, p =.02) than youth who never met criteria for SMD. Conclusions: Severe mood dysregulation is relatively common in childhood and predicts risk for early adulthood depressive disorders. Research should continue to explore the course of illness in children with SMD. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dev Epidemiol Program, Durham, NC 27706 USA. RP Brotman, MA (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, 15K N Dr,Room 208, Bethesda, MD 20892 USA. EM brotmanm@mail.nih.gov RI Brotman, Melissa/H-7409-2013; Dickstein, Daniel/L-3210-2016; OI Dickstein, Daniel/0000-0003-1647-5329; Egger, Helen/0000-0001-8447-5350 FU Intramural NIH HHS; NIDA NIH HHS [DA016977]; NIMH NIH HHS [MH01167] NR 27 TC 197 Z9 198 U1 3 U2 20 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 NOV 1 PY 2006 VL 60 IS 9 BP 991 EP 997 DI 10.1016/j.biopsych.2006.08.042 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600013 PM 17056393 ER PT J AU Keck, PE Mintz, J McElroy, SL Freeman, MP Frye, TSMA Altshuler, LL Kupka, R Nolen, WA Leverich, GS Denicoff, KD Grunze, H Duan, NH Post, RM AF Keck, Paul E., Jr. Mintz, Jim McElroy, Susan L. Freeman, Marlene P. Frye, Trisha Suppes Mark A. Altshuler, Lori L. Kupka, Ralph Nolen, Willem A. Leverich, Gabriele S. Denicoff, Kirk D. Grunze, Heinz Duan, Naihua Post, Robert M. TI Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY APR 16, 2005 CL Coral Gables, FL SP NIMH DE bipolar disorder; ethyl-eicosapenantoate; omega-31; fatty acid; clinical trial ID PROPENSITY SCORE; OMEGA-3-FATTY-ACIDS; SCHIZOPHRENIA; SCALE; ACID AB Background: The results of pilot trials suggest that omega-3 fatty acids may have efficacy in the treatment of mood symptoms in bipolar disorder. Methods: We conducted a 4-month, randomized, placebo-controlled, adjunctive trial of ethyl-eicosapentanoate (EPA) 6 g/day in the treatment of bipolar depression and rapid cycling bipolar disorder. Subjects were receiving mood-stabilizing medications at therapeutic doses or plasma concentrations. The measures of efficacy were early study discontinuation, changes from baseline in depressive symptoms (Inventory for Depressive Symptomology total score) and in manic symptoms (Young Mania Rating Scale total score), and manic exacerbations ("switches"). We also measured side effects and bleeding time, a biomarker of drug action. Results: Overall, there were no significant differences on any outcome measure between the EPA and placebo groups. Conclusions: This study did not find overall evidence of efficacy for adjunctive treatment with EPA 6 g/day in outpatients with bipolar depression or rapid cycling bipolar disorder. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH 45267 USA. Cincinnati VAMC, Gen Clin Res Ctr, Cincinnati, OH USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Arizona, Sch Med, Dept Psychiat, Tucson, AZ 85721 USA. SW Texas State Univ, Dept Psychiat, Dallas, TX USA. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Utrecht, Med Ctr, NL-3508 TC Utrecht, Netherlands. Univ Groningen Hosp, Groningen, Netherlands. NIMH, Biol Psychiat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Res Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Munich, Psychiat Klin, D-80539 Munich, Germany. RP Keck, PE (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, 231 Albert Sabin Way,ML 559, Cincinnati, OH 45267 USA. EM paul.keck@UC.edu RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014; OI Mintz, Jim/0000-0002-8299-5851; Grunze, Heinz/0000-0003-4712-8979 FU NIMH NIH HHS [R01 MH079261] NR 22 TC 129 Z9 132 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2006 VL 60 IS 9 BP 1020 EP 1022 DI 10.1016/j.biopsych.2006.03.056 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600017 PM 16814257 ER PT J AU Schmidt, AL Anderson, LM AF Schmidt, Adele L. Anderson, Lucy M. TI Repetitive DNA elements as mediators of genomic change in response to environmental cues SO BIOLOGICAL REVIEWS LA English DT Review DE repetitive DNA; transposable elements; retrotransposons; microsatellite; adaptive evolution; genome evolution ID MOUSE MINISATELLITE LOCUS; HEAD BLIGHT RESISTANCE; F-1 MICE BORN; TRANSPOSABLE ELEMENTS; GENE-EXPRESSION; TRINUCLEOTIDE REPEAT; GERMLINE MUTATION; HAEMOPHILUS-INFLUENZAE; NEISSERIA-MENINGITIDIS; MYOTONIC-DYSTROPHY AB There is no logical or theoretical barrier to the proposition that organismal and cell signaling could transduce environmental signals into specific, beneficial changes in primary structure of noncoding DNA via repetitive element movement or mutation. Repetitive DNA elements, including transposons and microsatellites, are known to influence the structure and expression of protein-coding genes, and to be responsive to environmental signals in some cases. These effects may create fodder for adaptive evolution, at rates exceeding those observed for point mutations. In many cases, the changes are no doubt random, and fitness is increased through simple natural selection. However, some transposons insert at specific sites, and certain regions of the genome exhibit selectively and beneficially high mutation rates in a range of organisms. In multicellular organisms, this could benefit individuals in situations with significant potential for clonal expansion: early life stages or regenerative tissues in animals, and most plant tissues. Transmission of the change to the next generation could occur in plants and, under some circumstances, in animals. C1 CSIRO, Plant Ind, Queensland Biosci Precint, St Lucia, Qld 4067, Australia. Univ Melbourne, Dept Zool, Parkville, Vic 3010, Australia. NCI, Cellular Pathogenesis Sect, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. RP Schmidt, AL (reprint author), CSIRO, Plant Ind, Queensland Biosci Precint, 306 Carmody Rd, St Lucia, Qld 4067, Australia. FU Intramural NIH HHS NR 163 TC 25 Z9 25 U1 2 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1464-7931 J9 BIOL REV JI Biol. Rev. PD NOV PY 2006 VL 81 IS 4 BP 531 EP 543 DI 10.1017/S146479310600710X PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 110DL UT WOS:000242358400004 PM 16893475 ER PT J AU Akimov, SA Frolov, VA Kumin, PI Cohen, FS Zimmerberg, J Chizmadzhev, YA AF Akimov, S. A. Frolov, VI. A. Kumin, P. I. Cohen, F. S. Zimmerberg, J. Chizmadzhev, Yu. A. TI Model for raft creation as a result of incomplete wetting of membrane protein SO BIOLOGICHESKIE MEMBRANY LA Russian DT Article ID LIPID RAFTS; BENDING ELASTICITY; FLUORESCENCE MICROSCOPY; CAPILLARY CONDENSATION; FLUID MEMBRANES; LINE TENSION; 2 DIMENSIONS; DOMAINS; CURVATURE; CHOLESTEROL AB We propose a model explaining a creation of specific membrane liquid-ordered phase, rich in sphingomyelin and cholesterol, in the vicinity of integral membrane proteins. We assume that global phase transition does not take place, i.e. membrane is undersaturated. We hypothesize a fort-nation of a thin 2D film of liquid-ordered phase near a protein by the mechanism of incomplete wetting, and determine the conditions for stability of this film. This mechanism is likely to account for the raft assembly in cell membranes. The work consists of three Sections. In the first Section, using the Landau technique, we calculate the film equilibrium width on condition that one knows effective line tension of the protein/surrounding membrane boundary. In the second Section we calculate the line tension assuming that it is defined by hydrophobic mismatch of the protein transmembrane region, thickness of the film and thickness of the surrounding membrane. In the calculations membrane is considered as continuous elastic medium. The line tension is estimated from splay and tilt. In the third Section the results of our calculations are illustrated graphically. We show that if the length of the transmembrane domain of the protein is not less than the liquid-ordered bilayer thickness, the equilibrium width of the film is about 4-6 nm. Moreover, at a slight undersaturation, a formation of metastable films of 10-14 nm width is possible. These results are practically not sensitive to variations in spontaneous curvature of rafts and surrounding membrane. C1 Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Moscow 119991, Russia. NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Rush Univ, Sch Med, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. RP Akimov, SA (reprint author), Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Leninsky Prospect 31,Bld 5, Moscow 119991, Russia. EM akimov_sergey@mail.ru RI Chizmadzhev, Yuri/L-1984-2013; Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 39 TC 0 Z9 0 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0233-4755 J9 BIOL MEMBRANY JI Biol. Membr. PD NOV-DEC PY 2006 VL 23 IS 6 BP 510 EP 524 PG 15 WC Cell Biology SC Cell Biology GA 120PZ UT WOS:000243098500009 ER PT J AU Hymes, SR Turner, ML Champlin, RE Couriel, DR AF Hymes, Sharon R. Turner, Maria L. Champlin, Richard E. Couriel, Daniel R. TI Cutaneous manifestations of chronic graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE stem cell transplant; GVHD; dermatology ID CONSENSUS DEVELOPMENT PROJECT; BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; CLINICAL-TRIALS; CRITERIA; INVOLVEMENT; DIAGNOSIS; LESIONS AB Cutaneous chronic graft versus host disease has traditionally been classified into lichenoid and scleroderma-like forms. However, the initial presentation is sometimes subtle and a variety of less common cutaneous manifestation may be prevalent. This clinical review focuses on the lesional morphology of chronic graft versus host disease, and presents a classification system that may prove useful in early diagnosis. In addition, this approach may help to facilitate the correlation of different morphologic entities with outcome and response to therapy. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Dermatol, Unit 434, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Hymes, SR (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Dermatol, Unit 434, FC5-3004, Houston, TX 77030 USA. EM srhymes@mdanderson.org NR 25 TC 37 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2006 VL 12 IS 11 BP 1101 EP 1113 DI 10.1016/j.bbmt.2006.08.043 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 104EH UT WOS:000241938700001 PM 17085303 ER PT J AU Fowler, DH Odom, J Steinberg, SM Chow, CK Foley, J Kogan, Y Hou, J Gea-Banacloche, J Sportes, C Pavletic, S Leitman, S Read, EJ Carter, C Kolstad, A Fox, R Beatty, GL Vonderheide, RH Levine, BL June, CH Gress, RE Bishop, MR AF Fowler, Daniel H. Odom, Jeanne Steinberg, Seth M. Chow, Catherine K. Foley, Jason Kogan, Yelena Hou, Jeannie Gea-Banacloche, Juan Sportes, Claude Pavletic, Steven Leitman, Susan Read, Elizabeth J. Carter, Charles Kolstad, Arne Fox, Rebecca Beatty, Gregory L. Vonderheide, Robert H. Levine, Bruce L. June, Carl H. Gress, Ronald E. Bishop, Michael R. TI Phase I clinical trial of costimulated, IL-4 polarized donor CD4(+) T cells as augmentation of allogeneic hematopoietic cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE graft versus host disease; Th2 cells; tetramers; cytokines ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ADOPTIVE TRANSFER; EX-VIVO; GRAFT; LEUKEMIA; LYMPHOMA; LYMPHOCYTES; ENGRAFTMENT; EXPRESSION AB The primary objective of this clinical trial was to evaluate the safety, feasibility, and biologic effects of administering costimulated, interleukin (IL)-4 polarized donor CD4(+) T cells in the setting of HILA-matched sibling, T cell-replete allogeneic hematopoietic cell transplantation (HCT). Forty-seven subjects with hematologic malignancy received granulocyte colony-stimulating factor-mobilized allogeneic hematopoietic cell transplants and cyclosporine graft-versus-host disease (GVHD) prophylaxis after reduced intensity conditioning. Initial subjects received no additional cells (n = 19); subsequent subjects received additional donor CD4(+) T cells generated ex vivo by CD3/CD28 costimulation in medium containing IL-4 and IL-2 (administered day 1 after HCT at 5, 25, or 125 x 10(6) cells/kg). Studies after HCT included measurement of monocyte IL-1 alpha and tumor necrosis factor alpha, detection of T cells with antitumor specificity, and characterization of T cell cytokine phenotype. The culture method generated donor CD4(+) T cells that secreted increased T helper 2 (Th2) cytolkines and decreased T helper 1 (Th1) cytokines. Such Th2-like cells were administered without infusional or dose-limiting toxicity. The Th2 cohort had accelerated lymphocyte reconstitution; both cohorts had rapid hematopoietic recovery and alloengraftment. Acute GVHD and overall survival were similar in the Th2 and non-Th2 cohorts. Th2 cell recipients tended to have increased monocyte IL-1a and had increased tumor necrosis factor alpha secretion. CD8(+) T cells with antitumor specificity were observed in Th2 and non-Th2 cohorts. Post-transplantation T cells from Th2 cell recipients secreted IL-4 and IL-10 (Th2 cytokines) and IL-2 and interferon gamma (Th1 cytokines). Allograft augmentation with costimulated, IL-4-polarized donor CD4(+) T cells resulted in activated Th1, Th2, and inflammatory cytokine pathways without an apparent increase in GVHD. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NIH, Ctr Canc Res, East Labs 3, Bethesda, MD 20892 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. Norwegian Radium Hosp, Oslo, Norway. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Fowler, DH (reprint author), NIH, Ctr Canc Res, East Labs 3, 9000 Rockville Pike,Bldg 10,3-3330, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov RI Levine, Bruce/D-1688-2009 NR 38 TC 43 Z9 49 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 NOV PY 2006 VL 12 IS 11 BP 1150 EP 1160 DI 10.1016/j.bbmt.2006.06.015 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 104EH UT WOS:000241938700006 PM 17085308 ER PT J AU Polikov, VS Block, ML Fellous, JM Hong, JS Reichert, WM AF Polikov, Vadim S. Block, Michelle L. Fellous, Jean-Marc Hong, Jau-Shyong Reichert, W. Monty TI In vitro model of glial scarring around neuroelectrodes chronically implanted in the CNS SO BIOMATERIALS LA English DT Article DE neural prosthesis; foreign-body response; in vitro test; cell culture; brain; biocompatibility ID NIGRAL DOPAMINERGIC-NEURONS; CEREBRAL-CORTEX; BRAIN-TISSUE; NEUROPROSTHETIC DEVICES; MICROELECTRODE ARRAYS; INFLAMMATORY DAMAGE; MICROGLIAL CELLS; CORTICAL-NEURONS; ELECTRODE ARRAYS; REACTIVE GLIOSIS AB A novel in vitro model of glial scarring was developed by adapting a primary cell-based system previously used for studying neuroinflammatory processes in neurodegenerative disease. Midbrains from embryonic day 14 Fischer 344 rats were mechanically dissociated and grown on poly-D-lysine coated 24 well plates to a confluent layer of neurons, astrocytes, and microglia. The culture was injured with either a mechanical scrape or foreign-body placement (segments of 50 mu m diameter stainless steel microwire), fixed at time points from 6 h to 10 days, and assessed by immunocytochemistry. Microglia invaded the scraped wound area at early time points and hypertrophied activated astrocytes repopulated the wound after 7 days. The chronic presence of microwire resulted in a glial scar forming at 10 days, with microglia forming an inner layer of cells coating the microwire, while astrocytes surrounded the microglial core with a network of cellular processes containing upregulated GFAP. Vimentin expressing cells and processes were present in the scrape at early times and within the astrocyte processes forming the glial scar. Neurons within the culture did not repopulate the scrape wound and did not respond to the microwire, although they were determined to be electrically active through patch clamp recording. The time course and relative positions of the glia in response to the different injury paradigms correlated well with stereotypical in vivo responses and warrant further work in the development of a functional in vitro test bed. (c) 2006 Elsevier Ltd. All rights reserved. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. NIEHS, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. RP Reichert, WM (reprint author), Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. EM reichert@duke.edu FU Intramural NIH HHS NR 41 TC 51 Z9 52 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD NOV PY 2006 VL 27 IS 31 BP 5368 EP 5376 DI 10.1016/j.biomaterials.2006.06.018 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 085NO UT WOS:000240611000004 PM 16842846 ER PT J AU Zhukovsky, MA Leikina, E Markovic, I Bailey, AL Chernomordik, LV AF Zhukovsky, Mikhail A. Leikina, Eugenia Markovic, Ingrid Bailey, Austin L. Chernomordik, Leonid V. TI Heterogeneity of early intermediates in cell-liposome fusion mediated by influenza hemagglutinin SO BIOPHYSICAL JOURNAL LA English DT Article ID INDUCED MEMBRANE-FUSION; VIRUS HEMAGGLUTININ; RECEPTOR-BINDING; PORE FORMATION; CONFORMATIONAL CHANGE; CYTOPLASMIC TAIL; LIPID VESICLES; 6-HELIX BUNDLE; EARLY-STAGE; PH AB To explore early intermediates in membrane fusion mediated by influenza virus hemagglutinin (HA) and their dependence on the composition of the target membrane, we studied lipid mixing between HA-expressing cells and liposomes containing phosphatidylcholine ( PC) with different hydrocarbon chains. For all tested compositions, our results indicate the existence of at least two types of intermediates, which differ in their lifetimes. The composition of the target membrane affects the stability of fusion intermediates at a stage before lipid mixing. For less fusogenic distearoyl PC-containing liposomes at 4 degrees C, some of the intermediates inactivate, and no intermediates advance to lipid mixing. Fusion intermediates that formed for the more fusogenic dioleoyl PC-containing liposomes did not inactivate and even yielded partial lipid mixing at 4 degrees C. Thus, a more fusogenic target membrane effectively blocks nonproductive release of the conformational energy of HA. Even for the same liposome composition, HA forms two types of fusion intermediates, dissimilar in their stability and propensity to fuse. This diversity of fusion intermediates emphasizes the importance of local membrane composition and local protein concentration in fusion of heterogeneous biological membranes. C1 NICHHD, Sect Membrane Biol, Cellular & Mol Biophys Lab, NIH, Bethesda, MD 20892 USA. RP Zhukovsky, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM Mikhail_Zhukovsky@dfci.harvard.edu FU Intramural NIH HHS NR 54 TC 5 Z9 5 U1 1 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2006 VL 91 IS 9 BP 3349 EP 3358 DI 10.1529/biophysj.106.088005 PG 10 WC Biophysics SC Biophysics GA 094GS UT WOS:000241228500021 PM 16905609 ER PT J AU Xu, SG Gu, J Belknap, B White, H Yu, LC AF Xu, Sengen Gu, Jin Belknap, Betty White, Howard Yu, Leepo C. TI Structural characterization of the binding of myosin center dot ADP center dot P-i to actin in permeabilized rabbit psoas muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID X-RAY-DIFFRACTION; HELICAL ORDER; THICK FILAMENTS; CROSS-BRIDGES; ATP STATE; CONTRACTION; ACTOMYOSIN; CONFORMATION; MECHANISM; COMPLEX AB When myosin is attached to actin in a muscle cell, various structures in the. laments are formed. The two strongly bound states (A center dot M center dot ADP and A center dot M) and the weakly bound A center dot M center dot ATP states are reasonably well understood. The orientation of the strongly bound myosin heads is uniform ("stereospecific'' attachment), and the attached heads exhibit little spatial fluctuation. In the prehydrolysis weakly bound A center dot M center dot ATP state, the orientations of the attached myosin heads assume a wide range of azimuthal and axial angles, indicating considerable flexibility in the myosin head. The structure of the other weakly bound state, A center dot M center dot ADP center dot P-i, however, is poorly understood. This state is thought to be the critical pre-power-stroke state, poised to make the transition to the strongly binding, force-generating states, and hence it is of particular interest for understanding the mechanism of contraction. However, because of the low affinity between myosin and actin in the A center dot M center dot ADP center dot P-i state, the structure of this state has eluded determination both in isolated form and in muscle cells. With the knowledge recently gained in the structures of the weakly binding M center dot ATP, M center dot ADP center dot P-i states and the weakly attached A center dot M center dot ATP state in muscle fibers, it is now feasible to delineate the in vivo structure of the attached state of A center dot M center dot ADP center dot P-i. The series of experiments presented in this article were carried out under relaxing conditions at 25 degrees C, where; 95% of the myosin heads in the skinned rabbit psoas muscle contain the hydrolysis products. The affinity for actin is enhanced by adding polyethylene glycol ( PEG) or by lowering the ionic strength in the bathing solution. Solution kinetics and binding constants were determined in the presence and in the absence of PEG. When the binding between actin and myosin was increased, both the myosin layer lines and the actin layer lines increased in intensity, but the intensity profiles did not change. The configuration (mode) of attachment in the A center dot M center dot ADP center dot P-i state is thus unique among the intermediate attached states of the cross-bridge ATP hydrolysis cycle. One of the simplest explanations is that both myosin filaments and actin filaments are stabilized (e.g., undergo reduced spatial fluctuations) by the attachment. The alignment of the myosin heads in the thick. laments and the alignment of the actin monomers in the thin. laments are improved as a result. The compact atomic structure of M center dot ADP center dot P-i with strongly coupled domains may contribute to the unique attachment configuration: the "primed'' myosin heads may function as "transient struts'' when attached to the thin. laments. C1 NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. E Virginia Med Sch, Norfolk, VA USA. RP Yu, LC (reprint author), NIH, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM yule@mail.nih.gov FU Intramural NIH HHS; NIBIB NIH HHS [EB00207] NR 30 TC 4 Z9 4 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2006 VL 91 IS 9 BP 3370 EP 3382 DI 10.1529/biophysj.106.086918 PG 13 WC Biophysics SC Biophysics GA 094GS UT WOS:000241228500023 PM 16905611 ER PT J AU Bakas, L Chanturiya, A Herlax, V Zimmerberg, J AF Bakas, Laura Chanturiya, Alexandr Herlax, Vanesa Zimmerberg, Joshua TI Paradoxical lipid dependence of pores formed by the Escherichia coli alpha-hemolysin in planar phospholipid bilayer membranes SO BIOPHYSICAL JOURNAL LA English DT Article ID ION CHANNELS; PEPTIDE; PROTEIN; ALAMETHICIN; CURVATURE; INSERTION; TEMPERATURE; MAGAININ-2; MECHANISM; BAX AB alpha-Hemolysin (HlyA) is an extracellular protein toxin (117 kDa) secreted by Escherichia coli that targets the plasma membranes of eukaryotic cells. We studied the interaction of this toxin with membranes using planar phospholipid bilayers. For all lipid mixtures tested, addition of nanomolar concentrations of toxin resulted in an increase of membrane conductance and a decrease in membrane stability. HlyA decreased membrane lifetime up to three orders of magnitude in a voltage-dependent manner. Using a theory for lipidic pore formation, we analyzed these data to quantify how HlyA diminished the line tension of the membrane (i.e., the energy required to form the edge of a new pore). However, in contrast to the expectation that adding the positive curvature agent lysophosphatidylcholine would synergistically lower line tension, its addition significantly stabilized HlyA-treated membranes. HlyA also appeared to thicken bilayers to which it was added. We discuss these results in terms of models for proteolipidic pores. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Natl Univ La Plata, Fac Ciencias Exactas, Dept Ciencias Biol, RA-1900 La Plata, Argentina. INIBIOLP, Inst Invest Bioquim, La Plata, Argentina. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov RI Wunder, Stephanie/B-5066-2012; Zdilla, Michael/B-4145-2011 FU Intramural NIH HHS NR 37 TC 18 Z9 19 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2006 VL 91 IS 10 BP 3748 EP 3755 DI 10.1529/biophysj.106.090019 PG 8 WC Biophysics SC Biophysics GA 100XC UT WOS:000241702500020 PM 16935953 ER PT J AU Xu, SG Martyn, D Zaman, J Yu, LPC AF Xu, Sengen Martyn, Donald Zaman, Jessica Yu, Leepo C. TI X-ray diffraction studies of the thick filament in permeabilized myocardium from rabbit SO BIOPHYSICAL JOURNAL LA English DT Article ID LIGHT-CHAIN PHOSPHORYLATION; CARDIAC-MUSCLE; SKELETAL-MUSCLE; PSOAS MUSCLE; CA2+ SENSITIVITY; HELICAL ORDER; CROSS-BRIDGES; MYOSIN; LENGTH; TEMPERATURE AB Low angle x-ray diffraction patterns from relaxed permeabilized rabbit cardiac trabeculae and psoas muscle fibers were compared. Temperature was varied from 25 degrees C to 5 degrees C at 200 mM and 50 mM ionic strengths (mu), respectively. Effects of temperature and mu on the intensities of the myosin layer lines (MLL), the equatorial intensity ratio I-1,I-1/I-1,I-0, and the spacing of the. lament lattice are similar in both muscles. At 25 degrees C, particularly at mu = 50 mM, the x-ray patterns exhibited up to six orders of MLL and sharp meridional reflections, signifying that myosin heads (cross-bridges) are distributed in a well-ordered helical array. Decreasing temperature reduced MLL intensities but increased I-1,I-1/I-1,I-0. Decreases in the MLL intensities indicate increasing disorder in the distribution of cross-bridges on the thick. laments surface. In the skeletal muscle, order/disorder is directly correlated with the hydrolysis equilibrium of ATP by myosin, [M.ADP.P-i]/[M.ATP]. Similar effects of temperature on MLL and similar biochemical ATP hydrolysis pathway found in both types of muscles suggest that the order/disorder states of cardiac cross-bridges may well be correlated with the same biochemical and structural states. This implies that in relaxed cardiac muscle under physiological conditions, the unattached cross-bridges are largely in the M.ADP.P-i state and with the lowering of the temperature, the equilibrium is increasingly in favor of [M.ATP] and [A.M.ATP]. There appear to be some differences in the diffraction patterns from the two muscles, however. Mainly, in the cardiac muscle, the MLL are weaker, the I-1,I-1/I-1,I-0 ratio tends to be higher, and the lattice spacing D-10, larger. These differences are consistent with the idea that under a wide range of conditions, a greater fraction of cross-bridges is weakly bound to actin in the myocardium. C1 NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. RP Yu, LC (reprint author), NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM yule@mail.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL067071, HL 67071] NR 33 TC 5 Z9 5 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2006 VL 91 IS 10 BP 3768 EP 3775 DI 10.1526/biophysj.106.088971 PG 8 WC Biophysics SC Biophysics GA 100XC UT WOS:000241702500022 PM 16950853 ER PT J AU Mishra, SH Shelley, CM Barrow, DJ Darby, MK Germann, MW AF Mishra, Subrata H. Shelley, Christopher M. Barrow, Doyle J., Jr. Darby, Martyn K. Germann, Markus W. TI Solution structures and characterization of human immunodeficiency virus Rev responsive element IIB RNA targeting zinc finger proteins SO BIOPOLYMERS LA English DT Article DE Rev responsive element; human immunodeficiency virus; RNA; zinc finger proteins; binding; phage display ID MESSENGER-RNA; CRYSTAL-STRUCTURE; GENE-EXPRESSION; DNA RECOGNITION; CHEMICAL-SHIFTS; BINDING-SITE; TYPE-1; COMPLEX; PEPTIDE; NMR AB The Rev responsive element (RRE), a part of unspliced human immunodeficiency virus (HIV) RNA, serves a crucial role in the production of infectious HIV virions. The viral protein Rev binds to RRE and facilitates transport of mRNA to the cytoplasm. Inhibition of the Rev-RRE interaction disrupts the viral life cycle. Using a phage display protocol, dual zinc finger proteins (ZNFs) were generated that bind specifically to RREIIB at the high affinity Rev binding site. These proteins were farther shortened and simplified, and they still retained their RNA binding affinity. The solution structures of ZNF29 and a mutant, ZNF29G29R, have been determined by nuclear magnetic resonance (NMR) spectroscopy. Both proteins form C2H2-type zinc fingers with essentially identical structures. RNA protein interactions were evaluated quantitatively by isothermal titration calorimetry, which revealed dissociation constants (K-d'S) in the nanomolar range. The interaction with the RNA is dependent upon the zinc finger structure; in the presence of EDTA, RNA binding is abolished. For both proteins, RNA binding is mediated by the a-helical portion of the zinc fingers and target the bulge region of RREIIB-TR. However, ZNF29G29R exhibits significantly stronger binding to the RNA target than ZNF29; this illustrates that the binding of the zinc finger scaffold is amenable to further improvements. (c) 2006 Wiley Periodicals, Inc. C1 Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Germann, MW (reprint author), Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. EM mwg@gsu.edu RI German, Markus/L-1531-2013 FU NIAID NIH HHS [R01 AI047459-06, R01 AI047459] NR 52 TC 3 Z9 3 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD NOV PY 2006 VL 83 IS 4 BP 352 EP 364 DI 10.1002/bip.20565 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 095YK UT WOS:000241344000003 PM 16826557 ER PT J AU Correa, A Min, YI Stewart, PA Lees, PSJ Breysse, P Dosemeci, M Jackson, LW AF Correa, Adolfo Min, Yuan-I Stewart, Patricia Ann Lees, Peter S. J. Breysse, Patrick Dosemeci, Mustafa Jackson, Leila W. TI Inter-rater agreement of assessed prenatal maternal occupational exposures to lead SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE inter-rater agreement; reliability; occupational exposure assessment; prenatal lead exposure ID PULMONARY VENOUS RETURN; CONGENITAL-MALFORMATIONS; RISK-FACTORS; SPONTANEOUS-ABORTION; PATERNAL OCCUPATION; CHEMICAL EXPOSURES; WEIGHTED KAPPA; GLYCOL ETHERS; DEFECTS; COEFFICIENT AB BACKGROUND: Industrial hygienists' assessments of prenatal occupational exposures based on parental job histories is a promising approach for population-based case-control studies of birth defects and other perinatal outcomes. However, evaluations of inter-rater agreement of such assessments have been limited. METHODS: We examined inter-rater agreement of occupational lead exposure assessments of maternal job reports by industrial hygienists in a population-based case-control study of parental occupational lead exposure and low birth weight. A total of 178 jobs with potential exposure to lead during the 6 months before pregnancy to the end of pregnancy were examined. Three industrial hygienists evaluated these jobs independently for exposure to lead including probability of exposure, type of exposure, route of entry, exposure frequency, duration, and intensity. Inter-rater agreement of these assessments beyond chance was evaluated using the kappa statistic (kappa). RESULTS: In general, inter-rater agreement was greater for assessment of direct exposures than assessment of indirect exposures. However, inter-rater agreement varied with the lead exposure metric under consideration, being: 1) fair to good for type of direct exposure (i.e., inorganic or organic), respiratory exposure and frequency of exposure to direct inorganic lead, hours per day of direct (i.e., inorganic or organic), and intensity of direct inorganic exposure; 2) poor for probability and type of indirect exposure (inorganic or organic); and 3) indeterminate for frequency of direct organic exposure, frequency of indirect exposures (organic or inorganic), and intensity of direct exposures (organic or inorganic). CONCLUSION: Retrospective assessment of maternal prenatal exposures to lead by industrial hygienists can provide some reliable metrics of exposure for studies of perinatal outcomes. Reliability studies of such exposure assessments may be useful for: quantifying the reliability of derived exposure metrics; identifying exposure metrics for exposure-outcome analyses; and determining the reliability of prenatal occupational exposures to other agents of interest. Birth Defects Research (Part A) 76:811-824, 2006. (C) 2006 Wiley-Liss, Inc.(dagger) C1 Ctr Dis Control & Prevent, Div Birth Defects & Dev Disabil, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Correa, A (reprint author), Ctr Dis Control & Prevent, Div Birth Defects & Dev Disabil, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd,MS E-86, Atlanta, GA 30333 USA. EM acorrea@cdc.gov OI Min, Yuan-I/0000-0003-2470-0004 FU Intramural NIH HHS; NIEHS NIH HHS [R29 ES06218] NR 39 TC 16 Z9 16 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD NOV PY 2006 VL 76 IS 11 BP 811 EP 824 DI 10.1002/bdra.20311 PG 14 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 106UO UT WOS:000242127400012 PM 17044050 ER PT J AU Alving, BM AF Alving, Barbara M. TI Heparin-induced thrombocytopenia: the female factor SO BLOOD LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Alving, BM (reprint author), NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2006 VL 108 IS 9 BP 2884 EP 2885 DI 10.1182/blood-2006-08-040816 PG 2 WC Hematology SC Hematology GA 099IE UT WOS:000241586100002 ER PT J AU Rader, C Barbas, CF AF Rader, Christoph Barbas, Carlos F., III TI Synthetic antibodies prey on B cells SO BLOOD LA English DT Editorial Material C1 NCI, Scripps Res Inst, Bethesda, MD 20892 USA. RP Rader, C (reprint author), NCI, Scripps Res Inst, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2006 VL 108 IS 9 BP 2889 EP 2890 DI 10.1182/blood-2006-08-041327 PG 2 WC Hematology SC Hematology GA 099IE UT WOS:000241586100008 ER PT J AU Salvucci, O Sierra, MD Martina, JA McCormick, PJ Tosato, G AF Salvucci, Ombretta Sierra, Maria de la Luz Martina, Jose A. McCormick, Peter J. Tosato, Giovanna TI EphB2 and EphB4 receptors forward signaling promotes SDF-1-induced endothelial cell chemotaxis and branching remodeling SO BLOOD LA English DT Article ID CHEMOKINE RECEPTOR; TYROSINE KINASE; FACTOR-I; CARDIOVASCULAR DEVELOPMENT; GROWTH-FACTOR; TUMOR-GROWTH; PROTEIN; MIGRATION; LIGAND; CXCR4 AB The complex molecular mechanisms that drive endothelial cell movement and the formation of new vessels are poorly understood and require further investigation. Eph receptor tyrosine kinases and their membrane-anchored ephrin ligands regulate cell movements mostly by cell-cell contact, whereas the G-protein-coupled receptor CXCR4 and its unique SDF-1 chemokine ligand regulate cell movement mostly through soluble gradients. By using biochemical and functional approaches, we investigated how ephrinB and SDF-1 orchestrate endothelial cell movement and morphogenesis into capillary-like structures. We describe how endogenous EphB2 and EphB4 signaling are required for the formation of extracellular matrix-dependent capillary-like structures in primary human endothelial cells. We further demonstrate that EphB2 and EphB4 activation enhance SDF-1-induced signaling and chemotaxis that are also required for extracellular matrix-dependent endothelial cell clustering. These results support a model in which SDF-1 gradients first promote endothelial cell clustering and then EphB2 and EphB4 critically contribute to subsequent cell movement and alignment into cordlike structures. This study reveals a requirement for endogenous Eph signaling in endothelial cell morphogenic processes, uncovers a novel link between EphB forward signaling and SDF-1-induced signaling, and demonstrates a mechanism for cooperative regulation of endothelial cell movement. C1 NCI, Basic Res Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), NCI, Basic Res Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov RI McCormick, Peter/E-7387-2012 OI McCormick, Peter/0000-0002-2225-5181 FU Intramural NIH HHS NR 63 TC 56 Z9 58 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2006 VL 108 IS 9 BP 2914 EP 2922 DI 10.1182/blood-2006-05-023341 PG 9 WC Hematology SC Hematology GA 099IE UT WOS:000241586100014 PM 16840724 ER PT J AU Hill, DA Wang, SS Cerhan, JR Davis, S Cozen, W Severson, RK Hartge, P Wacholder, S Yeager, M Chanock, SJ Rothman, N AF Hill, Deirdre A. Wang, Sophia S. Cerhan, James R. Davis, Scott Cozen, Wendy Severson, Richard K. Hartge, Patricia Wacholder, Sholom Yeager, Meredith Chanock, Stephen J. Rothman, Nathaniel TI Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes SO BLOOD LA English DT Article ID DOUBLE-STRAND BREAKS; EPITHELIAL OVARIAN-CANCER; V(D)J RECOMBINATION; CELL LYMPHOMAS; SKIN-CANCER; LIGASE-IV; MUTATIONS; TRANSLOCATIONS; POLYMORPHISMS; BRCA2 AB Chromosomal translocations, insertions, and deletions are common early events in non-Hodgkin lymphoma (NHL) carcinogenesis, and implicated in their formation are endogenous processes involved in antigen-receptor diversification, such as V(D)J recombination. DNA repair genes respond to the double- and single-strand breaks induced by these processes and may influence NHL etiology. We examined 34 genetic variants in 19 genes within or related to 5 DNA repair pathways among 1172 cases and 982 matched controls who participated in a population-based NHL study in Los Angeles, Seattle, Detroit, and Iowa from 1998 to 2000. Cases were more likely than controls to have the RAG1 820 R/R (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.4 to 5.0) than Lys/Lys genotypes, with evidence of a gene dosage effect (P trend <.001), and less likely to have the LIG4 (DNA ligase IV) 9 Ile/Ile (OR = 0.5; 95% Cl = 0.3 to 0.9) than TIT genotype (P trend =.03) in the nonhomologous end joining (NHEJ)/V(D)J pathway. These NHEJ/V(D)J-related gene variants represent promising candidates for further studies of NHL etiology and require replication in other studies. C1 Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Ctr Canc, Albuquerque, NM 87131 USA. DHHS, Div Canc Epidemiol & Genet, NCI, NIH, Bethesda, MD USA. Univ Iowa, Iowa City, IA USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. DHHS, Core Genotyping Facil, Adv Technol Corp, NCI,NIH, Gaithersburg, MD USA. RP Hill, DA (reprint author), Univ New Mexico, Sch Med, Dept Internal Med, 1 Univ New Mexico,MSC 10 5550, Albuquerque, NM 87131 USA. EM dahill@salud.unm.edu OI Cerhan, James/0000-0002-7482-178X FU NCI NIH HHS [N01-PC-67009, N01-PC-65064, N01-PC-67008, N01-PC-67010, N02-PC-71105] NR 43 TC 49 Z9 53 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2006 VL 108 IS 9 BP 3161 EP 3167 DI 10.1182/blood-2005-01-026690 PG 7 WC Hematology SC Hematology GA 099IE UT WOS:000241586100046 PM 16857995 ER PT J AU Pavletic, SZ Lee, SJ Socie, G Vogelsang, G AF Pavletic, S. Z. Lee, S. J. Socie, G. Vogelsang, G. TI Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials SO BONE MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; consensus; guidelines; stem cell transplantation ID WORKING GROUP-REPORT; BONE-MARROW-TRANSPLANTATION; ACTIVITY INDEXES; THERAPY; SCALE; SENSITIVITY; DIAGNOSIS; ADULTS; SF-36 AB Chronic graft-versus-host disease (GVHD) has been a difficult problem to address and clinical research in this area lags behind other innovations in hematopoietic stem cell transplantation (HCT). Recently the international transplant community has focused more on chronic GVHD. This new focus is well represented by the development of the National Institutes of Health sponsored chronic GVHD consensus project, which has unified the transplant community's approach to chronic GVHD through the activities of focused working groups. From December 2005 through May 2006, a series of consensus documents have been published addressing the areas of diagnosis and staging, histopathology, strategies for the development and validation of biomarkers, response criteria, ancillary therapy and supportive care and the design of clinical trials. This paper summarizes and discusses these reports, focusing specifically on diagnosis and scoring and response criteria. Although these documents represent a huge effort by the research community, they must be prospectively implemented and validated. These new criteria should advance the standards and uniformity of chronic GVHD clinical research. The ultimate success of this project is dependent on whether these recommendations move the field forward. This is an opportunity for the transplant community to unite and make a significant impact in chronic GVHD. C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA. APHP Hosp St Louis, Dept Hematol Transplantat, Serv Hematol Greffe, Paris, France. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU Intramural NIH HHS NR 26 TC 58 Z9 61 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2006 VL 38 IS 10 BP 645 EP 651 DI 10.1038/sj.bmt.1705490 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 101HP UT WOS:000241732200001 PM 16980994 ER PT J AU Masellis, M Momeni, P Meschino, W Heffner, R Elder, J Sato, C Liang, Y St George-Hyslop, P Hardy, J Bilbao, J Black, S Rogaeva, E AF Masellis, Mario Momeni, Parastoo Meschino, Wendy Heffner, Reid, Jr. Elder, Joshua Sato, Christine Liang, Yan St George-Hyslop, Peter Hardy, John Bilbao, Juan Black, Sandra Rogaeva, Ekaterina TI Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome SO BRAIN LA English DT Article DE corticobasal syndrome; frontotemporal lobar degeneration; progranulin; gene; mutation ID FRONTOTEMPORAL LOBAR DEGENERATION; PROGRESSIVE SUPRANUCLEAR PALSY; MOTOR-NEURON DISEASE; BASAL GANGLIONIC DEGENERATION; CLINICAL DIAGNOSTIC-CRITERIA; TAU GENE; DEMENTIA; CHROMOSOME-17; INCLUSIONS; TAUOPATHY AB Corticobasal syndrome (CBS) is a rare cognitive and movement disorder characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently been shown to segregate with truncating mutations in progranulin (PGRN), a multifunctional growth factor thought to promote neuronal survival. This study identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G -> A) that segregates with CBS in a Canadian family of Chinese origin. We confirmed the absence of the mutant PGRN allele in the RT-PCR product which supports the model of haploinsufficiency for PGRN-linked disease. This report of mutation in the PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in FTLD spectrum disorders. C1 Sunnybrook Hlth Sci Ctr, Linda C Campbell Cognit Neurol Res Unit, Toronto, ON, Canada. Univ Hlth Network, Toronto Western Hosp, Res Inst, Dept Med,Div Neurol, Toronto, ON, Canada. Univ Hlth Network, Toronto Western Hosp, Res Inst, Ctr Res Neurodegenerat Dis,Dept Med, Toronto, ON, Canada. Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Pathol, Toronto, ON, Canada. N York Gen Hosp, Genet Program, Toronto, ON, Canada. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Pathol, Buffalo, NY 14260 USA. RP Black, S (reprint author), Sunnybrook Hlth Sci Ctr, Dept Med, Div Neurol, Room A4 21,2075 Baview Ave, Toronto, ON M4N 3M5, Canada. EM sandra.black@sunnybrook.ca RI Hardy, John/C-2451-2009; OI Black, Sandra/0000-0001-7093-8289 FU Medical Research Council [G0701075] NR 48 TC 108 Z9 111 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2006 VL 129 BP 3115 EP 3123 DI 10.1093/brain/awl276 PN 11 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 102AT UT WOS:000241783800030 PM 17030534 ER PT J AU Anderson, WF Chen, BSE Jatoi, I Rosenberg, PS AF Anderson, William F. Chen, Bingshu E. Jatoi, Ismail Rosenberg, Philip S. TI Effects of estrogen receptor expression and histopathology on annual hazard rates of death from breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE hazard function; hazard regression; survival analysis; non-proportional hazards; risk factors ID PROGNOSTIC-FACTORS; AGE DISTRIBUTION; FEMALE BREAST; SURVIVAL; RECURRENCE; CARCINOMA; PATTERNS; SPLINES; CHEMOTHERAPY; MORTALITY AB Background Breast cancer incidence rates vary according to estrogen receptor expression (ER) and histopathology. We hypothesized that annual mortality rates from breast cancer after initial diagnosis (hazard rates) might also vary by ER and histopathology. Methods We accessioned the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER, 1992-2002) program to estimate hazard rates according to ER (positive and negative) and histopathology (duct, tubular, lobular, medullary, inflammatory, papillary, and mucinous types). We used spline functions to model hazard rates free of strongly parametric assumptions for ER negative and positive cases overall and by histopathology. Results Hazard rates for ER negative and ER positive cases were distinct and non-proportional. At 17 months, ER negative hazard rates peaked at 7.5% per year (95% CI, 7.3-7.8% per year) then declined, whereas ER positive hazard rates lacked a sharp early peak and were comparatively constant at 1.5-2% per year. Falling ER negative and constant ER positive hazard rates crossed at 7 years; after which, prognosis was better for ER negative cases. Among ER positive and negative cases, there were proportional and non-proportional hazards according to histopathologic type, but the two basic ER-associated patterns were maintained. Conclusions Hazard rates differed quantitatively and qualitatively according to ER and histopathology. These large-scale population-based results seem consistent with genomic studies, demonstrating two main classes of breast cancers with distinct prognoses according to ER expression. C1 NCI, DHHS, Div Canc Epidemiol & Genet, Biostat Branch,EPS,NIH, Rockville, MD 20852 USA. NCI, DHHS, Div Canc Epidemiol & Genet, Biostat Branch,NIH, Rockville, MD USA. Natl Naval Med Ctr, Dept Surg, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Anderson, WF (reprint author), NCI, DHHS, Div Canc Epidemiol & Genet, Biostat Branch,EPS,NIH, Room 8036,6120 Execut Blvd, Rockville, MD 20852 USA. EM wanderso@mail.nih.gov OI Chen, Bingshu/0000-0001-6139-0696 FU Intramural NIH HHS NR 34 TC 54 Z9 54 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2006 VL 100 IS 1 BP 121 EP 126 DI 10.1007/s10549-006-9231-y PG 6 WC Oncology SC Oncology GA 098RU UT WOS:000241541300015 PM 16685588 ER PT J AU Palmieri, D Bouadis, A Ronchetti, R Merino, MJ Steeg, PS AF Palmieri, Diane Bouadis, Amina Ronchetti, Ruban Merino, Maria J. Steeg, Patricia S. TI Rab11a differentially modulates epidermal growth factor-induced proliferation and motility in immortal breast cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast; DCIS; Rab11; EGF receptor ID CARCINOMA IN-SITU; PROTEIN-KINASE ACTIVITY; TRANSGENIC MOUSE MODEL; FACTOR-RECEPTOR; A431 CELLS; INTRACELLULAR TRAFFICKING; CANCER; ENDOSOMES; IDENTIFICATION; INTERNALIZATION AB The development of cancer prevention strategies depends on the elucidation of molecular pathways underlying oncogenesis. In a previous proteomic study of matched normal breast ducts and Ductal Carcinoma in Situ (DCIS), we identified overexpression of Rab11a in DCIS. Rab11a is not well studied in cancer, but is known to regulate the recycling of internalized cell surface proteins and receptors from the early endosome through the trans-Golgi network. Using immunohistochemistry, we confirmed our observation, noting increased Rab11a expression in 19 of 22 (86%) DCIS cases compared to matched normal breast epithelium. To study the function of Rab11a, immortal, nontumorigenic MCF10A breast cells were stimulated with ligands to the EGF receptor (EGFR) after transfection with empty vector (control), Rab11a, or a S25N dominant-negative (DN) Rab11a. Using an iodinated ligand:receptor recycling assay, transfection of Rab11a accelerated, while DN-Rab11a postponed EGFR recycling in vitro. The signaling and in vitro phenotypic consequences of Rab11a expression and function were studied. Transfection of DN-Rab11a increased Erk1/2 activation downstream of EGF, but exerted no effect on the Akt pathway. Expression of DN-Rab11a inhibited MCF10A proliferation by 50-60%, and also inhibited anchorage-dependent colonization. Notably, DN-Rab11a transfection increased motility toward EGFR ligands. The data provide a first demonstration that Rab11a modulates EGFR recycling, and promotes the proliferation but inhibits the motility of an immortal breast line, consistent with the DCIS phenotype. C1 NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Surg Pathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Palmieri, D (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res,NIH, 37 Convent Dr,Bldg 37,Rm 1222, Bethesda, MD 20892 USA. EM palmierd@mail.nih.gov RI Palmieri, Diane/B-4258-2015 FU Intramural NIH HHS NR 57 TC 28 Z9 29 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2006 VL 100 IS 2 BP 127 EP 137 DI 10.1007/s10549-006-9244-6 PG 11 WC Oncology SC Oncology GA 098RY UT WOS:000241541700001 PM 16791477 ER PT J AU Choi, JY Lee, KM Noh, DY Ahn, SH Lee, JE Han, W Jang, IJ Shin, SG Yoo, KY Hayes, RB Kang, D AF Choi, Ji-Yeob Lee, Kyoung-Mu Noh, Dong-Young Ahn, Sei-Hyun Lee, Jong-Eun Han, Wonshik Jang, In-Jin Shin, Sang-Goo Yoo, Keun-Young Hayes, Richard B. Kang, Daehee TI Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE eNOS; breast cancer; survival; estrogen receptor ID NITRIC-OXIDE SYNTHASE; PROTEIN EXPRESSION; ASSOCIATION; ESTROGEN; TUMOR; ACTIVATION; CELLS; RISK AB The endothelial cell-specific form of nitric oxide synthase (eNOS) may play an important role in tumor progression via angiogenesis or apoptosis. We studied eNOS -786T > C and 894G > T (Glu298Asp), two functionally significant SNPs, in relation to hazard of breast cancer recurrence or death in 873 women with incident, non-metastatic breast cancer, recruited from two teaching hospitals in Seoul, Korea, 1995-2002. Hazards were estimated by Cox proportional hazard models, in relation to genotype, adjusting for hormone receptor status, lymph node involvement, and tumor size. Women carriers of the eNOS -786C allele had significantly increased hazards of breast cancer recurrence or death, compared with women having the TT genotype (HR = 2.1, 95% CI = 1.03-4.33); risks increased up to 3-fold in ER positive cases (HR = 3.2, 95% CI = 0.95-10.50). The hazard was also increased in eNOS 894T carriers, however, it did not reach statistical significance (HR = 1.8, 95% CI = 0.85-3.93). The combined genotypes containing -786C or 894T was associated with a 2.5-fold risk, compared to the TT-GG genotypes, the most dominant genotype combination (95% CI = 1.29-4.68), with the greatest risks in ER positive cases (HR = 4.9, 95% CI = 1.31-18.36). These results indicate that the eNOS -786C polymorphism, and possibly the 894T polymorphism, are associated with breast cancer recurrence and death, particularly in women with ER positive tumors. C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Dept Gen Surg, Seoul 110799, South Korea. Univ Ulsan, Coll Med, Dept Gen Surg, Seoul, South Korea. DNA Link Inc, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Dept Canc Res Inst, Seoul 110799, South Korea. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yongon Dong, Seoul 110799, South Korea. EM dhkang@snu.ac.kr RI Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Choi, Ji-Yeob/J-2796-2012; Yoo, Keun-Young/J-5548-2012; Shin, Sang-Goo/J-5522-2012; OI Hayes, Richard/0000-0002-0918-661X NR 20 TC 28 Z9 28 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2006 VL 100 IS 2 BP 213 EP 218 DI 10.1007/s10549-006-9245-5 PG 6 WC Oncology SC Oncology GA 098RY UT WOS:000241541700010 PM 16821086 ER PT J AU McShane, LM Altman, DG Sauerbrei, W Taube, SE Gion, M Clark, GM AF McShane, Lisa M. Altman, Douglas G. Sauerbrei, Willi Taube, Sheila E. Gion, Massimo Clark, Gary M. CA NCI-EORTC Working Grp Canc Diagno TI REporting recommendations for tumor MARKer prognostic studies (REMARK) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE tumor markers; guidelines; NCI; EORTC; REMARK; prognostic ID NEGATIVE BREAST-CANCER; DIAGNOSTIC-ACCURACY; RANDOMIZED TRIALS; COLORECTAL-CANCER; CONSORT STATEMENT; GUIDELINES; FUTURE; EPIDEMIOLOGY; METAANALYSIS; ELABORATION AB Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply. C1 NCI, Biometr Res Branch, DCTD, Canc Diag Program, Bethesda, MD 20892 USA. Univ Oxford Wolfson Coll, Ctr Stat Med, Canc Res UK Med Stat Grp, Oxford OX2 6UD, England. Univ Freiburg Klinikum, Inst Med Biometrie & Med Informat, Freiburg, Germany. Osped Civile Venezia, Ctr Reg Indicatori Biochim Tumore, Venice, Italy. OSI Pharmaceut Inc, Boulder, CO USA. RP McShane, LM (reprint author), NCI, Biometr Res Branch, DCTD, Canc Diag Program, Room 8126,Execut Plaza N,6130 Execut Blvd, Bethesda, MD 20892 USA. EM lm5h@nih.gov NR 42 TC 420 Z9 426 U1 4 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2006 VL 100 IS 2 BP 229 EP 235 DI 10.1007/s10549-006-9242-8 PG 7 WC Oncology SC Oncology GA 098RY UT WOS:000241541700012 PM 16932852 ER PT J AU Lau, JYF Eley, TC AF Lau, Jennifer Y. F. Eley, Thalia C. TI Changes in genetic and environmental influences on depressive symptoms across adolescence and young adulthood SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID TWIN; AGE; CHILDHOOD; ETIOLOGY; CHILDREN; EVENTS; SAMPLE AB Background Depression rises markedly in adolescence, a time when increased and new genetic influences have been reported. Aims To examine 'new' and 'stable' genetic and environmental factors on depressive symptoms in adolescence and young adulthood. Method A questionnaire survey investigated a sample of twin and sibling pairs at three time points over an approximately 3-year period. Over 1800 twin and sibling pairs reported depressive symptoms at the three time points. Data were analysed using multivariate genetic models. Results Depressive symptoms at all time points were moderately heritable with substantial non-shared environmental contributions. Wave 1 genetic factors accounted for continuity of symptoms at waves 2 and 3. 'New' genetic effects at wave 2 also influenced wave 3 symptoms. New non-shared environmental influences emerged at each time point. Conclusions New genetic and environmental influences may explain age-related increases in depression across development. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Inst Psychiat, London, England. RP Lau, JYF (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15 N Dr,Room 211, Bethesda, MD 20892 USA. EM lauj@mail.nih.gov RI Eley, Thalia/D-4811-2011 FU Medical Research Council [G120/635] NR 18 TC 39 Z9 39 U1 0 U2 15 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 NOV PY 2006 VL 189 BP 422 EP 427 DI 10.1192/bjp.bp.105.018721 PG 6 WC Psychiatry SC Psychiatry GA 104PL UT WOS:000241970500007 PM 17077432 ER PT J AU Larson, PS Ungarelli, RA de las Morenas, A Cupples, LA Rowlings, K Palmer, JR Rosenberg, CL AF Larson, Pamela S. Ungarelli, Rosemarie A. de las Morenas, Antonio Cupples, L. Adrienne Rowlings, Kathleen Palmer, Julie R. Rosenberg, Carol L. TI In utero exposure to diethylstilbestrol (DES) does not increase genomic instability in normal or neoplastic breast epithelium SO CANCER LA English DT Article DE breast cancer; loss of heterozygosity; microsatellite; allele imbalance; genetic instability; in utero exposure; prenatal; diethylstilbestrol ID CHINESE-HAMSTER CELLS; MICROSATELLITE INSTABILITY; ESTROGEN CARCINOGENESIS; MITOTIC INHIBITION; WIDE SEARCH; CANCER; HETEROZYGOSITY; IMBALANCE; WOMEN; RISK AB BACKGROUND. in 1992, the National Cancer Institute (NCI) established the Continuation of Follow-Up of DES-Exposed Cohorts to study the long-term health effects of exposure to diethylstilbestrol (DES). Genetic effects on human breast tissue have not been examined. The authors investigated whether breast tissue of women exposed in utero to DES might exhibit the genetic abnormalities that characterize other DES-associated tumors. METHODS. Subjects enrolled in the NCI Cohort were queried about breast biopsies or breast cancer diagnoses. Available tissue blocks were obtained for invasive cancers (IC), in situ cancers (CIS), or atypical hyperplasia (AH). Exposure status was blinded, lesions were microdissected, and their DNA was analyzed for microsatellite instability (MI) and loss of heterozygosity (LOH), or allele imbalance (AI), at 20 markers on 9 chromosome arms. RESULTS. From 31 subjects (22 exposed, 9 unexposed), 273 samples were analyzed (167 normal epithelium, 16 AH, 30 CIS, 60 IC). Exposed and unexposed subjects exhibited no differences in breast cancer risk factors or demographic characteristics, except for age at diagnosis (exposed vs. unexposed: 43.2 vs. 48.8 years of age, P = .02). The authors found that MI was rare and that AI was common, with frequencies consistent with previous reports. The global age-adjusted relative rate (RR) of AI was 1.3, 95% CI = 0.8-2.4. No statistically significant associations were observed after adjustment for risk factors or after stratification by histology or by chromosome arm. CONCLUSION. In utero DES exposure does not appear to significantly increase genomic instability in breast epithelium, as measured by MI and AI. Breast tissue may respond differently from that of the reproductive tract to in utero DES exposure. Consequences of in utero DES exposure on the breast may be mediated by proliferative effects of estrogen. C1 Boston Univ, Sch Med, Dept Med, Med Ctr, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Pathol & Lab Med, Boston, MA 02118 USA. Boston Med Ctr, Dept Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02118 USA. Natl Canc Inst Collaborat Study DES Exposed Cohor, Bethesda, MD USA. RP Rosenberg, CL (reprint author), Boston Univ, Sch Med, Dept Med, Med Ctr, 650 Albany St,EBRC 4, Boston, MA 02118 USA. EM crosenbe@bu.edu OI De Las Morenas, Antonio/0000-0001-9908-4096; Palmer, Julie/0000-0002-6534-335X; Cupples, L. Adrienne/0000-0003-0273-7965 NR 36 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2006 VL 107 IS 9 BP 2122 EP 2126 DI 10.1002/cncr.22223 PG 5 WC Oncology SC Oncology GA 101YK UT WOS:000241777300003 PM 16998936 ER PT J AU Maxwell, GL Tian, C Risinger, J Brown, CL Rose, GS Thigpen, JT Fleming, GF Gallion, HH Brewster, WR AF Maxwell, G. Larry Tian, Chunqiao Risinger, John Brown, Carol L. Rose, G. Scott Thigpen, J. Tate Fleming, Gini F. Gallion, Holly H. Brewster, Wendy R. TI Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma - A Gynecologic Oncology Group study SO CANCER LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-of-Gynecologic-Oncologists CY MAR 19-23, 2005 CL Miami Beach, FL SP Soc Gynecol Oncol DE endometrial cancer; racial disparity; survival ID DOXORUBICIN PLUS CISPLATIN; PHASE-III TRIAL; CANCER STATISTICS; AFRICAN-AMERICAN; UTERINE CORPUS; WHITE WOMEN; CARCINOMA; FILGRASTIM; RACE AB BACKGROUND. Previous studies have reported shorter survival of black women compared with white women who had advanced/ recurrent endometrial cancer. It has been suggested that this may reflect racially based differences in treatment. METHODS. The authors retrospectively reviewed data from 169 black women and 982 white women with International Federation of Gynecologic Oncology (FIGO) Stage III, Stage IV, or recurrent endometrial carcinoma who were participants in 1 of 4 Gynecologic Oncology Group randomized treatment trials of doxorubicin alone or combined with paclitaxel and/or cisplatin. Demographic, histologic, treatment, and outcome data were analyzed to estimate survival, and between group comparisons were performed. RESULTS. The pooled data revealed that black women were more likely to have papillary serous histology (P < .001), Stage IV disease (P < .001), and higher tumor grade (P < .001) compared with white women, and survival was worse among black women than among white women (median survival, 10.6 months vs. 12.2 months, respectively; P < .001). A Cox proportional hazards regression analysis that was adjusted for performance status, disease stage, tumor histology, tumor grade, and treatment demonstrated worse survival for black women (hazards ratio, 1.26, 95% confidence interval, 1.06-1.51; P = .010). CONCLUSIONS. The data from a large group of women with advanced/ recurrent endometrial cancer suggested that a racial disparity in survival persists, despite the finding that black women and white women received similar treatment. Although the causes of racial disparity in endometrial cancer remain to be elucidated, socioeconomic, biologic, and cultural factors should be investigated to identify the etiologic origins of this multifactorial healthcare problem. C1 Walter Reed Army Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA. Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Gynecol Serv, Dept Surg, Div Gynecol Oncol,Dept Obstet & Gynecol, New York, NY 10021 USA. Univ Mississippi, Sch Med, Div Oncol, Dept Med, Jackson, MS 39216 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst, Pittsburgh, PA USA. Precis Therapeut Inc, Pittsburgh, PA USA. Univ Calif Irvine, Dept Obstet & Gynecol, Div Gynecol Oncol, Orange, CA 92668 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Orange, CA 92668 USA. RP Maxwell, GL (reprint author), Four Penn Ctr, Gynecol Oncol Grp, 1600 JFK Blvd,Suite 1020, Philadelphia, PA 19103 USA. EM sramsey@fhcrc.org FU NCI NIH HHS [CA 27469, CA 37517] NR 19 TC 50 Z9 50 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2006 VL 107 IS 9 BP 2197 EP 2205 DI 10.1002/cncr.22232 PG 9 WC Oncology SC Oncology GA 101YK UT WOS:000241777300013 PM 17001661 ER PT J AU Brown, EE Whitby, D Vitale, F Marshall, V Mbisa, G Gamache, C Lauria, C Alberg, AJ Serraino, D Cordiali-Fei, P Messina, A Goedert, JJ AF Brown, Elizabeth E. Whitby, Denise Vitale, Francesco Marshall, Vickie Mbisa, Georgina Gamache, Christine Lauria, Carmela Alberg, Anthony J. Serraino, Diego Cordiali-Fei, Paola Messina, Angelo Goedert, James J. TI Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma SO CANCER LA English DT Article DE Kaposi sarcoma; Kaposi sarcoma-associated herpesvirus; human herpesvirus-8; immunity; biomarker ID GENE-EXPRESSION; HERPESVIRUS-INFECTION; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 INFECTION; TRANSPLANT RECIPIENTS; IMMUNE-ACTIVATION; CELLS; AIDS; GROWTH; IMMUNODEFICIENCY AB BACKGROUND. Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood Counts, CD4-positive and CD8-positive lymphocytes, and serum beta-2-microglobulin and neopterin levels. METHODS. Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression adjusted for sex, age, and study site. RESULTS. Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P <= .0001) and high KSHV lytic (> 1:1745; P <= .0001) and latent (> 1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P <= .05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (< 37.4%; P = .03), hemoglobin (< 12g/dL; P = .04), and lymphocytes (< 1000 cells/mu L; P = .004), including CD4-positive (+) cells (< 457 cells/mu L; P = .07) and CD8+ cells (< 213cells/mu L; P = .04), and with increased monocytes (>= 638 cells/mu L; P = .009). Nonsignificant elevations of beta-2-microglobulin and neopterin were observed among cases regardless of disease burden (P >= .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95% CI, 1.4-5.3), a high KSHV lytic antibody titer (OR of 3.7; 95% CI, 1.9-7.4), and low lymphocytes, particularly among those patients age < 70 years (OR of 8.0; 95% CI, 2.7-23.7). CONCLUSIONS. The findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS. C1 Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NCI, SAIC Frederick, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD 21701 USA. Univ Palermo, Dipartimento Igiene & Microbiol Giuseppe Allessan, Palermo, Italy. Sez Ragusa, Lega Italiana Lotta Tumori, Ragusa, Italy. IRCCS, Ist Nazl Tumori Ctr Riferimento Oncol, SDC Epidemiol & Biostat, Aviano, Italy. Inst Ospitaliero San Gallicano, Clin Lab, Rome, Italy. Univ Catania, Dipartimento Sci Biomed, Catania, Italy. RP Brown, EE (reprint author), Univ Alabama, Dept Epidemiol, RPHB 220,1530 3rd Ave S, Birmingham, AL 35294 USA. EM elbrown@uab.edu OI Serraino, Diego/0000-0003-0565-8920 FU Intramural NIH HHS; NCI NIH HHS [CA-09314-23, N01-CO-12400] NR 39 TC 24 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2006 VL 107 IS 9 BP 2282 EP 2290 DI 10.1002/cncr.22236 PG 9 WC Oncology SC Oncology GA 101YK UT WOS:000241777300023 PM 16998933 ER PT J AU Smith, EK Price, DK Figg, WD AF Smith, Erika K. Price, Douglas K. Figg, William D. TI Piecing together the HIF-1 puzzle - The role of the CTGF as a molecular mechanism of HIF-1 regulation SO CANCER BIOLOGY & THERAPY LA English DT Article DE HIF-1 alpha; CTGF; VEGF-A; metastasis; human lung adenocarcinoma ID TISSUE GROWTH-FACTOR; ANGIOGENESIS; CANCER; CELLS AB Understanding the role that molecular compounds have in cancer is of significant interest, as the identification of molecular markers will aid in the prevention and elimination of cancer. Completing this expansive puzzle proves to be challenging because there is great diversity among tumors, specifically within the microenvironment. In a recent article by Chang et al. published in The Journal of the National Cancer Institute (Vol., 2006) new insight is provided of three specific molecular compounds: hypoxia-inducible factor-1 alpha (HIF-1 alpha), the connective tissue growth factor ( CTGF) and the vascular endothelial growth factor-A (VEGF-A). As shown by Chang et al., these molecular compounds have significant implications in the role of human lung adenocarcinoma, and are shown to be integral within this microenvironment. This journal club article reviews the study of Chang et al. and briefly discusses the broader implications of their findings. C1 NCI, Clin Pharmacol Program, Mol Pharmacol Sect, Med Oncol Branch,NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Mol Pharmacol Sect, Med Oncol Branch,NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 7 TC 1 Z9 1 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV PY 2006 VL 5 IS 11 BP 1443 EP 1444 PG 2 WC Oncology SC Oncology GA 122WA UT WOS:000243256800005 PM 17172812 ER PT J AU Zhang, YL Hua, YS Benbrook, DM Covey, JM Dai, GW Liu, ZF Chan, KK AF Zhang, Yilong Hua, Yousheng Benbrook, Doris M. Covey, Joseph M. Dai, Guowei Liu, Zhongfa Chan, Kenneth K. TI High performance liquid chromatographic analysis and preclinical pharmacokinetics of the heteroarotinoid antitumor agent, SHetA2 SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE preclinical pharmacokinetics; heteroarotinoid antitumor agent; SHetA2; Hplc ID RETINOIC ACID RECEPTOR; MASS-SPECTROMETRY; APOPTOSIS AB Background: SHetA2 {[(4-nitrophenyl)amino][2,2,4,4-tetramethylthiochroman-6-yl)amino]methane-thione], NSC 726189} is a sulfur-containing heteroarotinoid, which selectively inhibits cancer cell growth and induces apoptosis without activation of nuclear retinoic acid receptors (RARs). The objective was to develop and validate a HPLC/UV method for the determination of SHetA2, and study the pharmacokinetics of SHetA2 in the mouse. Methods: SHetA2 and the internal standard, methylated XK469 (MeXK469) were isolated from 0.2 ml of mouse plasma by solid phase extraction. The analytes were separated on a narrow-bore C18 column, with the mobile phase consisting of 60% acetonitrile in water at a flow rate of 0.2 ml/min. UV detection was set at 341 nm. Pharmacokinetic studies of SHetA2 were carried out in mice following i.v. bolus dose at 20 mg/kg and oral administrations at 20 and 60 mg/kg. Results: The standard curves were linear between 25 and 2,500 nM and the lower limit of quantification (LLOQ) was 25 nM. The within-run coefficients of variation (CVs) were 11.1% at 10, 9.4% at 100, and 5.2% at 2,500 nM and the respective between-run CVs were 10.9, 3.1, and 1.5% (all n=5). The recovery was 85.8% for SHetA2 and 80.6% for MeXK469. Following i.v. bolus dose, plasma concentrations of similar to 10 mu M were achieved at 5 min in mice and declined biexponentially with detectable levels at 60 h. The data were fitted with a two-compartment model, which gave a mean initial t (1/2) of 40 min and terminal t (1/2) of 11.4 h (n=6). The total body clearance was similar to 1.81 l/h/kg. The volume of distribution at steady state (V (dss)) was 20.8 l/kg. Plasma protein binding was found to be 99.3-99.5% at low micromolar concentrations. Plasma concentration data for the i.v. and p.o. doses were also fitted interactively to a two-compartment deconvolution model. From this result, oral bioavailability values of 15% at 20 mg/kg and 19% at 60 mg/kg were obtained. Conclusions: A highly sensitive HPLC/UV method for the quantification of SHetA2 in plasma has been developed to support pharmacokinetics of SHetA2 in the mouse. Pharmacokinetic behaviors of this drug appear to be favorable for future development. C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. NCI, Rockville, MD 20852 USA. RP Chan, KK (reprint author), Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 USA. EM chan.56@osu.edu RI Liu, Zhongfa/G-8549-2013 NR 11 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2006 VL 58 IS 5 BP 561 EP 569 DI 10.1007/s00280-006-0211-z PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 069YI UT WOS:000239485000001 PM 16534614 ER PT J AU Travis, LB AF Travis, Lois B. TI The epidemiology of second primary cancers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID ACUTE MYELOID-LEUKEMIA; ADVANCED HODGKINS-DISEASE; 2ND MALIGNANT NEOPLASMS; LONG-TERM SURVIVORS; BREAST-CANCER; LUNG-CANCER; TESTICULAR-CANCER; ALKYLATING-AGENTS; YOUNG-WOMEN; HIGH-RISK AB Background: Due to improvements in early detection, supportive care, and treatment, the number of cancer survivors in the United States has tripled since 1971 and is growing by 2% each year. In 2001, there were similar to 10 million cancer survivors, representing 3.5% of the population. As survival after a diagnosis of cancer improves, quantification of the late effects of cancer and its therapy become critical. One of the most serious events experienced by cancer survivors is the diagnosis of a new cancer. Second- or higher-order cancers now account for similar to 16% of incident cancers reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Subsequent neoplasms may not necessarily be attributable to prior cancer treatment but may also reflect the effect of shared etiologic factors, environmental exposures, host characteristics, and combinations of influences, including gene-environment and gene-gene interactions. Methods/Results: This review will focus on selected highlights and recent findings in treatment-associated malignancies, with an emphasis on survivors of adult cancer. Current study methods will also be summarized. Conclusions: Important opportunities for future research include the prospective identification of patient subgroups that might be at heightened susceptibility of developing therapy-associated second cancers to modify planned treatments or select alternative management strategies. For the burgeoning population of cancer survivors treated successfully with past regimens, including those therapies that have been subsequently refined, continued quantification of late effects, including second cancers, remains highly relevant in terms of raising clinician and patient awareness, for informed counseling, and for the development of risk-adapted long-term management strategies. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Travis, LB (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Execut Pl S,Suite 7086, Bethesda, MD 20892 USA. EM duongd@mail.nih.gov FU Intramural NIH HHS NR 51 TC 117 Z9 123 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2006 VL 15 IS 11 BP 2020 EP 2026 DI 10.1158/1055-9965.EPI-06-0414 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300003 PM 17057028 ER PT J AU Ambrosone, CB Rebbeck, TR Morgan, GJ Albain, KS Calle, EE Evans, WE Hayes, DF Kushi, LH McLeod, HL Rowland, JH Ulrich, CM AF Ambrosone, Christine B. Rebbeck, Timothy R. Morgan, Gareth J. Albain, Kathy S. Calle, Eugenia E. Evans, William E. Hayes, Daniel F. Kushi, Lawrence H. McLeod, Howard L. Rowland, Julia H. Ulrich, Cornelia M. TI New developments in the epidemiology of cancer prognosis: Traditional and molecular predictors of treatment response and survival SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID BREAST-CANCER; PHYSICAL-ACTIVITY; PROSTATE-CANCER; DIAGNOSIS; AMERICAN; OBESITY C1 Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Royal Marsden Hosp, Sutton, Surrey, England. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Amer Canc Soc, Atlanta, GA 30329 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Washington Univ, St Louis, MO USA. NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Ambrosone, CB (reprint author), Roswell Pk Canc Inst, Dept Epidemiol, Elm & Carlton St, Buffalo, NY 14263 USA. EM Christine.Ambrosone@roswellpark.edu OI Kushi, Lawrence/0000-0001-9136-1175 NR 22 TC 10 Z9 10 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 NOV PY 2006 VL 15 IS 11 BP 2042 EP 2046 DI 10.1158/1055-9965.EPI-06-0827 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300007 PM 17119026 ER PT J AU Rakowski, W Meissner, H Vernon, SW Breen, N Rimer, B Clark, MA AF Rakowski, William Meissner, Helen Vernon, Sally W. Breen, Nancy Rimer, Barbara Clark, Melissa A. TI Correlates of repeat and recent mammography for women ages 45 to 75 in the 2002 to 2003 Health Information National Trends Survey (HINTS 2003) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN WOMEN; SCREENING MAMMOGRAPHY; BREAST-CANCER; CERVICAL-CANCER; EX-SMOKERS; SMOKING-CESSATION; INTERVIEW SURVEY; SOCIAL SUPPORT; OLDER; RISK AB Background: Most national-level mammography data are for ever-had and most-recent screening. There are few national-level data on rates of repeat, on-schedule mammography, and on the prevalence and correlates of repeat mammography. It is. also important to investigate the similarity of correlates for repeat and recent mammography. Methods: Analyses were from data for women ages 45 to 75 in the 2002 to 2003 Health Information and National Trends Survey (HINTS 2003; N = 1,581). The two dependent variables were self-report of repeat mammography (two exams on schedule, based on an every-other-year interval) and recent mammography only (one mammogram within the past 2 years). Results: The prevalence of recent mammography was 81.6% (95% confidence interval, 79.1-84.1) and for repeat mammography was 72.2% (95% confidence interval, 69.0-75.4). 2093 An access to care variable combining insurance coverage and regular source of care was the strongest sociodemographic correlate of both mammography indicators. Most other sociodemographic variables were not associated with mammography status. Five psychosocial/behavioral variables were associated with both mammography indicators (smoking status, attention to health information, knowledge of screening interval, worry about breast cancer, and recent mood status). Correlates were very similar for repeat and recent mammography. Conclusions: Although access to care had the strongest association with mammography, psychosocial and behavioral variables did better as a group than the sociodemographic variables. A standard set of such variables should be considered for all national surveys. C1 Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. NCI, Behav Res Program, Rockville, MD USA. Univ Texas, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. RP Rakowski, W (reprint author), Brown Univ, Dept Community Hlth, Box G-H1, Providence, RI 02912 USA. EM William_Rakowski@brown.edu FU NCI NIH HHS [R01-CA105486, R01-CA76330, K07-CA87070, K05-CA90485, R01-CA97263] NR 76 TC 69 Z9 69 U1 4 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 NOV PY 2006 VL 15 IS 11 BP 2093 EP 2101 DI 10.1158/1055-9965.EPI-06-0301 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300016 PM 17119033 ER PT J AU Sutcliffe, S Giovannucci, E De Marzo, AM Leitzmann, MF Willett, WC Platz, EA AF Sutcliffe, Siobhan Giovannucci, Edward De Marzo, Angelo M. Leitzmann, Michael F. Willett, Walter C. Platz, Elizabeth A. TI Gonorrhea, syphilis, clinical prostatitis, and the risk of prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MIDDLE-AGED MEN; ASSOCIATION; PREVALENCE; COHORT; EPIDEMIOLOGY; INFECTION; VASECTOMY; DISEASES; SMOKING AB Background: Although previous case-control studies have observed positive associations among gonorrhea, syphilis, clinical prostatitis, and prostate cancer, many may have been susceptible to recall and interviewer biases due to their retrospective designs. Therefore, to investigate these associations without concerns of recall and interviewer biases, we conducted a large, prospective investigation in the Health Professionals Follow-up Study. Methods: In 1992, participants were asked to report their histories of gonorrhea, syphilis, and clinical prostatitis by mailed questionnaire. Prostate cancer diagnoses were ascertained by self-report on the 1994 and each subsequent biennial follow-up questionnaire and confirmed by medical record review. Results: Of the 36,033 participants in this analysis, 2,263 were diagnosed with prostate cancer between the date of return of the 1992 questionnaire and 2002. No association was observed between gonorrhea [adjusted relative risk (RR), 1.04; 95% confidence interval (95% CI), 0.79-1.36] or syphilis (RR, 1.06; 95% CI, 0.44-2.59) and prostate cancer. Overall null results were also observed between clinical prostatitis and prostate cancer (RR, 1.08; 95% CI, 0.96-1.20), although a significant positive association was observed among younger men (< 59 years) screened for prostate cancer (RR, 1.49; 95% CI, 1.08-2.06; P-interaction = 0.006). Conclusions: Gonorrhea and syphilis do not seem to be risk factors for prostate cancer in this cohort of men with a lower burden of sexually transmitted infections. Clinical prostatitis is also unlikely to be a risk factor, although possible roles for prostatitis in younger men and asymptomatic prostatic infection and inflammation cannot be ruled out. C1 Johns Hopkins Med Inst, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Platz, EA (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Room E6138,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu OI Sutcliffe, Siobhan/0000-0002-4613-8107 FU NCI NIH HHS [CA55075, P50CA58236]; NHLBI NIH HHS [HL35464] NR 39 TC 37 Z9 39 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 NOV PY 2006 VL 15 IS 11 BP 2160 EP 2166 DI 10.1158/1055-9965.EPI-05-0913 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300026 PM 17119041 ER PT J AU Sequoia, JSP Wright, ME McCarron, P Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Sequoia, Jacqueline S. P. Wright, Margaret E. McCarron, Peter Pietinen, Pirjo Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius TI A prospective investigation of height and prostate cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; GROWTH-FACTOR-I; PHYSICAL-ACTIVITY; NORWEGIAN MEN; FOLLOW-UP; UNITED-STATES; INTRAEPITHELIAL NEOPLASIA; LIFE-STYLE; SIZE; COHORT AB Greater adult height, which reflects a combination of early nutrition, exposure to androgens, growth hormones, and other factors during growth and development, as well as heredity, has been associated with increased prostate cancer risk in several observational studies, but findings have been inconsistent. We examined this relationship in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline, 29,119 Finnish male smokers 50 to 69 years old had height and weight measured by trained personnel, provided information on demographic, smoking, medical, and other characteristics, and completed an extensive diet history questionnaire. A total of 1,346 incident prostate cancer cases were identified during a follow-up period of up to 17.4 years (median, 14.1 years). In age-adjusted Cox proportional hazards models, the hazard ratios and 95% confidence intervals for prostate cancer according to increasing quintiles of height [<= 168, 169-171, 172-175, 176-178, and > 178 cm] were 1.00 (reference), 1.11 (0.93-1.32), 1.11 (0.95-1.31), 1.30 (1.01-1.55), and 1.14 (0.96-1.35); P-trend = 0.04. In analyses stratified by disease stage (available for 916 cases), a strong dose-response relationship was observed between greater height and advanced, but not earlier-stage, disease [tumor-node-metastasis stage III-IV, hazard ratio and 95% confidence interval for increasing quintiles of height: 1.77 (1.18-2.65), 1.82 (1.25-2.65), 1.93 (1.29-2.90), and 2.02 (1.37-2.97); P-trend = 0.0008, P-interaction = 0.002]. Our study provides additional evidence that increased height is a risk factor for prostate cancer and suggests that taller men are particularly susceptible to advanced disease. C1 NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Queens Univ, Dept Epidemiol & Publ Hlth, Belfast, Antrim, North Ireland. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Albanes, D (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM daa@nih.gov RI Albanes, Demetrius/B-9749-2015 FU Intramural NIH HHS NR 56 TC 13 Z9 14 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 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2006 VL 15 IS 11 BP 2174 EP 2178 DI 10.1158/1055-9965.EPI-06-0467 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300028 PM 17119043 ER PT J AU Taylor, KL Davis, JL Turner, RO Johnson, L Schwartz, MD Kerner, JF Leak, C AF Taylor, Kathryn L. Davis, Jackson L., III Turner, Ralph O. Johnson, Lenora Schwartz, Marc D. Kerner, Jon F. Leak, Chikarlo TI Educating African American men about the prostate cancer screening dilemma: A randomized intervention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SHARED DECISION-MAKING; CONTROLLED-TRIAL; ANTIGEN TEST; INFORMED-CONSENT; SELF-REPORTS; KNOWLEDGE; INFORMATION; CHALLENGES; INTENTION; ATTITUDES AB Background: Until there is a definitive demonstration that early diagnosis and treatment of prostate cancer reduces disease-related mortality, it is imperative to promote informed screening decisions by providing balanced information about the potential benefits and risks of prostate cancer screening. Within a community/academic collaboration, we conducted a randomized trial of a printed booklet and a videotape that were designed for African American (AA) men. The purpose of the trial was to determine the effect of the interventions on knowledge, decisional conflict, satisfaction with the screening decision, and self-reported screening. Methods: Participants were 238 AA men, ages 40 to 70 years, who were members of the Prince Hall Masons in Washington, DC. Men were randomly assigned to the (a) video-based information study arm, (b) print-based information study arm, or (c) wait list control study arm. Intervention materials were mailed to men at home. Assessments were conducted at baseline, 1 month, and 12 months postintervention. Multivariate analyses, including ANCOVA and logistic regression, were used to analyze group differences. Results: The booklet and video resulted in a significant improvement in knowledge and a reduction in decisional conflict about prostate cancer screening, relative to the wait list control. Satisfaction with the screening decision was not affected by the interventions. Self-reported screening rates increased between the baseline and the 1-year assessment, although screening was not differentially associated with either of the interventions. In exploratory analyses, prostate-specific antigen testing at 1 year was more likely among previously screened men and was associated with having low baseline decisional conflict. Conclusions: This study represents one of the first randomized intervention trials specifically designed to address AA men's informed decision making about prostate cancer screening. We have developed and evaluated culturally sensitive, balanced, and disseminable materials that improved knowledge and reduced decisional conflict about prostate cancer screening among AA men. Due to the high incidence and mortality rates among AA men, there is a need for targeted educational materials, particularly materials that are balanced in terms of the benefits and risks of screening. C1 Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20007 USA. Most Worshipful Prince Hall Grand Lodge Dist Colo, Washington, DC USA. Natl Canc Inst, Off Educ & Special Initiat, Rockville, MD USA. Natl Canc Inst, Div Canc Control & Populat Sci, Rockville, MD USA. RP Taylor, KL (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Control Program, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM TAYLORKL@georgetown.edu OI Kerner, Jon/0000-0002-8792-3830 FU ATSDR CDC HHS [TS290]; NCI NIH HHS [K07 CA72645-01] NR 51 TC 47 Z9 48 U1 1 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 NOV PY 2006 VL 15 IS 11 BP 2179 EP 2188 DI 10.1158/1055-9965.EPI-05-0417 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300029 PM 17119044 ER PT J AU Dodd, LE Sengupta, S Chen, IH den Boon, JA Cheng, YJ Westra, W Newton, MA Mittl, BF McShane, L Chen, CJ Ahlquist, P Hildesheim, A AF Dodd, Lori E. Sengupta, Srikumar Chen, I-How den Boon, Johan A. Cheng, Yu-Juen Westra, William Newton, Michael A. Mittl, Beth F. McShane, Lisa Chen, Chien-Jen Ahlquist, Paul Hildesheim, Allan TI Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CLASS-I; TAIWAN; RISK; POLYMORPHISMS AB Polymorphisms in nitrosamine metabolism, DNA repair, and immune response genes have been associated with nasopharyngeal carcinoma (NPC). Studies have suggested chromosomal regions involved in NPC. To shed light on NPC etiology, we evaluated host gene expression patterns in 31 NPC and 10 normal nasopharyngeal tissue specimens using the Affymetrix Human Genome U133 Plus 2.0 Array. We focused on genes in five a priori biological pathways and chromosomal locations. Rates of differential expression within these prespecified lists and overall were tested using a bootstrap method. Differential expression was observed for 7.6% of probe sets overall. Elevations in rate of differential expression were observed within the DNA repair (13.7%; P = 0.01) and nitrosamine metabolism (17.5%; P = 0.04) pathways. Differentially expressed probe sets within the DNA repair pathway were consistently overexpressed (93%), with strong effects observed for PRKDC, PCNA, and CHEK1. Differentially expressed probe sets within the nitrosamine metabolism pathway were consistently underexpressed (100%), with strong effects observed for NQ01, CYP2136, and CYP2E1. No significant evidence of increases in rate of differential expression was seen within the immune/inflammatory pathway. A significant elevation in rate of differential expression was noted for chromosome 4p15.1-4q12 (13.0%; P = 0.04); both overexpression and underexpression were evident (38% and 62%, respectively). An elevation in the rate of differential expression on chromosome 14q32 was observed (11.3%; P = 0.06) with a consistent pattern of gene underexpression (100%; P < 0.0001). These effects were similar when excluding late-stage tumors. Our results suggest that nitrosamine activation and DNA repair are important in NPC. The consistent down-regulation of expression on chromosome 14q32 suggests loss of heterozygosity in this region. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD 20852 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Westat Corp, Rockville, MD USA. Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA. Univ Wisconsin, Dept Stat & Biostat & Med Informat, Madison, WI 53706 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. Univ Wisconsin, Howard Hughes Med Inst, Madison, WI 53706 USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. McKay Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Hildesheim, A (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 6120 Execut Blvd,Room 7062, Rockville, MD 20852 USA. EM hildesha@exchange.nih.gov RI Chen, Chien-Jen/C-6976-2008 FU NCI NIH HHS [CA2243, CA64364, CA97944] NR 20 TC 26 Z9 29 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 NOV PY 2006 VL 15 IS 11 BP 2216 EP 2225 DI 10.1158/1055-9965.EPI-06-0455 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300034 PM 17119049 ER PT J AU Kim, S Vermeulen, R Waidyanatha, S Johnson, BA Lan, Q Smith, MT Zhang, LP Li, GL Shen, M Yin, SN Rothman, N Rappaport, SM AF Kim, Sungkyoon Vermeulen, Roel Waidyanatha, Suramya Johnson, Brent A. Lan, Qing Smith, Martyn T. Zhang, Luoping Li, Guilan Shen, Min Yin, Songnian Rothman, Nathaniel Rappaport, Stephen M. TI Modeling human metabolism of benzene following occupational and environmental exposures SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENERALIZED ADDITIVE-MODELS; HAZARDS REGRESSION-MODELS; CUBIC SPLINE FUNCTIONS; AIR-POLLUTION; PARTICULATE MATTER; UNEXPOSED SUBJECTS; MULTICITY PROJECT; LIVER-MICROSOMES; URINARY BENZENE; HYDROQUINONE AB We used natural spline (NS) models to investigate nonlinear relationships between levels of benzene metabolites (EEmuconic acid, S-phenylmercapturic acid, phenol, hydroquinone, and catechol) and benzene exposure among 386 exposed and control workers in Tianjin, China. After adjusting for background levels (estimated from the 60 control subjects with the lowest benzene exposures), expected mean trends of all metabolite levels increased with benzene air concentrations from 0.03 to 88.9 ppm. Molar fractions for phenol, hydroquinone, and EE-muconic acid changed continuously with increasing air concentrations, suggesting that competing CYP-mediated metabolic pathways favored EEmuconic acid and hydroquinone below 20 ppm and favored phenol above 20 ppm. Mean trends of dose-specific levels ([tmol/L/ppm benzene) of EE-muconic acid, phenol, hydroquinone, and catechol all decreased with increasing benzene exposure, with an overall 9-fold reduction of total metabolites. Surprisingly, about 90% of the reductions in dosespecific levels occurred below about 3 ppm for each major metabolite. Using generalized linear models with NSsmoothing functions (GLM + NS models), we detected significant effects upon metabolite levels of gender, age, and smoking status. Metabolite levels were about 20% higher in females and decreased between 1% and 2% per year of life. In addition, levels of hydroquinone and catechol were greater in smoking subjects. Overall, our results indicate that benzene metabolism is highly nonlinear with increasing benzene exposure above 0.03 ppm, and that current human toxicokinetic models do not accurately predict benzene metabolism below 3 ppm. Our results also suggest that GLM + NS models are ideal for evaluating nonlinear relationships between environmental exposures and levels of human biomarkers. C1 Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, CB 7431, Chapel Hill, NC 27599 USA. EM smr@unc.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS; NIEHS NIH HHS [P42ES04705, P30ES10126, P42ES05948, R01ES06721, P30ES01896] NR 50 TC 49 Z9 52 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 NOV PY 2006 VL 15 IS 11 BP 2246 EP 2252 DI 10.1158/1055-9965.EPI-06-0262 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300038 PM 17119053 ER PT J AU Glebov, OK Rodriguez, LM Soballe, P DeNobile, J Cliatt, J Nakahara, K Kirsch, IR AF Glebov, Oleg K. Rodriguez, Luz M. Soballe, Peter DeNobile, John Cliatt, Janet Nakahara, Kenneth Kirsch, Ilan R. TI Gene expression patterns distinguish colonoscopically isolated human aberrrant crypt foci from normal colonic mucosa SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SELECTIVE CYCLOOXYGENASE-2 INHIBITOR; CATENIN-ACCUMULATED CRYPTS; COLORECTAL-CANCER; RAT COLON; PRENEOPLASTIC LESIONS; GASTRIC-CARCINOMA; ABERRANT CRYPTS; CARCINOGENESIS; IDENTIFICATION; MUTATIONS AB Aberrant crypt foci (ACF) are considered the earliest identifiable preneoplastic colonic lesions; thus, a greater understanding of the nature of genetic changes underlying the transformation of normal colonic mucosa (NM) into ACF may provide insight into the mechanisms of carcinogenesis. ACF were identified by indigo carmine spraying onto colonic mucosa during colonoscopy and isolated as standard pinch biopsies of the mucosal areas containing the ACE RNAs isolated from ACF and matched NM biopsies from the ascending and descending colons of 13 patients were analyzed on arrays containing 9128 cDNAs. Thirty-four differentially expressed (P < 0.001) genes were found in a paired comparison of the ACF and NM samples, and 25 of 26 matched pairs of ACF and NM could be correctly classified in leave-one-out cross-validation. Differential expression for seven of eight genes was confirmed by real-time reverse transcription-PCR. Furthermore, ACF and NM samples, including six pairs of ACF and NM samples that had not previously been analyzed by array hybridization, can be correctly classified on the basis of the overexpression in ACF of three selected genes (REG4, SRPN-B5, and TRIM29) evaluated by real-time reverse transcription-PCR. In a separate analysis of 13 biopsy pairs from either ascending or descending colon, ACF and NM samples could also be correctly classified by the gene expression patterns. Analysis of gene expression differences in ACF from the ascending and descending colon versus NM samples indicates that ACF from these distinct colonic locations are converging toward similar gene expression profiles and losing differences in gene expression characteristic of NM from the ascending versus descending colon. C1 Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Genet Branch, Ctr Canc Res,Natl Canc Inst, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Dept Surg, Bethesda, MD 20814 USA. RP Kirsch, IR (reprint author), 1201 Amgen Court W,AQ1-J4144, Seattle, WA 98119 USA. EM lkirsch@amgen.com FU Intramural NIH HHS NR 73 TC 23 Z9 26 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 NOV PY 2006 VL 15 IS 11 BP 2253 EP 2262 DI 10.1158/1055-9965.EPI-05-0694 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300039 PM 17119054 ER PT J AU Pierre, F Peiro, G Tache, S Cross, AJ Bingham, SA Gasc, N Gottardi, G Corpet, DE Gueraud, F AF Pierre, Fabrice Peiro, Geraldine Tache, Sylviane Cross, Amanda J. Bingham, Sheila A. Gasc, Nicole Gottardi, Gaelle Corpet, Denis E. Gueraud, Francoise TI New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LIPID-PEROXIDATION; RED MEAT; URINARY METABOLITE; COLORECTAL-CANCER; OXIDATIVE STRESS; F-2-ISOPROSTANES; CONSUMPTION; MYOGLOBIN; ALDEHYDES; PROMOTE AB Background: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F-2 alpha (8-iso-PGF(2)alpha), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8-iso-PGF(2)alpha and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with nonheme iron). Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF(2)alpha increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans. Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. C1 INRA, UMR 1089, ENVT Xenobiot, F-31931 Toulouse, France. Ecole Natl Vet Toulouse, Toulouse, France. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. MRC, Dunn Human Nutr Unit, Cambridge, England. RP Gueraud, F (reprint author), INRA, UMR 1089, ENVT Xenobiot, 180 Chemin Tournefeuille, F-31931 Toulouse, France. EM fgueraud@toulouse.inra.fr RI PIERRE, Fabrice/C-9937-2010; CORPET, Denis/B-3544-2008 NR 21 TC 34 Z9 34 U1 1 U2 5 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 NOV PY 2006 VL 15 IS 11 BP 2274 EP 2279 DI 10.1158/1055-9965.EPI-06-0085 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300042 PM 17119057 ER PT J AU Cozen, W Gebregziabher, M Conti, DV Van den Berg, DJ Coetzee, GA Wang, SS Rothman, N Bernstein, L Hartge, P Morhbacher, A Coetzee, SG Salam, MT Wang, W Zadnick, J Ingles, SA AF Cozen, Wendy Gebregziabher, Mulugeta Conti, David V. Van den Berg, David J. Coetzee, Gerhard A. Wang, Sophia S. Rothman, Nathaniel Bernstein, Leslie Hartge, Patricia Morhbacher, Ann Coetzee, Simon G. Salam, Muhammad T. Wang, Wei Zadnick, John Ingles, Sue A. TI Interleukin-6-related genotypes, body mass index, and risk of multiple myeloma and plasmacytoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-I; PROMOTER POLYMORPHISMS; UNITED-STATES; CANCER-RISK; GENE POLYMORPHISMS; ADIPOSE-TISSUE; FAMILY-HISTORY; OBESITY; ASSOCIATION AB Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n ='112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions -174, -572, and -597; one variable number of tandem repeats (-373 AnTn); and one SNP in the IL-6 receptor (IL-6ra) gene at position -358. The variant allele of the IL-6 promoter SNP -572 was associated 2285 with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% Cb, 0.7-4.71 or population controls (OR, 2.4; 95% CI, 1.2-4.7). The -373 9A19A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI >= 30 kg/m(2)) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of < 25 kg/m(2). These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms. C1 Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Med, Los Angeles, CA 90089 USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Microbiol, Los Angeles, CA 90089 USA. Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cozen, W (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, 1441 Eastlake Ave,MC 9175, Los Angeles, CA 90089 USA. EM wcozen@usc.edu RI Coetzee, Simon/C-1218-2014; OI Coetzee, Simon/0000-0003-4267-5930; Salam, Muhammad/0000-0002-3565-8916; Gebregziabher, Mulugeta/0000-0002-4826-481X FU NCI NIH HHS [5 P30 CA14089-30, N01-PC-35139, CA17054]; PHS HHS [U55/CCU921930-02] NR 52 TC 39 Z9 41 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 NOV PY 2006 VL 15 IS 11 BP 2285 EP 2291 DI 10.1158/1055-9965.EPI-06-0446 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300044 PM 17119059 ER PT J AU Yazawa, H Murakami, T Li, HM Back, T Kurosaka, K Suzuki, Y Shorts, L Akiyama, Y Maruyama, K Parsoneault, E Wiltrout, RH Watanabe, M AF Yazawa, H. Murakami, T. Li, H-M Back, T. Kurosaka, K. Suzuki, Y. Shorts, L. Akiyama, Y. Maruyama, K. Parsoneault, E. Wiltrout, R. H. Watanabe, M. TI Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors SO CANCER GENE THERAPY LA English DT Article DE hydrodynamics; based gene delivery; VEGF; Flk-1; angiogenesis; renal cell carcinoma; lung carcinoma ID METASTATIC COLORECTAL-CANCER; PLASMID DNA; FACTOR RECEPTOR; IN-VIVO; MOUSE MODEL; INTRAVENOUS-INJECTION; RANDOMIZED-TRIAL; DENDRITIC CELLS; FACTOR ANTIBODY; SOLUBLE FORM AB Antiangiogenic gene therapy is a promising strategy for cancer treatment, which generally requires highly efficient delivery systems. To date, success of this strategy has depended almost exclusively on the delivery of high titers of viral vectors, which can result in effective transgene expression. However, their cytotoxicity and immunogenicity are a major concern for clinical applications. Recent advances in delivery efficiency of naked DNA could potentially meet the requirement for both high transgene expression and minimal side effects. To investigate whether naked DNA can be used for antiangiogenic cancer therapy, an expression plasmid was generated that encodes a soluble form of fetal liver kinase-1 (Flk-1) gene, a receptor for vascular endothelial growth factor (VEGF). Hydrodynamic injection of this plasmid resulted in close to 0.1 mg/ml of soluble Flk-1 protein in mouse serum and blocked VEGF-driven angiogenesis in matrigel in vivo. The same delivery significantly suppressed the growth of two different pre-existing subcutaneous tumors, Renca renal cell carcinoma and 3LL lung carcinoma. CD31 immunohistochemistry revealed that the tumor-associated angiogenesis was also highly attenuated in soluble Flk-1-treated mice. Thus, expression of genes by hydrodynamics-based gene delivery of naked DNA appears to be a promising approach for antiangiogenic cancer gene therapy. C1 NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Cell & Canc Biol Branch, Ctr Canc Res, Frederick, MD 21702 USA. SAIC Frederick Inc, NCI, Basic Res Program, Frederick, MD USA. Shizuoka Canc Ctr, Res Inst, Div Immunotherapy, Shizuoka, Japan. RP Watanabe, M (reprint author), NCI, Expt Immunol Lab, Ctr Canc Res, Bldg 560,Rm 31-16A, Frederick, MD 21702 USA. EM watanabm@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 59 TC 16 Z9 17 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV PY 2006 VL 13 IS 11 BP 993 EP 1001 DI 10.1038/sj.cgt.7700970 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 093HG UT WOS:000241158400002 PM 16763608 ER PT J AU Schiller, JT Lowy, DR AF Schiller, John T. Lowy, Douglas R. TI Prospects for cervical cancer prevention by human papillomavirus vaccination SO CANCER RESEARCH LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PARTICLE VACCINE; YOUNG-WOMEN; EFFICACY; TYPE-16; NEOPLASIA; INFECTION AB Recent clinical trials in young women have shown that subunit vaccines based on human papillornavirus (HPV) 16 and HPV18 L1 virus-like particles are similar to 100% effective in short-term prevention of persistent cervical infection and of cervical dysplasia by these major oncogenic types. These remarkable efficacy results, together with an excellent safety profile in thousands of vaccinated women, have led to the HPV prophylactic vaccine from one manufacturer having now been licensed for commercial use and the expectation that the vaccine from a second manufacturer will be approved in the near future. These vaccines seem to have great potential for reducing cervical cancer deaths and treatments to remove premalignant cervical lesions. However, before their public health effect can be fully estimated, several issues must be addressed. These include duration of protection, degree of cross-protection against nonvaccine types, efficacy in men, and vaccine availability to economically disadvantaged women. C1 NCI, Canc Res Ctr, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NIH, Bldg 37,Room 4106, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov NR 25 TC 40 Z9 41 U1 1 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 NOV 1 PY 2006 VL 66 IS 21 BP 10229 EP 10232 DI 10.1158/0008-5472.CAN-06-0630 PG 4 WC Oncology SC Oncology GA 101ZY UT WOS:000241781600001 PM 17079437 ER PT J AU Li, ZQ Mahesh, SP Shen, DF Liu, BY Siu, WO Hwang, FS Wang, QC Chan, CC Pastan, I Nussenblatt, RB AF Li, Zhuqing Mahesh, Sankaranarayana P. Shen, De Fen Liu, Baoyin Siu, Willie O. Hwang, Frank S. Wang, Qing-Chen Chan, Chi-Chao Pastan, Ira Nussenblatt, Robert B. TI Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary Intraocular lymphoma SO CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM LYMPHOMA; RECOMBINANT IMMUNOTOXIN; CHEMOKINE RECEPTORS; ANTITUMOR-ACTIVITY; BRAIN LYMPHOMA; DIAGNOSIS; INTERLEUKIN-10; EXPRESSION; MANAGEMENT; LEUKEMIA AB Human primary intraocular lymphoma (PIOL) is predominantly a B cell-originated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice. The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the marine model resembles human PIOL, closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Several putative molecular markers for human PIOL were expressed in vivo in this model. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL, resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL, and for the evaluation of new therapeutic approaches. The results of B cell-specific immunotoxin therapy may have clinical implications in treating human PIOL. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,9000 Rockville Pike, Bethesda, MD 20892 USA. EM DrBob@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 35 TC 14 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 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2006 VL 66 IS 21 BP 10586 EP 10593 DI 10.1158/0008-5472.CAN-06-1981 PG 8 WC Oncology SC Oncology GA 101ZY UT WOS:000241781600049 PM 17079483 ER PT J AU Robinson-White, AJ Leitner, WW Aleem, E Kaldis, P Bossis, I Stratakis, CA AF Robinson-White, Audrey J. Leitner, Wolfgang W. Aleem, Eiman Kaldis, Philipp Bossis, Ioannis Stratakis, Constantine A. TI PRKAR1A inactivation leads to increased proliferation and decreased apoptosis in human B lymphocytes SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-A; SCHWANNOMAS CARNEY COMPLEX; SPOTTY SKIN PIGMENTATION; ALPHA REGULATORY SUBUNIT; EPSTEIN-BARR-VIRUS; ENDOCRINE OVERACTIVITY; SIGNALING PATHWAYS; DEATH RECEPTOR; TUMOR-THERAPY; CELL-DEATH AB The multiple neoplasia syndrome Carney complex (CNC) is caused by heterozygote mutations in the gene, which codes for the RI alpha regulatory subunit (PRKAR1A) of protein kinase A. Inactivation of PRKAR1A and the additional loss of the normal allele lead to tumors in CNC patients and increased cyclic AMP signaling in their cells, but the oncogenetic mechanisms in affected tissues remain unknown. Previous studies suggested that PRKAR1A down-regulation may lead to increased mitogen-activated protein kinase (MAPK) signaling. Here, we show that, in lymphocytes with PRKAR1A-inactivating mutations, there is increased extracellular signal-regulated kinase (ERK) 1/2 and B-raf phosphorylation and MAPK/ERK kinase 1/2 and c-Myc activation, whereas c-Raf-1 is inhibited. These changes are accompanied by increased cell cycle rates and decreased apoptosis that result in an overall net gain in proliferation and survival. In conclusion, inactivation of PRKAR1A leads to widespread changes in molecular pathways that control cell cycle and apoptosis. This is the first study to show that human cells with partiafly inactivated RI alpha, levels have increased proliferation and survival, suggesting that loss of the normal allele in these cells is not necessary for these changes to occur. C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch,CRC, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD USA. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch,CRC, NIH, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Leitner, Wolfgang/F-5741-2011; Kaldis, Philipp/G-2714-2010; Aleem, Eiman/I-3777-2012; OI Leitner, Wolfgang/0000-0003-3125-5922; Kaldis, Philipp/0000-0002-7247-7591; Aleem, Eiman/0000-0002-9215-8213 FU Intramural NIH HHS NR 50 TC 22 Z9 23 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 NOV 1 PY 2006 VL 66 IS 21 BP 10603 EP 10612 DI 10.1158/0008-5472.CAN-06-2200 PG 10 WC Oncology SC Oncology GA 101ZY UT WOS:000241781600051 PM 17079485 ER PT J AU So, KJ Tamura, G Honda, T Homma, N Waki, T Togawa, N Nishizuka, S Motoyama, T AF So, Kanji Tamura, Gen Honda, Teiichiro Homma, Naoyuki Waki, Takayoshi Togawa, Naoyuki Nishizuka, Satoshi Motoyama, Teiichi TI Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia SO CANCER SCIENCE LA English DT Article ID CPG-ISLAND; HELICOBACTER-PYLORI; DNA METHYLATION; CANCER; HYPERMETHYLATION AB A number of tumor suppressor and tumor-related genes are silenced by promoter hypermethylation in gastric cancer. Hypermethylation is not restricted to cancer cells, but is also present in non-neoplastic cells during aging. Such age-related methylation in non-neoplastic gastric epithelia is postulated to constitute a field defect that increases the risk for development of gastric cancer. To quantitatively evaluate age-related methylation in non-neoplastic gastric epithelia, we used a fiber-type DNA microarray on which methylated and unmethylated sequence probes were mounted. After bisulfite modification, a part of the promoter CpG island of four tumor suppressor genes, lysyl oxidase (LOX), p16, RUNX3 and tazarotene-induced gene 1 (TIG1), were amplified by PCR using Cy5 end labeled primers. Methylation rates (MRs) were calculated as the ratio of the fluorescence intensity of a methylated sequence probe to the total fluorescence intensity of methylated and unmethylated probes. Non-neoplastic gastric mucosa was obtained from 24 non-cancer-bearing stomachs at autopsy. MRs ranged from 0.0% to 77.2% (mean, 15.8%) for LOX, 0.0% to 45.8% (mean, 10.0%) for p16, 0.0% to 83.8% (mean, 9.0%) for RUNX3, and 0.0% to 46.1% (mean, 6.6%) for TIG1, and significantly correlated with aging (P < 0.01). The regression curves were: y = 0.013x(2) - 0.6184x + 4.0512, R-2 = 0.5728 (P < 0.001) for LOX; y = 0.0107x(2) - 0.6055x + 5.2943, R-2 = 0.7891 (P < 0.00001) for p16; y = 0.0182x(2) - 1.2234x + 11.566, R-2 = 0.5595 (P < 0.001) for RUNX3; and y = 0.0068x(2) - 0.3586x + 2.4306, R-2 = 0.4670 (P < 0.01) for TIG1. Thus, our present results are consistent with the notion that age-related methylation is associated with cancer susceptibility in the elderly. Quantitative analysis of DNA methylation using DNA microarrays is a promising method for risk assessment in the development of gastric cancer. C1 Yamagata Univ, Sch Med, Dept Pathol, Yamagata 9909585, Japan. Yamagata Prefectural Cent Hosp, Div Pathol, Yamagata 9902292, Japan. Mitsubishi Rayon Co Ltd, Genom Device Project, Yokohama Res Labs, Yamagata 2300053, Japan. NCI, Mol Therapeut Program, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Tamura, G (reprint author), Yamagata Univ, Sch Med, Dept Pathol, 2-2-2 Iidanishi, Yamagata 9909585, Japan. EM gtamura@ypch.gr.jp FU NCI NIH HHS [N01-CO-12400] NR 17 TC 81 Z9 88 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD NOV PY 2006 VL 97 IS 11 BP 1155 EP 1158 DI 10.1111/j.1349-7006.2006.00302.x PG 4 WC Oncology SC Oncology GA 086GB UT WOS:000240660700004 PM 16952303 ER PT J AU Nakachi, K Harris, CC Tahara, E AF Nakachi, Kei Harris, Curtis C. Tahara, Eiichi TI Japan-US Cooperative Cancer Research Seminar on molecular epidemiological characteristics of lung and colon cancer development among atomic-bomb survivors, Bethesda, USA, February 23-24, 2006 SO CANCER SCIENCE LA English DT Editorial Material C1 Dept Radiobiol Mol Epidemiol, Minami Ku, Hiroshima 7320815, Japan. Radiat Effects Res Fdn, Minami Ku, Hiroshima 7320815, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Nakachi, K (reprint author), Dept Radiobiol Mol Epidemiol, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. EM nakachi@rerf.or.jp NR 0 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD NOV PY 2006 VL 97 IS 11 BP 1279 EP 1282 DI 10.1111/j.1349-7006.2006.00312.x PG 4 WC Oncology SC Oncology GA 086GB UT WOS:000240660700022 PM 16965394 ER PT J AU Mizuno, T Tokuoka, S Kishikawa, M Nakashima, E Mabuchi, K Iwamoto, KS AF Mizuno, Terumi Tokuoka, Shoji Kishikawa, Masao Nakashima, Eiji Mabuchi, Kiyohiko Iwamoto, Keisuke S. TI Molecular basis of basal cell carcinogenesis in the atomic-bomb survivor population: p53 and PTCH gene alterations SO CARCINOGENESIS LA English DT Article ID NONMELANOMA SKIN-CANCER; TUMOR-SUPPRESSOR GENE; CARCINOMA SYNDROME; IONIZING-RADIATION; GAMMA-IRRADIATION; GORLIN-SYNDROME; UNITED-STATES; HUMAN HOMOLOG; MUTATIONS; DNA AB Epidemiological studies suggest that UV exposure from sunlight is the major etiology for skin cancers, both melanocytic and non-melanocytic. However, the radiation-related risk for skin cancer among atomic bomb survivors of Hiroshima and Nagasaki is primarily derived from the excess risk of basal cell carcinoma (BCC), with no demonstrable excess in squamous cell carcinoma or melanoma. The BCCs in this cohort are therefore unusual in being potentially attributable to two types of radiation-UV and ionizing (IR). BCCs have been associated with PTCH and/or p53 tumor suppressor gene alterations. To investigate the roles of these genes in relation to IR and UV exposures, we analyzed both genes in BCC samples from atomic bomb survivors. We examined 47 tumors, of which 70% had non-silent base-substitution p53 mutations independent of IR or UV exposure. However, the distribution of mutation type depends on UV and/or IR exposure. For example, C-to-T transitions at CpG sites adjacent to pyrimidine-pyrimidine (PyPy) sequences were more prevalent in tumors from UV-exposed than UV-shielded body areas and CpG-mutations at non-PyPy sequences were more prevalent in tumors from UV-shielded body areas with high-IR (>= 1 Gy) than low-IR (< 0.2 Gy) exposure. And notably, although p53 deletion-frequencies demonstrated no IR-dose associations, deletions at the PTCH locus were more frequent (79% versus 44%) in tumors with high-IR than low-IR exposure. Moreover, 60% of high-IR tumors harbored both p53 and PTCH abnormalities compared with 23% of low-IR tumors. Therefore, alteration of both genes is likely to play a role in radiation-induced basal cell carcinogenesis. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Roy E Coats Res Labs, Los Angeles, CA 90095 USA. Radiat Effects Res Fdn, Dept Radiobiol Mol Epidemiol, Hiroshima 7320815, Japan. Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima 7320815, Japan. Radiat Effects Res Fdn, Dept Stat, Hiroshima 7320815, Japan. Nagasaki Inst Diagnost Pathol, Isahaya, Japan. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Iwamoto, KS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Roy E Coats Res Labs, Box 951714, Los Angeles, CA 90095 USA. EM kiwamoto@mednet.ucla.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CP-31012, N01-CP-71015] NR 65 TC 8 Z9 9 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2006 VL 27 IS 11 BP 2286 EP 2294 DI 10.1093/carcin/bg1107 PG 9 WC Oncology SC Oncology GA 099XD UT WOS:000241629700017 PM 16777989 ER PT J AU Sack, MN AF Sack, Michael N. TI Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance SO CARDIOVASCULAR RESEARCH LA English DT Review DE cardiac ischemia; mitochondrial respiration; uncoupling proteins; reactive oxygen species; mitochondrial depolarization ID CYTOCHROME-C-OXIDASE; SKELETAL-MUSCLE MITOCHONDRIA; POTASSIUM CHANNEL OPENERS; PREVENTS NEURONAL DEATH; STANDARD METABOLIC-RATE; FREE-RADICAL GENERATION; NITRIC-OXIDE; MYOCARDIAL-ISCHEMIA; OXIDATIVE-PHOSPHORYLATION; ENERGY-METABOLISM AB Modest depolarization of the mitochondrial inner membrane potential is known to attenuate mitochondrial reactive oxygen species generation. Transient pharmacologic uncoupling of mitochondrial oxidative phosphorylation results in modest depolarization of the mitochondrial membrane potential and confers protection against subsequent cardiac ischemia-reperfusion injury. Whether cardiac mitochondria have an innate capacity to temporally self-modulate their membrane potential as a possible adaptive mechanism in the context of cardiac ischemia and early reperfusion is supported by emerging data and is an intriguing concept that warrants further investigation. The objective of this review is to explore the various mechanisms whereby mitochondrial depolarization can be evoked in the context of both cardiac ischemia and reperfusion and in response to the cardioprotective program of ischemic preconditioning. The potential regulatory pathways orchestrating this biological perturbation of mitochondrial function are explored from the level of signal transduction to potential transcription-mediated modulations of nuclear-encoded mitochondrial inner membrane proteins, emphasizing the potential function of the mitochondrial uncoupling proteins. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10-CRC,Room 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov FU Intramural NIH HHS NR 109 TC 102 Z9 108 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV 1 PY 2006 VL 72 IS 2 BP 210 EP 219 DI 10.1016/j.cardiores.2006.07.010 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101AR UT WOS:000241711800004 PM 16914124 ER PT J AU Ambudkar, IS Bandyopadhyay, BC Liu, XB Lockwich, TP Paria, B Ong, HL AF Ambudkar, Indu S. Bandyopadhyay, Bidhan C. Liu, Xibao Lockwich, Timothy P. Paria, Biman Ong, Hwei L. TI Functional organization of TRPC-Ca2+ channels and regulation of calcium microdomains SO CELL CALCIUM LA English DT Article DE TRPC channels; calcium influx; plasma membrane; caveolae; caveolin-1; calcium signaling; protein complex; assembly ID OPERATED CA2+ INFLUX; RECEPTOR POTENTIAL CHANNELS; SALIVARY-GLAND CELLS; PLASMA-MEMBRANE; SIGNALING COMPLEXES; TRPC CHANNELS; TYROSINE PHOSPHORYLATION; ENDOTHELIAL PERMEABILITY; ENDOPLASMIC-RETICULUM; SURFACE EXPRESSION AB TRP family of proteins are components of unique cation channels that are activated in response to diverse stimuli ranging from growth factor and neurotransmitter stimulation of plasma membrane receptors to a variety of chemical and sensory signals. This review will focus on members of the TRPC sub-family (TRPC1-TRPC7) which currently appear to be the strongest candidates for the enigmatic Ca2+ influx channels that are activated in response to stimulation of plasma membrane receptors which result in phosphatidyl inositol-(4,5)-bisphosphate (PIP2) hydrolysis, generation of IP3 and DAG, and IP3-induced Ca2+ release from the intracellular Ca2+ store via inositol trisphosphate receptor (IP3R). Homomeric or selective heteromeric interactions between TRPC monomers generate distinct channels that contribute to store-operated as well as store-independent Ca2+ entry mechanisms. The former is regulated by the emptying/refilling of internal Ca2+ store(s) while the latter depends on PIP2 hydrolysis (due to changes in PIP2 per se or an increase in diacylglycerol, DAG). Although the exact physiological function of TRPC channels and how they are regulated has not yet been conclusively established, it is clear that a variety of cellular functions are controlled by Ca2+ entry via these channels. Thus, it is critical to understand how cells coordinate the regulation of diverse TRPC channels to elicit specific physiological functions. It is now well established that segregation of TRPC channels mediated by interactions with signaling and scaffolding proteins, determines their localization and regulation in functionally distinct cellular domains. Furthermore, both protein and lipid components of intracellular and plasma membranes contribute to the organization of these microdomains. Such organization serves as a platform for the generation of spatially and temporally dictated [Ca2+](i) signals which are critical for precise control of downstream cellular functions. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov NR 83 TC 52 Z9 52 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD NOV-DEC PY 2006 VL 40 IS 5-6 BP 495 EP 504 DI 10.1016/j.ceca.2006.08.011 PG 10 WC Cell Biology SC Cell Biology GA 112WP UT WOS:000242558800008 PM 17030060 ER PT J AU Dolman, NJ Tepikin, AV AF Dolman, Nick J. Tepikin, Alexei V. TI Calcium gradients and the Golgi SO CELL CALCIUM LA English DT Article DE Golgi; mitochondria; calcium; pancreas ID PANCREATIC ACINAR-CELLS; CYTOSOLIC CA2+ SIGNALS; HAILEY-HAILEY-DISEASE; SECRETORY-PATHWAY CA2+-ATPASE; ENDOPLASMIC-RETICULUM; HELA-CELLS; CALNUC NUCLEOBINDIN; PROTEIN-TRANSPORT; PLASMA-MEMBRANE; COS-1 CELLS AB Changes in intracellular free calcium regulate many intracellular processes. With respect to the secretory pathway and the Golgi apparatus, changes in calcium concentration occurring either in the adjacent cytosol or within the lumen of the Golgi act to regulate Golgi function. Conversely, the Golgi sequesters calcium to shape cytosolic calcium signals as well as initiate them by releasing calcium via inositol-1,4,5-triphosphate (IP3) receptors, located on Golgi membranes. Local calcium transients juxtaposed to the Golgi (arising from release by the Golgi or other organelles) can activate calcium dependent signalling molecules located on or around the Golgi. This review focuses on the reciprocal relationship between the cell biology of the Golgi apparatus and intracellular calcium homeostasis. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. RP Dolman, NJ (reprint author), NINDS, Synapt Physiol Unit, NIH, Bldg 35,Room 3C1004, Bethesda, MD 20892 USA. EM dolmann@ninds.nih.gov FU Wellcome Trust NR 63 TC 35 Z9 36 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD NOV-DEC PY 2006 VL 40 IS 5-6 BP 505 EP 512 DI 10.1016/j.ceca.2006.08.012 PG 8 WC Cell Biology SC Cell Biology GA 112WP UT WOS:000242558800009 PM 17023044 ER PT J AU Cui, CY Schlessinger, D AF Cui, Chang-Yi Schlessinger, David TI EDA signaling and skin appendage development SO CELL CYCLE LA English DT Review DE ectodysplasin; EDAR; hair follicles; sweat glands; NF kappa Bs; lymphotoxin; Troy ID NF-KAPPA-B; HYPOHIDROTIC ECTODERMAL DYSPLASIA; HAIR FOLLICLE DEVELOPMENT; LYMPHOID ORGAN DEVELOPMENT; ENCODES ECTODYSPLASIN-A; TNF-RECEPTOR; SONIC HEDGEHOG; INCONTINENTIA PIGMENTI; ADHESION MOLECULES; TRANSGENIC MICE AB The same morphogenetic signals are often involved in the development of different organs. For developing skin appendages, a model for tissue - specific regulation of signaling is provided by the EDA pathway, which accesses the otherwise ubiquitous NFkB transcription factors. EDA signaling is mediated by ectodysplasin, EDAR and EDARADD, which form a new TNF ligand - receptor - adaptor family that is restricted to skin appendages in vertebrates from fish to human. The critical function of the pathway was demonstrated in the hereditary genetic disorder Anhidrotic Ectodermal Dysplasia ( EDA), which is characterized by defective formation of hair follicles, sweat glands and teeth. The pathway does not appear to initiate the development of the appendages, but is regulated by and regulates the course of further morphogenesis. In mice, transgenic and knockout strains have increasingly revealed features of the mechanism, and suggest possible non - invasive interventions to alleviate EDA deficiency, especially in sweat glands and eyes. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Schlessinger, D (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM SchlessingerD@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 81 TC 55 Z9 56 U1 0 U2 12 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2006 VL 5 IS 21 BP 2477 EP 2483 DI 10.4161/cc.5.21.3403 PG 7 WC Cell Biology SC Cell Biology GA 117TY UT WOS:000242897400012 PM 17102627 ER PT J AU Miller, M AF Miller, Maria TI Phospho-dependent protein recognition motifs contained in C/EBP family of transcription factors - in silico studies SO CELL CYCLE LA English DT Article DE C/EBP transcription factors; protein protein recognition; Pin1; Polo-like kinase; BRCT ID PROLYL ISOMERASE PIN1; CELL-CYCLE CHECKPOINT; DOUBLE-STRAND BREAKS; POLO-LIKE KINASES; BINDING PROTEIN; BRCT DOMAIN; STRUCTURAL BASIS; DNA-DAMAGE; TRANSACTIVATION DOMAIN; INTRINSIC DISORDER AB CCAAT/enhancer-binding proteins (C/EBPs) are transcriptional regulators implicated in cell proliferation, differentiation, survival, and tumorigenesis. Their biological activities require interactions with several protein partners. This report presents insights from in silico analysis aimed at identifying phosphorylation-dependent protein recognition motifs in C/EBPs. ( 1) All C/EBP variants contain intrinsically disordered Ser/Thr- and Pro-rich segments with potential docking sites for WW and Polo-box domains of prolyl isomerase Pin1 and Polo-like kinases (Plks), respectively. ( 2) Consensus phosphorylation sequences for Plks are located in a highly conserved region of transactivation domains, suggesting that Plks might modulate transcriptional activities of C/EBPs in a cell cycle-dependent manner. ( 3) Phosphorylation at these positions, as well as at conserved Ser in the extended basic region, would create phosphoserine-containing motifs (pSXXF/Y/I/L), which could be recognized by BRCT repeats containing proteins such as the PAX-transactivation-dom ain- interacting protein ( PTIP), and the breast cancer-associated protein (BRCA1). Proteins containing BRCT domains serve as scaffolds, mediating protein-protein interactions and formation of functional multiprotein complexes involved in DNA repair and cell cycle control. These findings add a new perspective to studies aimed at elucidation of molecular mechanisms underlying the diverse functions of C/EBPs. C1 Natl Canc Inst, Macromol Crystallog Lab, Ft Detrick, MD 21702 USA. RP Miller, M (reprint author), Natl Canc Inst, Macromol Crystallog Lab, Ft Detrick, MD 21702 USA. EM millerm@ncifcrf.gov RI Miller, Maria/I-1636-2013 OI Miller, Maria/0000-0003-0252-5348 FU Intramural NIH HHS NR 74 TC 6 Z9 6 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2006 VL 5 IS 21 BP 2501 EP 2508 DI 10.4161/cc.5.21.3421 PG 8 WC Cell Biology SC Cell Biology GA 117TY UT WOS:000242897400016 PM 17102635 ER PT J AU Gautam, D Gavrilova, O Jeon, J Pack, S Jou, W Cui, YH Li, JH Wess, J AF Gautam, Dinesh Gavrilova, Oksana Jeon, Jongrye Pack, Stephanie Jou, William Cui, Yinghong Li, Jian H. Wess, Jurgen TI Beneficial metabolic effects of M-3 muscarinic acetylcholine receptor deficiency SO CELL METABOLISM LA English DT Article ID FATTY-ACID OXIDATION; SKELETAL-MUSCLE; UNCOUPLING PROTEINS; INSULIN-RESISTANCE; ENERGY-METABOLISM; MOLECULAR-BIOLOGY; ADIPOSE-TISSUE; MICE; OBESITY; HYPOTHESIS AB Most animal models of obesity and hyperinsulinemia are associated with increased vagal cholinergic activity. The M-3 muscarinic acetylcholine receptor subtype is widely expressed in the brain and peripheral tissues and plays a key role in mediating the physiological effects of vagal activation. Here, we tested the hypothesis that the absence Of M3 receptors in mice might protect against various forms of experimentally or genetically induced obesity and obesity-associated metabolic deficits. In all cases, the lack of M-3 receptors greatly ameliorated impairments in glucose homeostasis and insulin sensitivity but had less robust effects on overall adiposity. Under all experimental conditions tested, M3 receptor-deficient mice showed a significant elevation in basal and total energy expenditure, most likely due to enhanced central sympathetic outflow and increased rate of fatty-acid oxidation. These findings suggest that the M3 receptor may represent a potential pharmacologic target for the treatment of obesity and associated metabolic disorders. C1 NIDDK, Mol Signaling Sect, Lab Bioorgan Chem, Bethesda, MD 20892 USA. NIDDK, Mol Signaling Sect, Mouse Metab Core Lab, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Lab Bioorgan Chem, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Li, Jianhua/B-7671-2011 OI Li, Jianhua/0000-0002-5744-3182 FU Intramural NIH HHS NR 49 TC 44 Z9 46 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV PY 2006 VL 4 IS 5 BP 363 EP 375 DI 10.1016/j.cmet.2006.09.008 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 103JU UT WOS:000241882300007 PM 17084710 ER PT J AU Ciruela, F Ferre, S Casado, V Cortes, A Cunha, RA Lluis, C Franco, R AF Ciruela, F. Ferre, S. Casado, V. Cortes, A. Cunha, R. A. Lluis, C. Franco, R. TI Heterodimeric adenosine receptors: a device to regulate neurotransmitter release SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE adenosine A(1) receptor; adenosine A(2A) receptor; heteromeric receptor; glutamatergic neurotransmission ID BIOLUMINESCENCE ENERGY-TRANSFER; QUANTITATIVE ASSESSMENT; A(2A) RECEPTORS; RAT HIPPOCAMPUS; A(1) RECEPTORS; NEURONS; HOMODIMERIZATION; CELLS; ADENOSINE-A1-RECEPTORS; OLIGOMERIZATION AB Since 1990 it has been known that dimers are the basic functional form of nearly all G-protein-coupled receptors (GPCRs) and that homo- and heterodimerization may play a key role in correct receptor maturation and trafficking to the plasma membrane. Nevertheless, homo- and heterodimerization of GPCR has become a matter of debate especially in the search for the precise physiological meaning of this phenomenon. This article focuses on how heterodimerization of adenosine A(1) and A(2A) receptors, which are coupled to apparently opposite signalling pathways, allows adenosine to exert a fine-tuning modulation of striatal glutamatergic neurotransmission, providing a switch mechanism by which low and high concentrations of adenosine inhibit and stimulate, respectively, glutamate release. C1 Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA. Univ Coimbra, Fac Med, Ctr Neurosci Coimbra, P-3004504 Coimbra, Portugal. RP Ciruela, F (reprint author), Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Avda Diagonal,645, E-08028 Barcelona, Spain. EM fciruela@ub.edu RI Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Cunha, Rodrigo/E-7475-2015; Casado, Vicent/K-1660-2014; OI Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Cunha, Rodrigo/0000-0003-2550-6422; Casado, Vicent/0000-0002-1764-3825 FU Intramural NIH HHS NR 31 TC 43 Z9 43 U1 0 U2 2 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 NOV PY 2006 VL 63 IS 21 BP 2427 EP 2431 DI 10.1007/s00018-006-6216-2 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103OQ UT WOS:000241897000001 PM 17058035 ER PT J AU Wu, J Feng, Y Xie, D Li, X Xiao, W Tao, D Qin, J Hu, J Gardner, K Judge, SIV Li, QQ Gong, J AF Wu, J. Feng, Y. Xie, D. Li, X. Xiao, W. Tao, D. Qin, J. Hu, J. Gardner, K. Judge, S. I. V. Li, Q. Q. Gong, J. TI Unscheduled CDK1 activity in G1 phase of the cell cycle triggers apoptosis in X-irradiated lymphocytic leukemia cells SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE apoptosis; G1 arrest; cyclin B1; CDK1; CDK2; lymphocytic leukemia cells; MOLT-4 cells; X irradiation ID DNA-DAMAGE; NUCLEAR-LOCALIZATION; DEPENDENT KINASES; P34(CDC2) KINASE; CARCINOMA-CELLS; PROTEIN-KINASE; GROWTH ARREST; S-PHASE; ACTIVATION; EXPRESSION AB Cyclin-dependent kinase 1 (CDK1) is a major component of the cell cycle progression engine. Recently, several investigations provided evidence demonstrating that unscheduled CDK1 activation may also be involved in apoptosis in cancerous cells. In this article, we demonstrate that X-ray irradiation induced G1 arrest in MOLT-4 lymphocytic leukemia cells, the arrest being accompanied by reduction in the activity of CDK2, but increased CDK1 activity and cell apoptosis in the G1 phase. Interestingly, this increase in CDK1 and apoptosis by ionizing radiation was prevented by pretreatment with the CDK1 inhibitor, roscovitine, suggesting that CDK1 kinase activity is required for radiation-induced apoptotic cell death in this model system. Furthermore, cyclin B1 and CDK1 were detected co-localizing and associating in G1 phase MOLT-4 cells, with the cellular lysates from these cells revealing a genotoxic stress-induced increase in CDK1 phosphorylation (Thr-161) and dephosphorylation (Tyr-15), as analyzed by postsorting immunoprecipitation and immunoblotting. Finally, X-irradiation was found to increase Bcl-2 phosphorylation in G1 phase cells. Taken together, these novel findings suggest that CDK1 is activated by unscheduled accumulation of cyclin B1 in G1 phase cells exposed to X-ray, and that CDK1 activation, at the wrong time and in the wrong phase, may directly or indirectly trigger a Bcl-2-dependent signaling pathway leading to apoptotic cell death in MOLT-4 cells. C1 Cent China Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Canc Res Ctr, Wuhan 430030, Peoples R China. NCI, Ctr Adv Technol, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, MS Ctr Excellence E, VA Maryland Hlth Care Syst, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Gong, J (reprint author), Cent China Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Canc Res Ctr, Wuhan 430030, Peoples R China. EM liquenti@mail.nih.gov; jpgong@tjh.tjmu.edu.cn NR 38 TC 6 Z9 10 U1 1 U2 2 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 NOV PY 2006 VL 63 IS 21 BP 2538 EP 2545 DI 10.1007/s00018-006-6138-z PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103OQ UT WOS:000241897000011 PM 17013563 ER PT J AU Saavedra, JM Benicky, J Zhou, J AF Saavedra, Juan M. Benicky, Julius Zhou, Jin TI Mechanisms of the anti-ischemic effect of angiotensin II AT(1) receptor antagonists in the brain SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE renin-angiotensin system; angiotensin II receptors; stroke; brain circulation; nitric oxide; brain inflammation ID SPONTANEOUSLY HYPERTENSIVE-RATS; FACTOR-KAPPA-B; INTERCELLULAR-ADHESION MOLECULE-1; NITRIC-OXIDE; ENDOTHELIAL-CELLS; TYPE-2 RECEPTOR; CEREBRAL-ISCHEMIA; ICAM-1 EXPRESSION; OXIDATIVE STRESS; CHRONIC BLOCKADE AB 1. Circulating and locally formed Angiotensin II regulates the cerebral circulation through stimulation of AT(1) receptors located in cerebrovascular endothelial cells and in brain centers controlling cerebrovascular flow. 2. The cerebrovascular autoregulation is designed to maintain a constant blood flow to the brain, by vasodilatation when blood pressure decreases and vasoconstriction when blood pressure increases. 3. During hypertension, there is a shift in the cerebrovascular autoregulation to the right, in the direction of higher blood pressures, as a consequence of decreased cerebrovascular compliance resulting from vasoconstriction and pathological growth. In hypertension, when perfusion pressure decreases as a consequence of blockade of a cerebral artery, reduced cerebrovascular compliance results in more frequent and more severe strokes with a larger area of injured tissue. 4. There is a cerebrovascular angiotensinergic overdrive in genetically hypertensive rats, manifested as an increased expression of cerebrovascular AT(1) receptors and increased activity of the brain Angiotensin II system. Excess AT(1) receptor stimulation is a main factor in the cerebrovascular pathological growth and decreased compliance, the alteration of the cerebrovascular eNOS/iNOS ratio, and in the inflammatory reaction characteristic of cerebral blood vessels in genetic hypertension. All these factors increase vulnerability to brain ischemia and stroke. 5. Sustained blockade of AT(1) receptors with peripheral and centrally active AT(1) receptor antagonists (ARBs) reverses the cerebrovascular pathological growth and inflammation, increases cerebrovascular compliance, restores the eNOS/iNOS ratio and decreases cerebrovascular inflammation. These effects result in a reduction of the vulnerability to brain ischemia, revealed, when an experimental stroke is produced, in protection of the blood flow in the zone of penumbra and substantial reduction in neuronal injury. 6. The protection against ischemia resulting is related to inhibition of the Renin-Angiotensin System and not directly related to the decrease in blood pressure produced by these compounds. A similar decrease in blood pressure as a result of the administration of beta-adrenergic receptor and calcium channel blockers does not protect from brain ischemia. 7. In addition, sustained AT(1) receptor inhibition enhances AT(2) receptor expression, associated with increased eNOS activity and NO formation followed by enhanced vasodilatation. Direct AT(1) inhibition and indirect AT(2) receptor stimulation are associated factors normalizing cerebrovascular compliance, reducing cerebrovascular inflammation and decreasing the vulnerability to brain ischemia. 8. These results strongly suggest that inhibition of AT(1) receptors should be considered as a preventive therapeutic measure to protect the brain from ischemia, and as a possible novel therapy of inflammatory conditions of the brain. C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,US Dept HHS, Bethesda, MD USA. RP Saavedra, JM (reprint author), 10 Ctr Dr,MSC 1514,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM saavedrj@mail.nih.gov FU Intramural NIH HHS NR 49 TC 44 Z9 44 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD NOV PY 2006 VL 26 IS 7-8 BP 1099 EP 1111 DI 10.1007/s10571-006-9009-0 PG 13 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 114HO UT WOS:000242657500003 PM 16636899 ER PT J AU Rettmann, ME Kraut, MA Prince, JL Resnick, SM AF Rettmann, Maryam E. Kraut, Michael A. Prince, Jerry L. Resnick, Susan M. TI Cross-sectional and longitudinal analyses of anatomical sulcal changes associated with aging SO CEREBRAL CORTEX LA English DT Article DE aging; brain; cortex; cortical atrophy; cortical shape changes; sulci ID MAGNETIC-RESONANCE IMAGES; VOXEL-BASED MORPHOMETRY; HUMAN CEREBRAL-CORTEX; BRAIN VOLUME CHANGES; IN-VIVO; SEX-DIFFERENCES; OLDER-ADULTS; GRAY-MATTER; AGE; SEGMENTATION AB Imaging studies of the human brain indicate that the cortex undergoes anatomic changes during the aging process. With the ability to study the human brain in vivo using magnetic resonance imaging, understanding the nature and location of these changes is of increasing interest. In this work, we investigate cross-sectional and longitudinal age effects on the geometric shape and gray matter (GM) volume for regions of interest on the cortical surface. Each of the regions corresponds to the buried cortex surrounding the sulcal spaces and is termed a "sulcal region." The study consists of 35 older adults scanned three times over a 4-year time span. The group includes 19 women and 16 men ranging in ages from 59 to 84 years (mean 70.9, standard deviation 6.2). We analyze 8 sulcal regions-the buried cortex surrounding the left and right central, superior frontal, cingulate, and parietooccipital sulci. We examine surface area, GM thickness, GM volume, sulcal depth, local gyrification index, and measures of curvature. Results indicate cross-sectional age effects in mean thickness, GM volume, sulcal depth, and curvature characteristics of sulcal regions. In addition, we found longitudinal decreases in surface area, mean thickness, GM volume, and sulcal depth measures as well as changes in sulcal curvature. C1 NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Rettmann, ME (reprint author), NIA, NIH, Baltimore, MD 21224 USA. EM maryam.rettmann@nih.gov RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 FU Intramural NIH HHS [Z01 AG000191-11] NR 51 TC 63 Z9 63 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2006 VL 16 IS 11 BP 1584 EP 1594 DI 10.1093/cercor/bhj095 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 090CH UT WOS:000240927700006 PM 16400155 ER PT J AU Mares, J Muller, JU Skirgailiene, A Neumoin, A Bewley, CA Schmidt, RR Zerbe, O AF Mares, Jiri Mueller, Jan U. Skirgailiene, Audrone Neumoin, Alexey Bewley, Carole A. Schmidt, Richard R. Zerbe, Oliver TI A model for cell-surface-exposed carbohydrate moieties suitable for structural studies bv NMR spectroscopy SO CHEMBIOCHEM LA English DT Article DE carbohydrates; glycolipids; membranes; micelles; NMR spectroscopy ID HIV-INACTIVATING PROTEIN; PULSED-FIELD GRADIENTS; CYANOVIRIN-N; MEMBRANE-PROTEINS; BIOLOGICAL MACROMOLECULES; BINDING; INHIBITION; DIFFUSION; AFFINITY; COMPLEX AB In the present study a synthetic glycolipid system is presented that can be readily incorporated into phospholipid micelles and that allows the study of cell-surface-exposed carbohydrate units by high-resolution NMR techniques. Here, we present an efficient route for the synthesis of glycolipid compounds that contain mannose, mannobiose, or mannotriose coupled either directly to an alkyl chain or through a poly(ethylene glycol) linker. Furthermore, we hove validated our model system by measuring the binding of cyanovirin N (CV-N), a cyanobacterial protein that binds with nanomolar affinity to the terminal arms of high-mannose structures of the HIV surface-envelope glycoprotein gp120, to glycolipids the carbohydrate portions of which comprise the corresponding high-mannose moieties. From the results of chemical-shift mapping with uniformly N-15-labelled CV-N, we conclude that binding to the protein occurs at sites similar to those involved in binding the nonconjugated carbohydrates. We characterized the insertion of the glycolipids into dodecylphosphocholine (DPC) micelles by measuring translational diffusion, and we observed that the diffusion constants of the glycolipids were very similar to those of the DPC micelles themselves, but significantly deviated from those of the free glycolipids. We also present experimental proof that the glycolipids remain inserted in the micelles while binding to CV-N. Finally, by addition of a ligand that had a higher affinity to CV-N but which was not attached did not couple to a lipid anchor, CV-N could be released from the glycolipid and, hence, from the micelle-associated state. C1 Univ Zurich, Inst Organ Chem, CH-8057 Zurich, Switzerland. Univ Konstanz, Dept Chem, D-78457 Constance, Germany. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Zerbe, O (reprint author), Univ Zurich, Inst Organ Chem, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM oliver.zerbe@oci.unizh.ch NR 51 TC 2 Z9 2 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD NOV PY 2006 VL 7 IS 11 BP 1764 EP 1773 DI 10.1002/cbic.200600219 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 105TG UT WOS:000242054600022 PM 16952190 ER PT J AU Nikiforovich, GV Zhang, M Yang, Q Jagadeesh, G Chen, HC Hunyady, L Marshall, GR Catt, KJ AF Nikiforovich, Gregory V. Zhang, Meng Yang, Qing Jagadeesh, Gowraganahalli Chen, Hao-Chia Hunyady, Laszlo Marshall, Garland R. Catt, Kevin J. TI Interactions between conserved residues in transmembrane helices 2 and 7 during angiotensin AT(1) receptor activation SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE angiotensin receptor type 1; G protein-coupled receptors; molecular modeling; site-directed mutagenesis ID II TYPE-1 RECEPTOR; PROTEIN-COUPLED RECEPTORS; LIGAND-BINDING POCKET; SIGNAL-TRANSDUCTION; CONSTITUTIVE ACTIVATION; CONFORMATIONAL-ANALYSIS; ASPARAGINE RESIDUES; ENERGY PARAMETERS; HORMONE RECEPTOR; RHODOPSIN AB Site-directed mutagenesis studies and independent molecular modeling studies were combined to investigate the network of inter-residue interactions within the transmembrane region of the angiotensin AT(1a) receptor. Site-directed mutagenesis was focused on residues Tyr292, Asn294, Asn295, and Asn298 in transmembrane helix 7, and the conserved Asp74 in helix 2 and other polar residues. Functional interactions between pairs of residues were evaluated by determining the effects of single and double-reciprocal mutations on agonist-induced AT1a receptor activation. Replacement of Tyr292 by aspartate in helix 7 abolished radioligand binding to both Y292D and D74Y/Y292D mutant receptors. Reciprocal mutations of Asp74/Asn294, Ser115/Asn294, Ser252/Asn294, and Asn298/Sen115 caused additive impairment of function, suggesting that these pairs of residues make independent contributions to AT1a receptor activation. In contrast, mutations of the Asp74/Tyr298 pair revealed that the D74N/N298D reciprocal mutation substantially increased the impaired inositol phosphate responses of the D74N and N298D receptors. Extensive molecular modeling yielded 3D models of the TM region of the AT(1) receptor and the mutants as well as of their complexes with angiotensin II, which were used to rationalize the possible reasons of impairing of function of some mutants. These data indicate that Asp74 and Asn298 are not optimally positioned for direct strong interaction in the resting conformation of the AT1a receptor. Balance of interactions between residues in helix 2 (as D74) and helix 7 (as N294, N295 and N298) in the AT1 receptors, however, has a crucial role both in determining their functional activity and levels of their expression. C1 Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1088 Budapest, Hungary. RP Nikiforovich, GV (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. EM gregory@ccb.wustl.edu FU NIGMS NIH HHS [GM 68460] NR 50 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD NOV PY 2006 VL 68 IS 5 BP 239 EP 249 DI 10.1111/j.1747-0285.2006.00444.x PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 116WT UT WOS:000242835200002 PM 17177883 ER PT J AU Beigi, F Bertucci, C Zhu, WZ Chakir, K Wainer, IW Xiao, RP Abernethy, DR AF Beigi, Farideh Bertucci, Carlo Zhu, Weizhong Chakir, Khalid Wainer, Irving W. Xiao, Rui-Ping Abernethy, Darrell R. TI Enantioselective separation and online affinity chromatographic characterization of R,R- and S,S-fenoterol SO CHIRALITY LA English DT Article DE beta(2)-adrenergic agonist; fenoterol; enantiomers ID BETA(2)-ADRENERGIC RECEPTOR; ENANTIOMERS; MYOCYTES AB Background: rac-Fenoterol is a beta(2)-adrenoceptor agonist (beta(2)-AR) used in the treatment of asthma. It has two chiral centers and is marketed as a racemic mixture of R,R'- and S,S'-fenoterol (R-F and S-F). Here we report the separation of the R-F and S-F enantiomers and the evaluation of their binding to and activation of the beta(2)-AR. Methods: R-F and S-F were separated from the enantiomeric mixture by chiral chromatography and absolute configuration determined by circular dichroism. beta(2)-AR binding was evaluated using frontal affinity chromatography with a stationary phase containing immobilized membranes from HEK-293 cells that express human beta(2)-AR and standard membrane binding studies using the same membranes. The effect of R-F and S-F on cardiomyocyte contractility was also investigated using freshly isolated adult rat cardiomyocytes. Results: Chiral chromatography of rac-fenoterol yielded separated peaks with an enantioselectivity factor of 1.21. The less retained peak was assigned the absolute configuration of S-F and the more retained peak R-F. Frontal chromatography using membrane-bound beta(2)-AR as the stationary phase and rac-H-3-fenoterol as a marker ligand showed that addition of increasing concentrations of R-F to the mobile phase produced concentration-dependent decreases in rac-H-3-fenoterol retention, while similar addition of S-F produced no change in rac-H-3-fenoterol retention. The calculated dissociation constant of R-F was 472 nM and the number of available binding sites 176 pmol/column, which was consistent with the results from the membrane binding study 460 55 nM (R-F) and 109,000 10,400 nM (S-F). In the cardiomyocytes, RF increased maximum contractile response from (265 +/- 11.6)% to (306 +/- 11.8)% of resting cell length (P < 0.05) and reduced EC50 from -7.0 +/- 0.270 to -7.1 +/- 0.2 log[M] (P < 0.05), while S-F had no significant effect. Discussion: Previous studies have shown that rac fenoterol acts as an apparent beta(2)-AR/Gs selective agonist and fully restores diminished beta(2)-AR contractile response in cardiomyocytes from failing hearts of spontaneously hypertensive rats (SHR). Here we report the separation of the enantiomers of rac-fenoterol and that R-F is the active component of rac-fenoterol. Further evaluation of R-F will determine if it has enhanced selectivity and specificity for beta(2)-AR/GS activation and if it can be used in the treatment of congestive heart failure. C1 NIA, Gerontol Res Ctr, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Abernethy, DR (reprint author), NIA, Gerontol Res Ctr, Clin Invest Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM abernethyd@grc.nia.nih.gov FU Intramural NIH HHS NR 17 TC 22 Z9 23 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-0042 J9 CHIRALITY JI Chirality PD NOV PY 2006 VL 18 IS 10 BP 822 EP 827 DI 10.1002/chir.20317 PG 6 WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 096JE UT WOS:000241372600007 PM 16917835 ER PT J AU Cheng, YX Foster, B Holland, SM Klion, AD Nutman, TB Casale, TB Metcalfe, DD Prussin, C AF Cheng, Y. X. Foster, B. Holland, S. M. Klion, A. D. Nutman, T. B. Casale, T. B. Metcalfe, D. D. Prussin, C. TI CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of Fc epsilon RI SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE allergy; antigen-presenting cell; asthma; CD2; Fc epsilon RI; flow cytometry; IgE; monocyte; omalizumab ID EPIDERMAL LANGERHANS CELLS; HIGH-AFFINITY RECEPTOR; HUMAN PERIPHERAL-BLOOD; DENDRITIC CELLS; SERUM IGE; ALLERGIC RESPONSE; NONATOPIC DONORS; SUBSETS; OMALIZUMAB; BASOPHILS AB Background Fc epsilon RI expression by monocytes can affect monocyte function via multiple mechanisms, thereby potentially influencing the generation of allergic inflammation. Previous studies on the in vivo regulation of monocyte Fc epsilon RI expression by ambient IgE have yielded conflicting results. Objective We hypothesized that monocyte Fc epsilon RI expression is limited to a specific monocyte subset, and that within that subset Fc epsilon RI surface expression is correlated to serum IgE. Methods Study 1: Blood was obtained from non-allergic subjects (n = 14) and subjects with allergic asthma (n = 18), hypereosinophilic syndrome (n = 2), hyper-IgE syndrome (n = 6), and helminth infection (n = 4). Study 2: Blood was obtained from allergic subjects in a clinical trial of omalizumab before and during study drug treatment. Monocyte surface Fc epsilon RI expression was measured using flow cytometry. Results Fc epsilon RI expression was significantly greater in the CD2(high) vs. CD2(low) monocyte subsets (31% vs. 1.9% median Fc epsilon RI 1, respectively). In asthmatic and non-atopic healthy control subjects, CD2(low) monocytes expressed little or undetectable Fc epsilon RI. In study 1, Fc epsilon RI expression was highly correlated to serum IgE in the CD2(high), but not in the CD2(low) monocyte subpopulation (R values of 0.67 and 0.41, respectively). In study 2, omalizumab, but not placebo, caused a significant and sustained decline in Fc epsilon RI expression within the CD2(high) monocyte subset. Conclusions CD2 defines a monocyte subset with high Fc epsilon RI expression, whose magnitude is highly correlated to serum IgE. As such, this new description of CD2(high) monocytes as Fc epsilon RI-bearing cells suggests that they may be potential targets of anti-IgE immunomodulatory therapies. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Creighton Univ, Dept Med, Div Allergy Immunol, Omaha, NE 68178 USA. RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205, Bethesda, MD 20892 USA. EM cprussin@niaid.nih.gov RI Casale, Thomas/K-4334-2013 OI Casale, Thomas/0000-0002-3149-7377 FU NIAID NIH HHS [Z01 AI000761, 1 Z01-AI-000761-07] NR 35 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD NOV PY 2006 VL 36 IS 11 BP 1436 EP 1445 DI 10.1111/j.1365-2222.2006.02578.x PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 101IK UT WOS:000241734300012 PM 17083354 ER PT J AU Smolen, JS Aletaha, D AF Smolen, J. S. Aletaha, D. TI What should be our treatment goal in rheumatoid arthritis today? SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; remission; low disease activity; DAS28; SDAI; CDAI; pinals criteria ID NECROSIS-FACTOR-ALPHA; COLLEGE-OF-RHEUMATOLOGY; ERYTHROCYTE SEDIMENTATION-RATE; RANDOMIZED CONTROLLED-TRIAL; MEDIATED JOINT DESTRUCTION; DISEASE-ACTIVITY INDEX; C-REACTIVE PROTEIN; 2ND LINE DRUGS; DOUBLE-BLIND; MONOCLONAL-ANTIBODY AB Remission should be the treatment aim in management of rheumatoid arthritis (RA) today because joint damage may progress in RA patients with low disease activity but presumably does not progress in patients in clinical remission. However, stringent criteria are needed to define remission status, as some criteria in current use allow for considerable residual disease activity. Even using stringent criteria, remission is achievable in a sizable proportion of patients in clinical trials and practice. Defining remission requires an additional consideration: Should a patient who is receiving medication be regarded as in remission if disease is absent, or must the patient be off treatment to be considered to be in remission? A case is made for aiming for a definition of remission that includes patients who continue medication therapy. C1 Med Univ Vienna, Dept Rheumatol, A-1090 Vienna, Austria. Lainz Hosp, Dept Med 2, Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Smolen, JS (reprint author), Med Univ Vienna, Dept Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM josef.smolen@wienkav.at NR 95 TC 19 Z9 19 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 2006 VL 24 IS 6 SU 43 BP S7 EP S13 PG 7 WC Rheumatology SC Rheumatology GA 102KF UT WOS:000241809000002 ER PT J AU Stone, GW Barzee, S Snarsky, V Spina, CA Lifson, JD Pillai, VKB Amara, RR Villinger, F Kornbluth, RS AF Stone, Geoffrey W. Barzee, Suzanne Snarsky, Victoria Spina, Celsa A. Lifson, Jeffrey D. Pillai, Vinod Kumar Bhaskara Amara, Rama Rao Villinger, Francois Kornbluth, Richard S. TI Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-12; IMMUNOLOGICAL SELF-TOLERANCE; ANTIGEN-PRESENTING CELLS; SURFACTANT PROTEIN-D; INDUCED TNF RECEPTOR; REGULATORY T-CELLS; IMMUNE-RESPONSES; RHESUS-MONKEYS; DNA VACCINES; CDNA CLONING AB CD40 ligand (CD40L) and GITR ligand (glucocorticoid-induced tumor necrosis factor receptor-related protein ligand [GITRL]) are tumor necrosis factor superfamily molecules that can be used as vaccine adjuvants. In a previous human immunodeficiency virus (HIV) DNA vaccine study in mice, we found that plasmids expressing multimeric soluble forms of trimeric CD40L (i.e., many trimers) were stronger activators of CD8(+) T-cell responses than were single-trimer soluble forms or the natural membrane-bound molecule. This report describes similar multimeric soluble molecules that were constructed for studies in macaques. Both two-trimer and four-trimer forms of macaque CD40L were active in B-cell proliferation assays using macaque and human cells. With human cells, four-trimer macaque GITRL costimulated CD4(+) T-cell proliferation and abrogated the immunosuppressive effects of CD4(+) CD25(+) regulatory T cells on a mixed leukocyte reaction. These molecular adjuvants provide new tools for vaccine development in the simian immunodeficiency virus system and other macaque models. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. VA San Diego Healthcare Syst, La Jolla, CA USA. NCI, SAIC Frederick, AIDS Vaccine Progrm Inc, Frederick, MD USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Yerkes natl Primate Res Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Kornbluth, RS (reprint author), Univ Calif San Diego, Dept Med, Stein Clin Sci Bldg,Room 304,9500 Gilman Dr 0679, La Jolla, CA 92093 USA. EM rkornbluth@ucsd.edu FU NCI NIH HHS [N01CO12400, N01-CO-12400]; NCRR NIH HHS [R24 RR016988, R24-RR16988]; NIAID NIH HHS [T32AI007384, R21AI063982, R21 AI063982, P30 AI036214, T32 AI007384] NR 41 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2006 VL 13 IS 11 BP 1223 EP 1230 DI 10.1128/CVI.00198-06 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 107EC UT WOS:000242152500008 PM 16988005 ER PT J AU Martin, JE Sullivan, NJ Enama, ME Gordon, IJ Roederer, M Koup, RA Bailer, RT Chakrabarti, BK Bailey, MA Gomez, PL Andrews, CA Moodie, Z Gu, L Stein, JA Nabel, GJ Graham, BS AF Martin, Julie E. Sullivan, Nancy J. Enama, Mary E. Gordon, Ingelise J. Roederer, Mario Koup, Richard A. Bailer, Robert T. Chakrabarti, Bimal K. Bailey, Michael A. Gomez, Phillip L. Andrews, Charla A. Moodie, Zoe Gu, Lin Stein, Judith A. Nabel, Gary J. Graham, Barney S. CA VRC 204 Study Team TI A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID NONHUMAN-PRIMATES; HEMORRHAGIC-FEVER; GUINEA-PIGS; INFECTION; RESPONSES; GLYCOPROTEIN; HUMANS; IMMUNIZATION; PATHOGENESIS; FILOVIRUSES AB Ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8), or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4(+) T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8(+) T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98109 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC-3017,Room 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov RI Roederer, Mario/G-1887-2011 NR 33 TC 123 Z9 132 U1 3 U2 37 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 NOV PY 2006 VL 13 IS 11 BP 1267 EP 1277 DI 10.1128/CVI.00162-06 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 107EC UT WOS:000242152500013 PM 16988008 ER PT J AU Robles, AI Wright, MH Gandhi, B Feis, SS Hanigan, CL Wiestner, A Varticovski, L AF Robles, Ana I. Wright, Mollie H. Gandhi, Bheru Feis, Steven S. Hanigan, Christin L. Wiestner, Adrian Varticovski, Lyuba TI Schedule-dependent synergy between the heat shock protein 90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin and doxorubicin restores apoptosis to p53-mutant lymphoma cell lines SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; WILD-TYPE P53; BCR-ABL; LEUKEMIA-CELLS; DNA-DAMAGE; IN-VITRO; PHASE-I; MELANOMA MODELS; TUMOR-CELLS; S-PHASE AB Purpose: Loss of p53 function impairs apoptosis induced by DNA-damaging agents used for cancer therapy. Here, we examined the effect of the heat shock protein 90 (HSP90) inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) on doxorubicin-induced apoptosis in lymphoma. We aimed to establish the optimal schedule for administration of both drugs in combination and the molecular basis for their interaction. Experimental Design: Isogenic lymphoblastoid and nonisogenic lymphoma cell lines differing in p53 status were exposed to each drug or combination. Drug effects were examined using Annexin V, active caspase-3, cell cycle, and cytotoxicity assays. Synergy was evaluated by median effect/combination index. Protein expression and kinase inhibition provided insight into the molecular mechanisms of drug interaction. Results: Presence of mutant p53 conferred increased survival to single agents. Nevertheless, DMAG showed synergistic toxicity with doxorubicin independently of p53 status. Synergy required exposure to doxorubicin before DMAG. DMAG-mediated down-regulation of CHK1, a known HSP90 client, forced doxorubicin-treated cells into premature mitosis followed by apoptosis. A CHK1 inhibitor, SB-218078, reproduced the effect of DMAG. Administration of DMAG before doxorubicin resulted in G(1)-S arrest and protection from apoptosis, leading to additive or antagonistic interactions that were exacerbated by p53 mutation. Conclusions: Administration of DMAG to doxorubicin-primed cells induced premature mitosis and had a synergistic effect on apoptosis regardless of p53 status. These observations provide a rationale for prospective clinical trials and stress the need to consider schedule of exposure as a critical determinant of the overall response when DMAG is combined with chemotherapeutic agents for the treatment of patients with relapsed/refractory disease. C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Robles, AI (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, MSC 4258,Room 3060,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM roblesa@mail.nih.gov FU Intramural NIH HHS NR 55 TC 25 Z9 28 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2006 VL 12 IS 21 BP 6547 EP 6556 DI 10.1158/1078-0432.CCR-06-1178 PG 10 WC Oncology SC Oncology GA 104DB UT WOS:000241935100033 PM 17085670 ER PT J AU Bowen, RAR Drake, SK Vanjani, R Huey, ED Grafman, J Horne, MK AF Bowen, Raffick A. R. Drake, Steven K. Vanjani, Rachna Huey, Edward D. Grafman, Jordan Horne, McDonald K., III TI Markedly increased vitamin B-12 concentrations attributable to IgG-IgM-vitamin B-12 immune complexes SO CLINICAL CHEMISTRY LA English DT Article ID COBALAMIN-BINDING-PROTEINS; TRANSCOBALAMIN-I; SERUM VITAMIN-B12; BLOOD; ANTIBODY; DISEASE; INTERFERENCES; HAPTOCORRIN; LEUKOCYTES; ELEVATION AB Background: High serum vitamin B-12 concentrations have been reported in patients with hepatic disease, disseminated neoplasia, myeloproliferative disorders, and hypereosinophilic syndromes. We recently discovered an extraordinarily increased vitamin B-12 concentration in a patient without these underlying conditions. Methods: Affinity and size-exclusion chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and ELISA methods were used to determine the cause of the increased vitamin B-12 concentrations in this patient's serum. Results: The protein G column eluates from 2 apparently healthy volunteers and 2 patients with recent vitamin B-12 treatment for anemia had vitamin B-12 concentrations of < 74 pmol/L, whereas the vitamin B-12 concentration in the protein G column eluate from the patient was 7380 pmol/L. The elution profile from size-exclusion chromatography of vitamin B-12-binding proteins in the patient's serum revealed an abnormal vitamin-B-12-binding protein. SDS-PAGE analysis of the concentrated eluates from the protein G column, under reducing conditions, revealed an additional band with an apparent molecular mass of 76 kDa, which was not present in control column eluates. MALDI-TOF MS identified this band as an IgM heavy chain. By use of a modified ELISA, we determined that the IgM present in the patient's eluates was associated with the IgG to form IgG-IgM immune complexes. Conclusions: This case demonstrates the unusual circumstance of a patient with markedly increased vitamin B-12 concentrations attributed to immune complexes composed of IgG, IgM, and vitamin B-12 and illustrates techniques that can be used to identify this occurrence. (c) 2006 American Association for Clinical Chemistry. C1 NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 2C-306,10 Ctr Dr, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 32 TC 9 Z9 9 U1 2 U2 5 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 NOV PY 2006 VL 52 IS 11 BP 2107 EP 2114 DI 10.1373/clinchem.2006.073882 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 100FC UT WOS:000241652400019 PM 17068171 ER PT J AU Bergmann-Leitner, ES Leitner, WW Tsokos, GC AF Bergmann-Leitner, Elke S. Leitner, Wolfgang W. Tsokos, George C. TI Complement 3d: From molecular adjuvant to target of immune escape mechanisms SO CLINICAL IMMUNOLOGY LA English DT Review DE adjuvant; complement; DNA vaccine; immune escape; B lymphocyte ID FOLLICULAR DENDRITIC CELLS; SIMPLEX VIRUS GLYCOPROTEIN; B-CELLS; PLASMODIUM-BERGHEI; ANTIBODY-RESPONSE; CIRCUMSPOROZOITE PROTEIN; CD19/CD21 COMPLEX; ANTIGEN RECEPTOR; NATURAL ANTIBODY; CANDIDA-ALBICANS AB CM is a fragment of the complement factor C3 and is generated in the course of complement activation. When bound to antigen in single or multiple copies, the B cell receptor and complement receptor 2 become co-crosslinked resulting in decreased or increased B cell responses depending on the valence of the antigen-C3d construct. When antigen-CM constructs are used for the purpose of generating a protective immune response (vaccines), they may either enhance the expected response or suppress it depending on the nature of the antigen. Various pathogens use C3d to evade the immune system by inhibiting complement activation, invading and homing in host cells or masking immunogenic areas of pathogen proteins. Therefore, future vaccination strategies for infectious diseases and cancer employing CM as a molecular adjuvant need to be carefully evaluated before choosing a target antigen in order to take advantage of the adjuvant effect of the complement component white avoiding potential vaccine complications associated with immune escape mechanisms. (c) 2006 Elsevier Inc. All rights reserved. C1 Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. NCI, Dermatol Branch, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD 20910 USA. RP Bergmann-Leitner, ES (reprint author), Walter Reed Army Inst Res, Dept Immunol, 503 Robert Grant Ave,Room 3W76, Silver Spring, MD 20910 USA. EM elke.bergmannleitner@us.army.mil RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922 NR 83 TC 26 Z9 28 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2006 VL 121 IS 2 BP 177 EP 185 DI 10.1016/j.clim.2006.07.001 PG 9 WC Immunology SC Immunology GA 100AH UT WOS:000241638900005 PM 16914381 ER PT J AU Shibasaki, H Hallett, M AF Shibasaki, Hiroshi Hallett, Mark TI What is the Bereltschaftspotential? SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE BP; Bereitschaftspotential; pre-movement slow negativity; early BP; late BP (NS '); conscious will to move ID MOVEMENT-RELATED POTENTIALS; SUPPLEMENTARY MOTOR AREA; VOLUNTARY MUSCLE-RELAXATION; CONTINGENT NEGATIVE-VARIATION; EVENT-RELATED FMRI; REPETITIVE FINGER MOVEMENTS; CONGENITAL MIRROR MOVEMENTS; DIPOLE SOURCE ANALYSIS; HIGH-RESOLUTION EEG; CORTICAL POTENTIALS AB Since discovery of the slow negative electroencephalographic (EEG) activity preceding self-initiated movement by Kornhuber and Deecke [Kornhuber HH, Deecke L. Hirnpotentialanderungen bei Willkurbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale. Pflugers Archiv 1965;284:1-17], various source localization techniques in normal subjects and epicortical recording in epilepsy patients have disclosed the generator mechanisms of each identifiable component of movement-related cortical potentials (MRCPs) to some extent. The initial slow segment of BP, called 'early BY in this article, begins about 2 s before the movement onset in the pre-supplementary motor area (pre-SMA) with no site-specificity and in the SMA proper according to the somatotopic organization, and shortly thereafter in the lateral premotor cortex bilaterally with relatively clear somatotopy. About 400 ms before the movement onset, the steeper negative slope, called 'late BP' in this article (also referred to as NS'), occurs in the contralateral primary motor cortex (M1) and lateral premotor cortex with precise somatotopy. These two phases of BP are differentially influenced by various factors, especially by complexity of the movement which enhances only the late BP. Event-related desynchronization (ERD) of beta frequency EEG band before self-initiated movements shows a different temporospatial pattern from that of the BP, suggesting different neuronal mechanisms for the two. BP has been applied for investigating pathophysiology of various movement disorders. Volitional motor inhibition or muscle relaxation is preceded by BP quite similar to that preceding voluntary muscle contraction. Since BP of typical waveforms and temporospatial pattern does not occur before organic involuntary movements, BP is used for detecting the participation of the 'voluntary motor system' in the generation of apparently involuntary movements in patients with psychogenic movement disorders. In view of Libet et al.'s report [Libet B, Gleason CA, Wright EW, Pearl DK. Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential). The unconscious initiation of a freely voluntary act. Brain 1983;106:623-642] that the awareness of intention to move occurred much later than the onset of BP, the early BP might reflect, physiologically, slowly increasing cortical excitability and, behaviorally, subconscious readiness for the forthcoming movement. Whether the late BP reflects conscious preparation for intended movement or not remains to be clarified. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Takeda Gen Hosp, Fushimi Ku, Kyoto 6011495, Japan. NINDS, Human Motor Control Sect, 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 NR 100 TC 365 Z9 370 U1 3 U2 50 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2006 VL 117 IS 11 BP 2341 EP 2356 DI 10.1016/j.clinph.2006.04.025 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 108OT UT WOS:000242249800001 PM 16876476 ER PT J AU Barrett, T Choyke, PL Kobayashi, H AF Barrett, Tristan Choyke, Peter L. Kobayashi, Hisataka TI Imaging of the lymphatic system: new horizons SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Review DE lymphatic imaging; sentinel node imaging; lymphangiography; contrast agent; lymphoscintigraphy ID SUPERPARAMAGNETIC IRON-OXIDE; MAGNETIC RESONANCE LYMPHANGIOGRAPHY; INITIAL CLINICAL-EXPERIENCE; COLOR DOPPLER SONOGRAPHY; CONTRAST-ENHANCED MRI; BREAST-CANCER; NODE METASTASES; SENTINEL NODE; POWER DOPPLER; RADIONUCLIDE LYMPHOSCINTIGRAPHY AB The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast-enhanced MRI (DCE-MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra-lymphatic imaging methods have been developed. Direct lymphangiography is an all-but-extinct method of visualizing the lymphatic drainage from an extremity using oil-based iodine contrast agents. More recently, interstitially injected intra-lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide-based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi-modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd. C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural NIH HHS NR 89 TC 85 Z9 91 U1 2 U2 14 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD NOV-DEC PY 2006 VL 1 IS 6 BP 230 EP 245 DI 10.1002/cmmi.116 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 142MS UT WOS:000244654600002 PM 17191764 ER PT J AU Kalil, AC Sevransky, JE Myers, DE Esposito, C Vandivier, RW Eichacker, P Susla, GM Solomon, SB Csako, G Costello, R Sittler, KJ Banks, S Natanson, C Danner, RL AF Kalil, Andre C. Sevransky, Jonathan E. Myers, Daniela E. Esposito, Claire Vandivier, R. William Eichacker, Peter Susla, Greg M. Solomon, Steven B. Csako, Gyorgy Costello, Rene Sittler, Kelly J. Banks, Steve Natanson, Charles Danner, Robert L. TI Preclinical trial of L-arginine monotherapy alone or with N-acetylcysteine in septic shock SO CRITICAL CARE MEDICINE LA English DT Article DE L-arginine; N-acetylcysteine; sepsis; nitric oxide; immunonutrition ID NITRIC-OXIDE SYNTHASE; INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; CARDIOVASCULAR DYSFUNCTION; ENDOTHELIAL DYSFUNCTION; DIMETHYLARGININE ADMA; PARENTERAL-NUTRITION; ESCHERICHIA-COLI; CLINICAL-TRIAL; ADULT PATIENTS AB Objective: L-arginine supplementation in sepsis is controversial. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, an end-product Of L-arginine metabolism. Design. Randomized, placebo-controlled, and double-blinded (investigators, veterinarians, and pharmacists). Setting. Laboratory. Subjects. Purpose-bred, 1- to 2-yr-old, 10- to 12-kg beagles. Interventions. The effects of parenteral L-arginine alone or in combination with N-acetylcysteine were compared with vehicle alone in a well-characterized canine model of Escherichia coli peritonitis. Two doses were studied that delivered approximately 1.5-fold (10 mg.kg(-1).hr(-1)) and 15-fold (100 mg.kg(-1).hr(-1)) the L-arginine dose typically administered with standard total parenteral nutrition. Animals in the low- and high-dose L-arginine arms were further randomized to receive vehicle alone or N-acetylcysteine (20 mg.kg(-1).hr(-1)) as an antioxidant to prevent peroxynitrite formation. Measurements and Main Results., The main measurements were hemodynamics, plasma arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ injury, and survival. Both doses Of L-arginine similarly increased mortality (p =.02), and worsened shock (p =.001 for reduced mean arterial pressure). These effects were associated with significant increases in plasma arginine (p =.0013) and ornithine (p =.0021). In addition, serum nitrate/nitrite (p =.02), liver enzymes (p =.08), and blood urea nitrogen/creatinine ratios (p =.001) rose, whereas arterial pH (p =.001) and bicarbonate levels (p =.001) fell. N-acetylcysteine did not significantly decrease any of the harmful effects Of L-arginine. Thus, parenteral L-arginine monotherapy was markedly harmful in animals with septic shock. Conclusions. These findings suggest that supplemental parenteral L-arginine, at doses above standard dietary practices, should be avoided in critically ill patients with septic shock. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Kalil, AC (reprint author), Univ Nebraska, Med Ctr, 985400, Omaha, NE 68198 USA. EM akalil@unmc.edu NR 60 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2006 VL 34 IS 11 BP 2719 EP 2728 DI 10.1097/01.CCM.0000242757.26245.03 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 100AQ UT WOS:000241639900003 PM 16971848 ER PT J AU Gould, TD Picchini, AM Einat, H Manji, HK AF Gould, Todd D. Picchini, Alyssa M. Einat, Haim Manji, Husseini K. TI Targeting glycogen synthase kinase-3 in the CNS: Implications for the development of new treatments for mood disorders SO CURRENT DRUG TARGETS LA English DT Review DE manic-depressive illness; psychopharmacology; mania; depression; mood stabilizer; antidepressant; valproate ID FORCED SWIM TEST; EMERGING EXPERIMENTAL THERAPEUTICS; SINGLE NUCLEOTIDE POLYMORPHISM; INSULIN-MIMETIC ACTION; WNT SIGNALING PATHWAY; BIPOLAR DISORDER; IN-VIVO; ALZHEIMERS-DISEASE; BETA-CATENIN; LITHIUM-CARBONATE AB There exists an immediate need to develop novel medications for the treatment of mood disorders such as bipolar disorder and depression. Initial interest in glycogen synthase kinase-3 (GSK-3) as a target for the treatment of mood disorders arose from the finding that the mood stabilizing drug lithium directly inhibited the enzyme. More recent preclinical evidence implicates the modulation of GSK-3 in either the direct or downstream mechanism of action of many other mood stabilizer and antidepressant medications currently in use. One of the cellular targets of GSK-3, which may mediate some of the effects of lithium and other drugs, is P-catenin, a transcription factor that is rapidly degraded when GSK-3 is active. Recent rodent behavioral data (both genetic and pharmacological) supports GSK-3 representing a therapeutically relevant target of lithium. This includes antidepressant-like behavior in the forced swim test and antimanic-like response to amphetamine following administration of the GSK-3 inhibitor AR-A014418, a findings that is concomitant with an increase in brain beta-catenin. The evidence described in this review suggests that regulating GSK-3 may represent a target for novel medications to treat mood disorders. C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Coll Pharm, Dept Pharm Practice & Pharmaceut Sci, Duluth, MN 55812 USA. Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. RP Gould, TD (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Bldg 35,Room 1C-912, Bethesda, MD 20892 USA. EM gouldt@mail.nih.gov RI Einat, Haim/A-7203-2009 FU Intramural NIH HHS NR 152 TC 88 Z9 90 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD NOV PY 2006 VL 7 IS 11 BP 1399 EP 1409 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097ZK UT WOS:000241488700004 PM 17100580 ER PT J AU Kim, L Kimmel, AR AF Kim, Leung Kimmel, Alan R. TI GSK3 at the edge: Regulation of developmental specification and cell polarization SO CURRENT DRUG TARGETS LA English DT Review DE Wnt; frizzled; hedgehog; presenilin; PAR; cell motility; chemotaxis; Dictyostelium ID GLYCOGEN-SYNTHASE KINASE-3; WNT-SIGNALING PATHWAY; RECEPTOR-RELATED PROTEIN-5; BETA-CATENIN; C-ELEGANS; CUBITUS-INTERRUPTUS; NEURONAL POLARITY; HEDGEHOG SIGNAL; DICTYOSTELIUM DEVELOPMENT; REQUIRES PHOSPHORYLATION AB GSK3 is a multifunctional protein kinase that is pivotal for the regulation of metabolism, the cytoskeleton, and gene expression. Multicellular eukaryotes utilize GSK3 as a molecular switch to specify distinct cell fates, but also to organize these cells spatially within the developing organism. We discuss the central role of GSK3 in control of the Wnt, Hedgehog, cAMP (in Dictyostelium), and other signaling pathways, but also focus on significant new evidence that GSK3 is required to establish cell polarity. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov NR 104 TC 31 Z9 32 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD NOV PY 2006 VL 7 IS 11 BP 1411 EP 1419 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097ZK UT WOS:000241488700005 PM 17100581 ER PT J AU Podgornik, R Licer, M AF Podgornik, R. Licer, M. TI Polyelectrolyte bridging interactions between charged macromolecules SO CURRENT OPINION IN COLLOID & INTERFACE SCIENCE LA English DT Review DE polyelectrolytes; bridging interaction; colloidal stability ID NUCLEOSOME CORE PARTICLES; MONTE-CARLO-SIMULATION; SURFACE INTERACTIONS; DNA COMPACTION; AQUEOUS-MEDIA; HISTONE TAILS; POLYMER-CHAIN; 2 PLATES; FORCES; ADSORPTION AB Polyelectrolyte chains confined by oppositely charged macroions can significantly modify the interactions between them. This polyelectrolyte mediated interaction depends on various parameters characterizing the polyelectrolyte as well as the surface of the macroion and can be either repulsive or attractive. Though polymers are mostly used to stabilize various colloidal systems they can just as well induce flocculation either by depletion interaction or by bridging. In the case of charged polymers we refer to this additional attractive interaction as polyelectrolyte bridging. This review will focus on equilibrium properties of polyelectrolyte mediated attraction between macroions, its theoretical underpinnings and its phenomenology. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA. Univ Ljubljana, Fac Math & Phys, Dept Phys, SI-1000 Ljubljana, Slovenia. Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Podgornik, R (reprint author), Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA. EM podgornr@mail.nih.gov RI Podgornik, Rudolf/C-6209-2008; OI Podgornik, Rudolf/0000-0002-3855-4637; Licer, Matjaz/0000-0003-2304-2505 NR 62 TC 47 Z9 48 U1 2 U2 25 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1359-0294 J9 CURR OPIN COLLOID IN JI Curr. Opin. Colloid Interface Sci. PD NOV PY 2006 VL 11 IS 5 BP 273 EP 279 DI 10.1016/j.cocis.2006.08.001 PG 7 WC Chemistry, Physical SC Chemistry GA 118CK UT WOS:000242919400003 ER PT J AU Baird, K Pavletic, SZ AF Baird, Kristin Pavletic, Steven Z. TI Chronic graft versus host disease SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE allogeneic hematopoietic stem cell transplant; chronic graft versus host disease; immunosuppression ID STEM-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; REGULATORY T-CELLS; IDENTICAL SIBLING TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; MINOR SALIVARY-GLANDS; LOW-DOSE METHOTREXATE; CLINICAL-TRIALS; EXTRACORPOREAL PHOTOPHERESIS AB Purpose of review Chronic graft versus host disease is a debilitating and often fatal complication of allogeneic stem cell transplantation. The purpose of this review is to overview this disease and highlight recent findings in the literature over the past year. Recent findings A new focus on chronic graft versus host disease as a long-term complication of transplantation has resulted in increased research activity in this disease. Here we review the recent in-vitro and clinical studies that focus on the pathophysiology of the disease, treatment and prevention. Summary As more patients undergo and survive allogeneic stem cell transplantation more attention is being focused on the study of chronic graft versus host disease. Although the pathophysiology is still controversial, recent advances have been made in our understanding of this disease, including the balance of T helper type 1 and 2 cells, the role of B cells and autoantibodies, graft manipulation and prophylaxis, which may lead to advances in treatment and prevention. The series of recent publications put forward by the National Institutes of Health consensus project on criteria for clinical trials are expected to advance the standards and uniformity of chronic graft versus host disease clinical research. C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike,CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU Intramural NIH HHS NR 59 TC 69 Z9 72 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2006 VL 13 IS 6 BP 426 EP 435 PG 10 WC Hematology SC Hematology GA 100TB UT WOS:000241690600004 PM 17053454 ER PT J AU Roth, SM Metter, EJ Ling, S Ferrucci, L AF Roth, Stephen M. Metter, E. Jeffrey Ling, Shari Ferrucci, Luigi TI Inflammatory factors in age-related muscle wasting SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE aging; cytokines; inflammation; proteasome; sarcopenia ID GROWTH-FACTOR-I; NECROSIS-FACTOR-ALPHA; ALL-CAUSE MORTALITY; LOWER-EXTREMITY FUNCTION; CHRONIC HEART-FAILURE; KAPPA-B ACTIVATION; C-REACTIVE PROTEIN; SKELETAL-MUSCLE; RHEUMATOID-ARTHRITIS; BODY-COMPOSITION AB Purpose of review This review focuses on recent evidence pointing to the importance of inflammatory factors in the onset and progression of age-related muscle wasting, also known as sarcopenia, and discusses critical areas of uncertainty within the literature that require further development in order to identify novel therapeutics. Recent findings The research performed in recent years has only strengthened the evidence that inflammatory factors are important in the progression of a catabolic state in muscle wasting. Interactions among various inflammatory cytokines and anabolic factors have been observed, with the balance skewed in favor of catabolism in sarcopenia. Adiposity appears to play an important role in the inflammatory process and possibly the onset of sarcopenia. Inflammatory factors are likely to play an important role in the increased activity of the ubiquitin proteasome, which we argue should be a primary target for the development of molecular therapeutics. Summary Future research will need to delve into the molecular interactions that link inflammatory factors and the imbalance between muscle anabolism and catabolism that develops with aging. Identification of specific pathways of importance to sarcopenia will have relevance to a wide range of wasting disorders. C1 Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD USA. RP Ferrucci, L (reprint author), Harbor Hosp, Baltimore Longitudinal Study Aging, NIA, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov OI Roth, Stephen/0000-0002-7841-3695 FU NIA NIH HHS [AG022791] NR 88 TC 48 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD NOV PY 2006 VL 18 IS 6 BP 625 EP 630 DI 10.1097/01.bor.0000245722.10136.6d PG 6 WC Rheumatology SC Rheumatology GA 108VF UT WOS:000242266600010 PM 17053510 ER PT J AU Howard, OMZ AF Howard, O. M. Zack TI Autoantigen signalling through chemokine receptors SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoantigen; autoimmune; chemokine; chemokine receptor; dendritic cells ID IDIOPATHIC INFLAMMATORY MYOPATHIES; IMMATURE DENDRITIC CELLS; TRANSFER-RNA SYNTHETASE; BINDING-PROTEIN; CHEMOTAXIS; EXPRESSION; IMMUNITY; IDENTIFICATION; LYMPHOCYTES; CYTOKINES AB Purpose of review Recent studies have shown that disease-associated self-antigens activate chemokine receptors. This review focuses on the mechanics of autoantigen interaction with select chemokine receptors, how these migratory signals are amplified and discusses the possibility that chemokine receptors can be valuable therapeutic targets in the prevention and treatment of autoimmune disease. Recent findings We have recently shown that most autoantigens are chemotactic for immature dendritic cells, suggesting that autoantigens have the potential to bridge the innate and adaptive immune systems. Autoantigens also induce other leukocytes expressing their responsive chemokine receptor to migrate. These newly recruited leukocytes, in response to proinflammatory mediators, simulate the surrounding tissues to release chemokines. Several groups have reported increases in both select chemokines and chemokine receptors in inflamed tissues. Taken together, these studies suggest that autoantigens initiate leukocyte migration into damaged and inflamed tissue that leads to the subsequent amplification of the inflammatory response. Summary Most autoantigens induce chemokine receptor mediated cell migration, therefore targeting chemokine receptors for either prevention or therapy has great potential to limit autoimmune diseases. C1 NCI, CCR, LMI, Frederick, MD USA. RP Howard, OMZ (reprint author), POB B, Frederick, MD 21702 USA. EM howardz@mail.ncifcrf.gov RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 22 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD NOV PY 2006 VL 18 IS 6 BP 642 EP 646 DI 10.1097/01.bor.0000245728.40630.27 PG 5 WC Rheumatology SC Rheumatology GA 108VF UT WOS:000242266600013 PM 17053513 ER PT J AU Telford, W Kapoor, V Jackson, J Burgess, W Buller, G Hawley, T Hawley, R AF Telford, William Kapoor, Veena Jackson, James Burgess, Walter Buller, Gayle Hawley, Teresa Hawley, Robert TI Violet laser diodes in flow cytometry: An update SO CYTOMETRY PART A LA English DT Article DE violet laser diode; cascade blue; Alexa Fluor 405; cascade yellow; pacific orange ID RESONANCE ENERGY-TRANSFER; EXCITED FLUOROCHROMES; PROTEIN; YELLOW AB Introduction: In previous studies we and others have demonstrated the usefulness of violet laser diodes (VLDs) as replacement laser sources for krypton-ion lasers on stream-in-air cytometers. Previously available VLDs had a maximum available power of less than 25 mW; this was sufficient for excitation of densely labeled cell surface antigens using fluorochromes such as Cascade Blue or Pacific Blue, but may have been insufficient for applications requiring higher levels of photon saturation, such as low-level expression of Cyan Fluorescent Protein (ECFP) in CFP-YFP FRET applications. In this follow-up study, we have tested more powerful VLDs emitting at 55 mW, and a beam-merged dual module VLD with 100 mW combined output, for their ability to excite a variety of violet-excited fluorochromes, including CFP. Methods: A dual module VLD (two linear polarized VLDs with their beams merged by a polarized beam combiner) emitting at 404 nm was mounted on a BD FACSVantage DiVa stream-in-air cytometer. The individual polarized 5 5 mW beams or the 100 mW combined beams were used to analyze PBMCs labeled with the violet-excited probes Cascade Blue, Alexa Fluor 405, Cascade Yellow and Pacific Orange dyes. Violet-excited fluorescent microsphere mixtures with decreasing fluorescence levels were also used to detect the minimum sensitivity threshold and precision of these lasers. VLD excitation on a gel-coupled cuvette flow cytometer was used as a sensitivity baseline. Results: The dual module 100 mW VLD gave both sensitivity and precision levels approaching that observed for lower-power sources on a cuvette cytometer. Single polarized VLD modules at 55 mW gave slightly decreased sensitivity for the microspheres standards and all the tested fluorochromes compared to the 100 mW source. Conclusions: While 55 mW laser sources performed adequately in the stream-in-air format, increasing the power to 100 mW did give a small but detectable increase in instrument sensitivity. This sensitivity level approached that of cuvette systems. (c) 2006 international Society for Analytical Cytology. C1 NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Power Technol Inc, Alexander, AR USA. Mol Probes Invitrogen Inc, Eugene, OR USA. George Washington Univ, Dept Immunol, Washington, DC USA. RP Telford, W (reprint author), NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bldg,10 Room 12C121 9000 Rockville Pike, Bethesda, MD 20892 USA. EM telfordw@mail.nih.gov NR 13 TC 14 Z9 14 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD NOV 1 PY 2006 VL 69A IS 11 BP 1153 EP 1160 DI 10.1002/cyco.a.20340 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 100RI UT WOS:000241685900007 PM 17051581 ER PT J AU Sato, A Khadka, DK Liu, W Bharti, R Runnels, LW Dawid, IB Habas, R AF Sato, Akira Khadka, Deepak K. Liu, Wei Bharti, Ritu Runnels, Loren W. Dawid, Igor B. Habas, Raymond TI Profilin is an effector for Daam1 in non-canonical Wnt signaling and is required for vertebrate gastrulation SO DEVELOPMENT LA English DT Article DE profilin; Xenopus; Daam1 ID CONVERGENT EXTENSION MOVEMENTS; FORMIN HOMOLOGY PROTEIN; XENOPUS-LAEVIS; CELL POLARITY; ACTIN-FILAMENTS; SMALL GTPASE; RHO; CYTOSKELETON; ACTIVATION; MOTILITY AB Non-canonical Wnt signaling plays important roles during vertebrate embryogenesis and is required for cell motility during gastrulation. However, the molecular mechanisms of how Wnt signaling regulates modi. cation of the actin cytoskeleton remain incompletely understood. We had previously identified the Formin homology protein Daam1 as an important link between Dishevelled and the Rho GTPase for cytoskeletal modulation. Here, we report that Profilin1 is an effector downstream of Daam1 required for cytoskeletal changes. Profilin1 interacted with the FH1 domain of Daam1 and was localized with Daam1 to actin stress fibers in response to Wnt signaling in mammalian cells. In addition, depletion of Profilin1 inhibited stress fiber formation induced by non-canonical Wnt signaling. Inhibition or depletion of Profilin1 in vivo specifically inhibited blastopore closure in Xenopus but did not affect convergent extension movements, tissue separation or neural fold closure. Our studies de. ne a molecular pathway downstream of Daam1 that controls Wnt-mediated cytoskeletal reorganization for a specific morphogenetic process during vertebrate gastrulation. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. Natl Inst Child Hlth & Human Dev, Mol Genet Lab, Bethesda, MD 20892 USA. Canc Inst New Jersey, New Brunswick, NJ 08903 USA. RP Habas, R (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA. EM habasra@umdnj.edu RI LIU, WEI/A-8301-2013 FU Intramural NIH HHS NR 59 TC 56 Z9 56 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 1 PY 2006 VL 133 IS 21 BP 4219 EP 4231 DI 10.1242/dev.02590 PG 13 WC Developmental Biology SC Developmental Biology GA 094CR UT WOS:000241217400010 PM 17021034 ER PT J AU Ross, MD Martinka, S Mukherjee, A Sedor, JR Vinson, C Bruggeman, LA AF Ross, Michael D. Martinka, Scott Mukherjee, Amitava Sedor, John R. Vinson, Charles Bruggeman, Leslie A. TI Math6 expression during kidney development and altered expression in a mouse model of glomerulosclerosis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE podocyte; HIV-associated nephropathy; HIV-1; transcriptional regulation ID HIV-ASSOCIATED NEPHROPATHY; LOOP-HELIX PROTEIN; TRANSCRIPTION FACTOR; NERVOUS-SYSTEM; CELL-LINES; GENES; DIFFERENTIATION; NEPHROGENESIS; ORGANOGENESIS; MORPHOGENESIS AB Math6 is a tissue-restricted member of the Atonal family of basic helix-loop-helix (bHLH) transcription factors and has been implicated in specification and differentiation of cell lineages in the brain. We identify here Math6 as a podocyte-expressed bHLH protein that was down-regulated in human immunodeficiency virus-associated nephropathy (HIVAN); a collapsing glomerulopathy characterized by podocyte dedifferentiation. Early in metanephric development, Math6 was expressed in metanephric mesenchyme but not ureteric bud-derived cells, with overall Math6 expression most abundant in the nephrogenic zone, including developing glomeruli. In adult kidney, Math6 expression was restricted to podocytes. In adult podocyte cell lines and kidneys from the transgenic mouse model of HIVAN, Math6 podocyte expression was reduced concurrent with previously reported reductions in Nephrin and Synaptopodin expression, suggesting a correlation between the loss of Math6 expression and typical podocyte terminal differentiation markers. These studies suggest that Math6 may participate in kidney development and may be a permissive factor for podocyte differentiation. C1 Case Western Reserve Univ, Dept Med, Sch Med, Metrohlth Med Ctr, Cleveland, OH 44109 USA. Case Western Reserve Univ, Rammelkamp Ctr Educ & Res, Sch Med, Metrohlth Med Ctr, Cleveland, OH 44109 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Bruggeman, LA (reprint author), Case Western Reserve Univ, Dept Med, Sch Med, Metrohlth Med Ctr, Rammelkamp Bldg,Room R429,2500 Metrohlth Dr, Cleveland, OH 44109 USA. EM leslie.bruggeman@case.edu FU NIDDK NIH HHS [DK61395, R01 DK061395] NR 36 TC 18 Z9 19 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2006 VL 235 IS 11 BP 3102 EP 3109 DI 10.1002/dvdy.20934 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 103VW UT WOS:000241916000022 PM 16937370 ER PT J AU Bluher, M Engeli, S Kloting, N Berndt, J Fasshauer, M Batkai, S Pacher, P Schon, MR Jordan, J Stumvoll, M AF Blueher, Matthias Engeli, Stefan Kloeting, Nora Berndt, Janin Fasshauer, Mathias Batkai, Sandor Pacher, Pal Schoen, Michael R. Jordan, Jens Stumvoll, Michael TI Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity SO DIABETES LA English DT Article ID DIET-INDUCED OBESITY; CANNABINOID-1 RECEPTOR BLOCKER; CARDIOMETABOLIC RISK-FACTORS; MESSENGER-RNA EXPRESSION; ENERGY-BALANCE; ANTAGONIST SR141716; OVERWEIGHT PATIENTS; CB1 RECEPTORS; FOOD-INTAKE; RIMONABANT AB The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB1) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r = 0.45, P = 0.03), visceral fat mass (r = 0.44, P = 0.003), and fasting plasma insulin concentrations (r = 0.41, P = 0.001) but negatively correlated to glucose infusion rate during clamp (r = 0.39, P = 0.009). In visceral adipose tissue, CB, mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001). Our findings suggest that abdominal fat accumulation is a critical correlate of the dysregulation of the peripheral endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes. C1 Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. HELIOS Klinikum Berlin, Franz Volhard Clin Res Ctr, Berlin, Germany. Max Delbruck Ctr Mol Med, Berlin, Germany. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. Univ Leipzig, Dept Surg, D-7010 Leipzig, Germany. RP Stumvoll, M (reprint author), Univ Leipzig, Dept Med 3, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. EM michael.stumvoll@medizin.uni-leipzig.de RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; OI Pacher, Pal/0000-0001-7036-8108; Schon, Michael/0000-0002-0698-4130 FU Intramural NIH HHS [Z01 AA000375-02] NR 40 TC 282 Z9 290 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2006 VL 55 IS 11 BP 3053 EP 3060 DI 10.2337/db06-0812 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 104OA UT WOS:000241966500015 PM 17065342 ER PT J AU Muniyappa, R Karne, RJ Hall, G Crandon, SK Bronstein, JA Ver, MR Hortin, GL Quon, MJ AF Muniyappa, Ranganath Karne, Rajaram J. Hall, Gail Crandon, Sonja K. Bronstein, Joel A. Ver, Maria R. Hortin, Glen L. Quon, Michael J. TI Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects SO DIABETES LA English DT Article ID NITRIC-OXIDE SYNTHASE; SKELETAL-MUSCLE; IN-VIVO; KNEE OSTEOARTHRITIS; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; CHONDROITIN SULFATE; GLYCOGEN-SYNTHASE; SENSITIVITY; INFUSION; RECRUITMENT AB Glucosamine is a popular nutritional supplement used to treat osteoarthritis. Intravenous administration of glucosamine causes insulin resistance and endothelial dysfunction. However, rigorous clinical studies evaluating the safety of oral glucosamine with respect to metabolic and cardiovascular pathophysiology are lacking. Therefore, we conducted a randomized, placebo-controlled, double-blind, crossover trial of oral glucosamine at standard doses (500 mg p.o. t.i.d.) in lean (n = 20) and obese (n = 20) subjects. Glucosamine or placebo treatment for 6 weeks was followed by a 1-week washout and crossover to the other arm. At baseline, and after each treatment period, insulin sensitivity was assessed by hyperinsulinemic-isoglycemic glucose clamp (SIClamp) and endothelial function evaluated by brachial artery blood flow (BAF; Doppler ultrasound) and forearm skeletal muscle microvascular recruitment (ultrasound with microbubble contrast) before and during steady-state hyperinsulinemia. Plasma glucosamine pharmacokinetics after oral dosing were determined in each subject using a high-performance liquid chromatography method. As expected, at baseline, obese subjects had insulin resistance and endothelial dysfunction when compared with lean subjects (SIClamp [median (25th-75th percentile)] = 4.3 [2.9-5.3] vs. 7.3 [5.7-11.3], P < 0.0001; insulin-stimulated changes in BAF [% over basal] = 12 [-6 to 84] vs. 39 [2-108], P < 0.04). When compared with placebo, glucosamine did not cause insulin resistance or endothelial dysfunction in lean subjects or significantly worsen these findings in obese subjects. The half-life of plasma glucosamine after oral dosing was similar to 150 min, with no significant changes in steady-state glucosamine levels detectable after 6 weeks of therapy. We conclude that oral glucosamine at standard doses for 6 weeks does not cause or significantly worsen insulin resistance or endothelial dysfunction in lean or obese subjects. C1 Natl Ctr Complementary & Alternat Med, NIH, Diabet Unit, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), Natl Ctr Complementary & Alternat Med, NIH, Diabet Unit, 10 Ctr Dr,Bldg 10,Rm 6C-205, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS NR 52 TC 35 Z9 35 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2006 VL 55 IS 11 BP 3142 EP 3150 DI 10.2337/db06-0714 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 104OA UT WOS:000241966500027 PM 17065354 ER PT J AU Traurig, MT Permana, PA Nair, S Kobes, S Bogardus, C Baier, LJ AF Traurig, Michael T. Permana, Paska A. Nair, Saraswathy Kobes, Sayuko Bogardus, Clifton Baier, Leslie J. TI Differential expression of matrix metalloproteinase 3 (MMP3) in preadipocytes/stromal vascular cells from nonobese nondiabetic versus obese nondiabetic Pima Indians SO DIABETES LA English DT Article ID BODY-MASS INDEX; INFLAMMATION-RELATED GENES; MATRIX METALLOPROTEINASES; ADIPOSE-TISSUE; CORONARY ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; HUMAN STROMELYSIN-1; PROMOTER; INVOLVEMENT; GENOTYPE AB Prior microarray studies comparing global gene expression patterns in preadipocytes/stromal vascular cells isolated from nonobese nondiabetic versus obese nondiabetic Pima Indians showed that matrix metalloproteinase 9 (MMP9) is upregulated in obese subjects. The current study targeted analysis of nine additional MMP genes that cluster to a region on chromosome 11q22 that is linked to BMI and percent body fat. Differential-display PCR showed that MMP3 is downregulated in preadipocytes/stromal vascular cells from obese subjects, and real-time PCR showed that MMP3 expression levels are negatively correlated with percent body fat. To determine whether variants within MMP3 are responsible for its altered expression, MMPS was sequenced, and seven representative variants were genotyped in 1,037 Pima subjects for association analyses. Two variants were associated with both BMI and type 2 diabetes, and two additional variants were associated with type 2 diabetes alone; however, none of these variants were associated with MMP3 expression levels. We propose that the MMP3 pathway is altered in human obesity, but this alteration may be the result of a combination of genetic variation within the MMP3 locus itself, as well as variation in additional factors, either primary or secondary to obesity, that regulate expression of the MMP3 gene. C1 NIDDKD, Diabet Mol Genet Sect, Phoenix Epidemiol Clin Res Branch, NIH, Phoenix, AZ USA. RP Baier, LJ (reprint author), NIDDK, NIH, 445 N 5th St, Phoenix, AZ USA. EM lbaier@phx.niddk.nih.gov FU Intramural NIH HHS NR 25 TC 19 Z9 19 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2006 VL 55 IS 11 BP 3160 EP 3165 DI 10.2337/db06-0373 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 104OA UT WOS:000241966500029 PM 17065356 ER PT J AU Schinstine, M Filie, AC Torres-Cabala, C Abati, A Linehan, WM Merino, M AF Schinstine, Malcolm Filie, Armando C. Torres-Cabala, Carlos Abati, Andrea Linehan, W. Marston Merino, Maria TI Fine-needle aspiration of a xp11.2 translocation/TFE3 fusion renal cell carcinoma metastatic to the lung: Report of a case and review of the literature SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Review DE cytology; kidney; TFE3; FNA ID SOFT PART SARCOMA; TFE3 GENE; NEOPLASMS; PRCC; IMMUNOREACTIVITY; MICROPHTHALMIA; CHILDREN AB A 57-yr-old woman presented to the National Cancer Institute (NCI) with a history of nephrectomy for a clear cell renal cell carcinoma (RCC), Fuhrman grade 3 of 4 diagnosed I yr prior to admission to the NCI. A CT scan done upon admission revealed multiple bilateral lung masses. A CT-guided fine-needle aspiration (FNA) of one of the lung masses revealed a cellular specimen composed primarily of follicular structures surrounding dense hyalinized central cores. The cells in the follicular structures displayed bland nuclei and had granular to vacuolated cytoplasm. Papillary structures were also appreciated. Immunocytochemical studies showed tumor cells that were strongly vimentin and TFE3 positive. Focal staining for AE1/AE3 and CD10 was observed, as was negative staining for EMA. A surgical biopsy specimen reflected the FNA findings and demonstrated a similar immunoprofile. These findings correspond to the recently described Xp11.2 translocation/TFE3 fusion renal cell carcinoma. To our knowledge, this is the first report describing the cytologic features of an Xp11.2 translocation/TFE3 fusion RCC. (c) 2006 Wiley-Liss. Inc. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Schinstine, M (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, 940 SL Young Blvd,BMSB 451, Oklahoma City, OK 73104 USA. EM malcolm-schinstine@OUHSC.edu NR 26 TC 18 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD NOV PY 2006 VL 34 IS 11 BP 751 EP 756 DI 10.1002/dc.20548 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 100PS UT WOS:000241681600007 PM 17121198 ER PT J AU Sun, M Srikantan, V Ma, L Li, J Zhang, W Petrovics, G Makarem, M Strovel, JW Horrigan, SG Augustus, M Sesterhenn, IA Moul, JW Chandrasekharappa, S Zou, ZQ Srivastava, S AF Sun, Mei Srikantan, Vasantha Ma, Lanfeng Li, Jia Zhang, Wei Petrovics, Gyorgy Makarem, Mazen Strovel, Jeffrey W. Horrigan, Stephen G. Augustus, Meena Sesterhenn, Isabell A. Moul, Judd W. Chandrasekharappa, Settara Zou, Zhiqiang Srivastava, Shiv TI Characterization of frequently deleted 6q locus in prostate cancer SO DNA AND CELL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; NONCODING RNA GENES; BREAST-CANCER; CHROMOSOME 6Q; ALLELIC LOSS; HOMEOBOX GENE; CELL-LINES; GERMLINE MUTATIONS; PROXIMAL 6Q AB The long arm of chromosome 6 is frequently deleted in diverse human neoplasms. Our previous study showed a minimum deletion region between markers D6S1056 and D6S300 on chromosome 6q in primary prostate cancer (CaP). In this study, we further refined a 200-kb minimal region of deletion (6qTSG1) centered around D6S1013 marker. The 6qTSG1 transcripts contained complex multiple splicing variants with low or absent expression in CaP cells. None of the transcripts identified contained open reading frames that code for a protein in the NCBI database. The expression of 6qTSG transcripts revealed interesting hormonal regulation relevant to CaP biology. Expression of 6q TSG transcript was induced in LNCaP cells that were cultured in charcoal-stripped serum medium suggesting an upregulation of 6qTSG transcript by androgen ablation and cell growth inhibition/apoptosis. Induction of 6qTSG1 expression in response to androgen ablation was abrogated in androgen-independent derivatives of LNCaP cells. In summary, we have defined a candidate CaP suppressor locus on chromosome 6q16.1, and deletions of this locus are frequently associated with prostate tumorigenesis. In the light of emerging role of noncoding RNAs in cancer biology including CaP, future investigations of 6qTSG11 locus is warranted. C1 Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg, Rockville, MD 20832 USA. Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20306 USA. Walter Reed Army Med Ctr, Serv Urol, Dept Surg, Washington, DC 20307 USA. Duke Univ, Med Ctr, Div Urol Surg, Durham, NC 27706 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Avalon Pharmaceut, Germantown, MD USA. RP Srivastava, S (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg, 1530 E Jefferson St, Rockville, MD 20832 USA. EM ssrivastava@cpdr.or NR 80 TC 14 Z9 14 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD NOV PY 2006 VL 25 IS 11 BP 597 EP 607 DI 10.1089/dna.2006.25.597 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 112DC UT WOS:000242504500001 PM 17132090 ER PT J AU Daly, JW Camerini-Otero, C Shapiro, CA Ma, JY Ziffer, H Velez, L Harper, JL AF Daly, John W. Camerini-Otero, Carol Shapiro, Craig A. Ma, Jingyuan Ziffer, Herman Velez, Leykza Harper, Jacquie L. TI Further studies on the interaction of loperamide with capacitative calcium entry in leukemic HL-60 cells SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE capacitative calcium entry; calcium release; dihydropyridines; loperamide; ATP; pH; leukemic HL-60 cells ID INOSITOL TRISPHOSPHATE RECEPTOR; INTRACELLULAR CA2+ STORES; AGONIST-SENSITIVE POOLS; INDUCED DIABETIC-RATS; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE; EXTRACELLULAR PH; GUINEA-PIG; 2-AMINOETHOXYDIPHENYL BORATE; CHANNELS AB Loperamide at 3-110 mu M has augmentative effects on calcium levels elevated by capacitative calcium entry (CCE) in leukemic HL-60 cells after release of intracellular calcium by ATP or thapsigargin (Harper et al. [1997] Proc Natl Acad Sci USA 94:14912-14917). The effect of loperamide on calcium levels was absent at a pH value of 6.8, a pH at which CCE is not active in HL-60 cells. Further investigations of HL-60 cells in recent years revealed a great reduction in the magnitude of the loperamide response. However, when preceded by a CCE blocker, namely N-methylnitrendipine (MRS 1844) or N-propargylnitrendipine (MRS 1845), loperamide caused a significant reversal of the blockade. Six structural analogs of loperamide were synthesized, but only two showed loperamide-like activity. C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bldg 8,Rm 1A17, Bethesda, MD 20892 USA. EM johnd@intra.nih.gov RI Harper, Jacquie/A-8920-2014 NR 68 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV PY 2006 VL 67 IS 11 BP 842 EP 851 DI 10.1002/ddr.20150 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 134VL UT WOS:000244112300003 ER PT J AU Spurney, CF Lo, CW Leatherbury, L AF Spurney, Christopher F. Lo, Cecilia W. Leatherbury, Linda TI Fetal mouse imaging using echocardiography: A review of current technology SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Review DE echocardiography; fetal mouse; biomicroscope; cardiac ultrasound ID HEART DEVELOPMENT; MICE; EMBRYO; FLOW AB Advances in genetic research have led to the need for phenotypic analysis of small animal models. However, often these genetic alterations, especially when affecting the cardiovascular system, can result in fetal or perinatal death. Noninvasive ultrasound imaging is an ideal method for detecting and studying such congenital malformations, as it allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Two platforms for fetal mouse echocardiography exist, the clinical systems with 15-MHz phased array transducers and research systems with 20-55-MHz mechanical transducers. The clinical ultrasound system has limited two-dimensional (2D) resolution (axial resolution of 440 mu m), but the availability of color and spectral Doppler allows quick interrogations of blood flows, facilitating the detection of structural abnormalities. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. In comparison, the research biomicroscope system has significantly improved 2D resolution (axial resolution of 28 mu m). Spectral Doppler imaging is also available, but in the absence of color Doppler, imaging times are increased and the detection of flow abnormalities is more difficult. M-mode imaging is available and equivalent to the clinical ultrasound system. Overall, the research system, given its higher 2D resolution, is best suited for in-depth analysis of mouse fetal cardiovascular structure and function, while the clinical ultrasound systems, equipped with phase array transducers and color Doppler imaging, are ideal for high-throughput fetal cardiovascular screens. C1 Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA. NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Spurney, CF (reprint author), Childrens Natl Med Ctr, Div Cardiol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM cspurney@cnmc.org FU NICHD NIH HHS [K12HD001399-04] NR 17 TC 21 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD NOV PY 2006 VL 23 IS 10 BP 891 EP 899 DI 10.1111/j.1540-8175.2006.00335.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 098FX UT WOS:000241507500015 PM 17069613 ER PT J AU Sullivan, DC AF Sullivan, D. C. TI Functional imaging in drug development - a primary or secondary endpoint in cancer clinical trials SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 11 BP 8 EP 8 DI 10.1016/S1359-6349(06)70016-7 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500011 ER PT J AU Crowell, J AF Crowell, J. TI The cancer preventive agent identification and early development program at the NCI SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 20 BP 10 EP 10 DI 10.1016/S1359-6349(06)70025-8 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500020 ER PT J AU Stein, U Arlt, F Walther, W Smith, J Schlag, PM Birchmeier, W Shoemaker, RH AF Stein, U. Arlt, F. Walther, W. Smith, J. Schlag, P. M. Birchmeier, W. Shoemaker, R. H. TI Invasion knock down of human colon cancer cells by siRNA specific for S100A4, a newly identified target gene of beta-catenin/TCF signaling SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Max Delbruck Ctr Mol Med, Berlin, Germany. Charite Univ Med Berlin, Robert Rossle Klin, Berlin, Germany. Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 95 BP 32 EP 33 DI 10.1016/S1359-6349(06)70101-X PG 2 WC Oncology SC Oncology GA 114TM UT WOS:000242688500094 ER PT J AU Smith, MA Maris, JM Keir, ST Lock, RB Gorlick, R Kolb, EA Keshelava, N Reynolds, CP Morton, C Houghton, PJ AF Smith, M. A. Maris, J. M. Keir, S. T. Lock, R. B. Gorlick, R. Kolb, E. A. Keshelava, N. Reynolds, C. P. Morton, C. Houghton, P. J. TI Pediatric preclinical testing program (PPTP) evaluation of the VEGFR-2 inhibitor AZD2171 SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Duke Univ, Durham, NC USA. Childrens Canc Res Inst, Randwick, NSW, Australia. Albert Einstein Coll Med, New York, NY USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. NR 0 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 102 BP 34 EP 35 DI 10.1016/S1359-6349(06)70108-2 PG 2 WC Oncology SC Oncology GA 114TM UT WOS:000242688500101 ER PT J AU Kumar, D Patacsil, D Osayi, S Gokhale, PC Verma, M Clarke, R AF Kumar, D. Patacsil, D. Osayi, S. Gokhale, P. C. Verma, M. Clarke, R. TI Vitamin E succinate inhibits the in vitro growth of pancreatic cancer cells SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Dist Columbia, Dept Biol & Environm Sci, Washington, DC USA. Georgetown Univ, Dept Oncol, Washington, DC USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 128 BP 42 EP 42 DI 10.1016/S1359-6349(06)70134-3 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500127 ER PT J AU Tarasova, N AF Tarasova, N. TI Self-assembling nanoparticles targeting G-protein coupled receptors and ABC transporters SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NCI, Struct Biophys Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 148 BP 48 EP 48 DI 10.1016/S1359-6349(06)70154-9 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500147 ER PT J AU Zhao, H Gao, Y Conover, CD Greenberger, LM Horak, ID Pommier, Y Hollingshead, M Cushman, M AF Zhao, H. Gao, Y. Conover, C. D. Greenberger, L. M. Horak, I. D. Pommier, Y. Hollingshead, M. Cushman, M. TI Delivery of indenolsoquinoline using customized releasable PEG linkers SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Enzon Pharmaceut Inc, Res & Dev, Piscataway, NJ USA. NCI, Mol Pharmacol Lab, CCR, Bethesda, MD 20892 USA. NCI, DCTD, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21701 USA. Purdue Univ, Purdue Canc Ctr, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 151 BP 49 EP 49 DI 10.1016/S1359-6349(06)70157-4 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500150 ER PT J AU Nikolovska-Coleska, Z Sun, H Lu, J Qiu, S Meagher, J Stuckey, J Yi, H Jiang, S Roller, P Wang, S AF Nikolovska-Coleska, Z. Sun, H. Lu, J. Qiu, S. Meagher, J. Stuckey, J. Yi, H. Jiang, S. Roller, P. Wang, S. TI Characterization of novel Smac mimetics as highly potent and effective antagonists of X-linked inhibitor of apoptosis protein SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. NCI, NIH, Med Chem Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 163 BP 52 EP 52 DI 10.1016/S1359-6349(06)70169-0 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500162 ER PT J AU Chan, KK Jones, WP Xie, Z Cheng, H Liu, Z Covey, JM Ludwig, J Szakacs, G Gottesman, MM AF Chan, K. K. Jones, W. P. Xie, Z. Cheng, H. Liu, Z. Covey, J. M. Ludwig, J. Szakacs, G. Gottesman, M. M. TI Oral bioavailability and pharmacokinetics in CD2f1 mice of NSC73306, an antitumor agent that selectively kills multidrug-resistant cancer cells SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Natl Canc Inst, Dev Therapeut Program, Bethesda, MD USA. Natl Canc Inst, Cell Biol Lab, Bethesda, MD USA. RI Szakacs, Gergely/A-2580-2009 OI Szakacs, Gergely/0000-0002-9311-7827 NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 192 BP 60 EP 60 DI 10.1016/S1359-6349(06)70197-5 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500190 ER PT J AU Smith, M AF Smith, M. TI Testing program approaches to evaluating new agents - The Pediatric Preclinical Testing Program (PPTP) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Clin Invest Branch, Rockville, MD USA. NR 0 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 239 BP 77 EP 78 DI 10.1016/S1359-6349(06)70244-0 PG 2 WC Oncology SC Oncology GA 114TM UT WOS:000242688500236 ER PT J AU Keay, S Tocci, G Koch, K Zhang, C Grkovic, D Michejda, C AF Keay, S. Tocci, G. Koch, K. Zhang, C. Grkovic, D. Michejda, C. TI The frizzled 8-related anti proliferative factor from IC patients inhibits bladder and kidney carcinoma cell proliferation in vitro SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, VA Med Ctr, Baltimore, MD 21201 USA. Ctr Canc Res, Natl Canc Inst, Frederick, MD USA. NR 0 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 276 BP 87 EP 88 DI 10.1016/S1359-6349(06)70281-6 PG 2 WC Oncology SC Oncology GA 114TM UT WOS:000242688500272 ER PT J AU Michejda, CJ Kosakowska-Cholody, T Meyer, CJ Wick, MJ Monks, A Cholody, WM Hariprakasha, H AF Michejda, C. J. Kosakowska-Cholody, T. Meyer, C. J. Wick, M. J. Monks, A. Cholody, W. M. Hariprakasha, H. TI Selective targeting of critical components of DNA replication by HKH40A (RTA 502) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Mol Aspects Drug Design, Frederick, MD USA. Reata Pharmaceut Inc, Dallas, TX USA. Inst Drug Design, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 288 BP 91 EP 91 DI 10.1016/S1359-6349(06)70293-2 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500284 ER PT J AU Puzanov, I Lee, W Berlin, JD Calcutt, MW Hachey, DL Vermeulen, W Low, J Rothenberg, ML AF Puzanov, I. Lee, W. Berlin, J. D. Calcutt, M. W. Hachey, D. L. Vermeulen, W. Low, J. Rothenberg, M. L. TI Phase I and pharmacokinetic trial of SJG-136 administered on a daily x 5 schedule SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, Nashville, TN USA. Natl Canc Inst, CTEP, Bethesda, MD USA. RI Puzanov, Igor/A-7179-2009 NR 0 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 297 BP 93 EP 93 DI 10.1016/S1359-6349(06)70302-0 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500293 ER PT J AU Houghton, PJ Maris, JM Friedman, HS Keir, ST Lock, RB Gorlick, R Kolb, EA Reynolds, CP Morton, C Smith, MA AF Houghton, P. J. Maris, J. M. Friedman, H. S. Keir, S. T. Lock, R. B. Gorlick, R. Kolb, E. A. Reynolds, C. P. Morton, C. Smith, M. A. TI Pediatric preclinical testing program (PPTP) evaluation of the KSP inhibitor ispinesib (SB-715992) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 St Jude Childrens Hosp, Memphis, TN 38105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Duke Univ, Durham, NC USA. Childrens Canc Inst, Randwick, NSW, Australia. Albert Einstein Coll Med, New York, NY USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 313 BP 98 EP 98 DI 10.1016/S1359-6349(06)70318-4 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500309 ER PT J AU Smith, MA Maris, JM Keir, ST Friedman, HS Lock, RB Kolb, EA Keshelava, N Reynolds, CP Morton, C Houghton, PJ AF Smith, M. A. Maris, J. M. Keir, S. T. Friedman, H. S. Lock, R. B. Kolb, E. A. Keshelava, N. Reynolds, C. P. Morton, C. Houghton, P. J. TI Pediatric preclinical testing program (PPTP) evaluation of the Src-Abl inhibitor dasatinib (BMS-354825) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Duke Univ, Durham, NC USA. Childrens Canc Inst, Randwick, NSW, Australia. Albert Einstein Coll Med, New York, NY USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 322 BP 101 EP 101 DI 10.1016/S1359-6349(06)70327-5 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500318 ER PT J AU Sei, S Yang, Q Mussio, J Coffey, M Parchment, R Shoemaker, R Tomaszewski, J AF Sei, S. Yang, Q. Mussio, J. Coffey, M. Parchment, R. Shoemaker, R. Tomaszewski, J. TI Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents against non-small cell lung cancer (NSCLC) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 SAIC Frederick Inc, NCI, Frederick, MD USA. Oncolyt Biotech Inc, Calgary, AB, Canada. NCI, Bethesda, MD USA. NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 330 BP 103 EP 103 DI 10.1016/S1359-6349(06)70335-4 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500326 ER PT J AU Culotta, K Kirkpatrick, D Covey, J Schultz, C Mack, D Rhea, R Allen, T Powis, G Johansen, M Madden, T AF Culotta, K. Kirkpatrick, D. Covey, J. Schultz, C. Mack, D. Rhea, R. Allen, T. Powis, G. Johansen, M. Madden, T. TI Preclinical pharmacokinetic and comparative biodistribution studies of PX-866, a broad spectrum phosphatidylinositol-3-kinase (PI-3K) inhibitor, in F344 rats SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Pharm, Houston, TX 77030 USA. Prolx Pharmaceut Corp, Tucson, AZ USA. NCI, DTP, Rockville, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 434 BP 132 EP 132 DI 10.1016/S1359-6349(06)70439-6 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500430 ER PT J AU Shoemaker, R Glover, C Adelsberger, J Hollingshead, M Monks, A AF Shoemaker, R. Glover, C. Adelsberger, J. Hollingshead, M. Monks, A. TI Induction of myeloid differentiation by a novel sterol mesylate compound (NSC 67657) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Dev Therapeut Program, Frederick, MD USA. SAIC Frederick, AIDS Monitoring Lab, Frederick, MD USA. SAIC Frederick, Lab Funct Genom, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 492 BP 150 EP 150 DI 10.1016/S1359-6349(06)70497-9 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500487 ER PT J AU Monks, A Reifsnider, N Shoemaker, R Cardellina, J Baker, B AF Monks, A. Reifsnider, N. Shoemaker, R. Cardellina, J. Baker, B. TI Transcriptional profiling of palmerolide A, a putative inhibitor of V-ATPase, indicates perturbation of cholesterol biosynthesis SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NCI, Screening Technol Branch, Frederick, MD USA. Univ S Florida, Dept Chem, Tampa, FL 33620 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 515 BP 156 EP 157 DI 10.1016/S1359-6349(06)70520-1 PG 2 WC Oncology SC Oncology GA 114TM UT WOS:000242688500510 ER PT J AU Ansher, S Cristofaro, J Shoemaker, D Christian, M AF Ansher, S. Cristofaro, J. Shoemaker, D. Christian, M. TI Novel investigational agent clinical trials: Cancer therapy evaluation program initiatives to enhance combination studies SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NCI, Canc Therapy Evaluat Program, Rockville, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 540 BP 164 EP 164 DI 10.1016/S1359-6349(06)70545-6 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500535 ER PT J AU Duran, I Hotte, S Chen, E Hirte, H MacLean, M Turner, S Pond, G Wright, J Dancey, J Siul, L AF Duran, I. Hotte, S. Chen, E. Hirte, H. MacLean, M. Turner, S. Pond, G. Wright, J. Dancey, J. Siul, L. TI Dual inhibition of the MAPK pathway by combination targeted therapy: a phase I trial of sorafenib (SOR) and erlotinib (ERL) in advanced solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Princess Margaret Hosp Phase II Consortium, Toronto, ON, Canada. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 550 BP 167 EP 167 DI 10.1016/S1359-6349(06)70555-9 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500545 ER PT J AU Pino, MS Balsamo, M Di Modugno, F Conidi, A McConkey, D Cognetti, F Natali, R Milella, M Nistico, P AF Pino, M. S. Balsamo, M. Di Modugno, F. Conidi, A. McConkey, D. Cognetti, F. Natali, R. Milella, M. Nistico, P. TI Epithelial mesenchymal transition (EMT) and hMena expression as determinants of sensitivity of pancreatic adenocarcinorna (PDAC) cell lines to EGFR tyrosine kinase inhibitors (TKI) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NCI, DCTD, Dev Therapeut Program, Frederick, MD USA. SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 EI 1878-1217 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 558 BP 169 EP 169 DI 10.1016/S1359-6349(06)70563-8 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500552 ER PT J AU Pavlick, A Liebes, L Osman, I Brooks, P Yee, H Polsky, D Hamilton, A Wright, J Muggia, F AF Pavlick, A. Liebes, L. Osman, I. Brooks, P. Yee, H. Polsky, D. Hamilton, A. Wright, J. Muggia, F. TI Alteration of the RAS/BRAF/MEK/MAPK pathway by BAY 43-9006 (sorafenib) in metastatic melanoma SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NYU, Inst Canc, New York, NY USA. Sydney Canc Ctr, Sydney, NSW, Australia. CTEP NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 589 BP 178 EP 178 DI 10.1016/S1359-6349(06)70594-8 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500584 ER PT J AU Chan, KK Chen, P Xie, Z Kulp, SK Chen, CS Covey, JM AF Chan, K. K. Chen, P. Xie, Z. Kulp, S. K. Chen, C. S. Covey, J. M. TI Pharmacokinetics of Akt inhibitor NSC 728209 in the rat by LC/MS/MS method SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Natl Canc Inst, Dev Therapeut Program, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 602 BP 182 EP 182 DI 10.1016/S1359-6349(06)70607-3 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500597 ER PT J AU McCardle, P Chhabra, V AF McCardle, Peggy Chhabra, Vinita TI Commentary SO ELEMENTARY SCHOOL JOURNAL LA English DT Editorial Material ID LANGUAGE C1 NICHHD, Bethesda, MD 20892 USA. RP McCardle, P (reprint author), NICHHD, Bethesda, MD 20892 USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0013-5984 J9 ELEM SCHOOL J JI Elem. Sch. J. PD NOV PY 2006 VL 107 IS 2 BP 239 EP 248 DI 10.1086/510657 PG 10 WC Education & Educational Research SC Education & Educational Research GA 102TW UT WOS:000241837200007 ER PT J AU Lynch, TR Rosenthal, MZ Kosson, DS Cheavens, JS Lejuez, CW Blair, RJR AF Lynch, Thomas R. Rosenthal, M. Zachary Kosson, David S. Cheavens, Jennifer S. Lejuez, C. W. Blair, R. J. R. TI Heightened sensitivity to facial expressions of emotion in borderline personality disorder SO EMOTION LA English DT Article DE borderline personality disorder; facial affect recognition; emotional sensitivity; facial expressions ID DEPRESSED-PATIENTS; THOUGHT SUPPRESSION; NEGATIVE AFFECT; RECOGNITION; SCHIZOPHRENIA; EMPATHY; INDIVIDUALS; COMORBIDITY; IMPAIRMENT; PERCEPTION AB Individuals with borderline personality disorder (BPD) have been hypothesized to exhibit significant problems associated with emotional sensitivity. The current study examined emotional sensitivity (i.e., low threshold for recognition of emotional stimuli) in BPD by comparing 20 individuals with BPD and 20 normal controls on their accuracy in identifying emotional expressions. Results demonstrated that, as facial expressions morphed from neutral to maximum intensity, participants with BPD correctly identified facial affect at an earlier stage than did healthy controls. Participants with BPD were more sensitive than healthy controls in identifying emotional expressions in general, regardless of valence. These findings could not be explained by participants with BPD responding faster with more errors. Overall, results appear to support the contention that heightened emotional sensitivity may be a core feature of BPD. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Duke Univ, Dept Psychol Social & Hlth Sci, Durham, NC 27710 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Lynch, TR (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 2213 Elba St,POB 3026, Durham, NC 27710 USA. EM lynch011@mc.duke.edu RI Cheavens, Jennifer/A-4918-2012; OI Lynch, Thomas/0000-0003-1270-6097 FU NIMH NIH HHS [MH01614] NR 63 TC 132 Z9 133 U1 3 U2 23 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD NOV PY 2006 VL 6 IS 4 BP 647 EP 655 DI 10.1037/1528-35416.4.647 PG 9 WC Psychology, Experimental SC Psychology GA 111LO UT WOS:000242453400010 PM 17144755 ER PT J AU Loladze, AV Stull, MA Rowzee, AM DeMarco, J Lantry, JH Rosen, CJ LeRoith, D Wagner, KU Hennighausen, L Wood, TL AF Loladze, Aimee V. Stull, Malinda A. Rowzee, Anne M. DeMarco, Jean Lantry, James H., III Rosen, Clifford J. LeRoith, Derek Wagner, Kay-Uwe Hennighausen, Lothar Wood, Teresa L. TI Epithelial-specific and stage-specific functions of insulin-like growth factor-I during postnatal mammary development SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; CELL-CYCLE PROGRESSION; BREAST CANCER-CELLS; IGF-I; GLAND DEVELOPMENT; DUCTAL MORPHOGENESIS; SOMATOMEDIN RECEPTOR; BINDING-PROTEINS; CRE/LOXP SYSTEM; TRANSGENIC MICE AB Postnatal development of the mammary gland requires interactions between the epithelial and stromal compartments, which regulate actions of hormones and growth factors. IGF-I is expressed in both epithelial and stromal compartments during postnatal development of the mammary gland. However, little is known about how local expression of IGF-I in epithelium or stroma regulates mammary growth and differentiation during puberty and pregnancy-induced alveolar development. The goal of this study was to investigate the mechanisms of IGF-I actions in the postnatal mammary gland and test the hypothesis that IGF-I expressed in stromal and epithelial compartments has distinct functions. We established mouse lines with inactivation of the igf1 gene in mammary epithelium by crossing igf1/loxP mice with mouse lines expressing Cre recombinase under the control of either the mouse mammary tumor virus long-terminal repeat or the whey acidic protein gene promoter. Epithelial-specific loss of IGF-I during pubertal growth resulted in deficits in ductal branching. In contrast, heterozygous reduction of IGF-I throughout the gland decreased expression of cyclins A2 and B1 during pubertal growth and resulted in alterations in proliferation of the alveolar epithelium and milk protein levels during pregnancy-induced differentiation. Reduction in epithelial IGF-I at either of these stages had no effect on these indices. Taken together, our results support distinct roles for IGF-I expressed in epithelial and stromal compartments in mediating growth of the postnatal mammary gland. C1 Univ Med & Dent New Jersey, Dept Neurol & Neurosci H506, New Jersey Med Sch, Newark, NJ 07103 USA. Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. Univ Cincinnati, Coll Med, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA. St Joseph Hosp, Maine Ctr Osteoporosis Res & Educ, Bangor, ME 04401 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Univ Nebraska, Med Ctr, Omaha, NE 68198 USA. NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. RP Wood, TL (reprint author), Univ Med & Dent New Jersey, Dept Neurol & Neurosci H506, New Jersey Med Sch, 185 S Orange Ave, Newark, NJ 07103 USA. EM woodte@umdnj.edu RI Wagner, Kay-Uwe/B-6044-2009; OI Rowzee, Anne/0000-0003-1969-9133 FU NCI NIH HHS [CA83174]; NIDDK NIH HHS [DK60612] NR 37 TC 24 Z9 25 U1 0 U2 0 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 NOV PY 2006 VL 147 IS 11 BP 5412 EP 5423 DI 10.1210/en.2006-0427 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 095RG UT WOS:000241324900047 PM 16901968 ER PT J AU Schwartz, DA Martin, WJ AF Schwartz, David A. Martin, William J., II TI Focusing on global environmental health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Bethesda, MD USA. RP Schwartz, DA (reprint author), NIEHS, Bethesda, MD USA. EM david.schwartz@niehs.nih.gov; wjmartin@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 114 IS 11 BP A630 EP A630 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 102OS UT WOS:000241822300001 PM 17107828 ER PT J AU Thayer, KA Melnick, R Huff, J Burns, K Davis, D AF Thayer, Kristina A. Melnick, Ronald Huff, James Burns, Kathy Davis, Devra TI Hormesis: A new religion? SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID DOSE-RESPONSE; PUBLIC-HEALTH C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. Sci Corps, Lexington, MA USA. Univ Pittsburgh, Inst Canc, Grad Sch Publ Hlth, Ctr Environm Oncol,Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Thayer, KA (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. EM thayer@niehs.nih.gov NR 13 TC 16 Z9 17 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 NOV PY 2006 VL 114 IS 11 BP A632 EP A633 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 102OS UT WOS:000241822300002 PM 17107829 ER PT J AU Blair, A Freeman, LB AF Blair, Aaron Freeman, Laura Beane TI Lung cancer among nonsmokers SO EPIDEMIOLOGY LA English DT Editorial Material ID REPORTED SMOKING STATUS; UNITED-STATES; DEATH RATES; RISK; WOMEN; METAANALYSIS C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Room 8008, Bethesda, MD 20892 USA. EM blaira@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 FU Intramural NIH HHS NR 22 TC 9 Z9 9 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 BP 601 EP 603 DI 10.1097/01.ede.0000239724.89630.23 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 096VV UT WOS:000241405800003 PM 17068413 ER PT J AU Lyon, JL Alder, SC Stone, MB Scholl, A Reading, JC Holubkov, R Sheng, XM White, GL Hegmann, KT Anspaugh, L Hoffman, FO Simon, SL Thomas, B Carroll, R Meikle, AW AF Lyon, Joseph L. Alder, Stephen C. Stone, Mary Bishop Scholl, Alan Reading, James C. Holubkov, Richard Sheng, Xiaoming White, George L., Jr. Hegmann, Kurt T. Anspaugh, Lynn Hoffman, F. Owen Simon, Steven L. Thomas, Brian Carroll, Raymond Meikle, A. Wayne TI Thyroid disease associated with exposure to the Nevada Nuclear Weapons Test Site radiation - A reevaluation based on corrected dosimetry and examination data SO EPIDEMIOLOGY LA English DT Article ID ATOMIC-BOMB SURVIVORS; I-131 THERAPY; FALLOUT; COHORT; CANCER; ADOLESCENTS; CHILDREN; HYPOTHYROIDISM; NAGASAKI; RISK AB Background: A study was begun in 1965 to 1966 to determine whether children exposed to radioactive iodine from nuclear weapons testing at the Nevada Test Site from 1951 through 1962 were at higher risk of thyroid disease. In 1993, we reported that among those examined in 1985 to 1986 (Phase II) there was an association between radiation from the Nevada Test Site and thyroid neoplasms. Methods: We reevaluated the relationship between exposure to Nevada Test Site fallout and thyroid disease using newly corrected dose estimates and disease outcomes from the Phase II study. A prospective cohort of school children 12 to 18 years old living in Utah, Nevada, and Arizona was first examined for thyroid disease in 1965 to 1966 and reexamined in 1985 to 1986. In the Phase II report, 2497 subjects formed the basis for this analysis. Thyroid disease, including thyroid neoplasms and thyroiditis, was expressed as cumulative incidence and risk ratios (RRs) with a dose-response expressed as excess risk ratio (ERR/Gy). Results: The RR between thyroid radiation dose in the highest dose group and thyroid neoplasms increased from 3.4 (in the earlier analysis) to 7.5. The RR for thyroiditis increased from 1.1 to 2.7 with an ERR/Gy of 4.9 (95% confidence interval = 2.0 to 10.0). There were too few malignant thyroid neoplasms to estimate risk. Conclusions: Persons exposed to radioactive iodine as children have an increased risk of thyroid neoplasms and autoimmune thyroiditis up to 30 years after exposure. C1 Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84108 USA. Univ Utah, Sch Med, Dept Radiobiol, Salt Lake City, UT 84108 USA. Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84108 USA. SENES Oak Ridge Inc, Oak Ridge, TN USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Lyon, JL (reprint author), Univ Utah, Sch Med, Dept Family & Prevent Med, 375 Chipeta Way,Suite A, Salt Lake City, UT 84108 USA. EM jlyon@dfpm.utah.edu FU NCEH CDC HHS [1 R01 EH000055]; PHS HHS [U50/CCU816245] NR 32 TC 36 Z9 37 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 BP 604 EP 614 DI 10.1097/01.ede.0000240540.79983.7f PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 096VV UT WOS:000241405800004 PM 17028502 ER PT J AU Mellemkjaer, L Holmich, LR Gridley, G Rabkin, C Olsen, JH AF Mellemkjaer, Lene Hoelmich, Lisbet R. Gridley, Gloria Rabkin, Charles Olsen, Jorgen H. TI Risks for skin and other cancers up to 25 years after burn injuries SO EPIDEMIOLOGY LA English DT Article ID VITAMIN-D; TRANSPLANTATION; SCARS AB Background: Malignant degeneration of chronic ulcers such as nonhealed burn wounds has been described in the literature, but this phenomenon has never been quantified in an epidemiologic study. We investigated the risks for skin and other cancers among patients with a prior burn. Methods: We identified 16,903 patients from the Danish Hospital Discharge Register who had been admitted to a hospital with a thermal or chemical burn during 1978 to 1993. The cohort was followed for cancer in the Danish Cancer Registry through 2002, and the cancer incidence in the cohort was compared with that in the general population of Denmark. Results: Patients with burn had 139 skin cancers, with 189 expected, yielding a standardized incidence ratio of 0.7 (95% confidence interval = 0.6-0.9). This reduced risk was due mainly to deficits of basal cell carcinoma and malignant melanoma, whereas the number of squamous cell carcinomas observed was close to expected. We saw no consistent increases in risk for skin cancer in the subgroups of patients with the most severe injuries or with the longest periods of follow up. Conclusions: The tendency to malignant degeneration of burn scars, described in previous reports of case series, did not result in an excess of squamous cell carcinoma of the skin or of any other type of skin cancer during up to 25 years' follow up of a large unselected cohort of patients hospitalized for burn injuries. C1 Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. Copenhagen Univ Hosp, Dept Plast Surg, Herlev, Denmark. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Mellemkjaer, L (reprint author), Danish Canc Soc, Inst Canc Epidemiol, Strandblvd 49, DK-2100 Copenhagen, Denmark. EM lene@cancer.dk OI Holmich, Lisbet Rosenkrantz/0000-0002-1983-5222; Olsen, Jorgen Helge/0000-0001-9633-5662 FU NCI NIH HHS [MAO N01-CP-61111] NR 22 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 BP 668 EP 673 DI 10.1097/01.ede.0000239651.06579.a4 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 096VV UT WOS:000241405800012 PM 17028504 ER PT J AU Aharon, D Metayer, C Ward, M Aldrich, M Reynolds, P Buffler, P AF Aharon, D. Metayer, C. Ward, M. Aldrich, M. Reynolds, P. Buffler, P. TI Reliability of self-reported household pesticide use in a childhood leukemia study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 UCB, Berkeley, CA USA. NCI, DCEG, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S394 EP S394 DI 10.1097/00001648-200611001-01049 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443402070 ER PT J AU Alavanja, MCR Mahajan, R Beane-Freeman, LE Lubin, JH Hines, CJ Thomas, K Coble, J Sandler, DP Hoppin, JA Blair, A AF Alavanja, M. C. R. Mahajan, R. Beane-Freeman, L. E. Lubin, J. H. Hines, C. J. Thomas, K. Coble, J. Sandler, D. P. Hoppin, J. A. Blair, A. TI Pesticide use and prostate cancer incidence in a prospective cohort study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NIH, NCI, US Dept HHS, Div Canc Epidemiol & Genetics Occupat & Environm, Rockville, MD USA. NIH, NCI, US Dept HHS, Div Canc Epidemiol & Genet Biostat Branch, Rockville, MD USA. Ctr Dis Control, NIOSH, US Dept HHS, Cincinnati, OH USA. US EPA, Res Triangle Pk, NC 27711 USA. NIH, Natl Inst Environm Hlth Sci, US Dept HHS, Epidemiol Branch, Res Triangle Pk, NC USA. RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S116 EP S117 DI 10.1097/00001648-200611001-00285 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400285 ER PT J AU Bloom, M Buck-Louis, G Liu, A Schisterman, E Kostyniak, P AF Bloom, M. Buck-Louis, G. Liu, A. Schisterman, E. Kostyniak, P. TI Increases in serum PCBs during early pregnancy SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference on Evironmental Epidemiology and Exposure CY SEP 04, 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NIH, NICHD, DHHS, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S93 EP S93 DI 10.1097/00001648-200611001-00222 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400222 ER PT J AU Cantor, KP Villanueva, C Garcia-Closas, M Silverman, D Real, FX Dosemeci, M Malats, N Yeager, M Welch, R Chanock, S Tardon, A Garcia-Closas, R Serra, C Carrato, A Castano-Vinyals, G Samanic, C Rothman, N Kogevinas, M AF Cantor, K. P. Villanueva, C. Garcia-Closas, M. Silverman, D. Real, F. X. Dosemeci, M. Malats, N. Yeager, M. Welch, R. Chanock, S. Tardon, A. Garcia-Closas, R. Serra, C. Carrato, A. Castano-Vinyals, G. Samanic, C. Rothman, N. Kogevinas, M. TI Bladder cancer, disinfection byproducts, and markers of genetic susceptibility in a case-control study from Spain SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Natl Canc Inst, Bethesda, MD USA. Inst Municipal Invest Med, E-08003 Barcelona, Spain. Univ Hosp Canarias, San Cristobal la Laguna, Spain. Univ Olviedo, Olviedo, Spain. Hosp Parc Tauli, Sabadell, Spain. Elche Gen Hosp, Elche, Spain. RI Serra, C/E-6879-2014; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; NR 0 TC 7 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S150 EP S150 DI 10.1097/00001648-200611001-00375 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400375 ER PT J AU Collman, G Reinlib, L Maull, E Winn, D Trapido, E AF Collman, G. Reinlib, L. Maull, E. Winn, D. Trapido, E. TI The Breast Cancer and Environment Research Centers (BCERC): A mulitdisciplinary approach to understand how environmental exposures during critical windows of susceptibility affect breast cancer risk SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NIEHS, NIH, Res Triangle Park, Res Triangle Pk, NC USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S305 EP S305 DI 10.1097/00001648-200611001-00800 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401329 ER PT J AU Colt, J Hartge, P Davis, S Cerhan, J Cozen, W Severson, R AF Colt, J. Hartge, P. Davis, S. Cerhan, J. Cozen, W. Severson, R. TI Hobbies with solvent exposure and risk of non-Hodgkin lymphoma SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Natl Inst Hlth, US Dept HHS, Div Canc Epidemiol & Genetics, Natl Canc Inst, Bethesda, MD USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Mayo Clin Coll Med, Rochester, MN USA. Univ So Calif, Los Angeles, CA USA. Wayne State Univ, Karmanos Canc Inst, Dept Family Med, Detroit, MI 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S305 EP S306 DI 10.1097/00001648-200611001-00801 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401330 ER PT J AU Cross, A AF Cross, Amanda TI Improving exposure assessment to address the association between meat and cancer SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S78 EP S79 DI 10.1097/00001648-200611001-00181 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400181 ER PT J AU Curwin, B Misty, H Sanderson, W Striley, C Heederik, D Kromhout, H Reynolds, S Alavanjal, M AF Curwin, B. Misty, H. Sanderson, W. Striley, C. Heederik, D. Kromhout, H. Reynolds, S. Alavanjal, M. TI Pesticide dose estimates for children of Iowa farmers and non-farmers SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NIOSH, Cincinnati, OH 45226 USA. Univ Iowa, Iowa City, IA USA. Univ Utrecht, Utrecht, Netherlands. Colorado State Univ, Ft Collins, CO 80523 USA. Natl Canc Inst, Rockville, MD USA. RI Kromhout, Hans/A-9159-2008 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S92 EP S92 DI 10.1097/00001648-200611001-00220 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400220 ER PT J AU De Vathaire, F Brindel, P Doyon, F Paaoafaite, J Teuri, J Bouville, A Drozdovich, V AF De Vathaire, F. Brindel, P. Doyon, F. Paaoafaite, J. Teuri, J. Bouville, A. Drozdovich, V. TI Thyroid cancer in French Polynesia: A population based case control study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 INSERM, Villejuif, France. DHHS, NCI, NIH, Div Canc Epidemiol & Genetics, Bethesda, MD USA. IARC, Lyon, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S306 EP S306 DI 10.1097/00001648-200611001-00802 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401331 ER PT J AU Drozdovitch, V Doyon, F Bouville, A Cardis, E De Vathaire, F AF Drozdovitch, V. Doyon, F. Bouville, A. Cardis, E. De Vathaire, F. TI Estimation of radiation doses in a case-control study of thyroid cancer in Fench Polynesia SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 IARC, Lyon, France. INSERM, U605, Paris, France. DHHS, NIH, NCI, Divis Canc Epidemiol & Gent, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S457 EP S457 DI 10.1097/00001648-200611001-01227 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443402248 ER PT J AU Engel, L Laden, F Andersen, A Strickland, P Blair, A Needham, L Barr, D Wolff, M Helzlsouer, K Hunter, D Lan, Q Cantor, K Comstock, G Brock, J Bush, D Rothman, N AF Engel, L. Laden, F. Andersen, A. Strickland, P. Blair, A. Needham, L. Barr, D. Wolff, M. Helzlsouer, K. Hunter, D. Lan, Q. Cantor, K. Comstock, G. Brock, J. Bush, D. Rothman, N. TI PCBs and non-Hodgkin lymphoma: Results from three cohorts SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Channing Lab, Boston, MA 02115 USA. Canc Registry Norway, Oslo, Norway. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. NIH, NCI, US Dept HHS, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RI Needham, Larry/E-4930-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S116 EP S116 DI 10.1097/00001648-200611001-00284 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400284 ER PT J AU Han, YY Weissfeld, JL Dinse, GE Umbach, DM Davis, DL AF Han, Y. Y. Weissfeld, J. L. Dinse, G. E. Umbach, D. M. Davis, D. L. TI Age-period-cohort analysis of non-Hodgkin's lymphoma delay-adjusted incidence in the US, 1975-2002 SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Environm Oncol, Inst Canc, Pittsburgh, PA USA. Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S309 EP S309 DI 10.1097/00001648-200611001-00810 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401339 ER PT J AU Hatch, E Troisi, R Wise, L Hyer, M Palmer, J Titus-Ernstoff, L Strohsnitter, W Kaufmann, R Adam, E Noller, K Herbst, A Robboy, S Hartge, P Hoover, R AF Hatch, E. Troisi, R. Wise, L. Hyer, M. Palmer, J. Titus-Ernstoff, L. Strohsnitter, W. Kaufmann, R. Adam, E. Noller, K. Herbst, A. Robboy, S. Hartge, P. Hoover, R. TI Age at natural menopause in women exposed to diethylstilbestrol in utero SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Boston Univ, Sch Publ Hlth, Boston, MA USA. Natl Canc Inst, Bethesda, MD USA. Epidemiol Slone Ctr, Boston, MA USA. Informat Management Syst, Rockville, MD USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Tufts Univ New England Med Ctr, Boston, MA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Chicago, Chicago, IL 60637 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S192 EP S193 DI 10.1097/00001648-200611001-00488 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401017 ER PT J AU Kan, H Heiss, G Ross, K Whitsel, E Lurmann, F London, S AF Kan, H. Heiss, G. Ross, K. Whitsel, E. Lurmann, F. London, S. TI Traffic exposure and lung function in adults: The atherosclerosis risk in communities study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Natl Inst Hlth, Natl Inst Environm Hlth, Dept Epidemiol, Res Triangle Pk, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S257 EP S258 DI 10.1097/00001648-200611001-00666 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401195 ER PT J AU Landi, MT AF Landi, Maria Teresa TI Molecular epidemiology of dioxin illness in Seveso SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NIH, NCI, DHHS, Div Canc Epidemiol & Genet Genet Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S83 EP S83 DI 10.1097/00001648-200611001-00195 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400195 ER PT J AU Lewis, D Clegg, L Johnson, N AF Lewis, D. Clegg, L. Johnson, N. TI Smoking status, environment, and death from lung cancer and other lung diseases SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Natl Canc Inst, Bethesda, MD USA. US Bur Census, Suitland, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S312 EP S313 DI 10.1097/00001648-200611001-00821 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401350 ER PT J AU Lynch, D AF Lynch, D. TI Novel technologies for measuring human reproductive endpoints in field-based studies SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NIH, NICHHD, DHHS, Epidemiol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S378 EP S379 DI 10.1097/00001648-200611001-01008 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443402029 ER PT J AU Mendola, P Schoendorf, K Rappazzo, K Keim, S Galke, W Brenner, R Walsh, D Williams, A Messer, L AF Mendola, P. Schoendorf, K. Rappazzo, K. Keim, S. Galke, W. Brenner, R. Walsh, D. Williams, A. Messer, L. TI Recruiting for a longitudinal study of children's environmental health using a household-based probability sampling approach SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 US EPA, Human Studies Div, Chapel Hill, NC USA. Ctr Dis Control, Hyattsville, MD USA. NICHD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S224 EP S225 DI 10.1097/00001648-200611001-00574 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401103 ER PT J AU Metayer, C Smith, M Ward, M Reynolds, P Gunier, R Colt, J Guha, N Aharon, D Aldrich, M Buffler, P AF Metayer, C. Smith, M. Ward, M. Reynolds, P. Gunier, R. Colt, J. Guha, N. Aharon, D. Aldrich, M. Buffler, P. TI Model for chemical exposure assessment to study environmental risk factors of childhood leukemia SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. NCI, Dceg, Bethesda, MD USA. NR 0 TC 0 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S408 EP S408 DI 10.1097/00001648-200611001-01087 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443402108 ER PT J AU Peplonska, B Blair, A Szeszenia-Dabrowska, N Garcia-Closas, M Lissowska, J Bardin-Mikolajczak, A Brinton, LA Hartman, TJ AF Peplonska, B. Blair, A. Szeszenia-Dabrowska, N. Garcia-Closas, M. Lissowska, J. Bardin-Mikolajczak, A. Brinton, L. A. Hartman, T. J. TI Occupational physical activity and risk of breast cancer in Polish women SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. Natl Canc Inst, NIH, Occupat & Environm Epidemiol Branch, Bethesda, MD USA. Natl Canc Inst, NIH, Hormonal & Reproduct Epidemiol Branch, Bethesda, MD USA. Ctr Canc, M Sklodowska Curie Inst Oncol, Div Canc Epidemiol & Prevent, Warsaw, Poland. Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. RI Peplonska, Beata/F-6004-2010; Szeszenia-Dabrowska, Neonila/F-7190-2010; Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S315 EP S316 DI 10.1097/00001648-200611001-00830 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401359 ER PT J AU Quackenboss, J Mendola, P Galke, W AF Quackenboss, J. Mendola, P. Galke, W. CA Natl Children's Study Interagency TI In utero environmental exposures in the national children's study - Measurement strategies SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NICHD, NCS, PO, Bethesda, MD USA. RI Quackenboss, James/I-1960-2013 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S22 EP S22 DI 10.1097/00001648-200611001-00011 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400011 ER PT J AU Radican, L Wartenberg, D Rhoads, G Schneider, D Wedeen, R Stewart, P Blair, A AF Radican, L. Wartenberg, D. Rhoads, G. Schneider, D. Wedeen, R. Stewart, P. Blair, A. TI A retrospective cohort study of end-stage renal disease in workers exposed to trichloroethylene and other hydrocarbons SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Univ Med & Dent New Jersey, Sch Publ Hlth & Merck & Co, Piscataway, NJ USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Sch Publ Hlth, Piscataway, NJ USA. Rutgers State Univ, Piscataway, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Piscataway, NJ USA. Natl Canc Inst, Piscataway, NJ 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S520 EP S521 DI 10.1097/00001648-200611001-01401 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443402422 ER PT J AU Rusiecki, J Cash, J Raines, C Brinton, L Zahm, S Mason, T Needham, L Blair, A Sieber, S Hoover, R AF Rusiecki, J. Cash, J. Raines, C. Brinton, L. Zahm, S. Mason, T. Needham, L. Blair, A. Sieber, S. Hoover, R. TI Serum concentrations of organochlorine compounds and mammographic density in a highly exposed population in Triana, Alabama SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med, Bethesda, MD 20814 USA. Univ Alabama, Coll Nursing, Huntsville, AL 35899 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ S Florida, Coll Publ Hlth, Tampa, FL USA. Natl Ctr Environm Hlth, Ctr Dis Control, Atlanta, GA USA. RI Needham, Larry/E-4930-2011; Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S89 EP S89 DI 10.1097/00001648-200611001-00212 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400212 ER PT J AU Sinha, R AF Sinha, Rashmi TI Meat-cooking carcinogens: Heterocyclic amines, benzo[a]pyrene, and risk of human cancer SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S77 EP S77 DI 10.1097/00001648-200611001-00176 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400176 ER PT J AU Ward, M Colt, J Gunier, R Metayer, C Lubin, J Nishioka, M Reynolds, P Buffler, P AF Ward, M. Colt, J. Gunier, R. Metayer, C. Lubin, J. Nishioka, M. Reynolds, P. Buffler, P. TI Evaluation of two dust sampling methods for estimating pesticide exposures in a case-control study of childhood leukemia SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Calif Dept Hlth Serv, Oakland, CA USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Battelle Lab, Columbus, OH USA. NR 0 TC 0 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S169 EP S169 DI 10.1097/00001648-200611001-00425 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443400425 ER PT J AU Windham, G Wolff, M Pinney, S Teitelbaum, S Calafat, A Sjodin, A Pfeiffer, C Barr, D Erdmann, C Koblick, K Collmann, G AF Windham, G. Wolff, M. Pinney, S. Teitelbaum, S. Calafat, A. Sjodin, A. Pfeiffer, C. Barr, D. Erdmann, C. Koblick, K. Collmann, G. TI Biomarkers of environmental exposures in a multi-site study of young girls SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Dept Hlth Serv, Richmond, CA USA. Mt Sinai Sch Med, New York, NY USA. Univ Cincinnati, Sch Med, Cincinnati, OH 45221 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Cty Marin, San Rafael, CA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RI Sjodin, Andreas/F-2464-2010 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S419 EP S419 DI 10.1097/00001648-200611001-01120 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443402141 ER PT J AU Hoyer, SH Landis, SC AF Hoyer, Steny H. Landis, Story C. TI The 3rd Judith Hoyer Lecture in epilepsy, December 2, 2005 opening remarks SO EPILEPSY & BEHAVIOR LA English DT Article DE public lecture; NINDS; congress; patient voluntary organisations AB On December 2, 2005, Dr. Jeffrey L. Noebels presented the third lecture in a series highlighting the promise of epilepsy research. Opening remarks were provided by Dr. Story C. Landis, Director of the National Institute of Neurological Disorders and Stroke, and by Representative Steny Hoyer (D-MD). The lecture series is held in memory of Mrs. Judith Hoyer, an active member of the Board of Directors of the Epilepsy Foundation (EF) and the late wife of Rep. Hoyer. Mrs. Hoyer spent her life both helping families to cope with epilepsy and promoting research into a cure and a better quality of life for those with the disorder. The purpose of the lecture is to raise awareness of epilepsy among researchers and the public and provide intellectual stimulation that will encourage continuing progress toward finding a cure for epilepsy. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Inst Neurol Disroders & Stroke, NIH, Bethesda, MD 20892 USA. US House Representatives, Congress District Maryland 5, Washington, DC 20515 USA. RP Landis, SC (reprint author), Natl Inst Neurol Disroders & Stroke, NIH, Bethesda, MD 20892 USA. EM LandisS@ninds.nih.gov 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2006 VL 9 IS 3 BP 377 EP 378 DI 10.1016/j.yebeh.2006.08.011 PG 2 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 103TR UT WOS:000241910100003 PM 17005452 ER PT J AU Lisk, G Kang, M Cohn, JV Desai, SA AF Lisk, Godfrey Kang, Myungsa Cohn, Jamieson V. Desai, Sanjay A. TI Specific inhibition of the plasmodial surface anion channel by dantrolene SO EUKARYOTIC CELL LA English DT Article ID RED-BLOOD-CELLS; FALCIPARUM-INFECTED ERYTHROCYTES; NICOTINIC ACETYLCHOLINE-RECEPTOR; MALARIA PARASITE; CHLOROQUINE RESISTANCE; CHLORIDE CHANNELS; K+ CHANNEL; PERMEABILITY PATHWAYS; IONIC-STRENGTH; TRANSPORT AB The plasmodial surface anion channel (PSAC), induced on human erythrocytes by the malaria parasite Plasmodium falciparum, is an important target for antimalarial drug development because it may contribute to parasite nutrient acquisition. However, known antagonists of this channel are quite nonspecific, inhibiting many other channels and carriers. This lack of specificity not only complicates drug development but also raises doubts about the exact role of PSAC in the well-known parasite-induced permeability changes. We recently identified a family of new PSAC antagonists structurally related to dantrolene, an antagonist of muscle Ca++ release channels. Here, we explored the mechanism of dantrolene's actions on parasite-induced permeability changes. We found that dantrolene inhibits the increased permeabilities of sorbitol, two amino acids, an organic cation, and hypoxanthine, suggesting a common pathway shared by these diverse solutes. It also produced parallel reductions in PSAC single-channel and whole-cell Cl- currents. In contrast to its effect on parasite-induced permeabilities, dantrolene had no measurable effect on five other classes of anion channels, allaying concerns of poor specificity inherent to other known antagonists. Our studies indicate that dantrolene binds PSAC at an extracellular site distinct from the pore, where it inhibits the conformational changes required for channel gating. Its affinity for this site depends on ionic strength, implicating electrostatic interactions in dantrolene binding. In addition to the potential therapeutic applications of its derivatives, dantrolene's specificity and its defined mechanism of action on PSAC make it a useful tool for transport studies of infected erythrocytes. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009 FU Intramural NIH HHS [Z01 AI000882-07] NR 61 TC 27 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD NOV PY 2006 VL 5 IS 11 BP 1882 EP 1893 DI 10.1128/EC.00212-06 PG 12 WC Microbiology; Mycology SC Microbiology; Mycology GA 110RZ UT WOS:000242398100006 PM 16950925 ER PT J AU Goellner, S Steinbach, D Schenk, T Gruhn, B Zintl, F Ramsay, E Saluz, HP AF Goellner, Stefanie Steinbach, Daniel Schenk, Tino Gruhn, Bernd Zintl, Felix Ramsay, Edward Saluz, Hans P. TI Childhood acute myelogenous leukaemia: Association between PRAME, apoptosis- and MDR-related gene expression SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE AML, acute myelogenous leukaemia; apoptosis; drug resistance; cDNA microarray; differential gene expression ID ACUTE MYELOID-LEUKEMIA; MULTIDRUG-RESISTANCE; CELL-LINES; ANTIGEN; MELANOMA; CASPASES; RECEPTOR; MRP3; IAPS; BAX AB The gene PRAME (preferentially expressed antigen of melanoma) encodes an antigen recognised by autologous cytolytic T lymphocytes. The mRNA level of FRAME is used as a tumour marker due to its overexpression in various malignancies. Furthermore, it is known that the overexpression of genes encoding antiapoptotic proteins leads to the survival of leukaemic cells via exclusion of apoptosis. On the other hand, overexpression of genes encoding ABC transporters may lead to multi drug resistance (MDR). Therefore, we investigated whether there is a relationship between PRAME overexpression and the expression of apoptosis- and MDR-related genes in childhood de nouo acute myelogenous leukaemia (AML) patient samples and, furthermore, whether this is a general or an AML-subtype specific event. Microarray analysis and real time quantitative PCR revealed that clinical samples showing PRAME upregulation are associated with a decreasing expression of genes coding for apoptotic proteins and an overexpression of genes encoding ABC transporters. Our results indicate that patients showing PRAME upregulation may have an increased risk of MDR induction. (c) 2006 Elsevier Ltd. All rights reserved. C1 Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Cell & Mol Biol, D-07745 Jena, Germany. Univ Childrens Hosp, Jena, Germany. NINR, NIH, Bethesda, MD 20892 USA. Univ Childrens Hosp, Ulm, Germany. RP Saluz, HP (reprint author), Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Cell & Mol Biol, Beutenbergstr 11A, D-07745 Jena, Germany. EM Hanspeter.Saluz@hki-jena.de NR 30 TC 17 Z9 17 U1 0 U2 0 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 NOV PY 2006 VL 42 IS 16 BP 2807 EP 2814 DI 10.1016/j.ejca.2006.06.018 PG 8 WC Oncology SC Oncology GA 112CB UT WOS:000242501700031 PM 16978861 ER PT J AU Sissung, TM Mross, K Steinberg, SM Behringer, D Figg, WD Sparreboom, A Mielke, S AF Sissung, Tristan M. Mross, Klaus Steinberg, Seth M. Behringer, Dirk Figg, William D. Sparreboom, Alex Mielke, Stephan TI Association of ABCB1 genotypes with paclitaxel-mediated peripheral neuropathy and neutropenia SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE paclitaxel; polymorphisms; ABCB1; neutropenia; neuropathy ID BLOOD-BRAIN-BARRIER; P-GLYCOPROTEIN; CELLS; GENE; MDR1 AB Here, we evaluated the relationships between ABCB1 (P-glycoprotein, MDR1) polymorphisms and paclitaxel (Taxol)-induced toxicity and pharmacokinetics. Twenty-six patients were assessable for pharmacogenetics and pharmacokinetics, 22 for neurotoxicity and 18 for myelotoxicity. Patients carrying two reference alleles for the ABCB1 3435C > T polymorphism trended toward a reduced risk to develop neuropathy as compared to patients carrying at least one variant allele (P = 0.09). Additionally, patients who were homozygous variant at the 2677 and 3435 loci had a significantly greater percent decrease in absolute neutrophil count at nadir (P = 0.02). Neither polymorphism correlated with paclitaxel pharmacokinetics. This pilot study suggests that paclitaxel-induced neuropathy and neutropenia might be linked to inherited variants of ABCB1 through a mechanism that is unrelated to altered plasma pharmacokinetics. (c) 2006 Elsevier Ltd. All rights reserved. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Univ Freiburg, Tumor Biol Ctr, Freiburg, Germany. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Univ Freiburg, Dept Hematol & Oncol, Freiburg, Germany. RP Sparreboom, A (reprint author), NCI, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room SA01, Bethesda, MD 20892 USA. EM alex.sparreboom@stjude.org RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 14 TC 101 Z9 104 U1 0 U2 5 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 NOV PY 2006 VL 42 IS 17 BP 2893 EP 2896 DI 10.1016/j.ejca.2006.06.017 PG 4 WC Oncology SC Oncology GA 114SO UT WOS:000242686100017 PM 16950614 ER PT J AU Biesecker, L AF Biesecker, Leslie TI The challenges of Proteus syndrome: diagnosis and management SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE overgrowth; mosaicism; macrodactyly; cancer predisposition; thrombophilia ID PTEN MUTATIONS; GERMLINE MUTATION; LETHAL GENES; TUMOR; HEMIHYPERTROPHY; LIPOMATOSIS; CRITERIA; DEATH; SKIN AB Proteus syndrome (PS) is a disorder of patchy or mosaic postnatal overgrowth of unknown etiology. The onset of overgrowth typically occurs in infancy and can involve any tissue of the body. Commonly involved tissues include connective tissue and bone, skin, central nervous system, the eye, but it apparently can affect any tissue. Diagnosing of PS is difficult and the diagnostic criteria are controversial. Our group advocates stringent diagnostic criteria to facilitate research and appropriate clinical care. The benefit of strict criteria is that they define a clinical group that is reasonably homogenous with respect to manifestations and prognosis. The overgrowth of PS is progressive and can be difficult to manage. The progressive overgrowth most commonly causes severe orthopaedic complications, but it can cause many other complications. One of the most common complications in patients with PS is deep venous thrombosis and pulmonary embolism, which can cause premature death. Effective management requires knowledge of the wide array of manifestations and complications of the disorder and a team approach that includes the geneticist, surgeons, and other specialists. C1 NHGRI, Bethesda, MD 20892 USA. RP Biesecker, L (reprint author), NHGRI, Bldg 49 Room 4A80, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov FU Intramural NIH HHS NR 31 TC 95 Z9 100 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2006 VL 14 IS 11 BP 1151 EP 1157 DI 10.1038/sj.ejhg.5201638 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 099FE UT WOS:000241577900004 PM 16883308 ER PT J AU Romieu, I Ramirez-Aguilar, M Sienra-Monge, JJ Moreno-Macias, H del Rio-Navarro, BE David, G Marzec, J Hernandez-Avila, M London, S AF Romieu, I. Ramirez-Aguilar, M. Sienra-Monge, J. J. Moreno-Macias, H. del Rio-Navarro, B. E. David, G. Marzec, J. Hernandez-Avila, M. London, S. TI GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE asthmatic children; glutathione S-transferase M1; glutathione S-transferase P1; lung function; ozone; symptoms ID S-TRANSFERASE M1; ENVIRONMENTAL TOBACCO-SMOKE; LUNG-FUNCTION; ANTIOXIDANT SUPPLEMENTATION; GENETIC POLYMORPHISMS; RISK-FACTORS; MEXICO-CITY; GLUTATHIONE; SUSCEPTIBILITY; CANCER AB Acute exposure to ozone has been related to a wide spectrum of health effects in susceptible individuals. Genetic factors may influence interindividual variation in ozone response. The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress, i.e. glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), and both respiratory symptoms and lung function in response to ozone among childhood asthmatics. A total of 151 asthmatic children, who were participants in a randomised controlled trial of antioxidant vitamin supplementation in Mexico City, were studied. Children were genotyped using PCR methods and followed from October 1998-April 2000. Increases in reported breathing difficulty were associated with ozone exposure in children with GSTM1 null (8%, 95% confidence interval (CI) 1-15%, per 20-ppb increase in 1-h maximum daily average over 7 days) or GSTP1 Valine/Valine (VaI/Val) genotypes (14%,95% CI 5-25%). In children with both GSTM1 null and GSTP1 Val/Val genotypes, the increase in breathing difficulty associated with a 20-ppb increase in ozone exposure was even greater (21%, 95% CI 5-39%). GSTP1 genotypes were not significantly associated with ozone-related lung function changes. In conclusion, asthmatic children with glutathione S-transferase M1 null and glutathione S-transferase P1 Valine/Valine genotypes appear more susceptible to developing respiratory symptoms related to ozone exposure. C1 Inst Nacl Salud Publ, Cuernavaca 62508, Morelos, Mexico. Hosp Infantil Federico Gomez, Mexico City, DF, Mexico. Natl Inst Environm Hlth, Div Intramural Res, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Romieu, I (reprint author), Inst Nacl Salud Publ, 655 Ave Univ,Col Santa Maria Ahuacatitlan, Cuernavaca 62508, Morelos, Mexico. EM iromieu@correo.insp.mx OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES49019] NR 34 TC 88 Z9 90 U1 0 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD NOV PY 2006 VL 28 IS 5 BP 953 EP 959 DI 10.1183/09031936.06.00114905 PG 7 WC Respiratory System SC Respiratory System GA 104XP UT WOS:000241994200013 PM 16870661 ER PT J AU Puppo, P AF Puppo, Paolo TI Complications of transurethral resection of the prostate (TURP) - Incidence, management, and prevention - Editorial comment SO EUROPEAN UROLOGY LA English DT Editorial Material C1 Natl Canc Inst, IST, I-16100 Genoa, Italy. RP Puppo, P (reprint author), Natl Canc Inst, IST, I-16100 Genoa, Italy. EM p.puppo@uinet.it NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD NOV PY 2006 VL 50 IS 5 BP 980 EP 980 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 101AF UT WOS:000241710600024 ER PT J AU Elangbam, CS Wehe, JG Barton, JC Krull, DL Nyska, A Crabbs, T Kissling, GE AF Elangbam, Chandikumar S. Wehe, John G. Barton, Joanna C. Krull, David L. Nyska, Abraham Crabbs, Torrie Kissling, Grace E. TI Evaluation of glycosaminoglycans content and 5-hydroxytryptamine 2B receptor in the heart valves of Sprague-Dawley rats with spontaneous mitral valvulopathy - A possible exacerbation by dl-amphetamine sulfate in Fischer 344 rats? SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE mitral valve; valvulopathy; 5-hydroxytryptamine 2B receptor; anorexigens; dl-amphetamine; quantitative image analysis; Sprague-Dawley rats; Fischer 344 rats ID SEROTONIN 5-HT2B RECEPTORS; FENFLURAMINE-PHENTERMINE; DISEASE; PROLIFERATION; PATHOLOGY; PERGOLIDE; CHILDREN; ECSTASY; AGENTS; DRUGS AB Spontaneous valvulopathy has been described as nodular or segmental thickenings composed of fibromyxoid tissue in the subendocardium of various valve-leaflets in aging rats, but its pathogenesis and significance are incompletely understood. In this study, we examined the 5-hydroxytryptamine 213 receptor (5HT2BR) expression and characterization of extracellular matrix (ECM) components, and related these to the presence of valvulopathy in the mitral valve-leaflet (spontaneous mitral valvulopathy, SMV) of Sprague-Dawley (SD) rats. We also examined hearts from Fischer 344 (F344) rats treated with dl-amphetamine sulfate for 103 weeks to further explore the potential for drug-induced exacerbation of SMV. In SD rats, valve-leaflets with SMV exhibited a greater valve thickness, a higher amount of glycosaminoglycans, a lower amount of collagen and increased number of 5HT2BR-positive cells. Our data on morphology and ECM changes showed a striking similarity between SMV in SD rats and anorexigen-associated valvulopathy in humans, and increased 5HT2BR-positive cells in SMV implies that 5HT2BR may play a role in pathogenesis. Further, increased incidence and severity of SMV in F344 rats by treatment with dl-amphetamine suggest that a drug-induced exacerbation of SMV may exist in rats. However, additional research is needed to confirm a role for 5HT2BR in the pathogenesis of SMV in SD rats, and to further characterize the relationship between dl-amphetamine treatment and exacerbation of SMV in F344 rats. (c) 2006 Elsevier GmbH. All rights reserved. C1 GlaxoSmithKline Inc, Safety Assessment, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Elangbam, CS (reprint author), GlaxoSmithKline Inc, Safety Assessment, Res Triangle Pk, NC 27709 USA. EM chandi.s.elangbam@gsk.com NR 37 TC 16 Z9 17 U1 0 U2 1 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 NOV PY 2006 VL 58 IS 2-3 BP 89 EP 99 DI 10.1016/j.etp.2006.08.001 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 111YS UT WOS:000242492400002 PM 16996724 ER PT J AU Kioi, M Seetharam, S Puri, RK AF Kioi, Mitomu Seetharam, Saraswathy Puri, Raj K. TI N-linked glycosylation of IL-13R alpha 2 is essential for optimal IL-13 inhibitory activity SO FASEB JOURNAL LA English DT Article DE type I cytokine receptor; ECD; allergic and inflammatory diseases; cancer ID RECEPTOR-ALPHA CHAIN; INTERLEUKIN-13 RECEPTOR; SIGNAL-TRANSDUCTION; PSEUDOMONAS EXOTOXIN; EXTRACELLULAR DOMAIN; GLIOMA-CELLS; BINDING; PROTEIN; COMPONENT; CLONING AB A high-affinity receptor for interleukin (IL)-13 (interleukin-13R alpha 2) is over-expressed in disease-related fibroblasts and neoplastic cells and is involved in cancer, allergic, and inflammatory diseases. The extracellular domain of IL-13R alpha 2 (ECD alpha 2) could be cleaved, which serves as a decoy receptor. We have expressed and purified ECD alpha 2 in both Escherichia coli ( E. coli) and mammalian systems as a soluble fragment and studied its biological activities. Although both products of ECD alpha 2 showed IL-13 inhibitory activities, mammalian cell-derived ECD alpha 2 appeared to be superior compared with purified protein from E. coli. When expressed in E. coli, ECD alpha 2 appeared to be a monomer of 42 but a 60 kDa protein when purified from mammalian cells due to heavy glycosylation. The purified glycosylated ECD alpha 2 efficiently inhibited IL-13-induced STAT6 phosphorylation in immune and Hodgkin's lymphoma cell lines, IL-13 binding, and cytotoxicity of IL-13 cytotoxin in various cancer cell lines. The improved potency of mammalian cell-derived ECD alpha 2 was shown over ECD alpha 2/Fc fusion protein. The N-linked glycosylation of ECD alpha 2 was found to be essential for optimal IL-13 inhibitory activity as deglycosylation by PNGase F showed lower activity. ECD alpha 2 did not inhibit IL-4-induced STAT6 phosphorylation, indicating that inhibitory effects of ECD alpha 2 are receptor specific. These results indicate that glycosylated ECD alpha 2 can serve as a potent inhibitor of IL-13 in a variety of conditions in which IL-13 is a key mediator, e. g., pulmonary, allergic, fibrotic, and neoplastic diseases. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, NIH Bldg 29B,Rm 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 41 TC 17 Z9 19 U1 0 U2 0 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 NOV PY 2006 VL 20 IS 13 BP 2378 EP + DI 10.1096/fj.06-5995fje PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 100XD UT WOS:000241702600026 PM 17023392 ER PT J AU Wade, TK Saksena, R Shiloach, J Kovac, P Wade, WF AF Wade, Terri K. Saksena, Rina Shiloach, Joseph Kovac, Pavol Wade, William F. TI Immunogenicity of synthetic saccharide fragments of Vibrio cholerae O1 (Ogawa and Inaba) bound to Exotoxin A SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE Vibrio cholerae; Cholera vaccine; Ogawa O1 LPS; neoglycoconjugates; synthetic oligosaccharide antigens ID METHYL ALPHA-GLYCOSIDE; STAPHYLOCOCCUS-AUREUS TYPE-5; SEROTYPE-OGAWA; CRYSTAL-STRUCTURE; ANTIGENIC DETERMINANT; PROTEIN CARRIER; REPEATING UNIT; POLYSACCHARIDE; LIPOPOLYSACCHARIDE; ANTIBODIES AB Recombinant exotoxin A (rEPA) from Pseudomonas aeruginosa conjugated to Vibrio cholerae O1 serotype-specific polysaccharides (mono-, di- and hexasaccharide) were immunogenic in mice. Monosaccharide conjugates boosted the humoral responses to the hexasaccharide conjugates. Prior exposure to purified Ogawa lipopolysaccharide (LPS) enabled contra-serotype hexasaccharide conjugates to boost the vibriocidal response, but Inaba LPS did not prime for an enhanced vibriocidal response by a contra-serotype conjugate. Prior exposure to the carrier, and priming B cells with the LPS of either serotype, resulted in enhanced vibriocidal titers if the Ogawa hexasaccharides were used, but a diminished response to the Inaba LPS. These studies demonstrate that the 'functional' B cell epitopes on the LPS differ from those of the neoglycoconjugates and that the order of immunization and the serotype of the boosting conjugate can influence the epitope specificity and function of the antisera. C1 Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. NIH, NIDDK, Med Chem Lab, Bethesda, MD 20892 USA. NIH, NIDDK, Biotechnol Unit, Bethesda, MD 20892 USA. RP Wade, TK (reprint author), Dartmouth Coll Sch Med, Dept Microbiol & Immunol, 630W Borwell Bldg, Lebanon, NH 03756 USA. EM william.wade@dartmouth.edu FU Intramural NIH HHS NR 37 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD NOV PY 2006 VL 48 IS 2 BP 237 EP 251 DI 10.1111/j.1574-695X.2006.00143.x PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 094LZ UT WOS:000241242200010 PM 17010106 ER PT J AU Reid, SD Chaussee, MS Doern, CD Chaussee, MA Montgomery, AG Sturdevant, DE Musser, JM AF Reid, Sean D. Chaussee, Michael S. Doern, Christopher D. Chaussee, Michelle A. Montgomery, Alison G. Sturdevant, Daniel E. Musser, James M. TI Inactivation of the group A Streptococcus regulator srv results in chromosome wide reduction of transcript levels, and changes in extracellular levels of Sic and SpeB SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE group A Streptococcus; virulence gene regulation; streptococcal regulator of virulence; Srv; Streptococcus pyogenes ID COMPLETE GENOME SEQUENCE; HYALURONIC-ACID CAPSULE; M-PROTEIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; POPULATION-GENETICS; VIRULENCE FACTORS; RHEUMATIC-FEVER; BINDING PROTEIN; SEROTYPE M3; PYOGENES AB Group A Streptococcus is characterized by the ability to cause a diverse number of human infections including pharyngitis, necrotizing fasciitis, toxic shock syndrome, and acute rheumatic fever, yet the regulation of streptococcal genes involved in disease processes and survival in the host is not completely understood. Genome scale analysis has revealed a complex regulatory network including 13 two-component regulatory systems and more than 100 additional putative regulators, the majority of which remain uncharacterized. Among these is the streptococcal regulator of virulence, Srv, the first Group A Streptococcus member of the Crp/Fnr family of transcriptional regulators. Previous work demonstrated that the loss of srv resulted in a significant decrease in Group A Streptococcus virulence. To begin to define the gene products influenced by Srv, we combined microarray and two-dimensional gel electrophoresis analysis. Loss of srv results in a chromosome wide reduction of gene transcription and changes in the production of the extracellular virulence factors Sic (streptococcal inhibitor of complement) and SpeB (cysteine proteinase). Sic levels are reduced in the srv mutant, whereas the extracellular concentration and activity of SpeB is increased. These data link Srv to the increasingly complex GAS regulatory network. C1 Wake Forest Univ, Sch Med, Dept Immunol & Microbiol, Winston Salem, NC 27157 USA. Univ S Dakota, Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Baylor Coll Med, Ctr Human Bacterial Pathogenesis, Dept Pathol, Houston, TX 77030 USA. RP Reid, SD (reprint author), Wake Forest Univ, Sch Med, Dept Immunol & Microbiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM sreid@wfubmc.edu OI Doern, Christopher/0000-0003-2454-4355 FU NIAID NIH HHS [R01 AI063453-02]; PHS HHS [R01401507] NR 47 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD NOV PY 2006 VL 48 IS 2 BP 283 EP 292 DI 10.1111/j.1574-695X.2006.00150.x PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 094LZ UT WOS:000241242200015 PM 16999824 ER PT J AU Stratton, P AF Stratton, Pamela TI The tangled web of reasons for the delay in diagnosis of endometriosis in women with chronic pelvic pain: will the suffering end? SO FERTILITY AND STERILITY LA English DT Editorial Material ID COMMUNITY; SURGERY AB Understanding the woman's experience with chronic pelvic pain and endometriosis is critical to decreasing her suffering. Further investigation must continue to determine the relation between endometriosis ans pain, despite empirical treatment with GnRH agonists becoming routine in the United States. C1 NICHD, RBMB, NIH, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NICHD, RBMB, NIH, 10 Ctr Dr,MSC 1109,Bldg 10,CRC 1-3140, Bethesda, MD 20892 USA. EM strattop@cc1.nichd.nih.gov FU Intramural NIH HHS NR 17 TC 8 Z9 13 U1 0 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 NOV PY 2006 VL 86 IS 5 BP 1302 EP 1304 DI 10.1016/j.fertnstert.2006.06.044 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 102IL UT WOS:000241804100004 PM 17070184 ER PT J AU Kalantaridou, SN Calis, KA Vanderhoof, VH Bakalov, VK Corrigan, EC Troendle, JF Nelson, LM AF Kalantaridou, Sophia N. Calis, Karim A. Vanderhoof, Vien H. Bakalov, Vladimir K. Corrigan, Emily C. Troendle, James F. Nelson, Lawrence M. TI Testosterone deficiency in young women with 46,XX spontaneous premature ovarian failure SO FERTILITY AND STERILITY LA English DT Article DE free testosterone; total testosterone; premature ovarian failure; sex hormone-binding globulin; equilibrium dialysis; ovarian insufficiency ID SURGICALLY MENOPAUSAL WOMEN; FEMALE SEXUAL DYSFUNCTION; ANDROGEN DEFICIENCY; DEHYDROEPIANDROSTERONE-SULFATE; CIRCULATING ANDROGENS; SERUM TESTOSTERONE; BONE LOSS; INSUFFICIENCY; REPLACEMENT; TRANSITION AB Objective: to determine whether women with 46,XX spontaneous premature ovarian failure have lower serum free-T levels than do control women. Design: Cross-sectional. Setting: National Institutes of Health Clinical Research Center. Patient(s): Women with 46,XX spontaneous premature ovarian failure (n = 130). Intervention(s): Evaluation while off any estrogen therapy and then again after receiving a standardized hormone regimen. Regularity menstruating control women (n = 65) were sampled during the midfollicular phase. Main Outcome Measure(s): Serum total T by RIA after extraction and column chomotography, free T by equilibrium dialysis, and sex hormone-binding globulin by immunoradiometric assay. Result(s): While off estrogen therapy patients had a medium serum free-T concentration that was statistically significantly lower than controls (2.2 vs. 3.3 pg/mL). This dropped significantly lower to 1.9 pg/mL while the patients were on physiologic transdermal E-2 therapy. This is despite the fact that sex hormone-binding globulin levels did not change. While on E-2 therapy, 13% of women (95% confidence interval, 7.9%-20.3%) had serum free-T levels below the lower limit of normal (< 1.1 pg/mL). Conclusion(s): As a group, young woman with 46,XX spontaneous premature ovarian failure have reduced circulating free-T levels, both during an intervel off of estrogen therapy and while on physiologic transdermal E-2 therapy. C1 NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. NICHHD, Biometry & Math Stat Branch, NIH, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH,CRC, 1-330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM lawrence_nelson@nih.gov FU Intramural NIH HHS NR 51 TC 24 Z9 25 U1 2 U2 3 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 NOV PY 2006 VL 86 IS 5 BP 1475 EP 1482 DI 10.1016/j.fertnstert.2006.04.028 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 102IL UT WOS:000241804100033 PM 17070197 ER PT J AU Bonkovsky, HL Naishadham, D Lambrecht, RW Chung, RT Hoefs, JC Nash, SR Rogers, TE Banner, BF Sterling, RK Donovan, JA Fontana, RJ Di Bisceglie, AM Ghany, MG Morishima, C AF Bonkovsky, Herbert L. Naishadham, Deepa Lambrecht, Richard W. Chung, Raymond T. Hoefs, John C. Nash, S. Russell Rogers, Thomas E. Banner, Barbara F. Sterling, Richard K. Donovan, John A. Fontana, Robert J. Di Bisceglie, Adrian M. Ghany, Marc G. Morishima, Chihiro CA HALT-C Trial Grp TI Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID INTERFERON-ALPHA THERAPY; CHRONIC VIRAL-HEPATITIS; LONG-TERM RESPONSE; CONTROLLED-TRIAL; SERUM IRON; HEREDITARY HEMOCHROMATOSIS; GENETIC HEMOCHROMATOSIS; LIVER-DISEASES; RISK-FACTORS; FIBROSIS AB Background & Aims: Iron overload may cause or contribute to hepatic injury and fibrosis. Mutations in the HFE gene may influence development or progression of chronic liver disease by increasing iron stores or modulating immune responses. The aim of this work was to assess the influence of HFE mutations and serum and hepatic measures of iron status on baseline features and response to lead-in therapy in subjects with advanced chronic hepatitis C enrolled in the Hepatitis C Anti-viral Long-term Treatment to prevent Cirrhosis (HALT-C) Trial. Methods: Entry criteria included an Ishak fibrosis score > 2 and lack of iron overload (Scheuer iron grade < 3+) according to local study pathologists. All baseline biopsy specimens were rescored by consensus of study pathologists, and detailed assessment of stainable iron was performed. Hepatic iron concentrations were measured on portions of 144 liver biopsy specimens. A total of 1051 out of 1145 subjects agreed to HFE mutational testing (C282Y, H63D, S65C). Results: Thirty-five percent carried at least one HFE gene mutation. There were no significant differences in the prevalence of HFE gene mutations among subjects with fibrosis (35.5%) versus cirrhosis (32.9%). Thirty-three percent of subjects had end-of-treatment and 16% sustained virologic responses. Presence of HFE mutations, in particular the H63D variation, was associated with increased end-of-treatment (40% vs 29%, P=.0078) and sustained virologic responses (20% with HFE mutation vs 14% sustained virologic response without HFE mutation; P=.009). Conclusions: Although HFE mutations (especially the most frequent H63D mutation) are associated with increased iron loading, they are also associated with increased sustained virologic responses in US patients with advanced chronic hepatitis C. C1 Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT 06030 USA. New England Res Inst, Watertown, MA 02172 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Univ Colorado, Dept Pathol, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO 80202 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75216 USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA. Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. NIDDKD, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Bonkovsky, HL (reprint author), Univ Connecticut, Ctr Hlth, Dept Med, 263 Farmington Ave,MC-1119, Farmington, CT 06030 USA. EM bonkovsky@uchc.edu FU NCRR NIH HHS [M01RR-01066, M01RR-00633, M01RR-00827, M01RR-00042, M01RR-00043, M01RR-00065, M01RR-00051, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2323, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2322, N01-DK-9-2328, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2319, N01-DK-92324, N01-DK-9-2318, N01-DK-9-2325] NR 60 TC 62 Z9 66 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2006 VL 131 IS 5 BP 1440 EP 1451 DI 10.1053/j.gastro.2006.08.036 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 108DR UT WOS:000242221000016 PM 17101320 ER PT J AU Stein, U Arlt, F Walther, W Smith, J Waldman, T Harris, ED Mertins, SD Heizmann, CW Allard, D Birchmeier, W Schlag, PM Shoemaker, RH AF Stein, Ulrike Arlt, Franziska Walther, Wolfgang Smith, Janice Waldman, Todd Harris, Erik D. Mertins, Susan D. Heizmann, Claus W. Allard, David Birchmeier, Walter Schlag, Peter M. Shoemaker, Robert H. TI The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer SO GASTROENTEROLOGY LA English DT Article ID CALCIUM-BINDING PROTEIN; TRANSMEMBRANE TYROSINE PHOSPHATASE; COLORECTAL-CANCER; CARCINOMA-CELLS; FUNCTIONAL INTERACTION; TUMOR PROGRESSION; MTS1 GENE; EXPRESSION; MUTATIONS; PATHWAY AB Background & Aims: Activation of the Wnt/beta-catenin pathway is frequently observed in colorectal cancers. Our aim was to elucidate the impact of gain-of-function beta-catenin on the metastasis-associated gene S100A4 in human colon cancer cell lines and tumors. Methods: We analyzed cell lines hererozygous for gain-of-function and wild-type beta-catenin, and variants homozygous for gain- or loss-of-function mutation in beta-catenin, for S100A4 expression, cell motility, and in vivo metastasis. beta-catenin-mediated S100A4 promoter activation was tested by reporter assays. For human colon carcinomas, S100A4 expression, beta-catenin genotype, and metachronous metastasis were correlated. Results: We identified S100A4 as the most regulated gene by gain-of-function beta-catenin using a 10K microarray. Cell lines with gain-of-function beta-catenin expressed up to 60-fold elevated S100A4 levels, displayed strongly increased migration and invasion in vitro, and induced rnetastasis in mice. S100A4 small interfering RNA, beta-catenin small interfering RNA, or dominant negative T-cell factor (TCF) knocked down S100A4 and blocked biological effects. S100A4 complementary DNA transfection increased migration and invasion. We identified a TCF binding site within the S100A4 promoter and demonstrated the direct binding of heterodimeric beta-cateninnin/TCF complexes. Reporter assays confirmed the beta-catenin-induced S100A4 promoter activity. Furthermore, S100A4 mRNA expression was increased in primary colon cancers, which later developed distant metastases, compared to non-metastasizing tumors. Colon tumors heterozygous for gain-of-function beta-catenin showed concomitant nuclear beta-catenin localization, high S100A4 expression, and metastases. Conclusions: S100A4 is a direct beta-catenin/TCF target, induces migration and invasion in vitro and metastasis in vivo, and has value for prognosis of metastasis formation in colon cancer patients. C1 Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. Robert Rossle Canc Hosp, Dept Surg & Surg Oncol, Berlin, Germany. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD 21701 USA. SAIC, Frederick, MD USA. Univ Zurich, Div Clin Chem & Biochem, Dept Pediat, Zurich, Switzerland. Univ Liverpool, Canc & Polio Fund Labs, Liverpool L69 3BX, Merseyside, England. RP Stein, U (reprint author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13092 Berlin, Germany. EM ustein@mdc-berlin.de NR 56 TC 128 Z9 137 U1 3 U2 11 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 NOV PY 2006 VL 131 IS 5 BP 1486 EP 1500 DI 10.1053/j.gastro.2006.08.041 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 108DR UT WOS:000242221000020 PM 17101323 ER PT J AU Baek, SJ Okazaki, R Lee, SH Martinez, J Kim, JS Yamaguchi, K Mishina, Y Martin, DW Shoieb, A Mcentee, MF Eling, TE AF Baek, Seung Joon Okazaki, Ryuji Lee, Seong-Ho Martinez, Jeanelle Kim, Jong-Sik Yamaguchi, Kiyoshi Mishina, Yuji Martin, David W. Shoieb, Ahmed Mcentee, Michael F. Eling, Thomas E. TI Nonsteroidal anti-inflammatory drug-activated gene-1 over expression in transgenic mice suppresses intestinal neoplasia SO GASTROENTEROLOGY LA English DT Article ID TGF-BETA SUPERFAMILY; COLORECTAL-CANCER CELLS; MACROPHAGE INHIBITORY CYTOKINE; EARLY GROWTH RESPONSE-1; COLON CARCINOGENESIS; MORPHOGENETIC PROTEIN; CRE RECOMBINASE; GAMMA LIGAND; TUMOR-CELLS; DNA-DAMAGE AB Background & Aims: The nonsteroidal anti-inflammatory drug-activated gene (NAG-1) was identified as a proapoptotic, antitumorigenic protein in vitro, induced by many antitumorigenic and chemopreventive drugs including cyclooxygenase inhibitors. However, its antitumorigenic activity has not been elucidated in vivo. Methods: Transgenic mice were generated that ubiquitously overexpress human NAG-1 under the control of a chicken beta-actin promoter (CAG). The NAG-1 transgenic mice (NAG-(Tg+)) were characterized , and then the antitumorigenic activity was evaluated with 2 colorectal carcinogenesis models: chemical induction with azoxymethane and genetic induction using the Apc(Min+) mutation. Results: NAG-(Tg+) showed no apparent phenotype other than a reduction in body weight, particularly in males. To examine whether NAG-1 expression would suppress intestinal tumorigenesis, the NAG(-Tg+) mice were treated with the colorectal carcinogen azoxymethane, NAG-(Tg+) mice developed 50% fewer aberrant crypt foci and no tumors, in comparison with nontransgenic littermates. This result demonstrates that expression of this human protein in vivo can suppress chemically induced carcinogenesis in the colon. The NAG-(Tg+) mice were also crossed with Apc(Min+) mice to determine the effect of the transgene on intestinal polyp formation. NAG-(Tg+) mice heterozygous for the Apc(Min+) mutation had a significantly reduced polyp load (60%) compared with nontransgenic Apc(Min+) littermates. Conclusions: Our results support NAG-1 as an important regulator of intestinal adenoma growth in vivoand suggest that NAG-1 may act as a tumor suppressor gene. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Transgen Mouse Core Facil, Atlanta, GA 30322 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov OI Baek, Seung/0000-0001-7866-7778; McEntee, Michael/0000-0002-1616-3715 FU Intramural NIH HHS; NCI NIH HHS [N02-CB-07008]; NCRR NIH HHS [K26RR016645]; NIEHS NIH HHS [K22ES011657] NR 48 TC 72 Z9 76 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2006 VL 131 IS 5 BP 1553 EP 1560 DI 10.1053/j.gastro.2006.09.015 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 108DR UT WOS:000242221000025 PM 17101328 ER PT J AU Sokolov, MV Smimova, NA Camerini-Otero, RD Neumann, RD Panyutin, IG AF Sokolov, M. V. Smimova, N. A. Camerini-Otero, R. D. Neumann, R. D. Panyutin, I. G. TI Microarray analysis of differentially expressed genes after exposure of normal human fibroblasts to ionizing radiation from an external source and from DNA-incorporated iodine-125 radionuclide SO GENE LA English DT Article DE DNA microarrays; DNA damage; DNA double-strand breaks; auger electron emitters ID DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS; IN-VIVO; BINDING ACTIVITY; TUMOR-CELLS; RESPONSES; RADIOTOXICITY; REPAIR; RADIOTHERAPY; CANCER AB Exposure of cells to ionizing radiation (IR) produces changes in the expression level of a large number of genes. However, less is known of gene-expression changes caused by local radiation exposure from radionuclides within cells. We studied changes in the genome-wide gene expression induced by decay of 125, incorporated into DNA as [I-125]-iododeoxyuridine (I-125-IUdR) in normal IMR-90 human lung fibroblasts and compared them with the changes produced by external gamma-radiation delivered at high (HDR) or low (LDR) dose rate. We found that more than 2000 genes were consistently up- or down-regulated following HDR and LDR gamma-radiation. The profiles of differentially expressed genes following HDR and LDR shared about 64% (up) and 74% (down) genes in common, with many genes identified as radiation-responsive for the first time. In contrast, in all only 206 genes changed their expression level in the I-125-IUdR-treated cells, even though the total number of DNA double-strand breaks (DSB) produced by I-125-IUdR exceeded that produced by the gamma-radiation. With few exceptions, the expression levels of I-125-IUdR-responsive genes were also altered following gamma-irradiation. Therefore, nuclear DNA-localized decays of I-125 produce 10 times fewer differentially expressed genes than whole-cell exposure to gamma-radiation of comparable dose. These results suggest that the effect of IR on the changes in global gene expression depends on the distribution of energy depositions within the cell. In contrast to cell survival, DNA DSB may not be the major factor modulating changes in gene expression following irradiation. (c) 2006 Elsevier B.V. All rights reserved. C1 NIH, Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NIDDKD, NIH, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), NIH, Clin Ctr, Dept Nucl Med, Bldg 10,Room 4D45,9000 Rockville Pike, Bethesda, MD 20892 USA. EM igorp@helix.nih.gov FU Intramural NIH HHS NR 43 TC 34 Z9 35 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 1 PY 2006 VL 382 BP 47 EP 56 DI 10.1016/j.gene.2006.06.008 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 105RQ UT WOS:000242050400006 PM 16876969 ER PT J AU Chi, PB Duggal, P Kao, WHL Mathias, RA Grant, AV Stockton, ML Garcia, JGN Ingersoll, RG Scott, AF Beaty, TH Barnes, KC Fallin, MD AF Chi, Peter B. Duggal, Priya Kao, W. H. Linda Mathias, Rasika A. Grant, Audrey V. Stockton, Maria L. Garcia, Joe G. N. Ingersoll, Roxann G. Scott, Alan F. Beaty, Terri H. Barnes, Kathleen C. Fallin, M. Daniele TI Comparison of SNP tagging methods using empirical data: Association study of 713 SNPs on chromosome 12q14.3-12q24.21 for asthma and total serum IgE in an African Caribbean population SO GENETIC EPIDEMIOLOGY LA English DT Article DE LD blocks; SNP tags; FBAT; association ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; HUMAN GENOME; HAPLOTYPE; GENOTYPE; IDENTIFICATION; STRATEGIES; MARKERS; BLOCKS; GENES AB Few comparison studies have been performed on single nucleotide polymorphism (SNP) tagging methods to examine their consistency and effectiveness in terms of inferences about association with disease. We applied several SNP tagging methods to SNPs on chromosome 12q (n = 713) and compared the utility of these methods to detect association for asthma and serum IgE levels among a sample of African Caribbean families from Barbados selected through asthmatic probands. We found that a high level of information regarding association is retained in Clayton's htSNP, Stram's TagSNP, and de Bakker's Tagger. We also found a high degree of consistency between TagSNP and Tagger. Using this set of 713 SNPs on chromosome 12q, our study provides insight towards analytic strategies for future studies of complex traits. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Sch Med, Div Clin Immunol & Allergy, Dept Med, Baltimore, MD USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Johns Hopkins Sch Med, Div Pulm & Crit Care Med, Dept Med, Baltimore, MD USA. Johns Hopkins Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP Barnes, KC (reprint author), Johns Hopkins Asthma & Allergy Ctr, 3A62A,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM kbarnes@jhmi.edu RI Garcia, Joe/E-8862-2010 FU Intramural NIH HHS; NHLBI NIH HHS [U01 HL 66615]; NIAID NIH HHS [AI 50024-03] NR 34 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2006 VL 30 IS 7 BP 609 EP 619 DI 10.1002/gepi.20172 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 097PU UT WOS:000241461200006 PM 16830339 ER PT J AU Nadler, JJ Zou, F Huang, HW Moy, SS Lauder, J Crawley, JN Threadgill, DW Wright, FA Magnuson, TR AF Nadler, Jessica J. Zou, Fei Huang, Hanwen Moy, Sheryl S. Lauder, Jean Crawley, Jacqueline N. Threadgill, David W. Wright, Fred A. Magnuson, Terry R. TI Large-scale gene expression differences across brain regions and inbred strains correlate with a behavioral phenotype SO GENETICS LA English DT Article ID ADULT-MOUSE BRAIN; FOXP1; CEREBELLUM; MICE AB Behaviors are often highly heritable, polygenic traits. To investigate molecular mediators of behavior, we analyzed gene expression patterns across seven brain regions (amygdala, basal ganglia, cerebellum, frontal cortex, hippocampus, cingulate cortex, and olfactory bulb) of 10 different inbred mouse strains (129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ tf/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and FVB/NJ). Extensive variation was observed across both strain and brain region. These data provide potential transcriptional intermediates linking polygenic variation to differences in behavior. For example, mice from different strains had variable performance on the rotarod task, which correlated with the expression of > 2000 transcripts in the cerebellum. Correlation with this task was also found in the amygdala and hippocampus, but not in other regions examined, indicating the potential complexity of motor coordination. Thus we can begin to identify expression profiles contributing to behavioral phenotypes through variation in gene expression. C1 Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, N Carolina STAART Ctr, Chapel Hill, NC 27599 USA. NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. RP Magnuson, TR (reprint author), Univ N Carolina, Dept Genet, CB 7264,103 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM trm4@med.unc.edu RI Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 FU NICHD NIH HHS [P30 HD003110, 5P30HD003110]; NIMH NIH HHS [U54 MH066418, U54 MH66418] NR 24 TC 55 Z9 55 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2006 VL 174 IS 3 BP 1229 EP 1236 DI 10.1534/genetics.106.061481 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 112NH UT WOS:000242532600014 PM 16980393 ER PT J AU Anderson, RT Wenzel, L Walker, AP Ruggiero, A Acton, RT Hall, MA Tucker, DC Thomson, E Harrison, B Howe, E Holup, J Leiendecker-Foster, C Power, T Adams, P AF Anderson, Roger T. Wenzel, Lari Walker, Ann P. Ruggiero, Andrea Acton, Ronald T. Hall, Mark A. Tucker, Diane C. Thomson, Elizabeth Harrison, Barbara Howe, Edmund, III Holup, Joan Leiendecker-Foster, Catherine Power, Tara Adams, Paul TI Impact of hemochromatosis screening in patients with indeterminate results: The hemochromatosis and iron overload screening study SO GENETICS IN MEDICINE LA English DT Article DE hemochromatosis; screening; acceptance; ethics; primary care; HEIRS ID LONG-TERM SURVIVAL; HEREDITARY HEMOCHROMATOSIS; PRIMARY-CARE; CANCER SUSCEPTIBILITY; PSYCHOLOGICAL IMPACT; HUNTINGTONS-DISEASE; OVARIAN-CANCER; POPULATION; DISTRESS; HEALTH AB Purpose: Assess the quality of life impact of receiving indeterminate test results for hemochromatosis, a disorder involving HFE genetic mutations and/or elevated serum transferrin saturation and ferritin. Methods: The study sample was from the Hemochromatosis and Iron Overload Screening Study, a large observational study of hemochromatosis among primary care patients in the US and Canada using HFE genotype and serum transferrin saturation and ferritin screening. Study subjects included 2,304 patients found with hemochromatosis risk of uncertain clinical significance. Assessed was SF-36 general health and emotional well-being before screening and six weeks after participants received their test results. Health worries were assessed after screening. Results: Of the study subjects, 1,268 participants (51.5%) completed both assessments. Compared to normal controls, those with HFE mutations or elevated serum transferrin saturation and ferritin levels of uncertain significance were more likely to report diminished general health and mental well-being, and more health worries. These effects were associated with participants' belief of having tested positive for hemochromatosis or iron overload. Conclusion: Notification of indeterminate results from screening may be associated with mild negative effects on well-being, and might be a potential participant risk in screening programs for disorders with uncertain genotype-phenotype. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Univ Calif Irvine, Dept Med, Ctr Hlth Policy Res, Irvine, CA 92717 USA. Univ Calif Irvine, Ctr Med, Dept Pediat, Irvine, CA 92717 USA. Univ Alabama, Dept Microbiol, Div Human Genet, Birmingham, AL USA. Univ Alabama, Dept Epidemiol & Int Hlth, Div Human Genet, Birmingham, AL USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. NHGRI, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth, Dept Psychiat, Bethesda, MD USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Western Ontario, Dept Psychol, London, ON, Canada. RP Anderson, RT (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. NR 47 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV PY 2006 VL 8 IS 11 BP 681 EP 687 DI 10.1097/01.gim.0000245631.07117.ac PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 108LD UT WOS:000242240400002 PM 17108759 ER PT J AU Tang, JR Robertson, S Lem, KE Godwin, SC Kaler, SG AF Tang, Jingrong Robertson, Stephen Lem, Kristen E. Godwin, Sarah C. Kaler, Stephen G. TI Functional copper transport explains neurologic sparing in Occipital Horn syndrome SO GENETICS IN MEDICINE LA English DT Article ID LYSYL OXIDASE ACTIVITY; SPLICE-SITE MUTATIONS; DISEASE GENE HOMOLOG; MENKES-DISEASE; ATP7A GENE; SACCHAROMYCES-CEREVISIAE; CANDIDATE GENE; IRON UPTAKE; EXPRESSION; ENCODES AB Objective: A range of neurologic morbidity characterizes childhood-onset copper transport defects, including severe Menkes disease and milder occipital horn syndrome. Both phenotypes are caused by mutations in ATP7A, which encodes a copper-transporting adenosine triphosphatase, although defects causing occipital horn syndrome are rarely reported and nearly always involve exon-skipping (six of eight prior reports). Our objective was to characterize a novel occipital horn syndrome mutation (N1304S) not associated with aberrant splicing and to determine whether functional copper transport was associated with this allele. Methods: We studied two brothers with typical occipital horn syndrome and used yeast complementation and timed growth assays, exploiting a Saccharomyces cerevisiae mutant strain, to assess in vitro N1304S copper transport. Results: We documented that N1304S has approximately 33% residual copper transport, a result not inconsistent with a similar patient we reported with an exon-skipping mutation whose cells showed correctly spliced mRNA transcripts 36% of normal. Conclusion: These patients' mild neurologic phenotypes, together with our yeast complementation and growth experiments, imply that N1304S does not completely block copper transport to the developing brain early in life. The findings suggest that neurologic sparing in untreated occipital horn syndrome is associated with approximately 30% residual functional activity of ATP7A. C1 NICHHD, Unit Pediat Genet, Lab Clin Genet, NIH, Bethesda, MD 20892 USA. Dunedin Sch Med, Dept Pediat & Child Hlth, Dunedin, New Zealand. RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Lab Clin Genet, NIH, Bldg 10,Room 5-2571,10 Ctr Dr MSC 1832, Bethesda, MD 20892 USA. NR 41 TC 28 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV PY 2006 VL 8 IS 11 BP 711 EP 718 DI 10.1097/01.gim.0000245578.94312.le PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 108LD UT WOS:000242240400006 PM 17108763 ER PT J AU Hanover, JA AF Hanover, John A. TI Deciphering the 'O-GlcNAc code': Lessons from C. elegans and human disease SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 3 BP 1105 EP 1105 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300012 ER PT J AU Gerken, TA Jamison, O Ten Hagen, KG AF Gerken, Thomas A. Jamison, Oliver Ten Hagen, Kelly G. TI The mammalian and Drosophila orthologous UDP-GalNAc: Polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAc-Ts) T1 and T2 possess highly conserved peptide substrate specificities SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 14 BP 1107 EP 1107 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300022 ER PT J AU Tian, E Ten Hagen, KG AF Tian, E. Ten Hagen, Kelly G. TI A mucin-type O-glycosyltransferase is required during multiple stages of Drosophila development SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 22 BP 1108 EP 1108 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300030 ER PT J AU Huizing, M Klootwijk, R Galeano, B Manoli, I Sun, MS Ciccone, C Darvish, D Krasnewich, D Gahl, WA AF Huizing, Marjan Klootwijk, Riko Galeano, Belinda Manoli, Irini Sun, Mao-Sen Ciccone, Carla Darvish, Daniel Krasnewich, Donna Gahl, William A. TI N-acetylmannosamine treatment rescues a mouse model of hereditary inclusion body myopathy SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 NHGRI, NIH, Bethesda, MD 20892 USA. HIBM Res Grp, Encino, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 35 BP 1110 EP 1111 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300043 ER PT J AU Forsythe, ME Love, DC Kim, EJ Lazarus, BC Prinz, W Ashwell, G Krause, MW Hanover, JA AF Forsythe, Michele E. Love, Dona C. Kim, Eun Ju Lazarus, Brooke C. Prinz, William Ashwell, Gilbert Krause, Michael W. Hanover, John A. TI Disruption of O-GlcNAc cycling mimics diabetes mellitus in C-elegans SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 77 BP 1118 EP 1118 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300083 ER PT J AU Zhang, L Ten Hagen, KG AF Zhang, Liping Ten Hagen, Kelly G. TI Dissecting the biological role of mucin type O-glycosylation using RNA interference in Drosophila cell culture SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 153 BP 1133 EP 1133 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300159 ER PT J AU Zhang, Y Ten Hagen, K AF Zhang, Ying Ten Hagen, Kelly G. TI In vivo functional studies of the UDP-GalNAc: Polypeptide Nacetylgalactosaminyltransferases in Drosophila melanogaster SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 154 BP 1133 EP 1133 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300160 ER PT J AU Azurmendi, HF Wrightson, L Trinh, LB Shiloach, J Freedberg, DI AF Azurmendi, Hugo F. Wrightson, Lauren Trinh, Loc B. Shiloach, Joseph Freedberg, Daron I. TI Pathogen antigens probed by on-cell solution NMR SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 CBER, FDA, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 180 BP 1138 EP 1138 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300186 ER PT J AU Manoli, I Sparks, S Rakocevic, G Joe, G Shrader, J Sonies, B Dorward, H Ciccone, C Krasnewich, D Huizing, M Dalakas, M AF Manoli, Irini Sparks, Susan Rakocevic, Goran Joe, Galen Shrader, Joseph Sonies, Barbara Dorward, Heidi Ciccone, Carla Krasnewich, Donna Huizing, Marjan Dalakas, Marinos TI Intravenous immune globulin treatment for hereditary inclusion body myopathy: A pilot study SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 NHGRI, MGB, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NIH, RMD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 228 BP 1147 EP 1147 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300234 ER PT J AU Liu, M Borgert, A Ten Hagen, K Barany, G Live, D AF Liu, Mian Borgert, Andrew Ten Hagen, Kelly Barany, George Live, David TI A structural role for O-GalNAc protein glycosylation in alpha-dystroglycan SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 Univ Minnesota, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 237 BP 1149 EP 1149 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300243 ER PT J AU Tenno, M Ohtsubo, K Hagen, FK Tabak, LA Marth, JD AF Tenno, Mari Ohtsubo, Kazuaki Hagen, Fred K. Tabak, Lawrence A. Marth, Jamey D. TI O-glycosylation by polypeptide GalNAcT-1 directs tissue-specific lymphocyte retention, enables normal thrombosis, and sustains both humoral and innate immunity SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 Univ Calif San Diego, HHMI, La Jolla, CA 92093 USA. Univ Rochester, Rochester, NY 14627 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 296 BP 1160 EP 1161 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300302 ER PT J AU Fitzpatrick, MA Funk, MC Gius, D Huettner, PC Zhang, ZY Bidder, M Ma, DD Powell, MA Rader, JS AF Fitzpatrick, Margaret A. Funk, Margo C. Gius, David Huettner, Phyllis C. Zhang, Zhengyan Bidder, Miri Ma, Duanduan Powell, Matthew A. Rader, Janet S. TI Identification of chromosomal alterations important in the development of cervical intraepithelial neoplasia and invasive carcinoma using alignment of DNA microarray data SO GYNECOLOGIC ONCOLOGY LA English DT Article DE CIN; cervical cancer; microarray; gene expression; chromosomal loss and gain ID COMPARATIVE-GENOMIC-HYBRIDIZATION; GENE-EXPRESSION PROFILES; UTERINE CERVIX; IN-SITU; CANCER; PROGRESSION; DELETIONS; HETEROZYGOSITY; CARCINOGENESIS; VISUALIZATION AB Objective. To use microarray data to reveal regions of potential chromosomal loss or gain important in cervical intraepithelial neoplasia (CIN) and invasive cervical cancer by identifying mRNA expression biases in contiguous chromosomal regions. Methods. Data from three RNA expression microarray experiments were used: one primary experiment using cDNA arrays profiling gene expression in cervical epithelium from viral cytopathic effect to invasive cancer, one experiment using Affymetrix arrays profiling gene expression in invasive cancerous cervical epithelium, and one experiment using Affymetrix arrays profiling gene expression in CIN cervical biopsy specimens. Gene expression was aligned along chromosomes to reveal regions of significant chromosomal imbalance. Regions showing significant gain or loss and verified in more than one experiment are presented here. RT-PCR was performed to validate expression of one gene in a region. Results. Gain of 3q was detected from the CIN II (P = 0.018), CIN III (P = 0.005), and invasive cancer (P = 0.0002) cDNA arrays, and gain of 12q was detected from the CIN (P = 0.05) and invasive cancer (P = 0.05) Affymetrix arrays. Loss of 6p was detected from the CIN III (P = 0.004) cDNA arrays and invasive cancer (P = 0.05) Affymetrix arrays. Loss of 4q was detected from the invasive cancer (P = 0.04) cDNA arrays and invasive cancer (P = 0.05) Affymetrix arrays. RAN, located in the region of gain on 12q24.3, was overexpressed in CIN and invasive cancer. Conclusions. Alignment of microarray expression data by chromosomes can be used to estimate regions of potential chromosomal aberration and identify differentially expressed genes important in the development of CIN and invasive cancer. (c) 2006 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Washington Univ, Dept Genet, St Louis, MO 63110 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Rader, JS (reprint author), Washington Univ, Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, 660 S Euclid Ave,Campus Box 8064, St Louis, MO 63110 USA. EM RADERJ@MSNOTES.WUSTL.EDU FU Intramural NIH HHS; NCI NIH HHS [P30 CA91842, CA094141, CA82722]; NHLBI NIH HHS [2 T35 HL007815-10]; NIDDK NIH HHS [DK51612] NR 28 TC 14 Z9 14 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 NOV PY 2006 VL 103 IS 2 BP 458 EP 462 DI 10.1016/j.ygyno.2006.03.020 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 101SA UT WOS:000241759600014 PM 16647105 ER PT J AU Maxwell, GL Schildkraut, JM Calingaert, B Risinger, JI Dainty, L Marchbanks, PA Berchuck, A Barrett, JC Rodriguez, GC AF Maxwell, G. L. Schildkraut, J. M. Calingaert, B. Risinger, J. I. Dainty, L. Marchbanks, P. A. Berchuck, A. Barrett, J. C. Rodriguez, G. C. TI Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Gynecologic-Oncologists CY FEB 07-11, 2004 CL San Diego, CA SP Soc Gynecol Oncol DE endometrial cancer; oral contraceptives ID OVARIAN-CANCER; OVERWEIGHT; CARCINOMA; OBESITY; WOMEN AB Objective. Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. Methods. Subjects included 434 endometrial cancer cases and 2557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. Results. With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m(2) or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m(2) did not (OR=1.36, 95% CI=0.39 to 4.70). Conclusion. The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus. Published by Elsevier Inc. C1 Walter Reed Army Med Ctr, Div Gynecol Oncol, Washington, DC 20307 USA. US Mil Canc Inst, Washington, DC 20307 USA. Duke Univ, Med Ctr, Dept Family & Community Med, Div Canc Control, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Gynecol Oncol, Durham, NC 27710 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30333 USA. Northwestern Univ, Evanston NW Healthcare, Div Gynecol Oncol, Evanston, IL 60201 USA. RP Maxwell, GL (reprint author), Walter Reed Army Med Ctr, Div Gynecol Oncol, 6900 Georgia Ave, Washington, DC 20307 USA. EM george.maxwell@na.amedd.arymy.mil FU NICHD NIH HHS [3-Y01-HD-8-1037] NR 20 TC 31 Z9 33 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2006 VL 103 IS 2 BP 535 EP 540 DI 10.1016/j.ygyno.2006.03.046 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 101SA UT WOS:000241759600028 PM 16740300 ER PT J AU Wang, SS Sherman, ME Silverberg, SG Carreon, JD Lacey, JV Zaino, R Kurman, RJ Hildesheim, A AF Wang, Sophia S. Sherman, Mark E. Silverberg, Steven G. Carreon, Joseph D. Lacey, James V., Jr. Zaino, Richard Kurman, Robert J. Hildesheim, Allan TI Pathological characteristics of cervical adenocarcinoma in a multi-center US-based study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervix; adenocarcinoma; adenosquamous; in situ; subtype; pathology; histology ID SQUAMOUS-CELL CARCINOMAS; UTERINE CERVIX; UNITED-STATES; EARLY-STAGE; ENDOCERVICAL ADENOCARCINOMA; ORAL-CONTRACEPTIVES; PROGNOSTIC-FACTORS; RISK-FACTORS; SURVIVAL; POPULATION AB Objective. Difficulties in detecting cervical adenocarcinoma early are well known. We report a detailed pathology review of cervical adenocarcinoma subtypes, comparing growth patterns and appearance of non-neoplastic epithelium to inform possible clues for disease progression and early detection. Methods. This analysis includes 154 women aged 18-69 years and diagnosed with incident in situ or invasive adenocarcinoma (AC), adenosquamous (AS), or other rare cervical glandular tumors from 1992-1996 in six U.S. medical centers. A pathology review panel evaluated histological features from original diagnostic slides. Results. Higher turner grade (P < 0.001) and vascular invasion (P = 0.002) were more common in AS compared to AC. Adenocarcinoma in situ (AIS) was also more common among AC than AS (P = 0.002). Among AC with cervical intraepithelial carcinoma (CIN), AIS and cribriform patterns were more common than AC without CIN (P = 0.01). Further, non-endometrioid AC had higher tumor grade (P = 0.01) and stromal responses (P = 0.02) than endometrioid AC. Finally, although microglandular hyperplasia is historically thought to be related to oral contraceptive (OC) use, our data do not support this notion. Conclusion(s). AS appears to be either diagnosed later or histologically more aggressive than AC, and among AC subtypes, there are distinct histologic characteristics. Further research is needed to identify precursor lesions for early detection of AC and particularly for AS where AIS may not be a common precursor. Published by Elsevier Inc. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Rockville, MD 20852 USA. Univ Maryland, Baltimore, MD 21201 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Pathol, Hershey, PA 17033 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Obstet, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. RP Wang, SS (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, 6120 Execut Blvd,Room 7072, Rockville, MD 20852 USA. EM wangso@mail.nih.gov NR 32 TC 19 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2006 VL 103 IS 2 BP 541 EP 546 DI 10.1016/j.ygyno.2006.03.049 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 101SA UT WOS:000241759600029 PM 16697450 ER PT J AU Farley, J Birrer, MJ Christian, MC AF Farley, John Birrer, Michael J. Christian, Michaele C. TI The future of phase II trials SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT Ovarian Cancer State of the Science Meeting CY SEP 15-17, 2005 CL Rockville, MD SP AstraZeneca, Cti, Eli Lilly & Co, MGi Pharma, OSI Pharmacrut, NCI Office Ctr, Training, & Resources, & Gynecol Oncol Grp, Sanofi Aventis Pharmaceut, TriPath Imaging Inc, ABRAXIS Oncol, Cell Therapeut Inc AB Topics: How to complete phase II trials faster; stratification of patients in phase II trials, response end points; competition between NCI-sponsored and industry-sponsored phase II trials for patients. C1 Tripler Army Med Ctr, Div Gynecol Oncol, Honolulu, HI 96859 USA. NCI, Cell & Canc Biol Dept, Med Branch, Ctr Canc Res, Rockville, MD 20850 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Farley, J (reprint author), Tripler Army Med Ctr, Div Gynecol Oncol, 1 Jarrett White Rd, Honolulu, HI 96859 USA. EM john.farley@us.army.mil 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2006 VL 103 IS 2 SU 1 BP S20 EP S22 DI 10.1016/j.ygyno.2006.08.021 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 102XZ UT WOS:000241848200006 PM 17027074 ER PT J AU Farley, J Bast, RC Birrer, MJ AF Farley, John Bast, Robert C., Jr. Birrer, Michael J. TI Biomarkers and clinical trial design SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT Ovarian Cancer State of the Science Meeting CY SEP 15-17, 2005 CL Rockville, MD SP AstraZeneca, Cti, Eli Lilly & Co, MGi Pharma, OSI Pharmacrut, NCI Office Ctr, Training, & Resources, & Gynecol Oncol Grp, Sanofi Aventis Pharmaceut, TriPath Imaging Inc, ABRAXIS Oncol, Cell Therapeut Inc DE gynecologic; malignancies; biologic therapy ID GENE-EXPRESSION PROFILES; OVARIAN-CANCER; CLEAR-CELL AB Topics: Relevant biomarkers for the stratification of patients with ovarian cancer, prognostic markers, predictive markers, surrogate markers, tissue banking needs, core laboratories for multi-institutional trials, future trial design Phase II and Phase III. C1 NCI, Ctr Canc Res, Cell & Canc Biol Dept, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. RP Birrer, MJ (reprint author), NCI, Ctr Canc Res, Cell & Canc Biol Dept, 37 Convent Dr, Bethesda, MD 20892 USA. EM birrerm@bprb.nci.nih.gov RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 6 TC 2 Z9 2 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 NOV PY 2006 VL 103 IS 2 SU 1 BP S3 EP S5 DI 10.1016/j.ygyno.2006.08.017 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 102XZ UT WOS:000241848200002 PM 17027069 ER PT J AU Trimble, EL Alvarez, RD AF Trimble, Edward L. Alvarez, Ronald D. TI Intraperitoneal chemotherapy and the NCI clinical announcement SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT Ovarian Cancer State of the Science Meeting CY SEP 15-17, 2005 CL Rockville, MD SP AstraZeneca, Cti, Eli Lilly & Co, MGi Pharma, OSI Pharmacrut, NCI Office Ctr, Training, & Resources, & Gynecol Oncol Grp, Sanofi Aventis Pharmaceut, TriPath Imaging Inc, ABRAXIS Oncol, Cell Therapeut Inc ID EPITHELIAL OVARIAN-CANCER; THERAPY AB Topics: Integrating IP/IV regimens into Phase III clinical trials for women with stage III disease, novel approaches, new agents and combinations. C1 NCI, Div Canc Treatment & Diagnosis, Bethesda, MD USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35249 USA. RP Trimble, EL (reprint author), NCI, Canc Therapy Evaluat Program, 6130 Execut Blvd,Ste 741,MSC 7436, Bethesda, MD 20892 USA. EM tt6m@nih.gov NR 9 TC 24 Z9 24 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 NOV PY 2006 VL 103 IS 2 SU 1 BP S18 EP S19 DI 10.1016/j.ygyno.2006.08.020 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 102XZ UT WOS:000241848200005 PM 17027073 ER PT J AU Trimble, EL Fountain, J Birrer, MJ AF Trimble, Edward L. Fountain, Jane Birrer, Michael J. TI Proceedings from the 2005 Ovarian Cancer State of the Science Meeting - Introduction SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material C1 NCI, Ctr Canc Res, Cell & Canc Biol Dept, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), NCI, Ctr Canc Res, Cell & Canc Biol Dept, 37 Convent Dr, Bethesda, MD 20892 USA. EM birrerm@bprb.nci.nih.gov NR 0 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 NOV PY 2006 VL 103 IS 2 SU 1 BP S1 EP S1 DI 10.1016/j.ygyno.2006.08.016 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 102XZ UT WOS:000241848200001 ER PT J AU Trimble, EL Fountain, J Birrer, MJ AF Trimble, Edward L. Fountain, Jane Birrer, Michael J. TI Summary and discussion of session recommendations SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material DE ovarian cancer; clinical trials recruitment; clinical trials design; clinical trials endpoints; CA-125; intraperitoneal therapy C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Cell & Canc Biol Dept, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, Canc Therapy Evaluat Program, 6130 Execut Blvd,Ste 741,MSC 7436, Bethesda, MD 20892 USA. EM tt6m@nih.gov; birrerm@bprb.nci.nih.gov NR 0 TC 1 Z9 1 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 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2006 VL 103 IS 2 SU 1 BP S23 EP S25 DI 10.1016/j.ygyno.2006.08.022 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 102XZ UT WOS:000241848200007 ER PT J AU Ginsburg, M Goold, SD Danis, M AF Ginsburg, Marjorie Goold, Susan Dorr Danis, Marion TI (De)constructing 'basic' benefits: Citizens define the limits of coverage SO HEALTH AFFAIRS LA English DT Article ID BENEFICIARIES; PRIORITIES; MEDICARE; CARE AB Many initiatives for covering the uninsured call for "basic" health care coverage, yet few define that term. The Just Coverage project used a computer-based simulation exercise to learn how nearly 800 community members in northern California identified the inclusions and exclusions that would constitute basic coverage. Working with a limited budget, participants distinguished essential from nonessential health care needs, resisted high patient cost sharing, and tolerated tight restrictions on provider choice. They also supported practice guidelines and standards of effectiveness, and they excluded high-cost, low-value interventions. These results reinforce the importance of community input to policymakers. C1 Sacramento Healthcare Decis, Rancho Cordova, CA USA. Univ Michigan, Sch Med, Bioeth Program, Ann Arbor, MI USA. NIH, Sect Eth & Hlth Policy, Bethesda, MD 20892 USA. RP Ginsburg, M (reprint author), Sacramento Healthcare Decis, Rancho Cordova, CA USA. EM ginsburg@sacdecisions.org NR 9 TC 7 Z9 7 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2006 VL 25 IS 6 BP 1648 EP 1655 DI 10.1377/hlthaff.25.6.1648 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 105MD UT WOS:000242033300025 PM 17102190 ER PT J AU Pollak, KI Baucom, DH Peterson, BL Stanton, S McBride, CA AF Pollak, Kathryn I. Baucom, Donald H. Peterson, Bercedis L. Stanton, Susan McBride, Colleen A. TI Rated helpfulness and partner-reported smoking cessation support across the pregnancy-postpartum continuum SO HEALTH PSYCHOLOGY LA English DT Article DE smoking cessation; pregnancy; social support; couple's reports; trends over pregnancy-postpartum continuum ID SOCIAL SUPPORT; SELF-EFFICACY; RELAPSE; WOMEN; MAINTENANCE; ABSTINENCE; INTERVENTIONS; PREDICTORS; PROGRAM; GENDER AB Support interventions have not changed smoking cessation rates significantly. The pregnancy-postpartum continuum presents a unique opportunity to examine patterns of support. Expectant couples (N = 477) were surveyed twice during pregnancy and 3 times postpartum. Partners reported positive and negative smoking-specific support; women reported the helpfulness of partner support. Linear trends suggest that women viewed support as more helpful during pregnancy than during postpartum. Partners' provision of positive support across the continuum depended on their smoking; provision of negative support depended on women's smoking. Partners who smoked provided lower levels of both positive and negative support, especially postpartum. Women who smoked throughout the pregnancy perceived their partner's negative support as helpful. Implications are that partners who smoke may need help staying engaged in the support process. Partners may provide negative support in response to women's smoking cues. Women who are struggling with cessation may not view negative support as negative. C1 Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27706 USA. NCI, Social & Behav Res Branch, NHGRI, Bethesda, MD 20892 USA. RP Pollak, KI (reprint author), Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, 2424 Erwin Rd,Suite 602, Durham, NC 27705 USA. EM kathryn.pollak@duke.edu FU NCI NIH HHS [R01CA76945, R01CA89053, R01CA100387] NR 34 TC 10 Z9 10 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 2006 VL 25 IS 6 BP 762 EP 770 DI 10.1037/0278-6133.25.6.762 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 107PO UT WOS:000242183700011 PM 17100504 ER PT J AU Calderon, A Derr, A Stagner, BB Johnson, KR Martin, G Noben-Trauth, K AF Calderon, Alfredo Derr, Adam Stagner, Barden B. Johnson, Kenneth R. Martin, Glen Noben-Trauth, Konrad TI Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler (jc) mutant mouse SO HEARING RESEARCH LA English DT Article DE Jackson circler; hearing loss; vestibular deficits; cochlea malformation; genetic background ID PRODUCT OTOACOUSTIC EMISSIONS; ENLARGED VESTIBULAR AQUEDUCT; BRAIN-STEM RESPONSE; INNER-EAR; PENDRED-SYNDROME; MODIFIER GENES; JERKER MOUSE; MICE; STEREOCILIA; MUTATIONS AB Jackson circler (jc) is a spontaneous, recessive mouse mutation that results in circling behavior and an impaired acoustic startle response. In this study, we refined the phenotypic and genetic parameters of the original jc mutation and characterized a new mutant allele, jc(2J). In open-field behavior tests, homozygous jc mutants exhibited abnormal circling and ambulatory behavior that was indistinguishable from that of phenotypically similar mutants with defects in the vestibule of the inner ear. The jc/jc and jc(2J)/jc(2J) mice had stable elevated auditory-evoked brainstem response (ABR) thresholds at the 16 kHz stimulus of 88 +/- 9 dB sound pressure levels (SPL) and 43 +/- 11 dB SPL, respectively. Peak latencies and peak time intervals were normal in jc mutants. The jc mice showed no measurable distortion-product otoacoustic emissions (DPOAEs) above the system noise floor. In the mutant cochlea, the apical turn failed to form due to the developmental growth arrest of the cochlear duct at the level of the first turn at gestational day 13.5. In a large intrasubspecific intercross, jc localized to a 0.2cM interval at position 25cM on chromosome 10, which is homologous to the human 6q21 region. On CZECHII/Ei and CAST/Ei backgrounds jc/jc mutant hearing thresholds at the 16 kHz stimulus were significantly lower than those observed on the C57BL/6J background, with means of 62 +/- 22 dB SPL and 55 +/- 18 dB SPL, respectively. Genome-wide linkage scans of backcross, intercross, and congenic progeny revealed a complex pattern of genetic and stochastic effects. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDOCD, Neurogenet Sect, Inst Mol Biol, Rockville, MD 20850 USA. Jerry L Pettis Mem Vet Adm Med Ctr, Loma Linda, CA 92357 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Noben-Trauth, K (reprint author), NIDOCD, Neurogenet Sect, Inst Mol Biol, 5 Res Court, Rockville, MD 20850 USA. EM nobentk@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [DC 003114, DC 04301, DC 000613] NR 60 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD NOV PY 2006 VL 221 IS 1-2 BP 44 EP 58 DI 10.1016/j.heares.2006.07.008 PG 15 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 105RT UT WOS:000242050700005 PM 16962269 ER PT J AU Peters, MG Andersen, J Lynch, P Liu, T Alston-Smith, B Brosgart, CL Jacobson, JM Johnson, VA Poflard, RB Rooney, JF Sherman, KE Swindells, S Polsky, B AF Peters, Marion G. Andersen, Janet Lynch, Patrick Liu, Tun Alston-Smith, Beverly Brosgart, Carol L. Jacobson, Jeffrey M. Johnson, Victoria A. Poflard, Richard B. Rooney, James F. Sherman, Kenneth E. Swindells, Susan Polsky, Bruce CA ACTG Protocol A5127 Team TI Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127 SO HEPATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY; DISOPROXIL FUMARATE; IN-VITRO; LAMIVUDINE; DIPIVOXIL; ANTIGEN; RECOMMENDATIONS; INDIVIDUALS; COMBINATION; PREVALENCE AB Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in subjects coinfected with HIV. Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are licensed for the treatment of HIV-1 and HBV infection, respectively, but both have in vivo and in vitro activity against HBV. This study evaluated the anti-HBV activity of TDF compared to ADV in HIV/HBV-coinfected subjects. ACTG A5127 was a prospective randomized, double-blind, placebo-controlled trial of daily 10 mg of ADV versus 300 mg of TDF in subjects with HBV and HIV coinfection on stable ART, with serum HBV DNA >= 100,000 copies/mL, and plasma HIV-1 RNA:5 10,000 copies/mL. This study closed early based on results of a prespecified interim review, as the primary noninferiority end point had been met without safety issues. Fifty-two subjects were randomized. At baseline, 73% of subjects had a plasma HIV-1 RNA < 50 copies/mL, 86% were HBeAg positive, 94% were 3TC resistant, median serum ALT was 52 IU/L, and 98% had compensated liver disease. The mean time-weighted average change in serum HBV DNA from baseline to week 48 (DAVG(48)) was -4.44 log(10) copies/mL for TDF and -3.21 log(10) copies/mL for ADV. There was no difference in toxicity between the 2 treatment arms, with 11 subjects (5 ADV and 6 TDF) experiencing elevations of serum ALT on treatment. In conclusion, over 48 weeks, treatment with either ADV or TDF resulted in clinically important suppression of serum HBV DNA. Both drugs arc safe and efficacious for patients coinfected with HBV and HIV. C1 Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Chicago, IL USA. NIAID, NIH, AIDS Clin Trials Grp, Bethesda, MD USA. Gilead Sci Inc, Foster City, CA USA. Beth Israel Med Ctr, New York, NY 10003 USA. Albert Einstein Coll Med, New York, NY USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham Sch Med, Birmingham, AL USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Nebraska, Ctr Med, Omaha, NE 68198 USA. St Lukes Roosevelt Hosp, Div Infect Dis, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Peters, MG (reprint author), Univ Calif San Francisco, Div Gastroenterol, 513 Parnassus Ave,Room S-357, San Francisco, CA 94143 USA. EM marion.perers@ucsf.edu FU NCRR NIH HHS [M01-RR00096, RR-00052, RR00046, RR00047, RR00051]; NIAID NIH HHS [AI25915, 3U01AI38858-09S1, AI-27668, AI25868, AI32770, AI32782, AI38855, AI46370, AI46386, AI50410, P30 AI027767, P30 AI27767, U01 AI038855, U01 AI038858, U01 AI069502, U01AI38858]; NIDDK NIH HHS [P30 DK 26743, P30 DK026743]; PHS HHS [5 UO1 A1027665-18] NR 25 TC 111 Z9 123 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2006 VL 44 IS 5 BP 1110 EP 1116 DI 10.1002/hep.21388 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099IH UT WOS:000241586400006 PM 17058225 ER PT J AU Murray, JM Purcell, RH Wieland, SF AF Murray, John M. Purcell, Robert H. Wieland, Stefan F. TI The half-life of hepatitis B virions SO HEPATOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DYNAMICS IN-VIVO; VIRAL DYNAMICS; REVERSE-TRANSCRIPTASE; TRANSGENIC MICE; CLEARANCE; INFECTION; LAMIVUDINE; THERAPY; CELLS AB The virion half-life of hepatitis B virus (HBV) is currently estimated at approximately 1 day. This estimate has been obtained from drug perturbation experiments with reverse transcriptase inhibitors. However, the analyses of those experiments have not considered the export of virions produced from preformed mature DNA-containing HBV capsids in infected cells. Data from 3 acutely infected chimpanzees indicates that there is approximately 10-fold more total intracellular HBV DNA than HBV DNA in blood, and therefore the half-life of virions for chimpanzees during acute infection is 10-fold shorter at 3.8 hours than the half-life associated with export of total intracellular HBV DNA. Mathematical model simulations duplicating the viral dynamics observed in drug perturbation experiments suggest a half-life of at most 4.4 hours for HBV virions in chronically infected humans, significantly shorter than current estimates, but consistent with the half-lives of virions for hepatitis C virus and HIV. This faster turnover of HBV in blood indicates a correspondingly higher replication rate and risk of mutation against hepatitis B antiviral therapy. In conclusion, we find the half-life of HBV virions is approximately 4 hours, significantly shorter than current estimates of 1 day. This new value is consistent with virion half-life estimates for HIV and hepatitis C virus. C1 Univ New S Wales, Sch Math, Sydney, NSW 2052, Australia. Natl Ctr HIV Epidemol & Clin Res, Darlinghurst, NSW 2010, Australia. NIAID, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Murray, JM (reprint author), Univ New S Wales, Sch Math, Sydney, NSW 2052, Australia. EM J.Murray@unsw.edu.au RI Murray, John/B-5481-2009 OI Murray, John/0000-0001-9314-2283 FU Intramural NIH HHS; NIAID NIH HHS [AI20001] NR 22 TC 39 Z9 46 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2006 VL 44 IS 5 BP 1117 EP 1121 DI 10.1002/hep.21364 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099IH UT WOS:000241586400007 PM 17058221 ER PT J AU Moon, KH Hood, BL Kim, BJ Hardwick, JP Conrads, TP Veenstra, TD Song, BYJ AF Moon, Kwan-Hoon Hood, Brian L. Kim, Bong-Jo Hardwick, James P. Conrads, Thomas P. Veenstra, Timothy D. Song, Byoung J. TI Inactivation of oxidized and S-nitrosylated mitochondrial proteins in alcoholic fatty liver of rats SO HEPATOLOGY LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; NITRIC-OXIDE; DEPENDENT HEPATOTOXICITY; ALDEHYDE DEHYDROGENASE; CYTOCHROME-P450 CYP2E1; HEPATIC MITOCHONDRIA; ETHANOL-CONSUMPTION; NITROSATIVE STRESS; OXIDATIVE STRESS; MOUSE-LIVER AB Increased oxidative/nitrosative stress is a major contributing factor to alcohol-mediated mitochondrial dysfunction. However, which mitochondrial proteins are oxidatively modified under alcohol-induced oxidative/nitrosative stress is poorly understood. The aim of this study was to systematically investigate oxidized and/or S-nitrosylated mitochondrial proteins and to use a biotin-N-maleimide probe to evaluate their inactivation in alcoholic fatty livers of rats. Binge or chronic alcohol exposure significantly elevated nitric oxide, inducible nitric oxide synthase, and ethanol-inducible CYP21. The biotin-N-maleimide-labeled oxidized and/or S-nitrosylated mitochondrial proteins from pair-fed controls or alcohol-fed rat livers were subsequently purified with streptavidin-agarose. The overall patterns of oxidized and/or S-nitrosylated proteins resolved by 2-dimensional polyacrylamide gel electrophoresis were very similar in the chronic and binge alcohol treatment groups. Seventy-nine proteins that displayed differential spot intensities from those of control rats were identified by mass spectrometry. These include mitochondrial aldehyde dehydrogenase 2 (ALDH2), ATP synthase, acyl-CoA dehydrogenase, 3-ketoacyl-CoA thiolase, and many proteins involved in chaperone activity, mitochondrial electron transfer, and ion transport. The activity of 3-ketoacyl-CoA thiolase involved in mitochondrial beta-oxidation of fatty acids was significantly inhibited in alcohol-exposed rat livers, consistent with hepatic fat accumulation, as determined by biochemical and histological analyses. Measurement of activity and immunoblot results showed that ALDH2 and ATP synthase were also inhibited through oxidative modification of their cysteine or tyrosine residues in alcoholic fatty livers of rats. (In conclusion) under bar our results help to explain the underlying mechanism for mitochondrial dysfunction and increased susceptibility to alcohol-mediated liver damage. C1 NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD USA. Northeastern Ohio Univ Coll Med & Pharm, Dept Microbiol Immunol & Biochem, Rootstown, OH 44272 USA. RP Song, BYJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bjs@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 50 TC 83 Z9 83 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 NOV PY 2006 VL 44 IS 5 BP 1218 EP 1230 DI 10.1002/hep.21372 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099IH UT WOS:000241586400016 PM 17058263 ER PT J AU Landis, CS Yamanouchi, K Zhou, HC Mohan, S Roy-Chowdhury, N Shafritz, DA Koretsky, A Roy-Chowdhury, J Hetherington, HP Guha, C AF Landis, Charles S. Yamanouchi, Kosho Zhou, Hongchao Mohan, Sankar Roy-Chowdhury, Namita Shafritz, David A. Koretsky, Alan Roy-Chowdhury, Jayanta Hetherington, Hoby P. Guha, Chandan TI Noninvasive evaluation of liver repopulation by transplanted hepatocytes using P-31 MRS imaging in mice SO HEPATOLOGY LA English DT Article ID DIRECTED GENE-TRANSFER; FREE ADP LEVELS; CREATINE-KINASE; IN-VIVO; TRANSGENIC MICE; MARKER GENE; MOUSE-LIVER; RAT; EXPRESSION; THERAPY AB Flepatocyte transplantation (HT) is being explored as a substitute for liver transplantation for the treatment of liver diseases. For the clinical application of HT, a preparative regimen that allows preferential proliferation of transplanted cells in the host liver and a noninvasive method to monitor donor cell engraftment, proliferation, and immune rejection would be useful. We describe an imaging method that employs the creatine kinase (CK) gene as a marker of donor hepatocytes. Creatine kinase is unique among marker genes, because it is normally expressed in brain and muscle tissues and is therefore not immunogenic. Preferential proliferation of transplanted CK-expressing hepatocytes was induced by preparative hepatic irradiation and expression of hepatocyte growth factor using a recombinant adenoviral vector. CK is normally not expressed in mouse liver and its expression by the donor cells led to the production of phosphocreatine in the host liver, permitting (31)p magnetic resonance spectroscopic imaging of liver repopulation by engrafted hepatocytes. In conclusion, this study combined a noninvasive imaging technique to assess donor hepatocyte proliferation with a preparative regimen of partial liver irradiation that allowed regional repopulation of the host liver. Our results provide groundwork for future development of clinical protocols for HT. C1 Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiat Oncol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. Albert Einstein Coll Med, Magnet Resonance Res Ctr, Bronx, NY 10467 USA. Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Bronx, NY 10467 USA. NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Hetherington, HP (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiat Oncol, 111 E 210 St, Bronx, NY 10467 USA. EM hhether@aecom.yu.edu; cguhamd@pol.net RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS003047-01]; NIDDK NIH HHS [5 R01-DK 46057-07, DK-P30-41296, R01-DK064670-01] NR 37 TC 20 Z9 25 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2006 VL 44 IS 5 BP 1250 EP 1258 DI 10.1002/hep.21382 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099IH UT WOS:000241586400019 PM 17058269 ER PT J AU Kuiken, C Combet, C Bukh, J Shin-I, T Deleage, G Mizokami, M Richardson, R Sablon, E Yusim, K Pawlotsky, JM Simmonds, P AF Kuiken, Carla Combet, Christophe Bukh, Jens Shin, Tadasu, I Deleage, Gilbert Mizokami, Masashi Richardson, Russell Sablon, Envin Yusim, Karina Pawlotsky, Jean-Michel Simmonds, Peter CA Los Alamos HIV database grp TI A comprehensive system for consistent numbering of HCV sequences, proteins and epitopes SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; CHIMPANZEE C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Univ Lyon 1, IBCP, UMR5086, CNRS, F-69365 Lyon, France. BioSci Lyon Gerland, IFR128, Lyon, France. Univ Paris 12, Hop Henri Mondor, Dept Virol, F-94010 Creteil, France. Univ Paris 12, Hop Henri Mondor, INSERM U635, F-94010 Creteil, France. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD USA. Hvidovre Univ Hosp, Dept Infect Dis, Copenhagen, Denmark. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi, Japan. Innogenet NV, Ghent, Belgium. Univ Edinburgh, Ctr Infect Dis, Edinburgh, Midlothian, Scotland. RP Kuiken, C (reprint author), Los Alamos Natl Lab, MS K710, Los Alamos, NM 87545 USA. EM Kuiken@lanl.gov RI DELEAGE, Gilbert/F-7163-2010; OI Foley, Brian/0000-0002-1086-0296; Korber, Bette/0000-0002-2026-5757 FU PHS HHS [Y1-A1-1500] NR 9 TC 62 Z9 65 U1 0 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 NOV PY 2006 VL 44 IS 5 BP 1355 EP 1361 DI 10.1002/hep.21377 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099IH UT WOS:000241586400030 PM 17058236 ER PT J AU Kim, YM Romero, R Chaiworapongsa, T Espinoza, J Mor, G Kim, CJ AF Kim, Y. M. Romero, R. Chaiworapongsa, T. Espinoza, J. Mor, G. Kim, C. J. TI Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Toll-like receptors in epidermal keratinocytes SO HISTOPATHOLOGY LA English DT Article DE chorioamnionitis; dermatitis; fetal dermatitis; fetal inflammatory response syndrome; fetal skin; keratinocytes; Toll-like receptors ID PRETERM PARTURITION; AMNIOTIC CAVITY; MICROBIAL INVASION; UMBILICAL-CORD; EXPRESSION; TERM; INTERLEUKIN-6; LESIONS; TOLL-LIKE-RECEPTOR-2; CHORIOAMNIONITIS AB Microbial invasion of the amniotic cavity (MIAC) elicits a fetal inflammatory response such as funisitis and chorionic vasculitis. However, little is known about the changes of fetal skin during MIAC. Toll-like receptors recognize microbial products and initiate an immune response. The aims of this study were to examine histopathological features of fetal skin exposed to MIAC and to assess the changes in Toll-like receptor (TLR)-2 and TLR-4 expression. Skin samples were obtained from fetal autopsies (n = 12). The cases were classified according to the presence (n = 8) or absence (n = 4) of acute chorioamnionitis and analysed by immunohistochemistry using a panel of antibodies. Leucocytic infiltrates into the superficial dermis were observed in cases with chorioamnionitis; the majority of inflammatory cells were neutrophils, lymphocytes and histiocytes. TLR-2 immunoreactivity in the skin was stronger in fetuses with chorioamnionitis than in those without this condition. However, immunoreactivity of TLR-4 in the fetal skin was constitutively expressed, regardless of the presence or absence of chorioamnionitis. This study demonstrates for the first time that fetal dermatitis can be detected and is part of the fetal inflammatory response syndrome (FIRS). We propose that this 'FIRS-associated fetal dermatitis' is a fetal counterpart of chorioamnionitis. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NICHD, Perinatol Res Branch, NIH, DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS,Hutzel Womens Hosp, 3990 John R 4 Brush, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov; cjki@med.wayne.edu FU Intramural NIH HHS NR 31 TC 55 Z9 57 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD NOV PY 2006 VL 49 IS 5 BP 506 EP 514 DI 10.1111/j.1365-2559.2006.02542.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 098MI UT WOS:000241524800007 PM 17064297 ER PT J AU Insel, TR AF Insel, Thomas R. TI Translational research in the decade of discovery - Foreword SO HORMONES AND BEHAVIOR LA English DT Editorial Material ID AROUSAL C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, 6001 Execut Blvd,Room 8235, Bethesda, MD 20892 USA. EM insel@mail.nih.gov FU Intramural NIH HHS [001-1364-225, Z99 MH999999] NR 11 TC 4 Z9 4 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 0018-506X J9 HORM BEHAV JI Horm. Behav. PD NOV PY 2006 VL 50 IS 4 BP 504 EP 505 DI 10.1016/j.yhbeh.2006.06.024 PG 2 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 089GV UT WOS:000240869500002 PM 16916514 ER PT J AU Zheng, CY Goldsmith, CM Mineshiba, F Chiorini, JA Kerr, A Wenk, ML Vallant, M Irwin, RD Baum, BJ AF Zheng, Changyu Goldsmith, Corinne M. Mineshiba, Fumi Chiorini, John A. Kerr, Andrew Wenk, Martin L. Vallant, Molly Irwin, Richard D. Baum, Bruce J. TI Toxicity and biodistribution of a first-generation recombinant adenoviral vector, encoding aquaporin-1, after retroductal delivery to a single rat submandibular gland SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; QUALITY-OF-LIFE; SALIVARY-GLANDS; NONHUMAN-PRIMATES; NECK RADIOTHERAPY; PAROTID-GLANDS; IN-VIVO; SAFETY; HEAD; THERAPY AB Before conducting a phase 1/2 clinical trial of a serotype 5 adenovirus encoding human aquaporin-1 (AdhAQP1) for the treatment of radiation-damaged salivary glands, we have conducted a detailed toxicity and biodistribution study in adult rats. AdhAQP1 (2 x 10(8)-2 x 10(11) particles) was delivered to a single submandibular gland by retroductal cannulation. Administration of this vector resulted in no animal mortality or morbidities, and no adverse signs of clinical toxicity. In addition, over the 92-day time course of the study, with both male and female rats, there were no consistent treatment-related changes in serum indicators of hepatic, renal, and cardiac functions. Importantly, we also observed no vector-associated effects on either water consumption by, or hematocrit levels in, study animals. However, three suggestive mild gender-related response differences were seen. Female, but not male, rats exhibited small reductions in food consumption (similar to 10-15%) and body weight gain (5-10%), and evidence of persistent inflammation, after vector treatment. These were vector, but not dose, related. Three days after delivery of 2 x 10(11) particles of AdhAQP1, vector was detected primarily in the targeted gland; 9 of 10 samples from the targeted gland were positive, whereas only 5 of 90 nonoral samples were positive. There was no evidence of the generation of replication-competent adenovirus in saliva or blood samples. In aggregate, these findings show that localized delivery of AdhAQP1 to salivary glands appears to occur without significant toxicity. C1 NIDCR, GTTB, DHHS, NIH, Bethesda, MD 20892 USA. BioReliance Invitrogen Bioserv, Div Toxicol, Rockville, MD 20850 USA. NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, DHHS, NIH, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [N01-ES-75408] NR 29 TC 27 Z9 29 U1 3 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2006 VL 17 IS 11 BP 1122 EP 1133 DI 10.1089/hum.2006.17.1122 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 108AE UT WOS:000242211300006 PM 17069536 ER PT J AU Seth, P Wang, ZG Pister, A Zafar, MB Kim, S Guise, T Wakefield, L AF Seth, Prem Wang, Zhen-Guo Pister, Amanda Zafar, M. Behzad Kim, Sung Guise, Theresa Wakefield, Lalage TI Development of oncolytic adenovirus armed with a fusion of soluble transforming growth factor-beta receptor II and human immunoglobulin Fc for breast cancer therapy SO HUMAN GENE THERAPY LA English DT Article ID BONE METASTASES; GENE-THERAPY; EPITHELIAL-CELLS; TUMOR-CELLS; PROGRESSION; SUPPRESSOR; EXPRESSION; P27(KIP1); MUTANT; AGENTS AB We have developed an approach to cancer gene therapy in which the oncolytic effects of an adenoviral vector have been combined with selective expression of a soluble form of transforming growth factor (TGF)-beta receptor II fused with Fc (sTGF beta RIIFc). We chose to use adenoviral dl01/07 mutant because it can replicate in all cancer cells regardless of their genetic defects. An oncolytic adenovirus expressing sTGF beta RIIFc (Ad.sT beta RFc) was constructed by homologous recombination. Infection of MDA-MB-231 and MCF-7 human breast cancer cells with Ad.sT beta RFc produced sTGF beta RIIFc, which was released into the media. The conditioned media containing sTGF beta RIIFc could bind with TGF-beta(1) and inhibited TGF-beta-dependent transcription in target cells. Infection of MDA-MB-231, MCF-7, and 76NE human breast cancer cells with Ad.sT beta RFc resulted in high levels of viral replication, comparable to that of a wild-type dl309 virus. Although some viral replication was observed in actively dividing normal human lung fibroblasts, there was no replication in nonproliferating normal cells. Direct injection of Ad.sT beta RFc into MDA-MB-231 human breast xenograft tumors grown in nude mice resulted in a significant inhibition of tumor growth, causing tumor regression in more than 85% of the animals. These results indicate that it is possible to construct an oncolytic virus expressing sTGF beta RIIFc in which both viral replication and transgene expression remain intact, and the recombinant adenovirus is oncolytic in a human tumor xenograft model. On the basis of these results we believe that it may be feasible to develop a cancer gene therapy approach using Ad.sT beta RFc as an antitumor agent. C1 Evanston NW Healthcare Res Inst, Gene Therapy Program, Evanston, IL 60201 USA. Northwestern Univ, Evanston Hosp, Dept Med, Evanston, IL 60201 USA. Univ Virginia, Dept Internal Med, Div Endocrinol & Metab, Charlottesville, VA 22908 USA. NCI, Tumor Suppressor Grp, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Seth, P (reprint author), ENH Res Inst, 2650 Ridge Ave,Room B 624, Evanston, IL 60201 USA. EM pseth@northwestern.edu FU NCI NIH HHS [R21 CA11288-01] NR 36 TC 24 Z9 24 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2006 VL 17 IS 11 BP 1152 EP 1160 DI 10.1089/hum.2006.17.1152 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 108AE UT WOS:000242211300009 PM 17032151 ER PT J AU Rosenberg, S Templeton, AR Feigin, PD Lancet, D Beckmann, JS Selig, S Hamer, DH Skorecki, K AF Rosenberg, Shai Templeton, Alan R. Feigin, Paul D. Lancet, Doron Beckmann, Jacques S. Selig, Sara Hamer, Dean H. Skorecki, Karl TI The association of DNA sequence variation at the MAOA genetic locus with quantitative behavioural traits in normal males SO HUMAN GENETICS LA English DT Article DE monoamine oxidase A (MAOA); behavioural traits; quantitative trait loci; genetic association; population structure ID MONOAMINE-OXIDASE-A; PHENOTYPIC ASSOCIATIONS; CLADISTIC-ANALYSIS; HUMAN-GENOME; POLYMORPHISM; POPULATIONS; SEROTONIN; ADMIXTURE; DISORDER; MEDICINE AB Monoamine oxidase A (MAOA) catalyses the oxidative deamination of biogenic amines including neurotransmitters, mainly norepinephrine and serotonin in the brain and peripheral tissues. A nonsense mutation in the gene was shown to be involved in a rare X-linked behavioural syndrome, which includes impaired impulse control, aggression and borderline mental retardation (Brunner syndrome). Several recent studies have shown the association of genetic variation of a VNTR in the gene promoter with various pathological behavioural traits. In the present study the association of MAOA genetic variation with a large set of quantitative behavioural traits in normal individuals has been examined. DNA samples from 421 unrelated males were genotyped for 14 SNPs and for the promoter VNTR at the MAOA locus. An additional 16 SNPs were genotyped at apparently neutral loci across the X chromosome to serve as a genomic control for possible false positive associations due to population structure. Behavioural traits were measured using the NEO psychometric questionnaire, which is based on a 5-axis model of personality, and consists of 30 different quantitative traits. There was a robust association of the A2 ("straightforwardness") facet with common allelic variants at the promoter VNTR. Most of the tested traits were not associated with the VNTR despite reasonable power, thus demonstrating that the VNTR influence on quantitative behavioural traits in normal males may be very specific. In contrast, several traits of the C ("conscientiousness") axis were associated with less common SNP-defined haplotypes. Hence, it appears that common genetic variation at the VNTR contributes to the behavioural attribute of "straightforwardness", while rare haplotypes defined by SNPs downstream of the transcription start site may contribute to "conscientiousness". This study is used to address the validation, interpretation and limitation of genetic association studies of quantitative behavioural traits. C1 Technion Israel Inst Technol, Rappaport Fac Med, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel. Washington Univ, Dept Biol, St Louis, MO 63130 USA. Technion Israel Inst Technol, William Davidson Fac Ind Engn & Management, IL-32000 Haifa, Israel. Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Crown Human Genome Ctr, IL-76100 Rehovot, Israel. Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland. CHU Vaudois, Dept Med Genet, CH-1011 Lausanne, Switzerland. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Rambam Med Ctr, Dept Nephrol & Mol Med, IL-31096 Haifa, Israel. RP Rosenberg, S (reprint author), Technion Israel Inst Technol, Rappaport Fac Med, 1 Efron St, IL-31096 Haifa, Israel. EM rozenber@tx.technion.ac.il; skorecki@tx.technion.ac.il RI Beckmann, Jacques S /A-9772-2008; Templeton, Alan/F-5963-2011 OI Beckmann, Jacques S /0000-0002-9741-1900; NR 40 TC 17 Z9 18 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2006 VL 120 IS 4 BP 447 EP 459 DI 10.1007/s00439-006-0198-x PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 102DT UT WOS:000241791900001 PM 16896926 ER PT J AU Flanagan, JM Gerber, AL Cadet, JL Beutler, E Sipe, JC AF Flanagan, Jonathan M. Gerber, Alexandra L. Cadet, Jean Lud Beutler, Ernest Sipe, Jack C. TI The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an ancient missense mutation and validation of risk for drug addiction SO HUMAN GENETICS LA English DT Article ID HUMAN EVOLUTIONARY HISTORY; ENZYME; FAAH; POPULATIONS; ANANDAMIDE; INHIBITORS AB The human fatty acid amide hydrolase (FAAH) missense mutation c.385 C -> A, which results in conversion of a conserved proline residue to threonine (P129T), has been associated with street drug use and problem drug abuse. Although a link between the FAAH P129T variant and human drug abuse has been reported, the extent of risk and specific types of substance addiction vulnerability remain to be determined. Here, we investigated the relationship of the FAAH P129T variant to a number of linked single nucleotide polymorphisms to establish a haplotyping system, calculate the estimated age and origin of the FAAH 385 C -> A mutation and evaluate its association with clinically significant drug addiction in a case control study. The results showed a significant over-representation of the FAAH P129T homozygotes in 249 subjects with documented multiple different drug addictions compared to drug free individuals of the same ethnic backgrounds (P = 0.05) using logistic regression analysis controlling for ethnicity. To increase the logistic regression analysis power by increasing the sample size, the data from our previous study (Sipe et al. in Proc Natl Acad Sci USA 99:8394-8399, 2002) were pooled with the present cohort which increased the significance to P = 0.00003. Investigation of the FAAH chromosomal backgrounds of the P129T variant in both multiple different drug addicted and control subjects revealed a common ancestral haplotype, marked population differences in haplotype genetic diversity and an estimated P129T mutation age of 114,425-177,525 years. Collectively, these results show that the P129T mutation is the only common mutation in the FAAH gene and is significantly associated with addictive traits. Moreover, this mutation appears to have arisen early in human evolution and this study validates the previous link between the FAAH P129T variant and vulnerability to addiction of multiple different drugs. C1 Scripps Res Inst, Dept Mol & Expt Med, MEM215, La Jolla, CA 92037 USA. NIDA, Mol Neuropsychiat Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Sipe, JC (reprint author), Scripps Res Inst, Dept Mol & Expt Med, MEM215, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM jcsipe@scripps.edu RI Flanagan, Jonathan/C-2279-2009 FU Intramural NIH HHS; NIDA NIH HHS [DA015749-01] NR 22 TC 41 Z9 45 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2006 VL 120 IS 4 BP 581 EP 588 DI 10.1007/s00439-006-0250-x PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 102DT UT WOS:000241791900012 PM 16972078 ER PT J AU Oji, V Hautier, JM Ahvazi, B Hausser, I Aufenvenne, K Walker, T Seller, N Steijlen, PM Kuster, W Hovnanian, A Hennies, HC Traupe, H AF Oji, Vinzenz Hautier, Juliette Mazereeuw Ahvazi, Bijan Hausser, Ingrid Aufenvenne, Karin Walker, Tatjana Seller, Natalia Steijlen, Peter M. Kuester, Wolfgang Hovnanian, Alain Hennies, Hans Christian Traupe, Heiko TI Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECESSIVE CONGENITAL ICHTHYOSIS; CORNIFIED CELL-ENVELOPE; LAMELLAR ICHTHYOSIS; KERATINOCYTE TRANSGLUTAMINASE; GENETIC-HETEROGENEITY; HARLEQUIN ICHTHYOSIS; 1 MUTATIONS; MILD FORM; TGM1; ERYTHRODERMA AB Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by pronounced scaling on the bathing suit areas but sparing of the extremities and the central face. Here we report on a series of 10 BSI patients. Our genetic, ultrastructural and biochemical investigations show that BSI is caused by transglutaminase-1 (TGase-1) deficiency. Altogether, we identified 13 mutations in TGM1-among them seven novel missense mutations and one novel nonsense mutation. Structural modeling for the Tyr276Asn mutation reveals that the residue is buried in the hydrophobic interior of the enzyme and that the hydroxyl side chain of Tyr276 is exposed to solvent in a cavity of the enzyme. Cryosections of healthy skin areas demonstrated an almost normal TGase activity, in contrast to the affected BSI skin, which only showed a cytoplasmic and clearly reduced TGase-1 activity. The distribution of TGase-1 substrates in the epidermis of affected skin corresponded to the situation in TGase-1 deficiency. Interestingly, the expression of TGase-3 and cathepsin D was reduced. Digital thermography validated a striking correlation between warmer body areas and presence of scaling in patients suggesting a decisive influence of the skin temperature. In situ TGase testing in skin of BSI patients demonstrated a marked decrease of enzyme activity when the temperature was increased from 25 to 37 degrees C. We conclude that BSI is caused by TGase-1 deficiency and suggest that it is a temperature-sensitive phenotype. C1 Univ Munster, Dept Dermatol, D-48149 Munster, Germany. Hop Rangueil, Dept Dermatol, Toulouse, France. NIAMSD, Xray Crystallog Facil, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany. Univ Maastricht, Dept Dermatol, Maastricht, Netherlands. TOMESA Clin Dermatol, Bad Salzschlirf, Germany. INSERM, U563, F-31300 Toulouse, France. Univ Toulouse 3, F-31400 Toulouse, France. Univ Cologne, Cologne Ctr Genom, Div Dermatogenet, Cologne, Germany. RP Oji, V (reprint author), Univ Munster, Dept Dermatol, Von Esmarch Str 56, D-48149 Munster, Germany. EM ojiv@uni-muenster.de OI Oji, Vinzenz/0000-0003-1380-4828 NR 49 TC 34 Z9 34 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2006 VL 15 IS 21 BP 3083 EP 3097 DI 10.1093/hmg/ddl249 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 097EP UT WOS:000241430000001 PM 16968736 ER PT J AU Aggarwal, VS Liao, J Bondarev, A Schimmang, T Lewandoski, M Locker, J Shanske, A Campione, M Morrow, BE AF Aggarwal, Vimla S. Liao, Jun Bondarev, Alexei Schimmang, Thomas Lewandoski, Mark Locker, Joseph Shanske, Alan Campione, Marina Morrow, Bernice E. TI Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy SO HUMAN MOLECULAR GENETICS LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; CARDIAC OUTFLOW TRACT; ANTERIOR HEART FIELD; VERTEBRATE DEVELOPMENT; CARDIOVASCULAR DEVELOPMENT; PLACODE INDUCTION; PHARYNGEAL ARCH; NEURAL CREST; OTIC PLACODE; MUTANT MICE AB The 22q11 deletion syndrome (22q11DS) is characterized by abnormal development of the pharyngeal apparatus. Mouse genetic studies have identified Tbx1 as a key gene in the etiology of the syndrome, in part, via interaction with the fibroblast growth factor (Fgf) genes. Three murine Fgfs, Fgf3, Fgf8 and Fgf10 are coexpressed in different combinations with Tbx1. They are all strongly downregulated in Tbx1-/- embryos, implicating epistatic interactions. Supporting this, Tbx1 and Fgf8 have been shown to genetically interact in the development of the fourth pharyngeal arch artery (PAA) and Fgf10 was identified to be a direct downstream target of Tbx1. To dissect the epistatic relationships of these genes during embryonic development and the molecular pathogenesis of the Tbx1 mutant phenotype, we generated Fgf10+/-;Tbx1+/- and Fgf3-/-;Tbx1+/- mice. Despite strong hypotheses that Fgf10 is the key gene downstream of Tbx1 in the development of the anterior heart field, we do not find evidence for genetic interaction between Tbx1 and Fgf10. Also, the Fgf3-/-;Tbx1+/- mutant mice do not show an additive phenotype. Furthermore, more severe defects do not occur in Fgf8+/-;Tbx1+/- mutants by crossing in the Fgf3 null allele. There is a possible additive effect only in PAA remodeling in the Fgf10+/-;Tbx1+/-;Fgf8+/- embryos. Our findings underscore the importance of potential functional redundancy with additional Fgfs in the development of the pharyngeal apparatus and cardiovascular system via Tbx1. This redundancy should be considered when looking at individual FGF genes as modifiers of 22q11DS. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Super Res Council, Inst Mol Biol & Genet, E-47003 Valladolid, Spain. Univ Valladolid, E-47003 Valladolid, Spain. Frederick Canc Res & Dev Ctr, Genet Vertebrate Dev Sect, NCI, Frederick, MD 21702 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. CHAM, Ctr Craniofacial Disorders, Bronx, NY 10467 USA. Univ Padua, CNR, Inst Neurosci, Dept Biomed Sci, Padua, Italy. RP Morrow, BE (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM morrow@aecom.yu.edu RI Campione, Marina/G-9001-2013 FU NIDCD NIH HHS [R01DC05186-03] NR 68 TC 27 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2006 VL 15 IS 21 BP 3219 EP 3228 DI 10.1093/hmg/ddl399 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 097EP UT WOS:000241430000012 PM 17000704 ER PT J AU Oh, KS Khan, SG Jaspers, NGJ Raams, A Ueda, T Lehmann, A Friedmann, PS Emmert, S Gratchev, A Lachlan, K Lucassan, A Baker, CC Kraemer, KH AF Oh, Kyu-Seon Khan, Sikandar G. Jaspers, N. G. J. Raams, Anja Ueda, Takahiro Lehmann, Alan Friedmann, Peter S. Emmert, Steffen Gratchev, Alexi Lachlan, Katherine Lucassan, Anneke Baker, Carl C. Kraemer, Kenneth H. TI Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): Xeroderma pigmentosum without and with Cockayne syndrome SO HUMAN MUTATION LA English DT Article DE DNA repair; TFIIH; transcription; neurodegeneration; skin cancer; XPB; ERCC3 ID REPAIR/TRANSCRIPTION FACTOR TFIIH; EXCISION-REPAIR; TRANSCRIPTION GENE; GROUP-A; TRICHOTHIODYSTROPHY; MUTATIONS; DISORDERS; SITE; POLYMORPHISMS; DEFICIENCY AB Defects in the xeroderma pigmentosum type B (XPB) gene (ERCC3), a DNA helicase involved in nucleotide excision repair (NER) and an essential subunit of the basal transcription factor, TFIIH, have been described in only three families. We report three new XPB families: one has two sisters with relatively mild xeroderma pigmentosum (XT) symptoms not previously associated with XPB mutations and two have severe XP/Cockayne syndrome (CS) complex symptoms. All XP-B cells had reduced NER and post,ultraviolet (UV) cell viability. Surprisingly, cells from the milder XP sisters had the same missense mutation (c.296T > C, p.F99S) that was previously reported in two mild XP/CS complex brothers. These cells had higher levels of XTB protein than the severely affected XP/CS complex patients. An XTB expression vector with the p.F99S mutation partially complemented the NER defect in XP-B cells. The three severely affected XP/CS complex families all have the same splice acceptor site mutation (c.2218-6C > A, p.Q739insX42) in one allele. This resulted in alteration of 41 amino acids at the C terminus, producing partial NER complementation. This limited number of mutations probably reflects the very restricted range of alterations of this vital protein that are compatible with life. We found new mutations in the second allele yielding markedly truncated proteins in all five XT or XP/CS complex families: c.1273C > T, p.R425X; c-471+IG > A, p.K157insTSDSX; C.807-808delTT, p.F270X; c. 1421-1422insA, p.D474EfsX475; and c. 1633C > T, p.Q545X. The remarkable phenotypic heterogeneity of XPB is associated with partially active missense mutations in milder patients while severe XT/CS complex patients have nonsense mutations in both alleles with low levels of altered XTB proteins. C1 NCI, Basic Res Lab, DNA Repair Sect, CCR, Bethesda, MD 20892 USA. Erasmus Univ, Dept Genet, DNA Repair Sect, Rotterdam, Netherlands. Univ Sussex, Genome Damage & Stabil Ctr, Brighton, E Sussex, England. Univ Southampton, Dept Dermatol, Southampton, Hants, England. Goettingen Univ, Dept Dermatol, Gottingen, Germany. Univ Heidelberg, Dept Dermatol, D-6800 Mannheim, Germany. Wessex Reg Genet Serv, Southampton, Hants, England. NCI, Cellular Oncol Lab, CCR, Bethesda, MD 20892 USA. RP Kraemer, KH (reprint author), NCI, Basic Res Lab, DNA Repair Sect, CCR, Bldg 37 Roome 4002, Bethesda, MD 20892 USA. EM kraemerk@nih.gov RI Gratchev, Alexei/J-3170-2013; OI Gratchev, Alexei/0000-0003-2137-1866 FU Intramural NIH HHS [Z01 BC004517-31] NR 51 TC 63 Z9 65 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2006 VL 27 IS 11 BP 1092 EP 1103 DI 10.1002/humu.20392 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 098NM UT WOS:000241529500004 PM 16947863 ER PT J AU Bernstein, JL Teraoka, S Southey, MC Jenkins, MA Andrulis, IL Knight, JA John, EM Lapinski, R Wolitzer, AL Whittemore, AS West, D Seminara, D Olson, ER Spurdle, AB Chenevix-Trench, G Giles, GG Hopper, JL Concannon, P AF Bernstein, J. L. Teraoka, S. Southey, M. C. Jenkins, M. A. Andrulis, I. L. Knight, J. A. John, E. M. Lapinski, R. Wolitzer, A. L. Whittemore, A. S. West, D. Seminara, D. Olson, E. R. Spurdle, A. B. Chenevix-Trench, G. Giles, G. G. Hopper, J. L. Concannon, P. TI Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T > G and c.1066-6T > G (IVS10-6T > G) from the breast cancer family registry SO HUMAN MUTATION LA English DT Article DE ATM gene variants; breast cancer; DNA damage; segregation analysis; penetrance ID ATAXIA-TELANGIECTASIA FAMILIES; MISSENSE MUTATIONS; EARLY-ONSET; TRUNCATING MUTATIONS; ALLELIC VARIANTS; HETEROZYGOTES; SUSCEPTIBILITY; CONTRIBUTE; FREQUENCY; HISTORY AB The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T > G and c.1066-6T > G (IVS10-6T > G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T > G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR] = 5.5, 95% confidence interval [CI] = 1.2-25.5; P = 0.04) and delayed child-bearing (OR = 5.1; 95% CI = 1.0-25.6; P = 0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI = 28-80%; hazard ratio [HR] = 8.6; 95% Cl = 3.9-18.9; P < 0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T > G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P = 0.5). These findings suggest that although the more common c.1066-6T > G variant is not associated with breast cancer, the rare ATM c.7271T > G variant is associated with a substantially elevated risk. Since c.7271T > G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population. C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Benaroya Res Inst, Seattle, WA USA. Univ Melbourne, Melbourne, Vic, Australia. IARC, Lyon, France. Samuel Lunenfeld Res Inst, Toronto, ON, Canada. No Calif Canc Ctr, Fremont, CA USA. Mt Sinai Sch Med, New York, NY USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Natl Canc Inst, Bethesda, MD USA. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Canc Council Victoria, Melbourne, Vic, Australia. RP Bernstein, JL (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63rd St,3rd Floor, New York, NY 10021 USA. EM bernstej@mskcc.org RI Spurdle, Amanda/A-4978-2011; Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; Jenkins, Mark/P-7803-2015; OI Spurdle, Amanda/0000-0003-1337-7897; Jenkins, Mark/0000-0002-8964-6160; Concannon, Patrick/0000-0002-5801-1859; Giles, Graham/0000-0003-4946-9099 FU NCI NIH HHS [U01 CA069417, 5U01CA69417, 5U01CA69467, 5U01CA69638, R01 CA112450, U01 CA069417-10, U01CA83178] NR 41 TC 37 Z9 38 U1 0 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 NOV PY 2006 VL 27 IS 11 BP 1122 EP 1128 DI 10.1002/humu.20415 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 098NM UT WOS:000241529500007 PM 16958054 ER PT J AU Gustofson, RL Segars, JH Larsen, FW AF Gustofson, Robert L. Segars, James H. Larsen, Frederick W. TI Ganirelix acetate causes a rapid reduction in estradiol levels without adversely affecting oocyte maturation in women pretreated with leuprolide acetate who are at risk of ovarian hyperstimulation syndrome SO HUMAN REPRODUCTION LA English DT Article DE cycle cancellation; estradiol; ganirelix acetate; GnRH agonist and antagonist; OHSS ID IN-VITRO FERTILIZATION; FOLLICLE-STIMULATING-HORMONE; GNRH ANTAGONIST GANIRELIX; SERUM ESTRADIOL; ELECTIVE CRYOPRESERVATION; LUTEINIZING-HORMONE; PRONUCLEATE EMBRYOS; FEMALE FECUNDITY; PREGNANCY RATES; GONADOTROPIN AB BACKGROUND: Elevated estradiol (E-2) levels predispose to development of ovarian hyperstimulation syndrome (OHSS). Since GnRH antagonist is associated with a reduction in E-2 levels, we hypothesized that GnRH-antagonist treatment of women down-regulated with GnRH agonist who are at risk of OHSS might reduce E-2 levels and avoid cycle cancellation. METHODS: Retrospective study in a university-based assisted reproduction technology (ART) programme in 87 patients treated with long luteal (LL) or microdose flare (MDF) with ovarian hyperresponse and 87 control patients without ovarian hyperresponse. GnRH-antagonist (ganirelix acetate) treatment was started and leuprolide acetate discontinued in women who failed to respond to a reduction in gonadotrophin dosage. RESULTS: In the treatment group, there was a significant, reproducible reduction in serum E-2 levels. Mean E-2 at the start of ganirelix treatment was 4219.8 pg/ml and decreased in 24 h to 2613.7 pg/ml (36.7%; P < 0.001). An average of 24.9 +/- 8.8 oocytes were obtained at retrieval and an average of 19.1 +/- 8.0 were metaphase II (79.2%). Fertilization occurred in 13.9 +/- 8.1 embryos (72.8%). In this high risk group, two cases of severe OHSS (2.3%) occurred. The ongoing pregnancy rate was 51.8%. Compared with the control group, there were no statistically significant differences in the rate of oocyte recovery, oocyte maturity, 2PN rate, fertilization, cancellation, OHSS or pregnancy. CONCLUSIONS: GnRH-antagonist treatment of women pretreated with GnRH agonist rapidly reduced circulating serum E-2 without adversely affecting oocyte maturation, fertilization rates or embryo quality and resulted in a high pregnancy rate in this subgroup of patients at risk of OHSS. C1 Walter Reed Army Med Ctr, Assisted Reprod Technol Program, Washington, DC 20307 USA. NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Walter Reed Army Med Ctr, Natl Naval Med Ctr, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Larsen, FW (reprint author), Walter Reed Army Med Ctr, Assisted Reprod Technol Program, 6900 Georgia Ave NW,Ward 43, Washington, DC 20307 USA. EM frederick.larsen@na.amedd.army.mil FU Intramural NIH HHS NR 48 TC 17 Z9 17 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 2006 VL 21 IS 11 BP 2830 EP 2837 DI 10.1093/humrep/del059 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 094XO UT WOS:000241272700015 PM 16966348 ER PT J AU Durbin, AP McArthur, JH Marron, JA Blaney, JE Thumar, B Wanionek, K Murphy, BR Whitehead, SS AF Durbin, Anna P. McArthur, Julie H. Marron, Jennifer A. Blaney, Joseph E. Thumar, Bhavin Wanionek, Kimberli Murphy, Brian R. Whitehead, Stephen S. TI rDEN2/4 Delta 30(ME), a live attenuated chimeric dengue serotype 2 vaccine, is safe and highly immunogenic in healthy dengue-naive adults SO HUMAN VACCINES LA English DT Editorial Material DE live attenuated chimeric dengue vaccine; human trial; DEN2 ID WEST-NILE-VIRUS; RHESUS-MONKEYS; ANTIBODY-RESPONSE; DISEASE SEVERITY; RECOMBINANT; TYPE-4; FORMULATIONS; INFECTIONS; CANDIDATES; NEUROVIRULENCE AB rDEN2/4 Delta 30(ME) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 candidate vaccine rDEN4 Delta 30 have been replaced by those of the prototypic DEN2 NGC virus. rDEN2/4 Delta 30(ME) was evaluated at a dose of 1 000 PFU in 20 healthy dengue-naive adult volunteers. Eight volunteers received placebo. Volunteers were monitored closely for adverse events and serum was collected for determination of the level and duration of viremia and neutralizing antibody response. The vaccine was well tolerated by all volunteers. The most common adverse events observed were a transient asymptomatic rash and mild neutropenia. All vaccinees seroconverted to DEN2 and maintained significant antibody titers throughout the six-month trial duration. Eleven vaccinees had vaccine virus recovered from the blood during the study. RNA derived from virus isolates obtained from viremic volunteers was sequenced for confirmation of retention of the Delta 30 mutation in the 3' UTR. The Delta 30 mutation remained unchanged in each isolate, confirming the stability of the Delta 30 mutation. Further evaluation of this vaccine in a tetravalent formulation is warranted. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. EM adurbin@jhsph.edu FU NIAID NIH HHS [N01 AI15444]; PHS HHS [UAI057168A] NR 28 TC 68 Z9 72 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1554-8619 J9 HUM VACCINES JI Hum. Vaccines PD NOV-DEC PY 2006 VL 2 IS 6 BP 255 EP 260 PG 6 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 132ZA UT WOS:000243980200005 PM 17106267 ER PT J AU Cutler, JA Roccella, EJ AF Cutler, Jeffrey A. Roccella, Edward J. TI Salt reduction for preventing hypertension and cardiovascular disease - A population approach should include children SO HYPERTENSION LA English DT Editorial Material ID BLOOD-PRESSURE; RISK-FACTORS; BURDEN; DIET C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. NHLBI, Off Prevent Educ & Control, NIH, Bethesda, MD 20892 USA. RP Cutler, JA (reprint author), 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM cutlerj@nhlbi.nih.gov NR 13 TC 18 Z9 21 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2006 VL 48 IS 5 BP 818 EP 819 DI 10.1161/01.HYP.0000245673.93844.6d PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127PE UT WOS:000243598000007 PM 17015775 ER PT J AU Watford, WT O'Shea, JJ AF Watford, Wendy T. O'Shea, John J. TI Human Tyk2 kinase deficiency: Another primary immunodeficiency syndrome SO IMMUNITY LA English DT Editorial Material ID MICE C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Watford, WT (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. NR 10 TC 28 Z9 29 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2006 VL 25 IS 5 BP 695 EP 697 DI 10.1016/j.immuni.2006.10.005 PG 3 WC Immunology SC Immunology GA 105WN UT WOS:000242063100003 PM 17098200 ER PT J AU Wilbur, WJ Kim, W Xie, N AF Wilbur, W. John Kim, Won Xie, Natalie TI Spelling correction in the PubMed search engine SO INFORMATION RETRIEVAL LA English DT Article DE noisy channel model; user query logs; nonword error detection; trie; edit distance ID WEB; INFORMATION; QUERIES; LOGS AB It is known that users of internet search engines often enter queries with misspellings in one or more search terms. Several web search engines make suggestions for correcting misspelled words, but the methods used are proprietary and unpublished to our knowledge. Here we describe the methodology we have developed to perform spelling correction for the PubMed search engine. Our approach is based on the noisy channel model for spelling correction and makes use of statistics harvested from user logs to estimate the probabilities of different types of edits that lead to misspellings. The unique problems encountered in correcting search engine queries are discussed and our solutions are outlined. C1 Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wilbur, WJ (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,Rm 6S606,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wilbur@ncbi.nlm.nih.gov FU Intramural NIH HHS [Z01 LM000021-14, Z01 LM000090-07] NR 20 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-4564 J9 INFORM RETRIEVAL JI Inf. Retr. PD NOV PY 2006 VL 9 IS 5 BP 543 EP 564 DI 10.1007/s10791-006-9002-8 PG 22 WC Computer Science, Information Systems SC Computer Science GA 084RK UT WOS:000240551900002 PM 18080004 ER PT J AU Suffredini, AF Chanock, SJ AF Suffredini, Anthony F. Chanock, Stephen J. TI Genetic variation and the assessment of risk in septic patients SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID ASSOCIATION C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD USA. Ctr Canc Res, Sect Genom Varaiat, Pediat Oncol Branch, Bethesda, MD USA. RP Suffredini, AF (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM asuffredini@cc.nih.gov NR 5 TC 6 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 2006 VL 32 IS 11 BP 1679 EP 1680 DI 10.1007/s00134-006-0328-x PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 097MZ UT WOS:000241453400001 PM 16957906 ER PT J AU Meletiadis, J Dorsthorst, DTAT Verweij, PE AF Meletiadis, Joseph Dorsthorst, Debbie T. A. te Verweij, Paul E. TI The concentration-dependent nature of in vitro amphotericin B-itraconazole interaction against Aspergillus fumigates: isobolographic and response surface analysis of complex pharmacodynamic interactions SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE antifungal interaction; isobolography; synergy and antagonism; bliss independence; Loewe additivity; response surface analysis ID INVASIVE PULMONARY ASPERGILLOSIS; COMBINATION THERAPY; ANTIFUNGAL DRUGS; ANTAGONISM; SYNERGY; MODEL; SUSCEPTIBILITY; CANDIDIASIS; ERGOSTEROL; VORICONAZOLE AB The interaction between polyenes and azoles is not well understood. We therefore explored the in vitro combination of amphotericin B with itraconazole against 14 clinical Aspergillus fumigates isolates (9 itraconazole susceptible and 5 itraconazole resistant) with a colorimetric broth microdilution checkerboard technique using two drug interaction models able to explore complicated patterns of interactions: the response surface analysis of Bliss independence and the isobolographic analysis of Loewe additivity zero interaction theories. Synergy was found at combinations with low concentrations of amphotericin B (< 0.125 mg/L), whereas antagonism was found at combinations with higher concentrations of amphotericin B. For itraconazole-resistant isolates, synergistic interactions were observed at high concentrations of itraconazole (> 0.5 mg/L). Synergy was more frequently observed for the itraconazole-resistant isolates than for the itraconazole-susceptible isolates. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Radboud Univ Nijmegen Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands. RP Meletiadis, J (reprint author), NCI, Pediat Oncol Branch, NIH, Bg 10,CRC Rm 1C-5750,10 Ctr Dr MSC 1100, Bethesda, MD 20892 USA. EM meletiaj@mail.nih.gov RI Verweij, P.E./H-8108-2014 NR 46 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD NOV PY 2006 VL 28 IS 5 BP 439 EP 449 DI 10.1016/j.ijantimicag.2006.07.011 PG 11 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 114GB UT WOS:000242653600012 PM 17055706 ER PT J AU Park, SK Garcia-Closas, M Lissowska, J Sherman, ME McGlynn, KA Peponska, B Bardin-Mikoajczak, A Zatonski, W Szeszenia-Dabrowska, N Brinton, LA AF Park, Sue Kyung Garcia-Closas, Montserrat Lissowska, Jolanta Sherman, Mark E. McGlynn, Katherine A. Peponska, Beata Bardin-Mikoajczak, Alicja Zatonski, Witold Szeszenia-Dabrowska, Neonila Brinton, Louise A. TI Intrauterine environment and breast cancer risk in a population-based case-control study in Poland SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; perinatal factors; hormones; in utero exposures ID IN-UTERO EXPOSURES; BIRTH-WEIGHT; YOUNG-WOMEN; UNITED-STATES; SUBSEQUENT RISK; MATERNAL AGE; PREGNANCY ESTRIOL; PERINATAL FACTORS; MULTIPLE BIRTHS; ESTROGEN-LEVELS AB High estrogen exposure in utero may increase breast cancer risk later in life. However, studies of the associations between perinatal factors presumed to affect the fetal hormonal environment and breast cancer risk are inconsistent. We used data from a population-based case-control study of 2,386 incident breast cancers and 2,502 controls in Poland to evaluate risks associated with various perinatal characteristics. After adjusting for confounders, we found a significant trend (p = 0.01) of breast cancer risk with birth weight (OR = 1.54, 95% CI 1.08-2.19 for birth weights > 4,000 g vs. < 2,500 g). Subjects with a high birth order (>= 6) were at reduced risk (OR = 0.81, 0.61-1.06) when compared with first born subjects. Birth weight was somewhat a stronger risk predictor among subjects whose cancers were diagnosed at 50 years of age or older (OR = 1.84, 1.19-2.85) than among those with cancers diagnosed at younger ages (OR = 1.14, 0.61-2.12). Subjects whose mothers smoked during their pregnancies were at slightly higher risk than those who never smoked (OR = 1.21, 0.99-1.47), but the risk was similar to mothers who only smoked at other times (OR = 1.22, 0.81-1.84). Breast cancer risk was not related to paternal smoking, maternal age, gestational age or twin status. Our results add support to the growing evidence that some perinatal exposures may relate to breast cancer risk. Additional studies are needed to confirm associations and clarify the biologic mechanisms underlying these associations. Published 2006 Wiley-Liss, Inc. C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Ctr Canc, Dept Canc Control & Epidemiol, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. RP Park, SK (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yeongeon Dong, Seoul 110799, South Korea. EM suepark@snu.ac.kr RI Park, Sue Kyung/J-2757-2012; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 58 TC 13 Z9 14 U1 0 U2 3 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 NOV 1 PY 2006 VL 119 IS 9 BP 2136 EP 2141 DI 10.1002/ijc.21974 PG 6 WC Oncology SC Oncology GA 086LE UT WOS:000240674000019 PM 16804898 ER PT J AU Koushik, A Hunter, DJ Spiegelman, D Anderson, KE Buring, JE Freudenheim, JL Goldbohm, RA Hankinson, SE Larsson, SC Leitzmann, M Marshall, JR McCullough, ML Miller, AB Rodriguez, C Rohan, TE Ross, JA Schatzkin, A Schouten, LJ Willett, WC Wolk, A Zhang, SM Smith-Warner, SA AF Koushik, Anita Hunter, David J. Spiegelman, Donna Anderson, Kristin E. Buring, Julie E. Freudenheim, Jo L. Goldbohm, R. Alexandra Hankinson, Susan E. Larsson, Susanna C. Leitzmann, Michael Marshall, James R. McCullough, Marjorie L. Miller, Anthony B. Rodriguez, Carmen Rohan, Thomas E. Ross, Julie A. Schatzkin, Arthur Schouten, Leo J. Willett, Walter C. Wolk, Alicja Zhang, Shumin M. Smith-Warner, Stephanie A. TI Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ovarian cancer; carotenoids; pooled analysis; meta-analysis; cohort studies ID FOOD FREQUENCY QUESTIONNAIRE; BREAST-CANCER; VITAMIN-A; UNITED-STATES; VEGETABLE CONSUMPTION; DIETARY ASSESSMENT; NUTRIENT INTAKE; FAT INTAKE; EPIDEMIOLOGY; PREVENTION AB Carotenoids, found in fruits and vegetables, have the potential to protect against cancer because of their properties, including their functions as precursors to vitamin A and as antioxidants. We examined the associations between intakes of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed and then pooled. Carotenoid intakes were estimated from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 521,911 women, 2,012 cases of ovarian cancer occurred during a follow-up of 7-22 years across studies. The major carotenoids were not significantly associated with the risk of ovarian cancer. The pooled multivariate RRs (95% confidence intervals) were 1.00 (0.95-1.05) for a 600 mu g/day increase in alpha-carotene intake, 0.96 (0.93-1.03) for a 2,500 mu g/day increase in beta-carotene intake, 0.99 (0.97-1.02) for a 100 mu g/day increase in beta-cryptoxanthin intake, 0.98 (0.94-1.03) for a 2,500 mu g/day increase in lutein/zeaxanthin intake and 1.01 (0.97-1.05) for a 4,000 mu g/day increase in lycopene intake. These associations did not appreciably differ by study (p-values, tests for between-studies heterogeneity > 0.17). Also, the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer. These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer. (c) 2006 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. TNO, Qual Life, Dept Food & Chem Risk Anal, NL-3700 AJ Zeist, Netherlands. Karolinska Inst, Natl Inst Environm Med, Div Nutrit Epidemiol, Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Maastricht Univ, NUTRIM, Dept Epidemiol, Maastricht, Netherlands. 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 RI Schouten, Leo/G-3713-2012; Larsson, Susanna/F-6065-2015; OI Larsson, Susanna/0000-0003-0118-0341; Koushik, Anita/0000-0001-5304-7660 FU NCI NIH HHS [CA55075] NR 69 TC 25 Z9 27 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2006 VL 119 IS 9 BP 2148 EP 2154 DI 10.1002/ijc.22076 PG 7 WC Oncology SC Oncology GA 086LE UT WOS:000240674000021 PM 16823847 ER PT J AU Ohta, S Lai, EW Morris, JC Bakan, DA Klaunberg, B Cleary, S Powers, JF Tischler, AS Abu-Asab, M Schimel, D Pacak, K AF Ohta, Shoichiro Lai, Edwin W. Morris, John C. Bakan, Douglas A. Klaunberg, Brenda Cleary, Susannah Powers, James F. Tischler, Arthur S. Abu-Asab, Mones Schimel, Daniel Pacak, Karel TI MicroCT for high-resolution imaging of ectopic pheochromocytoma tumors in the liver of nude mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE microCT; mouse model; pheochromocytoma; liver tumor ID CONTRAST AGENTS; ANIMAL-MODELS; CELL-LINES; GROWTH; CT; NEUROBLASTOMA; CANCER AB Successful outcomes for patients with cancer often depend on the early detection of tumor and the prompt initiation of active therapy. Despite major advances in the treatment of many cancers, early-stage lesions often go undetected due to the suboptimal resolution of current anatomical and functional imaging modalities. This limitation also applies to preclinical animal tumor models that are crucial for the evaluation and development of new therapeutic approaches to cancer. We report a new mouse model of metastatic pheochromocytoma, generated using tail vein injection of the mouse pheochromocytoma cell (MPC) line that reproducibly generated multiple liver tumors in the animals. Furthermore, we show that in vivo microCT imaging enhanced using a hepatobiliary-specific contrast agent, glyceryl-2-oleyl-1,3-di-7-(3amino-2,4,6-triiodophenyl)-heptanoate (DHOG), detected tumors as small as 0.35 mm as early as 4 weeks after the injection of the tumor cells. This model may be useful for in vivo studies of tumor biology and for development of new strategies to treat metastatic pheochromocytoma. (c) 2006 Wiley-Liss, Inc. C1 NICHD, Unit Clin Neuroendocrinol, RBMB, NIH,CRC, Bethesda, MD 20892 USA. NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Aler Biomed Inc, San Diego, CA USA. NINDS, Mouse Imaging Facil, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. Murdoch Univ, Lab Div Hlth Sci, Perth, WA, Australia. Tufts Univ, Sch Med, New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. NCI, Pathol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Charles River Labs Inc, Germantown, MD USA. RP Pacak, K (reprint author), NICHD, Unit Clin Neuroendocrinol, RBMB, NIH,CRC, Bldg 10,Room 1-3140,10 Ctr Dr MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999]; NINDS NIH HHS [R01 NS037685, R01 NS 37685] NR 30 TC 24 Z9 25 U1 0 U2 4 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 NOV 1 PY 2006 VL 119 IS 9 BP 2236 EP 2241 DI 10.1002/ijc.22127 PG 6 WC Oncology SC Oncology GA 086LE UT WOS:000240674000035 PM 16841334 ER PT J AU Xin, LJ Wang, J Zhang, HL Shi, WF Yu, MX Li, QF Jiang, XD Gong, FL Gardner, K Li, QQD Li, ZY AF Xin, Lijun Wang, Jing Zhang, Hailong Shi, Wenfang Yu, Mingxia Li, Qingfen Jiang, Xiaodan Gong, Feili Gardner, Kevin Li, Qingdi Q. Li, Zhuoya TI Dual regulation of soluble tumor necrosis factor-alpha induced activation of human monocytic cells via modulating transmembrane TNF-alpha-mediated 'reverse signaling' SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE reverse signaling; mTNF-alpha; sTNF-alpha; sTNFRI; U937 monocytic cells ID T-CELLS; COSTIMULATORY SIGNAL; GENE-EXPRESSION; FACTOR RECEPTOR; PROTEIN-KINASE; MACROPHAGES; FORM; METALLOPROTEINASE; INTERLEUKIN-1; DISINTEGRIN AB Transmembrane tumor necrosis factor-alpha (mTNF-alpha) is known to be he precursor of soluble TNF-alpha (sTNF-alpha). mTNF-alpha can act as a ligand on the TNF receptor- (TNFR)-bearing cell through 'forward signaling' or as a receptor on the TNF producing cell through 'reverse signaling'. In the current study, we investigated the role of mTNF-alpha-mediated reverse signaling in regulating sTNF-alpha-induced activation of human monocytic U937 cells. We demonstrated that pretreatment with sTNFRI, for inducing reverse signaling through mTNF-a, sensitized U937 :ells to sTNF-a stimulation, as evidenced by an increase in reactive oxygen production and mRNA levels of proinflammatory cytokines (TNF-alpha, IL-1 beta, and IL-8) in these cells. Further experiments revealed that I kappa B-alpha degradation was increased in the monocytic cells primed with sTNFRI, implying that reverse signaling of mTNF-alpha sensitizes U937 cells via art NF-kappa B-dependent mechanism. On the other hand, binding of sTNFRI to mTNF-alpha after sTNF-alpha-induced activation of U937 cells reduced mRNA stability (half-life) of IL-1 beta and IL-8. The involvement of reverse signaling in the process was verified by using a mutated form of mTNF-alpha lacking the majority of the cytoplasmic domain. Our results clearly showed that enhanced mRNA degradation of the cytokines occurred only in U937 cells transfected with a wild-type mTNF-alpha, but not in those cells transfected with the mutant mTNF-alpha. Taken together, these data suggest that reverse signaling through mTNF-alpha may exert a double role in modulating sTNF-alpha bioactivity. It is positive when reverse signaling occurs prior to sTNF-alpha stimulation, while it is negative when reverse signaling occurs after the sTNF-alpha signal. Thus, our findings strengthen a role of mTNF-alpha-mediated reverse signaling in the regulation of immune-inflammatory response and control of inflammatory reaction. C1 Cent China Univ Sci & Technol, Tongji Med Coll, Dept Immunol, Wuhan 430030, Peoples R China. NCI, Adv Technol Ctr, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Li, ZY (reprint author), Cent China Univ Sci & Technol, Tongji Med Coll, Dept Immunol, Wuhan 430030, Peoples R China. EM liquenti@mail.nih.gov; zhuoyali@mails.tjmu.edu.cn NR 29 TC 24 Z9 24 U1 0 U2 7 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD NOV PY 2006 VL 18 IS 5 BP 885 EP 892 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 097WE UT WOS:000241479300011 PM 17016618 ER PT J AU Ullmannova, V Popescu, NC AF Ullmannova, Veronika Popescu, Nicholas C. TI Expression profile of the tumor suppressor genes DLC-1 and DLC-2 in solid tumors SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE DLC-l; DLC-2; tumor suppressor gene; solid tumor; transcriptional down-regulation; silencing; breast cancer metastasis ID HUMAN HEPATOCELLULAR-CARCINOMA; CELL LUNG CARCINOMAS; HUMAN BREAST-CANCER; RHO GTPASES; PLC-DELTA(1)-BINDING PROTEIN; CHROMOSOME 13Q12; PROSTATE-CANCER; GROWTH; METASTASIS; TUMORIGENICITY AB Several years after the isolation of deleted in liver cancer I (DLC-1), a gene that encodes a Rho GTPase activating protein, the closely related DLC-2 gene was identified. DLC-1 and DLC-2 are similar to 50% identical and share the same SAM-RhoGAP-START domain organization. Since DLC-1 and -2 are located at chromosome regions that are commonly deleted in cancer cells and have been found to function as tumor suppressor genes, we sought to compare their expression profiles in several common types of cancer and to determine whether dlc1 and dlc2 proteins cooperate in tumor development. Using cancer-profiling arrays, we detected for the first time down-regulation of DLC-1 expression in renal, uterine and rectal cancers and down-regulation of DLC-2 expression in lung, ovarian, renal, breast, uterine, gastric, colon and rectal tumors. Since DLC-1 also functions as a metastasis suppressor gene in breast cancer, DLC-1 and DLC-2 expression were examined in a series of primary ductal carcinomas derived from patients with regional lymph node metastases. Using quantitative RT-PCR we detected a significantly lower expression of DLC-1 and DLC-2 in high percentage of tumors, suggesting that deficiency of either DLC gene facilitates dissemination of breast carcinoma cells to secondary sites. We examined DLC-2 expression in DLC-1-negative cell lines derived from human breast, non-small cell lung, and hepatocellular carcinomas, that could be rendered less or non-tumorigenic by ectopic expression of DLC-1. DLC-2 transcripts were detected in all cell lines, indicating that none of the cells were deficient in both members of the DLC family. This comparative expression analysis of DLC-1 and -2 identifies down-regulation of the two emerging bona fide tumor suppressor genes in additional types of solid tumors. The large spectrum of cancers with dysregulated DLC genes underlines the involvement of this family of genes in cancer development. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 4128B,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI Benson, Veronika/D-9942-2014 OI Benson, Veronika/0000-0003-4770-9909 FU Intramural NIH HHS NR 39 TC 55 Z9 66 U1 0 U2 4 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 2006 VL 29 IS 5 BP 1127 EP 1132 PG 6 WC Oncology SC Oncology GA 097VB UT WOS:000241476100010 PM 17016643 ER PT J AU Goldstein, RZ Cottone, LA Jia, ZR Maloney, T Volkow, ND Squires, NK AF Goldstein, Rita Z. Cottone, Lisa A. Jia, Zhiru Maloney, Thomas Volkow, Nora D. Squires, Nancy K. TI The effect of graded monetary reward on cognitive event-related potentials and behavior in young healthy adults SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE ERP; reaction time; monetary reward; P3; CNV ID CONTINGENT NEGATIVE-VARIATION; HUMAN BRAIN; NEURAL RESPONSES; VARIATION CNV; STROOP TASK; P300; STIMULI; ASYMMETRIES; EXPECTANCY; ACTIVATION AB Temporal correlates of the brain circuit underlying reward processing in healthy adults remain unclear. The current study investigated the P3 and contingent negative variation (CNV) as putative reward-related temporal markers. The effect of sustained monetary reward on these event-related potentials and on behavior was assessed using a warned reaction-time paradigm in 16 young healthy subjects. Monetary reward (0, 1 and 45 cents) varied across blocks of trials. While the CNV was unaffected by money, P3 amplitude was significantly larger for 45 than the 1 and 0 cent conditions. This effect corresponded to the monotonically positive subjective ratings of interest and excitement on the task (45 > 1 > 0). These findings suggest a difference between the P3 and CNV; the P3 is sensitive to the sustained effect of relative reward value, while the CNV does not vary with reward magnitude. (c) 2006 Elsevier B.V All rights reserved. C1 Brookhaven Natl Lab, Upton, NY 11973 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. NIDA, Bethesda, MD 20892 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, POB 5000, Upton, NY 11973 USA. EM rgoldstein@bnl.gov FU NCRR NIH HHS [M01 RR010710-070110, M01 RR010710, 5-M01-RR-10710]; NIAAA NIH HHS [R01 AA009481-06, AA/ODO9481-04]; NIDA NIH HHS [R01 DA006891-03, T32 DA007316, T32 DA07316-01A1, DA06891-06, R01 DA006891, T32 DA007316-01A1, K23 DA015517-01, K23 DA015517, 1K23 DA15517-01] NR 46 TC 44 Z9 50 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD NOV PY 2006 VL 62 IS 2 BP 272 EP 279 DI 10.1016/j.ijpsycho.2006.05.006 PG 8 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 097XB UT WOS:000241481700009 PM 16876894 ER PT J AU Greenberg, DE Porcella, SF Stock, F Wong, A Conville, PS Murray, PR Holland, SM Zelazny, AM AF Greenberg, David E. Porcella, Stephen F. Stock, Frida Wong, Alexandra Conville, Patricia S. Murray, Patrick R. Holland, Steven M. Zelazny, Adrian M. TI Granulibacter bethesdensis gen. nov., sp nov., a distinctive pathogenic acetic acid bacterium in the family Acetobacteraceae SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; TRANSCRIBED SPACER REGIONS; ALPHA-PROTEOBACTERIA; GENOME SEQUENCE; IDENTIFICATION; INFECTION; STRAINS; RDNA; PSEUDOMONAS AB A Gram-negative, aerobic, coccobacillus to rod-shaped bacterium was isolated from three patients with chronic granulomatous disease. The organism was subjected to a polyphasic taxonomic study. A multilocus phylogenetic analysis based on the 16S rRNA gene, the internal transcribed spacer (ITS) region and the RecA protein demonstrated that the organism belongs to a new sublineage within the acetic acid bacteria in the family Acetobacteraceae. Phenotypic features are summarized as follows: the organism grew at an optimum temperature of 35-37 degrees C and optimum pH of 5.0-6.5. It produced a yellow pigment, oxidized lactate and acetate, the latter weakly, produced little acetic acid from ethanol and could use methanol as a sole carbon source. The two major fatty acids were a straight-chain unsaturated acid (Cl 8: 1 omega 7c) and C16:0. The DNA base composition was 59.1 mol% G + C. The very weak production of acetic acid from ethanol, the ability to use methanol, the yellow pigmentation and high optimum temperature for growth distinguished this organism from other acetic acid bacteria. The unique phylogenetic and phenotypic characteristics suggest that the bacterium should be classified within a separate genus, for which the name Granulibacter bethesdensis gen. nov., sp. nov. is proposed. The type strain is CGDNIH1(T) (= ATCC BAA-1260T =DSM 17861(T)). C1 NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. US Dept Hlth Human Serv, Microbiol Serv, Dept Lab Med, Clin Ctr,NIH, Bethesda, MD 20892 USA. NIAID, Rocky Mt Labs, Res Technol Sect, NIH,US Dept Hlth & Human Serv, Hamilton, MT 59840 USA. RP Greenberg, DE (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. EM degreenberg@niaid.nih.gov NR 42 TC 57 Z9 58 U1 2 U2 6 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD NOV PY 2006 VL 56 BP 2609 EP 2616 DI 10.1099/ijs.0.64412-0 PN 11 PG 8 WC Microbiology SC Microbiology GA 108SQ UT WOS:000242259900019 PM 17082400 ER PT J AU Doroshow, JH McCoy, S Macdonald, JS Issell, BF Patel, T Cobb, PW Yost, KJ Abbruzzese, JL AF Doroshow, James H. McCoy, Sheryl Macdonald, John S. Issell, Brian F. Patel, Taral Cobb, Patrick W. Yost, Kathleen J. Abbruzzese, James L. TI Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: A Southwest Oncology Group study SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE gastric cancer; 5-FU; leucovorin; PN401 ID ADVANCED GASTRIC-CANCER; DELAYED URIDINE RESCUE; HIGH-DOSE URIDINE; BIOCHEMICAL MODULATION; COLORECTAL-CANCER; 5-FLUOROURACIL; FLUOROURACIL; CARCINOMA; CISPLATIN; DOXORUBICIN AB From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m(2) of 5-FU, 500 mg/m(2) of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines. C1 Natl Canc Inst, Div Canc Treatment & Diag, City Hope Natl Med Ctr, Duarte, CA 91010 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. St Vincents Canc Ctr, New York, NY USA. Univ Hawaii, Community Clin Oncol Program, Honolulu, HI 96822 USA. Columbus Community Clin Oncol Program, Columbus, OH USA. Montana Canc Consortium, Community Clin Oncol Program, Billings, MT USA. Grand Rapids Community Clin Oncol Program, Grand Rapids, MI USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Doroshow, JH (reprint author), Natl Canc Inst, Div Canc Treatment & Diag, City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM doroshoj@mail.nih.gov FU NCI NIH HHS [CA58723, CA04919, CA12644, CA16385, CA20319, CA22433, CA27057, CA32102, CA35119, CA35176, CA35178, CA35261, CA35431, CA38926, CA42777, CA45560, CA45807, CA45808, CA46368, CA46441, CA52654, CA58861, CA63844, CA63850, CA67575, CA74647, CA76447, CA76462] NR 29 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 2006 VL 24 IS 6 BP 537 EP 542 DI 10.1007/s10637-006-9244-8 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 076LL UT WOS:000239959400011 PM 16832602 ER PT J AU Simirskii, VN Lee, RS Wawrousek, EF Duncan, MK AF Simirskii, Vladimir N. Lee, Robert S. Wawrousek, Eric F. Duncan, Melinda K. TI Inbred FVB/N mice are mutant at the cp49/Bfsp2 locus and lack beaded filament proteins in the lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID A-CRYSTALLIN PROMOTER; TRANSGENIC MICE; DOMINANT CATARACT; DBA/2J MICE; MOUSE; MUTATION; ETHYLNITROSOUREA; GLAUCOMA; DISEASE; RETINA AB PURPOSE. FVB/N is considered an ideal inbred mouse strain for transgenic mouse production because of the ease of pronuclear microinjection and its overall fecundity. It is well established that vertebrate lens fiber cells normally express a modified intermediate filament network consisting of the proteins filensin and CP49, and it was recently reported that the mouse strain 129 harbors mutations in CP49 that have the potential to confound the interpretation of gene knockout studies of the lens. The purpose of this study was to evaluate the status of the CP49/Bfsp2 gene in the FVB/N strain. METHODS. PCR analysis of genomic DNA was used to evaluate the status of the CP49 gene in FVB/N mice procured from the four major US distributors of these animals-Harlan Laboratories, Taconic Farms, Jackson Laboratory, and the NIH/NCI/DCT production facility run by Charles River Laboratories. The structure of the CP49 transcript was evaluated by RT-PCR, and the presence of CP49 protein in the lens was evaluated by immunofluorescence. RESULTS. FVB/N mice obtained from all four US distributors were shown to harbor a 6-kb deletion of the CP49 gene identical with that previously reported in mouse strain 129; C57BL/6 mice did not have this modification. Immunofluorescence demonstrated that FVB/N mice do not have detectable CP49 or filensin protein in the lens, whereas C57BL/6 mice have the expected protein distribution. CONCLUSIONS. In humans, mutations in the CP49/BFSP2 gene have been linked to familial, congenital cataract, demonstrating an important role of this gene in lens transparency. The demonstration that FVB/N mice lack CP49 protein in the lens suggests that it may be necessary to reevaluate the mechanisms underlying lens phenotypes obtained as a result of transgenic manipulation of this strain. C1 Univ Delaware, Dept Sci Biol, Newark, DE 19716 USA. NEI, Transgen Anim & Genome Manipulat Sect, Mol & Dev Biol Lab, Bethesda, MD USA. RP Duncan, MK (reprint author), Univ Delaware, Dept Sci Biol, Newark, DE 19716 USA. EM duncanm@udel.edu RI Wawrousek, Eric/A-4547-2008; Simirskii, Vladimir/J-3920-2013; OI Simirskii, Vladimir/0000-0001-5069-2939; Duncan, Melinda/0000-0003-1570-322X FU Intramural NIH HHS; NCRR NIH HHS [P20 RR 16472]; NEI NIH HHS [EY 015279] NR 26 TC 30 Z9 30 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2006 VL 47 IS 11 BP 4931 EP 4934 DI 10.1167/iovs.06-0423 PG 4 WC Ophthalmology SC Ophthalmology GA 098XS UT WOS:000241557500041 PM 17065509 ER PT J AU Gomez-Roman, VP Florese, RH Peng, B Montefiori, DC Kalyanaraman, VS Venzon, D Srivastava, I Barnett, SW Robert-Guroff, M AF Gomez-Roman, V. Paul Florese, Ruth H. Peng, Bo Montefiori, David C. Kalyanaraman, Vaniambadi S. Venzon, David Srivastava, Indresh Barnett, Susan W. Robert-Guroff, Marjorie TI An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS vaccine; adenovirus; antibody-dependent cellular cytotoxicity; HIV clades; chimpanzee ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODIES; RHESUS MACAQUES; CLADE-B; NEUTRALIZING ANTIBODIES; SIVMAC251 CHALLENGE; IMMUNE-RESPONSES; ENVELOPE PROTEIN; PASSIVE TRANSFER; PARTIAL DELETION AB Although HIV subtype B predominates in North America and Western Europe, most HIV infections worldwide are non-subtype B. Globally effective AIDS vaccines need to elicit broad immunity against multiple HIV strains. In this study, 10 chimpanzees were intranasally primed sequentially with adenovirus type 5 (Ad5)and Ad7-HIVNTNenv/rev recombinants and boosted twice intramuscularly with heterologous oligomeric HIVSF162 gp140AV2 protein in MF59 adjuvant. Sera were evaluated for binding, neutralizing, and antibody-dependent cellular cytotoxicity (ADCC) against HIV clades A, B, C, and CRF01_AE. The vaccine regimen elicited high-titered HIV subtype A, B, C and CRFOIAE gp120-binding antibodies. Sera from 7 of 10 vaccinated chimpanzees cross-neutralized the heterologous South African subtype C primary HIVTV-1 isolate. Significant cross-clade neutralization against other subtype A, C and E isolates was not observed. Sera from all animals mediated ADCC of cells coated with gp 120 from HIV subtypes A and B. Nine of 10 animals also exhibited ADCC activity against HIV subtype C and CRT01_AE gp120-coated targets. This subtype B Ad-HTV recombinant prime/envelope protein boost regimen is a promising approach for eliciting broad ADCC activity against diverse HIV clades. Incorporating additional non-subtype B envelope genes and protein boosts in a multivalent strategy may be required to elicit broader neutralizing antibodies against non-subtype B HIV strains. C1 NCI, NIH, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Novartis Vaccines, Emeryville, CA USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Adv BioSci Labs Inc, Kensington, MD USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, NIH, Vaccine Branch, Ctr Canc Res, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [P01 AI48225-03] NR 47 TC 37 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2006 VL 43 IS 3 BP 270 EP 277 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 099KB UT WOS:000241592000003 PM 16940858 ER PT J AU Khurana, S Needham, J Park, S Mathieson, B Busch, MP Nemo, G Nyambi, P Zolla-Pazner, S Laal, S Mulenga, J Chomba, E Hunter, E Allen, S McIntyre, J Hewlett, I Lee, S Tang, SX Cowan, E Beyrer, C Altfeld, M Yu, XG Tounkara, A Koita, O Kamali, A Nguyen, N Graham, BS Todd, D Mugenyi, P Anzala, O Sanders, E Ketter, N Fast, P Golding, H AF Khurana, Surender Needham, James Park, Susan Mathieson, Bonnie Busch, Michael P. Nemo, George Nyambi, Phillipe Zolla-Pazner, Susan Laal, Suman Mulenga, Joseph Chomba, Elwyn Hunter, Eric Allen, Susan McIntyre, James Hewlett, Indira Lee, Sherwin Tang, Shixing Cowan, Elliot Beyrer, Chris Altfeld, Marcus Yu, Xu G. Tounkara, Anatole Koita, Ousmane Kamali, Anatoli Nguyen, Nga Graham, Barney S. Todd, Deborah Mugenyi, Peter Anzala, Omu Sanders, Eduard Ketter, Nzeera Fast, Patricia Golding, Hana TI Novel approach for differential diagnosis of HIV infections in the face of vaccine-generated antibodies: Utility for detection of diverse HIV-1 subtypes SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; AIDS; diagnosis; vaccine; clinical trials; phage display; peptides; epitope mapping ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD-DONORS; EFFICACY TRIALS; RURAL VILLAGES; IMMUNOGENICITY; CAMEROON; LESSONS; RATES; RISK AB Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV scrodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from > 3000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST performed at > 99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide. C1 FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NIH, Off Aids Res, Bethesda, MD 20892 USA. Blood Syst Res Inst, San Francisco, CA USA. NHLBI, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Pathol, New York, NY USA. Zambia Emory HIV Res Project, Lusaka, Zambia. Zambia Blood Transfus Serv, Lusaka, Zambia. Emory Vaccine Res Ctr, Atlanta, GA USA. Emory Univ, Sch Publ Hlth, Atlanta, GA USA. Univ Witwatersrand, Chris Hani Baragwanath Hosp, Johannesburg, South Africa. FDA, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. MA Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Univ Bamako, Bamako, Mali. FDA, CBER, Core Facil, Bethesda, MD USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Joint Clin Res Ctr, Mengo, Uganda. Int AIDS Vaccine Initiat, New York, NY USA. Univ Nairobi, Nairobi, Kenya. Ctr Geog Med Cost Res, Kilifi, Kenya. RP Golding, H (reprint author), FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Room 1A21,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov FU Intramural NIH HHS [Z99 AI999999]; NHLBI NIH HHS [BY1-HB-5026-01]; NIAID NIH HHS [R01 AI051231, AI-51231, AI36085, AI47053, R01 AI036085, R01 AI047053, R37 AI051231]; NICHD NIH HHS [HD-40125, R01 HD040125]; NIMH NIH HHS [MH-766767] NR 24 TC 19 Z9 22 U1 1 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 NOV 1 PY 2006 VL 43 IS 3 BP 304 EP 312 DI 10.1097/01.qai.0000242465.50947.5f PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 099KB UT WOS:000241592000007 PM 17019363 ER PT J AU Shrestha, S Smith, MW Broman, KW Farzadegan, H Vlahov, D Strathdee, SA AF Shrestha, Sadeep Smith, Michael W. Broman, Karl W. Farzadegan, Homayoon Vlahov, David Strathdee, Steffanie A. TI Multiperson use of syringes among injection drug users in a needle exchange program: A gene-based molecular epidemiologic analysis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE genetic biomarkers; needle exchange program; needle circulation theory; syringe sharing; syringe-sharing risk factors ID C VIRUS-INFECTION; SHORT TANDEM REPEATS; HIV RISK BEHAVIORS; HEPATITIS-C; DINUCLEOTIDE REPEAT; BIOLOGICAL MIXTURES; DNA; TRANSMISSION; BALTIMORE; SEROCONVERSION AB Syringe-sharing behaviors among injection drug users (IDUs) are typically based on self-reports and subject to socially desirable responding. We used 3 short tandem repeat (STR) genetic biomarkers to detect sharing in 2512 syringes exchanged by 315 IDUs in the Baltimore needle exchange program (NEP; 738 personvisits). Demographic characteristics as well as direct and indirect needle-sharing behaviors corresponding to the closest AIDS Link to Intravenous Experience (ALIVE) study visits were examined for association with multiperson use (MPU) of syringes. Overall, 56% of the syringes exchanged at the Baltimore NEP had evidence of MPU Less MPU of syringes (48% vs. 71%; P < 0.0001) was seen with more rapid syringe turnaround (< 3 days). IDUs always exchanging their own syringes ("primary" syringes) were less likely to return syringes with evidence of MPU (52%) than those who exchanged syringes for others ("secondary" syringes; 64%; P = 0.0001) and those exchanging primary and secondary syringes (58%; P = 0.004). In a multivariate analysis restricted to primary exchangers, MPU of syringes was associated with sharing cotton (adjusted odds ratio [AOR] = 2.06, 95% confidence interval [CI]: 1.30 to 3.28), lending syringes (AOR = 1.70, 95% Cl: 1.24 to 2.34), and injecting less than daily (AOR = 0.64, 95% CI: 0.43 to 0.95). These findings support additional public health interventions such as expanded syringe access to prevent HIV and other blood-bome infections. Testing of STRs represents a promising approach to examining and accessing complex behavioral data, including syringe sharing. C1 NCI, Lab Genomic Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. Univ Calif San Diego, Sch Med, Div Int Hlth & Cross Cultural Med, La Jolla, CA 92093 USA. RP Smith, MW (reprint author), NCI, Lab Genomic Divers, SAIC Frederick Inc, Bldg 560,Room 21-74, Frederick, MD 21702 USA. EM smithm@ncifcrf.gov RI Strathdee, Steffanie/B-9042-2009; Smith, Michael/B-5341-2012 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIDA NIH HHS [DA04334, DA09225, DA12568] NR 74 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2006 VL 43 IS 3 BP 335 EP 343 DI 10.1097/01.qai.0000230528.25083.0b PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 099KB UT WOS:000241592000012 PM 16980914 ER PT J AU Sarin, S Undem, B Sanico, A Togias, A AF Sarin, Seema Undem, Bradley Sanico, Alvin Togias, Alkis TI The role of the nervous system in rhinitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE neuroimmune interactions; nasal reflexes; nasal hyperresponsiveness; neurogenic inflammation; neuropeptides; nerve growth factor; capsaicin; nociception; allergic rhinins; nonallergic rhinitis ID HUMAN NASAL-MUCOSA; SEASONAL ALLERGIC RHINITIS; COLD DRY AIR; NONINFECTIOUS PERENNIAL RHINITIS; VASOACTIVE-INTESTINAL-PEPTIDE; PRIMARY AFFERENT NEURONS; NECROSIS-FACTOR-ALPHA; GENE-RELATED PEPTIDE; MAJOR BASIC-PROTEIN; PIG ISOLATED AIRWAY AB The nose provides defensive and homeostatic functions requiring rapid responses to physical and chemical stimuli. As a result, it is armed with a complex nervous system that includes sensory, parasympathetic, and sympathetic nerves. Sensory nerves transmit signals from the mucosa, generating sensations, such as pruritus; motor reflexes, such as sneezing; and parasympathetic and sympathetic reflexes that affect the glandular and vascular nasal apparatuses. Reflexes directed to the nose are also generated by inputs from other body regions. Hence all symptoms that constitute the nosologic entity of rhinitis can be triggered through neural pathways. In addition, neural signals generated in the nose can influence distal physiology, such as that of the bronchial tree and the cardiovascular system. Neural function can be chronically upregulated in the presence of mucosal inflammation, acutely with an allergic reaction, or even in the absence of inflammation, as in cases of nonallergic rhinitis. Upregulation of the nasal nervous system can occur at various levels of the reflex pathways, resulting in exaggerated responses (neural hyperresponsiveness), as well as in increased capacity for generation of neurogenic inflammation, a phenomenon that depends on the release of neuropeptides on antidromic stimulation of nociceptive sensory nerves. The molecular mechanisms of hyperresponsiveness are not understood, but several inflammatory products appear to be playing a role. Neurotrophins, such as the nerve growth factor, are prime candidates as mediators of neural hyperresponsiveness. The many interactions between the nervous and immune systems contribute to nasal physiology but also to nasal disease. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Clin Immunol & Allergy, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Resp & Crit Care Med, Baltimore, MD 21218 USA. RP Togias, A (reprint author), NIAID, DAIT, Room 3060,6610 Rockledge Dr, Bethesda, MD 20817 USA. EM a_togias@comcast.net NR 215 TC 89 Z9 100 U1 1 U2 7 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 NOV PY 2006 VL 118 IS 5 BP 999 EP 1014 DI 10.1016/j.jaci.2006.09.013 PG 16 WC Allergy; Immunology SC Allergy; Immunology GA 137GY UT WOS:000244282300002 PM 17088122 ER PT J AU Arbes, SJ Sever, ML Vaughn, B Cohen, EA Zeldin, DC AF Arbes, Samuel J., Jr. Sever, Michelle L. Vaughn, Ben Cohen, Eric A. Zeldin, Darryl C. TI Oral pathogens and allergic disease: Results from the Third National Health and Nutrition Examination Survey SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; wheeze; hay fever; hygiene hypothesis; periodontal disease; epidemiology; survey; antibodies; oral pathogens; Actinobacillus actinomycetemcomitans; Porphyromonas gingivalis ID CORONARY-HEART-DISEASE; SERUM ANTIBODY-LEVELS; PORPHYROMONAS-GINGIVALIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PERIODONTAL-DISEASE; UNITED-STATES; HAY-FEVER; RESPONSES; MICROBIOTA; CHILDREN AB Background: The hygiene hypothesis contends that fewer opportunities for infection have led to increases in the prevalences of asthma and other allergic diseases. Objective: This study evaluated the association between asthma, wheeze, and hay fever and antibodies to 2 oral bacteria associated with periodontal disease. Methods: Data were obtained from the Third National Health and Nutrition Examination Survey. Serum levels of IgG antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were quantified by enzyme-linked immunoassays in 9385 subjects age 12 years and older. The outcomes were current asthma, wheeze, and hay fever. Odds ratios (ORs) representing a 1-log-unit increase in IgG concentrations were estimated with logistic regression. ORs were adjusted for 8 confounders and weighted to represent the US population. Results: For each disease outcome, geometric mean antibody concentrations were higher in persons without the disease outcome than with the disease outcome. For a I-log-unit increase in P gingivalis antibody concentration, adjusted ORs were 0.41 (95% CI, 0.20-0.87) for asthma, 0.43 (0.23-0.78) for wheeze, and 0.45 (0.23-0.93) for hay fever. For A actinomytetemcomitans, those ORs were 0.56 (0.19-1.72), 0.39 (0.17-0.86), and 0.48 (0.23-1.03), respectively. Conclusion: Consistent with the hygiene hypothesis, higher concentrations of IgG antibodies to P gingivalis were significantly associated with lower prevalences of asthma, wheeze, and hay fever, and higher concentrations of IgG antibodies to A actinomycetemcomitans were significantly associated with a lower prevalence of wheeze. Clinical implications: Colonization of the oral cavity by bacteria and other microbes might play a protective role in the etiology of allergic disease. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Rho Inc, Durham, NC USA. RP Zeldin, DC (reprint author), NIEHS, NIH, POB 12233,Mail Drop D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Sever, Michelle/0000-0002-2435-1214 FU Intramural NIH HHS [Z01 ES025041-10] NR 36 TC 18 Z9 18 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2006 VL 118 IS 5 BP 1169 EP 1175 DI 10.1016/j.jaci.2006.07.029 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 137GY UT WOS:000244282300025 PM 17088145 ER PT J AU Savory, J Herman, MM Ghribi, O AF Savory, John Herman, Mary M. Ghribi, Othman TI Mechanisms of aluminum-induced neurodegeneration in animals: Implications for Alzheimer's disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article ID AMYLOID PRECURSOR PROTEIN; BCL-X-L; INDUCED NEUROFIBRILLARY DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; RABBIT HIPPOCAMPUS; TAU-PROTEIN; ENDOPLASMIC-RETICULUM; CYTOCHROME-C; INDUCED NEUROTOXICITY; INDUCED APOPTOSIS AB For four decades the controversial question concerning a possible role for aluminum neurotoxicity in contributing to the pathogenesis of Alzheimer's disease has been debated, and studies by different investigators have yielded contradictory results. The lack of sensitivity to aluminum neurotoxicity in transgenic mouse models of Alzheimer's disease has not allowed the system to be used to explore important aspects of this toxicity. Rabbits are particularly sensitive to aluminum neurotoxicity and they develop severe neurological changes that are dependent on dose, age and route of administration. The most prominent feature induced by aluminum in rabbit brain is a neurofibrillary degeneration that shares some similarity with the neurofibrillary tangles found in Alzheimer's disease patients. In the present review we discuss data from our laboratory and others, on the effects of aluminum on behaviour, neurologic function and morphology, using aluminum administered to rabbits via different routes. Finally, we will examine data on the possible cellular mechanisms underlying aluminum neurotoxicity, and potential neuroprotective strategies against aluminum toxicity. C1 Univ Virginia, Dept Pathol, Hlth Sci Ctr, Charlottesville, VA 22903 USA. NIMH, IRP, NIH, Bethesda, MD 20892 USA. Univ N Dakota, Sch Med, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58202 USA. RP Savory, J (reprint author), Univ Virginia, Dept Pathol, Hlth Sci Ctr, POB 800168, Charlottesville, VA 22903 USA. NR 60 TC 59 Z9 63 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD NOV PY 2006 VL 10 IS 2-3 BP 135 EP 144 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 125SC UT WOS:000243461700002 PM 17119283 ER PT J AU Kempf, AM Strother, ML Li, CY Kaur, H Huang, TTK AF Kempf, Angela M. Strother, Myra L. Li, Chaoyang Kaur, Harsohena Huang, Terry T-K. TI Leptin as a marker of body fat and hyperinsulinemia in college students SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE insulin resistance; insulin secretion; leptin; obesity ID INSULIN-RESISTANCE SYNDROME; PLASMA LEPTIN; METABOLIC SYNDROME; PUBERTAL CHILDREN; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; OBESE CHILDREN; MASS INDEX; SENSITIVITY; ADOLESCENTS AB Little is known about obesity and insulin resistance in college students. Leptin is a hormone secreted by fat cells and has been shown to strongly correlate with both obesity and insulin resistance in children and adults. We investigated associations of leptin with insulin secretion and action in 119 normal-weight students aged 18-24 years. Leptin was strongly correlated with total fat mass (r =.67, p < .001), percentage body fat (r =.81, p < .001), and to a lesser degree Body Mass Index, or BMI, (r =.23, p < .02). Leptin was associated with fasting insulin (beta +/- SE = 0.30 +/- 0.06, p < .001) and insulin resistance (beta +/- SE = 0.41 +/- 0.20, p < .001) independent of total fat, gender, and age, suggesting other mechanisms of leptin and insulin regulation besides obesity. Leptin resistance is present even among young and normal-weight college students. Leptin, even more so than BMI, is an important marker of adiposity and hyperinsulinemia in normal-weight college students and may potentially be used to predict type 2 diabetes. C1 Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. Univ Kansas, Student Hlth Serv, Lawrence, KS 66045 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Tufts Univ, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Medford, MA 02155 USA. RP Huang, TTK (reprint author), NICHHD, Ctr Res Mothers & Children, Endocrinol Nutr & Growth Branch, 20852 MSC 7510, Rockville, MD 20852 USA. EM huangter@mail.nih.gov NR 41 TC 8 Z9 10 U1 0 U2 2 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD NOV-DEC PY 2006 VL 55 IS 3 BP 175 EP 180 DI 10.3200/JACH.55.3.175-180 PG 6 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 109JB UT WOS:000242302900008 PM 17175904 ER PT J AU Maggio, M Blackford, A Taub, D Carducci, M Ble, A Metter, EJ Braga-Basaria, M Dobs, A Basaria, S AF Maggio, Marcello Blackford, Amanda Taub, Dennis Carducci, Michael Ble, Alessandro Metter, E. Jeffrey Braga-Basaria, Milena Dobs, Adrian Basaria, Shehzad TI Circulating inflammatory cytokine expression in men with prostate cancer undergoing androgen deprivation therapy SO JOURNAL OF ANDROLOGY LA English DT Article DE hypogonadism; inflammation ID TESTOSTERONE AB Prostate cancer (PCa) is one of the most common cancers in men. Androgen deprivation therapy (ADT) is employed in the treatment of patients with metastatic or recurrent PCa, resulting in castrate levels of testosterone. Recent studies have shown that male hypogonadism is associated with increased levels of proinflammatory and diminished concentrations of anti-inflammatory cytokines, which normalize upon testosterone treatment. Furthermore, an inflammatory state is associated with osteoporosis, sarcopenia and metabolic abnormalities. We examined 3 groups of men: 1) 20 men with PCa undergoing ADT for at least 12 months prior to the onset of the study (ADT group); 2) 18 age-matched men with non-metastatic PCa who had undergone local surgery and/or radiotherapy and had not yet received ADT and were eugonadal (non-ADT group); and 3) 20 age-matched healthy eugonadal men (control group). None of the subjects were suffering from any acute or chronic inflammatory conditions. Mean age was similar in the 3 groups (P =.41). Men in the ADT and non-ADT groups had higher BMI compared to the control group (P =.0005 and P =.01, respectively). Men in the ADT group had significantly lower mean serum total (P <.0001) and free (P <.0001) testosterone and estradiol (P <.0001) levels compared to the other 2 groups. No significant differences in serum levels of pro-inflammatory or antiinflammatory cytokines were observed between the 3 groups. These data suggest that men with PCa undergoing long-term ADT do not have elevated levels of pro-inflammatory cytokines compared to age and disease matched controls. Prospective studies are needed to evaluate for any acute changes in these inflammatory markers that might occur after the initiation of ADT. C1 Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Med,Div Endocrinol & Metab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Biostat, Dept Oncol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Kimmel Canc Ctr, Dept Oncol, Prostate Canc Res Program, Baltimore, MD 21224 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Basaria, S (reprint author), Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Med,Div Endocrinol & Metab, 4940 Eastern Ave,Suite B-114, Baltimore, MD 21224 USA. EM sbasari1@jhmi.edu FU NCRR NIH HHS [M01RR00052] NR 11 TC 19 Z9 19 U1 0 U2 1 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 NOV-DEC PY 2006 VL 27 IS 6 BP 725 EP 728 DI 10.2164/jandrol.106.000141 PG 4 WC Andrology SC Endocrinology & Metabolism GA 104QI UT WOS:000241973200004 PM 16775253 ER PT J AU Sharpless, KE Anderson, DL Betz, JM Butler, TA Capar, SG Cheng, J Fraser, CA Gardner, G Gay, ML Howell, DW Ihara, T Khan, MA Lam, JW Long, SE McCooeye, M Mackey, EA Mindak, WR Mitvalsky, S Murphy, KE NguyenPho, A Phinney, KW Porter, BJ Roman, M Sander, LC Satterfield, MB Scriver, C Sturgeon, R Thomas, JB Vocke, RD Wise, SA Wood, LJ Yang, L Yen, JH Ziobro, GC AF Sharpless, Katherine E. Anderson, David L. Betz, Joseph M. Butler, Therese A. Capar, Stephen G. Cheng, John Fraser, Catharine A. Gardner, Graeme Gay, Martha L. Howell, Daniel W. Ihara, Toshihide Khan, Mansoor A. Lam, Joseph W. Long, Stephen E. McCooeye, Margaret Mackey, Elizabeth A. Mindak, William R. Mitvalsky, Staci Murphy, Karen E. NguyenPho, Agnes Phinney, Karen W. Porter, Barbara J. Roman, Mark Sander, Lane C. Satterfield, Mary B. Scriver, Christine Sturgeon, Ralph Thomas, Jeanice Brown Vocke, Robert D., Jr. Wise, Stephen A. Wood, Laura J. Yang, Lu Yen, James H. Ziobro, George C. TI Preparation and characterization of a suite of ephedra-containing standard reference materials SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PLASMA-MASS SPECTROMETRY; DIETARY-SUPPLEMENTS; ALKALOIDS; STEREOISOMERS AB The National Institute of Standards and Technology, the U.S. Food and Drug Administration, Center for Drug Evaluation and Research and Center for Food Safety and Applied Nutrition, and the National Institutes of Health, Office of Dietary Supplements, are collaborating to produce a series of Standard Reference Materials (SRMs) for dietary supplements. A suite of ephedra materials is the first in the series, and this paper describes the acquisition, preparation, and value assignment of these materials: SRMs 3240 Ephedra sinica Stapf Aerial Parts, 3241 E. sinca Stapf Native Extract, 3242 E. sinica Stapf Commercial Extract, 3243 Ephedra-Containing Solid Oral Dosage Form, and 3244 Ephedra-Containing Protein Powder. Values are assigned for ephedrine alkaloids and toxic elements in all 5 materials. Values are assigned for other analytes (e.g., caffeine, nutrient elements, proximates, etc.) in some of the materials, as appropriate. Materials in this suite of SRMs are intended for use as primary control materials when values are assigned to in-house (secondary) control materials and for validation of analytical methods for the measurement of alkaloids, toxic elements, and, in the case of SRM 3244, nutrients in similar materials. C1 Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Natl Res Council Canada, Ottawa, ON K1A 0R9, Canada. Food Prod Assoc, Washington, DC 20005 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. ChromaDex Inc, Clearwater, FL 33760 USA. Natl Inst Stand & Technol, Stat Engn Div, Gaithersburg, MD 20899 USA. RP Sharpless, KE (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. EM katherine.sharpless@nist.gov OI Lam, Joseph/0000-0001-6402-0535; Sturgeon, Ralph/0000-0001-7304-3034; McCooeye, Margaret/0000-0001-9424-9111; Yang, Lu/0000-0002-4351-2503 NR 28 TC 15 Z9 15 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2006 VL 89 IS 6 BP 1483 EP 1495 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 116SO UT WOS:000242822800006 PM 17225593 ER PT J AU Tourand, Y Bankhead, T Wilson, SL Putteet-Driver, AD Barbour, AG Byram, R Rosa, PA Chaconas, G AF Tourand, Yvonne Bankhead, Troy Wilson, Sandra L. Putteet-Driver, Adrienne D. Barbour, Alan G. Byram, Rebecca Rosa, Patricia A. Chaconas, George TI Differential telomere processing by Borrelia telomere resolvases in vitro but not in vivo SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; LINEAR PLASMIDS; RELAPSING FEVER; NORTH-AMERICA; STRAIN B31; BURGDORFERI; SEQUENCE; GENOME; REST; RECOMBINATION AB Causative agents of Lyme disease and relapsing fever, including Borrelia burgdorferi and Borrelia hermsii, respectively, are unusual among bacteria in that they possess a segmented genome with linear DNA molecules terminated by hairpin ends, known as telomeres. During replication, these telomeres are processed by the essential telomere resolvase, ResT, in a unique biochemical reaction known as telomere resolution. In this study, we report the identification of the B. hermsii resT gene through cross-species hybridization. Sequence comparison of the B. hermsii protein with the B. burgdorferi orthologue revealed 67% identity, including all the regions currently known to be crucial for telomere resolution. In vitro studies, however, indicated that B. hermsii ResT was unable to process a replicated B. burgdorferi type 2 telomere substrate. In contrast, in vivo cross-species complementation in which the native resT gene of B. burgdorferi was replaced with B. hermsii resT had no discernible effect, even though B. burgdorferi strain B31 carries at least two type 2 telomere ends. The B. burgdorferi ResT protein was also able to process two telomere spacing mutants in vivo that were unresolvable in vitro. The unexpected differential telomere processing in vivo versus in vitro by the two telomere resolvases suggests the presence of one or more accessory factors in vivo that are normally involved in the reaction. Our current results are also expected to facilitate further studies into ResT structure and function, including possible interaction with other Borrelia proteins. C1 Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada. Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA. NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chaconas, G (reprint author), Univ Calgary, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM chaconas@ucalgary.ca RI Barbour, Alan/B-3160-2009; OI Barbour, Alan/0000-0002-0719-5248; Bankhead, Troy/0000-0002-4336-0298 NR 46 TC 25 Z9 26 U1 0 U2 3 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 NOV PY 2006 VL 188 IS 21 BP 7378 EP 7386 DI 10.1128/JB.00760-06 PG 9 WC Microbiology SC Microbiology GA 097TM UT WOS:000241471600008 PM 16936037 ER PT J AU Kuban, W Banach-Orlowska, M Schaaper, RM Jonczyk, P Fijalkowska, IJ AF Kuban, Wojciech Banach-Orlowska, Magdalena Schaaper, Roel M. Jonczyk, Piotr Fijalkowska, Iwona J. TI Role of DNA polyrnerase IV in Escherichia coli SOS mutator activity SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POLYMERASE-III HOLOENZYME; POL-IV; ADAPTIVE MUTATION; LAGGING-STRAND; RECA PROTEIN; UNTARGETED MUTAGENESIS; GENETIC REQUIREMENTS; BASE SUBSTITUTION; FIDELITY; REPLICATION AB Constitutive expression of the SOS regulon in Escherichia coli recA730 strains leads to a mutator phenotype (SOS mutator) that is dependent on DNA polymerase V (umuDC gene product). Here we show that a significant fraction of this effect also requires DNA polymerase IV (dinB gene product). C1 Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Fijalkowska, IJ (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Pawinskiego 5A, PL-02106 Warsaw, Poland. EM iwonaf@ibb.waw.pl RI Fijalkowska, Iwona/I-7796-2016 FU Intramural NIH HHS NR 46 TC 23 Z9 23 U1 0 U2 3 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 NOV PY 2006 VL 188 IS 22 BP 7977 EP 7980 DI 10.1128/JB.01088-06 PG 4 WC Microbiology SC Microbiology GA 104EB UT WOS:000241938100029 PM 16980447 ER PT J AU Spencer, RG Calton, EF Camacho, NP AF Spencer, Richard G. Calton, Ericka F. Camacho, Nancy Pleshko TI Statistical comparison of Fourier transform infrared spectra SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE infrared spectroscopy; signal-to-noise; statistical comparison; signal averaging; sample stability ID TO-NOISE RATIOS; CARTILAGE DEGRADATION; SPECTROSCOPY; COLLAGEN; FTIR; PROBE AB Spectroscopic assessment of whether a biological sample has changed as a result of processing or degradation is generally carried out by qualitative comparison of spectra, without statistical analysis, resulting in a subjective evaluation of sample stability. Here, we present a formalism for quantitative statistical comparison of signal-averaged Fourier transform infrared spectra, commonly used to assess molecular properties of biological samples. Expressions are derived permitting the comparison of 1. single beam spectra; 2. transmittance spectra obtained by calculating the ratio of single beam spectra of a sample and background; and 3. absorbance spectra derived from transmittance spectra. An application of these results to the degradation of cartilage is presented. Two absorbance spectra of a cartilage sample taken in succession are found to be statistically identical with respect to the ratio of the amplitude of the amide I band to the amplitude of the amide II band. However, a spectrum of the same sample acquired after a 24-h degradation period, while similar to the spectrum of the fresh sample, is found to have an altered ratio of these spectral band amplitudes, consistent with degradation of the cartilage matrix. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Hosp Special Surg, Div Res, Musculoskeletal Imaging & Spect Lab, New York, NY 10021 USA. NIA, NIH, Nucl Magnet Resonance Unit, Baltimore, MD 21224 USA. RP Camacho, NP (reprint author), Hosp Special Surg, Div Res, Musculoskeletal Imaging & Spect Lab, 535 E 70th St, New York, NY 10021 USA. EM camachon@hss.edu FU Intramural NIH HHS; NIBIB NIH HHS [R01 EB00744, R01 EB000744] NR 15 TC 1 Z9 1 U1 0 U2 5 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2006 VL 11 IS 6 AR 064023 DI 10.1117/1.2393231 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 132UU UT WOS:000243968700026 PM 17212546 ER PT J AU Sviridov, AP Ulissi, Z Chernomordik, V Hassan, M Gandjbakhche, AH AF Sviridov, Alexander P. Ulissi, Zachary Chernomordik, Victor Hassan, Moinuddin Gandjbakhche, Amir H. TI Visualization of biological texture using correlation coefficient images SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE image enhancement; texture analysis; correlation coefficients; polarization images; tissues ID MICROCALCIFICATIONS; ENHANCEMENT; MAMMOGRAMS AB Subsurface structural features of biological tissue are visualized using polarized light images. The technique of Pearson correlation coefficient analysis is used to reduce blurring of these features by unpolarized backscattered light and to visualize the regions of high statistical similarities within the noisy tissue images. It is shown that under certain conditions, such correlation coefficient maps are determined by the textural character of tissues and not by the chosen region of interest, providing information on tissue structure. As an example, the subsurface texture of a demineralized tooth sample is enhanced from a noisy polarized light image. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Laser & Informat Technol, Troitsk 142190, Moscow Region, Russia. RP Hassan, M (reprint author), NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. EM hassanm@mail.nih.gov NR 13 TC 2 Z9 2 U1 0 U2 3 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2006 VL 11 IS 6 AR 06185LR DI 10.1117/1.2400248 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 132UU UT WOS:000243968700002 ER PT J AU Loucks, EB Sullivan, LM D'Agostino, RB Larson, MG Berkman, LF Benjamin, EJ AF Loucks, Eric B. Sullivan, Lisa M. D'Agostino, Ralph B., Sr. Larson, Martin G. Berkman, Lisa F. Benjamin, Emelia J. TI Social networks and inflammatory markers in the Framingham Heart Study SO JOURNAL OF BIOSOCIAL SCIENCE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MYOCARDIAL-INFARCTION; GENDER DIFFERENCES; DISEASE; HEALTH; RISK; MORTALITY; STRESS; INTERLEUKIN-6; ASSOCIATION AB Lack of social integration predicts coronary heart disease mortality in prospective studies; however, the biological pathways that may be responsible are poorly understood. The specific aims of this study were to examine whether social networks are associated with serum concentrations of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Participants in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were eligible for inclusion in the study. Social networks were assessed using the Berkman-Syme Social Network Index (SNI). Concentrations of IL-6, CRP, sICAM-1 and MCP-1 were measured in fasting serum samples. Multivariable linear regression analyses were used to assess the association of social networks with inflammatory markers adjusting for potential confounders including age, smoking, blood pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and antihypertensive medication, diabetes, cardiovascular disease, depression and socioeconomic status. Results found that the SNI was significantly inversely associated with IL-6 in men (p=0-03) after adjusting for potential confounders. In age-adjusted analyses, social networks also were significantly inversely associated with IL-6 for women (p=0-03) and were marginally to modestly associated with CRP and sICAM-1 for men (P=0-08 and 0-02, respectively), but these associations were not significant in the multivariate analyses. In conclusion, social networks were found to be inversely associated with interleukin-6 levels in men. The possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Development & Hlth, Boston, MA 02115 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Med & Prevent Med, Boston, MA 02215 USA. NHLBI, Heart Study, Framingham, MA USA. RP Loucks, EB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Development & Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Loucks, Eric/I-1272-2014; OI Loucks, Eric/0000-0002-9962-0386; Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [HL64753, HL76784, N01-HC-25195] NR 25 TC 58 Z9 59 U1 3 U2 19 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0021-9320 J9 J BIOSOC SCI JI J. Biosoc. Sci. PD NOV PY 2006 VL 38 IS 6 BP 835 EP 842 DI 10.1017/S0021932005001203 PG 8 WC Demography; Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Demography; Public, Environmental & Occupational Health; Biomedical Social Sciences GA 104TD UT WOS:000241981300009 PM 16441967 ER PT J AU Cho, J Choi, K Darden, T Reynolds, PR Petitte, JN Shears, SB AF Cho, Jaiesoon Choi, Kuicheon Darden, Thomas Reynolds, Paul R. Petitte, James N. Shears, Stephen B. TI Avian multiple inositol polyphosphate phosphatase is an active phytase that can be engineered to help ameliorate the planet's "phosphate crisis" SO JOURNAL OF BIOTECHNOLOGY LA English DT Article DE phytase; InSP6; MINPP; chickens ID MYOINOSITOL HEXAKISPHOSPHATE PHOSPHOHYDROLASES; HISTIDINE ACID PHYTASES; BIOCHEMICAL-CHARACTERIZATION; ENDOPLASMIC-RETICULUM; IN-VITRO; PHOSPHORUS; 3-PHOSPHATASE; NUTRIENT; MANURE; SIZE AB Contemporary phytase research is primarily concerned with ameliorating the problem of inadequate digestion of inositol hexakisphosphate (phytate; InSP6) in monogastric farm animal feed, so as to reduce the pollution that results from the high phosphate content of the manure. In the current study we pursue a new, safe and cost-effective solution. We demonstrate that the rate of hydrolysis of InSP6 by recombinant avian MINPP (0.7 mu mol/mg protein/min) defines it as by far the most active phytase found to date in any animal cell (the corresponding activity of recombinant mammalian MINPP is only 0.006 mu mol/mg protein/min). Although avian MINPP has less than 20% sequence identity with microbial phytases, we create a homology model of MINPP in which it is predicted that the structure of the phytase active site is well-conserved. This model is validated by site-directed mutagenesis and by use of a substrate analogue, scyllo-InSP6, which we demonstrate is only a weak MINPP substrate. In a model chicken cell line, we overexpressed a mutant form of MINPP that is secretion-competent. This version of the enzyme was actively secreted without affecting either cell viability or the cellular levels of any inositol phosphates. Our studies offer a genetic strategy for greatly improving dietary InSP6 digestion in poultry. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, DHSS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Struct Biol, NIH, DHSS, Res Triangle Pk, NC 27709 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. N Carolina State Univ, Coll Agr & Life Sci, Raleigh, NC 27695 USA. RP Shears, SB (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, DHSS, POB 12233, Res Triangle Pk, NC 27709 USA. EM Shears@niehs.nih.gov FU Intramural NIH HHS [Z01 ES080046-19] NR 41 TC 18 Z9 19 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD NOV 1 PY 2006 VL 126 IS 2 BP 248 EP 259 DI 10.1016/j.jbiotec.2006.04.028 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 102AO UT WOS:000241783300015 PM 16759730 ER PT J AU Strotmeyer, ES Cauley, JA Schwartz, AV de Rekeneire, N Resnick, HE Zmuda, JM Shorr, RI Tylavsky, FA Vinik, AI Harris, TB Newman, AB AF Strotmeyer, Elsa S. Cauley, Jane A. Schwartz, Ann V. de Rekeneire, Nathalie Resnick, Helaine E. Zmuda, Joseph M. Shorr, Ronald I. Tylavsky, Frances A. Vinik, Aaron I. Harris, Tamara B. Newman, Anne B. CA ABC Study TI Reduced peripheral nerve function is related to lower hip BMD and calcaneal QUS in older white and black adults: The health, aging, and body composition study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE peripheral nerve; aging; BMD; bone ultrasound ID DEPENDENT DIABETES-MELLITUS; BONE-MINERAL DENSITY; ARTERIAL-DISEASE; FOOT ULCERATION; WOMENS HEALTH; RISK-FACTORS; AGE; FRACTURE; NEUROPATHY; FALLS AB Bone tissue is innervated, and peripheral nerve function may impact BMD. Older black and white men and women (N = 2200) in the Health, Aging, and Body Composition Study with worse sensory and motor peripheral nerve function had lower hip BMD and calcaneal BUA independent of lean mass, strength, physical ability, and diabetes. Poor peripheral nerve function may directly affect bone. Introduction: Bone tissue is innervated, yet little is known about the impact of nerve function on BMD. Poor peripheral nerve function may contribute to lower BMD and higher fracture risk, particularly in those with diabetic neuropathy. Materials and Methods: The Health, Aging, and Body Composition (Health ABC) Study included annual exams in white and black men and women 70-79 years of age recruited from Pittsburgh and Memphis. Nerve function in legs/feet was assessed by 1.4- and 10-g monofilament detection, vibration threshold, and peroneal motor nerve conduction velocity (NCV) and amplitude (CMAP). Total hip BMD, heel broadband ultrasound attenuation (BUA), and total fat and lean mass were measured I year later (QDR 4500A, Sahara QUS; Hologic). Results: Participants (N = 2200) were 48% men and 37% black. Poor nerve function (lower monofilament detection, higher vibration threshold, lower CMAP, lower NCV) was associated with 1.4-5.7% lower BUA and significant for all but NCV, adjusted for demographics, diabetes, body composition, and physical ability. Results were similar for adjusted hip BMD, with 1.0-2.9% lower BMD, significant for monofilament and CMAP testing. When considering the components of BMD, total hip area was 1.8-4.9% higher in those with the worst nerve function, although BMC showed little difference. Lower monofilament detection and CMAP were independently associated with lower heel BUA (p < 0.01), and monofilament detection was associated with lower hip BMD (p < 0.05) in regression additionally adjusted for lifestyle factors, bone-active medications, and diabetes-related complications. Conclusions: Poor peripheral nerve function may directly related to lower BMD, likely through an increase in bone area in older adults, independent of lean mass, strength, physical ability, and diabetes. Whether those with impaired nerve function are at higher risk for fracture independent of falls needs to be studied. C1 Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Ctr Dis Control, Atlanta, GA USA. MedStar Res Inst, Dept Epidemiol & Stat, Hyattsville, MD USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Div Geriatr Med, Pittsburgh, PA USA. Sch Med, Pittsburgh, PA USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 N Bellfield Ave,Room 515, Pittsburgh, PA 15213 USA. EM StrotmeyerE@edc.pitt.edu RI Newman, Anne/C-6408-2013; Strotmeyer, Elsa/F-3015-2014; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Strotmeyer, Elsa/0000-0002-4093-6036 FU Intramural NIH HHS; NIA NIH HHS [N-01-AG-6-2103, N01-AG-6-2101, N01-AG-6-2106] NR 56 TC 22 Z9 23 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2006 VL 21 IS 11 BP 1803 EP 1810 DI 10.1359/JBMR.060725 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 099MR UT WOS:000241599600017 PM 17002569 ER PT J AU Kuznetsova, SA Issa, P Perruccio, EM Zeng, BX Sipes, JM Ward, Y Seyfried, NT Fielder, HL Day, AJ Wight, TN Roberts, DD AF Kuznetsova, Svetlana A. Issa, Philip Perruccio, Elizabeth M. Zeng, Bixi Sipes, John M. Ward, Yvona Seyfried, Nicholas T. Fielder, Helen L. Day, Anthony J. Wight, Thomas N. Roberts, David D. TI Versican-thrombospondin-1 binding in vitro and colocalization in microfibrils induced by inflammation on vascular smooth muscle cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE matricellular proteins; proteoglycan; link modules; vascular biology; inflammation ID RETROVIRALLY MEDIATED OVEREXPRESSION; RECEPTOR-RELATED PROTEIN; ALPHA-TRYPSIN INHIBITOR; EXTRACELLULAR-MATRIX; HEPARIN-BINDING; PLATELET THROMBOSPONDIN; VERSICAN INTERACTS; TERMINAL DOMAIN; AMINO-TERMINUS; PG-M/VERSICAN AB We identified a specific interaction between two secreted proteins, thrombospondin-1 and versican, that is induced during a toll-like receptor-3-dependent inflammatory response in vascular smooth muscle cells. Thrombospondin-1 binding to versican is modulated by divalent cations. This interaction is mediated by interaction of the G1 domain of versican with the N-module of thrombospondin-1 but only weakly with the corresponding N-terminal region of thrombospondin-2. The G1 domain of versican contains two Link modules, which are known to mediate TNF alpha-stimulated gene-6 protein binding to thrombospondin-1, and the related G1 domain of aggrecan is also recognized by thrombospondin-1. Therefore, thrombospondin-1 interacts with three members of the Link-containing hyaladherin family. On the surface of poly-I:C-stimulated vascular smooth muscle cells, versican organizes into fibrillar structures that contain elastin but are largely distinct from those formed by hyaluronan. Endogenous and exogenously added thrombospondin-1 incorporates into these structures. Binding of exogenous thrombospondin-1 to these structures, to purified versican and to its G1 domain is potently inhibited by heparin. At higher concentrations, exogenous thrombospondin-1 delays the poly-I: C induced formation of structures containing versican and elastin, suggesting that thrombospondin-1 negatively modulates this component of a vascular smooth muscle inflammatory response. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Oxford, Dept Biochem, MRC, Immunochem Unit, Oxford OX1 3QU, England. Virginia Mason, Benaroya Res Inst, Hope Heart Program, Seattle, WA 98101 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Day, Anthony/O-1658-2015 OI Roberts, David/0000-0002-2481-2981; Day, Anthony/0000-0002-1415-3134 FU Intramural NIH HHS; Medical Research Council [MC_U138274352]; NHLBI NIH HHS [HL 18645] NR 57 TC 25 Z9 27 U1 0 U2 2 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 NOV 1 PY 2006 VL 119 IS 21 BP 4499 EP 4509 DI 10.1242/jcs.03171 PG 11 WC Cell Biology SC Cell Biology GA 103NI UT WOS:000241893200015 PM 17046999 ER PT J AU Rafii, MS Hagiwara, H Mercado, ML Seo, NS Xu, TS Dugan, T Owens, RT Hook, M McQuillan, DJ Young, MF Fallon, JR AF Rafii, Michael S. Hagiwara, Hiroki Mercado, Mary Lynn Seo, Neung S. Xu, Tianshun Dugan, Tracey Owens, Rick T. Hook, Magnus McQuillan, David J. Young, Marian F. Fallon, Justin R. TI Biglycan binds to alpha- and gamma-sarcoglycan and regulates their expression during development SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID DYSTROPHIN-GLYCOPROTEIN COMPLEX; GIRDLE MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; VACCINIA VIRUS; SMOOTH-MUSCLE; PROTEOGLYCANS BIGLYCAN; OVERLAP EXTENSION; AGRIN RECEPTOR; DECORIN; DYSTROGLYCAN AB The dystrophin-associated protein complex (DAPC), which links the cytoskeleton to the extracellular matrix, is essential for muscle cell survival, and is defective in a wide range of muscular dystrophies. The DAPC contains two transmembrane subcomplexes-the dystroglycans and the sarcoglycans. Although several extracellular binding partners have been identified for the dystroglycans, none have been described for the sarcoglycan subcomplex. Here we show that the small leucine-rich repeat (LRR) proteoglycan biglycan binds to alpha- and gamma-sarcoglycan as judged by ligand blot overlay and co-immunoprecipitation assays. Our studies with biglycan-decorin chimeras show that alpha-and gamma-sarcoglycan bind to distinct sites on the polypeptide core of biglycan. Both biglycan proteoglycan as well as biglycan polypeptide lacking glycosaminoglycan (GAG) side chains are components of the dystrophin glycoprotein complex isolated from adult skeletal muscle membranes. Finally, our immunohistochemical and biochemical studies with biglycan null mice show that the expression of alpha- and gamma-sarcoglycan is selectively reduced in muscle from young (P14-P21) animals, while levels in adult muscle (>= P35) are unchanged. We conclude that biglycan is a ligand for two members of the sarcoglycan complex and regulates their expression at discrete developmental ages. C1 Brown Univ, Dept Neurosci, Providence, RI 02912 USA. LifeCell Corp, Branchburg, NJ USA. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Syst Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX USA. RP Fallon, JR (reprint author), Brown Univ, Dept Neurosci, 190 Thayer St,Box 1953, Providence, RI 02912 USA. EM Justin_Fallon@Brown.edu FU NCRR NIH HHS [RR15578, P20 RR015578]; NICHD NIH HHS [HD23924, R01 HD023924, R01 HD023924-13A1, R01 HD023924-14, R01 HD023924-17, R01 HD023924-15, R01 HD023924-14S1, R01 HD023924-12, R01 HD023924-16] NR 59 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 2006 VL 209 IS 2 BP 439 EP 447 DI 10.1002/jcp.20740 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 089MG UT WOS:000240884100023 PM 16883602 ER PT J AU Fu, YM Zhang, H Ding, MJ Li, YQ Fu, X Yu, ZX Meadows, GG AF Fu, Ya-Min Zhang, Hui Ding, Mingjie Li, Yi-Qi Fu, Xing Yu, Zu-Xi Meadows, Gary G. TI Selective amino acid restriction targets mitochondria to induce apoptosis of androgen-independent prostate cancer cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID FOCAL ADHESION KINASE; PLASMINOGEN-ACTIVATOR INHIBITORS; BCL-2 FAMILY-MEMBERS; SIGNAL-TRANSDUCTION; PHENYLALANINE RESTRICTION; METHIONINE RESTRICTION; SURVIVAL PATHWAY; CARCINOMA-CELLS; CYCLE ARREST; GENE-THERAPY AB Relative specific amino acid dependency is one of the metabolic abnormalities of cancer cells, and restriction of specific amino acids induces apoptosis of Prostate cancer cells. This study shows that restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (GIn), or methionine (Met), modulates Raf and Akt survival pathways and affects the function of mitochondria in DUI 45 and PC3, in vitro. These three restrictions inhibit energy production (ATP synthesis) and induce generation of reactive oxygen species (ROS). Restriction of Tyr/Phe or Met in DUI 45 and Met in PC3 reduces mitochondrial membrane potential (Delta Psi m) and induces caspase-dependent and -independent apoptosis. In DUI 45, Tyr/Phe or Met restriction reduces activity of Akt, mitochondrial distribution of phosphorylated Raf and apoptosis inducing factor (AIF), and increases mitochondrial distribution of Bak. Mitochondrial BcI-XL is increased in Tyr/Phe-restricted but decreased in Met-restricted cells. Under Tyr/Phe or Met restriction, reduced mitochondrial Raf does not inactivate the pro-apoptotic function of Bak. Tyr/Phe restriction also inhibits BcI-2 and Met restriction inhibits BcI-XL in mitochondria. These comprehensive actions damage the integrity of the mitochondria and induce apoptosis of DU145. In PC3, apoptosis induced by Met restriction was not associated with alterations in intracellular distribution of Raf, BcI-2 family proteins, or AIF. All of the amino acid restrictions inhibited Akt activity in this cell line. We conclude that specific amino acid restriction differentially interferes with homeostasis/balance between the Raf and Akt survival pathways and with the interaction of Raf and BcI-2 family proteins in mitochondria to induce apoptosis of DU145 and PC3 cells. C1 Washington State Univ, Coll Pharm, Canc Prevent & Res Ctr, Dept Pharmaceut Sci, Pullman, WA 99164 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. RP Meadows, GG (reprint author), Washington State Univ, Coll Pharm, Canc Prevent & Res Ctr, Dept Pharmaceut Sci, Box 646713, Pullman, WA 99164 USA. EM meadows@wsu.edu FU NCI NIH HHS [R01CA101035] NR 78 TC 16 Z9 17 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 2006 VL 209 IS 2 BP 522 EP 534 DI 10.1002/jcp.20766 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 089MG UT WOS:000240884100031 PM 16897757 ER PT J AU Bhattacharjee, AK Chang, L White, L Bazinet, RP Rapoport, SI AF Bhattacharjee, Abesh K. Chang, Lisa White, Laura Bazinet, Richard P. Rapoport, Stanley I. TI D-Amphetamine stimulates D-2 dopamine receptor-mediated brain signaling involving arachidonic acid in unanesthetized rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE amphetamine; arachidonic acid; brain; dopamine; D-2; phospholipase A(2); raclopride; receptor ID CEREBRAL GLUCOSE-UTILIZATION; PHOSPHOLIPASE A(2) ACTIVATION; POSITRON-EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; BLOOD-FLOW; IN-VIVO; MAMMALIAN BRAIN; INVIVO MICRODIALYSIS; STRIATAL DOPAMINE; PREFRONTAL CORTEX AB In rat brain, dopaminergic D-2-like but not D-1-like receptors can be coupled to phospholipase A(2) (PLA(2)) activation, to release the second messenger, arachidonic acid (AA, 20:4n-6), from membrane phospholipids. In this study, we hypothesized that D-amphetamine, a dopamine-releasing agent, could initiate such AA signaling. The incorporation coefficient, k* (brain radioactivity/ integrated plasma radioactivity) for AA, a marker of the signal, was determined in 62 brain regions of unanesthetized rats that were administered i.p. saline, D-amphetamine (2.5 or 0.5mg/kg i.p.), or the D-2-like receptor antagonist raclopride (6 mg/kg, i.v.) before saline or 2.5 mg/kg D-amphetamine. After injecting [1-C-14] AA intravenously, k* was measured by quantitative autoradiography. Compared to saline-treated controls, D-amphetamine 2.5 mg/kg i.p. increased k* significantly in 27 brain areas rich in D-2-like receptors. Significant increases were evident in neocortical, extrapyramidal, and limbic regions. Pretreatment with raclopride blocked the increments, but raclopride alone did not alter baseline values of k*. In independent experiments, D-amphetamine 0.5 mg/kg i.p. increased k* significantly in only seven regions, including the nucleus accumbens and layer IV neocortical regions. These results indicate that D-amphetamine can indirectly activate brain PLA2 in the unanesthetized rat, and that activation is initiated entirely at D-2-like receptors. D-Amphetamine's low-dose effects are consistent with other evidence that the nucleus accumbens, considered a reward center, is particularly sensitive to the drug. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bhattacharjee, AK (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM abeshb@mail.nih.gov FU Intramural NIH HHS NR 102 TC 20 Z9 20 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 2006 VL 26 IS 11 BP 1378 EP 1388 DI 10.1038/sj.jcbfm.9600290 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 098AZ UT WOS:000241493700004 PM 16511499 ER PT J AU Ari, M Bakalov, VK Hill, S Bondy, CA AF Ari, Mim Bakalov, Vladimir K. Hill, Suvimol Bondy, Carolyn A. TI The effects of growth hormone treatment on bone mineral density and body composition in girls with Turner syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SHORT-TERM; MASS; CHILDREN; GH; DEFICIENCY; THERAPY; HEIGHT AB Background: Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition. Objective: The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS. Method: In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006. Results: The two groups were similar in age (12.3 yr, SD 2.9), bone age (11.5 yr, SD 2.6), and weight (42.8 kg, SD 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (SD 3.2) yr (range 1-14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1-L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P < 0.001), whereas body fat percent was lower (P < 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously. Conclusions: Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity. C1 NICHHD, Chief Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Chief Dev Endocrinol Branch, NIH, BG10,Room 1E-3330, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS NR 20 TC 29 Z9 29 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4302 EP 4305 DI 10.1210/jc.2006-1351 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300018 PM 16940444 ER PT J AU Khoromi, S Muniyappa, R Nackers, L Gray, N Baldwin, H Wong, KA Matheny, LA Moquin, B Rainer, A Hill, S Remaley, A Johnson, LL Max, MB Blackman, MR AF Khoromi, Suzan Muniyappa, Ranganath Nackers, Lisa Gray, Nora Baldwin, Howard Wong, Kelli Anne Matheny, Leigh Ann Moquin, Barbara Rainer, Aliya Hill, Suvimol Remaley, Alan Johnson, Laura Lee Max, Mitchell B. Blackman, Marc R. TI Effects of chronic osteoarthritis pain on neuroendocrine function in men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; LOW-BACK-PAIN; RHEUMATOID-ARTHRITIS; FIBROMYALGIA SYNDROME; CORTISOL; TESTOSTERONE; DEXAMETHASONE; HORMONES; HYPOGONADISM; INTENSITY AB Context: Chronic pain has been associated with elevated cortisol, reduced LH and testosterone (T), and/or augmented circulating or excreted catecholamines. Most endocrine studies have been conducted in patients in whom the potentially confounding effects of depression, inflammatory disease, or coexistent medication use have not been controlled. Objective: The objective of the study was to test the hypothesis that chronic pain activates ACTH-cortisol and suppresses LH-T. Design and Setting: This was a case control study conducted at a clinical research center. Participants: Participants included 16 opioid-naive men with chronic osteoarthritis pain, aged 35-65 yr with body mass index 20-30 kg/m(2), and 12 healthy, opioid- and pain-free men of similar ages and body mass indexes. Methods: We compared circulating concentrations of ACTH, cortisol, LH, and T derived from every 20-min blood sampling (2000-0800 h), and 24-h urinary excretion of cortisol, epinephrine, norepinephrine, and dopamine. Results: There were no significant differences in mean or integrated concentrations of ACTH, cortisol, LH, or T, or in the corresponding approximate entropy scores in osteoarthritis patients, compared with control subjects. The 0800-h serum LH concentrations were elevated in patients vs. controls (6.42 +/- 1.65 vs. 3.99 +/- 1.54 IU/liter, mean +/- SD, P = 0.02), whereas there were no significant group differences in total or free T, SHBG, cortisol binding globulin, dehydroepiandrosterone sulfate, or urinary cortisol and catecholamines. Conclusions: These data suggest that neuroendocrine function is not significantly altered in otherwise healthy men with chronic musculoskeletal pain and that prior reports of such hormonal abnormalities may have resulted from the confounding effects of coexistent illness or medication use. C1 NIH, Dept Hlth & Human Serv, Div Intertramural Res,Clin Invest Lab, Natl Ctr Complementary & Alernat Med, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Dept Nursing, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Dept Radiol, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Dept Lab Med, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Clin Pain Res Sect, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Khoromi, S (reprint author), NIH, Dept Hlth & Human Serv, Div Intertramural Res,Clin Invest Lab, Natl Ctr Complementary & Alernat Med, Bldg 10,4-1741, Bethesda, MD 20892 USA. EM khoromisu@mail.nih.gov RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU Intramural NIH HHS NR 45 TC 11 Z9 11 U1 0 U2 5 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 NOV PY 2006 VL 91 IS 11 BP 4313 EP 4318 DI 10.1210/jc.2006-1122 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300020 PM 16912126 ER PT J AU Tronko, MD Brenner, AV Olijnyk, VA Robbins, J Epstein, OV McConnell, RJ Bogdanova, TI Fink, DJ Likhtarev, IA Lubin, JH Markov, VV Bouville, AC Terekhova, GM Zablotska, LB Shpak, VM Brill, AB Tereshchenko, VP Masnyk, IJ Ron, E Hatch, M Howe, GR AF Tronko, M. D. Brenner, A. V. Olijnyk, V. A. Robbins, J. Epstein, O. V. McConnell, R. J. Bogdanova, T. I. Fink, D. J. Likhtarev, I. A. Lubin, J. H. Markov, V. V. Bouville, A. C. Terekhova, G. M. Zablotska, L. B. Shpak, V. M. Brill, A. B. Tereshchenko, V. P. Masnyk, I. J. Ron, E. Hatch, M. Howe, G. R. TI Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: Results from the first screening cycle (1998-2000) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ATOMIC-BOMB SURVIVORS; SERUM THYROGLOBULIN; TG AUTOANTIBODIES; RADIATION; CHILDREN; ADOLESCENTS; PREVALENCE; DEFICIENCY; DISORDERS; EXCRETION AB Context: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 ((131)I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. Objective: The objective of the study was to quantify risk of AIT after (131)I exposure. Design/Setting/Participants: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. Outcomes: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. Results: No significant association was found between (131)I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with (131)I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease- free individuals. Conclusions: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which (131)I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Inst Endocrinol & Metab, UA-04114 Kiev, Ukraine. Acad Med Sci, Sci Ctr Radiat Med, UA-04050 Kiev, Ukraine. NCI, Div Canc Epidemol & Genet, Natl Inst Diabet & Digest & Kidney Dis, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Inst Diabet & Digest & Kidney Dis, Clin Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Med, Thyroid Ctr, New York, NY 10032 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Pathol, Coll Phys & Surg, New York, NY 10032 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. Vanderbilt Univ, Sch Med, Dept Radiat & Radiol Sci, Nashville, TN 37232 USA. RP Brenner, AV (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7090, Bethesda, MD 20892 USA. EM brennera@mail.nih.gov RI Brill, Aaron/H-3732-2014 OI Brill, Aaron/0000-0001-7538-086X FU Intramural NIH HHS NR 44 TC 26 Z9 29 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 NOV PY 2006 VL 91 IS 11 BP 4344 EP 4351 DI 10.1210/jc.2006-0498 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300024 PM 16912122 ER PT J AU Hadigan, C Liebau, J Torriani, M Andersen, R Grinspoon, S AF Hadigan, Colleen Liebau, James Torriani, Martin Andersen, Rebecca Grinspoon, Steven TI Improved triglycerides and insulin sensitivity with 3 months of acipimox in human immunodeficiency virus-infected patients with hypertriglyceridemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FREE FATTY-ACIDS; INTRAMYOCELLULAR LIPID-ACCUMULATION; ACTIVE ANTIRETROVIRAL THERAPY; DIABETES-MELLITUS; HIV-LIPODYSTROPHY; ADIPOSE-TISSUE; DISEASE RISK; LIPOLYSIS; REDISTRIBUTION; DYSLIPIDEMIA AB Context: Metabolic abnormalities such as hypertriglyceridemia remain a challenge for optimizing long-term health in HIV- infected patients. Objective: Elevation of free fatty acids ( FFAs) may contribute to hyperlipidemia and insulin resistance in HIV. We evaluated the efficacy and safety of chronic inhibition of lipolysis in HIV- infected men and women with hypertrigyceridemia. We hypothesized that acipimox would lead to significant reductions in triglycerides and improved insulin sensitivity, compared with placebo. Design: A 3- month, randomized, double- blind, controlled trial of acipimox ( 250 mg thrice daily) vs. placebo was conducted in 23 HIV-infected men and women with hypertriglyceridemia ( > 150 mg/ dl), abnormal fat distribution, and no current lipid-lowering therapy. The primary outcome variable was triglyceride concentration, and insulin sensitivity measured by hyperinsulinemic euglycemic clamp was a secondary outcome. Setting: The study was conducted at an academic medical center. Results: Acipimox resulted in significant reductions in FFAs [ mean change -0.38 (0.06) vs. 0.08 ( 0.06) mEq/ liter with placebo, -68 vs. + 17% change from mean baseline, P < 0.0001], decreased rates of lipolysis ( P < 0.0001), and a median triglyceride decrease from 238 mg/ dl at baseline to 190 mg/ dl, compared with an increase from 290 to 348 mg/ dl in the placebo group ( P < 0.01). Acipimox improved insulin sensitivity [ acipimox + 2.31 ( 0.74) vs. placebo - 0.21 ( 0.90) mg glucose per kilogram lean body mass per minute, or + 31 vs. - 2% change from mean baseline values, P = 0.04]. Improvements in insulin sensitivity were significantly correlated with reductions in FFAs ( r = -0.62, P = 0.003) and lipolysis ( r = -0.59, P = 0.005). Conclusions: Acipimox resulted in significant sustained reductions in lipolysis, improved glucose homeostasis, and significant but modest reductions in triglycerides in HIV- infected individuals with abnormal fat distribution and hypertriglyceridemia. Improvement in overall metabolic profile with acipimox suggests a potential clinical utility for this agent that requires further investigation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Hadigan, C (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 11C103, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov FU NCRR NIH HHS [K23 RR018715, K23-RR-18715, M01 RR001066, M01-RR-01066]; NHLBI NIH HHS [R21-HL73675, R21 HL073675]; NIDDK NIH HHS [P30 DK040561-11, P30 DK040561, K23-DK-02844, R01-DK-59535, K23 DK002844, R01 DK059535] NR 42 TC 23 Z9 24 U1 0 U2 4 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 NOV PY 2006 VL 91 IS 11 BP 4438 EP 4444 DI 10.1210/jc.2006-1174 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300037 PM 16940448 ER PT J AU Muniyappa, R Wong, KA Baldwin, HL Sorkin, JD Johnson, ML Bhasin, S Harman, SM Blackman, MR AF Muniyappa, Ranganath Wong, Kelli A. Baldwin, Howard L. Sorkin, John D. Johnson, Michael L. Bhasin, Shalender Harman, S. Mitchell Blackman, Marc R. TI Dehydroepiandrosterone secretion in healthy older men and women: Effects of testosterone and growth hormone administration in older men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HUMAN ADRENOCORTICAL-CELLS; VIRUS-INFECTED WOMEN; POSTMENOPAUSAL WOMEN; ADRENAL ANDROGENS; IGF-I; DEHYDROISOANDROSTERONE SULFATE; SEX-DIFFERENCES; INSULIN; REPLACEMENT AB Context: Aging is associated with diminished gonadal steroid and GH/ IGF-I axis activity; whether these changes contribute to the parallel declines of dehydroepiandrosterone ( DHEA) and DHEA sulfate ( DHEAS) production is unknown, as are the effects of sex steroid and/ or GH administration on DHEA and DHEAS production. Objective: Our objective was to evaluate morning DHEAS concentrations and nocturnalDHEAsecretory dynamics in healthy older men and women, before and after chronic administration of sex steroid(s) alone, GH alone, sex steroid( s) combined with GH, or placebo alone. Design: We compared nocturnal DHEA secretory dynamics ( 2000 h to 0800 h, sampling every 20 min, analyzed by multiparameter deconvolution and approximate entropy algorithms) in healthy older ( 65 - 88 yr) men ( n = 68) and women ( n = 36), both before and after 26 wk of administration of sex steroid( s) alone [ testosterone ( T) in men or estrogen/ progesterone in women], GH alone, sex steroid( s) combined with GH, or placebo alone. Results: Morning concentrations of DHEAS were lower; nocturnal DHEA pulsatile production rate, burst frequency, and amplitude were higher; and half- life was shorter in women ( P < 0.05). Nocturnal integrated DHEA concentrations, total production rate, and approximate entropy did not differ significantly by sex. Because of small treatment group sizes in women, only hormone intervention results in men are presented. In men, T and T plus GH administration significantly decreased nocturnal integrated DHEA but not morning DHEAS concentrations. GH alone exerted no significant effects on nocturnal DHEA secretion or morning DHEAS. Conclusions: Spontaneous nocturnal DHEA secretion is sexually dimorphic in healthy older individuals, and T administration decreases nocturnal DHEA secretion in older men. The clinical significance of sex steroid modulation of DHEA secretion in older persons remains to be elucidated. C1 NIH, Endocrine Sect, Lab Clin Invest, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIA, Endocrine Sect, NIH, Baltimore, MD 21224 USA. NIA, Metab Sect, NIH, Baltimore, MD 21224 USA. Dept Vet Affairs & Vet Affairs Med Ctr, Baltimore Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. Univ Maryland, Sch Med, Div Gerontol, Baltimore, MD 21201 USA. Univ Virginia Hlth Syst, Dept Pharmacol, Charlottesville, VA 22908 USA. Univ Virginia Hlth Syst, Dept Internal Med, Charlottesville, VA 22908 USA. Boston Univ, Sch Med, Endocrine Sect, Boston, MA 02218 USA. Boston Univ, Sch Med, Dept Med, Endocrine Sect, Boston, MA 02118 USA. Kronos Longev Res Inst, Phoenix, AZ 85016 USA. RP Blackman, MR (reprint author), NIH, Endocrine Sect, Lab Clin Invest, Natl Ctr Complementary & Alternat Med, 9 Mem Dr,Room 1N-119, Bethesda, MD 20892 USA. EM blackmam@mail.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [R01 RR019991, M0-1-RR-02719, M01 RR002719, R0-1 RR019991, R01 RR019991-03, R01 RR019991-05]; NIA NIH HHS [P30 AG028747, P60 AG012583, P60-AG12583, R0-1 AG11005, R0-1AG14369, R01 AG014369]; NIDDK NIH HHS [P30 DK072488, R25 DK064122, R25 DK064122-03] NR 41 TC 4 Z9 4 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4445 EP 4452 DI 10.1210/jc.2006-0867 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300038 PM 16926252 ER PT J AU Batista, DL Zhang, X Gejman, R Ansell, PJ Zhou, YL Johnson, SA Swearingen, B Hedley-Whyte, ET Stratakis, CA Klibanski, A AF Batista, Dalia L. Zhang, Xun Gejman, Roger Ansell, Peter J. Zhou, Yunli Johnson, Sarah A. Swearingen, Brooke Hedley-Whyte, E. Tessa Stratakis, Constantine A. Klibanski, Anne TI The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOSTATIN RECEPTOR SUBTYPES; CUSHINGS-SYNDROME; MEDICAL THERAPY; ANALOG SOM230; IN-VITRO; DISEASE; EXPRESSION; TUMORS; MANAGEMENT; MACROADENOMAS AB Context: There is no tumor-directed medical therapy available for Cushing's disease. Objective: The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors. Design/Methods: Expression of somatostatin receptors (SSTR 1-5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas. Results: In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10-70%; P = 0.045-0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23-56%; P = 0.042-0.001). Conclusion: Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuropathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NICHHD, Sect Endocrinol & Genet, NIH, Bethesda, MD 02892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL457, Boston, MA 02114 USA. EM aklibanski@partners.org OI Tersey, Sarah/0000-0003-0667-2361 FU Intramural NIH HHS NR 39 TC 122 Z9 128 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4482 EP 4488 DI 10.1210/jc.2006-1245 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300044 PM 16940446 ER PT J AU Brouwers, FM Eisenhofer, G Tao, JJ Kant, JA Adams, KT Linehan, WM Pacak, K AF Brouwers, Frederieke M. Eisenhofer, Graeme Tao, Jessica J. Kant, Jeffrey A. Adams, Karen T. Linehan, W. Marston Pacak, Karel TI High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: Implications for genetic testing SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HEREDITARY PARAGANGLIOMA; BIOCHEMICAL-DIAGNOSIS; B GENE; PHEOCHROMOCYTOMA; PLASMA; FEATURES; BENIGN AB Context: Adrenal and extraadrenal paragangliomas are tumors of chromaffin cells that are usually benign but that may also develop into malignant disease. Mutations of the gene for succinate dehydrogenase subunit B ( SDHB) are associated with a high risk of malignancy, but establishing the precise contribution requires relatively large numbers of patients with well-defined malignancy. Objective: We assessed the prevalence of SDHB mutations in a series of patients with malignant paraganglioma. Design: SDHB mutation testing was carried out in 44 consecutive patients with malignant paraganglioma. Clinical characteristics of patients with malignant disease due to SDHB mutations were compared with those without mutations. Results: Pathogenic SDHB mutations were found in 13 of the 44 patients ( 30%). Close to one third of patients had metastases originating from an adrenal primary tumor, compared with a little over two thirds from an extraadrenal tumor. Among the latter patients, the frequency of SDHB mutations was 48%. Conclusion: This study establishes that missense, nonsense, frame-shift, and splice site mutations of the SDHB gene are associated with about half of all malignancies originating from extraadrenal paragangliomas. The high frequency of SDHB germline mutations among patients with malignant disease, particularly when originating from an extraadrenal paraganglioma, may justify a high priority for SDHB germline mutation testing in these patients. C1 NICHHD, Sect Med Neuroendocrinol Reprod Biol, Bethesda, MD USA. NICHHD, Med Branch, Bethesda, MD USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Div Mol Diagnost, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Pathol & Human Genet, Pittsburgh, PA 15213 USA. RP Pacak, K (reprint author), Bldg 10,CRC,Room 1E 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Intramural NIH HHS NR 22 TC 153 Z9 163 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4505 EP 4509 DI 10.1210/jc.2006-0423 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300048 PM 16912137 ER PT J AU Zhu, MZ Chin, RK Christiansen, PA Lo, JC Liu, XJ Ware, C Siebenlist, U Fu, YX AF Zhu, Mingzhao Chin, Robert K. Christiansen, Peter A. Lo, James C. Liu, Xiaojuan Ware, Carl Siebenlist, Ulrich Fu, Yang-Xin TI NF-kappa B2 is required for the establishment of central tolerance through an Aire-dependent pathway SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; EPITHELIAL-CELL DIFFERENTIATION; PROMISCUOUS GENE-EXPRESSION; SECONDARY LYMPHOID-TISSUES; REGULATORY T-CELLS; LT-BETA-R; DENDRITIC CELLS; MURINE THYMUS; SPLENIC MICROARCHITECTURE; AUTOIMMUNE REGULATOR AB NF-kappa B2-deficient mice have impaired T and B cell responses. We found, however, that in these mice there was severe infiltration of lymphocytes into multiple organs and increased activity of autoantibodies to peripheral tissue antigens in a manner similar to that of autoimmune regulator-deficient (Aire-deficient) mice. We further demonstrated that NF-kappa B2 was required for thymic Aire gene transcriptional regulation. The Njkb2(-/-) thymus had distinct cortical and medullar structures, but reduced Aire and target gene expression of peripheral tissue antigens. Engraftment of Nfkb(-/-) thymic stroma to nude mice recapitulated the autoimmune phenotype of the native Nfkb2(-/-) mice, confirming a key defect in central tolerance. Lymphotoxin beta receptor (LT beta R) ligation-induced Aire gene expression was also largely abolished in the absence of NF-kappa B2. Thus NF-kappa B2 downstream of LTOR plays an important role in the regulation of central tolerance in an Aire-dependent manner. C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. La Jolla Inst Allergy & Immunol, Div Mol Immunol, San Diego, CA USA. NIAID, Immune Activat Sect, Lab Immune Regulat, NIH, Bethesda, MD 20892 USA. RP Fu, YX (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave,Room J541,MC3083, Chicago, IL 60637 USA. EM yfu@uchicago.edu OI Zhu, Mingzhao/0000-0003-2001-2669 FU NICHD NIH HHS [HD062026]; NIDDK NIH HHS [R01 DK058897, DK58897] NR 45 TC 67 Z9 71 U1 0 U2 1 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 NOV PY 2006 VL 116 IS 11 BP 2964 EP 2971 DI 10.1172/JCI28326 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 102KW UT WOS:000241810900020 PM 17039258 ER PT J AU Ying, H Furuya, F Zhao, L Araki, O West, BL Hanover, JA Willingham, MC Cheng, SY AF Ying, Hao Furuya, Fumihiko Zhao, Li Araki, Osamu West, Brian L. Hanover, John A. Willingham, Mark C. Cheng, Sheue-yann TI Aberrant accumulation of PTTG1 induced by a mutated thyroid hormone beta receptor inhibits mitotic progression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-TRANSFORMING GENE; TRANSCRIPTIONAL ACTIVITY; CAUSES ANEUPLOIDY; NUCLEAR RECEPTOR; LIGAND-BINDING; MOUSE MODEL; RESISTANCE; EXPRESSION; ACTIVATION; PROTEASOME AB Overexpression of pituitary tumor-transforming 1 (PTTG1) is associated with thyroid cancer. We found elevated PTTG 1 levels in the thyroid tumors of a mouse model of follicular thyroid carcinoma (TR beta(PV/PV) mice). Here we examined the molecular mechanisms underlying elevated PTTG1 levels and the contribution of increased PTTG1 to thyroid carcinogenesis. We showed that PTTG I was physically associated with thyroid hormone 0 receptor (TR beta) as well as its mutant, designated PV. Concomitant with thyroid hormone-induced (T3-induced) degradation of TR beta, PTTG1 proteins were degraded by the proteasomal machinery, but no such degradation occurred when PTTG1 was associated with PV. The degradation of PTTG1/TRP was activated by the direct interaction of the liganded TR beta with steroid receptor coactivator 3 (SRC-3), which recruits proteasome activator PA28 gamma. PV, which does not bind T3, could not interact directly with SRC-3/PA28 gamma to activate proteasome degradation, resulting in elevated PTTG1 levels. The accumulated PTTG1 impeded mitotic progression in cells expressing PV. Our results unveil what we believe to be a novel mechanism by which PTTG1, an oncogene, is regulated by the liganded TR beta. The loss of this regulatory function in PV led to an aberrant accumulation of PTTG1 disrupting mitotic progression that could contribute to thyroid carcinogenesis. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Cellular Biochem & Biol, NIH, Bethesda, MD USA. Plexxikon Inc, Berkeley, CA USA. Wake Forest Univ, Winston Salem, NC 27109 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 NIH HHS NR 40 TC 59 Z9 60 U1 2 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2006 VL 116 IS 11 BP 2972 EP 2984 DI 10.1172/JCI28598 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 102KW UT WOS:000241810900021 PM 17039256 ER PT J AU Shin, EC Seifert, U Kato, T Rice, CM Feinstone, SM Kloetzel, PM Rehermann, B AF Shin, Eui-Cheol Seifert, Ulrike Kato, Takanobu Rice, Charles M. Feinstone, Stephen M. Kloetzel, Peter-M. Rehermann, Barbara TI Virus-induced type IIFN stimulates generation of immunoproteasomes at the site of infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEPATITIS-C VIRUS; CD8(+) T-CELLS; MHC CLASS-I; CELLULAR IMMUNE-RESPONSES; B-VIRUS; RIG-I; LYMPHOCYTE EPITOPE; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; GENOMIC ANALYSIS AB IFN-gamma is known as the initial and primary inducer of immunoproteasomes during viral infections. We now report that type IIFN induced the transcription and translation of immunoproteasome subunits, their incorporation into the proteasome complex, and the generation of an immunoproteasome-dependent CD8 T cell epitope in vitro and provide in vivo evidence that this mechanism occurs prior to IFN-gamma responses at the site of viral infection. Type I IFN-mediated generation of immunoproteasomes was initiated by either poly(I:C) or HCV RNA in human hepatoma cells and was inhibited by neutralization of type IIFN. In serial liver biopsies of chimpanzees with acute HCV infection, increases in immunoproteasome subunit mRNA preceded intrahepatic IFN-gamma responses by several weeks, instead coinciding with intrahepatic type IIFN responses. Thus, viral RNA-induced innate immune responses regulate the antigen-processing machinery, which occurs prior to the detection of IFN-gamma at the site of infection. This mechanism may contribute to the high effectiveness (95%) of type IIFN-based therapies if administered early during HCV infection. C1 NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. Charite Univ Med Berlin CCM, Inst Biochem, Berlin, Germany. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10 Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU Intramural NIH HHS; NCI NIH HHS [CA85883-01, R01 CA085883] NR 55 TC 80 Z9 83 U1 0 U2 0 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 NOV PY 2006 VL 116 IS 11 BP 3006 EP 3014 DI 10.1172/JCI29832 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 102KW UT WOS:000241810900024 PM 17039255 ER PT J AU Zhang, J Stirling, B Temmerman, ST Ma, CA Fuss, IJ Derry, JMJ Jain, A AF Zhang, Jun Stirling, Brigid Temmerman, Stephane T. Ma, Chi A. Fuss, Ivan J. Derry, Jonathan M. J. Jain, Ashish TI Impaired regulation of NF-kappa B and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; TUMOR-SUPPRESSOR CYLD; IMMUNE-SYSTEM; ACTIVATION; UBIQUITINATION; CANCER; PATHWAY; ENZYME; RECEPTOR-1; DYSPLASIA AB Cylindromatosis (CYLD) is a deubiquitinating enzyme that is altered in patients with familial cylindromatosis, a condition characterized by numerous benign adnexal tumors. However, the regulatory function of CYLD remains unsettled. Here we show that the development of B cells, T cells, and myeloid cells was unaffected in CYLD-deficient mice, but that the activation of these cells with mediators of innate and adaptive immunity resulted in enhanced NF-kappa B and JNK activity associated with increased TNF receptor-associated factor 2 (TRAF2) and NF-kappa B essential modulator (NEMO) ubiquitination. CYLD-deficient mice were more susceptible to induced colonic inflammation and showed a dramatic increase in the incidence of tumors compared with controls in a colitis-associated cancer model. These results suggest that CYLD limits inflammation and tumorigenesis by regulating ubiquitination in vivo. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Amgen Inc, Seattle, WA USA. RP Jain, A (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,Room 11N228, Bethesda, MD 20892 USA. EM ajain@niaid.nih.gov NR 33 TC 139 Z9 147 U1 1 U2 5 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 NOV PY 2006 VL 116 IS 11 BP 3042 EP 3049 DI 10.1172/JCI28746 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 102KW UT WOS:000241810900028 PM 17053834 ER PT J AU Castle, PE Sadorra, M Garcia, F Holladay, EB Kornegay, J AF Castle, Philip E. Sadorra, Mark Garcia, Francisco Holladay, E. Blair Kornegay, Janet TI Pilot study of a commercialized human papillomavirus (HPV) genotyping assay: Comparison of HPV risk group to cytology and histology SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID WOMEN; PREVALENCE; NEOPLASIA; CANCER; CERVIX AB We evaluated a commercialized PCR assay, Linear Array, that detects 37 human papillomavirus (HPV) genotypes, using a sample of liquid cytology specimens (n = 534). We found a strong association of an increasing level of HPV risk (HPV type 16 [HPV16] > HPV18 > other carcinogenic types > noncarcinogenic types > negative specimens) with increasing severities of cytologic interpretations (P-Trend < 0.0005) and histologic diagnoses (P-Trend < 0.0005). C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Roche Mol Syst, Alameda, CA USA. Univ Arizona, Hlth Sci Ctr, Tucson, AZ 85721 USA. Med Univ S Carolina, Charleston, SC USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5123,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov NR 15 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2006 VL 44 IS 11 BP 3915 EP 3917 DI 10.1128/JCM.01305-06 PG 3 WC Microbiology SC Microbiology GA 105UC UT WOS:000242056800011 PM 16971652 ER PT J AU McGinnis, KA Fultz, SL Skanderson, M Conigliaro, J Bryant, K Justice, AC AF McGinnis, Kathleen A. Fultz, Shawn L. Skanderson, Melissa Conigliaro, Joseph Bryant, Kendall Justice, Amy C. TI Hepatocellular carcinoma and non-Hodgkin's lymphoma: The roles of HIV, hepatitis C infection, and alcohol abuse SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 15th International AIDS Conference CY JUL 11-17, 2004 CL Bangkok, THAILAND ID VIRUS-INFECTION; UNITED-STATES; CONNECTICUT WOMEN; AIDS; COHORT; VETERANS; RISK; PREVALENCE; SCHIZOPHRENIA; ASSOCIATION AB Purpose To explore the relationship of HIV, hepatitis C (HCV), and alcohol abuse/dependence to risk for hepatocellular carcinoma and non-Hodgkin's lymphoma (NHL). Patients and Methods Male veterans ( n = 14,018) with a first HIV diagnosis in the Veterans Affairs Healthcare System from October 1997 to September 2004; and 28,036 age-, race-, sex-, and location-matched HIV-negative veterans were identified. We examined the incidence of hepatocellular carcinoma and NHL and presence of HCV and alcohol abuse/dependence using International Classification of Diseases, ninth revision (ICD-9-CM) codes. HIV-positive to HIV-negative incident rate ratios (IRRs) and 95% CIs for the occurrence of hepatocellular carcinoma and NHL were calculated using Poisson regression models. Results HIV-positive veterans were at greater risk for hepatocellular carcinoma than HIV-negative veterans (IRR = 1.68; 95% CI, 1.02 to 2.77). After adjusting for HCV infection and alcohol abuse/ dependence, HIV status was not independently associated with hepatocellular cancer ( IRR = 0.96; 95% CI, 0.56 to 1.63). HIV-positive veterans had 9.71 times ( 95% CI, 6.99 to 13.49) greater risk of NHL than HIV-negative veterans. After adjusting for HCV and alcohol abuse/ dependence, the IRR for NHL comparing HIV-positive with HIV-negative veterans is similar ( IRR = 10.03, 95% CI, 7.19 to 13.97). Conclusion HIV-positive veterans have a higher relative incidence of hepatocellular carcinoma and NHL than HIV-negative veterans. For hepatocellular carcinoma, this association appears to be largely explained by the higher prevalence of HCV and alcohol abuse/ dependence. Efforts to decrease hepatocellular carcinoma among persons with HIV should focus primarily on detecting and treating HCV and reducing heavy alcohol use. C1 Yale Univ, Sch Med, Dept Med, West Haven, CT 06516 USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Univ Kentucky, Lexington, KY USA. NIAAA, NIH, Bethesda, MD USA. RP Justice, AC (reprint author), Yale Univ, Sch Med, Dept Med, 950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@va.gov FU PHS HHS [U01-13566] NR 31 TC 41 Z9 41 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2006 VL 24 IS 31 BP 5005 EP 5009 DI 10.1200/JCO.2006.05.7984 PG 5 WC Oncology SC Oncology GA 102PX UT WOS:000241825900011 PM 17075119 ER PT J AU Cai, QY Gao, YT Chow, WH Shu, XO Yang, G Ji, BT Wen, WQ Rothman, N Li, HL Morrow, JD Zheng, W AF Cai, Qiuyin Gao, Yu-Tang Chow, Wong-Ho Shu, Xiao-Ou Yang, Gong Ji, Bu-Tian Wen, Wanqing Rothman, Nathaniel Li, Hong-Lan Morrow, Jason D. Zheng, Wei TI Prospective study of urinary prostaglandin E-2 metabolite and colorectal cancer risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INFLAMMATORY-BOWEL-DISEASE; FAMILIAL ADENOMATOUS POLYPOSIS; HUMAN COLON-CANCER; CYCLOOXYGENASE-2 EXPRESSION; MOLECULAR TARGET; CARCINOGENESIS; CELLS; CHEMOPREVENTION; DEHYDROGENASE AB Purpose Overexpression of cyclooxygenase-2 (COX-2) has been shown to play a major role in colorectal cancer pathogenesis. However, no human study has directly investigated whether biomarkers of COX-2 overexpression may predict colorectal cancer risk. We evaluated the association of urinary prostaglandin E-2 metabolite (PGE-M) levels and colorectal cancer risk Methods A nested case-control study was conducted within the Shanghai Women's Health Study, in which 74,942 Chinese women ages 40 to 70 years were recruited from 1997 to 2000. Urinary PGE-M in 150 cohort members who developed colorectal cancer during the follow-up were compared with 150 matched controls. Results The baseline level of urinary PGE-M was more than 50% higher in cases than in controls. The relative risks (RRs) of developing colorectal cancer were elevated from 1.0 to 2.5 (95% CI, 1.1 to 5.8), 4.5 ( 95% CI, 1.9 to 10.9), and 5.6 ( 95% CI, 2.4 to 13.5) with increasing quartiles of urinary PGE-M levels ( P for trend <.001). The positive association was observed for both colon cancer (RR = 4.9; 95% CI, 1.7 to 14.7 for the highest v lowest quartile; P for trend =.009) and rectal cancer ( RR = 7.2; 95% CI, 1.7 to 30.7; P for trend =.048), and for colorectal cancer cases diagnosed in the first 30 months ( RR = 7.6; 95% CI, 1.8 to 32.0; P for trend =.035) and subsequent months ( RR = 4.4, 95% CI, 1.5 to 13.3; P for trend =.012) of follow-up. Conclusion Given its strong association with colorectal cancer risk, urinary PGE-M may be a promising biomarker for risk assessment of this common malignancy. C1 Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Med, Ctr Epidemiol Res, Nashville, TN 37232 USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Zheng, W (reprint author), Vanderbilt Univ, Med Ctr, Sch Med, Vanderbilt Ctr Epidemiol Res, N,S-1121,1161 21st Ave S, Nashville, TN 37232 USA. EM wei.zheng@vanderbilt.edu FU Intramural NIH HHS NR 42 TC 48 Z9 49 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2006 VL 24 IS 31 BP 5010 EP 5016 DI 10.1200/JCO.2006.06.4931 PG 7 WC Oncology SC Oncology GA 102PX UT WOS:000241825900012 PM 17075120 ER PT J AU Kim, NK Xie, J AF Kim, Nak-Kyeong Xie, Jun TI Protein multiple alignment incorporating primary and secondary structure information SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE Gibbs sampling; likelihood function; protein sequence motifs; secondary structures; segment overlap ID SEQUENCE ALIGNMENT; BAYESIAN MODELS; EM ALGORITHM; PREDICTION; ACCURACY; PROGRAMS; DATABASE; IDENTIFICATION; MATRICES; MOTIFS AB Identifying common local segments, also called motifs, in multiple protein sequences plays an important role for establishing homology between proteins. Homology is easy to establish when sequences are similar (sharing an identity > 25%). However, for distant proteins, it is much more difficult to align motifs that are not similar in sequences but still share common structures or functions. This paper is a first attempt to align multiple protein sequences using both primary and secondary structure information. A new sequence model is proposed so that the model assigns high probabilities not only to motifs that contain conserved amino acids but also to motifs that present common secondary structures. The proposed method is tested in a structural alignment database BAliBASE. We show that information brought by the predicted secondary structures greatly improves motif identification. A website of this program is available at www.stat.purdue.edu/similar to junxie/2ndmodel/sov.html. C1 Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Xie, J (reprint author), Purdue Univ, Dept Stat, 150 N Univ St, W Lafayette, IN 47907 USA. EM junxie@stat.purdue.edu NR 28 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD NOV PY 2006 VL 13 IS 9 BP 1615 EP 1629 DI 10.1089/cmb.2006.13.1615 PG 15 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 115YT UT WOS:000242770400010 ER PT J AU Mao, JJ Giannobile, WV Helms, JA Hollister, SJ Krebsbach, PH Longaker, MT Shi, S AF Mao, J. J. Giannobile, W. V. Helms, J. A. Hollister, S. J. Krebsbach, P. H. Longaker, M. T. Shi, S. TI Craniofacial tissue engineering by stem cells SO JOURNAL OF DENTAL RESEARCH LA English DT Review DE stem cells; tissue engineering; biomaterials; wound healing; regenerative medicine ID BONE MORPHOGENETIC PROTEIN-2; HUMAN ADIPOSE-TISSUE; HUMAN DENTAL-PULP; MATRIX DERIVATIVE EMDOGAIN(R); MESENCHYMAL PROGENITOR CELLS; RADIATION-INDUCED CHANGES; FIBROBLAST-GROWTH-FACTOR; III FURCATION DEFECTS; REGIONAL GENE-THERAPY; MUSCLE-DERIVED CELLS AB Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures-such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue-have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss. C1 Columbia Univ, Coll Dent Med & Biomed Engn, New York, NY 10032 USA. Univ Michigan, Michigan Ctr Oral Hlth Res, Clin Res Ctr, Ann Arbor, MI 48106 USA. Stanford Univ, Dept Surg, Sch Med, Stanford, CA 94305 USA. Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Mao, JJ (reprint author), Columbia Univ, Coll Dent Med & Biomed Engn, 630 W 168 St PH7 CDM, New York, NY 10032 USA. EM jmao@columbia.edu OI Giannobile, William/0000-0002-7102-9746 FU NIBIB NIH HHS [R01 EB002332, EB02332]; NIDCR NIH HHS [DE007057, DE012462, DE013608, DE013835, DE016129, DE016530, DE13028, DE13194, DE13397, DE13964, DE14526, DE15384, DE16619, R01 DE012462, R01 DE013028, R01 DE013194, R01 DE013397, R01 DE013397-07, R01 DE013608, R01 DE013835, R01 DE013964, R01 DE013964-01, R01 DE014526, R01 DE015384, R01 DE015384-04, R01 DE015391, R01 DE016129, R01 DE016530, R21 DE016619, R21 DE016619-02, R29 DE012462, RC2 DE020767, RC2 DE020767-02, T32 DE007057] NR 197 TC 163 Z9 174 U1 5 U2 38 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2006 VL 85 IS 11 BP 966 EP 979 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 098KY UT WOS:000241520600001 PM 17062735 ER PT J AU Lee, EJ Jang, SI Pallos, D Kather, J Hart, TC AF Lee, E. J. Jang, S. I. Pallos, D. Kather, J. Hart, T. C. TI Characterization of fibroblasts with son of Sevenless-1 mutation SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE hereditary gingival fibromatosis; Son of Sevenless-1; fibroblast; collagen ID HEREDITARY GINGIVAL FIBROMATOSIS; EPIDERMAL-GROWTH-FACTOR; EPITHELIAL-CELLS; PROLIFERATION; EXPRESSION; COLLAGEN; TISSUE; LOCUS; HYPERPLASIA; RECEPTOR AB Although non-syndromic hereditary gingival fibromatosis (HGF) is genetically heterogeneous, etiologic mutations have been identified only in the Son of Sevenless-1 gene (SOS1). To test evidence of increased cell proliferation, we studied histological, morphological, and proliferation characteristics in monolayer and three-dimensional cultures of fibroblasts with the SOS1 g. 126,142-126,143insC mutation. Histological assessment of HGF gingiva indicated increased numbers of fibroblasts (30%) and increased collagen (10%). Cell proliferation studies demonstrated increased growth rates and 5-bromo-2-deoxyuridine incorporation for HGF fibroblasts. Flow cytometry showed greater proportions of HGF fibroblasts in the G2/M phase. Attachment of HGF fibroblasts to different extracellular matrix surfaces demonstrated increased formation of protrusions with lamellipodia. HGF fibroblasts in three-dimensional culture showed greater cell proliferation, higher cell density, and alteration of surrounding collagen matrix. These findings revealed that increased fibroblast numbers and collagen matrix changes are associated with mutation of the SOS1 gene in vitro and in vivo. C1 DHHS, Human Craniofacial Genet Sect, NIDCR, NIH, Bethesda, MD 20892 USA. RP Hart, TC (reprint author), DHHS, Human Craniofacial Genet Sect, NIDCR, NIH, Bldg 10,Room 5-2523,10 Ctr Dr, Bethesda, MD 20892 USA. EM thart@mail.nih.gov FU Intramural NIH HHS [Z01 DE000711-04] NR 33 TC 13 Z9 13 U1 0 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2006 VL 85 IS 11 BP 1050 EP 1055 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 098KY UT WOS:000241520600015 PM 17062749 ER PT J AU Barimo, JF Walsh, PJ AF Barimo, John F. Walsh, Patrick J. TI Use of urea as a chemosensory cloaking molecule by a bony fish SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE urea; ammonia; chemosensory; predator-prey interaction; toadfish; snapper ID EARLY-LIFE STAGES; NITROGENOUS WASTES; GULF TOADFISH; OPSANUS-BETA; AMMONIA; CONTROVERSIES; RESPONSES; EVOLUTION; DOGMAS AB Because urea is bioenergetically expensive to synthesize, few aquatic teleostean (bony) fish make or excrete much urea beyond early development and excrete the majority of nitrogenous waste as the readily diffusible ammonia. The gulf toadfish is one of a few adult teleostean fish that excretes predominately urea. Most studies of chemosensing by fish predators have focused on amino acids as odorants, but we tested the chemo-attractiveness of both urea and ammonia. We report that characteristic 'prey-attack' behaviors by a key toadfish predator, gray snapper, were elicited by low ammonia concentrations (< 100 nmol N l(-1)) and similar urea concentrations blunted the ammonia-induced component of attacks. Thus, urea functions as a cloaking molecule, explaining why toadfish co-excrete urea with ammonia. Furthermore, ammonia waste is an important chemical attractant for piscine predators. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr,Div Marine Bio, Miami, FL 33149 USA. RP Barimo, JF (reprint author), Portland State Univ, Dept Biol, POB 75, Portland, OR 97207 USA. EM jfb@pdx.edu NR 33 TC 23 Z9 24 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 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV 1 PY 2006 VL 209 IS 21 BP 4254 EP 4261 DI 10.1242/jeb.02533 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 106WK UT WOS:000242132500017 PM 17050840 ER PT J AU Schwartz, DA AF Schwartz, David A. TI The importance of gene-environment interactions and exposure assessment in understanding human diseases SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Editorial Material ID TWINS; EPIGENOME C1 NIEHS, Res Triangle Pk, NC 27709 USA. Natl Toxicol Program, 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 NR 12 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD NOV PY 2006 VL 16 IS 6 BP 474 EP 476 DI 10.1038/sj.jes.7500531 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110UJ UT WOS:000242406500002 PM 17109021 ER PT J AU Hurst, SA Slowther, AM Forde, R Pegoraro, R Reiter-Theil, S Perrier, A Garrett-Mayer, E Danis, M AF Hurst, Samia A. Slowther, Anne-Marie Forde, Reidun Pegoraro, Renzo Reiter-Theil, Stella Perrier, Arnaud Garrett-Mayer, Elizabeth Danis, Marion TI Prevalence and determinants of physician bedside rationing: Data from Europe SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE health care rationing; health resources; attitude of health personnel; ethics; clinical; Europe ID HEALTH-CARE; MEDICAL RESOURCES; RESPONSE RATES; COST-CONTROL; DOCTORS; ATTITUDES; ETHICS; ALLOCATION; DECISIONS; SCARCITY AB BACKGROUND: Bedside rationing by physicians is controversial. The debate, however, is clouded by lack of information regarding the extent and character of bedside rationing. DESIGN, SETTING, AND PARTICIPANTS: We developed a survey instrument to examine the frequency, criteria, and strategies used for bedside rationing. Content validity was assessed through expert assessment and scales were tested for internal consistency. The questionnaire was translated and administered to General Internists in Norway, Switzerland, Italy, and the United Kingdom. Logistic regression was used to identify the variables associated with reported rationing. RESULTS: Survey respondents (N=656, response rate 43%) ranged in age from 28 to 82, and averaged 25 years in practice. Most respondents (82.3%) showed some degree of agreement with rationing, and 56.3% reported that they did ration interventions. The most frequently mentioned criteria for rationing were a small expected benefit (82.3%), low chances of success (79.8%), an intervention intended to prolong life when quality of life is low (70.6%), and a patient over 85 years of age (70%). The frequency of rationing by clinicians was positively correlated with perceived scarcity of resources (odds ratio [OR]=1.11, 95% confidence interval [CI] 1.06 to 1.16), perceived pressure to ration (OR=2.14, 95% CI 1.52 to 3.01), and agreement with rationing (OR=1.13, 95% CI 1.05 to 1.23). CONCLUSION: Bedside rationing is prevalent in all surveyed European countries and varies with physician attitudes and resource availability. The prevalence of physician bedside rationing, which presents physicians with difficult moral dilemmas, highlights the importance of discussions regarding how to ration care in the most ethically justifiable manner. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Geneva, Sch Med, Bioeth Inst, CH-1211 Geneva, Switzerland. Univ Oxford, Ethox Ctr, Oxford, England. Norwegian Med Assoc, Res Inst, Oslo, Norway. Univ Oslo, Oslo, Norway. Fondaz Lanza, Padua, Italy. Univ Basel, Inst Appl Eth & Med Eth, Basel, Switzerland. Univ Hosp Geneva, Gen Internal Med Serv, Geneva, Switzerland. Johns Hopkins Univ, John Hopkins Kimmel Canc Ctr, Baltimore, MD USA. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room IC118, Bethesda, MD 20892 USA. EM mdanis@cc.nih.gov RI Perrier, Arnaud/M-2263-2014; Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 41 TC 55 Z9 55 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2006 VL 21 IS 11 BP 1138 EP 1143 DI 10.1111/j.1525-1497.2006.00551.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 089ZQ UT WOS:000240920800006 PM 16836629 ER PT J AU Snyder, LD Hartwig, MG Ganous, T Davis, D Herczyk, WF Reinsmoen, NL Schwartz, DA Palmer, SM AF Snyder, Laurie D. Hartwig, Matthew G. Ganous, Tonya Davis, Duane Herczyk, Walter F. Reinsmoen, Nancy L. Schwartz, David A. Palmer, Scott M. TI Cytokine gene polymorphisms are not associated with bronchiolitis obliterans syndrome or survival after lung transplant SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA GENE; PRODUCTION GENOTYPE; ALLOGRAFT FIBROSIS; INNATE IMMUNITY; REJECTION; HEART; INTERLEUKIN-6; IL-10; BETA AB Background: Cytokine polymorphisms are inconsistently associated with transplant rejection and other adverse outcomes. To address this controversy, we evaluated cytokine single nucleotide polymorphisms (SNPs) in a lung transplant cohort. Methods: All patients who underwent lung transplantation from 1993 to 1998 and had post-transplant survival of at least 6 months were included in the initial analysis. Subjects were genotyped for: TNF-alpha -308 G/A; IFN-gamma +874 A/T; TGF-beta 1 +869 T/C and +915 G/C; IL-10 - 1082 A/G, -819 C/T and -592 C/A; and IL-6 -174 G/C. End-points were onset of broncholitis obliterans syndrome (BOS) and survival. Results: In the cohort, 78 subjects, with an overall mean +/- SE survival 2,339 - 117 days, had no correlation between onset of BOS1, BOS2 or survival with TNF-alpha, IFN-gamma, TGF-beta 1 or IL-10 gene polymorphisms. However, IL-6 polymorphisms GG or GC were associated with an earlier onset of BOS1 (P = 0.039), BOS2 (p = 0.021), and decreased overall post-transplant survival (p = 0.038). A second cohort of more recent lung transplant recipients did not validate an association between IL-6 polymorphisms and earlier onset of BOS1 (p = 0.70), BOS2 (p = 0.54) or overall post-transplant survival (p = 0.25). Conclusions: Polymorphisms of TNF-alpha, IFN-gamma, TGF-beta 1, IL-10 and IL-6 do not appear to influence the onset of BOS or graft survival in recipients. C1 Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Snyder, LD (reprint author), Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care, Durham, NC 27710 USA. EM snyde014@mc.duke.edu NR 24 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2006 VL 25 IS 11 BP 1330 EP 1335 DI 10.1016/j.healun.2006.07.001 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 108EC UT WOS:000242222100009 PM 17097497 ER PT J AU Borrego, F AF Borrego, Francisco TI The first molecular basis of the "missing self" hypothesis SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID NATURAL-KILLER-CELLS; CLASS-I MOLECULES; MARROW GRAFT-REJECTION; NK CELLS; TARGET-CELLS; RECOGNITION; RESISTANCE; ANTIGEN; SUSCEPTIBILITY; RECEPTOR C1 NIAID, NIH, Rockville, MD 20852 USA. RP Borrego, F (reprint author), NIAID, NIH, Twinbrook 2,Room 205,12440 Parklawn Dr, Rockville, MD 20852 USA. EM Fborrego@niaid.nih.gov NR 20 TC 3 Z9 3 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 NOV 1 PY 2006 VL 177 IS 9 BP 5759 EP 5760 PG 2 WC Immunology SC Immunology GA 097VN UT WOS:000241477400001 PM 17056497 ER PT J AU Graham, DB Bell, MP Huntoon, CJ Griffin, MD Tai, XG Singer, A McKean, DJ AF Graham, Daniel B. Bell, Michael P. Huntoon, Catherine J. Griffin, Matthew D. Tai, Xuguang Singer, Alfred McKean, David J. TI CD28 ligation costimulates cell death but not maturation of double-positive thymocytes due to defective ERK MAPK signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXCHANGE FACTOR VAV; NEGATIVE SELECTION; T-CELLS; CD28-MEDIATED COSTIMULATION; AUTOREACTIVE THYMOCYTES; CD4(+)CD8(+) THYMOCYTES; CD28-DEFICIENT MICE; CYTOPLASMIC DOMAIN; SURFACE MOLECULES; CLONAL DELETION AB The differentiation of double-positive (DP) CD4(+)CD8(+) thymocytes to single-positive CD4(+) or CD8(+) T cells is regulated by signals that are initiated by coengagement of the Ag (TCR) and costimulatory receptors. CD28 costimulatory receptors, which augment differentiation and antiapoptotic responses in mature T lymphocytes, have been reported to stimulate both differentiation and apoptotic responses in TCR-activated DP thymocytes. We have used artificial APCs that express ligands for TCR and CD28 to show that CD28 signals increase expression of CD69, Bim, and cell death in TCR-activated DP thymocytes but do not costimulate DP thymocytes to initiate the differentiation program. The lack of a differentiation response is not due to defects in CD28-initiated TCR proximal signaling events but by a selective defect in the activation of ERK MAPK. To characterize signals needed to initiate the death response, a mutational analysis was performed on the CD28 cytoplasmic domain. Although mutation of all of CD28 cytoplasmic domain signaling motifs blocks cell death, the presence of any single motif is able to signal a death response. Thus, there is functional redundancy in the CD28 cytoplasmic domain signaling motifs that initiate the thymocyte death response. In contrast, immobilized Abs can initiate differentiation responses and cell death in DP thymocytes. However, because Ab-mediated differentiation occurs through CD28 receptors with no cytoplasmic domain, the response may be mediated by increased adhesion to immobilized anti-TCR Abs. C1 Mayo Clin & Mayo Fdn, Dept Immunol, Coll Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Nephrol, Coll Med, Rochester, MN 55905 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP McKean, DJ (reprint author), Mayo Clin & Mayo Fdn, Dept Immunol, Coll Med, 301 Guggenheim Bldg, Rochester, MN 55905 USA. EM mckean.david@mayo.edu RI Griffin, Matthew/A-1688-2009 OI Griffin, Matthew/0000-0002-8701-8056 FU NIAID NIH HHS [AI 44959] NR 58 TC 10 Z9 10 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 NOV 1 PY 2006 VL 177 IS 9 BP 6098 EP 6107 PG 10 WC Immunology SC Immunology GA 097VN UT WOS:000241477400040 PM 17056536 ER PT J AU Belyakov, IM Isakov, D Zhu, Q Dzutsev, A Klinman, D Berzofsky, JA AF Belyakov, Igor M. Isakov, Dmitry Zhu, Qing Dzutsev, Amiran Klinman, Dennis Berzofsky, Jay A. TI Enhancement of CD8(+) T cell immunity in the lung by CpG oligodeoxynucleotides increases protective efficacy of a modified vaccinia ankara vaccine against lethal poxvirus infection even in a CD4-deficient host SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ATTENUATED MVA STRAIN; SMALLPOX VACCINE; GENITAL-TRACT; INTRANASAL IMMUNIZATION; MUCOSAL IMMUNIZATION; INFLUENZA-VIRUS; DENDRITIC CELLS; RHESUS-MONKEYS; BACTERIAL-DNA AB Immunostimulatory CpG oligodeoxynucleotides (ODN) have proven effective as adjuvants for protein-based vaccines, but their impact on immune responses induced by live viral vectors is not known. We found that addition of CpG ODN to modified vaccinia Ankara (MVA) markedly improved the induction of longer-lasting adaptive protective immunity in BALB/c mice against intranasal pathogenic vaccinia virus (Western Reserve; WR). Protection was mediated primarily by CD8(+) T cells in the lung, as determined by CD8-depletion studies, protection in B cell-deficient mice, and greater protection correlating with CD8(+) IFN-gamma-producing cells in the lung but not with those in the spleen. Intranasal immunization was more effective at inducing CD8(+) T cell immunity in the lung, and protection, than i.m. immunization. Addition of CpG ODN increased the CD8(+) response but not the Ab response. Depletion of CD4 T cells before vaccination with MVA significantly diminished protection against pathogenic WR virus. However, CpG ODN delivered with MVA was able to substitute for CD4 help and protected CD4-depleted mice against WR vaccinia challenge. This study demonstrates for the first time a protective adjuvant effect of CpG ODN for a live viral vector vaccine that may overcome CD4 deficiency in the induction of protective CD8(+) T cell-mediated immunity. C1 NCI, Vaccine Branch, Ctr Canc Res, Mol Immunogenet & Vaccine Res Sect,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Belyakov, IM (reprint author), NCI, Vaccine Branch, Ctr Canc Res, Mol Immunogenet & Vaccine Res Sect,NIH, Bldg 10,Room 6B-12,10 Ctr Dr, Bethesda, MD 20892 USA. EM belyakov@mail.nih.gov NR 65 TC 37 Z9 40 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 NOV 1 PY 2006 VL 177 IS 9 BP 6336 EP 6343 PG 8 WC Immunology SC Immunology GA 097VN UT WOS:000241477400068 PM 17056564 ER PT J AU Kushnir-Sukhov, NM Gilfillan, AM Coleman, JW Brown, JM Bruening, S Toth, M Metcalfe, DD AF Kushnir-Sukhov, Nataliya M. Gilfillan, Alasdair M. Coleman, John W. Brown, Jared M. Bruening, Sandra Toth, Miklos Metcalfe, Dean D. TI 5-hydroxytryptamine induces mast cell adhesion and migration SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALLERGIC CONTACT-DERMATITIS; IN-VITRO; SEROTONIN RELEASE; 5-HT1A RECEPTORS; KIT-LIGAND; C-KIT; ACTIVATION; DEGRANULATION; INHIBITION; EXPRESSION AB The neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) is implicated in enhancing inflammatory reactions of skin, lung, and gastrointestinal tract. To determine whether 5-HT acts, in part, through mast cells (MC), we first established that mouse bone marrow-derived MC (mBMMC) and human CD34(+)-derived MC (huMC) expressed mRNA for multiple 5-HT receptors. We next determined the effect of 5-HT on mouse and human MC degranulation, adhesion, and chemotaxis. We found no evidence that 5-HT degranulates MC or modulates IgE-dependent activation. 5-HT did induce mBMMC and huMC adherence to fibronectin; and immature and mature mBMMC and huMC migration. Chemotaxis was accompanied by actin polymerization. Using receptor antagonists and pertussis toxin, we identified 5-HT1A as the principal receptor mediating the effects of 5-HT on MC. mBMMC from the 5-HT1A receptor knockout mouse (5-HT1AR-/-) did not respond to 5-HT. 5-HT did induce accumulation of MC in the dermis of 5-HT1AR+/+ mice, but not in 5-HT1AR-/- mice. These studies are the first to demonstrate an effect of 5-HT on MC. Furthermore, both mouse and human MC respond to 5-HT through the 5-HT1A receptor. Our data are consistent with the conclusion that 5-HT promotes inflammation by increasing MC at the site of tissue injury. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. RP Kushnir-Sukhov, NM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C208,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM nkushnir@maid.nih.gov FU Intramural NIH HHS NR 56 TC 66 Z9 71 U1 1 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2006 VL 177 IS 9 BP 6422 EP 6432 PG 11 WC Immunology SC Immunology GA 097VN UT WOS:000241477400078 PM 17056574 ER PT J AU Powell, DJ Dudley, ME Hogan, KA Wunderlich, JR Rosenberg, SA AF Powell, Daniel J., Jr. Dudley, Mark E. Hogan, Katherine A. Wunderlich, John R. Rosenberg, Steven A. TI Adoptive transfer of vaccine-induced peripheral blood mononuclear cells to patients with metastatic melanoma following lymphodepletion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; TUMOR-REGRESSION; TRANSFER THERAPY; IN-VIVO; CANCER REGRESSION; ANTIGEN GP100; CD8-T-CELL MEMORY; IMMUNE-RESPONSES; CD4-T-CELL HELP; LYMPHOCYTES AB Cancer vaccines can induce the in vivo generation of tumor Ag-specific T cells in patients with metastatic melanoma yet seldom elicit objective clinical responses. Alternatively, adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in 50% of lymphodepleted patients, but are logistically and technically difficult to generate. In this study, we evaluated the capability of vaccine-induced PBMC to mediate tumor regression after transfer to patients receiving the same chemotherapy-induced lymphodepletion used for TIL transfer therapy. Autologous PBMC from nine gp100-vaccinated patients with metastatic melanoma were stimulated ex vivo with the gp100:209-217(210M) peptide and transferred in combination with high-dose IL-2 and cancer vaccine. Transferred PBMC contained highly avid, gp100:209-217 peptide-reactive CD8(+) T cells. One week after transfer, lymphocyte counts peaked (median of 14.3 x 10(3) cells/mu l; range of 0.9-59.7 x 10(3) cells/mu l), with 56% of patients experiencing a lymphocytosis. gp100:209-217 peptide-specific CD8(+) T cells persisted at high levels in the blood of all patients and demonstrated significant tumor-specific IFN-gamma secretion in vitro. Mellanocyte-directed autoimmunity was noted in two patients; however, no patient experienced an objective clinical response. These studies demonstrate the feasibility and safety of using vaccine-induced PBMC for cell transfer, but suggests that they are not as effective as TIL in adoptive immunotherapy even when transferred into lymphodepleted hosts. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Powell, DJ (reprint author), NCI, Surg Branch, NIH, CRC Room 3W,3888-10 Ctr Dr, Bethesda, MD 20892 USA. EM Daniel_Powell@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 51 TC 87 Z9 88 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 NOV 1 PY 2006 VL 177 IS 9 BP 6527 EP 6539 PG 13 WC Immunology SC Immunology GA 097VN UT WOS:000241477400089 PM 17056585 ER PT J AU Johnson, LA Heemskerk, B Powell, DJ Cohen, CJ Morgan, RA Dudley, ME Robbins, PF Rosenberg, SA AF Johnson, Laura A. Heemskerk, Bianca Powell, Daniel J., Jr. Cohen, Cyrille J. Morgan, Richard A. Dudley, Mark E. Robbins, Paul F. Rosenberg, Steven A. TI Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; VIVO ANTITUMOR EFFICACY; ADOPTIVE IMMUNOTHERAPY; MELANOMA PATIENTS; TRANSFER THERAPY; FUNCTIONAL AVIDITY; CANCER REGRESSION; ANTIGEN RECEPTOR; IN-VITRO; ACTIVATION AB Cell-based antitumor immunity is driven by CD8(+) cytotoxic T cells bearing TCR that recognize specific tumor-associated peptides bound to class I MHC molecules. Of several cellular proteins involved in T cell:target-cell interaction, the TCR determines specificity of binding; however, the relative amount of its contribution to cellular avidity remains unknown. To study the relationship between TCR affinity and cellular avidity, with the intent of identifying optimal TCR for gene therapy, we derived 24 MART-1:27-35 (MART-1) melanoma Ag-reactive tumor-infiltrating lymphocyte (TIL) clones from the tumors of five patients. These MART-1-reactive clones displayed a wide variety of cellular avidities. alpha and ss TCR genes were isolated from these clones, and TCR RNA was electroporated into the same non-MART-1-reactive allogeneic donor PBMC and TIL. TCR recipient cells gained the ability to recognize both MART-1 peptide and MART-1-expressing tumors in vitro, with avidities that closely corresponded to the original TCR clones (p = 0.018-0.0003). Clone DMF5, from a TIL infusion that mediated tumor regression clinically, showed the highest avidity against MART-1 expressing tumors in vitro, both endogenously in the TIL clone, and after RNA electroporation into donor T cells. Thus, we demonstrated that the TCR appeared to be the core determinant of MART-I Ag-specific cellular avidity in these activated T cells and that nonreactive PBMC or TIL could be made tumor-reactive with a specific and predetermined avidity. We propose that inducing expression of this highly avid TCR in patient PBMC has the potential to induce tumor regression, as an "off-the-shelf" reagent for allogeneic melanoma patient gene therapy. C1 NCI, Surg Branch, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Clin Res Ctr, NIH, 10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM Steven_Rosenberg@nih.gov RI Heemskerk, Bianca/C-4635-2012; Johnson, Laura/H-4861-2013 FU Intramural NIH HHS [Z01 SC003811-32] NR 57 TC 150 Z9 157 U1 3 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2006 VL 177 IS 9 BP 6548 EP 6559 PG 12 WC Immunology SC Immunology GA 097VN UT WOS:000241477400091 PM 17056587 ER PT J AU Lotem, M Zhao, YB Riley, J Hwu, P Morgan, RA Rosenberg, SA Parkhurst, MR AF Lotem, Michal Zhao, Yangbing Riley, John Hwu, Patrick Morgan, Richard A. Rosenberg, Steven A. Parkhurst, Maria R. TI Presentation of tumor antigens by dendritic cells genetically modified with viral and nonviral vectors SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE dendritic cells; electroporation; nonviral vectors; adenovirus; retrovirus ID MHC CLASS-I; COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; MELANOMA ANTIGEN; MESSENGER-RNA; INFILTRATING LYMPHOCYTES; PRESENTING CELLS; PROTEIN; EXPRESSION; EPITOPES AB Genetic modification of dendritic cells (DCs) with recombinant vectors encoding tumor antigens may aid in developing new immunotherapeutic treatments for patients with cancer. Here, we characterized antigen presentation by human DCs genetically modified with plasmid cDNAs, RNAs, adenoviruses, or retroviruses, encoding the melanoma antigen gp100 or the tumor-testis antigen NY-ESO-1. Monocyte-derived DCs were electroporated with cDNAs or RNAs, or transduced with adenoviruses. CD34(+) hematopoietic stem cell-derived DCs were used for retroviral transduction. Genetically modified DCs were coincubated with CD8(+) and CD4(+) T cells that recognized major histocompatibility complex class I- and class II-restricted epitopes from gp100 and NY-ESO-1, and specific recognition was evaluated by interferon gamma secretion. Cytokine release by both CD8(+) and CD4(+) T cells was consistently higher in response to DCs modified with adenoviruses than cDNAs or RNAs, and maturation of DCs after genetic modification did not consistently alter patterns of recognition. Also, retrovirally transduced DCs encoding gp100 were well recognized by both CD8(+) and CD4(+) T cells. These data suggest that DCs transduced with viral vectors may be more efficient than DCs transfected with cDNAs or RNAs for the induction of tumor reactive CD8(+) and CD4(+) T cells in vitro and in human vaccination trials. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Sharett Inst Oncol, IL-91120 Jerusalem, Israel. Univ Texas, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. RP Parkhurst, MR (reprint author), NCI, NIH, Surg Branch, Bldg CRC Room 4-5744,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Maria_Parkhurst@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 43 TC 17 Z9 19 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 616 EP 627 DI 10.1097/01.cji.0000211312.36363.56 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900005 PM 17063124 ER PT J AU Jensen, SM Antony, PA Irvine, KR Muranski, P Restifo, NP Fox, BA Franz, RW AF Jensen, Shawn M. Antony, Paul A. Irvine, Kari R. Muranski, Pavel Restifo, Nicholas P. Fox, Bernard A. Franz, Robert W. TI Regression of large tumor burden after transfer of CD4 and CD8 TCR-transgenic T cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR USA. Oregon Grad Inst, Portland, OR USA. NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 629 EP 630 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900012 ER PT J AU Onda, M Nagata, S Ho, M Tapan, BK Hassan, R Alexander, RH Pastan, I AF Onda, Masanori Nagata, Satoshi Ho, Mitchell Tapan, Bera K. Hassan, Raffit Alexander, Richard H. Pastan, Ira TI Megakaryocyte potentiation factor (MPF) is a useful tumor marker in the serum of patients with mesothelioma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 NCI, LMB, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 635 EP 636 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900033 ER PT J AU Sportes, C Hakim, F Memon, S Zhang, H Chua, K Krumlauf, M Babb, R Fry, T Engels, J Buffet, R Morre, M Mackall, C Gress, R AF Sportes, Claude Hakim, Frances Memon, Sarfraz Zhang, Hua Chua, Kevin Krumlauf, Michael Babb, Rebecca Fry, Terry Engels, Julie Buffet, Renaud Morre, Michel Mackall, Crystal Gress, Ronald TI rhIL7 administration in humans results in preferential expansion of naive, and memory subsets of CD4+ & CD8+ T-Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Cytheris Inc, Rockville, MD USA. RI Memon, Sarfraz/E-1198-2013 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 641 EP 641 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900052 ER PT J AU Wigginton, J Hixon, JA Stauffer, JK Brooks, AD Khan, T Lincoln, E Back, TC Powell, D Hurwitz, AA Sayers, TJ Kastelein, R Salcedo, R AF Wigginton, Jon Hixon, Julie A. Stauffer, Jimmy K. Brooks, Alan D. Khan, Tahira Lincoln, Eric Back, Timothy C. Powell, Douglas Hurwitz, Arthur A. Sayers, Thomas J. Kastelein, Robert Salcedo, Rosalba TI The antitumor activity of IL-27 and IL-2: Synergistic enhancement of immune-responsiveness and induction of the complete regression of disseminated neuroblastoma metastases in the liver and bone marrow SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NCI, Data Management Serv, Frederick, MD 21701 USA. NCI, Pediat Oncol Branch, Frederick, MD 21701 USA. NCI, Expt Immunol Lab, CCR, Frederick, MD 21701 USA. NCI, Mol Immunoregulat Lab, CCR, Frederick, MD 21701 USA. Schering Plough Biopharma, Dept Discovery Biol, Palo Alto, CA USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 642 EP 642 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900055 ER PT J AU Arndt, M Vu, BK Martin, AC Liu, H Newton, DL Seeber, S Rybak, SM Krauss, J AF Arndt, Michaela Vu, Bang K. Martin, Andrew C. Liu, Huaitian Newton, Dianne L. Seeber, Siegfried Rybak, Susanna M. Krauss, J. rgen TI A humanized diabody-ribonuclease fusion protein mediates potent and selective killing of CD22-positive tumor cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 Univ Duisburg Essen, Essen, Germany. NCI, SAIC, Frederick, MD 21701 USA. UCL, London, England. 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 671 EP 671 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900148 ER PT J AU Baskar, S Kwong, KY Hofer, T Levy, JM Kennedy, MG Wilson, WH Wiestner, A Rader, C AF Baskar, Sivasubramanian Kwong, Ka Yin Hofer, Thomas Levy, Jessica M. Kennedy, Michael G. Wilson, Wyndham H. Wiestner, Adrian Rader, Christoph TI Receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a potential target antigen for immunotherapy of human B cell chronic lymphocytic leukemia SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 NCI, Expt Transplantat & Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 671 EP 672 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900149 ER PT J AU Kim, SY Guimond, M Meany, HJ Strahan, S Cook, L Cohen, SA Khanna, C Jones, B Aziz, N Helman, LJ AF Kim, Su Young Guimond, Martin Meany, Holly J. Strahan, Stephanie Cook, Larry Cohen, Seth A. Khanna, Chand Jones, Barry Aziz, Nazneen Helman, Lee J. TI Dipeptidyl peptidase inhibition decreases osteosarcoma tumor formation by targeting stromal elements and immune stimulation SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. Point Therapeut Corp, Boston, MA 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 681 EP 681 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900180 ER PT J AU Stauffer, JK Lincoln, E Greer, B Khan, T Salcedo, R Hixon, JA Back, TC Ye, M Stephens, R Tsokos, M Whiteford, C Eisenhofer, G Weiss, W Khan, J Wigginton, J AF Stauffer, Jimmy K. Lincoln, Eric Greer, Braden Khan, Tahira Salcedo, Rosalba Hixon, Julie A. Back, Timothy C. Ye, Ming Stephens, Robert Tsokos, Maria Whiteford, Craig Eisenhofer, Graeme Weiss, William Khan, Javed Wigginton, Jon TI Molecular profiling of a novel transplantable model of murine neuroblastoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 NCI, Pediat Oncol Branch, Frederick, MD 21701 USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD USA. NCI, Pathol Lab, CCR, Frederick, MD 21701 USA. NINDS, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 682 EP 683 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900184 ER PT J AU Wheeler, CM Hunt, WC Schiffman, M Castle, PE AF Wheeler, Cosette M. Hunt, William C. Schiffman, Mark Castle, Philip E. CA ALTS Grp TI Human papillomavirus genotypes and the cumulative 2-year risk of cervical precancer SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ATYPICAL SQUAMOUS-CELLS; UNDETERMINED SIGNIFICANCE; RANDOMIZED-TRIAL; CYTOLOGY INTERPRETATIONS; MANAGEMENT STRATEGIES; HPV TYPE-16; INFECTION; WOMEN; NEOPLASIA; CANCER AB Background. Prospective data on the risks of cervical precancer associated with specific human papillomavirus (HPV) genotypes are limited. Methods. In 5060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS), we determined the cumulative 2-year risks of cervical intraepithelial neoplasia (CIN) grade 2 or more severe (>= CIN2) and of grade 3 or more severe (>= CIN3) for 38 individual HPV genotypes, as detected by polymerase chain reaction. Results. The most common HPV genotypes detected at baseline, in descending order of prevalence, were 16, 52, 51, 31, 18, 53, 39, 56, 62, 59, and 58. When detected as a single-type HPV infection, HPV-16 had a 2-year cumulative risk of 50.6% (95% confidence interval [CI], 44.1%-57.2%) for >= CIN2 and 39.1% (95% CI, 32.9%-45.7%) for >= CIN3. For other singly detected carcinogenic HPV types, the risk of >= CIN2 ranged from 4.7% (for HPV-59) to 29.5% (for HPV-31), and the risk of >= CIN3 ranged from 0.0% (for HPV-59) to 14.8% (for HPV-31). Multiple infections with HPV genotypes of different risk classes resulted in a risk that was similar to, and not significantly different from, the risk observed for the HPV genotype of the highest risk class. Conclusions. Genotype-specific HPV testing may be useful for identifying women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions who are at higher and lower risk of prevalent and incipient cervical precancer. C1 Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Sch Med, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Sch Med, Albuquerque, NM 87131 USA. Div Canc Epidemiol & Genet, Bethesda, MD USA. NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Wheeler, CM (reprint author), Univ New Mexico, Hope Clin, Dept Mol Genet & Microbiol, 1816 Sigma Chi Rd NE, Albuquerque, NM 87131 USA. EM cwheeler@salud-unm.edu FU NCI NIH HHS [CN-55153, CN-55105, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159] NR 25 TC 74 Z9 84 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2006 VL 194 IS 9 BP 1291 EP 1299 DI 10.1086/507909 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 097AJ UT WOS:000241418100015 PM 17041856 ER PT J AU Solomon, S Natanson, C Eichacker, P AF Solomon, Steven Natanson, Charles Eichacker, Peter TI Elevated plasma levels of limulus amoebocyte lysate-reactive material - Reply to Rossignol et al. SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Solomon, S (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 9000 Rockville Pike,Bldg 10-7D43, Bethesda, MD 20892 USA. EM ssolomon@cc.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2006 VL 194 IS 9 BP 1340 EP 1341 DI 10.1086/508225 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 097AJ UT WOS:000241418100022 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI Seasonal and pandemic influenza preparedness: Science and countermeasures SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Seasonal and Pandemic Influenza Conference 2006 CY FEB 01-02, 2006 CL Washington, DC SP Infect Dis Soc Amer, Soc Hlthcare Epidemiol Amer, Natl Inst Allergy & Infect Dis, Ctr Dis Control & Prevent ID UNITED-STATES AB Influenza has not been treated with the degree of medical attention that the disease warrants. As such, there is not an adequate baseline of preparedness in the United States to deal with the potential of pandemic influenza. The National Institute of Allergy and Infectious Diseases (NIAID) has been working to enact measures to deal more effectively with a potential influenza pandemic and also to assist in the management of seasonal influenza. The majority of the NIAID's efforts have been dedicated to basic research aimed ultimately at developing and testing, in clinical trials, countermeasures in the form of antiviral drugs and vaccines. Some of the NIAID's current and planned antiviral projects include the (1) assessment of oseltamivir therapy in infants, (2) conduct of clinical trials of higher doses of osteltamivir for avian influenza, (3) appraisal of combination therapies, and (4) evaluation of the next generation of neuraminidase inhibitors. In addition, the NIAID is screening potential new antiviral drugs and evaluating novel drug targets. Similarly, significant funding has been committed to vaccine preparedness, and numerous novel candidate influenza vaccines are in various stages of development. Importantly, there is an integral relationship between preparation for seasonal influenza and preparation for pandemic influenza. Until these approaches are firmly linked, the community will not have optimized its preparedness for a pandemic. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Rm 7A03,31 Ctr Dr,MSC 2520, Bethesda, MD 20892 USA. EM af10r@nih.gov NR 11 TC 32 Z9 31 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 NOV 1 PY 2006 VL 194 SU 2 BP S73 EP S76 DI 10.1086/507550 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 098EE UT WOS:000241503000003 PM 17163392 ER PT J AU Niedermeier, A Talanin, N Chung, EJ Sells, RE Borris, DL Orenstein, JM Trepel, JB Blauvelt, A AF Niedermeier, Andrea Talanin, Nickolai Chung, Eun Joo Sells, Ryan E. Borris, Debra L. Orenstein, Jan M. Trepel, Jane B. Blauvelt, Andrew TI Histone deacetylase inhibitors induce apoptosis with minimal viral reactivation in cells infected with Kaposi's sarcoma-associated herpesvirus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; PROMYELOCYTIC LEUKEMIA; DEPSIPEPTIDE FR901228; GENE-EXPRESSION; RETINOIC ACID; IN-VIVO; HUMAN-HERPESVIRUS-8; LYMPHOMA; BUTYRATE; LATENCY AB Kaposi's sarcoma-associated herpesvirus ( KSHV) latently infects tumor cells in patients with Kaposi's sarcoma and primary effusion lymphoma (PEL). The purpose of this study was to determine whether histone deacetylase inhibitors (HDAI) could induce apoptosis, with minimal viral replication, in cells latently infected with KSHV. Four HDAI ( depsipeptide, suberoylanilide hydroxamic acid, MS-275, and trichostatin A) were studied in two PEL B cell lines (BCBL-1, BC-3). As expected, histone hyperacetylation was readily induced in all PEL cells exposed to HDAI. HDAI also triggered KSHV reactivation in a time- and dose-dependent manner. Flow cytometric and transmission electron microscopic studies, however, revealed that reactivation occurred in only a minor percentage (3-14%) of treated cells. Importantly, and in contrast to viral reactivation, HDAI induced apoptotic cell death in a dose-dependent manner in a large percentage (up to 90%) of KSHV-infected cells. In summary, all four HDAI tested induced histone hyperacetylation in all cells, KSHV reactivation in a minority of cells, and apoptotic cell death in a majority of cells latently infected with KSHV. These findings suggest that HDAI may be a therapeutic option for patients with KSHV-mediated diseases by rendering cells infected with KSHV susceptible to apoptosis. C1 NCI, Ctr Canc Res, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD USA. George Washington Univ, Dept Pathol, Washington, DC USA. RP Blauvelt, A (reprint author), Oregon Hlth Sci Univ, Dept Dermatol, 3710 SW US Vet Hosp Rd,Mail Code R&D 55, Portland, OR 97239 USA. EM blauvela@ohsu.edu FU Intramural NIH HHS NR 48 TC 8 Z9 8 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2006 VL 126 IS 11 BP 2516 EP 2524 DI 10.1038/sj.jid.5700438 PG 9 WC Dermatology SC Dermatology GA 096EG UT WOS:000241359600021 PM 16810301 ER PT J AU Emmert, S Wetzig, T Imoto, K Khan, SG Oh, KS Laspe, P Zachmann, K Simon, JC Kraemer, KH AF Emmert, Steffen Wetzig, Tino Imoto, Kyoko Khan, Sikandar G. Oh, Kyu-Seon Laspe, Petra Zachmann, Karolin Simon, Jan C. Kraemer, Kenneth H. TI A novel complex insertion/deletion mutation in the XPC DNA repair gene leads to skin cancer in an Iraqi family SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID XERODERMA-PIGMENTOSUM; POLYMORPHISM; FEATURES C1 Univ Gottingen, Dept Dermatol, D-3400 Gottingen, Germany. Univ Leipzig, Dept Dermatol Venerol & Allergol, D-7010 Leipzig, Germany. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Emmert, S (reprint author), Univ Gottingen, Dept Dermatol, D-3400 Gottingen, Germany. EM semmert@gwdg.de FU Intramural NIH HHS [Z01 BC004517-31] NR 9 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2006 VL 126 IS 11 BP 2542 EP 2544 DI 10.1038/sj.jid.5700452 PG 3 WC Dermatology SC Dermatology GA 096EG UT WOS:000241359600025 PM 16794584 ER PT J AU Wahl, SM Greenwell-Wild, T Vazquez, N AF Wahl, Sharon M. Greenwell-Wild, Teresa Vazquez, Nancy TI HIV accomplices and adversaries in macrophage infection SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE APOBEC; monocyte; SLPI; annexin II; IFN; retrovirus; p21; Vpr; Vif ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE PROTEASE INHIBITOR; ENVELOPE GLYCOPROTEIN GP120; LONG TERMINAL REPEAT; REPLICATION IN-VIVO; DENDRITIC CELLS; ANNEXIN-II; T-CELLS; VIRAL ENTRY; HOST-CELLS AB Cell surface and intracellular proteins in macrophages influence various steps in the life cycle of lentiviruses. Characterization of these restriction and/or cofactors is essential to understanding how macrophages become unwitting HIV hosts and in fact, can coexist with a heavy viral burden. Although many of the cellular pathways co-opted by HIV in macrophages mimic those seen in CD4(+) T cells, emerging evidence reveals cellular constituents of the macrophage, which may be uniquely usurped by HIV. For example, in addition to CD4 and CCR5, membrane annexin 11 facilitates early steps in infection of macrophages, but not in T cells. Blockade of this pathway effectively diminishes macrophage infection. Viral binding engages a macrophage-centric signaling pathway and a transcriptional profile, including genes such as p21, which benefit the virus. Once inside the cell, multiple host cell molecules are engaged to facilitate virus replication and assembly. Although the macrophage is an enabler, it also possesses innate antiviral mechanisms, including apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3) family DNA-editing enzymes to inhibit replication of HIV. Differential expression of these enzymes, which are largely neutralized by HIV to protect its rebirth, is associated with resistance or susceptibility to the virus. Higher levels of the cytidine deaminases endow potential HIV targets with a viral shield, and IFN-alpha, a natural inducer of macrophage APOBEC expression, renders macrophages tougher combatants to HIV infection. These and other manipulatable pathways may give the macrophage a fighting chance in its battle against the virus. J. Leukoc. Biol. 80: 973-983;2006. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov FU Intramural NIH HHS NR 140 TC 30 Z9 31 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2006 VL 80 IS 5 BP 973 EP 983 DI 10.1189/jlb.0306130 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MJ UT WOS:000243016100003 PM 16908514 ER PT J AU Vazquez, N Greenwell-Wild, T Rekka, S Orenstein, JM Wahl, SM AF Vazquez, Nancy Greenwell-Wild, Teresa Rekka, Sofia Orenstein, Jan M. Wahl, Sharon M. TI Mycobacterium avium-induced SOCS contributes to resistance to IFN-gamma-mediated mycobactericidal activity in human macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE AIDS; STAT; HIV ID TUMOR-NECROSIS-FACTOR; MURINE PERITONEAL-MACROPHAGES; CYTOKINE SIGNALING 3; INTERFERON-GAMMA; HUMAN-MONOCYTES; GENE-EXPRESSION; INTRACELLULARE COMPLEX; FACTOR-ALPHA; IN-VITRO; INFECTION AB Mycobacterium avium is an opportunistic pathogen that commonly infects individuals colonized with HIV-1, although it is less frequent in the post-HAART era. These microorganisms invade macrophages after interacting with TLR2 and/or CD14 co-receptors, but signaling pathways promoting survival in macrophages are not well defined. Although IFN-gamma plays an important role in protective immunity against bacterial infections, IFN-gamma responses are compromised in AIDS patients and evidence suggests that exogenous IFN-gamma is inadequate to clear the mycobacteria. To determine the mechanism by which M. avium survives intracellularly, even in the presence of IFN-gamma, we studied the effect of mycobacteria infection in macrophages during early IFN-gamma signaling events. M. avium infected cells exhibited a reduced response to IFN-gamma, with suppressed phosphorylation of STAT-I compared with uninfected cells. Interaction of M. avium with macrophage receptors increased gene expression of the suppressors of cytokine signaling (SOCS) to diminish IFN responsiveness. Specifically, we observed an increase in mRNA for both SOCS-3 and SOCS-1, which correlates with elevated levels of SOCS protein and positive immunostaining in M. avium/HIV-1 co-infected tissues. We also linked the p38 MAPK signalling pathway to mycobacterial-induced SOCS gene transcription. The induction of SOCS may be part of the strategy that allows the invader to render the macrophages unresponsive to IFN-gamma, which otherwise promotes clearance of the infection. Our data provide new insights into the manipulation of the host response by this opportunistic pathogen and the potential for modulating SOCS to influence the outcome of M. avium infection in immunocompromised. hosts. J. Leukoc. Biol. 80: 1136-1144; 2006. C1 NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC USA. RP Vazquez, N (reprint author), NIDCR, OIIB, NIH, Bldg 30,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM nvazquez@mail.nih.gov FU Intramural NIH HHS NR 73 TC 40 Z9 40 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2006 VL 80 IS 5 BP 1136 EP 1144 DI 10.1189/jlb.0306206 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MJ UT WOS:000243016100019 PM 16943387 ER PT J AU Moutsopoulos, NM Vazquez, N Greenwell-Wild, T Ecevit, I Horn, J Orenstein, J Wahl, SM AF Moutsopoulos, Niki M. Vazquez, Nancy Greenwell-Wild, Teresa Ecevit, Ismail Horn, Judith Orenstein, Jan Wahl, Sharon M. TI Regulation of the tonsil cytokine milieu favors HIV susceptibility SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE mucosal associated lymphoid tissue; TH2; IL-4; IFN; SOCS ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE PROTEASE INHIBITOR; CD4(+) T-CELLS; LYMPHOID-TISSUE; GENE-EXPRESSION; EX-VIVO; ANTIRETROVIRAL THERAPY; HUMAN SALIVA; ORAL SEX; INFECTION AB Mucosal associated lymphoid tissues are major targets of HIV during early infection and disease progression but can also provide a viral safe haven during highly active antiretroviral therapy. Among these tissues, the tonsils remain enigmatic regarding their status as primary and/or secondary sites of retroviral infection. To dissect the mechanisms underlying susceptibility to HIV in this compartment, isolated tonsil cells were studied for phenotypic and functional characteristics, which may account for their permissiveness to infection. For this, tonsil cells and PBMC were infected in parallel with HIV, and viral replication was monitored by p24 ELISA. Our results demonstrate that unstimulated tonsil cells were more readily infected than PBMC with HIV. Phenotypic characterization of the tonsil cells revealed heterogeneous lymphoid populations but with increased expression of early activation markers and the viral co-receptor CXCR4, relative to PBMC, all of which may contribute to viral susceptibility. Furthermore, the cytokine microenvironment appeared to be key in facilitating HIV infection and tonsil-secreted products enhanced HIV infection in PBMC. Of the cytokines detected in the tonsil supernatants, TH2 cytokines, particularly IL-4, promoted HIV infection and replication. Interestingly, this TH2 profile appeared to dominate, even in the presence of the TH1 cytokine IFN gamma and the antiviral factor IFN alpha, likely due to the enhanced expression of suppressor of cytokine signaling (SOCS) proteins, which may disengage IFN signaling. These and other local environmental factors may render tonsil cells increasingly susceptible to HIV infection. J. Leukoc. Biol. 80: 1145-1155; 2006. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Pathol, Washington, DC USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@mail.nih.gov FU Intramural NIH HHS NR 47 TC 24 Z9 25 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2006 VL 80 IS 5 BP 1145 EP 1155 DI 10.1189/jlb.0306142 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MJ UT WOS:000243016100020 PM 16943383 ER PT J AU Kennedy, PE Bera, TK Wang, QC Gallo, M Wagner, W Lewis, MG Berger, EA Pastan, I AF Kennedy, Paul E. Bera, Tapan K. Wang, Qing-Cheng Gallo, Maria Wagner, Wendeline Lewis, Mark G. Berger, Edward A. Pastan, Ira TI Anti-HIV-1 immunotoxin 3B3(Fv)-PE38: enhanced potency against clinical isolates in human PBMCs and macrophages, and negligible hepatotoxicity in macaques SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE HAART; reservoirs persistence; targeted killing ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; PHASE-I TRIAL; NONSPECIFIC ANIMAL TOXICITY; EXOTOXIN HYBRID PROTEIN; RECOMBINANT SOLUBLE CD4; CD4-PSEUDOMONAS EXOTOXIN; T-CELLS; DIPHTHERIA-TOXIN AB Highly active antiretroviral therapy (HAART) against human immunodeficiency virus type 1 (HIV-1) infection dramatically suppresses viral load, leading to marked reductions in HIV-1 associated morbidity and mortality. However, infected cell reservoirs and low-level replication persist in the face of suppressive HAART, leading invariably to viral rebound upon cessation of treatment. Toxins engineered to target the Env glycoprotein on the surface of productively infected cells represent a complementary strategy to deplete these reservoirs. We described previously highly selective killing of Env-expressing cell lines by CD4(178)-PE40 and 3B3(Fv)-PE38, recombinant derivatives of Pseudomonas aeruginosa exotoxin A containing distinct targeting moieties against gp120. In the present report, we compare the in vitro potency and breadth of these chimeric toxins against multiple clinical HIV-1 isolates, replicating in biologically relevant primary human target cell types. In PBMCs, 3B3(Fv)-PE38 blocked spreading infection by all isolates examined, with greater potency than CD4(178)-PE40. 3B3(Fv)-PE38 also potently inhibited spreading HIV-1 infection in primary macrophages. Control experiments demonstrated that in both target cell types, most of the 3B3(Fv)-PE38 activity was due to selective killing of infected cells, and not merely to neutralization by the antibody moiety of the chimeric toxin. High-dose treatment of rhesus macaques with 3B3(Fv)-PE38 did not induce liver toxicity, whereas equivalent dosage of CD4(178)-PE40 induced mild hepatotoxicity. These findings highlight the potential use of 3B3(Fv)-PE38 for depleting HIV-infected cell reservoirs persisting in the face of HAART. J. Leukoc. Biol. 80: 1175-1182; 2006. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 237, Bethesda, MD 20892 USA. EM edward_berger@nih.gov FU Intramural NIH HHS NR 60 TC 23 Z9 24 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2006 VL 80 IS 5 BP 1175 EP 1182 DI 10.1189/jlb.0306139 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MJ UT WOS:000243016100023 PM 16923920 ER PT J AU Magra, AL Mertz, PS Torday, JS Londos, C AF Magra, Amy L. Mertz, Pamela S. Torday, John S. Londos, Constantine TI Role of adipose differentiation-related protein in lung surfactant production: a reassessment SO JOURNAL OF LIPID RESEARCH LA English DT Article DE lipid droplets; surfactant phospholipid; PAT proteins ID ALVEOLAR EPITHELIAL-CELLS; LIPID DROPLETS; TIP47; METABOLISM; PERILIPINS; MEMBRANE; FAMILY; LIPASE; TISSUE; ADRP AB Based on data developed with the use of isolated lipid droplets from neonatal rat lung lipofibroblasts, we speculated previously that the droplet coat protein, adipose differentiation-related protein (ADFP), mediated the transfer of lipids into type 2 lung epithelial cells for the production of surfactant phospholipids. The present studies were designed to test the role of ADFP in this transfer with the use of ADFP-coated lipid droplets from CHO fibroblast cells and a cultured human lung epithelial cell line. We found no role for ADFP in the lipid transfer and conclude that a lipase associated with the lipid droplets hydrolyzes their core triacylglycerols, releasing fatty acids that are taken up by the epithelial cells. C1 NIDDK, Membrane Regulat Sect, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Harbor UCLA Med Ctr, Res & Educ Inst, Dept Pediat, Torrance, CA 90502 USA. Univ Calif Los Angeles, Harbor UCLA Med Ctr, Res & Educ Inst, Dept Obstet & Gynecol, Torrance, CA 90502 USA. RP Londos, C (reprint author), NIDDK, Membrane Regulat Sect, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM deanl@intra.niddk.nih.gov OI Torday, John/0000-0001-9071-3052 FU Intramural NIH HHS NR 19 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 2006 VL 47 IS 11 BP 2367 EP 2373 DI 10.1194/jlr.M600157-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KI UT WOS:000241667300002 PM 16936283 ER PT J AU Prats, C Donsmark, M Qvortrup, K Londos, C Sztalryd, C Holm, C Galbo, H Ploug, T AF Prats, Clara Donsmark, Morten Qvortrup, Klaus Londos, Constantine Sztalryd, Carole Holm, Cecilia Galbo, Henrik Ploug, Thorkil TI Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine SO JOURNAL OF LIPID RESEARCH LA English DT Article DE lipid metabolism regulation; skeletal muscle; hormone-sensitive lipase; adipocyte differentiation-related protein; tail-interacting protein of 47 kDa ID HORMONE-SENSITIVE LIPASE; HUMAN SKELETAL-MUSCLE; DIFFERENTIATION-RELATED PROTEIN; A-MEDIATED LIPOLYSIS; INSULIN-RESISTANCE; ADIPOSE-TISSUE; PERILIPIN-A; EXERCISE; CELLS; ADRENALINE AB A better understanding of skeletal muscle lipid metabolism is needed to identify the molecular mechanisms relating intramuscular triglyceride (IMTG) to muscle metabolism and insulin sensitivity. An increasing number of proteins have been reported to be associated with intracellular triglyceride (TG), among them the PAT family members: perilipin, ADRP ( for adipocyte differentiation-related protein), and TIP47 ( for tail-interacting protein of 47 kDa). Hormone-sensitive lipase (HSL) is thought to be the major enzyme responsible for IMTG hydrolysis in skeletal muscle. In adipocytes, regulation of HSL by intracellular redistribution has been demonstrated. The existence of such regulatory mechanisms in skeletal muscle has long been hypothesized but has never been demonstrated. The aim of this study was to characterize the PAT family proteins associated with IMTG and to investigate the effect of epinephrine stimulation or muscle contraction on skeletal muscle TG content and HSL intracellular distribution. Rat soleus muscles were either incubated with epinephrine or electrically stimulated for 15 min. Single muscle fibers were used for morphological analysis by confocal and transmission electron microscopy. We show a decrease in IMTG in response to both lipolytic stimuli. Furthermore, we identify two PAT family proteins, ADRP and TIP47, associated with IMTG. Finally, we demonstrate HSL translocation to IMTG and ADRP after stimulation with epinephrine or contraction. C1 Univ Copenhagen, Panum Inst, Dept Med Physiol, Copenhagen Muscle Res Ctr, DK-2200 Copenhagen N, Denmark. Univ Copenhagen, Panum Inst, Dept Med Anat, DK-2200 Copenhagen, Denmark. NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore Vet Affairs Hlth Care Ctr, Geriatr Res Educ & Clin Ctr,Dept Med, Baltimore, MD 21201 USA. Lund Univ, Dept Expt Med Sci, SE-22184 Lund, Sweden. Bispebjerg Hosp, Dept Rheumatol, Copenhagen Muscel Res Ctr, DK-2400 Copenhagen NV, Denmark. RP Prats, C (reprint author), Univ Copenhagen, Panum Inst, Dept Med Physiol, Copenhagen Muscle Res Ctr, DK-2200 Copenhagen N, Denmark. EM cprats@mfi.ku.dk RI Prats, Clara/F-5993-2014 FU Intramural NIH HHS NR 42 TC 55 Z9 59 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 2006 VL 47 IS 11 BP 2392 EP 2399 DI 10.1194/jlr.M600247-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KI UT WOS:000241667300005 PM 16905768 ER PT J AU Hanniman, EA Lambert, G Inoue, Y Gonzalez, FJ Sinal, CJ AF Hanniman, Elyhisha A. Lambert, Gilles Inoue, Yusuke Gonzalez, Frank J. Sinal, Christopher J. TI Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha SO JOURNAL OF LIPID RESEARCH LA English DT Article DE glucocorticoid receptor; fasting; diabetes; adrenalectomy; hepatic nuclear factor-4 alpha; peroxisome proliferator-activated-receptor gamma coactivator-1 alpha ID GENE-EXPRESSION; LIPOPROTEIN METABOLISM; DIABETES-MELLITUS; TARGETED DISRUPTION; INSULIN-RESISTANCE; GLUCOSE-PRODUCTION; LIPID HOMEOSTASIS; DEFICIENT MICE; BILE-ACID; RECEPTOR AB Apolipoprotein A-IV ( apoA-IV) is a 46 kDa glycoprotein that associates with triglyceride-rich and high density lipoproteins. Blood levels of apoA-IV generally correlate with triglyceride levels and are increased in diabetic patients. This study investigated the mechanisms regulating the in vivo expression of apoA-IV in the liver and intestine of mice in response to changes in nutritional status. Fasting markedly increased liver and ileal apoA-IV mRNA and plasma protein concentrations. This induction was associated with increased serum glucocorticoid levels and was abolished by adrenalectomy. Treatment with dexamethasone increased apoA-IV expression in adrenalectomized mice. Marked increases of apoA-IV expression were also observed in two murine models of diabetes. Reporter gene analysis of the murine and human apoA-IV/C-III promoters revealed a conserved cooperative activation by the hepatic nuclear factor-4 alpha (HNF-4 alpha) and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) but no evidence of a direct regulatory role for the glucocorticoid receptor. Consistent with these in vitro data, induction of apoA-IV in response to fasting was accompanied by increases in HNF-4 alpha and PGC-1 alpha expression and was abolished in liver-specific HNF-4 alpha-deficient mice. Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions. C1 Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 3J5, Canada. Univ Nantes, CHU Nantes, Hotel Dieu, Med Sch,INSERM,U539, F-44035 Nantes, France. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Sinal, CJ (reprint author), Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 3J5, Canada. EM csinal@dal.ca NR 51 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 2006 VL 47 IS 11 BP 2503 EP 2514 DI 10.1194/jlr.M600303-JLR200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KI UT WOS:000241667300016 PM 16929032 ER PT J AU Asbury, T Quine, JR Achuthan, S Hu, J Chapman, MS Cross, TA Bertram, R AF Asbury, T. Quine, J. R. Achuthan, S. Hu, J. Chapman, M. S. Cross, T. A. Bertram, R. TI PIPATH: An optimized algorithm for generating alpha-helical structures from PISEMA data SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE solid-state NMR; PISEMA; membrane proteins; alpha-helices; automated structure determination ID SOLID-STATE NMR; MEMBRANE-PROTEIN STRUCTURE; ORIENTATIONAL RESTRAINTS; REFINEMENT; TOPOLOGY; WHEELS AB An optimized algorithm for finding structures and assignments of solid-state NMR PISEMA data obtained from a-helical membrane proteins is presented. The description of this algorithm, PIPATH, is followed by an analysis of its performance on simulated PISEMA data derived from synthetic and experimental structures. PIPATH transforms the assignment problem into a path-finding problem for a directed graph, and then uses techniques of graph theory to efficiently find candidate assignments from a very large set of possibilities. (c) 2006 Elsevier Inc. All rights reserved. C1 Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Bertram, R (reprint author), Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu FU NIGMS NIH HHS [P01-GM064676] NR 24 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2006 VL 183 IS 1 BP 87 EP 95 DI 10.1016/j.jmr.2006.07.020 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 106VW UT WOS:000242131100010 PM 16914335 ER PT J AU de Alba, E Tjandra, N AF de Alba, Eva Tjandra, Nico TI On the accurate measurement of amide one-bond N-15-H-1 couplings in proteins: Effects of cross-correlated relaxation, selective pulses and dynamic frequency shifts SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE NMR; scalar couplings; cross-correlated relaxation; selective pulses; dynamic frequency shifts ID RESIDUAL DIPOLAR COUPLINGS; QUANTITATIVE J-CORRELATION; MAGNETIC-FIELD DEPENDENCE; 2-DIMENSIONAL NMR-SPECTRA; BACKBONE; INTERFERENCE; SPECTROSCOPY; CONSTANTS; UBIQUITIN; NITROGEN AB Amide one-bond N-15-H-1 scalar couplings of N-15- and [N-15,H-2]-isotopically enriched ubiquitin have been measured with the Quantitative J approach by monitoring NMR signal intensity modulation. Scalar couplings of the non-deuterated protein are in average similar to 0.6 Hz larger than values of deuterated ubiquitin. This deviation is 30 times the error derived from experiment reproducibility. Refocusing dipole/dipole cross-correlated relaxation decreases the discrepancy to similar to 0.1 Hz, suggesting that it likely originates from relaxation interference. Alternatively, the subtraction of J values obtained at different magnetic fields largely reduces the relaxation effects. In contrast, the dynamic frequency shift whose main contribution to (1)J(15N-H-1) arises from N-15 chemical shielding anisotropy/NH dipole cross-correlation, is not eliminated by refocusing spin evolution under this interaction. Furthermore, the average difference of (1)J(N-15-H-1) values at two magnetic fields closely agrees with the theoretical expected difference in the dynamic frequency shift. Published by Elsevier Inc. C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP de Alba, E (reprint author), NHLBI, Lab Mol Biophys, NIH, 50 S Dr, Bethesda, MD 20892 USA. EM dealbae@nhlbi.nih.gov FU Intramural NIH HHS NR 30 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2006 VL 183 IS 1 BP 160 EP 165 DI 10.1016/j.jmr.2006.08.003 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 106VW UT WOS:000242131100019 PM 16949845 ER PT J AU Syed, MA Carlson, K Murphy, M Ingkanisorn, WP Rhoads, KL Arai, AE AF Syed, Mushabbar A. Carlson, Karen Murphy, Mandy Ingkanisorn, W. Patricia Rhoads, Kenneth L. Arai, Andrew E. TI Long-term safety of cardiac magnetic resonance imaging performed in the first few days after bare-metal stent implantation SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; heart; safety; stent; myocardial infarction ID CORONARY STENTS; PLACEMENT; ABSENCE AB Purpose: To investigate the long-term safety of cardiac magnetic resonance imaging (CMR) performed one to seven days after coronary artery stent (bare metal) implantation. Materials and Methods: We analyzed 119 consecutive patients with acute myocardial infarction (MI) who underwent emergency coronary stent implantation with a bare-metal stent. CMR using a 1.5T scanner was performed on 51 patients (42.9%) at a mean of 2.7 +/- 3.1 days after stent implantation (CMR+ group), and the remaining 68 patients (57.1%) served as controls (CMR-group). The patients were followed up to six months for major adverse cardiac events. Results: The average stent size was 3.3 +/- 0.5 X 18.4 +/- 6.7 turn, and 86% of the stents were made of 316L stainless steel. There were no significant differences between the CMR+ and CMR- groups in terms of infarct features, angiographic findings, or stent characteristics. Over a mean follow-up of 4.4 +/- 2.1 months, 12 patients (10.1%) had 16 events (13.4%). Two patients had adverse events after early MRI scan (4.3%), a rate that is lower than the event rate in the patients who did not undergo MRI (16%, P = 0.04), and one of the two events was clearly not MRI related. Conclusion: CMR on a 1.5T scanner can be safely per formed within one to seven days after coronary bare-metal stent implantation and is not associated with an increased risk of adverse clinical cardiac outcomes. In the light of accumulating data, the guidelines by stent manufacturers should be revised. C1 NHLBI, Cardiovasc MRI, Lab Cardiac Energet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Kentucky, Div Cardiol, Gill Heart Inst, Lexington, KY USA. Suburban Hosp, Bethesda, MD USA. RP Arai, AE (reprint author), NHLBI, Cardiovasc MRI, Lab Cardiac Energet, NIH,Dept Hlth & Human Serv, Bldg 10,MSC 1061,BLD 416,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nhlbi.nih.gov NR 8 TC 18 Z9 18 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2006 VL 24 IS 5 BP 1056 EP 1061 DI 10.1002/jmri.20740 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 100DS UT WOS:000241648400014 PM 17036357 ER PT J AU Caplan, LJ Schooler, C AF Caplan, Leslie J. Schooler, Carmi TI Household work complexity, intellectual - Functioning, and self-esteem in men and women SO JOURNAL OF MARRIAGE AND FAMILY LA English DT Article DE family roles; housework/division of labor; personality; self-esteem ID DIVISION-OF-LABOR; LONGITUDINAL ASSESSMENT; PSYCHOLOGICAL DISTRESS; GENDER; HOUSEWORK; FAIRNESS; COUPLES; WIVES; SENSE; PERSONALITY AB Using data from a U.S. longitudinal investigation of psychological effects of occupational conditions (a project of the National Institute of Mental Health's unit on Socioenvironmental Studies), we examined the relationship between the complexity of household work and 2 psychological variables: intellectual flexibility and self-esteem. Longitudinal reciprocal effects analyses revealed that for men (n = 351) and women (n = 355), more complex household work was associated with increased intellectual flexibility. For women, complex household work was also associated with increased self-confidence and decreased self-deprecation. For men, complex household work was associated with decreased self-confidence. The results are discussed in terms of theories of the cognitive and neurological effects of environmental complexity and of theories of self-esteem. C1 NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. RP Caplan, LJ (reprint author), NIMH, Sect Socioenvironm Studies, 6006 Execut Blvd,Room 321, Bethesda, MD 20892 USA. EM leslie.caplan@nih.gov NR 51 TC 8 Z9 8 U1 2 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-2445 J9 J MARRIAGE FAM JI J. Marriage Fam. PD NOV PY 2006 VL 68 IS 4 BP 883 EP 900 DI 10.1111/j.1741-3737.2006.00302.x PG 18 WC Family Studies; Sociology SC Family Studies; Sociology GA 092QH UT WOS:000241111900012 ER PT J AU Seal, JL Gornick, MC Gogtay, N Shaw, P Greenstein, DK Coffey, M Gochman, PA Stromberg, T Chen, Z Merriman, B Nelson, SF Brooks, J Arepalli, S Wavrant-De Vrieze, F Hardy, J Rapoport, JL Addington, AM AF Seal, J. L. Gornick, M. C. Gogtay, N. Shaw, P. Greenstein, D. K. Coffey, M. Gochman, P. A. Stromberg, T. Chen, Z. Merriman, B. Nelson, S. F. Brooks, J. Arepalli, S. Wavrant-De Vrieze, F. Hardy, J. Rapoport, J. L. Addington, A. M. TI Segmental uniparental isodisomy on 5q32-qter in a patient with childhood-onset schizophrenia SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID DISOMY UPD; AFFECTIVE-DISORDERS; K-SADS; GENE; AGE; SUSCEPTIBILITY; RELIABILITY; PSYCHOSIS; SCHEDULE; SCAN AB Schizophrenia is a severe mental disorder affecting approximately 1% of the world's population. Although the aetiology of schizophrenia is complex and multifactorial, with estimated heritabilities as high as 80%, genetic factors are the most compelling. Childhood-onset schizophrenia ( COS), defined as onset of schizophrenia before the age of 13 years, is a rare and malignant form of the illness that may have more salient genetic influence. The first known case of paternal segmental uniparental isodisomy ( iUPD) on 5q32-qter in a patient with COS is described, which adds to the previously known high rates of chromosomal abnormalities reported in this sample. iUPD is a rare genetic condition in which the offspring receives two chromosomal homologues from one parent. Segmental UPD is defined as UPD on a portion of a chromosome with biparental inheritance seen in the rest of the homologous pair. Complications owing to this abnormality may arise from malfunctioning imprinted genes or homozygosity of recessive disease-causing mutations. This aberration became apparent during whole-genomic screening of a COS cohort and is of particular interest because 5q has been implicated in schizophrenia by several genomewide linkage studies and positive gene associations. This report, therefore, presents more evidence that schizophrenia susceptibility gene, or genes, may be found on distal 5q. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Addington, AM (reprint author), 10 Ctr Dr,Bldg 10,Room 3N202, Bethesda, MD 20892 USA. EM addingta@mail.nih.gov RI Gogtay, Nitin/A-3035-2008; Nelson, Stanley/D-4771-2009; Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 28 TC 15 Z9 15 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2006 VL 43 IS 11 BP 887 EP 892 DI 10.1136/jmg.2006.043380 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 101YW UT WOS:000241778500009 PM 16763011 ER PT J AU Murphy, E Eisner, DA AF Murphy, Elizabeth Eisner, David A. TI How does endothelin-1 cause a sustained increase in intracellular sodium and calcium which lead to hypertrophy? SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID NA+/H+ EXCHANGE; HEART-FAILURE; MYOCARDIAL-INFARCTION; CARDIAC-HYPERTROPHY; GROWTH-FACTORS; INHIBITION; KINASE; FIBROBLASTS; MECHANISM; AMILORIDE C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27707 USA. Univ Manchester, Unit Cardiac Physiol, Core Technol Facil 3 18, Manchester M13 9NT, Lancs, England. RP Murphy, E (reprint author), NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27707 USA. EM murphy1@niehs.nih.gov OI Eisner, David/0000-0002-7002-3748 NR 22 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 2006 VL 41 IS 5 BP 782 EP 784 DI 10.1016/j.yjmcc.2006.08.003 PG 3 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 111EW UT WOS:000242435200005 PM 17027026 ER PT J AU Sigman, L Sanchez, VM Turjanski, AG AF Sigman, Lucas Sanchez, Veronica Muriel Turjanski, Adrian Gustavo TI Characterization of the farnesyl pyrophosphate synthase of Trypanosoma cruzi by homology modeling and molecular dynamics SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE Chagas' disease; homology modeling; molecular dynamics; bisphosphonates; farnesyl pyrophosphate synthase ID NITROGEN-CONTAINING BISPHOSPHONATES; DIPHOSPHATE SYNTHASE; POTENT INHIBITORS; CHAGAS-DISEASE; SWISS-MODEL; IN-VITRO; ISOPRENOID BIOSYNTHESIS; BONE-RESORPTION; FATTY-ACIDS; VIVO AB Chagas' disease, caused by the Topanosoma cruzi parasite, is one of the largest public health problems in the Western hemisphere, with 16-18 million people infected, and approximately 100 million people at risk. Many efforts towards the development of targeted antiparasitic agents have recently been described. Of interest, bisphosphonates, pyrophosphate analogs in which the oxygen bridge between the two phosphorus atoms has been replaced by a carbon substituted with different side chains, are able to inhibit the growth of T cruzi. The enzyme T cruzi farnesyl pyrophosphate synthase (TcFPPS) involved in the mevalonate pathway, has been recently identified as the target of bisphosphonates. The protein has 362 amino acids and a molecular mass of 41.2 kDa. Several sequence motifs found in other FPPSs are present in TcFPPS. In this study we have modeled the structure of TcFPPS based on the structure of the avian FPPS. We have characterized the interaction with its substrates, isopentyl pyrophosphate and dimethylallyl pyrophosphate, and the mechanism of inhibition by the potent bisphosphonate risedronate (K-i of 0.032 +/- 0.002 mu M) by means of molecular dynamics techniques. We propose that homorisedronate, which has an extra methylene and a K-i of 8.17 +/- 1.36 mu M, does not form strong hydrogen bonds with TYR 211 and THR 208, which may be responsible for its lower activity as compared to risedronate. Moreover, we were able to reproduce the structural changes that occur upon the binding of the third Mg2+ to the active site of the protein. Taken together, our results provide a structural model for the design of novel inhibitors that may prove useful for the treatment of Chagas' disease. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Inorgan Analit & Quim Fis,INQUIMAE, CONICET, RA-1428 Buenos Aires, DF, Argentina. RP Turjanski, AG (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. EM adrian@qi.fcen.uba.ar NR 36 TC 7 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD NOV PY 2006 VL 25 IS 3 BP 345 EP 352 DI 10.1016/j.jmgm.2006.02.001 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 114WR UT WOS:000242696800009 PM 16540358 ER PT J AU Claus, M Neumann, S Kleinau, G Krause, G Paschke, R AF Claus, Maren Neumann, Susanne Kleinau, Gunnar Krause, Gerd Paschke, Ralf TI Structural determinants for G-protein activation and specificity in the third intracellular loop of the thyroid-stimulating hormone receptor SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE G-protein coupled receptors; G protein; thyroid; site-directed mutagenesis; intracellular loops ID HUMAN THYROTROPIN RECEPTOR; 3RD INTRACELLULAR LOOP; COUPLED RECEPTORS; MUSCARINIC RECEPTOR; CYTOPLASMIC LOOP; ALPHA-SUBUNIT; TSH-RECEPTOR; LUTROPIN/CHORIOGONADOTROPIN RECEPTOR; CONSTITUTIVE ACTIVATION; GONADOTROPIN RECEPTORS AB The selectivity of G-protein recognition is determined by the intracellular loops (ICLs) of seven-transmembrane-spanning receptors. In a previous study, we have shown that the N-terminal and central portions of ICL2 from F525 to D530 participate in dual G(alpha s)-/G(alpha q)-protein activation by the thyroid-stimulating hormone receptor (TSHR). ICL3 is another major determinant for G-protein activation. Therefore, the aim of our study was to identify important amino acids within ICL3 of the TSHR to gain insight in more detail about its specific function for G(alpha s)-and G(alpha q)-protein activation and selectivity. Single-alanine substitutions of residues in the N-terminal, middle, and C-terminal region of ICL3 were generated. N-terminal residues Y605 and V608 and C-terminal positions K618, K621, and I622 were identified as selectively important for Gaq activation, whereas mutations in the center of ICL3 had no effect on TSHR signaling. Our findings provide evidence for an amino acid pattern in the N-and C-terminal part of ICL3, which is involved in G(alpha q)-mediated signaling. Furthermore, molecular modeling of interaction of TSHR. C1 Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. NIDDK, NIH, CEB, Bethesda, MD 20892 USA. Forschungsinst Mol Pharmakol, D-13125 Berlin, Germany. RP Paschke, R (reprint author), Univ Leipzig, Dept Med 3, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. EM pasr@medizin.uni-leipzig.de OI Claus, Maren/0000-0001-8732-0645 FU Intramural NIH HHS NR 59 TC 24 Z9 27 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD NOV PY 2006 VL 84 IS 11 BP 943 EP 954 DI 10.1007/s00109-006-0087-8 PG 12 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 099JD UT WOS:000241589100007 PM 16955277 ER PT J AU Bian, XW Wang, QL Xiao, HL Wang, JM AF Bian, Xiu-Wu Wang, Qing-Liang Xiao, Hua-Liang Wang, Ji Ming TI Tumor microvascular architecture phenotype (T-MAP) as a new concept for studies of angiogenesis and oncology SO JOURNAL OF NEURO-ONCOLOGY LA English DT Letter DE glioma; angiogenesis; tumor microvascular architecture phenotype (T-MAP); heterogeneity ID ENDOTHELIAL-CELLS; HETEROGENEITY AB Heterogeneities exist in endothelial cells and microvascular architecture during tumor angiogenesis. We found significantly variable expression profiles of EC markers, including ephrinB2 and its receptor EphB4, and various types of the architecture. We propose a new concept of tumor microvascular architecture phenotype (T-MAP), reflecting the density, morphology, structure and the three-dimensional distribution of newly formed vessels. The pattern of T-MAP may represent the invasiveness of the tumor therefore predict the outcome of therapy. The presence of T-MAP heterogeneity (T-MAPH) may be utilized as additional diagnostic criteria and for therapeutic designs for antiangiogenesis. C1 Mil Med Univ 3, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Bian, XW (reprint author), Mil Med Univ 3, Inst Pathol, Southwest Hosp, Gaotanyan 30, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 7 TC 11 Z9 18 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD NOV PY 2006 VL 80 IS 2 BP 211 EP 213 DI 10.1007/s11060-006-9167-4 PG 3 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 098LL UT WOS:000241521900016 PM 16708278 ER PT J AU Bruening, S Oh, E Hetzenauer, A Escobar-Alvarez, S Westphalen, RI Hemmings, HC Singewald, N Shippenberg, T Toth, M AF Bruening, S. Oh, E. Hetzenauer, A. Escobar-Alvarez, S. Westphalen, R. I. Hemmings, H. C., Jr. Singewald, N. Shippenberg, T. Toth, M. TI The anxiety-like phenotype of 5-HT1A receptor null mice is associated with genetic background-specific perturbations in the prefrontal cortex GABA-glutamate system SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE anxiety; GABA; genetic modifiers; glutamate; 5-HT1A receptor; prefrontal cortex ID PROBE BURYING TESTS; ELEVATED-PLUS-MAZE; PANIC DISORDER; RAT-BRAIN; SEROTONIN(1A) RECEPTOR; NERVOUS-SYSTEM; FOS EXPRESSION; MODIFIER GENES; BINDING; MICRODIALYSIS AB A deficit in the serotonin 5-HT1A receptor has been found in panic and post-traumatic stress disorders, and genetic inactivation of the receptor results in an anxiety-like phenotype in mice on both the C57Bl6 and Swiss-Webster genetic backgrounds. Anxiety is associated with increased neuronal activity in the prefrontal cortex and here we describe changes in glutamate and GABA uptake of C57Bl6 receptor null mice. Although these alterations were not present in Swiss-Webster null mice, we have previously reported reductions in GABA(A) receptor expression in these but not in C57Bl6 null mice. This demonstrates that inactivation of the 5-HT1A receptor elicits different and genetic background-dependent perturbations in the prefrontal cortex GABA/glutamate system. These perturbations can result in a change in the balance between excitation and inhibition, and indeed both C57Bl6 and Swiss-Webster null mice show signs of increased neuronal excitability. Because neuronal activity in the prefrontal cortex controls the extent of response to anxiogenic stimuli, the genetic background-specific perturbations in glutamate and GABA neurotransmission in C57Bl6 and Swiss-Webster 5-HT1A receptor null mice may contribute to their shared anxiety phenotype. Our study shows that multiple strains of genetically altered mice could help us to understand the common and individual features of anxiety. C1 Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Anesthesiol, New York, NY 10021 USA. NIDA, Integrat Neurosci Unit, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD USA. Univ Innsbruck, Dept Pharmacol & Toxicol, A-6020 Innsbruck, Austria. RP Toth, M (reprint author), Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. EM mtoth@med.cornell.edu OI Escobar Alvarez, Sindy/0000-0002-8294-5918 FU NIMH NIH HHS [MH-58669] NR 40 TC 19 Z9 19 U1 0 U2 1 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 NOV PY 2006 VL 99 IS 3 BP 892 EP 899 DI 10.1111/j.1471-4159.2006.04129.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 095YV UT WOS:000241345100020 PM 16925594 ER PT J AU Lu, CY Fu, ZY Karavanov, I Yasuda, RP Wolfe, BB Buonanno, A Vicini, S AF Lu, Congyi Fu, Zhanyan Karavanov, Irina Yasuda, Robert P. Wolfe, Barry B. Buonanno, Andres Vicini, Stefano TI NMDA receptor subtypes at autaptic synapses of cerebellar granule neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID METHYL-D-ASPARTATE; RAT-BRAIN; HIPPOCAMPAL-NEURONS; SUBUNIT EXPRESSION; SILENT SYNAPSES; SINGLE-CHANNEL; NR2 SUBUNITS; CURRENTS; MODULATION; MATURATION AB We studied the action potential-evoked autaptic N-methyl-D-aspartate receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) using solitary cerebellar neurons cultured in microislands from wild-type (+/+), NR2A subunit knockout (NR2A-/-), and NR2C subunit knockout (NR2C-/-) mice. The peak amplitude of autaptic NMDA-EPSCs increased for all genotypes between days in vitro 8 (DIV8) and DIV13. Compared with +/+ cells at DIV13, NR2A-/- cells had smaller and NR2C-/- cells had larger NMDA-EPSCs. The decay time of these currents were all unexpectedly fast, except in NR2A-/- neurons, and showed small but significant shortening with development. Comparison of quantal parameters during development indicated an increase in quantal content in all genotypes. The synaptic portion of NMDA receptors measured using MK-801 blockade was roughly 50% in all genotypes at DIV8, and this percentage became slightly larger in NR2A-/- and NR2C-/- neurons at DIV12. The NR2B-selective antagonists Conantokin G and CP101,606 differed in their blocking actions with development, suggesting the presence of both heterodimeric NR1/NR2B and heterotrimeric NR1/NR2A/NR2B receptors. The most striking result we obtained was the significant increase of NMDA-EPSC peak amplitude and charge transfer in NR2C-/- mice. This was mainly the result of an increase in quantal size as estimated from miniature NMDA-EPSCs. The expression of NR2C subunit containing receptors was supported by the decreased Mg2+ sensitivity of NMDA receptors at DIV13 in +/+ but not in NR2C-/- cells. Thus solitary cerebellar granule neurons provide a novel model to investigate the role of receptor subtypes in the developmental changes of synaptic NMDA receptors. C1 Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Vicini, S (reprint author), Georgetown Univ, Sch Med, Dept Physiol & Biophys, BSB225,3900 Reservoir Rd, Washington, DC 20007 USA. EM svicin01@georgetown.edu RI Lu, Congyi/G-3984-2013 FU NINDS NIH HHS [NS-047700] NR 47 TC 23 Z9 24 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2006 VL 96 IS 5 BP 2282 EP 2294 DI 10.1152/jn.00078.2006 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 095SP UT WOS:000241328900013 PM 16885526 ER PT J AU Yang, Q Sumner, AD Puhl, HL Ruiz-Velasco, V AF Yang, Qing Sumner, Andrew D. Puhl, Henry L. Ruiz-Velasco, Victor TI M-1 and M-2 muscarinic acetylcholine receptor subtypes mediate Ca2+ channel current inhibition in rat sympathetic stellate ganglion neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MAMBA DENDROASPIS-ANGUSTICEPS; PROTEIN-COUPLED RECEPTORS; NORADRENALINE RELEASE; CALCIUM-CHANNELS; N-TYPE; KNOCKOUT MICE; INTRACARDIAC NEURONS; CARDIAC-MUSCLE; P-TYPE; MODULATION AB Muscarinic acetylcholine receptors (mAChRs) are known to mediate the acetylcholine inhibition of Ca2(+) channels in central and peripheral neurons. Stellate ganglion (SG) neurons provide the main sympathetic input to the heart and contribute to the regulation of heart rate and myocardial contractility. Little information is available regarding mAChR regulation of Ca2(+) channels in SG neurons. The purpose of this study was to identify the mAChR subtypes that modulate Ca2+ channel currents in rat SG neurons innervating heart muscle. Accordingly, the modulation of Ca2+ channel currents by the muscarinic cholinergic agonist, oxotremorine-methiodide (Oxo-M), and mAChR blockers was examined. Oxo-M-mediated mAChR stimulation led to inhibition of Ca2+ currents through voltage-dependent (VD) and voltage-independent (VI) pathways. Pre-exposure of SG neurons to the M-1 receptor blocker, M-1-toxin, resulted in VD inhibition of Ca2+ currents after Oxo-M application. On the other hand, VI modulation of Ca2+ currents was observed after pretreatment of cells with methoctramine (M-2 mAChR blocker). The Oxo-M-mediated inhibition was nearly eliminated in the presence of both M-1 and M-2 mAChR blockers but was unaltered when SG neurons were exposed to the M-4 mAChR toxin, M-4-toxin. Finally, the results from single-cell RT-PCR and immunofluorescence assays indicated that M-1 and M-2 receptors are expressed and located on the surface of SG neurons. Overall, the results indicate that SG neurons that innervate cardiac muscle express M-1 and M-2 mAChR, and activation of these receptors leads to inhibition of Ca2+ channel currents through VI and VD pathways, respectively. C1 Penn State Univ, Coll Med, Dept Anesthesiol, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Med, Hershey, PA 17033 USA. NIAAA, Lab Mol Physiol, Bethesda, MD USA. RP Ruiz-Velasco, V (reprint author), Penn State Univ, Coll Med, Dept Anesthesiol, H187,500 Univ Dr, Hershey, PA 17033 USA. EM vruizvelasco@psu.edu OI Puhl, Henry/0000-0003-3095-7201 FU NHLBI NIH HHS [HL-074311] NR 38 TC 10 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2006 VL 96 IS 5 BP 2479 EP 2487 DI 10.1152/jn.00093.2006 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 095SP UT WOS:000241328900029 PM 17005606 ER PT J AU Marks, CA Cheng, K Cummings, DM Belluscio, L AF Marks, Carolyn A. Cheng, Kai Cummings, Diana M. Belluscio, Leonardo TI Activity-dependent plasticity in the olfactory intrabulbar map SO JOURNAL OF NEUROSCIENCE LA English DT Article DE external tufted cell; olfactory bulb; development; neural tracer; axon targeting; mouse ID PRIMARY AUDITORY-CORTEX; GATED CHANNEL SUBUNIT; TOPOGRAPHIC ORGANIZATION; ODORANT REPRESENTATIONS; ASSOCIATIONAL SYSTEM; CORTICAL CIRCUITS; TRANSGENIC MICE; BULB; PROJECTIONS; EXPRESSION AB In mammals, each olfactory bulb contains two mirror-symmetric glomerular maps. Isofunctional glomeruli within each bulb are specifically linked through a set of reciprocal intrabulbar projections (IBPs) to form an intrabulbar map. We injected neural tracers into the glomerular layer on one side of the bulb and examined the resulting projection on the opposite side. In adult mice, the size of the projection tuft is directly proportional to the size of the injected region. Using this ratio as a measure of IBP maturity, we find an immature 5: 1 projection to injection ratio at 1 week of age that gradually refines to a mature 1: 1 by 7 weeks. Moreover, whereas the glomerular map is able to form despite the elimination of odorant-induced activity, the intrabulbar map shows clear activity dependence for its precise formation. Here we show through experiments with both naris-occluded and anosmic mice that odorant-induced activity is not required to establish IBPs but is crucial for projection refinement. In contrast, increased glomerular activation through exposure to distinct odorants during map development can accelerate the refinement of projections associated with the activated glomeruli. These findings illustrate a clear role for odorant-induced activity in shaping the internal circuitry of the bulb. Interestingly, activity deprivation can alter the organization of both the developing and the mature map to the same degree, demonstrating that intrabulbar map plasticity is maintained into adulthood with no discernible critical period. C1 NINDS, Dev Neural Plast Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Belluscio, L (reprint author), NINDS, Dev Neural Plast Unit, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 3A-116,35 Covent Dr,MSC 3703, Bethesda, MD 20892 USA. EM belluscl@ninds.nih.gov FU Intramural NIH HHS NR 42 TC 29 Z9 29 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2006 VL 26 IS 44 BP 11257 EP 11266 DI 10.1523/JNEUROSCI.2805-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 101GF UT WOS:000241727500004 PM 17079653 ER PT J AU Cavanaugh, J Alvarez, BD Wurtz, RH AF Cavanaugh, James Alvarez, Bryan D. Wurtz, Robert H. TI Enhanced performance with brain stimulation: Attentional shift or visual cue? SO JOURNAL OF NEUROSCIENCE LA English DT Article DE colliculus; attention; visual; phosphene; macaque; stimulation ID MONKEY SUPERIOR COLLICULUS; SACCADIC EYE-MOVEMENTS; ELECTRICAL-STIMULATION; STRIATE CORTEX; CORTICAL PROJECTIONS; SPATIAL ATTENTION; GUIDED SACCADES; MACACA-MULATTA; MACAQUE MONKEY; MICROSTIMULATION AB The premotor theory of visual spatial attention proposes that the same brain activity that prepares for saccades to one part of the visual field also facilitates visual processing at that same region of the visual field. Strong support comes from improvements in performance by electrical stimulation of presaccadic areas, including the frontal eye field and superior colliculus (SC). Interpretations of these stimulation experiments are hampered by the possibility that stimulation might be producing an internal visual flash or phosphene that attracts attention as a real flash would. We tested this phosphene hypothesis in the SC by comparing the effect of interchanging real visual stimuli and electrical stimulation. We first presented a veridical visual cue at the time SC stimulation improved performance; if a phosphene improved performance at this time, a real cue should do so in the same manner, but it did not. We then changed the time of SC visual-motor stimulation to when we ordinarily presented the veridical visual cue, and failed to improve performance. Last, we shifted the site of SC stimulation from the visual-motor neurons of the SC intermediate layers to the visual neurons of the superficial layers to determine whether stimulating visual neurons produced a larger improvement in performance, but it did not. Our experiments provide evidence that a phosphene is not responsible for the shift of attention that follows SC stimulation. This added evidence of a direct shift of attention is consistent with a key role of the SC in the premotor theory of attention. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20982 USA. RP Cavanaugh, J (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Covent Dr, Bethesda, MD 20982 USA. EM jrc@lsr.nei.nih.gov FU Intramural NIH HHS NR 36 TC 33 Z9 33 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2006 VL 26 IS 44 BP 11347 EP 11358 DI 10.1523/JNEUROSCI.2376-06.2006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 101GF UT WOS:000241727500014 PM 17079663 ER PT J AU Blair, K Marsh, AA Morton, J Vythilingam, M Jones, M Mondillo, K Pine, DC Drevets, WC Blair, JR AF Blair, Karina Marsh, Abigail A. Morton, John Vythilingam, Meena Jones, Matthew Mondillo, Krystal Pine, Daniel C. Drevets, Wayne C. Blair, James R. TI Choosing the lesser of two evils, the better of two goods: specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE decision; fMRI; reward; punishment; vmPFC; ACd ID HUMAN ORBITOFRONTAL CORTEX; DECISION-MAKING; EXPECTED OUTCOMES; FRONTAL-CORTEX; REWARD; CONFLICT; BEHAVIOR; REPRESENTATIONS; RESPONSES; AMYGDALA AB The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e. g., choosing between mousse au chocolat or creme caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning. C1 NIMH, Mood & Anxiety Disorders Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. UCL, Inst Cognit Neurosci, London WC1X 8EE, England. RP Blair, K (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, US Dept HHS, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM blairka@mail.nih.gov FU Intramural NIH HHS NR 32 TC 92 Z9 92 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2006 VL 26 IS 44 BP 11379 EP 11386 DI 10.1523/JNEUROSCI.1640-06.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 101GF UT WOS:000241727500017 PM 17079666 ER PT J AU Imamura, K Takeshima, T Kashiwaya, Y Nakaso, K Nakashima, K AF Imamura, Keiko Takeshima, Takao Kashiwaya, Yoshihiro Nakaso, Kazuhiro Nakashima, Kenji TI D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE ketone body; mitochondria; alamarBlue; LDH; caspase ID COMPLEX-I DEFICIENCY; NEURO-BLASTOMA CELLS; FATTY-ACID OXIDATION; KETONE-BODIES; SUCCINATE-DEHYDROGENASE; KETOGENIC DIET; CYTO-TOXICITY; CYTOCHROME-C; ALAMAR BLUE; RAT-LIVER AB It has been postulated that the pathogenesis of Parkinson's disease (PD) is associated with mitochondrial dysfunction. Rotenone, an inhibitor of mitochondrial complex I, provides models of PD both in vivo and in vitro. We investigated the neuroprotective effect of D-beta-hydroxybutyrate (bHB), a ketone body, against rotenone toxicity by using SH-SY5Y dopaminergic neuroblastoma cells. SH-SY5Y cells, differentiated by all-trans-retinoic acid, were exposed to rotenone at concentrations ranging from 0 to 1,000 nM. We evaluated cellular oxidation reduction by the alamarBlue assay, viability by lactate dehydrogenase (LDH) assay, and survival/death ratio by live/dead assays. Exposure to rotenone for 48 hr oxidized cells and decreased their viability and survival rate in a concentration-dependent manner. Pretreatment of cells with 8 mM bHB provided significant protection to SH-SY5Y cells. Whereas rotenone caused the loss of mitochondrial membrane potential, released cytochrome c into the cytosol, and reduced cytochrome c content in mitochondria, addition of bHB blocked this toxic effect. bHB also attenuated the rotenone-induced activation of caspase-9 and caspase-3. Administration of 0-10 mM 3-nitropropionic acid, a complex II inhibitor, also decreased the reducing power of SH-SY5Y cells measured by alamarBlue assay. Pretreatment with 8 mM bHB attenuated the decrease of alamarBlue fluorescence. These data demonstrated that bHB had a neuroprotective effect that supported the mitochondrial respiration system by reversing the inhibition of complex I or II. Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD. (c) 2006 Wiley-Liss, Inc. C1 Tottori Univ, Fac Med, Dept Neurol, Inst Neurol Sci, Yonago, Tottori 6838504, Japan. NIAAA, Lab Metab Control, NIH, Bethesda, MD USA. RP Imamura, K (reprint author), Tottori Univ, Fac Med, Dept Neurol, Inst Neurol Sci, 36-1 Nishicho, Yonago, Tottori 6838504, Japan. EM imamurakeiko@nifty.com NR 41 TC 54 Z9 54 U1 0 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 2006 VL 84 IS 6 BP 1376 EP 1384 DI 10.1002/jnr.21021 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 105AZ UT WOS:000242003000023 PM 16917840 ER PT J AU Le Meunier, L Maass-Moreno, R Carrasquillo, JA Dieckmann, W Bacharach, SL AF Le Meunier, Ludovic Maass-Moreno, Roberto Carrasquillo, Jorge A. Dieckmann, William Bacharach, Stephen L. TI PET/CT imaging: Effect of respiratory motion on apparent myocardial uptake SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE PET/CT imaging; fluorine-18; attenuation and scatter correction; image artefacts ID CT ATTENUATION CORRECTION; IMAGES; REGISTRATION; QUANTITATION; ARTIFACTS; ONCOLOGY; SCANNER; THORAX AB Background. Positron emission tomography (PET) attenuation correction (AC) using computed tomography (CT) can be affected by respiratory motion: hi-speed CT captures I point of the respiratory cycle while PET emission data averages many cycles. We quantified the changes in apparent myocardial uptake due to this respiratory-induced CT attenuation mismatch. Methods. Twenty-two patients undergoing fluorine-18 fluorodexyglucose (FDG) PET/CT received 3 sequential CT scans at normal resting end-inspiration (CTINSPIR), ending expiration (CTEXPIR), and at midvolume between end-expiration and end-inspiration (CTMIDVOL), A pneumotachometer measured absolute changes in lung volume. Seven subjects also underwent a 3-minute transmission scan with a Ge-68 rotating rod source (RRS). The PET emission data set was reconstructed up to 4 times using CTEXPIR, CTINSPIR, CTMIDVOL, and RRS AC maps. Relative heart position and cardiac uptake was measured for each CT attenuation correction. Results. Respiratory motion produced marked changes in global and regional myocardial uptake. Changes were large in the lateral and anterior regions at the lung-soft tissue interface (up to 30% using CTINSPIR compared to CTEXPIR for AC) and smaller in the septal region (10% or less). Data corrected with CTEXPIR agreed best with the RRS. Conclusion. Respiratory effects can introduce large inhomogeneities in apparent myocardial uptake when CT is used for attenuation correction. C1 NIH, Dept Nucl Med, Bethesda, MD USA. RP Bacharach, SL (reprint author), Univ Calif San Francisco, 185 Berry st,Suite 350, San Francisco, CA 94107 USA. EM steve.bacharach@radiology.ucsf.edu RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 FU CLC NIH HHS [Z01 CL000416-07] NR 17 TC 43 Z9 44 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD NOV-DEC PY 2006 VL 13 IS 6 BP 821 EP 830 DI 10.1016/j.nuclcard.2006.09.003 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 120MW UT WOS:000243090000013 PM 17174813 ER PT J AU Mello, MA Tuan, RS AF Mello, Maria A. Tuan, Rocky S. TI Effects of TGF-beta 1 and triiodothyronine on cartilage maturation: In vitro analysis using long-term high-density micromass cultures of chick embryonic limb mesenchymal cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE apoptosis; hypertrophy; collagen type X ID GROWTH-PLATE; CHONDROCYTE DIFFERENTIATION; DNA FRAGMENTATION; CALCIUM DEFICIENCY; FEMORAL EPIPHYSIS; THYROID-HORMONES; EXPRESSION; RECEPTOR; CALCIFICATION; APOPTOSIS AB Endochondral ossification is initiated by differentiation of mesenchymal cells into chondrocytes, which produce a cartilaginous matrix, proliferate, mature, and undergo hypertrophy, followed by matrix calcification, and substitution of cartilage by bone. A number of hormones and growth factors have been implicated in this process. Using in vitro, long-term, high-density, micromass cultures of chick embryonic mesenchyme, that recapitulate the process of chondrogenesis, chondrocyte maturation, and hypertrophy, we have investigated the importance of a balance between proliferation and apoptosis in cartilage maturation, focusing specifically on the effects of transforming growth factor-beta 1 (TGF-P1) and the thyroid hormone, triiodothyronine (T3). Our results showed that TGF-P1 stimulates proliferation, by week 2 of culture, and T3 inhibits proliferation by week 3. Cell size increases in cultures treated with T3. Collagen type X is expressed in all culture, and delay in matrix deposition is seen only in the cultures treated with TGF-beta 1. T3 stimulates alkaline phosphatase activity, but not calcification. T3 enhances apoptosis, as seen by TUNEL staining, and internucleosomal DNA fragmentation. The results support the roles of T3 and TGF-beta in cartilage maturation, i.e., TGF-beta 1 stimulates proliferation and suppresses hypertrophy, while T3 stimulates hypertrophy and apoptosis. (c) 2006 Orthopaedic Research Society. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1523,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS NR 42 TC 44 Z9 46 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD NOV PY 2006 VL 24 IS 11 BP 2095 EP 2105 DI 10.1002/jor.20233 PG 11 WC Orthopedics SC Orthopedics GA 099DV UT WOS:000241573600009 PM 16955422 ER PT J AU Vortmeyer, AO Tran, MGB Zeng, W Glasker, S Riley, C Tsokos, M Ikejiri, B Merrill, MJ Raffeld, M Zhuang, Z Lonser, RR Maxwell, PH Oldfield, EH AF Vortmeyer, A. O. Tran, M. G. B. Zeng, W. Glasker, S. Riley, C. Tsokos, M. Ikejiri, B. Merrill, M. J. Raffeld, M. Zhuang, Z. Lonser, R. R. Maxwell, P. H. Oldfield, E. H. TI Evolution of VHL tumourigenesis in nerve root tissue SO JOURNAL OF PATHOLOGY LA English DT Article DE VHL disease; nerve root; haemangioblastoma; hypoxia-inducible factor; VEGF ID ENDOTHELIAL GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE; VASCULAR-PERMEABILITY FACTOR; TUMOR-SUPPRESSOR GENE; UP-REGULATION; HEMANGIOBLASTOMA; DEFICIENCY; EXPRESSION; BRAIN; CELLS AB Haemangioblastomas are the key central nervous system manifestation of von Hippel-Lindau (VHL) disease, which is caused by germline mutation of the VHL gene. We have recently shown that 'tumour-free' spinal cord from patients with VHL disease contains microscopic, poorly differentiated cellular aggregates in nerve root tissue, which we descriptively designated 'mesenchymal tumourlets'. Here we have investigated spinal cord tissue affected by multiple tumours. We show that a small subset of mesenchymal tumourlets extends beyond the nerve root to form proliferative VHL-deficient mesenchyme and frank haemangioblastoma. We thus demonstrate that tumourlets present potential, but true precursor material for haemangioblastoma. We further show that intraradicular tumourlets consist of scattered VHL-deficient cells with activation of HIF-2 alpha and HIF-dependent target proteins including CAIX and VEGF, and are associated with an extensive angiogenic response. In contrast, activation of HIF-1 alpha was only observed in the later stages of tumour progression. In addition, ultrastructural examination reveals gradual transition from poorly differentiated VHL-deficient cells into vacuolated cells with a 'stromal' cell phenotype. The evolution of frank haemangioblastoma seems to involve multiple steps from a large pool of precursor lesions. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John C1 NINDS, Surg Neurol Branch, NIH, Rockville, MD 20852 USA. Univ London Imperial Coll Sci Technol & Med, Renal Sect, London W12 0NN, England. NCI, Pathol Lab, Ultrastruct Pathol Sect, Bethesda, MD 20892 USA. NCI, Pathol Lab, Mol Pathol Sect, Bethesda, MD 20892 USA. RP Vortmeyer, AO (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,10 Ctr Dr, Rockville, MD 20852 USA. EM vortmeyera@ninds.nih.gov RI Maxwell, Patrick/C-5557-2008 OI Maxwell, Patrick/0000-0002-0338-2679 FU Intramural NIH HHS NR 30 TC 25 Z9 25 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD NOV PY 2006 VL 210 IS 3 BP 374 EP 382 DI 10.1002/path.2062 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 101PM UT WOS:000241752700014 PM 16981244 ER PT J AU Merke, DP Stratakis, CA AF Merke, Deborah P. Stratakis, Constantine A. TI The adrenal life cycle: The fetal and adult cortex and the remaining questions (see paper by Heckmann et al. on p. 1303) SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE adrenal development; fetal cortex; zona reticularis; DHEAS ID ANDROGENS; ZONE C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Pediat Endocrinol Inter Inst Training Program, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), NIH, Ctr Clin, Bldg 10,CRC,Room 1-2740 10 Ctr Dr MSC 1932, Bethesda, MD 20892 USA. EM dmerke@nih.gov NR 14 TC 2 Z9 2 U1 0 U2 1 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV PY 2006 VL 19 IS 11 BP 1299 EP 1302 PG 4 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 124LN UT WOS:000243369400003 PM 17220057 ER PT J AU Fleisch, AF Ning, C Yanovski, JA AF Fleisch, Abby F. Ning, Cong Yanovski, Jack A. TI Osler-Weber-Rendu syndrome as a cause of poor growth during adolescence SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE pulmonary arteriovenous malformation; hereditary hemorrhagic telangiectasia; Osler-Weber-Rendu syndrome; constitutional delay of growth and development; chronic disease; weight loss ID CONGENITAL HEART-DISEASE; INFANTS; ENERGY; BALANCE AB We report an adolescent boy with poor growth and delayed skeletal age who was found to have pulmonary arteriovenous malformations (PAVMs) consistent with hereditary hemorrhagic telangiectasia (Osier-Weber-Rendu syndrome). While a host of chronic diseases, including a number of cardiopulmonary diseases, have previously been associated with poor growth or short stature, to our knowledge this is the first documented case of PAVM presenting with poor growth, manifesting as weight loss and delayed adolescence. This case highlights the importance of a thorough physical examination for identifying rare, occult, chronic diseases in patients who present with poor growth. C1 NICHD, Unit Growth & Obes, DEB, NIH,CRC, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHD, Unit Growth & Obes, DEB, NIH,CRC, Room 1-3330 10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [Z01-HD-00641] NR 13 TC 0 Z9 0 U1 0 U2 1 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV PY 2006 VL 19 IS 11 BP 1367 EP 1370 PG 4 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 124LN UT WOS:000243369400013 PM 17220067 ER PT J AU Chiou, CC Seibel, NL Derito, FA Bulas, D Walsh, TJ Groll, AH AF Chiou, Christine C. Seibel, Nita L. Derito, Francis A. Bulas, Dorothy Walsh, Thomas J. Groll, Andreas H. TI Concomitant Candida epiglottitis and disseminated Varicella zoster virus infection associated with acute lymphoblastic leukemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE Candida; Varicella; epiglottitis; children; cancer ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; LARYNGEAL CANDIDIASIS; IMMUNOCOMPROMISED PATIENTS; LARYNGITIS; STRIDOR; ESOPHAGITIS; ADULT; CHILD AB Acute epiglottitis by nonbacterial pathogens is an uncommon but life-threatening clinical entity. Herein, we report the concomitant occurrence of Candida epiglottitis and mucosal and visceral Varicella zoster virus infection in a child with acute lymphoblastic leukemia. Both infections were atypical in their presentation, occurred in a severely immunocompromised host, and required invasive procedures for diagnosis. C1 Univ Munster, Childrens Hosp, Dept Pediat Hematol Oncol, D-48129 Munster, Germany. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Otolaryngol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Radiol, Washington, DC 20010 USA. RP Groll, AH (reprint author), Univ Munster, Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Albert Schweitzer Str 33, D-48129 Munster, Germany. EM grollan@ukmuenster.de NR 23 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV PY 2006 VL 28 IS 11 BP 757 EP 759 DI 10.1097/01.mph.0000243654.18314.c1 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 112DO UT WOS:000242505800011 PM 17114965 ER PT J AU Gaedigk, A Baker, DW Totah, RA Gaedigk, R Pearce, RE Vyhlidal, CA Zeldin, DC Leeder, JS AF Gaedigk, Andrea Baker, Darren W. Totah, Rheem A. Gaedigk, Roger Pearce, Robin E. Vyhlidal, Carrie A. Zeldin, Darryl C. Leeder, J. Steven TI Variability of CYP2J2 expression in human fetal tissues SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INFORMATION-THEORY; ESCHERICHIA-COLI; ARACHIDONIC-ACID; IDENTIFICATION; INVOLVEMENT; METABOLISM; MUTATIONS; VARIANTS; CLONING; LIVER AB CYP2J2 metabolizes arachidonic acid to 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids (EETs), which play a critical role in the regulation of renal, pulmonary, cardiac, and vascular function. However, the contribution of CYP2J2 to EET formation in the liver remains poorly characterized. Likewise, information is sparse regarding the extent and variability of CYP2J2 expression during human development. This investigation was undertaken to characterize the variability of CYP2J2 expression in fetal liver, heart, kidney, lung, intestine, and brain and in postnatal liver samples. CYP2J2 mRNA expression was measured using quantitative polymerase chain reaction, and immunoreactive CYP2J2 was examined using two anti-CYP2J2 antibodies. CYP2J2 mRNA was ubiquitously expressed in pre-and postnatal samples. Fetal hepatic mRNA expression varied 127-fold (1351 +/- 717 transcripts/ng total RNA), but this variation was reduced to 8-fold after exclusion of four samples with extremely low levels of mRNA. Amounts of immunoreactive protein also varied substantially among samples without an apparent relationship with transcript number or genotype. Western blot analysis revealed a different protein pattern between prenatal and postnatal liver samples. DNA resequencing of selected subjects identified a single novel single-nucleotide polymorphism (CYP2J2*10), which was found in only one subject and therefore did not explain the large variability in CYP2J2 protein content. In vitro expression suggests that the protein product of CYP2J2*10 confers reduced enzymatic activity. Aberrant splicing produces three minor transcripts, which were present in all samples tested. Due to premature termination codons, none encodes functional protein. The mechanisms leading to variable amounts of immunoreactive protein and distinct pre- and postnatal CYP2J2 protein patterns warrant further investigation. C1 Childrens Mercy Hosp & Clin, Div Clin Pharmacol & Expt Therapeut, Kansas City, MO USA. Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. RP Gaedigk, A (reprint author), Childrens Mercy Hosp, Div Clin Pharmacol, 2401 Gillham Rd, Kansas City, MO 64108 USA. EM agaedigk@cmh.edu FU Intramural NIH HHS; NIEHS NIH HHS [R01 ES010855, R01 ES10855-05] NR 26 TC 30 Z9 32 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2006 VL 319 IS 2 BP 523 EP 532 DI 10.1124/jpet.106.109215 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096UY UT WOS:000241403500003 PM 16868033 ER PT J AU Yang, SF Yang, J Yang, ZQ Chen, P Fraser, A Zhang, W Pang, H Gao, X Wilson, B Hong, JS Block, ML AF Yang, Sufen Yang, Jun Yang, Zhengqin Chen, Posee Fraser, Alison Zhang, Wei Pang, Hao Gao, Xi Wilson, Belinda Hong, Jau-Shyong Block, Michelle L. TI Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 and PACAP4-6 are neuroprotective through inhibition of NADPH oxidase: Potent regulators of microglia-mediated oxidative stress SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; VASOACTIVE-INTESTINAL-PEPTIDE; MESENCEPHALIC DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; FEMTOMOLAR CONCENTRATIONS; INFLAMMATORY DAMAGE; REACTIVE MICROGLIA; SUBSTANTIA-NIGRA; RAT; RECEPTORS AB Microglial activation is implicated in the progressive nature of numerous neurodegenerative diseases, including Parkinson's disease. Using primary rat mesencephalic neuron-glia cultures, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) 38, PACAP27, and its internal peptide, Gly-IlePhe (GIF;PACAP4-6), are neuroprotective at 10(-13) M against lipopolysaccharide (LPS)-induced dopaminergic (DA) neurotoxicity, as determined by [H-3]DA uptake and the number of tyrosine hydroxylase-immunoreactive neurons. PACAP38 and GIF also protected against 1-methyl-4-phenylpyridinium (+) -induced neurotoxicity but only in cultures containing microglia. PACAP38 and GIF ameliorated the production of microgliaderived reactive oxygen species (ROS), where both LPS- and phorbol 12-myristate 13-acetate-induced superoxide and intracellular ROS were inhibited. The critical role of NADPH oxidase for GIF and PACAP38 neuroprotection against LPS-induced DA neurotoxicity was demonstrated using neuron-glia cultures from mice deficient in NADPH oxidase (PHOX-/-), where PACAP38 and GIF reduced tumor necrosis factor alpha production and were neuroprotective only in PHOX+/+ cultures and not in PHOX-/- cultures. Pretreatment with PACAP6-38 (3 mu M; PACAP-specific receptor antagonist) was unable to attenuate PACAP38, PACAP27, or GIF (10(-13) M) neuroprotection. PACAP38 and GIF (10(-13) M) failed to induce cAMP in neuronglia cultures, supporting that the neuroprotective effect was independent of traditional high-affinity PACAP receptors. Pharmacophore analysis revealed that GIF shares common chemical properties (hydrogen bond acceptor, positive ionizable, and hydrophobic regions) with other subpicomolar-acting compounds known to inhibit NADPH oxidase: naloxone, dextromethorphan, and Gly-Gly-Phe. These results indicate a common high-affinity site of action across numerous diverse peptides and compounds, revealing a basic neuropeptide regulatory mechanism that inhibits microglia-derived oxidative stress and promotes neuron survival. C1 Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Natl Cheng Kung Univ, Coll Med, Dept Psychiat, Tainan 70101, Taiwan. Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 70101, Taiwan. RP Block, ML (reprint author), Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM block@niehs.nih.gov FU Intramural NIH HHS NR 40 TC 43 Z9 45 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 NOV PY 2006 VL 319 IS 2 BP 595 EP 603 DI 10.1124/jpet.106.102236 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096UY UT WOS:000241403500010 PM 16891616 ER PT J AU Mantey, SA Gonzalez, N Schumann, M Pradhan, TK Shen, L Coy, DH Jensen, RT AF Mantey, Samuel A. Gonzalez, Nieves Schumann, Michael Pradhan, Tapas K. Shen, Lin Coy, David H. Jensen, Robert T. TI Identification of bombesin receptor subtype-specific ligands: Effect of N-methyl scanning, truncation, substitution, and evaluation of putative reported selective ligands SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GASTRIN-RELEASING-PEPTIDE; HUMAN ORPHAN RECEPTOR; HIGH-AFFINITY; NEUROMEDIN-B; STRUCTURAL REQUIREMENTS; POTENT; AGONISTS; PHARMACOLOGY; ANTAGONISTS; DESIGN AB Mammalian bombesin (Bn) receptors include the gastrin-releasing peptide receptor, neuromedin B receptor, and bombesin receptor subtype 3 (BRS-3). These receptors are involved in a variety of physiological/pathologic processes, including thermoregulation, secretion, motility, chemotaxis, and mitogenic effects on both normal and malignant cells. Tumors frequently overexpress these receptors, and their presence is now used for imaging and receptor-mediated cytotoxicity. For these reasons, there is an increased need to develop synthetic, selective receptor subtype-specific ligands, especially agonists for these receptors. In this study, we used a number of strategies to identify useful receptor subtype-selective ligands, including synthesizing new analogs (N-methyl-substituted constrained analogs, truncations, and substitutions) in [D-Tyr(6), beta Ala(11), Phe(13), Nle(14)]Bn(6-14), which has high affinity for all Bn receptors and is metabolically stable, as well as completely pharmacologically characterized analogs recently reported to be selective for these receptors in [Ca2+](i) assays. Affinities and potencies of each analog were determined for each human Bn receptor subtype. N-Methyl substitutions in positions 14, 12, 11, 10, 9, and 8 did not result in selective analogs, with the exception of position 11, which markedly decreased affinity/potency. N-Terminal truncations or position 12 substitutions did not increase selectivity as previously reported by others. Of the four shortened analogs of [D-Phe(6), beta Ala(11), Phe(13), Nle(14)]Bn(6-14) reported to be potent selective BRS-3 ligands on [Ca2+](i) assays, only Ac-Phe,Trp,Ala,His(tau Bzl),Nip,Gly,Arg-NH2 had moderate selectivity for hBRS-3; however, it was less selective than previously reported Apa(11) analogs, demonstrating these are still the most selective BRS-3 analogs available. However, both of these analogs should be useful templates to develop more selective BRS-3 ligands. C1 NIDDK, DDB, US Dept HHS, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Med, New Orleans, LA 70118 USA. RP Jensen, RT (reprint author), NIDDK, DDB, US Dept HHS, NIH, Bldg 10,Rm 9C103,31 Ctr Dr, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Schumann, Michael/K-6426-2013 OI Schumann, Michael/0000-0001-6391-9979 FU Intramural NIH HHS NR 41 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2006 VL 319 IS 2 BP 980 EP 989 DI 10.1124/jpet.106.107011 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096UY UT WOS:000241403500054 PM 16943256 ER PT J AU Zhong, Z Connor, HD Li, XL Mason, RP Forman, DT Lemasters, JJ Thurman, RG AF Zhong, Zhi Connor, Henry D. Li, Xiangli Mason, Ronald P. Forman, Donald T. Lemasters, John J. Thurman, Ronald G. TI Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenols SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID GREEN TEA EXTRACT; INDUCED OXIDATIVE STRESS; FREE-RADICAL METABOLITE; BLACK TEA; RAT-KIDNEY; INHIBITION; FK-506; FK506; LIVER; IRON AB The immunosuppressants ciclosporin (cyclosporin A, CsA) and tacrolimus can cause severe nephrotoxicity. Since CsA increases free radical formation, this study investigated whether an extract from Camellia sinensis, which contains several polyphenolic free radical scavengers, could prevent nephrotoxicity caused by CsA and tacrolimus. Rats were fed powdered diet containing polyphenolic extract (0-0.1%) starting 3 days before CsA or tacrolimus. Free radicals were trapped with alpha-(4-pyridyl-1-oxide)-N-tert-butyinitrone (POBN) and measured using an electron spin resonance spectrometer. Both CsA and tacrolimus decreased glomerular filtration rates (GFR) and caused tubular atrophy, vacuolization and calcification and arteriolar hyalinosis, effects that were blunted by treatment with dietary polyphenols. Moreover, CsA and tacrolimus increased POBN/radical adducts in urine nearly 3.5 fold. Hydroxyl radicals attack dimethyl sulfoxide (DMSO) to produce a methyl radical fragment. Administration of CsA or tacrolimus with C-12-DMSO produced a 6-line spectrum, while CsA or tacrolimus given with C-13-DMSO produced a 12-line ESR spectrum, confirming formation of hydroxyl radicals. 4-Hydroxynonenal (4-HNE), a product of lipid peroxidation, accumulated in proximal and distal tubules after CsA or tacrolimus treatment. ESR changes and 4-HNE formation were largely blocked by polyphenols. Taken together, these results demonstrate that both CsA and tacrolimus stimulate free radical production in the kidney, most likely in tubular cells, and that polyphenols minimize nephrotoxicity by scavenging free radicals. C1 Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Zhong, Z (reprint author), Med Univ S Carolina, Dept Pharmaceut Sci, POB 2501400, Charleston, SC 29425 USA. EM zhong@musc.edu FU NIDDK NIH HHS [DK37034, DK62089, DK70844] NR 52 TC 7 Z9 7 U1 0 U2 1 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD NOV PY 2006 VL 58 IS 11 BP 1533 EP 1543 DI 10.1211/jpp.58.11.0015 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 111CU UT WOS:000242429500015 PM 17132217 ER PT J AU McCarron, RM Chen, Y Tomori, T Strasser, A Mechoulam, R Shohami, E Spatz, M AF McCarron, R. M. Chen, Y. Tomori, T. Strasser, A. Mechoulam, R. Shohami, E. Spatz, M. TI ENDOTHELIAL-MEDIATED REGULATION OF CEREBRAL MICROCIRCULATION SO JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE ischemia/reperfusion; endothelin; brain endothelium; nitric oxide; 2-AG AB Vascular endothelial cells are important not only for maintaining homeostasis, but also in pathogenesis of vascular disorders. Cerebral capillary and microvascular endothelial cells play an active role in maintaining cerebral blood flow, microvascular tone and blood brain barrier functions. Factors produced and released by endothelial cells, other brain cells and circulating blood cells participate in these regulatory functions. In particular, endothelin-1 (ET-1) and nitric oxide (NO) are known to contribute to the functional vascular changes under pathological conditions (e. g., hypertension, arteriosclerosis, and stroke). This report describes the involvement of endothelial cell mediators in the post-ischemic hypoperfusion induced by brain ischemia and in vitro endothelial responses (Ca(2+) mobilization and cytoskeletal rearrangements) to ET-1 and its interactions with NO or 2-AG. The capacity of NO and endocannabinoids to counteract ET-1-induced cerebral capillary and microvascular endothelial responses indicates that they may actively participate in EC function and implicates them in physiological and pathophysiological conditions. C1 [McCarron, R. M.; Chen, Y.; Tomori, T.; Strasser, A.; Spatz, M.] USN, Med Res Ctr, Trauma & Resuscitat Med Dept, Bethesda, MD 20084 USA. [McCarron, R. M.] Univ Uniformed Serv, Dept Surg, Bethesda, MD USA. [Spatz, M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Mechoulam, R.; Shohami, E.] Hebrew Univ Jerusalem, Jerusalem, Israel. RP Spatz, M (reprint author), Natl Inst Neurol Disorders & Stroke, Stroke Branch, NIH, 49 Convent Dr,MSC 4476, Bethesda, MD 20892 USA. EM spatzm@ninds.nih.gov FU NINDS, NIH FX This paper is dedicated to the memory of Professors Maria Dambska, Hanna Jedrzejowska, and Miroslaw J. Mossakowski who all collaborated and actively promoted scientific interactions between America and Poland. This work was supported in part by Intramural Research, NINDS, NIH. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of the Navy, Department of Defence or U. S. Goverment. NR 38 TC 26 Z9 31 U1 0 U2 1 PU POLISH PHYSIOLOGICAL SOC PI GRZEGORZECKA PA JAGIELLONIAN UNIV SCHOOL MED, INST PHYSIOLOGY, 31-531 KRAKOW, 16 GRZEGORZECKA, POLAND SN 0867-5910 J9 J PHYSIOL PHARMACOL JI J. Physiol. Pharmacol. PD NOV PY 2006 VL 57 SU 11 BP 133 EP 144 PG 12 WC Physiology SC Physiology GA V19RD UT WOS:000208088600011 PM 17244945 ER PT J AU Stepanyan, R Belyantseva, IA Griffith, AJ Friedman, TB Frolenkov, GI AF Stepanyan, Ruben Belyantseva, Inna A. Griffith, Andrew J. Friedman, Thomas B. Frolenkov, Gregory I. TI Auditory mechanotransduction in the absence of functional myosin-XVa SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID COCHLEAR HAIR-CELLS; INNER-EAR; UNCONVENTIONAL MYOSIN; SENSORY TRANSDUCTION; FAST ADAPTATION; MOUSE COCHLEA; STEREOCILIA; MICE; SHAKER-2; CHANNELS AB In hair cells of all vertebrates, a mechanosensory bundle is formed by stereocilia with precisely graded heights. Unconventional myosin-XVa is critical for formation of this bundle because it transports whirlin and perhaps other molecular components responsible for programmed elongation of stereocilia to the stereocilia tips. A tip of a stereocilium is the site of stereocilia growth and one of the proposed sites of mechano-electrical transduction. In adult shaker 2 mice, a mutation that disables the motor function of myosin-XVa results in profound deafness and abnormally short stereocilia that lack stereocilia links, an indispensable component of mechanotransduction machinery. Therefore, it was assumed that myosin-XVa is required for proper formation of the mechanotransduction apparatus. Here we show that in young postnatal shaker 2 mice, abnormally short stereocilia bundles of auditory hair cells have numerous stereocilia links and 'wild type' mechano-electrical transduction. We compared the mechanotransduction current in auditory hair cells of young normal-hearing littermates, myosin-XVa-deficient shaker 2 mice, and whirler mice that have similarly short stereocilia but intact myosin-XVa at the stereocilia tips. This comparison revealed that the absence of functional myosin-XVa does not disrupt adaptation of the mechanotransduction current during sustained bundle deflection. Thus, the hair cell mechanotransduction complex forms and functions independently from myosin-XVa-based hair bundle morphogenesis. C1 Univ Kentucky, Dept Physiol, Chandler Med Ctr, Lexington, KY 40536 USA. Nat Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD USA. Nat Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD USA. RP Frolenkov, GI (reprint author), Univ Kentucky, Dept Physiol, Chandler Med Ctr, MS508,800 Rose St, Lexington, KY 40536 USA. EM gregory.frolenkov@uky.edu OI Frolenkov, Gregory/0000-0002-9810-5024 FU Intramural NIH HHS NR 31 TC 22 Z9 22 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 2006 VL 576 IS 3 BP 801 EP 808 DI 10.1113/jphysiol.2006.118547 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 108JX UT WOS:000242237200018 PM 16973713 ER PT J AU Klein, RC Yakel, JL AF Klein, Rebecca C. Yakel, Jerrel L. TI Functional somato-dendritic alpha 7-containing nicotinic acetylcholine receptors in the rat basolateral amygdala complex SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HIPPOCAMPAL SLICES; ACH RECEPTORS; SYNAPTIC-TRANSMISSION; INTERNEURONS; NEURONS; ACTIVATION; SUBTYPES; DESENSITIZATION; INVOLVEMENT; PROJECTIONS AB Multiple subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed in the CNS. The amygdala complex, the limbic structure important for emotional memory formation, receives cholinergic innervation from the basal forebrain. Although cholinergic drugs have been shown to regulate passive avoidance performance via the amygdala, the neuronal subtypes and circuits involved in this regulation are unknown. In the present study, whole-cell patch-clamp electrophysiological techniques were used to identify and characterize the presence of functional somato-dendritic nAChRs within the basolateral complex of the amygdala. Pressure-application of acetylcholine (ACh; 2 mm) evoked inward current responses in a subset of neurons from both the lateral (49%) and basolateral nuclei (72%). All responses displayed rapid activation kinetics, and were blocked by the alpha 7-selective antagonist methyllycaconitine. In addition, the alpha 7-selective agonist choline induced inward current responses that were similar to ACh-evoked responses. Spiking patterns were consistent with pyramidal class I neurons (the major neuronal type in the basolateral complex); however, there was no correlation between firing frequency and the response to ACh. The local photolysis of caged carbachol demonstrated that the functional expression of nAChRs is located both on the soma and dendrites. This is the first report demonstrating the presence of functional nAChR-mediated current responses from rat amygdala slices, where they may be playing a significant role in fear and aversively motivated memory. C1 NIEHS, Neurobiol Lab, DHHS, NIH, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, DHHS, NIH, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU Intramural NIH HHS NR 39 TC 27 Z9 27 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 2006 VL 576 IS 3 BP 865 EP 872 DI 10.1113/jphysiol.2006.118232 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 108JX UT WOS:000242237200023 PM 16931547 ER PT J AU Pasnak, R Cooke, WD Hendricks, C AF Pasnak, Robert Cooke, Willa D. Hendricks, Charlene TI Enhancing academic performance by strengthening class-inclusion reasoning SO JOURNAL OF PSYCHOLOGY LA English DT Article DE abstraction; achievement; class inclusion; reasoning ID TRADITIONAL INTELLIGENCE; PIAGETIAN TASKS; ACHIEVEMENT; PREDICTORS; CHILDREN; TESTS AB Class inclusion is an early form of abstract thought that requires logical rather than perceptually based inferences plus an appreciation of part-whole relationships (B. Inhelder & J. Piaget, 1959/1964). The authors randomly assigned 2 groups of first graders who were having academic difficulties to be instructed on either class inclusion or phonics. Results showed a significant linear relation between individual children's mastery of class inclusion and their scores on the Cognitive Abilities Test Form 6 (D. F. Lohman & E. P. Hagen, 2001) verbal and quantitative measures of reasoning. The authors also found a significant linear relation between mastery of class inclusion and improvement in report card marks issued by teachers who were blind to the children's group assignment. C1 George Mason Univ, Fairfax, VA 22030 USA. NICHHD, Child & Family Res, Bethesda, MD USA. RP Pasnak, R (reprint author), George Mason Univ, 3F5, Fairfax, VA 22030 USA. EM rpasnak@gmu.edu NR 22 TC 6 Z9 6 U1 0 U2 4 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0022-3980 J9 J PSYCHOL JI J. Psychol. PD NOV PY 2006 VL 140 IS 6 BP 603 EP 613 DI 10.3200/JRLP.140.6.603-613 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 107WF UT WOS:000242201000007 PM 17144155 ER PT J AU Perry, MB Suwannarat, P Furst, GP Gahl, WA Gerber, LH AF Perry, Monique B. Suwannarat, Pim Furst, Gloria P. Gahl, William A. Gerber, Lynn H. TI Musculoskeletal findings and disability in alkaptonuria SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE alkaptonuria; function; rehabilitation; disability ID OCHRONOSIS AB Objective. To describe the musculoskeletal (MSK) findings in patients with alkaptonuria and to show which of these factors are associated with disability in this population. Methods. This is a prospective cross-sectional MSK assessment of subjects. Participants included 53 patients with alkaptonuria across the life span, 22 female and 31 male, mean age 43.6 years (10-80 yrs), participating in a natural history study supported by the National Human Genome Research Institute (NHGRI). Assessments included objective measures of the MSK system (range of motion, radiographic assessment of joints and spine, etc.) and questionnaires including the Human Activity Profile (HAP), Health Assessment Questionnaire (HAQ), SF-36 health survey, and the Fatigue Assessment Instrument. Results. There were 18 patients with kyphosis, 16 with scoliosis, 16 with marked reduction in range of motion of at least one major joint, 15 with joint replacements of major joints, 11 with tendon ruptures. A positive Schober's test was highly correlated with substantial functional loss and associated with disability as measured by the HAP (p < 0.0001), HAQ (p < 0.0001), and the physical component summary (p < 0.0001) of the SF-36 health survey. Severity of lumbar spine involvement had the greatest correlation with disability measures (p < 0.0001). All objective and subjective physical measures worsened with age. Conclusion. Disability is common and severe in patients with alkaptonuria and correlates well with physical findings. Disability does not correlate with self-reports of mental competencies. Aging with alkaptonuria is associated with progressive disability. C1 NIH, Clin Ctr, Rehabil Med Dept, Bethesda, MD 20892 USA. NIH, Med Genet Branch, Sect Human Biochem Genet, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Perry, MB (reprint author), NIH, Clin Ctr, Rehabil Med Dept, Bldg 10 CRC Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM mperry@cc.nih.gov FU Intramural NIH HHS NR 24 TC 14 Z9 15 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2006 VL 33 IS 11 BP 2280 EP 2285 PG 6 WC Rheumatology SC Rheumatology GA 105DX UT WOS:000242010700029 PM 16981292 ER PT J AU Berger, VW AF Berger, Vance W. TI Can pain be quantified numerically? SO JOURNAL OF RHEUMATOLOGY LA English DT Letter C1 NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2006 VL 33 IS 11 BP 2364 EP 2365 PG 2 WC Rheumatology SC Rheumatology GA 105DX UT WOS:000242010700048 PM 17086620 ER PT J AU Rosen, RC Catania, JA Ehrhardt, AA Burnett, AL Lue, TF McKenna, K Heiman, JR Schwarcz, S Ostrow, DG Hirshfield, S Purcell, DW Fisher, WA Stall, R Halkitis, PN Latini, DM Elford, J Laumann, EO Sonenstein, FL Greenblatt, DJ Kloner, RA Lee, J Malebranche, D Janssen, E Diaz, R Klausner, JD Caplan, AL Jackson, G Shabsigh, R Khalsa, JH Stoff, DM AF Rosen, Raymond C. Catania, Joseph A. Ehrhardt, Anke A. Burnett, Arthur L. Lue, Tom F. McKenna, Kevin Heiman, Julia R. Schwarcz, Sandy Ostrow, David G. Hirshfield, Sabina Purcell, David W. Fisher, William A. Stall, Ron Halkitis, Perry N. Latini, David M. Elford, Jonathan Laumann, Edward O. Sonenstein, Freya L. Greenblatt, David J. Kloner, Robert A. Lee, Jay Malebranche, David Janssen, Erick Diaz, Rafael Klausner, Jeffrey D. Caplan, Arthur L. Jackson, Graham Shabsigh, Ridwan Khalsa, Jag H. Stoff, David M. TI The Bolger Conference on PDE-5 Inhibition and HIV Risk: Implications for health policy and prevention SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE phosphodiesterase type 5 (PDE-5) inhibitor; HIV; AIDS; sexual risk behavior ID ACTIVE ANTIRETROVIRAL THERAPY; SEXUAL DYSFUNCTION; ERECTILE DYSFUNCTION; GAY MEN; PROTEASE INHIBITORS; SENSATION SEEKING; INFECTED PATIENTS; BISEXUAL MEN; VIAGRA USE; DRUG-USE AB Introduction. Recent reports have linked the use of phosphodiesterase type 5 (PDE-5) inhibitors with increased rates of high-risk sexual behavior and HIV transmission in some individuals. Aim. A National Institute of Mental Health (NIMH)-funded, multidisciplinary conference was convened to evaluate scientific research, clinical and ethical considerations, and public policy implications of this topic. Main Outocme Measures. Published and unpublished findings on effects of PDE-5 inhibitors on sexual behavior; published guidelines and management recommendations. Methods. Leading investigators in relevant disciplines (e.g., public health, epidemiology, medical ethics, urology, psychology) participated in a 2-day meeting, including representatives of government, scientific, and regulatory agencies (the Centers for Disease Control, Food and Drug Administration, NIMH, and the National Institute on Drug Abuse). Panelists provided critical reviews of substantive areas of research, followed by question and answer sessions on each topic. On the second day, working groups were convened to identify critical gaps and priorities in three major areas: (i) research and evaluation needs; (ii) prevention strategies and clinical management issues; and (iii) policy and prevention implications. Results. Research needs and priorities were categorized into four specific areas: (i) basic and clinical/laboratory research; (ii) epidemiology and risk factors; (iii) social-behavioral processes and interventions; and (iv) prevention/policy and educational needs. Identified gaps in the available data include populations at risk (e.g., risk among heterosexuals, risk profiles among subpopulations of men who have sex with men) and the specific role of PDE-5 inhibitors in HIV seroconversion. Specific areas of emphasis were the need for safer sex counseling, comprehensive sexually transmitted infection (STI) screening and follow-up when indicated, avoidance of potentially dangerous drug interactions, and potential benefits of testosterone replacement for HIV-positive men with decreased androgen and other symptoms of hypogonadism. Conclusions. A conference was convened on the topic of PDE-5 inhibition and HIV risk. This "white paper" summarizes the findings of the conference and recommendations for future research. C1 New England Res Inst, Watertown, MA 02472 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, Piscataway, NJ 08854 USA. Univ San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA 94117 USA. Columbia Univ, New York State Psychiat Inst, HIV Ctr Clin & Behav Studies, New York, NY USA. Johns Hopkins Univ Hosp, Dept Urol, Baltimore, MD 21287 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Northwestern Univ, Sch Med, Dept Physiol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA. Indiana Univ, Kinsey Inst Res Sex Gender & Reprod, Bloomington, IN USA. San Francisco Publ Hlth Dept, HIV AIDS Stat & Epidemiol, San Francisco, CA USA. David Ostrow & Associates, Lakewood, IL USA. Med & Hlth Res Assoc, New York, NY USA. Ctr Dis Control & Prevent, Prevent Res Branch, Div HIV AIDS Prevent, Atlanta, GA USA. Univ Western Ontario, Dept Psychol, London, ON, Canada. Univ Western Ontario, Dept Obstet & Gynecol, London, ON, Canada. Univ Pittsburgh, Dept Behav Sci & Community Hlth, Pittsburgh, PA USA. NYU, Ctr Hlth Ident Beahv & Prevent Studies, New York, NY USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. City Univ London, Inst Hlth Sci, London EC1V 0HB, England. Univ Chicago, Dept Sociol, Chicago, IL 60637 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Adolescent Hlth, Baltimore, MD USA. Tufts Univ, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. San Francisco State Univ, Cesar Chavez Inst, San Francisco, CA 94132 USA. San Francisco Dept Publ Hlth, STD Prevent & Control Serv, San Francisco, CA USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. St Thomas Hosp, London, England. Columbia Univ, Columbia Presbyterian Med Ctr, Dept Urol, New York, NY 10032 USA. NIDA, Med Consequences Branch, Bethesda, MD 20892 USA. NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. RP Rosen, RC (reprint author), New England Res Inst, Watertown, MA 02472 USA. EM rrosen@neriscience.com RI Kloner, Robert/B-2971-2012; Janssen, Erick/H-9106-2015; OI Janssen, Erick/0000-0002-0049-0703; Purcell, David/0000-0001-8125-5168; Latini, David/0000-0002-6161-4861 FU NIMH NIH HHS [R13 MH074345] NR 38 TC 26 Z9 26 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD NOV PY 2006 VL 3 IS 6 BP 960 EP 973 DI 10.1111/j.1743-6109.2006.00323.x PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 098ZL UT WOS:000241562200004 PM 17100928 ER PT J AU Zimmerman, SB AF Zimmerman, Steven B. TI Shape and compaction of Escherichia coli nucleoids SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Review DE bacteria; chloramphenicol; DNA-binding proteins; DNA condensation; Escherichia coli; doublet; macromolecular crowding; mecillinam; nucleoid; phase; polyamines; puromycin; spermidine; toroid ID DOUBLE-STRANDED DNA; PHASE-SEPARATION; EXCLUDED VOLUME; CYTOPLASM; CONSEQUENCES; SPERMIDINE; PROTEINS; BACTERIA; CELLS; CHLORAMPHENICOL AB The genomic DNA in cells of Escherichia coli is localized in one or two compact, phase-like regions with characteristic shapes. Nucleoids undergo progressive changes in shape and compaction in the presence of drugs such as chloramphenicol or puromycin. Forces which influence nucleoid shape and compaction are reviewed, with particular emphasis on crowding effects of the cytoplasm and confinement effects of the cell envelope. Based in part on the theory of Kornyshev and Leikin for interaction between DNA duplexes, the folding of DNA caused by binding of DNA-associated proteins is suggested to antagonize DNA condensation and, thereby, increase access to DNA sequences. These views are incorporated into a working model for nucleoid organization. Published by Elsevier Inc. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zimmerman, SB (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 50 TC 62 Z9 62 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD NOV PY 2006 VL 156 IS 2 BP 255 EP 261 DI 10.1016/j.jsb.2006.03.022 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 105CY UT WOS:000242008100003 PM 16697220 ER PT J AU Jin, DJ Cabrera, JE AF Jin, Ding Jun Cabrera, Julio E. TI Coupling the distribution of RNA polymerase to global gene regulation and the dynamic structure of the bacterial nucleoid in Escherichia coli SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Review DE RNA polymerase; RNA polymerase distribution; nucleoid; rRNA synthesis; stable RNA synthesis; global gene regulation; transcription foci; transcription factories; Escherichia coli ID CHROMOSOME SEGREGATION; BACILLUS-SUBTILIS; ELECTRON-MICROSCOPY; TRANSCRIPTION; ORGANIZATION; PROTEIN; DNA; LOCALIZATION; TRANSLATION; CHROMATIN AB Prokaryotic genomes are contained in a cellular structure termed the nucleoid. However, despite a complete genome sequence and years of intensive study of Escherichia coli, our knowledge of nucleoid structure remains quite rudimentary. Moreover, little is known about the in vivo relationship between nucleoid structure and global gene regulation. Recent studies have shown that the structure of the nucleoid responds dynamically to changing environmental conditions and that this metastable nature of the nucleoid is mediated to a large extent by the distribution and activity of RNA polymerase (RNAP). For example, during rapid growth, the nucleoid is highly condensed with RNAP concentrated into transcription foci or factories, structures analogous to the eukaryotic nucleolus, where active transcription of rRNA genes occurs. However, during nutrient starvation and/or limitation, RNAP is redistributed throughout the genome and this is accompanied by a decondensation of the nucleoid. Thus, the distribution of RNAP, global gene regulation and the dynamic structure of the nucleoid are coupled in the bacterial cell. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Canc Inst, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. RP Jin, DJ (reprint author), Natl Canc Inst, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, 1050 Boyles St, Frederick, MD 21702 USA. EM djjin@helix.nih.gov FU Intramural NIH HHS NR 45 TC 51 Z9 55 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD NOV PY 2006 VL 156 IS 2 BP 284 EP 291 DI 10.1016/j.jsb.2006.07.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 105CY UT WOS:000242008100006 PM 16934488 ER PT J AU Harford, TC Yi, HY Hilton, ME AF Harford, Thomas C. Yi, Hsiao-Ye Hilton, Michael E. TI Alcohol abuse and dependence in college and noncollege samples: A ten-year prospective follow-up in a national survey SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID HEALTH INTERVIEW SURVEY; USE DISORDERS; YOUNG-ADULTS; HIGH-SCHOOL; EPIDEMIOLOGIC SURVEY; ANTISOCIAL-BEHAVIOR; EDUCATIONAL STATUS; DRINKING PATTERNS; HEAVY DRINKING; BINGE-DRINKING AB Objective: This prospective study examines the association of educational status in 1984 and the risk for past-year Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), alcohol-use disorders (AUDs) in 1994, 10 years later. Method: A sample of 8,661 respondents was drawn from the National Longitudinal Survey of Labor Market Experience in Youth. Measures included baseline heavy episodic drinking, alcohol-dependence symptoms, early problem behaviors (antisocial behaviors, illicit substance use, family history of alcoholism, and age at onset of alcohol use), demographic characteristics (gender, race/ethnicity, age, marital status), and 1994 assessment for past-year DSM-IV AUDs. Results: Findings from this 10-year prospective study indicate that education beyond high school had a protective effect for alcohol dependence, and dropping out of high school resulted in an elevated long-term risk for alcohol dependence. These associations remained significant when other early behavioral problems were included in the models. Conclusions: The risk of alcohol dependence and, consequently, the need for appropriately tailored prevention efforts is greater among high school dropouts and college nonattenders than among college students, although much of the current literature has focused on the latter. C1 CSR Inc, Arlington, VA 22201 USA. NIAAA, Bethesda, MD 90034 USA. RP Yi, HY (reprint author), CSR Inc, 2107 Wilson Blvd,Suite 1000, Arlington, VA 22201 USA. EM hyi@csrincorporated.com FU NIAAA NIH HHS [N0AA32007] NR 49 TC 27 Z9 27 U1 8 U2 14 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD NOV PY 2006 VL 67 IS 6 BP 803 EP 809 PG 7 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 095EE UT WOS:000241290200002 PM 17060996 ER PT J AU Schuckit, MA Smith, TL Waylen, A Horwood, J Danko, GP Hibbeln, JR Davis, JM Pierson, J AF Schuckit, Marc A. Smith, Tom L. Waylen, Andrea Horwood, Jeremy Danko, George P. Hibbeln, Joseph R. Davis, John M. Pierson, Juliann TI An evaluation of the performance of the self-rating of the effects of alcohol questionnaire in 12-and 35-year-old subjects SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID ACUTE TOLERANCE; GENETIC-DIFFERENCES; USE DISORDERS; LOW-LEVEL; WORKING-MEMORY; UCHB RATS; FOLLOW-UP; SENSITIVITY; ETHANOL; RISK AB Objective: A low level of response (LR) to alcohol was originally established through evidence of less alcohol-related change in several parameters at a given blood alcohol level. This is a genetically influenced phenotype associated with an increased risk for alcoholism. When measured by a retrospective questionnaire (the Self-Rating of the Effects of Alcohol [SRE] scale), a lower LR (here indicated by a report that more drinks were historically needed for various effects) correlates with a family history of alcoholism and numerous alcohol use-related variables. The current analyses address the questions of how higher SRE scores (as indicators of a low LR) relate to alcohol use and problems across different age groups and when considered in the context of demography (e.g., age, gender, and weight), as well as the number of items endorsed on the questionnaire. Method: SRE data (scores and numbers of items endorsed), demography, and alcohol-related variables (quantity, frequency, and problems) were evaluated in two populations. The first population included 334 12-year-old children from the Avon Longitudinal Study of Parents and Children, and the second included more than 400 35-year-old men from the San Diego Prospective Study. In each group, Pearson correlations were established among all variables, and items that were significantly linked to alcohol-related outcomes were entered into regression analyses as predictors of these outcomes. Results: In both samples, SRE scores correlated with all alcohol-related outcomes, with the highest values for the maximum quantity of alcohol consumed. Relationships between the SRE score and alcohol-related variables remained robust in both populations when entered into regression analyses incorporating demography and the number of SRE items answered by subjects. Conclusions: The SRE score appears to perform relatively similarly across the two populations regarding relationships with alcohol quantity, frequency, and problems. The most consistent results were observed for the maximum quantity of alcohol consumed. C1 Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Bristol, Bristol BS8 1TH, Avon, England. Longitudinal Study Parents & Children, Bristol, Avon, England. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Univ Illinois, Illinois State Psychiat Inst, Chicago, IL USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. RP Schuckit, MA (reprint author), Univ Calif San Diego, Dept Psychiat, 116A, San Diego, CA 92103 USA. EM mschuckit@ucsd.edu RI Waylen, Andrea/H-7332-2014 FU Medical Research Council [G9815508]; PHS HHS [05526] NR 60 TC 19 Z9 19 U1 1 U2 1 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD NOV PY 2006 VL 67 IS 6 BP 841 EP 850 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 095EE UT WOS:000241290200007 PM 17061001 ER PT J AU Kollins, S Greenhill, L Swanson, J Wigal, S Abikoff, H McCracken, J Riddle, M McGough, J Vitiello, B Wigal, T Skrobala, A Posner, K Ghuman, J Davies, M Cunningham, C Bauzo, A AF Kollins, Scott Greenhill, Laurence Swanson, James Wigal, Sharon Abikoff, Howard McCracken, James Riddle, Mark McGough, James Vitiello, Benedetto Wigal, Tim Skrobala, Anne Posner, Kelly Ghuman, Jaswinder Davies, Mark Cunningham, Charles Bauzo, Audrey TI Rationale, design, and methods of the preschool ADHD Treatment Study (PATS) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; preschool; methylphenidate; clinical trials ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; TREATMENT STRATEGIES; CONTROLLED TRIAL; CHILDREN; METHYLPHENIDATE; VALIDITY; AGE; SYMPTOMS; MTA AB Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS). Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with attention-deficit/ hyperactivity disorder (ADHD). Three hundred three subjects ages 3 to 5.5 years old who met criteria for a primary DSM-IV diagnosis of ADHD entered the trial. Subjects participated in an 8-phase, 70-week trial that included screening, parent training, baseline, open-label safety lead-in, double-blind crossover titration, double-blind parallel efficacy, open-label maintenance, and double-blind discontinuation. Medication response was assessed during the crossover titration phase using a combination of parent and teacher ratings. Special ethical considerations throughout the trial warranted a number of design changes. Results: This report describes the design of this trial, the rationale for reevaluation and modification of the design, and the methods used to conduct the trial. Conclusions: The PATS adds to a limited literature and improves our understanding of the safety and efficacy of MPH in the treatment of preschoolers with ADHD, but changes in the design and problems in implementation of this study impose some specific limitations that need to be addressed in future studies. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27705 USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. Univ Calif Irvine, Irvine, CA USA. NYU, Ctr Child Study, New York, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. NIMH, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. McMaster Univ, Hamilton, ON, Canada. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Kollins, S (reprint author), Duke Univ, Med Ctr, Dept Psychiat, 718 Rutherford St, Durham, NC 27705 USA. EM kolli001@mc.duke.edu RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [U01 MH60833, K23 MH001883-05, U01 MH60642, U01 MH60848, U01 MH60900, U01 MH60903, U01 MH60943] NR 65 TC 68 Z9 69 U1 9 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2006 VL 45 IS 11 BP 1275 EP 1283 DI 10.1097/01.chi.0000235074.86919.dc PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600001 PM 17023869 ER PT J AU Greenhill, L Kollins, S Abikoff, H McCracken, J Riddle, M Swanson, J McGough, J Wigal, S Wigal, T Vitiello, B Skrobala, A Posner, K Ghuman, J Cunningham, C Davies, M Chuang, S Cooper, T AF Greenhill, Laurence Kollins, Scott Abikoff, Howard McCracken, James Riddle, Mark Swanson, James McGough, James Wigal, Sharon Wigal, Tim Vitiello, Benedetto Skrobala, Anne Posner, Kelly Ghuman, Jaswinder Cunningham, Charles Davies, Mark Chuang, Shirley Cooper, Tom TI Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE preschool; attention-deficit/hyperactivity disorder; psychopharmacology; treatment; adverse events ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HYPERACTIVE-CHILDREN; TREATMENT STRATEGIES; CRITERION VALIDITY; MEDICATION; MTA; RELIABILITY; RELEVANCE; TRIAL AB The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylpheniclate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). Method: The 8-phase, 70-week PATS protocol included two double-blind, controlled phases, a crossover-titration trial followed by a placebo-controlled parallel trial. The crossover-titration phase's primary efficacy measure was a combined score from the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney, and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was excellent response, based on composite scores on the Swanson, Nolan, and Pelham (SNAP) rating scale. Results: Of 303 preschoolers enrolled, 165 were randomized into the titration trial. Compared with placebo, significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p < .01), 5 mg (p < .001), and 7.5 mg (p < .001) t.i.d. doses, but not for 1.25 mg (p < .06). The mean optimal MPH total daily dose for the entire group was 14.2 +/- 8.1 mg/day (0.7 +/- 0.4 mg/kg/day). For the preschoolers (n = 114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD. Conclusions: MPH-IR, delivered in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD symptom scales in preschoolers compared to placebo, although effect sizes (0.4-0.8) were smaller than those cited for school-age children on the same medication. C1 Columbia Univ, Div Child & Adolescent Psychiat, New York State Psychiat Inst, New York, NY 10032 USA. Duke Univ, Durham, NC USA. NYU, Ctr Child Study, New York, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Arizona, Tucson, AZ USA. McMaster Univ, Hamilton, ON, Canada. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif Irvine, Irvine, CA USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NIMH, Bethesda, MD 20892 USA. RP Greenhill, L (reprint author), Columbia Univ, Div Child & Adolescent Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA. EM larrylgreenhill@cs.com RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [K23 MH001883-05, U01 MH60642, U01 MH60833, U01 MH60848, U01 MH60900, U01 MH60903, U01 MH60943] NR 23 TC 185 Z9 187 U1 6 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2006 VL 45 IS 11 BP 1284 EP 1293 DI 10.1097/01.chi.0000235077.32661.61 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600002 PM 17023867 ER PT J AU Wigal, T Greenhill, L Chuang, S McGough, J Vitiello, B Skrobala, A Swanson, J Wigal, S Abikoff, H Kollins, S McCracken, J Riddle, M Posner, K Ghuman, J Davies, M Thorp, B Stehli, A AF Wigal, Tim Greenhill, Laurence Chuang, Shirley McGough, James Vitiello, Benedetto Skrobala, Anne Swanson, James Wigal, Sharon Abikoff, Howard Kollins, Scott McCracken, James Riddle, Mark Posner, Kelly Ghuman, Jaswinder Davies, Mark Thorp, Ben Stehli, Annamarie TI Safety and tolerability of methylphenidate in preschool children with ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE preschoolers; attention-deficit/hyperactivity disorder; methylphenidate; adverse events; safety; tolerability ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; TREATMENT STRATEGIES; MEDICATION; TRIAL; AGE AB To report on the safety and tolerability of methylphenidate (MPH) 3- to 5-year-old children with attention-deficit/ hyperactivity disorder (ADHD) during 1 year of treatment. Method: Exactly 183 children (3-5 years old) entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n = 183); a 5-week placebo-controlled, double-blind phase (n = 165); a 5-week double-blind, parallel phase (n = 114); and 10 months of open-label maintenance (n = 140 entered, 95 completed). Mean total daily MPH doses rose from the titration trial best dose, 14.1 (+/- 8.1) mg/day, to 20.5 (+/- 9.7) mg/day mean total daily dose at the end of maintenance. Pulse, blood pressure, and the presence of treatment emergent adverse events (AEs), parent and teacher AE ratings, and vital signs were recorded in each phase. Results: Thirty percent of parents spontaneously reported moderate to severe AEs in all study phases after baseline. These included emotional outbursts, difficulty falling asleep, repetitive behaviors/thoughts, appetite decrease, and irritability. During titration, decreased appetite (chi(2) = 5.4, p < .03), trouble sleeping (chi(2) = 5.4, p < .03), and weight loss (chi(2) = 4.0, p < .05) occurred statistically more often on MPH than on placebo. During maintenance, trouble sleeping and appetite loss persisted and other MPH-related AEs decreased. There were transient, one-time pulse and blood pressure elevations in five children. Twenty-one children (11%) discontinued because of drug-attributed AEs. Conclusions: Eleven percent of preschoolers discontinued treatment because of intolerable MPH AEs. Of the serious AEs reported, one occurred in baseline, two in lead-in, three in titration, one in parallel, and one in maintenance. Only one was possibly related to MPH. C1 Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. Univ Calif Irvine, Irvine, CA USA. NYU, Ctr Child Study, New York, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Duke Univ, Med Ctr, Durham, NC USA. NIMH, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. RP Greenhill, L (reprint author), Columbia Univ, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA. EM larrylgreenhill@cs.com RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [U01 MH60833, K23 MH001883-05, U01 MH60642, U01 MH60848, U01 MH60900, U01 MH60903, U01 MH60943] NR 22 TC 117 Z9 120 U1 3 U2 16 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 NOV PY 2006 VL 45 IS 11 BP 1294 EP 1302 DI 10.1097/01.chi.0000235082.63156.27 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600003 PM 17028508 ER PT J AU Swanson, J Greenhill, L Wigal, T Kollins, S Stehli, A Davies, M Chuang, S Vitiello, B Skrobala, A Posner, K Abikoff, H Oatis, M McCracken, J McGough, J Riddle, M Ghuman, J Cunningham, C Wigal, S AF Swanson, James Greenhill, Laurence Wigal, Tim Kollins, Scott Stehli, Annamarie Davies, Mark Chuang, Shirley Vitiello, Benedetto Skrobala, Anne Posner, Kelly Abikoff, Howard Oatis, Melvin McCracken, James McGough, James Riddle, Mark Ghuman, Jaswinder Cunningham, Charles Wigal, Sharon TI Stimulant-related reductions of growth rates in the PATS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; growth; stimulant medication ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; EXTRACELLULAR DOPAMINE; CHILDREN; METHYLPHENIDATE; ADHD; WEIGHT; HEIGHT; PRESCHOOLERS; TRANSPORTER AB Objective: To investigate growth of children with attention-deficit/hyperactivity disorder (ADHD) in the Preschool ADHD Treatment Study (PATS) before and after initiation of treatment with methylphenidate at titrated doses (average, 14.2 mg/day) administered three times daily, 7 days/week for approximate to 1 year. Method: The heights and weights of 140 children with ADHD were measured up to 29 times in the PATS protocol, starting at an average age of 4.4 years. The relationship between standard (z) scores and time on medication was examined using mixed-effect regression to estimate change in relative size (slope). Results: Average relative size at baseline was significantly (p < .0001) greater than zero for zheight (+0.45) and z weight (+0.78), indicating greater than expected height (by 2.04 cm) and weight (by 1.78 kg). During treatment, slopes were significantly (p < .0001) less than zero for z height (-0.304/yr) and z weight (-0.530/yr), indicating reduction of growth rates. For 95 children who remained on medication, annual growth rates were 20.3% less than expected for height (5.41 cm/yr -6.79 cm/yr = -1.38 cm/yr) and 55.2% for weight (1.07 kg/yr - 2.39 kg/yr = - 1.32 kg/yr). Conclusions: Risks of reduced growth rates should be balanced against expected benefits when preschool-age children are treated with stimulant medication. C1 Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. Duke Univ, Med Ctr, Durham, NC USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. NYU, Ctr Child Study, New York, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Arizona, Tucson, AZ USA. NIMH, Bethesda, MD 20892 USA. McMaster Univ, Hamilton, ON, Canada. RP Swanson, J (reprint author), Univ Calif Irvine, Child Dev Ctr, 19722 MacArthur Blvd, Irvine, CA 92612 USA. EM jmswanso@uci.edu RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [U01 MH60833, K23 MH001883-05, U01 MH60642, U01 MH60848, U01 MH60900, U01 MH60903, U01 MH60943] NR 30 TC 100 Z9 101 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2006 VL 45 IS 11 BP 1304 EP 1313 DI 10.1097/01.chi.0000235075.25038.5a PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600004 PM 17023868 ER PT J AU McGough, J McCracken, J Swanson, J Riddle, M Kollins, S Greenhill, L Abikoff, H Davies, M Chuang, S Wigal, T Wigal, S Posner, K Skrobala, A Kastelic, E Ghuman, J Cunningham, C Shigawa, S Moyzis, R Vitiello, B AF McGough, James McCracken, James Swanson, James Riddle, Mark Kollins, Scott Greenhill, Laurence Abikoff, Howard Davies, Mark Chuang, Shirley Wigal, Tim Wigal, Sharon Posner, Kelly Skrobala, Anne Kastelic, Elizabeth Ghuman, Jaswinder Cunningham, Charles Shigawa, Sharon Moyzis, Robert Vitiello, Benedetto TI Pharmacogenetics of methylphenidate response in preschoolers with ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; methylphenidate; pharmacogenetics; dopamine receptor (DRD4); synaptosomal-associated protein-25 ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; DUPLICATION POLYMORPHISM UPSTREAM; CRITERION VALIDITY; RECEPTOR VARIANTS; ASSOCIATION; CHILDREN; ALLELE; DRD4 AB Objective: The authors explored genetic moderators of symptom reduction and side effects in methylphenidate-treated preschool-age children diagnosed with attention-deficit/hyperactivity disorder (ADHD). Method: DNA was isolated from 81 subjects in a double-blind, placebo-controlled, crossover methylphenidate titration. Parents and teachers completed ADHD symptom scales and side effect ratings for each of five randomly administered weekly conditions that included immediate-release methylphenidate 1.25, 2.5, 5.0, 7.5 mg and placebo given three times daily. Candidate genes hypothesized to influence stimulant effects or individual risks for ADHD were genotyped. Results: Although the primary analysis did not indicate significant genetic effects, secondary analyses revealed associations between symptom response and variants at the dopamine receptor (DRD4) promoter (p = .05) and synaptosomal-associated protein 25 (SNAP25) allelesT1065G (p=.03) andT1069C(p=.05). SNAP25 variants were also associated with tics (p=.02), buccallingual movements (p=.01), and irritability (p=.04). DRD4 variants were also associated with picking (p=.03). Increasing dose predicted irritability (p=.05) and social withdrawal (p=.03) with DRD4 variants. There were no significant effects for the dopamine transporter (DAT1). Conclusions: Emerging evidence suggests the potential for understanding the individual variability of response to and side effects of ADHD medications from the study of genetics, although additional research is required before these findings are proven to have clinical utility. C1 Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Univ Calif Irvine, Irvine, CA USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Duke Univ, Med Ctr, Durham, NC USA. NYU, Ctr Child Study, New York, NY USA. Univ Arizona, Tucson, AZ USA. McMaster Univ, Hamilton, ON, Canada. NIMH, Bethesda, MD 20892 USA. RP McGough, J (reprint author), 300 UCLA Med Plaza,Suite 1414, Los Angeles, CA 90095 USA. EM jmcgough@mednet.ucla.edu RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [U01 MH60642, K23 MH001883-05, U01 MH60833, U01 MH60848, U01 MH60900, U01 MH60903, U01 MH60943] NR 34 TC 72 Z9 73 U1 1 U2 7 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 NOV PY 2006 VL 45 IS 11 BP 1314 EP 1322 DI 10.1097/01.chi.0000235083.40285.08 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600005 PM 17023870 ER PT J AU Shaw, P Rapoport, JL AF Shaw, Philip Rapoport, Judith L. TI Decision making about children with psychotic symptoms: Using the best evidence in choosing a treatment SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID CHILDHOOD-ONSET SCHIZOPHRENIA; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; EMOTIONAL DISORDERS; TREATMENT-RESISTANT; HIGH-RISK; OLANZAPINE; CLOZAPINE; HALOPERIDOL; ANTIPSYCHOTICS C1 NIMH, Child Psychiat Branch, Bethesda, MD 20932 USA. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, Bldg 10,3N202, Bethesda, MD 20932 USA. EM shawp@mail.nih.gov FU Intramural NIH HHS NR 34 TC 9 Z9 10 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2006 VL 45 IS 11 BP 1381 EP 1386 DI 10.1097/01.chi.0000233780.53785.a4 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600013 PM 17075361 ER PT J AU Blonde, L Dempster, J Gallivan, JM Warren-Boulton, E AF Blonde, Lawrence Dempster, Judith Gallivan, Joanne M. Warren-Boulton, Elizabeth TI Reducing cardiovascular disease risk in patients with diabetes: A message from the National Diabetes Education Program SO JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS LA English DT Review DE cardiovascular disease risk reduction; diabetes complications; diabetes ABCs; NDEP ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; MYOCARDIAL-INFARCTION; MICROVASCULAR COMPLICATIONS; SUBGROUP-ANALYSES; ARTERY-DISEASE; INSULIN; MELLITUS; THERAPY; GLUCOSE AB Purpose: To provide nurse practitioners (NPs) a review of current practice guidelines that help clinicians' efforts to reduce the morbidity and mortality associated with diabetes and its major macrovascular complications. Data sources: This paper presents data from major evidence-based studies and clinical trials that define the scope of the problem the rationale for risk, reduction, and a patient-centered action plan for NPs to effectively manage cardiovascular risk factors in people with diabetes. Conclusions: NPs are active partners with the National Diabetes Education Program and play a key role in efforts to effectively manage cardiovascular risk factors in people with diabetes and improve their awareness of the link between diabetes and heart disease and stroke. Implications for practice: The action plan to reduce cardiovascular risk in people with diabetes will help NPs to implement the most effective management strategies for medical nutrition therapy, physical activity, and pharmacological therapy required for patient-centered proactive management of hyperglycemia, hypertension, and lipid abnormalities. C1 Ochsner Clin Fdn, Ochsner Diabet Clin Res Unit, Sect Endocrinol Diabet & Metab Dis, New Orleans, LA 70121 USA. Amer Acad Nurse Practitioners, Austin, TX USA. NIH, Natl Diabet Educ Program, Bethesda, MD 20892 USA. Hager Sharp Inc, Washington, DC USA. RP Blonde, L (reprint author), Ochsner Clin Fdn, Ochsner Diabet Clin Res Unit, Sect Endocrinol Diabet & Metab Dis, Brent House Room 629,1514 Jefferson Highway, New Orleans, LA 70121 USA. EM lblonde@ochsner.org NR 43 TC 8 Z9 8 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1041-2972 J9 J AM ACAD NURSE PRAC JI J. Am. Acad. Nurse Pract. PD NOV PY 2006 VL 18 IS 11 BP 524 EP 533 DI 10.1111/j.1745-7599.2006.00171.x PG 10 WC Health Care Sciences & Services; Nursing SC Health Care Sciences & Services; Nursing GA 109AJ UT WOS:000242280000005 PM 17064330 ER PT J AU Kastenmayer, RJ Fain, MA Perdue, KA AF Kastenmayer, Robin J. Fain, Michele A. Perdue, Kathy A. TI A retrospective study of idiopathic ulcerative dermatitis in mice with a C57BL/6 background SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID NITRIC-OXIDE-SYNTHASE; STAPHYLOCOCCUS-XYLOSUS; STRAINS AB Idiopathic ulcerative dermatitis is a well-recognized disease in C57BL mice and related strains. This disease manifests as a pruritic dermatitis with resulting self-mutilation, dermal ulceration, necrosis, and fibrosis. Ulcerative dermatitis has the ability to confound ongoing research by causing systemic pathologic changes, such as lymphadenopathy and splenomegaly. Although various treatments have been described, none has been curative consistently; therefore, minimizing negative effects on research through prevention of disease is ideal. To identify etiologic factors, we conducted a 2-y retrospective study of 1352 mice with a C57BL/6 genetic background; these mice demonstrated an overall prevalence of 4.1% and a seasonal effect with a peak incidence during midsummer. Corroborating previous studies, our study revealed a disease predilection for female mice. In contrast to prior reports, the disease prevalence was greatest in 10- to 16-mo-old mice. In addition, mice with a C57BL/6 background that were deficient in the gene for inducible nitric oxide synthase had a 50% disease incidence, suggesting a potential animal model for further characterizing the pathogenesis, prevention, and treatment of ulcerative dermatitis. C1 NIAID, NIH, Rockville, MD 20852 USA. RP Kastenmayer, RJ (reprint author), NIAID, NIH, Rockville, MD 20852 USA. EM rkastenmayer@niaid.nih.gov FU Intramural NIH HHS NR 16 TC 36 Z9 36 U1 2 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2006 VL 45 IS 6 BP 8 EP 12 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 105IY UT WOS:000242024800003 PM 17089984 ER PT J AU Langham, GL Hoyt, RF Johnson, TE AF Langham, Gregory L. Hoyt, Robert F. Johnson, Thomas E. TI Particulate matter in animal rooms housing mice in microisolation caging SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID INDIVIDUALLY VENTILATED PIV; WORKING ENVIRONMENT; LABORATORY-ANIMALS; AIRBORNE ALLERGENS; MOUSE ALLERGEN; CAGES; REDUCTION; FACILITY; SYSTEM; RATS AB Reactions to allergens created by laboratory animals are among the most frequently encountered occupational illnesses associated with research animals. Personnel are exposed to these allergens through airborne particulate matter. Although the use of microisolation caging systems can reduce particulate matter concentrations in rooms housing mice, the operating parameters of ventilated caging systems vary extensively. We compared room air in mouse rooms containing 5 different types of caging: 1) individually ventilated caging under positive pressure with filtered intake air and exhaust air returned to the room (VCR+), 2) individually ventilated caging under negative pressure with exhaust air returned to the room (VCR-), 3) individually ventilated caging under positive pressure with exhaust air returned to the heating, ventilation, and air-conditioning (HVAC) system, 4) individually ventilated caging under negative pressure with exhaust air returned to the HVAC system, and 5) static microisolation cages. We found that rooms under VCR conditions had fewer large particles than did those under other conditions, but the numbers of 0.3 gm particles did not differ significantly among systems. Static, positive or negative pressure applied to caging units as well as route of air exhaust were found to have little influence on the total number of particles in the atmosphere. Therefore, considering the heat load, odor, and overall particulate concentration in the room, placing individually ventilated caging under negative pressure with exhaust air returned to the HVAC system appears to be the optimal overall choice when using microisolation housing for rodents. C1 Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Sci Resources Program, Anim Resources ranch, Lawrenceville, GA USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Johnson, TE (reprint author), Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. EM Thomas.Johnson@colostate.edu NR 40 TC 3 Z9 3 U1 1 U2 5 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2006 VL 45 IS 6 BP 44 EP 48 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 105IY UT WOS:000242024800010 PM 17089991 ER PT J AU Gozalo, AS Schwiebert, RS Lawson, GW AF Gozalo, Alfonso S. Schwiebert, Rebecca S. Lawson, Gregory W. TI Mortality associated with fenbendazole administration in pigeons (Columba livia) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID BIRDS; NEMATODIASIS; POULTRY AB A group of 12 domestic pigeons (Columba livia domestica) was treated for capillariasis by use of fenbendazole at 30 mg/kg orally once daily for 5 d. After treatment, 8 of the 12 pigeons exhibited signs of anorexia, lethargy, and dehydration; these birds died within 2 d after the onset of clinical signs. A total of 6 birds were necropsied, and all had unremarkable gross findings. Microscopic examination of tissues revealed acute hemorrhagic enteritis, diffuse lymphoplasmacytic enteritis, small intestinal crypt necrosis, periportal lymphoplasmacytic hepatitis, bile duct hyperplasia, and renal tubular necrosis. Erythrocytes in blood samples collected from surviving birds demonstrated polychromasia compatible with a regenerative anemia. The clinical and histopathologic findings in these pigeons were consistent with recent reports of fenbendazole toxicity in domestic pigeons and other columbiform birds. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Lab Anim Med, Los Angeles, CA 90024 USA. RP Gozalo, AS (reprint author), NIAID, NIH, Comparat Med Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov NR 14 TC 16 Z9 16 U1 2 U2 8 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2006 VL 45 IS 6 BP 63 EP 66 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 105IY UT WOS:000242024800014 PM 17089995 ER PT J AU Nahin, RL Fitzpatrick, AL Williamson, JD Burke, GL DeKosky, ST Furberg, C AF Nahin, Richard L. Fitzpatrick, Annette L. Williamson, Jeff D. Burke, Gregory L. DeKosky, Steven T. Furberg, Curt CA GEM Study Investigators TI Use of herbal medicine and other dietary supplements in community-dwelling older people: Baseline data from the Ginkgo Evaluation of Memory study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cross-sectional study; dietary supplements; herbal medicine; elderly ID HEALTH INTERVIEW SURVEY; UNITED-STATES; NATIONAL-HEALTH; MINERAL SUPPLEMENTS; VITAMIN; POPULATION; VALIDITY; ADULTS; NONVITAMIN; PHYSICIANS AB To analyze baseline data from the Ginkgo Evaluation of Memory (GEM) study, in which information was collected on the use of all dietary supplements. Cross-sectional regression analysis. GEM study sites in California, Maryland, North Carolina, and Pennsylvania. The GEM study enrolled 3,072 ambulatory individuals aged 75 and older between September 2000 and June 2002. Self-reported use of dietary supplements and use identified through bottles brought to the clinic. Respectively, 59.4%, 66.6%, and 27.4% of the GEM study cohort used a multivitamin, at least one individual vitamin or mineral supplement, and some type of nonvitamin/nonmineral dietary supplement (NVNMDS). In logistic regression models, multivitamin use was associated with female sex, a higher income, a higher modified Mini-Mental State Examination score, difficulty with mobility, and asthma history; use of any other vitamin or mineral was associated with female sex, white race, nonsmoking, more years of schooling, difficulty walking, a history of osteoporosis, and reading health and senior magazines; and NVNMDS use was associated with residing in California, having difficulties with muscle strength, and reading health and senior magazines. There were substantial differences between individuals who used vitamins and minerals and those who used NVNMDS. These data require that trial investigators pay close attention to participant use of off-protocol dietary supplements. In addition, these findings may help identify elderly individuals likely to combine NVNMDS and prescription drugs. C1 NCCAM, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Wake Forest Univ, Bowman Gray Sch Med, Kulynych Ctr Memory & Cognit, Winston Salem, NC USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Nahin, RL (reprint author), NCCAM, NIH, 9000 Rockville Pike,Bldg 2B11,Msc 2182, Bethesda, MD 20892 USA. EM nahinr@mail.nih.gov RI Kim, Hyung Woo /G-7525-2011; OI Nahin, Richard/0000-0002-3682-4816 FU NCCIH NIH HHS [U19 AT1998, 5 U01 AT000162, R21 AT2152, U01 AT000162]; NHLBI NIH HHS [R01 HL80698]; NIA NIH HHS [P01 AG14449, P50 AG5133] NR 47 TC 30 Z9 32 U1 3 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2006 VL 54 IS 11 BP 1725 EP 1735 DI 10.1111/j.1532-5415.2006.00942.x PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 100NS UT WOS:000241676400014 PM 17087700 ER PT J AU Kim, DH Lipsitz, LA Ferrucci, L Varadhan, R Guralnik, JM Carlson, MC Fleisher, LA Fried, LP Chaves, PHM AF Kim, Dae Hyun Lipsitz, Lewis A. Ferrucci, Luigi Varadhan, Ravi Guralnik, Jack M. Carlson, Michelle C. Fleisher, Lee A. Fried, Linda P. Chaves, Paulo H. M. TI Association between reduced heart rate variability and cognitive impairment in older disabled women in the community: Women's Health and Aging Study I SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc DE heart rate variability; cognition; autonomic nervous system ID BLOOD-PRESSURE VARIABILITY; CARDIAC AUTONOMIC CONTROL; ELDERLY SUBJECTS; RISK; MORTALITY; DISEASE; HYPERTENSION; DEMENTIA; ATHEROSCLEROSIS; POPULATION AB To examine the independent association between heart rate variability (HRV), a marker of cardiac autonomic function, and cognitive impairment. Cross-sectional analysis of baseline data from Women's Health and Aging Study I. Urban community in Baltimore, Maryland. A subset of 311 physically disabled, community-dwelling women aged 65 and older whose HRV data were obtained. Reduced HRV was defined as the lowest quartile of each of several HRV measures exploring time and frequency domains and compared with the remaining three quartiles. Cognitive impairment was defined as a Mini-Mental State Examination score less than 24. Multiple logistic regression was used to model the independent relationship between reduced HRV and prevalent cognitive impairment. The age-, education-, and race-adjusted prevalence of cognitive impairment was higher in those with reduced HRV than in those with nonreduced HRV. After adjusting for relevant demographic and clinical characteristics, participants with reduced HRV were significantly more likely than those with nonreduced HRV to have cognitive impairment; these findings were consistent across different HRV indices. In particular, reduced high-frequency power, indicative of decreased parasympathetic activity, was associated with 6.7 times greater odds of cognitive impairment (95% confidence interval = 2.27-20.0). Cardiac autonomic dysfunction, particularly decreased parasympathetic activity, was independently associated with cognitive impairment in older disabled women in the community. This finding may improve understanding of the pathophysiological basis of cognitive impairment. The potential role of HRV as a cause or consequence of cognitive impairment needs to be elucidated in future studies. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. Harvard Univ, Sch Med, Boston, MA USA. NIA, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Ctr Aging & Hlth, Baltimore, MD USA. Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Kim, DH (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, 1025 Walnut St,Suite 804, Philadelphia, PA 19107 USA. EM dae-hyun.kim@mail.tju.edu FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [R37 AG025037, R37 AG025037-01A1, P30 AG021334, R37 AG019905, R37 AG19905] NR 31 TC 36 Z9 36 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2006 VL 54 IS 11 BP 1751 EP 1757 DI 10.1111/j.1532-5415.2006.00940.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 100NS UT WOS:000241676400018 PM 17087704 ER PT J AU Williams, JG Tomer, KB Hioe, CE Zolla-Pazner, S Norris, PJ AF Williams, Jason G. Tomer, Kenneth B. Hioe, Catarina E. Zolla-Pazner, Susan Norris, Philip J. TI The antigenic determinants on HIV p24 for CD4(+) T cell inhibiting antibodies as determined by limited proteolysis, chemical modification, and mass spectrometry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article; Proceedings Paper CT 18th Sanibel Conference on Mass Spectrometry CY JAN, 2006 CL Sanibel Island, FL ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISCONTINUOUS EPITOPE; BINDING DOMAIN; TYPE-1; RESPONSES; VACCINE; GLYCOPROTEIN-120; REACTIVITY; INFECTION; OXIDATION AB In the last decade, mass spectrometry has been employed by more and more researchers for identifying the proteins in a macromolecular complex as well as for defining the surfaces of their binding interfaces. This characterization of protein-protein interfaces usually involves at least one of several different methodologies in addition to the actual mass spectrometry. For example, limited proteolysis is often used as a first step in defining regions of a protein that are protected from proteolysis when the protein of interest is part of a macromolecular complex. Other techniques used in conjunction with mass spectrometry for determining regions of a protein involved in protein-protein interactions include chemical modification, such as covalent cross-linking, acetylation of lysines, hydrogen-deuterium exchange, or other forms of modification. In this report, both limited proteolysis and chemical modification were combined with several mass spectrometric techniques in efforts to define the protein surface on the HIV core protein, p24, recognized by two different monoclonal human antibodies that were isolated from HIV+ patients. One of these antibodies, 1571, strongly inhibits the CD4(+) T cell proliferative response to a known epitope (PEVIPMFSALSEGATP), while the other antibody, 241-D, does not inhibit as strongly. The epitopes for both of these antibodies were determined to be discontinuous and localized to the N-terminus of p24. Interestingly, the epitope recognized by the strongly inhibiting antibody, 1571, completely overlaps the T cell epitope PEVIPMFSALSEGATP, while the antibody 241-D binds to a region adjacent to the region of p24 recognized by the antibody 1571. These results suggest that, possibly due to epitope competition, antibodies produced during HIV infection can negatively affect CD4(+) T cell-mediated immunity against the virus. C1 NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NYU, Sch Med, New York Vet Affairs Med Ctr, New York, NY USA. NYU, Sch Med, Dept Pathol, New York, NY USA. Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,MD F0-03, Res Triangle Pk, NC 27709 USA. EM tomer@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS; NIAID NIH HHS [K08 AI001698, AI-48371] NR 45 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD NOV PY 2006 VL 17 IS 11 BP 1560 EP 1569 DI 10.1016/j.jasms.2006.06.011 PG 10 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 108MC UT WOS:000242242900011 PM 16875837 ER PT J AU Harris, PC Bae, KT Rossetti, S Torres, VE Grantham, JJ Chapman, AB Guay-Woodford, LM King, BF Wetzel, LH Baumgarten, DA Kenney, PJ Consugar, M Klahr, S Bennett, WM Meyers, CM Zhang, Q Thompson, PA Zhu, F Miller, JP AF Harris, Peter C. Bae, Kyongtae T. Rossetti, Sandro Torres, Vicente E. Grantham, Jared J. Chapman, Arlene B. Guay-Woodford, Lisa M. King, Bernard F. Wetzel, Louis H. Baumgarten, Deborah A. Kenney, Philip J. Consugar, Mark Klahr, Saulo Bennett, William M. Meyers, Catherine M. Zhang, Qin (Jean) Thompson, Paul A. Zhu, Fang Miller, J. Philip CA CRISP Consortium TI Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Nephrology CY NOV 17, 2006 CL San Diego, CA SP Amer Soc Nephrol ID PKD1 GENE; RENAL-FUNCTION; CELLS; PROGRESSION; EXPRESSION; SEVERITY; ENCODES; PROTEIN; TYPE-2; MODEL AB Data from serial renal magnetic resonance imaging of the Consortium of Radiologic Imaging Study of PKD (CRISP) autosomal dominant polycystic kidney disease (PKD) population showed that cystic expansion occurs at a consistent rate per individual, although it is heterogeneous in the population, and that larger kidneys are associated with more rapid disease progression. The significance of gene type to disease progression is analyzed in this study of the CRISP cohort. Gene type was determined in 183 families (219 cases); 156 (85.2%) had PKD1, and 27 (14.8%) had PKD2. PKD1 kidneys were significantly larger, but the rate of cystic growth (PKD1 5.68%/yr; PKD2 4.82%/yr) was not different (P = 0.24). Cyst number increased with age, and more cysts were detected in PKD1 kidneys (P < 0.0001). PKD1 is more severe because more cysts develop earlier, not because they grow faster, implicating the disease gene in cyst initiation but not expansion. These insights will inform the development of targeted therapies in autosomal dominant PKD. C1 Mayo Clin, Coll Med, Div Nephrol & Hypertens, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Radiol, Rochester, MN 55905 USA. Washington Univ, Sch Med, Dept Med Radiol, St Louis, MO 63130 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63130 USA. Univ Kansas, Med Ctr, Kidney Inst, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. Emory Univ, Sch Med, Div Nephrol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Univ Alabama, Div Genet & Translat Med, Birmingham, AL USA. Univ Alabama, Dept Radiol, Birmingham, AL USA. Legacy Good Samaritan Hosp, Portland, OR USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Harris, PC (reprint author), Mayo Clin, Coll Med, Div Nephrol & Hypertens, 200 1st St SW, Rochester, MN 55905 USA. EM harris.peter@mayo.edu OI Miller, J Philip/0000-0003-4568-6846 FU NIDDK NIH HHS [DK56934, DK56957-S1, DK56956, DK56957, DK56961] NR 41 TC 99 Z9 106 U1 0 U2 2 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2006 VL 17 IS 11 BP 3013 EP 3019 DI 10.1681/ASN.2006080835 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 103UL UT WOS:000241912100012 PM 17035604 ER PT J AU Liu, YM Berthier-Schaad, Y Plantinga, L Fink, NE Tracy, RP Kao, WH Klag, MJ Smith, MW Coresh, J AF Liu, Yongmei Berthier-Schaad, Yvette Plantinga, Laura Fink, Nancy E. Tracy, Russell P. Kao, Wen Hong Klag, Michael J. Smith, Michael W. Coresh, Josef TI Functional variants in the lymphotoxin-alpha gene predict cardiovascular disease in dialysis patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CORONARY-ARTERY-DISEASE; SINGLE-NUCLEOTIDE POLYMORPHISMS; MYOCARDIAL-INFARCTION; LINKAGE-DISEQUILIBRIUM; BETA PRODUCTION; TNF LOCUS; RISK; ASSOCIATION; POPULATION AB TNF-beta that is encoded by lymphotoxin-alpha gene (LTA) regulates adhesion molecules and IL-6. Previously, a genome-wide case-control study showed that LTA gene variants predisposed to cardiovascular disease (CVD). In a prospective study of 775 dialysis patients, LTA and IL-6 gene variants were tested as independent predictors of CVD risk. Four polymorphisms in the LTA gene and one in the IL-6 gene were genotyped. CVD events were ascertained from medical records. During a mean follow-up of 2.6 yr, 294 first-incident CVD events occurred. The LTA 26Asn variant predicted higher adjusted CVD risk (hazard ratio HR 1.33 for each additional copy of Asn allele; 95% confidence interval 1.14 to 1.55; P = 0.0003). Two other nonsynonymous polymorphisms in the LTA, 13Agr and 51Pro, were associated with lower inflammatory activity and CVD risk. LTA haplotypes (based on all four single-nucleotide polymorphisms) were associated with inflammatory markers and predicted CVD risk (P = 0.005) after adjustment. These LTA genotype associations were independent of the IL-6 -174G/C genotype association that was reported recently. LTA and IL-6 gene variants independently predicted risk for CVD among dialysis patients, suggesting that susceptibility in multiple inflammatory pathways contribute to the development of CVD. C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NCI, Lab Genomic Divers, SAIC Frederick, Frederick, MD USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD USA. Univ Vermont, Burlington, VT USA. RP Coresh, J (reprint author), Johns Hopkins Univ, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA. EM coresh@jhu.edu RI Smith, Michael/B-5341-2012 FU AHRQ HHS [R01-HS-08365]; Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [R01-HL-62985, HL 46696, HL 58329]; NIDDK NIH HHS [R01-DK-59616, K24-DK-02856] NR 27 TC 8 Z9 8 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2006 VL 17 IS 11 BP 3158 EP 3166 DI 10.1681/ASN.2006030299 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 103UL UT WOS:000241912100028 PM 16988060 ER PT J AU Ron, E AF Ron, Elaine TI Childhood cancer - Treatment at a cost SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MODULATED RADIATION-THERAPY; 2ND CANCERS; SURVIVOR; RISK; TUMOR C1 NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ron, E (reprint author), NCI, Radiat Epidemiol Branch, NIH, MS7238,6120 Execut Blvd,Rm 7054, Bethesda, MD 20892 USA. EM eron@mail.nih.gov NR 20 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 1 PY 2006 VL 98 IS 21 BP 1510 EP 1511 DI 10.1093/jnci/djj437 PG 2 WC Oncology SC Oncology GA 110LE UT WOS:000242379600002 PM 17077348 ER PT J AU Carter, HB Ferrucci, L Kettermann, A Landis, P Wright, EJ Epstein, JI Trock, BJ Metter, EJ AF Carter, H. Ballentine Ferrucci, Luigi Kettermann, Anna Landis, Patricia Wright, E. James Epstein, Jonathan I. Trock, Bruce J. Metter, E. Jeffrey TI Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RADICAL PROSTATECTOMY; PSA VELOCITY; MEN; FEATURES; DISEASE; LEVEL; NG/ML; TIMES AB Background. Prostate-specific antigen (PSA) level is typically used as a dichotomous test for prostate cancer, resulting in overdiagnosis for a substantial number of men. The rate at which serum PSA levels change (PSA velocity) may be an important indicator of the presence of life-threatening disease. Methods: PSA velocity was determined in 980 men (856 without prostate cancer, 104 with prostate cancer who were alive or died of another cause, and 20 who died of prostate cancer) who were participants in the Baltimore Longitudinal Study of Aging for up to 39 years. The relative risks (RRs) of prostate cancer death and prostate cancer-specific survival stratified by PSA velocity were evaluated in the three groups of men by Cox regression and Kaplan-Meier analyses. Statistical tests were two-sided. Results: PSA velocity measured 10-15 years before diagnosis (when most men had PSA levels below 4.0 ng/mL) was associated with cancer-specific survival 25 years later; survival was 92% (95% confidence interval [CI] = 84% to 96%) among men with PSA velocity of 0.35 ng/mL per year or less and 54% (95% Cl = 15% to 82%) among men with PSA velocitv above 0.35 ng/mL per year (P <.001). Furthermore, men with PSA velocity above 0.35 ng/mL per year had a higher relative risk of prostate cancer death than men with PSA velocity of 0.35 ng/mL per year or less (RR = 4.7, 95% CI = 1.3 to 16.5; P =.02); the rates per 100 000 person-years were 1240 for men with a PSA velocity above 0.35 ng/mL per year and 140 for men with a PSA velocity of 0.35 ng/mL per year or less. Conclusions: PSA velocitv may help identify men with life-threatening prostate cancer during a period when their PSA levels are associated with the presence of curable disease. C1 Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst,John Hopkins Hosp, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, James Buchanan Brady Urol Inst,John Hopkins Hosp, Baltimore, MD 21287 USA. NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Carter, HB (reprint author), Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst,John Hopkins Hosp, 600 N Wolfe St,Marburg 403, Baltimore, MD 21287 USA. EM hcarter@jhmi.edu FU Intramural NIH HHS [Z01 AG000015-49] NR 22 TC 201 Z9 207 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 1 PY 2006 VL 98 IS 21 BP 1521 EP 1527 DI 10.1093/jnci/djj410 PG 7 WC Oncology SC Oncology GA 110LE UT WOS:000242379600007 PM 17077354 ER PT J AU Neglia, JP Robison, LL Stovall, M Liu, Y Packer, RJ Hammond, S Yasui, Y Kasper, CE Mertens, AC Donaldson, SS Meadows, AT Inskip, PD AF Neglia, Joseph P. Robison, Leslie L. Stovall, Marilyn Liu, Yan Packer, Roger J. Hammond, Sue Yasui, Yutaka Kasper, Catherine E. Mertens, Ann C. Donaldson, Sarah S. Meadows, Anna T. Inskip, Peter D. TI New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the childhood cancer survivor study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; 2ND MALIGNANT NEOPLASMS; SECONDARY BRAIN-TUMORS; IONIZING-RADIATION; 5-YEAR SURVIVORS; RADIOTHERAPY; CHILDREN; EXPOSURE; MEDULLOBLASTOMA; ADOLESCENCE AB Background: Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the dose-response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined. Methods: Subsequent primary neoplasms of the CNS occurring within a cohort of 14361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site-specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data. Results: Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% Cl = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 [95% CI = 0.07 to 1.71] per Gy, and for meningioma, slope = 1.06 [95% Cl = 0.21 to 8.15] per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10000 person-years. Conclusions: Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation. C1 Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Fred Hutchinson Canc Res Ctr, Dept Publ Hlth Stat, Seattle, WA 98104 USA. George Washington Univ, Washington, DC USA. Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. Childrens Hosp, Dept Lab Med, Columbus, OH 43205 USA. Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB, Canada. Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Neglia, JP (reprint author), MMC 484,420 Delaware St SE, Minneapolis, MN 55455 USA. EM jneglia@umn.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU Intramural NIH HHS; PHS HHS [U24 55727] NR 26 TC 239 Z9 244 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 1 PY 2006 VL 98 IS 21 BP 1528 EP 1537 DI 10.1093/jnci/djj411 PG 10 WC Oncology SC Oncology GA 110LE UT WOS:000242379600008 PM 17077355 ER PT J AU Christiani, DC Pao, W DeMartini, JC Linnoila, RI Malkinson, AM Onn, A Politi, KA Sharp, M Kwok-Kim AF Christiani, David C. Pao, William DeMartini, James C. Linnoila, R. Ilona Malkinson, Alvin M. Onn, Amir Politi, Katerina A. Sharp, Michael Kwok-Kim TI BAC Consensus Conference, November 4-6. 2004: Epidemiology, pathogenesis, and preclinical models SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Bronchioloalveolar Cell Carcinoma (BAC) CY NOV 04-06, 2004 CL New York, NY SP Int Assoc Study Lung Canc, Amer Soc Clin Oncol DE bronchioloalveolar carcinoma; preclinical models; epidemiology; pathogenesis; lung cancer ID JAAGSIEKTE SHEEP RETROVIRUS; OVINE PULMONARY ADENOCARCINOMA; HUMAN LUNG-CANCER; K-RAS ONCOGENE; EPIDERMAL-GROWTH-FACTOR; ATHYMIC NUDE-MICE; BRONCHIOLOALVEOLAR CARCINOMA; CONDITIONAL EXPRESSION; CELL-LINE; BUTYLATED HYDROXYTOLUENE AB Introduction: Human bronchioloalveolar carcinoma (BAC) is a disease with an evolving definition. "Pure" BAC, characterized by a bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion, represents only 2 to 6% of non-small cell lung cancer (NSCLC) cases, but up to 20% of NSCLC cases may contain elements of BAC. This imprecise definition makes it difficult to perform epidemiologic analyses or to generate accurate animal models. However, because BAC appears to behave clinically differently from adenocarcinoma, a better understanding of this disease entity is imperative. Methods/Results: At the BAC Consensus Conference in 2004, our committee discussed issues relevant to BAC epidemiology, pathogenesis, and preclinical models. Conclusions: Elucidation of molecular events involved in BAC tumorigenesis will allow for more precise epidemiologic studies and improved animal models, which will enable development of more effective treatments against the disease. C1 Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10021 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. NCI, Rockville, MD USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Texas, MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. Vet Labs Agcy, Dept Pathol, Penicuik, Midlothian, Scotland. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pao, W (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, 1275 York Ave, New York, NY 10021 USA. EM paow@mskcc.org RI Sharp, Mike/D-1467-2009; APHA, Staff publications/E-6082-2010 FU NCI NIH HHS [CA 092824, CA 074386, CA 0940578, CA 59116]; NIA NIH HHS [K08AG 2400401] NR 80 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2006 VL 1 IS 9 SU S BP S2 EP S7 DI 10.1097/01243894-200611001-00002 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 110AM UT WOS:000242350700002 PM 17409996 ER PT J AU Gandara, DR Aberle, D Lau, D Jett, J Akhurst, T Mulshine, J Berg, C Patz, EF AF Gandara, David R. Aberle, Denise Lau, Derick Jett, James Akhurst, Tim Mulshine, James Berg, Christine Patz, Edward F., Jr. TI Radiographic imaging of bronchioloalveolar carcinoma: Screening, patterns of presentation and response assessment SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Bronchioloalveolar Cell Carcinoma (BAC) CY NOV 04-06, 2004 CL New York, NY SP Int Assoc Study Lung Canc, Amer Soc Clin Oncol ID GROUND-GLASS OPACITY; HIGH-RESOLUTION CT; POSITRON-EMISSION-TOMOGRAPHY; HELICAL COMPUTED-TOMOGRAPHY; CELL LUNG-CANCER; DOSE SPIRAL CT; PATHOLOGICAL CORRELATION; PROGNOSTIC-SIGNIFICANCE; FOLLOW-UP; BASE-LINE AB Bronchioloalveolar carcinoma (BAC) is a previously uncommon subset of adenocarcinoma with unique epidemiology, pathology, radiographic presentation, clinical features, and natural history compared with other non-small cell lung cancer (NSCLC) subtypes. Classically, BAC demonstrates a relatively slow growth pattern and indolent clinical course. However, in a subset of patients, rapid growth and death from bilateral diffuse consolidative disease occurs within months of diagnosis or recurrence. Recent data suggest that the incidence of BAC is increasing, notably in younger nonsmoking women. The initial radiographic presentation of BAC varies considerably, from single ground glass opacities (GGOs) or nodules of mixed ground glass and solid attenuation to diffuse consolidative or bilateral multinodular disease. The rising incidence of BAC is also reflected in recent lung cancer screening studies employing helical computed tomography (CT), where the differential diagnosis of GGOs includes not only BAC and overt adenocarcinoma, but inflammatory disease, focal fibrosis, and atypical adenomatous hyperplasia. Because advanced-stage BAC presents as measurable mass lesions in fewer than 50% of cases, determination of radiographic response to therapy by standard criteria is often difficult. Here, we review current data regarding the radiographic imaging of BAC: its radiographic presentations in asymptomatic early-stage and in advanced-stage disease, the functional imaging characteristics of BAC, and challenges of response assessment, including evolving opportunities for computer-assisted image analysis. C1 Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Univ Calif Los Angeles, DAvid Geffen Sch Med, Los Angeles, CA USA. Mayo Sch Med, Rochester, MN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. RP Gandara, DR (reprint author), Univ Calif Davis, Med Ctr, Dept Internal Med, Hematol Oncol Canc Ctr, Sacramento, CA 95817 USA. EM david.gandara@ucdmc.ucdavis.edu NR 65 TC 34 Z9 36 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2006 VL 1 IS 9 SU S BP S20 EP S26 DI 10.1097/01243894-200611001-00005 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 110AM UT WOS:000242350700005 PM 17409997 ER PT J AU Yu, JS Liao, HX Gerdon, AE Huffman, B Scearce, RM McAdams, M Alam, SM Popernack, PM Sullivan, NJ Wright, D Cliffel, DE Nabel, GJ Haynes, BF AF Yu, Jae-Sung Liao, Hua-Xin Gerdon, Aren E. Huffman, Brian Scearce, Richard M. McAdams, Mille Alam, S. Munir Popernack, Paul M. Sullivan, Nancy J. Wright, David Cliffel, David E. Nabel, Gary J. Haynes, Barton F. TI Detection of Ebola virus envelope using monoclonal and polyclonal antibodies in ELISA, surface plasmon resonance and a quartz crystal microbalance immunosensor SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Ebola virus; glycoprotein detection; monoclonal antibody; surface plasmon resonance; quartz crystal microbalance immunosensor ID LINKED-IMMUNOSORBENT-ASSAY; SUBTYPE RESTON VIRUS; VIRION GLYCOPROTEINS; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; ANTIGEN; GP; IDENTIFICATION; CYTOTOXICITY; PHILIPPINES AB Ebola virus (EBOV) Zaire, Sudan, as well as Ivory Coast are virulent human EBOV species. Both polyclonal and monoclonal antibodies (MAbs) were developed against soluble EBOV envelope glycoprotein (GP) for the study of EBOV envelope diversity and development of diagnostic reagents. Three EBOV Sudan-Gulu GP peptides, from the N-terminus, mid-GP, and C-terminus regions were used to immunize rabbits for the generation of anti-EBOV polyclonal antibodies. Polyclonal antisera raised against the C-terminus peptide could detect both Sudan-Gulu as well as Zaire GPs, while anti-N and mid-region peptide polyclonal sera recognized only EBOV Sudan-Gulu GP. Of the three anti-EBOV GP mouse MAbs produced. MAb 15H10 recognized all human EBOV GP species tested (Zaire, Sudan and Ivory Coast), and as well as reacted with the Reston non-human primate BBOV GPs. In addition, MAb 15H10 bound virion-associated GP of all known EBOV species. MAb 17A3 recognized GPs of both EBOV Sudan-Gulu and Zaire, while MAb 6D11 recognized only EBOV Sudan-Gulu GP. To detect EBOV GP, these antibody reagents were used in ELISA, surface plasmon resonance and in a quartz crystal microbalance immunosensor. Thus, polyclonal and monoclonal antibodies can be used in combination to identify and differentiate both human and non-human primate EBOV GPs. (c) 2006 Elsevier B.V. All rights reserved. C1 Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC 27710 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA. RP Yu, JS (reprint author), Duke Univ, Med Ctr, Human Vaccine Inst, 214 CARL Bldg,Res Dr, Durham, NC 27710 USA. EM yu000022@mc.duke.edu; hayne002@mc.duke.edu FU NIAID NIH HHS [U54 AI 057157]; NIGMS NIH HHS [T32 GM065086] NR 38 TC 26 Z9 29 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2006 VL 137 IS 2 BP 219 EP 228 DI 10.1016/j.jviromet.2006.06.014 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 097FM UT WOS:000241432400007 PM 16857271 ER PT J AU Bukreyev, A Skiadopoulos, MH Murphy, BR Collins, PL AF Bukreyev, Alexander Skiadopoulos, Mario H. Murphy, Brian R. Collins, Peter L. TI Nonsegmented negative-strand viruses as vaccine vectors SO JOURNAL OF VIROLOGY LA English DT Review ID VESICULAR STOMATITIS-VIRUS; RESPIRATORY SYNCYTIAL VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; NEWCASTLE-DISEASE VIRUS; AFRICAN-GREEN MONKEYS; PROVIDES COMPLETE PROTECTION; CELLULAR IMMUNE-RESPONSES; RECOMBINANT RABIES VIRUS; L-POLYMERASE PROTEIN; ATTENUATION IN-VIVO C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Bukreyev, A (reprint author), NIAID, NIH, Bldg 50,Room 6505,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. EM AB176v@nih.gov FU Intramural NIH HHS NR 137 TC 58 Z9 58 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2006 VL 80 IS 21 BP 10293 EP 10306 DI 10.1128/JVI.00919-06 PG 14 WC Virology SC Virology GA 099OZ UT WOS:000241606100001 PM 17041210 ER PT J AU Emerson, SU Nguyen, H Torian, U Purcell, RH AF Emerson, Suzanne U. Nguyen, Hanh Torian, Udana Purcell, Robert H. TI ORF3 protein of hepatitis E virus is not required for replication, virion assembly, or infection of hepatoma cells in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID CIS-REACTIVE ELEMENT; MONOCLONAL-ANTIBODIES; CAPSID PROTEIN; HEV; NEUTRALIZATION; INTERACTS; GENOMES AB A subclone of Huh-7 cells that could be relatively efficiently transfected and infected with hepatitis E virus was identified. Following transfection, infectious virus was produced but remained predominantly cell associated. Intracellular virus, recovered by lysis of transfected cells, infected naive cells. This in vitro-produced virus appeared to be antigenically identical to virus isolated from clinical samples. Lysates from cells transfected with mutant viral genomes unable to synthesize ORF3 protein contained infectious virions that were similar in number, thermostability, and sedimentation characteristics to those in lysates transfected with wild-type viral genomes. Therefore, in contrast to its requirement in vivo, ORF3 protein is not required for infection of Huh-7 cells or production of infectious virus in vitro. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6537,50 S Dr,MSC 8009, Bethesda, MD 20892 USA. EM semerson@niaid.nih.gov FU Intramural NIH HHS NR 23 TC 61 Z9 61 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 NOV PY 2006 VL 80 IS 21 BP 10457 EP 10464 DI 10.1128/JVI.00892-06 PG 8 WC Virology SC Virology GA 099OZ UT WOS:000241606100016 PM 16928762 ER PT J AU Ravichandran, V Sabath, BF Jensen, PN Houff, SA Major, EO AF Ravichandran, Veerasarny Sabath, Bruce F. Jensen, Peter N. Houff, Sidney A. Major, Eugene O. TI Interactions between c-Jun, nuclear factor 1, and JC virus promoter sequences: Implications for viral tropism SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HEMATOPOIETIC PROGENITOR CELLS; HUMAN NEUROTROPIC VIRUS; CELLULAR PROTEINS YB-1; DNA-BINDING DOMAIN; HUMAN POLYOMAVIRUS; REGULATORY REGION; STROMAL CELLS; GLIAL-CELLS; T-ANTIGEN AB The infectious cycle of the human polyornavirus JC (JCV) is ultimately regulated in cellular nuclei at the level of viral protein expression and genomic replication. Such activity is prompted by interactions between variant nucleotide sequences within the JCV regulatory region (promoter) and cellular transcription factors that bind specific DNA consensus sites. In previous work we identified an NF-1 class member, NF-1X, as a critical transcription factor affecting the JCV cellular host range. Within variant JCV promoters, as well as other viral and cellular promoters, adjacently located NF-1 and AP-1 consensus sites are often found. The close proximity of these two binding sites suggests the opportunity for interaction between NF-1 and AP-1 proteins. Here, by electrophoretic mobility shift assays, we show temporal and dose-dependent interference by an AP-1 family member, c-Jun, upon NF-1 proteins binding an NF-1 consensus site derived from JCV promoter sequence. Moreover, as demonstrated by protein-protein interaction assays, we identify specific binding affinity independent of DNA binding between NF-1X and c-Jun. Finally, to compare the binding profiles of NF-1X and c-Jun on JCV promoter sequence in parallel with in vivo detection of viral activity levels, we developed an anchored transcriptional promoter (ATP) assay. With use of extracts from JCV-infected cells transfected to overexpress either NF-1X or c-Jun, ATP assays showed concurrent increases in NF-1X binding and viral protein expression. Conversely, increased c-Jun binding accompanied decreases in both NF-1X binding and viral protein expression. Therefore, inhibition of NF-1X binding by c-Jun appears to play a role in regulating levels of JCV activity. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, 10 Ctr Dr,Bldg 10,Room 3B14,MSC1296, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov FU Intramural NIH HHS NR 35 TC 21 Z9 21 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 NOV PY 2006 VL 80 IS 21 BP 10506 EP 10513 DI 10.1128/JVI.01355-06 PG 8 WC Virology SC Virology GA 099OZ UT WOS:000241606100021 PM 16928756 ER PT J AU Okazaki, T Terabe, M Catanzaro, AT Pendleton, CD Yarchoan, R Berzofsky, JA AF Okazaki, Takahiro Terabe, Masaki Catanzaro, Andrew T. Pendleton, C. David Yarchoan, Robert Berzofsky, Jay A. TI Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; HIGH-LEVEL RESISTANCE; IN-VITRO; HIV-1; RECOGNITION; IMMUNOGENICITY; IDENTIFICATION; INDUCTION; PROTEIN; EPITOPE AB Mutation of human immunodeficiency virus (HIV) leading to escape from anti-HIV drugs is the greatest challenge to the treatment of HIV infection. High-grade resistance to the nucleoside reverse transcriptase (RT) inhibitor lamivudine (also known as 3TC) is associated with a substitution of valine for methionine at position 184 of RT. This amino acid residue is contained within the HLA-A2-restricted epitope VIYQYMDDL (RT-WT). Here, we sought to determine whether a peptide vaccine could be developed using an epitope enhancement strategy that could induce a cytotoxic T-lymphocyte (CTL) response specific for an epitope containing the drug resistance mutation M184V to exert an opposing selective pressure. RT-WT-specific CTLs developed from HLA-A2 transgenic mice did not recognize the M184V mutation of RT-WT (RT-M184V). However, RT-M184V exhibited higher binding affinity for HLA-A2 than RT-WT. Also, both anchor-enhanced RT-WT (RT-2L9V) and RT-2L9V-M184V-specific CTLs recognized RT-M184V and displayed cross-reactivity to RT-WT. Nevertheless, the CTL repertoire elicited by the epitope-enhanced RT-2L9V-MI84V appeared more selective for the RT inhibitor-induced M184V mutation. Peptide vaccines based on such strategies may be worth testing for their ability to exert selective pressure against drug-resistant strains and thus delay or prevent the development of HIV with the M184V resistance mutation. C1 NCI, Ctr Canc Res, Vaccine Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Ctr Canc Res, Vaccine Branch, NIH, Bldg 10,Room 6B-04 MSC 1578, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov FU Intramural NIH HHS NR 22 TC 11 Z9 11 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 NOV PY 2006 VL 80 IS 21 BP 10645 EP 10651 DI 10.1128/JVI.01351-05 PG 7 WC Virology SC Virology GA 099OZ UT WOS:000241606100034 PM 16920824 ER PT J AU Gilbert, J Ou, W Silver, J Benjamin, T AF Gilbert, Joanna Ou, Wu Silver, Jonathan Benjamin, Thomas TI Downregulation of protein disulfide isomerase inhibits infection by the mouse polyomavirus SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; CAVEOLAR ENDOCYTOSIS; SIMIAN-VIRUS-40; VIRUS; TRANSPORT; PATHWAY AB Early stages of infection by the mouse polyomavirus have been studied using HeLa cells stably expressing small interfering RNA to protein disulfide isomerase (PDI). Infectibility measured by nuclear T antigen expression was reduced commensurately with the degree of PDI downregulation. Infectibillity was restored by transfection with a plasmid expressing PDI but not with a control expressing catalytically inactive enzyme. Deconvolution microscopy using fluorescently labeled virus and cellular markers showed that virus reaches the endoplasmic reticulum (ER) normally in cells with reduced PDI but subsequently fails to exit the ER. Simian virus 40 infection was not inhibited in PDI-down regulated cells. The results are discussed in terms of structural differences between the two viruses and current knowledge of virus disassembly in the ER. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Benjamin, T (reprint author), Harvard Univ, Sch Med, Dept Pathol, NRB 9391,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM thomas_benjamin@hms.harvard.edu FU NCI NIH HHS [R01 CA-082395, R01 CA082395] NR 13 TC 49 Z9 49 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2006 VL 80 IS 21 BP 10868 EP 10870 DI 10.1128/JVI.01117-06 PG 3 WC Virology SC Virology GA 099OZ UT WOS:000241606100057 PM 16928750 ER PT J AU Sun, Y Schmitz, JE Buzby, AP Barker, BR Rao, SS Xu, L Yang, ZY Mascola, JR Nabel, GJ Letvin, NL AF Sun, Yue Schmitz, Jorn E. Buzby, Adam P. Barker, Brianne R. Rao, Srinivas S. Xu, Ling Yang, Zhi-yong Mascola, John R. Nabel, Gary J. Letvin, Norman L. TI Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge SO JOURNAL OF VIROLOGY LA English DT Article ID CD8(+) T-CELLS; RHESUS-MONKEYS; CENTRAL MEMORY; HIV VACCINE; LYMPHOCYTES; SUBSETS; GENERATION; INFECTION; RESPONSES; VIREMIA AB Understanding the characteristics of the virus-specific T-lymphocyte response that will confer optimal protection against the clinical progression of AIDS will inform the development of an effective cellular immunity-based human immunodeficiency virus vaccine. We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4(+) T lymphocytes and robust gamma interferon (IFN-gamma) -producing SIV-specific CD8(+) and CD4(+) T-lymphocyte responses. The present studies were initiated to extend these observations to determine which virus-specific T-lymphocyte subpopulations play a primary role in controlling disease progression and to characterize the functional repertoire of these cells. We show that the preservation of the SIV-specific central memory CD8(+) T-lymphocyte population and a linked SIV-specific CD4(+) T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge. Furthermore, we demonstrate that SIV-specific IFN-gamma-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression. These findings underscore the contribution of virus-specific central memory T lymphocytes to controlling clinical progression in vaccinated individuals following a primate immunodeficiency virus infection. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02215 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, RE113, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu OI Barker, Brianne/0000-0001-6932-479X FU Intramural NIH HHS; NIAID NIH HHS [AI060354, P30 AI060354] NR 29 TC 45 Z9 45 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 NOV PY 2006 VL 80 IS 22 BP 10950 EP 10956 DI 10.1128/JVI.01458-06 PG 7 WC Virology SC Virology GA 102OI UT WOS:000241821300005 PM 16943292 ER PT J AU Adamson, CS Ablan, SD Boeras, I Goila-Gaur, R Soheilian, F Nagashima, K Li, F Salzwedel, K Sakalian, M Wild, CT Freed, EO AF Adamson, Catherine S. Ablan, Sherimay D. Boeras, Ioana Goila-Gaur, Ritu Soheilian, Ferri Nagashima, Kunio Li, Feng Salzwedel, Karl Sakalian, Michael Wild, Carl T. Freed, Eric O. TI In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat) SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 GAG POLYPROTEIN; MEMBRANE-BINDING; CAPSID PROTEIN; BETULINIC ACID; AMINO-ACID; PARTICLE MATURATION; DIMERIZATION DOMAIN; VIRION MATURATION; HELICAL STRUCTURE; CLEAVAGE SITES AB 3-O-(3',3'-dimethylsuceinyl)betulinic acid (PA-457 or bevirimat) potently inhibits human immunodeficiency virus type 1 (HIV-1) maturation by blocking a late step in the Gag processing pathway, specifically the cleavage of SP1 from the C terminus of capsid (CA). To gain insights into the mechanism(s) by which HIV-1 could evolve resistance to PA-457 and to evaluate the likelihood of such resistance arising in PA-457-treated patients, we sought to identify and characterize a broad spectrum of HIV-1 variants capable of conferring resistance to this compound. Numerous independent rounds of selection repeatedly identified six single-amino-acid substitutions that independently confer PA-457 resistance: three at or near the C terminus of CA (CA-H226Y, -L231F, and -L231M) and three at the first and third residues of SP1 (SP1-A1V, -A3T, and -A3V). We determined that mutations CA-H226Y, CA-L231F, CA-L231M, and SP1-A1V do not impose a significant replication defect on HIV-1 in culture. In contrast, mutations SP1-A3V and -A3T severely impaired virus replication and inhibited virion core condensation. The replication defect imposed by SP1-A3V was reversed by a second-site compensatory mutation in CA (CA-G225S). Intriguingly, high concentrations of PA-457 enhanced the maturation of SP1 residue 3 mutants. The different phenotypes associated with mutations that confer PA-457 resistance suggest the existence of multiple mechanisms by which HIV-1 can evolve resistance to this maturation inhibitor. These findings have implications for the ongoing development of PA-457 to treat HIV-1 infection in vivo. C1 NCI Frederick, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. NCI Frederick, Image Anal Lab, Res Technol Program, SAIC Frederick, Frederick, MD 21702 USA. Panacos Pharmaceut Inc, Gaithersburg, MD 20877 USA. RP Freed, EO (reprint author), NCI Frederick, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535,Rm 108,1050 Boyles St, Frederick, MD 21702 USA. EM efreed@nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 48 TC 65 Z9 69 U1 1 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 NOV PY 2006 VL 80 IS 22 BP 10957 EP 10971 DI 10.1128/JVI.01369-06 PG 15 WC Virology SC Virology GA 102OI UT WOS:000241821300006 PM 16956950 ER PT J AU Ferrucci, L Simonsick, EM AF Ferrucci, Luigi Simonsick, Eleanor M. TI A little exercise SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID LOWER-EXTREMITY FUNCTION; HEALTHY OLDER-ADULTS; SUBSEQUENT DISABILITY; PHYSICAL PERFORMANCE; SKELETAL-MUSCLE; BODY-COMPOSITION; CONTROLLED-TRIAL; GAIT SPEED; STRENGTH; TRENDS C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA ASTRA Unit, 3001 S Hanover St,NM540, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 23 TC 5 Z9 5 U1 8 U2 8 PU GERONTOLOGICAL SOCIETY 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 NOV PY 2006 VL 61 IS 11 BP 1154 EP 1156 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120WZ UT WOS:000243118800006 PM 17167155 ER PT J AU Motivala, SJ Sollers, J Thayer, J Irwin, MR AF Motivala, Sarosh J. Sollers, John Thayer, Julian Irwin, Michael R. TI Tai Chi Chih acutely decreases sympathetic nervous system activity in older adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CARDIOVASCULAR-RESPONSES; AEROBIC EXERCISE; STRESS; REACTIVITY; ZOSTER; VIRUS; CHUAN; WOMEN AB Background. Aging is associated with increases of sympathetic nervous system activation implicated in the onset of hypertension and cardiovascular disease. The purpose of this study was to examine whether the practice of Tai Chi Chih (TCC), a movement-based relaxation practice, would acutely promote decreases of sympathetic activity in elderly persons. Method. The sample included two groups of older men and women (age >= 60 years): TCC practitioners (n = 19) and TCC-naive participants (n = 13). Participants were recruited after completing a 25-week randomized trial of TCC or health education. TCC practitioners performed TCC for 20 minutes, and TCC-naive participants passively rested. Preejection period, blood pressure, and heart rate were measured before and after the task. A subsample (n = 8) returned for a second evaluation and performed videotape-guided stretching for 20 minutes to evaluate the effects of slow-moving physical activity on sympathetic activity. Results. Results showed that TCC performance significantly. decreased sympathetic activity as indexed by preejection period (p =.01). In contrast, there was no change in preejection period following passive rest or slow-moving physical activity. Neither blood pressure nor heart rate changed after TCC performance. Discussion. This study is the first to our knowledge to assess the acute effects of TCC practice on sympathetic activity in older adults. TCC performance led to acute decreases in sympathetic activity, which could not be explained by physical activity alone. Further study is needed to determine whether the acute salutary effects of TCC on autonomic functioning are sustained with ongoing practice in older adults. C1 Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA. NIA, Emot & Quantitat Psychophysiol Sect, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Motivala, SJ (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Cousins Ctr Psychoneuroimmunol, 300 Med Plaza,Suite 3148, Los Angeles, CA 90095 USA. EM smotivala@mednet.ucla.edu RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU NIA NIH HHS [AG18367]; NIMH NIH HHS [T32-MH19925, MH55253] NR 22 TC 35 Z9 38 U1 1 U2 8 PU GERONTOLOGICAL SOCIETY 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 NOV PY 2006 VL 61 IS 11 BP 1177 EP 1180 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120WZ UT WOS:000243118800010 PM 17167159 ER PT J AU Marsh, AP Miller, ME Saikin, AM Rejeski, WJ Hu, N Lauretani, F Bandinelli, S Guralnik, JM Ferrucci, L AF Marsh, Anthony P. Miller, Michael E. Saikin, Aaron M. Rejeski, W. Jack Hu, Nan Lauretani, Fulvio Bandinelli, Stefania Guralnik, Jack M. Ferrucci, Luigi TI Lower extremity strength and power are associated with 400-meter walk time in older adults: The InCHIANTI study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MUSCLE STRENGTH; FUNCTIONAL PERFORMANCE; PHYSICAL PERFORMANCE; MUSCULAR STRENGTH; LEG EXTENSION; 400 METERS; MOBILITY; WOMEN; SPEED; AGE AB Background. It has been suggested that lower extremity muscle power is more important for physical function in older adults compared to strength, and that there is a nonlinear relationship between power or strength and physical function that might be indicative of a threshold above which the association between muscle function and physical function is no longer evident. This study examined the association between lower extremity strength or power with the time to complete a 400-meter walk, and attempted to identify thresholds within the relationship. Methods. A cross-sectional analysis of a sample of 384 females and 336 males aged >= 65 years from the InCHIANTI study ("Invecchiare in Chianti," i.e., Aging in the Chianti Area) was conducted. Measures included 400-meter walk time, lower extremity strength and power, comorbidities, and sociodemographic variables (age, gender, height, education, cognitive function, depression). Results. Linear regression models showed that both lower extremity strength and power were significant predictors of 400-meter walk time, although power explained marginally more of the variance in 400-meter walk time. Quadratic models of lower extremity strength and power fit the data slightly better than the linear models. Regardless of gender, comorbidities, or normalization scheme for strength and power, the curvilinear form of the relationship between strength or power and 400-meter walk time remained the same. Conclusions. Lower extremity muscle strength and power are both important predictors of the 400-meter walk time. Although curvilinear relationships existed between muscle strength and power and the 400-meter walk time, the data do not indicate a clear threshold for either strength or power above which the performance in the 400-meter walk test plateaus. C1 Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC 27109 USA. Florence Local Hlth Unit, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. RP Marsh, AP (reprint author), Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA. EM marshap@wfu.edu; mmiller@wfubmc.edu RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [P30-AG-021332-01, N01-AG-821336, N01-AG-916413, P30 AG021332]; NIMHD NIH HHS [R01 MD009164] NR 38 TC 49 Z9 51 U1 1 U2 8 PU GERONTOLOGICAL SOCIETY 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 NOV PY 2006 VL 61 IS 11 BP 1186 EP 1193 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120WZ UT WOS:000243118800012 PM 17167161 ER PT J AU Pavkov, ME Knowler, WC Bennett, PH Looker, HC Krakoff, J Nelson, RG AF Pavkov, M. E. Knowler, W. C. Bennett, P. H. Looker, H. C. Krakoff, J. Nelson, R. G. TI Increasing incidence of proteinuria and declining incidence of end-stage renal disease in diabetic Pima Indians SO KIDNEY INTERNATIONAL LA English DT Article DE ACE inhibitors; end-stage renal disease; diabetes mellitus; proteinuria ID BLOOD-PRESSURE; RECEPTOR ANTAGONISTS; TYPE-2 DIABETES/; UNITED-STATES; MELLITUS; NEPHROPATHY; CHILDREN; MORTALITY; ADOLESCENTS; IRBESARTAN AB The introduction of more efficacious treatments for diabetic kidney disease may slow its progression, but evidence for their effectiveness in populations is sparse. We examined trends in the incidence of clinical proteinuria, defined as a urinary protein-to-creatinine ratio > 0.5 g/g, and diabetic end-stage renal disease (ESRD), defined as death from diabetic nephropathy or onset of dialysis, in Pima Indians with type 2 diabetes between 1967 and 2002. The study included 2189 diabetic subjects >= 25 years old. During follow-up, 366 incident cases of proteinuria occurred in the subset of 1715 subjects without proteinuria at baseline. The age-sex-adjusted incidence rate of proteinuria increased from 24.3 cases/1000 person-years (pyrs) (95% confidence interval (CI) 18.7-30.0) in 1967-1978 to 35.4 cases/1000 pyrs (95% CI 28.1-42.8) in 1979-1990 and 38.9 cases/1000 pyrs (95% CI 31.2-46.5) in 1991-2002 (P-trend < 0.0002). In each period, the age-sex-adjusted incidence of proteinuria increased with diabetes duration, but diabetes duration-specific incidence was stable throughout the study period (P = 0.8). The age-sex-adjusted incidence of ESRD increased between 1967 and 1990 and declined thereafter. The incidence of proteinuria increased over 36 years in Pima Indians as the proportion of people with diabetes of long duration increased. On the other hand, the incidence of ESRD declined after 1990, coinciding with improved control of blood pressure, hyperglycemia, and perhaps other risk factors. C1 NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. RP Pavkov, ME (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM mpavkov@phx.niddk.nih.gov RI Nelson, Robert/B-1470-2012 FU Intramural NIH HHS NR 39 TC 29 Z9 32 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2006 VL 70 IS 10 BP 1840 EP 1846 DI 10.1038/sj.ki.5001882 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 104DO UT WOS:000241936500026 PM 17003816 ER PT J AU Zhou, H Pisitkun, T Aponte, A Yuen, PST Hoffert, JD Yasuda, H Hu, X Chawla, L Shen, RF Knepper, MA Star, RA AF Zhou, H. Pisitkun, T. Aponte, A. Yuen, P. S. T. Hoffert, J. D. Yasuda, H. Hu, X. Chawla, L. Shen, R-F Knepper, M. A. Star, R. A. TI Exosomal Fetuin-A identified by proteomics: A novel urinary biomarker for detecting acute kidney injury SO KIDNEY INTERNATIONAL LA English DT Article DE exosomes; AKI; cisplatin; ischemia; sepsis; mass spectrometry ID ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; ALPHA(2)-HEREMANS-SCHMID GLYCOPROTEIN/FETUIN-A; ACUTE TUBULAR-NECROSIS; INSULIN-RESISTANCE; REPERFUSION INJURY; CARDIAC-SURGERY; PROTEIN; MARKER; SERUM AB Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We aimed to discover biomarkers in urinary exosomes to detect acute kidney injury (AKI), which has a high mortality and morbidity. Animals were injected with cisplatin. Urinary exosomes were isolated by differential centrifugation. Protein changes were evaluated by two-dimensional difference in gel electrophoresis and changed proteins were identified by mass spectrometry. The identified candidate biomarkers were validated by Western blotting in individual urine samples from rats subjected to cisplatin injection; bilateral ischemia and reperfusion (I/R); volume depletion; and intensive care unit (ICU) patients with and without AKI. We identified 18 proteins that were increased and nine proteins that were decreased 8 h after cisplatin injection. Most of the candidates could not be validated by Western blotting. However, exosomal Fetuin-A increased 52.5-fold at day 2 (1 day before serum creatinine increase and tubule damage) and remained elevated 51.5-fold at day 5 (peak renal injury) after cisplatin injection. By immunoelectron microscopy and elution studies, Fetuin-A was located inside urinary exosomes. Urinary Fetuin-A was increased 31.6-fold in the early phase (2-8 h) of I/R, but not in prerenal azotemia. Urinary exosomal Fetuin-A also increased in three ICU patients with AKI compared to the patients without AKI. We conclude that (1) proteomic analysis of urinary exosomes can provide biomarker candidates for the diagnosis of AKI and (2) urinary Fetuin-A might be a predictive biomarker of structural renal injury. C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. NIDDK, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD USA. NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Bldg 10,Room 3N108, Bethesda, MD 20892 USA. EM robert_star@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999, Z01 DK043400-08] NR 43 TC 187 Z9 198 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2006 VL 70 IS 10 BP 1847 EP 1857 DI 10.1038/sj.ki.5001874 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 104DO UT WOS:000241936500027 PM 17021608 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. APHIS, USDA, AC, Washington, DC USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2006 VL 35 IS 10 BP 18 EP 18 DI 10.1038/laban1106-18 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 182QJ UT WOS:000247518800006 PM 17077829 ER PT J AU Fung, HC Scholz, S Matarin, M Simon-Sanchez, J Hernandez, D Britton, A Gibbs, JR Langefeld, C Stiegert, ML Schymick, J Okun, MS Mandel, RJ Fernandez, HH Foote, KD Rodriguez, RL Peckham, E De Vrieze, FW Gwinn-Hardy, K Hardy, JA Singleton, A AF Fung, Hon-Chung Scholz, Sonja Matarin, Mar Simon-Sanchez, Javier Hernandez, Dena Britton, Angela Gibbs, J. Raphael Langefeld, Carl Stiegert, Matt L. Schymick, Jennifer Okun, Michael S. Mandel, Ronald J. Fernandez, Hubert H. Foote, Kelly D. Rodriguez, Ramon L. Peckham, Elizabeth De Vrieze, Fabienne Wavrant Gwinn-Hardy, Katrina Hardy, John A. Singleton, Andrew TI Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data SO LANCET NEUROLOGY LA English DT Article ID EARLY-ONSET; GENE; ASSOCIATION; MUTATIONS AB Background Several genes underlying rare monogenic forms of Parkinson's disease have been identified over the past decade. Despite evidence for a role for genetics in sporadic Parkinson's disease, few common genetic variants have been unequivocally linked to this disorder. We sought to identify any common genetic variability exerting a large effect in risk for Parkinson's disease in a population cohort and to produce publicly available genome-wide genotype data that can be openly mined by interested researchers and readily augmented by genotyping of additional repository subjects. Methods We did genome-wide, single-nucleotide-polymorphism (SNP) genotyping of publicly available samples from a cohort of Parkinson's disease patients (n=267) and neurologically normal controls (n=270). More than 408 000 unique SNPs were used from the Iflumina Infinium, I and HumanHap300 assays. Findings We have produced around 220 million genotypes in 537 participants. This raw genotype data has been publicly posted and as such is the first publicly accessible high-density SNP data outside of the International HapMap Project. We also provide here the results of genotype and allele association tests. Interpretation We generated publicly available genotype data for Parkinson's disease patients and controls so that these data can be mined and augmented by other researchers to identify common genetic variability that results in minor and moderate risk for disease. C1 NIA, Mol Genet Unit, NIH, Computat Biol Core, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC 27109 USA. Univ Florida, Movement Disorders Ctr, Dept Neurol, Gainesville, FL 32611 USA. Univ Florida, Movement Disorders Ctr, Dept Neurosci, Gainesville, FL 32611 USA. Univ Florida, Movement Disorders Ctr, Dept Neurosurg, Gainesville, FL 32611 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. CSIC, Inst Biomed Valencia, Unitat Genet Mol, Dept Genom & Proteom, E-46010 Valencia, Spain. Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan. Chang Gung Univ, Coll Med, Taipei, Taiwan. UCL, Reta Lila Weston Inst Neurol Studies, London WC1E 6BT, England. RP Singleton, A (reprint author), NIA, Mol Genet Unit, NIH, Computat Biol Core, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; Gibbs, J. Raphael/A-3984-2010; Hardy, John/C-2451-2009; Matarin, Mar/F-1771-2016; OI Matarin, Mar/0000-0002-4717-5735; Okun, Michael/0000-0002-6247-9358; Gwinn, Katrina/0000-0002-8277-651X; Scholz, Sonja/0000-0002-6623-0429 FU Intramural NIH HHS; Medical Research Council [G0701075] NR 22 TC 247 Z9 251 U1 0 U2 8 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 NOV PY 2006 VL 5 IS 11 BP 911 EP 916 DI 10.1016/S1474-4422(06)70578-6 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 099JY UT WOS:000241591600013 PM 17052657 ER PT J AU Garcia-Closas, M Sherman, ME Brinton, LA AF Garcia-Closas, Montserrat Sherman, Mark E. Brinton, Louise A. TI Clarifying breast cancer risks associated with menopausal hormone therapy SO LANCET ONCOLOGY LA English DT Editorial Material ID INITIATIVE RANDOMIZED-TRIAL; ESTROGEN-PLUS-PROGESTIN; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; CARCINOMA; HEALTH; VARIANT C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP Garcia-Closas, M (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Suite 550, Rockville, MD 20852 USA. RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562 NR 11 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2006 VL 7 IS 11 BP 885 EP 886 DI 10.1016/S1470-2045(06)70915-9 PG 2 WC Oncology SC Oncology GA 106LW UT WOS:000242103000004 PM 17081912 ER PT J AU Ishikawa, K Tamagawa, Y Takahashi, K Iino, Y Murakami, Y Kakizaki, K Kimura, H Kusakari, J Hara, A Ichimura, K AF Ishikawa, Kotaro Tamagawa, Yuya Takahashi, Katsumasa Iino, Yukiko Murakami, Yoshihiko Kakizaki, Keiko Kimura, Hiroshi Kusakari, Jun Hara, Akira Ichimura, Keiiehi TI Temporal bone histopathologic abnormalities associated with mitochondrial mutation T7511C SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 27th Midwinter Research Meeting of the Association-for-Research-in-Otolaryngology CY FEB 21-26, 2004 CL Daytona Beach, FL SP Assoc Res Otolaryngol DE temporal bone histopathology; sensorineural hearing loss; mitochondrial DNA ID NONSYNDROMIC HEARING-LOSS; KEARNS-SAYRE SYNDROME; RIBOSOMAL-RNA GENE; TRNA(SER(UCN)) GENE; SENSORINEURAL DEAFNESS; POINT MUTATION; DNA; FAMILY; SUSCEPTIBILITY AB Objectives. We previously reported a mitochondrial T7511C mutation in the tRNA(Ser(UCN)) gene in a Japanese family with nonsyndromic hearing loss (HL). However, the temporal bone histopathology associated with T7511C has not been reported. The aim of the present study is to report histopathologic findings of a temporal bone from a patient in the Japanese family with this mutation. Study Design: Single case study. Methods. A temporal bone was obtained from the right ear of a male subject with progressive HL from 5 years of age and who died at 60 years of age from cerebral infarction. The bone was embedded, sectioned, and stained with hematoxylin-eosin for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht to determine loss of the stria vascularis and neurosensory elements including hair cells and spiral ganglion neurons. Results. The most significant histopathologic finding was severe loss of spiral ganglion cells in all turns of the cochlea. Severe loss of neuronal filaments in Rosenthal's canal was also observed. The organ of Corti showed scattered loss of inner and outer hair cells in the basal turn. Partial atrophy of the stria vascularis was observed in all turns of the cochlea. Conclusion. Our results suggest that severe loss of spiral ganglion cells was the main cause of sensorineural HL associated with the T7511C mutation. C1 Jichi Med Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Shimotsuke, Tochigi, Japan. NIDCD, Otolaryngol Branch, Mol Biol & Genet Sect, NIH, Rockville, MD 20850 USA. Gunma Univ, Grad Sch Med, Gunma, Japan. Jichi Med Univ, Omiya Med Ctr, Dept Otolaryngol Head & Neck Surg, Saitama, Japan. Univ Yamanashi, Fac Med, Dept Otolaryngol, Yamanashi, Japan. Teikyo Univ, Sch Med, Dept Otolaryngol, Itabashi Ku, Tokyo 173, Japan. Tsukuba Med Ctr Hosp, Dept Neurosurg, Tsukuba, Ibaraki, Japan. Univ Tsukuba, Inst Clin Med, Dept Otolaryngol, Tsukuba, Ibaraki 305, Japan. RP Ishikawa, K (reprint author), NIDCD, Otolaryngol Branch, Mol Biol & Genet Sect, NIH, 5 Res Court,Room 2B-44, Rockville, MD 20850 USA. EM ishikawak@nidcd.nih.gov NR 20 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2006 VL 116 IS 11 BP 1982 EP 1986 DI 10.1097/01.mlg.0000237440.51542.81 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 102JG UT WOS:000241806300009 PM 17075421 ER PT J AU Branford, S Cross, NCP Hochhaus, A Radich, J Saglio, G Kaeda, J Goldman, J Hughes, T AF Branford, S. Cross, N. C. P. Hochhaus, A. Radich, J. Saglio, G. Kaeda, J. Goldman, J. Hughes, T. TI Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia SO LEUKEMIA LA English DT Review DE BCR-ABL; real-time quantitative PCR; measurement reliability; quality assurance ID POLYMERASE-CHAIN-REACTION; TIME QUANTITATIVE PCR; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; RESIDUAL DISEASE DETECTION; KINASE DOMAIN MUTATIONS; ALPHA PLUS CYTARABINE; MESSENGER-RNA; RT-PCR; CHRONIC-PHASE AB Molecular monitoring for patients with chronic myeloid leukaemia (CML) has become an important practice in the era of imatinib therapy. For successful widespread introduction into the mainstream patient monitoring schedule, many procedural aspects of the complex real-time quantitative polymerase chain reaction (RQ-PCR) technique for measuring BCR-ABL transcripts require optimization. Recommendations for harmonizing the differing methodologies have recently been proposed. These recommendations were designed to maximize reliability of analysis for clinical decision making and proposed the adoption of an International Scale of measurement. The purpose of this review is to present the evidence and supporting data for specific recommendations. These recommendations include use of the same source of cells, either blood or marrow, for analysis; for validation of equal PCR amplification efficiencies of cDNA and standards when using a plasmid to construct standard curves and for ensuring ongoing high-level performance by undertaking a quality assurance programme. Clinicians must know the measurement reliability of an RQ- PCR assay to be able to determine the significance of a change in BCR-ABL level. An assay with poor precision limits the clinical usefulness of results. International harmonization should establish RQ- PCR measurement of BCR-ABL as the best method for monitoring treatment response for patients with CML. C1 Inst Med & Vet Sci, Div Mol Pathol, Adelaide, SA 5000, Australia. Univ Southampton, Natl Genet Ref Lab, Salisbury, Wilts, England. Univ Heidelberg, Fac Clin Med Mannheim, D-6800 Mannheim, Germany. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Univ Turin, Div Hematol & Internal Med, Orbassano, Italy. Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London, England. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Inst Med & Vet Sci, Div Haematol, Adelaide, SA 5000, Australia. RP Branford, S (reprint author), Inst Med & Vet Sci, Div Mol Pathol, Frome Rd, Adelaide, SA 5000, Australia. EM susan.branford@imvs.sa.gov.au RI Cross, Nicholas/B-4817-2009; OI Cross, Nicholas/0000-0001-5481-2555; Hochhaus, Andreas/0000-0003-0626-0834 NR 41 TC 113 Z9 119 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2006 VL 20 IS 11 BP 1925 EP 1930 DI 10.1038/sj.leu.2404388 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 098XJ UT WOS:000241556100002 PM 16990771 ER PT J AU Michel, RB Abu-Asab, M Tsokos, M Mattes, MJ AF Michel, Rosana B. Abu-Asab, Mones Tsokos, Maria Mattes, M. Jules TI Characterization of antibody-containing vesicles shed from B-lymphoma cell lines: exposure of annexin V binding sites SO LEUKEMIA & LYMPHOMA LA English DT Article DE B-cell lymphoma; antibody therapy; CD20; HLA-DR; antibody shedding; annexin V ID MHC CLASS-II; MONOCLONAL-ANTIBODIES; CYTOPLASMIC FRAGMENTS; CD20; APOPTOSIS; MEMBRANE; BODIES; LYMPHOCYTES; RELEASE; ANTIGEN AB Antibodies (Abs) to CD20 or HLA-DR, after binding to the B-lymphoma cell line RL following an overnight incubation at 37 degrees C, accumulate in the form of shed vesicles, which develop in the center of the cell clusters that are spontaneously formed by this cell line. These vesicles coalesce into fairly stable large structures, which we refer to as conglomerates of shed vesicles (CSVs). In the present study, we have extended our previous investigations into the nature of this material. Electron microscopy revealed a conglomerate of heterogeneous vesicles, which looked like pinched-off cytoplasmic projections. CSVs developed similarly either with or without Ab, demonstrating that CSV production is a spontaneous process that incorporates bound Abs if they are present. Before delivery to CSVs, the Abs capped on the cell surface. CSVs had high expression of annexin V binding sites, which are phagocytic signals that are exposed on damaged cells. For CSVs that were cell bound, which are frequently observed, the annexin V binding sites were only in the CSVs, and not on the surface of the intact cell. Although all CSVs contained both Abs and annexin V binding sites, the precise distribution of these two ligands was generally different. Annexin V binding sites were present on caps as well as on CSVs, and appear as soon as caps are formed. In cells incubated with anti-HLA-DR, CD20 was delivered to the CSVs together with HLA-DR, suggesting an association between these two molecules. CSVs prepared with anti-HLA-DR, but not CSVs prepared with anti-CD20, contained considerable numbers of nuclear fragments, identified by propidium iodide staining. C1 Ctr Mol Med & Immunol, Belleville, NJ 07109 USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. RP Mattes, MJ (reprint author), Ctr Mol Med & Immunol, 520 Belleville Ave, Belleville, NJ 07109 USA. EM mjmattes@gscancer.org OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD NOV PY 2006 VL 47 IS 11 BP 2388 EP 2399 DI 10.1080/10428190600783494 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 105PH UT WOS:000242044200025 PM 17107914 ER PT J AU Burgess, JP Wintermute, JS Thomas, BF Kapetanovic, IM AF Burgess, Jason P. Wintermute, James S. Thomas, Brian F. Kapetanovic, Izet M. TI Complete H-1 and C-13 assignments of fluorinated analogs of dehydroepiandrosterone SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE NMR; 2D NMR; gDQCOSY; gHSQC; gHMBC; ROESY; fluasterone ID RAT-LIVER AB The complete assignments of all H-1 and C-13 chemical shifts were made for the fluorinated dehydroepiandrosterone (DHEA) analog fluasterone, 2, and two potential in vivo metabolites 3 and 4. The assignments were made using a combination of one- and two-dimensional NMR techniques (H-1, C-13, gDQCOSY, gHSQC, gHMBC). Once the proton chemical shifts were assigned, the stereochemistry of the two hydroxylated analogs was determined using 2D ROESY experiments. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 RTI Int, Sci & Engn Grp, Res Triangle Pk, NC 27709 USA. NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Burgess, JP (reprint author), RTI Int, Sci & Engn Grp, William F Little Bldg,POB 12194, Res Triangle Pk, NC 27709 USA. EM jpb@rti.org OI Thomas, Brian/0000-0002-0097-4804 FU NCI NIH HHS [N01-CN-25132] NR 5 TC 5 Z9 5 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD NOV PY 2006 VL 44 IS 11 BP 1051 EP 1053 DI 10.1002/mrc.1874 PG 3 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 100XK UT WOS:000241703300010 PM 16835888 ER PT J AU McVeigh, ER Guttman, MA Lederman, RJ Li, M Kocaturk, O Hunt, T Kozlov, S Horvath, KA AF McVeigh, Elliot R. Guttman, Michael A. Lederman, Robert J. Li, Ming Kocaturk, Ozgur Hunt, Timothy Kozlov, Shawn Horvath, Keith A. TI Real-time interactive MRI-guided cardiac surgery: Aortic valve replacement using a direct apical approach SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE surgery; valves; imaging; real-time; cardiac ID PERCUTANEOUS HEART-VALVE; SWINE; OPERATIONS; FEASIBILITY; EXPERIENCE; POSITION; TSENSE AB Minimally invasive cardiac surgery requires arresting and emptying of the heart, which compromises visualization of the surgical field. In this feasibility study a novel surgical procedure is demonstrated in which real-time MRI is used to guide the placement of a prosthetic aortic valve in the beating heart via direct apical access in eight porcine hearts. A clinical stentless bioprosthetic valve affixed to a platinum stent was compressed onto a balloon-tipped catheter. This was fed through a 15-18-mm delivery port inserted into the left ventricular (LV) apex via a minimally invasive subxyphoid incision. Using interactive real-time MRI, the surgeon implanted the prosthetic valve in the correct location at the aortic annulus within 90 s. In four of the animals immediately after implantation, ventricular function, blood flow through the valve, and myocardial perfusion were evaluated with MRI. MRI-guided beating-heart surgery may provide patients with a less morbid and more durable solution to structural heart disease. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RP McVeigh, ER (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM mcveigh@nih.gov RI Kocaturk, Ozgur/A-1419-2016; OI lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z01 HL004608-08] NR 20 TC 66 Z9 67 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2006 VL 56 IS 5 BP 958 EP 964 DI 10.1002/mrm.21044 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 101SX UT WOS:000241761900003 PM 17036300 ER PT J AU Heyn, C Ronald, JA Ramadan, SS Snir, JA Barry, AM MacKenzie, LT Mikulis, DJ Palmieri, D Bronder, JL Steeg, PS Yoneda, T MacDonald, IC Chambers, AF Rutt, BK Foster, PJ AF Heyn, Chris Ronald, John A. Ramadan, Soha S. Snir, Jonatan A. Barry, Andrea M. MacKenzie, Lisa T. Mikulis, David J. Palmieri, Diane Bronder, Julie L. Steeg, Patricia S. Yoneda, Toshiyuki MacDonald, Ian C. Chambers, Ann F. Rutt, Brian K. Foster, Paula J. TI In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cellular MRI; iron oxide; metastasis; cancer; cell tracking ID POSITRON-EMISSION-TOMOGRAPHY; MAMMARY-CARCINOMA CELLS; RANDOMIZED TRIAL; MICE; PARTICLES; DORMANCY; MICROMETASTASES; EXPRESSION; REPORTER; GROWTH AB Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease. C1 Robarts Res Inst, Imaging Res Labs, London, ON N6A 5K8, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. Univ Western Ontario, Dept Med Biophys, London, ON, Canada. London Reg Canc Program, London, ON, Canada. Univ Hlth Network, Toronto Western Hosp, Dept Med Imaging, Toronto, ON, Canada. NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. RP Foster, PJ (reprint author), Robarts Res Inst, Imaging Res Labs, 100 Perth Dr, London, ON N6A 5K8, Canada. EM pfoster@imaging.robarts.ca RI Foster, Paula/M-2201-2013; Palmieri, Diane/B-4258-2015; Chambers, Ann/L-6285-2015; Ronald, John/B-7123-2008; OI Foster, Paula/0000-0002-4868-3395; Chambers, Ann/0000-0002-9509-5123; Ronald, John/0000-0003-3665-173X; Mason, Julie/0000-0002-5144-175X FU Intramural NIH HHS NR 34 TC 160 Z9 164 U1 3 U2 21 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2006 VL 56 IS 5 BP 1001 EP 1010 DI 10.1002/mrm.21029 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 101SX UT WOS:000241761900009 PM 17029229 ER PT J AU Kellman, P Aletras, AH Hsu, LY McVeigh, ER Arai, AE AF Kellman, Peter Aletras, Anthony H. Hsu, Li-yueh McVeigh, Elliot R. Arai, Andrew E. TI T-2(*) measurement during first-pass contrast-enhanced cardiac perfusion imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; T-2*; first-pass perfusion; heart; EPI ID CARDIOVASCULAR MAGNETIC-RESONANCE; ARTERIAL INPUT FUNCTION; MYOCARDIAL-PERFUSION; MRI AB First-pass contrast-enhanced (CE) myocardial perfusion imaging will experience T-2* effects at peak concentrations of contrast agent. A reduction in the signal intensity of left ventricular (LV) blood due to T-2* losses may effect estimates of the arterial input function (AIF) used for quantitative perfusion measurement. Imaging artifacts may also result from T-2* losses as well as off-resonance due to the bolus susceptibility. We hypothesized that T-2* losses would not be significant for measurement of the AIF in full-dose studies using a short echo time (TE = 0.6 ms). The purpose of this study was to directly measure T-2* in the LV cavity during first-pass perfusion. For single-dose Gd-DTPA (0.1 mmol/kg at 5 ml/s), the LV blood pool 72 had a mean value of 9 ms (N = 10) at peak enhancement. Distortion of the AIF due to T-2* signal intensity loss will be less than 10% using TE = 0.6 ms. C1 NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, DHHS, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM kellman@nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS [Z01 HL004608-08] NR 13 TC 16 Z9 16 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2006 VL 56 IS 5 BP 1132 EP 1134 DI 10.1002/mrm.21061 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 101SX UT WOS:000241761900024 PM 17029226 ER PT J AU Wells, TS Wang, LZ Spooner, CN Smith, TC Hiliopoulos, KM Kamens, DR Gray, GC Sato, PA AF Wells, Timothy S. Wang, Linda Z. Spooner, Christina N. Smith, Tyler C. Hiliopoulos, Katia M. Kamens, Deborah R. Gray, Gregory C. Sato, Paul A. TI Self-reported reproductive outcomes among male and female 1991 Gulf War era US military veterans SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Gulf War; reproductive outcomes; birth weight; military ID POSTWAR HOSPITALIZATION EXPERIENCE; POPULATION-BASED SURVEY; BIRTH-DEFECTS; PREGNANCY OUTCOMES; UK VETERANS; VIETNAM VETERANS; HEALTH-STATUS; RISK-FACTORS; PREVALENCE; ILLNESS AB Background: Following the 1991 Gulf War, some veterans expressed concerns regarding their reproductive health. Our objective was to assess whether an association exists between deployment to the 1991 Gulf War and self-reported adverse pregnancy outcomes. Methods: Using a modified Dillman technique with telephone follow-up, we conducted a survey via a postal questionnaire from February 1996-August 1997 to compare selected reproductive outcomes among 10,000 US veterans deployed to the 1991 Gulf War with those of 10,000 nondeployed Gulf War era veterans. Results: A total of 8742 individuals responded to the survey, a response rate of 51 percent. Using multivariable analyses, results showed no differences in number of reported pregnancies between Gulf War veterans and nondeployed veterans. Among 2233 female and 2159 male participants, there were no differences in birth weight of infants born to Gulf War veterans compared with nondeployed Gulf War era veterans. In multivariable models, male and female Gulf War veterans did not significantly differ in risk for ectopic pregnancies, stillbirths, or miscarriages when compared with nondeployed veterans of the same era. Conclusions: These results do not suggest an association between service in the 1991 Gulf War and adverse reproductive outcomes for both male and female veterans during the 4 years after the war. C1 USAF, Res Lab, Wright Patterson AFB, OH 45433 USA. USN, Hlth Sci Ctr, Dept Def Ctr Deployment Hlth Res, San Diego, CA 92152 USA. PRA Int Inc, San Diego, CA USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA 52240 USA. NIH, Bethesda, MD 20892 USA. RP Wells, TS (reprint author), USAF, Res Lab, Bldg 824,Rm 206,2800 Q St, Wright Patterson AFB, OH 45433 USA. EM Timothy.Wells@wpafb.af.mil NR 64 TC 13 Z9 13 U1 4 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD NOV PY 2006 VL 10 IS 6 BP 501 EP 510 DI 10.1007/s10995-006-0122-y PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 120UU UT WOS:000243112500005 PM 16832610 ER PT J AU Atkinson, JJ Toennies, H Holmbeck, K Senior, RM AF Atkinson, J. J. Toennies, H. Holmbeck, K. Senior, R. M. TI MT1-MMP is required for repair of acute airway injury SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 Washington Univ, St Louis, MO 63130 USA. NIH, NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S48 EP S48 DI 10.1016/j.matbio.2006.08.134 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600133 ER PT J AU Barnes, A Chang, W Morello, R Cabral, W Weis, M Eyre, D Leikin, S Mulvihill, J Lee, B Marini, J AF Barnes, A. Chang, W. Morello, R. Cabral, W. Weis, M. Eyre, D. Leikin, S. Mulvihill, J. Lee, B. Marini, J. TI Recessive lethal form of OI caused by null mutations in CRTAP SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NICHD, BEMB, NIH, Bethesda, MD USA. Baylor Coll Med, Waco, TX USA. Univ Washington, Seattle, WA 98195 USA. NICHD, SPB, NIH, Bethesda, MD USA. Childrens Hosp Oklahoma, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S61 EP S62 DI 10.1016/j.matbio.2006.08.170 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600169 ER PT J AU Cabral, WA Chang, W Barnes, AM Eyre, DR Weis, MA Leikin, S Makareeva, E Kuznetsova, NV Bulas, DI Marini, JC AF Cabral, W. A. Chang, W. Barnes, A. M. Eyre, D. R. Weis, M. A. Leikin, S. Makareeva, E. Kuznetsova, N. V. Bulas, D. I. Marini, J. C. TI Null mutations of P3H1 cause recessive OI-like bone dysplasia SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NICHD, BEMB, NIH, Bethesda, MD 20892 USA. Univ Washington, Orthop Res Labs, Seattle, WA 98195 USA. NICHD, SPB, NIH, Bethesda, MD 20892 USA. CNMC, Dept Radiol, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S62 EP S62 DI 10.1016/j.matbio.2006.08.171 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600171 ER PT J AU Chang, W Nou, D Marini, JC AF Chang, W. Nou, D. Marini, J. C. TI Increased TGF-beta receptor on osteoblasts from Brtl mouse for OI SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NICHD, BEMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S62 EP S62 DI 10.1016/j.matbio.2006.08.172 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600170 ER PT J AU Gagarina, VV Carlberg, A Pereira-Mouries, L Hall, DJ AF Gagarina, V. V. Carlberg, A. Pereira-Mouries, L. Hall, DJ. TI COMP enhances cell survival by elevating the IAP proteins SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S89 EP S89 DI 10.1016/j.matbio.2006.08.244 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600243 ER PT J AU Inkson, CA Bi, Y Kuznetsov, S Robey, P Young, MF AF Inkson, C. A. Bi, Y. Kuznetsov, S. Robey, P. Young, M. F. TI Wnt-induced secreted protein 1 regulates osteoblastic activity SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NIDCR, NIH, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S24 EP S24 DI 10.1016/j.matbio.2006.08.068 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600067 ER PT J AU Isenberg, JS Wink, DA Roberts, DD AF Isenberg, J. S. Wink, D. A. Roberts, D. D. TI Thrombospondin-1 blocks redox signaling in vascular cells SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S55 EP S55 DI 10.1016/j.matbio.2006.08.153 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600152 ER PT J AU Kuznetsova, NV Makareeva, E Cabral, WA Visse, R Nagase, H Marini, JC Leikin, S AF Kuznetsova, N. V. Makareeva, E. Cabral, W. A. Visse, R. Nagase, H. Marini, J. C. Leikin, S. TI Chain register shift in type I collagen alters MMP1 cleavage SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NICHHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Kennedy Inst, Dept Matrix Biol, Div Rheumatol, London W6 8LH, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S75 EP S75 DI 10.1016/j.matbio.2006.08.206 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600205 ER PT J AU Lozito, TP Kuo, CK Taboas, JM Tuan, RS AF Lozito, T. P. Kuo, C. K. Taboas, J. M. Tuan, R. S. TI Endothelial cell matrix influences MSC stem cell differentiation SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NIAMS, CBOB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S24 EP S24 DI 10.1016/j.matbio.2006.08.067 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600066 ER PT J AU Makareeva, E Kuznetsova, NV Sutter, MB Cabral, WA Marini, JC Leikin, S AF Makareeva, E. Kuznetsova, N. V. Sutter, M. B. Cabral, W. A. Marini, J. C. Leikin, S. TI Structural domains in type I collagen and their role in OI SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NICHHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S77 EP S77 DI 10.1016/j.matbio.2006.08.212 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600211 ER PT J AU Mertz, EL McBride, D Lekin, S AF Mertz, E. L. McBride, D. Lekin, S. TI Deformation of collagen triple helix in brittle bone under stress SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NICHD, NIH, Bethesda, MD USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S79 EP S80 DI 10.1016/j.matbio.2006.08.218 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600217 ER PT J AU Posey, K Yang, Y Bales, ES Veerisetty, A Haynes, R Sharan, SK Hecht, JT AF Posey, K. Yang, Y. Bales, E. S. Veerisetty, A. Haynes, R. Sharan, S. K. Hecht, J. T. TI Skeletal phenotype of mice overexpressing mutant human COMP SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 Univ Texas, Sch Med, Dept Pediat, Houston, TX 77030 USA. NCI, Frederick, MD 21702 USA. Shriners Hosp Children, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S67 EP S68 DI 10.1016/j.matbio.2006.08.186 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600185 ER PT J AU Rebustini, IT Myers, C Hoffman, MP AF Rebustini, I. T. Myers, C. Hoffman, M. P. TI Role of MMPs during submandibular gland morphogenesis SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NIDCR, CDBRB, Matrix & Morphogenesis Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S28 EP S29 DI 10.1016/j.matbio.2006.08.080 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600079 ER PT J AU Sweeney, SM DiLullo, G Fertala, A Turner, K Antipova, O Perumal, S Orgel, JP Ala-Kokko, L Forlino, A Cabral, WA Barnes, AM Marini, JC San Antonio, JD AF Sweeney, S. M. DiLullo, G. Fertala, A. Turner, K. Antipova, O. Perumal, S. Orgel, J. P. Ala-Kokko, L. Forlino, A. Cabral, W. A. Barnes, A. M. Marini, J. C. San Antonio, J. D. TI Cell and matrix interaction domains on the type I collagen fibril SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. IIT, Chicago, IL 60616 USA. Univ Oulu, Oulu, Finland. NICHD, NIH, Bethesda, MD USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S75 EP S76 DI 10.1016/j.matbio.2006.08.207 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600206 ER PT J AU Tuan, RS AF Tuan, R. S. TI Nanofibrous scaffold for skeletal tissue engineering SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NIAMS, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S3 EP S3 DI 10.1016/j.matbio.2006.08.010 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600009 ER PT J AU Uveges, TE Meganck, JA Daley, EL Goldstein, SA Marini, JC AF Uveges, T. E. Meganck, J. A. Daley, E. L. Goldstein, S. A. Marini, J. C. TI Brtl/Mov13 mice have a milder OI phenotype than Brtl/+ mice SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 NICHD, BEMB, NIH, Bethesda, MD USA. Univ Michigan, Ortho Res Lab, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S61 EP S61 DI 10.1016/j.matbio.2006.08.169 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600168 ER PT J AU Ponce, NA Chawla, N Babey, SH Gatchell, MS Etzioni, DA Spencer, BA Brown, ER Breen, N AF Ponce, Ninez A. Chawla, Neetu Babey, Susan H. Gatchell, Melissa S. Etzioni, David A. Spencer, Benjamin A. Brown, E. Richard Breen, Nancy TI Is there a language divide in Pap test use? SO MEDICAL CARE LA English DT Article DE Pap test; language disparities ID VIETNAMESE-AMERICAN WOMEN; HEALTH INTERVIEW SURVEY; UNITED-STATES; MULTIETHNIC POPULATION; DEMOGRAPHIC-PREDICTORS; CANCER; BREAST; CARE; DISPARITIES; HISPANICS AB Objective: We sought to determine whether primary language use, measured by language of interview, is associated with disparities in cervical cancer screening. Data sources: We undertook a secondary data analysis of a pooled sample of the 2001 and 2003 California Health Inter-view Surveys. The surveys were conducted in English, Spanish, Cantonese, Mandarin, Korean, and Vietnamese. Study Design: The study was a cross-sectional analysis of 3-year Pap test use among women ages 18 to 64, with no reported cervical cancer diagnosis or hysterectomy (n = 38,931). In addition to language of interview, other factors studied included race/ethnicity, marital status, income, educational attainment, years lived in the United States, insurance status, usual source of care, smoking status, area of residence, and self-rated health status. Data Collection/Extraction Methods: We fit weighted multivariate logit models predicting 3-year Pap test use as a function of language of interview, adjusting for the effects of specified covariates. Principal Findings: Compared with the referent English interview group, women who interviewed in Spanish were 1.65 times more likely to receive a Pap test in the past 3 years. In contrast, we observed a significantly reduced risk of screening among women who interviewed in Vietnamese (odds ratio [OR] 0.67; confidence interval [CI] 0.48-0.93), Cantonese (OR 0.44; 95% CI 0.30-0.66), Mandarin (OR 0.48; 95% CI 0.33-0.72), and Korean (OR 0.62; 0.40-0.98). Conclusions: Improved language access could reduce cancer screening disparities, especially in the Asian immigrant community. C1 Univ Calif Los Angeles, Ctr Hlth Policy Res, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Div Canc Control & Prevent Res, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. Columbia Univ, Med Ctr, New York, NY USA. NCI, Hlth Serv & Econ Branch, Appl Res Program, Rockville, MD USA. RP Ponce, NA (reprint author), Univ Calif Los Angeles, Dept Hlth Serv, Room 31-254B CHS, Los Angeles, CA 90095 USA. EM nponce@ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NCI NIH HHS [1 K07 CA100097, N02PC95057]; NIA NIH HHS [AG-02-004] NR 49 TC 38 Z9 38 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2006 VL 44 IS 11 BP 998 EP 1004 DI 10.1097/01.mlr.0000233676.61237.ef PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 104KF UT WOS:000241956600006 PM 17063131 ER PT J AU Reeve, BB AF Reeve, Byyce B. TI Special issues for building computerized-adaptive tests for measuring patient-reported outcomes: The National Institute of Health's investment in new technology - Commentary SO MEDICAL CARE LA English DT Editorial Material C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Outcomes Res Branch,NIH, Bethesda, MD 20892 USA. RP Reeve, BB (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Outcomes Res Branch,NIH, 6130 Execut Blvd,MSC 7344,EPN Room 4005, Bethesda, MD 20892 USA. EM reeveb@mail.nih.gov NR 29 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2006 VL 44 IS 11 SU 3 BP S198 EP S204 DI 10.1097/01.mlr.0000245146.77104.50 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 105IS UT WOS:000242024200025 PM 17060828 ER PT J AU Stahl, SM Hahn, AA AF Stahl, Sidney M. Hahn, Anneliese A. TI The National Institute on Aging's Resource Centers for Minority Aging Research - Contributions to measurement in research on ethnically and racially diverse populations - Preface SO MEDICAL CARE LA English DT Editorial Material C1 NIA, NIH, Bethesda, MD 20892 USA. RP Stahl, SM (reprint author), NIA, NIH, Bethesda, MD 20892 USA. EM StahlS@nia.nih.gov NR 4 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2006 VL 44 IS 11 SU 3 BP S1 EP S2 DI 10.1097/01.mlr.0000245180.20814.9c PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 105IS UT WOS:000242024200001 PM 17060815 ER PT J AU Teresi, JA Stewart, AL Morales, LS Stahl, SM AF Teresi, Jeanne A. Stewart, Anita L. Morales, Leo S. Stahl, Sidney M. TI Measurement in a multi-ethnic society - Overview to the special issue SO MEDICAL CARE LA English DT Editorial Material ID HEALTH-CARE; DISPARITIES; POLITICS C1 Columbia Univ, Stroud Ctr, Resource Ctr Minor Aging Res, New York State Psychiat Inst, Bronx, NY 10471 USA. Hebrew Home Aged, Div Res, Riverdale, NY USA. Univ Calif San Francisco, Inst Hlth & Aging, Ctr Aging Diverse Communities, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RAND, Sch Med, Div Gen Internal Med & Hlth Serv Res, Santa Monica, CA USA. NIA, Behav & Social Res Program, NIH, Bethesda, MD 20892 USA. RP Teresi, JA (reprint author), Columbia Univ, Stroud Ctr, Resource Ctr Minor Aging Res, New York State Psychiat Inst, 5901 Palisade Ave, Bronx, NY 10471 USA. EM Teresimeas@aol.com NR 28 TC 8 Z9 8 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2006 VL 44 IS 11 SU 3 BP S3 EP S4 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 105IS UT WOS:000242024200002 ER PT J AU Berna, MJ Hoffmann, KM Serrano, J Gibril, F Jensen, RT AF Berna, Marc J. Hoffmann, K. Martin Serrano, Jose Gibril, Fathia Jensen, Robert T. TI Serum gastrin in Zollinger-Ellison Syndrome - I. Prospective study of fasting serum gastrin in 309 patients from National Institutes of Health and Comparison with 2229 cases from the literature SO MEDICINE LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; ISLET-CELL-CARCINOMA; LONG-TERM TREATMENT; HELICOBACTER-PYLORI INFECTION; SECRETIN INJECTION TEST; PLASMA CHROMOGRANIN-A; PROTON PUMP INHIBITOR; GASTROESOPHAGEAL SPHINCTER PRESSURE; HISTAMINE H-2-RECEPTOR ANTAGONISTS AB The assessment of fasting serum gastrin (FSG) is essential posis and management of patients with the Zollingerfor the diag Ellison syndrome (ZES). Although many studies have analyzed FSG levels in patients with gastrinoma, limited information has resulted from these studies because of their small size, different methodologies, and lack of correlations of FSG levels with clinical, laboratory, or tumor features in ZES patients. To address this issue, we report the results of a prospective National Institutes of Health (NIH) study of 309 patients with ZES and compare our results with those of 2229 ZES patients in 513 small series and case reports in the literature. In the NIH and literature ZES patients, normal FSG values were uncommon (0.3%-3%), as were very high FSG levels > 100-fold normal (4.9%-9%). Two-thirds of gastrinoma patients had FSG values < 10-fold normal that overlap with gastrin levels seen in more common conditions, like Helicobacter pylori infection or antral G-cell hyperplasia/hypeifunction. In these patients, FSG levels are not diagnostic of ZES, and gastrin provocative tests are needed to establish the diagnosis. Most clinical variables (multiple endocrine neoplasia type I status, presence or absence of the most common symptoms, prior medical treatment) are not correlated with FSG levels, while a good correlation of FSG values was found with other clinical features (prior gastric surgery, diarrhea, duration from onset to diagnosis). Increasing basal acid output, but not maximal acid output correlated closely with increasing FSG. Numerous tumoral features correlated with the magnitude of FSG in our study, including tumor location (pancreatic > duodenal), primary size (larger > smaller) and extent (liver metastases > local disease). In conclusion, this detailed analysis of FSG in a large number of patients with ZES allowed us to identify important clinical guidelines that should contribute to improved diagnosis and management of patients with ZES. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 489 TC 76 Z9 77 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 2006 VL 85 IS 6 BP 295 EP 330 DI 10.1097/01.md.0000236956.74128.76 PG 36 WC Medicine, General & Internal SC General & Internal Medicine GA 108PK UT WOS:000242251500001 PM 17108778 ER PT J AU Berna, MJ Hoffmann, KM Long, SH Serrano, J Gibril, F Jensen, RT AF Berna, Marc J. Hoffmann, K. Martin Long, Scott H. Serrano, Jose Gibril, Fathia Jensen, Robert T. TI Serum gastrin in Zollinger-Ellison Syndrome - II. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and Comparison with 537 cases from hte literature. Evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features SO MEDICINE LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; SECRETIN INJECTION TEST; LONG-TERM TREATMENT; ISLET-CELL TUMORS; HELICOBACTER-PYLORI INFECTION; DUODENAL-ULCER DISEASE; HISTAMINE H-2-RECEPTOR ANTAGONISTS; ESOPHAGEAL SPHINCTER PRESSURE; CALCIUM-SENSING RECEPTOR AB In two-thirds of patients with Zollinger-Ellison syndrome (ZES), fasting serum gastrin (FSG) levels overlap with values seen in other conditions. In these patients, gastrin provocative tests are needed to establish the diagnosis of ZES. Whereas numerous gastrin provocative tests have been proposed, only the secretin, calcium, and meal tests are widely used today. Many studies have analyzed gastrin provocative test results in ZES, but they are limited by small patient numbers and methodologic differences. To address this issue, we report the results of a prospective National Institutes of Health (NIH) study of gastrin provocative tests in 293 patients with ZES and compare these data with those from 537 ZES and 462 non-ZES patients from the literature. In 97%-99% of gastrinoma patients, an increase in serum gastrin post secretin (A secretin) or post calcium (A calcium) occurred. In NIH ZES patients with < 10-fold increase in FSG, the sensitivity/specificity of the widely used criteria were as follows: A secretin >= 200 pg/mL (83%/100%), Delta secretin > 50% (86%/93%), Delta calcium >= 395 pg/mL (54%/100%), and Delta calcium > 50% (78%/83%). A systematic analysis of the sensitivity and specificity of other possible criteria for a positive secretin or calcium test allowed us to identify a new criterion for secretin testing (Delta >= 120 pg/mL) with the highest sensitivity/ specificity (94%/100%) and to confirm the commonly used criterion for calcium tests (Delta >= 395 pg/mL) (62%/100%). This analysis further showed that the secretin test was more sensitive than the calcium test (94% vs. 62%). Our results suggest that secretin stimulation should be used as the first-line provocative test because of its greater sensitivity and simplicity and lack of side effects. In ZES patients with a negative secretin test, 38%-50% have a positive calcium test. Therefore the calcium test should be considered in patients with a strong clinical suspicion of ZES but a negative secretin test. Furthermore, we found that some clinical (diarrhea, duration of medical treatment), laboratory (basal acid output), and tumoral (size, extent) characteristics correlate with the serum gastrin increase post secretin and post calcium. However, using the proposed criteria, the result of these provocative tests (that is, positive or negative) is minimally influenced by these factors, so secretin and calcium provocative tests are reliable in patients with different clinical, laboratory, and tumor characteristics. A systematic analysis of meal testing showed that 54%-77% of ZES patients have a < 50% postprandial serum gastrin increase. However, 9%-20% of ZES patients had a > 100% increase post meal, causing significant overlap with antral syndromes. Furthermore, we could not confirm the usefulness of meal tests for localization of duodenal gastrinomas. We conclude that the secretin test is a crucial element in the diagnosis of most ZES patients, the calcium test may be useful in selected patients, but the meal test is not helpful in the management of ZES. For secretin testing, the criterion with the highest sensitivity and specificity is an increase of >= 120 pg/mL, which should replace other criteria commonly used today. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 411 TC 75 Z9 75 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 2006 VL 85 IS 6 BP 331 EP 364 DI 10.1097/MD.0b013e18026518c PG 34 WC Medicine, General & Internal SC General & Internal Medicine GA 108PK UT WOS:000242251500002 PM 17108779 ER PT J AU Corrigan, EC Nelson, LM Bakalov, VK Yanovski, JA Vanderhoof, VH Yanoff, LB Bondy, CA AF Corrigan, Emily C. Nelson, Lawrence M. Bakalov, Vladimir K. Yanovski, Jack A. Vanderhoof, Vien H. Yanoff, Lisa B. Bondy, Carolyn A. TI Effects of ovarian failure and X-chromosome deletion on body composition and insulin sensitivity in young women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE adiposity; Turner syndrome; premature ovarian failure; menopause; estrogen ID CARDIOVASCULAR RISK-FACTORS; ADIPOSE-TISSUE METABOLISM; ADULT TURNERS-SYNDROME; FAT DISTRIBUTION; HORMONE STATUS; MENOPAUSE; OBESITY; IMPACT AB Objective: Menopause is associated with increased visceral adiposity and reduced insulin sensitivity. It remains unclear whether these changes are due primarily to ovarian failure or aging. The aim of this study was to clarify the impact of ovarian failure on body composition and insulin sensitivity in young women. Design: In a cross-sectional study, we compared main outcome measures (body mass index, body composition by dual-energy x-ray absorptiometry, and insulin sensitivity by Quantitative Insulin Sensitivity Check Index) in three groups: women with 46,XX premature ovarian failure (POF), women with premature ovarian failure associated with 45,X or Turner syndrome (TS), and normal control women (NC). Participants were enrolled in National Institutes of Health Clinical Center protocols between years 2000 and 2005. Results: Mean body mass index (+/- SD) was lower in women with POF (n = 398): 24.3 +/- 5 kg/m(2) versus 27.8 +/- 7 for women with TS (n = 131) and 26.6 +/- 4 for controls (n = 73) (both P < 0.001). Only 33% of women with POF were overweight or obese, compared with 56% of those with TS and 67% of NC women (P < 0.0001 for both). Despite less obesity, women with POF had lower insulin sensitivity (0.367 +/- 0.03) compared with those with TS (0.378 +/- 0.03, P = 0.003) and NC women (0.376 +/- 0.03, P = 0.04). In groups selected for similar age and body mass index, women with POF (n = 89), women with TS (n = 48), and NC women (n = 40) had similar total body and trunk adiposity. After adjustment for age and truncal adiposity, women with POF had significantly lower insulin sensitivity than women with TS (P = 0.03) and NC women (P = 0.049). Conclusions: In contrast to observations in middle-aged postmenopausal women, ovarian failure in young women is not associated with increased total or central adiposity. In fact, women with TS were similar to NC women, whereas women with POF were leaner. The lower insulin sensitivity observed in women with POF deserves further investigation. C1 NIH, NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, NICHHD, Dev Endocrinol Branch, Bethesda, MD USA. RP Bondy, CA (reprint author), NIH, NICHHD, Dev Endocrinol Branch, 10 Ctr Dr,CRC,Rm 1-3330, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z99 HD999999] NR 22 TC 12 Z9 14 U1 0 U2 1 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 NOV-DEC PY 2006 VL 13 IS 6 BP 911 EP 916 DI 10.1097/01.gme.0000248702.25259.00 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 108QT UT WOS:000242255000008 PM 17019382 ER PT J AU Schmidt, PJ AF Schmidt, Peter J. TI Reproductive aging, sex steroids, and depression SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 17th Annual Meeting of the North-American-Menopause-Society CY OCT 11-14, 2006 CL Nashville, TN SP N Amer Menopause Soc C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2006 VL 13 IS 6 BP 984 EP 984 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 108QT UT WOS:000242255000033 ER PT J AU Cherkasova, VA AF Cherkasova, Vera A. TI Measuring MAP kinase activity in immune complex assays SO METHODS LA English DT Article DE MAP kinase; phosphorylation; immunoprecipitation; immune complex; whole-cell extracts; Fus3; Kss1; Hog1; Mpk1; Saccharomyces cerevisiae ID PHEROMONE RESPONSE PATHWAY; SIGNAL-TRANSDUCTION PATHWAY; ACTIVATED PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; INVASIVE GROWTH; YEAST DIFFERENTIATION; STRESS-RESPONSE; MITOGEN; FUS3; SPECIFICITY AB I present an overview of published methods for measuring mitogen activated protein (MAP) kinase activity on endogenous associated substrates, exogenously added substrates as well as determination of activation loop phosphorylation as a read-out of kinase activity in vivo. Detailed procedures for these assays are given for two MAP kinases (MAPKs) Fus3 and Kss1 and compared with other published protocols, including the protocols for Hog1 and Mpk1 MAPKs. Measuring kinase activity in immune complex assays can serve as an approach for identification of potential substrates of protein kinases as well as for detecting other kinase-associated proteins. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Cherkasova, VA (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM cherkasv@mail.nih.gov NR 41 TC 5 Z9 5 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 2006 VL 40 IS 3 BP 234 EP 242 DI 10.1016/j.ymeth.2006.06.005 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 109TV UT WOS:000242332600005 PM 16890454 ER PT J AU Zhou, W Hashimoto, K Moore, ML Elias, JA Zhu, Z Durbin, J Colasurdo, G Rutigliano, JA Chiappetta, CL Goleniewska, K O'Neal, JF Graham, BS Peebles, RS AF Zhou, Weisong Hashimoto, Koichi Moore, Martin L. Elias, Jack A. Zhu, Zhou Durbin, Joan Colasurdo, Giuseppe Rutigliano, John A. Chiappetta, Constance L. Goleniewska, Kasia O'Neal, Jarnye F. Graham, Barney S. Peebles, R. Stokes, Jr. TI IL-13 is associated with reduced illness and replication in primary respiratory syncytial virus infection in the mouse SO MICROBES AND INFECTION LA English DT Article DE virus; IL-13; interferon ID IN-VIVO; AIRWAY HYPERRESPONSIVENESS; GLYCOPROTEIN-G; T-CELLS; MICE; INTERLEUKIN-13; MACROPHAGES; RESPONSES; EOSINOPHILIA; EXPRESSION AB The role of IL-13 in respiratory syncytial virus (RSV) immunopathogenesis is incompletely described. To assess the effect of IL-13 on primary RSV infection, transgenic mice which either overexpress IL-13 in the lung (IL-13 OE) or non-transgenic littermates (IL-13 NT) were challenged intranasally with RSV. IL-13 OE mice had significantly decreased peak viral titers four days after infection compared to non-transgenic littermates. In addition, IL-13 OE mice had significantly lower RSV-induced weight loss and reduced lung IFN-gamma protein expression compared with IL-13 NT mice. In contrast, primary RSV challenge of IL-13 deficient mice resulted in a small, but statistically significant increase in viral titers on day four after infection, no difference in RSV-induced weight loss compared to wild type mice, and augmented IFN-gamma production on day 6 after infection. In STAT1-deficient (STAT1 KO) mice, where primary RSV challenge produced high levels of IL-13 production in the lungs, treatment with an IL-13 neutralizing protein resulted in greater peak viral titers both four and six days after RSV and greater RSV-induced weight loss compared to mice treated with a control protein. These results suggest that IL-13 modulates illness from RSV-infection. (c) 2006 Elsevier Masson SAS. All rights reserved. C1 Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Fukushima Med Univ, Dept Microbiol, Fukushima 9601295, Japan. Yale Univ, Dept Med, New Haven, CT 06520 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. Ohio State Univ, Columbus Childrens Res Inst, Dept Pediat, Columbus, OH 43205 USA. Univ Texas, Houston Med Sch, Dept Pediat, Houston, TX 77030 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Peebles, RS (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, T-1218 MCN, Nashville, TN 37232 USA. EM stokes.peebles@vanderbilt.edu FU NHLBI NIH HHS [R01 HL069949, R01 HL069449, R01-HL-069949]; NIAID NIH HHS [R01-AI-045512, R01-AI-054660, R01 AI045512, R01 AI054660] NR 42 TC 16 Z9 17 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 NOV-DEC PY 2006 VL 8 IS 14-15 BP 2880 EP 2889 DI 10.1016/j.micinf.2006.09.007 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 127GU UT WOS:000243574300008 PM 17110149 ER PT J AU Marotta, DE Gerald, N Dwyer, DM AF Marotta, Diane E. Gerald, Noel Dwyer, Dennis M. TI Rab5b localization to early endosomes in the protozoan human pathogen Leishmania donovani SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE endocytosis; GFP chimera; Leishmania; Rab5b; trafficking ID GREEN FLUORESCENT PROTEIN; SMALL GTPASES; ENDOCYTOSIS; FAMILY; ACQUISITION; SURFACE; FUSION; POCKET; EEA1 AB Leishmania donovani is a primitive trypanosomatid pathogen of humans. This protozoan is apically polarized such that the flagellar reservoir, the exclusive site of endocytosis and exocytosis, is situated at the anterior end. Recent evidence for the existence of an endocytic pathway in Leishmania has prompted us to investigate candidate temporal markers for endocytosis. In this study we identify the L. donovani Rab5b gene, and demonstrate the localization of a Rab5b chimera to early endosomes. A full-length Rab5b protein was fused to green fluorescent protein (GFP) to generate a chimeric protein GFP::Rab5b. Transfected L. donovani promastigotes carrying this chimeric construct displayed GFP::Rab5b localization. Additionally, incubation of transfected promastigotes with the fluid-phase marker Texas Red dextran demonstrated anterior co-localization of GFP::Rab5b and dye. This suggests Rab5b may act as a marker for early endosomes in L. donovani. C1 Univ Penn, Philadelphia, PA 19104 USA. NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Marotta, DE (reprint author), Univ Penn, B1 13-15 Anat Chem Bldg 3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM marottad@mail.med.upenn.edu FU Intramural NIH HHS NR 28 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2006 VL 292 IS 1-2 BP 107 EP 117 DI 10.1007/s11010-006-9224-5 PG 11 WC Cell Biology SC Cell Biology GA 102DZ UT WOS:000241792500013 PM 16752082 ER PT J AU Hoodbhoy, T Aviles, M Baibakov, B Epifano, O Jimenez-Movilla, M Gauthier, L Dean, J AF Hoodbhoy, Tanya Aviles, Manuel Baibakov, Boris Epifano, Olga Jimenez-Movilla, Maria Gauthier, Lyn Dean, Jurrien TI ZP2 and ZP3 traffic independently within oocytes prior to assembly into the extracellular zona pellucida SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; SPERM BINDING; MOUSE OOCYTES; MICE; PROTEINS; GLYCOPROTEINS; SECRETION; GLYCANS; EGGS; FOLLICULOGENESIS AB The extracellular zona pellucida surrounds mammalian eggs and mediates taxon-specific sperm-egg recognition at fertilization. In mice, the zona pellucida is composed of three glycoproteins, but the presence of ZP2 and ZP3 is sufficient to form a biologically functional structure. Each zona pellucida glycoprotein is synthesized in growing oocytes and traffics through the endomembrane system to the cell surface, where it is released from a transmembrane domain and assembled into the insoluble zona pellucida matrix. ZP2 and ZP3 colocalize in the endoplasmic reticulum and in 1- to 5-mu m post-Golgi structures comprising multivesicular aggregates (MVA), but a coimmunoprecipitation assay does not detect physical interactions. In addition, ZP2 traffics normally in growing oocytes in the absence of ZP3 or if ZP3 has been mutated to prevent incorporation into the zona pellucida matrix, complementing earlier studies indicating the independence of ZP3 secretion in Zp2 null mice. N glycosylation has been implicated in correct protein folding and intracellular trafficking of secreted proteins. Although ZP3 contain five N-glycans, enhanced green fluorescent protein-tagged ZP3 lacking N glycosylation sites is present in WA and is incorporated into the zona pellucida matrix of transgenic mice. Thus, ZP2 secretion is seemingly unaffected by ZP3 lacking N-glycans. Taken together, these observations indicate that ZP2 and ZP3 traffic independently through the oocyte prior to assembly into the zona pellucida. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Murcia, Sch Med, Dept Cell Biol, E-30071 Murcia, Spain. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3134, Bethesda, MD 20892 USA. EM jurrien@helix.nih.gov RI Aviles, Manuel/H-6390-2015; Jimenez-Movilla, Maria/I-1004-2015 OI Aviles, Manuel/0000-0003-4396-4718; Jimenez-Movilla, Maria/0000-0002-1572-8219 FU Intramural NIH HHS NR 41 TC 15 Z9 16 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2006 VL 26 IS 21 BP 7991 EP 7998 DI 10.1128/MCB.00904-06 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 097QF UT WOS:000241462400015 PM 17047254 ER PT J AU Soung, NK Kang, YH Kim, K Kamijo, K Yoon, H Seong, YS Kuo, YL Miki, T Kim, SR Kuriyama, R Giam, CZ Ahn, CH Lee, KS AF Soung, Nak-Kyun Kang, Young Hwi Kim, Keetae Kamijo, Keiju Yoon, Heejeong Seong, Yeon-Sun Kuo, Yu-Liang Miki, Toru Kim, Seung R. Kuriyama, Ryoko Giam, Chou-Zen Ahn, Chang H. Lee, Kyung S. TI Requirement of hCenexin for proper mitotic functions of polo-like kinase 1 at the centrosomes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POLO-LIKE KINASE-1; DENSE FIBER PROTEINS; KINESIN-LIKE PROTEIN; SUBCELLULAR-LOCALIZATION; MICROTUBULE NUCLEATION; MOTHER CENTRIOLES; MAMMALIAN-CELLS; BOX DOMAIN; SPERM TAIL; PLK1 AB Outer dense fiber 2 (Odf2) was initially identified as a major component of sperm tail cytoskeleton and later was suggested to be a widespread component of centrosomal scaffold that preferentially associates with the appendages of the mother centrioles in somatic cells. Here we report the identification of two Odf2-related centrosomal components, hCenexin1 and hCenexin1 variant 1, that possess a unique C-terminal extension. Our results showed that hCenexin1 is the major isoform expressed in HeLa cells, whereas hOdf2 is not detectably expressed. Mammalian polo-like kinase 1 (Plk1) is critical for proper mitotic progression, and its association with the centrosome is important for microtubule nucleation and function. Interestingly, depletion of hCenexin1 by RNA interference (RNAi) dellocalized Plk1 from the centrosomes and the C-terminal extension of hCenexin1 was crucial to recruit Plk1 to the centrosomes through a direct interaction with the polo-box domain of Plk1. Consistent with these findings, the hCenexin1 RNAi cells exhibited weakened gamma-tubulin localization and chromosome segregation defects. We propose that hCenexin1 is a critical centrosomal component whose C-terminal extension is required for proper recruitment of Plk1 and other components crucial for normal mitosis. Our results further suggest that the anti-Odf2 immunoreactive centrosomal antigen previously detected in non-germ line cells is likely hCenexin1. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Rexahn Pharmaceut Inc, Rockville, MD 20850 USA. Dankook Univ, Coll Med, Dept Biochem, Chunan, South Korea. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. Chungbuk Natl Univ, Coll Med, Dept Biochem & Mol Biol, Cheongju, South Korea. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [F32 CA075638, R01 CA115884, R01CA 75638]; NIGMS NIH HHS [GM55735, R01 GM055735] NR 36 TC 31 Z9 31 U1 0 U2 1 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 NOV PY 2006 VL 26 IS 22 BP 8316 EP 8335 DI 10.1128/MCB.00671-06 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103ZQ UT WOS:000241926100009 PM 16966375 ER PT J AU To, KKW Zhan, Z Bates, SE AF To, Kenneth K. W. Zhan, Z. Bates, Susan E. TI Aberrant promoter methylation of the ABCG2 gene in renal carcinoma SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CANCER-RESISTANCE-PROTEIN; TUMOR-SUPPRESSOR GENE; HISTONE DEACETYLASE INHIBITION; DNA METHYLATION; BINDING-PROTEIN; MULTIDRUG-RESISTANCE; REPRESS TRANSCRIPTION; H3K9 METHYLATION; IN-VIVO; CELLS AB ABCG2 is a ubiquitous ATP-binding cassette transmembrane protein that is important in clinical drug resistance. Little is known about the mechanism(s) regulating the expression of ABCG2. We hypothesized that DNA methylation could play a role in the epigenetic regulation of ABCG2 gene expression. The promoter methylation status of three renal carcinoma cell lines was assessed with restriction enzyme digestion-coupled PCR and bisulfite genomic sequencing. Both UOK121 and UOKI43, with known methylation of the VHL promoter, showed induction of ABCG2 expression after 5-aza-2 '-deoxycytidine (5-aza-dC) treatment, suggesting that aberrant methylation of the ABCG2 gene was associated with gene silencing. In vitro methylation of the ABCG2 promoter-driven luciferase reporter vector resulted in a significant inhibition of transcription. Our data suggested that the ABCG2 gene is regulated coordinately at both histone and DNA levels. A chromatin immunoprecipitation assay demonstrated that the methylated promoter in UOK121 and UOKI43, but not the unmethylated one in UOK181, is associated with the methyl CpG binding domain proteins (MBDs), MBD2 and MeCP2. Histone deacetylase 1 and a corepressor, mSin3A, were identified binding to the promoter region containing the CpG island, thereby suppressing ABCG2 transcription. Reactivation of ABCG2 was achieved by treatment with 5-aza-dC, a demethylating agent, concomitant with the release of MBDs from the promoter. Furthermore, the association of methylated lysine 9 on histone H3, a hallmark of promoter methylation, with the promoter was reduced following 5-aza-dC treatment. These data suggest that DNA methylation-dependent formation of a repressor complex in the CpG island contributes to inactivation of ABCG2. C1 NCI, Expt Therapeut Sect, Med Oncol Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP To, KKW (reprint author), NCI, Expt Therapeut Sect, Med Oncol Branch, Canc Res Ctr,NIH, Bldg 10,Room 13N220,10 Ctr Dr, Bethesda, MD 20892 USA. EM tok@mail.nih.gov RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU Intramural NIH HHS NR 59 TC 73 Z9 82 U1 0 U2 3 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 NOV PY 2006 VL 26 IS 22 BP 8572 EP 8585 DI 10.1128/MCB.00650-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103ZQ UT WOS:000241926100031 PM 16954373 ER PT J AU Kim, Y McLaughlin, N Lindstrom, K Tsukiyama, T Clark, DJ AF Kim, Yeonjung McLaughlin, Neil Lindstrom, Kim Tsukiyama, Toshio Clark, David J. TI Activation of Saccharomyces cerevisiae HIS3 results in Gcn4p-dependent, SWI/SNF-dependent mobilization of nucleosomes over the entire gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN-REMODELING FACTORS; YEAST CUP1 CHROMATIN; IN-VIVO; PREFERENTIAL ACCESSIBILITY; TRANSCRIPTIONAL ACTIVATION; HISTONE ACETYLTRANSFERASE; REGULATORY SEQUENCES; MASTER REGULATOR; DNA-SEQUENCE; PROMOTER AB The effects of transcriptional activation on the chromatin structure of the Saccharomyces cerevisiae HIS3 gene were addressed by mapping the precise positions of nucleosomes in uninduced and induced chromatin. In the absence of the Gcn4p activator, the HIS3 gene is organized into a predominant nucleosomal array. In wild-type chromatin, this array is disrupted, and several alternative overlapping nucleosomal arrays are formed. The disruption of the predominant array also requires the SWI/SNF remodeling machine, indicating that the SWI/SNF complex plays an important role in nucleosome mobilization over the entire HIS3 gene. The Isw1 remodeling complex plays a more subtle role in determining nucleosome positions on HIS3, favoring positions different from those preferred by the SWI/SNF complex. Both the SWI/SNF and Isw1 complexes are constitutively present in HIS3 chromatin, although Isw1 tends to be excluded from the HIS3 promoter. Despite the apparent disorder of HIS3 chromatin generated by the formation of multiple nucleosomal arrays, nucleosome density profiles indicate that some long-range order is always present. We propose that Gcn4p stimulates nucleosome mobilization over the entire HIS3 gene by the SWI/SNF complex. We suggest that the net effect of interplay among remodeling machines at HIS3 is to create a highly dynamic chromatin structure. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. RP Clark, DJ (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6A,Room 2A14,6 Ctr Dr, Bethesda, MD 20892 USA. EM clarkda@mail.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM058465, GM58465] NR 45 TC 35 Z9 35 U1 0 U2 1 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 NOV PY 2006 VL 26 IS 22 BP 8607 EP 8622 DI 10.1128/MCB.00678-06 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103ZQ UT WOS:000241926100034 PM 16982689 ER PT J AU Fu, Z Larson, KA Chitta, RK Parker, SA Turk, BE Lawrence, MW Kaldis, P Galaktionov, K Cohn, SM Shabanowitz, J Hunt, DF Sturgill, TW AF Fu, Zheng Larson, Katherine A. Chitta, Raghu K. Parker, Sirlester A. Turk, Benjamin E. Lawrence, Matthew W. Kaldis, Philipp Galaktionov, Konstantin Cohn, Steven M. Shabanowitz, Jeffrey Hunt, Donald F. Sturgill, Thomas W. TI Identification of yin-yang regulators and a phosphorylation consensus for male germ cell-associated kinase (MAK)-related kinase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CDK-ACTIVATING KINASE; PROTEIN-SERINE/THREONINE PHOSPHATASE; MEDIATED DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; STRUCTURAL BASIS; SPORE FORMATION; BUDDING YEAST; MAP KINASES; TPR DOMAIN; MEIOSIS AB MAK (male germ cell-associated protein kinase) and MRK/ICK (MAK-related kinase/intestinal cell kinase) are human homologs of Ime2p in Saccharomyces cerevisiae and of Mde3 and Pill in Schizosaccharomyces pombe and are similar to human cyclin-dependent kinase 2 (CDK2) and extracellular signal-regulated kinase 2 (ERK2). MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation. Herein, we establish that human CDK-related kinase CCRK (cell cycle-related kinase) is an activating T157 kinase for MRK, whereas active CDK7/cyclin H/MAT1 complexes phosphorylate CDK2 but not MRK. Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylates MRK at T157 in vitro and in situ. Thus, CCRK and PP5 are yin-yang regulators of T157 phosphorylation. To determine a substrate consensus, we screened a combinatorial peptide library with active MRK. MRK preferentially phosphorylates R-P-X-S/T-P sites, with the preference for arginine at position -3 (P-3) being more stringent than for prolines at P-2 and P+1. Using the consensus, we identified a putative phosphorylation site ((RPLTS)-S-1080) for MRK in human Scythe, an antiapoptotic protein that interacts with MRK. MRK phosphorylates Scythe at T1080 in vitro as determined by site-directed mutagenesis and mass spectrometry, supporting the consensus and suggesting Scythe as a physiological substrate for MRK. C1 Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Chem, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. NCI, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Sturgill, TW (reprint author), Univ Virginia, Sch Med, Dept Pharmacol, 1300 Jefferson Pk Ave, Charlottesville, VA 22908 USA. EM Thomas_Sturgill@virginia.edu RI Kaldis, Philipp/G-2714-2010; Hunt, Donald/I-6936-2012 OI Kaldis, Philipp/0000-0002-7247-7591; Hunt, Donald/0000-0003-2815-6368 FU NIDDK NIH HHS [DK064751, R01 DK064751]; NIGMS NIH HHS [GM62890, GM37537, R01 GM037537, R01 GM062890] NR 69 TC 37 Z9 38 U1 1 U2 1 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 NOV PY 2006 VL 26 IS 22 BP 8639 EP 8654 DI 10.1128/MCB.00816-06 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103ZQ UT WOS:000241926100036 PM 16954377 ER PT J AU Yang, AX Mejido, J Bhattacharya, B Petersen, D Han, J Kawasaki, ES Puri, RK AF Yang, Amy X. Mejido, Josef Bhattacharya, Bhaskar Petersen, David Han, Jing Kawasaki, Ernest S. Puri, Raj K. TI Analysis of the quality of contact pin fabricated oligonucleotide microarrays SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE quality control; printed microarrays; 70-mer oligonucleotide array; autofluorescence 9-mer nucleotide hybridization; quality testing ID COMPLEMENTARY-DNA MICROARRAY; CDNA MICROARRAYS; GENE-EXPRESSION; IDENTIFICATION; ATTACHMENT; ARRAYS AB As the quality of microarrays is critical to successful experiments for data consistency and validity, a reliable and convenient quality control method is needed. We describe a systematic quality control method for large-scale genome oligonucleotide arrays. This method is comprised of three steps to assess the quality of printed arrays. The first step involves assessment of the autofluorescence property of DNA. This step is convenient, quick to perform, and allowed reuse of every array. The second step involves hybridization of arrays with Cy3-labeled 9-mer oligonucleotide target to assess the quality and stability of oligonucleotides. Because this step consumed arrays, one or two arrays from each batch were used to complement the quality control data from autofluorescence. The third step involves hybridization of arrays from every batch with transcripts derived from two cell lines to assess data consistency. These hybridizations were able to distinguish two closely related tissue samples by identifying a cluster of 20 genes that were differently expressed in U87MG and T98G glioblastoma cell lines. In addition, we standardized two parameters that significantly enhanced the quality of arrays. We found that longer pin contact time and crosslinking oligonucleotides at 400 mJ/cm(2) were optimal for the highest hybridization intensity. Taken together, these results indicate that the quality of spotted oligonucleotide arrays should be assessed by at least two methods, autofluorescence and 9-mer hybridization before arrays are used for hybridization experiments. C1 US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Ctr Canc Res, Gaithersburg, MD 20877 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, RM2NN20,Bldg 29B,8800 Rockville Pike, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 22 TC 6 Z9 6 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD NOV PY 2006 VL 34 IS 3 BP 303 EP 315 DI 10.1385/MB:34:3:303 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 112CH UT WOS:000242502300002 PM 17284778 ER PT J AU Weinstein, JN AF Weinstein, John N. TI Spotlight on molecular profiling: "Integromic" analysis of the NCI-60 cancer cell lines SO MOLECULAR CANCER THERAPEUTICS LA English DT Editorial Material ID ANTICANCER DRUG SCREEN; EXPRESSION DATABASE; PHARMACOLOGY; RESISTANCE; PATTERNS; IDENTIFICATION; AGENTS; MAP C1 NCI, Mol Pharmacol Lab, Genom & Bioinformat Grp, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NCI, Mol Pharmacol Lab, Genom & Bioinformat Grp, Ctr Canc Res,NIH, 37 Convent Dr,Room 5056B, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov FU Intramural NIH HHS NR 25 TC 51 Z9 53 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 NOV PY 2006 VL 5 IS 11 BP 2601 EP 2605 DI 10.1158/1535-7163.MCT-06-0640 PG 5 WC Oncology SC Oncology GA 106YN UT WOS:000242138000001 PM 17088435 ER PT J AU Ikediobi, ON Davies, H Bignell, G Edkins, S Stevens, C O'Meara, S Santarius, T Avis, T Barthorpe, S Brackenbury, L Buck, G Butler, A Clements, J Cole, J Dicks, E Forbes, S Gray, K Halliday, K Harrison, R Hills, K Hinton, J Hunter, C Jenkinson, A Jones, D Kosmidou, V Lugg, R Menzies, A Mironenko, T Parker, A Perry, J Raine, K Richardson, D Shepherd, R Small, A Smith, R Solomon, H Stephens, P Teague, J Tofts, C Varian, J Webb, T West, S Widaa, S Yates, A Reinhold, W Weinstein, JN Stratton, MR Futreal, PA Wooster, R AF Ikediobi, Ogechi N. Davies, Helen Bignell, Graham Edkins, Sarah Stevens, Claire O'Meara, Sarah Santarius, Thomas Avis, Tim Barthorpe, Syd Brackenbury, Lisa Buck, Gemma Butler, Adam Clements, Jody Cole, Jennifer Dicks, Ed Forbes, Simon Gray, Kristian Halliday, Kelly Harrison, Rachel Hills, Katy Hinton, Jonathan Hunter, Chris Jenkinson, Andy Jones, David Kosmidou, Vivienne Lugg, Richard Menzies, Andrew Mironenko, Tatiana Parker, Adrian Perry, Janet Raine, Keiran Richardson, David Shepherd, Rebecca Small, Alex Smith, Raffaella Solomon, Helen Stephens, Philip Teague, Jon Tofts, Calli Varian, Jennifer Webb, Tony West, Sofie Widaa, Sara Yates, Andy Reinhold, William Weinstein, John N. Stratton, Michael R. Futreal, P. Andrew Wooster, Richard TI Mutation analysis of 24 known cancer genes in the NCI-60 cell line set SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ANTICANCER DRUG SCREEN; GROWTH-FACTOR RECEPTOR; DNA COPY NUMBER; LUNG-CANCER; MOLECULAR PHARMACOLOGY; SOMATIC MUTATIONS; EXPRESSION; SENSITIVITY; PANEL; INHIBITORS AB The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens. C1 Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. Natl Canc Inst, Mol Pharmacol Lab, Genom & Bioinformat Grp, Bethesda, MD USA. Inst Canc Res, Sutton, Surrey, England. RP Stratton, MR (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Trust Genome Campus, Cambridge CB10 1SA, England. EM mrs@sanger.ac.uk OI Jenkinson, Andrew/0000-0002-0703-6984; Yates, Andrew/0000-0002-8886-4772; Hunter, Christopher/0000-0002-1335-0881; Gray, Kristian/0000-0002-7035-7107; Richardson, David/0000-0003-0247-9118 FU Intramural NIH HHS; Wellcome Trust [077012] NR 32 TC 222 Z9 226 U1 0 U2 9 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 NOV PY 2006 VL 5 IS 11 BP 2606 EP 2612 DI 10.1158/1535-7163.MCT-06-0433 PG 7 WC Oncology SC Oncology GA 106YN UT WOS:000242138000002 PM 17088437 ER PT J AU Lorenzi, PL Reinhold, WC Rudelius, M Gunsior, M Shankavaram, U Bussey, KJ Scherf, U Eichler, GS Martin, SE Chin, K Gray, JW Kohn, EC Horak, ID Von Hoff, DD Raffeld, M Goldsmith, PK Caplen, NJ Weinstein, JN AF Lorenzi, Philip L. Reinhold, William C. Rudelius, Martina Gunsior, Michele Shankavaram, Uma Bussey, Kimberly J. Scherf, Uwe Eichler, Gabriel S. Martin, Scott E. Chin, Koei Gray, Joe W. Kohn, Elise C. Horak, Ivan D. Von Hoff, Daniel D. Raffeld, Mark Goldsmith, Paul K. Caplen, Natasha J. Weinstein, John N. TI Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ANTICANCER DRUG SCREEN; HUMAN-BREAST CANCER; GENE-EXPRESSION PATTERNS; HUMAN LEUKEMIA-CELLS; MOLECULAR PHARMACOLOGY; GLUTAMINE DEPLETION; RECEPTOR EXPRESSION; LINES; RESISTANCE; GROWTH AB L-Asparaginase (L-ASP), a bacterial enzyme used since the 1970s to treat acute lymphoblastic leukemia, selectively starves cells that cannot synthesize sufficient asparagine for their own needs. Molecular profiling of the NCI-60 cancer cell lines using five different microarray platforms showed strong negative correlations of asparagine synthetase (ASNS) expression and DNA copy number with sensitivity to L-ASP in the leukemia and ovarian cancer cell subsets. To assess whether the ovarian relationship is causal, we used RNA interference to silence ASNS in three ovarian lines and observed 4- to 5-fold potentiation of sensitivity to L-ASP with two of the lines. For OVCAR-8, the line that expresses the least ASNS, the potentiation was > 500-fold. Significantly, that potentiation was > 700-fold in the multidrug-resistant derivative OVCAR-8/ADR, showing that the causal relationship between ASNS expression and L-ASP activity survives development of classical multidrug resistance. Tissue microarrays confirmed low ASNS expression in a subset of clinical ovarian cancers as well as other tumor types. Overall, this pharmacogenomic/pharmacoproteomic study suggests the use Of L-ASP for treatment of a subset of ovarian cancers (and perhaps other tumor types), with ASNS as a biomarker for patient selection. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Antibody & Prot Purificat Unit, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Gene Silencing Sect, NIH, Off Sci & Technol Partnerships,Off Director,Ctr C, Bethesda, MD 20892 USA. NCI, Mol Signaling Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA. Enzon Pharmaceut Inc, Piscataway, NJ USA. Translat Genom Res Inst, Phoenix, AZ USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH,Ctr Canc Res, Bethesda, MD 20892 USA. EM jw4i@nih.gov RI Caplen, Natasha/H-2768-2016 OI Bussey, Kimberly/0000-0003-1001-8207; Caplen, Natasha/0000-0002-0001-9460 FU Intramural NIH HHS; NCI NIH HHS [CA 109552] NR 53 TC 46 Z9 50 U1 0 U2 5 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 NOV PY 2006 VL 5 IS 11 BP 2613 EP 2623 DI 10.1158/1535-7163.MCT-06-0447 PG 11 WC Oncology SC Oncology GA 106YN UT WOS:000242138000003 PM 17088436 ER PT J AU Oh, SH Lee, OH Schroeder, CP Oh, YW Ke, S Cha, HJ Park, RW Onn, A Herbst, RS Li, C Lee, HY AF Oh, Seung-Hyun Lee, Ok-Hee Schroeder, Claudia P. Oh, Yun W. Ke, Shi Cha, Hee-Jae Park, Rang-Woon Onn, Amir Herbst, Roy S. Li, Chun Lee, Ho-Young TI Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor-independent urokinase-type plasminogen activator inhibition SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FACTOR-BINDING PROTEIN-3; FACTOR-I-RECEPTOR; MATRIX METALLOPROTEINASES; CLINICAL-SIGNIFICANCE; TUMOR PROGRESSION; PLASMA-LEVELS; UP-REGULATION; CELL-LINES; EXPRESSION; METASTASIS AB Insulin-like growth factor binding protein-3 (IGFBP-3), a major IGF-binding protein in human serum, regulates the growth of non-small cell lung cancer (NSCLC) cells through IGF-dependent and IGIF-independent mechanisms. However, the role of IGFBP-3 in lung cancer metastasis is not well known. In the present study, we showed that noncytotoxic doses of adenoviral or recombinant IGFBP-3 significantly decreased the migration and invasion of H1299 and A549 NSCLC cells. Furthermore, treatment of human lung fibroblasts with recombinant IGFBP-3 suppressed their ability to stimulate the invasion of H1299 cells. Overexpression of IGFBP-3 markedly reduced lung metastasis of A549 cells in an experimental animal model system and prolonged the survival time of the animals. Urokinase-type plasminogen activator (uPA) inhibitor treatment or uPA small interfering RNA transfection of A549 and H1299 cells resulted in a significant decrease in invasion. Corresponding ELISA, Western blot, gelatin zymogram, and semiquantitative reverse transcription-PCR analyses revealed that IGFBP-3 reduced the expression of uPA mRNA through IGF-independent mechanisms. The specific role of uPA in anti-invasive activity of IGFBP-3 was further confirmed in NSCLC cells, in which uPA expression/activity was suppressed by the transfection with synthetic small interfering RNA or by the treatment with uPA inhibitor or induced by the infection with an adenoviral vector. IGFBP-3 also decreased the expression/ activity of matrix metalloproteinase-2 through IGF-dependent but uPA-independent pathways. Taken together, our data suggest that IGFPB-3 effectively block uPA- and matrix metalloproteinase-2-stimulated invasion pathways, ultimately reducing lung cancer cell metastasis. Our findings indicate that IGFBP-3 may be a promising anti-invasive and antimetastatic therapeutic agent in lung cancer. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. Kyungpook Natl Univ, Sch Med, Dept Biochem, Taegu, South Korea. RP Lee, HY (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM hlee@mdanderson.org FU NCI NIH HHS [CA16672, R01 CA100816-01, R01 CA109520-01] NR 44 TC 34 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2006 VL 5 IS 11 BP 2685 EP 2695 DI 10.1158/1535-7163.MCT-06-0142 PG 11 WC Oncology SC Oncology GA 106YN UT WOS:000242138000010 PM 17121915 ER PT J AU Yu, MJ Pisitkun, T Wang, GH Shen, RF Knepper, MA AF Yu, Ming-Jiun Pisitkun, Trairak Wang, Guanghui Shen, Rong-Fong Knepper, Mark A. TI LC-MS/MS analysis of apical and basolateral plasma membranes of rat renal collecting duct cells SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID AQUAPORIN-2 TRAFFICKING; UREA TRANSPORTER; BRATTLEBORO RAT; WATER-EXCRETION; VASOPRESSIN; KIDNEY; PROTEINS; IDENTIFICATION; SURFACE; PHOSPHORYLATION AB We used biotinylation and streptavidin affinity chromatography to label and enrich proteins from apical and basolateral membranes of rat kidney inner medullary collecting ducts (IMCDs) prior to LC-MS/MS protein identification. To enrich apical membrane proteins and bound peripheral membrane proteins, IMCDs were perfusion-labeled with primary amine-reactive biotinylation reagents at 2 C using a double barreled pipette. The perfusion-biotinylated proteins and proteins bound to them were isolated with CaptAvidin-agarose beads, separated with SDS-PAGE, and sliced into continuous gel pieces for LC-MS/MS protein identification (LTQ, Thermo Electron Corp.). 17 integral and glycosylphosphatidylinositol (GPI)-linked membrane proteins and 44 non-integral membrane proteins were identified. Immunofluorescence confocal microscopy confirmed ACVRL1, H(+)/K(+)-ATPase alpha 1, NHE2, and TauT expression in the IMCDs. Basement membrane and basolateral membrane proteins were biotinylated via incubation of IMCD suspensions with biotinylation reagents on ice. 23 integral and GPI-linked membrane proteins and 134 non-integral membrane proteins were identified. Analyses of non- integral membrane proteins preferentially identified in the perfusion-biotinylated and not in the incubation-biotinylated IMCDs revealed protein kinases, scaffold proteins, SNARE proteins, motor proteins, small GTP-binding proteins, and related proteins that may be involved in vasopressin-stimulated AQP2, UT-A1,and ENaC regulation. A World Wide Web-accessible database was constructed of 222 membrane proteins ( integral and GPI-linked) from this study and prior studies. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271; YU, MING-JIUN/0000-0003-0393-4696 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01 HL001285, Z01-HL-01285-KE] NR 45 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2006 VL 5 IS 11 BP 2131 EP 2145 DI 10.1074/mcp.M600177-MCP200 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 112IZ UT WOS:000242520500011 PM 16899541 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, Kimberly D. Rosenberg, Helene F. TI The RNase a superfamily: Generation of diversity and innate host defense SO MOLECULAR DIVERSITY LA English DT Review DE angiogenin; antibacterial; antiviral; antihelminth; cytotoxin; eosinophils ID EOSINOPHIL CATIONIC PROTEIN; BOVINE SEMINAL RIBONUCLEASE; RESPIRATORY SYNCYTIAL VIRUS; AMINO-ACID-SEQUENCE; PANCREATIC-TYPE RIBONUCLEASES; ELEVATED SERUM RIBONUCLEASE; GROWTH PROMOTER ANGIOGENIN; RANA-CATESBEIANA BULLFROG; LEUKEMIC MYELOID CELLS; DOUBLE-STRANDED-RNA AB The Ribonuclease A superfamily includes an extensive network of distinct and divergent gene lineages. Although all ribonucleases of this superfamily share invariant structural and catalytic elements and some degree of enzymatic activity, the primary sequences have diverged significantly, ostensibly to promote novel function. We will review the literature on the evolution and biology of the RNase A ribonuclease lineages that have been characterized specifically as involved in host defense including: (1) RNases 2 and RNases 3, also known as the eosinophil ribonucleases, which are rapidly-evolving cationic proteins released from eosinophilic leukocytes, (2) RNase 7, an anti-pathogen ribonuclease identified in human skin, and (3) RNase 5, also known as angiogenin, another rapidly-evolving ribonuclease known to promote blood vessel growth with recently-discovered antibacterial activity. Interestingly, some of the characterized anti-pathogen activities do not depend on ribonuclease activity per se. We discuss the ways in which the anti-pathogen activities characterized in vitro might translate into experimental confirmation in vivo. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU Intramural NIH HHS NR 147 TC 74 Z9 76 U1 1 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1381-1991 J9 MOL DIVERS JI Mol. Divers. PD NOV PY 2006 VL 10 IS 4 BP 585 EP 597 DI 10.1007/s11030-006-9028-2 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 126VD UT WOS:000243542700008 PM 16969722 ER PT J AU Voss, TC John, S Hager, GL AF Voss, Ty C. John, Sam Hager, Gordon L. TI Single-cell analysis of glucocorticoid receptor action reveals that stochastic post-chromatin association mechanisms regulate ligand-specific transcription SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TUMOR VIRUS PROMOTER; GENE-EXPRESSION; LIVING CELLS; IN-VIVO; ANTAGONIST COMPLEXES; HORMONE INDUCTION; AGONIST ACTIVITY; MMTV PROMOTER; BINDING; COREPRESSOR AB The glucocorticoid receptor (GR) dynamically interacts with response elements in the mouse mammary tumor virus (MMTV) promoter to regulate steroid-dependent transcription. In a clonal mammary carcinoma cell line containing a tandem array of MMTV promoter-reporter gene cassettes integrated at a single genomic locus, direct binding of a green fluorescent protein (GFP)-GR fusion protein to the MMTV regulatory elements can be observed in living cells. After ligand treatment, MMTV-dependent transcription in individual cells was detected by RNA fluorescence in situ hybridization (FISH). High-resolution fluorescence images were acquired from large numbers of randomly selected cells. Images were analyzed with a novel automated computer algorithm, measuring the RNA FISH signal and the relative GFP-GR fluorescence intensity at the MMTV array for each cell. Although dexamethasone increased the mean RNA FISH signal approximately 10-fold, RU486 produced only about a 2-fold induction, as expected for this mixed antagonist. For all treatment conditions, the relative GFP-GR fluorescence at the array for the averaged cells paralleled the RNA FISH measurements, suggesting that image analysis accurately detected an increase in steady-state GR association with the MMTV array that was responsible for the increase in transcriptional activity. The antagonist-dependent decreases in GR association with the MMTV promoter were confirmed by chromatin immunoprecipitation experiments, supporting the image analysis results. A pronounced cell-to-cell variability was observed in RNA FISH signal and GR-MMTV association within treatment groups. We observed a nonlinear relationship between GR-MMTV association and RNA FISH in individual cells, indicating that differences in GR-MMTV interaction account for some, but not all, of the transcriptional heterogeneity between individual cells. In selected cell subpopulations with equal levels of GR-MMTV association, there was a decrease in RNA FISH signal with RU486 treatment compared with dexamethasone treatment. These results indicate that stochastic events occurring after GR-promoter association, such as the actions of chromatin remodeling complexes or other cofactors, change in a ligand-dependent manner and regulate heterogeneous transcription in individual cells. C1 NCI, Lab Receptor Biol & Gene Express, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov NR 44 TC 26 Z9 26 U1 0 U2 0 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 NOV PY 2006 VL 20 IS 11 BP 2641 EP 2655 DI 10.1210/me.2006-0091 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 098WH UT WOS:000241553100004 PM 16873444 ER PT J AU Nguyen, AD Pan, CJ Weinstein, DA Chou, JY AF Nguyen, Andrew D. Pan, Chi-Jiunn Weinstein, David A. Chou, Janice Y. TI Increased scavenger receptor class B type I-mediated cellular cholesterol efflux and antioxidant capacity in the sera of glycogen storage disease type Ia patients SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE glycogen storage disease type Ia; scavenger receptor class B type I; antioxidant; cholesterol efflux; atherosclerosis ID APOLIPOPROTEIN A-IV; E-DEFICIENT MICE; URIC-ACID; SR-BI; ATHEROSCLEROSIS; PLASMA; LIPIDS; 1A; LIPOPROTEINS; EXPRESSION AB Glycogen storage disease type la (GSD-Ia) is characterized by hypercholesterolemia, hypertriglyceridemia, decreased cholesterol in high density lipoprotein and increased cholesterol in low and very low density lipoprotein fractions. Despite this pro-atherogenic lipid profile, GSD-Ia patients are not at elevated risk for atherosclerosis. Studies have shown that reverse cholesterol transport and antioxidant capacity can be protective against atherosclerosis. In this study, we show that sera from GSD-Ia patients are more efficient than sera from control subjects in promoting the scavenger receptor class B type I (SR-BI)-mediated cellular cholesterol efflux, a key component in reverse cholesterol transport. The major determinants of the SR-BI-mediated cholesterol efflux are serum phospholipid (PL) and HDL-PL. Phospholipid and. that ratio of HDL-PL to HDL are increased in GSD-Ia patients. We further show that sera from GSD-Ia patients have increased total antioxidant capacity compared to controls and this increase correlates with elevated levels of uric acid, a powerful plasma antioxidant. Taken together, the results suggest that the increase in SR-BI-mediated cellular cholesterol efflux and antioxidant capacity in the sera of GSD-Ia patients may contribute to protection against premature atherosclerosis. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Div Pediat Endocrinol, Gainesville, FL 32610 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov FU NCRR NIH HHS [M01RR02172, K23 RR017560] NR 34 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2006 VL 89 IS 3 BP 233 EP 238 DI 10.1016/j.ymgme.2006.05.002 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 108RD UT WOS:000242256000007 PM 16777453 ER PT J AU Knodler, LA Bertero, M Yip, C Strynadka, NCJ Steele-Mortimer, O AF Knodler, Leigh A. Bertero, Michela Yip, Calvin Strynadka, Natalie C. J. Steele-Mortimer, Olivia TI Structure-based mutagenesis of SigE verifies the importance of hydrophobic and electrostatic residues in type III chaperone function SO MOLECULAR MICROBIOLOGY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; SECRETION CHAPERONE; SALMONELLA-TYPHIMURIUM; YERSINIA-ENTEROCOLITICA; VIRULENCE FACTORS; TETRATRICOPEPTIDE REPEATS; 3-DIMENSIONAL STRUCTURE; PATHOGENICITY ISLAND; CRYSTAL-STRUCTURE; EUKARYOTIC CELLS AB Despite sharing little sequence identity, most type III chaperones display a similar homodimeric structure characterized by negative charges distributed broadly over their entire surface, interspersed with hydrophobic patches. Here we have used SigE from Salmonella as a model for class IA type III chaperones to investigate the role of these surface-exposed residues in chaperone function. SigE is essential for the stability, secretion and translocation of its cognate effector, SopB (SigD). We analysed the effect of mutating nine conserved hydrophobic and electronegative surface-exposed amino acids of SigE on SopB binding, stability, secretion and translocation. Six of these mutations affected some aspect of SigE function (Leu14, Asp20, Leu22, Leu23, Ile25 and Asp51) and three were without effect (Leu54, Glu92 and Glu99). Our results highlight that both hydrophobic and electronegative surfaces are required for the function of SigE and provide an important basis for the prediction of side-chain requirements for other chaperone-effector pairs. C1 NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. RP Knodler, LA (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM lknodler@niaid.nih.gov FU Intramural NIH HHS NR 58 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2006 VL 62 IS 4 BP 928 EP 940 DI 10.1111/j.1365-2958.2006.05418.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 098ZK UT WOS:000241562100002 PM 17038123 ER PT J AU Belousova, N Harris, R Zinn, K Rhodes-Selser, MA Kotov, A Kotova, O Wang, MH Aurigemma, R Zhu, ZB Curiel, DT Alvarez, RD AF Belousova, Natalya Harris, Raymond Zinn, Kurt Rhodes-Selser, Mary Ann Kotov, Alexander Kotova, Olga Wang, Minghui Aurigemma, Rosemarie Zhu, Zeng B. Curiel, David T. Alvarez, Ronald D. TI Circumventing recombination events encountered with production of a clinical-grade adenoviral vector with a double-expression cassette SO MOLECULAR PHARMACOLOGY LA English DT Article ID REPORTER GENE-EXPRESSION; MOLECULAR CHEMOTHERAPY; OVARIAN-CANCER; IN-VIVO; RECEPTOR; THERAPY; CELLS; INTEGRINS AB Delivery of multiple exogenous genes into target cells is important for a broad range of gene therapy applications, including combined therapeutic gene expression and noninvasive imaging. Previous studies (Mol Ther 4: 223-231, 2001) have described the adenoviral vector RGDTKSSTR with a double-expression cassette that encodes herpes simplex virus thymidine kinase (HSVtk) for molecular chemotherapy and human somatostatin receptor subtype-2 (hSSTR2) for indirect imaging. In this vector, both genes are inserted in place of the E1 region of the adenoviral genome and expressed independently from two cytomegalovirus (CMV) promoters. During production of clinical-grade RGDTKSSTR, we found that the CMV promoters and simian virus 40 (SV40) poly(A) regions located in both expression cassettes provoked homologous recombination and deletion of one of the cassettes. To resolve this problem, we designed a strategy for substituting the duplicate promoters and poly(A) regions. We placed the hSSTR2 gene in the new Ad5.SSTR/TK.RGD vector under the control of a CMV promoter with a bovine growth hormone poly(A) region, whereas the SV40 promoter, enhancer, and poly(A) signal controlled HSVtk expression. This use of different regulatory sequences allowed independent expression of both transgenes from a single adenoviral vector and circumvented the recombination problem. Reconstruction of the vector with a double-expression cassette enables its use in human clinical trials. C1 Univ Alabama, Gene Therapy Ctr, Div Human Gene Therapy, Dept Med, Birmingham, AL 35249 USA. Univ Alabama, Gene Therapy Ctr, Dept Pathol, Birmingham, AL USA. Univ Alabama, Gene Therapy Ctr, Dept Surg, Birmingham, AL USA. Univ Alabama, Vaccine & Vector Prod Facil, Birmingham, AL USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. NCI, SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick, MD 21701 USA. RP Curiel, DT (reprint author), Univ Alabama, Gene Therapy Ctr, Div Human Gene Therapy, Dept Med, 901-19th St S,BMR2-502, Birmingham, AL 35249 USA. EM curiel@uab.edu OI Zinn, Kurt/0000-0001-7463-4741 FU NCI NIH HHS [N01-CO12400] NR 21 TC 8 Z9 8 U1 0 U2 0 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 NOV PY 2006 VL 70 IS 5 BP 1488 EP 1493 DI 10.1124/mol.106.025619 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097GV UT WOS:000241436100003 PM 16896072 ER PT J AU Jensen, LH Liang, H Shoemaker, R Grauslund, M Sehested, M Hasinoff, BB AF Jensen, Lars H. Liang, Hong Shoemaker, Robert Grauslund, Morten Sehested, Maxwell Hasinoff, Brian B. TI A three-dimensional quantitative structure-activity relationship study of the inhibition of the ATPase activity and the strand passing catalytic activity of topoisomerase II alpha by substituted purine analogs SO MOLECULAR PHARMACOLOGY LA English DT Article ID MEDIATED DNA-DAMAGE; IN-VITRO; CELL-LINES; ETOPOSIDE; ICRF-187; VP-16; CYTOTOXICITY; MECHANISM; RESISTANT; POISONS AB Based on the topoisomerase II alpha catalytic inhibitory activity of a previous hit compound, NSC35866, we screened 40 substituted purines or purine-like compounds from the National Cancer Institute repository for their ability to inhibit the ATPase activity of human topoisomerase II alpha. Several compounds, including NSC348400, NSC348401 and NSC348402, were inhibitory at submicromolar concentrations. Three-dimensional quantitative structure-activity relationship models using comparative molecular field and comparative molecular similarity indices analyses were constructed using 24 of these compounds. The ability of 10 selected compounds to inhibit the complete DNA strand passage reaction of topoisomerase II alpha correlated well with their potency as ATPase inhibitors. None of the 40 compounds significantly increased levels of the topoisomerase II alpha-DNA covalent complex, suggesting that they functioned as catalytic topoisomerase II inhibitors and not as topoisomerase II poisons. Although some of these compounds could antagonize the effect of etoposide on the level of topoisomerase II alpha-DNA covalent complex formation in vitro, in contrast to NSC35866, they were not capable of antagonizing etoposide-induced cytotoxicity and DNA strand breaks in cells. Two independently selected human SCLC cell lines with reduced topoisomerase II alpha expression displayed cross-resistance to NSC348400, NBSC348401, and NSC348402, whereas an MDR1 line was fully sensitive. These results suggest that topoisomerase II alpha is a functional cellular target for most of these substituted purine compounds and that these compounds do not display MDR1 liability. C1 Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. TopoTarget AS, Copenhagen, Denmark. Univ Copenhagen Hosp, Dept Pathol, Ctr Diagnost, DK-2100 Copenhagen, Denmark. NCI, Dev Therapeut Program, Frederick, MD 21701 USA. RP Hasinoff, BB (reprint author), Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. EM b_hasinoff@umanitoba.ca NR 33 TC 15 Z9 16 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2006 VL 70 IS 5 BP 1503 EP 1513 DI 10.1124/mol.106.026856 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097GV UT WOS:000241436100005 PM 16880287 ER PT J AU Hamel, E Day, BW Miller, JH Jung, MK Northcote, PT Ghosh, AK Curran, DP Cushman, M Nicolaou, KC Paterson, I Sorensen, EJ AF Hamel, Ernest Day, Billy W. Miller, John H. Jung, M. Katherine Northcote, Peter T. Ghosh, Arun K. Curran, Dennis P. Cushman, Mark Nicolaou, K. C. Paterson, Ian Sorensen, Erik J. TI Synergistic effects of peloruside a and laulimalide with taxoid site drugs, but not with each other, on tubulin assembly SO MOLECULAR PHARMACOLOGY LA English DT Article ID MICROTUBULE-STABILIZING AGENTS; BIOLOGICAL EVALUATION; PACLITAXEL TAXOL; MARINE SPONGE; ABSOLUTE-CONFIGURATIONS; (-)-LAULIMALIDE ANALOGS; PURIFIED TUBULIN; CELLS RESISTANT; BINDING; POLYMERIZATION AB Previous studies on the drug content of pelleted tubulin polymers suggest that peloruside A binds in the laulimalide site, which is distinct from the taxoid site. In a tubulin assembly system containing microtubule-associated proteins and GTP, however, peloruside A was significantly less active than laulimalide, inducing assembly in a manner that was most similar to sarcodictyins A and B. Because peloruside A thus far seems to be the only compound that mimics the action of laulimalide, we examined combinations of microtubule-stabilizing agents for synergistic effects on tubulin assembly. We found that peloruside A and laulimalide showed no synergism but that both compounds could act synergistically with a number of taxoid site agents [paclitaxel, epothilones A/B, discodermolide, dictyostatin, eleutherobin, the steroid derivative 17 beta-acetoxy-2-ethoxy-6-oxo-B-homo-estra-1,3,5(10)-trien-3-ol, and cyclostreptin]. None of the taxoid site compounds showed any synergism with each other. From an initial study with peloruside A and cyclostreptin, we conclude that the synergism phenomenon derives, at least in part, from an apparent lowering of the tubulin critical concentration with drug combinations compared with single drugs. The apparent binding of peloruside A in the laulimalide site led us to attempt construction of a pharmacophore model based on superposition of an energy-minimized structure of peloruside A on the crystal structure of laulimalide. Although the different sizes of the macrocycles limited our ability to superimpose the two molecules, atom correspondences that were observed were consistent with the difficulty so far experienced in creation of fully active analogs of laulimalide. C1 NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Frederick, MD 21702 USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. Univ Pittsburgh, Dept Chem, Pittsburgh, PA USA. Victoria Univ Wellington, Sch Biol Sci, Wellington, New Zealand. Victoria Univ Wellington, Sch Chem & Phys Sci, Wellington, New Zealand. NCI, SAIC Frederick Inc, NIH, Frederick, MD 21701 USA. Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, Sch Pharm & Pharmaceut Sci, W Lafayette, IN 47907 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. Scripps Res Inst, Dept Chem, La Jolla, CA USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. RP Hamel, E (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Bldg 469,Room 104, Frederick, MD 21702 USA. EM hamele@mail.nih.gov FU NCI NIH HHS [N0-1-CO-12400] NR 42 TC 89 Z9 92 U1 1 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2006 VL 70 IS 5 BP 1555 EP 1564 DI 10.1124/mol.106.027847 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097GV UT WOS:000241436100010 PM 16887932 ER PT J AU Martin, NP Mohney, RP Dunn, S Das, M Scappini, E O'Bryan, JP AF Martin, Negin P. Mohney, Robert P. Dunn, Sara Das, Margaret Scappini, Erica O'Bryan, John P. TI Intersectin regulates epidermal growth factor receptor endocytosis, ubiquitylation, and signaling SO MOLECULAR PHARMACOLOGY LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; UBIQUITIN-PROTEASOME SYSTEM; PROTEIN INTERSECTIN; DOWN-REGULATION; EGF RECEPTORS; CBL; DOMAINS; PATHWAY; BINDING; MOTIF AB Receptor tyrosine kinases (RTKs) are critical for normal cell growth, differentiation, and development, but they contribute to various pathological conditions when disrupted. Activation of RTKs stimulates a plethora of pathways, including the ubiquitylation and endocytosis of the receptor itself. Although endocytosis terminates RTK signaling, it has emerged as a requisite step in RTK activation of signaling pathways. We have discovered that the endocytic scaffolding protein intersectin (ITSN) cooperated with epidermal growth factor receptor (EGFR) in the regulation of cell growth and signaling. However, a biochemical link between ITSN and EGFR was not defined. In this study, we demonstrate that ITSN is a scaffold for the E3 ubiquitin ligase Cbl. ITSN forms a complex with Cbl in vivo mediated by the Src homology (SH) 3 domains binding to the Prorich COOH terminus of Cbl. This interaction stimulates the ubiquitylation and degradation of the activated EGFR. Furthermore, silencing ITSN by RNA interference attenuated EGFR internalization as well as activation of the extracellular signal-regulated kinase-mitogen-activated protein kinase pathway, thereby demonstrating the importance of ITSN in EGFR function. Given the cooperativity between ITSN and additional RTKs, these results point to an important evolutionarily conserved, regulatory role for ITSN in RTK function that is necessary for both signaling from receptors as well as the ultimate termination of receptor signaling. C1 Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP O'Bryan, JP (reprint author), Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA. EM obryanj@uic.edu OI Martin, Negin/0000-0003-3166-8989 FU Intramural NIH HHS NR 38 TC 36 Z9 43 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 NOV PY 2006 VL 70 IS 5 BP 1643 EP 1653 DI 10.1124/mol.106.028274 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097GV UT WOS:000241436100019 PM 16914641 ER PT J AU Chen, SY Fariss, R Kutty, R Nelson, R Wiggert, B AF Chen, Shanyi Fariss, Robert N. Kutty, R. Krishnan Nelson, Ralph Wiggert, Barbara TI Fenretinide-induced neuronal differentiation of ARPE-19 human retinal pigment epithelial cells is associated with the differential expression of Hsp70, 14-3-3, pax-6, tubulin beta-III, NSE, and bag-1 proteins SO MOLECULAR VISION LA English DT Article ID EMBRYONIC STEM-CELLS; GENE-EXPRESSION; LINE; ACID; TRANSCRIPTION; FATE; REGULATOR; CULTURES; SURVIVAL; MARKER AB Purpose: We reported earlier that fenretinide can induce neuronal differentiation of ARPE-19 human retinal pigment epithelial cells in culture. The purpose of this study was to investigate the potential involvement of key proteins involved in gene transcription, signal transduction, cell cycle check point, differentiation, neuronal cell survival, and stress response in the neuronal differentiation of ARPE-19 cells by fenretinide. Methods: Cells in culture were treated with 1.0 mu M fenretinide. Cells were analyzed using antibodies against pax-6, neuronal specific enolase (NSE), tubulin beta-III, 14-3-3, bag-1, and Hsp-70 proteins using immunocytochemistry, western blot and ELISA methodologies. Results: We found that pax-6 and NSE were both expressed in the control ARPE-19 cells. Fenretinide induced neuronal differentiation of ARPE-19 cells led to a decrease in pax-6 protein and an increase in tubulin beta-III protein expression after 5 days fenretinide treatment. There was a translocation of 14-3-3 from the cytoplasm to the nucleus, and an increase in nuclear expression of bag-1 after treatment. We also found a time-dependent increase in Hsp70 protein expression in ARPE-19 cells treated with fenretinide. D-407, another human retinal pigment epithelial cell line, but not either Y-79 or PC-12 cells, was also able to be induced into neuronal morphologies by fenretinide. Conclusions: The fenretinide-induced neuronal differentiation of ARPE-19 cells is associated with an increase in expression of the neuronal specific protein tubulin beta-III, and a decrease in expression of the progenitor cell marker pax-6. Neuronal differentiation of ARPE-19 cells is also associated with nuclear translocation of 14-3-3, a protein involved in signal transduction, cell cycle check point and cell growth, and an increase in expression of bag-1, a protein involved in neuronal cell survival and axon elongation. These results suggest that ARPE-19 cells could be a progenitor cell line that can be differentiated into neuronal cells when treated with factors such as fenretinide. C1 NEI, Biochem Sect, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. NEI, Biol Imaging Core, Bethesda, MD 20892 USA. NINDS, Neural Circuits Unit, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Wiggert, B (reprint author), NEI, Biochem Sect, Lab Retinal Cell & Mol Biol, NIH, Bldg 7,Room 300,7 Mem Dr,MSC 0706, Bethesda, MD 20892 USA. EM bnwigg@helix.nih.gov FU Intramural NIH HHS NR 50 TC 8 Z9 8 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 1 PY 2006 VL 12 IS 151-52 BP 1355 EP 1363 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 105NM UT WOS:000242037100002 PM 17110918 ER PT J AU Simon-Sanchez, J Marti-Masso, JF Sanchez-Mut, JV Paisan-Ruiz, C Martinez-Gil, A Ruiz-Martinez, J Saenz, A Singleton, AB de Munain, AL Perez-Tur, J AF Simon-Sanchez, Javier Marti-Masso, Jose-Felix Sanchez-Mut, Jose Vicente Paisan-Ruiz, Coro Martinez-Gil, Angel Ruiz-Martinez, Javier Saenz, Amets Singleton, Andrew B. de Munain, Adolfo Lopez Perez-Tur, Jordi TI Parkinson's disease due to the R1441G mutation in Dardarin: A founder effect in the Basques SO MOVEMENT DISORDERS LA English DT Article DE Dardarin; LRRK2; Parkinson's disease; Basque country; founder effect ID FAMILIES; GENE AB The recent discovery of mutations in Dardarin (LRRK2) have been related to the appearance of Parkinson's disease in several families. Notably, one single mutation in this gene (R1441G) not only appeared in familial, but also in apparently sporadic Parkinson disease (PD) patients of Basque descent. A clinical population was ascertained, and subjects were classified into Basque and non-Basque descent according to their known ancestry. The R1441G mutation was assayed using an allele-specific polymerase chain reaction, and several single nucleotide polymorphisms surrounding this mutation were analyzed by direct sequencing. In addition to 22 members of the original Basque families where R1441G was identified, we observed 17 carriers of the mutation who were apparently related through a common ancestor. From a clinical perspective, the disease observed in mutation carriers is indistinguishable from that in noncarriers. The R1441G mutation causes a form of Parkinson's disease that is equivalent to that observed in idiopathic Parkinson's disease. This mutation appears in 16.4% and 4.0% of familial and sporadic PD in this Basque population, respectively. (c) 2006 Movement Disorder Society C1 CSIC, Inst Biomed Valencia, Unitat Genet Mol, Dept Genom & Proteom, E-46010 Valencia, Spain. Hosp Donostia, Serv Neurol, San Sebastian, Spain. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Ntra, Serv Neurol, Zumarraga, Spain. Hosp Mendaro, Serv Neurol, Medaro, Spain. Hosp Donostia, Unidad Expt, San Sebastian, Spain. RP Perez-Tur, J (reprint author), CSIC, Inst Biomed Valencia, Unitat Genet Mol, Dept Genom & Proteom, C Jaime Roig 11, E-46010 Valencia, Spain. EM jpereztur@ibv.csic.es RI Paisan-Ruiz, Coro/C-2912-2009; Perez-Tur, Jordi/A-2143-2010; Singleton, Andrew/C-3010-2009 OI Perez-Tur, Jordi/0000-0002-9111-1712; FU Intramural NIH HHS NR 8 TC 39 Z9 41 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2006 VL 21 IS 11 BP 1954 EP 1959 DI 10.1002/mds.21114 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 108GT UT WOS:000242229000022 PM 16991141 ER PT J AU Chand, P Grafman, J Dickson, D Ishizawa, K Litvan, I AF Chand, Pratap Grafman, Jordan Dickson, Dennis Ishizawa, Keisuke Litvan, Irene TI Alzheimer's disease presenting as corticobasal syndrome SO MOVEMENT DISORDERS LA English DT Article DE Alzheimer's disease; corticobasal degeneration; corticobasal syndrome; myoclonus; alien limb phenomenon; neuropathology ID PROGRESSIVE SUPRANUCLEAR PALSY; DEGENERATION AB A 60-year-old man presented with slowly progressive left hemi-Parkinsonism, left hand apraxia, myoclonus, dystonia, visuospatial disturbances, and alien limb phenomenon, resembling corticobasal syndrome. Eight years later, neuropathology revealed features of Alzheimer's disease, with asymmetrical (right more than left) cortical tau burden with image analysis. The videotaped clinical features, neuropsychological aspects, and neuropathological correlates are presented and discussed. (c) 2006 Movement Disorder Society C1 Univ Louisville, Dept Neurol, Sch Med, Louisville, KY 40202 USA. Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bethesda, MD USA. Mayo Clin Jacksonville, Dept Pathol, Jacksonville, FL 32224 USA. RP Litvan, I (reprint author), Univ Louisville, Dept Neurol, Sch Med, 500 S Preston St,A Bldg,HSC 113, Louisville, KY 40202 USA. EM i.litvan@louisville.edu OI Dickson, Dennis W/0000-0001-7189-7917; Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 10 TC 26 Z9 26 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2006 VL 21 IS 11 BP 2018 EP 2022 DI 10.1002/mds.21055 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 108GT UT WOS:000242229000039 PM 16977625 ER PT J AU Hosaka, K Bates, ST Beever, RE Castellano, MA Colgan, W Dominguez, LS Nouhra, ER Geml, J Giachini, AJ Kenney, SR Simpson, NB Spatafora, JW Trappe, JM AF Hosaka, Kentaro Bates, Scott T. Beever, Ross E. Castellano, Michael A. Colgan, Wesley, III Dominguez, Laura S. Nouhra, Eduardo R. Geml, Jozsef Giachini, Admir J. Kenney, S. Ray Simpson, Nicholas B. Spatafora, Joseph W. Trappe, James M. TI Molecular phylogenetics of the gomphoid-phalloid fungi with an establishment of the new subclass Phallomycetidae and two new orders SO MYCOLOGIA LA English DT Article DE atp6; EF-1 alpha; homobasidiomycetes; rDNA; RPB2; systematics ID TRUFFLE-LIKE FUNGI; WESTERN-AUSTRALIA; MAXIMUM-LIKELIHOOD; RDNA SEQUENCES; BASIDIOMYCOTINA; EVOLUTION; PROTUBERA; CORTINARIACEAE; MITOCHONDRIAL; HYSTERANGIUM AB Molecular phylogenetic analyses for the gomphoid-phalloid fungi were conducted based on the five gene dataset with extensive taxon sampling. The monophyly of the gomphoid-phalloid clade was strongly supported, and four well Supported major subclades were recognized. Three of the four subclades were represented entirely by gastroid taxa, and only Gomphales contained both gastroid and nongastroid taxa. While the gastroid morphology is derived from epigeous, nongastroid taxa in Gomphales, the topology of Phallales indicated that truffle-like form is an ancestral morphology of the stinkhorn fruiting bodies. Although basidiospore maturation occurs within the enclosed fruiting bodies of the stinkhorn, the elevation of the mature spore-producing tissue represents an independent origin of the stipe among Basidiomycota. Comparisons are made between previous and new classification schemes, which are based on the results of phylogenetic analyses. Based on the results of these analyses, a new subclass Phallomycetidae, and two new orders, Hysterangiales and Geastrales, are proposed. C1 Field Museum, Dept Bot, Chicago, IL 60605 USA. Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. Landcare Res, Auckland, New Zealand. USDA, Forest Serv, Pacific NW Res Stn, Forestry Sci Lab, Corvallis, OR 97331 USA. ADInstruments, Colorado Springs, CO 80906 USA. Univ Nacl Cordoba, Inst Muiltidisciplinario Biol Vegetal, RA-5000 Cordoba, Argentina. Univ Alaska, Inst Arct Biol, Fairbanks, AK 99775 USA. SBW Brasil Agrifloricultura Ltda, BR-13825000 Sao Paulo, Brazil. NIH, Bethesda, MD 20892 USA. Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. Oregon State Univ, Dept Bot & Plant Physiol, Corvallis, OR 97331 USA. Oregon State Univ, Dept Forest Sci, Corvallis, OR 97331 USA. RP Hosaka, K (reprint author), Field Museum, Dept Bot, 1400 S Lake Shore Dr, Chicago, IL 60605 USA. EM khosaka@fieldmuseum.org RI Giachini, Admir/C-4007-2014 OI Giachini, Admir/0000-0001-8347-003X NR 56 TC 93 Z9 110 U1 2 U2 17 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD NOV-DEC PY 2006 VL 98 IS 6 BP 949 EP 959 DI 10.3852/mycologia.98.6.949 PG 11 WC Mycology SC Mycology GA 159IK UT WOS:000245858800012 PM 17486971 ER PT J AU Weinstein, JN Pommier, Y AF Weinstein, John N. Pommier, Yves TI Connecting genes, drugs and diseases SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID MOLECULAR PHARMACOLOGY; CELL-LINES; CANCER; SCREEN AB A large- scale chemical genetic approach for systematically linking gene expression profiles with compounds and phenotypes offers promise for both basic and applied biomedical research. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Room 5068,37 Convent Dr, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov; pommiery@mail.nih.gov NR 14 TC 8 Z9 9 U1 0 U2 3 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 NOV PY 2006 VL 24 IS 11 BP 1365 EP 1366 DI 10.1038/nbt1106-1365 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 106TP UT WOS:000242124700031 PM 17093484 ER PT J AU Swedlow, JR Lewis, SE Goldberg, IG AF Swedlow, Jason R. Lewis, Suzanna E. Goldberg, Ilya G. TI Modelling data across labs, genomes, space and time SO NATURE CELL BIOLOGY LA English DT Review ID QUANTITATIVE-ANALYSIS; HUMAN-CELLS; MICROSCOPY; DYNAMICS; INFORMATICS; MOVEMENT; ONTOLOGY; BIOLOGY; SCREEN; FILE AB Logical models and physical specifications provide the foundation for storage, management and analysis of complex sets of data, and describe the relationships between measured data elements and metadata - the contextual descriptors that define the primary data. Here, we use imaging applications to illustrate the purpose of the various implementations of data specifications and the requirement for open, standardized, data formats to facilitate the sharing of critical digital data and metadata. C1 Univ Dundee, Fac Life Sci, Div Gene Regulat & Express, Wellcome Trust Bioctr, Dundee DD1 5EH, Scotland. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94729 USA. NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Swedlow, JR (reprint author), Univ Dundee, Fac Life Sci, Div Gene Regulat & Express, Wellcome Trust Bioctr, Dow St, Dundee DD1 5EH, Scotland. EM jason@lifesci.dundee.ac.uk RI Goldberg, Ilya/H-5307-2011; OI Goldberg, Ilya/0000-0001-8514-6110; Lewis, Suzanna/0000-0002-8343-612X; Swedlow, Jason/0000-0002-2198-1958 FU Biotechnology and Biological Sciences Research Council [BB/D006589/1]; Wellcome Trust NR 28 TC 21 Z9 23 U1 0 U2 1 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 NOV PY 2006 VL 8 IS 11 BP 1190 EP 1194 DI 10.1038/ncb1496 PG 5 WC Cell Biology SC Cell Biology GA 101HR UT WOS:000241732400003 PM 17060903 ER PT J AU Gavard, J Gutkind, JS AF Gavard, Julie Gutkind, J. Silvio TI VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin SO NATURE CELL BIOLOGY LA English DT Article ID COUPLED RECEPTOR TRAFFICKING; FOCAL ADHESION KINASE; VASCULAR-PERMEABILITY; TYROSINE PHOSPHORYLATION; ADRENERGIC-RECEPTOR; DOWN-REGULATION; SRC ACTIVITY; GROWTH; PROTEIN; ANGIOGENESIS AB How vascular endothelial growth factor (VEGF) induces vascular permeability, its first described function, remains poorly understood. Here, we provide evidence of a novel signalling pathway by which VEGF stimulation promotes the rapid endocytosis of a key endothelial cell adhesion molecule, VE-cadherin, thereby disrupting the endothelial barrier function. This process is initiated by the activation of the small GTPase Rac by VEGFR-2 through the Src-dependent phosphorylation of Vav2, a guanine nucleotide-exchange factor. Rac activation, in turn, promotes the p21-activated kinase (PAK)-mediated phosphorylation of a highly conserved motif within the intracellular tail of VE-cadherin. Surprisingly, this results in the recruitment of beta-arrestin2 to serine-phosphorylated VE-cadherin, thereby promoting its internalization into clathrin-coated vesicles and the consequent disassembly of intercellular junctions. Ultimately, this novel biochemical route by which VEGF promotes endothelial permeability through the beta-arrestin2-dependent endocytosis of VE-cadherin may help identify new therapeutic targets for the treatment of many human diseases that are characterized by vascular leakage. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012 OI Gavard, Julie/0000-0002-7985-9007 FU Intramural NIH HHS NR 49 TC 497 Z9 523 U1 2 U2 47 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 NOV PY 2006 VL 8 IS 11 BP 1223 EP U17 DI 10.1038/ncb1486 PG 17 WC Cell Biology SC Cell Biology GA 101HR UT WOS:000241732400011 PM 17060906 ER PT J AU Zimmerberg, J Gawrisch, K AF Zimmerberg, Joshua Gawrisch, Klaus TI The physical chemistry of biological membranes SO NATURE CHEMICAL BIOLOGY LA English DT Editorial Material ID DOCOSAHEXAENOIC-ACID; PROTEIN; FUSION; RHODOPSIN; RECEPTOR; BILAYERS; LIPIDS; MODEL; ORGANIZATION; MODULATION C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov; gawrisch@helix.nih.gov NR 33 TC 53 Z9 54 U1 2 U2 35 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 NOV PY 2006 VL 2 IS 11 BP 564 EP 567 DI 10.1038/nchembio1106-564 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 098BC UT WOS:000241494000003 PM 17051226 ER PT J AU Mittleman, BB Lipsky, PE AF Mittleman, Barbara B. Lipsky, Peter E. TI Optimizing care for patients with rheumatic disease worldwide: a concept of global rheumatology SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Editorial Material C1 NIH, Program Publ Private Partnerships, Off Sci Policy, Bethesda, MD 20892 USA. RP Mittleman, BB (reprint author), NIH, Program Publ Private Partnerships, Off Sci Policy, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD NOV PY 2006 VL 2 IS 11 BP 575 EP 575 DI 10.1038/ncprheum0321 PG 1 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 098CH UT WOS:000241498100001 PM 17075591 ER PT J AU Nikolov, NP Smith, JA Patronas, NJ Illei, GG AF Nikolov, Nikolay P. Smith, Janine A. Patronas, Nicholas J. Illei, Gabor G. TI Diagnosis and treatment of vasculitis of the central nervous system in a patient with systemic lupus erythematosus SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Article DE cyclophosphamide; neuroimaging; retinal vasculitis; systemic lupus erythematosus; vasculitis of the central nervous system ID NEUROLOGICAL MANIFESTATIONS; INTRAVENOUS IMMUNOGLOBULIN; DISEASE; CYCLOPHOSPHAMIDE AB Background A 23-year-old white woman with a 3-year history of systemic lupus erythematosus and a 15-month history of lupus nephritis and retinal vasculitis was successfully treated with antibiotics for Pseudomonas aeruginosa pneumonia while on moderate doses of corticosteroids. Even though her pneumonia had improved, she developed acute changes in her mental status that rapidly progressed to encephalopathy with coma. Investigations Physical examination, fundoscopic examination, laboratory tests for metabolic abnormalities, cerebrospinal fluid analysis, microbiology and serologic testing, electroencephalogram, tests for IgM and IgG anticardiolipin antibodies, neuroimaging including CT of the brain and T1-weighted MRI before and after gadolinium contrast, and flow-attenuated inversion recovery MRI. Diagnosis Vasculitis of the central nervous system associated with systemic lupus erythematosus. Management Intravenous methylprednisolone 1,000 mg/day for 3 days, one dose of intravenous pulse cyclophosphamide 750 mg/m(2), intravenous immunoglobulin 400 mg/kg/day for 4 days, plasmapheresis on alternate days for five cycles, and prednisone 40 mg/day. She continued monthly doses of intravenous pulse cyclophosphamide and intravenous pulse methylprednisolone for 6 months, followed by maintenance infusions every 3 months over 2 years. Prednisone was tapered over 18 months. Cyclophosphamide was discontinued after 2 years because of poor bone-marrow tolerance, and was replaced with mycophenolate mofetil 3,000 mg/day and ciclosporin 50 mg twice daily. C1 Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. NIH, Neuroradiol Sect, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N-114, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov NR 16 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD NOV PY 2006 VL 2 IS 11 BP 627 EP 633 DI 10.1038/ncprheum0337 PG 7 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 098CH UT WOS:000241498100012 PM 17075602 ER PT J AU Lattouf, JB Srinivasan, R Pinto, PA Linehan, WM Neckers, L AF Lattouf, Jean-Baptiste Srinivasan, Ramaprasad Pinto, Peter A. Linehan, W. Marston Neckers, Leonard TI Mechanisms of Disease: the role of heat-shock protein 90 in genitourinary malignancy SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Review DE 17AAG; geldanamycin; heat-shock protein 90; prostate cancer; renal cell carcinoma ID HEAT-SHOCK-PROTEIN; PROSTATE-CANCER CELLS; UROKINASE PLASMINOGEN-ACTIVATOR; EMBRYONAL CARCINOMA-CELLS; EPIDERMAL-GROWTH-FACTOR; ANDROGEN RECEPTOR; IN-VIVO; BREAST-CANCER; PHASE-I; ONCOGENIC TRANSFORMATION AB Insight into the molecular biology of cancer has allowed the development of novel therapeutic strategies that target specific oncogenic pathways. Molecular therapeutic strategies are now part of the armamentarium available against urologic malignancy. Among the many targets of interest in urologic cancer, heat-shock protein 90 (HSP90) shows great promise. This molecule has a major role in prostate as well as in renal malignancy. In contrast to other targets, where cancer might escape inhibition via alternative pathways, HSP90 operates at multiple checkpoints in a cancer cell. Its inhibition could, therefore, prove more difficult for neoplastic cells to overcome. Inhibitors of HSP90, such as geldanamycin and its derivatives (17-allylamino-17-demethoxygeldanamycin and 17-dimethylaminoethylamino-17-demethoxygeldanamycin, known as 17AAG and 17DMAG, respectively) are available and have shown activity both in vivo and in vitro. 17AAG is currently being tested for efficacy in humans after having completed phase I trials, while 17DMAG is still in phase I evaluation. Phase II trials of HSP90 inhibitors in urologic malignancy are being conducted in kidney and advanced prostate cancer. Beyond monotherapy, HSP90 inhibitors might also prove to be beneficial in combination therapy with other chemotherapeutic agents in advanced disease. Studies being conducted in prostate cancer will hopefully help to define this potential application better. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, NIH, Room 1-5942,Bldg 10 CRC,9000 Rockville Pike, Bethesda, MD 20892 USA. EM neckersl@mail.nih.gov FU Intramural NIH HHS NR 80 TC 31 Z9 32 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD NOV PY 2006 VL 3 IS 11 BP 590 EP 601 DI 10.1038/ncpuro0604 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 102NE UT WOS:000241818100010 PM 17088927 ER PT J AU Salomon, DS AF Salomon, David S. TI Melanoma pathogenesis and Nodal: a partial picture? SO NATURE MEDICINE LA English DT Letter C1 NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov NR 3 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2006 VL 12 IS 11 BP 1231 EP 1231 DI 10.1038/nm1106-1231a PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 102WU UT WOS:000241844900009 PM 17088882 ER PT J AU Tegeder, I Costigan, M Griffin, RS Abele, A Belfer, I Schmidt, H Ehnert, C Nejim, J Marian, C Scholz, J Wu, TX Allchorne, A Diatchenko, L Binshtok, AM Goldman, D Adolph, J Sama, S Atlas, SJ Carlezon, WA Parsegian, A Lotsch, J Fillingim, RB Maixner, W Geisslinger, G Max, MB Woolf, CJ AF Tegeder, Irmgard Costigan, Michael Griffin, Robert S. Abele, Andrea Belfer, Inna Schmidt, Helmut Ehnert, Corina Nejim, Jemiel Marian, Claudiu Scholz, Joachim Wu, Tianxia Allchorne, Andrew Diatchenko, Luda Binshtok, Alexander M. Goldman, David Adolph, Jan Sama, Swetha Atlas, Steven J. Carlezon, William A. Parsegian, Aram Loetsch, Joern Fillingim, Roger B. Maixner, William Geisslinger, Gerd Max, Mitchell B. Woolf, Clifford J. TI GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence SO NATURE MEDICINE LA English DT Article ID PERIPHERAL-NERVE INJURY; MAINE LUMBAR SPINE; NITRIC-OXIDE; DORSAL-HORN; I GENE; LAPAROSCOPIC CHOLECYSTECTOMY; NONSURGICAL MANAGEMENT; GABAERGIC INHIBITION; NEUROPATHIC PAIN; PROTEIN AB We report that GTP cyclohydrolase (GCH1), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, is a key modulator of peripheral neuropathic and inflammatory pain. BH4 is an essential cofactor for catecholamine, serotonin and nitric oxide production. After axonal injury, concentrations of BH4 rose in primary sensory neurons, owing to upregulation of GCH1. After peripheral inflammation, BH4 also increased in dorsal root ganglia (DRGs), owing to enhanced GCH1 enzyme activity. Inhibiting this de novo BH4 synthesis in rats attenuated neuropathic and inflammatory pain and prevented nerve injury-evoked excess nitric oxide production in the DRG, whereas administering BH4 intrathecally exacerbated pain. In humans, a haplotype of the GCH1 gene (population frequency 15.4%) was significantly associated with less pain following diskectomy for persistent radicular low back pain. Healthy individuals homozygous for this haplotype exhibited reduced experimental pain sensitivity, and forskolinstimulated immortalized leukocytes from haplotype carriers upregulated GCH1 less than did controls. BH4 is therefore an intrinsic regulator of pain sensitivity and chronicity, and the GTP cyclohydrolase haplotype is a marker for these traits. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Frankfurt, Pharmazentrum, Inst Klin Pharmakol, Zentrum Arzneimittelforsch Entwicklung & Sicherhe, D-60590 Frankfurt, Germany. NIAAA, Neurogenet Lab, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Ctr Neurosensory Disorders, Sch Dent, Chapel Hill, NC 27599 USA. Univ Florida, Coll Dent, Gainesville, FL 32608 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Belmont, MA 02478 USA. Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20892 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM cwoolf@partners.org RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lotsch, Jorn/0000-0002-5818-6958; Tegeder, Irmgard/0000-0001-7524-8025 FU NIAAA NIH HHS [Z01 AA000301]; NIDCR NIH HHS [DE07509, DE16558, Z01 DE00366]; NINDS NIH HHS [NS038253, NS039518, NS045685, NS052623] NR 49 TC 299 Z9 313 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2006 VL 12 IS 11 BP 1269 EP 1277 DI 10.1038/nm1490 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 102WU UT WOS:000241844900024 PM 17057711 ER PT J AU Szabo, E AF Szabo, Eva TI Selecting targets for cancer prevention: where do we go from here? SO NATURE REVIEWS CANCER LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; CELL LUNG-CANCER; RANDOMIZED-TRIAL; BREAST-CANCER; BETA-CAROTENE; COLORECTAL ADENOMAS; CYCLOOXYGENASE-2 INHIBITOR; ADJUVANT CHEMOTHERAPY; VITAMIN-E; CHEMOPREVENTION AB Given the lack of progress in curing metastatic epithelial cancers, there is intense interest in, and a sound scientific rationale for, pursuing strategies to prevent cancer. However, although several clinical trials have shown efficacy in cancer prevention, few have resulted in changes to medical practice, and some trials have even shown harm. Recent experiences with serious side effects identified in cancer prevention trials underscore the need to re-evaluate our approach to clinical chemopreventive drug development, and to establish a framework for agent selection for future trials. C1 NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, 6130 Execut Blvd,Room 2132, Bethesda, MD 20892 USA. EM szaboe@mail.nih.gov NR 47 TC 24 Z9 24 U1 0 U2 1 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 NOV PY 2006 VL 6 IS 11 BP 867 EP 874 DI 10.1038/nrc.2008 PG 8 WC Oncology SC Oncology GA 098BA UT WOS:000241493800011 PM 17036038 ER PT J AU Wu, L KewalRamani, VN AF Wu, Li KewalRamani, Vineet N. TI Dendritic-cell interactions with HIV: infection and viral dissemination SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; SIGN-MEDIATED INTERNALIZATION; C-TYPE LECTIN; DC-SIGN; LANGERHANS CELLS; HUMAN BLOOD; IN-VITRO; ANTIGEN PRESENTATION; INTRAVAGINAL INOCULATION AB Dendritic cells (DCs) are crucial for the generation and the regulation of adaptive immunity. Because DCs have a pivotal role in marshalling immune responses, HIV has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. Defining the mechanisms that underlie cell-cell transmission of HIV and understanding the role of DCs in this process should help us in the fight against HIV infection. This Review highlights the latest advances in our understanding of the interactions between DCs and HIV, focusing on the mechanisms of DC-mediated viral dissemination. C1 Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. Natl Canc Inst, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. RP Wu, L (reprint author), Med Coll Wisconsin, Dept Microbiol & Mol Genet, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM liwu@mcw.edu RI Wu, Li/E-4330-2011 OI Wu, Li/0000-0002-5468-2487 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI068493] NR 128 TC 320 Z9 327 U1 4 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2006 VL 6 IS 11 BP 859 EP 868 DI 10.1038/nri1960 PG 10 WC Immunology SC Immunology GA 099DZ UT WOS:000241574000016 PM 17063186 ER PT J AU Kelley, MW AF Kelley, Matthew W. TI Regulation of cell fate in the sensory epithelia of the inner ear SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID FIBROBLAST-GROWTH-FACTOR; AUDITORY-SYSTEM DEVELOPMENT; OTIC PLACODE INDUCTION; NOTCH LIGAND JAGGED1; COCHLEAR HAIR-CELLS; MATURE GUINEA-PIGS; MIND-BOMB MUTANT; MAMMALIAN COCHLEA; SUPPORTING CELLS; FUNCTIONAL CONSERVATION AB The sensory epithelia of the inner ear contain mechanosensory hair cells and non-sensory supporting cells. Both classes of cell are heterogeneous, with phenotypes varying both between and within epithelia. The specification of individual cells as distinct types of hair cell or supporting cell is regulated through intra- and extracellular signalling pathways that have been poorly understood. However, new methodologies have resulted in significant steps forward in our understanding of the molecular pathways that direct cells towards these cell fates. C1 Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Kelley, MW (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM Kelleymt@nidcd.nih.gov FU Intramural NIH HHS NR 126 TC 152 Z9 160 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD NOV PY 2006 VL 7 IS 11 BP 837 EP 849 DI 10.1038/nrn1987 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 097HI UT WOS:000241437500010 PM 17053809 ER PT J AU Klote, MM Agodoa, LY Abbott, KC AF Klote, Mary M. Agodoa, Lawrence Y. Abbott, Kevin C. TI Risk factors for Mycobacterium tuberculosis in US chronic dialysis patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE dialysis; end-stage renal disease; risk factors; tuberculosis ID STAGE RENAL-DISEASE; HEMODIALYSIS; PREVALENCE; INFECTION AB Background. End-stage renal disease is known to disrupt the cell-mediated immune response that is responsible for the killing of intracellular organisms such as Mycobacterium tuberculosis. Risk factors that contribute to the development of tuberculosis (TB) disease in the US dialysis population have not been studied on a large scale. Methods. A retrospective cohort study of TB disease in 272 024 patients in the US Renal Data System initiated on dialysis therapy between 1 April 1995 and 31 December 1999 with Medicare or Medicaid as primary payer were analysed. A total of 21 risk factors were analysed. Results. Among the US population studied, there is a 1.2 and 1.6% cumulative incidence of TB in patients undergoing either peritoneal or haemodialysis, respectively. Ten risk factors for TB that proved to be statistically significant included advanced age (P < 0.001), unemployment (P < 0.001), Medicaid insurance (P < 0.001), reduced body mass index (P < 0.001), decreased serum albumin (P < 0.001), haemodialysis (P = 0.019), both Asian (P = 0.010) and Native American (P = 0.020) race, ischaemic heart disease (P = 0.032), smoking (P = 0.010), illicit drug use (P = 0.018) and anaemia (P = 0.028). TB was independently associated with increased mortality, adjusted hazard ratio (AHR) 1.42 (95% CI 1.18-1.70, P < 0.001). Conclusions. The prevalence of TB disease in the US dialysis population is low compared with worldwide rates; however, the disease is associated with increased mortality. Of the 10 significant risk factors identified, five are potentially modifiable. C1 Walter Reed Army Med Ctr, Allergy Immunol Dept, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Klote, MM (reprint author), Walter Reed Army Med Ctr, Allergy Immunol Dept, Washington, DC 20307 USA. EM mary.klote@amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 20 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD NOV PY 2006 VL 21 IS 11 BP 3287 EP 3292 DI 10.1093/ndt/gfl488 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 094ZD UT WOS:000241277100044 PM 16968724 ER PT J AU Araya, R Noguchi, T Yuhki, M Kitamura, N Higuchi, M Saido, TC Seki, K Itohara, S Kawano, M Tanemura, K Takashima, A Yamada, K Kondoh, Y Kanno, I Wess, J Yamada, M AF Araya, Runa Noguchi, Takanori Yuhki, Munehiro Kitamura, Naohito Higuchi, Makoto Saido, Takaomi C. Seki, Kenjiro Itohara, Shigeyoshi Kawano, Masako Tanemura, Kentaro Takashima, Akihiko Yamada, Kazuyuki Kondoh, Yasushi Kanno, Iwao Wess, Jurgen Yamada, Masahisa TI Loss of M-5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice SO NEUROBIOLOGY OF DISEASE LA English DT Article DE cognition; cerebral blood flow; muscarinic acetylcholine receptor; neuronal atrophy ID CEREBRAL-BLOOD-FLOW; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; KNOCKOUT MICE; KAINATE RECEPTORS; HIPPOCAMPUS; RAT; AUTOREGULATION; CORTEX; ACTIVATION AB The M-5 muscarinic acetylcholine receptor (M5R) has been shown to play a crucial role in mediating acetylcholine- dependent dilation of cerebral blood vessels. We show that male M5R(-/-) mice displayed constitutive constriction of cerebral arteries using magnetic resonance angiography in vivo. Male M5R(-/-) mice exhibited a significantly reduced cerebral blood flow (CBF) in the cerebral cortex, hippocampus, basal ganglia, and thalamus. Cortical and hippocampal pyramidal neurons from M5R mice showed neuronal atrophy. Hippocampusdependent spatial and nonspatial memory was also impaired in M5R-"mice. In M5R(-/-) mice, CA3 pyramidal cells displayed a significantly attenuated frequency of the spontaneous postsynaptic current and long-term potentiation was significantly impaired at the mossy fiberCA3 synapse. Our findings suggest that impaired M5R signaling may play a role in the pathophysiology of cerebrovascular deficits. The M5 receptor may represent an attractive novel therapeutic target to ameliorate memory deficits caused by impaired cerebrovascular function. (c) 2006 Elsevier Inc. All rights reserved. C1 RIKEN Brain Sci Inst, Yamada Res Unit, Saitama 3510198, Japan. RIKEN Brain Sci Inst, Lab Behav Genet, Saitama 3510198, Japan. RIKEN Brain Sci Inst, Lab Proteolyt Neurosci, Saitama 3510198, Japan. RIKEN Brain Sci Inst, Lab Cell Culture Dev, Saitama 3510198, Japan. RIKEN Brain Sci Inst, Lab Alzheimers Dis, Saitama 3510198, Japan. RIKEN Brain Sci Inst, Adv Technol Dev Grp, Res Resources Ctr, Saitama 3510198, Japan. Akita Res Inst Brain & Blood Vessels, Dept Radiol & Nucl Med, Akita 0100874, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Yamada, M (reprint author), RIKEN Brain Sci Inst, Yamada Res Unit, Saitama 3510198, Japan. EM masahisa@brain.riken.jp RI Itohara, Shigeyoshi/I-8769-2012 OI Itohara, Shigeyoshi/0000-0002-2410-9989 NR 64 TC 31 Z9 32 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2006 VL 24 IS 2 BP 334 EP 344 DI 10.1016/j.nbd.2006.07.010 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 099LA UT WOS:000241594900013 PM 16956767 ER PT J AU Friedman, L Glover, GH AF Friedman, Lee Glover, Gary H. CA FBIRN Consortium TI Reducing interscanner variability of activation in a multicenter fMRI study: Controlling for signal-to-fluctuation-noise-ratio (SFNR) differences SO NEUROIMAGE LA English DT Article ID PHYSIOLOGICAL NOISE; MRI; REPRODUCIBILITY; RELIABILITY; ACQUISITION; GROWTH; TRIAL AB Variation in scanner performance will lead to variation in activation patterns in multicenter fMRI studies. The purpose of this investigation was to evaluate the effect of statistically covarying for scanner differences in signal-to-fluctuation-noise-ratio (SFNR) on reducing scanner differences in activation effect size as part of a multicenter fMRI project (FIRST BIRN). For SFNR, "signal" is typically the mean intensity over time and "fluctuation noise" is the temporal standard deviation. Five subjects were sent to 9 centers (10 scanners) and scanned on two consecutive days using a sensorimotor fMRI protocol. High-field (4 T and 3 T) and low-field (1.5 T) scanners from three vendors (GE, Siemens and Picker) were included. The effect size for the detection of neural activation during a sensorimotor task was evaluated as the percent of temporal variance accounted for by our model (percent of variance accounted for, or PVAF). Marked scanner effects were noted for both PVAF as well as SFNR. After covariate adjustment with one of several measures of SFNR, there were dramatic reductions in scanner-to-scanner variations in activation effect size. Variance components analyses revealed 75%-81% reductions in variance due to scanner with this method. Thus, controlling for scanner variation in SFNR may he an effective method to homogenize activation effect sizes in multicenter studies. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA. Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. NIH, FBIRN Funct Testbed Biomed Informat Res Network, NCRR, Bethesda, MD USA. RP Friedman, L (reprint author), Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA. EM lfriedman10@comcast.net FU NCRR NIH HHS [1 U24 RR021992] NR 37 TC 87 Z9 88 U1 3 U2 6 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 NOV 1 PY 2006 VL 33 IS 2 BP 471 EP 481 DI 10.1016/j.neuroimage.2006.07.012 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 096WF UT WOS:000241406800005 PM 16952468 ER PT J AU Boyce-Rustay, JM Holmes, A AF Boyce-Rustay, Janel M. Holmes, Andrew TI Genetic inactivation of the NMDA receptor NR2A subunit has anxiolytic- and antidepressant-like effects in mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE NMDA; NR2A; glutamate; anxiety; depression; knockout ID METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; ANXIETY-LIKE BEHAVIOR; TAIL SUSPENSION TEST; ELEVATED PLUS-MAZE; FORCED SWIM TEST; SEROTONIN TRANSPORTER; EPSILON-1 SUBUNIT; KNOCKOUT MICE; TETRAMERIC STRUCTURE AB There is growing evidence implicating the glutamate system in the pathophysiology and treatment of mood and anxiety disorders. Glutamatergic neurotransmission is mediated by several receptor subfamilies including multiple NMDA receptor subunits ( NR2A-D). However, little is currently understood about the specific roles of NMDA subunits in the mediation of emotional behavior due to a lack of subunit-specific ligands. In the present study, we employed a mouse gene-targeting approach to examine the role of the NR2A subunit in the mediation of anxiety- and depressive-related behaviors. Results showed that NR2A knockout ( KO) mice exhibit decreased anxiety- like behavior relative to wild-type littermates ( WT) across multiple tests ( elevated plus maze, light-dark exploration test, novel open field). NR2A KO mice showed antidepressant-like profiles in the forced swim test and tail suspension test, as compared to WT controls. Locomotor activity in the nonaversive environments of the home cage or a familiar open field were normal in the NR2A KO mice, as were gross neurological and sensory functions, including prepulse inhibition of startle. Taken together, these data demonstrate a selective and robust reduction in anxiety- and depression-related behavior in NMDA receptor NR2A subunit KO mice. Present results support a role for the NR2A subunit in the modulation of emotional behaviors in rodents and provide insight into the role of glutamate in the pathophysiology and treatment of mood and anxiety disorders. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Boyce-Rustay, JM (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane Rm 2N-09, Bethesda, MD 20892 USA. EM boycej@mail.nih.gov NR 81 TC 129 Z9 133 U1 1 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 NOV PY 2006 VL 31 IS 11 BP 2405 EP 2414 DI 10.1038/sj.npp.1301039 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 096MJ UT WOS:000241380900011 PM 16482087 ER PT J AU Cutler, CM Lee, JS Butman, JA FitzGibbon, EJ Kelly, MH Brillante, BA Feuillan, P Robey, PG DuFresne, CR Collins, MT AF Cutler, Carolee M. Lee, Janice S. Butman, John A. FitzGibbon, Edmond J. Kelly, Marilyn H. Brillante, Beth A. Feuillan, Penelope Robey, Pamela G. DuFresne, Craig R. Collins, Michael T. TI Long-term outcome of optic nerve encasement and optic nerve decompression in patients with fibrous dysplasia: Risk factors for blindness and safety of observation SO NEUROSURGERY LA English DT Article DE bone; GNAS; growth hormone; G,alpha; McCune-Albright syndrome ID MCCUNE-ALBRIGHT-SYNDROME; GROWTH-HORMONE EXCESS; MUTATIONS; EFFICACY; REGION; BASE; GENE AB OBJECTIVE: Fibrous dysplasia (FD) of bone may occur solely as a skeletal condition or it may occur in association with extraskeletal manifestations, including growth hormone (GH) excess. Uncertainty exists as to the management of FD involving the optic nerves. In an effort to clarify management, the authors studied a large population of patients. METHODS: One hundred four patients underwent an evaluation that included review of records, endocrine testing, cranial computed tomography, and neuroophthalmological examination. RESULTS: Ninety-one of 104 patients had craniofacial FD; complete records were available for 87 patients (174 nerves). Seventeen percent of the optic nerves were less than 50% encased, 22% were 50 to 99% encased, and 61% were 100% encased. Twelve percent of the nerves that were 100% encased showed evidence of optic neuropathy, but 88% did not. The group with optic neuropathy was not older than the group without. Patients with GH excess were significantly more likely to have nerves that were 100% encased (relative risk, 4.1; 95% confidence interval, 1.5-11.1; P = 0.0017) and to have optic neuropathy (relative risk, 3.8; 95% confidence interval, 2.0-7.1; P = 0.0019). Six prophylactic optic nerve decompressions were performed; in five patients, vision was stable after surgery, and one patient was blind after surgery. Thirteen interventional optic nerve decompression procedures were performed; six of the 13 patients showed some improvement and seven of the 13 showed no improvement or worsened vision. CONCLUSION: The vast majority of optic nerves encased with FD do not exhibit symptoms of optic neuropathy and seem to be stable over time. GH excess is associated with increased risk of nerve encasement and optic neuropathy. Patients with craniofacial FD should be screened for GH excess, and optic nerve decompression should be performed only when there is objective evidence of progressive optic neuropathy. C1 Univ Utah, Dept Gen & Plast Reconstruct Surg, Salt Lake City, UT 84112 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Plast Surg, Washington, DC 20057 USA. RP Cutler, CM (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, NIH, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Butman, John/0000-0002-1547-9195 NR 19 TC 37 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 2006 VL 59 IS 5 BP 1011 EP 1017 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 128GI UT WOS:000243645800009 PM 17143235 ER PT J AU Ma, Y Lang, LX Kiesewetter, D Jagoda, E Eckelman, WC AF Ma, Ying Lang, Lixin Kiesewetter, Dale Jagoda, Elaine Eckelman, William C. TI Species differences in metabolites of PET ligands: serotonergic 5-HT1A receptor antagonists 3-trans-FCWAY and 3-cis-FCWAY SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE PET; 5-HT1A; FCWAY; in vitro metabolism ID MASS-SPECTROMETRY IDENTIFICATION; POSTSYNAPTIC 5-HT(1A) RECEPTORS; SELECTIVE ANTAGONIST; ISOLATED HEPATOCYTES; RAT HEPATOCYTES; HUMAN BRAIN; WAY-100635; TRANS-4-FLUOROCYCLOHEXANECARBOXAMIDE; DERIVATIVES; DELINEATION AB Liquid chromatography/mass spectrometry (LC/MS), combined with commercially available hepatocytes, has become an indispensable tool in evaluating the presence of these metabolites in target tissues, especially in the brain. Results from in vitro metabolism studies using hepatocytes from different species can demonstrate species differences. Using these techniques, we evaluated the metabolic profile of 3-cis-FCWAY and 3-traps-FCWAY in rat, monkey and human hepatocytes. Hepatocytes were used to produce metabolites in vitro, and liquid chromatography/tandem mass spectrometry was used to identify these metabolites. We found that the metabolic profiles of rat, monkey and human hepatocytes differ dramatically. In rats, aromatic ring oxidation was the major metabolic pathway for both 3-cis-FCWAY and 3-traps-FCWAY; 3-traps-FCWAY had more metabolites (cyclohexane ring oxidation) than 3-cis-FCWAY. In humans, hydrolysis of amide linkage was the major metabolic pathway. In monkeys, both pathways (oxidation and amide hydrolysis) were found in the metabolites. We also found that 3-cis-FCWAY had the slowest defluorination of FCWAY analogues in all species. (c) 2006 Elsevier Inc. All rights reserved. C1 Mol Tracer LLC, Bethesda, MD 20892 USA. Natl Inst Biomed Imaging & Bioengn, PET Radiochem Grp, NIH, Bethesda, MD 20892 USA. RP Eckelman, WC (reprint author), Mol Tracer LLC, Bethesda, MD 20892 USA. NR 17 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 2006 VL 33 IS 8 BP 1013 EP 1019 DI 10.1016/j.nucmedbio.2006.09.006 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 116YU UT WOS:000242840500010 PM 17127175 ER PT J AU Yu, YK Gertz, EM Agarwala, R Schaffer, AA Altschul, SF AF Yu, Yi-Kuo Gertz, E. Michael Agarwala, Richa Schaeffer, Alejandro A. Altschul, Stephen F. TI Retrieval accuracy, statistical significance and compositional similarity in protein sequence database searches SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACID SUBSTITUTION MATRICES; HIDDEN MARKOV-MODELS; PSI-BLAST; COILED COILS; P-VALUES; COMPLEXITY; ALIGNMENT; DISTRIBUTIONS; PREDICTION; TOOL AB Protein sequence database search programs may be evaluated both for their retrieval accuracy the ability to separate meaningful from chance similarities-and for the accuracy of their statistical assessments of reported alignments. However, methods for improving statistical accuracy can degrade retrieval accuracy by discarding compositional evidence of sequence relatedness. This evidence may be preserved by combining essentially independent measures of alignment and compositional similarity into a unified measure of sequence similarity. A version of the BLAST protein database search program, modified to employ this new measure, outperforms the baseline program in both retrieval and statistical accuracy on ASTRAL, a SCOP-based test set. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, US Dept HHS, NIH, Bethesda, MD 20894 USA. RP Altschul, SF (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, US Dept HHS, NIH, Bethesda, MD 20894 USA. EM altschul@ncbi.nlm.nih.gov RI Schaffer, Alejandro/F-2902-2012; OI Gertz, E. Michael/0000-0001-8390-4387 FU Intramural NIH HHS NR 43 TC 36 Z9 37 U1 0 U2 4 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 NOV PY 2006 VL 34 IS 20 BP 5966 EP 5973 DI 10.1093/nar/gkl731 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111SM UT WOS:000242474800030 PM 17068079 ER PT J AU Gardner, DB AF Gardner, Deborah B. TI Let's push the 110th congress to tackle the health care crisis SO NURSING ECONOMICS LA English DT Editorial Material AB center dot The all too gradual rise of health care as a key campaign issue came out of the context of stark problems in large scale policy design and implementation over the past decade. center dot Bipartisan agreement that the health care system needs to be improved is very different from a bipartisan agreement on the goals and how to achieve them. center dot Creating nursing unity through the development of a shared mental model for health care reform would have a huge impact in providing policy context around the issues and offering policy solutions to our elected officials. C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gardner, DB (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD NOV-DEC PY 2006 VL 24 IS 6 BP 333 EP 335 PG 3 WC Nursing SC Nursing GA 121SH UT WOS:000243176800010 PM 17266012 ER PT J AU Ulrich, CM Danis, M Ratcliffe, SJ Garrett-Mayer, E Koziol, D Soeken, KL Grady, C AF Ulrich, Connie M. Danis, Marion Ratcliffe, Sarah J. Garrett-Mayer, Elizabeth Koziol, Deloris Soeken, Karen L. Grady, Christine TI Ethical conflict in nurse practitioners and physician assistants in managed care SO NURSING RESEARCH LA English DT Article DE conflict; ethics; practitioners; professionalism ID NONPHYSICIAN CLINICIAN; INSURANCE COMPANIES; MEDICAL-ETHICS; ORGANIZATIONS; AUTONOMY; ISSUES; SAMPLE; IMPACT; MODEL AB Background: More patients are receiving healthcare services from nurse practitioners (NPs) and physician assistants (PAs). These providers are likely to be confronted with a variety of ethical issues as they balance quality care with their patients' rising cost concerns. However, very little is known about the ethical conflicts and causes of these conflicts experienced by these clinicians in their daily practice. Objective: To identify ethical concerns and conflicts NPs and PAs encounter related to managed care in the delivery of primary care to patients and the factors that influence ethical conflict. Methods: A cross-sectional self-administered mailed questionnaire was sent to 3,900 NPs and PAs randomly selected from primary care and primary care subspecialties in the United States (adjusted response rate, 50.6%). Respondents were surveyed on ethical issues and concerns, ethics preparedness, and ethical conflict. Bivariate and multiple linear regression analyses were used to evaluate predictors of ethical conflict. Results: Insurance constraints were reported to have interfered with the ability to provide quality patient care by 72% of respondents, with 55.3% reporting daily to weekly interferences. Nearly half of respondents (47%) have been asked by a patient to mislead insurers to assist them in receiving care. A perceived obligation to advocate for patients, even if it means exaggerating the severity of a patient's condition, was the single most significant predictor of ethical conflict, explaining 25% of the variance. Discussion: NPs and PAs are experiencing ethical conflict often associated with their perceived professional obligations to advocate for patients. Being well-prepared in ethics and having sufficient professional independence help clinicians balance the ethical complexities and demands of meeting patients' needs within a constrained healthcare 'system. C1 Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. NIH, Ctr Clin, Dept Clin Bioeth, Sect Eth & Hlth Policy, Bethesda, MD 20892 USA. Johns Hopkins Univ, Johns Hopkins Kimmel Canc Ctr, Dept Biostat & Oncol, Baltimore, MD 21218 USA. NIH, Ctr Clin, Clin Epidemiol Serv, Bethesda, MD 20892 USA. Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. RP Ulrich, CM (reprint author), Univ Penn, Sch Nursing, Room 357 NEB,20 Guardian Dr, Philadelphia, PA 19104 USA. EM culrich@nursing.upenn.edu NR 36 TC 4 Z9 4 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD NOV-DEC PY 2006 VL 55 IS 6 BP 391 EP 401 DI 10.1097/00006199-200611000-00003 PG 11 WC Nursing SC Nursing GA 109ZW UT WOS:000242349100003 PM 17133146 ER PT J AU Aagaard-Tillery, K Sibai, B Spong, CY Momirova, V Wendel, G Wenstrom, K Samuels, P Cotroneo, M Moawad, A Sorokin, Y Miodovnik, M Meis, P O'Sullivan, MJ Conway, D Wapner, RJ AF Aagaard-Tillery, Kjersti Sibai, Baha Spong, Catherine Y. Momirova, Valerija Wendel, George, Jr. Wenstrom, Katharine Samuels, Philip Cotroneo, Margaret Moawad, Atef Sorokin, Yoram Miodovnik, Menachem Meis, Paul O'Sullivan, Mary J. Conway, Deborah Wapner, Ronald J. CA Natl Inst Child Hlth Human Dev Mat TI Sample bias among women with retained DNA samples for future genetic studies SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID V-LEIDEN MUTATION; AFRICAN-AMERICANS; CLINICAL-TRIALS; HUMAN-DISEASE; PARTICIPATION; CANCER; RECRUITMENT; DISPARITIES; POPULATION; PREVENTION AB OBJECTIVE: To evaluate whether women who agree to future use of their biologic specimens for genetic studies reflect the larger study population from which they are derived. METHODS: Women were questioned as to the future disposition of their maternal and fetal DNA samples upon enrollment in a multicenter, observational study originally designed to identify factor V Leiden mutation carriers and prospectively ascertain the estimated rate of pregnancy-related venous thromboembolism and adverse pregnancy outcome. Univariate and multivariate analyses was carried out on the 5,003 of 5,188 enrolled women who indicated their desire regarding future disposition of their DNA samples. RESULTS: Among these 5,003 women, 20.1% desired that their samples be discarded and not available for future genetic studies. Multivariate analysis demonstrated that women who agreed to subsequent use of samples were less likely African-American (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.7) or Hispanic (OR 0.4, 95% CI 0.3-0.5), and more likely to use tobacco (OR 1.2, 95% CI 1.0-1.6) than those who desired that their samples be discarded. CONCLUSION: Genetic samples from women agreeing to their use in a sample repository may not be representative of the index study cohort. This should be considered in their subsequent interpretation and generalizability. C1 Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. NICHHD, Rockville, MD USA. Univ Tennessee, Knoxville, TN 37996 USA. George Washington Univ, Biostat Coordinating Ctr, Washington, DC 20052 USA. Univ Texas San Antonio SW, Dept Obstet, Dallas, TX 75230 USA. Univ Texas San Antonio SW, Dept Gynecol, Dallas, TX USA. Univ Alabama Birmingham, Birmingham, AL USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Univ Chicago, Chicago, IL 60637 USA. Wayne State Univ, Detroit, MI 48202 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Miami, Coral Gables, FL 33124 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Aagaard-Tillery, K (reprint author), Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, 30 North 1900 East,Room 2B200, Salt Lake City, UT 84132 USA. EM kjersti131@prodigy.net RI Samuels, Philip/E-4011-2011 FU NICHD NIH HHS [U10-HD27905, U10-HD27860, U10-HD34116, U10-HD34136, U10-HD34208, U10-HD27861, U01-HD36801, U10-HD21410, U10-HD21414, U10-HD27869, U10-HD27915, U10-HD27917, U10-HD34122, U10-HD34210] NR 27 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2006 VL 108 IS 5 BP 1115 EP 1120 DI 10.1097/01.AOG.0000241536.19539.14 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XU UT WOS:000246769500010 PM 17077232 ER PT J AU Lacey, JV Greene, MH Buys, SS Reding, D Riley, TL Berg, CD Fagerstrom, RM Hartge, P AF Lacey, James V., Jr. Greene, Mark H. Buys, Saundra S. Reding, Douglas Riley, Thomas L. Berg, Christine D. Fagerstrom, Richard M. Hartge, Patricia TI Ovarian cancer screening in women with a family history of breast or ovarian cancer SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SURGICAL ADJUVANT BREAST; GENETIC RISK-ASSESSMENT; BOWEL PROJECT P-1; RANDOMIZED-TRIAL; RECOMMENDATION STATEMENT; BRCA MUTATIONS; TAMOXIFEN; SUSCEPTIBILITY; OOPHORECTOMY; PREVENTION AB OBJECTIVE: To evaluate positive predictive values of CA 125 or transvaginal ultrasonography screening for ovarian cancer according to family history of breast or ovarian cancer. METHODS: In the screening arm of a randomized controlled trial of screening compared with usual care, 28,460 women with family history data received baseline and annual CA 125 and transvaginal ultrasonography examinations. We analyzed CA 125 and transvaginal ultrasonography results from the first four rounds of screening. We classified women as average (n=22,687), moderate (n=2,572), or high (n=2,163) risk based on family history, or high risk due to a personal history of breast cancer (n=1,038). Cancers were identified by active follow-up of women with abnormal screening results and annual questionnaires. We calculated positive predictive values for screening combinations. RESULTS: Similar proportions (4.8-5.0%) of women in each group had abnormal screening results. Higher-risk women were more likely than lower-risk women to undergo biopsy after a positive screen. Screening identified 43 invasive ovarian cancers. The positive predictive values for abnormal screening results were 0.7% in average-risk, 1.3% in moderate-risk, and 1.6% in high-risk groups; one ovarian cancer occurred among the breast cancer survivors. The positive predictive values for post-baseline abnormal screening results were also higher in the higher-risk groups. The positive predictive values did not significantly differ across risk groups. CONCLUSION: Probabilities of abnormal annual CA 125 and transvaginal ultrasonography screens were similar across groups based on family history of breast or ovarian cancer. However, ovarian cancer was more likely to be diagnosed after an abnormal screening result among women at higher family history-based risk than among women at lower risk. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. Informat Management Syst Inc, Rockville, MD USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Lacey, JV (reprint author), 6120 Execut Blvd MSC 7234, Rockville, MD 20852 USA. EM jimlacey@nih.gov FU Intramural NIH HHS NR 36 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2006 VL 108 IS 5 BP 1176 EP 1184 DI 10.1097/01.AOG.0000239105.39149.d8 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XU UT WOS:000246769500018 PM 17077240 ER PT J AU Bloom, SL Leveno, KJ Gilbert, S Spong, CY AF Bloom, Steven L. Leveno, Kenneth J. Gilbert, Sharon Spong, Catherine Y. TI Decision-to-incision times and maternal and infant outcomes - Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. NICHHD, Bethesda, MD 20892 USA. RP Bloom, SL (reprint author), Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2006 VL 108 IS 5 BP 1298 EP 1298 DI 10.1097/01.AOG.0000245057.90776.a8 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XU UT WOS:000246769500040 ER PT J AU Wang, X Zhou, YX Qiao, W Tominaga, Y Ouchi, M Ouchi, T Deng, CX AF Wang, X. Zhou, Y-X Qiao, W. Tominaga, Y. Ouchi, M. Ouchi, T. Deng, C-X TI Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation SO ONCOGENE LA English DT Article DE cyclin D1; mTOR; centrosome; chromosome tetraploidization; premature sister chromatid segregation ID SPINDLE ASSEMBLY CHECKPOINT; BREAST-CANCER; CENTROSOME AMPLIFICATION; MITOTIC SPINDLE; CHROMOSOME SEGREGATION; CELL-CYCLE; COLORECTAL CANCERS; AMPLIFIED KINASE; MAMMALIAN-CELLS; PROTEIN-KINASE AB Aurora-A/ STK15/ BTAK, which encodes a centrosome-associated kinase, is amplified and overexpressed in multiple types of human tumors, including breast cancer. However, the causal relationship between overexpression of Aurora-A and tumorigenesis has not been fully established due to contradictory data obtained from different experimental systems. To investigate this, we generated a mouse strain that carries an MMTV-Aurora-A transgene. We showed that all the MMTV-Aurora-A mice displayed enhanced branch morphogenesis in the mammary gland and about 40% developed mammary tumors at 20 months of age. The tumor incidence was significantly increased in a p53(+/-) mutation background with about 70% MMTV-Aurora-A; p53(+/-) animals developed tumors at 18 months of age. Of note, overexpression of Aurora-A led to genetic instability, characterized by centrosome amplification, chromosome tetraploidization and premature sister chromatid segregation, at stages prior to tumor formation. Most notably, the severe chromosomal abnormality did not cause cell death owing to the activation of AKT pathway, including elevated levels of phosphorylated AKT and mammalian target of rapamycin, and nuclear accumulation of cyclin D1, which enabled continuous proliferation of the tetraploid cells. These data establish Aurora-A as an oncogene that causes malignant transformation through inducing genetic instability and activating oncogenic pathways such as AKT and its downstream signaling. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NYU, Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 51 TC 147 Z9 151 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2006 VL 25 IS 54 BP 7148 EP 7158 DI 10.1038/sj.onc.1209707 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 105QH UT WOS:000242046900004 PM 16715125 ER PT J AU Sano, M Genkai, N Yajima, N Tsuchiya, N Homma, J Tanaka, R Miki, T Yamanaka, R AF Sano, Masakazu Genkai, Nobuyuki Yajima, Naoki Tsuchiya, Naoto Homma, Junpei Tanaka, Ryuichi Miki, Toru Yamanaka, Ryuya TI Expression level of ECT2 proto-oncogene correlates with prognosis in glioma patients SO ONCOLOGY REPORTS LA English DT Article DE epithelial cell transforming gene 2; glioma; siRNA ID CYTOKINESIS REGULATOR ECT2; GTP-BOUND RHOA; EXCHANGE FACTOR; G2/M PHASE; GTPASES; PHOSPHORYLATION; ACCUMULATION; BIOLOGY AB The ECT2 (epithelial cell transforming sequence 2) proto-oncogene encodes a guanine nucleotide exchange factor for Rho GTPases, and regulates cytokinesis. ECT2 plays a critical role in Rho activation during cytokinesis, and thus may play a role in the pathogenesis of glioma. In this study, we investigated relationships between ECT2 expression, tumor histology, and prognosis in glioma patients. ECT2 mRNA expression was examined using quantitative real-time PCR, while its protein expression was examined by immunohistochemistry of 54 glioma tissue samples. Expressions of ECT2 mRNA and protein were markedly increased in high-grade gliomas compared to low-grade gliomas. Patients in whom expression of ECT2 mRNA and protein in tumor tissues was the lowest survived longer than patients who had higher expression. In vitro, ECT2 siRNA inhibited glioma cell proliferation and invasion. These data suggest that increased expression of ECT2 contribute to promotion of tumor invasiveness and progression, implying that evaluation of ECT2 expression is a prognostic marker for glioma patients. C1 Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 9518585, Japan. NCI, Mol Tumor Biol Sect, Cell Biol Lab, Bethesda, MD 20892 USA. RP Yamanaka, R (reprint author), Kurume Univ, Res Ctr Innovat Canc Therapy, Sch Med, Asahimachi 67, Kurume, Fukuoka 8300011, Japan. EM ryaman@med.kurume-u.ac.jp NR 19 TC 35 Z9 36 U1 1 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD NOV PY 2006 VL 16 IS 5 BP 1093 EP 1098 PG 6 WC Oncology SC Oncology GA 097OU UT WOS:000241458500024 PM 17016598 ER PT J AU Garibaldi, DC Robinson, MR Lee, SS Park, DJJ Fine, HF Deitz, L D'Anna, S Yuan, P Ranson, N Grant, MP Iliff, NT Merbs, SL AF Garibaldi, Daniel C. Robinson, Michael R. Lee, Susan S. Park, Dong Jun J. Fine, Howard F. Deitz, Luke D'Anna, Sam Yuan, Peng Ranson, Nicholas Grant, Michael P. Iliff, Nicholas T. Merbs, Shannath L. TI New corticosteroid-eluting porous polyethylene implant for the management of lower eyelid retraction: A pilot study SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID LOWER-LID RETRACTION; HARD-PALATE MUCOSA; RAT MODEL; RECONSTRUCTION; MEDPOR; NEOVASCULARIZATION; TRIAMCINOLONE; STEROIDS; GRAFTS AB Purpose: Lower eyelid retraction after trauma presents a challenging management problem. We postulated that a porous polyethylene (pPE) eyelid spacer coated with a polyvinyl alcohol (PVA) and triamcinolone acetonide (TA) matrix could deliver corticosteroid locally over extended periods and modulate inflammation and scar formation. We designed a pPE corticosteroid-eluting implant and evaluated its characteristics in vitro and in vivo. Methods: The release characteristics of pPE implants coated with a PVA/TA matrix of low, intermediate, and high doses of TA were studied in vitro. The implants were then placed in the posterior lamella of lower eyelids of Dutch Belted rabbits for 12 weeks. Clinical events were recorded and eyelids were examined for gross and histologic features, including capsular thickness and degree of vascularity, fibrovascular ingrowth, and inflammatory response. Results: In vitro, implants coated with the intermediate and high doses of TA released the drug at a steady rate for at least 78 days. In rabbits, the PVA and PVA/TA coating prevented fibrovascular ingrowth, except where breaks in the PVA/TA coat were present. Implants with PVA/TA coating demonstrated less inflammation and capsule vascularity. An inverse correlation between TA dose and capsule thickness was noted. Conclusions: We describe a novel drug-release pPE eyelid implant. The corticosteroid-eluting implant demonstrated antiangiogenic and anti-inflammatory properties, which could prove beneficial in the treatment of lower eyelid retraction. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. RP Merbs, SL (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Maumenee 505,600 N Wolfe St, Baltimore, MD 21205 USA. EM smerbs@jhmi.edu NR 32 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2006 VL 22 IS 6 BP 424 EP 429 DI 10.1097/01.iop.0000245487.61479.56 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 112AA UT WOS:000242496200004 PM 17117094 ER PT J AU Lodde, BM Mineshiba, F Kok, MR Wang, J Zheng, C Schmidt, M Cotrim, AP Kriete, M Tak, PP Baum, BJ AF Lodde, B. M. Mineshiba, F. Kok, M. R. Wang, J. Zheng, C. Schmidt, M. Cotrim, A. P. Kriete, M. Tak, P. P. Baum, B. J. TI NOD mouse model for Sjogren's syndrome: lack of longitudinal stability SO ORAL DISEASES LA English DT Article DE Sjogren's syndrome; NOD mouse model; phenotype; salivary gland; autoimmune disease ID ADENOASSOCIATED VIRUS VECTORS; OBESE DIABETIC MOUSE; SALIVARY-GLANDS; GENE-TRANSFER; ENVIRONMENTAL-STRESS; MURINE MODEL; MICE; MELLITUS; TRANSDUCTION; EXPRESSION AB OBJECTIVES: The non-obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjogren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno-associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS-like disease in NOD mice. Data collected over a 2-year period indicated a changing SS phenotype in these mice and this phenomenon was investigated. METHODS: 10(10) particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared. RESULTS: Salivary flow rate, focus score, and SMG cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12(p70), tumor necrosis factor-alpha and IFN gamma showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non-diabetic mice. CONCLUSION: This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice. C1 NIDCR, GTTB, NIH, DHHS, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. NIDCR, Vet Resoures Core, NIH, DHHS, Bethesda, MD USA. RP Lodde, BM (reprint author), NIDCR, GTTB, NIH, DHHS, 10 Ctr Dr,Bldg 10,Room 1N114, Bethesda, MD 20892 USA. EM blodde@nidcr.nih.gov RI e-, a/F-9947-2012 FU Intramural NIH HHS NR 34 TC 17 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD NOV PY 2006 VL 12 IS 6 BP 566 EP 572 DI 10.1111/j.1601-0825.2006.01241.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 096WR UT WOS:000241408000009 PM 17054769 ER PT J AU Stanford, JB Dunson, DB AF Stanford, Joseph B. Dunson, David B. TI Expanding methodologies for capturing day-specific probabilities of conception - Foreword SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Editorial Material ID CHILDRENS; HEALTH C1 Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT 84108 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Stanford, JB (reprint author), Univ Utah, Dept Family & Prevent Med, 375 Chipeta Way,Suite A, Salt Lake City, UT 84108 USA. EM jstanford@dfpm.utah.edu NR 5 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD NOV PY 2006 VL 20 SU 1 BP 1 EP 2 DI 10.1111/j.1365-3016.2006.00764.x PG 2 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 111IA UT WOS:000242443400001 PM 17061967 ER PT J AU Lynch, CD Jackson, LW Louis, GMB AF Lynch, Courtney D. Jackson, Leila W. Louis, Germaine M. Buck TI Estimation of the day-specific probabilities of conception: current state of the knowledge and the relevance for epidemiological research SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Workshop Entitled Expanding Methodologies for Capturing Day-Specific Probabilities of Conception CY MAY 17-18, 2004 CL Rockville, MD SP Natl Children's Study, Natl Inst Child Health & Human Develop (NICHD), US Dept Health & Human Serv DE ovulation; fertilisation; conception ID URINARY HORMONE MEASUREMENTS; BASAL BODY-TEMPERATURE; MENSTRUAL-CYCLE; HUMAN-FERTILITY; LUTEINIZING-HORMONE; FEMALE INFERTILITY; MUCUS OBSERVATIONS; CHILDRENS HEALTH; OVULATION METHOD; PREGNANCY AB Conception, as defined by the fertilisation of an ovum by a sperm, marks the beginning of human development. Currently, a biomarker of conception is not available; as conception occurs shortly after ovulation, the latter can be used as a proxy for the time of conception. In the absence of serial ultrasound examinations, ovulation cannot be readily visualised leaving researchers to rely on proxy measures of ovulation that are subject to error. The most commonly used proxy measures include: charting basal body temperature, monitoring cervical mucus, and measuring urinary metabolites of oestradiol and luteinising hormone. Establishing the timing of the ovulation and the fertile window has practical utility in that it will assist couples in appropriately timing intercourse to achieve or avoid pregnancy. Identifying the likely day of conception is clinically relevant because it has the potential to facilitate more accurate pregnancy dating, thereby reducing the iatrogenic risks associated with uncertain gestation. Using data from prospective studies of couples attempting to conceive, several researchers have developed models for estimating the day-specific probabilities of conception. Elucidating these will allow researchers to more accurately estimate the day of conception, thus spawning research initiatives that will expand our current limited knowledge about the effect of exposures at critical periconceptional windows. While basal body temperature charting and cervical mucus monitoring have been used with success in field-based studies for many years, recent advances in science and technology have made it possible for women to get instant feedback regarding their daily fertility status by monitoring urinary metabolites of reproductive hormones in the privacy of their own homes. Not only are innovations such as luteinising hormone test kits and digital fertility monitors likely to increase study compliance and participation rates, they provide valuable prospective data that can be used in epidemiological research. Although we have made great strides in estimating the timing and length of the fertile window, more work is needed to elucidate the day-specific probabilities of conception using proxy measures of ovulation that are inherently subject to error. Modelling approaches that incorporate the use of multiple markers of ovulation offer great promise to fill these important data gaps. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Rockville, MD USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Lynch, CD (reprint author), NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, 6100 Execut Blvd,Room 7B03P, Rockville, MD 20852 USA. EM lynchcd@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 NR 59 TC 23 Z9 23 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD NOV PY 2006 VL 20 SU 1 BP 3 EP 12 DI 10.1111/j.1365-3016.2006.00765.x PG 10 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 111IA UT WOS:000242443400002 PM 17061968 ER PT J AU Scarpa, B Dunson, DB AF Scarpa, Bruno Dunson, David B. TI Bayesian selection of predictors of conception probabilities across the menstrual cycle SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Workshop Entitled Expanding Methodologies for Capturing Day-Specific Probabilities of Conception CY MAY 17-18, 2004 CL Rockville, MD SP Natl Children's Study, Natl Inst Child Health & Human Develop (NICHD), US Dept Health & Human Serv DE fecundability; ovulation; prior distribution; Bayesian techniques; cervical mucus ID CAFFEINE CONSUMPTION; DECREASED FERTILITY; PESTICIDE EXPOSURE; MUCUS OBSERVATIONS; CIGARETTE-SMOKING; FEMALE FECUNDITY; CERVICAL-MUCUS; SEMEN QUALITY; MALE AGE; PREGNANCY AB There is increasing interest in identifying predictors of human fertility, including environmental exposures, behavioural factors, and biomarkers, such as mucus or reproductive hormones. Epidemiological studies typically measure fecundability, the per menstrual cycle probability of conception, using time to pregnancy data. A critical predictor, which is often ignored in the design or analysis, is the timing of non-contracepting intercourse in the menstrual cycle. In order to limit confounding by behavioural differences between exposure groups, it may be preferable to base inferences on day-specific conception probabilities in relation to intercourse timing. This article proposes Bayesian methods for selection of predictors of day-specific conception probabilities. A particular focus is the case in which data on ovulation timing are not available. We focus on the selection of fertile days in the cycle during which conception probabilities are non-negligible and predictors may play a role. Data from recent European and Italian prospective studies of daily fecundability are presented, and the proposed approach is used to estimate cervical mucus effects within a mid-cycle potentially fertile window using data from the Italian study. C1 Univ Pavia, Dept Appl Stat & Econ, I-27100 Pavia, Italy. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Scarpa, B (reprint author), Univ Pavia, Dept Appl Stat & Econ, Corso Str Nuova 65, I-27100 Pavia, Italy. EM bruno.scarpa@unipv.it FU Intramural NIH HHS NR 55 TC 6 Z9 6 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD NOV PY 2006 VL 20 SU 1 BP 30 EP 37 DI 10.1111/j.1365-3016.2006.00768.x PG 8 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 111IA UT WOS:000242443400005 PM 17061971 ER PT J AU Ahmed, AA Nava, VE Pham, T Taubenberger, JK Lichy, JH Sorbara, L Raffeld, M Mackall, CL Tsokos, M AF Ahmed, Atif A. Nava, Victor E. Pham, Thu Taubenberger, Jeffery K. Lichy, Jack H. Sorbara, Lynn Raffeld, Mark Mackall, Crystal L. Tsokos, Maria TI Ewing sarcoma family of tumors in unusual sites: Confirmation by RT-PCR SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE adrenal glands; Ewing sarcoma; palate; reverse transcriptase-polymerase chain reaction ID PRIMITIVE NEUROECTODERMAL TUMOR; POLYMERASE-CHAIN-REACTION; ROUND-CELL TUMORS; DIFFERENTIATED SYNOVIAL SARCOMA; PARAFFIN-EMBEDDED TISSUES; ADRENAL-GLAND; IMMUNOHISTOCHEMICAL ANALYSIS; TRANSCRIPTION FACTOR; MOLECULAR DIAGNOSIS; FUSION TRANSCRIPTS AB Ewing sarcoma family tumors originating in the palate or adrenal gland are extremely rare and may cause difficulty in diagnosis. More common tumors primary to these sites need to be excluded before one arrives at the correct diagnosis. We have recently diagnosed 2 such cases. The Ist case was that of a 24-year-old woman who presented with a swelling in the right side of the hard palate. The 2nd case was diagnosed in a 28-year-old woman who presented with a mass in the right adrenal gland. In both cases, the diagnosis of Ewing sarcoma family of tumors was confirmed by immunohistochemical studies and reverse transcriptase-polymerase chain reaction (RT-PCR). The hard palate case is the I st and the adrenal gland the 3rd case of Ewing sarcoma family of tumors arising in these sites, in which the diagnosis was confirmed by RT-PCR and/or cytogenetics. Accurate diagnosis of Ewing sarcoma family of tumors is crucial for the management of patients, and when found in such rare locations, diagnosis should be supported by immunohistochemical and/or molecular genetic studies. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. USAF, Inst Pathol, Dept Mol Pathol, Rockville, MD 20850 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Tsokos, M (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM mtsokos@mail.nih.gov OI Ahmed, Atif/0000-0002-8791-5785 FU Intramural NIH HHS NR 46 TC 15 Z9 16 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD NOV-DEC PY 2006 VL 9 IS 6 BP 488 EP 495 DI 10.2350/06-01-0007.1 PG 8 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 197ZN UT WOS:000248596200009 PM 17163788 ER PT J AU Wendler, D Cornelio, M AF Wendler, David Cornelio, Maria TI Overcoming language barriers in medical care SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. Translat Literacy & Language Consulting, New York, NY USA. RP Wendler, D (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 3 TC 2 Z9 2 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 NOV PY 2006 VL 47 IS 6 BP 747 EP 747 DI 10.1002/pbc.20862 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 091CR UT WOS:000241004200001 PM 16628678 ER PT J AU Ambalavanan, N Carlo, WA Shankaran, S Bann, CM Emrich, SL Higgins, RD Tyson, JE O'Shea, TM Laptook, AR Ehrenkranz, RA Donovan, EF Walsh, MC Goldberg, RN Das, A AF Ambalavanan, Namasivayam Carlo, Waldemar A. Shankaran, Seetha Bann, Carla M. Emrich, Steven L. Higgins, Rosemary D. Tyson, Jon E. O'Shea, T. Michael Laptook, Abbot R. Ehrenkranz, Richard A. Donovan, Edward F. Walsh, Michele C. Goldberg, Ronald N. Das, Abhik CA Natl Inst Child Hlth Human Dev Neo TI Predicting outcomes of neonates diagnosed with hypoxemic-ischemic encephalopathy SO PEDIATRICS LA English DT Article DE logistic models; decision trees; asphyxia neonatorum; hypoxia-ischemia; brain; predictive value of tests ID FETAL SHEEP; HYPOTHERMIA; CHILDREN; BRAIN; BIRTH; CLASSIFICATION; ASPHYXIA; INFANTS; MOTOR; TERM AB OBJECTIVE. The goals were to identify predictor variables and to develop scoring systems and classification trees to predict death/disability or death in infants with hypoxic-ischemic encephalopathy. METHODS. Secondary analysis of data from the multicenter, randomized, controlled, National Institute of Child Health and Human Development Neonatal Research Network trial of hypothermia in hypoxic-ischemic encephalopathy was performed. Data for 205 neonates diagnosed as having hypoxic-ischemic encephalopathy were studied. Logistic regression analysis was performed by using clinical and laboratory variables available within 6 hours of birth, with death or moderate/severe disability at 18 to 22 months or death as the outcomes. By using the identified variables and odds ratios, scoring systems to predict death/disability or death were developed, weighting each predictor in proportion to its odds ratio. In addition, classification and regression tree analysis was performed, with recursive partitioning and automatic selection of optimal cutoff points for variables. Correct classification rates for the scoring systems, classification and regression tree models, and early neurologic examination were compared. RESULTS. Correct classification rates were 78% for death/disability and 71% for death with the scoring systems, 80% and 77%, respectively, with the classification and regression tree models, and 67% and 73% with severe encephalopathy in early neurologic examination. Correct classification rates were similar in the hypothermia and control groups. CONCLUSIONS. Among neonates diagnosed as having hypoxic-ischemic encephalopathy, the classification and regression tree model, but not the scoring system, was superior to early neurologic examination in predicting death/disability. The 3 models were comparable in predicting death. Only a few components of the early neurologic examination were associated with poor outcomes. These scoring systems and classification trees, if validated, may help in assessments of prognosis and may prove useful for risk-stratification of infants with hypoxic-ischemic encephalopathy for clinical trials. C1 Univ Alabama, Dept Pediat, Birmingham, AL 35249 USA. Wayne State Univ, Dept Pediat, Detroit, MI USA. RTI Int, Res Triangle Pk, NC USA. NICHHD, Neonatal Res Network, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, Houston, TX USA. Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC USA. Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Duke Univ, Dept Pediat, Durham, NC 27706 USA. RP Ambalavanan, N (reprint author), Univ Alabama, Dept Pediat, 525 New Hillman Bldg,619 S 20th St, Birmingham, AL 35249 USA. EM ambal@uab.edu OI Ambalavanan, Namasivayam/0000-0003-0731-9092 FU NCRR NIH HHS [5 M01 RR00044, M01 RR 00039, M01 RR 00070, M01 RR 00125, M01 RR 0039-43, M01 RR 00750, M01 RR 08084]; NICHD NIH HHS [U10 HD21397, U01 HD36790, U10 HD21373, U10 HD21385, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, U10 HD40689] NR 23 TC 59 Z9 63 U1 1 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2006 VL 118 IS 5 BP 2084 EP 2093 DI 10.1542/peds.2006-1591 PG 10 WC Pediatrics SC Pediatrics GA 101HK UT WOS:000241731700034 PM 17079582 ER PT J AU Sanger, TD Chen, DF Delgado, MR Gaebler-Spira, D Hallett, M Mink, JW Disorders, TCM AF Sanger, Terence D. Chen, Daofen Delgado, Mauricio R. Gaebler-Spira, Deborah Hallett, Mark Mink, Jonathan W. Disorders, Taskforce Childhood Motor TI Definition and classification of negative motor signs in childhood SO PEDIATRICS LA English DT Review DE weakness; selective motor control; ataxia; apraxia; dyspraxia; developmental coordination disorder; cerebral palsy; movement disorders ID STRETCH REFLEX THRESHOLD; CEREBRAL-PALSY; CEREBELLAR-ATAXIA; CLUMSY CHILDREN; QUANTITATIVE-EVALUATION; MOVEMENT-DISORDERS; ABNORMAL CONTROL; ARM MOVEMENTS; MUSCLE; SPASTICITY AB In this report we describe the outcome of a consensus meeting that occurred at the National Institutes of Health in Bethesda, Maryland, March 12 through 14, 2005. The meeting brought together 39 specialists from multiple clinical and research disciplines including developmental pediatrics, neurology, neurosurgery, orthopedic surgery, physical therapy, occupational therapy, physical medicine and rehabilitation, neurophysiology, muscle physiology, motor control, and biomechanics. The purpose of the meeting was to establish terminology and definitions for 4 aspects of motor disorders that occur in children: weakness, reduced selective motor control, ataxia, and deficits of praxis. The purpose of the definitions is to assist communication between clinicians, select homogeneous groups of children for clinical research trials, facilitate the development of rating scales to assess improvement or deterioration with time, and eventually to better match individual children with specific therapies. "Weakness" is defined as the inability to generate normal voluntary force in a muscle or normal voluntary torque about a joint. "Reduced selective motor control" is defined as the impaired ability to isolate the activation of muscles in a selected pattern in response to demands of a voluntary posture or movement. "Ataxia" is defined as an inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity about the affected joints. "Apraxia" is defined as an impairment in the ability to accomplish previously learned and performed complex motor actions that is not explained by ataxia, reduced selective motor control, weakness, or involuntary motor activity. "Developmental dyspraxia" is defined as a failure to have ever acquired the ability to perform age-appropriate complex motor actions that is not explained by the presence of inadequate demonstration or practice, ataxia, reduced selective motor control, weakness, or involuntary motor activity. C1 Stanford Univ, Med Ctr, Div Child Neurol & Movement Disorders, Stanford, CA 94305 USA. NINDS, Bethesda, MD 20892 USA. Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. Rehabil Inst Chicago, Chicago, IL 60611 USA. Univ Rochester, Med Ctr, Dept Child Neurol, Rochester, NY 14642 USA. RP Sanger, TD (reprint author), Stanford Univ, Med Ctr, Div Child Neurol & Movement Disorders, 300 Pasteur,Room A345, Stanford, CA 94305 USA. EM sanger@stanford.edu FU NINDS NIH HHS [U13-NS043180] NR 84 TC 62 Z9 64 U1 1 U2 20 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD NOV PY 2006 VL 118 IS 5 BP 2159 EP 2167 DI 10.1542/peds.2005-3016 PG 9 WC Pediatrics SC Pediatrics GA 101HK UT WOS:000241731700042 PM 17079590 ER PT J AU Strehl, U Leins, U Goth, G Klinger, C Hinterberger, T Birbaumer, N AF Strehl, Ute Leins, Ulrike Goth, Gabriella Klinger, Christoph Hinterberger, Thilo Birbaumer, Niels TI Self-regulation of slow cortical potentials: A new treatment for children with attention-deficit/hyperactivity disorder SO PEDIATRICS LA English DT Article DE ADHD; biofeedback; neurobehavioral outcome; EEG; electroencephalogram ID HEALTH MULTIMODAL TREATMENT; EEG BIOFEEDBACK; ADHD; SYMPTOMS; EPILEPSY; END; SMR AB OBJECTIVE. We investigated the effects of self-regulation of slow cortical potentials for children with attention-deficit/hyperactivity disorder. Slow cortical potentials are slow event-related direct-current shifts of the electroencephalogram. Slow cortical potential shifts in the electrical negative direction reflect the depolarization of large cortical cell assemblies, reducing their excitation threshold. This training aims at regulation of cortical excitation thresholds considered to be impaired in children with attention-deficit/hyperactivity disorder. Electroencephalographic data from the training and the 6-month follow-up are reported, as are changes in behavior and cognition. METHOD. Twenty-three children with attention-deficit/hyperactivity disorder aged between 8 and 13 years received 30 sessions of self-regulation training of slow cortical potentials in 3 phases of 10 sessions each. Increasing and decreasing slow cortical potentials at central brain regions was fed back visually and auditorily. Transfer trials without feedback were intermixed with feedback trials to allow generalization to everyday-life situations. In addition to the neurofeedback sessions, children exercised during the third training phase to apply the self-regulation strategy while doing their homework. RESULTS. For the first time, electroencephalographic data during the course of slow cortical potential neurofeedback are reported. Measurement before and after the trials showed that children with attention-deficit/hyperactivity disorder learn to regulate negative slow cortical potentials. After training, significant improvement in behavior, attention, and IQ score was observed. The behavior ratings included Diagnostic and Statistical Manual of Mental Disorders criteria, number of problems, and social behavior at school and were conducted by parents and teachers. The cognitive variables were assessed with the Wechsler Intelligence Scale for Children and with a computerized test battery that measures several components of attention. All changes proved to be stable at 6 months' follow-up after the end of training. Clinical outcome was predicted by the ability to produce negative potential shifts in transfer sessions without feedback. CONCLUSIONS. According to the guidelines of the efficacy of treatments, the evidence of the efficacy of slow cortical potential feedback found in this study reaches level 2: "possibly efficacious." In the absence of a control group, no causal relationship between observed improvements and the ability to regulate brain activity can be made. However, it could be shown for the first time that good performance in self-regulation predicts clinical outcome. "Good performance" was defined as the ability to produce negative potential shifts in trials without feedback, because it is known that the ability to self-regulate without feedback is impaired in children and adults with attention problems. Additional research should focus on the control of unspecific effects, medication, and subtypes to confirm the assumption that slow cortical potential feedback is a viable treatment option for attention-deficit/hyperactivity disorder. Regulation of slow cortical potentials may involve similar neurobiological pathways as medical treatment. It is suggested that regulation of frontocentral negative slow cortical potentials affects the cholinergic-dopaminergic balance and allows children to adapt to task requirements more flexibly. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. Univ Tubingen, Univ Hosp Psychiat & Psychotherapy, D-72074 Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. RP Strehl, U (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM ute.strehl@uni-tuebingen.de NR 36 TC 88 Z9 91 U1 7 U2 31 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2006 VL 118 IS 5 BP E1530 EP E1540 DI 10.1542/peds.2005-2478 PG 11 WC Pediatrics SC Pediatrics GA 101HK UT WOS:000241731700107 PM 17060480 ER PT J AU Walsh, MC Yao, Q Horbar, JD Carpenter, JH Lee, SK Ohlsson, A AF Walsh, Michele C. Yao, Qing Horbar, Jeffrey D. Carpenter, Joseph H. Lee, Shoo K. Ohlsson, Arne TI Changes in the use of postnatal steroids for bronchopulmonary dysplasia in 3 large neonatal networks SO PEDIATRICS LA English DT Article DE bronchopulmonary dysplasia; corticosteroids ID CHRONIC LUNG-DISEASE; BIRTH-WEIGHT INFANTS; PRETERM INFANTS; DEXAMETHASONE TREATMENT; CONTROLLED TRIAL; CEREBRAL-PALSY; CORTICOSTEROIDS; RISK AB BACKGROUND. Postnatal corticosteroids were widely used in the 1990s in an attempt to reduce the incidence of bronchopulmonary dysplasia. However, high rates of short-term adverse effects and impaired neurodevelopmental outcomes were seen. In early 2002, a joint statement of the American Academy of Pediatrics and Canadian Paediatric Society called for limitation in the use of postnatal corticosteroids. The impact of this statement is not known. OBJECTIVES. The purpose of this work was to determine the frequency of postnatal corticosteroid use and mortality and morbidities over time, particularly before and after the joint statement. DESIGN/METHODS. We conducted a retrospective analysis of cohort data within 3 large network registries (the National Institute of Child Health and Development Neonatal Research Network [18 centers], the Vermont Oxford Network [444 centers], and the Canadian Neonatal Network [10 centers]) for the following 3 periods: prestatement (2001), statement (2002), and poststatement (2003) of very low birth-weight infants (501-1500g). The National Institute of Child Health and Development Neonatal Research Network and the Vermont Oxford Network were also analyzed for longer-term trends from 1990 to 2003. Postnatal corticosteroid use, mortality at discharge, and neonatal morbidities ( bronchopulmonary dysplasia at 36 weeks, late-onset infection > 72 hours of age, necrotizing enterocolitis treated with surgery, and length of stay) between periods were compared. RESULTS. Mean birth weight (range: 1022-1060g), postmenstrual age (28 weeks), and gender (51% male) were similar between the networks. Race differed with more black infants in the National Institute of Child Health and Development Neonatal Research Network than the Vermont Oxford Network (38% vs 24%). Antenatal steroid use was similar (range: 61%-75%). Postnatal corticosteroid use rose from 1990 (8%-16%), peaked in 1996-1998 (24%-28%), and began todecline in 1999. Use in 2003 was significantly less than in 2001. Mortality and major morbidities were similar. CONCLUSIONS. Postnatal corticosteroid use had decreased significantly in 3 large neonatal networks before the joint statement with further decreases after the statement with no apparent impact on mortality and short-term morbidity. Despite substantial decreases, similar to 8% of very low birth-weight infants continue to be treated with postnatal corticosteroid. C1 NICHHD, Neonatal Res Network, NIH, Bethesda, MD 20892 USA. Vermont Oxford Network, Burlington, VT USA. Canadian Neonatal Network, Edmonton, AB, Canada. RP Walsh, MC (reprint author), Rainbow Babies & Childrens Hosp, 11100 Euclid Avc, Cleveland, OH 44106 USA. EM michele.walsh@case.edu RI Lee, Shoo/P-3016-2015 FU NICHD NIH HHS [U10 HD27880, U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27904, U10 HD34216] NR 16 TC 49 Z9 52 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2006 VL 118 IS 5 BP E1328 EP E1335 DI 10.1542/peds.2006-0359 PG 8 WC Pediatrics SC Pediatrics GA 101HK UT WOS:000241731700084 PM 17079534 ER PT J AU Beaton, EA Schmidt, LA Ashbaugh, AR Santesso, DL Antony, MM McCabe, RE Segalowitz, SJ Schulkin, J AF Beaton, Elliott A. Schmidt, Louis A. Ashbaugh, Andrea R. Santesso, Diane L. Antony, Martin M. McCabe, Randi E. Segalowitz, Sidney J. Schulkin, Jay TI Low salivary cortisol levels among socially anxious young adults: Preliminary evidence from a selected and a non-selected sample SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE salivary cortisol; heart rate; social stress; shyness; social anxiety; social phobia ID URINARY FREE CORTISOL; PSYCHOLOGICAL STRESS; SHY CHILDREN; PHOBIA; SHYNESS; DISORDERS; RESPONSES; ANXIETY; HYPOCORTISOLISM; ANTICIPATION AB We investigated salivary cortisol levels among socially anxious adults in two separate non-clinical samples using different participant designs. Study 1 examined salivary cortisol, heart rate, and subjective measures of anxiety in response to a self-presentation task in undergraduate students meeting DSM-IV criteria for social phobia. Adults with social phobia displayed significantly lower salivary cortisol compared to their non-socially phobic counterparts, despite being more anxious. Study 2 examined the relation between trait shyness and salivary cortisol in a different sample of undergraduate students who were not selected for individual differences in personality. High trait shyness was related to low salivary cortisol. We speculate that relatively low levels of salivary cortisol in socially anxious people may reflect how the adrenocortical system responds to social stress, allowing socially anxious individuals to cope and adapt to their environment. (c) 2006 Elsevier Ltd. All rights reserved. C1 McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON L8S 4K1, Canada. McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. Ryerson Univ, Dept Psychol, Toronto, ON, Canada. Brock Univ, Dept Psychol, St Catharines, ON L2S 3A1, Canada. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Schmidt, LA (reprint author), McMaster Univ, Dept Psychol Neurosci & Behav, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM schmidtl@mcmaster.ca RI Antony, Martin/K-1991-2012; Page, Andrew/G-5438-2012; OI Antony, Martin/0000-0002-3508-377X; Page, Andrew/0000-0003-3133-2844; Beaton, Elliott/0000-0001-7631-4637 NR 39 TC 27 Z9 27 U1 1 U2 7 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 NOV PY 2006 VL 41 IS 7 BP 1217 EP 1228 DI 10.1016/j.paid.2006.02.0230 PG 12 WC Psychology, Social SC Psychology GA 093XO UT WOS:000241203800004 ER PT J AU Savage, SA AF Savage, Sharon A. TI Genetic association studies: where are we now? SO PERSONALIZED MEDICINE LA English DT Editorial Material ID HUMAN GENOME; CANCER-RISK; EPIDEMIOLOGY; SELECTION; FALSE; MAP; SUSCEPTIBILITY; POLYMORPHISMS; METAANALYSIS; DISORDERS C1 NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA. RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Execut Blvd,EPS 7018, Rockville, MD 20852 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 33 TC 2 Z9 2 U1 0 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PD NOV PY 2006 VL 3 IS 4 BP 371 EP 374 DI 10.2217/17410541.3.4.371 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V44BO UT WOS:000202978400002 ER EF