FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Moaddel, R Hamid, R Patel, S Bullock, PL Wainer, IW AF Moaddel, Ruin Hamid, Rachid Patel, Sharvil Bullock, Peter L. Wainer, Irving W. TI Identification of P-glycoprotein substrates using open tubular chromatography on an immobilized P-glycoprotein column: Comparison of chromatographic results with Caco-2 permeability SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT Symposium on Immobilization and Applications of Functional Proteins, Nucleic Acids and Cells at Solid Interfaces CY 2005 CL Honolulu, HI DE online screening; drug absorption; affinity chromatography AB The Caco-2 cell monolayer model was used to classify 13 compounds as P-glycoprotein (Pgp) substrates or non-substrates. The apparent permeability coefficients (Papp) in the basal-to-apical direction (Papp(B-A)) and in the apical-to-basal direction (Papp(A-B)) were determined for each compound and a compound was designated as a Pgp substrate if Papp(B-A)/Papp(A-B), the permeability ratio, exceeded 2.0. The same compounds were chromatographed on open tubular glass columns containing membranes from cell lines that either expressed Pgp (Pgp(+)-OT column) or did not express Pgp (Pgp(-)-OT column). The differential retentions in min, Delta t values, of the compounds were determined using the following relationship Delta t=t((Pgp(+)-OT)) - t((Pgp(-)-OT)). A statistically significant correlation was observed between the Delta t values and the permeability ratios, r(2) = 0.7749 (p = 0.0063), indicating that the differential chromatography approach could be used to quantitatively assess permeability ratios. The results also indicated that a Delta t value >= 0.5 min was a reliable measure of a permeability ratios > 2 and could be used as a rapid qualitative determination of whether a test compound was a Pgp substrate. The chromatographic study took 1 h to complete and a single pair of columns could be used to screen at least 150 compounds a week and 600 compounds during the 4-week lifetime of the columns. Published by Elsevier B.V. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Purdue Pharma LP, Ardsley, NY 10502 USA. RP Moaddel, R (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov NR 11 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD SEP 18 PY 2006 VL 578 IS 1 BP 25 EP 30 DI 10.1016/j.aca.2006.03.007 PG 6 WC Chemistry, Analytical SC Chemistry GA 089LK UT WOS:000240881900005 PM 17723691 ER PT J AU Pearson, NJ Johnson, LL Nahin, RL AF Pearson, Nancy J. Johnson, Laura Lee Nahin, Richard L. TI Insomnia, trouble sleeping, and complementary and alternative medicine - Analysis of the 2002 National Health Interview Survey data SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID OLDER-ADULTS; METAANALYSIS; POPULATION; PREVALENCE; SECONDARY; AGE AB Background: Insomnia and other disorders that result in trouble sleeping are common in the United States and are often associated with chronic health conditions. Some individuals with insomnia or trouble sleeping use complementary and alternative medicine ( CAM) therapies to treat their condition, but the prevalence of such use and the most common types of CAM therapies selected are not known. Methods: Prevalence of insomnia or trouble sleeping and of CAM use for treating such conditions was examined using the 2002 National Health Interview Survey. Logistic regression was used to examine associations between insomnia or trouble sleeping, comorbid conditions, and use of CAM treatments. Results: The 12-month prevalence rate of insomnia or trouble sleeping was 17.4%. There was a strong positive association between adults who reported having insomnia or trouble sleeping and adults who reported 4 of 5 common conditions: obesity ( adjusted odds ratio [ OR], 1.15; 99% confidence interval [CI], 1.01-1.31), hypertension ( OR, 1.32; 99% CI, 1.16-1.51), congestive heart failure ( OR, 2.24; 99% CI, 1.60-3.14), and anxiety or depression ( OR, 5.64; 99% CI, 5.07-6.29). Of those with insomnia or trouble sleeping, 4.5% used some form of CAM therapy to treat their condition. Conclusions: According to the National Health Interview Survey analysis, over 1.6 million civilian, noninstitutionalized adult US citizens use CAM to treat insomnia or trouble sleeping. The details of this analysis will serve as a guide for future research on CAM therapies for sleep disorders. C1 NIH, Natl Ctr Complementary & Alternat Med, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pearson, NJ (reprint author), NIH, Natl Ctr Complementary & Alternat Med, US Dept Hlth & Human Serv, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM pearsonn@mail.nih.gov NR 27 TC 100 Z9 104 U1 0 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 18 PY 2006 VL 166 IS 16 BP 1775 EP 1782 DI 10.1001/archinte.166.16.1775 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 085GZ UT WOS:000240593400016 PM 16983058 ER PT J AU Schwartz, DA AF Schwartz, David A. TI Future of toxicology - A shift in the paradigm: Focus on human disease SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SCIENCE; ACID C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), Natl Inst Environm Hlth Sci, POB 12233, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov NR 15 TC 1 Z9 2 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP 18 PY 2006 VL 19 IS 9 BP 1121 EP 1124 DI 10.1021/tx060149- PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 084OS UT WOS:000240543400003 PM 16978015 ER PT J AU Wang, Z Wang, H Rhie, JK Covey, JM Liang, P Wang, SY Wang, C Hu, YX Prasad, G Nan, L Hill, DL Zhang, RW AF Wang, Zhi Wang, Hui Rhie, Julie K. Covey, Joseph M. Liang, Ping Wang, Shuyi Wang, Chun Hu, Yanxue Prasad, Gautam Nan, Li Hill, Donald L. Zhang, Ruiwen TI Determination of desoxyepothilone B in nude mice plasma by liquid-liquid extraction and reversed-phase high-performance liquid chromatography SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE desoxyepothilone B; high-performance liquid chromatography; nude mice plasma ID TANDEM MASS-SPECTROMETRY; SENSITIVE DETERMINATION; EPOTHILONE-B; PACLITAXEL; DOCETAXEL; QUANTIFICATION AB A novel reversed-phase high-performance liquid chromatographic (HPLC) method has been established for the determination of a newly developed anti-cancer agent desoxyepothilone B (dEpo B) in nude mice plasma. The sample preparation involved deproteination of 200 mu l of plasma sample first, followed by liquid-liquid extraction of the resultant supernatant with chloroform. The compound taxol was used as the internal standard. Chromatographic separations were carried out on a 250 mm x 4.6 mm Zorbax SB-phenyl column with acetonitrile-0.25% orthophosphoric acid (50150, v/v) as mobile phase and UV detection at 250 nm. For dEpo B and taxol at the concentration level of 10 mu g/ml in nude mice plasma, the absolute extraction recoveries were 85.3 and 87.2%, respectively. The linear quantification range of the method was 0.1-100 mu g/ml in nude mice plasma with linear correlation coefficients greater than 0.999. The within-day and between-day relative standard deviations (R.S.D.s) for dEpo B at 0.5, 2.5 and 10 mu g/ml levels in nude mice plasma fell in the range of 2.8-4.8 and 1.5-4.6%, and the within-day and between-day recoveries were in the range of 96.5-101.7 and 97.7-101.2%, respectively. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Alabama, Div Clin Pharmacol, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Agr Univ Hebei Baoding, Coll Sci, Baoding 071001, Peoples R China. Natl Canc Inst, Bethesda, MD 20852 USA. RP Zhang, RW (reprint author), Univ Alabama, Div Clin Pharmacol, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. EM wangzhi@mail.hebau.edu.cn; ruiwen.zhang@ccc.uab.edu FU NCI NIH HHS [N01-CM-07111] NR 12 TC 5 Z9 5 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD SEP 18 PY 2006 VL 42 IS 2 BP 272 EP 276 DI 10.1016/j.jpba.2006.02.047 PG 5 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 092IL UT WOS:000241090100017 PM 16616824 ER PT J AU Li, XJ Zeng, XZ AF Li, Xiaojin Zeng, Xingzhong TI Sequential transhalogenation and Heck reaction for efficient access to dioxo-tetrasubstituted 2,4 E,E-dienes: synthesis of segment C1-C6 of apoptolidin SO TETRAHEDRON LETTERS LA English DT Article ID MYCOBACTERIUM-ULCERANS; STEREOSELECTIVE-SYNTHESIS; TRANSFORMED-CELLS; APOPTOSIS INDUCER; HALOGEN EXCHANGE; PHENYL SULFONE; FD-891; MYCOLACTONE; HALIDES; VINYL AB Efficient access to dioxo-tetrasubstituted 2,4 E,E-dienes is developed in three steps from commercially available starting materials via sequential trans halogenation and Heck reaction, which provides potentially useful synthons for the synthesis of a tetrasubstituted conjugated diene structure in complex molecules. Thereby, segment C1-C6 of apoptolidin is synthesized. (c) 2006 Elsevier Ltd. All rights reserved. C1 Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. RP Li, XJ (reprint author), NCI, NIH, POB B,Bldg 538, Ft Detrick, MD 21702 USA. EM lix@ncifcrf.gov NR 40 TC 10 Z9 10 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD SEP 18 PY 2006 VL 47 IS 38 BP 6839 EP 6842 DI 10.1016/j.tetlet.2006.07.058 PG 4 WC Chemistry, Organic SC Chemistry GA 086JY UT WOS:000240670800030 ER PT J AU Calcagno, AM Chewning, KJ Wu, CP Ambudkar, SV AF Calcagno, Anna Maria Chewning, Katherine J. Wu, Chung-Pu Ambudkar, Suresh V. TI Plasma membrane calcium ATPase (PMCA4): A housekeeper for RT-PCR relative quantification of polytopic membrane proteins SO BMC MOLECULAR BIOLOGY LA English DT Article ID BREAST-CANCER CELLS; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; CARCINOMA-CELLS; GENE-PRODUCTS; EXPRESSION; OVEREXPRESSION; NORMALIZATION; LOCALIZATION; TRANSPORTERS AB Background: Although relative quantification of real-time RT-PCR data can provide valuable information, one limitation remains the selection of an appropriate reference gene. No one gene has emerged as a universal reference gene and much debate surrounds some of the more commonly used reference genes, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). At this time, no gene encoding for a plasma membrane protein serves as a reference gene, and relative quantification of plasma membrane proteins is performed with genes encoding soluble proteins, which differ greatly in quantity and in targeting and trafficking from plasma membrane proteins. In this work, our aim was to identify a housekeeping gene, ideally one that codes for a plasma membrane protein, whose expression remains the same regardless of drug treatment and across a wide range of tissues to be used for relative quantification of real-time RT-PCR data for ATP binding cassette (ABC) plasma membrane transporters. Results: In studies evaluating the expression levels of two commonly used reference genes coding for soluble proteins and two genes coding for membrane proteins, one plasma membrane protein, plasma membrane calcium-ATPase 4 (PMCA4), was comparable to the two reference genes already in use. In addition, PMCA4 expression shows little variation across eight drug-treated cell lines and was found to be superior to GAPDH and HPRT1, commonly used reference genes. Finally, we show PMCA4 used as a reference gene for normalizing ABC transporter expression in a drug-resistant lung carcinoma cell line. Conclusion: We have found that PMCA4 is a good housekeeping gene for normalization of gene expression for polytopic membrane proteins including transporters and receptors. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. EM calcagnoa@mail.nih.gov; chewningk@mail.nih.gov; wuchung@mail.nih.gov; ambudkar@helix.nih.gov RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural NIH HHS NR 29 TC 20 Z9 21 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2199 J9 BMC MOL BIOL JI BMC Mol. Biol. PD SEP 17 PY 2006 VL 7 AR 29 DI 10.1186/1471-2199-7-29 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 090YK UT WOS:000240992000001 PM 16978418 ER PT J AU Bella, JN Palmieri, V Roman, MJ Paranicas, MF Welty, TK Lee, ET Fabsitz, RR Howard, BV Devereux, RB AF Bella, Jonathan N. Palmieri, Vittorio Roman, Mary J. Paranicas, Mary F. Welty, Thomas K. Lee, Elisa T. Fabsitz, Richard R. Howard, Barbara V. Devereux, Richard B. TI Gender differences in left ventricular systolic function in American Indians (from the strong heart study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; AORTIC-STENOSIS; RISK-FACTORS; HYPERTROPHY; GEOMETRY; CHAMBER; VALVE; MASS AB Data from population-based studies indicate that men have a higher incidence and worse prognoses of congestive heart failure than women. Echocardiography was used to compare left ventricular (LV) myocardial and chamber contractility between 490 male and 861 female American Indian participants in the second Strong Heart Study examination. After adjusting for fat-free mass, baseline hypertension, diabetes mellitus, coronary heart disease, and alcohol consumption, LV ejection fractions were higher in women than men (66 +/- 8% vs 63 +/- 9%, p = 0.002), as were stress-corrected mid-wall shortening (106 +/- 13% vs 104 +/- 15%, p = 0.006) and the circumferential end-systolic stress/end-systolic volume index (7.1 x 10(4) +/- 1.9 x 10(4) vs 6.5 x 10(4) +/- 2.1 x 10(4) kdyne/cm(3), all p values < 0.001). LV ejection fractions were less than the predefined partition value in 4.7% of women and in 16.7% of men (odds ratio 0.25, 95% confidence interval 0.18 to 0.34, p < 0.001). Stress-corrected mid-wall shortening was less than the predetermined lower limit of normal in 2.9% of women and in 6.2% of men (odds ratio 0,45, 95% confidence interval 0.29 to 0.70, p < 0.001). There was no significant gender difference in supranormal function by either measure of LV systolic function. Estimated mean independent effects of female gender were a 3% greater ejection fraction, 2.7% greater stress-corrected mid-wall shortening, and a 0.4 x 10(4) kdyne/cm(3) greater circumferential end-systolic stress/end-systolic volume index. In conclusion, in a population-based sample aged 45 to 74 years, women had greater LV myocardial and chamber function than men. Gender-specific partition values for measures of LV systolic function may be necessary to detect abnormal contractility in clinical and epidemiologic studies. (c) 2006 Elsevier Inc. All rights reserved. C1 Bronx Lebanon Hosp Ctr, Dept Med, Bronx, NY 10456 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Aberdeen Area Tribal Charimens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Sch Publ Hlth Serv, Oklahoma City, OK USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. MedStar Res Inst, Washington, DC USA. RP Bella, JN (reprint author), Bronx Lebanon Hosp Ctr, Dept Med, Bronx, NY 10456 USA. EM jonnbella@earthlink.net OI Palmieri, Vittorio/0000-0003-3732-524X FU NCRR NIH HHS [M10RR0047-34]; NHLBI NIH HHS [HL41642, HL65521, HL41652, HL41654] NR 20 TC 23 Z9 23 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2006 VL 98 IS 6 BP 834 EP 837 DI 10.1016/j.amjcard.2006.03.069 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 087AR UT WOS:000240715100031 PM 16950198 ER PT J AU Pucino, F Harbus, PT Goldbach-Mansky, R AF Pucino, Frank, Jr. Harbus, Phyllis Tish Goldbach-Mansky, Raphaela TI Use of biologics in rheumatoid arthritis: Where are we going? SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article; Proceedings Paper CT Midyear Clinical Meeting of the American-Society-of-Health-System-Pharmacists CY DEC 04-06, 2005 CL Las Vegas, NV SP Amer Soc Hlth Syst Pharmacists DE arthritis; biologicals; costs; quality of life; toxicity ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA ANTAGONISTS; MUCKLE-WELLS-SYNDROME; QUALITY-OF-LIFE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; MODIFYING ANTIRHEUMATIC DRUGS; PLACEBO-CONTROLLED TRIAL; B-LYMPHOCYTE STIMULATOR; INTERNATIONAL CLINICAL-EVALUATION; LISTERIA-MONOCYTOGENES INFECTION AB Purpose. The pharmacology, efficacy, safety, and costs of biologic agents that are approved by the Food and Drug Administration or are under review for the management of rheumatoid arthritis (RA) are discussed. Biologic therapies that are currently under investigation in early- and late-phase clinical trials are summarized at the end of this report. Summary. The use of biologic agents for the treatment of RA has significantly improved the management of this disease. Experimental and clinical studies have shown that these agents ameliorate the signs and symptoms of RA, slow radiographic progression of disease, and improve physical function and quality of life. Data also support that early initiation of therapy with these agents improves long-term outcomes. However, biologic agents are associated with adverse effects that health care providers need to recognize and manage. Conclusion. Biologic agents have revolutionized the treatment of RA by reducing the signs and symptoms of RA, slowing radiographic progression of joint destruction, and improving physical function and quality of life in affected patients. C1 Howard Univ, Coll Pharm, Washington, DC 20059 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Pucino, F (reprint author), 2300 4th St NW, Washington, DC 20059 USA. EM fpucinojr@yahoo.com NR 203 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD SEP 15 PY 2006 VL 63 IS 18 SU 4 BP S19 EP S41 DI 10.2146/ajhp060365 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 088WM UT WOS:000240841800004 PM 16960244 ER PT J AU Sharma, S Doherty, KM Brosh, RM AF Sharma, Sudha Doherty, Kevin M. Brosh, Robert M., Jr. TI Mechanisms of RecQ helicases in pathways of DNA metabolism and maintenance of genomic stability SO BIOCHEMICAL JOURNAL LA English DT Review DE aging; cancer; DNA repair; genomic instability; helicase; RecQ ID WERNER-SYNDROME PROTEIN; BLOOMS-SYNDROME HELICASE; SYNDROME GENE-PRODUCT; ESCHERICHIA-COLI RECQ; STRAND BREAK REPAIR; ROTHMUND-THOMSON-SYNDROME; TOPOISOMERASE-III-ALPHA; STALLED REPLICATION FORKS; SUBSTRATE-SPECIFIC INHIBITION; SISTER-CHROMATID EXCHANGE AB Helicases are molecular motor proteins that couple the hydrolysis of NTP to nucleic acid unwinding. The growing number of DNA helicases implicated in human disease suggests that their vital specialized roles in cellular pathways are important for the maintenance of genome stability. In particular, mutations in genes of the RecQ family of DNA helicases result in chromosomal instability diseases of premature aging and/or cancer predisposition. We will discuss the mechanisms of RecQ helicases in pathways of DNA metabolism. A review of RecQ helicases from bacteria to human reveals their importance in genomic stability by their participation with other proteins to resolve DNA replication and recombination intermediates. In the light of their known catalytic activities and protein interactions, proposed models for RecQ function will be summarized with an emphasis on how this distinct class of enzymes functions in chromosomal stability maintenance and prevention of human disease and cancer. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM broshr@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 FU Intramural NIH HHS NR 285 TC 147 Z9 152 U1 1 U2 6 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 SEP 15 PY 2006 VL 398 BP 319 EP 337 DI 10.1042/BJ20060450 PN 3 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 088EH UT WOS:000240793800001 PM 16925525 ER PT J AU Winterer, G Egan, MF Kolachana, BS Goldberg, TE Coppola, R Weinberger, DR AF Winterer, Georg Egan, Michael F. Kolachana, Bhaskar S. Goldberg, Terry E. Coppola, Richard Weinberger, Daniel R. TI Prefrontal electrophysiologic "noise" and catechol-O-methyltransferase genotype in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; dopamine; COMT; prefrontal; P300; noise ID VAL(108/158) MET GENOTYPE; GENETIC RISK; WORKING-MEMORY; INTRACEREBRAL POTENTIALS; VISUAL-STIMULI; RARE TARGET; PHYSIOLOGICAL DYSFUNCTION; FUNCTIONAL POLYMORPHISM; DOPAMINE RELEASE; FRONTAL-CORTEX AB Background. Increased variability of stimulus-induced prefrontal electromagnetic activity (''noise'') has been associated with genetic risk for schizophrenia. on the basis of animal experiments and computational models, we have predicted that this prefrontal "noise" phenotype would be related to variation in prefrontal dopamine (DA) signaling, which itself might be abnormal in schizophrenia. In the present study, the effect of a functional single nucleotide polymorphism (val(108/158)met) within the catechol-O-methyltranferase (COMT) gene on prefrontal "noise" was examined, because the COMT enzyme is involved in cortical synaptic dopamine metabolism and weakly predictive of risk for schizophrenia. Methods: A Caucasian sample comprising 112 unrelated normal subjects, 83 schizophrenic probands, and 87 of their unaffected siblings was investigated, all of whom bad measures of prefrontal "noise" estimated from event-related electroencephalogram during an auditory oddball task. Results: The val(108/158)met genotype was significantly associated with prefrontal "noise"; homozygous Val-carriers had greatest prefrontal "noise" values; odds ratio (OR) = 2.37 (95% confidence interval [CI] 1.37-4.10), p = 003. The genotype-phenotype association was stronger when only considering male subjects with an OR = 3.37 (95% CI: 1.63-6.98), p = 002. Conclusions: The results suggest that COMT genotype impacts the level of prefrontal physiologic "noise." C1 NIMH, Clin Brain Disorders Branch, Genes & Cognit & Psychosis Program IRP, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Genes & Cognit & Psychosis Program IRP, NIH, 10 Ctr Dr,Room 4S-235, Bethesda, MD 20892 USA. EM daniel.weinberger@mail.nih.gov NR 62 TC 49 Z9 49 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2006 VL 60 IS 6 BP 578 EP 584 DI 10.1016/j.biopsych.2006.03.023 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 088WB UT WOS:000240840700009 PM 16730334 ER PT J AU Lipska, BK Deep-Soboslay, A Weickert, CS Hyde, TM Martin, CE Herman, MM Kleinman, JE AF Lipska, Barbara K. Deep-Soboslay, Amy Weickert, Cynthia Shannon Hyde, Thomas M. Martin, Catherine E. Herman, Mary M. Kleinman, Joel E. TI Critical factors in gene expression in postmortem human brain: Focus on studies in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; smoking; RNA integrity; postmortem studies; brain bank; hippocampus; prefrontal cortex ID TIME RT-PCR; MESSENGER-RNA; BIPOLAR DISORDER; PREFRONTAL CORTEX; OXIDATIVE STRESS; SMOKING; NEUROPATHOLOGY; PREMORTEM; MATTER; TISSUE AB Background: Studies of postmortem human brain are important for investigating underlying pathogenic molecular mechanisms of neuropsychiatric disorders. They are, however, confounded by pre- and postmortem factors. The purpose of this study was to identify sources of variation that will enable a better design of gene expression studies and higher reliability of gene expression data. Methods. We assessed the contribution of multiple variables to messenger RNA (mRNA) expression of reference (housekeeping) genes measured by reverse transcriptase-polymerase chain reaction (RT-PCR) by multiple regression analysis in a large number (N = 143) of autopsy samples from the hippocampus and white and grey matter of the dorsolateral Prefrontal cortex (DLPFC) of patients with schizophrenia and normal control subjects. Results: The strongest predictor of gene expression was total RNA quality. Other significant factors included pH, postmortem interval, age and the duration of the agonal state, but the importance of these factors depended on transcript measured, brain region analyzed, and diagnosis. The quality of RNA obtained from the DLPFC white matter was also adversely affected by smoking. Conclusions: Our results show that normalization of expression data of target genes with a geometric mean of multiple housekeeping genes should be used to control for differences in RNA quality between samples. The results also suggest that accurate assessment Of other confounding factors and their inclusion as regressors in the analysis is critical for obtaining reliable and accurate quantification of mRNA expression. C1 NIMH, Brain Disorders Branch, DIRP, NIH, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), NIMH, Brain Disorders Branch, DIRP, NIH, 10 Ctr Dr,Room 4N306, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011; Lipska, Barbara/E-4569-2017 FU Intramural NIH HHS NR 52 TC 124 Z9 122 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2006 VL 60 IS 6 BP 650 EP 658 DI 10.1016/j.biopsych.2006.06.019 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 088WB UT WOS:000240840700019 PM 16997002 ER PT J AU Tangirala, RS Antony, S Agama, K Pommier, Y Anderson, BD Bevins, R Curran, DP AF Tangirala, Raghuram S. Antony, Smitha Agama, Keli Pommier, Yves Anderson, Bradley D. Bevins, Robert Curran, Dennis P. TI Synthesis and biological assays of E-ring analogs of camptothecin and homocamptothecin SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE camptothecin; anti-cancer agents; topoisomerase 1; cascade radical annulation ID TOPOISOMERASE-I; NOTHAPODYTINE-B; PERSPECTIVES; CYCLIZATION; MECHANISM; DRUGS AB Analogs of the anti-tumor agent camptothecin with both closed E-rings (lactone and ether) and open E-rings (reduced acid, hydrazide, and protected Weinreb amide) have been prepared and tested in topoisomerase and cellular assays. The results provide insights into the structural features of the camptothecin E-ring that affect biological activity. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Univ Kentucky, Dept Pharmaceut Sci, Lexington, KY 40506 USA. Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA. RP Curran, DP (reprint author), Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. EM curran@pitt.edu FU NCI NIH HHS [CA 87061] NR 31 TC 23 Z9 25 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP 15 PY 2006 VL 14 IS 18 BP 6202 EP 6212 DI 10.1016/j.bmc.2006.05.073 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 085PF UT WOS:000240615300009 PM 16793274 ER PT J AU Li, PX Evans, CD Forbeck, EM Park, H Bai, RL Hamel, E Joullie, MM AF Li, Pixu Evans, Cory D. Forbeck, Erin M. Park, Haengsoon Bai, Ruoli Hamel, Ernest Joullie, M. M. TI Total synthesis and biological evaluation of ustiloxin natural products and two analogs SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE ustiloxins D and F; tubulin inhibitor; phomopsin; total synthesis; biological evalution; antimitotic agent ID ANTIMITOTIC AGENTS; PHOMOPSIS-LEPTOSTROMIFORMIS; TUBULIN; LUPINOSIS; PEPTIDES; ESTERS AB Synthetic investigations of ustiloxin natural products are described. The first total synthesis of ustiloxin F was completed in 15 steps via ethynyl aziridine ring-opening by a phenol derivative. The results of biological tests of synthetic ustiloxins D and F, and two analogs, O-Me-ustiloxin D and 6-Ile-ustiloxin, demonstrated that the free hydroxyl group ortho to the ether linkage is critical for activity and variations at the Val/Ala site produce changes in the biological activity suggesting the need for further perturbations at this site to more extensively study the tubulin binding. (c) 2006 Elsevier Ltd. All rights reserved. C1 NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Ft Detrick, MD 21702 USA. Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. RP Joullie, MM (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Ft Detrick, MD 21702 USA. EM mjoullie@sas.upenn.edu FU NCI NIH HHS [CA-40081] NR 22 TC 17 Z9 18 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 15 PY 2006 VL 16 IS 18 BP 4804 EP 4807 DI 10.1016/j.bmcl.2006.06.071 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 082OD UT WOS:000240395300021 PM 16837194 ER PT J AU Yarchoan, R Haque, M AF Yarchoan, Robert Haque, Muzammel TI KSHV wages a 2-front war on PECAM/CD31 SO BLOOD LA English DT Editorial Material ID CLASS-I MOLECULES; PROTEIN AB In this issue of Blood, Mansouri and colleagues show that in addition to suppressing expression of histocompatibility complex class I molecules, the K5 gene product of KSHV also targets CD31. It does this by 2 separate mechanisms, one that targets newly synthesized CD31 and one that targets CD31 already expressed on the cell surface. C1 NCI, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, 9000 Rockville Pike,Bldg 31,Rm 10A03, 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 SEP 15 PY 2006 VL 108 IS 6 BP 1790 EP 1791 DI 10.1182/blood-2006-06-031559 PG 2 WC Hematology SC Hematology GA 082NY UT WOS:000240394800006 ER PT J AU Baccarani, M Saglio, G Goldman, J Hochhaus, A Simonsson, B Appelbaum, F Apperley, J Cervantes, F Cortes, J Deininger, M Gratwohl, A Guilhot, F Horowitz, M Hughes, T Kantarjian, H Larson, R Niederwieser, D Silver, R Hehlmann, R AF Baccarani, Michele Saglio, Giuseppe Goldman, John Hochhaus, Andreas Simonsson, Bengt Appelbaum, Frederick Apperley, Jane Cervantes, Francisco Cortes, Jorge Deininger, Michael Gratwohl, Alois Guilhot, Frangois Horowitz, Mary Hughes, Timothy Kantarjian, Hagop Larson, Richard Niederwieser, Dielger Silver, Richard Hehlmann, Rudiger TI Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet SO BLOOD LA English DT Review ID CHRONIC MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; IMATINIB MESYLATE THERAPY; KINASE DOMAIN MUTATIONS; ABL TYROSINE KINASE; GIMEMA WORKING PARTY; LOW-DOSE CYTARABINE; CLONAL CYTOGENETIC ABNORMALITIES; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION AB The introduction of imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML). Although experience is too limited to permit evidence-based evaluation of survival, the available data fully justify critical reassessment of CML management. The panel therefore reviewed treatment of CML since 1998. It confirmed the value of IM (400 mg/day) and of conventional allogeneic hematopoietic stem cell transplantation (alloHSCT). It recommended that the preferred initial treatment for most patients newly diagnosed in chronic phase should now be 400 mg IM daily. A dose increase of IM, alloHSCT, or investigational treatments were recommended in case of failure, and could be considered in case of suboptimal response. Failure was defined at 3 months (no hematologic response [HR]), 6 months (incomplete HR or no cytogenetic response [CgR]), 12 months (less than partial CgR [Philadelphia chromosome-positive (Ph(+)) > 35%]), 18 months (less than complete CgR), and in case of HR or CgR loss, or appearance of highly IM-resistant BCR-ABL mutations. Suboptimal response was defined at 3 months (incomplete HR), 6 months (less than partial CgR), 12 months (less than complete CgR), 18 months (less than major molecular response [MMolR]), and, in case of MMolR loss, other mutations or other chromosomal abnormalities. The importance of regular monitoring at experienced centers was highlighted. C1 Univ Bologna, Dept Hematol Oncol L&A Seragnoli, Bologna, Italy. Univ Turin Orbassano, Dept Clin & Biol Sci, Turin, Italy. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Fac Clin Med Mannheim, D-6800 Mannheim, Germany. Univ Uppsala Hosp, Dept Hematol, Uppsala, Sweden. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Hammersmith Hosp, Dept Hematol, London, England. Univ Barcelona, Dept Hematol, Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Inst Canc, Portland, OR 97201 USA. Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland. CHU La Miletrie, Dept Oncol Hematol & Cell Therapy, Equipe Accueil 3805, Poitiers, France. CHU La Miletrie, Clin Res Ctr, Poitiers, France. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Inst Med & Vet Sci, Adelaide, NSW, Australia. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Univ Leipzig, Dept Hematol & Oncol, D-7010 Leipzig, Germany. New York Presbyterian Weill Cornell Med Ctr, New York, NY USA. RP Baccarani, M (reprint author), St Orsola Marcello Malpighi Hosp, Dept Hematol Oncol L&A Seragnoli, Via Massarenti 9, I-40138 Bologna, Italy. EM baccarani@med.unibo.it RI apperley, jane/B-4367-2009; OI Hochhaus, Andreas/0000-0003-0626-0834; Larson, Richard/0000-0001-9168-3203 NR 192 TC 750 Z9 808 U1 0 U2 28 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 SEP 15 PY 2006 VL 108 IS 6 BP 1809 EP 1820 DI 10.1182/blood-2006-02-005686 PG 12 WC Hematology SC Hematology GA 082NY UT WOS:000240394800013 PM 16709930 ER PT J AU Shen, RR Ferguson, DO Renard, M Hoyer, KK Kim, U Hao, XP Alt, FW Roeder, RG Morse, HC Teitell, MA AF Shen, Rhine R. Ferguson, David O. Renard, Mathilde Hoyer, Katrina K. Kim, Unkyu Hao, Xingpei Alt, Frederick W. Roeder, Robert G. Morse, Herbert C., III Teitell, Michael A. TI Dysregulated TCL1 requires the germinal center and genome instability for mature B-cell transformation SO BLOOD LA English DT Article ID INDUCED-CYTIDINE-DEAMINASE; FAS-MEDIATED APOPTOSIS; CLASS SWITCH RECOMBINATION; C-MYC; CHROMOSOMAL TRANSLOCATIONS; ANTIGEN RECEPTOR; BURKITT-LYMPHOMA; PROLYMPHOCYTIC LEUKEMIA; DEREGULATED EXPRESSION; FOLLICULAR LYMPHOMA AB Most lymphomas arise by transformation of germinal center (GC) B cells. TCL1, a proto-oncogene first recognized for its role in T-cell transformation, also induces GC B-cell malignancies when dysregulated in pE mu-B29-TCL1 transgenic (TCL1-tg) mice. Clonal B-cell lymphomas develop from polyclonal populations with latencies of 4 months or more, suggesting that secondary genetic events are required for full transformation. The goals of this study were to determine the GC-related effects of TCL1 dysregulation that contribute to tumor initiation and to identify companion genetic alterations in tumors that function in disease progression. We report that compared with wildtype (WT) cells, B cells from TCL1-tg mice activated in a manner resembling a T-dependent GC reaction show enhanced resistance to FAS-mediated apoptosis with CD40 stimulation, independent of a B-cell antigen receptor (BCR) rescue signal. Mitogenic stimulation of TCL1-tg B cells also resulted in increased expression of Aicda. These GC-related enhancements in survival and Aicda expression could underlie B-cell transformation. Supporting this notion, no B-cell lymphomas developed for 20 months when TCL1-tg mice were crossed onto an Oct coactivator from B cell (OCA-B)-deficient background to yield mice incapable of forming GCs. Spectral karyotype analyses showed that GC lymphomas from TCL1-tg mice exhibit recurrent chromosome translocations and trisomy 15, with corresponding MYC overexpression. We conclude that pE mu-B29-TCL1 transgenic B cells primed for transformation must experience the GC environment and, for at least some, develop genome instability to become fully malignant. C1 Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NIAID, Immunopathol Lab, NIH, Rockville, MD USA. RP Teitell, MA (reprint author), Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mteitell@ucla.edu OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA 107300, CA 90571, CA 109901, CA 113872, CA 92625]; NIAID NIH HHS [T32 AI 07126] NR 66 TC 11 Z9 13 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 SEP 15 PY 2006 VL 108 IS 6 BP 1991 EP 1998 DI 10.1182/blood-2006-02-001354 PG 8 WC Hematology SC Hematology GA 082NY UT WOS:000240394800039 PM 16728701 ER PT J AU Quintanilla-Martinez, L Pittaluga, S Miething, C Klier, M Rudelius, M Davies-Hill, T Anastasov, N Martinez, A Vivero, A Duyster, J Jaffe, ES Fend, F Raffeld, M AF Quintanilla-Martinez, Leticia Pittaluga, Stefania Miething, Cornelius Klier, Margit Rudelius, Martina Davies-Hill, Theresa Anastasov, Natasa Martinez, Antonio Vivero, Angelica Duyster, Justus Jaffe, Elaine S. Fend, Falko Raffeld, Mark TI NPM-ALK-dependent expression of the transcription factor CCAAT/enhancer binding protein beta in ALK-positive anaplastic large cell lymphoma SO BLOOD LA English DT Article ID C/EBP-BETA; T-CELLS; TYROSINE KINASE; MAMMARY-GLAND; DIFFERENTIATION; PATHWAY; FUSION; MICE; GENE; IDENTIFICATION AB CCAAT/enhancer binding protein P (C/EBP beta) is one of a 6-member family of C/EBPs. These transcription factors are involved in the regulation of various aspects of cellular growth and differentiation. Although C/EBP beta has important functions in B- and T-cell differentiation, its expression has not been well studied in lymphoid tissues. We, therefore, analyzed its expression by immunohistochemistry and Western blot in normal lymphoid tissues and in 248 well-characterized lymphomas and lymphoma cell lines. Nonneoplastic lymphoid tissues and most B-cell, T-cell, and Hodgkin lymphomas lacked detectable levels of C/EBP beta. In contrast, most (40 of 45; 88%) cases of ALK-positive anaplastic large cell lymphoma (ALCL) strongly expressed C/EBP beta. Western blot analysis confirmed C/EBP beta expression in the ALK-positive ALCLs and demonstrated elevated levels of the LIP isoform, which has been associated with increased proliferation and aggressiveness in carcinomas. Transfection of Ba/F3 and 32D cells with NPM-ALK and a kinase-inhibitable modified NPM-ALK resulted in the induction of C/EBPP and demonstrated dependence on NPM-ALK kinase activity. In conclusion, we report the constitutive expression of C/EBPP in ALK-positive ALCL and show its relationship to NPM-ALK. We suggest that C/EBPP is likely to play an important role in the pathogenesis and unique phenotype of this lymphoma. C1 Natl Res Ctr Hlth & Environm, GSF, Inst Pathol, Neuherberg, Germany. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, Dept Internal Med 3, D-8000 Munich, Germany. Tech Univ Munich, Inst Pathol, D-8000 Munich, Germany. RP Raffeld, M (reprint author), NCI, Pathol Lab, Bldg 10,Rm 2N110,9000 Rockville Pike, Rockville, MD 20852 USA. EM mraff@box-m.nih.gov RI Martinez, Antonio/D-8188-2012; Anastasov, Natasa/M-9848-2014 OI Martinez, Antonio/0000-0003-0790-9017; Anastasov, Natasa/0000-0002-4088-1119 NR 53 TC 26 Z9 27 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 SEP 15 PY 2006 VL 108 IS 6 BP 2029 EP 2036 DI 10.1182/blood-2005-10-014258 PG 8 WC Hematology SC Hematology GA 082NY UT WOS:000240394800044 PM 16709933 ER PT J AU Medhurst, AL Laghmani, EH Steltenpool, J Ferrer, M Fontaine, C de Groot, J Rooimans, MA Scheper, RJ Meetei, AR Wang, WD Joenje, H de Winter, JP AF Medhurst, Annette L. Laghmani, El Houari Steltenpool, Jurgen Ferrer, Miriam Fontaine, Chantal de Groot, Jan Rooimans, Martin A. Scheper, Rik J. Ruhikanta Meetei, Amorn Wang, Weidong Joenje, Hans de Winter, Johan P. TI Evidence for subcomplexes in the Fanconi anemia pathway SO BLOOD LA English DT Article ID NUCLEAR-COMPLEX; PROTEINS FANCA; POSITIONAL CLONING; CORE COMPLEX; DNA-REPAIR; S-PHASE; GENE; COMPLEMENTATION; ACCUMULATION; FANCG/XRCC9 AB Fanconi anemia (FA) is a genomic instability disorder, clinically characterized by congenital abnormalities, progressive bone marrow failure, and predisposition to malignancy. Cells derived from patients with FA display a marked sensitivity to DNA cross-linking agents, such as mitomycin C (MMC). This observation has led to the hypothesis that the proteins defective in FA are involved in the sensing or repair of interstrand cross-link lesions of the DNA. A nuclear complex consisting of a majority of the FA proteins plays a crucial role in this process and is required for the monoubiquitination of a downstream target, FANCD2. Two new FA genes, FANCB and FANCL, have recently been identified, and their discovery has allowed a more detailed study into the molecular architecture of the FA pathway. We demonstrate a direct interaction between FANCB and FANCL and that a complex of these proteins binds FANCA. The interaction between FANCA and FANCL is dependent on FANCB, FANCG, and FANCM, but independent of FANCC, FANCE, and FANCF. These findings provide a framework for the protein interactions that occur "upstream" in the FA pathway and suggest that besides the FA core complex different subcomplexes exist that may have specific functions other than the monoubiquitination of FANCD2. C1 VU Univ, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands. VU Univ, Med Ctr, Dept Med Oncol, Div Gene Therapy, NL-1081 BT Amsterdam, Netherlands. VU Univ, Med Ctr, Dept Pathol, NL-1081 BT Amsterdam, Netherlands. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. Cincinnati Childrens Res Fdn, Div Expt Hematol, Cincinnati, OH USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP de Winter, JP (reprint author), VU Univ, Med Ctr, Dept Clin Genet & Human Genet, Boechorstr 7, NL-1081 BT Amsterdam, Netherlands. EM j.dewinter@vumc.nl FU Intramural NIH HHS NR 36 TC 66 Z9 68 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2006 VL 108 IS 6 BP 2072 EP 2080 DI 10.1182/blood-2005-11-008151 PG 9 WC Hematology SC Hematology GA 082NY UT WOS:000240394800050 PM 16720839 ER PT J AU Oneal, PA Gantt, NM Schwartz, JD Bhanu, NV Lee, YT Moroney, JW Reed, CH Schechter, AN Luban, NLC Miller, JL AF Oneal, Patricia A. Gantt, Nicole M. Schwartz, Joseph D. Bhanu, Natarajan V. Lee, Y. Terry Moroney, John W. Reed, Christopher H. Schechter, Alan N. Luban, Naomi L. C. Miller, Jeffery L. TI Fetal hemoglobin silencing in humans SO BLOOD LA English DT Article ID SICKLE-CELL-ANEMIA; GLOBIN-GENE; ERYTHROPOIESIS; EXPRESSION; HYDROXYUREA; INFANTS; SWITCH; LOCUS; MOUSE; SHEEP AB Interruption of the normal fetal-to-adult transition of hemoglobin expression should largely ameliorate sickle cell and betathalassemia syndromes. Achievement of this clinical goal requires a robust understanding of gamma-globin gene and protein silencing during human development. For this purpose, age-related changes in globin phenotypes of circulating human erythroid cells were examined from 5 umbilical cords, 99 infants, and 5 adult donors. Unexpectedly, an average of 95% of the cord blood erythrocytes and reticulocytes expressed HbA and the adult beta-globin gene, as well as HbF and the gamma-globin genes. The distribution of hemoglobin and globin gene expression then changed abruptly due to the expansion of cells lacking HbF or gamma-globin mRNA (silenced cells). In adult reticulocytes, less than 5% expressed gamma-globin mRNA. These data are consistent with a "switching" model in humans that initially results largely from gamma- and beta-globin gene coexpression and competition during fetal development. In contrast, early postnatal life is marked by the rapid accumulation of cells that possess undetectable gamma-globin mRNA and HbF. The silencing phenomenon is mediated by a mechanism of cellular replacement. This novel silencing pattern may be important for the development of HbF-enhancing therapies. C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Dept Obstet & Gynecol, Bethesda, MD USA. Childrens Natl Med Ctr, Lab Med & Pathol, Washington, DC 20010 USA. RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 9B17, Bethesda, MD 20892 USA. EM jm7f@nih.gov OI Schechter, Alan N/0000-0002-5235-9408 FU Intramural NIH HHS NR 35 TC 18 Z9 18 U1 1 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 SEP 15 PY 2006 VL 108 IS 6 BP 2081 EP 2086 DI 10.1182/blood-2006-04-015859 PG 6 WC Hematology SC Hematology GA 082NY UT WOS:000240394800051 PM 16735596 ER PT J AU Kioi, M Kawakami, M Shimamura, T Husain, SR Puri, RK AF Kioi, Mitomu Kawakami, Mariko Shimamura, Takeshi Husain, Syed R. Puri, Raj K. TI Interleukin-13 receptor alpha 2 chain - A potential biomarker and molecular target for ovarian cancer therapy SO CANCER LA English DT Article DE ovarian cancer; biomarker; interleukin-13; receptor; targeted therapy ID CLEAR-CELL CARCINOMA; ANTITUMOR-ACTIVITY; CYTOTOXIN; IL-13; SERUM; EXPRESSION; XENOGRAFT; SUBUNIT; P53 AB BACKGROUND. Epithelial ovarian cancer demonstrates high mortality due to diagnosis at an advanced stage. In the search for a biomarker for early diagnosis and a target for therapy, the issue of whether interleukin-13 receptor (IL-13R), shown to be expressed on a variety of human cancers, is expressed in ovarian tumor samples was explored. In addition, whether this receptor serves as a biomarker and can be targeted by IL-13 cytotoxin was examined. METHODS. IL-13R expression in 15 normal and 68 ovarian tumor tissue samples was determined by immunohistochemistry. Correlation between clinicopathologic features and IL-13R expression was analyzed. The efficacy of IL-13R-directed cytotoxin was determined in mice with subcutaneous, orthotopic, and peritoneal metastatic ovarian cancer. RESULTS. Immunohistochemical analyses revealed that 83% of ovarian cancer specimens express IL-13R alpha 2, a high-affinity IL-13R subunit chain, whereas normal ovary samples expressed none or very low levels. The majority of clear cell ovarian carcinomas with the worst prognosis showed strong staining for IL-13R alpha 2. IL-13 cytotoxin was highly cytotoxic to the IGROV-1 ovarian cancer cell line in vitro, and it mediated significant antitumor activity against a xenografted tumor model. The antitumor effects were confirmed by treating orthotopically implanted or peritoneal metastatic ovarian tumors, which showed significant extension of survival in immunodeficient mice. IL-13 cytotoxin also prevented cachexia in treated mice. The soluble form of IL-13R alpha 2 was detected in the serum of mice with peritoneal metastasis, and the level decreased to baseline in the treated group. CONCLUSIONS. IL-13R alpha 2 is a promising target for ovarian cancer therapy, and the soluble form of IL-13R may be a possible surrogate marker for disease monitoring. C1 NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluation & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluation & Res, Bldg 29B,Room 2NN20,HFM-710,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 23 TC 41 Z9 44 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2006 VL 107 IS 6 BP 1407 EP 1418 DI 10.1002/cncr.22134 PG 12 WC Oncology SC Oncology GA 084MR UT WOS:000240537700026 PM 16902988 ER PT J AU Fernandez, CV Shurin, S Kodish, E AF Fernandez, Conrad V. Shurin, Susan Kodish, Eric TI Providing research participants with findings from completed cancer-related clinical trials - Not quite as simple as it sounds SO CANCER LA English DT Letter C1 IWK Hlth Ctr, Dept Bioeth, Dept Pediat, Halifax, NS, Canada. Dalhousie Univ, Halifax, NS, Canada. NIH, NHLBI, Bethesda, MD USA. Cleveland Clin Fdn, Dept Bioeth, Cleveland, OH 44195 USA. RP Fernandez, CV (reprint author), IWK Hlth Ctr, Dept Bioeth, Dept Pediat, Halifax, NS, Canada. NR 3 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 15 PY 2006 VL 107 IS 6 BP 1419 EP 1420 DI 10.1002/cncr.22140 PG 2 WC Oncology SC Oncology GA 084MR UT WOS:000240537700027 PM 16862571 ER PT J AU Tolliday, N Clemons, PA Ferraiolo, P Koehler, AN Lewis, TA Li, XH Schreiber, SL Gerhard, DS Eliasof, S AF Tolliday, Nicola Clemons, Paul A. Ferraiolo, Paul Koehler, Angela N. Lewis, Timothy A. Li, Xiaohua Schreiber, Stuart L. Gerhard, Daniela S. Eliasof, Scott TI Small molecules, big players: The National Cancer Institute's initiative for chemical genetics SO CANCER RESEARCH LA English DT Article ID SMALL ORGANIC-MOLECULES; AUTOMATED MICROSCOPY; INHIBITORS; PATHWAY; CYTOKINESIS; DEGRADATION; PROTEASOME; DIVERSITY; RAPAMYCIN; PROTEINS AB In 2002, the National Cancer Institute created the Initiative for Chemical Genetics (ICG), to enable public research using small molecules to accelerate the discovery of cancer-relevant small-molecule probes. The ICG is a public-access research facility consisting of a tightly integrated team of synthetic and analytical chemists, assay developers, high-throughput screening and automation engineers, computational scientists, and software developers. The ICG seeks to facilitate the cross-fertilization of synthetic chemistry and cancer biology by creating a research environment in which new scientific collaborations are possible. To date, the ICG has interacted with 76 biology laboratories from 39 institutions and more than a dozen organic synthetic chemistry laboratories around the country and in Canada. All chemistry and screening data are deposited into the ChemBank web site (http://chembank. broad.harvard.edu/) and are available to the entire research community within a year of generation. ChemBank is both a data repository and a data analysis environment, facilitating the exploration of chemical and biological information across many different assays and small molecules. This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings. C1 Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02139 USA. Howard Hughes Med Inst, Cambridge, MA USA. NCI, Off Canc Gen, Bethesda, MD 20892 USA. RP Eliasof, S (reprint author), Harvard Univ, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM seliasof@broad.harvard.edu FU NCI NIH HHS [N01-CO-12400] NR 36 TC 54 Z9 57 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2006 VL 66 IS 18 BP 8935 EP 8942 DI 10.1158/0008-5472.CAN-06-2552 PG 8 WC Oncology SC Oncology GA 086CI UT WOS:000240650300003 PM 16982730 ER PT J AU Nesterova, MV Johnson, N Cheadle, C Bates, SE Mani, S Stratakis, CA Kahn, I Gupta, RK Cho-Chung, YS AF Nesterova, Maria V. Johnson, Natalie Cheadle, Christopher Bates, Susan E. Mani, Sridhar Stratakis, Constantine A. Kahn, Islam Gupta, Rishab K. Cho-Chung, Yoon S. TI Autoantibody cancer biomarker: Extracellular protein kinase A SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER; COLORECTAL-CANCER; ANTIBODIES; SUBUNIT; P53; MARKERS; ALPHA; SERA AB in cancer cells, cyclic AMP-dependent protein kinase (PKA) is secreted into the conditioned medium. This PKA, designated as extracellular protein kinase A (ECPKA), is markedly upregulated in the sera of patients with cancer. The currently available tumor markers are based on the antigen determination method and lack specificity and sensitivity. Here, we present an ECPKA autoantibody detection method for a universal biomarker that detects cancer of various cell types. We tested sera from 295 patients with cancers of various cell types, 155 normal controls, and 55 patients without cancer. The specificity and sensitivity of this autoantibody enzyme immunoassay method were compared with the conventional antigen determination method by receiver-operating characteristic plots. In the sera, the presence of autoantibody directed against ECPKA was highly correlated with cancer. High anti-ECPKA autoantibody titers (frequency, 90%; mean titer, 3.0) were found in the sera of patients with various cancers, whereas low or negative titers (frequency, 12%; mean titer, 1.0) were found in the control group. The receiver-operating characteristic plot showed that autoantibody enzyme immunoassay exhibited 90% sensitivity and 88% specificity, whereas the enzymatic assay exhibited 83% sensitivity and 80% specificity. These results show that the autoantibody method distinguished between patients with cancer and controls better than the antigen method could. Our results show that autoantibody ECPKA is a universal serum biomarker for cancers of various cell types. C1 NCI, Cellular Biochem Sect, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10467 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. John Wayne Canc Inst, Santa Monica, CA USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov FU Intramural NIH HHS NR 20 TC 34 Z9 39 U1 0 U2 4 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 SEP 15 PY 2006 VL 66 IS 18 BP 8971 EP 8974 DI 10.1158/0008-5472.CANT-06-1049 PG 4 WC Oncology SC Oncology GA 086CI UT WOS:000240650300009 PM 16982736 ER PT J AU Reinert, LS Shi, B Nandi, S Mazan-Mamczarz, K Vitolo, M Bachman, KE He, HL Gartenhaus, RB AF Reinert, Line S. Shi, Bo Nandi, Suvobroto Mazan-Mamczarz, Krystyna Vitolo, Michele Bachman, Kurtis E. He, Huili Gartenhaus, Ronald B. TI MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles SO CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; BINDING-PROTEIN; DYSKERATOSIS-CONGENITA; CANDIDATE ONCOGENE; INITIATION; EXPRESSION; GENE; IDENTIFICATION; TRANSFORMATION; MALIGNANCIES AB MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification enzymes. Here, we established that MCT-1 protein interacts with the cap complex through its PUA domain and recruits the density-regulated protein (DENR/DRP), containing the SU11 translation initiation domain. Through the use of microarray analysis on polysome-associated mRNAs, we showed that up-regulation of MCT-1 was able to modulate the translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1 in translational regulation, and support a linkage between translational control and onco-genesis. C1 Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NIA, Intramural Res Program, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Northwestern Univ, Freinberg Sch Med, Dept Med, Div Rheumatol, Chicago, IL 60611 USA. RP Gartenhaus, RB (reprint author), Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, 9-01 BRB,655 W Baltimore St, Baltimore, MD 21201 USA. EM rgartenhaus@som.umaryland.edu NR 44 TC 22 Z9 25 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 SEP 15 PY 2006 VL 66 IS 18 BP 8994 EP 9001 DI 10.1158/0008-5472.CAN-06-1999 PG 8 WC Oncology SC Oncology GA 086CI UT WOS:000240650300013 PM 16982740 ER PT J AU Dote, H Burgan, WE Camphausen, K Tofilon, PJ AF Dote, Hideaki Burgan, William E. Camphausen, Kevin Tofilon, Philip J. TI Inhibition of Hsp90 compromises the DNA damage response to radiation SO CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; TUMOR-CELL RADIOSENSITIVITY; DEPENDENT PROTEIN-KINASE; HISTONE H2AX; ATM ACTIVATION; GLUCOCORTICOID-RECEPTOR; IONIZING IRRADIATION; NUCLEAR-LOCALIZATION; MRE11 COMPLEX; COMET ASSAY AB Inhibitors of the molecular chaperone Hsp90 have been shown to enhance tumor cell radiosensitivity. To begin to address the mechanism responsible, we have determined the effect of the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG) on the DNA damage response to radiation. Exposure of MiaPaCa tumor cells to 17DMAG, which results in radiosensitization, inhibited the repair of DNA double-strand breaks according to gamma H2AX foci dispersal and the neutral comet assay. This repair inhibition was associated with reduced DNA-PK catalytic subunit (DNA-PKcs) phosphorylation after irradiation and a disruption of DNA-PKcs/ ErbBI interaction. These data suggest that the previously established 17DMAG-mediated reduction in ErbBI activity reduces its interaction with DNA-PKcs and thus accounts for the attenuation of radiation-induced DNA-PK activation. 17DNIAG was also found to abrogate the activation of the G(2)- and S-phase cell cycle checkpoints. Associated with these events was a reduction in radiation-induced ataxia-telangiectasia mutated (ATM) activation and foci formation in 17DMAG-treated cells. Although no interaction between ATM and Hsp90 was detected, Hsp90 was found to interact with the MREII/Rad5O/NBSI (MRN) complex. 17DMAG exposure reduced the ability of the MRN components to form nuclear foci after irradiation. Moreover, 17DMAG exposure reduced the interaction between NBSI and ATM, although no degradation of the MRN complex was detected. These results suggest that the diminished radiation-induced activation of ATM in 17DMAG-treated cells was the result of a compromise in the function of the MRN complex. These data indicate that Hsp90 can contribute to the DNA damage response to radiation affecting both DNA repair and cell cycle checkpoint activation. C1 Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Drug Discovery Program, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA. NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. RP Tofilon, PJ (reprint author), Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Drug Discovery Program, Dept Interdisciplinary Oncol, 12902 magnolia Dr,SRB2-DRDIS, Tampa, FL 33612 USA. EM tofilopj@moffitt.usf.edu NR 50 TC 90 Z9 93 U1 0 U2 3 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 SEP 15 PY 2006 VL 66 IS 18 BP 9211 EP 9220 DI 10.1158/0008-5472.CAN-06-2181 PG 10 WC Oncology SC Oncology GA 086CI UT WOS:000240650300038 PM 16982765 ER PT J AU Prevost, GP Lonchampt, MO Holbeck, S Attoub, S Zaharevitz, D Alley, M Wright, J Brezak, MC Coulomb, H Savola, A Huchet, M Chaumeron, S Nguyen, QD Forgez, P Bruyneel, E Bracke, M Ferrandis, E Roubert, P Demarquay, D Gespach, C Kasprzyk, PG AF Prevost, Gregoire P. Lonchampt, Marie O. Holbeck, Susan Attoub, Samir Zaharevitz, Daniel Alley, Mike Wright, John Brezak, Marie C. Coulomb, Helene Savola, Ann Huchet, Marion Chaumeron, Sophie Nguyen, Quang-De Forgez, Patricia Bruyneel, Erik Bracke, Mark Ferrandis, Eric Roubert, Pierre Demarquay, Daniele Gespach, Christian Kasprzyk, Philip G. TI Anticancer activity of BIM-46174, a new inhibitor of the heterotrimeric G alpha/G beta gamma protein complex SO CANCER RESEARCH LA English DT Article ID HORMONE-RELEASING-HORMONE; CELLULAR INVASION; COUPLED RECEPTORS; EPITHELIAL-CELLS; GROWTH-FACTOR; CANCER-CELLS; IN-VIVO; ACTIVATION; CARCINOMA; ANDROGEN AB A large number of hormones and local agonists activating guanine-binding protein-coupled receptors (GPCR) play a major role in cancer progression. Here, we characterize the new imidazo-pyrazine derivative BIM-46174, which acts as a selective inhibitor of heterotrimeric G-protein complex. BIM46174 prevents the heterotrimeric G-protein signaling linked to several GPCRs mediating (a) cyclic AMP generation (Gets), (b) calcium release (G(alpha q), and (c) cancer cell invasion by Wnt-2 frizzled receptors and high-affinity neurotensin receptors (G alpha o/i and G alpha q). BIM-46174 inhibits the growth of a large panel of human cancer cell lines, including anticancer drug-resistant cells. Exposure of cancer cells to BIM-46174 leads to caspase-3-dependent apoptosis and poly(ADP-ribose) polymerase cleavage. National Cancer Institute COMPARE analysis for BIM-46174 supports its novel pharmacologic profile compared with 12,000 anticancer agents. The growth rate of human tumor xenografts in athymic mice is significantly reduced after administration of BIM-46174 combined with either cisplatin, farnesyltransferase inhibitor, or topoisomerase inhibitors. Our data validate the feasibility of targeting heterotrimeric G-protein functions downstream the GPCRs to improve anticancer chemotherapy. C1 Inst Henri Beaufour, IPSEN, F-91966 Les Ulis, France. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Bethesda, MD 20892 USA. Univ Paris 06, Hop St Antoine, INSERM, U673, Paris, France. State Univ Ghent Hosp, Expt Cancerol Lab, B-9000 Ghent, Belgium. IPSEN Albert Beaufour Res Inst, Milford, MA USA. RP Prevost, GP (reprint author), Inst Henri Beaufour, IPSEN, 5 Ave Canada, F-91966 Les Ulis, France. EM gregoire.prevost@ipsen.com NR 45 TC 33 Z9 34 U1 0 U2 6 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 SEP 15 PY 2006 VL 66 IS 18 BP 9227 EP 9234 DI 10.1158/0008-5472.CAN-05-4205 PG 8 WC Oncology SC Oncology GA 086CI UT WOS:000240650300040 PM 16982767 ER PT J AU de Gramont, A Ganier, O Cohen-Fix, O AF de Gramont, Armand Ganier, Olivier Cohen-Fix, Orna TI Before and after the spindle assembly checkpoint - An APC/C point of view SO CELL CYCLE LA English DT Article DE anaphase promoting complex; APC/C cyclin A; Emi1; Rassf1A; Mad3; Nek2A; UbcH10; spindle assembly checkpoint ID ANAPHASE-PROMOTING COMPLEX; EARLY MITOTIC DEGRADATION; CYCLIN-A; MITOSIS; DESTRUCTION; PROTEOLYSIS; DEPENDS; BOX AB On May 17-21, 2006 the Cold Spring Harbor Laboratory meeting on the cell cycle reunited over 350 researchers to discuss new findings in the cell cycle field. A common thread that connected numerous presentations was the regulation of the anaphase promoting complex/cyclosome (APC/C). This was also the main theme of the lecture given by the keynote speaker, Marc Kirschner (Harvard), who talked about "The unexpected importance of UbcH10 in both the G(1)/S transition and the initiation of anaphase", and it is also the main focus in this summary. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD USA. Univ Paris 06, CNRS, UMR 7098, Paris, France. RP Cohen-Fix, O (reprint author), 8 Ctr Dr,Bldg 8,Room 319, Bethesda, MD 20892 USA. EM ornacf@helix.nih.gov FU Intramural NIH HHS NR 15 TC 12 Z9 12 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2006 VL 5 IS 18 BP 2168 EP 2171 PG 4 WC Cell Biology SC Cell Biology GA 089EC UT WOS:000240862100020 PM 16969093 ER PT J AU Xu, X Francis, R Wei, CJ Linask, KL Lo, CW AF Xu, Xin Francis, Richard Wei, Chih Jen Linask, Kaari L. Lo, Cecilia W. TI Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells SO DEVELOPMENT LA English DT Article DE connexin 43; neural crest cell; focal contact; actin cytoskeleton; cell motility ID GAP JUNCTIONAL COMMUNICATION; NEURONAL GROWTH CONES; N-CADHERIN; INTEGRIN FUNCTION; HEART DEVELOPMENT; HINDBRAIN REGION; UP-REGULATION; NIH3T3 CELLS; IN-VIVO; EXPRESSION AB Connexin 43 knockout (Cx43 alpha 1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing. bronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing. bronectin density. However, compared with wild-type CNCs, Cx43 alpha 1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43 alpha 1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43 alpha 1KO and CMV43 CNCs to beta 1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43 alpha 1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43 alpha 1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43 alpha 1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and. bronectin plating density. Overall, these findings indicate Cx43 alpha 1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs. C1 Natl Heart Lung & Blood Inst, Lab Dev Biol, NIH, Bethesda, MD 20580 USA. RP Lo, CW (reprint author), Natl Heart Lung & Blood Inst, Lab Dev Biol, NIH, Bethesda, MD 20580 USA. EM loc@nhlbi.nih.gov RI Francis, Richard/P-2524-2015 FU Intramural NIH HHS NR 47 TC 102 Z9 106 U1 0 U2 4 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 SEP 15 PY 2006 VL 133 IS 18 BP 3629 EP 3639 DI 10.1242/dev.02543 PG 11 WC Developmental Biology SC Developmental Biology GA 077RC UT WOS:000240046500014 PM 16914489 ER PT J AU Mak, KK Chen, MH Day, TF Chuang, PT Yang, YZ AF Kinglun Mak, Kingston Chen, Miao-Hsueh Day, Timothy F. Chuang, Pao-Tien Yang, Yingzi TI Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation SO DEVELOPMENT LA English DT Article DE Wnt; beta-catenin; Ihh; patched; cartilage; endochondral bone; joint; chondrocyte hypertrophy; osteoblast differentiation ID CHONDROCYTE DIFFERENTIATION; INDIAN-HEDGEHOG; GROWTH-PLATE; PTH/PTHRP RECEPTOR; CARTILAGE; PROLIFERATION; PROTEIN; OSTEOBLAST; PATHWAYS; SKELETON AB Both the Wnt/beta-catenin and Ihh signaling pathways play essential roles in crucial aspects of endochondral ossification: osteoblast differentiation, chondrocyte proliferation and hypertrophy. To understand the genetic interaction between these two signaling pathways, we have inactivated the beta-catenin gene and upregulated Ihh signaling simultaneously in the same cells during endochondral skeletal development using beta-catenin and patched 1 floxed alleles. We uncovered previously unexpected roles of Ihh signaling in synovial joint formation and the essential function of Wnt/beta-catenin signaling in regulating chondrocyte survival. More importantly, we found that Wnt and Ihh signaling interact with each other in distinct ways to control osteoblast differentiation, chondrocyte proliferation, hypertrophy, survival and synovial joint formation in the developing endochondral bone. beta-catenin is required downstream of Ihh signaling and osterix expression for osteoblast differentiation. But in chondrocyte survival, beta-catenin is required upstream of Ihh signaling to inhibit chondrocyte apoptosis. In addition, Ihh signaling can inhibit chondrocyte hypertrophy and synovial joint formation independently of beta-catenin. However, there is a strong synergistic interaction between Wnt/beta-catenin and Ihh signaling in regulating synovial joint formation. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Chuang, PT (reprint author), Natl Human Genome Res Inst, Genet Dis Res Branch, Bethesda, MD 20892 USA. EM pao-tien.chuang@ucsf.edu; yingzi@mail.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL66600, HL67822] NR 53 TC 102 Z9 110 U1 0 U2 14 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 SEP 15 PY 2006 VL 133 IS 18 BP 3695 EP 3707 DI 10.1242/dev.02546 PG 13 WC Developmental Biology SC Developmental Biology GA 077RC UT WOS:000240046500020 PM 16936073 ER PT J AU Dierker, LC Canino, G Merikangas, KR AF Dierker, Lisa C. Canino, Glorisa Merikangas, Kathleen R. TI Association between parental and individual psychiatric/substance use disorders and smoking stages among Puerto Rican adolescents SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE smoking; psychiatric disorders; nicotine dependence; migrant family study; Puerto Rico ID INTERNATIONAL DIAGNOSTIC INTERVIEW; TEST-RETEST RELIABILITY; SUBSTANCE USE DISORDERS; CIGARETTE-SMOKING; HIGH-RISK; CRITERION VALIDITY; DRUG-USE; CHILDREN; SCHEDULE; PSYCHOPATHOLOGY AB Objective: To examine the associations between parental and individual psychiatric disorders and smoking stages among Puerto Rican youth from migrant and non-migrant families. Method: Analyses were conducted drawing on data collected as part of a migrant family study examining youth at high and low risk for substance use disorders based on the presence or absence of a parental history of substance abuse or dependence. Parents and their offspring were recruited in San Juan, Puerto Rico (n=450) and New Haven, CT, USA (n=350). Results: Experimental smoking among adolescent offspring was associated with parent proband disorders. In contrast, regular smoking behavior, defined as at least weekly smoking for a month or more, and DSM-IV nicotine dependence were more strongly associated with the adolescents' own psychiatric disorders. With the exception of anxiety disorders, significant bivariate associations were shown between each psychiatric/substance use disorder and nicotine dependence. Once comorbidity was statistically controlled, only attention deficit hyperactivity disorder (ADHD), and alcohol and drug use disorders were significantly associated with nicotine dependence. After controlling for adolescents' psychiatric comorbidity, there was an association between parental disorders and both experimental and regular smoking in their adolescent offspring. Conclusions: By combining family and migrant research strategies within a single study, the present investigation was able to simultaneously examine familial, individual and sociocultural factors that may play a role in development and/or persistence of smoking behavior among Puerto Rican adolescents. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. Univ Puerto Rico, Behav Sci Res Inst, San Juan, PR 00936 USA. NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. RP Dierker, LC (reprint author), Wesleyan Univ, Dept Psychol, 207 High St, Middletown, CT 06459 USA. EM ldierker@wesleyan.edu FU NIDA NIH HHS [R01 DA09055, K01 DA15454] NR 55 TC 11 Z9 11 U1 11 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 15 PY 2006 VL 84 IS 2 BP 144 EP 153 DI 10.1016/j.drugalcdep.2006.01.008 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 080EW UT WOS:000240231700002 PM 16481127 ER PT J AU Levrand, S Vannay-Bouchiche, C Pesse, B Pacher, P Feihl, F Waeber, B Liaudet, L AF Levrand, Sandra Vannay-Bouchiche, Christine Pesse, Benoit Pacher, Pal Feihl, Francois Waeber, Bemard Liaudet, Lucas TI Peroxynitrite is a major trigger of cardiomyocyte apoptosis in vitro and in vivo SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE peroxynitrite; apoptosis; necrosis; poly(ADP-ribose) polymerase; caspase; myocardium; cardiomyocyte ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE SYNTHASE; HEART-FAILURE; POLY(ADP-RIBOSE) POLYMERASE; CELL-DEATH; DECOMPOSITION CATALYST; SUPEROXIDE-DISMUTASE; NITROSATIVE STRESS; TYROSINE NITRATION; MYOCARDIAL INJURY AB Recent evidence indicates that peroxynitrite represents a major cytotoxic effector in heart diseases, but its mechanisms of action are still not known exactly. Notably, the ability of peroxynitrite to trigger cardiomyocyte apoptosis, a crucial mode of cell death in many cardiac conditions, remains poorly defined. We evaluated apoptotic and necrotic cell death in cultured H9C2 cardiomyocytes, following a brief (20 min) exposure to peroxynitrite (50-500 mu M). Peroxynitrite-dependent myocardial toxicity was then investigated in a rat model of myocardial ischemia-reperfusion (MIR), where the effects of peroxynitrite were blocked by the superoxide dismutase mimetics and peroxynitrite scavenger Mn(III)-tetrakis(4-benzoic acid) porphyrin (MnTBAP). In vitro, peroxynitrite killed cardiomyocytes mostly through apoptosis (DNA fragmentation, apoptotic nuclear alterations, caspase-3 activation, and PARP cleavage), but not necrosis (propidium iodide staining and LDH release). In vivo, MIR triggered myocardial oxidative stress (malondialdehyde generation), nitrotyrosine formation, neutrophil accumulation, and the cleavage of caspase-3 and PARP, indicating ongoing myocardial apoptosis. MnTBAP suppressed these alterations, allowing a considerable reduction of myocardial injury. Thus, peroxynitrite triggers apoptosis in cardiomyocytes in vitro and in the myocardium in vivo, through a pathway involving caspase-3 activation and the cleavage of PARR These results provide important novel information on the mechanisms of myocardial toxicity of peroxynitrite. (c) 2006 Published by Elsevier Inc. C1 Univ Lausanne Hosp, Dept Intens Care Med, CH-1011 Lausanne, Switzerland. Univ Lausanne Hosp, Div Clin Pathophysiol, CH-1011 Lausanne, Switzerland. NIAAA, NIH, Rockville, MD 20852 USA. RP Liaudet, L (reprint author), Univ Lausanne Hosp, Dept Intens Care Med, BH 10-982, CH-1011 Lausanne, Switzerland. EM Lucas.Liaudet@chuv.ch RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02] NR 54 TC 84 Z9 92 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 15 PY 2006 VL 41 IS 6 BP 886 EP 895 DI 10.1016/j.freeradbiomed.2006.04.034 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 081MQ UT WOS:000240322100007 PM 16934671 ER PT J AU Ghiorzo, P Gargiulo, S Pastorino, L Nasti, S Cusano, R Bruno, W Gliori, S Sertoli, MR Burroni, A Savarino, V Gensini, F Sestini, R Queirolo, P Goldstein, AM Scarra, GB AF Ghiorzo, Paola Gargiulo, Sara Pastorino, Lorenza Nasti, Sabina Cusano, Roberto Bruno, William Gliori, Sara Sertoli, Mario R. Burroni, Anna Savarino, Vincenzo Gensini, Francesca Sestini, Roberta Queirolo, Paola Goldstein, Alisa M. Scarra, Giovanna Bianchi TI Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma SO HUMAN MOLECULAR GENETICS LA English DT Article ID PRONE FAMILIES; MALIGNANT-MELANOMA; HAPLOTYPE ANALYSIS; PHENOTYPE ANALYSIS; INTRONIC MUTATION; GENE; DELETION; LOCUS; P16(INK4A); RISK AB Mutations in the CDKN2A gene underlie melanoma susceptibility in as many as 50% of melanoma kindreds in selected populations, and several CDKN2A founder mutations have been described. Inherited mutations in CDKN2A have been found to be associated with other, non-melanoma cancers including pancreatic cancer (PC) and neural system tumors (NST). Here we report a novel germline mutation in exon 1 of the CDKN2A gene, E27X, which we first detected in melanoma patients living in or originally from a small geographic area bordering Liguria in north-western Italy. A subset of melanoma kindreds positive for this mutation displayed PC and neuroblastoma. E27X generates a premature stop codon, leading to dramatically reduced protein levels of p16 and leaving p14ARF unaltered. As PC and NSTs have been postulated to be preferentially associated with CDKN2A mutations located in exon 2 and/or affecting p14ARF alone, the position of E27X in exon 1 alpha provides interesting insights towards clarifying the mechanisms by which the CDKN2A/ARF locus is involved in cancer predisposition. C1 Univ Genoa, Dept Oncol Biol & Genet, Med Genet Serv, I-16129 Genoa, Italy. Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. Natl Canc Inst, Genoa, Italy. San Martino Hosp, Dermatol Unit, Genoa, Italy. Univ Florence, Dept Clin Pathophysiol, Med Genet Serv, Florence, Italy. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Ghiorzo, P (reprint author), Univ Genoa, Dept Oncol Biol & Genet, Med Genet Serv, V Benedetto 15,6, I-16129 Genoa, Italy. EM paola.ghiorzo@unige.it RI Bianchi Scarra, Giovanna/G-8933-2014; Bruno, William/N-7477-2013; Queirolo, Paola/K-6778-2016; OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; Bruno, William/0000-0002-0337-0168; Queirolo, Paola/0000-0002-9917-6633; GENSINI, FRANCESCA/0000-0001-6669-420X; SESTINI, ROBERTA/0000-0002-7500-9988 FU Intramural NIH HHS; NCI NIH HHS [1 R01 CA83115-01A2] NR 52 TC 25 Z9 25 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 SEP 15 PY 2006 VL 15 IS 18 BP 2682 EP 2689 DI 10.1093/hmg/ddl199 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 085FZ UT WOS:000240590400003 PM 16893909 ER PT J AU Lipska, BK Mitkus, S Caruso, M Hyde, TM Chen, JS Vakkalanka, R Straub, RE Weinberger, DR Kleinman, JE AF Lipska, Barbara K. Mitkus, Shruti Caruso, Mark Hyde, Thomas M. Chen, Jingshan Vakkalanka, Radhakrishna Straub, Richard E. Weinberger, Daniel R. Kleinman, Joel E. TI RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity SO HUMAN MOLECULAR GENETICS LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; SUSCEPTIBILITY GENE; DOPAMINE-RECEPTORS; HUMAN BRAIN; PREFRONTAL CORTEX; RAT STRIATUM; SCHIZOPHRENIA; PROTEIN; POLYMORPHISMS; AMPHETAMINE AB Linkage, association and postmortem studies have implicated regulator of G-protein signaling 4 (RGS4), which negatively modulates signal transduction at G-protein-coupled receptors, as a candidate schizophrenia susceptibility gene. We compared RGS4 mRNA expression in the dorsolateral prefrontal cortex (DLPFC), between normal controls and patients with schizophrenia in two independent cohorts (> 100 subjects each) (the CBDB/NIMH Collection and the Stanley Array Collection), and in the hippocampus in the CBDB/NIMH Collection. We also examined the effects of the four previously identified putative RGS4 risk SNPs (rs10917670, rs951436, rs951439, rs2661319) on RGS4 expression levels in these cohorts. As dopamine signaling is linked to RGS4 expression and there is evidence for statistical epistasis between COMT Val158Met polymorphism and RGS4 alleles, we also examined relationships between the COMT Val158Met genotype and RGS4 expression in the DLPFC. We did not detect a difference in RGS4 expression levels between schizophrenic patients (or bipolar disorder patients in the Stanley Collection) and controls and found no significant association between any of the RGS4 risk SNPs and RGS4 expression. However, COMT Val158Met genotype was associated with prefrontal and hippocampal RGS4 mRNA expression in an allele dose-dependent manner, with carriers of the COMT Val allele showing significantly lower expression than heterozygous individuals or subjects homozygous for the Met allele. Consistent with these genotype effects, RGS4 mRNA was inversely correlated with the COMT enzyme activity in the DLPFC. These data suggest that RGS4 mRNA expression is associated with cortical dopamine signaling and illustrate the importance of genetic and/or environmental background in gene expression studies in schizophrenia. C1 NIMH, CBDB, Genes Cognit & Psycosis Program, NIH,DHHS, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), NIMH, CBDB, Genes Cognit & Psycosis Program, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 4N306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov FU Intramural NIH HHS NR 41 TC 36 Z9 39 U1 1 U2 2 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 SEP 15 PY 2006 VL 15 IS 18 BP 2804 EP 2812 DI 10.1093/hmg/ddl222 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 085FZ UT WOS:000240590400015 PM 16905560 ER PT J AU Cardis, E Krewski, D Boniol, M Drozdovitch, V Darby, SC Gilbert, ES Akiba, S Benichou, J Ferlay, J Gandini, S Hill, C Howe, G Kesminiene, A Moser, M Sanchez, M Storm, H Voisin, L Boyle, P AF Cardis, Elisabeth Krewski, Daniel Boniol, Mathieu Drozdovitch, Vladimir Darby, Sarah C. Gilbert, Ethel S. Akiba, Suminori Benichou, Jacques Ferlay, Jacques Gandini, Sara Hill, Catherine Howe, Geoffrey Kesminiene, Ausrele Moser, Mirjana Sanchez, Marie Storm, Hans Voisin, Laurent Boyle, Peter TI Estimates of the cancer burden in Europe from radioactive fallout from the Chernobyl accident SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ionizing radiation; Chernobyl accident; radiation risk; time trends; cancer incidence; cancer mortality ID THYROID-CANCER; CHILDHOOD LEUKEMIA; POOLED ANALYSIS; TIME TRENDS; MORTALITY; RISK; CONTAMINATION; RADIATION; EXPOSURE; BYELARUS AB The Chernobyl accident, which occurred April 26, 1986, resulted in a large release of radionuclides, which were deposited over a very wide area, particularly in Europe. Although an increased risk of thyroid cancer in exposed children has been clearly demonstrated in the most contaminated regions, the impact of the accident on the risk of other cancers as well as elsewhere in Europe is less clear. The objective of the present study was to evaluate the human cancer burden in Europe as a whole from radioactive fallout from the accident. Aver age country- and region-specific whole-body and thyroid doses from Chernobyl were estimated using new dosimetric models and radiological data. Numbers of cancer cases and deaths possibly attributable to radiation from Chernobyl were estimated, applying state-of-the-art risk models derived from studies of other irradiated populations. Simultaneously, trends in cancer incidence and mortality were examined over time and by dose level. The risk projections suggest that by now Chernobyl may have caused about 1,000 cases of thyroid cancer and 4,000 cases of other cancers in Europe, representing about 0.01% of all incident cancers since the accident. Models predict that by 2065 about 16,000 (95% UI 3,400-72,000) cases of thyroid cancer and 25,000 (95% UI 11,000-59,000) cases of other cancers may be expected due to radiation from the accident, whereas several hundred million cancer cases are expected from other causes. Although these estimates are subject to considerable uncertainty, they provide an indication of the order of magnitude of the possible impact of the Chernobyl accident. It is unlikely that the cancer burden from the largest radiological accident to date could be detected by monitoring national cancer statistics. Indeed, results of analyses of time trends in cancer incidence and mortality in Europe do not, at present, indicate any increase in cancer rates-other than of thyroid cancer in the most contaminated regions-that can be clearly attributed to radiation from the Chernobyl accident. (c) 2006 Wiley-Liss, Inc. C1 Int Agcy Res Canc, Radiat Grp, F-69372 Lyon 08, France. Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Inst Populat Hlth, Ottawa, ON, Canada. Univ Oxford, Clin Trial Serv Unit, Oxford, England. NCI, Div Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima 890, Japan. Univ Rouen, Sch Med, Biostat Unit, Rouen, France. Rouen Univ Hosp, Rouen, France. European Inst Oncol, Milan, Italy. Inst Gustave Roussy, Villejuif, France. Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. Fed Off Publ Hlth, Bern, Switzerland. Danish Canc Soc, Copenhagen, Denmark. RP Cardis, E (reprint author), Int Agcy Res Canc, Radiat Grp, 150,Cours Albert Thomas, F-69372 Lyon 08, France. EM cardis@iarc.fr RI Boniol, Mathieu/F-9623-2011; Boyle, Peter/A-4380-2014; Cardis, Elisabeth/C-3904-2017; OI Boniol, Mathieu/0000-0003-1052-5604; Boyle, Peter/0000-0001-6251-0610; Hill, Catherine/0000-0002-0004-0905; Storm, Hans/0000-0001-7223-8198; Gandini, Sara/0000-0002-1348-4548 NR 53 TC 61 Z9 63 U1 3 U2 17 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 SEP 15 PY 2006 VL 119 IS 6 BP 1224 EP 1235 DI 10.1002/ijc.22037 PG 12 WC Oncology SC Oncology GA 075ID UT WOS:000239877200002 PM 16628547 ER PT J AU Gao, GF Roth, MJ Wei, WQ Abnet, CC Chen, F Lu, N Zhao, FH Li, XQ Wang, GQ Taylor, PR Pan, QJ Chen, W Dawsey, SM Qiao, YL AF Gao, Guo-Fu Roth, Mark J. Wei, Wen-Qiang Abnet, Christian C. Chen, Feng Lu, Ning Zhao, Fang-Hui Li, Xin-Qing Wang, Guo-Qing Taylor, Philip R. Pan, Qin-Jing Chen, Wen Dawsey, Sanford M. Qiao, You-Lin TI No association between HPV infection and the neoplastic progression of esophageal squamous cell carcinoma: Result from a cross-sectional study in a high-risk region of China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE esophageal squamous cell carcinoma; HPV; Hybrid Capture II ID HIGH-INCIDENCE AREA; HUMAN-PAPILLOMAVIRUS INVOLVEMENT; POLYMERASE CHAIN-REACTION; GASTRIC CANCERS; FAMILIAL AGGREGATION; INCIDENT ESOPHAGEAL; PRECANCER LESIONS; SHANXI PROVINCE; DNA; LINXIAN AB Esophageal cancer is a leading cause of cancer death, especially in developing countries. In high-risk regions, squamous cell carcinoma is the most common type of esophageal cancer, and its etiology remains poorly understood. The purpose of this study was to evaluate the association between human papillomavirus (HPV) infection and esophageal squamous cell carcinoma (ESCC) and related precursor lesions in a high-risk area of China. We conducted a cross-sectional study among adult inhabitants of Linxian, China. All subjects were interviewed about potential risk factors, had the length of their esophagus sampled by a balloon cytology examination and underwent endoscopy with mucosal iodine staining and biopsy of all unstained lesions. A multivalent HPV hybridization probe, Digene Hybrid Capture 11 (Gaithersburg, MD), which recognizes high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV infection status of the cytologic specimens, and the endoscopic biopsies were used to classify each subject's esophageal disease. 740 subjects completed the cytologic and endoscopic exams, and 702 had adequate cytologic and biopsy specimens. Using a cutpoint of >= 3.0 pg/ml of HPV DNA to define a positive test, HPV positivity was identified in 13% (61/475) of subjects without squamous dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16% (6/38) with severe dysplasia and zero (0/4) with invasive ESCC. Changing the cutpoint defining a positive test did not change the association of HPV infection and dysplasia grade. In this high-risk population, infection of esophageal cells with high-risk HPV types occurs in 13% of asymptomatic adults with no evidence of squamous dysplasia and a similar proportion of individuals with mild, moderate or severe dysplasia. This suggests that HPV infection is not a major risk factor for ESCC in this high-risk Chinese population. Further studies are warranted to determine if infection with this agent is associated with neoplastic progression in a subset of cases. (c) 2006 Wiley-Liss, Inc. C1 Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100021, Peoples R China. NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Dawsey, SM (reprint author), Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, 17 S Panjiayuan Lane, Beijing 100021, Peoples R China. EM dawseys@mail.nih.gov; qiaoy@public.bta.net.cn RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS; NCI NIH HHS [N01-SC-91019] NR 48 TC 45 Z9 51 U1 0 U2 6 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 SEP 15 PY 2006 VL 119 IS 6 BP 1354 EP 1359 DI 10.1002/ijc.21980 PG 6 WC Oncology SC Oncology GA 075ID UT WOS:000239877200019 PM 16615110 ER PT J AU Bonner, MR Bennett, WP Xiong, WY Lan, Q Brownson, RC Harris, CC Field, RW Lubin, JH Alavanja, MCR AF Bonner, Matthew R. Bennett, William P. Xiong, Wenying Lan, Qing Brownson, Ross C. Harris, Curtis C. Field, R. William Lubin, Jay H. Alavanja, Michael C. R. TI Radon, secondhand smoke, glutathione-S-transferase M1 and lung cancer among women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE radon; secondhand smoke; glutathione-S-transferase; lung cancer; epidemiology ID ENVIRONMENTAL TOBACCO-SMOKE; PARAFFIN-EMBEDDED TISSUES; RESIDENTIAL RADON; GENETIC POLYMORPHISMS; NONSMOKING WOMEN; ALPHA-PARTICLES; INDOOR RADON; RISK; EXPOSURE; GSTM1 AB Tobacco smoke and ionizing radiation induce oxidative stress by transmitting or generating reactive oxygen species (ROS). We hypothesized that glutathione-S-transferase M1 (GSTM1) null homozygotes would have decreased ability to neutralize ROS that might increase their susceptibility to lung cancer. A case-only design was used with lung cancer cases pooled from 3 previously completed case-control studies using archival tissue samples from 270 lung cancer cases to genotype GSTM1. Radon concentrations were measured with long-term a-track radon detectors. Secondhand smoke (SHS) was measured with questionnaires and interviews. Unconditional logistic regression was used to calculate the interaction odds ratios (OR) and 95% confidence intervals (95% Cl). Radon concentrations > 121 Bq m(-3) were associated with a > 3-fold interaction OR (OR = 3.41; 95% CI = 1.10, 10.61) for GSTM1 null homozygotes compared to GSTM1 carriers; the linear trend was significant (p trend = 0.03). The SHS and GSTM1 interaction OR was also elevated (OR = 2.28; 95% CI = 1.15-4.51) among never-smokers. This may be the first study to provide evidence of a GSTM1 and radon interaction in risk of lung cancer. Additionally, these findings support the hypothesis that radon and SHS promote neoplasia through shared elements of a common pathway. (c) 2006 Wiley-Liss, Inc. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, US Dept HHS, Rockville, MD USA. City Hope Natl Med Ctr, Beckman Res Inst, Div Mol Med, Duarte, CA 91010 USA. St Louis Univ, Sch Publ Hlth, Dept Community Hlth, St Louis, MO 63103 USA. NCI, Human Carcinogenesis Lab, Div Canc Biol, NIH,US Dept HHS, Rockville, MD USA. Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, Iowa City, IA 52242 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD USA. RP Bonner, MR (reprint author), SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14214 USA. EM mrbonner@buffalo.edu NR 39 TC 17 Z9 20 U1 1 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 SEP 15 PY 2006 VL 119 IS 6 BP 1462 EP 1467 DI 10.1002/ijc.22002 PG 6 WC Oncology SC Oncology GA 075ID UT WOS:000239877200034 PM 16642467 ER PT J AU Abnet, CC Fan, JH Kamangar, F Sun, XD Taylor, PR Ren, JS Mark, SD Zhao, P Fraumeni, JF Qiao, YL Dawsey, SM AF Abnet, Christian C. Fan, Jin-Hu Kamangar, Farin Sun, Xiu-Di Taylor, Philip R. Ren, Jian-Song Mark, Steven D. Zhao, Ping Fraumeni, Joseph F., Jr. Qiao, You-Lin Dawsey, Sanford M. TI Self-reported goiter is associated with a significantly increased risk of gastric noncardia adenocarcinoma in a large population-based Chinese cohort SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE gastric cancer; esophageal cancer; iodine deficiency; goiter; China ID HELICOBACTER-PYLORI; CANCER; LINXIAN AB Iodine is concentrated by the gastric mucosa, where it may act as an antioxidant. Therefore, iodine deficiency, and its sequelae goiter, may be associated with an increased risk of gastric cancer. We examined the association between self-reported goiter and upper gastrointestinal cancer in a Chinese cohort of 29,584 adults. Using multivariate adjusted Cox models, we found goiter associated with a significantly increased risk of gastric noncardia adenocarcinoma, HR (95% CI) 2.04 (1.01, 4.11) and nonsignificantly with gastric cardia adenocarcinoma, HR (95% CI) 1.45 (0.91, 2.30). We also found a borderline, insignificant increased risk of esophageal squamous cell carcinoma, HR (95% CI) 1.37 (0.97,1.94). Our findings are consistent with the hypothesis that iodine deficiency is associated with an increased risk of gastric cancer. Published 2006 Wiley-Liss, Inc. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP Abnet, CC (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 305,MSC 7232, Bethesda, MD 20892 USA. EM abnetc@mail.nih.gov; qiaoy@public.bta.net.cn RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS NR 12 TC 10 Z9 12 U1 0 U2 1 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 SEP 15 PY 2006 VL 119 IS 6 BP 1508 EP 1510 DI 10.1002/ijc.21993 PG 3 WC Oncology SC Oncology GA 075ID UT WOS:000239877200042 PM 16642482 ER PT J AU Thangaraju, M Ananth, S Martin, PM Roon, P Smith, SB Sterneck, E Prasad, PD Ganapathy, V AF Thangaraju, Muthusamy Ananth, Sudha Martin, Pamela M. Roon, Penny Smith, Sylvia B. Sterneck, Esta Prasad, Puttur D. Ganapathy, Vadivel TI c/ebp delta null mouse as a model for the double knock-out of slc5a8 and slc5a12 in kidney SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-PROTEIN-DELTA; NA+-COUPLED TRANSPORTER; FUNCTIONAL IDENTIFICATION; TUMOR-SUPPRESSOR; MICE LACKING; LACTATE; EXPRESSION; PHYSIOLOGY; FAMILY; ACID AB slc5a8 and slc5a12 represent the high affinity and low affinity Na+/lactate co-transporters, respectively, in the kidney. Here we show that these transporters are expressed in the apical membrane of the proximal tubular cells in mouse kidney, indicating that these transporters are likely to mediate the first step in the renal reabsorption of lactate. Interestingly, the renal expression of both transporters is almost completely ablated in mice homozygous for the deletion of the transcription factor c/ebp delta. This effect is tissue-specific since the expression of the transporters is not affected in non-renal tissues. The functional role of C/EBP delta in the expression of SLC5A8 and SLC5A12 is demonstrable in HEK293 cells in reporter assays using gene-specific promoters. The ablation of the transporters in the kidney is accompanied by a marked increase in urinary excretion of lactate as well as a decrease in blood levels of lactate in c/ebp delta(-/-). These data provide evidence for an obligatory role for slc5a8 and slc5a12 in the renal absorption of lactate. In addition, we show that urinary excretion of urate is significantly elevated in c/ebp delta(-/-) mice even though the expression of URAT1, the transporter responsible for the apical membrane uptake of urate in renal proximal tubule, is not altered. These data provide in vivo evidence for the functional coupling between lactate reabsorption and urate reabsorption in the kidney. Thus, the fortuitous double knock-out of slc5a8 and slc5a12 in kidney in c/ebp delta(-/-) mice reveals the physiologic role of these transporters in the renal handling of lactate and urate. C1 Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Ganapathy, V (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. EM vganapat@mail.mcg.edu NR 20 TC 43 Z9 48 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 2006 VL 281 IS 37 BP 26769 EP 26773 DI 10.1074/jbc.C600189200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082PB UT WOS:000240397700002 PM 16873376 ER PT J AU Wang, XD Bryan, NS MacArthur, PH Rodriguez, J Gladwin, MT Feelisch, M AF Wang, Xunde Bryan, Nathan S. MacArthur, Peter H. Rodriguez, Juan Gladwin, Mark T. Feelisch, Martin TI Measurement of nitric oxide levels in the red cell - Validation of tri-iodide-based chemiluminescence with acid-sulfanilamide pretreatment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S-NITROSOTHIOLS; BLOOD-CELLS; HUMAN PLASMA; IN-VIVO; NO; NITROSOHEMOGLOBIN; HEMOGLOBIN; NITROSOALBUMIN; TISSUES; FLOW AB The tri-iodide-based chemiluminescence assay is the most widely used methodology for the detection of S-nitrosothiols (RSNOs) in biological samples. Because of the low RSNO levels detected in a number of biological compartments using this assay, criticism has been raised that this method underestimates the true values in biological samples. This claim is based on the beliefs that (i) acidified sulfanilamide pretreatment, required to remove nitrite, leads to RSNO degradation and (ii) that there is auto- capture of released NO by heme in the reaction vessel. Because our laboratories have used this assay extensively without ever encountering evidence that corroborated these claims, we sought to experimentally address these issues using several independent techniques. We find that RSNOs of glutathione, cysteine, albumin, and hemoglobin are stable in acidified sulfanilamide as determined by the tri-iodide method, copper/cysteine assay, Griess-Saville assay and spectrophotometric analysis. Quantitatively there was no difference in S-nitroso-hemoglobin (SNOHb) or S-nitroso-albumin (SNOA1b) using the tri-iodide method and a recently described modified assay using a ferricyanide-enhanced reaction mix at biologically relevant NO: heme ratios. Levels of SNOHb detected in human blood ranged from 20-100 nM with no arterial-venous gradient. We further find that 90% of the total NO-related signal in blood is caused by erythrocytic nitrite, which may partly be bound to hemoglobin. We conclude that all claims made thus far that the tri-iodide assay underestimates RSNO levels are unsubstantiated and that this assay remains the "gold standard" for sensitive and specific measurement of RSNOs in biological matrices. C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mgladwin@nhlbi.nih.gov; feelisch@bu.edu RI Feelisch, Martin/C-3042-2008 OI Feelisch, Martin/0000-0003-2320-1158 FU Intramural NIH HHS; NCRR NIH HHS [P20 RR16456]; NHLBI NIH HHS [HL 69029] NR 41 TC 55 Z9 55 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 2006 VL 281 IS 37 BP 26994 EP 27002 DI 10.1074/jbc.M603953200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082PB UT WOS:000240397700026 PM 16845122 ER PT J AU Asano, S Park, JE Yu, LR Zhou, M Sakchaisri, K Park, CJ Kang, YH Thorner, J Veenstra, TD Lee, KS AF Asano, Satoshi Park, Jung-Eun Yu, Li-Rong Zhou, Ming Sakchaisri, Krisada Park, Chong J. Kang, Young H. Thorner, Jeremy Veenstra, Timothy D. Lee, Kyung S. TI Direct phosphorylation and activation of a Nim1-related kinase Gin4 by Elm1 in budding yeast SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREVISIAE CELL-CYCLE; MITOTIC SIGNALING NETWORK; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; GENE-PRODUCT; SEPTIN FUNCTION; EVENTS; MORPHOGENESIS; LOCALIZATION; ORGANIZATION AB In budding yeast, Gin4, a Nim1-related kinase, plays an important role in proper organization of the septin ring at the mother-bud neck, a filamentous structure that is critical for diverse cellular processes including mitotic entry and cytokinesis. How Gin4 kinase activity is regulated is not known. Here we showed that a neck-associated Ser/Thr kinase Elm1, which is important for septin assembly, is critical for proper modification of Gin4 and its physiological substrate Shs1. In vitro studies with purified recombinant proteins demonstrated that Elm1 directly phosphorylates and activates Gin4, which in turn phosphorylates Shs1. Consistent with these observations, acute inhibition of Elm1 activity abolished mitotic Gin4 phosphorylation and Gin4-dependent Shs1 modification in vivo. In addition, a gin4 mutant lacking the Elm1-dependent phosphorylation sites exhibited an impaired localization to the bud-neck and, as a result, induced a significant growth defect with an elongated bud morphology. Thus, Elm1 regulates the septin assembly-dependent cellular events by directly phosphorylating and activating the Gin4-dependent pathway(s). C1 NCI, NIH, Lab Metab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Lab Proteom & Analyt Technol, NIH, Ft Detrick, MD 21702 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Lee, KS (reprint author), NCI, NIH, Lab Metab, Canc Res Ctr, 9000 Rockville Pike,Bldg 37,Rm 3118, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM21841] NR 35 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 2006 VL 281 IS 37 BP 27090 EP 27098 DI 10.1074/jbc.M601483200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082PB UT WOS:000240397700036 PM 16861226 ER PT J AU Ma, K Forbes, JG Gutierrez-Cruz, G Wang, K AF Ma, Kan Forbes, Jeffrey G. Gutierrez-Cruz, Gustavo Wang, Kuan TI Titin as a giant scaffold for integrating stress and Src homology domain 3-mediated signaling pathways - The clustering of novel overlap ligand motifs in the elastic PEVK segment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE TITIN; POLYPROLINE-II HELIX; SH3 DOMAIN; BINDING-SPECIFICITY; PEPTIDE RECOGNITION; MOLECULAR-DYNAMICS; AFFINITY PROFILES; KINASE DOMAIN; TERMINAL SH3; IN-VITRO AB The richness of proline sequences in titins qualifies these giant proteins as the largest source of intrinsically disordered structures in nature. An extensive search and analysis for Src homology domain 3 (SH3) ligand motifs revealed a myriad of broadly distributed SH3 ligand motifs, with the highest density in the PEVK segments of human titin. Besides the canonical class I and II motifs with opposite orientations, novel overlapping motifs consisting of one or more of each canonical motif are abundant. Experimentally, the binding affinity and critical residues of these putative titin-based SH3 ligands toward nebulin SH3 and other SH3-containing proteins in muscle and non-muscle cell extracts were validated with peptide array technology and by the sarcomere distribution of SH3-containing proteins. A 28-mer overlapping motif-containing PEVK module binds to nebulin SH3 in and around the canonical cleft, especially to the acidic residues in the loops, as revealed by NMR titration. Molecular dynamics and molecular docking studies indicated that the overlapping motif can bind in opposite orientations with comparable energy and contact areas and predicts correctly orientation-specific contacts in NMR data. We propose that the overlap ligand motifs are a new class of ligands with innate ability to dictate SH3 domain orientation and to facilitate the rate, strength, and stereospecificity of receptor interactions. Proline-rich sequences of titins are candidates as major hubs of SH3- dependent signaling pathways. The interplay of elasticity and dense clustering of mixed receptor orientations in titin PEVK segment have important implications for the mechanical sensing, force sensitivity, and inter-adapter interactions in signaling pathways. C1 NIAMS, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAMS, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, Bldg 50,Rm 1140, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov FU Intramural NIH HHS NR 61 TC 23 Z9 23 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 2006 VL 281 IS 37 BP 27539 EP 27556 DI 10.1074/jbc.M604525200 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082PB UT WOS:000240397700080 PM 16766517 ER PT J AU Schieke, SM Phillips, D Mccoy, JP Aponte, AM Shen, RF Balaban, RS Finkel, T AF Schieke, Stefan M. Phillips, Darci McCoy, J. Philip, Jr. Aponte, Angel M. Shen, Rong-Fong Balaban, Robert S. Finkel, Toren TI The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYSTEMATIC RNAI SCREEN; LIFE-SPAN; CALORIE RESTRICTION; C-ELEGANS; SACCHAROMYCES-CEREVISIAE; BINDING PARTNER; CELL-GROWTH; TOR; PROTEIN; RAPTOR AB Metabolic rate and the subsequent production of reactive oxygen species are thought to contribute to the rate of aging in a wide range of species. The target of rapamycin (TOR) is a well conserved serine/threonine kinase that regulates cell growth in response to nutrient status. Here we demonstrate that in mammalian cells the mammalian TOR (mTOR) pathway plays a significant role in determining both resting oxygen consumption and oxidative capacity. In particular, we demonstrate that the level of complex formation between mTOR and one of its known protein partners, raptor, correlated with overall mitochondrial activity. Disruption of this complex following treatment with the mTOR pharmacological inhibitor rapamycin lowered mitochondrial membrane potential, oxygen consumption, and ATP synthetic capacity. Subcellular fractionation revealed that mTOR as well as mTOR-raptor complexes can be purified in the mitochondrial fraction. Using two-dimensional difference gel electrophoresis, we further demonstrated that inhibiting mTOR with rapamycin resulted in a dramatic alteration in the mitochondrial phosphoproteome. RNA interference-mediated knockdown of TSC2, p70 S6 kinase (S6K1), raptor, or rictor demonstrates that mTOR regulates mitochondrial activity independently of its previously identified cellular targets. Finally we demonstrate that mTOR activity may play an important role in determining the relative balance between mitochondrial and non-mitochondrial sources of ATP generation. These results may provide insight into recent observations linking the TOR pathway to life span regulation of lower organisms. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10CR-5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 33 TC 319 Z9 326 U1 4 U2 28 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 2006 VL 281 IS 37 BP 27643 EP 27652 DI 10.1074/jbc.M603536200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082PB UT WOS:000240397700089 PM 16847060 ER PT J AU Young, ARJ Chan, EYW Hu, XW Koch, R Crawshaw, SG High, S Hailey, DW Lippincott-Schwartz, J Tooze, SA AF Young, Andrew R. J. Chan, Edmond Y. W. Hu, Xiao Wen Koch, Robert Crawshaw, Samuel G. High, Stephen Hailey, Dale W. Lippincott-Schwartz, Jennifer Tooze, Sharon A. TI Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes SO JOURNAL OF CELL SCIENCE LA English DT Article DE autophagy; Golgi; Rab proteins; intracellular transport; transmembrane protein ID PRE-AUTOPHAGOSOMAL STRUCTURE; TRANS-GOLGI NETWORK; NITRIC-OXIDE SYNTHASE; GTP-BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; RAT HEPATOCYTES; VESICLE FORMATION; MEMBRANE-PROTEIN; 3-KINASE COMPLEX; PATHWAY AB Autophagy, fundamentally a lysosomal degradation pathway, functions in cells during normal growth and certain pathological conditions, including starvation, to maintain homeostasis. Autophagosomes are formed through a mechanism that is not well understood, despite the identification of many genes required for autophagy. We have studied the mammalian homologue of Atg9p, a multi-spanning transmembrane protein essential in yeast for autophagy, to gain a better understanding of the function of this ubiquitious protein. We show that both the N- and C-termini of mammalian Atg9 (mAtg9) are cytosolic, and predict that mAtg9 spans the membrane six times. We find that mAtg9 is located in the trans-Golgi network and late endosomes and colocalizes with TGN46, the cation-independent mannose-6-phosphate receptor, Rab7 and Rab9. Amino acid starvation or rapamycin treatment, which upregulates autophagy, causes a redistribution of mAtg9 from the TGN to peripheral, endosomal membranes, which are positive for the autophagosomal marker GFP-LC3. siRNA-mediated depletion of the putative mammalian homologue of Atg1p, ULK1, inhibits this starvation-induced redistribution. The redistribution of mAtg9 also requires PI 3-kinase activity, and is reversed after restoration of amino acids. We speculate that starvation-induced autophagy, which requires mAtg9, may rely on an alteration of the steady-state trafficking of mAtg9, in a Atg1-dependent manner. C1 Canc Res UK, London Res Inst, London WC2A 3PX, England. Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. NICHD, CBMB, NIH, Bethesda, MD 20892 USA. RP Tooze, SA (reprint author), Canc Res UK, London Res Inst, 44 Lincolns Inn Fields, London WC2A 3PX, England. EM Sharon.tooze@cancer.org.uk OI High, Stephen/0000-0002-4532-8152 NR 55 TC 312 Z9 328 U1 2 U2 27 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 SEP 15 PY 2006 VL 119 IS 18 BP 3888 EP 3900 DI 10.1242/jcs.03172 PG 13 WC Cell Biology SC Cell Biology GA 082KS UT WOS:000240386300017 PM 16940348 ER PT J AU Cao, XL Xu, YT Zhang, GM Xie, SM Dong, YM Ito, Y AF Cao, Xue-Li Xu, Ya-Tao Zhang, Guang-Ming Xie, Sheng-Meng Dong, Ying-Mao Ito, Yoichiro TI Purification of coenzyme Q(10) from fermentation extract: High-speed counter-current chromatography versus silica gel column chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE high-speed counter-current chromatography (HSCCC); coenzyme Q(10); purification ID PARKINSONS-DISEASE; BACTERIA AB High-speed counter-current chromatography (HSCCC) is applied to the purification of coenzyme Q(10) (CoQ(10)) for the first time. CoQ(10) was obtained from a fermentation broth extract. Anon-aqueous two-phase solvent system composed of heptane-acetonitrile-dichloromethane (12:7:3.5, v/v/v) was selected by analytical HSCCC and used for purification of CoQ(10) from 500 mg of the crude extract. The separation yielded 130 mg of CoQ(10) at an HPLC purity of over 99%. The overall results of the present studies show the advantages of HSCCC over an alternative of silica gel chromatography followed by recrystallization. These advantages extend to higher purity (97.8% versus 93.3%), recovery (88% versus 74.3%) and yield (26.4% versus 23.4%). An effort to avoid the toxic, expensive solvent CH2Cl2 was unsuccessful, but at least its percentage is low in the solvent system. (c) 2006 Elsevier B.V. All rights reserved. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. Beijing Technol & Business Univ, Sch Chem & Environm Engn, Beijing Key Lab Plant Resource Res & Dev, Beijing 100037, Peoples R China. Chinese Acad Space Technol, Space Biol Lab, Beijing 100081, Peoples R China. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 20 TC 17 Z9 19 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 15 PY 2006 VL 1127 IS 1-2 BP 92 EP 96 DI 10.1016/j.chroma.2006.05.083 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 082TW UT WOS:000240411100013 PM 16797569 ER PT J AU Bafica, A Santiago, HC Goldszmid, R Ropert, C Gazzinelli, RT Sher, A AF Bafica, Andre Santiago, Helton Costa Goldszmid, Romina Ropert, Catherine Gazzinelli, Ricardo T. Sher, Alan TI Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-2; NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE; PROINFLAMMATORY CYTOKINES; PROTOZOAN PARASITES; HOST-RESISTANCE; RESPONSES; MICE; MACROPHAGES; PATHOGENESIS AB Activation of innate immune cells by Trypanosoma cruzi-derived molecules such as GPI anchors and DNA induces proinflammatory cytokine production and host defense mechanisms. In this study, we demonstrate that DNA from T. cruzi stimulates cytokine production by APCs in a TLR9-dependent manner and synergizes with parasite-derived GPI anchor, a TLR2 agonist, in the induction of cytokines by macrophages. Compared with wild-type animals, T. cruzi-infected Tlr9(-/-) mice displayed elevated parasitemia and decreased survival. Strikingly, infected Tlr2(-/-) Tlr9(-/-) mice developed a parasitemia equivalent to animals lacking MyD88, an essential signaling molecule for most TLR, but did not show the acute mortality displayed by MyD88(-/-) animals. The enhanced susceptibility of Tlr9(-/-) and Tlr2(-/-) Tlr9(-/-) mice was associated with decreased in vivo IL-12/IFN-gamma responses. Our results reveal that TLR2 and TLR9 cooperate in the control of parasite replication and that TLR9 has a primary role in the MyD88-dependent induction of IL-12/IFN-gamma synthesis during infection with T. cruzi. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. Univ Fed Minas Gerais, Dept Bioquim & Imunol, ICB, Belo Horizonte, MG, Brazil. Fiocruz MS, CPqRR, Lb Imunopatol, Belo Horizonte, MG, Brazil. RP Bafica, A (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, 50 NIH S Dr Room 6146, Bethesda, MD 20892 USA. EM abafica@niaid.nih.gov; ritoga@cpqrr.fiocruz.br RI Santiago, Helton/F-8704-2012; Ropert, Catherine/G-2463-2012 OI Santiago, Helton/0000-0002-5695-8256; NR 21 TC 169 Z9 173 U1 2 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 SEP 15 PY 2006 VL 177 IS 6 BP 3515 EP 3519 PG 5 WC Immunology SC Immunology GA 083RG UT WOS:000240475300002 PM 16951309 ER PT J AU Bertholet, S Goldszmid, R Morrot, A Debrabant, A Afrin, F Collazo-Custodio, C Houde, M Desjardins, M Sher, A Sacks, D AF Bertholet, Sylvie Goldszmid, Romina Morrot, Alexandre Debrabant, Alain Afrin, Farhat Collazo-Custodio, Carmen Houde, Mathieu Desjardins, Michel Sher, Alan Sacks, David TI Leishmania antigens are presented to CD8(+) T cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; DENDRITIC CELLS; CROSS-PRESENTATION; CUTANEOUS LEISHMANIASIS; TOXOPLASMA-GONDII; MYCOBACTERIUM-TUBERCULOSIS; LISTERIA-MONOCYTOGENES; EXOGENOUS ANTIGENS; IMMUNE-RESPONSES; MAJOR INFECTION AB CD8(+) T cells are generated in response to Leishmania major (Lm) or Toxoplasma gondii parasitic infections, indicating that exogenously delivered Ag can be processed for presentation by MHC class I molecules. We show that presentation of Lm nucleotidase (NT)-OVA is TAP independent in vivo and in vitro, and is inhibited by chloroquine, but not by proteasome inhibitors. In contrast, the presentation of T. gondii P30-OVA relies on the TAP/proteasome pathway. Presentation of OVA- or rNT-OVA-coated beads also bypassed TAP requirement above a certain Ag threshold. TAP was also dispensable for the presentation of wild-type Lm Ags to primed CD8(+) T cells in vitro. Finally, in vivo priming of CD8(+) T cells involved in acquired resistance to Lm was not compromised in TAP-deficient mice. Thus, Leishmania Ags, appear to be confined to an intraphagosomal processing pathway that requires higher concentrations of Ags, suggesting that these parasites may have evolved strategies to impair the efficient endoplasmic reticulum-based, TAP-dependent cross-presentation pathway to avoid or delay CD8(+) T cell priming. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Montreal, Dept Pathol & Biol Cellulaire, Montreal, PQ, Canada. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,Ctr Dr MSC 0425, Bethesda, MD 20892 USA. EM dsacks@nih.gov OI Morrot, Alexandre/0000-0001-9432-9701 NR 53 TC 63 Z9 63 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 SEP 15 PY 2006 VL 177 IS 6 BP 3525 EP 3533 PG 9 WC Immunology SC Immunology GA 083RG UT WOS:000240475300004 PM 16951311 ER PT J AU Li, HF Wojciechowski, W Dell'Agnola, C Lopez, NE Espinoza-Delgado, I AF Li, Huifen Wojciechowski, Wojciech Dell'Agnola, Chiara Lopez, Natalia E. Espinoza-Delgado, Igor TI IFN-gamma and T-bet expression in human dendritic cells from normal donors and cancer patients is controlled through mechanisms involving ERK-1/2-dependent and IL-12-independent pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; INTERFERON-GAMMA; CYTOKINE PRODUCTION; PHORBOL ESTERS; SERINE PHOSPHORYLATION; ANTICANCER AGENT; BREAST-CANCER; HUMAN NK; IN-VIVO; BRYOSTATIN-1 AB Dendritic cells (DC) play a major role in priming naive T cells and modulating the immune response. We have previously reported that bryostatin-1, a potent immune modulator with antitumor activity, activates monocytes and lymphocytes to produce cytokines. Studies have shown that tumor-bearing hosts have a Th1/Th2 cytokine pattern that is associated with decreased production of IFN-gamma. We investigated the expression of IFN-gamma in bryostatin-1-treated human DC. Bryostatin-1 induced both IFN-gamma and T-bet mRNA expression in a dose- and time-dependent manner. As little as 1 ng/ml bryostatin-1 induced IFN-gamma and T-bet transcripts within 3 h and protein at 12 h. Treatment of DC with cycloheximide revealed that bryostatin-1-induced T-bet expression requires de novo protein synthesis, but bryostatin-l-induced IFN-gamma expression is independent of protein synthesis. Furthermore, dexamethasone inhibits bryostatin-1-induced IFN-gamma mRNA expression but increases bryostatin-l-induced T-bet mRNA expression. Experiments with ERK-1/2 inhibitors demonstrated that bryostatin-1 induction of IFN-gamma and T-bet was ERK-dependent and IL-12-independent. Similar results were obtained from both normal donors and cancer patients. In summary, our results suggest that bryostatin-1-induced IFN-gamma expression is T-bet independent. They also suggest for the first time that IFN-gamma and T-bet can be induced in human DC through an ERK-dependent pathway. Bryostatin-1-induced IFN-gamma may play a crucial role in the initiation of the immune response, before specific recognition by T cells that could be beneficial in the treatment of cancer. C1 NIA, Gerontol Res Ctr, Hematol Oncol Sect, Baltimore, MD 21224 USA. RP Espinoza-Delgado, I (reprint author), 5600 Nathan Shock Dr,Room 4C10, Baltimore, MD 21224 USA. EM espinozaig@grc.nia.nih.gov NR 57 TC 11 Z9 12 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 SEP 15 PY 2006 VL 177 IS 6 BP 3554 EP 3563 PG 10 WC Immunology SC Immunology GA 083RG UT WOS:000240475300007 PM 16951314 ER PT J AU Mazzoni, A Siraganian, RP Leifer, CA Segal, DM AF Mazzoni, Alessandra Siraganian, Reuben P. Leifer, Cynthia A. Segal, David M. TI Dendritic cell modulation by mast cells controls the Th1/Th2 balance in responding T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ADAPTIVE IMMUNE-RESPONSES; EPITHELIAL-CELLS; ACTIVATION; POLARIZATION; EXPRESSION; INDUCTION; INFECTION; ANTIGEN; ALPHA AB The cytokines secreted by pathogen-activated human dendritic cells (DC) are strongly regulated in vitro by histamine, a major component of mast cell granules, ultimately modulating the capacity of the DC to polarize naive T cells. Because DC and mast cells are located in-close proximity in peripheral compartments, we hypothesized that mast cell products would influence the maturation of DC and hence the Th balance of an immune response in vivo. In this study, we show that specific mast cell degranulation stimuli, given s.c. in mice with Ag and adjuvant, produce effector T cells that proliferate to Ag but secrete dramatically reduced levels of IFN-gamma and increased amounts of IL-4 compared with control T cells primed in the absence of a mast cell stimulus. Immunization with Ag and adjuvant in the presence of a degranulation stimulus also resulted in the accumulation of DC in the draining lymph nodes that had reduced capacity to induce Ag-specific Th1 cells, in comparison with DC from mice lacking a degranulation stimulus. Therefore, by acting upon DC at sites of inflammation, mast cells play a critical role in determining the polarity of Ag-specific T cell responses in vivo. C1 Natl Inst Dent & Craniofacial Res, Expt Immunol Branch, NCI, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral Infect Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. RP Segal, DM (reprint author), Natl Inst Dent & Craniofacial Res, Expt Immunol Branch, NCI, NIH, Bldg 10,Room 4B36,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dave_Segal@nih.gov FU Intramural NIH HHS; NCI NIH HHS [K22 CA113705] NR 31 TC 61 Z9 63 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 SEP 15 PY 2006 VL 177 IS 6 BP 3577 EP 3581 PG 5 WC Immunology SC Immunology GA 083RG UT WOS:000240475300009 PM 16951316 ER PT J AU Masilamani, M Nguyen, C Kabat, J Borrego, F Coligan, JE AF Masilamani, Madhan Nguyen, Connie Kabat, Juraj Borrego, Francisco Coligan, John E. TI CD94/NKG2A inhibits NK cell activation by disrupting the actin network at the immunological synapse SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL; LIPID RAFTS; ERM PROTEINS; TYROSINE PHOSPHORYLATION; PLASMA-MEMBRANE; SIGNALING PATHWAYS; IMMUNE SYNAPSES; APC CONJUGATION; HOMOLOGY DOMAIN; HLA-E AB An adequate immune response is the result of the fine balance between activation and inhibitory signals. The exact means by which inhibitory signals obviate activation signals in immune cells are not totally elucidated. Human CD94/NKG2A is an ITIM-containing inhibitory receptor expressed by NK cells and some CD8(+) T cells that recognize HLA-E. We show that the engagement of this receptor prevents NK cell activation by disruption of the actin network and exclusion of lipid rafts at the point of contact with its ligand (inhibitory NK cell immunological synapse, iNKIS). CD94/NKG2A engagement leads to recruitment and activation of src homology 2 domain-bearing tyrosine phosphatase 1. This likely explains the observed dephosphorylation of guanine nucleotide exchange factor and regulator of actin, Vav1, as well as ezrin-radixin-moesin proteins that connect actin filaments to membrane structures. In contrast, NK cell activation by NKG2D induced Vav1 and ezrin-radixin-moesin phosphorylation. Thus, CD94/NKG2A prevents actin-dependent recruitment of raft-associated activation receptors complexes to the activating synapse. This was further substantiated by showing that inhibition of actin polymerization abolished lipid rafts exclusion at the iNKIS, whereas cholesterol depletion had no effect on actin disruption at the iNKIS. These data indicate that the lipid rafts exclusion at the iNKIS is an active process which requires an intact cytoskeleton to maintain lipid rafts outside the inhibitory synapse. The net effect is to maintain an inhibitory state in the proximity of the iNKIS, while allowing the formation of activation synapse at distal points within the same NK cell. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. NIAID, Biol Imaging Facil, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM JCOLIGAN@niaid.nih.gov FU Intramural NIH HHS NR 55 TC 56 Z9 61 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2006 VL 177 IS 6 BP 3590 EP 3596 PG 7 WC Immunology SC Immunology GA 083RG UT WOS:000240475300011 PM 16951318 ER PT J AU Florese, RH Van Rompay, KKA Aldrich, K Forthal, DN Landucci, G Mahalanabis, M Haigwood, N Venzon, D Kalyanaraman, VS Marthas, ML Robert-Guroff, M AF Florese, Ruth H. Van Rompay, Koen K. A. Aldrich, Kris Forthal, Donald N. Landucci, Gary Mahalanabis, Madhumita Haigwood, Nancy Venzon, David Kalyanaraman, Vaniambadi S. Marthas, Marta L. Robert-Guroff, Marjorie TI Evaluation of passively transferred, nonneutralizing antibody-dependent cellular cytotoxicity-mediating IgG in protection of neonatal rhesus macaques against oral SIVmac251 challenge SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; INFECTED MACAQUES; NATURAL-KILLER; NONHUMAN-PRIMATES; VAGINAL CHALLENGE; IMMUNE-RESPONSES; HIV TYPE-1; IN-VITRO; SIV AB Previously, Ab-dependent cellular cytotoxicity (ADCC) was significantly correlated with reduced acute viremia upon intrarectal SIVmac251 challenge of immunized rhesus macaques. To directly assess ADCC protective efficacy, six neonatal macaques were infused s.c. with immune IgG (220 mg/kg) purified from the immunized animals and positive for ADCC and Ab-dependent cell-mediated viral inhibition (ADCVI) activities. Six neonates received control IgG. The neonates were challenged twice orally with 10(5)50% inhibiting tissue culture-infective dose of SIVmac251 2 days post-IgG infusion. At challenge, plasma of neonates that received immune IgG did not neutralize SIVmac251 but had geometric mean ADCC titers of 48,130 and 232,850 against SIVmac251-infected and gp120-coated targets, respectively. Peak ADCVI activity varied from 62 to 81%. ADCC activity declined with the 2-wk IgG half-life but was boosted at wk 4, together with de novo ADCC-mediating Abs in controls, by postchallenge viremia. ADCVI activity was similarly induced. No protection, assessed by viral burdens, CD4 counts, and time to euthanasia was observed. Possible factors contributing to the discrepancy between the previous correlation and lack of protection here include: the high oral challenge dose compared with the 400-fold lower intrarectal dose; the challenge route with regard to viral dissemination and distribution of infused IgG; insufficient NK effector activity and/or poor functionality in newborns; insufficient immune IgG; and the possibility that the previous correlation of ADCC with protection was augmented by cellular immune responses also present at challenge. Future studies should explore additional challenge routes in juvenile macaques using higher amounts of potent IgG preparations. C1 NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Univ Calif Orange, Irvine Sch Med, Orange, CA 92868 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. Adv Biosci Labs, Kensington, NSW 20895, Australia. RP Robert-Guroff, M (reprint author), NCI, NIH, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [RR00169]; NIAID NIH HHS [R02 AI52039] NR 43 TC 53 Z9 55 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2006 VL 177 IS 6 BP 4028 EP 4036 PG 9 WC Immunology SC Immunology GA 083RG UT WOS:000240475300059 PM 16951366 ER PT J AU Streeck, H Jessen, H Alter, G Teigen, N Waring, MT Jessen, A Stahmer, I van Lunzen, J Lichterfeld, M Gao, XJ Allen, TM Carrington, M Walker, BD Rockstroh, JK Altfeld, M AF Streeck, Hendrik Jessen, Heiko Alter, Galit Teigen, Nickolas Waring, Mike T. Jessen, Arne Stahmer, Ingrid van Lunzen, Jan Lichterfeld, Mathias Gao, Xiaojiang Allen, Todd M. Carrington, Mary Walker, Bruce D. Rockstroh, Juergen K. Altfeld, Marcus TI Immunological and virological impact of highly active antiretroviral therapy initiated during acute HIV-1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-LYMPHOCYTES; DISCONTINUATION; CELLS; IDENTIFICATION; RESPONSES AB The immunological and virological impact of short-term treatment initiated during acute human immunodeficiency virus type 1 (HIV-1) infection was assessed prospectively in 20 subjects, 12 of whom initiated highly active antiretroviral therapy (HAART) for 24 weeks and then terminated treatment. Treatment resulted in suppression of viremia, an increase in the CD4(+) T cell count, enhanced differentiation of HIV-1-specific CD8(+) T cells from effector memory to effector cells at week 24 of HAART, and significantly higher virus-specific interferon-gamma(+) CD8(+) T cell responses after viral rebound (at week 48). However, despite these immunological changes, no differences in viremia or in the CD4(+) T cell count were found 6 months after HAART was stopped, when treated subjects were compared with untreated subjects. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Lab Genom Divers, Frederick, MD 21701 USA. Univ Hamburg, Hosp Eppendorf, Med Ctr, Infect Dis Unit, D-20246 Hamburg, Germany. Univ Bonn, Dept Internal Med, Bonn, Germany. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Bldg 149,13th St,6th Floor, Boston, MA 02129 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011 NR 15 TC 56 Z9 56 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 SEP 15 PY 2006 VL 194 IS 6 BP 734 EP 739 DI 10.1086/503811 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 081KN UT WOS:000240316600003 PM 16941338 ER PT J AU Amexis, G Young, NS AF Amexis, Georgios Young, Neal S. TI Parvovirus B19 empty Capsids as antigen carriers for presentation of antigenic determinants of dengue 2 virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DENGUE; VIRUS; PARTICLES; GLYCOPROTEIN; VACCINES; SAFETY; ELICIT; FEVER; CELLS AB For the production of dengue-vaccine candidates, empty capsids, or virus-like particles (VLPs), of parvovirus B19 that carry dengue 2-specific epitopes were employed as antigen carriers. Two epitopes ( comprising amino acids 352-368 and 386-397) of domain BIII of the envelope glycoprotein were chosen to produce recombinant B19 VLPs for immunization of BALB/c mice. Serum samples from immunized mice revealed that recombinant B19 VLPs elicited strong humoral immune responses. In summary, this B19 VLP-vaccine platform produced high (>= 2.0 x 105) anti-dengue 2 titers and robust ( <= 1: 120) 50%-plaque-reduction neutralization test (PRNT50) titers, which effectively neutralized live dengue 2 virus in PRNT50 assays. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Amexis, G (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 3-5216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM amexis@nih.gov FU Intramural NIH HHS NR 16 TC 20 Z9 22 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 SEP 15 PY 2006 VL 194 IS 6 BP 790 EP 794 DI 10.1086/506361 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 081KN UT WOS:000240316600010 PM 16941345 ER PT J AU Chefer, VI Zapata, A Shippenberg, TS Bungay, PM AF Chefer, Vladimir I. Zapata, Agustin Shippenberg, Toni S. Bungay, Peter M. TI Quantitative no-net-flux microdialysis permits detection of increases and decreases in dopamine uptake in mouse nucleus accumbens SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE dopamine; uptake; mouse; nucleus accumbens; no-net-flux microdialysis; kappa-opioid receptor antagonist ID EXTRACELLULAR DOPAMINE; EXTRACTION FRACTION; RELEASE; COCAINE; VOLTAMMETRY; ABSTINENCE; RECOVERY; VALIDITY; INVIVO; LEVEL AB A number of investigators are using the quantitative no-net-flux microdialysis technique to monitor basal neurotransmitter dynamics in discrete brain regions of behaving animals. The predictive validity of the probe extraction fraction (E(d)) for quantifying decreases in the rate of dopamine (DA) clearance from the extracellular space is well documented. It was recently suggested, however, that E(d) may be insensitive to increases in DA clearance. Here we report that the E(d) for DA in the nucleus accumbens (NAc) of the behaving mouse is increased following pharmacological inactivation of kappa-opioid receptors, a treatment previously shown to augment DA uptake. The E(d) obtained in control mice and those that received the long-acting kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), satisfied the requirement that the mean values of each were lower than the mean value in vitro for the same probes immersed in well-stirred artificial cerebrospinal fluid. The E(d) was increased in the NAc of nor-BNI-treated mice as compared to saline-treated control animals. The corresponding increase in the DA uptake rate was quantified by using the E(d) values to calculate a change in the apparent clearance rate constant. Nor-BNI treatment did not alter the apparent extracellular dopamine concentration represented by the point of no-net-flux indicating that the rates of DA uptake and release were both increased. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, IRP,NIH, Baltimore, MD 21224 USA. NIH, Drug Delivery & Kinet Resource, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Chefer, VI (reprint author), NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, IRP,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vchefer@intra.nida.nih.gov FU NIAAA NIH HHS [AA U01 13486] NR 22 TC 28 Z9 28 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 15 PY 2006 VL 155 IS 2 BP 187 EP 193 DI 10.1016/j.jneumeth.2005.12.018 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 094CP UT WOS:000241217200004 PM 16466808 ER PT J AU Ingehohn, JE Dold, GR Pfeffer, LE Ide, D Goldstein, SR Johnson, KO Van Boven, RW AF Ingehohn, John E. Dold, George R. Pfeffer, Lawerence E. Ide, David Goldstein, Seth R. Johnson, Kenneth O. Van Boven, Robert W. TI The Helix: A multi-modal tactile stimulator for human functional neuroimaging SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE tactile stimulator; functional MRI; somatosensory; MRI-compatible device; human brain mapping ID SOMATOSENSORY CORTEX; MEDIAN NERVE; HUMAN BRAIN; FMRI DATA; VISUALIZATION; SOFTWARE AB In order to expand the repertoire of somatosensory functions that can be effectively studied through functional MRI, we have developed a tactile stimulator which can deliver rich and varied combinations of stimulation that simulate natural tactile exploration. The system is computer controlled and compatible with an MRI environment. Complex aspects of somesthesis can thus be studied independent of confounds introduced by motor activity or problems with precision, accuracy or reproducibility of stimulus delivery. Published by Elsevier B.V. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NIMH, Res Serv Branch, NIH, Bethesda, MD 20892 USA. NIH, Biomed Engn & Phys Sci Program, OD, Bethesda, MD 20892 USA. Johns Hopkins Univ, Krieger Mind Brain Inst, Baltimore, MD USA. RP Ingehohn, JE (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr,Room 4C104, Bethesda, MD 20892 USA. EM ingeholm@nih.gov FU Intramural NIH HHS NR 13 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 15 PY 2006 VL 155 IS 2 BP 217 EP 223 DI 10.1016/j.jneumeth.2006.01.018 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 094CP UT WOS:000241217200008 PM 16522331 ER PT J AU Hidler, J Hodics, T Xu, B Dobkin, B Cohen, LG AF Hidler, Joseph Hodics, Timea Xu, Benjamin Dobkin, Bruce Cohen, Leonardo G. TI MR compatible force sensing system for real-time monitoring of wrist moments during fMRI testing SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE functional magnetic resonance imaging; fMRI; stroke; brain function; neural plasticity ID INDUCED MOVEMENT THERAPY; FUNCTIONAL MRI; CORTICAL REORGANIZATION; MOTOR RECOVERY; CHRONIC STROKE; ACTIVATION; IMPROVEMENTS; TRIAL; BRAIN AB Functional magnetic resonance imaging (fMRI) of brain function is used in neurorehabilitation to gain insight into the mechanisms of neural recovery following neurological injuries such as stroke. The behavioral paradigms involving the use of force motor tasks utilized in the scanner often lack the ability to control details of motor performance. They are often limited by subjectiveness, lack of repeatability, and complexity that may exclude evaluation of patients with poor function. In this paper we describe a novel MR compatible wrist device that is capable of measuring isometric forces generated at the hand and joint moments along wrist flexion-extension and wrist ulnar-radial deviation axes. Joint moments measured by the system can be visually displayed to the individual and used during target matching block or event related paradigms. Through a small set of pilot testing both inside and outside the MR environment, we have found that the force tracking tasks and performance in the scanner are reproducible, and that high quality force and moment recordings can be made during fMRI studies without compromising the fMRI images. Furthermore, the device recordings are extremely sensitive making it possible for individuals with poor hand and wrist function to be tested. (c) 2006 Elsevier B.V. All rights reserved. C1 Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. Natl Rehabil Hosp, Ctr Appl Biomech & Rehabil Res, Washington, DC 20010 USA. Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA. NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Reed Neurol Res Ctr, Geffen Sch Med, Neurol Rehabil & Res Program, Los Angeles, CA 90095 USA. RP Hidler, J (reprint author), Catholic Univ Amer, Dept Biomed Engn, Pangborn Hall,104b,620 Michigan Ave NE, Washington, DC 20064 USA. EM hidler@cua.edu; tmh33@gunet.georgetown.edu; benxu1@mail.nih.gov; bdobkin@mednet.ucla.edu; cohenl@ninds.nih.gov FU NICHD NIH HHS [K23 HD050267, R01 HD046740] NR 23 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 15 PY 2006 VL 155 IS 2 BP 300 EP 307 DI 10.1016/j.jneumeth.2006.01.016 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 094CP UT WOS:000241217200018 PM 16490258 ER PT J AU Jiang, S Li, P Lai, CC Kelley, JA Roller, PP AF Jiang, Sheng Li, Peng Lai, Christopher C. Kelley, James A. Roller, Peter P. TI Design and concise synthesis of fully protected analogues of L-gamma-carboxyglutamic acid SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CYCLIC PEPTIDE ANTAGONISTS; VITAMIN-K; GRB2-SH2 DOMAIN; SIGNAL-TRANSDUCTION; ANNONACEOUS ACETOGENIN; STRUCTURAL BASIS; HIGH-AFFINITY; SH2 DOMAINS; AMINO-ACID; ALCOHOLS AB The design and synthesis of four nonnaturally occurring amino acid analogues of L-gamma-carboxyglutamic acid (Gla), appropriately protected for Fmoc-based solid-phase peptide synthesis (SPPS), is described. These amino acids are Bu-Mal 2, BCAH 3, Pen-Mal 4, and Cm-Gla 5. These Gla analogues have been designed to replace the glutamic acid of position 1 in the cyclic decapeptide G1TE, which is a potent inhibitor of tyrosine kinase, to further enhance binding to the Grb2-SH2 domain of signal transduction receptors. In the new amino acids, the propionic acid side chain of Glu has been replaced by a malonyl or a carboxymethylmalonyl moiety located at different distances from the alpha-carbon to optimize interactions in the phosphotyrosine-binding cavity of the Grb2-SH2 domain. Additionally, a direct and efficient synthetic route for the preparation of Fmoc-protected L-gamma-carboxyglutamic acid, which is amenable to large-scale production, has been developed to provide this important and unique amino acid(1) in 55% overall yield. C1 NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. RP Roller, PP (reprint author), NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. EM proll@helix.nih.gov FU Intramural NIH HHS NR 43 TC 10 Z9 10 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD SEP 15 PY 2006 VL 71 IS 19 BP 7307 EP 7314 DI 10.1021/jo061037q PG 8 WC Chemistry, Organic SC Chemistry GA 082FK UT WOS:000240371900020 PM 16958524 ER PT J AU Rogawski, MA Suber, P AF Rogawski, Michael A. Suber, Peter TI Support for the NIH public access policy SO SCIENCE LA English DT Letter C1 NINDS, NIH, Bethesda, MD 20892 USA. Publ Knowledge, Washington, DC 20009 USA. RP Rogawski, MA (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 7 U2 27 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 15 PY 2006 VL 313 IS 5793 BP 1572 EP 1572 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 083YS UT WOS:000240498900018 PM 16973859 ER PT J AU Betzig, E Patterson, GH Sougrat, R Lindwasser, OW Olenych, S Bonifacino, JS Davidson, MW Lippincott-Schwartz, J Hess, HF AF Betzig, Eric Patterson, George H. Sougrat, Rachid Lindwasser, O. Wolf Olenych, Scott Bonifacino, Juan S. Davidson, Michael W. Lippincott-Schwartz, Jennifer Hess, Harald F. TI Imaging intracellular fluorescent proteins at nanometer resolution SO SCIENCE LA English DT Article ID STRUCTURED-ILLUMINATION MICROSCOPY; DIFFRACTION LIMIT; LIVING CELLS; LOCALIZATION; SPECTROSCOPY; MOLECULES AB We introduce a method for optically imaging intracellular proteins at nanometer spatial resolution. Numerous sparse subsets of photoactivatable fluorescent protein molecules were activated, localized ( to similar to 2 to 25 nanometers), and then bleached. The aggregate position information from all subsets was then assembled into a superresolution image. We used this method - termed photoactivated localization microscopy - to image specific target proteins in thin sections of lysosomes and mitochondria; in fixed whole cells, we imaged vinculin at focal adhesions, actin within a lamellipodium, and the distribution of the retroviral protein Gag at the plasma membrane. C1 Howard Hughes Med Inst, Ashburn, VA USA. New Millennium Res LLC, Okemos, MI 48864 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. NuQuest Res LLC, La Jolla, CA 92037 USA. RP Betzig, E (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA USA. EM betzige@janelia.hhmi.org OI Sougrat, Rachid/0000-0001-6476-1886; Bonifacino, Juan S./0000-0002-5673-6370 NR 29 TC 2979 Z9 3044 U1 168 U2 1144 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 15 PY 2006 VL 313 IS 5793 BP 1642 EP 1645 DI 10.1126/science.1127344 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 083YS UT WOS:000240498900047 PM 16902090 ER PT J AU Holmes, EC Lipman, DJ Zamarin, D Yewdell, JW AF Holmes, Edward C. Lipman, David J. Zamarin, Dmitriy Yewdell, Jonathan W. TI Comment on "Large-scale sequence analysis of avian influenza isolates SO SCIENCE LA English DT Editorial Material C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lipman, DJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM lipman@ncbi.nlm.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; OI Holmes, Edward/0000-0001-9596-3552 NR 4 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 15 PY 2006 VL 313 IS 5793 DI 10.1126/science.1131729 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 083YS UT WOS:000240498900022 ER PT J AU Korn, EL Freidlin, B AF Korn, Edward L. Freidlin, Boris TI Conditional power calculations for clinical trials with historical controls SO STATISTICS IN MEDICINE LA English DT Article DE conditional power; historical control; predictive power; sample size calculation ID SAMPLE-SIZE CONSIDERATIONS; PHASE-II; RANDOMIZED TRIALS; RADIATION-THERAPY; CHEMOTHERAPY; GLIOMAS AB A trial of a new therapy is to be compared to results from a previous trial of patients treated with a standard therapy. For a given sample size for the trial of the new therapy, we desire the power, against a specific alternative hypothesis, for the hypothesis test of the null hypothesis that the therapies are equivalent. Alternatively, the sample size required for the trial of the new therapy is needed for a target power. We explain why a popular method for doing these calculations is wrong, and discuss alternative methods in the context of normal outcomes, binary outcomes, and time-to-event outcomes. Published in 2006 by John Wiley & Sons, Ltd. C1 NCI, Biomet Res Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biomet Res Branch, EPN-8129, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov; freidlinb@ctep.nci.nih.gov NR 17 TC 9 Z9 10 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 15 PY 2006 VL 25 IS 17 BP 2922 EP 2931 DI 10.1002/sim.2516 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 077RI UT WOS:000240047100004 PM 16479548 ER PT J AU Yu, BB Tiwari, RC AF Yu, Binbing Tiwari, Ram C. TI Multiple imputation methods for modelling relative survival data SO STATISTICS IN MEDICINE LA English DT Article DE multiple imputation; relative survival; SEER ID RACIAL-DIFFERENCES; REGRESSION-MODELS; MORTALITY AB in population-based cancer survival studies, the cause-specific survival measures the net survival (excess mortality) due to cancer when the cause of death information is available and reliable. In contrast, when the cause of death is uncertain or unavailable, relative survival, the ratio of the survival rate due to all causes to the expected survival rate, is more appropriate. There is a large body of work on the modelling and hypothesis testing of cause-specific survival, but many of these methods are not directly applicable to relative survival. In this paper, we extend the multiple imputation (MI) methods (Stat. Methods Med. Res. 1999; 8:3-15) to the case of relative survival data. The MI methodology is combined with relative survival to estimate the net survival by changing relative survival data to cause-specific data. This facilitates the direct application to statistical methods developed for the cause-specific survival to the special situation of relative survival. The parameter estimates and the log-rank statistics are obtained by combining the results from multiple imputed cause-specific data. The likelihood-based methods for modelling relative survival data have been implemented by a Windows application called CANSURV (Comput. Meth. Prog. Biomed 2005). Although these methods produce accurate parameter estimates, the choice for models and diagnostic tools is limited. The MI method is presented as a simpler alternative. The relative survival data for the colorectal cancer patients from Surveillance, Epidemiology, and End Results (SEER) program (SEER Cancer Statistics Review, 1973-1999. National Cancer Institute: Bethesda, 2002) is used as an illustration. The results are compared with those obtained from the likelihood-based relative survival analysis methods. A sample SAS macro for the MI method is provided. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Informat Management Serv Inc, Silver Spring, MD 20904 USA. NCI, Stat Appl & Res Branch, Bethesda, MD 20892 USA. RP Yu, BB (reprint author), Informat Management Serv Inc, 12501 Prosper Dr Suite 200, Silver Spring, MD 20904 USA. EM yub@imsweb.com NR 20 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 15 PY 2006 VL 25 IS 17 BP 2946 EP 2955 DI 10.1002/sim.2289 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 077RI UT WOS:000240047100006 PM 16013033 ER PT J AU Waalkes, MP Liu, J Ward, JM Diwan, BA AF Waalkes, Michael P. Liu, Jie Ward, Jerrold M. Diwan, Bhalchandra A. TI Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arsenic; carcinogenesis; diethylstilbestrol; tamoxifen; liver; urinary bladder ID DIMETHYLARSINIC ACID; ESTROGEN-RECEPTOR; PROLIFERATIVE LESIONS; TRANSGENIC MICE; CD-1 MICE; F344 RATS; IN-UTERO; TUMORS; INDUCTION; CANCER AB Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 mu g/pup/day) or tamoxifen (TAM; 10 mu g/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-a, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NIAID, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. RP Waalkes, MP (reprint author), NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 47 TC 56 Z9 57 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP 15 PY 2006 VL 215 IS 3 BP 295 EP 305 DI 10.1016/j.taap.2006.03.010 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 084KW UT WOS:000240532800006 PM 16712894 ER PT J AU Toyoshiba, H Sone, H Yamanaka, T Parham, FM Irwin, RD Boorman, GA Portier, CJ AF Toyoshiba, Hiroyoshi Sone, Hideko Yamanaka, Takeharu Parham, Frederick M. Irwin, Richard D. Boorman, Gary A. Portier, Christopher J. TI Gene interaction network analysis suggests differences between high and low doses of acetaminophen SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE systems biology; oxidative stress; apoptosis; toxicogenomics; dose-dependent toxicity; risk assessment ID ACTIVATED RECEPTOR-GAMMA; MITOCHONDRIAL PERMEABILITY TRANSITION; NITRIC-OXIDE SYNTHASE; FACTOR-KAPPA-B; INDUCED HEPATOTOXICITY; INDUCED APOPTOSIS; OXIDATIVE STRESS; HEME OXYGENASE-1; GENOTOXIC STRESS; EXPRESSION DATA AB Bayesian networks for quantifying linkages between genes were applied to detect differences in gene expression interaction networks between multiple doses of acetaminophen at multiple time points. Seventeen (17) genes were selected from the gene expression profiles from livers of rats orally exposed to 50, 150 and 1500 mg/kg acelaminophen (APAP) at 6, 24 and 48 h after exposure using a variety of statistical and bioinformatics approaches. The selected genes are related to three biological categories: apoptosis, oxidative stress and other. Gene interaction networks between all 17 genes were identified for the nine dose-time observation points by the TAO-Gen algorithm. Using k-means clustering analysis, the estimated nine networks could be clustered into two consensus networks, the first consisting of the low and middle dose groups, and the second consisting of the high dose. The analysis suggests that the networks could be segregated by doses and were consistent in structure over time of observation within grouped doses. The consensus networks were quantified to calculate the probability distribution for the strength of the linkage between genes connected in the networks. The quantifying analysis showed that, at lower doses, the genes related to the oxidative stress signaling pathway did not interact with the apoptosis-related genes. In contrast, the high-dose network demonstrated significant interactions between the oxidative stress genes and the apoptosis genes and also demonstrated a different network between genes in the oxidative stress pathway. The approaches shown here could provide predictive information to understand high- versus low-dose mechanisms of toxicity. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Inst Environm Studies, Tsukuba, Ibaraki 3058506, Japan. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Fdn Biomed Res & Innovat, Translat Res Informat Ctr, Dept Clin Trial Management, Kobe, Hyogo, Japan. RP Toyoshiba, H (reprint author), Natl Inst Environm Studies, 16-2 Onogawa, Tsukuba, Ibaraki 3058506, Japan. EM toyoshiba.hiroyoshi@nies.go.jp RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 57 TC 13 Z9 15 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP 15 PY 2006 VL 215 IS 3 BP 306 EP 316 DI 10.1016/j.taap.2006.03.009 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 084KW UT WOS:000240532800007 PM 16701773 ER PT J AU Kirk, AD AF Kirk, Allan D. TI Induction immunosuppression SO TRANSPLANTATION LA English DT Review ID RENAL-ALLOGRAFT REJECTION; RANDOMIZED PROSPECTIVE TRIAL; OKT3 MONOCLONAL-ANTIBODY; T-CELL-ACTIVATION; CORTICOSTEROID-FREE IMMUNOSUPPRESSION; ANTITHYMOCYTE GLOBULIN INDUCTION; DONOR-SPECIFIC TRANSFUSION; ANTIGEN-PRESENTING CELLS; NONHUMAN PRIMATE MODEL; PHASE-I TRIAL AB Induction immunusuppression is intense, prophylactic therapy used at the time of transplantation based on the empiric observation that more powerful immunosuppression is required to prevent acute rejection early. In the past decade, there has been a growing trend towards the use of specialized agents such as antibody therapies for induction. In general, these agents have been shown to reduce the rate of acute rejection. However, their use has not been clearly shown to improve long-term transplant outcomes. This overview will review the biological basis for induction immunosuppression and the mechanisms of action of those specialized induction agents currently in clinical use. Clinical trials investigating induction regimens will be evaluated, and an individualized approach to the use of induction immunosuppressants will be presented. C1 NIDDKD, Transplantat Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), Room 5-5752,Bldg 10CRC,Ctr Dr, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 116 TC 77 Z9 82 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 2006 VL 82 IS 5 BP 593 EP 602 DI 10.1097/01.tp.0000234905.56926.7f PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 084CQ UT WOS:000240509800001 PM 16969280 ER PT J AU Kowalski, RJ Post, DR Mannon, RB Sebastian, A Wright, HI Sigle, G Burdick, J Abu Elmagd, K Zeevi, A Lopez-Cepero, M Daler, JA Gritsch, HA Reed, EF Jonsson, J Hawkins, D Britz, JA AF Kowalski, Richard J. Post, Diane R. Mannon, Roslyn B. Sebastian, Anthony Wright, Harlan I. Sigle, Gary Burdick, James Abu Elmagd, Kareem Zeevi, Adriana Lopez-Cepero, Mayra Daler, John A. Gritsch, H. Albin Reed, Elaine F. Jonsson, Johann Hawkins, Douglas Britz, Judith A. TI Assessing relative risks of infection and rejection: A meta-analysis using an immune function assay SO TRANSPLANTATION LA English DT Article DE CD4; immune function; relative risk; infection; rejection ID KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; LIVER-TRANSPLANTATION; HEPATITIS-C; IMMUNOSUPPRESSION; RECIPIENTS; DIAGNOSIS; ETIOLOGY AB Background. Long-term use of immunosuppressants is associated with significant morbidity and mortality in transplant recipients. A simple whole blood assay that has U.S. Food and Drug Administration clearance directly assesses the net state of immune function of allograft recipients for better individualization of therapy. A meta-analysis of 504 solid organ transplant recipients (heart, kidney, kidney-pancreas, liver and small bowel) from 10 U.S. centers was performed using the Cylex ImmuKnow assay. Methods. Blood samples were taken from recipients at various times posttransplant and compared with clinical course (stable, rejection, infection). In this analysis, 39 biopsy-proven cellular rejections and 66 diagnosed infections occurred. Odds ratios of infection or rejection were calculated based on measured immune response values. Results. A recipient with an immune response value of 25 ng/ml adenosine triphosphate (ATP) was 12 times (95% confidence of 4 to 36) more likely to develop an infection than a recipient with a stronger immune response. Similarly, a recipient with an immune response of 700 ng/ml ATP was 30 times (95% confidence of 8 to 112) more likely to develop a cellular rejection than a recipient with a lower immune response value. Of note is the intersection of odds ratio curves for infection and rejection in the moderate immune response zone (280 ng/ml ATP). This intersection of risk curves provides an immunological target of immune function for solid organ recipients. Conclusion. These data show that the Cylex ImmuKnow assay has a high negative predictive value and provides a target immunological response zone for minimizing risk and managing patients to stability. C1 Cylex Inc, Dept Clin Studies, Columbia, MD 21045 USA. NIDDK, Transplantat Branch, US Dept HHS, NIH, Bethesda, MD USA. Nazih Zuhdi Transplant Inst, Oklahoma City, OK USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Pittsburgh, Med Ctr, Starzl Transplant Inst, Pittsburgh, PA USA. Lifelink Fdn, Tampa, FL USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA 90024 USA. INOVA, Fairfax, VA USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Kowalski, RJ (reprint author), Cylex Inc, Dept Clin Studies, 8980-I Old Annapolis Rd, Columbia, MD 21045 USA. EM rkowalski@cylex.net NR 18 TC 206 Z9 237 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 2006 VL 82 IS 5 BP 663 EP 668 DI 10.1097/01.tp.0000234837.02126.70 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 084CQ UT WOS:000240509800011 PM 16969290 ER PT J AU Thomas, JA Gagliardi, TD Alvord, WG Lubomirski, M Bosche, WJ Gorelick, RJ AF Thomas, James A. Gagliardi, Tracy D. Alvord, W. Gregory Lubomirski, Mariusz Bosche, William J. Gorelick, Robert J. TI Human immunodeficiency virus type 1 nucleocapsid zinc-finger mutations cause defects in reverse transcription and integration SO VIROLOGY LA English DT Article DE HIV-1; integration; kinetics; mutation; nucleocapsid; provirus; reverse transcription; strand transfer; zinc-finger ID ACID-CHAPERONE ACTIVITY; MURINE LEUKEMIA-VIRUS; COMPLEXES IN-VITRO; VIRAL-DNA; SECONDARY STRUCTURE; STRAND TRANSFER; GENOMIC RNA; PROTEIN; REPLICATION; INFECTION AB The nucleocapsid (NC) protein from HIV-1 contains two zinc-fingers, both of which are necessary for virus replication. This is the first in-depth study that presents the effects of nucleocapsid zinc-finger substitutions on the kinetics of reverse transcription and integration. Over a 72-h time-course of infection, the quantities of viral DNA (vDNA) observed with viruses containing either the nucleocapsid His23Cys or His44Cys mutations were significantly lower than those observed in infections with virus containing wild-type NC. In addition, the kinetics of vDNA formation and loss were significantly different from wild-type. The kinetic profiles observed indicated reduced vDNA stability, as well as defects in reverse transcription and integration. Overall, the defect in integration was much more pronounced than the reverse transcription defects. This suggests that the principal reason for the replication defectiveness of these mutant viruses is impairment of integration, and thus demonstrates the critical importance of NC in HIV-1 infection. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Basic Res Program,AIDS Vaccine Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Comp & Stat Serv, Stat Consulting Serv, Frederick, MD 21702 USA. RP Gorelick, RJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Basic Res Program,AIDS Vaccine Program, POB B,Bldg 535,Room 410, Frederick, MD 21702 USA. EM jathomas@ncifcrf.gov; gagliardi@ncifcrf.gov; gwa@css.ncifcrf.gov; mlubomir@prdus.jnj.com; bosche@ncifcrf.gov; gorelick@ncifcrf.gov OI Thomas, James/0000-0002-2509-490X FU NCI NIH HHS [N01-CO-12400] NR 55 TC 48 Z9 51 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2006 VL 353 IS 1 BP 41 EP 51 DI 10.1016/j.virol.2006.05.014 PG 11 WC Virology SC Virology GA 084DL UT WOS:000240512100006 PM 16784767 ER PT J AU Basmaciogullari, S Pacheco, B Bour, S Sodroski, J AF Basmaciogullari, Stephane Pacheco, Beatriz Bour, Stephan Sodroski, Joseph TI Specific interaction of CXCR4 with CD4 and CD8 alpha: Functional analysis of the CD4/CXCR4 interaction in the context of HIV-1 envelope glycoprotein-mediated membrane fusion SO VIROLOGY LA English DT Article DE CD4; CD8 alpha; CXCR4; membrane fusion; fusion inhibitors; HIV-1; immunological synapse ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYROSINE-PROTEIN-KINASE; TYPE-1 VPU PROTEIN; AMINO-TERMINAL DOMAIN; CHEMOKINE RECEPTOR; CYTOPLASMIC DOMAIN; T-LYMPHOCYTES; TETRASPAN MICRODOMAINS; CONFORMATIONAL-CHANGES; IMMUNOLOGICAL SYNAPSE AB We investigated possible interactions between HIV-1 receptor (CD4) and the main coreceptors CXCR4 and CCR5. We found that CD4 and CXCR4 coexpressed in 293T cells form a complex that can be immunoprecipitated with antibodies directed against the extracellular domain of either protein. Mutagenesis revealed that the CD4/CXCR4 interaction maps to two previously uncharacterized basic motifs in the cytoplasmic domain of CD4. HIV-1 envelope glycoprotein-mediated membrane fusion was found to be independent of the ability of CD4 and CXCR4 to interact, whether fusion was studied in a virus-cell or a cell-cell model. However, this interaction might explain the adaptation of HIV-1 to CXCR4 as an alternative to CCR5. We found that CXCR4 also interacts with the cytoplasmic domain of CD8 alpha in a way that is similar to the CD4/CXCR4 interaction. The CD4/CXCR4 and CD8 alpha/CXCR4 interactions may thus be involved in cellular signaling pathways shared by the CD4 and CD8 alpha molecules. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIAID, Off Technol Informat Syst, Bioinformat & Computat Biol Program, Bethesda, MD 20892 USA. RP Basmaciogullari, S (reprint author), Inst Cochin Genet Mol, Dept Malad Infect, Batiment Gustave Roussy,28 Rue Faubourg St Jacque, F-75014 Paris, France. EM basmaciogullari@cochin.inserm.fr NR 93 TC 14 Z9 14 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 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2006 VL 353 IS 1 BP 52 EP 67 DI 10.1016/j.virol.2006.05.027 PG 16 WC Virology SC Virology GA 084DL UT WOS:000240512100007 PM 16808956 ER PT J AU Malkevitch, NV Patterson, LJ Aldrich, MK Wu, YC Venzon, D Florese, RH Kalyanaraman, VS Pal, R Lee, EM Zhao, J Cristillo, A Robert-Guroff, M AF Malkevitch, Nina V. Patterson, L. Jean Aldrich, M. Kristine Wu, Yichen Venzon, David Florese, Ruth H. Kalyanaraman, V. S. Pal, Ranajit Lee, Eun Mi Zhao, Jun Cristillo, Anthony Robert-Guroff, Marjorie TI Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: Role of SIV-specific CD8+ T cell responses SO VIROLOGY LA English DT Article DE AIDS; HIV; SIV; adenovirus; rhesus macaque; cellular immunity ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CD8(+) LYMPHOCYTES; ANTIBODY-RESPONSE; ADULT MACAQUES; C4 DOMAIN; INFECTION; LIVE; CD4(+); VIREMIA; RECHALLENGE AB Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIVmac251 challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIVmac251. Strong protection was observed in 8/11 vaccinees, including two exhibiting < 50 SIV RNA copies. Decreased viremia compared to naive controls was observed in the other three. The SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4 counts <= 200, unlike the protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained < 50 SIV RNA copies; SIV RNA emerged in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular immunity coincided with viremia suppression. Overall, cellular immunity induced by vaccination and/or low-level, inapparent viremia post-first SIVmac251 challenge, was associated with durable protection against re-challenge. Published by Elsevier Inc. C1 NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, NIH, 41 Medlars Dr MSC 5065,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU NCRR NIH HHS [RR016001]; NIAID NIH HHS [AI040101] NR 57 TC 54 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2006 VL 353 IS 1 BP 83 EP 98 DI 10.1016/j.virol.2006.05.012 PG 16 WC Virology SC Virology GA 084DL UT WOS:000240512100009 PM 16814356 ER PT J AU Berezhkovskii, A Szabo, A AF Berezhkovskii, Alexander Szabo, Attila TI Perturbation theory of Phi-value analysis of two-state protein folding: Relation between p(fold) and Phi values SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; TRANSITION-STATES; DIFFUSION; KINETICS; PATHWAY; REGIME; MODELS AB In protein folding, the transition state ensemble is defined as the set of conformations with p(fold)=1/2, where the p(fold) of a conformation is the probability that starting from this conformation the protein folds before it unfolds. Experimentally, this ensemble is probed by the Phi-value analysis, where Phi is the ratio of the changes in the logarithms of the folding rate and the equilibrium constant when the system is perturbed by a mutation. We show that for a two-state protein the Phi value can be expressed in terms of the perturbation and only the first two eigenfunctions of the evolution operator (e.g., a rate matrix) of the wild-type protein. The first eigenfunction is the equilibrium probability distribution while the second is proportional to p(fold), thus establishing a formal relation between p(fold) and Phi values. In addition to providing insight into the theoretical foundation of the Phi-value analysis, our results may prove practically useful in performing such analyses within the framework of models containing a large number of states. (c) 2006 American Institute of Physics. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Berezhkovskii, A (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM berezh@mail.nih.gov RI Szabo, Attila/H-3867-2012 FU Intramural NIH HHS NR 22 TC 8 Z9 8 U1 1 U2 3 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 14 PY 2006 VL 125 IS 10 AR 104902 DI 10.1063/1.2347708 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 083ZK UT WOS:000240500700037 PM 16999545 ER PT J AU Larkin, JD Bhat, KL Markham, GD Brooks, BR Schaefer, HF Bock, CW AF Larkin, Joseph D. Bhat, Krishna L. Markham, George D. Brooks, Bernard R. Schaefer, Henry F., III Bock, Charles W. TI Structure of the boronic acid dimer and the relative stabilities of its conformers SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID CROSS-COUPLING REACTIONS; CORRELATED MOLECULAR CALCULATIONS; POLARIZABLE CONTINUUM MODEL; METHYL TRANSFER-REACTIONS; GAUSSIAN-BASIS SETS; AB-INITIO; AFFINITY-CHROMATOGRAPHY; BORIC-ACID; WAVE-FUNCTIONS; ANISOTROPIC DIELECTRICS AB Despite the widespread use of boronic acids in materials science and as pharmaceutical agents, many aspects of their structure and reactivity are not well understood. In this research the boronic acid dimer, [HB(OH)(2)](2), was studied by second-order Moller-Plesset (MP2) perturbation theory and coupled cluster methodology with single and double excitations (CCSD). Pople split-valence 6-31 + G*, 6-311G**, and 6-311++G** and Dunning-Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets were employed for the calculations. A doubly hydrogen-bonded conformer (1) of the dimer was consistently found to be lowest in energy; the structure of 1 was planar (C2h) at most computational levels employed but was significantly nonplanar (C-2) at the MP2/6-311++G** and CCSD/6-311++G** levels, the result of an intrinsic problem with Pople-type sp-diffuse basis functions on heavy atoms. The dimerization energy, enthalpy, and free energy for the formation of (1) from the exo-endo conformer of the monomer were -10.8, -9.2, and + 1.2 kcal/mol, respectively, at the MP2/aug-cc-pVTZ level. Several other hydrogen-bonded conformers of the dimer were local minima on the potential energy surface (PES) and ranged from 2 to 5 kcal/mol higher in energy than 1. Nine doubly OH-bridged conformers, in which the boron atoms were tetracoordinated, were also local minima on the PES, but they were all greater than 13 kcal/mol higher in energy than 1; doubly H-bridged structures proved to be transition states. MP2 and CCSD results were compared to those from the BLYP, B3LYP, OLYP, O3LYP, PBE1PBE, and TPSS functionals with the 6-311++G** and aug-ccpVTZ basis sets; the PBE1PBE functional performed best relative to the MP2 and CCSD results. Self-consistent reaction field (SCRF) calculations predict that boronic acid dimerization is less favorable in solution than in vacuo. C1 Univ Georgia, Ctr Computat Chem, Athens, GA 30602 USA. Philadelphia Univ, Sch Sci & Hlth, Dept Chem & Biochem, Philadelphia, PA 19144 USA. Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. NHLBI, NIH, Bethesda, MD 20851 USA. RP Larkin, JD (reprint author), Univ Georgia, Ctr Computat Chem, Athens, GA 30602 USA. EM jlarkin@ccqc.uga.edu FU Intramural NIH HHS; NCI NIH HHS [CA 06927]; NIGMS NIH HHS [GM 31186] NR 87 TC 21 Z9 21 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD SEP 14 PY 2006 VL 110 IS 36 BP 10633 EP 10642 DI 10.1021/jp062407h PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 081PR UT WOS:000240330000014 PM 16956246 ER PT J AU Sanchez, VM Crespo, A Gutkind, JS Turjanski, AG AF Muriel Sanchez, Veronica Crespo, Alejandro Gutkind, J. Silvio Gustavo Turjanski, Adrian TI Investigation of the catalytic mechanism of farnesyl pyrophosphate synthase by computer simulation SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID NITROGEN-CONTAINING BISPHOSPHONATES; PLANE-WAVE CALCULATIONS; DIPHOSPHATE SYNTHASE; TRYPANOSOMA-CRUZI; IN-VITRO; MOLECULAR-DYNAMICS; POTENT INHIBITORS; BONE-RESORPTION; CHAGAS-DISEASE; EFFICIENT PSEUDOPOTENTIALS AB Farnesyl pyrophosphate synthase (FPPS) catalyses the formation of a key cellular intermediate in isoprenoid metabolic pathways, farnesyl pyrophosphate, by the sequential head-to-tail condensation of two molecules of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP). Recently, FPPS has been shown to represent an important target for the treatment of parasitic diseases such as Chagas disease and African trypanosomiasis. Bisphosphonates, pyrophosphate analogues 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 FPPS enzyme. Moreover, nitrogen-containing bisphosphonates have been proposed as carbocation transition state analogues of FPPS. On the basis of structural and kinetic data, different catalytic mechanisms have been proposed for FPPS. By analyzing different reaction coordinates we propose that the reaction occurs in one step through a carbocationic transition state and the subsequent transfer of a hydrogen atom from IPP to the pyrophosphate moiety of DMAPP. Moreover, we have analyzed the role of the active site amino acids on the activation barrier and the reaction mechanism. The structure of the active site is well conserved in the isoprenyl diphosphate synthase family; thus, our results are relevant for the understanding of this important class of enzymes and for the design of more potent and specific inhibitors for the treatment of parasitic diseases. C1 Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Inorgan Analit & Quim, INQUIMAE,CONICET, Buenos Aires, DF, Argentina. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. RP Turjanski, AG (reprint author), Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Inorgan Analit & Quim, INQUIMAE,CONICET, Buenos Aires, DF, Argentina. EM turjanskia@mail.nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 57 TC 18 Z9 18 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD SEP 14 PY 2006 VL 110 IS 36 BP 18052 EP 18057 DI 10.1021/jp063099q PG 6 WC Chemistry, Physical SC Chemistry GA 081TT UT WOS:000240340600048 PM 16956297 ER PT J AU Pellegrini, M Celeste, A Difilippantonio, S Guo, R Wang, WD Feigenbaum, L Nussenzweig, A AF Pellegrini, Manuela Celeste, Arkady Difilippantonio, Simone Guo, Rong Wang, Weidong Feigenbaum, Lionel Nussenzweig, Andre TI Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo SO NATURE LA English DT Article ID TELANGIECTASIA MUTATED ATM; DOUBLE-STRAND BREAKS; DNA-DAMAGE; MRE11-RAD50-NBS1 COMPLEX; CHECKPOINT; KINASE; SITES; CELLS; NBS1; PHOSPHORYLATION AB The ATM ( ataxia telangiectasia mutated) protein kinase is activated under physiological and pathological conditions that induce DNA double-strand breaks (DSBs). Loss of ATM or failure of its activation in humans and mice lead to defective cellular responses to DSBs, such as cell cycle checkpoints, radiation sensitivity, immune dysfunction, infertility and cancer predisposition. A widely used biological marker to identify the active form of ATM is the autophosphorylation of ATM at a single, conserved serine residue (Ser 1981 in humans; Ser 1987 in mouse)(1). Here we show that Atm-dependent responses are functional at the organismal and cellular level in mice that express a mutant form of Atm ( mutation of Ser to Ala at position 1987) as their sole Atm species. Moreover, the mutant protein does not exhibit dominant-negative interfering activity when expressed physiologically or overexpressed in the context of Atm heterozygous mice. These results suggest an alternative mode for stimulation of Atm by DSBs in which Atm autophosphorylation at Ser 1987, like transphosphorylation of downstream substrates, is a consequence rather than a cause of Atm activation. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov FU Intramural NIH HHS NR 30 TC 115 Z9 116 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 14 PY 2006 VL 443 IS 7108 BP 222 EP 225 DI 10.1038/nature05112 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 083OB UT WOS:000240467000049 PM 16906133 ER PT J AU Bennett, JE AF Bennett, John E. TI Echinocandins for candidemia in adults without neutropenia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INVASIVE CANDIDIASIS; AMPHOTERICIN-B; FUNGAL-INFECTIONS; CASPOFUNGIN; SUSCEPTIBILITY; GUIDELINES; MICAFUNGIN; RESISTANT; ALBICANS; OUTCOMES C1 NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 65 Z9 67 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 14 PY 2006 VL 355 IS 11 BP 1154 EP 1159 DI 10.1056/NEJMct060052 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 083NJ UT WOS:000240462800009 PM 16971721 ER PT J AU Liu, Y Borchert, GL Surazynski, A Hu, CA Phang, JM AF Liu, Y. Borchert, G. L. Surazynski, A. Hu, C. -A Phang, J. M. TI Proline oxidase activates both intrinsic and extrinsic pathways for apoptosis: the role of ROS/superoxides, NFAT and MEK/ERK signaling SO ONCOGENE LA English DT Article DE proline oxidase; apoptosis; superoxide radicals; NFAT; ERK; metabolism ID COLORECTAL-CANCER CELLS; MITOCHONDRIAL SUPEROXIDE ANIONS; T-CELLS; P53-INDUCED GENE-6; PROTEIN-KINASES; RECEPTOR GENE; EXPRESSION; DEATH; PUMA; FAS AB Proline oxidase (POX), often considered a 'housekeeping enzyme' might play an important role in apoptosis. We have shown that POX generated proline-dependent reactive oxygen species (ROS), specifically superoxide radicals, and induced apoptosis through the mitochondrial (intrinsic) pathway. In our current report, we used DLD-1 colorectal cancer cells stably transfected with the POX gene under the control of a tetracycline-inducible promoter and found POX-stimulated expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL), DR5 and cleavage of caspase-8. Importantly, apoptosis measured by flow cytometry was partially inhibited by Z-IETD-FMK, a specific inhibitor of caspase-8. These findings suggest that the extrinsic (death receptor) pathway also is activated by POX. Furthermore, the mechanism of this effect on the extrinsic pathway, specifically, the induction of TRAIL by POX, may be mediated by NFAT transcription factors. Additionally, POX expression also dramatically decreased phosphorylation of MEK and ERK, and the decrease was partially reversed by expression of manganese superoxide dismutase (MnSOD). Overexpression of constitutively active form of MEK, acMEK, partially blocked POX-induced apoptosis. These findings suggest the involvement of MEK/ERK signaling and further confirm the role of ROS/superoxides in POX-induced apoptosis. Combined with previously published data, we conclude that POX may induce apoptosis through both intrinsic and extrinsic pathways and is involved in nuclear factor of activated T cells (NFAT) signaling and regulation of the MEK/ERK pathway. It is suggested that, as a nutrition factor, POX may modulate apoptosis signals induced by p53 or other anti-cancer agents and enhance apoptosis in stress situations. C1 Natl Canc Inst, Ctr Canc Res, Comparat Carcinogenesis Lab, Metab & Canc Susceptibil Sect, Frederick, MD 21702 USA. SAIC Federick Inc, Basic Res Program, Frederick, MD USA. Univ New Mexico, Hlth Sci Ctr, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. RP Liu, Y (reprint author), Natl Canc Inst, Ctr Canc Res, Comparat Carcinogenesis Lab, Metab & Canc Susceptibil Sect, Frederick, MD 21702 USA. EM liuy@ncifcrf.gov; phang@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 38 TC 89 Z9 90 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD SEP 14 PY 2006 VL 25 IS 41 BP 5640 EP 5647 DI 10.1038/sj.onc.1209564 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 085IZ UT WOS:000240599100005 PM 16619034 ER PT J AU Nienborg, H Cumming, BG AF Nienborg, Hendrikje Cumming, Bruce G. TI Macaque V2 neurons, but not V1 neurons, show choice-related activity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE V2; macaque monkey; binocular disparity; striate cortex; choice probability; disparity discrimination ID PRIMARY VISUAL-CORTEX; STRUCTURE-FROM-MOTION; AREA MT; STEREOSCOPIC DEPTH; CORTICAL AREA; EYE-MOVEMENTS; PSYCHOPHYSICAL PERFORMANCE; DISPARITY MODULATION; AWAKE MONKEYS; RESPONSES AB In the macaque extrastriate cortex, robust correlations between perceptual choice and neuronal response have been demonstrated, frequently quantified as choice probabilities (CPs). Such correlations are modest in early visual cortex, suggesting that CPs may depend on the position of a neuron in the hierarchy of visual processing. However, previous studies have not compared neurons with similar precision in equivalent tasks. We investigated the role of cortical hierarchy on CP using a task for which significant CPs have been described previously for middle temporal area (MT). We measured CPs in disparity-selective neurons from both V1 and V2. The stimulus was a dynamic random dot stereogram, presented with a near or a far disparity, masked by varying numbers of binocularly uncorrelated dots. Two macaque monkeys reported whether they perceived a circular patch in front or behind a surrounding annulus in a forced choice task. For V2(n = 69), CP was on average 0.56, the first demonstration of systematic CPs in a visual area as early as V2. In V1(n = 74), average CP was at chance level (0.51). The pattern was similar in a subgroup of neurons selected such that the statistical precision in the task was on average identical to that reported for MT(mean CP, 0.51 for V1, n = 33; 0.58 for V2, n = 54). This difference between V1 and V2 could not be explained by eye movements, stimulus size relative to the receptive field, or differences in disparity tuning. Rather, it seems to reflect a functional difference (at least in disparity processing) between striate and extrastriate cortex. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Nienborg, H (reprint author), 49-2A50 Convent Dr, Bethesda, MD 20892 USA. EM hn@lsr.nei.nih.gov FU Intramural NIH HHS NR 45 TC 71 Z9 72 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 SEP 13 PY 2006 VL 26 IS 37 BP 9567 EP 9578 DI 10.1523/JNEUROSCI.2256-06.2006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 083YM UT WOS:000240495500025 PM 16971541 ER PT J AU Jenkins, LMM Durell, SR Maynard, AT Stahl, SJ Inman, JK Appella, E Legault, P Omichinski, JG AF Jenkins, Lisa M. Miller Durell, Stewart R. Maynard, Andrew T. Stahl, Stephen J. Inman, John K. Appella, Ettore Legault, Pascale Omichinski, James G. TI Comparison of the specificity of interaction of cellular and viral zinc-binding domains with 2-mercaptobenzamide thioesters SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HIV-1 NUCLEOCAPSID PROTEIN; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR GATA-1; ESCHERICHIA-COLI ADA; MAMMARY-TUMOR VIRUS; DNA-BINDING; FINGER PROTEINS; ANTI-HIV; ESTROGEN-RECEPTOR; METAL-BINDING AB The interactions of two 2-mercaptobenzamide thioester compounds with six diverse zinc-binding domains (ZBDs) have been analyzed by UV/visible spectroscopy, NMR spectroscopy, and nucleic acid binding assays. These thioester compounds serve as useful tools for probing the intrinsic chemical stability of ZBDs that exist within a variety of cellular and viral proteins. In our studies, the classical (Cys(2)His(2)) zinc finger ZBDs, the interleaved RING like ZBDs of protein kinase C delta (Cys(2)HisCys and HisCys(3)), and the carboxyl-terminal (Cys(2)HisCys) ZBD of Mouse Mammary Tumor Virus nucleocapsid protein (MMTV NCp10) were resistant to reaction with the thioester compounds. In contrast, the thioester compounds were able to efficiently eject zinc from the amino-terminal (Cys(2)HisCys) ZBD of MMTV NCp10, a Cys(2)HisCys ZBD from Friend of GATA-1 (FOG-1), and from both Cys(4) ZBDs of GATA-1. In all cases, zinc ejection led to a loss of protein structure. Interestingly, GATA-1 was resistant to reaction with the thioester compounds when bound to its target DNA sequence. The electronic and steric screening was calculated for select ZBDs to further explore their reactivity. Based on these results, it appears that both first and second zinc-coordination shell interactions within ZBDs, as well as nucleic acid binding, play important roles in determining the chemical stability and reactivity of ZBDs. These studies not only provide information regarding the relative reactivity of cysteine residues within structural ZBDs but also are crucial for the design of future therapeutic agents that selectively target ZBDs, such as those that occur in the HIV-1 nucleocapsid protein. C1 Univ Georgia, Dept Biochem, Athens, GA 30602 USA. Univ Georgia, Dept Mol Biol, Athens, GA 30602 USA. Univ Georgia, Dept Chem, Athens, GA 30602 USA. NIAMSD, Lab Cell Biol, NCI, Prot Express Lab, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Icagen, Computat Chem & Informat, Res Triangle Pk, NC 27709 USA. Univ Montreal, Dept Biochem, Montreal, PQ, Canada. RP Legault, P (reprint author), Univ Georgia, Dept Biochem, Athens, GA 30602 USA. EM pascale.legault@umontreal.ca; jg.omichinski@umontreal.ca FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM60298-01] NR 62 TC 16 Z9 18 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 13 PY 2006 VL 128 IS 36 BP 11964 EP 11976 AR JA063329E DI 10.1021/ja063329e PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 081BJ UT WOS:000240291900047 PM 16953638 ER PT J AU Tsaparas, P Marino-Ramirez, L Bodenreider, O Koonin, EV Jordan, IK AF Tsaparas, Panayiotis Marino-Ramirez, Leonardo Bodenreider, Olivier Koonin, Eugene V. Jordan, I. King TI Global similarity and local divergence in human and mouse gene co-expression networks SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID SCALE-FREE NETWORKS; EVOLUTIONARY DYNAMICS; EXPRESSION PROFILES; ORTHOLOGOUS GENES; DUPLICATE GENES; BIOLOGY; TRANSCRIPTOMES; CONSERVATION; COEVOLUTION; CHIMPANZEES AB Background: A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results: At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction (< 10%) of coexpressed gene pair relationships are conserved between the two species. A series of controls for experimental and biological variance show that most of this divergence does not result from experimental noise. We further show that, while the expression divergence between species is genuinely rapid, expression does not evolve free from selective (functional) constraint. Indeed, the coexpression networks analyzed here are demonstrably functionally coherent as indicated by the functional similarity of coexpressed gene pairs, and this pattern is most pronounced in the conserved human-mouse intersection network. Numerous dense network clusters show evidence of dedicated functions, such as spermatogenesis and immune response, that are clearly consistent with the coherence of the expression patterns of their constituent gene members. Conclusion: The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Helsinki, Helsinki Inst Informat Technol, Basic Res Unit, Helsinki, Finland. Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM tsaparas@cs.helsinki.fi; marino@ncbi.nlm.nih.gov; olivier@nlm.nih.gov; koonin@ncbi.nlm.nih.gov; king.jordan@biology.gatech.edu RI Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Intramural NIH HHS [Z99 LM999999] NR 45 TC 43 Z9 44 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD SEP 12 PY 2006 VL 6 AR 70 DI 10.1186/1471-2148-6-70 PG 13 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 095BQ UT WOS:000241283600001 PM 16968540 ER PT J AU Gheorghiade, M Sopko, G De Luca, L Velazquez, EJ Parker, JD Binkley, PF Sadowski, Z Golba, KS Prior, DL Rouleau, JL Bonow, RO AF Gheorghiade, Mihai Sopko, George De Luca, Leonardo Velazquez, Eric J. Parker, John D. Binkley, Philip F. Sadowski, Zygmunt Golba, Krzysztof S. Prior, David L. Rouleau, Jean L. Bonow, Robert O. TI Navigating the crossroads of coronary artery disease and heart failure SO CIRCULATION LA English DT Review ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; ISCHEMIC MITRAL REGURGITATION; CARDIAC-RESYNCHRONIZATION THERAPY; CONVERTING-ENZYME-INHIBITORS; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; LONG-TERM SURVIVAL; HIGH-RISK PATIENTS C1 Northwestern Univ, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA. NHLBI, Bethesda, MD 20892 USA. European Hosp, Rome, Italy. Duke Univ, Med Ctr, Durham, NC USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Ohio State Univ, Columbus, OH 43210 USA. Natl Inst Cardiol, Warsaw, Poland. Med Univ Silesia, Katowice, Poland. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. St Vincents Hosp, Melbourne, Vic, Australia. RP Bonow, RO (reprint author), Northwestern Univ, Div Cardiol, Feinberg Sch Med, Galter 10-240,201 E Huron St, Chicago, IL 60611 USA. EM r-bonow@northwestern.edu OI Parker, John/0000-0003-1949-2669 NR 124 TC 121 Z9 122 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 12 PY 2006 VL 114 IS 11 BP 1202 EP 1213 DI 10.1161/CIRCULATIONAHA.106.623199 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 083ED UT WOS:000240437800014 PM 16966596 ER PT J AU Goker-Alpan, O Giasson, BI Eblan, MJ Nguyen, J Hurtig, HI Lee, VMY Trojanowski, JQ Sidransky, E AF Goker-Alpan, O. Giasson, B. I. Eblan, M. J. Nguyen, J. Hurtig, H. I. Lee, V. M. -Y. Trojanowski, J. Q. Sidransky, E. TI Glucocerebrosidase mutations are an important risk factor for Lewy body disorders SO NEUROLOGY LA English DT Article ID PARKINSONS-DISEASE; GAUCHER-DISEASE; GENE AB The synucleinopathies are neurodegenerative disorders defined by inclusions composed of aberrantly fibrillized alpha-synuclein, but factors contributing to this process remain largely unknown. The authors examined the glucocerebrosidase gene in 75 autopsy specimens with different synucleinopathies and identified mutations in 23% of cases of dementia with Lewy bodies, expanding on previous findings in subjects with Parkinson disease. Mutations in this lysosomal protein may interfere with the clearance or promote aggregation of alpha-synuclein. C1 NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A100,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov FU Intramural NIH HHS; NIA NIH HHS [AG09215] NR 10 TC 120 Z9 121 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 12 PY 2006 VL 67 IS 5 BP 908 EP 910 DI 10.1212/01.wnl.0000230215.41296.18 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 083EC UT WOS:000240437700044 PM 16790605 ER PT J AU Sherwood, CC Stimpson, CD Raghanti, MA Wildmand, DE Uddin, M Grossman, LI Goodman, M Redmond, JC Bonar, CJ Erwin, JM Hof, PR AF Sherwood, Chet C. Stimpson, Cheryl D. Raghanti, Mary Ann Wildmand, Derek E. Uddin, Monica Grossman, Lawrence I. Goodman, Morris Redmond, John C. Bonar, Christopher J. Erwin, Joseph M. Hof, Patrick R. TI Evolution of increased glia-neuron ratios in the human frontal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allometry; human evolution; prefrontal cortex; brain energy metabolism; language evolution ID QUANTITATIVE-ANALYSIS; PREFRONTAL CORTEX; PYRAMIDAL NEURONS; MACAQUE MONKEY; NEUROFILAMENT PROTEIN; ALZHEIMERS-DISEASE; PROJECTION NEURONS; ENERGY-METABOLISM; VULNERABLE SUBSET; PRIMATE BRAINS AB Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia-neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia-neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as "theory of mind" (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain. C1 George Washington Univ, Dept Anthropol, Washington, DC 20052 USA. Kent State Univ, Dept Anthropol, Kent, OH 44242 USA. Kent State Univ, Sch Biomed Sci, Kent, OH 44242 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Neurosci, Atlanta, GA 30329 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Ctr Behav Neurosci, Atlanta, GA 30329 USA. Fdn Comparat & Conservat Biol, Needmore, PA 17238 USA. Cleveland Metropk Zoo, Cleveland, OH 44109 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. New York Consortium Evolutionary Primatol, New York, NY USA. RP Sherwood, CC (reprint author), George Washington Univ, Dept Anthropol, 2110 G St NW, Washington, DC 20052 USA. EM sherwood@gwu.edu; mgoodwayne@aol.com FU NIA NIH HHS [P30 AG013854, P30 AG13854] NR 63 TC 133 Z9 135 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 2006 VL 103 IS 37 BP 13606 EP 13611 DI 10.1073/pnas.0605843103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086BO UT WOS:000240648300012 PM 16938869 ER PT J AU Cheong, CG Hall, TMT AF Cheong, Cheorn-Gil Hall, Traci M. Tanaka TI Engineering RNA sequence specificity of Pumilio repeats SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein design; Puf proteins; protein-RNA interaction; adenosine-uracil-rich elements ID GERMLINE STEM-CELLS; HUNCHBACK MESSENGER-RNA; 3' UNTRANSLATED REGION; STRUCTURE-BASED DESIGN; BINDING PROTEINS; CAENORHABDITIS-ELEGANS; DROSOPHILA EMBRYOS; DEPENDENT CONTROL; HOMOLOGY DOMAIN; ZINC FINGERS AB Puf proteins bind RNA sequence specifically and regulate translation and stability of target mRNAs. A "code" for RNA recognition has been deduced from crystal structures of the Puf protein, human Pumilio1, where each of eight repeats binds an RNA base via a combination of three side chains at conserved positions. Here, we report the creation of seven soluble mutant proteins with predictably altered sequence specificity, including one that binds tightly to adenosine-uracil-rich element RNA. These data show that Pumilio1 can be used as a scaffold to engineer RNA-binding proteins with designed sequence specificity. C1 Natl Inst Environm Hlth Sci, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Hall, TMT (reprint author), Natl Inst Environm Hlth Sci, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. EM hall4@niehs.nih.gov FU Intramural NIH HHS NR 41 TC 114 Z9 116 U1 4 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 2006 VL 103 IS 37 BP 13635 EP 13639 DI 10.1073/pnas.0606294103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086BO UT WOS:000240648300017 PM 16954190 ER PT J AU Liu, X Shu, S Hong, MSS Levine, RL Korn, ED AF Liu, Xiong Shu, Shi Hong, Myoung-Soon S. Levine, Rodney L. Korn, Edward D. TI Phosphorylation of actin Tyr-53 inhibits filament nucleation and elongation and destabilizes filaments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE actin polymerization; dictyostelium; phosphorylated actin ID I-BINDING LOOP; DICTYOSTELIUM MYOSIN-II; TYROSINE PHOSPHORYLATION; DNASE-I; F-ACTIN; ACANTHAMOEBA-CASTELLANII; CRYSTAL-STRUCTURE; POLYMERIZATION; STATE; CYTOSKELETON AB Dictyostelium actin was shown to become phosphorylated on Tyr-53 late in the developmental cycle and when cells in the amoeboid stage are subjected to stress but the phosphorylated actin had not been purified and characterized. We have separated phosphorylated and unphosphorylated actin and shown that Tyr-53 phosphorylation substantially reduces actin's ability to inactivate DNase 1, increases actin's critical concentration, and greatly reduces its rate of polymerization. Tyr-53 phosphorylation substantially, if not completely, inhibits nucleation and elongation from the pointed end of actin filaments and reduces the rate of elongation from the barbed end. Negatively stained electron microscopic images of polymerized Tyr-53-phosphorylated actin show a variable mixture of small oligomers and filaments, which are converted to more typical, long filaments upon addition of myosin subfragment 1. Tyr-53-phosphorylated and unphosphorylated actin copolymerize in vitro, and phosphorylated and unphosphorylated actin colocalize in amoebae. Tyr-53 phosphorylation does not affect the ability of filamentous actin to activate myosin ATPase. C1 NIH, Cell Biol Lab, NHLBI, Bethesda, MD 20892 USA. NIH, Biochem Lab, NHLBI, Bethesda, MD 20892 USA. RP Korn, ED (reprint author), NIH, Cell Biol Lab, NHLBI, Bldg 50,Room 2517, Bethesda, MD 20892 USA. EM edk@nih.gov RI Korn, Edward/F-9929-2012; Levine, Rodney/D-9885-2011 NR 42 TC 24 Z9 24 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 2006 VL 103 IS 37 BP 13694 EP 13699 DI 10.1073/pnas.0606321103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086BO UT WOS:000240648300027 PM 16945900 ER PT J AU Nemeth, MJ Kirby, MR Bodine, DM AF Nemeth, Michael J. Kirby, Martha R. Bodine, David M. TI Hmgb3 regulates the balance between hematopoietic stem cell self-renewal and differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hematopoiesis; Wnt ID SIGNALING PATHWAY; PROTEIN HMG1; PROGENITORS; MICE; DNA; ACTIVATION; EXPRESSION; INTERACTS; BINDING; FAMILY AB Hmgb3 is an X-linked member of a family of sequence-independent chromatin-binding proteins that is preferentially expressed in hematopoietic stem cells (HSC). Hmgb3-deficient mice (Hmgb3(-/Y)) contain normal numbers of HSCs, capable of self-renewal and hematopoietic repopulation, but fewer common lymphoid (CLIP) and common myeloid progenitors (CMP). In this study, we tested the hypothesis that Hmgb3(-/Y) HSCs are biased toward self-renewal at the expense of progenitor production. Wild-type and Hmgb3(-/Y) CLPs and CMPs proliferate and differentiate equally in vitro, indicating that CLP and CMP function normally in Hmgb3(-/Y) mice. Hmgb3(-/Y) HSCs exhibit constitutive activation of the canonical Wnt signaling pathway, which regulates stem cell self-renewal. increased Wnt signaling in Hmgb3(-/Y) HSCs corresponds to increased expression of Dvl1, a positive regulator of the canonical Wnt pathway. To induce hematopoietic stress and a subsequent response from HSCs, we treated Hmgb3(-/Y) mice with 5-fluorouracil. Hmgb3(-/Y) mice exhibit a faster recovery of functional HSCs after administration of 5-fluorouracil compared with wild-type mice, which may be due to the increased Wnt signaling. Furthermore, the recovery of HSC number in Hmgb3(-/Y) mice occurs more rapidly than CLP and CMP recovery. From these data, we propose a model in which Hmgb3 is required for the proper balance between HSC self-renewal and differentiation. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Bodine, DM (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. EM tedyaz@nhgri.nih.gov NR 28 TC 47 Z9 48 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 2006 VL 103 IS 37 BP 13783 EP 13788 DI 10.1073/pnas.0604006103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086BO UT WOS:000240648300043 PM 16945912 ER PT J AU Enquist, IB Nilsson, E Ooka, A Mansson, JE Olsson, K Ehinger, M Brady, RO Richter, J Karlsson, S AF Enquist, Ida Berglin Nilsson, Eva Ooka, Andreas Mansson, Jan-Eric Olsson, Karin Ehinger, Mats Brady, Roscoe O. Richter, Johan Karlsson, Stefan TI Effective cell and gene therapy in a murine model of Gaucher disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEMATOPOIETIC STEM-CELLS; HUMAN GLUCOCEREBROSIDASE GENE; BONE-MARROW TRANSPLANTATION; ENZYME REPLACEMENT THERAPY; ACID BETA-GLUCOSIDASE; IN-VIVO; N-BUTYLDEOXYNOJIRIMYCIN; RETROVIRAL VECTOR; MEDIATED TRANSFER; MOUSE MODEL AB Gaucher disease (GD) is a lysosomal storage disorder due to an inherited deficiency in the enzyme glucosylceramidase (GCase) that causes hepatosplenomegaly, cytopenias, and bone disease as key clinical symptoms. Previous mouse models with GCase deficiency have been lethal in the perinatal period or viable without displaying the clinical features of GD. We have generated viable mice with characteristic clinical symptoms of type 1 GD by conditionally deleting GCase exons 9-11 upon postnatal induction. Both transplantation of WT bone marrow (BM) and gene therapy through retroviral transduction of BM from GD mice prevented development of disease and corrected an already established GD phenotype. The gene therapy approach generated considerably higher GCase activity than transplantation of WT BM. Strikingly, both therapeutic modalities normalized glucosylceramide levels and practically no infiltration of Gaucher cells could be observed in BM, spleen, and liver, demonstrating correction at 5-6 months after treatment. The findings demonstrate the feasibility of gene therapy for type 1 GD in vivo. Our type 1 GD mice will serve as an excellent tool in the continued efforts toward development of safe and efficient cell and gene therapy for type 1 GD. C1 Lund Univ, Inst Lab Med, Dept Mol Med & Gene Therapy, S-22184 Lund, Sweden. Lund Univ, Lund Strateg Res Ctr Stem Cell Biol & Cell Therap, S-22184 Lund, Sweden. Univ Lund Hosp, Dept Pathol, S-22100 Lund, Sweden. Sahlgrens Univ Hosp, Inst Clin Neurosci, S-43180 Molndal, Sweden. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), Lund Univ, Inst Lab Med, Dept Mol Med & Gene Therapy, BMC A12, S-22184 Lund, Sweden. EM bradyr@ninds.nih.gov; stefan.karlsson@med.lu.se NR 39 TC 58 Z9 63 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 2006 VL 103 IS 37 BP 13819 EP 13824 DI 10.1073/pnas.0606016103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086BO UT WOS:000240648300049 PM 16954197 ER PT J AU van Zandbergen, G Bollinger, A Wenzel, A Kamhawi, S Voll, R Klinger, M Muller, A Holscher, C Herrmann, M Sacks, D Solbach, W Laskay, T AF van Zandbergen, Ger Bollinger, Annalena Wenzel, Alexander Kamhawi, Shaden Voll, Reinhard Klinger, Matthias Mueller, Antje Hoelscher, Christoph Herrmann, Martin Sacks, David Solbach, Werner Laskay, Tamas TI Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; immune evasion; neutrophils; parasitic-protozoan; phosphatidyl serine ID PROGRAMMED CELL-DEATH; PROTOZOAN PARASITE LEISHMANIA; ANNEXIN-V; IN-VITRO; MAJOR INFECTION; TGF-BETA; MACROPHAGES; PROTEIN; SURFACE; PHOSPHATIDYLSERINE AB The obligate intracellular pathogen Leishmania major survives and multiplies in professional phagocytes. The evasion strategy to circumvent killing by host phagocytes and establish a productive infection is poorly understood. Here we report that the virulent inoculum of Leishmania promastigotes contains a high ratio of annexin A5-binding apoptotic parasites. This subpopulation of parasites is characterized by a round body shape, a swollen kinetoplast, nuclear condensation, and a lack of multiplication and represents dying or already dead parasites. After depleting the apoptotic parasites from a virulent population, Leishmania do not survive in phagocytes in vitro and lose their disease-inducing ability in vivo. TGF-beta induced by apoptotic parasites is likely to mediate the silencing of phagocytes and lead to survival of infectious Leishmania populations. The data demonstrate that apoptotic promastigotes, in an altruistic way, enable the intracellular survival of the viable parasites. C1 Univ Lubeck, Inst Med Microbiol & Hyg, D-23538 Lubeck, Germany. Univ Lubeck, Inst Anat, D-23538 Lubeck, Germany. Univ Lubeck, Inst Clin Rheumatol, D-23538 Lubeck, Germany. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Clin Immunol & Rheumatol, D-91054 Erlangen, Germany. Res Ctr, D-23845 Borstel, Germany. RP van Zandbergen, G (reprint author), Univ Lubeck, Inst Med Microbiol & Hyg, D-23538 Lubeck, Germany. EM zandbergen@uni-luebeck.de RI Solbach, Werner/F-9217-2012; Laskay, Tamas/E-9190-2013; van Zandbergen, Ger/M-1571-2013; herrmann, martin/A-9597-2013; Solbach, Werner/O-8582-2015 OI Laskay, Tamas/0000-0002-4212-8366; herrmann, martin/0000-0002-0258-2484; Solbach, Werner/0000-0002-3608-8652 NR 39 TC 116 Z9 121 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 2006 VL 103 IS 37 BP 13837 EP 13842 DI 10.1073/pnas.0600843103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086BO UT WOS:000240648300052 PM 16945916 ER PT J AU Merritt, M Grady, C AF Merritt, Maria Grady, Christine TI Reciprocity and post-trial access for participants in antiretroviral therapy trials SO AIDS LA English DT Review DE bioethical issues; antiretroviral therapy; research subjects; clinical trials; developing countries ID HIV/AIDS C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Phoebe R berman Bioeth Inst, Baltimore, MD USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Merritt, M (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. EM mmerritt@jhsph.edu NR 16 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 11 PY 2006 VL 20 IS 14 BP 1791 EP 1794 DI 10.1097/01.aids.0000244197.88134.45 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 092BK UT WOS:000241071800001 PM 16954719 ER PT J AU Aweeka, FT Rosenkranz, SL Segal, Y Coombs, RW Bardeguez, A Thevanayagam, L Lizak, P Aberg, J Watts, DH AF Aweeka, Francesca T. Rosenkranz, Susan L. Segal, Yoninah Coombs, Robert W. Bardeguez, Arlene Thevanayagam, Lourdes Lizak, Patricia Aberg, Judith Watts, D. Heather CA NIAID AIDS Clinical Trials Grp TI The impact of sex and contraceptive therapy on the plasma and intracellular pharmacokinetics of zidovudine SO AIDS LA English DT Article DE zidovudine; intracellular triphosphates; female sex; contraceptive therapy; pharmacokinetics ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; HIV-INFECTED PATIENTS; GENITAL-TRACT; TRIPHOSPHATE; STEROIDS; GENDER; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHOSPHORYLATION; METABOLISM AB Objectives: Zidovudine remains part of combination antiretroviral therapy. Pharmacological studies rely on quantitation of active triphosphates in peripheral blood mononuclear cells. This study evaluated the impact of female sex and contraceptive therapy on zidovudine plasma and intracellular pharmacokinetics and the impact of contraceptive therapy on HIV viral load. Methods: Serial plasma and intracellular zidovudine pharmacokinetics following oral and intravenous dosing were determined in 18 men and 20 women treated with zidovudine. Women could repeat pharmacokinetics assessment following 2 months oral or injectable contraceptive therapy. Zidovudine plasma and intracellular mono-, di- and triphosphate concentrations were determined by liquid chromatography tandem mass spectrometry. Plasma and cervical viral loads were determined preceding and following 2 months of contraceptive therapy in women. Results: Men exhibited higher area under the concentration versus time curve for intracellular zidovudine and zidovudine-monophosphate following oral and intravenous dosing and higher zidovudine triphosphate following oral dosing. There was no difference between men and women in plasma zidovudine parameters. Furthermore, contraceptive therapy had no effect on zidovudine plasma or intracellular pharmacokinetics or on plasma or cervical HIV-1 RNA levels. Conclusions: Using an optimized pharmacokinetic design, this study indicated men exhibit significantly higher zidovudine-monophosphate and zidovudine-triphosphate exposure following zidovudine oral administration, having implications for drug toxicity and overall tolerance of zidovudine therapy. The lack of an effect of contraceptive therapy on zidovudine pharmacokinetics is surprising in light of previous pharmacokinetic studies for drugs eliminated primarily through glucuronidation. Contraceptive therapy had no effect on plasma or cervical viral load, results consistent with previous findings. (c) 2006 Lippincott Williams & Wilkins. C1 Univ Calif San Francisco, Drug Res Unit, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Univ Med & Dent New Jersey, Newark, NJ USA. Washington Univ, Sch Med, St Louis, MO USA. NICHD, NIH, Rockville, MD USA. RP Aweeka, FT (reprint author), Univ Calif San Francisco, Drug Res Unit, 521 Parnassus Ave, San Francisco, CA 94143 USA. EM faweeka@sfghsom.ucsf.edu FU NIAID NIH HHS [AI34832, AI27665, AI27663, P30 AI027763, AI27664, AI25868, AI38858] NR 30 TC 23 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 11 PY 2006 VL 20 IS 14 BP 1833 EP 1841 DI 10.1097/01.aids.0000244202.18629.36 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 092BK UT WOS:000241071800006 PM 16954724 ER PT J AU Bennion, BJ Kulp, KS Montgomery, JL Lightstone, FC Knize, MG Bennett, LM Felton, JS AF Bennion, Brian J. Kulp, Kristen S. Montgomery, Jennifer L. Lightstone, Felice C. Knize, Mark G. Bennett, L. Michelle Felton, James S. TI Computational characterization and prediction of estrogen receptor coactivator binding inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bennion, Brian J.; Kulp, Kristen S.; Montgomery, Jennifer L.; Lightstone, Felice C.; Knize, Mark G.; Felton, James S.] Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA 94550 USA. [Bennett, L. Michelle] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 8-COMP BP 12 EP 12 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604009 ER PT J AU Chaka, AM Bayly, CI Brown, S Collins, JR Gilson, MK Head, MS Kapur, AJO Merz, KM Muchmore, SW Nicholls, A Ravichandran, S Roitberg, AE Schwarz, FP Webb, SP AF Chaka, Anne M. Bayly, Christopher I. Brown, Scott Collins, Jack R. Gilson, Michael K. Head, Martha S. Kapur, A. Jayne Oliver Merz, Kenneth M., Jr. Muchmore, Steven W. Nicholls, Anthony Ravichandran, Sarangan Roitberg, Adrian E. Schwarz, Frederick P. Webb, Simon P. TI Workshop report on validating modeling and experimental methods to enable drug discovery SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chaka, Anne M.; Kapur, A. Jayne Oliver; Schwarz, Frederick P.] NIST, Phys & Chem Properties Div, Gaithersburg, MD 20899 USA. [Bayly, Christopher I.] Merck Frosst Ctr Therapeut Res, Dept Med Chem, Kirkland, PQ H9H 3L1, Canada. [Brown, Scott; Muchmore, Steven W.] Abbott Labs, Dept R42T, Abbott Pk, IL 60064 USA. [Brown, Scott; Muchmore, Steven W.] Abbott Labs, Dept R46Y, Abbott Pk, IL 60064 USA. [Collins, Jack R.] NCI Frederick, Adv Biomed Comp Ctr, SAIC, Frederick, MD 21702 USA. [Gilson, Michael K.] Univ Maryland, Ctr Adv Res Biotechnol, Inst Biotechnol, Rockville, MD 20850 USA. [Head, Martha S.] GlaxoSmithKline Inc, Computat Analyt & Struct Sci, Div Res & Dev, Collegeville, PA 19426 USA. [Merz, Kenneth M., Jr.] Univ Florida, Dept Chem, Gainesville, FL 32611 USA. [Merz, Kenneth M., Jr.] Univ Florida, Quantum Theory Project, Gainesville, FL 32611 USA. [Nicholls, Anthony] OpenEye Sci Software Inc, Santa Fe, NM 87507 USA. [Ravichandran, Sarangan] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 323-COMP BP 24 EP 24 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604021 ER PT J AU Woodcock, HL Brooks, BR AF Woodcock, H. Lee, III Brooks, Bernard R. TI Development and application of CHARMM's hybrid QM/MM reaction path methods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Woodcock, H. Lee, III; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RI Woodc, Henry/D-9275-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 131-COMP BP 44 EP 44 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604040 ER PT J AU Peach, ML Nicklaus, MC AF Peach, Megan L. Nicklaus, Marc C. TI Combining docking and pharmacophore filtering methods for improved virtual screening SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Peach, Megan L.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Nicklaus, Marc C.] NCI, Med Chem Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 355-COMP BP 58 EP 58 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604054 ER PT J AU Bolton, E AF Bolton, Evan TI Intramural research at the National Center for Biotechnology Information SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bolton, Evan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 12-COMP BP 68 EP 68 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604064 ER PT J AU Wehrle, JP AF Wehrle, Janna P. TI Guiding health science - and having fun! SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wehrle, Janna P.] Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 11-COMP BP 89 EP 89 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604085 ER PT J AU Weidlich, IE Nicklaus, MC AF Weidlich, Iwona E. Nicklaus, Marc C. TI Conformational energy of bioactive ligand-protein complexes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Weidlich, Iwona E.; Nicklaus, Marc C.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Weidlich, Iwona E.] Univ Med Sci, Fac Pharm, Poznan, Poland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 219-COMP BP 151 EP 151 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604147 ER PT J AU Hassan, SA AF Hassan, Sergio A. TI Electrostatic and solvent-structure forces in molecular interactions: Competition of forces in solution and semi-continuum representation of solvent-induced forces SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hassan, Sergio A.] NIH, Ctr Mol Modeling, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 26-COMP BP 195 EP 195 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604191 ER PT J AU Tikhonova, I Sum, CS Childress, J Neumann, S Thomas, CJ Raaka, BM Costanzi, S Gershengorn, MC AF Tikhonova, Irina Sum, Chi Shing Childress, John Neumann, Susanne Thomas, Craig J. Raaka, Bruce M. Costanzi, Stefano Gershengorn, Marvin C. TI Bi-directional, iterative approach to the structural determination of the binding site of anti-diabetic drugs at GPR40 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tikhonova, Irina; Costanzi, Stefano] NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. [Sum, Chi Shing; Childress, John; Neumann, Susanne; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Thomas, Craig J.] NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 206-COMP BP 215 EP 215 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604211 ER PT J AU Abashkin, YG Burt, SK AF Abashkin, Yuri G. Burt, Stanley K. TI Mechanism-based tuning of the desired properties of biomimetics: (Salen)Mn biomimetic compounds as therapeutic agents and synthetic catalysts SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Abashkin, Yuri G.; Burt, Stanley K.] NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 250-COMP BP 313 EP 313 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604309 ER PT J AU Deflorian, F Costanzi, S Neumann, S Engel, S Jiang, JK Thomas, CJ Raaka, BM Gershengorn, MC AF Deflorian, Francesca Costanzi, Stefano Neumann, Susanne Engel, Stanislav Jiang, Jian-Kang Thomas, Craig J. Raaka, Bruce M. Gershengorn, Marvin C. TI Molecular modeling study of TRH-R1 and TRH-R2 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Deflorian, Francesca; Costanzi, Stefano] NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. [Neumann, Susanne; Engel, Stanislav; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Jiang, Jian-Kang; Thomas, Craig J.] NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 259-COMP BP 340 EP 340 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604336 ER PT J AU Liu, J Nussinov, R AF Liu, Jin Nussinov, Ruth TI Homology modeling and molecular dynamics simulations of BRCA1 BRCT domain bound to p53 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Liu, Jin; Nussinov, Ruth] NCI, SAIC, Basic Res Program, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 361-COMP BP 401 EP 401 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604397 ER PT J AU Chacko, G AF Chacko, George TI Peer review at the National Institutes of Health SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chacko, George] NIH, Ctr Sci Review, Bethesda, MD 20817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 10-COMP BP 405 EP 405 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604401 ER PT J AU O'Brien, EP Brooks, BR Thirumalai, D AF O'Brien, Edward P., Jr. Brooks, Bernard R. Thirumalai, D. TI Macromolecular crowding destabilizes ordered oligomers of an amyloidogenic peptide SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [O'Brien, Edward P., Jr.; Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. [Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Thirumalai, D.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RI O'Brien, Edward/C-3587-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 385-COMP BP 418 EP 418 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604414 ER PT J AU Koivunen, ME Dettmer, K Vermeulen, R Bakke, B Gee, SJ Hammock, BD AF Koivunen, Marja E. Dettmer, Katja Vermeulen, Roel Bakke, Berit Gee, Shirley J. Hammock, Bruce D. TI Assessment of an improved enzyme-linked immunosorbent assay (ELISA) and a novel LC-MS method for urinary atrazine mercapturate analysis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Koivunen, Marja E.] Antibodies Inc, Davis, CA 95617 USA. [Dettmer, Katja] Univ Regensburg, Inst Funct Genom, D-93053 Regensburg, Germany. [Vermeulen, Roel] NCI, Div Canc Epidemiol, NIH, Rockville, MD USA. [Bakke, Berit] Natl Inst Occupat Hlth, Oslo, Norway. [Gee, Shirley J.; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Hammock, Bruce D.] Univ Calif Davis, Canc Res Ctr, Davis, CA 95616 USA. RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 224-AGRO BP 448 EP 448 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600391 ER PT J AU Rahman, M Kelley, VR Sutter, CH Emmert, GL Strickland, PT Bell, DA Sutter, TR AF Rahman, Mostafizur Kelley, Victor R. Sutter, Carrie Hayes Emmert, Gary L. Strickland, Paul T. Bell, Douglas A. Sutter, Thomas R. TI Functional analysis of polymorphic CYP1B1 allelic variants in African-Americans and their effects on the metabolism of (-)-benzo[a]pyrene-trans-7,8-dihydrodiol (B[a]P-7,8-diol) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sutter, Thomas R.] Univ Memphis, Dept Chem, Dept Biol, W Harry Feinstone Ctr Genom Res, Memphis, TN 38152 USA. [Strickland, Paul T.] Johns Hopkings Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Bell, Douglas A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 222-BIOL BP 842 EP 842 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600745 ER PT J AU Herzberg, O Lim, K Teplyakov, A Reddy, P Peterkofsky, A Dunaway-Mariano, D AF Herzberg, Osnat Lim, Kap Teplyakov, Alexey Reddy, Prasad Peterkofsky, Alan Dunaway-Mariano, Debra TI BIOL 75-Swiveling mechanism in phosphotransfer reactions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Herzberg, Osnat; Lim, Kap; Teplyakov, Alexey] Univ Maryland, Ctr Adv Res Biotechnol, Inst Biotechnol, Rockville, MD 20850 USA. [Reddy, Prasad] NIST, Gaithersburg, MD 20899 USA. [Peterkofsky, Alan] NHLBI, Cell Biol Lab, Bethesda, MD USA. [Dunaway-Mariano, Debra] Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 75-BIOL BP 889 EP 889 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600792 ER PT J AU Sucato, CA Upton, TG Kashemirov, BA McKenna, CE Warshel, A Florian, J Wilson, SH Goodman, MF AF Sucato, Christopher A. Upton, Thomas G. Kashemirov, Boris A. McKenna, Charles E. Warshel, Arieh Florian, Jan Wilson, Samuel H. Goodman, Myron F. TI BIOL 237 - Leaving-group substituent effects on DNA polymerase beta catalysis and fidelity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sucato, Christopher A.; Upton, Thomas G.; Kashemirov, Boris A.; McKenna, Charles E.; Warshel, Arieh; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Florian, Jan] Loyola Univ Chicago, Dept Chem, Chicago, IL 60626 USA. [Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RI Upton, Thomas/E-3749-2012; OI Florian, Jan/0000-0003-2669-4293 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 237-BIOL BP 933 EP 933 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600836 ER PT J AU Guo, H Guo, HB Xu, Q Wlodawer, A AF Guo, Hong Guo, Haobo Xu, Qin Wlodawer, Alex TI BIOL 282 - Understanding general acid-base catalysis of enzyme-catalyzed reactions from computer simulations: Serine-carboxyl peptidases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Guo, Hong; Guo, Haobo; Xu, Qin] Univ Tennessee, Dept Biocehmistry & Cellular & Mol Biol, Knoxville, TN 37996 USA. [Wlodawer, Alex] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RI Guo, Hao-Bo/B-7486-2009 OI Guo, Hao-Bo/0000-0003-1321-1758 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 282-BIOL BP 947 EP 947 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600850 ER PT J AU Dudko, OK Hummer, G Szabo, A AF Dudko, Olga K. Hummer, Gerhard Szabo, Attila TI BIOL 36 - Intrinsic rates and activation free energies from single-molecule pulling experiments SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Dudko, Olga K.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Hummer, Gerhard; Szabo, Attila] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 36-BIOL BP 950 EP 950 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600853 ER PT J AU Adachi, H Palaniappan, KK Gao, ZG Jacobson, KA AF Adachi, Hayamitsu Palaniappan, Krishnan K. Gao, Zhan-Guo Jacobson, Kenneth A. TI MEDI 437-Structure-activity relationships of 2, N6, 5'-substituted adenosine derivatives as human A2B adenosine receptor agonists SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Adachi, Hayamitsu; Palaniappan, Krishnan K.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 437-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607233 ER PT J AU Barchi, JJ AF Barchi, Joseph J., Jr. TI FLUO 20-Structural studies of biologically interesting fluorinated nucleosides SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Barchi, Joseph J., Jr.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 20-FLUO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781602839 ER PT J AU Bax, A AF Bax, Ad TI ANYL 38-Weak alignment: A new dimension in NMR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bax, Ad] NIH, Chem Phys Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 38-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601189 ER PT J AU Becker, ED AF Becker, Edwin D. TI ANYL 35-Advances in NMR over a half-century SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Becker, Edwin D.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 35-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601297 ER PT J AU Bewley, CA Hussan, S Williams, D Cai, ML AF Bewley, Carole A. Hussan, Syed Williams, David Cai, Mengli TI CARB 32-Blocking HIV-1 entry and other lessons learned from novel cyanobacterial proteins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bewley, Carole A.; Hussan, Syed; Williams, David; Cai, Mengli] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 32-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781602080 ER PT J AU Bolton, E AF Bolton, Evan TI CINF 1-PubChem: An information resource linking chemistry and biology SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bolton, Evan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 1-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603028 ER PT J AU Bratko, D Cellmer, T Prausnitz, JM Blanch, HW AF Bratko, Dusan Cellmer, Troy Prausnitz, John M. Blanch, Harvey W. TI BIOT 196-Effect of single point mutations on the aggregation propensity of a model protein SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bratko, Dusan] Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA. [Bratko, Dusan] Univ Calif, Dept Chem Engn, Richmond, VA 23284 USA. [Cellmer, Troy] NIH, Chem Phys Lab, Bethesda, MD 20892 USA. [Prausnitz, John M.; Blanch, Harvey W.] Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA. [Prausnitz, John M.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Chem Sci, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 196-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601739 ER PT J AU Brooks, BR Zheng, WJ AF Brooks, Bernard R. Zheng, Wenjun TI PHYS 602-Development of new multi-scale methods for examining macromolecular systems SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Brooks, Bernard R.; Zheng, Wenjun] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 602-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609523 ER PT J AU Cai, LS Innis, RB Pike, VW AF Cai, Lisheng Innis, Robert B. Pike, Victor W. TI MEDI 506-Binding sites identification of Abeta-amyloid plaques in Alzheimer's disease based on small molecule ligands SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Cai, Lisheng; Pike, Victor W.] NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 506-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607464 ER PT J AU Chen, JY Nikolovska-Coleska, Z Gomez, C Yang, CY Gao, W Krajewski, K Jiang, S Roller, P Wang, SM AF Chen, Jianyong Nikolovska-Coleska, Zaneta Gomez, Cindy Yang, Chao-Yie Gao, Wei Krajewski, Krzysztof Jiang, Sheng Roller, Peter Wang, Shaomeng TI MEDI 124-Design and synthesis of potent small-molecule inhibitors of Stat-3 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chen, Jianyong; Nikolovska-Coleska, Zaneta; Gomez, Cindy; Yang, Chao-Yie; Gao, Wei; Wang, Shaomeng] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Krajewski, Krzysztof; Jiang, Sheng; Roller, Peter] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 124-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607468 ER PT J AU Cherukuri, MK Subramanian, S Mitchell, JB AF Cherukuri, Murali Krishna Subramanian, Sankaran Mitchell, James B. TI NUCL 96-In vivo imaging of oxygen using Overhauser enhanced MRI: Applications to small animal imaging research and clinical oncology SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Cherukuri, Murali Krishna; Subramanian, Sankaran; Mitchell, James B.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 96-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781605418 ER PT J AU Childers, ML Bishwokarma, B Brechbiel, MW Park, G Rheingold, AL Planalp, RP AF Childers, Matt L. Bishwokarma, Bimjhana Brechbiel, Martin W. Park, Gyungse Rheingold, Arnold L. Planalp, Roy P. TI INOR 666-Evaluation of substituent effects in four- and six-coordinate aminopyridyl metal chelators SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Childers, Matt L.; Bishwokarma, Bimjhana; Park, Gyungse; Planalp, Roy P.] Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. [Brechbiel, Martin W.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rheingold, Arnold L.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 666-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607725 ER PT J AU Chong, HS Le, T Bui, P Ma, X Birch, N Brechbiel, MW Venkatasubramanian, PN AF Chong, Hyun-Soon Le, Thien Bui, Phuong Ma, Xiang Birch, Noah Brechbiel, Martin W. Venkatasubramanian, Palamadai N. TI NUCL 97-Novel bimodal ligand-based MRI contrast enhancement agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chong, Hyun-Soon; Le, Thien; Bui, Phuong; Ma, Xiang; Birch, Noah] IIT, Dept Biol, Chicago, IL 60616 USA. [Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, CCR, Bethesda, MD 20892 USA. [Venkatasubramanian, Palamadai N.] Northwestern Univ, Ctr MR Res, ENH Res Inst, Chicago, IL 60208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 97-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781605439 ER PT J AU Costanzi, S Ohno, M Roh, EJ Joshi, BV Colson, AO Houston, D Maddileti, S Harden, TK Jacobson, K AF Costanzi, Stefano Ohno, Michihiro Roh, Eun Joo Joshi, Bhalchandra V. Colson, Anny-Odile Houston, Dayle Maddileti, Savitri Harden, T. Kendall Jacobson, Kenneth TI MEDI 428-P2Y1 antagonists: An analysis of the structural elements of ligand recognition based on molecular docking and 3D-QSAR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Costanzi, Stefano; Colson, Anny-Odile] NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. [Ohno, Michihiro; Roh, Eun Joo; Joshi, Bhalchandra V.; Jacobson, Kenneth] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. [Houston, Dayle; Maddileti, Savitri; Harden, T. Kendall] Univ N Carolina, Sch Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 428-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607711 ER PT J AU Dandapani, S Lan, P Beeler, AB Beischel, S Abbas, A Roth, BR Porco, JA Panek, JS AF Dandapani, Sivaraman Lan, Ping Beeler, Aaron B. Beischel, Scott Abbas, Athier Roth, Bryan R. Porco, John A., Jr. Panek, James S. TI ORGN 908-Synthesis of diketopiperazines and skeletally diverse compounds using tetrahydropyridine scaffolds SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Dandapani, Sivaraman; Lan, Ping; Beeler, Aaron B.; Porco, John A., Jr.; Panek, James S.] Boston Univ, Dept Chem, Boston, MA 02135 USA. [Dandapani, Sivaraman; Lan, Ping; Beeler, Aaron B.; Porco, John A., Jr.; Panek, James S.] Boston Univ, Ctr Chem Methodol & Lib Dev CMLD BU, Boston, MA 02135 USA. [Beischel, Scott; Abbas, Athier; Roth, Bryan R.] Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. [Beischel, Scott; Abbas, Athier; Roth, Bryan R.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 908-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781608637 ER PT J AU Edidin, M Gousset, K Detre, C Gheber, L AF Edidin, Michael Gousset, Karine Detre, Cynthia Gheber, Levi TI PHYS 199-Membrane domains: Probing the floating world SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Edidin, Michael; Detre, Cynthia] Johns Hopkins Univ, Biol Johns Hopkins U, Baltimore, MD 21218 USA. [Gousset, Karine] NCI, Retroviral Replicat Lab, Frederick, MD 27102 USA. [Gheber, Levi] Ben Gurion Univ Negev, Dept Biotechnol Engn, IL-84105 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 199-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609284 ER PT J AU Fowler, JS Logan, J Wang, GJ Volkow, ND AF Fowler, Joanna S. Logan, Jean Wang, Gene-Jack Volkow, Nora D. TI NUCL 106-Radiotracer development for imaging studies in addiction SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Fowler, Joanna S.; Logan, Jean] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. [Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 106-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781605494 ER PT J AU Gawrisch, K Soubias, O Eldho, NV Teague, WE Feller, SE AF Gawrisch, Klaus Soubias, Olivier Eldho, Nadukkudy V. Teague, Walter E. Feller, Scott E. TI PHYS 290-Structure and dynamics of polyunsaturated hydrocarbon chains in lipid bilayers and their interaction with G-protein coupled membrane receptors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gawrisch, Klaus; Soubias, Olivier; Eldho, Nadukkudy V.; Teague, Walter E.] NIAAA, NIH, Bethesda, MD 20892 USA. [Feller, Scott E.] Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 290-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609524 ER PT J AU Gawrisch, K Soubias, O Yeliseev, AA Gaede, HC Polozov, IV Teague, WE AF Gawrisch, Klaus Soubias, Olivier Yeliseev, Alexei A. Gaede, Holly C. Polozov, Ivan V. Teague, Walter E. TI COLL 626-Nanoporous anodic aluminum oxide as substrate for functional reconstitution of G-protein coupled membrane receptors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gawrisch, Klaus; Soubias, Olivier; Yeliseev, Alexei A.; Teague, Walter E.] NIAAA, NIH, Bethesda, MD 20892 USA. [Gaede, Holly C.] Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA. [Polozov, Ivan V.] NICHD, Lab Cell & Mol Biophys, NIH, Bethesda, MD 20892 USA. RI Gaede, Holly/B-7392-2015 OI Gaede, Holly/0000-0003-4444-4394 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 626-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603618 ER PT J AU Gonzalez, FJ Idle, JR AF Gonzalez, Frank J. Idle, Jeffrey R. TI TOXI 110-Mouse metabolomics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. [Idle, Jeffrey R.] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 110-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609716 ER PT J AU Gopich, I Szabo, A AF Gopich, Irina Szabo, Attila TI PHYS 583-Theory of the statistics of kinetic transitions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gopich, Irina; Szabo, Attila] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 583-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609515 ER PT J AU Horkay, F Lin, DC Dimitriadis, EK Horkayne-Szakaly, I Basser, PJ AF Horkay, Ferenc Lin, David C. Dimitriadis, Emilios K. Horkayne-Szakaly, Iren Basser, Peter J. TI BIOT 374-Comprehensive analysis of the swelling and biomechanical properties of tissue engineered cartilage SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Horkay, Ferenc; Lin, David C.; Horkayne-Szakaly, Iren; Basser, Peter J.] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Dimitriadis, Emilios K.] NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 374-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601544 ER PT J AU Horkay, F AF Horkay, Ferenc TI POLY 274-Osmotic and structural properties of biopolymer solutions and gels SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Horkay, Ferenc] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 274-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DC UT WOS:000207781701026 ER PT J AU Jiang, S Li, P Peach, ML Fisher, RJ Nicklaus, MC Roller, PP AF Jiang, Sheng Li, Peng Peach, Megan L. Fisher, Robert J. Nicklaus, Marc C. Roller, Peter P. TI MEDI 527-Potent antagonists of the Grb2-SH2 domain: Not relying on phosphotyrosine mimics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Jiang, Sheng; Li, Peng; Nicklaus, Marc C.; Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Peach, Megan L.] NCI, Basic Res Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. [Fisher, Robert J.] SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 527-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607363 ER PT J AU Kang, JH Peach, ML Pu, YM Blumberg, PM Marquez, VE AF Kang, Ji-Hye Peach, Megan L. Pu, Yongmei Blumberg, Peter M. Marquez, Victor E. TI MEDI 179-Site-directed mutagenesis of the C1b domain of protein kinase C (PKC) delta provides a unique platform for the development of selective ligands for the atypical PKC zeta SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kang, Ji-Hye; Marquez, Victor E.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Peach, Megan L.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Pu, Yongmei; Blumberg, Peter M.] NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 179-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607232 ER PT J AU Ko, HJ Fricks, I Ivanov, AA Harden, TK Jacobson, KA AF Ko, Hyojin Fricks, Ingrid Ivanov, Andrei A. Harden, T. Kendall Jacobson, Kenneth A. TI MEDI 438-Structure activity relationship of uridine 5'-diphosphoglucose (UDP-glucose) analogs at the human P2Y14 receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Ko, Hyojin; Ivanov, Andrei A.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. [Fricks, Ingrid; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 438-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607360 ER PT J AU Krajewski, K Nikolovska-Coleska, Z Wang, SM Roller, PP AF Krajewski, Krzysztof Nikolovska-Coleska, Zaneta Wang, Shaomeng Roller, Peter P. TI MEDI 93-MDM2 inhibitory peptides: Side chains cyclization as a method of stabilization of the biologically active helical conformation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Krajewski, Krzysztof; Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Nikolovska-Coleska, Zaneta; Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Nikolovska-Coleska, Zaneta; Wang, Shaomeng] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Nikolovska-Coleska, Zaneta; Wang, Shaomeng] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Nikolovska-Coleska, Zaneta; Wang, Shaomeng] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 93-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607222 ER PT J AU Li, J Wang, L Hashimoto, Y Tsao, CY Wood, TK Valdes, JJ Zafiriou, E Bentley, WE AF Li, Jun Wang, Liang Hashimoto, Yoshifumi Tsao, Chen-Yu Wood, Thomas K. Valdes, James J. Zafiriou, Evanghelos Bentley, William E. TI BIOT 91-A stochastic model of E. coli AI-2 quorum sensing circuit reveals alternative synthesis pathways SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Li, Jun; Zafiriou, Evanghelos] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Wang, Liang] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Hashimoto, Yoshifumi] Univ Maryland, Inst Biotechnol, CBR, College Pk, MD 20742 USA. [Tsao, Chen-Yu] Univ Maryland, Dept Chem Engn, UMBI, Ctr Biosyst Res, College Pk, MD 20742 USA. [Wood, Thomas K.] Texas A&M Univ, Artie McFerrin Dept Chem Engn, College Stn, TX 77843 USA. [Wood, Thomas K.] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. [Wood, Thomas K.] Texas A&M Univ, Dept Civil Environm Engn, College Stn, TX 77843 USA. [Valdes, James J.] USA, Mol Engn Team, Edgewood Chem Biol Ctr, Aberdeen Proving Ground, MD USA. [Bentley, William E.] Univ Maryland, Dept Chem & Biomol Engn, Ctr Biosyst Res, UMBI, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 91-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601664 ER PT J AU Liao, CZ Karki, RG Nicklaus, MC AF Liao, Chenzhong Karki, Rajeshri G. Nicklaus, Marc C. TI MEDI 246-Virtual screening application of a model of full-length HIV-1 integrase complexed with viral DNA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nicklaus, Marc C.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 246-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607359 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, Jennifer TI PHYS 108-Deciphering protein turnover, topology and transport in living cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lippincott-Schwartz, Jennifer] NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 108-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609616 ER PT J AU Liu, F Stephen, AG Adamson, C Freed, EO Fisher, RJ Burke, TR AF Liu, Fa Stephen, Andrew G. Adamson, Catherine Freed, Eric O. Fisher, Robert J. Burke, Terrence R., Jr. TI MEDI 243-Hydrazone amides as novel peptoid surrogates for expedited library synthesis: Application to the preparation of TSG101-directed HIV-1 budding antagonists SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Liu, Fa; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Stephen, Andrew G.; Fisher, Robert J.] SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. [Freed, Eric O.; Fisher, Robert J.] HIV Drug Resistance Program, Retroviral Replicat Lab, Virus Cell Interact Sect, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 243-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607436 ER PT J AU Manimala, JC Roach, T Li, ZT Gildersleeve, JC AF Manimala, Joseph C. Roach, Tim Li, Zhitao Gildersleeve, Jeffrey C. TI MEDI 51-Development of a novel carbohydrate microarray and its application in cancer diagnostics and therapeutics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Manimala, Joseph C.; Roach, Tim; Li, Zhitao; Gildersleeve, Jeffrey C.] NCI, Med Chem Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 51-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607224 ER PT J AU Martin, SE Jones, TL Caplen, NJ AF Martin, Scott E. Jones, Tamara L. Caplen, Natasha J. TI MEDI 41-Applications of RNAi against cancer-associated genes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Martin, Scott E.; Jones, Tamara L.; Caplen, Natasha J.] NCI, Gene Silencing Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 41-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607320 ER PT J AU Mihailescu, M Gawrisch, K Worcester, DL AF Mihailescu, Mihaela Gawrisch, Klaus Worcester, David L. TI PHYS 490-In-depth structure of polyunsaturated lipid bilayers important for Rhodopsin function: A neutron diffraction study SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Mihailescu, Mihaela] Univ Calif Irvine, Dept Physiol & Biophys, Gaithersburg, MD 20899 USA. [Mihailescu, Mihaela] NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 20892 USA. [Worcester, David L.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 490-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609465 ER PT J AU Miller, LH Mayer, DCG Jiang, LB Gowda, DC AF Miller, Louis H. Mayer, D. C. Ghislaine Jiang, Lubin Gowda, D. Channe TI CARB 33-The glycobiology of host receptors for blood stage malarial parasites SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Miller, Louis H.; Jiang, Lubin] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Gowda, D. Channe] Penn State Univ, Dept Biochem & Mol Biol, Coll Med, Hershey, PA 17033 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 33-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781602077 ER PT J AU Morrell, A Kohlhagen, G Antony, S Pommier, Y Cushman, M AF Morrell, Andrew Kohlhagen, Glenda Antony, Smitha Pommier, Yves Cushman, Mark TI MEDI 282-A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Morrell, Andrew; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Morrell, Andrew; Cushman, Mark] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. [Kohlhagen, Glenda; Antony, Smitha; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 282-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607722 ER PT J AU Nelson, ME Padia, JK Zuck, KM Inglese, J Austin, CP AF Nelson, Michael E. Padia, Janak K. Zuck, Karim M. Inglese, James Austin, Christopher P. TI MEDI 176-Parallel synthesis and high-throughput solubility determination of NCGC produced libraries: Models for probe development SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nelson, Michael E.; Padia, Janak K.; Zuck, Karim M.; Inglese, James; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, NCGC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 176-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607223 ER PT J AU Nicklaus, MC Sitzmann, M Filippov, IV Ihlenfeldt, WD AF Nicklaus, Marc C. Sitzmann, Markus Filippov, Igor V. Ihlenfeldt, Wolf-Dietrich TI CINF 42-Rapid structure lookup and distributed substructure searches in very large databases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nicklaus, Marc C.; Sitzmann, Markus; Filippov, Igor V.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Ihlenfeldt, Wolf-Dietrich] Xemistry GmbH, D-35094 Lahntal, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 42-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603064 ER PT J AU Planalp, RP Lu, GA Kennedy, DP Brechbiel, MW Rogers, RD Ma, R Torti, FM Torti, SV AF Planalp, Roy P. Lu, Giang Kennedy, Daniel P. Brechbiel, M. W. Rogers, Robin D. Ma, Rong Torti, Frank M. Torti, Suzy V. TI MEDI 260-The metal-complexation properties of cytotoxic tripodal hexadentate chelators: Effects of heterocycle donor arms on Fe(II) chelation and fibroblast IC50 value SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Planalp, Roy P.; Kennedy, Daniel P.] Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. [Lu, Giang] NCI, NIH, Bethesda, MD 20892 USA. [Brechbiel, M. W.] NCI, Radioimmune & Inorgan Chem Sect, ROB, DCS,NIH, Bethesda, MD 20892 USA. [Rogers, Robin D.] Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. [Rogers, Robin D.] Univ Alabama, Ctr Green Mfg, Tuscaloosa, AL 35487 USA. [Ma, Rong; Torti, Suzy V.] Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 USA. [Torti, Frank M.] Wake Forest Univ Hlth Sci, Dept Canc Biol, Winston Salem, NC 27157 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 260-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607547 ER PT J AU Pohl, LR AF Pohl, Lance R. TI TOXI 23-Role of reactive metabolites and other risk factors in determining susceptibility to drug-induced liver disease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Pohl, Lance R.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 23-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609712 ER PT J AU Polozov, IV Gawrisch, K Zimmerberg, J AF Polozov, Ivan V. Gawrisch, Klaus Zimmerberg, Joshua TI PHYS 660-NMR for detection of lipid rafts SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Polozov, Ivan V.] NICHD, Lab Cell & Mol Biophys, NIH, Bethesda, MD 20892 USA. [Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 20892 USA. [Zimmerberg, Joshua] NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 660-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609489 ER PT J AU Qin, DD Ding, K Wang, GP Nikolovska-Coleska, Z Lu, YP Qiu, S Kumar, S Gao, W Stuckey, J Krajewski, K Roller, P Wang, SM AF Qin, Dongguang Ding, Ke Wang, Guoping Nikolovska-Coleska, Zaneta Lu, Yipin Qiu, Su Kumar, Sanjeev Gao, Wei Stuckey, Jeanne Krajewski, Krzysztof Roller, Peter Wang, Shaomeng TI MEDI 94-Design, synthesis and evaluation of spirooxindoles as potent and specific non-peptide small-molecule inhibitors of the MDM2-p53 interaction SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Qin, Dongguang; Ding, Ke; Wang, Guoping; Nikolovska-Coleska, Zaneta; Lu, Yipin; Qiu, Su; Kumar, Sanjeev; Gao, Wei; Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Qin, Dongguang; Ding, Ke; Wang, Guoping; Nikolovska-Coleska, Zaneta; Lu, Yipin; Qiu, Su; Kumar, Sanjeev; Gao, Wei; Wang, Shaomeng] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Qin, Dongguang; Ding, Ke; Wang, Guoping; Nikolovska-Coleska, Zaneta; Lu, Yipin; Qiu, Su; Kumar, Sanjeev; Gao, Wei; Wang, Shaomeng] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Qin, Dongguang; Ding, Ke; Wang, Guoping; Nikolovska-Coleska, Zaneta; Lu, Yipin; Qiu, Su; Kumar, Sanjeev; Gao, Wei; Wang, Shaomeng] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. [Stuckey, Jeanne] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Krajewski, Krzysztof; Roller, Peter] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 94-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607460 ER PT J AU Rodriguez, FA Tang, YJ Sayer, JM Jerina, DM Geacintov, NE AF Rodriguez, Fabian A. Tang, Yijin Sayer, Jane M. Jerina, Donald M. Geacintov, Nicholas E. TI TOXI 51-Conformation of a 14S(-)-trans-anti-dibenzo[a,l]pyrene diol epoxide-dG adduct in an 11-mer DNA duplex investigated by NMR methods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rodriguez, Fabian A.; Tang, Yijin; Geacintov, Nicholas E.] NYU, Dept Chem, New York, NY 10003 USA. [Sayer, Jane M.; Jerina, Donald M.] NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 51-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609763 ER PT J AU Rodriguez, FA Tang, YJ Sayer, JM Jerina, DM Geacintov, NE AF Rodriguez, Fabian A. Tang, Yijin Sayer, Jane M. Jerina, Donald M. Geacintov, Nicholas E. TI TOXI 4-Mechanistic studies on the DNA cross-linking agent azinomycin B SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rodriguez, Fabian A.; Tang, Yijin; Geacintov, Nicholas E.] NYU, Dept Chem, New York, NY 10003 USA. [Sayer, Jane M.; Jerina, Donald M.] NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 51-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609738 ER PT J AU Rodriguez, FA Tang, YJ Sayer, JM Jerina, DM Geacintov, NE AF Rodriguez, Fabian A. Tang, Yijin Sayer, Jane M. Jerina, Donald M. Geacintov, Nicholas E. TI PHYS 260-Photochemical production of the Ring-closed form of N3 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rodriguez, Fabian A.; Tang, Yijin; Geacintov, Nicholas E.] NYU, Dept Chem, New York, NY 10003 USA. [Sayer, Jane M.; Jerina, Donald M.] NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 51-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609297 ER PT J AU Roth, BL AF Roth, Bryan L. TI MEDI 262-Selectively non-selective drugs ("Magic Shotguns") vs. selective drugs ("Magic Bullets") for CNS disorders SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Roth, Bryan L.] NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. [Roth, Bryan L.] CWRU Med Sch, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 262-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607664 ER PT J AU Rusling, JF Yu, X Jensen, G Gong, J Bhirde, A Munge, BS Patel, V Papadimitrakopoulos, F Kim, SN Gutkind, S AF Rusling, James F. Yu, Xin Jensen, Gary Gong, Joseph Bhirde, Ashwinkumar Munge, Bernard S. Patel, Voymesh Papadimitrakopoulos, Fotios Kim, Sang-Nyon Gutkind, Silvio TI ANYL 215-Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Papadimitrakopoulos, Fotios; Kim, Sang-Nyon] Univ Connecticut, Dept Chem, Nanomat Optoelect Lab, Polymer Program,Inst Mat Sci, Storrs, CT 06269 USA. [Munge, Bernard S.] Salve Regina Univ, Dept Chem, Newport, RI 02840 USA. [Patel, Voymesh; Gutkind, Silvio] NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 215-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601129 ER PT J AU Salnikow, K AF Salnikow, Konstantin TI TOXI 104-Metal-induced carcinogenesis: The role of ascorbate SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Salnikow, Konstantin] NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 104-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609762 ER PT J AU Sigano, DM Malolanarasimhan, K Kedei, N Lewin, NE Blumberg, PM Marquez, VE AF Sigano, Dina M. Malolanarasimhan, Krishnan Kedei, Noemi Lewin, Nancy E. Blumberg, Peter M. Marquez, Victor E. TI MEDI 173-Targeting protein kinase C (PKC) to specific cellular membrane domains with the use of DAG-lactones containing rigid oligo(p-phenylene ethynylene) acyl units SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sigano, Dina M.; Malolanarasimhan, Krishnan; Marquez, Victor E.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Kedei, Noemi; Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. RI Sigano, Dina/M-6144-2014 OI Sigano, Dina/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 173-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607236 ER PT J AU Sitzmann, M Ihlenfeldt, WD Nicklaus, MC AF Sitzmann, Markus Ihlenfeldt, Wolf-Dietrich Nicklaus, Marc C. TI CINF 59-Normalizing ionic resonance structures SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sitzmann, Markus; Nicklaus, Marc C.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Ihlenfeldt, Wolf-Dietrich] Xemistry GmbH, D-35094 Lahntal, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 59-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603045 ER PT J AU Tan, X Mizuuchi, M Mizuuchi, K AF Tan, Xin Mizuuchi, Michiyo Mizuuchi, Kiyoshi TI PHYS 335-Probing Mu transposition target complex via single-molecule TIRFM and 2P-FCS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tan, Xin; Mizuuchi, Michiyo; Mizuuchi, Kiyoshi] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 335-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609012 ER PT J AU Tang, GZ Ding, K Guo, J Nikolovska-Coleska, Z Yang, CY Wang, RX Long, JT Qiu, S Kumar, S Gao, W Stuckey, J Krajewski, K Jiang, S Roller, PP Wang, SM AF Tang, Guozhi Ding, Ke Guo, Jie Nikolovska-Coleska, Zaneta Yang, Chao Yie Wang, Renxiao Long, Jianting Qiu, Su Kumar, Sanjeev Gao, Wei Stuckey, Jeanne Krajewski, Krzysztof Jiang, Sheng Roller, Peter P. Wang, Shaomeng TI MEDI 97-Design, synthesis and evaluation of a new class of potent and cell-permeable small molecule inhibitors of Bcl-2 and Mcl-1 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tang, Guozhi; Ding, Ke; Guo, Jie; Nikolovska-Coleska, Zaneta; Yang, Chao Yie; Wang, Renxiao; Long, Jianting; Qiu, Su; Kumar, Sanjeev; Gao, Wei; Wang, Shaomeng] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Tang, Guozhi; Ding, Ke; Guo, Jie; Nikolovska-Coleska, Zaneta; Yang, Chao Yie; Wang, Renxiao; Long, Jianting; Qiu, Su; Kumar, Sanjeev; Gao, Wei; Wang, Shaomeng] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. [Ding, Ke; Nikolovska-Coleska, Zaneta; Qiu, Su; Kumar, Sanjeev; Gao, Wei; Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Stuckey, Jeanne] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Krajewski, Krzysztof; Jiang, Sheng; Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 97-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607218 ER PT J AU Tsao, CY Wang, L Yi, H Hashimoto, Y DeLisa, MP Wood, TK Valdes, JJ Bentley, WE AF Tsao, Chen-Yu Wang, Liang Yi, Hyunmin Hashimoto, Yoshifumi DeLisa, Matthew P. Wood, Thomas K. Valdes, James J. Bentley, William E. TI BIOT 2-Manipulating cells by tuning quorum signaling to enhance recombinant protein production in Escherichia coli SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tsao, Chen-Yu] Univ Maryland, Dept Chem Engn, Ctr Biosyst Res, UMBI, College Pk, MD 20742 USA. [Wang, Liang] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Yi, Hyunmin] Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. [Hashimoto, Yoshifumi] Univ Maryland, Inst Biotechnol, CBR, College Pk, MD 20742 USA. [DeLisa, Matthew P.] Cornell Univ, Sch Chem & Biomol Engn, Ithaca, NY 14853 USA. [Wood, Thomas K.] Texas A&M Univ, Artie McFerrin Dept Chem Engn, College Stn, TX 77843 USA. [Wood, Thomas K.] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. [Wood, Thomas K.] Texas A&M Univ, Dept Civil Environm Engn, College Stn, TX 77843 USA. [Valdes, James J.] USA, Engn Res & Dev Ctr, Edgewood, MD USA. [Bentley, William E.] Univ Maryland, Dept Chem & Biomol Engn, Ctr Biosyst Res, UMBI, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 2-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601673 ER PT J AU Veatch, SL Cicuta, P Gawrisch, K Keller, SL AF Veatch, Sarah L. Cicuta, Pietro Gawrisch, Klaus Keller, Sarah L. TI PHYS 15-Composition and 2D diffusion of liquid domains in lipid vesicle membranes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Veatch, Sarah L.] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z4, Canada. [Cicuta, Pietro] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England. [Cicuta, Pietro] Univ Cambridge, Nanosci Ctr, Cambridge CB3 0HE, England. [Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 20892 USA. [Keller, Sarah L.] Univ Washington, Dept Chem, Seattle, WA 98195 USA. [Keller, Sarah L.] Univ Washington, Dept Phys, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 15-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609160 ER PT J AU Wang, SM Sun, HY Lu, JF Nikolovska-Coleska, Z Qiu, S Qin, DG Peng, YF Yi, H Gao, W Yang, CY Stuckey, J Meagher, J Krajewski, K Jiang, S Roller, PP AF Wang, Shaomeng Sun, Haiying Lu, Jianfeng Nikolovska-Coleska, Zaneta Qiu, Su Qin, Dongguang Peng, Yuefeng Yi, Han Gao, Wei Yang, Chao-Yie Stuckey, Jeanne Meagher, Jennifer Krajewski, Krzysztof Jiang, Sheng Roller, Peter P. TI MEDI 17-Design of bivalent Smac mimetics as highly effective and specific apoptosis inducers in cancer cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wang, Shaomeng; Sun, Haiying; Lu, Jianfeng; Nikolovska-Coleska, Zaneta; Qiu, Su; Qin, Dongguang; Peng, Yuefeng; Yi, Han; Gao, Wei; Yang, Chao-Yie] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Wang, Shaomeng; Sun, Haiying; Lu, Jianfeng; Nikolovska-Coleska, Zaneta; Qiu, Su; Qin, Dongguang; Peng, Yuefeng; Yi, Han; Gao, Wei; Yang, Chao-Yie] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Wang, Shaomeng; Sun, Haiying; Lu, Jianfeng; Nikolovska-Coleska, Zaneta; Qiu, Su; Qin, Dongguang; Peng, Yuefeng; Yi, Han; Gao, Wei; Yang, Chao-Yie] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Wang, Shaomeng; Sun, Haiying; Lu, Jianfeng; Nikolovska-Coleska, Zaneta; Qiu, Su; Qin, Dongguang; Peng, Yuefeng; Yi, Han; Gao, Wei; Yang, Chao-Yie] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. [Stuckey, Jeanne; Meagher, Jennifer] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Krajewski, Krzysztof; Jiang, Sheng; Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 17-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607537 ER PT J AU Weidlich, IE Sobiak, S AF Weidlich, Iwona E. Sobiak, Stanislaw TI MEDI 155-Synthesis of 5-nitroimidazole derivatives of tert-butyl ester of aminoacids SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Weidlich, Iwona E.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Sobiak, Stanislaw] Univ Med Sci, Fac Pharm, Dept Chem Technol & Drugs, PL-60780 Poznan, Poland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 155-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607623 ER PT J AU Wilde, TC Showalter, BM Saavedra, JE Shami, PJ Tew, KD Townsend, DM Ji, XH Keefer, LK AF Wilde, Thomas C. Showalter, Brett M. Saavedra, Joseph E. Shami, Paul J. Tew, Kenneth D. Townsend, Danyelle M. Ji, Xinhua Keefer, Larry K. TI MEDI 27-Design of glutathione transferase-activated nitric oxide-releasing prodrugs as anticancer agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wilde, Thomas C.; Showalter, Brett M.; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. [Shami, Paul J.] Univ Utah, Div Med Oncol, Dept Internal Med, Salt Lake City, UT 84148 USA. [Shami, Paul J.] SLC VA Med Ctr, Salt Lake City, UT 84148 USA. [Tew, Kenneth D.; Townsend, Danyelle M.] Med Univ S Carolina, Charleston, SC USA. [Ji, Xinhua] NCI, Biomol Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 27-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607482 ER PT J AU Zhao, XZ Semenova, EA Johnson, A Marchand, C Liao, CZ Nicklaus, MC Pommier, Y Burke, TR AF Zhao, Xue Zhi Semenova, Elena A. Johnson, Allison Marchand, Christophe Liao, Chenzhong Nicklaus, Marc C. Pommier, Yves Burke, Terrence R., Jr. TI MEDI 248-Click chemistry-derived biotin-tagged diketo acid-containing biphenyl ketones designed as HIV-1 integrase photoaffinity ligands SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhao, Xue Zhi; Liao, Chenzhong; Nicklaus, Marc C.; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Semenova, Elena A.; Johnson, Allison; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. RI Marchand, Christophe/D-8559-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 248-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607191 ER PT J AU Zimmerberg, J AF Zimmerberg, Joshua TI PHYS 107-Towards understanding the organization of membrane protein microdomains in cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zimmerberg, Joshua] NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 107-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609591 ER PT J AU Kassis, JN Guancial, EA Doong, H Virador, V Kohn, EC AF Kassis, Jareer N. Guancial, Elizabeth A. Doong, Howard Virador, Victoria Kohn, Elise C. TI CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE FAK; paxillin; collagen type IV; signalosome ID PHOSPHOLIPASE C-GAMMA; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; TUMOR INVASION; KINASE; SRC; MOTILITY; RECEPTOR; FAK; SH2 AB CAIR-1/BAG-3 is a stress and survival protein that has been shown to bind SH3 domain-containing proteins through its proline-rich (PXXP) domain. Because stress and survival pathways are active during invasion and metastasis, we hypothesized that CAIR-1 is a regulator of signaling pathways that modulate cell adhesion and migration. MDA-435 human breast carcinoma cells were stably transfected with full-length CAIR-1 (FL) or a proline-rich domain deleted mutant (dPXXP). FL cells migrated poorly through collagen IV-coated filters to serum (14% of control, p=0.0004), whereas migration of dPXXP cells was more robust (228%, p=0.00001). Adhesion to collagen IV-coated surfaces was reduced in FL cells and augmented in dPXXP cells (FL 64%, p=0.03; dPXXP 138%, p=0.01). Rhodamine-phalloidin staining highlighted more stress fibers and thicker filopodial protrusions in dPXXP cells. Fewer focal adhesions were also seen in FL cells. A reduction in tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin occurred in FL cells under these conditions. In contrast, increased FAK and paxillin phosphorylation was documented in dPXXP cells. Differential FAK phosphorylation occurred at the major autophosphorylation site Y-397 and Src phosphorylation site Y-861. Concordant with these findings, there was decreased interaction between FAK and its downstream partners p(130)Cas and Crk observed in FL cells but not in dPXXP cells. These results collectively indicate that CAIR-1 may negatively regulate adhesion, focal adhesion assembly, signaling, and migration via its PXXP domain. (c) Published by Elsevier Inc. C1 NCI, Mol Signalling Sect, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. RP Kassis, JN (reprint author), NCI, Mol Signalling Sect, Pathol Lab, Canc Res Ctr, 10 Ctr Drv,MSC 1500, Bethesda, MD 20892 USA. EM kassisj@mail.nih.gov FU Intramural NIH HHS NR 39 TC 41 Z9 43 U1 1 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 10 PY 2006 VL 312 IS 15 BP 2962 EP 2971 DI 10.1016/j.yexcr.2006.05.023 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 080NT UT WOS:000240255300024 PM 16859681 ER PT J AU Patel, DN Bailey, SR Gresham, JK Schuchman, DB Shelhamer, JH Goldstein, BJ Foxwell, BM Stemerman, MB Maranchie, JK Valente, AJ Mummidi, S Chandrasekar, B AF Patel, Devang N. Bailey, Steven R. Gresham, John K. Schuchman, David B. Shelhamer, James H. Goldstein, Barry J. Foxwell, Brian M. Stemerman, Michael B. Maranchie, Jodi K. Valente, Anthony J. Mummidi, Srinivas Chandrasekar, Bysam TI TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE atherosclerosis; coronary disease; endotoxins; signal transduction; MAP kinase ID N-TERMINAL KINASE; SCAVENGER RECEPTOR; KAPPA-B; OXIDIZED LIPOPROTEIN; ENDOTHELIAL-CELLS; CHEMOKINE CXCL16; INTERFERON-GAMMA; CUTTING EDGE; ACTIVATION; LIGAND AB CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappa B (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis. (c) 2006 Elsevier Inc. All rights reserved. C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. Univ London Imperial Coll Sci Technol & Med, London, England. Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. Univ Massachusetts, Dept Surg, Worcester, MA 01605 USA. Univ Massachusetts, Dept Cell Biol, Worcester, MA 01605 USA. RP Chandrasekar, B (reprint author), S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. EM chandraseka@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008; OI Mummidi, Srinivas/0000-0002-4068-6380; Maranchie, Jodi/0000-0002-8534-9468 FU NHLBI NIH HHS [HL68020] NR 35 TC 38 Z9 41 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 8 PY 2006 VL 347 IS 4 BP 1113 EP 1120 DI 10.1016/j.bbre.2006.07.015 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 072NW UT WOS:000239681100038 PM 16870145 ER PT J AU Tharakaraman, K Marino-Ramirez, L Sheetlin, SL Landsman, D Spouge, JL AF Tharakaraman, Kannan Marino-Ramirez, Leonardo Sheetlin, Sergey L. Landsman, David Spouge, John L. TI Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements SO BMC BIOINFORMATICS LA English DT Article ID DNA-BINDING; SACCHAROMYCES-CEREVISIAE; REGULATORY ELEMENTS; CELL-CYCLE; YEAST; TRANSCRIPTION; PROTEIN; SITES; REPRESSOR; LAMBDA AB Background: Many DNA regulatory elements occur as multiple instances within a target promoter. Gibbs sampling programs for finding DNA regulatory elements de novo can be prohibitively slow in locating all instances of such an element in a sequence set. Results: We describe an improvement to the A-GLAM computer program, which predicts regulatory elements within DNA sequences with Gibbs sampling. The improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling produces a position specific scoring matrix (PSSM). The new scanning step resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an "individual score" to each subsequence of appropriate length within the input sequences using the initial PSSM. Second, it computes an E-value from each individual score, to assess the agreement between the corresponding subsequence and the PSSM. Third, it permits subsequences with E-values falling below a threshold to contribute to the underlying PSSM, which is then updated using the Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which point no new subsequences contribute to the PSSM. After convergence, A-GLAM reports predicted regulatory elements within each sequence in order of increasing E-values, so users have a statistical evaluation of the predicted elements in a convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds at most one regulatory element per input sequence, the scanning step can now rapidly locate further instances of the element in each sequence. Conclusion: Datasets from experiments determining the binding sites of transcription factors were used to evaluate the improvement to A-GLAM. Typically, the datasets included several sequences containing multiple instances of a regulatory motif. The improvements to A-GLAM permitted it to predict the multiple instances. C1 Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,MSC 6075, Bethesda, MD 20894 USA. EM tharakar@ncbi.nlm.nih.gov; marino@ncbi.nlm.nih.gov; sheetlin@ncbi.nlm.nih.gov; landsman@ncbi.nlm.nih.gov; spouge@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 43 TC 2 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD SEP 8 PY 2006 VL 7 AR 408 DI 10.1186/1471-2105-7-408 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 094IA UT WOS:000241231900001 PM 16961919 ER PT J AU Witschi, H Espiritu, I Maronpot, RR AF Witschi, Hanspeter Espiritu, Imelda Maronpot, Robert R. TI Lung tumors in 2 year old strain A/J mice exposed for 6 months to tobacco smoke SO CANCER LETTERS LA English DT Article DE tobacco smoke; strain A/J mice; lung tumors ID CIGARETTE-SMOKE; MOUSE LUNG; INHALATION EXPOSURE; GAS-PHASE; A MICE; CANCER AB Young adult strain A/J mice were exposed for 6 months in a whole-body inhalation chamber to a mixture of 89% sidestream and 11% mainstream cigarette smoke generated from Kentucky 1R417 research cigarettes. Chamber concentrations of smoke constituents were 158 mg/m(3) of total suspended particulate matter (TSP). After an additional 4 months in air, some of the animals were killed. Lung tumor multiplicities in the smoke exposed animals were 1.8 +/- 0.2 versus 0.9 +/- 0.2 in controls. In animals kept beyond the age of 12 months, lung tumor multiplicities increased in both groups, but remained at all times twice the control values in the smoke exposed animals compared to controls (4.3 +/- 0.7 vs. 2.1 +/- 0.5 tumors per lung in 24 months old animals). Histopathology showed that, in 2 year old animals, still about 80% of tumors were of benign nature. No tumors were found in the nasal passages. It was concluded that tobacco smoke exposure not simply accelerates the development of lesions that eventually would have developed spontaneously, but induced de novo formation of lung tumors in A/J mice. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Davis, Ctr Hlth & Environm, Davis, CA 95616 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Witschi, H (reprint author), 86733 Lower Fourmile Lane, Bandon, OR 97411 USA. EM hrwitschi@ucdavis.edu FU Intramural NIH HHS; NCI NIH HHS [CA96217]; NIEHS NIH HHS [ES05707] NR 14 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD SEP 8 PY 2006 VL 241 IS 1 BP 64 EP 68 DI 10.1016/j.canlet.2005.10.002 PG 5 WC Oncology SC Oncology GA 086ZQ UT WOS:000240712200008 PM 16290922 ER PT J AU Kim, IY Kim, SJ AF Kim, Isaac Yi Kim, Seong Jin TI Role of bone morphogenetic proteins in transitional cell carcinoma cells SO CANCER LETTERS LA English DT Article DE bone morphogenetic proteins (BMPs); BMP receptor; transitional cell carcinoma (TCC); bladder TCC cell line ID URINARY-BLADDER CANCER; RECEPTOR-TYPE-II; GROWTH-FACTOR RECEPTORS; PROSTATE-CANCER; BREAST-CANCER; C-ERBB-2 GENE; OSTEOGENIC PROTEIN-1; DECREASED EXPRESSION; ALTERED EXPRESSION; PROGNOSTIC VALUE AB Bone morphogenetic proteins (BMPs) are pleiotropic growth factors that signal through an interaction with the membrane receptors-type-IA, -IB, and -II (BMP-RIA, -RIB, and -RII, respectively). Although the prototypical members of this group of growth factors were isolated as osteoinductive factors, recently accumulated data have suggested that these factors regulate malignant cells. Herein, we review the data concerning BMPs in transitional cell carcinoma cells. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Canc Inst New Jersey, Div Urol Oncol, New Brunswick, NJ 08903 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Kim, IY (reprint author), Canc Inst New Jersey, Div Urol Oncol, 195 Little Albany St 4560, New Brunswick, NJ 08903 USA. EM kimiy@umdnj.edu FU Intramural NIH HHS NR 57 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD SEP 8 PY 2006 VL 241 IS 1 BP 118 EP 123 DI 10.1016/j.canlet.2005.10.009 PG 6 WC Oncology SC Oncology GA 086ZQ UT WOS:000240712200015 PM 16500023 ER PT J AU Janz, S AF Janz, Siegfried TI Myc translocations in B cell and plasma cell neoplasms SO DNA REPAIR LA English DT Review DE oncogene-activating chromosomal translocations; immunoglobulin genes; class switch recombination ID HEAVY-CHAIN LOCUS; CLASS-SWITCH RECOMBINATION; T(12/15)-POSITIVE BALB/C PLASMACYTOMAS; PEYERS PATCH FOLLICLES; C-MYC; CHROMOSOMAL TRANSLOCATIONS; BURKITTS-LYMPHOMA; MOUSE PLASMACYTOMAS; MURINE PLASMACYTOMAS; TRANSGENIC MICE AB Chromosomal translocations that join the cellular oncogene Myc (c-myc) with immunoglobulin (19) heavy-chain (Igh) or light-chain (Igk, Igl) loci are widely believed to be the crucial initiating oncogenic events in the development of B cell and plasma cell neoplasms in three mammalian species: Burkitt lymphoma (BL) in human beings, plasmacytoma (PCT) in mice, and immunocytoma in rats. Among the Myc-Ig translocations found in these neoplasms, mouse PCT T(12;15)(Igh-Myc) is of special interest because it affords a uniquely useful model system to study the fundamental outstanding questions on the mechanisms, genetics, and biological consequences of Myc translocations. Mouse T(12;15) is the direct counterpart of the human BL t(8;14)(q24;q32) translocation. and thus of great relevance for human cancer. Mouse T(12;15) is the only cancer-associated translocation. in mice that occurs with high incidence, spontaneity, and cell-type specificity. Due to the development of PCR methods for the detection of the underlying reciprocal Myc-Igh junction fragments, it is now known that mouse T(12;15) can be a dynamic process that begins with the genetic exchange of Myc and the Igh switch L region (S mu), progresses by class switch recombination (CSR) just 3' of the translocation break site, and then undergoes further clonal diversification by micro-deletions in the junction flanks. The molecular pathway that subverts CSR to mediate trans-chromosomal joining of Myc and S mu (translocation origin) and secondary modification of Myc-Igh junctions (translocation "remodeling") has not been elucidated, but recent evidence indicates that it includes CSR factors, such as the activation-induced cytidine deaminase (AID), that may also be involved in the ongoing neoplastic progression of the translocation-bearing tumor precursor. Transgenic mouse models of T(12;15)/t(8;14), including newly developed "iMyc" gene-insertion mice, will be useful in elucidating the role of these CSR factors in the progression of Myc-induced B cell tumors. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Ctr Canc Res, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, Ctr Canc Res, Genet Lab, NIH, Bldg 37,Room 3140A, Bethesda, MD 20892 USA. EM sj4s@nih.gov FU Intramural NIH HHS NR 117 TC 62 Z9 66 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 8 PY 2006 VL 5 IS 9-10 BP 1213 EP 1224 DI 10.1016/j.dnarep.2006.05.017 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 087EH UT WOS:000240725000022 PM 16815105 ER PT J AU Gabrea, A Berysagel, PL Kuehl, WM AF Gabrea, Ana Berysagel, P. Leif Kuehl, W. Michael TI Distinguishing primary and secondary translocations in multiple myeloma SO DNA REPAIR LA English DT Review DE multiple myeloma; immunoglobulin heavy chain; MGUS; switch recombination; somatic hypermutation; enhancer ID GROWTH-FACTOR RECEPTOR-3; CYCLIN-D DYSREGULATION; CHAIN SWITCH REGIONS; C-MYC; CHROMOSOMAL TRANSLOCATIONS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; BURKITTS-LYMPHOMA; CELL DEVELOPMENT; LOCUS AB Multiple myeloma (MM) is a malignant post-germinal center tumor of somatically-mutated, isotype-switched plasma cells that accumulate in the bone marrow. It often is preceded by a stable pre-malignant tumor called monoclonal gammopathy of undetermined significance (MGUS), which can sporadically progress to MM. Five recurrent primary translocations involving the immunoglobulin heavy chain (IgH) locus on chromosome 14q32 have been identified in MGUS and MM tumors. The five partner loci include 11q13, 6p21, 4p16, 16q23, and 20q12, with corresponding dysregulation of CYCLIN D1, CYCLIN D3, FGFR3/MMSET, c-MAF, and MAFB, respectively, by strong enhancers in the IgH locus. The five recurrent translocations, which are present in 40% of MM tumors, typically are simple reciprocal translocations, mostly having breakpoints within or near IgH switch regions but sometimes within or near VDJ or JH sequences. It is thought that these translocations are caused by aberrant IgH switch recombination, and possibly by aberrant somatic hypermutation. in germinal center B cells, thus providing an early and perhaps initiating event in transformation. A MYC gene is dysregulated by complex translocations and insertions as a very late event during the progression of MM tumors. Since the IgH switch recombination and somatic hypermutation mechanism are turned off in plasma cells and plasma cell tumors, the MYC rearrangements are thought to be mediated by unknown mechanisms that contribute to structural genomic instability in all kinds of tumors. These rearrangements, which often but not always juxtapose MYC near one of the strong immunoglobulin enhancers, provide a paradigm for secondary translocations. It is hypothesized that secondary translocations not involving a MYC gene can occur at any stage of tumorigenesis, including in pre-malignant MGUS tumor cells. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Bethesda, MD 20889 USA. Mayo Clin, Scottsdale, AZ 85259 USA. RP Kuehl, WM (reprint author), NCI, Bethesda, MD 20889 USA. EM wmk@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA100707] NR 61 TC 37 Z9 39 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 8 PY 2006 VL 5 IS 9-10 BP 1225 EP 1233 DI 10.1016/j.dnarep.2006.05.012 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 087EH UT WOS:000240725000023 PM 16829212 ER PT J AU Aplan, PD AF Aplan, Peter D. TI Chromosomal translocations involving the MLL gene: Molecular mechanisms SO DNA REPAIR LA English DT Review DE MLL; chromosomal translocation; infant leukemia; DNA topoisomerase II; non-homologous end joining ID ACUTE MYELOID-LEUKEMIA; BREAKPOINT CLUSTER REGION; TOPOISOMERASE-II CLEAVAGE; ACUTE LYMPHOBLASTIC-LEUKEMIA; PARTIAL TANDEM DUPLICATION; INFANT LEUKEMIA; DNA CLEAVAGE; CONGENITAL LEUKEMIA; ALU ELEMENTS; CELL-DEATH AB A wide array of recurrent, non-random chromosomal translocations are associated with hematologic malignancies; experimental models have clearly demonstrated that many of these translocations are causal events during malignant transformation. Tyanslocations involving the MLL gene are among the most common of these non-random translocations. Leukemias with MLL translocations have been the topic of intense interest because of the unusual, biphenotypic immunophenotype of these leukemias, because of the unique clinical presentation of some MLL translocations (infant leukemia and therapy-related leukemia), and because of the large number of different chromosomal loci that partner with MLL in these translocations. This review is focused on the potential mechanisms that lead to MLL translocations, and will discuss aberrant VDJ recombination, Alv.-mediated recombination, non-homologous end joining, as well as the effect of DNA topoisomerase II poisons and chromatin structure. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Genet Branch,Ctr Canc Res, NIH, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Aplan, PD (reprint author), NCI, Genet Branch,Ctr Canc Res, NIH, Natl Naval Med Ctr, Bldg 8 Rm 5101,8901 Rockville Pike, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU Intramural NIH HHS NR 71 TC 35 Z9 36 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 8 PY 2006 VL 5 IS 9-10 BP 1265 EP 1272 DI 10.1016/j.dnarep.2006.05.034 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 087EH UT WOS:000240725000027 PM 16797254 ER PT J AU Thomas, DD Ridnour, LA Espey, MG Donzelli, S Ambs, S Hussain, SP Harris, CC DeGraff, W Roberts, DD Mitchell, JB Wink, DA AF Thomas, Douglas D. Ridnour, Lisa A. Espey, Michael Graham Donzelli, Sonia Ambs, Stefan Hussain, S. Perwez Harris, Curtis C. DeGraff, William Roberts, David D. Mitchell, James B. Wink, David A. TI Superoxide fluxes limit nitric oxide-induced signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE NITRATION; PEROXYNITRITE-MEDIATED OXIDATION; ENDOTHELIAL GROWTH-FACTOR; HUMAN BREAST-CANCER; INDUCIBLE FACTOR-1-ALPHA; XANTHINE-OXIDASE; REGULATED KINASE; CARCINOMA-CELLS; SYNTHASE GENE; TUMOR-GROWTH AB Independently, superoxide (O(2)(-)) and nitric oxide (NO) are biologically important signaling molecules. When co-generated, these radicals react rapidly to form powerful oxidizing and nitrating intermediates. Although this reaction was once thought to be solely cytotoxic, herein we demonstrate using MCF7, macrophage, and endothelial cells that when nanomolar levels of NO and O(2)(-) were produced concomitantly, the effective NO concentration was established by the relative fluxes of these two radicals. Differential regulation of sGC, pERK, HIF-1 alpha, and p53 were used as biological dosimeters for NO concentration. Introduction of intracellular-or extracellular-generated O(2)-during NO generation resulted in a concomitant increase in oxidative intermediates with a decrease in steady-state NO concentrations and a proportional reduction in the levels of sGC, ERK, HIF-1 alpha, and p53 regulation. NO responses were restored by addition of SOD. The intermediates formed from the reactions of NO with O(2)(-) were non-toxic, did not form 3-nitrotyrosine, nor did they elicit any signal transduction responses. H(2)O(2) in bolus or generated from the dismutation of O(2)-by SOD, was cytotoxic at high concentrations and activated p53 independent of NO. This effect was completely inhibited by catalase, suppressed by NO, and exacerbated by intracellular catalase inhibition. We conclude that the reaction of O(2)(-) with NO is an important regulatory mechanism, which modulates signaling pathways by limiting steady-state levels of NO and preventing H(2)O(2) formation from O(2)(-). C1 NCI, Radiat Biol Branch, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Thomas, DD (reprint author), NCI, Radiat Biol Branch, Tumor Biol Sect, NIH, Bldg 10,Rm B3-B69, Bethesda, MD 20892 USA. EM thomasdo@mail.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS NR 56 TC 66 Z9 66 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 25984 EP 25993 DI 10.1074/jbc.M602242200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500013 PM 16829532 ER PT J AU Isenberg, JS Ridnour, LA Dimitry, J Frazier, WA Wink, DA Roberts, DD AF Isenberg, Jeff S. Ridnour, Lisa A. Dimitry, Julie Frazier, William A. Wink, David A. Roberts, David D. TI CD47 is necessary for inhibition of nitric oxide-stimulated vascular cell responses by thrombospondin-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTEGRIN-ASSOCIATED PROTEIN; FACTOR-INDUCED ANGIOGENESIS; C-TERMINAL DOMAIN; TYPE-1 REPEATS; IN-VITRO; RECEPTOR; ADHESION; ALPHA(V)BETA(3); PROLIFERATION AB CD36 is necessary for inhibition of some angiogenic responses by the matricellular glycoprotein thrombospondin-1 and is therefore assumed to be the receptor that mediates its anti-angiogenic activities. Although ligation of CD36 by antibodies, recombinant type 1 repeats of thrombospondin-1, or CD36-binding peptides was sufficient to inhibit nitric oxide (NO)-stimulated responses in both endothelial and vascular smooth muscle cells, picomolar concentrations of native thrombospondin-1 similarly inhibited NO signaling in vascular cells from wild-type and CD36-null mice. Ligation of the thrombospondin-1 receptor CD47 by recombinant C-terminal regions of thrombospondin-1, thrombospondin-1 peptides, or CD47 antibodies was also sufficient to inhibit NO-stimulated phenotypic responses and cGMP signaling in vascular cells. Thrombospondin-1 did not inhibit NO signaling in CD47-null vascular cells or NO-stimulated vascular outgrowth from CD47-null muscle explants in three-dimensional cultures. Furthermore, the CD36-binding domain of thrombospondin-1 and anti-angiogenic peptides derived from this domain failed to inhibit NO signaling in CD47-null cells. Therefore, ligation of either CD36 or CD47 is sufficient to inhibit NO-stimulated vascular cell responses and cGMP signaling, but only CD47 is necessary for this activity of thrombospondin-1 at physiological concentrations. C1 NCI, Pathol Lab, Canc Res Ctr, Lab Pathol,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, Radiat Biol Branch,NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Canc Res Ctr, Lab Pathol,NIH, Bldg 10,Rm 2A33,10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS; NHLBI NIH HHS [HL54390]; NIGMS NIH HHS [GM57573] NR 57 TC 124 Z9 126 U1 3 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26069 EP 26080 DI 10.1074/jbc.M605040200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500022 PM 16835222 ER PT J AU Kotsyfakis, M Sa-Nunes, A Francischetti, IMB Mather, TN Andersen, JF Ribeiro, JMC AF Kotsyfakis, Michalis Sa-Nunes, Anderson Francischetti, Ivo M. B. Mather, Thomas N. Andersen, John F. Ribeiro, Jose M. C. TI Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick Ixodes scapularis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIPEPTIDYL PEPTIDASE-I; LYSOSOMAL CYSTEINE PROTEASES; CATHEPSIN-L; EXTRACELLULAR-MATRIX; ANOPHELES-GAMBIAE; IMMUNE-RESPONSES; ARTHROPOD SALIVA; CHICKEN CYSTATIN; STRUCTURAL BASIS; PROTEINASES AB Here we report the ability of the tick Ixodes scapularis, the main vector of Lyme disease in the United States, to actively and specifically affect the host proteolytic activity in the sites of infestation through the release of a cystatin constituent of its saliva. The cystatin presence in the saliva was verified both biochemically and immunologically. We named the protein sialostatin L because of its inhibitory action against cathepsin L. We also show that the proteases it targets, although limited in number, have a prominent role in the proteolytic cascades that take place in the extracellular and intracellular environment. As a result, sialostatin L displays an antiinflammatory role and inhibits proliferation of cytotoxic T lymphocytes. Beyond unraveling another component accounting for the properties of tick saliva, contributing to feeding success and pathogen transmission, we describe a novel tool for studying the role of papain-like proteases in diverse biologic phenomena and a protein with numerous potential pharmaceutical applications. C1 NIAID, Lab Malaria & Vector Res, Vector Biol Sect, NIH, Rockville, MD 20852 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA. RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, Vector Biol Sect, NIH, 12735 Twinbrook Pkwy,Rm 2E-32, Rockville, MD 20852 USA. EM jribeiro@niaid.nih.gov RI Sa-Nunes, Anderson/D-8667-2012; Kotsyfakis, Michail/G-9525-2014; OI Sa-Nunes, Anderson/0000-0002-1859-4973; Kotsyfakis, Michail/0000-0002-7526-1876; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS NR 64 TC 101 Z9 103 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26298 EP 26307 DI 10.1074/jbc.M513010200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500047 PM 16772304 ER PT J AU Croteau, DL DellaVecchia, MJ Wang, H Bienstock, RJ Melton, MA Van Houten, B AF Croteau, Deborah L. DellaVecchia, Matthew J. Wang, Hong Bienstock, Rachelle J. Melton, Mark A. Van Houten, Bennett TI The C-terminal zinc finger of UvrA does not bind DNA directly but regulates damage-specific DNA binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI UVRA; NUCLEOTIDE EXCISION-REPAIR; SITE-SPECIFIC MUTAGENESIS; ATP-BINDING; CRYSTAL-STRUCTURE; ABC TRANSPORTER; (A)BC EXCINUCLEASE; CASSETTE DIMER; XPA PROTEIN; RECOGNITION AB In prokaryotic nucleotide excision repair, UvrA recognizes DNA perturbations and recruits UvrB for the recognition and processing steps in the reaction. One of the most remarkable aspects of UvrA is that it can recognize a wide range of DNA lesions that differ in chemistry and structure. However, how UvrA interacts with DNA is unknown. To examine the role that the UvrA C-terminal zinc finger domain plays in DNA binding, an eleven amino acid deletion was constructed (ZnG UvrA). Biochemical characterization of the ZnG UvrA protein was carried out using UvrABC DNA incision, DNA binding and ATPase assays. Although ZnG UvrA was able to bind dsDNA slightly better than wild-type UvrA, the ZnG UvrA mutant only supported 50-75% of wild type incision. Surprisingly, the ZnG UvrA mutant, while retaining its ability to bind dsDNA, did not support damage-specific binding. Furthermore, this mutant protein only provided 10% of wild-type Bca UvrA complementation for UV survival of an uvrA deletion strain. In addition, ZnG UvrA failed to stimulate the UvrB DNA damage-associated ATPase activity. Electrophoretic mobility shift analysis was used to monitor UvrB loading onto damaged DNA with wildtype UvrA or ZnG UvrA. The ZnG UvrA protein showed a 30-60% reduction in UvrB loading as compared with the amount of UvrB loaded by wild-type UvrA. These data demonstrate that the C-terminal zinc finger of UvrA is required for regulation of damage-specific DNA binding. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Sci Comp Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Summers Discovery Program, NIH, Res Triangle Pk, NC 27709 USA. RP Van Houten, B (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM vanhout1@niehs.nih.gov RI Messier, Claude/A-2322-2008; Wang, Hong/F-3164-2014; OI Messier, Claude/0000-0002-4791-1763; Wang, Hong/0000-0003-0165-3559; Bienstock, Rachelle/0000-0001-5228-3610 FU Intramural NIH HHS [Z01 ES061060-09] NR 45 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26370 EP 26381 DI 10.1074/jbc.M603093200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500054 PM 16829526 ER PT J AU Sauna, ZE Nandigama, K Ambudkar, SV AF Sauna, Zuben E. Nandigama, Krishnamachary Ambudkar, Suresh V. TI Exploiting reaction intermediates of the ATPase reaction to elucidate the mechanism of transport by P-glycoprotein (ABCB1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOSIN MOTOR DOMAIN; ENZYMATIC TRANSITION-STATES; POWER STROKE STATE; MULTIDRUG-RESISTANCE; CATALYTIC CYCLE; GLUTAMATE RESIDUES; CRYSTAL-STRUCTURE; BERYLLIUM FLUORIDE; ANALOG DESIGN; HYDROLYSIS AB The transport cycle of ABC transporters in general and P-glycoprotein in particular has been extensively studied, but the molecular mechanism remains controversial. We identify stable reaction intermediates in the progression of the P-glycoprotein-mediated ATPase reaction equivalent to the enzyme-substrate (E.S, P-glycoprotein.ATP) and enzyme-product (E.P, P.glycoprotein.ADP.P-i) reaction intermediates. These have been characterized using the photoaffinity analog 8-azido-[alpha-P-32] ATP as well as under equilibrium conditions using [alpha-P-32] ATP, in which a cross-linking step is not involved. Similar results were obtained when 8-azido[alpha-32P] ATP or [alpha-32P] ATP was used. The reaction intermediates were characterized basedontheir kinetic properties and the nature (triphosphate/diphosphate) of the trapped nucleotide. Using this defined framework and the Walker B E556Q/ E1201Q mutant that traps nucleotide in the absence of vanadate or beryllium fluoride, the high to low affinity switch in the transport substrate binding site can be attributed to the formation of the E.S reaction intermediate of the ATPase reaction. Importantly, the posthydrolysis E.P state continues to have low affinity for substrate, suggesting that conformational changes that form the E.S complex are coupled to the conformational change at the transport substrate site to do mechanical work. Thus, the formation of E.S reaction intermediate duringasingleturnoverofthecatalyticcycleappearstoprovidethe initial power stroke for movement of drug substrate from inner leaflet to outer leaflet of lipid bilayer. This novel approach applies transition state theory to elucidate the mechanism of P-glycoprotein and other ABC transporters and has wider applications in testing cause-effect hypotheses in coupled systems. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU Intramural NIH HHS NR 59 TC 34 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26501 EP 26511 DI 10.1074/jbc.M601917200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500068 PM 16844693 ER PT J AU Ding, X Lichti, K Kim, I Gonzalez, FJ Staudinger, JL AF Ding, Xunshan Lichti, Kristin Kim, Insook Gonzalez, Frank J. Staudinger, Jeff L. TI Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor alpha, and the coactivator peroxisome proliferator-activated receptor gamma coactivator-1 alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PREGNANE-X-RECEPTOR; THYROID-HORMONE METABOLISM; BILE-ACIDS; TRANSCRIPTIONAL COACTIVATOR; HEPATIC GLUCONEOGENESIS; FACTOR 4-ALPHA; ADAPTIVE THERMOGENESIS; XENOBIOTIC RESPONSE; DRUG-METABOLISM; AGONIST GC-1 AB Animal studies reveal that fasting and caloric restriction produce increased activity of specific metabolic pathways involved in resistance to weight loss in liver. Evidence suggests that this phenomenon may in part occur through the action of the constitutive androstane receptor ( CAR, NR1I3). Currently, the precise molecular mechanisms that activate CAR during fasting are unknown. We show that fasting coordinately induces expression of genes encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), CAR, cytochrome P-450 2b10 (Cyp2b10), UDP-glucuronosyltransferase 1a1 (Ugt1a1), sulfotransferase 2a1 (Sult2a1), and organic anion-transporting polypeptide 2 (Oatp2) in liver in mice. Treatments that elevate intracellular cAMP levels also produce increased expression of these genes in cultured hepatocytes. Our data show that PGC-1 alpha interaction with hepatocyte nuclear factor 4 alpha(HNF4 alpha, NR2A1) directly regulates CAR gene expression through a novel and evolutionarily conserved HNF4-response element (HNF4RE) located in its proximal promoter. Expression of PGC-1 alpha in cells increases CAR expression and ligand-independent CAR activity. Genetic studies reveal that hepatic expression of HNF4 alpha is required to produce fasting-inducible CAR expression and activity. Taken together, our data show that fasting produces increased expression of genes encoding key metabolic enzymes and an uptake transporter protein through a network of interactions involving cAMP, PGC-1 alpha, HNF4 alpha, CAR, and CAR target genes in liver. Given the recent finding that mice lacking CAR exhibit a profound decrease in resistance to weight loss during extended periods of caloric restriction, our findings have important implications in the development of drugs for the treatment of obesity and related diseases. C1 Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA. NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staudinger, JL (reprint author), Univ Kansas, Dept Pharmacol & Toxicol, 1251 Wescoe Hall Dr,5044 Malott Hall, Lawrence, KS 66045 USA. EM stauding@ku.edu FU NCRR NIH HHS [P20 RR017708, RR17708]; NIDDK NIH HHS [R01 DK068443, R01 DK068443-01A1, R01DK068443] NR 67 TC 79 Z9 84 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26540 EP 26551 DI 10.1074/jbc.M600931200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500072 PM 16825189 ER PT J AU Yang, ST Jeong, JH Brown, AL Lee, CH Pandolfi, PP Chung, JH Kim, MK AF Yang, Shutong Jeong, Jae-Hoon Brown, Alexandra L. Lee, Chang-Hun Pandolfi, Pier Paolo Chung, Jay H. Kim, Myung K. TI Promyelocytic leukemia activates Chk2 by mediating Chk2 autophosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE RESPONSE; PML NUCLEAR-BODIES; RETINOIC ACID; RAR-ALPHA; TUMOR-SUPPRESSOR; HISTONE H2AX; CHECKPOINT; PROTEIN; PHOSPHORYLATION; APOPTOSIS AB Chk2 is a kinase critical for DNA damage- induced apoptosis and is considered a tumor suppressor. Chk2 is essential for p53 transcriptional and apoptotic activities. Although mutations of p53 are present in more than half of all tumors, mutations of Chk2 in cancers are rare, suggesting that Chk2 may be inactivated by unknown alternative mechanisms. Here we elucidate one such alternative mechanism regulated by PML (promyelocytic leukemia) that is involved in acute promyelocytic leukemia (APL). Although p53 inactivating mutations are extremely rare in APL, t(15; 17) chromosomal translocation which fuses retinoic acid receptor (RAR alpha) to PML is almost always present in APL, while the other PML allele is intact. We demonstrate that PML interacts with Chk2 and activates Chk2 by mediating its autophosphorylation step, an essential step for Chk2 activity that occurs after phosphorylation by the upstream kinase ATM (ataxia telangiectasia- mutated). PML/ RAR alpha in APL suppresses Chk2 by dominantly inhibiting the autophosphorylation step, but inactivation of PML/ RAR alpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Thus, by fusing PML with RAR alpha, the APL cells appear to have achieved functional suppression of Chk2 compromising the Chk2- p53 apoptotic pathway. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Chung, JH (reprint author), NHLBI, Lab Biochem Genet, NIH, 10 Ctr Dr,Bldg 10,Rm 7D14, Bethesda, MD 20892 USA. EM ChungJ@nhlbi.nih.gov; KimM@nhlbi.nih.gov FU Intramural NIH HHS NR 46 TC 33 Z9 35 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26645 EP 26654 DI 10.1074/jbc.M604391200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500082 PM 16835227 ER PT J AU O'Brien, JE Peterson, TJ Tong, MH Lee, EJ Pfaff, LE Hewitt, SC Korach, KS Weiss, J Jameson, JL AF O'Brien, Jeanne E. Peterson, Theresa J. Tong, Ming Han Lee, Eun-Jig Pfaff, Liza E. Hewitt, Sylvia C. Korach, Kenneth S. Weiss, Jeffrey Jameson, J. Larry TI Estrogen-induced proliferation of uterine epithelial cells is independent of estrogen receptor alpha binding to classical estrogen response elements SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED CYCLIN D1; BETA ER-BETA; PROGESTERONE-RECEPTOR; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; REPRODUCTIVE PHENOTYPES; LUMINAL EPITHELIUM; GENE-EXPRESSION; KNOCKOUT MOUSE; UTERUS AB Acting via the estrogen receptor (ER), estradiol exerts pleomorphic effects on the uterus, producing cyclical waves of cellular proliferation and differentiation in preparation for embryo implantation. In the classical pathway, the ER binds directly to an estrogen response element to activate or repress gene expression. However, emerging evidence supports the existence of nonclassical pathways in which the activated ER alters gene expression through protein-protein tethering with transcription factors such as c-Fos/ c-Jun B (AP-1) and Sp1. In this report, we examined the relative roles of classical and nonclassical ER signaling in vivo by comparing the estrogen-dependent uterine response in mice that express wild-type ER alpha, a mutant ER alpha (E207A/G208A) that selectively lacks ERE binding, or ER alpha null. In the compound heterozygote (AA/-) female, the nonclassical allele (AA) was insufficient to mediate an acute uterotrophic response to 17 beta-estradiol (E-2). The uterine epithelial proliferative response to E-2 and 4-hydroxytamoxifen was retained in the AA/-females, and uterine luminal epithelial height increased commensurate with the extent of ER alpha signaling. This proliferative response was confirmed by 5-bromo-2 '-deoxyuridine incorporation. Microarray experiments identified cyclin-dependent kinase inhibitor 1A as a nonclassical pathway-responsive gene, and transient expression experiments using the cyclin-dependent kinase inhibitor 1A promoter confirmed transcriptional responses to the ER alpha (E207A/ G208A) mutant. These results indicate that nonclassical ER alpha signaling is sufficient to restore luminal epithelial proliferation but not other estrogen-responsive events, such as fluid accumulation and hyperemia. We conclude that nonclassical pathway signaling via ER alpha plays a critical physiologic role in the uterine response to estrogen. C1 Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. Yonsei Univ, Coll Med, Div Endocrinol, Seoul 120749, South Korea. NIEHS, NIH, Receptor Biol Sect, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. RP Jameson, JL (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Div Reprod Endocrinol & Infertil, Lurie 7-220,303 E Superior St, Chicago, IL 60611 USA. EM ljameson@northwestern.edu OI Jameson, James/0000-0001-9538-4059; Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS; NICHD NIH HHS [P01 HD21921, T32 HD07068] NR 54 TC 61 Z9 64 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26683 EP 26692 DI 10.1074/jbc.M601522200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500086 PM 16847062 ER PT J AU Dam, J Baber, J Grishaev, A Malchiodi, EL Schuck, P Bax, A Mariuzza, RA AF Dam, Julie Baber, James Grishaev, Alexander Malchiodi, Emilio L. Schuck, Peter Bax, Ad Mariuzza, Roy A. TI Variable dimerization of the Ly49A natural killer cell receptor results in differential engagement of its MHC class I ligand SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE NMR; NK cell receptor; Ly49A; MHQ; residual dipolar coupling ID SEDIMENTATION COEFFICIENT DISTRIBUTIONS; RESIDUAL DIPOLAR COUPLINGS; CRYSTAL-STRUCTURE; BIOLOGICAL MACROMOLECULES; PROTEIN INTERACTIONS; NMR STRUCTURES; COMPLEX; H-2D(D); DECOMPOSITION; BIOMOLECULES AB Natural killer (NK) cells play a vital role in the detection and elimination of virally infected and tumor cells. The Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class 1 molecules on target cells. Previous crystal studies revealed that the Ly49A homodimer binds one MHC molecule in an asymmetric interaction, whereas the Ly49C homodimer binds two MHC in a symmetrical fashion. Moreover, the bound receptors adopt distinctly different homodimeric forms: a "closed state" for Ly49A and an "open state" for Ly49C. Steric clashes between MHC molecules would preclude the closed Ly49A dimer from engaging two MHC in the manner of the open Ly49C dimer. To determine whether individual Ly49 receptors can undergo a conformational switch enabling them to bind MHC in different ways, we carried out a solution NMR study of unbound Ly49A, aided by dipolar coupling technology. This study reveals that, in solution, unligated Ly49A adopts a symmetric, open-state, homodimer conformation similar to that seen previously for Ly49C. Hence, Ly49A can assume both closed and open states. To address whether the Ly49A dimer can bind two MHC molecules in solution, besides the binding of one MHC observed in the crystal, we carried out analytical ultracentrifugation experiments. Velocity sedimentation demonstrates that the Ly49A dimer can engage two MHC molecules in solution, in agreement with NMR results showing that unbound Ly49A exists predominantly in the open state. Published by Elsevier Ltd. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov; mariuzza@carb.nist.gov OI Dam, Julie/0000-0001-6871-2678; Schuck, Peter/0000-0002-8859-6966; Malchiodi, Emilio/0000-0001-7501-3330 FU Intramural NIH HHS; NIAID NIH HHS [AI47990, R01 AI047990] NR 38 TC 21 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 8 PY 2006 VL 362 IS 1 BP 102 EP 113 DI 10.1016/j.jmb.2006.0.005 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 084QI UT WOS:000240549100009 PM 16899255 ER PT J AU Novak, JP Kim, SY Xu, J Modlich, O Volsky, DJ Honys, D Slonczewski, JL Bell, DA Blattner, FR Blumwald, E Boerma, M Cosio, M Gatalica, Z Hajduch, M Hidalgo, J McInnes, RR Miller, MC Penkowa, M Rolph, MS Sottosanto, J St-Arnaud, R Szego, MJ Twell, D Wang, C AF Novak, Jaroslav P. Kim, Seon-Young Xu, Jun Modlich, Olga Volsky, David J. Honys, David Slonczewski, Joan L. Bell, Douglas A. Blattner, Fred R. Blumwald, Eduardo Boerma, Marjan Cosio, Manuel Gatalica, Zoran Hajduch, Marian Hidalgo, Juan McInnes, Roderick R. Miller, Merrill C., III Penkowa, Milena Rolph, Michael S. Sottosanto, Jordan St-Arnaud, Rene Szego, Michael J. Twell, David Wang, Charles TI Generalization of DNA microarray dispersion properties: microarray equivalent of t-distribution SO BIOLOGY DIRECT LA English DT Article ID GENE-EXPRESSION DATA; OLIGONUCLEOTIDE ARRAY EXPERIMENTS; ESCHERICHIA-COLI K-12; MEASUREMENT ERROR; MODEL; IDENTIFICATION; ARABIDOPSIS; VARIANCE; REPRODUCIBILITY; NORMALIZATION AB Background: DNA microarrays are a powerful technology that can provide a wealth of gene expression data for disease studies, drug development, and a wide scope of other investigations. Because of the large volume and inherent variability of DNA microarray data, many new statistical methods have been developed for evaluating the significance of the observed differences in gene expression. However, until now little attention has been given to the characterization of dispersion of DNA microarray data. Results: Here we examine the expression data obtained from 682 Affymetrix GeneChips (R) with 22 different types and we demonstrate that the Gaussian ( normal) frequency distribution is characteristic for the variability of gene expression values. However, typically 5 to 15% of the samples deviate from normality. Furthermore, it is shown that the frequency distributions of the difference of expression in subsets of ordered, consecutive pairs of genes ( consecutive samples) in pair-wise comparisons of replicate experiments are also normal. We describe a consecutive sampling method, which is employed to calculate the characteristic function approximating standard deviation and show that the standard deviation derived from the consecutive samples is equivalent to the standard deviation obtained from individual genes. Finally, we determine the boundaries of probability intervals and demonstrate that the coefficients defining the intervals are independent of sample characteristics, variability of data, laboratory conditions and type of chips. These coefficients are very closely correlated with Student's t-distribution. Conclusion: In this study we ascertained that the non-systematic variations possess Gaussian distribution, determined the probability intervals and demonstrated that the K(alpha) coefficients defining these intervals are invariant; these coefficients offer a convenient universal measure of dispersion of data. The fact that the K(alpha) distributions are so close to t-distribution and independent of conditions and type of arrays suggests that the quantitative data provided by Affymetrix technology give "true" representation of physical processes, involved in measurement of RNA abundance. C1 McGill Univ, Montreal, PQ H3A 1A4, Canada. Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. Genome Res Ctr, Human Genom Lab, Taejon 305333, South Korea. Cedars Sinai Med Ctr, Transcript Genom Core, Los Angeles, CA 90048 USA. Univ Dusseldorf, Inst Onkol Chem, D-40225 Dusseldorf, Germany. St Lukes Roosevelt Hosp, New York, NY 10019 USA. Columbia Univ, New York, NY 10019 USA. Acad Sci Czech Republic, Inst Expt Bot, CR-16502 Prague 6, Czech Republic. Charles Univ Prague, Dept Plant Physiol, CR-12844 Prague 2, Czech Republic. Dept Biol, Gambier, OH 43022 USA. Natl Inst Environm Hlth Sci, Environm Genom Sect, Res Triangle Pk, NC 27709 USA. Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Univ Calif Davis, Dept Plant Sci, Davis, CA 95616 USA. Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. McGill Univ, Dept Med, Resp Div, Montreal, PQ H3A 2T5, Canada. Creighton Univ, Sch Med, Dept Pathol, Omaha, NE 68131 USA. Palacky Univ, Fac Med & Dent, Dept Pediat, Lab Expt Med, Olomouc 77520, Czech Republic. Autonomous Univ Barcelona, Fac Sci, Inst Neurosci, Anim Physiol Unit, E-08193 Barcelona, Spain. Autonomous Univ Barcelona, Fac Sci, Dept Cellular Biol Physiol & Immunol, Anim Physiol Unit, E-08193 Barcelona, Spain. Hosp Sick Children, Res Inst, Genet Program, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A1, Canada. Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada. NIEHS, Environm Genom Sect, Res Triangle Pk, NC 27709 USA. Univ Copenhagen, Fac Hlth Sci, Ctr Inflammat & Metab, Sect Neuroprotect, DK-2200 Copenhagen, Denmark. Garvan Inst Med Res, Arthrit & Inflammat Res Program, Darlinghurst, NSW 2010, Australia. Univ Calif Davis, Dept Plant Sci, Davis, CA 95616 USA. McGill Univ, Shriners Hosp Children, Genet Unit, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Surg & Human Genet, Montreal, PQ H3A 2T5, Canada. Hosp Sick Children, Res Inst, Genet Program, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A1, Canada. Univ Leicester, Dept Biol, Leicester LE1 7RH, Leics, England. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. RP Novak, JP (reprint author), McGill Univ, 740 Docteur Penfield Ave, Montreal, PQ H3A 1A4, Canada. EM jaroslav.novak@mail.mcgill.ca; kimsy@kribb.re.kr; jun.xu@cshs.org; omodlich@onkochemie.uni-duesseldorf.de; djv4@columbia.edu; david.honys@gmail.com; slonczewski@kenyon.edu; bell1@niehs.nih.gov; fred@genome.wisc.edu; eblumwald@ucdavis.edu; mboerma@uams.edu; manuel.cosio@mcgill.ca; zorangatalica@creighton.edu; marian.hajduch@fnol.cz; juan.hidalgo@uab.es; mcinnes@sickkids.ca; miller9418@yahoo.com; m.penkowa@mai.ku.dk; m.rolph@garvan.org.au; jbso@ucdavis.edu; rst-arnaud@shriners.mcgill.ca; michael.szego@utoronto.ca; twe@leicester.ac.uk; charles.wang@cshs.org RI Modlich, Olga/A-3958-2008; Hidalgo, Juan/C-9082-2011; Twell, David/D-8043-2011; Honys, David/I-6707-2013; Hajduch, Marian/J-4015-2014 OI Hidalgo, Juan/0000-0003-0921-1122; Twell, David/0000-0003-0483-1461; FU NINDS NIH HHS [P01 NS031492] NR 52 TC 12 Z9 12 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD SEP 7 PY 2006 VL 1 AR 27 DI 10.1186/1745-6150-1-27 PG 24 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133TJ UT WOS:000244036100001 PM 16959036 ER PT J AU Baker, SG Kramer, BS AF Baker, Stuart G. Kramer, Barnett S. TI Identifying genes that contribute most to good classification in microarrays SO BMC BIOINFORMATICS LA English DT Article ID EXPRESSION; CANCER; PREDICTION; TUMOR; COLON; SERGLYCIN; SELECTION; MACHINE; MARKERS AB Background: The goal of most microarray studies is either the identification of genes that are most differentially expressed or the creation of a good classification rule. The disadvantage of the former is that it ignores the importance of gene interactions; the disadvantage of the latter is that it often does not provide a sufficient focus for further investigation because many genes may be included by chance. Our strategy is to search for classification rules that perform well with few genes and, if they are found, identify genes that occur relatively frequently under multiple random validation (random splits into training and test samples). Results: We analyzed data from four published studies related to cancer. For classification we used a filter with a nearest centroid rule that is easy to implement and has been previously shown to perform well. To comprehensively measure classification performance we used receiver operating characteristic curves. In the three data sets with good classification performance, the classification rules for 5 genes were only slightly worse than for 20 or 50 genes and somewhat better than for 1 gene. In two of these data sets, one or two genes had relatively high frequencies not noticeable with rules involving 20 or 50 genes: desmin for classifying colon cancer versus normal tissue; and zyxin and secretory granule proteoglycan genes for classifying two types of leukemia. Conclusion: Using multiple random validation, investigators should look for classification rules that perform well with few genes and select, for further study, genes with relatively high frequencies of occurrence in these classification rules. C1 NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. EM sb16i@nih.gov; KramerB@OD.NIH.GOV NR 23 TC 39 Z9 39 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD SEP 7 PY 2006 VL 7 AR 407 DI 10.1186/1471-2105-7-407 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 086PN UT WOS:000240685600001 PM 16959042 ER PT J AU Besada, P Shin, DH Costanzi, S Ko, H Mathe, C Gagneron, J Gosselin, G Maddileti, S Harden, TK Jacobson, KA AF Besada, Pedro Shin, Dae Hong Costanzi, Stefano Ko, Hyojin Mathe, Christophe Gagneron, Julien Gosselin, Gilles Maddileti, Savitri Harden, T. Kendall Jacobson, Kenneth A. TI Structure-activity relationships of uridine 5 '-diphosphate analogues at the human P2Y(6) receptor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NUCLEOTIDE RECEPTORS; P2 RECEPTORS; MOLECULAR MECHANICS; PHOSPHOLIPASE-C; FORCE-FIELDS; CLONING; ATP; IDENTIFICATION; DERIVATIVES; EXPRESSION AB The structure-activity relationships and molecular modeling of the uracil nucleotide activated P2Y(6) receptor have been studied. Uridine 5'-diphosphate (UDP) analogues bearing substitutions of the ribose moiety, the uracil ring, and the diphosphate group were synthesized and assayed for activity at the human P2Y6 receptor. The uracil ring was modified at the 4 position, with the synthesis of 4-substituted-thiouridine 5'-diphosphate analogues, as well as at positions 2, 3, and 5. The effect of modifications at the level of the phosphate chain was studied by preparing a cyclic 3', 5'-diphosphate analogue, a 3'-diphosphate analogue, and several dinucleotide diphosphates. 5-Iodo-UDP 32 (EC50 = 0.15 mu M) was equipotent to UDP, while substitutions of the 2'-hydroxyl (amino, azido) greatly reduce potency. The 2-and 4-thio analogues, 20 and 21, respectively, were also relatively potent in comparison to UDP. However, most other modifications greatly reduced potency. Molecular modeling indicates that the beta-phosphate of 5'-UDP and analogues is essential for the establishment of electrostatic interactions with two of the three conserved cationic residues of the receptor. Among 4-thioether derivatives, a 4-ethylthio analogue 23 displayed an EC50 of 0.28 mu M, indicative of favorable interactions predicted for a small 4-alkylthio moiety with the aromatic ring of Y33 in TM1. The activity of analogue 19 in which the ribose was substituted with a 2-oxabicyclohexane ring in a rigid (S)-conformation (P = 126 degrees, 1'-exo) was consistent with molecular modeling. These results provide a better understanding of molecular recognition at the P2Y(6) receptor and will be helpful in designing selective and potent P2Y(6) receptor ligands. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. Univ Montpellier 2, CNRS, Lab Chi Organ Biomol Synth, UMR 5625,UM 2, F-34095 Montpellier, France. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Besada Pereira, Pedro/E-6051-2012; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z01 DK031116-20]; NHLBI NIH HHS [HL34322, P01 HL034322]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 48 TC 47 Z9 48 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 7 PY 2006 VL 49 IS 18 BP 5532 EP 5543 DI 10.1021/jm060485n PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079AX UT WOS:000240149000016 PM 16942026 ER PT J AU Balboni, G Onnis, V Congiu, C Zotti, M Sasaki, Y Ambo, A Bryant, SD Jinsmaa, Y Lazarus, LH Trapella, C Salvadori, S AF Balboni, Gianfranco Onnis, Valentina Congiu, Cenzo Zotti, Margherita Sasaki, Yusuke Ambo, Akihiro Bryant, Sharon D. Jinsmaa, Yunden Lazarus, Lawrence H. Trapella, Claudio Salvadori, Severo TI Effect of lysine at C-terminus of the Dmt-Tic opioid pharmacophore SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MU-AGONIST/DELTA ANTAGONIST; RECEPTOR KNOCKOUT MICE; PEPTIDE ANTAGONISTS; BIOLOGICAL-ACTIVITY; OPIATE RECEPTOR; AMINO-ACIDS; DELTA; POTENT; SELECTIVITY; AFFINITY AB Substitution of Gly with side-chain-protected or unprotected Lys in lead compounds containing the opioid pharmacophore Dmt-Tic [H-Dmt-Tic-Gly-NH-CH2-Ph, A agonist/% antagonist; H-Dmt-Tic-Gly-NH-Ph, A agonist/% agonist; and H-Dmt-Tic-NH-CH2-Bid, delta agonist ( Bid) 1H-benzimidazole-2-yl)] yielded a new series of compounds endowed with distinct pharmacological activities. Compounds (1-10) included high delta- (K-i(delta) 0.068-0.64 nM) and mu-opioid affinities (K-i(u)) 0.13-5.50 nM), with a bioactivity that ranged from mu-opioid agonism {10, H-Dmt-Tic-NH-CH[(CH2)4-NH2]-Bid (IC50 GPI = 39.7 nM)} to a selective mu-opioid antagonist [3, H-Dmt-Tic-Lys-NH-CH2-Ph (pA(2)(mu) = 7.96)] and a selective mu-opioid antagonist [5, H-Dmt-Tic-Lys(Ac)-NH-Ph (pA(2)(delta) = 12.0)]. The presence of a Lys linker provides new lead compounds in the formation of opioid peptidomimetics containing the Dmt-Tic pharmacophore with distinct agonist and/or antagonist properties. C1 Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Tohoku Pharmaceut Univ, Aoba Ku, Sendai, Miyagi 9818558, Japan. NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Balboni, G (reprint author), Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. EM gbalboni@unica.it RI Onnis, Valentina/B-1649-2008; Trapella, Claudio/I-2128-2012; OI Onnis, Valentina/0000-0002-2438-725X; Trapella, Claudio/0000-0002-6666-143X; Congiu, Cenzo/0000-0003-2600-4221; SALVADORI, Severo/0000-0002-8224-2358 FU Intramural NIH HHS [Z01 ES090053-20] NR 47 TC 21 Z9 21 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 7 PY 2006 VL 49 IS 18 BP 5610 EP 5617 DI 10.1021/jm060741w PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079AX UT WOS:000240149000024 PM 16942034 ER PT J AU Neumeyer, JL Peng, XM Knapp, BI Bidlack, JM Lazarus, LH Salvadori, S Trapella, C Balboni, G AF Neumeyer, John L. Peng, Xuemei Knapp, Brian I. Bidlack, Jean M. Lazarus, Lawrence H. Salvadori, Severo Trapella, Claudio Balboni, Gianfranco TI New opioid designed multiple ligand from Dmt-Tic and morphinan pharmacophores SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BIVALENT LIGANDS; DELTA-ANTAGONIST; MU; PEPTIDES; DERIVATIVES; SELECTIVITY; GENERATION; RECEPTORS AB Here, we report the synthesis of a designed multi-pharmacophore ligand derived from the linkage of a delta selective peptide antagonist (Dmt-Tic) and a mu/kappa morphinan agonist butorphan (MCL 101) through a two methylene spacer. The new compound MCL 450 maintains the same characteristics as those the two reference compounds. MCL 450 represents a useful starting point for the synthesis of other multiple opioid ligands endowed with analgesic properties with low tolerance and dependence. C1 Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. Univ Rochester, Sch Med & Dent, Dept Pharmacol & Physiol, Rochester, NY 14642 USA. NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. RP Balboni, G (reprint author), Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM gbalboni@unica.it RI Trapella, Claudio/I-2128-2012; OI Trapella, Claudio/0000-0002-6666-143X; SALVADORI, Severo/0000-0002-8224-2358 FU Intramural NIH HHS [Z01 ES090053-20, Z01 ES100472-06, Z99 ES999999]; NIDA NIH HHS [K05 DA000360, K05-DA 00360, R01 DA014251, R01-DA14251] NR 19 TC 25 Z9 26 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 7 PY 2006 VL 49 IS 18 BP 5640 EP 5643 DI 10.1021/jm0605785 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079AX UT WOS:000240149000030 PM 16942040 ER PT J AU Day, J Rubin, J Vodovotz, Y Chow, CC Reynolds, A Clermont, G AF Day, Judy Rubin, Jonathan Vodovotz, Yoram Chow, Carson C. Reynolds, Angela Clermont, Gilles TI A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE immunology; mathematical modeling; anti-inflammatory cytokines; endotoxin tolerance; inflammation ID TUMOR NECROSIS FACTOR; GROWTH-FACTOR-BETA; IMMUNE-RESPONSE; IFN-GAMMA; IN-VIVO; TOLERANCE; INTERLEUKIN-10; MICE; SHOCK; MECHANISMS AB Bacterial lipopolysaccharide (LPS; endotoxin) is a potent immunostimulant that can induce an acute inflammatory response comparable to a bacterial infection. Experimental observations demonstrate that this biological response can be either blunted (tolerance) or augmented (potentiation) with repeated administration of endotoxin. Both phenomena are of clinical relevance. We show that a four-dimensional differential equation model of this response reproduces many scenarios involving repeated endotoxin administration. In particular, the model can display both tolerance and potentiation from a single parameter set, under different administration scenarios. The key determinants of the outcome of our simulations are the relative time-scales of model components. These findings support the hypothesis that endotoxin tolerance and other related phenomena can be considered as dynamic manifestations of a unified acute inflammatory response, and offer specific predictions related to the dynamics of this response to endotoxin. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA. CIRM, Pittsburgh, PA 15219 USA. Univ Pittsburgh, CRISMA Lab, Pittsburgh, PA 15261 USA. NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA 15261 USA. RP Rubin, J (reprint author), Univ Pittsburgh, Dept Math, 301 Thackeray, Pittsburgh, PA 15260 USA. EM rubin@math.pitt.edu RI Chow, Carson/A-7970-2009 FU Intramural NIH HHS; NIGMS NIH HHS [P50-GM-53789, R01-GM67240] NR 65 TC 77 Z9 79 U1 0 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD SEP 7 PY 2006 VL 242 IS 1 BP 237 EP 256 DI 10.1016/j.jtbi.2006.02.015 PG 20 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 084HZ UT WOS:000240525300020 PM 16616206 ER PT J AU Levine, RJ Lam, C Qian, C Yu, KF Maynard, SE Sachs, BP Sibai, BM Epstein, FH Romero, R Thadhani, R Karumanchi, SA AF Levine, Richard J. Lam, Chun Qian, Cong Yu, Kai F. Maynard, Sharon E. Sachs, Benjamin P. Sibai, Baha M. Epstein, Franklin H. Romero, Roberto Thadhani, Ravi Karumanchi, S. Ananth CA CPEP Study Grp TI Soluble endoglin and other circulating antiangiogenic factors in preeclampsia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; ANGIOGENIC FACTORS; PREGNANCY; RISK; RECEPTOR; WOMEN; HYPERTENSION; TRIAL; PATHOPHYSIOLOGY AB Background: Alterations in circulating soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a proangiogenic protein, appear to be involved in the pathogenesis of preeclampsia. Since soluble endoglin, another antiangiogenic protein, acts together with sFlt1 to induce a severe preeclampsia-like syndrome in pregnant rats, we examined whether it is associated with preeclampsia in women. Methods: We performed a nested case-control study of healthy nulliparous women within the Calcium for Preeclampsia Prevention trial. The study included all 72 women who had preterm preeclampsia (<37 weeks), as well as 480 randomly selected women - 120 women with preeclampsia at term (at >= 37 weeks), 120 women with gestational hypertension, 120 normotensive women who delivered infants who were small for gestational age, and 120 normotensive controls who delivered infants who were not small for gestational age. Results: Circulating soluble endoglin levels increased markedly beginning 2 to 3 months before the onset of preeclampsia. After the onset of clinical disease, the mean serum level in women with preterm preeclampsia was 46.4 ng per milliliter, as compared with 9.8 ng per milliliter in controls (P<0.001). The mean serum level in women with preeclampsia at term was 31.0 ng per milliliter, as compared with 13.3 ng per milliliter in controls (P<0.001). Beginning at 17 weeks through 20 weeks of gestation, soluble endoglin levels were significantly higher in women in whom preterm preeclampsia later developed than in controls (10.2 ng per milliliter vs. 5.8 ng per milliliter, P<0.001), and at 25 through 28 weeks of gestation, the levels were significantly higher in women in whom term preeclampsia developed than in controls (8.5 ng per milliliter vs. 5.9 ng per milliliter, P<0.001). An increased level of soluble endoglin was usually accompanied by an increased ratio of sFlt1:PlGF. The risk of preeclampsia was greatest among women in the highest quartile of the control distributions for both biomarkers but not for either biomarker alone. Conclusions: Rising circulating levels of soluble endoglin and ratios of sFlt1:PlGF herald the onset of preeclampsia. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Ctr Vasc Biol, Boston, MA 02215 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Mol & Vasc Med Div, Ctr Vasc Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Allied Technol Grp, Rockville, MD USA. George Washington Univ, Sch Med, Dept Med, Washington, DC USA. Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, Cincinnati, OH 45267 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Levine, RJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Ctr Vasc Biol, 330 Brookline Ave,RW 663B, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL-079594]; NICHD NIH HHS [N01-HD-3123, N01-HD-1-3121, N01-HD-3122, N01-HD-3124, N01-HD-3125, N01-HD-3126, N01-HD-3154, N01-HD-5-3246, R01 HD-39223]; NIDDK NIH HHS [R01 DK-065997, R01 DK-67397] NR 36 TC 861 Z9 911 U1 4 U2 38 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 7 PY 2006 VL 355 IS 10 BP 992 EP 1005 DI 10.1056/NEJMoa055352 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 080UF UT WOS:000240273300005 PM 16957146 ER PT J AU Dave, SS Staudt, LM AF Dave, Sandeep S. Staudt, Louis M. TI Genomic diagnosis of Burkitt's lymphoma - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Dave, SS (reprint author), NCI, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 7 PY 2006 VL 355 IS 10 BP 1064 EP 1064 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 080UF UT WOS:000240273300021 ER PT J AU Padayatty, SJ Levine, M AF Padayatty, Sebastian J. Levine, Mark TI Vitamins C and E and the prevention of preeclampsia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID RECOMMENDED DIETARY ALLOWANCE C1 NIH, Bethesda, MD 20892 USA. RP Padayatty, SJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 5 TC 6 Z9 7 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 7 PY 2006 VL 355 IS 10 BP 1065 EP 1065 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 080UF UT WOS:000240273300023 PM 16957157 ER PT J AU Binzoni, T Leung, TS Gandjbakhche, AH Ruefenacht, D Delpy, DT AF Binzoni, T. Leung, T. S. Gandjbakhche, A. H. Ruefenacht, D. Delpy, D. T. TI The use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; TIME-RESOLVED REFLECTANCE; PHOTON MIGRATION; LIGHT TRANSPORT; TISSUE; MODEL; TRANSMITTANCE; SCATTERING AB Monte Carlo (MC) simulations are often at the heart of the testing procedure in biomedical optics. One of the critical points in MC simulations is to define the new photon direction after each scattering event. One of the most popular solutions is to use the Henyey-Greenstein phase function or some linear combinations of it. In this note, we demonstrate that randomly generating the angle defining the new direction of a photon after a collision, by means of the Henyey-Greenstein phase function, is not equivalent to generating the cosine of this angle, as is classically done. In practice, it is demonstrated that for a nearly isotropic medium (asymmetry parameter g similar to 0) this discrepancy is not large, however for an anisotropic medium as is typically found in vivo (e.g. g = 0.98) the two methods give completely different results. C1 Univ Geneva, Dept Neurosci Fondamentales, CH-1211 Geneva 4, Switzerland. Univ Hosp Geneva, Dept Radiol & Informat Med, Geneva, Switzerland. UCL, Dept Med Phys & Bioengn, London, England. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Binzoni, T (reprint author), Univ Geneva, Dept Neurosci Fondamentales, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM Tiziano.Binzoni@medecine.unige.ch NR 24 TC 35 Z9 39 U1 3 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 7 PY 2006 VL 51 IS 17 BP N313 EP N322 DI 10.1088/0031-9155/51/17/N04 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 091SO UT WOS:000241048800023 PM 16912370 ER PT J AU Emanuel, EJ AF Emanuel, Ezekiel J. TI Changing premed requirements and the medical curriculum SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID EDUCATION; CARE; QUALITY C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 21 TC 35 Z9 35 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 6 PY 2006 VL 296 IS 9 BP 1128 EP 1131 DI 10.1001/jama.296.9.1128 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 081DW UT WOS:000240298400014 PM 16954492 ER PT J AU Pozdeyev, N Taylor, C Haque, R Chaurasia, SS Visser, A Thazyeen, A Du, YH Fu, H Weller, J Klein, DC Iuvone, PM AF Pozdeyev, Nikita Taylor, Carla Haque, Rashidul Chaurasia, Shyam S. Visser, Amy Thazyeen, Aamera Du, Yuhong Fu, Haian Weller, Joan Klein, David C. Iuvone, P. Michael TI Photic regulation of arylalkylamine N-acetyltransferase binding to 14-3-3 proteins in retinal photoreceptor cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE arylalkylamine-N-acetyltransferase; melatonin; 14-3-3 proteins; retina; photoreceptors; phosphorylation; light ID MELATONIN SYNTHESIS; PINEAL-GLAND; PROTEASOMAL PROTEOLYSIS; CIRCADIAN EXPRESSION; MESSENGER-RNA; MOUSE RETINA; LIGHT; LOCALIZATION; ENZYME; AMP AB 14-3-3 proteins are a ubiquitous, highly conserved family of chaperone proteins involved in signal transduction, regulation of cell cycle, intracellular trafficking/targeting, cytoskeletal structure, and transcription. Although 14-3-3 proteins are among the most abundant proteins in the CNS, very little is known about their functional roles in the vertebrate retina. In the present study, we demonstrated that photoreceptors express 14-3-3 protein(s) and identified a 14-3-3 binding partner in photoreceptor cells, the melatonin-synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT). Importantly, our data demonstrate that the binding of 14-3-3 to AANAT is regulated by light, with dramatic functional consequences. During the night in darkness, retinal AANAT is phosphorylated and forms a complex with 14-3-3 proteins with an apparent molecular weight of similar to 90 kDa. Phosphorylation of AANAT facilitates the binding of enzyme to 14-3-3 proteins. Within the complex, AANAT is catalytically activated and protected from dephosphorylation and degradation. Light disrupts the AANAT/14-3-3 complex, leading to catalytic inactivation, dephosphorylation, and proteolytic degradation of the enzyme. In the presence of the proteasome inhibitor, lactacystin, light results in the formation of a high molecular weight complex (> 150 kDa), which may represent an intermediate in the AANAT degradation process. These findings provide new insight into the roles of 14-3-3 proteins in photoreceptor cells and to the mechanisms controlling melatonin synthesis in the vertebrate retina. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. NICHHD, Neuroendocrinol Lab, NIH, Bethesda, MD 20892 USA. RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Pharmacol, 1510 Clifton Rd, Atlanta, GA 30322 USA. EM miuvone@pharm.emory.edu FU NEI NIH HHS [P30 EY06360, R01 EY04864, R01 EY004864] NR 42 TC 26 Z9 27 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 SEP 6 PY 2006 VL 26 IS 36 BP 9153 EP 9161 DI 10.1523/JNEUROSCI.1384-06.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 081NN UT WOS:000240324400012 PM 16957072 ER PT J AU Ying, JF Grishaev, A Bryce, DL Bax, A AF Ying, Jinfa Grishaev, Alexander Bryce, David L. Bax, Ad TI Chemical shift tensors of protonated base carbons in helical RNA and DNA from NMR relaxation and liquid crystal measurements SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; MOLECULAR-WEIGHT PROTEINS; NUCLEIC-ACID; IMPROVED SENSITIVITY; ROTATIONAL DIFFUSION; STRUCTURE REFINEMENT; BACKBONE DYNAMICS; SPIN RELAXATION; BOND LENGTHS; CSA TENSORS AB Knowledge of C-13 chemical shift anisotropy (CSA) tensors in nucleotide bases is important for interpretation of NMR relaxation data in terms of local dynamic properties of nucleic acids and for analysis of residual chemical shift anisotropy (RCSA) resulting from weak alignment. CSA tensors for protonated nucleic acid base carbons have been derived from measurements on a uniformly C-13-enriched helical A-form RNA segment and a helical B-form DNA dodecamer at natural C-13 abundance. The magnitudes of the derived CSA principal values are tightly restricted by the magnetic field dependencies of the 13C transverse relaxation rates, whereas the tensor orientation and asymmetry follow from quantitative measurements of interference between C-13-{H-1} dipolar and C-13 CSA relaxation mechanisms. Changes in the chemical shift between the isotropic and aligned states, Delta delta, complement these measurements and permit cross-validation. The CSA tensors are determined from the experimental Delta delta values and relaxation rates, under the assumption that the CSA tensor of any specific carbon in a given type of base is independent of the base position in either the RNA or DNA helix. However, the experimental data indicate that for pyrimidine C-6 carbons in A-form RNA the CSA magnitude is considerably larger than in B-form DNA. This result is supported by quantum chemical calculations and is attributed in part to the close proximity between intranucleotide C6H and O-5' atoms in RNA. The magnitudes of the measured CSA tensors, on average, agree better with previous solid-state NMR results obtained on powdered nucleosides than with prior results from quantum chemical calculations on isolated bases, which depend rather strongly on the level of theory at which the calculations are carried out. In contrast, previously computed orientations of the chemical shift tensors agree well with the present experimental results and exhibit less dependence on the level of theory at which the computations are performed. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Ottawa, Dept Chem, Ottawa, ON K1N 6N5, Canada. RP Ying, JF (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM jinfaying@niddk.nih.gov; alexanderg@intra.niddk.nih.gov; dbryce@uottawa.ca; bax@nih.gov RI Bryce, David/A-3534-2008 OI Bryce, David/0000-0001-9989-796X FU Intramural NIH HHS NR 90 TC 32 Z9 32 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 6 PY 2006 VL 128 IS 35 BP 11443 EP 11454 DI 10.1021/ja061984g PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 078PS UT WOS:000240116300037 PM 16939267 ER PT J AU Li, ZT Gildersleeve, JC AF Li, Zhitao Gildersleeve, Jeffrey C. TI Mechanistic studies and methods to prevent aglycon transfer of thioglycosides SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SEQUENTIAL GLYCOSYLATION STRATEGY; POT OLIGOSACCHARIDE SYNTHESIS; SELECTIVE OXIDATION; N-ACETYLGLUCOSAMINE; EFFICIENT SYNTHESIS; DONORS; SULFOXIDES; TRICHLOROACETIMIDATE; PENTASACCHARIDE; DERIVATIVES AB Thioglycosides have been employed extensively for the synthesis of complex oligosaccharides, carbohydrate libraries, and mimetics of O-glycosides. While very useful, aglycon transfer is a problematic side reaction with thioglycosides. In this paper, a series of mechanistic studies are described. The aglycon transfer process is shown to affect both armed and disarmed thioglycosides, cause anomerization of the carbon-sulfur bond of a thioglycoside, and destroy the product of a glycosylation reaction. The results indicate that the aglycon transfer process can be a major problem for a wide range of thioglycosides. This side reaction is especially important to consider when carrying out complex reactions such as solid-phase glycosylations, one-pot or orthogonal multicomponent glycosylations, and construction of carbohydrate libraries. To prevent transfer, a number of modified aglycons were examined. The 2,6-dimethylphenyl ( DMP) aglycon was found to effectively block transfer in a variety of model studies and glycosylation reactions. The DMP group can be installed in one step from a commercially available thiol ( 2,6-dimethylthiophenol) and is useable as a glycosyl donor. On the basis of these features, the DMP group is proposed as a convenient and improved aglycon for thioglycosides. C1 NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Gildersleeve, JC (reprint author), NCI, Med Chem Lab, Ctr Canc Res, 376 Boyles St,Bldg 376,Room 109, Frederick, MD 21702 USA. EM gildersleevej@ncifcrf.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU Intramural NIH HHS NR 61 TC 74 Z9 74 U1 3 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 6 PY 2006 VL 128 IS 35 BP 11612 EP 11619 DI 10.1021/ja063247q PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 078PS UT WOS:000240116300056 PM 16939286 ER PT J AU Simon, R AF Simon, Richard TI Development and evaluation of therapeutically relevant predictive classifiers using gene expression profiling SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ERROR ESTIMATION; BREAST-CANCER C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 16 TC 53 Z9 55 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 SEP 6 PY 2006 VL 98 IS 17 BP 1169 EP 1171 DI 10.1093/jnci/djj364 PG 3 WC Oncology SC Oncology GA 101EF UT WOS:000241721000001 PM 16954463 ER PT J AU Barlow, WE White, E Ballard-Barbash, R Vacek, PM Titus-Ernstoff, L Carney, PA Tice, JA Buist, DSM Geller, BM Rosenberg, R Yankaskas, BC Kerlikowske, K AF Barlow, William E. White, Emily Ballard-Barbash, Rachel Vacek, Pamela M. Titus-Ernstoff, Linda Carney, Patricia A. Tice, Jeffrey A. Buist, Diana S. M. Geller, Berta M. Rosenberg, Robert Yankaskas, Bonnie C. Kerlikowske, Karla TI Prospective breast cancer risk prediction model for women undergoing screening mammography SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HORMONE-REPLACEMENT THERAPY; ESTROGEN-PLUS-PROGESTIN; BODY-MASS INDEX; HEALTHY POSTMENOPAUSAL WOMEN; INITIATIVE RANDOMIZED-TRIAL; GAIL MODEL; FAMILY-HISTORY; RECEPTOR STATUS; IN-SITU; DENSITY AB Background. Risk prediction models for breast cancer can be improved by the addition of recently identified risk factors, including breast density and use of hormone therapy. We used prospective risk information to predict a diagnosis of breast cancer in a cohort of 1 million women undergoing screening mammography. Methods: There were 2 392 998 eligible screening mammograms from women without previously diagnosed breast cancer who had had a prior mammogram in the preceding 5 years. Within 1 year of the screening mammogram, 11638 women were diagnosed with breast cancer. Separate logistic regression risk models were constructed for premenopausal and postmenopausal examinations by use of a stringent (P <.0001) criterion for the inclusion of risk factors. Risk models were constructed with 75% of the data and validated with the remaining 25%. Concordance of the predicted with the observed outcomes was assessed by a concordance (c) statistic after logistic regression model fit. All statistical tests were two-sided. Results: Statistically significant risk factors for breast cancer diagnosis among premenopausal women included age, breast density, family history of breast cancer, and a prior breast procedure. For postmenopausal women, the statistically significant factors included age, breast density, race, ethnicity, family history of breast cancer, a prior breast procedure, body mass index, natural menopause, hormone therapy, and a prior false-positive mammogram. The model may identify high-risk women better than the Gail model, although predictive accuracy was only moderate. The c statistics were 0.631 (95% confidence interval [CI] = 0.618 to 0.644) for premenopausal women and 0.624 (95% CI = 0.619 to 0.630) for postmenopausal women. Conclusion: Breast density is a strong additional risk factor for breast cancer, although it is unknown whether reduction in breast density would reduce risk. Our risk model may be able to identify women at high risk for breast cancer for preventive interventions or more intensive surveillance. C1 Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Med Biostat, Vermont Reg Canc Ctr, Burlington, VT USA. Norris Cotton Canc Ctr, Lebanon, NH USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Lebanon, NH USA. Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Vermont, Coll Med, Off Hlth Promot Res, Burlington, VT USA. Univ New Mexico, Dept Radiol, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Univ Calif San Francisco, Dept Vet Affairs, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Barlow, WE (reprint author), 1730 Minor Ave,Suite 1900, Seattle, WA 98101 USA. EM williamb@crab.org FU NCI NIH HHS [U01CA63736, U01 CA086082, U01CA63731, U01CA63740, U01CA69976, U01CA70013, U01CA70040, U01CA86076, U01CA86082] NR 87 TC 235 Z9 241 U1 2 U2 11 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 SEP 6 PY 2006 VL 98 IS 17 BP 1204 EP 1214 DI 10.1093/jnci/djj331 PG 11 WC Oncology SC Oncology GA 101EF UT WOS:000241721000011 PM 16954473 ER PT J AU Chen, JB Pee, D Ayyagari, R Graubard, B Schairer, C Byrne, C Benichou, J Gail, MH AF Chen, Jinbo Pee, David Ayyagari, Rajeev Graubard, Barry Schairer, Catherine Byrne, Celia Benichou, Jacques Gail, Mitchell H. TI Projecting absolute invasive breast cancer risk in white women with a model that includes mammographic density SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PREDICTION; VALIDATION; TAMOXIFEN AB Background. To improve the discriminatory power of the Gail model for predicting absolute risk of invasive breast cancer, we previously developed a relative risk model that incorporated mammographic density (DENSITY) from data on white women in the Breast Cancer Detection Demonstration Project (BCDDP). That model also included the variables age at birth of first live child (AGEFLB), number of affected mother or sisters (NUMREL), number of previous benign breast biopsy examinations (NBIOPS), and weight (WEIGHT). In this study, we developed the corresponding model for absolute risk. Methods: We combined the relative risk model with data on the distribution of the variables AGEFLB, NUMREL, NBIOPS, and WEIGHT from the 2000 National Health Interview Survey, with data on the conditional distribution of DENSITY given other risk factors in BCDDP, with breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, and with national mortality rates. Confidence intervals (CIs) accounted for variability of estimates of relative risks and of risk factor distributions. We compared the absolute 5-year risk projections from the new model with those from the Gail model on 1744 white women. Results: Attributable risks of breast cancer associated with DENSITY, AGEFLB, NUMREL, NBIOPS, and WEIGHT were 0.779 (95% CI = 0.733 to 0.819) and 0.747 (95% CI = 0.702 to 0.788) for women younger than 50 years and 50 years or older, respectively. The model predicted higher risks than the Gail model for women with a high percentage of dense breast area. However, the average risk projections from the new model in various age groups were similar to those from the Gail model, suggesting that the new model is well calibrated. Conclusions: This new model for absolute invasive breast cancer risk in white women promises modest improvements in discriminatory power compared with the Gail model but needs to be validated with independent data. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Informat Management Syst, Rockville, MD USA. Georgetown Univ, Canc Genet & Epidemiol Program, Lombardi Comprehens Canc Ctr, Washington, DC USA. Rouen Univ Hosp, Sch Med, INSERM, U657, Rouen, France. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 18 TC 189 Z9 196 U1 0 U2 10 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 SEP 6 PY 2006 VL 98 IS 17 BP 1215 EP 1226 DI 10.1093/jnci/djj332 PG 12 WC Oncology SC Oncology GA 101EF UT WOS:000241721000012 PM 16954474 ER PT J AU Bobb, AJ Castellanos, FX Addington, AM Rapoport, JL AF Bobb, Aaron J. Castellanos, F. Xavier Addington, Anjene M. Rapoport, Judith L. TI Molecular genetic studies of ADHD: 1991 to 2004 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE review; attention deficit disorder with hyperactivity; candidate gene; polymorphism ID ATTENTION-DEFICIT HYPERACTIVITY; DOPAMINE-D4 RECEPTOR GENE; CATECHOL-O-METHYLTRANSFERASE; SEROTONIN TRANSPORTER GENE; DEPENDENT PROTEIN-KINASE; CASE-CONTROL ASSOCIATION; MONOAMINE-OXIDASE-A; MAJOR HISTOCOMPATIBILITY COMPLEX; ALPHA-2A ADRENERGIC-RECEPTOR; PROMOTER REGION POLYMORPHISM AB Attention deficit hyperactivity disorder (ADHD) is highly heritable but is likely a complex disorder involving multiple genes of moderate effect (Smalley [1997: Am J Hum Genet 60:1276-1282]). Over 100 studies have examined the genetics of ADHD by linkage or association, though no article has presented a comprehensive overview of all published reports. We reviewed all ADHD studies, including 3 genome-wide linkage studies, and association studies of 94 polymorphisms in 33 candidate genes. To simplify comparisons across heterogeneous articles, demographics and comorbidity were ignored; analyses of subtype and haplotypes were excluded; and only the most positive finding for each polymorphism in a study was reported. Thirty-six percent of all findings were positive (P <= 0.05), 17% were trends (0.05 < P < 0.15), and 47% were negative (P > 0.15). Studies utilizing dimensional measures of ADHD tended to result in higher rates of positive findings than those using categorical diagnoses (chi(2) = 5.6, P = 0.018). and case-control studies tended to result in higher rates of positive findings than family-based studies (chi(2) = 18.8, P < 0.001). However, for either dichotomy, no significant difference remained when analyzing only studies using both methods within the same population and polymorphism. Evidence for association exists for four genes in ADHD: the dopamine D4 and D5 receptors, and the dopamine and serotonin transporters; others are promising but need further replication, including the dopamine D2 and serotonin 2A receptors. All candidate gene approaches continue to face the problem of relatively low power, given modest odds ratios for even the best replicated genes. Published 2004 Wiley-Liss, Inc. C1 NIMH, Child Psychiat Branch, IRP, NIH, Bethesda, MD 20892 USA. NYU, Child Study Ctr, New York, NY USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, IRP, NIH, 10 Ctr Dr,Bldg 10,Room 3N-202, Bethesda, MD 20892 USA. EM rapoport@helix.nih.gov NR 217 TC 15 Z9 16 U1 9 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2006 VL 141B IS 6 BP 551 EP 565 DI 10.1002/ajmg.b.30086 PG 15 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 077RZ UT WOS:000240049100001 ER PT J AU Enoch, MA Schwartz, L Albaugh, B Virkkunen, M Goldman, D AF Enoch, Mary-Anne Schwartz, Lori Albaugh, Bernard Virkkunen, Matti Goldman, David TI Dimensional anxiety mediates linkage of GABRA2 haplotypes with alcoholism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE SNPs; polymorphisms; GABAA; American Indian; harm avoidance ID GABA(A) RECEPTOR; SEX-DIFFERENCES; DEPENDENCE; POPULATION; ASSOCIATION; BRAIN; GENE; PERSONALITY; SUBUNIT; VARIANT AB The GABAA(alpha 2) receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-onfiguration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P = 0.007, OR = 2.1, Plains Indians: P = 0.040, OR = .9). Nonalcoholics had intermediate frequencies. Our results suggest that within the distal GABP,42 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety. (c) 2006 Wiley-Liss, Inc. C1 Ctr Human Behav Studies Inc, Weatherford, OK USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NIAAA, NIH, DICBR, LNG, Bethesda, MD 20892 USA. RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM maenoch@niaaa.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS [Z01 AA000305-04] NR 32 TC 77 Z9 79 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2006 VL 141B IS 6 BP 599 EP 607 DI 10.1002/ajmg.b.30336 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 077RZ UT WOS:000240049100007 PM 16874763 ER PT J AU Hardy, J AF Hardy, John TI Bad luck: An unappreciated limitation in the interpretation of twin studies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Letter C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM hard3j@mail.nih.gov RI Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 5 TC 3 Z9 3 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2006 VL 141B IS 6 BP 681 EP 681 DI 10.1002/ajmg.b.30353 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 077RZ UT WOS:000240049100021 PM 16823802 ER PT J AU McGinnis, JM Birt, DF Brannon, PM Carroll, RJ Gibbons, RD Hazzard, WR Kamerow, DB Levin, B Ntambi, JM Paneth, N Rogers, D Saftlas, AF Vaughan, W AF McGinnis, J. Michael Birt, Diane F. Brannon, Patsy M. Carroll, Raymond J. Gibbons, Robert D. Hazzard, William R. Kamerow, Douglas B. Levin, Bernard Ntambi, James M. Paneth, Nigel Rogers, Douglas Saftlas, Audrey F. Vaughan, William CA NIH State of Science TI National Institutes of Health state-of-the-science conference statement: Multivitamin/mineral supplements and chronic disease prevention SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; NUTRITION INTERVENTION TRIALS; AGE-RELATED CATARACT; BETA-CAROTENE; VITAMIN-E; CARDIOVASCULAR-DISEASE; ALPHA-TOCOPHEROL; LUNG-CANCER; COLORECTAL-CANCER; PROSTATE-CANCER C1 Natl Acad, Inst Med, Washington, DC USA. Iowa State Univ, Dept Food Sci & Human Nutr, Ctr Res Bot Dietary Supplements, Ames, IA USA. Iowa State Univ, Coll Agr, Ames, IA USA. Iowa State Univ, Coll Human Sci, Ames, IA USA. Cornell Univ, Div Nutrit Sci, Ithaca, NY USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. Univ Illinois, Ctr Hlth Stat, Chicago, IL USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Georgetown Univ, Washington, DC USA. RTI Int, Washington, DC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. Univ Wisconsin, Dept Nutrit Sci, Madison, WI 53705 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Cleveland Clin, Sect Pediat & Adolescent Endocrinol, Cleveland, OH 44106 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Consumers Union, Washington, DC USA. NIH, Bethesda, MD 20892 USA. RP McGinnis, JM (reprint author), Natl Acad, Inst Med, Washington, DC USA. NR 27 TC 56 Z9 58 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 5 PY 2006 VL 145 IS 5 BP 364 EP 371 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 080NZ UT WOS:000240255900007 ER PT J AU Anantharaman, V Balaji, S Aravind, L AF Anantharaman, Vivek Balaji, S. Aravind, L. TI The signaling helix: a common functional theme in diverse signaling proteins SO BIOLOGY DIRECT LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; HISTIDINE-KINASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; LIGAND-BINDING; DOMAIN COMMON; TRANSMEMBRANE RECEPTORS; COILED COILS; SWISS-MODEL; GAF DOMAINS AB Background: The mechanism by which the signals are transmitted between receptor and effector domains in multi-domain signaling proteins is poorly understood. Results: Using sensitive sequence analysis methods we identify a conserved helical segment of around 40 residues in a wide range of signaling proteins, including numerous sensor histidine kinases such as Sln1p, and receptor guanylyl cyclases such as the atrial natriuretic peptide receptor and nitric oxide receptors. We term this helical segment the signaling (S)-helix and present evidence that it forms a novel parallel coiled-coil element, distinct from previously known helical segments in signaling proteins, such as the Dimerization-Histidine phosphotransfer module of histidine kinases, the intra-cellular domains of the chemotaxis receptors, inter-GAF domain helical linkers and the alpha-helical HAMP module. Analysis of domain architectures allowed us to reconstruct the domain-neighborhood graph for the S-helix, which showed that the S-helix almost always occurs between two signaling domains. Several striking patterns in the domain neighborhood of the S-helix also became evident from the graph. It most often separates diverse N-terminal sensory domains from various C-terminal catalytic signaling domains such as histidine kinases, cNMP cyclase, PP2C phosphatases, NtrC-like AAA+ ATPases and diguanylate cyclases. It might also occur between two sensory domains such as PAS domains and occasionally between a DNA-binding HTH domain and a sensory domain. The sequence conservation pattern of the S-helix revealed the presence of a unique constellation of polar residues in the dimer-interface positions within the central heptad of the coiled-coil formed by the S-helix. Conclusion: Combining these observations with previously reported mutagenesis studies on different S-helix-containing proteins we suggest that it functions as a switch that prevents constitutive activation of linked downstream signaling domains. However, upon occurrence of specific conformational changes due to binding of ligand or other sensory inputs in a linked upstream domain it transmits the signal to the downstream domain. Thus, the S- helix represents one of the most prevalent functional themes involved in the flow of signals between modules in diverse prokaryote-type multi-domain signaling proteins. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM ananthar@mail.nih.gov; sbalaji@mail.nih.gov; aravind@mail.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 NR 75 TC 65 Z9 65 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD SEP 5 PY 2006 VL 1 AR 25 DI 10.1186/1745-6150-1-25 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133TF UT WOS:000244035700001 PM 16953892 ER PT J AU Solomon, SD Pfeffer, MA McMurray, JJV Fowler, R Finn, P Levin, B Eagle, C Hawk, E Lachuga, M Zauber, AG Bertagnolli, MM Arber, N Wittes, J AF Solomon, Scott D. Pfeffer, Marc A. McMurray, John J. V. Fowler, Rob Finn, Peter Levin, Bernard Eagle, Craig Hawk, Ernest Lachuga, Mariajose Zauber, Ann G. Bertagnolli, Monica M. Arber, Nadir Wittes, Janet CA APC PreSAP Trial Investigator TI Effect of Celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas SO CIRCULATION LA English DT Article DE antiinflammatory agents, nonsteroidal; cyclooxygenase inhibitors; pharmacology ID CYCLOOXYGENASE-2 INHIBITOR; COX-2; ROFECOXIB; HYPERTENSION; RISK AB Background - Cyclooxygenase-2 (COX-2) inhibitors have been shown to reduce colorectal adenomas but have been associated with increased cardiovascular risk. Methods and Results - The Adenoma Prevention With Celecoxib (APC) trial studied celecoxib 200 mg twice daily and 400 mg twice daily and the Prevention of Spontaneous Adenomatous Polyps (PreSAP) trial used 400 mg once daily to test the efficacy and safety of celecoxib against placebo in reducing colorectal adenoma recurrence after polypectomy. An independent safety committee for both studies adjudicated and categorized serious cardiovascular events and then combined individual patient data from these long-term trials to improve the estimate of the cardiovascular risk and blood pressure changes associated with celecoxib compared with placebo. For adjudicated cardiovascular events, 77% and 54% in APC and PreSAP, respectively, had 37 months of follow-up. For APC and PreSAP combined, 83 patients experienced cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure. The hazard ratio for this prespecified composite end point was 2.6 (95% confidence interval [CI], 1.1 to 6.1) in patients taking 200 mg twice daily, 3.4 (95% CI, 1.5 to 7.9) in patients taking 400 mg twice daily in APC, and 1.3 (95% CI, 0.6 to 2.6) in patients taking 400 mg once daily in PreSAP (P for heterogeneity = 0.13 comparing the combined doses in APC with the dose in PreSAP). The overall hazard ratio for this composite end point was 1.9 (95% CI, 1.1 to 3.1). Both dose groups in APC showed significant systolic blood pressure elevations at 1 and 3 years ( 200 mg twice daily: 1 year, 2.0 mm Hg; 3 years, 2.6 mm Hg; 400 mg twice daily: 1 year, 2.9 mm Hg; 3 years, 5.2 mm Hg); however, the 400 mg once daily group in PreSAP did not (P < 0.0001 between studies). Conclusions - Celecoxib at 200 or 400 mg twice daily or 400 mg once daily showed a nearly 2-fold-increased cardiovascular risk. The trend for a dose-related increase in cardiovascular events and blood pressure raises the possibility that lower doses or other dose intervals may be associated with less cardiovascular risk. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Western Infirm & Associated Hosp, Glasgow, Lanark, Scotland. Stat Collaborat Inc, Washington, DC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Pfizer Inc, New York, NY USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Solomon, Scott/I-5789-2013; OI mcmurray, john/0000-0002-6317-3975 NR 18 TC 181 Z9 187 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 5 PY 2006 VL 114 IS 10 BP 1028 EP 1035 DI 10.1161/CIRCULATIONAHA.106.636746 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 080JV UT WOS:000240244700007 PM 16943394 ER PT J AU Kathiresan, S Gona, P Larson, MG Levy, D Newton-Cheh, C Wang, TJ Benjamin, EJ Vasan, RS Vita, JA Mitchell, GF Tofler, GH AF Kathiresan, Sekar Gona, Philimon Larson, Martin G. Levy, Daniel Newton-Cheh, Christopher Wang, Thomas J. Benjamin, Emelia J. Vasan, Ramachandran S. Vita, Joseph A. Mitchell, Gary F. Tofler, Geoffrey H. TI Response to letter regarding article,"Cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function" SO CIRCULATION LA English DT Letter ID BRAIN NATRIURETIC PEPTIDE; HEART-FAILURE C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Evans Dept Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Cardiovasc Engn Inc, Holliston, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. RP Kathiresan, S (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM vasan@bu.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 5 PY 2006 VL 114 IS 10 BP E384 EP E384 DI 10.1161/CIRCULATIONAHA.106.638577 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 080JV UT WOS:000240244700019 ER PT J AU Lin, P Pedersen, LC Batra, VK Beard, WA Wilson, SH Pedersen, LG AF Lin, Ping Pedersen, Lars C. Batra, Vinod K. Beard, William A. Wilson, Samuel H. Pedersen, Lee G. TI Energy analysis of chemistry for correct insertion by DNA polymerase beta SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE quantum mechanics; molecular mechanics; reaction mechanism ID INDUCED-FIT MECHANISM; SITE-DIRECTED MUTAGENESIS; PARTICLE MESH EWALD; ACTIVE-SITE; COMPUTER-SIMULATIONS; ALKALINE-PHOSPHATASE; REPLICATION FIDELITY; STRUCTURAL INSIGHTS; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURES AB X-ray crystallographic structures of human DNA polymerase beta with nonhydrolyzable analogs containing all atoms in the active site required for catalysis provide a secure starting point for a theoretical analysis (quantum mechanics/molecular mechanics) of the mechanism of chemistry without biasing of modeling assumptions as required in previous studies. These structures provide the basis for a detailed quantum mechanics/molecular mechanics study of the path for the complete transfer of a monophosphate nucleoside donor to the sugar acceptor in the active site. The reaction is largely associative with the main energetic step preceded by proton transfer from the terminal primer deoxyribose O3' to Asp-256. The key residues that provide electrostatic stabilization of the transition state are identified and compared with those identified by mutational studies. C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. EM pedersen@email.unc.edu RI Pedersen, Lee/E-3405-2013; Lin, Ping/C-7115-2008 OI Pedersen, Lee/0000-0003-1262-9861; Lin, Ping/0000-0003-1200-4423 FU Intramural NIH HHS; NCI NIH HHS [1U19CA105010, U19 CA105010]; NHLBI NIH HHS [P01 HL006350, HL-06350] NR 75 TC 65 Z9 66 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 5 PY 2006 VL 103 IS 36 BP 13294 EP 13299 DI 10.1073/pnas.0606006103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 084DR UT WOS:000240512700009 PM 16938895 ER PT J AU Liu, J Wang, L Harvey-White, J Osei-Hyiaman, D Razdan, R Gong, Q Chan, AC Zhou, ZF Huang, BX Kim, HY Kunos, G AF Liu, Jie Wang, Lei Harvey-White, Judith Osei-Hyiaman, Douglas Razdan, Raj Gong, Qian Chan, Andrew C. Zhou, Zhifeng Huang, Bill X. Kim, Hee-Yong Kunos, George TI A biosynthetic pathway for anandamide SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biosynthesis; phosphatase; phospholipase C; phosphoanandamide ID CANNABINOID-RECEPTOR; TYROSINE-PHOSPHATASE; ENDOGENOUS CANNABINOIDS; CELLS; CB1; ACTIVATION; MACROPHAGES; CIRRHOSIS; NEURONS; ACID AB The endocannabinoid arachiclonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released "on demand" by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N-arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE-PLD). Here we document a biosynthetic pathway for anandamide in mouse brain and RAW264.7 macrophages that involves the phospholipase C (PLC)-catalyzed cleavage of NAPE to generate a lipid, phosphoanandamide, which is subsequently dephosphorylated by phosphatases, including PTPN22, previously described as a protein tyrosine phosphatase. Bacterial endotoxin (LPS)-induced synthesis of anandamide in macrophages is mediated exclusively by the PLC/phosphatase pathway, which is up-regulated by LIPS, whereas NAPE-PLD is down-regulated by LPS and functions as a salvage pathway of anandamide synthesis when the PLC/phosphatase pathway is compromised. Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Mol Signaling Lab, NIH, Bethesda, MD 20892 USA. Organix Inc, Woburn, MA 01801 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Liu, J (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM jiel@mail.nih.gov; gkunos@mail.nih.gov FU Intramural NIH HHS NR 31 TC 238 Z9 249 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 5 PY 2006 VL 103 IS 36 BP 13345 EP 13350 DI 10.1073/pnas.0601832103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 084DR UT WOS:000240512700018 PM 16938887 ER PT J AU Wang, HY Parry, S Macones, G Sammel, MD Kuivaniemi, H Tromp, G Argyropoulos, G Halder, I Shriver, MD Romero, R Strauss, JF AF Wang, Hongyan Parry, Samuel Macones, George Sammel, Mary D. Kuivaniemi, Helena Tromp, Gerard Argyropoulos, George Halder, Indrani Shriver, Mark D. Romero, Roberto Strauss, Jerome F., II TI A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Hsp47 ID BACTERIAL VAGINOSIS; CIGARETTE-SMOKING; COLLAGEN CONTENT; FETAL MEMBRANES; BIRTH-WEIGHT; WHITE WOMEN; POLYMORPHISM; EXPRESSION AB Prematurity is more prevalent in African Americans than in European Americans. We investigated the contribution of a functional SNP in the promoter of the SERPINH1 gene, enriched among those of African ancestry, to preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth. SERPINH1 encodes heat-shock protein 47, a chaperone essential for collagen synthesis. The SERPINH1 -656 minor T allele had a greater frequency in African populations and African Americans than in European Americans (12.4% vs. 4.1%). The -656 T allele displayed significantly reduced promoter activity compared to the major -656 C allele in amnion fibroblasts, which lay down the fibrillar collagen that gives tensile strength to the amnion. An initial case-control study demonstrated that the -656 T allele is significantly more frequent in African-American neonates (P < 0.0009) born from pregnancies complicated by PPROM compared with controls (odds ratio of 3.22, 95% confidence interval 1.50, 7.22). There was no significant difference in ancestry among cases and controls using a dihybrid model based on 29 ancestry-informative markers. Adjusting the results of the case-control study for admixture still yielded a statistically significant association between the -656 T allele and PPROM (P < 0.002). A follow-up case-control study gave similar results. The combined case-control findings showed a highly significant (P < 0.0000045) association between the -656 T allele and PPROM. The SERPINH1 -656 T allele is the first example of an ancestry-informative marker associated with preterm birth in African Americans. C1 Virginia Commonwealth Univ, Dept Obstet & Gynecol, Richmond, VA 23298 USA. Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. Hutzel Hosp, NICHHD, Perinatal Res Branch, Detroit, MI 48201 USA. Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Dept Obstet & Gynecol, Sanger Hall,1st Floor,Room 1071,1101 E Marshall S, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu RI Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU Intramural NIH HHS; NICHD NIH HHS [R01 HD034612, HD34612] NR 18 TC 61 Z9 65 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 5 PY 2006 VL 103 IS 36 BP 13463 EP 13467 DI 10.1073/pnas.0603676103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 084DR UT WOS:000240512700038 PM 16938879 ER PT J AU Henry, T Couillault, C Rockenfeller, P Boucrot, E Dumont, A Schroeder, N Hermant, A Knodler, LA Lecine, P Steele-Mortimer, O Borg, JP Gorvel, JP Meresse, S AF Henry, Thomas Couillault, Carole Rockenfeller, Patrick Boucrot, Emmanuel Dumont, Audrey Schroeder, Nina Hermant, Aurelie Knodler, Leigh A. Lecine, Patrick Steele-Mortimer, Olivia Borg, Jean-Paul Gorvel, Jean-Pierre Meresse, Stephane TI The Salmonella effector protein PipB2 is a linker for kinesin-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sifA; molecular motor ID III SECRETION SYSTEM; LYSOSOMAL MEMBRANE-GLYCOPROTEINS; PATHOGENICITY ISLAND 2; IN-VIVO; BACTERIAL VIRULENCE; EPITHELIAL-CELLS; HOST-CELLS; TYPHIMURIUM; MACROPHAGES; IDENTIFICATION AB Understanding the mechanisms of Salmonella virulence is an important challenge. The capacity of this intracellular bacterial pathogen to cause diseases depends on the expression of virulence factors including the second type III secretion system (TTSS-2), which is used to translocate into the eukaryotic cytosol a set of effector proteins that divert the biology of the host cell and shape the bacterial replicative niche. Yet little is known about the eukaryotic functions affected by individual Salmonella effectors. Here we report that the TTSS-2 effector PipB2 interacts with the kinesin light chain, a subunit of the kinesin-1 motor complex that drives anterograde transport along microtubules. Translocation of PipB2 is both necessary and sufficient for the recruitment of kinesin-1 to the membrane of the Salmonella-containing vacuole. In vivo, PipB2 contributes to the attenuation of Salmonella mutant strains in mice. Taken together, our data indicate that the TTSS-2-mediated fine-tuning of kinesin-1 activity associated with the bacterial vacuole is crucial for the virulence of Salmonella. C1 Univ Mediterranee, INSERM, CNRS, Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. INSERM, UMR 599, F-13009 Marseille, France. Inst J Paoli I Calmettes, F-13009 Marseille, France. NIAID, Rocky Mt Lab, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. RP Meresse, S (reprint author), Univ Mediterranee, INSERM, CNRS, Ctr Immunol Marseille Luminy, Parc Sci Luminy,Case 906, F-13288 Marseille 9, France. EM meresse@ciml.univ-mrs.fr RI Meresse, Stephane/E-2192-2012; henry, thomas/G-3160-2013; Lecine, Patrick/H-9338-2016; OI Meresse, Stephane/0000-0001-6578-5177; henry, thomas/0000-0002-0687-8565; Gorvel, Jean-Pierre/0000-0002-2829-9804 FU Intramural NIH HHS NR 35 TC 82 Z9 84 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 5 PY 2006 VL 103 IS 36 BP 13497 EP 13502 DI 10.1073/pnas.0605443103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 084DR UT WOS:000240512700044 PM 16938850 ER PT J AU Tu, X Latifi, T Bougdour, A Gottesman, S Groisman, EA AF Tu, Xuanlin Latifi, Tammy Bougdour, Alexandre Gottesman, Susan Groisman, Eduardo A. TI The PhoP/PhoQ two-component system stabilizes the alternative sigma factor RpoS in Salmonella enterica SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE iraP; magnesium; Escherichia coli ID RESPONSE REGULATOR RSSB; ACID TOLERANCE RESPONSE; ESCHERICHIA-COLI; GENE-EXPRESSION; PHOP-PHOQ; MOLECULAR CHARACTERIZATION; TYPHIMURIUM VIRULENCE; SIGNAL-TRANSDUCTION; SEROVAR TYPHIMURIUM; RECOGNITION FACTOR AB The sigma factor RpoS regulates the expression of many stress response genes and is required for virulence in several bacterial species. We now report that RpoS accumulates when Salmonella enterica serovar Typhimurium is growing logarithmically in media with low Mg2+ concentrations. This process requires the two-component regulatory system PhoP/PhoQ, which is specifically activated in low Mg2+. We show that PhoP controls RpoS protein turnover by serving as a transcriptional activator of the iraP (yaiB) gene, which encodes a product that enhances RpoS stability by interacting with RssB, the protein that normally delivers RpoS to the ClpXP protease for degradation. Mutation of the phoP gene rendered Salmonella as sensitive to hydrogen peroxide as an rpoS mutant after growth in low Mg2+. In Escherichia coli, low Mg2+ leads to only modest RpoS stabilization, and iraP is not regulated by PhoP/PhoQ. These findings add the sigma factor RpoS to the regulatory proteins and two-component systems that are elevated in a PhoP/PhoQ-dependent fashion when Salmonella face low Mg2+ environments. Our data also exemplify the critical differences in regulatory circuits that exist between the closely related enteric bacteria Salmonella and E. coli. C1 Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. EM susang@helix.nih.gov; groisman@borcim.wusti.edu RI Bougdour, Alexandre/K-3795-2014 OI Bougdour, Alexandre/0000-0002-5895-0020 FU Intramural NIH HHS; NIAID NIH HHS [AI49561, R01 AI049561] NR 54 TC 68 Z9 72 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 5 PY 2006 VL 103 IS 36 BP 13503 EP 13508 DI 10.1073/pnas.0606026103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 084DR UT WOS:000240512700045 PM 16938894 ER PT J AU Kato, H Anderson, JM Kamhawi, S Oliveira, F Lawyer, PG Pham, VM Sangare, CS Samake, S Sissoko, I Garfield, M Sigutova, L Volf, P Doumbia, S Valenzuela, JG AF Kato, Hirotomo Anderson, Jennifer M. Kamhawi, Shaden Oliveira, Fabiano Lawyer, Phillip G. Pham, Van My Sangare, Constance Souko Samake, Sibiry Sissoko, Ibrahim Garfield, Mark Sigutova, Lucie Volf, Petr Doumbia, Seydou Valenzuela, Jesus G. TI High degree of conservancy among secreted salivary gland proteins from two geographically distant Phlebotomus duboscqi sandflies populations (Mali and Kenya) SO BMC GENOMICS LA English DT Article ID FLY LUTZOMYIA-LONGIPALPIS; SAND FLY; ADENOSINE-DEAMINASE; AEDES-AEGYPTI; CUTANEOUS LEISHMANIASIS; VASODILATORY PEPTIDE; FEMALE MOSQUITO; IDENTIFICATION; VECTOR; MAXADILAN AB Background: Salivary proteins from sandflies are potential targets for exploitation as vaccines to control Leishmania infection; in this work we tested the hypothesis that salivary proteins from geographically distant Phlebotomus duboscqi sandfly populations are highly divergent due to the pressure exerted by the host immune response. Salivary gland cDNA libraries were prepared from wild-caught P. duboscqi from Mali and recently colonised flies of the same species from Kenya. Results: Transcriptome and proteome analysis resulted in the identification of the most abundant salivary gland-secreted proteins. Orthologues of these salivary proteins were identified by phylogenetic tree analysis. Moreover, comparative analysis between the orthologues of these two different populations resulted in a high level of protein identity, including the predicted MHC class II T-cell epitopes from all these salivary proteins. Conclusion: These data refute the hypothesis that salivary proteins from geographically distinct populations of the same Phlebotomus sandfly species are highly divergent. They also suggest the potential for using the same species-specific components in a potential vector saliva-based vaccine. C1 Yamaguchi Univ, Fac Agr, Dept Vet Hyg, Yamaguchi 753, Japan. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Fed Bahia, Fac Med, Salvador, BA, Brazil. Fdn Oswaldo Cruz, Ctr Pesquia Goncalo Moniz, Salvador, BA, Brazil. Univ Bamako, Fac Sci & Technol, Bamako, Mali. Univ Bamako, Malaria Res & Training Ctr, Fac Med, Bamako, Mali. NIAID, Res Technol Branch, NIH, Rockville, MD USA. Charles Univ, Dept Parasitol, Prague, Czech Republic. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Maalaria & Vector Res, NIH, Rockville, MD USA. EM katoh@yamaguchi-u.ac.jp; jenanderson@niaid.nih.gov; skamhawi@niaid.nih.gov; loliveira@niaid.nih.gov; PhillipL@niaid.nih.gov; vpham@niaid.nih.gov; sangaremaman36@yahoo.fr; ssam@MRTCBKO.org; siib197012@yahoo.fr; MGARFIELD@niaid.nih.gov; volf@cesnet.cz; volf@cesnet.cz; sdoumbi@MRTCBKO.org; jvalenzuela@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; Kato, Hirotomo/A-4820-2012; Volf, Petr/C-4300-2012 OI Oliveira, Fabiano/0000-0002-7924-8038; Kato, Hirotomo/0000-0001-5429-9536; Volf, Petr/0000-0003-1790-1123 FU Intramural NIH HHS; NIAID NIH HHS [Z01 AI000932] NR 51 TC 50 Z9 51 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD SEP 4 PY 2006 VL 7 AR 226 DI 10.1186/1471-2164-7-226 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 087HC UT WOS:000240732500001 PM 16952314 ER PT J AU Goedert, JJ Schairer, C McNeel, TS Hessol, NA Rabkin, CS Engels, EA AF Goedert, J. J. Schairer, C. McNeel, T. S. Hessol, N. A. Rabkin, C. S. Engels, E. A. CA HIV AIDS Canc Match Study TI Risk of breast, ovary, and uterine corpus cancers among 85 268 women with AIDS SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; endometrial cancer; ovarian cancer; human immunodeficiency virus (HIV); acquired immunodeficiency syndrome (AIDS); risk factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED WOMEN; NON-HODGKINS-LYMPHOMA; INTERAGENCY HIV; EPITHELIAL-CELLS; UNITED-STATES; PREMENOPAUSAL WOMEN; ENDOMETRIAL CANCER; TYPE-1 INFECTION; BODY-COMPOSITION AB By linking HIV/AIDS and cancer surveillance data in 12 US regions, breast and reproductive cancer risks with AIDS were compared to those in the general population. Trends in standardized incidence ratios (SIRs) were assessed by CD4 count, AIDS-relative time, and calendar time. Standardized incidence ratios were indirectly adjusted for cancer risk factors using data from AIDS cohort participants and the general population. With AIDS, 313 women developed breast cancer (SIR 0.69, 95% confidence interval (CI) 0.62 - 0.77), 42 developed ovary cancer (SIR 1.05, 95% CI, 0.75 - 1.42), and 31 developed uterine corpus cancer (SIR 0.57, 95% CI, 0.39 - 0.81). Uterine cancer risk was reduced significantly after age 50 (SIR 0.33). Breast cancer risk was reduced significantly both before (SIR 0.71) and after (SIR 0.66) age 50, and was lower for local or regional (SIR 0.54) than distant (SIR 0.89) disease. Breast cancer risk varied little by CD4 count (P-trend = 0.47) or AIDS-relative time (P-trend = 0.14) or after adjustment for established cancer risk factors. However, it increased significantly between 1980 and 2002 (P-trend = 0.003), approaching the risk of the general population. We conclude that the cancer deficit reflected direct or indirect effects of HIV/AIDS and that anti-HIV therapy reduced these effects. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94122 USA. Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. EM goedertj@mail.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [M01-RR-00083, M01 RR000083, M01 RR000071, M01 RR000079, M01-RR-00071, M01-RR-00079]; NIAID NIH HHS [U01 AI031834, U01 AI034989, U01 AI034994, U01-AI-31834, U01-AI-34989, U01-AI-34994, U01 AI034993, U01 AI035004, U01 AI042590, U01-AI-34993, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [U01 HD032632, U01-HD-32632] NR 53 TC 43 Z9 43 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 4 PY 2006 VL 95 IS 5 BP 642 EP 648 DI 10.1038/sj.bjc.6603282 PG 7 WC Oncology SC Oncology GA 088ZW UT WOS:000240850600013 PM 16868538 ER PT J AU Fekete, A Hoogerhout, P Zomer, G Kubler-Kielb, J Schneerson, R Robbins, JB Pozsgay, V AF Fekete, Aniko Hoogerhout, Peter Zomer, Gijsbert Kubler-Kielb, Joanna Schneerson, Rachel Robbins, John B. Pozsgay, Vince TI Synthesis of octa- and dodecamers of D-ribitol-1-phosphate and their protein conjugates SO CARBOHYDRATE RESEARCH LA English DT Article DE glycoconjugate; phosphodiester; ribitol phosphate; synthesis; teichoic acid; vaccine ID INFLUENZAE TYPE-B; GRAM-POSITIVE BACTERIA; CAPSULAR POLYSACCHARIDE; TEICHOIC-ACIDS; HYDROGENOLYTIC DEPROTECTION; N-ALKYLATION; ALLYL ETHERS; CHEMISTRY; FRAGMENTS; ISOMERIZATION AB The bacterial cell-wall-associated teichoic acids contain predominantly D-ribitol residues interconnected by phosphodiester linkages. Because of their location, these antigens may be vaccine candidates as part of conjugate vaccines. Here, we describe the synthesis of extended oligomers of D-ribitol-1-phosphate linked to a spacer having an amino group at its terminus. The synthesis utilized a fully protected D-ribitol-phosphoramidite that was oligomerized in a stepwise fashion followed by deprotection. The free oligomers were connected to bovine serum albumin using oxime chemistry. Thus, the ribitol phosphate oligorners were converted into keto derivatives, and the albumin counterpart was decorated with aminooxy groups. Reaction of the functionalized saccharide and protein moieties afforded conjugates having up to 20 ribitol phosphate chains. (c) 2005 Elsevier Ltd. All rights reserved. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Hungarian Acad Sci, Res Grp Carbohydrates, H-4010 Debrecen, Hungary. Netherlands Vaccine Inst, Unit Res & Dev, Bilthoven, Netherlands. RP Pozsgay, V (reprint author), NICHHD, NIH, 31 Ctr Dr,MSC 2423, Bethesda, MD 20892 USA. EM pozsgayv@mail.nih.gov FU Intramural NIH HHS NR 32 TC 13 Z9 13 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 4 PY 2006 VL 341 IS 12 BP 2037 EP 2048 DI 10.1016/j.carres.2005.10.023 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 068MG UT WOS:000239377600008 PM 16458277 ER PT J AU Simons-Morton, BG Hartos, JL Leaf, WA Preusser, DF AF Simons-Morton, Bruce G. Hartos, Jessica L. Leaf, William A. Preusser, David F. TI The effect on teen driving outcomes of the Checkpoints Program in a state-wide trial SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE behavioral intervention; persuasion; education; adolescents; parenting; parent limits; teen passengers; night driving; risky driving; traffic violations; crashes ID PARENTAL RESTRICTIONS; YOUNG DRIVERS; RISK; PASSENGERS; CRASHES; PERSISTENCE; PRIVILEGES; RATES AB Crash rates among teenagers are highly elevated during the first months of licensure. Parent-imposed driving restrictions on initial driving privileges can reduce exposure to high-risk driving conditions, thus reducing crash risk while teens' driving proficiency develops. This report describes the effect of the Checkpoints Program on driving limits and outcomes. Connecticut teens who obtained a learners permit over a 9-month period were recruited, providing a final sample of 3743 who obtained driver licenses. Families were randomized to the intervention or comparison condition. Intervention families received by mail a series of persuasive communications related to high-risk teen driving and a parent-teen driving agreement, while comparison families received on the same schedule general information on driving and vehicle maintenance. Relative to the comparison group, teens and parents in the Checkpoints Program reported significantly greater limits on high-risk teen driving conditions at licensure, 3-, and 6-months post-licensure; and intervention teens reported significantly less risky driving at each reporting period. By the 12-month follow up teens in the intervention group were significantly less likely than those in the comparison group to have had a traffic violation. However, no treatment group effect was found for crashes. This is the first study to report significant effects on teen driving behavior and performance of education designed to increase parental-imposed teen driving limits. Published by Elsevier Ltd. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. RP Simons-Morton, BG (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Rockville, MD 20852 USA. EM MortonB@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [1-HD-8-3285, Y3-HD8318] NR 26 TC 35 Z9 35 U1 10 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD SEP PY 2006 VL 38 IS 5 BP 907 EP 912 DI 10.1016/j.aap.2006.03.001 PG 6 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 070NA UT WOS:000239528200010 PM 16620739 ER PT J AU Torres-Cabala, C Bibbo, M Panizo-Santos, A Barazi, H Krutzsch, H Roberts, DD Merino, MJ AF Torres-Cabala, Carlos Bibbo, Marluce Panizo-Santos, Angel Barazi, Heba Krutzsch, Henry Roberts, David D. Merino, Maria J. TI Proteomic identification of new biomarkers and application in thyroid cytology SO ACTA CYTOLOGICA LA English DT Article DE aspiration biopsy; fine-needle; proteomics; tumor; thyroid; tumor markers ID MESSENGER-RIBONUCLEIC-ACID; NEEDLE ASPIRATION BIOPSY; DIFFERENTIAL EXPRESSION; NUCLEAR-LOCALIZATION; HUMAN FIBROBLASTS; GALECTIN-3; BENIGN; CARCINOMA; NODULES; LESIONS AB Objective To validate proteins identified,by proteomics as potentially usable markers in thyroid pathology. Study Design Frozen sections of thyroid tumors were manually micro-dissected and proteins extracted. Two-dimensional (2D) gel electrophoresis and subsequent liquid chromatography/mass spectroscopy were performed, and differentially expressed proteins were identified. Validation of candidates for tumor markers (galectin-1, galectin-3, S100C and voltage-dependent anion channel 1 [VDAC1]) was done by immunohistochemistry in 21 cell blocks from fine needle aspiration biopsies (FNAB) and corresponding histology specimens (13 cases). Results Galectin-3 was negative in benign lesions and positive in FNAB from papillary carcinoma (5 of 5), follicular variant of papillary carcinoma (I of 4) and follicular carcinoma (1 of 2). S100C was positive in some benign lesions. hyperplasia (2 of 4), goiter (1 of 3) and follicular adenoma (I of 3), with predominantly nuclear pattern of staining. S100C was positive in malignant lesions, showing cytoplasmic location. Galectin-1 was negative in benign lesions and positive in follicular carcinoma (1 of 2), papillary carcinoma (2 of 5) and follicular variant of papillary carcinoma (I of 4). VDAC1 was detected in benign and malignant lesions, showing a strong positivity in follicular carcinomas. Conclusion Immunohistochemical validation of potential markers is a crucial step before clinical application in diagnosis. Galectin-3, galcctin-1 and S100C can he used to help in discriminating benign and malignant thyroid lesions. C1 NCI, Surg Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ Hosp, Cytol Lab, Philadelphia, PA 19107 USA. RP Merino, MJ (reprint author), NCI, Surg Pathol Sect, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 2N212, Bethesda, MD 20892 USA. EM mjmerina@mail.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 45 TC 28 Z9 31 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD SEP-OCT PY 2006 VL 50 IS 5 BP 518 EP 528 DI 10.1159/000326006 PG 11 WC Pathology SC Pathology GA 085WZ UT WOS:000240636400007 PM 17017437 ER PT J AU Zajicek, A AF Zajicek, Anne TI Juvenile animal studies in pediatric drug development: What is the evidence? SO ACTA PHARMACOLOGICA SINICA LA English DT Meeting Abstract C1 NICHHD, Obstet & Pediat Pharmacol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD SEP PY 2006 VL 27 IS 9 BP 1272 EP 1272 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 084SN UT WOS:000240554800023 ER PT J AU Cottler, LB Grant, BF AF Cottler, Linda B. Grant, Bridget F. TI Characteristics of nosologically informative data sets that address key diagnostic issues facing the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) and International Classification of Diseases, eleventh edition (ICD-II) substance use disorders workgroups SO ADDICTION LA English DT Article DE diagnostic issues; DSM; ICD; nomenclature; nosology; substance use disorders ID NATIONAL EPIDEMIOLOGIC SURVEY; WORLD-HEALTH-ORGANIZATION; IV ALCOHOL DEPENDENCE; DRUG-DEPENDENCE; NO DIAGNOSIS; FIELD TRIAL; ABUSE; ADOLESCENTS; PREVALENCE; SEVERITY AB Aims Over the past two decades, many nosological issues have been addressed by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD) substance use disorders workgroups. Even with those efforts, there are key issues that have not been resolved and must be revisited, or addressed de novo, by the workgroups. These lingering points are broad, due to the array of substances classified under the diagnostic umbrella of substance use disorders. They include substantive issues ranging from dimensional approaches, similar criteria for each substance, cut-points and thresholds, distinct abuse and dependence classifications, new criteria and drugs, to less substantive ones, such as the adjectives used to describe the severity of the behaviors. Results This paper describes the characteristics of the data sets that will be needed to resolve the key nosological issues. Ten points are described: (1) data must be true to nomenclature under study; (2) flexible regarding rearrangements of scoring algorithms; (3-4) able to assess substances individually and retain former versions of the criteria; (5) not rely on shortened versions; (6) utilize samples that are generalizable; (7) make diagnoses with transparent algorithms; (8) combine mixed methods for corroborating data; (9) utilize assessments that collect reliable and valid diagnoses and criteria; and (10) stretch the limits by allowing for new discoveries. Conclusions This paper describes each of these and gives examples of the limitations and strengths of data for the purpose of defining a useful, unified concept of addictive behaviors. C1 Washington Univ, Sch Med, Epidemiol & Prevent Res Grp, Dept Psychiat, St Louis, MO 63108 USA. NIAAA, NIH, Bethesda, MD USA. RP Cottler, LB (reprint author), Washington Univ, Sch Med, Epidemiol & Prevent Res Grp, Dept Psychiat, 40 N Kingshighway,Suite 4, St Louis, MO 63108 USA. EM cottler@epl.wustl.edu FU NIDA NIH HHS [DA005585, DA07313, DA005688, DA015984, DA014854]; PHS HHS [GB67741] NR 35 TC 13 Z9 13 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD SEP PY 2006 VL 101 SU 1 BP 161 EP 169 DI 10.1111/j.1360-0443.2006.01590.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 071QT UT WOS:000239617400019 PM 16930173 ER PT J AU Sommer, W Hyytia, P Kiianmaa, K AF Sommer, Wolfgang Hyytia, Petri Kiianmaa, Kalervo TI The alcohol-preferring AA and alcohol-avoiding ANA rats: neurobiology of the regulation of alcohol drinking SO ADDICTION BIOLOGY LA English DT Review DE cannabinoid; dopamine; expression analysis; microarray; opioid; reinforcement ID ALDEHYDE DEHYDROGENASE-ACTIVITY; VOLUNTARY ETHANOL INTAKE; RECEPTOR KNOCKOUT MICE; OPEN-FIELD BEHAVIOR; DRUG-ABUSE RESEARCH; NUCLEUS-ACCUMBENS; NONPREFERRING RATS; DOPAMINE RELEASE; GENE-EXPRESSION; BETA-ENDORPHIN AB The AA (alko, alcohol) and ANA (alko, non-alcohol) rat lines were among the earliest rodent lines produced by bidirectional selection for ethanol preference. The purpose of this review is to highlight the strategies for understanding the neurobiological factors underlying differential alcohol-drinking behavior in these lines. Most early work evaluated functioning of the major neurotransmitter systems implicated in drug reward in the lines. No consistent line differences were found in the dopaminergic system either under baseline conditions or after ethanol challenges. However, increased opioidergic tone in the ventral striatum and a deficiency in endocannabinoid signaling in the prefrontal cortex of AA rats may comprise mechanisms leading to increased ethanol consumption. Because complex behaviors, such as ethanol drinking, are not likely to be controlled by single factors, system-oriented molecular-profiling strategies have been used recently. Microarray based expression analysis of AA and ANA brains and novel data-mining strategies provide a system biological view that allows us to formulate a hypothesis on the mechanism underlying selection for ethanol preference. Two main factors appear active in the selection: a recruitment of signal transduction networks, including mitogen-activated protein kinases and calcium pathways and involving transcription factors such as Creb, Myc and Max, to mediate ethanol reinforcement and plasticity. The second factor acts on the mitochondrion and most likely provides metabolic flexibility for alternative substrate utilization in the presence of low amounts of ethanol. C1 Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki 00251, Finland. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RP Kiianmaa, K (reprint author), Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, POB 33, Helsinki 00251, Finland. EM kalervo.kiianmaa@ktl.fi OI Sommer, Wolfgang/0000-0002-5903-6521; Hyytia, Petri/0000-0002-0284-1298 NR 155 TC 92 Z9 92 U1 2 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD SEP PY 2006 VL 11 IS 3-4 BP 289 EP 309 DI 10.1111/j.1369-1600.2006.00037.x PG 21 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 081GH UT WOS:000240304700004 PM 16961760 ER PT J AU Barr, CS Goldman, D AF Barr, Christina S. Goldman, David TI Non-human primate models of inheritance vulnerability to alcohol use disorders SO ADDICTION BIOLOGY LA English DT Review DE alcoholism; genetics; HTTLPR; MAO-A; OPRMI; primate ID TRANSPORTER GENE VARIATION; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; SINGLE NUCLEOTIDE POLYMORPHISM; DIMINISHED SOCIAL COMPETENCE; MONKEYS MACACA-MULATTA; PITUITARY-ADRENAL AXIS; RHESUS MACAQUES; MONOAMINE-OXIDASE; PROMOTER POLYMORPHISM; AGGRESSIVE-BEHAVIOR AB Many animal species have been used to model certain aspects of alcohol use and addiction. However, there are complex behavioral and social features of alcohol use disorders that are not easily modeled in animal species. This review considers both the limitations and advantages of using a non-human primate to model alcohol use disorders and discusses how non-human primates can be particularly useful for studying how genetic variants interact with social factors, temperament and alcohol response as motivating factors for alcohol consumption and abstinence. Genetic variants in rhesus macaques (Macaca mulatta) that are functionally equivalent to those increasing addiction vulnerability in humans influence temperament, stress reactivity and alcohol response in addition to voluntary alcohol consumption. Non-human primate models may also have translational value for understanding of how variants within addiction and abuse vulnerability genes influence alcohol-induced neuroadaptation, neuropathology and treatment response. C1 NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD 20837 USA. RP Barr, CS (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, POB 529, Poolesville, MD 20837 USA. EM cbarr@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 89 TC 34 Z9 35 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD SEP PY 2006 VL 11 IS 3-4 BP 374 EP 385 DI 10.1111/j.1369-1600.2006.00034.x PG 12 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 081GH UT WOS:000240304700009 PM 16961765 ER PT J AU Gallagher, M Colantuoni, C Eichenbaum, H Haberman, RP Rapp, PR Tanila, H Wilson, IA AF Gallagher, Michela Colantuoni, Carlo Eichenbaum, Howard Haberman, Rebecca P. Rapp, Peter R. Tanila, Heikki Wilson, Iain A. TI Individual differences in neurocognitive aging of the medial temporal lobe SO AGE LA English DT Article DE spatial memory; hippocampal formation; successful aging; rats; cognitive impairment ID SPATIAL-LEARNING IMPAIRMENT; ENTORHINAL CORTEX NEURONS; MILD COGNITIVE IMPAIRMENT; HIPPOCAMPAL PLACE CELLS; AGE-RELATED IMPAIRMENTS; RAT DENTATE GYRUS; ALZHEIMERS-DISEASE; NEUROPEPTIDE-Y; OLD RATS; AXOSPINOUS SYNAPSES AB A wide spectrum of outcomes in the cognitive effects of aging is routinely observed in studies of the elderly. Individual differences in neurocognitive aging are also a characteristic of other species, such as rodents and non-human primates. In particular, investigations at behavioral, brain systems, cellular and molecular levels of analysis have provided much information on the basis for individual differences in neurocognitive aging among healthy outbred rats. These findings are likely to be relevant to an understanding of the effects of aging on the brain, apart from neurodegenerative conditions, such as Alzheimer's disease, which do not naturally occur in rodents. Here we review and integrate those findings in a model supporting the concept that certain features of cognitive decline are caused by distributed alterations in the medial temporal lobe, which alter the information processing functions of the hippocampal formation. An additional emerging concept from this research is that preserved abilities at older ages may depend on adaptive changes in the hippocampal system that distinguish successful aging. C1 Johns Hopkins Univ, Krieger Sch Arts & Sci, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Mt Sinai Sch Med, Neurobiol Aging Labs, New York, NY USA. Univ Kuopio, Dept Neurosci & Neurol, FIN-70211 Kuopio, Finland. Univ Edinburgh, Div Neurosci, Edinburgh EH8 9YL, Midlothian, Scotland. RP Gallagher, M (reprint author), Johns Hopkins Univ, Krieger Sch Arts & Sci, Dept Psychol & Brain Sci, 103 Ames Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM michela@jhu.edu; ccolantu@jhsph.edu; hbe@bu.edu; rahabs@jhu.edu; peter.rapp@mssm.edu; Heikki.Tanila@uku.fi; Iain.Wilson@ed.ac.uk NR 73 TC 19 Z9 19 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD SEP PY 2006 VL 28 IS 3 BP 221 EP 233 DI 10.1007/s11357-006-9017-5 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 122CP UT WOS:000243203600002 PM 22253491 ER PT J AU Wiggs, CL Weisberg, J Martin, A AF Wiggs, Cheri L. Weisberg, Jill Martin, Alex TI Repetition priming across the adult lifespan - The long and short of it SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article ID IMPLICIT MEMORY; VISUAL COMPLEXITY; NAME AGREEMENT; OLDER ADULTS; EXPLICIT RETRIEVAL; ALZHEIMERS-DISEASE; AGE-DIFFERENCES; RECOGNITION; PICTURES; AMNESIA AB Previous reports suggest that repetition priming (i.e., enhanced processing of a stimulus after experience with that stimulus) is long lasting and impervious to the effects of age, in contrast to the pattern found with explicit memory. However, the nature of repetition priming in aged individuals remains unclear, as conflicting findings have also been reported. We used a longitudinal design to examine how repetition priming is affected by multiple stimulus repetitions (three presentations) and different delay intervals (no delay, 1 day, 1 week, and 1 month) in young adults, as well as in two groups of aging adults (young-elderly and old-elderly). Our findings extend previous reports that priming is long lasting, even when 1 month intervenes between the initial experience with an item and the subsequent priming test of that item (Cave, 1997), and is relatively impervious to the effects of age (Mitchell, et al., 1990). In addition, a more detailed characterization of priming and the effects of aging was revealed. Although priming is long lasting, remaining significant even at the month delay for all groups, it did decline over time and the rate of that decline differed with age. Both young-elderly and old-elderly groups showed a marked drop-off at 1 day, whereas young adults did not show a decline until 1 week. All groups benefited from multiple repetitions; however, this benefit disappeared at the month delay (in contrast to recognition memory, where the benefit remained significant). These findings support the assertion that repetition priming and explicit memory reflect the operation of distinct systems, and that these systems may undergo different rates of change in aging. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Wiggs, CL (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr MSC 1366,Bldg 10 Rm 4C104, Bethesda, MD 20892 USA. EM wiggsc@mail.nih.gov RI martin, alex/B-6176-2009 NR 57 TC 25 Z9 26 U1 0 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1382-5585 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PD SEP-DEC PY 2006 VL 13 IS 3-4 BP 308 EP 325 DI 10.1080/138255890968718 PG 18 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 071AM UT WOS:000239569100003 ER PT J AU Pau, AK McLaughlin, MM Hu, ZH Agyemang, AF Polis, MA Kottilil, S AF Pau, Alice K. McLaughlin, Mary M. Hu, Zonghui Agyemang, Amma F. Polis, Michael A. Kottilil, Shyam TI Predictors for hematopoietic growth factors use in HIV/HCV-coinfected patients treated with peginterferon alfa 2b and ribavirin SO AIDS PATIENT CARE AND STDS LA English DT Article ID CHRONIC HEPATITIS-C; HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS-INFECTION; RANDOMIZED CONTROLLED-TRIAL; COMBINATION THERAPY; DARBEPOETIN-ALPHA; PLUS RIBAVIRIN; ANTIRETROVIRAL THERAPY; LIVER-DISEASE; DOUBLE-BLIND AB HIV/hepatitis C virus ( HCV)-coinfected individuals have accelerated liver disease, increased drug toxicities, and modest responses to peginterferon and ribavirin. Hematologic toxicities necessitating dose reduction or discontinuation are limiting factors to HCV treatment in the coinfected patient. This study aimed to identify predictors for the need of filgrastim and darbepoetin to manage hematologic toxicities so as to maintain patients on full doses of study drugs for the duration of study. The primary study was a single-center, open-label, prospective study to evaluate the safety, efficacy, and viral kinetics of 48-week peginterferon alfa 2b and ribavirin in HIV/HCV-coinfected patients. Complete blood count was monitored at baseline, days 3, 7, 10, 14, and then weekly for the first month, fortnightly until week 8, then monthly from week 12 to 48. Filgrastim was initiated when absolute neutrophil count ( ANC) fell below 750 cells/mm(3) and darbepoetin was used when hemoglobin dropped to less than 10 g/dL. All patients experienced decrease in ANC and hemoglobin. Twenty of 30 ( 66.6%) of patients required hematopoeitic growth factors, 15 ( 50%) received filgrastim, and 12 ( 40%) received darbepoetin. Seven ( 23.3%) required both. Baseline ANC of less than 2250 cells per millimeter and negative rate of change of hemoglobin on day 3 of therapy were excellent predictors for filgrastim and darbepoetin use, respectively. Supplemental growth factors were associated with substantial increase in overall cost for HCV treatment. Larger clinical trials will be needed to address the cost effectiveness of supplemental growth factor use in the HIV/HCV-coinfected patients. C1 NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pau, AK (reprint author), NIAID, Div Clin Res, NIH, Bldg 10,Room 11C103,10 Ctr Dr,MSC 1880, Bethesda, MD 20892 USA. EM apau@niaid.nih.gov OI Polis, Michael/0000-0002-9151-2268 FU Intramural NIH HHS NR 22 TC 6 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2006 VL 20 IS 9 BP 612 EP 619 DI 10.1089/apc.2006.20.612 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 088YL UT WOS:000240846900004 PM 16987047 ER PT J AU Pace, C Grady, C Wendler, D Bebchuk, JD Tavel, JA McNay, LA Forster, HP Killen, J Emanuel, EJ AF Pace, Christine Grady, Christine Wendler, David Bebchuk, Judith D. Tavel, Jorge A. McNay, Laura A. Forster, Heidi P. Killen, Jack Emanuel, Ezekiel J. CA ESPRIT Grp TI Post-trial access to tested interventions: The views of IRB/REC chair, investigators, and research participants in a multinational HIV/AIDS study SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID DEVELOPING-COUNTRIES; ISSUES; TRIALS; DESIGN AB Controversy exists regarding an ethical requirement to make products proven effective in research available after the trial. Little is known about the views of several stakeholders. Phone or self-administered questionnaires were completed by 65 IRB/REC chairs, 117 investigators, and 500 research participants in a multinational HIV trial to assess their views about posttrial access to interventions proven effective in the study. A total of 83% of research participants, 29% of IRB/REC chairs, and 42% of researchers (p = 0.046) thought IL-2 should be guaranteed for every HIV-infected person in the world if proven effective. Most European and Latin American research participants thought IL-2 should be provided free, while North American, Australian, and Thai participants commonly said at a price the average person could afford (p < 0.001). Most IRB/REC chairs and researchers thought the CIOMS "reasonable availability" requirement applied to people in the country where the study was conducted and meant a drug should be available at a price the average person could afford and that host country governments had primary responsibility for making it available. Most research participants believe an HIV drug proven effective in research should be made available to everyone in the world who needs it. IRB/REC chairs and researchers were less expansive both in who and how they thought a drug should be guaranteed. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM cgrady@cc.nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U122886352] NR 11 TC 9 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2006 VL 22 IS 9 BP 837 EP 841 DI 10.1089/aid.2006.22.837 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 090JG UT WOS:000240946700003 PM 16989607 ER PT J AU Bedoya, VI Boasso, A Hardy, AW Rybak, S Shearer, GM Rugeles, MT AF Bedoya, Victoria I. Boasso, Adriano Hardy, Andrew W. Rybak, Susanna Shearer, Gene M. Rugeles, Maria T. TI Ribonucleases in HIV type 1 inhibition: Effect of recombinant RNases on infection of primary T cells and immune activation-induced RNase gene and protein expression SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID EOSINOPHIL CATIONIC PROTEIN; ALLOANTIGEN RECOGNITION; VIRUS; ANGIOGENIN; LOCALIZATION; DEGRADATION; NEUROTOXIN; CHEMOKINES; LEUKOCYTES; PLACENTA AB Ribonucleases (RNases) have therapeutic potential against cancer and viral diseases and have been reported to inhibit replication of the human immunodeficiency virus type 1 (HIV-1) in chronically infected cell lines. The ribonuclease eosinophil-derived neurotoxin (EDN) is responsible for the anti-HIV- 1 activity of a soluble factor produced in response to human alloantigens (ASF). Four recombinant RNases (EDN; a four amino acid extension of the N-terminus EDN, -4EDN; RNase A; and angiogenin) were tested for inhibition of HIV-1 replication in PHA blasts. All RNases showed anti-HIV-1 activity, irrespective of whether the RNases were added before, during, or 2 h after infection. Polyclonal antibodies against the four RNases blocked the antiviral activity. ASF inhibited HIV-1 replication in vitro if added up to 4 h after infection. We demonstrated that allostimulation induced EDN, RNase A, and angiogenin mRNA expression in peripheral blood mononuclear cells (PBMCs), although only EDN protein was detected. We identified monocytes and dendritic cells, but not macrophages or T cells, as EDN-producing cells. These findings raise the possibilities that multiple naturally occurring RNases may contribute to protection against HIV-1 infection and could be considered for utilization in HIV-1 therapy. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Antioquia, Immunivirol Grp, Medellin, Colombia. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10 Rm 4B-36, Bethesda, MD 20892 USA. EM shearerg@mail.nih.gov OI Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS NR 42 TC 21 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 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2006 VL 22 IS 9 BP 897 EP 907 DI 10.1089/aid.2006.22.897 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 090JG UT WOS:000240946700012 PM 16989616 ER PT J AU Li, TK AF Li, Ting-Kai CA NIAAA TI Is there a future for quantifying drinking in the diagnosis, treatment and prevention of alcohol use disorders? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 45A EP 45A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900002 ER PT J AU Twombly, DA AF Twombly, Dennis A. TI Plasticity in the CNS: Implications for long-term effects of alcohol use in aging SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 52A EP 52A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900031 ER PT J AU Tabakoff, B Hoffman, P Snell, L Griffeth, V Wu, C Herion, D Heilig, M AF Tabakoff, Boris Hoffman, Paula Snell, Lawrence Griffeth, Valerie Wu, Christine Herion, David Heilig, Markus TI Proteomic analysis for markers of hazardous/harmful drinking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 Univ Colorado, Sch Med, Boulder, CO 80309 USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 53A EP 53A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900035 ER PT J AU Grant, B Cottler, L AF Grant, Bridget Cottler, Linda TI Nosological issues facing the DSM-V substance abuse and dependence workgroup SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Sect Epidemiol & Biometr, Rockville, MD 20852 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 64A EP 64A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900078 ER PT J AU Grant, B AF Grant, Bridget TI The role of alcohol consumption in the classification of alcohol use disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, US Dept HHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 70A EP 70A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900102 ER PT J AU Enoch, MA Schwartz, LS Yuan, QP Albaugh, B Virkkunen, M Goldman, D AF Enoch, Mary-Anne Schwartz, Lori S. Yuan, Qiaoping Albaugh, Bernard Virkkunen, Matti Goldman, David TI Linkage of GABRA2 and GABRB1 haplotypes to alcoholism in two independent populations SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. Univ Helsinki, FIN-00014 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 71A EP 71A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900106 ER PT J AU Thorsell, A AF Thorsell, Annika TI Neuropeptide Y, and its receptors, in alcohol dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 72A EP 72A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900113 ER PT J AU Le, DA Funk, D Shaham, Y AF Le, Dzung Anh Funk, Douglas Shaham, Yavin TI Role of the noradrenergic (NA) systems in alcohol self-administration and reinstatement of alcohol seeking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. NIDA, Intramural Res, Melbourne, FL 32904 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 77A EP 77A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900130 ER PT J AU Eskay, R Hamelink, C Damadzic, R Eiden, L AF Eskay, Robert Hamelink, C. Damadzic, R. Eiden, L. TI Characterization of ethanol-induced molecular events that lead to neurodegeneration and therapeutic treatments that are neuroprotective in the rodent SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Lab Clin & Transit Studies, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 86A EP 86A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900169 ER PT J AU Barr, CS Newman, TK Goldman, D Suomi, SJ Higley, JD AF Barr, Christina S. Newman, Timothy K. Goldman, David Suomi, Stephen J. Higley, James D. TI Serotonin transporter genotype and the effects of early life stress on alcohol self-administration in primates SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 90A EP 90A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900183 ER PT J AU Heilig, M Hansson, AC Cippitelli, A Sommer, WH Fideli, A Massi, M Ciccocioppo, R AF Heilig, Markus Hansson, Anita C. Cippitelli, Andrea Sommer, Wolfgang H. Fideli, Amalia Massi, Mauricio Ciccocioppo, Roberto TI Validation of CRH1 receptors as a treatment target in alcohol dependence using alcohol-preferring msP rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. Univ Camerino, I-62032 Camerino, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 93A EP 93A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900197 ER PT J AU Holmes, A AF Holmes, Andrew TI Stress, monoamine transporters and the behavioral effects of ethanol in mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 99A EP 99A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900218 ER PT J AU Zhang, L Sun, H Miko, A Hu, XQ AF Zhang, Li Sun, Hui Miko, Angela Hu, XiangQun TI Regulation of 5-HT3 receptor function and receptor sensitivity to alcohol by interaction with a cytoskeleton-signaling complex SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 106A EP 106A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900249 ER PT J AU Zakhari, S AF Zakhari, Samir TI Alcohol metabolism: Role in cellular stress, adaptation, and tissue damage SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 107A EP 107A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900252 ER PT J AU Pawlosky, R Crutchfield, C Kashiwaya, Y Kunos, G Volkow, N Veech, RL AF Pawlosky, Robert Crutchfield, Calvin Kashiwaya, Yoshihiro Kunos, George Volkow, Nora Veech, Richard L. TI The effects ethanol and its metabolite acetate on brain energetics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Labs Metab Control Physiol Studies & Neuroimaging, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 108A EP 108A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900254 ER PT J AU Enoch, MA Xu, K Hodgkinson, C Shen, PH Yuan, QP Goldman, D AF Enoch, Mary-Anne Xu, Ke Hodgkinson, Colin Shen, Pei-Hong Yuan, Qiaoping Goldman, David TI Candidate gene association studies using an addictions microarray SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 110A EP 110A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900264 ER PT J AU Higley, JD AF Higley, J. Dee TI The use of nonhuman primate models to longitudinally study the interacting influences of genetic and early environmental factors on alcohol intake SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Sect Study Primate Models Psychopathol, LCTS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 111A EP 111A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900267 ER PT J AU Lovinger, DM Zhu, PJ AF Lovinger, David M. Zhu, Ping J. TI Gabaergic synapses in basolateral amygdala: Site of ethanol-cannabinoid interactions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 115A EP 115A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900283 ER PT J AU Kunos, G Wang, L Nikas, S Makriyannis, A Batkai, S Liu, J Harvey-White, J AF Kunos, George Wang, Lei Nikas, Spyridon Makriyannis, Alexandros Batkai, Sandor Liu, Jie Harvey-White, Judith TI Endogenous anandamide is involved in alcohol preference and its increase following alcohol deprivation in mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD 02115 USA. Northeastern Univ, Boston, MA USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 116A EP 116A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900286 ER PT J AU Hansson, AC Cippitelli, A Sommer, WH Bjoerk, K Terasmaa, A Fedeli, A Heilig, M Ciccocioppo, R AF Hansson, Anita C. Cippitelli, Andrea Sommer, Wolfgang H. Bjoerk, Karl Terasmaa, Anton Fedeli, Amalia Heilig, Markus Ciccocioppo, Roberto TI Interaction between corticotropin-releasing hormone 1 receptor gene polymorphism and expression with environmental stress in relapse to alcohol seeking behavior by rats selected for high ethanol preference SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, Lab Clin & Translat Studies, NIH, I-62032 Bethesda, MD USA. Univ Camerino, Dept Expt Med & Publ Hlth, Camerino, Italy. RI Terasmaa, Anton/I-3312-2015 OI Terasmaa, Anton/0000-0002-5139-1764 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 130A EP 130A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900345 ER PT J AU Lourdusamy, AA Ubaldi, M Soverchia, L Ciccocioppo, R Hyytia, P Sommer, W AF Lourdusamy, Anbarasu A. Ubaldi, Massimo Soverchia, Laura Ciccocioppo, Roberto Hyytia, Petri Sommer, Wolfgang TI Regional patterns of gene expression in alcohol-preferring and -nonpreferring rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, Italy. Natl Publ Hlth Inst, Helsinki, Finland. NIAAA, NIH, Bethesda, MD USA. RI Lourdusamy, Anbarasu/G-3387-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 153A EP 153A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900435 ER PT J AU Matsushita, S Hara, S Miyakawa, T Maesato, H Suzuki, G Ramchandani, VA O'Connor, S Higuchi, S AF Matsushita, Sachio Hara, Sachiko Miyakawa, Tomohiro Maesato, Hitoshi Suzuki, Go Ramchandani, Vijay A. O'Connor, Sean Higuchi, Susumu TI Association between subjective responses to clamped alcohol concentration and ADH, ALDH, and GABAA receptor alpha-2 subunit genes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 Natl Hosp Org, Kurihama Alcoholism Ctr, Kanagawa, Japan. Natl Def Med Coll, Saitama, Japan. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 154A EP 154A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900438 ER PT J AU Sommer, WH Bjork, K Rimondini, R Hansson, AC Hyytia, P Lefkowitz, RF Heilig, M AF Sommer, Wolfgang H. Bjork, Karl Rimondini, Roberto Hansson, Anita C. Hyytia, Petri Lefkowitz, Robert F. Heilig, Markus TI A role for beta-arrestin 2 in mediating the rewarding properties of ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. Univ Bologna, Bologna, Italy. Natl Publ Hlth Inst, Helsinki, Finland. Howard Hughes Med Inst, Durham, NC USA. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 156A EP 156A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900447 ER PT J AU Li, Q Lazarus, LH Okada, Y Wilson, WA Swartzwelder, SH AF Li, Qiang Lazarus, Lawrence H. Okada, Yoshio Wilson, Wilkie A. Swartzwelder, Scott H. TI N-allyl-[Dmt1]-endomorphin-2, a novel opioid receptor antagonist attenuates alcohol-induced gabaergic neurotransmission in rat hippocampus SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. LPC, Natl Inst Environm Hlth Sci, Med Chem Grp, Res Triangle Pk, NC 27709 USA. Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo 6512180, Japan. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 164A EP 164A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900478 ER PT J AU Sun, H Miko, A Hosoi, M Zhang, L AF Sun, Hui Miko, Angela Hosoi, Masako Zhang, Li TI The cytoplasmic domain is involved in differential sensitivity of human and mouse 5-HT3A receptors to ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 165A EP 165A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900485 ER PT J AU Zimatkin, SM Pronko, SP Vasiliou, V Gonzalez, FJ Deitrich, RA AF Zimatkin, Sergey M. Pronko, Sergey P. Vasiliou, Vasilis Gonzalez, Frank J. Deitrich, Richard A. TI Enzymatic mechanisms of ethanol oxidation in the brain SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol metabolism; brain; enzymes; acetaldehyde; acetate ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; ALDEHYDE DEHYDROGENASE; ALCOHOL-DEHYDROGENASE; ACETALDEHYDE; METABOLISM; CATALASE; INHIBITION; CYP2E1 AB Background: The exact enzymatic mechanisms of ethanol oxidation in the brain are still unclear. The catalase-mediated oxidation of ethanol was demonstrated in rat brain using incubation of brain homogenates with catalase inhibitors. The role of the alcohol dehydrogenase (ADH) or cytochrome P450-dependent system in this process is possible, but has not been confirmed. The objective of the study was to determine the contribution of the different enzymatic pathways to ethanol oxidation in brain homogenates from mice and rats. Methods: Three approaches were used to investigate the enzymatic mechanisms of ethanol oxidation in the brain of rats and mice: (1) preincubation of brain homogenates with inhibitors of the ethanol-metabolizing enzymes (catalase, CYP2E1, ADH, and ALDH); (2) utilization of mice with genetic deficiency in ethanol-metabolizing enzymes (catalase, CYP2E1, or both enzymes); and (3) determination of ethanol oxidation in brain subcellular fractions known to have differential activity of ethanol-metabolizing enzymes. The ethanol-derived acetaldehyde (AC) and acetate were determined in brain samples by gas chromatography. Results: The catalase inhibitors sodium azide (5 mM) and aminotriazole (5 mM) as well as CYP2E1 inhibitors diallyl sulfide (2 mM) and beta-phenethyl isothiocyanate (0.1 mM) lowered significantly the accumulation of the ethanol-derived AC and acetate in brain homogenates. The ADH inhibitor 4-methyl pyrazole (5 mM) significantly decreased the acetate but not the AC accumulation. Ethanol-derived AC accumulation in brain homogenates of acatalasemic mice was 47% of the control value, 91% in CYP2E1-null mice, and 24% in double mutants (with deficiency of both catalase and CYP2E1). The highest levels of ethanol oxidation were found in microsomal and peroxisomal subcellular brain fractions, where CYP2E1 and catalase are located, respectively. Conclusions: Catalase is the key enzyme of ethanol oxidation in the brain of rodents: it may be responsible for about 60% of the process. CYP2E1 plays an important role in ethanol oxidation in the rodent brains. Alcohol dehydrogenase plays a minor role, if any, in this process. Aldehyde dehydrogenase plays the crucial role in the further oxidation of ethanol-derived AC in the brain homogenates. C1 Grodno State Med Univ, Grodno 230015, Byelarus. Univ Colorado, Hlth Sci Ctr, Mol Toxicol & Environm Hlth Sci Program, Dept Pharmaceut Sci, Denver, CO USA. NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO USA. RP Zimatkin, SM (reprint author), Grodno State Med Univ, 80 Gorkogo St, Grodno 230015, Byelarus. EM zimatkin@grsmu.by FU NIAAA NIH HHS [K05AA00093, P50AA03527, R01 AA011885, R01-AA12650, R21AA12284] NR 26 TC 100 Z9 101 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 BP 1500 EP 1505 DI 10.1111/j.1530-0277.2006.00181.x PG 6 WC Substance Abuse SC Substance Abuse GA 076EJ UT WOS:000239939500006 PM 16930212 ER PT J AU Pan, HN Sun, R Jaruga, B Hong, F Kim, WH Gao, B AF Pan, Hong-na Sun, Rui Jaruga, Barbara Hong, Feng Kim, Won-Ho Gao, Bin TI Chronic ethanol consumption inhibits hepatic natural killer cell activity and accelerates murine cytomegalovirus-induced hepatitis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; hepatitis; NK cells; poly I : C; MCMV ID NF-KAPPA-B; INDUCED LIVER-INJURY; TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; C VIRUS-INFECTION; POLY I-C; NK CELLS; PIT CELLS; CYTOLYTIC ACTIVITY; BETA-ENDORPHIN AB Background: Chronic alcohol drinking accelerates the progression of liver disease in patients with hepatitis viral infection; however, the underlying mechanisms are not fully understood. Methods: Here, we examined the effects of chronic ethanol feeding on hepatic natural killer (NK) cells and liver injury in 2 murine models of liver injury: injection of synthetic double-stranded RNA polyinosinic-polycytidylic acid (poly I:C), which mimics viral infection, and infection with murine cytomegalovirus (MCMV). Mice were fed the Lieber-DeCarli liquid diet containing 5% (vol/vol) ethanol for 8 weeks, resulting in a significant decrease in the percentage and total number of NK cells in the liver. Results: In control, pair-fed mice, poly I:C injection induced NK cell accumulation in the liver and activated hepatic NK cell cytotoxicity, whereas such induction and activation were diminished in ethanol-fed mice. Treatment with poly I:C also induced expression of NKG2D, granzyme B, perforin, Fas L, TRAIL, and IFN-gamma on liver lymphocytes, which were delayed or reduced in ethanol-treated mice compared with pair-fed mice. In contrast, chronic ethanol feeding did not affect poly I:C-induced mild liver injury. Furthermore, MCMV infection activated hepatic NK cells and induced hepatic inflammation and injury. Chronic ethanol consumption inhibited hepatic NK cell activation during MCMV infection, but enhanced MCMV-induced liver injury, viral titer, and inflammation in the liver. Conclusions: Taken together, these findings suggest that chronic ethanol consumption decreases hepatic NK activity, thereby accelerating MCMV-induced hepatitis and liver injury. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth, Div Intractable Dis, Ctr Biomed Sci, Seoul, South Korea. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 45 TC 28 Z9 29 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 BP 1615 EP 1623 DI 10.1111/j.1530-0277.2006.00194.x PG 9 WC Substance Abuse SC Substance Abuse GA 076EJ UT WOS:000239939500019 PM 16930225 ER PT J AU Bostom, AG Carpenter, MA Kusek, JW Hunsicker, LG Pfeffer, MA Levey, AS Jacques, PF McKenney, J AF Bostom, Andrew G. Carpenter, Myra A. Kusek, John W. Hunsicker, Lawrence G. Pfeffer, Marc A. Levey, Andrew S. Jacques, Paul F. McKenney, Joyce CA FAVORIT Invest TI Rationale and design of the folic acid for vascular outcome reduction in transplantation (FAVORIT) trial SO AMERICAN HEART JOURNAL LA English DT Article ID CHRONIC RENAL-DISEASE; TOTAL HOMOCYSTEINE LEVELS; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; NATURAL-HISTORY; CLINICAL-TRIALS; RISK-FACTOR; HYPERHOMOCYSTEINEMIA; RECIPIENTS; PLASMA AB Background Patients with chronic kidney disease, including kidney transplant recipients, are at high risk for cardiovascular disease (CVD). In addition to the constellation of traditional CVD risk factors in chronic kidney disease, elevated total homocysteine (tHcy) is notably Tore prevalent among the general population. The Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial is designed to evaluate whether lowering tHcy using vitamin supplementation reduces CVD events in renal transplant recipients. Methods FAVORIT is a multicenter double-blind randomized controlled clinical trial. Participants are clinically stable renal transplant recipients who are 6 months or longer posttransplant with elevated tHcy. Patients are randomized to a multivitamin that includes either a high-dose or low-dose of folic acid (5 or 0 mg), vitamin B-6 (50 or 1.4 mg), and vitamin B-12 (1000 or 2 mu g). The primary end point is a composite of incident or recurrent CVD outcomes, that is, coronary heart, cerebrovascular, or abdominal aortic/lower extremity arterial events. A sample size of,4000 is estimated to provide 87% power to detect a 20% treatment effect. Recruitment is expected to continue until July 2006, with follow-up through June 2010. Results From August 2002 through December 2004, 2234 of the target 4000 patients were enrolled. In accordance with trial design, mean (SD) screening tHcy was elevated (17.4 +/- 6.2 mu mol/L), and mean (SD) estimated creatinine clearance was consistent with stable renal function (58.0 +/- 18.6 mL/min). Evaluating baseline results to date, 42% of the randomized participants had a history of diabetes mellitus, and 21% had prevalent CVD. Conclusions The FAVORIT trial is designed with sufficient power and follow-up time to detect a clinically relevant change in CVD risk between renal transplant recipients receiving a high or low tHcy-lowering folic acid multivitamin. Preliminary screening and baseline data support the trial's objectives. C1 Rhode Isl Hosp, Providence, RI 02903 USA. Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Sch Publ Hlth, Chapel Hill, NC USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Bostom, AG (reprint author), Rhode Isl Hosp, 593 Eddy St,POB 242, Providence, RI 02903 USA. NR 35 TC 19 Z9 19 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2006 VL 152 IS 3 BP 448 EP 453 DI 10.1016/j.ahj.2006.03.004 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 084WJ UT WOS:000240564800009 ER PT J AU Wasson, K AF Wasson, Katherine TI Altruism and pediatric oncology trials: It does not tip the decision-making scales SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NCI, NIH, Bethesda, MD 20892 USA. RP Wasson, K (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 1 TC 2 Z9 2 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD SEP-OCT PY 2006 VL 6 IS 5 BP 48 EP 48 DI 10.1080/15265160600862429 PG 1 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 096UE UT WOS:000241401500019 PM 16997826 ER PT J AU Mirkhel, A Peyster, E Sundeen, J Greene, L Michelson, AD Hasan, A Domanski, M AF Mirkhel, Ahmadshah Peyster, Eliot Sundeen, James Greene, Linda Michelson, Alan D. Hasan, Ahmed Domanski, Michael TI Frequency of aspirin resistance in a community hospital SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; TOTAL HIP-REPLACEMENT; MYOCARDIAL-INFARCTION; DOSE ASPIRIN; HIGH-RISK; STROKE; COMPRESSION; PROPHYLAXIS; PREVENTION; THROMBOSIS AB Aspirin resistance and its predictors were studied in community hospital patients who required antiplatelet therapy for thrombotic event prophylaxis. Demographic and antiplatelet medication data were collected and medication response followed. Aspirin resist tance was assayed with the VerifyNow System with >= 550 aspirin reaction units (ARUs) used as a dichotomous indicator of aspirin resistance. Patients (n = 123) were 21 to 95 years old; 49.6% were women, 77.2% were black, 95.1% were hypertensive, 85.4% had coronary disease, and 30.1% were smokers. ARU score for 325 versus 81 mg/day was 435.2 +/- 93.7 versus 401.9 +/- 83.9 ARU (p = 0.04), with a 12.1% (8 of 66 patietns) nonresponse rate to 81 mg/day. Of the 8 patients who were unresponsive to 81 mg/day of aspirin, 7 responded to 325 mg/day. The 5.3% (3 of 57 patients) who were resistant to 325 mg/day received clopidogrel; 2 became responders. Multivariate analysis demonstrated significant associations of aspirin resistance with smoking (risk ratio 11.47, 95% confidence interval 6.69 to 18.63, p < 0.0001), including a significant interaction between smoking and aspirin resistance. In conclusion, this study estimates aspirin resistance prevalence and shows a strong association of smoking with platelet hyperactivity in a diverse community hospital population. Nonresponders to 81 mg/day frequently responded to 325 mg/day or to the addition of clopidogrel. (c) 2006 Elsevier Inc. C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. Prince Georges Gen Hosp & Med Ctr, Dept Internal Med, Cheverly, MD USA. Prince Georges Gen Hosp & Med Ctr, Dept Pathol, Cheverly, MD USA. Univ Massachusetts, Sch Med, Ctr Platelet Funct Studies, Dept Pediat, Worcester, MA USA. Univ Massachusetts, Sch Med, Ctr Platelet Funct Studies, Dept Med, Worcester, MA USA. RP Domanski, M (reprint author), NHLBI, Clin Trials Grp, Bldg 10, Bethesda, MD 20892 USA. EM domanskm@nhlbi.nih.gov NR 15 TC 45 Z9 55 U1 0 U2 1 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2006 VL 98 IS 5 BP 577 EP 579 DI 10.1016/j.amjcard.2006.03.029 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 081NM UT WOS:000240324300002 PM 16923439 ER PT J AU Shizukuda, Y Bolan, CD Tripodi, DJ Yau, YY Smith, KP Sachdev, V Birdsall, CW Sidenko, S Waclawiw, MA Leitman, SF Rosing, DR AF Shizukuda, Yukitaka Bolan, Charles D. Tripodi, Dorothy J. Yau, Yu-Ying Smith, Kevin P. Sachdev, Vandana Birdsall, Charles W. Sidenko, Stanislav Waclawiw, Myron A. Leitman, Susan F. Rosing, Douglas R. TI Left ventricular systolic function during stress echocardiography exercise in subjects with asymptomatic hereditary hemochromatosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; CHANNELS; HFE AB There is no information available on left ventricular (LV) systolic function and the response to stress echocardiography in asymptomatic subjects with hereditary hemochromatosis (HH). To evaluate this topic, 43 asymptomatic subjects with HH homozygous for the C282Y HFE gene mutation (22 untreated subjects [group A] and 21 long-term treated subjects [group B]) were compared with 21 age- and gender-matched normal volunteers negative for FIFE mutations. Contractile reserve, as a measure of LV systolic function, was assessed using continuous echocardiographic imaging and electrocardiography during supine bicycle exercise. Nineteen subjects in group A had repeat tests after 6 months of induction phlebotomy therapy to assess the effect of iron removal. Exercise performance and hemodynamic variables of supine bicycle exercise were comparable between subjects with HH and controls. LV contractile reserve of asymptomatic subjects with HH Was not impaired at either a 75-W submaximal exercise level (mean +/- SD difference in ejection fraction from baseline 13.8 +/- 6.2%, 11.5 +/- 6.8%, and 13.4 +/- 7.8% in groups A, B, and C, respectively; p = NS for all by analysis of variance) or at peak exercise (difference in ejection fraction from baseline 18.9 +/- 6.9%, 18.4 +/- 7.8%, and 20.3 +/- 8.1% in groups A, B, and C, respectively; p = NS for all by analysis of variance). However, the incidence of abnormal ischemic stress electrocardiographic responses was more frequent in subjects with HH as a whole (33%) compared with normal subjects (10%). Stress imaging revealed no regional wall motion abnormalities, suggesting that these were false-positive results. Iron removal by induction phlebotomy did not affect stress echocardiographic performance. In conclusion, LV systolic function during exercise in asymptomatic subjects with HH is preserved, and 6-month induction phlebotomy does not affect stress echocardiographic performance. (c) 2006 Elsevier Inc. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shizukuda, Y (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM shizukuy@nhlbi.nih.gov FU Intramural NIH HHS NR 20 TC 18 Z9 18 U1 0 U2 2 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2006 VL 98 IS 5 BP 694 EP 698 DI 10.1016/j.amjcard.2006.03.055 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 081NM UT WOS:000240324300027 PM 16923464 ER PT J AU Pannacciulli, N Bunt, JC Koska, J Bogardus, C Krakoff, J AF Pannacciulli, Nicola Bunt, Joy C. Koska, Juraj Bogardus, Clifton Krakoff, Jonathan TI Higher fasting plasma concentrations of glucagon-like peptide 1 are associated with higher resting energy expenditure and fat oxidation rates in humans SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE glucagon-like peptide 1; GLP-1; energy expenditure; substrate oxidation ID PANCREATIC-POLYPEPTIDE; SUBSTRATE METABOLISM; 7-36 AMIDE; SECRETION; OBESITY; DETERMINANTS; SATIATION; SATIETY; SYSTEM; VAGAL AB Background: Glucagon-like peptide I (GLP-1) is a gut hormone that decreases appetite and promotes satiety. Its role in energy metabolism regulation is still poorly understood. Objective: The aim of the study was to investigate the relation of fasting plasma GLP-1 concentrations to rates of energy expenditure (EE) and substrate oxidation-ie, respiratory quotient (RQ). Design: Forty-six glucose-tolerant white subjects (22 men, 24 women) aged 18-49 y whose adiposity spanned a wide range [body mass index (in kg/m(2)): 18.5-50] were studied in an inpatient clinic. Main outcome measures included resting EE and RQ (ventilated hood technique), body composition (dual-energy X-ray absorptiometry), and fasting plasma concentrations of GLP-1, pancreatic polypeptide, glucose, and insulin. Results: Fasting plasma GLP-1 concentrations were positively associated with resting EE (after adjustment for age, sex, and body composition) and negatively correlated with RQ (after adjustment for age, sex, and percentage body fat) and fasting plasma pancreatic polypeptide concentrations (both before and after adjustment for age, sex, percentage body fat, and fasting plasma glucose and insulin concentrations). Adjustment for fasting plasma pancreatic polypeptide concentrations, a marker of parasympathetic outflow to the gut, attenuated the strength of the association of fasting plasma GLP-1 concentrations with resting EE and RQ. Conclusions: Higher fasting plasma GLP-1 concentrations are associated with higher rates of EE and fat oxidation independent of age, sex, and body composition. The autonomic nervous system may have a role in this relation. This effect, along with the established role of GLP-1 in promoting satiety, may further foster its therapeutic potential in the treatment of obesity. C1 NIDDK, ODCRS, PECRB, NIH,DHHS, Phoenix, AZ 85016 USA. RP Pannacciulli, N (reprint author), NIDDK, ODCRS, PECRB, NIH,DHHS, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM nicolap@mail.nih.gov FU Intramural NIH HHS NR 31 TC 42 Z9 43 U1 0 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2006 VL 84 IS 3 BP 556 EP 560 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 084JP UT WOS:000240529500013 PM 16960169 ER PT J AU Dupuis, G Kennedy, E Lindquist, R Barton, FB Terrin, ML Hoogwerf, BJ Czajkowski, SM Herd, JA AF Dupuis, Gilles Kennedy, Elaine Lindquist, Ruth Barton, Franca B. Terrin, Michael L. Hoogwerf, Byron J. Czajkowski, Susan M. Herd, J. Alan CA Post CABG Biobehav Study Investiga TI Coronary artery bypass graft surgery and cognitive performance SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article AB BACKGROUND Some studies have indicated a decline inpatients' cognitive performance after coronary artery bypass graft surgery. OBJECTIVE To evaluate cognitive performance before and after coronary artery bypass graft surgery. METHODS Patients' cognitive performance before and after coronary artery bypass graft surgery was evaluated in a prospective observational multicenter study in 5 academic medical centers. A total of 242 men and 123 women were evaluated before surgery; 333 men and 216 women, 5 to 11 months after surgery (197 men and 99 women were evaluated both before and after surgery). Verbal ability, attention/concentration, logical/verbal and visual memory, and facial recognition were measured. Data on demographic, medical, and psychosocial characteristics also were collected. RESULTS After surgery, patients' overall performance improved (P < .001) for attention/concentration, verbal fluency, and logical/verbal memory. Patients with more education (high school or greater) performed better on each test (P < .001) than did patients with less education. No strong effects of sex or age on cognitive performance were observed before or after surgery, and no important differences in sex, age, or education were associated with changes in scores from before to after surgery. CONCLUSION On average, cognitive performance improved rather than declined after coronary artery bypass graft surgery. The improvements were consistent across sex, age, and education. C1 Montreal Heart Inst, Dept Psychosomat Med, Montreal, PQ H1T 1C8, Canada. Univ Quebec, Dept Psychol, Montreal, PQ H3C 3P8, Canada. Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. Maryland Med Res Inst, Baltimore, MD USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Dupuis, G (reprint author), Montreal Heart Inst, Dept Psychosomat Med, 5000 Belanger St E, Montreal, PQ H1T 1C8, Canada. EM dupuis.gilles@uqam.ca FU NHLBI NIH HHS [N01-HC-7501-7506] NR 45 TC 4 Z9 4 U1 2 U2 2 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD SEP PY 2006 VL 15 IS 5 BP 471 EP 478 PG 8 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA V44BT UT WOS:000202978900006 PM 16926368 ER PT J AU Chalasani, N Fontana, R Watkins, PB Bonkovsky, HL Davern, T Serrano, J Rochon, J AF Chalasani, N. Fontana, R. Watkins, P. B. . Bonkovsky, H. L. Davern, T. Serrano, J. Rochon, J. TI Drug induced liver injury network (DILIN) prospective study: Initial results SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 Indiana Univ, Sch Med, Bloomington, IN 47405 USA. Univ Connecticut, Storrs, CT 06269 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Clin Res Inst, Durham, NC 27706 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 375 BP S169 EP S169 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656100376 ER PT J AU Tsai, CJ Leitzmann, M Willett, W Giovannucci, E AF Tsai, Chung-Jyi Leitzmann, Michael Willett, Walter Giovannucci, Edward TI Weight cycling and risk of gallstone disease in men SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40506 USA. Harvard Univ, Sch Med, NIH, Div Canc Epidemiol & Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 174 BP S101 EP S101 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656100175 ER PT J AU Pearson, JL AF Pearson, Jane L. TI Progress in identifying risk and protective factors in older suicidal adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; IDEATION C1 NIMH, Bethesda, MD 20892 USA. RP Pearson, JL (reprint author), NIMH, 6001 Execut Blvd,Rm 7160, Bethesda, MD 20892 USA. EM jp36u@nih.gov NR 12 TC 6 Z9 6 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SEP PY 2006 VL 14 IS 9 BP 721 EP 723 DI 10.1097/01.JGP.0000235867.63255.0c PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 078UI UT WOS:000240129400001 PM 16943168 ER PT J AU Beek, KH Hartos, JL Simons-Morton, BG AF Beek, Kenneth H. Hartos, Jessica L. Simons-Morton, Bruce G. TI Relation of parent-teen agreement on restrictions to teen risky driving over 9 months SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article; Proceedings Paper CT 3rd Scientific Meeting of the American-Academy-of-Health-Behavior CY MAR 16-19, 2003 CL ST AUGUSTINE, FL SP Amer Acad Hlth Behav DE adolescent driving; parenting; restrictions; discordance ID BRIEF INTERVENTION; FAMILY-RELATIONS; ADOLESCENT; DRIVERS; CHILD; PASSENGERS; PUBERTY; LIMITS; PERCEPTIONS; 16-YEAR-OLD AB Objectives: To determine the relations among parent-teen discordance for restrictions on driving conditions, driving rules, and consequences for rule violations at licensure and subsequent risky teen driving. Methods: Parents and teens completed telephone interviews at 1, 4, and 9 months after teens became licensed. Results: At each time interval, the degree of disagreement with parent restrictions on driving conditions was positively associated with teen risky driving. Conclusions: These results demonstrate a positive association between parent-teen discordance for driving conditions and teen risky driving. Initial establishment of restrictions and agreement with them may have longer term protective effects against teen driving risk. C1 Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. Univ N Carolina, Dept Hlth Behav & Adm, Coll Hlth & Human Serv, Charlotte, NC 28223 USA. NICHD, Prevent Res Branch, DESPR, NIH, Bethesda, MD USA. RP Beek, KH (reprint author), Univ Maryland, Dept Publ & Community Hlth, 2366 Hlth & Human Performance Bldg, College Pk, MD 20742 USA. EM kbeck1@umd.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 53 TC 1 Z9 1 U1 3 U2 3 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD SEP-OCT PY 2006 VL 30 IS 5 BP 533 EP 543 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 076VL UT WOS:000239986100010 ER PT J AU Collins, FS AF Collins, Francis S. TI No longer just looking under the lamppost SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID GILFORD-PROGERIA-SYNDROME; NUCLEAR FACTOR-4-ALPHA GENE; HUMAN GENOME; CYSTIC-FIBROSIS; MAP; POLYMORPHISM; LINKAGE C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. EM fc23a@nih.gov NR 15 TC 10 Z9 10 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2006 VL 79 IS 3 BP 421 EP 426 DI 10.1086/507611 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 074RY UT WOS:000239830700002 PM 16909378 ER PT J AU Gillanders, EM Pearson, JV Sorant, AJM Trent, JM O'Connell, JR Bailey-Wilson, JE AF Gillanders, E. M. Pearson, J. V. Sorant, A. J. M. Trent, J. M. O'Connell, J. R. Bailey-Wilson, J. E. TI The value of molecular haplotypes in a family-based linkage study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LONG-RANGE PCR; FREQUENCY ESTIMATION; DENSITY; DISEASE; SUSCEPTIBILITY; ASSOCIATION; ALGORITHM; LOCI; MICROSATELLITES AB Novel methods that could improve the power of conventional methods of gene discovery for complex diseases should be investigated. In a simulation study, we aimed to investigate the value of molecular haplotypes in the context of a family-based linkage study. The term "haplotype" ( or "haploid genotype") refers to syntenic alleles inherited on a single chromosome, and we use the term "molecular haplotype" to refer to haplotypes that have been determined directly by use of a molecular technique such as long-range allele-specific polymerase chain reaction. In our study, we simulated genotype and phenotype data and then compared the powers of analyzing these data under the assumptions that various levels of information from molecular haplotypes were available. ( This information was available because of the simulation procedure.) Several conclusions can be drawn. First, as expected, when genetic homogeneity is expected or when marker data are complete, it is not efficient to generate molecular haplotyping information. However, with levels of heterogeneity and missing data patterns typical of complex diseases, we observed a 23% - 77% relative increase in the power to detect linkage in the presence of heterogeneity with heterogeneity LOD scores > 3.0 when all individuals are molecularly haplotyped ( compared with the power when only standard genotypes are used). Furthermore, our simulations indicate that most of the increase in power can be achieved by molecularly haplotyping a single individual in each family, thereby making molecular haplotyping a valuable strategy for increasing the power of gene mapping studies of complex diseases. Maximization of power, given an existing family set, can be particularly important for late-onset, often-fatal diseases such as cancer, for which informative families are difficult to collect. C1 NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. Univ Maryland, Baltimore, MD 21201 USA. Translat Gen TGen Res Inst, Phoenix, AZ USA. RP Gillanders, EM (reprint author), NHGRI, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM lgilland@mail.nih.gov RI Pearson, John/F-2249-2011; OI Pearson, John/0000-0003-0904-4598; Bailey-Wilson, Joan/0000-0002-9153-2920 NR 29 TC 8 Z9 8 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2006 VL 79 IS 3 BP 458 EP 468 DI 10.1086/506626 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 074RY UT WOS:000239830700008 PM 16909384 ER PT J AU Lo, JC Zhao, XH Scuteri, A Brockwell, S Sowers, MR AF Lo, Joan C. Zhao, Xinhua Scuteri, Angelo Brockwell, Sarah Sowers, MaryFran R. TI The association of genetic polymorphisms in sex hormone biosynthesis and action with insulin sensitivity and diabetes mellitus in women at midlife SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE diabetes mellitus; genetics; haplotype; 17-hydroxysteroid dehydrogenase; insulin sensitivity; metabolic syndrome ID HOMEOSTASIS MODEL ASSESSMENT; POLYCYSTIC-OVARY-SYNDROME; DEFICIENT ARKO MICE; BETA-CELL FUNCTION; METABOLIC SYNDROME; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; PROGRAM; HEALTH; PREMENOPAUSAL AB We evaluated associations of insulin sensitivity, metabolic syndrome, and diabetes mellitus with single nucleotide polymorphism (SNP) variants from sex hormone biosynthesis and action in women of 4 races/ethnicities. DNA was extracted from transformed cell samples of 1,538 women in the Study of Women's Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women in SWAN enrolled in the Sex Steroid Hormone Genetics Protocol from whom fasting glucose and insulin measures (for estimating insulin sensitivity), diabetes status, and metabolic syndrome classification were obtained. SNPs from the genes encoding aromatase (CYP 19), 17 beta-hydroxysteroid dehydrogenase (17HSD) type 1, and the estrogen receptors-alpha (ESR1) and -beta (ESR2) were measured. The prevalence of metabolic syndrome was 20% in Chinese women, 22% in Japanese women, 28% in Caucasian women, and 43% in African American women. The prevalence of diabetes was 3% in Chinese women, 4% in Japanese women, 7% in Caucasian women, and 19% in African American women. Significant associations of CYP 19 genotypes and insulin sensitivity were observed in African American, Caucasian, and Japanese women. Selected ESR1 and ESR2 genotypes were associated with insulin sensitivity and metabolic syndrome only in Japanese and Chinese women. The strongest associations related 17HSD genotypes to diabetes in Caucasian women, with odds ratios ranging from 4.4 to 7.5 and confidence intervals that excluded the null value. We observed strong associations between variations in sex hormone biosynthesis and function genes with insulin sensitivity, the metabolic syndrome, and diabetes that varied by race/ethnicity. The strong association of 17HSD and diabetes in Caucasian women has not been previously reported and should be further investigated. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48104 USA. Italian Natl Res Ctr, Unita Operat Geriatr, Rome, Italy. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Kaiser Permanente, Div Res, Oakland, CA USA. RP Sowers, MR (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 339 E Liberty,Suite 310, Ann Arbor, MI 48104 USA. EM mfsowers@umich.edu FU NIA NIH HHS [AG012553, AG012495, AG012505, AG012531, AG012535, AG012539, AG012546, AG012554, AG017719, U01 AG017719]; NINR NIH HHS [NR004061] NR 32 TC 6 Z9 6 U1 1 U2 2 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2006 VL 119 IS 9 SU 1 BP 69 EP 78 DI 10.1016/j.amjmed.2006.07.009 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 079XV UT WOS:000240212100009 PM 16949391 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, Chung-Jyi Leitzmann, Michael F. Willett, Walter C. Giovannucci, Edward L. TI Fruit and vegetable consumption and risk of cholecystectomy in women SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE fruit; vegetable; gallstone; gallbladder; woman; cholecystectomy; prospective study ID GALLBLADDER-DISEASE; GALLSTONES; FOOD; ADULTS; DIET; ACID AB PURPOSE: Many constituents of fruits and vegetables may reduce the risk for gallstones, but prospective data relating fruit and vegetable intake to gallstone disease are sparse. METHODS: We prospectively studied fruit and vegetable consumption in relation to the risk of cholecystectomy in a cohort of 77,090 women in the Nurses' Health Study, 37 to 64 years of age, who had no history of gallstone disease. Women reported on follow-up questionnaires both their consumption of fruits and vegetables and whether they had undergone cholecystectomy. RESULTS: During 1,060,033 person-years of follow-up from 1984 to 2000, participants reported 6608 cases of cholecystectomy. After adjusting for established or suspected risk factors, the relative risk for women in the highest quintile of overall consumption of fruits and vegetables was 0.79 ( 95% confidence interval [ CI], 0.73-0.87, P for trend < .0001) compared with those in the lowest quintile. Similar results were seen for both total fruits and total vegetables separately. The composite items of fruits and vegetables including green leafy vegetables, citrus fruits, vitamin C-rich fruits and vegetables, and cruciferous vegetables also were each inversely associated with the risk. CONCLUSIONS: Our findings suggest a protective role of greater fruit and vegetable consumption against risk of cholecystectomy in women. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 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, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA55075]; NIDDK NIH HHS [DK46200] NR 24 TC 25 Z9 25 U1 0 U2 1 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2006 VL 119 IS 9 BP 760 EP 767 DI 10.1016/j.amjmed.2006.02.040 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 079TC UT WOS:000240199800011 PM 16945611 ER PT J AU Assaf, Y Ben-Sira, L Constantini, S Chang, LC Beni-Adani, L AF Assaf, Y. Ben-Sira, L. Constantini, S. Chang, L. C. Beni-Adani, L. TI Diffusion tensor imaging in hydrocephalus: Initial experience SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CEREBRAL WHITE-MATTER; INTRACRANIAL-PRESSURE; AXONAL DAMAGE; HUMAN BRAIN; COMPRESSION; ANISOTROPY; DEVIATION; TRACT; EDEMA; RAT AB PURPOSE AND BACKGROUND: Diffusion tensor imaging (DTI) is an MR imaging-based technique that provides an in vivo tool for visualization of white matter tracts. In this preliminary study, we used this technique to investigate the diffusion characteristics of white matter tracts in patients with hydrocephalus before and after surgery and compared them with age-matched volunteers. MATERIALS AND METHODS: Seven patients with different types of acute hydrocephalus (defined by acute clinical signs of increased intracranial pressure and imaging evidence of enlarged ventricles) underwent MR imaging including a DTI protocol before and after surgery for shunt placement/revision or ventriculostomy. Eight age-matched healthy subjects served as a control group. The DTI was acquired in a clinical setting that included 6 gradient directions with a b value of 1000 s/mm(2). RESULTS: Before surgery, in fiber systems lateral to the ventricles (corona radiata), the diffusion parallel to the fibers was increased (+10%) and the diffusion perpendicular to the fibers was decreased (-25%) in all patients, resulting in an overall increase in the fractional diffusion anisotropy (FA, +28%). Following surgery, the FA values approached those of control values in all except I patient. In the corpus callosum, the presurgery FA values in patients with hydrocephalus (HCP) were lower than those of control values, and no significant changes were seen following surgery. CONCLUSIONS: DTI can distinguish the compression characteristics of white matter before and after surgery in patients with HCP. At the acute stage of the disease, DTI characteristics point to white matter compression as a possible cause of the observed changes. C1 Tel Aviv Univ, Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. Tel Aviv Sourasky Med Ctr, Levie Edersheim Gitter Inst Funct Brain Imaging, Tel Aviv, Israel. Tel Aviv Sourasky Med Ctr, Dept Neuroradiol, Tel Aviv, Israel. Dana Childrens Hosp, Tel Aviv Sourasky Med Ctr, Dept Pediat Neurosurg, Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Assaf, Y (reprint author), Tel Aviv Univ, Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. EM asafyan@zahav.net.il NR 38 TC 77 Z9 77 U1 2 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2006 VL 27 IS 8 BP 1717 EP 1724 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 086AJ UT WOS:000240645200031 PM 16971621 ER PT J AU Wapner, RJ Sorokin, Y Thom, EA Johnson, F Dudley, DJ Spong, CY Peaceman, AM Leveno, KJ Harper, M Caritis, SN Miodovnik, M Mercer, B Thorp, JM Moawad, A O'Sullivan, MJ Ramin, S Carpenter, MW Rouse, DJ Sibai, B Gabbe, SG AF Wapner, Ronald J. Sorokin, Yoram Thom, Elizabeth A. Johnson, Francee Dudley, Donald J. Spong, Catherine Y. Peaceman, Alan M. Leveno, Kenneth J. Harper, Margaret Caritis, Steve N. Miodovnik, Menachem Mercer, Brian Thorp, John M. Moawad, Atef O'Sullivan, Mary Jo Ramin, Susan Carpenter, Marshall W. Rouse, Dwight J. Sibai, Baha Gabbe, Steven G. CA Natl Inst Child Hlth Human Dev TI Single versus weekly courses of antenatal corticosteroids: Evaluation of safety and efficacy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LA SP Soc Maternal Fetal Med DE antenatal corticosteroids; prematurity ID CLINICAL-TRIALS; INFANTS AB Objective: The purpose of this study was to determine if weekly corticosteroids improve neonatal outcome without undue harm. Study design: Women 23 to 32 weeks receiving 1 course of corticosteroids 7 to 10 days prior were randomized to weekly betamethasone or placebo. Results: The study was terminated by the independent data and safety monitoring committee with 495 of the anticipated 2400 patients enrolled. There was no significant reduction in the composite primary morbidity outcome (8.0% vs 9.1%, P =.67). Repeated courses significantly reduced neonatal surfactant administration (P =.02), mechanical ventilation (P =.004), CPAP (P =.05), pneumothoraces (P =.03). There was no significant difference in mean birth weight or head circumference. The repeat group had a reduction in multiples of the birth weight median by gestational age (0.88 vs 0.91) (P =.01) and more neonates weighing less than the 10th percentile (23.7 vs 15.3%, P=.02). Significant weight reductions occurred for the group receiving >= 4 courses. Conclusion: Repeat antenatal corticosteroids significantly reduce specific neonatal morbidities but do not improve composite neonatal outcome. This is accompanied by reduction in birth weight and increase in small for gestational age infants. (c) 2006 Mosby, Inc. All rights reserved. C1 Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. George Washington Univ, Biostat Ctr, Rockville, MD USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. NICHHD, Bethesda, MD 20892 USA. Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Wake Forest Univ, Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Univ Cincinnati, Cincinnati, OH USA. Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Texas, Dept Obstet & Gynecol, Houston, TX USA. Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA. RP Wapner, RJ (reprint author), Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, 622 W 168th St,PH 16-66, New York, NY 10032 USA. EM rw2191@columbia.edu OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850 FU NCRR NIH HHS [M01-RR-000080]; NICHD NIH HHS [HD27869, HD21410, HD21414, HD27860, HD27861, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 17 TC 131 Z9 136 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2006 VL 195 IS 3 BP 633 EP 642 DI 10.1016/j.ajog.2006.03.087 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 083QO UT WOS:000240473500001 PM 16846587 ER PT J AU Reddy, UM Ko, CW Willinger, M AF Reddy, Uma M. Ko, Chia-Wen Willinger, Marian TI Maternal age and the risk of stillbirth throughout pregnancy in the United States SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE stillbirth; maternal age; medical disease ID FETAL-DEATH; UNEXPLAINED STILLBIRTH; COMPLICATIONS; CERTIFICATES AB Objective: The objective of the study was to examine the relationship of maternal age with stillbirth risk throughout gestation. Study design: A total of 5,458,735 singleton gestations without reported congenital anomalies from the 2001 to 2002 National Center for Health Statistics perinatal mortality and natality files were analyzed. Hazard rates (risk) of stillbirth (fetal death 20 weeks or longer) were calculated for each week of gestation. Results: The risk of stillbirth at 37 to 41 weeks for women 35 to 39 years old was 1 in 382 ongoing pregnancies and for women 40 years old or older, I in 267 ongoing pregnancies. Compared with women younger than 35 years old, the relative risk of stillbirth was 1.32 (95% confidence interval 1.22, 1.43) for women 35 to 39 years old and 1.88 (95% confidence interval 1.64, 2.16) for women 40 years old or older at 37 to 41 weeks. This effect of maternal age persisted despite accounting for medical disease, parity, and race/ethnicity. Conclusion: Women who are of advanced maternal age are at higher risk of stillbirth throughout gestation; the peak risk period is 37 to 41 weeks. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHHD, Pregnancy & Perinatol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Reddy, UM (reprint author), NICHHD, Pregnancy & Perinatol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 22 TC 98 Z9 101 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2006 VL 195 IS 3 BP 764 EP 770 DI 10.1016/j.ajog.2006.06.019 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 083QO UT WOS:000240473500019 PM 16949411 ER PT J AU Haddad, R Gould, BR Romero, R Tromp, G Farookhi, R Edwin, SS Kim, MR Zingg, HH AF Haddad, Ramsi Gould, Barbara R. Romero, Roberto Tromp, Gerard Farookhi, Riaz Edwin, Sam S. Kim, Mi Ran Zingg, Hans H. TI Uterine transcriptomes of bacteria-induced and ovariectomy-induced preterm labor in mice are characterized by differential expression of arachidonate metabolism genes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE mouse; cyclooxygenase pathway; lipoxygenase pathway; parturition; infection; progesterone ID LIPOXYGENASE METABOLITES; INTRAUTERINE TISSUES; FETAL MEMBRANES; AMNIOTIC-FLUID; MOUSE; PARTURITION; PREGNANCY; WOMEN; ACID; PROGESTERONE AB Objective: The purpose of this study was to identify changes in gene expression that are associated with preterm labor induced by either bacteria or ovariectomy. Study design: Pregnant mice (14.5 days of gestation) were allocated to: (1) intrauterine injection of heat-inactivated Escherichia coli; (2) media alone; (3) ovariectomy; or (4) sham operation. The uterine transcriptome was studied with photolithographic, very short oligonucleotide-based microarrays, and arachidonate metabolism genes were assayed with quantitative reverse transcriptase-polymerase chain reaction. Significance was determined by analysis of variance. Results: Microarray-based gene expression changes in the arachidonate metabolism pathway are associated globally with bacteria-induced preterm labor (P <= .0031) and ovariectomy-induced preterm, labor (P <= .00036). Quantitative real-time reverse transcriptase-polymerase chain reaction measurements demonstrated that bacteria-induced preterm labor substantially increased the expression of genes involved in prostaglandin synthesis, In contrast, ovariectomy-induced preterm labor increased the expression of genes involved in lipoxin, leukotriene, and hydroxyeicosatetraenoic acid synthesis. Conclusion: Bacteria-induced and ovariectomy-induced preterm labor each express a different balance of genes that are required for the synthesis of prostaglandins, lipoxins, leukotrienes, and hydroxycicosatetraenoic acids. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. McGill Univ, Dept Physiol, Montreal, PQ, Canada. RP Haddad, R (reprint author), Hutzel Womens Hosp, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM haddadr@karmanos.org RI Tromp, Gerard/B-2677-2017 OI Tromp, Gerard/0000-0002-7761-0806 FU Intramural NIH HHS NR 25 TC 11 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2006 VL 195 IS 3 BP 822 EP 828 DI 10.1016/j.ajog.2006.06.053 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 083QO UT WOS:000240473500029 PM 16949419 ER PT J AU Kim, CJ Kim, JS Kim, YM Cushenberry, E Richani, K Espinoza, J Romero, R AF Kim, Chong Jai Kim, Jung-Sun Kim, Yeon Mee Cushenberry, Enota Richani, Karina Espinoza, Jimmy Romero, Roberto TI Fetal macrophages are not present in the myometrium of women with labor at term SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE macrophage; myometrium; labor; laser capture microdissection; chromogenic in situ hybridization ID MONOCYTE CHEMOTACTIC PROTEIN-1; LOWER UTERINE SEGMENT; ADHESION MOLECULES; HUMAN PARTURITION; PRETERM LABOR; LEUKOCYTES; EXPRESSION; INFLAMMATION; PREGNANCY; MEMBRANES AB Objective: The basic mechanisms responsible for human parturition remain to be elucidated. The influx of fetal leukocytes into the myometrium has been recently proposed to be a crucial event in the onset of murine parturition. Surfactant protein-A has been implicated in the initiation of labor. In mice, it is thought that surfactant protein-A induces migration and subsequent activation of amniotic fluid macrophages of fetal origin, which then invades the myometrium. The present study was conducted to determine whether fetal macrophages invade the myometrium of women in labor. Study design: Placental bed biopsy specimens were obtained from patients in labor who delivered male neonates at term (n = 7). Myometrial sections of postpartum hysterectomy specimens obtained from women who delivered of male neonates (n = 3) were also analyzed. Formalin-fixed, paraffin-embedded sections were immunostained for CD68 or CD14 (which are markers for macrophages); immunoreactive myometrial macrophages were specifically procured by laser capture microdissection. Sex typing was done by polymerase chain reaction for the amelogenin gene with genomic DNA that was isolated from the macrophages. Chromogenic in situ hybridization with a Y chromosome-specific probe was also performed on paraffin-embedded histologic sections. Results: Amelogenin allelotypes of the macrophages were consistent with female alleles in all cases that were tested, indicating a maternal origin. Chromogenic in situ hybridization demonstrated the absence of Y chromosome-positive mononuclear cells in the myometrium in all cases. Conclusion: These observations, from a limited number of cases, suggest that migration of fetal macrophages from the amniotic cavity or the chorioamniotic membranes into the myometrium does not occur during human labor. The trafficking of fetal macrophages in labor seems to be different in humans and mice. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHD, DHHS, Perinatol Res Branch, Hutzel Womens Hosp,NIH, Detroit, MI 48201 USA. NICHD, DHHS, Perinatol Res Branch, Hutzel Womens Hosp,NIH, Bethesda, MD USA. Wayne State Univ, Dept Pathol, Detroit, MI USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Kim, CJ (reprint author), NICHD, DHHS, Perinatol Res Branch, Hutzel Womens Hosp,NIH, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 25 TC 13 Z9 13 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2006 VL 195 IS 3 BP 829 EP 833 DI 10.1016/j.ajog.2006.06.052 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 083QO UT WOS:000240473500030 PM 16949420 ER PT J AU Graham, MR Virtaneva, K Porcella, SF Gardner, DJ Long, RD Welty, DM Barry, WT Johnson, CA Parkins, LD Wright, FA Musser, JM AF Graham, Morag R. Virtaneva, Kimmo Porcella, Stephen F. Gardner, Donald J. Long, R. Daniel Welty, Diane M. Barry, William T. Johnson, Claire A. Parkins, Larye D. Wright, Fred A. Musser, James M. TI Analysis of the transcriptome of group A Streptococcus in mouse soft tissue infection SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID EXTRACELLULAR CYSTEINE PROTEASE; HYALURONIC-ACID CAPSULE; ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS; 2-COMPONENT REGULATORY SYSTEM; VIRULENCE FACTOR REGULATION; GENOMIC-SCALE ANALYSIS; PYOGENES M-PROTEIN; IN-VIVO; GENE-EXPRESSION; STREPTOLYSIN-S AB Molecular mechanisms mediating group A Streptococcus (GAS)-host interactions remain poorly understood but are crucial for diagnostic, therapeutic, and vaccine development. An optimized high-density microarray was used to analyze the transcriptome of GAS during experimental mouse soft tissue infection. The transcriptome of a wild-type serotype MI GAS strain and an isogenic transcriptional regulator knockout mutant (covR) also were compared. Array datasets were verified by quantitative real-time reverse transcriptase-polymerase chain reaction and in situ immunohistochemistry The results unambiguously demonstrate that coordinated expression of proven and putative GAS virulence factors is directed toward overwhelming innate host defenses leading to severe cellular damage. We also identified adaptive metabolic responses triggered by nutrient signals and hypoxic/acidic conditions in the host, likely facilitating pathogen persistence and proliferation in soft tissues. Key discoveries included that oxidative stress genes, virulence genes, genes related to amino acid and maltodextrin utilization, and several two-component transcriptional regulators were highly expressed in vivo. This study is the first global analysis of the GAS transcriptome during invasive infection. Coupled with parallel analysis of the covR mutant strain, novel insights have been made into the regulation of GAS virulence in vivo, resulting in new avenues for targeted therapeutic and vaccine research. C1 Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Vet Branch, NIH, Hamilton, MT 59840 USA. Methodist Hosp, Ctr Mol & Translat Human Infect Dis Res, Res Inst, Houston, TX 77030 USA. RP Musser, JM (reprint author), Methodist Hosp, Ctr Mol & Translat Human Infect Dis Res, Res Inst, 6535 Fannin St,B490, Houston, TX 77030 USA. EM jmmusser@tmh.tmc.edu FU Intramural NIH HHS NR 116 TC 67 Z9 67 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2006 VL 169 IS 3 BP 927 EP 942 DI 10.2353/ajpath.2006.060112 PG 16 WC Pathology SC Pathology GA 077RY UT WOS:000240048900019 PM 16936267 ER PT J AU Clase, AC Dimcheff, DE Favara, C Dorward, D McAtee, FJ Parrie, LE Ron, D Portis, JL AF Clase, Amanda C. Dimcheff, Derek E. Favara, Cynthia Dorward, David McAtee, Frank J. Parrie, Lindsay E. Ron, David Portis, John L. TI Oligodendrocytes are a major target of the toxicity of spongiogenic murine retroviruses SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANT; ENDOPLASMIC-RETICULUM STRESS; CENTRAL-NERVOUS-SYSTEM; LEUKEMIA-VIRUS-TB; INDUCED SPONGIFORM NEURODEGENERATION; N-LINKED GLYCOSYLATION; C RNA VIRUS; TRANSCRIPTION FACTORS; TRANSLATIONAL CONTROL; ECOTROPIC RETROVIRUS AB The neurovirulent retroviruses FrCasE and Moloney MLV-ts1 cause noninflammatory spongiform neuro-degeneration in mice, manifested clinically by progressive spasticity and paralysis. Neurons have been thought to be the primary target of toxicity of these viruses. However the neurons themselves appear not to be infected, and the possible indirect mechanisms driving the neuronal toxicity have remained enigmatic. Here we have re-examined the cells that are damaged by these viruses, using lineage-specific markers. Surprisingly, these cells expressed the basic helix-loop-helix transcription factor Olig2, placing them in the oligodendrocyte lineage. Olig2(+) cells were found to be infected, and many of these cells exhibited focal cytoplasmic vacuolation, suggesting that infection by spongiogenic retroviruses; is directly toxic to these cells. As cytoplasmic vacuolation progressed, however, signs of viral protein expression appeared to wane, although residual viral RNA was detectable by in situ hybridization. Cells with the most advanced cytoplasmic effacement expressed the C/EBP-homologous protein (CHOP). This protein is up-regulated as a late event in a cellular response termed the integrated stress response. This observation may link the cellular pathology observed in the brain with cellular stress responses known to be induced by these viruses. The relevance of these observations to oligodendropathy in humans is discussed. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Unit, NIH, Hamilton, MT 59840 USA. CUNY, Sch Med, Skirball Inst Biomol Med, New York, NY 10031 USA. RP Portis, JL (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jportis@niaid.nih.gov OI Ron, David/0000-0002-3014-5636 FU Intramural NIH HHS; NIDDK NIH HHS [DK47119, R37 DK047119, R01 DK047119]; NIEHS NIH HHS [ES086981] NR 57 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2006 VL 169 IS 3 BP 1026 EP 1038 DI 10.2353/ajpath.2006.051357 PG 13 WC Pathology SC Pathology GA 077RY UT WOS:000240048900027 PM 16936275 ER PT J AU Berrigan, D Troiano, RP McNeel, T DiSogra, C Ballard-Barbash, R AF Berrigan, David Troiano, Richard P. McNeel, Timothy DiSogra, Charles Ballard-Barbash, Rachel TI Active transportation increases adherence to activity recommendations SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY GUIDELINES; US ADULTS; ALL-CAUSE; HEALTH; OBESITY; PREVALENCE; MORTALITY; FITNESS; WOMEN; TIME AB Background: Levels of physical activity (PA) contribute to health statits and outcomes directly and indirectly via the effects of PA on obesity and other risk factors. Much past surveillance has focused on leisure-time physical activity (LTPA), but this may bias estimates of prevalence. This study explores inclusion of non-leisure-time walking and bicycling (NLTWB) used for transportation on the prevalence of adherence to PA recommendations and the magnitude of apparent disparities in adherence for California adults. Methods: Results of the 2001 California Health Interview Survey, a large (n =55,151) telephone survey were analyzed in 2005 using tabulation and logistic regression. Results: Higher levels of LTPA were associated with youth, males, education, income, Pacific Islanders, and non-Hispanic (NH) whites. Inclusion of NLTWTB reduced these differences for all five variables. The largest decreases in disparities in adherence occurred for race/ethnicity, education, and income, with decreases in adherence differences from similar to 18% to 7% for NH white vs Latino, similar to 27% to 16% for more than high school versus less than high school, and similar to 25% to 11% for more than 300% versus less than 100% of poverty level. Logistic regression comparing adherence gives similar results. For example, in respondents with more than high school education versus less than high school education (referent), the odds ratio changed from 2.23 (95% confidence interval [Cl]=2.0-2.4) to 1.7 (1.6-1.9) after the inclusion of NLTWB. Conclusions: Assessment of PA in multiple domains is required to understand differences in total levels of PA for people with different incomes, education levels, and racial/ethnic backgrounds. Inclusion of NLTWB reduces but does not eliminate disparities in adherence to recommended levels of PA. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Univ Calif Los Angeles, Calif Hlth Interview Survey, Ctr Hlth Policy Res, Los Angeles, CA USA. Univ Calif Oakland, Tobacco Related Dis Res Program, Off President, Oakland, CA USA. RP Berrigan, D (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Plaza N,MSC 7344,Room 4095B, Bethesda, MD 20892 USA. EM berrigad@mail.nih.gov OI Troiano, Richard/0000-0002-6807-989X NR 30 TC 58 Z9 59 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2006 VL 31 IS 3 BP 210 EP 216 DI 10.1016/j.amepre.2006.04.007 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 077QM UT WOS:000240044800003 PM 16905031 ER PT J AU Patel, KV Coppin, AK Manini, TM Lauretani, F Bandinelli, S Ferrucci, L Guralnik, JM AF Patel, Kushang V. Coppin, Antonia K. Manini, Todd M. Lauretani, Fulvio Bandinelli, Stefania Ferrucci, Luigi Guralnik, Jack M. TI Midlife physical activity and mobility in older age - The InCHIANTI Study SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID LOWER-EXTREMITY FUNCTION; CORONARY-HEART-DISEASE; SUBSEQUENT DISABILITY; LIFE EXPECTANCY; WOMENS HEALTH; ADULTS; RELIABILITY; LIMITATION; MORTALITY; WALK AB Background: Among older adults, loss of mobility represents a critical stage in the disablement process, whereby the risk for disability is significantly increased. Physical activity is a modifiable risk factor that is associated with reduced risk of losing mobility in older adulthood; however, few studies have examined physical activity performed earlier in life in relation to mobility later in life. Methods: Data from a population-based study of 1155 adults aged 65 years and older living in the Chianti region of Italy in 1998-2000 were analyzed in 2005 and 2006. Participants retrospectively recalled their physical activity levels in midlife and underwent mobility testing and medical examination. Two objective mobility outcomes were examined as a function of past physical activity: the Short Physical Performance Battery (SPPB) and the ability to walk 400 meters. Results: Older Italian adults (mean age 74.8, standard deviation 7.3) who engaged in higher levels of physical activity in midlife were significantly more likely to perform better on the SPPB than individuals who were less physically active in midlife. In addition, failure to complete the 400-meter walk test was significantly less likely among physically active men (Level II) (odds ratio [OR]=0.37, 95% confidence interval [Cl]=0.15-0.93) and very active men (Level III) (OR=0.23, 95% CI=0.09-0.63) when compared to men who were less active (Level I) in the past (p for trend, 0.008). These associations remained after adjustment for demographic factors, medical conditions, and physiologic impairments. Conclusions: Older adults who reported higher levels of physical activity in midlife had better mobility in old age than less physically active ones. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Tuscany Reg Hlth Agcy, Florence, Italy. Azienda Sanitaria Firenze, Dept Geriatr Rehabil, Florence, Italy. NIA, Longitudinal Studies Section, Clin Res Branch, Baltimore, MD 21224 USA. RP Patel, KV (reprint author), 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM Patelku@mail.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999] NR 32 TC 61 Z9 61 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2006 VL 31 IS 3 BP 217 EP 224 DI 10.1016/j.amepre.2006.05.005 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 077QM UT WOS:000240044800004 PM 16905032 ER PT J AU Nierenberg, AA Fava, M Trivedi, MH Wisniewski, SR Thase, ME McGrath, PJ Alpert, JE Warden, D Luther, JF Niederehe, G Lebowitz, B Shores-Wilson, K Rush, AJ AF Nierenberg, Andrew A. Fava, Maurizio Trivedi, Madhukar H. Wisniewski, Stephen R. Thase, Michael E. McGrath, Patrick J. Alpert, Jonathan E. Warden, Diane Luther, James F. Niederehe, George Lebowitz, Barry Shores-Wilson, Kathy Rush, A. John CA STAR D Study Team TI A comparison of lithium and T-3 augmentation following two failed medication treatments for depression: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE; INTERACTIVE VOICE RESPONSE; ILLNESS RATING-SCALE; REPORT QIDS-SR; TRIIODOTHYRONINE AUGMENTATION; REFRACTORY DEPRESSION; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS AB Objective: More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T-3) augmentation as a third-step treatment for patients with major depressive disorder. Method: A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T-3 (up to 50 mu g/day; N= 73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score <= 7 on the 17-item Hamilton Depression Rating Scale. Results: After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T-3 augmentation, although the difference between treatments was not statistically significant. Lithium was more frequently associated with side effects (p=0.045), and more participants in the lithium group left treatment because of side effects (23.2% versus 9.6%; p=0.027). Conclusions: Remission rates with lithium and T-3 augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. The lower side effect burden and ease of use of T-3 augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. NIMH, Bethesda, MD 20892 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St, Boston, MA 02114 USA. EM anierenberg@partners.org RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH-90003] NR 49 TC 205 Z9 209 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2006 VL 163 IS 9 BP 1519 EP 1530 DI 10.1176/appi.ajp.163.9.1519 PG 12 WC Psychiatry SC Psychiatry GA 079VD UT WOS:000240205100011 PM 16946176 ER PT J AU McGrath, PJ Stewart, JW Fava, M Trivedi, MH Wisniewski, SR Nierenberg, AA Thase, ME Davis, L Biggs, MM Shores-Wilson, K Luther, JF Niederehe, G Warden, D Rush, AJ AF McGrath, Patrick J. Stewart, Jonathan W. Fava, Maurizio Trivedi, Madhukar H. Wisniewski, Stephen R. Nierenberg, Andrew A. Thase, Michael E. Davis, Lori Biggs, Melanie M. Shores-Wilson, Kathy Luther, James F. Niederehe, George Warden, Diane Rush, A. John CA STAR D Study Team TI Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DIAGNOSTIC SCREENING QUESTIONNAIRE; SEQUENCED TREATMENT ALTERNATIVES; TREATMENT-RESISTANT DEPRESSION; INTERACTIVE VOICE RESPONSE; VAGUS NERVE-STIMULATION; ILLNESS RATING-SCALE; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; MAJOR DEPRESSION; QUICK INVENTORY AB Objective: The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials. Method: Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine (N=51). The primary outcome measure was whether patients achieved remission, which was defined as a score <= 7 at exit on the 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D was administered by telephone by raters to whom treatment was masked. Results: Remission rates were not significantly different between the two treatment groups (6.9% for the tranylcypromine group and 13.7% for the venlafaxine plus mirtazapine group). The mean daily dose at exit for tranylcypromine was 36.9 mg (SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and for mirtazapine, 35.7 mg (SD=17.6). Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance. Conclusions: Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments. C1 New York State Psychiat Inst & Hosp, Depress Evaluat Serv, New York, NY 10032 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Austin, TX USA. Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Columbia Coll Phys & Surg, Dept Psychiat, New York, NY USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15260 USA. NIMH, Bethesda, MD 20892 USA. RP McGrath, PJ (reprint author), New York State Psychiat Inst & Hosp, Depress Evaluat Serv, 1051 Riverside Dr,Unit 51, New York, NY 10032 USA. EM mcgrath@pi.cpmc.columbia.edu RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH-90003] NR 40 TC 171 Z9 177 U1 1 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2006 VL 163 IS 9 BP 1531 EP 1541 DI 10.1176/appi.ajp.163.9.1531 PG 11 WC Psychiatry SC Psychiatry GA 079VD UT WOS:000240205100012 PM 16946177 ER PT J AU Kessler, RC Akiskal, HS Ames, M Birnbaum, H Greenberg, P Hirschfeld, RMA Jin, R Merikangas, KR Simon, GE Wang, PS AF Kessler, Ronald C. Akiskal, Hagop S. Ames, Minnie Birnbaum, Howard Greenberg, Paul Hirschfeld, Robert M. A. Jin, Robert Merikangas, Kathleen R. Simon, Gregory E. Wang, Philip S. TI Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. workers SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HEALTH-ORGANIZATION HEALTH; BIPOLAR-I DISORDER; DEPRESSIVE SYMPTOMS; ECONOMIC BURDEN; GENERAL-POPULATION; QUESTIONNAIRE HPQ; CARE COSTS; US; COMMUNITY; EPIDEMIOLOGY AB Objective: Research on the workplace costs of mood disorders has focused largely on major depressive episodes. Bipolar disorder has been overlooked both because of the failure to distinguish between major depressive disorder and bipolar disorder and by the failure to evaluate the workplace costs of mania/hypomania. Method: The National Comorbidity Survey Replication assessed major depressive disorder and bipolar disorder with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) and work impairment with the WHO Health and Work Performance Questionnaire. A regression analysis of major depressive disorder and bipolar disorder predicting Health and Work Performance Questionnaire scores among 3,378 workers was used to estimate the workplace costs of mood disorders. Results: A total of 1.1% of the workers met CIDI criteria for 12-month bipolar disorder (I or II), and 6.4% meet criteria for 12-month major depressive disorder. Bipolar disorder was associated with 65.5 and major depressive disorder with 27.2 lost workdays per ill worker per year. Subgroup analysis showed that the higher work loss associated with bipolar disorder than with major depressive disorder was due to more severe and persistent depressive episodes in those with bipolar disorder than in those with major depressive disorder rather than to stronger effects of mania/hypomania than depression. Conclusions: Employer interest in workplace costs of mood disorders should be broadened beyond major depressive disorder to include bipolar disorder. Effectiveness trials are needed to study the return on employer investment of coordinated programs for workplace screening and treatment of bipolar disorder and major depressive disorder. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Calif San Diego, Int Mood Ctr, San Diego, CA 92103 USA. VA Psychiat Serv, San Diego, CA USA. Anal Grp Inc, Boston, MA USA. Univ Texas, Med Branch, Dept Psychiat & Behav Sci, Galveston, TX 77550 USA. NIMH, Grp Hlth Cooperat, Intramural Res Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu FU NIDA NIH HHS [R01 DA016558, R01 DA016558-02]; NIMH NIH HHS [R01 MH069864, R01 MH069864-02, R13 MH066849, R13 MH066849-03, U01 MH060220, U01 MH060220-05, U13 MH066849] NR 45 TC 355 Z9 363 U1 3 U2 38 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2006 VL 163 IS 9 BP 1561 EP 1568 DI 10.1176/appi.ajp.163.9.1561 PG 8 WC Psychiatry SC Psychiatry GA 079VD UT WOS:000240205100016 PM 16946181 ER PT J AU Zalsman, G Huang, YY Oquendo, MA Burke, AK Hu, XZ Brent, DA Ellis, SP Goldman, D Mann, JJ AF Zalsman, Gil Huang, Yung-yu Oquendo, Maria A. Burke, Ainsley K. Hu, Xian-zhang Brent, David A. Ellis, Steven P. Goldman, David Mann, J. John TI Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; SUICIDAL-BEHAVIOR; ENVIRONMENT; SYSTEM; AVAILABILITY; NEUROBIOLOGY; METAANALYSIS; DISORDERS; RECEPTORS; TWIN AB Objective: The lower expressing allele of the serotonin transporter gene 5' promoter region (5-HTTLPR) polymorphism is reported to be associated with susceptibility to depression and suicidality in response to stressful life events. The authors examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events, severity of major depression, and suicidality. Method: Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasian subjects of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism (higher expressing allele: LA; lower expressing alleles: LG, S). All subjects underwent structured clinical interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed in a subgroup of subjects. Results: Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate to severe life events compared with the higher expressing LA allele. No associations with suicidal behavior and CSF 5- HIAA were found. Conclusions: Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated. C1 New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Univ Pittsburgh, Med Ctr, Dept Child Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Mann, JJ (reprint author), New York State Psychiat Inst & Hosp, Dept Neurosci, 1051 Riverside Dr,Box 42, New York, NY 10032 USA. EM jjm@columbia.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIMH NIH HHS [MH-48514, MH-056612, MH-62185] NR 40 TC 247 Z9 258 U1 6 U2 25 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2006 VL 163 IS 9 BP 1588 EP 1593 DI 10.1176/appi.ajp.163.9.1588 PG 6 WC Psychiatry SC Psychiatry GA 079VD UT WOS:000240205100020 PM 16946185 ER PT J AU Outram, D Brown, TM Fee, E AF Outram, Dorinda Brown, Theodore M. Fee, Elizabeth TI An enlightenment view of school health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Univ Rochester, Dept Hist, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. Natl Lib Med, Hist Med Div, Bethesda, MD USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM theodore_brown@urmc.rochester.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2006 VL 96 IS 9 BP 1560 EP 1560 DI 10.2105/AJPH.2006.094185 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 079LY UT WOS:000240179100010 PM 16873732 ER PT J AU Bergmann-Leitner, ES Duncan, EH Mullen, GE Burge, JR Khan, F Long, CA Angov, E Lyon, JA AF Bergmann-Leitner, Elke S. Duncan, Elizabeth H. Mullen, Gregory E. Burge, John Robert Khan, Farhat Long, Carole A. Angov, Evelina Lyon, Jeffrey A. TI Critical evaluation of different methods for measuring the functional activity of antibodies against malaria blood stage antigens SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID APICAL MEMBRANE ANTIGEN-1; PARASITE PLASMODIUM-FALCIPARUM; MEROZOITE SURFACE PROTEIN-1; IN-VITRO; INHIBITION; GROWTH; INVASION; ERYTHROCYTE; SCHIZONTS; IMMUNITY AB Antibodies are thought to be the primary immune effectors in the defense against erythrocytic stage Plasmodium falciparum. Thus, malaria vaccines directed to blood stages of infection are evaluated based on their ability to induce antibodies with anti-parasite activity. Such antibodies may have different effector functions (e.g., inhibition of invasion or inhibition of parasite growth/development) depending on the target antigen. We evaluated four methods with regards to their ability to differentiate between invasion and/or growth inhibitory activities of antibodies specific for two distinct blood stage antigens: AMA1. and MSP1(42). We conclude that antibodies induced by these vaccine candidates have different modes of action that vary not only by the antigen, but also by the strain of parasite being tested. Analysis based on parasitemia and viability was essential for defining the full range of anti-parasite activities in immune sera. C1 Walter Reed Army Inst Res, Dept Immunol, CD&I, Silver Spring, MD 20910 USA. NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Bergmann-Leitner, ES (reprint author), Walter Reed Army Inst Res, Dept Immunol, CD&I, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM bergmannleitner@us.army.mil RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 27 TC 57 Z9 57 U1 1 U2 2 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 SEP PY 2006 VL 75 IS 3 BP 437 EP 442 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 083RR UT WOS:000240476400011 PM 16968918 ER PT J AU Almeida, AM AF Almeida, Andrea M. TI Mitochondrial DNA damage associated with lipid peroxidation of the mitochondrial membrane induced by Fe2+-citrate SO ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS LA English DT Article ID OXIDATIVE STRESS; STRAND BREAKS; IRON HOMEOSTASIS; YEAST FRATAXIN; IN-VIVO; CITRATE; LIVER; CA2+; 8-HYDROXYDEOXYGUANOSINE; PERMEABILITY AB Iron imbalance/accumulation has been implicated in oxidative injury associated with many degenerative diseases such as hereditary hemochromatosis, beta-thalassemia, and Friedreich's ataxia. Mitochondria are particularly sensitive to iron-induced oxidative stress - high loads of iron cause extensive lipid peroxidation and membrane permeabilization in isolated mitochondria. Here we detected and characterized mitochondrial DNA damage in isolated rat liver mitochondria exposed to a Fe2+-citrate complex, a small molecular weight complex. Intense DNA fragmentation was induced after the incubation of mitochondria with the iron complex. The detection of 3' phosphoglycolate ends at the mtDNA strand breaks by a P-32-postlabeling assay, suggested the involvement of hydroxyl radical in the DNA fragmentation induced by Fe2+-citrate. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine also suggested that Fe2+-citrate-induced oxidative stress causes mitochondrial DNA damage. In conclusion, our results show that iron-mediated lipid peroxidation was associated with intense mtDNA damage derived from the direct attack of reactive oxygen species. C1 Univ Estadual Campinas, Fac Ciencias Med, NCME, Dept Patol Clin, BR-13083970 Campinas, SP, Brazil. Univ Fed Sao Paulo, CEDEME, Lab Controle Genet, BR-04023900 Sao Paulo, Brazil. Univ Fed Vicosa, Dept Biol Vegetal, BR-36570000 Vicosa, MG, Brazil. NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Almeida, AM (reprint author), Univ Estadual Campinas, Fac Ciencias Med, NCME, Dept Patol Clin, Cx Postal 6111, BR-13083970 Campinas, SP, Brazil. RI Bertoncini, Clelia/B-5942-2014 OI Bertoncini, Clelia/0000-0001-9025-5370 NR 47 TC 18 Z9 20 U1 0 U2 7 PU ACAD BRASILEIRA DE CIENCIAS PI RIO JANEIRO PA RUA ANFILOFIO DE CARVALHO, 29, 3 ANDAR, 20030-060 RIO JANEIRO, BRAZIL SN 0001-3765 J9 AN ACAD BRAS CIENC JI An. Acad. Bras. Cienc. PD SEP PY 2006 VL 78 IS 3 BP 505 EP 514 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 076ZV UT WOS:000239998400010 PM 16936939 ER PT J AU Guszczynski, T Specht, SI Copeland, TD AF Guszczynski, Tad Specht, Suzanne I. Copeland, Terry D. TI A microtiter plate fraction collector for the sequencing of radioactive phosphorylated peptides SO ANALYTICAL BIOCHEMISTRY LA English DT Editorial Material ID KINASE; RECEPTOR; RAF-1; SITES; YEAST C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Guszczynski, T (reprint author), NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. EM guszczyn@ncifcrf.gov FU Intramural NIH HHS NR 13 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 1 PY 2006 VL 356 IS 1 BP 151 EP 153 DI 10.1016/j.ab.2006.05.06.034 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 079JA UT WOS:000240170700021 PM 16814243 ER PT J AU Barnes, C Portnoy, J Sever, M Arbes, S Vaughn, B Zeldin, DC AF Barnes, Charles Portnoy, Jay Sever, Michelle Arbes, Samuel, Jr. Vaughn, Ben Zeldin, Darryl C. TI Comparison of enzyme immunoassay-based assays for environmental Alternaria alternata SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; MAJOR ALLERGEN; NATIONAL-HEALTH; HOUSE-DUST; ALT A1; ALT-A-1; PURIFICATION; CLONING; QUANTITATION; PRODUCTS AB Background: Alternaria alternata-derived allergenic materials are causes of human disease. Several immunoassays exist to quantify these materials. Objective: To compare methods for evaluating Alternaria content. Methods: Four methods, including 1 monoclonal antibody (MAb)-based assay specific for recombinant Alt a 1, 1 MAb-based assay for chromatographically purified Alt a 1, 1 polyclonal antibody (PAb)-based assay for chromatographically purified Alt a 1, and I PAb-based assay for whole Alternaria extract, were evaluated. Environmental samples collected as part of the National Survey of Lead and Allergens in Housing were examined. Alternaria spore counts were determined in dust by observation. Results: The MAb-based assay for recombinant Alt a I detected Alternaria in few samples (25%); the PAb-based assay for whole Alternaria proteins detected antigen in 97% of the samples. The PAb- and MAb-based assays for purified Alt a I detected antigen in 100% of the samples. There was a significant positive correlation between the 2 assays directed against purified Alt a 1. There was a positive correlation between the PAb-based assay for whole Alternaria and the PAb-based assay for Alt a 1. Nearly all the dust samples contained Alternaria spores, and there was a strong positive correlation between counts and all assays. Conclusion: Because of the multifaceted nature of Alternaria, the disparities between methods for quantifying Alternaria, the cross-reactivity between fungal allergens, and the documented genetic promiscuity of this fungus, enzyme immunoassays using PAbs against a range of Alternaria proteins will probably produce the most reliable estimation of overall Alternaria exposure in house dust. C1 Childrens Mercy Hosp, Kansas City, MO 64108 USA. Natl Inst Environm Hlth Sci, Div Intramural Res, Natl Inst Hlth, Res Triangle Pk, NC USA. Rho Inc, Chapel Hill, NC USA. RP Barnes, C (reprint author), Childrens Mercy Hosp, 2400 Gillham Rd, Kansas City, MO 64108 USA. EM cbarnes@cmh.edu FU Intramural NIH HHS [Z99 ES999999] NR 44 TC 14 Z9 15 U1 0 U2 2 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD SEP PY 2006 VL 97 IS 3 BP 350 EP 356 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 087RI UT WOS:000240759400015 PM 17042141 ER PT J AU Iqbal, J He, G Biesecker, LG Rosen, P Duray, PH Schwartzentruber, D Beg, M Kahn, E AF Iqbal, Jabed He, Gary Biesecker, Leslie G. Rosen, Peter Duray, Paul H. Schwartzentruber, Douglas Beg, Mansor Kahn, Ellen TI Morphological characterization of the breast in Proteus syndrome complicated by ductal carcinoma in situ SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE Proteus syndrome; intraductal carcinoma; intraductal papilloma; breast proliferative changes ID NEOPLASMS AB Proteus syndrome (PS) is a severe, variable, and rare disorder with asymmetric and disproportionate overgrowth of body parts, cerebriform connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. It is associated with benign and occasionally malignant tumors. We report the first case of ductal carcinoma in situ (DCIS) in a 28-yr-old woman with PS who underwent a mastectomy for asymmetric overgrowth. The cut surface of the tissue showed a discrete, white, lobulated, solid mass with multiple cysts with occasional small polypoid nodules. Microscopically, the tissue was characterized by neoplastic and non-neoplastic changes. The former consisted of multiple intraductal papillomas and low-grade intraductal papillary, solid, and cribriform carcinoma. The non-neoplastic changes were characterized by cysts of various sizes, lined by cuboidal or apocrine cells, focally with epithelial papillary proliferation; the lumens contained eosinophilic, mucicarmine-positive, and PAS-positive material. Variable ductal proliferation and periductal, peri- and intra-lobular fibrosis with loose fibrous connective tissue was present. The carcinoma was positive for ER, PR, CK7, and MIB-1 (40%), and negative for p53 and CK20 staining. We conclude that DCIS may be one of the tumors associated with PS and that the proliferative phenotype serves as an initiator for carcinogenesis. This case highlights the difficulty of recognizing small foci of carcinoma in an asymmetrical overgrowth of the breast in a young woman with PS. C1 NYU, Sch Med, N Shore Univ Hosp, Manchester, Lancs, England. NHGRI, NIH, Bethesda, MD 20892 USA. NYU, New York Presbyterian Hosp, New York, NY USA. NIH, Ctr Clin, Dept Pathol, Bethesda, MD 20892 USA. Goshen Hlth Syst Canc Ctr, Goshen, IN USA. RP Kahn, E (reprint author), 9 Sheep Pasture Rd, Moscow 117437, Russia. EM ellenkahn@optonline.net FU Intramural NIH HHS NR 9 TC 2 Z9 2 U1 0 U2 0 PU ASSN CLINICAL SCIENTISTS PI MIDDLEBURY PA PO BOX 1287, MIDDLEBURY, VT 05753 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD FAL PY 2006 VL 36 IS 4 BP 469 EP 474 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 107FH UT WOS:000242155600015 PM 17127737 ER PT J AU Geerlings, MI Strozyk, D Masaki, K Remaley, AT Petrovitch, H Ross, GW White, LR Launer, LJ AF Geerlings, Mirjam I. Strozyk, Dorothea Masaki, Kamal Remaley, Alan T. Petrovitch, Helen Ross, G. Webster White, Lon R. Launer, Lenore J. TI Endogenous sex hormones, cognitive decline, and future dementia in old men SO ANNALS OF NEUROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; JAPANESE-AMERICAN MEN; CONJUGATED EQUINE ESTROGENS; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; FREE TESTOSTERONE; APOLIPOPROTEIN-E; ELDERLY-MEN; RISK-FACTOR AB Objective: To estimate the association of endogenous levels of bioavailable testosterone and estradiol with risk for cognitive decline and dementia in old men. Methods: Within the population-based, prospective Honolulu-Asia Aging Study, 2,974 men, aged 71 to 93 years, without dementia were reexamined 3 times over an average of 6 years for development of dementia and cognitive decline. Cognitive decline was measured with the Cognitive Abilities Screening Instrument. Incident dementia was diagnosed according to standard criteria. A total of 134 men experienced development of Alzheimer's disease (AD; including 40 cases with contributing cerebrovascular disease) and 44 experienced development of vascular dementia. Results: Adjusting for age and other covariates, testosterone was not associated with risk for dementia (using Cox regression analyses) or cognitive decline (using random coefficient analyses). However, higher levels of estradiol were associated with risk for AD (hazard ratio per standard deviation increase, 1.25; 95% confidence interval, 1.05-1.47) and AD with cerebrovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.38). Also, compared with the lowest tertile of estradiol, men in the middle and highest tertile of estradiol had 0.24 and 0.28 points lower Cognitive Abilities Screening Instrument scores, respectively, for each year increase in age. Interpretation: In old men, endogenous testosterone levels are not associated with risk for cognitive decline and AD, whereas higher estrogen levels increase risk for cognitive decline and AD. C1 Univ Utrecht, Med Ctr, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Pacific Hlth Res Inst, Honolulu, HI USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Geerlings, MI (reprint author), Univ Utrecht, Med Ctr, Julius Ctr Hlth Sci & Primary Care, Stratenum 6-131,POB 85500, NL-3508 GA Utrecht, Netherlands. EM m.geerlings@umcutrecht.nl FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [5UO1AG09349, 2 R01AG07155] NR 43 TC 33 Z9 37 U1 0 U2 2 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 SEP PY 2006 VL 60 IS 3 BP 346 EP 355 DI 10.1002/ana.20918 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 091DX UT WOS:000241007600011 PM 16865684 ER PT J AU Huey, ED Grafman, J Wassermann, EM Pietrini, P Tierney, MC Ghetti, B Spina, S Baker, M Hutton, M Elder, JW Berger, SL Heflin, KA Hardy, J Momeni, P AF Huey, Edward D. Grafman, Jordan Wassermann, Eric M. Pietrini, Pietro Tierney, Michael C. Ghetti, Bernardino Spina, Salvatore Baker, Matt Hutton, Mike Elder, Joshua W. Berger, Stephen L. Heflin, Kyle A. Hardy, John Momeni, Parastoo TI Characteristics of frontotemporal dementia patients with a progranulin mutation SO ANNALS OF NEUROLOGY LA English DT Article ID TAU GENE-MUTATIONS; PREVALENCE; FREQUENCY; NETHERLANDS; TAUOPATHIES; ASSOCIATION; FTLD AB Objective: Mutations in the Progrdnulin gene (PGRN) recently have been discovered to be associated with frontotemporal dementia (FTD) linked to 17q21 without identified MAPT mutations. The range of mutations of PGRN that can result in the FTD phenotype and the clinical presentation of patients with PGRN mutations have yet to be determined. Methods: In this study, we examined 84 FTD patients from families not known previously to have illness linked to chromosome 17 for identified PGRN and MAPT mutations and sequenced the coding exons and the flanking intronic regions of PGRN. We compared the prevalence, clinical characteristics, magnetic resonance imaging and 18-fluoro-deoxyglucose positron emission tomography results, and neuropsychological testing of patients with the PGRN R493X mutation with those patients without identified PGRN mutations. Results: We discovered a new PGRN mutation (R493X) resulting in a stop codon in two patients. This was the only PGRN mutation identified in our sample. The patients with the PGRN R493X mutation had a rapid illness course and had predominant right-sided atrophy and hypometabolism on magnetic resonance imaging and 18-fluoro-deoxyglucose positron emission tomography. The affected father of one of the patients with the PGRN R493X mutation showed frontal and temporal atrophy without neurofibrillary tangles on neuropathological examination. Interpretation: Known PGRN and MAPT mutations were rare and of similar prevalence in our sample (2 compared with 1/84). The patients with the PGRN R493X mutation had a clinical presentation comparable with other behavior-predominant FTD patients. The neuropathology of an affected family member of a patient with the PGRN R493X mutation appears not to be Alzheimer's disease. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. Univ Pisa, Lab Clin Biochem & Mol Biol, I-56100 Pisa, Italy. Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA. Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Hardy, John/C-2451-2009; OI Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS [Z99 NS999999]; Medical Research Council [G0701075]; NIA NIH HHS [P30 AG010133, P30 AG10133] NR 36 TC 58 Z9 58 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 SEP PY 2006 VL 60 IS 3 BP 374 EP 380 DI 10.1002/ana.20969 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 091DX UT WOS:000241007600014 PM 16983677 ER PT J AU Beecken, WDC Engl, T Ringel, EM Camphausen, K Michaelis, M Jonas, D Folkman, J Shing, Y Blaheta, RA AF Beecken, Wolf-Dietrich C. Engl, Tobias Ringel, Eva M. Camphausen, Kevin Michaelis, Martin Jonas, Dietger Folkman, Judah Shing, Yuen Blaheta, Roman A. TI An endogenous inhibitor of angiogenesis derived from a transitional cell carcinoma: Clipped beta 2-glycoprotein-I SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE beta 2-glycoprotein-I; transitional cell carcinoina; angiogenesis; tumor dormancy ID APOLIPOPROTEIN-H BETA-2-GLYCOPROTEIN-I; BETA(2) GLYCOPROTEIN-I; ANNEXIN-II; BETA(2)-GLYCOPROTEIN I; BLADDER-CANCER; ANTIPHOSPHOLIPID SYNDROME; ANTIANGIOGENIC THERAPY; HUMAN-PLATELETS; NICKED FORM; DOMAIN-V AB Background: Invasive cell carcinoma of the bladder often develops after complete transurethral excision of superficial transitional cell carcinoma. It has been postulated that primary tumors release angiogenesis-blocking proteins which suppress distant metastases. We have identified an endogenous protein which might be responsible for tumor dormancy. Methods: A transitional cell carcinoma cell line was developed (UMUC-3i) which inhibits the growth of a tumor implant at a distant site in SCID mice. Conditioned media of UMUC-3i cultured cells was first pooled and then fractioned, and the capacity of individual components to block endothelial cell growth was tested. The protein fraction responsible for blocking endothelial cell growth was identified by N-terminal amino acid sequencing as well as by mass-spectrometry. The effects of the purified protein in preventing endothelial cell proliferation and tube formation in an in vitro angiogenesis assay was investigated. Results: The plasma protein beta(2)-glycoprotein-I (beta(2)gpI) was isolated and identified from conditioned medium of UMUC-3i cultured cells. Based on the in vitro angiogenesis assay, beta(2)gpI strongly inhibited endothelial cell growth and tube formation, whereby the inhibitory activity corresponded to the clipped version of beta(2)gpI (c beta(2)gpI) Clipping was induced by adding plasmin at a molar ratio 1:15 (plasmin: substrate). Further analysis indicated that beta(2)gpI effects were mediated by annexin II surface receptors expressed on endothelial cells. Conclusions: c beta(2)gpI may be involved in blocking angiogenic processes and bladder cancer progression. In this case, c beta(2)gpI may be a promising tool in bladder cancer therapy. C1 Univ Frankfurt, Dept Urol, D-6000 Frankfurt, Germany. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Univ Frankfurt, Inst Hyg, D-6000 Frankfurt, Germany. Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Blaheta, RA (reprint author), JW Goethe Univ Klin, Zentrum Chirurg, Klin Urol & Kinderurol, Interdisziplinares Forsch & Laborgebaude, Haus 25,Raum 204,Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM blaheta@em.uni-frankfurt.de NR 49 TC 17 Z9 17 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 2006 VL 13 IS 9 BP 1241 EP 1251 DI 10.1245/s10434-006-9009-9 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 094HC UT WOS:000241229500011 PM 16955386 ER PT J AU Lakhani, N Sparreboom, A Venitz, J Dahut, WL Figg, WD AF Lakhani, Nehal Sparreboom, Alex Venitz, Jurgen Dahut, William L. Figg, William D. TI Plasma protein binding of the investigational anticancer agent 2-methoxyestradiol SO ANTI-CANCER DRUGS LA English DT Article DE equilibrium dialysis; 2-methoxyestradiol; protein binding ID BREAST-CANCER CELLS; TUMORS AB 2-Methoxyestradiol (2ME2) is an endogenously produced metabolite of estradiol currently being tested in phase I and II clinical trials as an anticancer agent. Here, we examined the role of protein binding as a possible determinant of the pharmacokinetic behavior of 2ME2. The distribution of 2ME2 in plasma was studied in vitro using plasma from healthy human volunteers and ex vivo using plasma from patients with cancer receiving the drug orally. The equilibrium dialysis method used to characterize plasma protein binding of 2ME2 utilized a tracer amount of [H-3]-2-methoxyestradiol on a 96-well microdialysis plate with a 5-kDa cutoff membrane and 250 mu l of plasma. The time to equilibrium was approximately 24 h and the mean unbound fraction of 2ME2 (f(u)) over the observed concentration range in plasma of patients receiving 2ME2 orally was 0.019 +/- 0.0043. The mean fu was 0.027 +/- 0.0019 in plasma of healthy human volunteers. The binding was concentration independent, indicating a low-affinity, possibly nonspecific and nonsaturable process. The binding was also unaffected by the presence of 2-methoxyestrone, one of the major metabolites of 2ME2. 2ME2 was found to bind in decreasing order to plasma > albumin >alpha(1)-acidglycoprotein > sex-hormonebinding globulin. Plasma concentration-time profiles of total 2ME2 and unbound 2ME2 concentrations in a patient with cancer receiving 2ME2 as a single oral dose were parallel to each other. Thus, indicating that plasma protein binding is not an important consideration in pharmacolkinetic monitoring of 2ME2. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Med Oncol Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10 Room 5A01,MSC1910, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 13 TC 9 Z9 9 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD SEP PY 2006 VL 17 IS 8 BP 977 EP 983 DI 10.1097/01.cad.0000224447.08706.92 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 090SS UT WOS:000240972300012 PM 16940808 ER PT J AU Steele, VE Arnold, JT Le, H Izmirlian, G Blackman, MR AF Steele, Vernon E. Arnold, Julia T. Le, Hanh Izmirlian, Grant Blackman, Marc R. TI Comparative effects of DHEA and DHT on gene expression in human LNCaP prostate cancer cells SO ANTICANCER RESEARCH LA English DT Article DE DHEA; DHT; gene expression; prostate cancer ID PERIPHERAL TARGET TISSUES; DEHYDROEPIANDROSTERONE-SULFATE; ESTROGEN-RECEPTORS; ER-BETA; ANDROGEN; PROTEIN; MODEL; S100P; CHEMOPREVENTION; CARCINOGENESIS AB Background: DHEA is widely used as a dietary supplement in older men. Because DHEA can be converted to androgens or estrogens, such use may promote prostate cancer. In this study, the effects of DHEA were compared with those of DHT using gene expression array profiles in human LNCaP prostate cancer cells. Materials and Methods: LNCaP cells were exposed to DHEA (300 nM), DHT (300 nM), or vehicle for 48 h, and mRNA expression was measured using Affymetrix HU-95 gene chips. Gene expression values were sorted in ascending order on the p-values corresponding to the extent Of differential RNA expression between control and either hormone treatment. Results: S100 calcium binding protein, neurotensin, 24-dehydrocholesterol reductase, and anterior-gradient 2 homologue were the four most differentially expressed genes (p-values all < 3x10(-5)). Nested tests of differential expression revealed lesser effects of DHEA versus DHT treatment (p < 0.01) for the S100 calcium binding-protein and neurotensin genes. Microarray findings were confirmed by QRT-PCR. The top 83 genes exhibiting differential expression after DHEA or DHT were used for pathway analysis. DHT decreased expression of more genes involved in intercellular communication, signal transduction, nucleic acid binding and transport, and in structural components, such as myosin and golgin, than DHEA. Conclusion: These data revealed consistent, measurable changes in gene expression patterns following treatment of LNCaP prostate cancer cells with DHEA and DHT Understanding the mechanisms of DHEA versus DHT actions in the prostate may help clarify the separate and interactive effects of androgenic and estrogenic actions in prostate cancer progression. C1 NCCAM, LCI, Endocrine Sect, Div Intramural Res,NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Steele, VE (reprint author), NCCAM, LCI, Endocrine Sect, Div Intramural Res,NIH, 9 Mem Dr,Rm 1N105, Bethesda, MD 20892 USA. EM vs1y@nih.gov FU Intramural NIH HHS NR 52 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 SEP-OCT PY 2006 VL 26 IS 5A BP 3205 EP 3215 PG 11 WC Oncology SC Oncology GA 100YY UT WOS:000241707300001 PM 17094431 ER PT J AU Leto, TL Geiszt, M AF Leto, Thomas L. Geiszt, Miklos TI Role of Nox family NADPH oxidases in host defense SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID CHRONIC GRANULOMATOUS-DISEASE; INFLAMMATORY-BOWEL-DISEASE; AIRWAY EPITHELIAL-CELLS; SUPEROXIDE-GENERATING OXIDASE; RESPIRATORY BURST OXIDASE; SMOOTH-MUSCLE-CELLS; REACTIVE OXYGEN; NAD(P)H OXIDASE; HYDROGEN-PEROXIDE; OXIDATIVE BURST AB The phagocytic NADPH oxidase is recognized as a critical component of innate immunity, responsible for generation of microbicidal reactive oxygen species (ROS). This enzyme is one representative of the Nox family of oxidases (Nox1-Nox5, Duox1, and Duox2) that exhibit diverse expression patterns and appear to serve a variety of functions related to ROS generation. Mounting evidence now suggests that several of these novel oxidases also serve in host defense, particularly those showing high expression along epithelial surfaces exposed to the external environment. Within these sites, Nox enzymes tend to be located on apical cell surfaces and release ROS into extracellular environments, where they can be used by known antimicrobial peroxidases. Moreover, microbial factors were shown in several cases to cause higher ROS production, either by direct oxidase activation or by inducing higher oxidase expression. Several oxidases are also induced by immune cytokines, including interferon-gamma, interleukin (IL)-4, and IL-13. Although most of the evidence supporting host defense roles for mammalian nonphagocytic oxidases remains circumstantial, recent evidence indicates that Drosophila Duox plays a role in host resistance to infection. Finally, oxidative defense against invading pathogens appears to be an ancient protective mechanism, because related oxidases are known to participate in disease resistance in plants. C1 NIAID, Mol Def Sect, Host Def Lab, NIH, Rockville, MD 20852 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1085 Budapest, Hungary. RP Leto, TL (reprint author), NIAID, Mol Def Sect, Host Def Lab, NIH, Twinbrook 2,Room 203,12241 Parklawn Dr, Rockville, MD 20852 USA. EM tleto@nih.gov NR 115 TC 123 Z9 127 U1 2 U2 11 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 SEP-OCT PY 2006 VL 8 IS 9-10 BP 1549 EP 1561 DI 10.1089/ars.2006.8.1549 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 084HL UT WOS:000240523900012 PM 16987010 ER PT J AU Sun, JH Steenbergen, C Murphy, E AF Sun, Junhui Steenbergen, Charles Murphy, Elizabeth TI S-nitrosylation: NO-related redox signaling to protect against oxidative stress SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID NITRIC-OXIDE SYNTHASE; MITOCHONDRIAL COMPLEX-I; CALCIUM-RELEASE CHANNEL; NF-KAPPA-B; ENDOTHELIAL-CELLS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ISCHEMIA/REPERFUSION INJURY; NITROSATIVE STRESS; CARDIOVASCULAR-SYSTEM; ISCHEMIA-REPERFUSION AB Nitric oxide (NO) plays an important role in the regulation of cardiovascular function. S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl residues of proteins, resulting in the formation of S-nitrosothiols (SNOs), is a prevalent posttranslational protein modification involved in redox-based cellular signaling. Under physiologic conditions, protein S-nitrosylation and SNOs provide protection preventing further cellular oxidative and nitrosative stress. However, oxidative stress and the resultant dysfunction of NO signaling have been implicated in the pathogenesis of cardiovascular diseases. C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Sun, JH (reprint author), NIEHS, Lab Signal Transduct, 111 TW Alexander Dr,POB 12233,MDF2-07, Res Triangle Pk, NC 27709 USA. EM sun@niehs.nih.gov RI Sun, Junhui/C-3499-2011 FU NHLBI NIH HHS [R01 HL039752] NR 139 TC 97 Z9 101 U1 1 U2 7 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 SEP-OCT PY 2006 VL 8 IS 9-10 BP 1693 EP 1705 DI 10.1089/ars.2006.8.1693 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 084HL UT WOS:000240523900024 PM 16987022 ER PT J AU Finkel, T AF Finkel, Toren TI Intracellular redox regulation by the family of small GTPases SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID SMOOTH-MUSCLE-CELLS; GUANINE-NUCLEOTIDE EXCHANGE; REACTIVE-OXYGEN; OXIDATIVE STRESS; ANGIOTENSIN-II; SUPEROXIDE GENERATION; SIGNAL-TRANSDUCTION; S-GLUTATHIOLATION; EPITHELIAL-CELLS; OXIDASE NOX1 AB There is growing experimental evidence that the production of intracellular reactive oxygen species (ROS) represents a tightly regulated process. In particular, numerous observations have suggested a role for the Ras superfamily of small GTPases in redox regulation. This article reviews the evidence that ROS can serve as important downstream effectors for both Ras and Rac proteins. Given the prominent role these proteins play in regulating growth, senescence, and transformation, understanding the role of the small GTPase family in redox regulation may significantly alter our current concepts as to how free radicals contribute to diverse processes from aging to cancer. C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, Bldg 10,CRC 5-3330, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 53 TC 37 Z9 40 U1 0 U2 1 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 SEP-OCT PY 2006 VL 8 IS 9-10 BP 1857 EP 1863 DI 10.1089/ars.2006.8.1857 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 084HL UT WOS:000240523900040 PM 16987038 ER PT J AU Marquez, VE Hughes, SH Sei, S Agbaria, R AF Marquez, Victor E. Hughes, Stephen H. Sei, Shizuko Agbaria, Riad TI The history of N-methanocarbathymidine: The investigation of a conformational concept leads to the discovery of a potent and selective nucleoside antiviral agent SO ANTIVIRAL RESEARCH LA English DT Review DE herpes simplex virus; Kaposi's sarcoma-associated herpesvirus; kinases; DNA polymerases; HIV reverse transcriptase; delayed chain termination ID SIMPLEX-VIRUS TYPE-1; THYMIDINE KINASE; BICYCLIC NUCLEOSIDES; CARBOCYCLIC THYMIDINE; CRYSTAL-STRUCTURE; SUGAR; OLIGONUCLEOTIDES; CELLS; HERPESVIRUS; PUCKER AB Conformationally locked (North)-methanocarbathymidine (N-MCT) and (South)-methanocarbathymidine (S-MCT) have been used to investigate the conformational preferences of kinases and polymerases. The herpes kinases show a distinct bias for S-MCT, while DNA polymerases almost exclusively incorporate the North 5 '-triphosphate (N-MCT-TP). Only N-MCT demonstrated potent antiviral activity against herpes simplex viruses (HSV-1 and 2) and Kaposi's sarcoma-associated herpesvirus (KSHV). The activity of N-MCT depends on its metabolic transformation to N-MCTTP by the herpes kinases (HSV-tk or KSHV-tk), which catalyze the mono and diphosphorylation steps; cellular kinases generate the triphosphate. N-MCT at a dose of 5.6 mg/kg was totally protective for mice inoculated intranasally with HSV-1. Tumor cells that are not responsive to antiviral therapy became sensitive to N-MCT if the cells expressed HSV-tk. N-MCT given twice daily (100 mg/kg) for 7 days completely inhibited the growth of MC38 tumors derived from cells that express HSV-tk in mice while exhibiting no effect on tumors derived from non-transduced cells. After i.p. administration, N-MCT was rapidly absorbed and distributed in all organs examined with slow penetration into brain and testes. N-MCT-TP was also a potent inhibitor of HIV replication in human osteosarcoma (HOS) cells expressing HSV-tk. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Med Chem Lab, Frederick, MD 21702 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Lab Antiviral Drug Mech, Dev Therapeut Program, NCI, Frederick, MD 21702 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. RP Marquez, VE (reprint author), NCI, Med Chem Lab, POB B,Bldg 539, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 24 TC 34 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD SEP PY 2006 VL 71 IS 2-3 BP 268 EP 275 DI 10.1016/j.antiviral.2006.04.012 PG 8 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 082IY UT WOS:000240381200025 PM 16730077 ER PT J AU Sakurai, T Kojima, C Waalkes, MP Himeno, S AF Sakurai, Teruaki Kojima, Chikara Waalkes, Michael P. Himeno, Seiichiro TI Effects of exogenous cysteine on inorganic and organic arsenicals-induced cytolethality SO APPLIED ORGANOMETALLIC CHEMISTRY LA English DT Article; Proceedings Paper CT 12th Symposium of the Japanese-Arsenic-Scientists-Society (JASS) CY NOV 05-06, 2005 CL Takizawa, JAPAN SP Japanese Arsen Sci Soc DE arsenic; cysteine; dimethylarsinic; monomethylarsonic; Cys; Cys conjugate ID MONOMETHYLARSONIC ACID; DIMETHYLARSINIC ACID; CELLULAR GLUTATHIONE; TRIOXIDE AS2O3; CELLS; METABOLITES; TRIVALENT; IDENTIFICATION; DERIVATIVES; EXCRETION AB Inorganic arsenicals are distinctly toxic and carcinogenic to humans. Inorganic arsenite (As-III) and arsenate (As-V) are enzymatically methylated to monomethylarsonic acid (MMAsV) and dimethylarsinic acid (DMAsV) in mammals. Recent reports indicate that cytotoxic trivalent methylated arsenicals are produced through methylation of inorganic arsenicals and are involved in arsenic poisoning. Some previous studies have suggested that a typical thiol reagent cysteine (Cys) can reduce pentavalent arsenicals to trivalent arsenicals and might be able to enhance arsenic cytolethality. However, not much is known concerning the effects of exogenous Cys on the cytolethality of arsenicals. In this study, we examined the effects of exogenous Cys on the cytolethality induced by inorganic and organic arsenicals using rat liver cells. Cys prevented inorganic As-III-induced cytolethality. In contrast, when more than 5 mm Cys was incubated with millimolar levels of MMAsV or DMAsV, MMAsV- and DMAsV-induced cytolethality significantly increased; this cytolethality might have been caused by the generation of trivalent methylated arsenicals. However, Cys at a concentration of less than 5 mm decreased the MMAsV- and DMAsV-induced cytolethality. These findings suggest that high concentrations of both arsenicals and Cys are required to form trivalent methylated arsenicals and to induce significant cytolethality. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Yamashiro, Tokushima 7708514, Japan. NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH, Res Triangle Pk, NC 27709 USA. RP Sakurai, T (reprint author), Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Yamashiro, Tokushima 7708514, Japan. EM teruaki@ph.bunri-u.ac.jp NR 34 TC 0 Z9 0 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0268-2605 J9 APPL ORGANOMET CHEM JI Appl. Organomet. Chem. PD SEP PY 2006 VL 20 IS 9 BP 549 EP 556 DI 10.1002/aoc.1072 PG 8 WC Chemistry, Applied; Chemistry, Inorganic & Nuclear SC Chemistry GA 088CS UT WOS:000240789700004 ER PT J AU Karakurt, A Aytemir, MD Stables, JP Ozalp, M Kaynak, FB Ozbey, S Dalkara, S AF Karakurt, Arzu Aytemir, Mutlu D. Stables, James P. Ozalp, Meral Kaynak, F. Betul Ozbey, Suheyla Dalkara, Sevim TI Synthesis of some oxime ether derivatives of 1-(2-naphthyl)-2(1,2,4-triazol-1-yl)ethanone and their anticonvulsant and antimicrobial activities SO ARCHIV DER PHARMAZIE LA English DT Article DE anticonvulsant; antimicrobial; (arylalkyl)triazoles; oxime ethers; X-ray crystallography ID DENZIMOL; DRUG AB In this study, oxime and oxime ether derivatives of [1-(2-naphthyl)-2-(1,2,4-triazol-1-yl)ethanone] were prepared as potential anticonvulsant and antimicrobial compounds. The oxime was synthesized by the reaction of ketone and hydroxylamine hydrochloride. O-Alkylation of the oxime by various alkyl halides gave the oxime ether derivatives. Anticonvulsant activity of the compounds was determined by maximal electroshock and subcutaneous metrazole tests in mice and rats according to procedures of the Anticonvulsant Screening Program of National Institutes of Health. Neurotoxicity was determined by the rotorod test in mice and the positional sense test, gait and stance test in rats. In addition to anticonvulsant tests, all compounds were also evaluated against the following microorganisms: S. aureus, E. coli, P. aeruginosa, E. faecalis, C. albicans, C. parapsilosis, and C. krusei using microdilution broth method for possible antibacterial and antifungal activities. Although most of the O-alkyl substituted oxime ethers 2-6 exhibited both anticonvulsant and antimicrobial activities, the O-arylalkyl substituted compounds 7-10 were found to be inactive in both screening paradigms. C1 Univ Hacettepe, Fac Pharm, Dept Pharmaceut Chem, TR-06100 Ankara, Turkey. NINDS, Anticonvulsant Screening Program, Rockville, MD USA. Hacettepe Univ, Fac Pharm, Pharmaceut Microbiol Dept, Ankara, Turkey. Hacettepe Univ, Fac Engn, Dept Engn Phys, Ankara, Turkey. RP Dalkara, S (reprint author), Univ Hacettepe, Fac Pharm, Dept Pharmaceut Chem, TR-06100 Ankara, Turkey. EM sdalkara@hacettepe.edu.tr RI Kaynak, Filiz Betul/E-7489-2013 NR 29 TC 18 Z9 18 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0365-6233 J9 ARCH PHARM JI Arch. Pharm. PD SEP PY 2006 VL 339 IS 9 BP 513 EP 520 DI 10.1002/ardp.200500248 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 088EB UT WOS:000240793200004 PM 16941729 ER PT J AU Piszczek, G AF Piszczek, Grzegorz TI Luminescent metal-ligand complexes as probes of macromolecular interactions and biopolymer dynamics SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Review DE metal ligand complex; RET; FRET; anisotropy decay; microsecond dynamics; long lifetime probe ID RESONANCE ENERGY-TRANSFER; FLUORESCENCE POLARIZATION IMMUNOASSAY; INTRAMOLECULAR CONTACT FORMATION; RUTHENIUM(II) MOLECULAR PROBES; WEIGHT PROTEIN HYDRODYNAMICS; LIFETIME RU(II) COMPLEXES; LONG-LIFETIME; LATERAL DIFFUSION; SPECTRAL CHARACTERIZATION; CORRELATION SPECTROSCOPY AB The knowledge of microsecond dynamics is important for an understanding of the mechanism and function of biological systems. Fluorescent techniques are well established in biophysical studies, but their applicability to probe microsecond timescale processes is limited. Luminescent metal-ligand complexes (MLCs) have created interest mainly due to their unique luminescent properties, such as the exceptionally long decay times and large fundamental anisotropy values, allowing examination of microsecond dynamics by fluorescence methods. MLC properties also greatly simplify instrumentation requirements and enable the use of light emitting diode excitation for time-resolved measurements. Recent literature illustrates how MLC labels take full advantage of well developed fluorescence techniques and how those methods can be extended to timescales not easily accessible with nanosecond probes. MLCs are now commercially available as reactive labels which give researchers access to methods that previously required more complex approaches. The present paper gives an overview of the applications of MLC probes to studies of molecular dynamics and interactions of proteins, membranes and nucleic acids. Published by Elsevier Inc. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Piszczek, G (reprint author), NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM grzegorz_piszczek@nih.gov FU Intramural NIH HHS NR 97 TC 18 Z9 18 U1 0 U2 16 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 SEP 1 PY 2006 VL 453 IS 1 BP 54 EP 62 DI 10.1016/j.abb.2006.03.007 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 087CT UT WOS:000240720800008 PM 16603119 ER PT J AU Li, TW Santockyte, R Shen, RF Tekle, E Wang, GH Yang, DCH Chock, PB AF Li, Tianwei Santockyte, Rasa Shen, Rong-Fong Tekle, Ephrem Wang, Guanghui Yang, David C. H. Chock, P. Boon TI A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE ubiquitin-like modifiers; SUMO; NEDD8; mass spec; proteomics ID NUCLEAR-PORE COMPLEX; NEDD8 CONJUGATION; SUMO MODIFICATION; PROTEIN; IDENTIFICATION; ENZYMES; SYSTEM; YEAST; ISG15; SUMOYLATION AB Ubiquitin-like modifiers (UBLs) contain ubiquitin homology domains and can covalently modify target proteins in a manner similar to ubiquitylation. In this study, we revealed a general proteomic approach to elucidate the enzymatic pathways and identify target proteins for three UBLs: SUMO-2, SUMO-3, and NEDD8. Expression plasmids containing the cDNAs of Myc/6x His doubly-tagged processed or non-conjugatable forms of these UBLs were constructed. The constructed vectors were then used to transfect HEK 293 Tet-On cells, and stable cell lines expressing these UBLs and their mutants were established. The epitope-tagged proteins were purified by immunoprecipitation under native conditions or by affinity chromatography on nickel resin under denaturing conditions. Purified proteins were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS/MS). Most of the El-like activating enzymes, E2-like conjugating enzymes and the majorities of the known target as well as some previously unreported proteins for SUMO-2, SUMO-3, and NEDD8 pathways were identified. Published by Elsevier Inc. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM BChock@nih.gov RI Yang, David/A-7294-2009 FU Intramural NIH HHS NR 35 TC 17 Z9 21 U1 1 U2 4 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 SEP 1 PY 2006 VL 453 IS 1 BP 70 EP 74 DI 10.1016/j.abb.2006.03.002 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 087CT UT WOS:000240720800010 PM 16620772 ER PT J AU Peterkofsky, A Wang, GS Seok, YJ AF Peterkofsky, Alan Wang, Guangshun Seok, Yeong-Jae TI Parallel PTS systems SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Review ID PHOSPHORYL TRANSFER COMPLEX; TRANSDUCING PROTEIN IIA(GLUCOSE); SUGAR PHOSPHOTRANSFERASE SYSTEM; ESCHERICHIA-COLI GENOME; ENZYME I-NTR; GLUCOSE-TRANSPORTER; ADENYLATE-CYCLASE; LACTOSE PERMEASE; ALLOSTERIC REGULATION; DOMAIN C1 NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. Seoul Natl Univ, Dept Biol Sci, Seoul, South Korea. Seoul Natl Univ, Inst Microbiol, Seoul, South Korea. RP Peterkofsky, A (reprint author), NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. EM peterkofsky@nih.gov NR 38 TC 14 Z9 14 U1 1 U2 3 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 SEP 1 PY 2006 VL 453 IS 1 BP 101 EP 107 DI 10.1016/j.abb.2006.01.004 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 087CT UT WOS:000240720800014 PM 17022110 ER PT J AU Perlis, C Robinson-Bostom, L Telang, GH DiGiovanna, J AF Perlis, Clifford Robinson-Bostom, Leslie Telang, Gladys H. DiGiovanna, John TI A thick lichenified plaque on the ventral penile shaft SO ARCHIVES OF DERMATOLOGY LA English DT Article ID POROKERATOSIS; MIBELLI C1 Brown Med Sch, Providence, RI 02912 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Perlis, C (reprint author), Brown Med Sch, Providence, RI 02912 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 2006 VL 142 IS 9 PG 2 WC Dermatology SC Dermatology GA 085GW UT WOS:000240593100016 ER PT J AU Neumeister, A Hu, XZ Luckenbaugh, DA Schwarz, M Nugent, AC Bonne, O Herscovitch, P Goldman, D Drevets, WC Charney, DS AF Neumeister, Alexander Hu, Xian-Zhang Luckenbaugh, David A. Schwarz, Markus Nugent, Allison C. Bonne, Omer Herscovitch, Peter Goldman, David Drevets, Wayne C. Charney, Dennis S. TI Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses to tryptophan depletion in patients with major depression and controls SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SEROTONIN TRANSPORTER GENE; POSITRON-EMISSION-TOMOGRAPHY; KNOCK-OUT MICE; DORSAL RAPHE NUCLEUS; HUMAN BRAIN; IN-VIVO; RECEPTOR-BINDING; PROMOTER REGION; EXTRACELLULAR SEROTONIN; FUNCTIONAL POLYMORPHISM C1 Yale Univ, Sch Med, Clin Neurosci Div, Mol Imaging Program, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. Inst Mental Hlth, Sect Expt Therapeut, Mood & Antiety Disorders Program, Bethesda, MD USA. Inst Mental Hlth, Sect Pathophysiol, Mood & Antiety Disorders Program, Bethesda, MD USA. NIAAA, Neurogenet Lab, Bethesda, MD USA. Univ Hosp Psychiat, Dept Neurochem, Munich, Germany. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Neumeister, A (reprint author), Yale Univ, Sch Med, Clin Neurosci Div, Mol Imaging Program, 950 Campbell Ave,Bldg 1,Room 9-174,MSC 151E, West Haven, CT 06516 USA. EM alexander.neumeister@yale.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Nugent, Allison/0000-0003-2569-2480 NR 51 TC 113 Z9 115 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2006 VL 63 IS 9 BP 978 EP 986 DI 10.1001/archpsyc.63.9.978 PG 9 WC Psychiatry SC Psychiatry GA 080GA UT WOS:000240234700004 PM 16953000 ER PT J AU Volkow, ND Wang, GJ Begleiter, H Porjesz, B Fowler, JS Telang, F Wong, C Ma, YM Logan, J Goldstein, R Alexoff, D Thanos, PK AF Volkow, Nora D. Wang, Gene-Jack Begleiter, Henri Porjesz, Bernice Fowler, Joanna S. Telang, Frank Wong, Christopher Ma, Yeming Logan, Jean Goldstein, Rita Alexoff, David Thanos, Peter K. TI High levels of dopamine D-2 receptors in unaffected members of alcoholic families - Possible protective factors SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BRAIN METABOLIC-RESPONSE; D2 RECEPTORS; BINDING CHARACTERISTICS; NUCLEUS-ACCUMBENS; D-2 RECEPTORS; IN-VIVO; DEPENDENCE; HUMANS; RATS; PET AB Context: Predisposition to alcoholism is likely an interaction between genetic and environmental factors that confer vulnerability and protection. Alcoholic subjects have low levels of dopamine D-2 receptors in striatum, and increasing D-2 receptor levels in laboratory animals reduces alcohol consumption. Objectives: To test whether high levels of D-2 receptors may be protective against alcoholism and whether this is mediated by their modulation of activity in orbitofrontal cortex and cingulate gyrus (regions involved in salience attribution, emotional reactivity, and inhibitory control). Design: Research (nonalcoholic subjects with a family history of alcoholism) and comparison (nonalcoholic subjects with a negative family history) sample. Setting: Outpatient setting. Participants: Fifteen nonalcoholic subjects who had an alcoholic father and at least 2 other first- or second-degree relatives who were alcoholics (family-positive group) and 16 nonalcoholic controls with no family history of alcoholism (family-negative group). Main Outcome Measures: Results of positron emission tomography with raclopride C 11 to assess D-2 receptors and with fludeoxyglucose F 18 to assess brain glucose metabolism (marker of brain function). Personality measures were obtained with the Multidimensional Personality Questionnaire. Results: Availability of D2 receptors was significantly higher in caudate and ventral striatum in family-positive than family-negative subjects. In family-positive but not family-negative subjects, striatal D-2 receptors were associated with metabolism in anterior cingulate (Brodmann area 24/25) and orbitofrontal (Brodmann area 11) and prefrontal (Brodmann area 9/10) cortices, and with personality scores of positive emotionality. Conclusions: The higher-than-normal D-2 receptor availability in nonalcoholic members of alcoholic families supports the hypothesis that high levels of D-2 receptors may protect against alcoholism. The significant associations between D-2 receptors and metabolism in frontal regions involved with emotional reactivity and executive control suggest that high levels of D-2 receptors could protect against alcoholism by regulating circuits involved in inhibiting behavioral responses and in controlling emotions. C1 Natl Inst Drug Abuse, Rockville, MD 20857 USA. NIDA, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. SUNY Hlth Sci Ctr, Dept Psychiat, Brooklyn, NY 11203 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274, Rockville, MD 20857 USA. EM nvolkow@nida.nih.gov FU NIAAA NIH HHS [AA 09481] NR 69 TC 153 Z9 160 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2006 VL 63 IS 9 BP 999 EP 1008 DI 10.1001/archpsyc.63.9.999 PG 10 WC Psychiatry SC Psychiatry GA 080GA UT WOS:000240234700006 PM 16953002 ER PT J AU Shankaran, S Das, A Bauer, CR Bada, H Lester, B Wright, L Higgins, R Poole, K AF Shankaran, Seetha Das, Abhik Bauer, Charles R. Bada, Henrietta Lester, Barry Wright, Linda Higgins, Rosemary Poole, Kenneth TI Fetal origin of childhood disease - Intrauterine growth restriction in term infants and risk for hypertension at 6 years of age SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID INCREASED BLOOD-PRESSURE; MATERNAL LIFE-STYLE; COCAINE EXPOSURE; BIRTH-WEIGHT; CARDIOVASCULAR-DISEASE; CHILDREN; ADOLESCENTS; PREGNANCY; INTERVENTION; OVERWEIGHT AB Objective: To examine the association between intrauterine growth restriction (IUGR) status at birth among full-term infants, exposure to substance use during pregnancy, and risk of hypertension at 6 years of age. Design: Prospective evaluation of high-risk children. Setting: Four centers of the National Institute of Child Health and Human Development Neonatal Research Network. Participants: One thousand three hundred eighty-eight infants (600 cocaine exposed, 781 nonexposed, and 7 indeterminate, matched by gestational age, race, and sex), were enrolled at these sites. Nine hundred fifty children (415 exposed, 535 nonexposed) were followed up for 6 years. Intervention: Right arm blood pressure was measured using the Dinamap portable adult/pediatric monitor with appropriate cuff size. Main Outcome Measure: Blood pressure levels. Hypertension was defined as either systolic or diastolic blood pressure higher than the 95th percentile for sex, age, and height. Results: Eight hundred ninety-one children had blood pressure data at 6 years of age: 516 were born at full term; 144 (28%) of the 516 children had a diagnosis of IUGR at birth. At 6 years of age, 93 (19%) of 516 children had hypertension. Of 144 children with IUGR, 35 (24%) had hypertension as compared with 58 (16%) of 372 children without IUGR (P <.05). Twenty percent of cocaine-exposed children had hypertension as compared with 16% of nonexposed children (P=.20). Intrauterine growth restriction status at birth was significantly associated with hypertension (relative risk, 1.8 [95% confidence interval, 1.2-2.7]) when multivariable Poisson regression analysis was performed adjusting for site; maternal race, education, and tobacco, marijuana, alcohol, and cocaine use during pregnancy; and child's current body mass index (calculated as weight in kilograms divided by height in meters squared). Conclusion: In term infants, IUGR is linked to risk of hypertension in early childhood, which may be a marker for adult cardiovascular disease. C1 NICHHD, Neonatal Res Network, Bethesda, MD 20892 USA. RP Shankaran, S (reprint author), Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM sshankar@med.wayne.edu FU NICHD NIH HHS [N01-HD-2-3159, U01 HD 36790, U10 HD 21385, U10 HD 21397, U10 HD 21415, U10 HD 27904] NR 36 TC 37 Z9 38 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2006 VL 160 IS 9 BP 977 EP 981 DI 10.1001/archpedi.160.9.977 PG 5 WC Pediatrics SC Pediatrics GA 080GB UT WOS:000240234800018 PM 16953023 ER PT J AU Vasconcelos, OM Prokhorenko, OA Kelley, KF Vo, AH Olsen, CH Dalakas, MC Halstead, LS Jabbari, B Campbell, WW AF Vasconcelos, Olavo M., Jr. Prokhorenko, Olga A. Kelley, Kay F. Vo, Alexander H. Olsen, Cara H. Dalakas, Marinos C. Halstead, Lauro S. Jabbari, Bahman Campbell, William W. TI A comparison of fatigue scales in postpoliomyelitis syndrome SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the American-Academy-of-Neurology CY APR 09-16, 2005 CL Miami Beach, FL SP Amer Acad Neurol DE fatigue; poliomyelitis; postpoliomyelitis syndrome; rehabilitation ID PLACEBO-CONTROLLED TRIAL; MULTIPLE-SCLEROSIS; POLIO SURVIVORS; DOUBLE-BLIND; PYRIDOSTIGMINE; AMANTADINE AB Objective: To examine the applicability and validity of traditional fatigue questionnaires in postpoliomyelitis syndrome (PPS) patients with disabling fatigue. Design: Cross-sectional study. PPS and disabling fatigue were ascertained according to published criteria. Descriptiveness was determined using the McNemar test, and interscale Z-score agreement was estimated with Pearson's coefficients. Setting: PPS clinic. Participants: Fifty-six survivors of poliomyelitis: 39 met criteria for PPS, 25 of whom met criteria for disabling fatigue. Interventions: Not applicable. Main Outcome Measures: The Fatigue Severity Scale (FSS), visual analog scale (VAS) for fatigue, and Fatigue Impact Scale (FIS). Results: Twenty-four patients scored 50% or higher on the scale range for FSS, compared with 19 patients for VAS for fatigue (P=.042), and 7 patients for FIS (P <.001). Scores for patients with disabling fatigue averaged 81.5%, 62%, and 40.9% of the scale range for FSS, VAS for fatigue, and FIS, respectively. Agreement was moderate between the FSS and VAS for fatigue (r=.45, P=.02), but low between FSS and FIS (r=.29, P=.15), and FIS and VAS for fatigue (r=.20, P=33). Two sample t tests showed significant differences between those with disabling fatigue and those without, based on FSS scores (t=3.8, P <.001), but not for VAS for fatigue or FIS scores. Conclusions: FSS was the most descriptive of the instruments tested. Scores generated by the scales were not interchangeable. Of the 3 scales, FFS seemed to be the most informative for the clinical assessment of fatigue in patients with PPS. C1 Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. NIH, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Natl Rehabil Hosp, Dept Neurosci, Washington, DC USA. RP Vasconcelos, OM (reprint author), 4301 Jones Bridge Rd,Bldg 53,Rm 101, Bethesda, MD 20814 USA. EM ovasconcelos@usuhs.mil NR 26 TC 18 Z9 19 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2006 VL 87 IS 9 BP 1213 EP 1217 DI 10.1016/j.apmr.2006.06.009 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 082SO UT WOS:000240407700009 PM 16935057 ER PT J AU Aletaha, D Smolen, J Ward, MM AF Aletaha, Daniel Smolen, Josef Ward, Michael M. TI Measuring function in rheumatoid arthritis - Identifying reversible and irreversible components SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTITUMOR NECROSIS FACTOR; DISEASE-ACTIVITY INDEX; CONCOMITANT METHOTREXATE; MONOCLONAL-ANTIBODY; COST-EFFECTIVENESS; RADIOLOGIC DAMAGE; CLINICAL-TRIALS; JOINT DAMAGE; DOUBLE-BLIND; PROGRESSION AB Objective. Measurement of physical function at one point in time cannot distinguish impairment caused by the active disease process from chronic irreversible impairment. We aimed to dissect these two components of functional limitation in rheumatoid arthritis (RA) by using the disability index of the Health Assessment Questionnaire (HAQ) as the measure of function. Methods. We performed a secondary analysis of data from 6 contemporary clinical trials of RA (2,763 patients). Patients in whom remission was achieved in the trials, based on a simplified disease activity index, were identified. In an individual patient, HAQ scores at trial entry represented both reversible and irreversible impairments, while HAQ scores at the time of RA remission represented the mostly irreversible component, and the difference between these corresponded to the component related to disease activity. We tested the concept that the HAQ has a reversible and an irreversible component by associating the HAQ score during remission with 2 measures associated with the degree of accrued damage: duration of RA and radiographic severity. Results. Among patients in whom clinical remission was achieved (n = 295), average HAQ scores despite clinical remission increased progressively with the duration of RA, from 0.19 (< 2 years of RA) to 0.36 (2-< 5 years) to 0.38 (5-< 10 years) to 0.55 (>= 10 years) (P < 0.001). The reversibility of HAQ scores decreased with the duration of RA (median 100%, 83.3%, 81.9%, and 66.7%, respectively; P < 0.001). Findings were similar in patients subgrouped by quartile of radiographic scores. Conclusion. Differences in the sources of functional limitations should be considered in the interpretation of functional measures, and in their use for prediction and in cost analyses. C1 Med Univ Vienna, Dept Rheumatol, A-1090 Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. Hietzing Hosp, Vienna, Austria. RP Aletaha, D (reprint author), Med Univ Vienna, Dept Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM daniel.aletaha@meduniwien.ac.at FU Intramural NIH HHS NR 34 TC 175 Z9 179 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 SEP PY 2006 VL 54 IS 9 BP 2784 EP 2792 DI 10.1002/art.22052 PG 9 WC Rheumatology SC Rheumatology GA 089IB UT WOS:000240872900009 PM 16947781 ER PT J AU Aksentijevich, I Balow, J Dozmorov, I Sun, HW Jones, J Dailey, N Canna, S Goldbach-Mansky, R Kastner, DL AF Aksentijevich, Ivona Balow, James, Jr. Dozmorov, Igor Sun, Hong-Wei Jones, Janet Dailey, Natalie Canna, Scott Goldbach-Mansky, Raphaela Kastner, Daniel L. TI Gene expression studies in neonatal-onset multisystem inflammatory disease (NOMID) patients broaden the role of Cias1 in the regulation of inflammation. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. Oklahoma Med Res Fdn, Dept Arthrit & Immunol, Oklahoma City, OK 73104 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S38 EP S38 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200010 ER PT J AU Albuquerque, SM Ward, MM Diekman, L Zhou, XD Davis, JC Weisman, MH Reveille, JD AF Albuquerque, Sheila M. Ward, Michael M. Diekman, Laura Zhou, Xiaodong Davis, John C. Weisman, Michael H. Reveille, John D. TI Comparison of clinical features and genetic markers in familial and sporadic ankylosing spondylitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Med Ctr, Houston, TX USA. NIAMS, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S712 EP S712 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204072 ER PT J AU Aletaha, D Smolen, JS Ward, MM AF Aletaha, Daniel Smolen, Josef S. Ward, Michael M. TI Measurement of health status in rheumatoid arthritis: Accumulation of irreversible limitations over time. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Inst Arthrit & Musculoskeletal & Skin Dis, NIH, Bethesda, MD USA. Hietzing Hosp, Vienna, Austria. 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S198 EP S198 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200439 ER PT J AU Baker, TA Boudreau, R Newman, A Laura, C Hepei, C Harris, T Ibrahim, S Nevitt, M Kwoh, CK AF Baker, Tamara A. Boudreau, Robert Newman, Anne Laura, Carbone Hepei, Chen Harris, Tamara Ibrahim, Said Nevitt, Michael Kwoh, C. Kent TI Race differences in osteoarthritis-related knee pain in the elderly: Finding from the health aging, body, composition study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ S Florida, Tampa, FL USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S769 EP S769 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204237 ER PT J AU Bingham, C Mamyrova, G Cochran, E Oral, E James-Newton, L Pokrovnichka, A Imundo, L Miller, F Rider, L Premkumar, A AF Bingham, C. Mamyrova, G. Cochran, E. Oral, E. James-Newton, L. Pokrovnichka, A. Imundo, L. Miller, F. Rider, L. Premkumar, A. TI Magnetic resonance imaging characterization of regional fat loss in patients with lipodystrophy complicating dermatomyositis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Penn State Childrens Hosp, Hershey, PA USA. DHHS, NIEHS, NIH, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S169 EP S170 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200360 ER PT J AU Blair-Levy, JM Watts, CE Fiorentino, NM Wylie, J Lipsky, PE AF Blair-Levy, Joy M. Watts, Christopher E. Fiorentino, Niccolo M. Wylie, James Lipsky, Peter E. TI The relationship between subchondral bone and bone mineral density in a non-human primate model of osteoarthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S532 EP S532 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202423 ER PT J AU Blumenkron, F Phillips, TM Fischer, R Lugar, P Withers, D Pavlovitch, C Nagase, H Lipsky, PE Grammer, AC AF Blumenkron, Fernando Phillips, Terry M. Fischer, Randy Lugar, Patricia Withers, Dave Pavlovitch, Christine Nagase, Hideaki Lipsky, Peter E. Grammer, Amrie C. TI Timp-3 mediates T cell-B cell collaboration by inhibitinp ADAM17/TACE-mediated shedding of CD154. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. Kennedy Inst Rheumatol Div, London, England. NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S748 EP S748 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204171 ER PT J AU Cannon, GW Remmers, EF Corsi, T Wilder, RL Griffiths, MM AF Cannon, Grant W. Remmers, Elaine F. Corsi, Tim Wilder, Ronald L. Griffiths, Marie M. TI Analysis of adjuvant-induced arthritis quantitative trait loci on chromosome 4: Impact of Aia2 and Aia3 on arthritis severity. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Utah, Salt Lake City, UT USA. VA, Salt Lake City, UT USA. NIAMS, NIH, Bethesda, MD USA. MacroGen, Rockville, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S810 EP S810 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204346 ER PT J AU Chae, JJ Wood, G Richard, K Masters, S Jaffe, H Colburn, N Gumucio, DL Shoham, NG Kastner, DL AF Chae, Jae Jin Wood, Geryl Richard, Katharina Masters, Seth Jaffe, Howard Colburn, Nona Gumucio, Deborah L. Shoham, Nitza G. Kastner, Daniel L. TI The familial mediterranean fever protein, pyrin, modulates IL-1 beta production by C-terminal interaction with caspase-1, and activates Nf-kappa B through its n-terminal cleaved fragment. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Bethesda, MD USA. NINDS, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Ann Arbor, MI 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S323 EP S323 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201282 ER PT J AU Chae, JJ Wood, G Richard, K Masters, S Jaffe, H Colburn, N Gumucio, DL Shoham, NG Kastner, DL AF Chae, Jae Jin Wood, Geryl Richard, Katharina Masters, Seth Jaffe, Howard Colburn, Nona Gumucio, Deborah L. Shoham, Nitza G. Kastner, Daniel L. TI The familial mediterranean fever protein, pyrin, modulates Il-1 beta production by C-terminal interaction with caspase-1, and activates Nf-kappa B through its N-terminal cleaved fragment. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Bethesda, MD USA. NINDS, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Ann Arbor, MI 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S38 EP S38 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200009 ER PT J AU Chakravarty, EF Bush, TM Manzi, S Clarke, A Ward, MM AF Chakravarty, Eliza F. Bush, Thomas M. Manzi, Susan Clarke, Ann Ward, Michael M. TI Prevalence of systemic lupus erythematosus in adults in the United States: Estimates from hospitalization data. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Stanford Univ, Stanford, CA 94305 USA. Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. Univ Pittsburgh, Pittsburgh, PA USA. McGill Univ, Montreal, PQ, Canada. NIAMS, NIH, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S267 EP S268 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201131 ER PT J AU Christodoulou, MI Kapsogeorgou, EK Moutsopoulos, NM Moutsopoulos, HM AF Christodoulou, Maria I. Kapsogeorgou, Efstathia K. Moutsopoulos, Niki M. Moutsopoulos, Haralampos M. TI T regulatory cells in Sjogren's syndrome (SS): correlation with the progression of the autoimmune lesion. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Athens, Sch Med, Dept Pathophysiol, GR-11527 Athens, Greece. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S706 EP S706 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204056 ER PT J AU Colburn, NT Mogul, D Chae, JJ Richard, K Barham, B Park, G Haverkamp, M Sun, HW Wood, G Balow, J Aksentijevich, I Kastner, D AF Colburn, Nona T. Mogul, Douglas Chae, Jae-Jin Richard, Katharina Barham, Beverly Park, Grace Haverkamp, Marta Sun, Hong-Wei Wood, Geryl Balow, James, Jr. Aksentijevich, Ivona Kastner, Daniel TI Chemokine profiling in familial Mediterranean fever patients with and without colchicine. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S143 EP S143 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200289 ER PT J AU Danielides, M Kotys, M Leakan, RA Lee, C Thomasson, D Baker, EH Illei, GG AF Danielides, Matina Kotys, Melanie Leakan, Rose Anne Lee, Christabel Thomasson, David Baker, Eva H. Illei, Gabor G. TI Quantitative MR1 assessment of salivary glands in healthy controls and patients with Sjogren's syndrome using apparent diffusion coefficient (ADC) and T1 and T2 parametric maps. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIDCR, Bethesda, MD USA. NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S253 EP S253 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201091 ER PT J AU Duryea, J Alli, S Magalnick, M Wilson, M Goldbach-Mansky, R AF Duryea, Jeffrey Alli, Shaan Magalnick, Michael Wilson, Margaret Goldbach-Mansky, Raphaela TI Quantification of erosion volumes on wrist CT scans for rheumatoid arthritis assessment. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NIAMS, NIH, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S626 EP S626 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203263 ER PT J AU Fiorini, C Lougaris, V Lugar, PL Slota, R van der Zouwen, B Melchers, M Withers, DR Fischer, RT Phillips, T Plebani, A Lipsky, PE Grammer, AC AF Fiorini, Claudia Lougaris, Vassilios Lugar, Patricia L. Slota, Rebecca van der Zouwen, Boris Melchers, Mark Withers, David R. Fischer, Randy T. Phillips, Terry Plebani, Alessandro Lipsky, Peter E. Grammer, Amrie C. TI TNFSF5/CD154/CD40L engagement on activated B cells from SLE periphery or the tonsil induces proximal signaling events and differentiation to plasma cells. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. Univ Brescia, Angelo Nocivelli Inst Mol Med, Spedali Civili, Brescia, Italy. Univ Brescia, Dept Pediat, Spedali Civili, Brescia, Italy. OD, Ultramicro Analyt Immunochem Resource, NIH, Bethesda, MD USA. RI Melchers, Mark/C-1438-2008; Plebani, Alessandro/C-8593-2011 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S567 EP S568 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203094 ER PT J AU Gensler, LS Ward, MM Reveille, JD Learch, TJ Weisman, M Davis, JC AF Gensler, Lianne S. Ward, Michael M. Reveille, John D. Learch, Thomas J. Weisman, Michael Davis, John C., Jr. TI Juvenile-onset ankylosing spondylitis versus adult-onset ankylosin spondylitis: Results from the PSOAS cohort. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIAMS, NIH, Bethesda, MD USA. UT Houston, Houston, TX USA. USC, Los Angeles, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 1 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S723 EP S723 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204102 ER PT J AU Goldbach-Mansky, RT Wilson, M Alli, S Pham, TH Kivitz, A Silverfield, J Kempf, P Olsen, N Fleischmann, R Tao, X Lipsky, PE AF Goldbach-Mansky, Raphaela T. Wilson, Mildred Alli, Shaan Pham, Tuyet H. Kivitz, Alan Silverfield, Joel Kempf, Philip Olsen, Nancy Fleischmann, Roy Tao, Xuelian Lipsky, Peter E. TI A multi-center, double blind, randomized study in patients with active rheumatoid arthritis (RA) comparing an extract from a Chinese vine, tripterygium wilfordii hook F (TWHF), to sulfasalazine. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. Altoona Ctr Clin Res, Duncansville, PA USA. Tampa Med Grp, Tampa, FL USA. Arthrit Clin No Virginia, Arlington, VA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Radiant Res, Dallas, TX USA. NR 2 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S238 EP S238 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201054 ER PT J AU Gourley, MF Diamond, SB Rosing, D Naeem, M James-Newton, L Miller, F AF Gourley, Mark F. Diamond, Shari B. Rosing, Douglas Naeem, Mehmooda James-Newton, Laura Miller, Frederick TI Race is a risk factor for ECG abnormalities in polymyositis (PM)/dermatomyositis (DM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, Bethesda, MD USA. George Washington Univ Hosp, Washington, DC USA. NIHLB, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S661 EP S661 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203367 ER PT J AU Hirakata, M Harima, H Takada, T Sato, S Kuwana, M Suwa, A Hardin, JA AF Hirakata, Michito Harima, Hidemi Takada, Tetsuya Sato, Shinji Kuwana, Masataka Suwa, Akira Hardin, John A. TI Heterogeneity of autoimmune responses to the signal recognition particle (SRP): Clinical associations in Japanese patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Keio Univ, Sch Med, Tokyo, Japan. Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. NIAMSD, Bethesda, MD 20892 USA. RI Kuwana, Masataka/L-2918-2013 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S664 EP S664 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203375 ER PT J AU Huber, A Dugan, E Lachenbruch, P Feldman, BM Perez, M Zemel, L Lindsley, C Rennebohm, R Wallace, C Passo, M Reed, AM Bowyer, S Ballinger, S Miller, F Rider, L AF Huber, A. Dugan, E. Lachenbruch, P. Feldman, B. M. Perez, M. Zemel, L. Lindsley, C. Rennebohm, R. Wallace, C. Passo, M. Reed, A. M. Bowyer, S. Ballinger, S. Miller, F. Rider, L. TI Construct and content validity, responsiveness and clinical meaning of the cutaneous assessment tool (CAT) in juvenile idiopathic inflammatory myopathy (IIM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 IWK Hlth Ctr, Halifax, NS, Canada. NIEHS, NIH, DHHS, Bethesda, MD USA. RI Feldman, Brian/A-8586-2011 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S804 EP S805 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204331 ER PT J AU Hubert, HB Luggen, M Sibley, J Fries, JF Ward, M Lingala, B Wasko, MC AF Hubert, Helen B. Luggen, Michael Sibley, John Fries, James F. Ward, Michael Lingala, Bharathi Wasko, Mary Chester TI Arthritis therapies and risk of myocardial infarction. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Stanford Univ, Palo Alto, CA 94304 USA. Univ Cincinnati, Cincinnati, OH USA. NIAMS, NIH, Bethesda, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada. RI Fries, James/F-6271-2011 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S784 EP S785 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204281 ER PT J AU Hunter, DJ Zhang, Y Niu, J Goodpaster, BH Harris, TB Kwoh, K Newman, A Carbone, LD Nevitt, M AF Hunter, D. J. Zhang, Y. Niu, J. Goodpaster, B. H. Harris, T. B. Kwoh, K. Newman, A. Carbone, L. D. Nevitt, M. TI Muscle mass predicts patellofemoral osteoarthritis (PF OA) progression. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Knoxville, TN 37996 USA. UCSF, San Francisco, CA USA. RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S820 EP S821 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204372 ER PT J AU Irigoyen, P Lee, HS Vlietinck, R Wolfe, F Kern, M Lee, AT Batliwalla, F Massarotti, E Weisman, M Bombardier, C Wener, MH Kastner, DL Seldin, MF Criswell, L Gregersen, PK AF Irigoyen, Patricia Lee, Hye-Soon Vlietinck, Robert Wolfe, Frederick Kern, Marlena Lee, Annette T. Batliwalla, Franak Massarotti, Elena Weisman, Michael Bombardier, Claire Wener, Mark H. Kastner, Daniel L. Seldin, Michael F. Criswell, Lindsey Gregersen, Peter K. TI Lack of association between smoking and anti CCP antibodies in three large north American rheumatoid arthritis cohorts. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 LIJ Med Ctr, Manhasset, NY USA. Wichita Arthrit Ctr, Wichita, KS USA. Tufts Univ New England Med Ctr, Boston, MA USA. Cedars Sinai Med Ctr, Los Angeles, CA USA. Univ Toronto, Toronto, ON, Canada. Univ Washington, Seattle, WA 98195 USA. NIAMSD, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Calif San Francisco, San Francisco, CA 94143 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S819 EP S820 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204370 ER PT J AU Jackson, AJ Chae, JJ Raben, N Wood, G Siegel, RM Kastner, DL Komarow, HD AF Jackson, Adrianna J. Chae, Jae J. Raben, Nina Wood, Geryl Siegel, Richard M. Kastner, Daniel L. Komarow, Hirsh D. TI Genetic and functional studies of traps (TNF receptor associated periodic syndrome) knockin mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Howard Hughes Med Inst, Bethesda, MD 20817 USA. NIAMSD, NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S37 EP S37 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200006 ER PT J AU Katsifis, GE Rekka, SA Moutsopoulos, NM Kapsogeorgou, EK Moutsopoulos, HM Wahl, SM AF Katsifis, G. E. Rekka, S. A. Moutsopoulos, N. M. Kapsogeorgou, E. K. Moutsopoulos, H. M. Wahl, S. M. TI Imbalance between pro- and anti-inflammatory roles of TGF-beta in Sjogren's syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Univ Athens, Sch Med, Dept Pathophysiol, Athens, Greece. NIDCR, NIH, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S313 EP S313 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201256 ER PT J AU Katsuki, Y Hirakata, M Kaneko, Y Sato, S Kuwana, M Suwa, A Hardin, JA AF Katsuki, Yumiko Hirakata, Michito Kaneko, Yuko Sato, Shinji Kuwana, Masataka Suwa, Akira Hardin, John A. TI Anti-Glycyl tRNA synthetase antibodies are associated with interstitial lung disease and dermatomyositis in Japanese patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Keio Univ, Sch Med, Tokyo, Japan. Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. NIAMSD, Bethesda, MD 20892 USA. RI Kaneko, Yuko/L-2897-2013; Kuwana, Masataka/L-2918-2013 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S663 EP S663 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203372 ER PT J AU Kuchen, S Robbins, R Sims, GP Phillips, T Lipsky, PE Ettinger, R AF Kuchen, Stefan Robbins, Rachel Sims, Gary P. Phillips, Terry Lipsky, Peter E. Ettinger, Rachel TI Blockade of IL-21 inhibits B cell proliferation and plasma cell differentiation induced by activated T cells in vitro. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. NIH, Off Res Serv, OD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S70 EP S70 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200089 ER PT J AU Kwoh, CK Boudreau, R Newman, AB Harris, T Satterfield, S Nevitt, M Ibrahim, SA AF Kwoh, C. Kent Boudreau, Robert Newman, Anne B. Harris, Tamara Satterfield, Suzanne Nevitt, Michael Ibrahim, Said A. TI Racial differences in attitudes toward joint replacement: The health ABC study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Pittsburgh VAHS, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Washington, DC USA. Univ Tennessee, Memphis, TN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S533 EP S533 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203001 ER PT J AU Kwoh, CK Boudreau, R Newman, AB Harris, T Satterfield, S Nevitt, M Ibrahim, S AF Kwoh, C. Kent Boudreau, Robert Newman, Anne B. Harris, Tamara Satterfield, Suzanne Nevitt, Michael Ibrahim, Said TI Racial differences in attitudes toward joint replacement: the Health ABC study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh HS, Pittsburgh, PA USA. NIA, Washington, DC USA. Univ Tennessee, Memphis, TN USA. Univ Calif San Francisco, San Francisco, CA 94143 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S62 EP S62 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200070 ER PT J AU Lapteva, L Yarboro, CH Roebuck-Spencer, T Weickert, T Nowak, M Takada, K Bleiberg, J Lipsky, PE Phillips, T Illei, GG AF Lapteva, Larissa Yarboro, Cheryl H. Roebuck-Spencer, Tresa Weickert, Thomas Nowak, Miroslawa Takada, Kazuki Bleiberg, Joseph Lipsky, Peter E. Phillips, Terry Illei, Gabor G. TI Cognitive dysfunction and serum neuropeptides in systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. Natl Rehabil Hosp, Washington, DC USA. NIMH, NIH, Bethesda, MD 20892 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S293 EP S293 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201201 ER PT J AU Mamyrova, G Sillers, L O'Hanlon, T Pandey, J Parks, C Malley, J James-Newton, L Wallace, C Sherry, D Imundo, L Lindsley, C Madson, K Perez, M Cooper, GS Miller, F Rider, L AF Mamyrova, G. Sillers, L. O'Hanlon, T. Pandey, J. Parks, C. Malley, J. James-Newton, L. Wallace, C. Sherry, D. Imundo, L. Lindsley, C. Madson, K. Perez, M. Cooper, G. S. Miller, F. Rider, L. CA CMH Study Grp TI Interleukin-1 and tumor necrosis factor alpha polymorphisms are risk and protective factors for juvenile dermatomyositis (JDM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, DHHS, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S831 EP S831 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204400 ER PT J AU Mamyrova, G Sillers, L O'Hanlon, T Pandey, J Malley, J Adams, S James-Newton, L Wallace, C Sherry, D Imundo, L Lindsley, C Madson, K Perez, M Miller, F Rider, L AF Mamyrova, G. Sillers, L. O'Hanlon, T. Pandey, J. Malley, J. Adams, S. James-Newton, L. Wallace, C. Sherry, D. Imundo, L. Lindsley, C. Madson, K. Perez, M. Miller, F. Rider, L. CA Childhood Myositis Heterogeneity TI Cytokine and HLA alleles modulate disease severity in juvenile dermatomyositis (JDM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, Childhood Myositis Heterogene Study Grp, NIH, DHHS, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S692 EP S692 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204017 ER PT J AU Masi, AT Aldag, JC Sipe, JD Malamet, RL AF Masi, Alfonse T. Aldag, Jean C. Sipe, Jean D. Malamet, Raymond L. TI Women before clinical onset of RA (PRE-RA) had strong correlations of baseline serum IL-6 with VEGF and IL-1 ss with acute serum amyloid a (ASAA) plus soluble TNF receptor type I (STNF-R1), not observed in cohort controls (CN). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UICOMP, Peoria, IL USA. NIH, Bethesda, MD USA. OCTC, Hagerstown, MD USA. NR 0 TC 1 Z9 1 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 SEP PY 2006 VL 54 IS 9 SU S BP S203 EP S203 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200454 ER PT J AU Masi, AT Aldag, JC Sipe, JD Malamet, RL AF Masi, Alfonse T. Aldag, Jean C. Sipe, Jean D. Malamet, Raymond L. TI Immunological network differences in women before clinical onset of RA (pre-RA) exhibiting significantly strengthened VEGF and IL-1 beta correlations vs community-based controls (CN). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UICOMP, Peoria, IL USA. NIH, Bethesda, MD 20892 USA. OCTC, Hagerstown, MD USA. NR 0 TC 0 Z9 0 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-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S402 EP S402 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202066 ER PT J AU Masi, AT Aldag, JC Sipe, JD Malamet, RL AF Masi, Alfonse T. Aldag, Jean C. Sipe, Jean D. Malamet, Raymond L. TI C-reactive protein (CRP) levels correlated negatively with serum IL-1 beta in women before clinical onset of rheumatoid arthritis (pre-RA), but not in community-based controls (CN). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UICOMP, Peoria, IL USA. NIH, Bethesda, MD 20892 USA. OCTC, Hagerstown, MD USA. NR 0 TC 0 Z9 0 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-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S402 EP S402 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202065 ER PT J AU Masters, SL Chae, JJ Yao, S Nicola, NA Norton, RS Nicholson, SE Smith, BJ Kastner, DL AF Masters, Seth L. Chae, Jae Jin Yao, Shenggen Nicola, Nicos A. Norton, Raymond S. Nicholson, Sandra E. Smith, Brian J. Kastner, Daniel L. TI Structural analysis of the pyrin B30.2 domain and its interaction with caspase-1 - The consequences of FMF mutations. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, Bethesda, MD 20892 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RI Nicola, Nicos/D-2989-2011; Smith, Brian/F-8282-2011 OI Nicola, Nicos/0000-0003-1054-7889; Smith, Brian/0000-0003-0498-1910 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S538 EP S538 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203015 ER PT J AU Masters, SL Chae, JJ Yao, S Nicola, NA Norton, RS Nicholson, SE Smith, BJ Kastner, DL AF Masters, Seth L. Chae, Jae Jin Yao, Shenggen Nicola, Nicos A. Norton, Raymond S. Nicholson, Sandra E. Smith, Brian J. Kastner, Daniel L. TI Structural analysis of the pyrin B30.2 domain and its interaction with caspase-1 - the consequences of FMF mutations. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, Bethesda, MD 20892 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RI Nicola, Nicos/D-2989-2011; Smith, Brian/F-8282-2011 OI Nicola, Nicos/0000-0003-1054-7889; Smith, Brian/0000-0003-0498-1910 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S45 EP S45 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200031 ER PT J AU Mavragani, CP Niewold, TB Moutsopoulos, NM Hua, J Stanley, P Wahl, S Crow, MK AF Mavragani, Clio P. Niewold, Timothy B. Moutsopoulos, Niki M. Hua, Jing Stanley, Pillemer Wahl, Sharon Crow, Mary K. TI Exagerration of interferon-alpha pathway and BAFF production in patients with Sjogren's syndrome after Anti-TNF treatment. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Hosp Special Surg, Mary Kirkland Ctr Lupus Res, New York, NY 10021 USA. NIDCR, Oral Infect & Immun Branch, NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S312 EP S313 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201254 ER PT J AU Namde, MC Hill, S Duryea, J Plass, N Snyder, C Goldbach-Mansky, R AF Namde, Madjimbaye C. Hill, Suvimol Duryea, Jeffrey Plass, Nicole Snyder, Christopher Goldbach-Mansky, Raphaela TI Arthropathy in patients with neonatal onset multisystem inflammatory disease (NOMID). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S803 EP S803 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204328 ER PT J AU Neugebauer, K Herzog, C Pundt, N Meyer, LH Meinecke, I Kollias, G Blackshear, PJ Schett, G Pap, T Echtermeyer, F AF Neugebauer, Katja Herzog, Christine Pundt, Noreen Meyer, Lars-Henrik Meinecke, Ingmar Kollias, Georg Blackshear, Perry J. Schett, Georg Pap, Thomas Echtermeyer, Frank TI Expression and regulation of syndecan-4 in human rheumatoid arthritis and in TNFalpha-Dependent animal models of destructive arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Hosp Munster, Munster, Germany. Alexander Fleming Biomed Sci Res Ctr, Vari, Greece. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Hosp Erlangen, Erlangen, Germany. RI Kollias, George/A-7079-2012 OI Kollias, George/0000-0003-1867-3150 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S219 EP S220 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201003 ER PT J AU Nikolov, NP Illei, GG Yarboro, C Hakim, F Leitman, S Read, E Khuu, H Gramrner, A Fischer, R Balow, J Austin, H Gea-Banacloche, J Muraro, P Babb, R Krumlauf, M Sportes, C Lipsky, P Gress, R Pavletic, S AF Nikolov, Nikolay P. Illei, Gabor G. Yarboro, Cheryl Hakim, Frances Leitman, Susan Read, Elizabeth Khuu, Hanh Gramrner, Amrie Fischer, Randy Balow, James Austin, Howard Gea-Banacloche, Juan Muraro, Paolo Babb, Rebecca Krumlauf, Michael Sportes, Claude Lipsky, Peter Gress, Ronald Pavletic, Steven TI Effective immune depletion following novel lymphoablative regimen for autologous hematopoietic stem cell transplantation (AutoHSCT) in systemic lupus erythematosus (SLE). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIDCR, NIH, Bethesda, MD USA. NIAMS, NIH, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S790 EP S790 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204294 ER PT J AU Nikolov, NP Bailey, D Candotti, F Schwartzberg, PL Strom, T Siegel, RM AF Nikolov, Nikolay P. Bailey, Daniel Candotti, Fabio Schwartzberg, Pamela L. Strom, Ted Siegel, Richard M. TI Autoimmunity and impaired T cell apoptosis in Wiskott-Aldrich syndrome protein deficiency: A FasL connection. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIDCR, NIH, Bethesda, MD USA. NIAMS, NIH, Bethesda, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S749 EP S749 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204174 ER PT J AU Pisitkun, P Deane, JA Difilippantonio, MJ Tarasenko, T Satterthwaite, AB Bolland, S AF Pisitkun, Prapaporn Deane, Jonathan A. Difilippantonio, Michael J. Tarasenko, Tatyana Satterthwaite, Anne B. Bolland, Silvia TI Genetic modifiers of SLE and Btk-dependent Anti-RNA B cells in Yaa mice due to TLR7 gene duplication. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAID, NIH, LIG, AFGS, Rockville, MD USA. NCI, NIH, CCR, Genet Branch,Sect Canc Genom, Bethesda, MD 20892 USA. UT SW, Dept Internal Med, Dallas, TX USA. NR 0 TC 1 Z9 1 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 SEP PY 2006 VL 54 IS 9 SU S BP S776 EP S776 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204256 ER PT J AU Plenge, RM Lee, AT Li, W Criswell, LA Remmers, EF Kastner, DL Seldin, MF Amos, CI Gregersen, PK AF Plenge, Robert M. Lee, Annette T. Li, Wentian Criswell, Lindsey A. Remmers, Elaine F. Kastner, Daniel L. Seldin, Michael F. Amos, Christopher I. Gregersen, Peter K. TI Dense SNP genotyping under 5 linkage peaks in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 N Shore LIJ Hlth Syst, Feinstein Inst, Manhasset, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIAMSD, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S400 EP S400 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202059 ER PT J AU Puppo, F Tintle, L Wong, A Aksentijevich, I Avery, A Remmers, E Kastner, D AF Puppo, Francesca Tintle, Linda Wong, Austin Aksentijevich, Ivona Avery, Anne Remmers, Elaine Kastner, Daniel TI The Chinese Shar-Pei dog is a natural model of human autoinflammatory diseases: Screening for mutations in the canine Mefv, Tnfrsfla, Cias1 and Mvk. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. Wurtsboro Vet Clin, Wurtsboro, NY USA. Colorado State Univ, Coll Vet Med & Biomed Sci, Ft Collins, CO 80523 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S39 EP S39 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200012 ER PT J AU Remmers, EF Le, JM Li, W Lee, AT Chen, W Seldin, MF Criswell, LA Amos, CI Gregersen, PK Kastner, DL AF Remmers, Elaine F. Le, Julie M. Li, Wentian Lee, Annette T. Chen, Wei Seldin, Michael F. Criswell, Lindsey A. Amos, Christopher I. Gregersen, Peter K. Kastner, Daniel L. TI High density SNP-typing identifies two regions on chromosome 18q that are associated with susceptibility to rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Genet & Genom Branch, Bethesda, MD USA. N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Calif Davis, Dept Med, Rowe Program Human Genet, Davis, CA 95616 USA. Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S392 EP S392 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202037 ER PT J AU Reveille, JD Zhou, XD Ward, MM Davis, JC Learch, T Xiong, M Weisman, MH AF Reveille, John D. Zhou, Xiaodong Ward, Michael M. Davis, John C. Learch, Thomas Xiong, Momiao Weisman, Michael H. TI Interleukin-1 alpha affects susceptibility to but not severity of AS. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Houston Hlth Sci Ctr, Houston, TX USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Los Angeles, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S808 EP S808 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204341 ER PT J AU Saleh, A Najjar, SS Muller, D Ferrucci, L Gelber, AC Ling, SM AF Saleh, Assil Najjar, Samer S. Muller, Denis Ferrucci, Luigi Gelber, Allan C. Ling, Shari M. TI Does hand osteoarthritis predict vascular stiffness? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. NIA, Cardiovasc Res Branch, Baltimore, MD USA. NIA, Intramural Res Program, Baltimore, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S150 EP S151 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200310 ER PT J AU Skapenko, A Prots, I Wendler, J Mattyasovszky, S Yone, CL Spriewald, B Burkhardt, H Rau, R Kalden, JR Lipsky, PE Schulze-Koops, H AF Skapenko, Alla Prots, Iryna Wendler, Jorg Mattyasovszky, Stefan Yone, Clarisse L. Spriewald, Bernd Burkhardt, Harald Rau, Rolf Kalden, Joachim R. Lipsky, Peter E. Schulze-Koops, Hendrik TI The loss-of-function IL4R single nucleotide polymorphism I50V predisposes to rapidly erosive disease in patients with rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Erlangen Nurnberg, Erlangen, Germany. Fachkrankenhaus Ratingen, Ratingen, Germany. NIAMS, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S299 EP S300 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201220 ER PT J AU Smith, JA Goldstein, D Mackensen, F Sen, N Friedlin, J Watkins, A Pyatetsky, D Nussenblatt, R Tessler, H Rosenbaum, J Smith, JR AF Smith, Janine A. Goldstein, Deborah Mackensen, Friederike Sen, Nida Friedlin, Julie Watkins, Angela Pyatetsky, Dimitry Nussenblatt, Robert Tessler, Howard Rosenbaum, Jim Smith, Justine R. TI Epidemiology of childhood uveitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NEI, Bethesda, MD USA. Univ Illinois, Chicago, IL USA. Oregon Hlth Sci Univ, Portland, OR 97201 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S166 EP S166 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200351 ER PT J AU Smolen, JS Aletaha, D van der Heijde, DM Clair, EW Gathany, T Yan, S Baker, D AF Smolen, J. S. Aletaha, D. van der Heijde, D. M. St. Clair, E. W. Gathany, T. Yan, S. Baker, D. TI Patterns of erosion and joint space narrowing development in patients with early rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Med U Vienna, Vienna, Austria. Hietzing Hosp, Vienna, Austria. NIH, Bethesda, MD 20892 USA. U Hosp Maastricht, Maastricht, Netherlands. Duke Univ, Durham, NC USA. Centocor R&D, Malvern, PA 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S198 EP S199 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200441 ER PT J AU Smolen, J van der Heijde, D Aletaha, D Pedersen, R Fatenejad, S Chang, D Freundlich, B AF Smolen, Joseph van der Heijde, Desiree Aletaha, Daniel Pedersen, Ronald Fatenejad, Saeed Chang, David Freundlich, Bruce TI A clinical score that does not require an acute phase response measure, the clinical disease activity index (CDAI), is of similar value as DAS and DAS28 as an indicator of low disease activity in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Med Univ Vienna, Vienna, Austria. Hietzing Hosp, Vienna, Austria. Univ Hosp, Maastricht, Netherlands. NIAMSD, Bethesda, MD 20892 USA. Wyeth Res, Collegeville, PA USA. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S199 EP S199 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200442 ER PT J AU Stojanov, S Sun, HW Balow, J Aksentijevich, I Kastner, DL Chae, JJ AF Stojanov, Silvia Sun, Hong-Wei Balow, James Aksentijevich, Ivona Kastner, Daniel L. Chae, Jae J. TI Comparative gene expression analyses in pyrin-null mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. NIAMS, Biodata Min & Discovery Sect, Off Sci & Technol, NIH, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S636 EP S636 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203293 ER PT J AU Targoff, IN Trieu, EP Levy-Neto, M Prasertsuntarasai, T Miller, FW AF Targoff, Ira N. Trieu, Edward P. Levy-Neto, Mauricio Prasertsuntarasai, Therapol Miller, Frederick W. TI Autoantibodies to transcriptional intermediary factor 1-garnma (TIF1-g) in dermatomyositis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Oklahoma, Hlth Sci Ctr, VAMC, OMRF, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. NIEHS, NIH, US Dept HHS, Bethesda, MD USA. NR 0 TC 41 Z9 43 U1 1 U2 2 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 SEP PY 2006 VL 54 IS 9 SU S BP S518 EP S518 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202383 ER PT J AU Valencia, X Simone, J Goldbach-Mansky, R Wilson, M Lipsky, P AF Valencia, Xavier Simone, James Goldbach-Mansky, Raphaela Wilson, Mildred Lipsky, Peter TI Successful anti-TNF therapy improves the suppressor function of CD4+ CD25hi T regulatory cells in RA. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S300 EP S300 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201223 ER PT J AU Ward, MM Reveille, JD Davis, JC Learch, T Weisman, MH AF Ward, Michael M. Reveille, John D. Davis, John C., Jr. Learch, Thomas Weisman, Michael H. TI Risk factors for total hip arthroplasty in patients with long-standing ankylosing spondylitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Texas, Houston, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Los Angeles, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S720 EP S720 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204095 ER PT J AU Ward, MM Guthrie, L AF Ward, Michael M. Guthrie, Lori TI Patients' ratings of important improvement in physical function in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S363 EP S363 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201389 ER PT J AU Ward, MM AF Ward, Michael M. TI Socioeconomic status and the incidence of end-stage renal disease due to lupus nephritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S267 EP S267 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201130 ER PT J AU Ward, MM AF Ward, Michael M. TI Race, socioeconomic status, and laboratory abnormalities at the onset of treatment of end-stage renal disease in patients with lupus nephritis: Are there disparities in pre-end stage renal disease care? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S102 EP S102 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200179 ER PT J AU Ward, MM AF Ward, Michael M. TI Race, socioeconomic status, and laboratory abnormalities at the onset of treatment of end-stage renal disease in patients with lupus nephritis: Are there disparities in pre-end stage renal disease care? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S53 EP S53 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200047 ER PT J AU Ward, MM AF Ward, Michael M. TI Socioeconomic status and the incidence of end-stage renal disease due to lupus nephritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S53 EP S53 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200046 ER PT J AU Wood, GM AF Wood, Geryl M. TI RNA interference of MEFV reveals potential genes regulated by pyrin, the familial mediterranean fever protein. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S636 EP S636 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203291 ER PT J AU Wood, GM AF Wood, Geryl M. TI RNA interference of MEFV reveals potential genes regulated by pyrin, the Familial Mediterranean fever protein. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S38 EP S39 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200011 ER PT J AU Zhou, X Xiong, M Ward, MM Davis, JC Zhang, G Jin, L Weisman, MH Reveille, JD AF Zhou, Xiaodong Xiong, Momiao Ward, Michael M. Davis, John C. Zhang, Ge Jin, Li Weisman, Michael H. Reveille, John D. TI A genetic network involved in inflammatory reaction may contribute to disease susceptibility to ankylosing spondylitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Sch Med, Houston, TX USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Cincinnati, Cincinnati, OH USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S467 EP S468 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202247 ER PT J AU Gasior, M Rogawski, MA Hartman, AL AF Gasior, Maciej Rogawski, Michael A. Hartman, Adam L. TI Neuroprotective and disease-modifying effects of the ketogenic diet SO BEHAVIOURAL PHARMACOLOGY LA English DT Review DE Alzheimer's disease; cellular energetics; epilepsy; ketone bodies; ketogenic diet; mitochondria; neuroprotection; Parkinson's disease; stroke; traumatic brain injury ID PROTECTS HIPPOCAMPAL-NEURONS; TRAUMATIC BRAIN-INJURY; MALE ICR MICE; TRANSIENT CEREBRAL-ISCHEMIA; INCIDENT ALZHEIMER-DISEASE; FUNCTION IMPROVING AGENT; TRANSGENIC MOUSE MODEL; CENTRAL-NERVOUS-SYSTEM; ANIMAL SEIZURE MODELS; 6-YEAR FOLLOW-UP AB The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially P-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet. C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, John M Freeman Pediat Epilepsy Ctr, Baltimore, MD 21287 USA. RP Gasior, M (reprint author), NINDS, Epilepsy Res Sect, NIH, Bldg 35,Room 1BC 108, Bethesda, MD 20892 USA. EM gasiorm@ninds.nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU Intramural NIH HHS [Z01 NS002877-15] NR 114 TC 134 Z9 143 U1 10 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2006 VL 17 IS 5-6 BP 431 EP 439 DI 10.1097/00008877-200609000-00009 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 089UB UT WOS:000240905500008 PM 16940764 ER PT J AU Li, X Li, Y Peterkofsky, A Wang, GS AF Li, Xia Li, Yifeng Peterkofsky, Alan Wang, Guangshun TI NMR studies of aurein 1.2 analogs SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE antimicrobial peptides; aurein 1.2; LL-37; peptide-lipid interaction; phenylglycine; random-coil chemical shifts ID HELICAL ANTIMICROBIAL PEPTIDES; SODIUM DODECYL-SULFATE; ESCHERICHIA-COLI; ANTIBIOTIC PEPTIDES; AQUEOUS-SOLUTIONS; HYDROPHOBIC CORE; MEMBRANE ANCHOR; INNATE IMMUNITY; CHEMICAL-SHIFT; LIPID-BILAYERS AB Aurein 1.2 is an antimicrobial and anticancer peptide isolated from an Australian frog. To improve our understanding of the mechanism of action, two series of peptides were designed. The first series includes the N-terminal membrane anchor of bacterial glucose-specific enzyme IIA, aurein 1.2, and a newly identified aurein 1.2 analog from human LL-37 (LLAA). The order of antibacterial activity is LLAA > aurein 1.2 >> the membrane anchor (inactive). The structure of LLAA in detergent micelles was determined by H-1 NMR spectroscopy, including structural refinement by natural abundance C-13(alpha),C-13(beta), and N-15 chemical shifts. The hydrophobic surface area of the 3D structure is related to the retention time of the peptide on a reverse-phase HPLC column. The higher activity of LLAA compared to aurein 1.2 was attributed to additional cationic residues that enhance the membrane perturbation potential. The second peptide series was created by changing the C-terminal phenylalanine (F13) of aurein 1.2 to either phenylglycine or tryptophan. A closer or further location of the aromatic rings to the peptide backbone in the mutants relative to F13 is proposed to cause a drop in activity. Phenylglycine with unique chemical shifts may be a useful NMR probe for structure-activity relationship studies of antimicrobial peptides. To facilitate potential future use for NMR studies, random-coil chemical shifts for phenylglycine (X) were measured using the synthetic peptide GGXGG. Aromatic kings of phenylalanines in all the peptides penetrated 2-5 angstrom below the lipid head group and are essential for membrane targeting as illustrated by intermolecular peptide-lipid NOE patterns. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Nebraska Med Ctr, Eppley Inst, Struct Fun Lab, Omaha, NE 68198 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, GS (reprint author), Univ Nebraska Med Ctr, Eppley Inst, Struct Fun Lab, 986805 Nebraska Med Ctr, Omaha, NE 68198 USA. EM gwang@unmc.edu FU Intramural NIH HHS NR 50 TC 33 Z9 35 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD SEP PY 2006 VL 1758 IS 9 BP 1203 EP 1214 DI 10.1016/j.bbamem.2006.03.032 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 098LX UT WOS:000241523100004 PM 16716252 ER PT J AU DeMar, JC Lee, HJ Ma, KZ Chang, L Bell, JM Rapoport, SI Bazinet, RP AF DeMar, James C., Jr. Lee, Ho-Joo Ma, Kaizong Chang, Lisa Bell, Jane M. Rapoport, Stanley I. Bazinet, Richard P. TI Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE arachidonic; brain; incorporation; linoleic; phospholipid; rat ID POLYUNSATURATED FATTY-ACIDS; DE-NOVO LIPOGENESIS; ACYL-COENZYME-A; DOCOSAHEXAENOIC ACID; IN-VIVO; NUTRITIONAL DEPRIVATION; METABOLIC TRANSFORMATIONS; SIGNAL-TRANSDUCTION; ALPHA-LINOLENATE; LIVER AB The extent to which the adult brain can derive some of its arachidonic acid (AA) through internalized synthesis from linoleic acid (LA) is uncertain. Thus, we determined for plasma-derived LA in vivo rates for brain incorporation, beta-oxidation, and conversion to AA. Adult male unanesthetized rats, reared on a diet enriched in LA but low in AA, were infused intravenously for 5 min with [1-C-14]LA. Timed arterial samples were collected until the animals were killed at 5 min and the brain was removed after microwaving. Within plasma lipids, > 96% of radioactivity was in the form of unchanged [1-C-14]LA, but [C-14]AA was insignificant (< 0.2%). Eighty-six percent of brain radioactivity at 5 min was present as beta-oxidation products, whereas the remainder was mainly in 'stable' phospholipid or triglyceride as LA or AA (11 and < 1%, respectively). Unesterified unlabeled LA rapidly enters brain from plasma, but its incorporation into brain total phospholipid and triglyceride, in the form of synthesized AA, is < 1% of the amount that enters the brain. Thus, in rats fed even a diet containing low amounts of AA, the LA that enters brain is largely beta-oxidized, and is not a major source of AA in brain. Published by Elsevier B.V. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bazinet, RP (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S 126, Bethesda, MD 20892 USA. EM rbazinet@mail.nih.gov NR 57 TC 83 Z9 83 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD SEP PY 2006 VL 1761 IS 9 BP 1050 EP 1059 DI 10.1016/j.bbalip.2006.06.006 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 094XX UT WOS:000241273700008 PM 16920015 ER PT J AU Deeg, HJ Friedman, D Bohr, VA Constine, L Jones, IM Sigurdson, A Socie, G Van Zant, G Wei, QY Martin, P AF Deeg, H. Joachim Friedman, Debra Bohr, Vilhelm A. Constine, Louis Jones, Irene M. Sigurdson, Alice Socie, Gerard Van Zant, Gary Wei, Qingyi Martin, Paul TI Transplantation and aging SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT Workshop on Graft-Versus-Host Disease CY NOV 09, 2005 CL Seattle, WA SP Seattle Canc & Aging Program DE hematopoietic cell transplantation; aging; epidemiology; radiation biology; stem cell physiology; molecular mechanisms ID HEMATOPOIETIC-CELL TRANSPLANTATION; ATOMIC-BOMB SURVIVORS; DNA-REPAIR GENES; CHILDHOOD-CANCER SURVIVOR; WERNER-SYNDROME PROTEIN; RADIOLOGIC TECHNOLOGISTS; MALIGNANT NEOPLASMS; EXCISION-REPAIR; THYROID-CANCER; UNITED-STATES AB Report from a workshop conducted at the Fred Hutchinson Cancer Research Center, Seattle, Wash; November 9, 2005. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. Univ Rochester, Rochester, NY USA. Lawrence Livermore Natl Lab, Livermore, CA USA. NIH, Radiat Epidemiol Branch, Rockville, MD USA. Hop St Louis, Paris, France. Univ Kentucky, Lexington, KY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Deeg, HJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM jdeeg@fhcrc.org FU NCI NIH HHS [5 P20 CA103728] NR 44 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2006 VL 12 IS 9 BP 893 EP 898 DI 10.1016/j.bbmt.2006.04.003 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 082AK UT WOS:000240358500001 PM 16920554 ER PT J AU Jung, US Foley, JE Erdmann, AA Toda, Y Borenstein, T Mariotti, J Fowler, DH AF Jung, Unsu Foley, Jason E. Erdmann, Andreas A. Toda, Yoko Borenstein, Todd Mariotti, Jacopo Fowler, Daniel H. TI Ex vivo rapamycin generates Th1/Tc1 or Th2/Tc2 effector T cells with enhanced in vivo function and differential sensitivity to post-transplant rapamycin therapy SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE rapamycin; Th1/Th2; graft-versus-host disease ID VERSUS-HOST-DISEASE; LETHAL ACUTE GVHD; L-SELECTIN CD62L; RESISTANT PROLIFERATION; GRAFT-REJECTION; CENTRAL MEMORY; SIROLIMUS; DONOR; TRANSPLANTATION; TACROLIMUS AB Rapamycin prevention of murine graft-versus-host disease (GVHD) is associated with a shift toward Th2- and Tc2-type cytokines. Recently, we found that use of rapamycin during ex vivo donor Th2 cell generation enhances the ability of adoptively transferred Th2 cells to prevent murine GVHD. In this study, using a method, without antigen-presenting cells, of T-cell expansion based on CD3,CD28 costimulation, we evaluated whether (1) rapamycin preferentially promotes the generation of Th2/Tc2 cells relative to Th1/Tc1 cells, (2) rapamycin-generated T-cell subsets induce cytokine skewing after allogeneic bone marrow transplantation (BMT), and (3) such in vivo cytokine skewing is sensitive to post-BAIT rapamycin therapy. Contrary to our hypothesis, rapamycin did not preferentially promote Th2/Tc2 cell polarity, because rapamycin-generated Th1/Tc1 cells secreted type I cytokines (interleukin [IL]-2 and interferon-gamma) did not secrete type II cytokines (IL-4, IL-5, IL-10, or IL-13) and mediated fasL-based cytolysis. Rapamycin influenced T-cell differentiation, because each of the Th1, Th2, Tc1, and Tc2 subsets generated in rapamycin had increased expression of the central-memory T-cell marker, L-selectin (CD62L). Rapamycin-generated Th1/Tc1 and Th2/Tc2 cells were not anergic but instead had increased expansion after costimulation in vitro, increased expansion in vivo after BAIT, and maintained full capacity to skew toward type I or II cytokines after BMT, respectively; further, rapamycin-generated Th1/Tc1 cells mediated increased lethal GVHD relative to control Th1/Tc1 cells. Rapamycin therapy after BMT in recipients of rapamycin-generated Th1/Tc1 cells greatly reduced Th1/Tc1 cell number, greatly reduced type I cytokines, and reduced lethal GVHD; in marked contrast, rapamycin therapy in recipients of rapamycin-generated Th2/Tc2 cells nominally influenced the number of Th2/Tc2 cells in vivo and did not abrogate post-BMT type II cytokine skewing. In conclusion, ex vivo and in vivo usage of rapamycin may be used to modulate the post-BMT balance of Th1/Tc1 and Th2/Tc2 cell subsets. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NIH, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NIH, Ctr Canc Res, Expt Transplantat & Immunol Branch, 10 Ctr Dr,Bldg 10,CRC,3 E Labs,3-3330, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov NR 33 TC 31 Z9 35 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 SEP PY 2006 VL 12 IS 9 BP 905 EP 918 DI 10.1016/j.bbmt.2006.05.014 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 082AK UT WOS:000240358500003 PM 16920556 ER PT J AU Winger, Q Huang, J Auman, HJ Lewandoski, M Williams, T AF Winger, Quinton Huang, Jian Auman, Heidi J. Lewandoski, Mark Williams, Trevor TI Analysis of transcription factor AP-2 expression and function during mouse preimplantation development SO BIOLOGY OF REPRODUCTION LA English DT Article DE developmental biology; early development; embryo; gene regulation; trophoblast ID EARLY EMBRYONIC-DEVELOPMENT; GENE-EXPRESSION; DNA-BINDING; PROTEIN-2-GAMMA AP-2-GAMMA; FACTOR AP-2-BETA; MICE; AP-2-ALPHA; ACTIVATION; OOCYTES; CLONING AB The activating protein 2 (AP-2) transcription factor family is required for multiple aspects of mouse postimplantation development, but much less is known about the expression and possible function of these genes during the preimplantation period. In the present study, we have examined the expression of all five members of the mouse AP-2 gene family in the unfertilized oocyte and from zygote formation to the blastocyst stage of development. Four AP-2 genes are differentially expressed during the preimplantation period, Tcfap2a, Tcfap2b, Tcfap2c, and Tcfap2e. Furthermore, with the exception of Tcfap2a, these genes are also expressed in unfertilized oocytes, indicating that they may be important for oogenesis, maternal-effect functions, or both. Given these findings, we have initiated studies to assess how various combinations of maternal and zygotic AP-2 gene expression might function together to regulate pre- and peri-implantation development. The present study focuses on the interplay between the expression of zygotic Tcfap2a and maternal and zygotic Tcfap2c. These studies indicate that zygotic, but not maternal, Tcfap2c expression is required for normal embryogenesis. In addition, the combined loss of both Tcfap2a and Tcfap2c accelerates embryonic lethality compared to the loss of either gene alone, demonstrating that genetic redundancy exists between these two AP-2 family members during the peri-implantation period of embryogenesis. C1 Univ Colorado, Hlth Sci Ctr Fitzsimons, Dept Craniofacial Biol, Aurora, CO 80045 USA. Univ Colorado, Hlth Sci Ctr Fitzsimons, Dept Cell & Dev Biol, Aurora, CO 80045 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA. NCI, Frederick Canc Res & Dev Ctr, Genet Vertebrate Dev Sect, Frederick, MD 21702 USA. RP Williams, T (reprint author), Mailstop 8120,POB 6511, Aurora, CO 80045 USA. EM trevor.williams@uchsc.edu NR 57 TC 26 Z9 26 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD SEP PY 2006 VL 75 IS 3 BP 324 EP 333 DI 10.1095/biolreprod.106.052407 PG 10 WC Reproductive Biology SC Reproductive Biology GA 075VE UT WOS:000239912800003 PM 16672719 ER PT J AU Garcia-Closas, M Moore, LE Rabkin, CS Franklin, T Struewing, J Ginzinger, D Alguacil, J Rothman, N AF Garcia-Closas, M. Moore, L. E. Rabkin, C. S. Franklin, T. Struewing, J. Ginzinger, D. Alguacil, J. Rothman, N. TI Quantitation of DNA in buccal cell samples collected in epidemiological studies SO BIOMARKERS LA English DT Article DE buccal cells; DNA; epidemiology; quantitation ID GENOMIC DNA; MOUTHWASH AB Buccal cell samples are increasingly used in epidemiological studies as a source of genomic DNA. The accurate and precise quantitation of human DNA is critical for the optimal use of these samples. However, it is complicated by the presence of bacterial DNA and wide interindividual variation in DNA concentration from buccal cell collections. The paper evaluated the use of ultraviolet light (UV) spectroscopy, Hoechst (H33258) and PicoGreen (TM) as measures of total DNA, and real-time quantitative polymerase chain reaction (PCR) as a measure of human amplifiable DNA in buccal samples. Using serially diluted white blood cell DNA samples (at a concentration range of 300 to 0.5 ng mu l(-1)), UV spectroscopy showed the largest bias, followed by Hoechst, especially for low concentrations. PicoGreen and real-time PCR provided the most accurate and precise estimates across the range of concentrations evaluated, although an increase in bias with decreasing concentrations was observed. The ratio of real-time PCR to PicoGreen provided a reasonable estimate of the percentage of human DNA in samples containing known mixtures of human and bacterial DNA. Quantification of buccal DNA from samples collected in a breast cancer case-control study by PicoGreen and real-time PCR indicated that cytobrush and mouthwash DNA samples contain similar percentages of human amplifiable DNA. Real-time PCR is recommended for the quantification of buccal cell DNA in epidemiological studies since it provides precise estimates of human amplifiable DNA across the wide range of DNA concentrations commonly observed in buccal cell DNA samples. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. ATCC, Manassas, VA USA. RP Garcia-Closas, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM garciacm@exchange.nih.gov RI Struewing, Jeffery/C-3221-2008; Garcia-Closas, Montserrat /F-3871-2015; Struewing, Jeffery/I-7502-2013 OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Struewing, Jeffery/0000-0002-4848-3334 FU Intramural NIH HHS NR 8 TC 12 Z9 12 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD SEP-OCT PY 2006 VL 11 IS 5 BP 472 EP 479 DI 10.1080/13547500600733820 PG 8 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 083YE UT WOS:000240494400007 PM 16966163 ER PT J AU Proschan, MA AF Proschan, Michael A. TI Are flexible designs sound? Discussion SO BIOMETRICS LA English DT Editorial Material ID CLINICAL-TRIALS; SAMPLE-SIZE C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. EM proscham@niaid.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2006 VL 62 IS 3 BP 674 EP 676 DI 10.1111/j.1541-0420.2006.00628.x PG 3 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 086YE UT WOS:000240708300004 ER PT J AU Fay, MP Tiwari, RC Feuer, EJ Zou, ZH AF Fay, Michael P. Tiwari, Ram C. Feuer, Eric J. Zou, Zhaohui TI Estimating average annual percent change for disease rates without assuming constant change SO BIOMETRICS LA English DT Article DE age-adjusted rates; annual percent change; percent change annualized; rate ratio; relative risk; surveillance; trends ID DIRECTLY STANDARDIZED RATES; CONFIDENCE-INTERVALS AB The annual percent change (APC) is often used to measure trends in disease and mortality rates, and a common estimator of this parameter uses a linear model on the log of the age-standardized rates. Under the assumption of linearity on the log scale, which is equivalent to a constant change assumption, APC can be equivalently defined in three ways as transformations of either (1) the slope of the line that runs through the log of each rate, (2) the ratio of the last rate to the first rate in the series, or (3) the geometric mean of the proportional changes in the rates over the series. When the constant change assumption fails then the first definition cannot be applied as is, while the second and third definitions unambiguously define the same parameter regardless of whether the assumption holds. We call this parameter the percent change annualized (PCA) and propose two new estimators of it. The first, the two-point estimator, uses only the first and last rates, assuming nothing about the rates in between. This estimator requires fewer assumptions and is asymptotically unbiased as the size of the population gets large, but has more variability since it uses no information from the middle rates. The second estimator is an adaptive one and equals the linear model estimator with a high probability when the rates are not significantly different from linear on the log scale, but includes fewer points if there are significant departures from that linearity. For the two-point estimator we can use confidence intervals previously developed for ratios of directly standardized rates. For the adaptive estimator, we show through simulation that the bootstrap confidence intervals give appropriate coverage. C1 NIAID, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD 20904 USA. RP Fay, MP (reprint author), NIAID, Bethesda, MD 20892 USA. EM mfay@niaid.nih.gov RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 13 TC 39 Z9 56 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2006 VL 62 IS 3 BP 847 EP 854 DI 10.1111/j.1541-0420.2006.00528.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 086YE UT WOS:000240708300028 PM 16984328 ER PT J AU Kaura, N Monga, V Josan, JS Lu, X Gershengorn, MC Jain, R AF Kaura, Navneet Monga, Vikramdeep Josan, Jatinder S. Lu, Xinping Gershengorn, Marvin C. Jain, Rahul TI Synthesis, receptor binding, and activation studies of N(1)-alkyl-L-histidine containing thyrotropin-releasing hormone (TRH) analogues SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE 1-alkyl-L-histidine; TRH; TRH receptor subtype 1; TRH receptor subtype 2; peptides ID CLONING; SUBTYPE; MODEL AB Thyrotropin-releasing hormone (TRH) analogues in which the N(1)-position of the imidazole ring of the centrally placed histidine residue is substituted with various alkyl groups were synthesized and studied as agonists for TRH receptor subtype 1 (TRH-R1) and subtype 2 (TRH-R2). Analogue 3 (R = C2H5) exhibited binding affinity (K-i) of 0.012 mu M to TRH-R1 that is about 1.1-fold higher than that of TRH. Several analogues were found to selectively activate TRH-R2 with greater potency than TRH-R1. The most selective agonist of the series 5 [R = CH(CH3)(2)] was found to activate TRH-R2 with a potency (EC50) of 0.018 mu M but could only activate TRH-R1 at EC50 value of 1.6 mu M; that is, exhibited 88-fold greater potency for TRH-R2 versus TRH-R1. The results of this study indicate that modulation of central histidine residue is important for designing analogues which were selective agonist at TRH receptor subtypes. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Inst Pharmaceut Educ & Res, Dept Med Chem, SAS Nagar 160062, Punjab, India. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Jain, R (reprint author), Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sector 67, SAS Nagar 160062, Punjab, India. EM rahuljain@niper.ac.in RI Josan, Jatinder/F-8033-2013; Josan, Jatinder/N-4485-2013; OI Josan, Jatinder/0000-0003-2877-9717; Kaur, Navneet/0000-0002-0012-6151 FU Intramural NIH HHS NR 24 TC 14 Z9 14 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP 1 PY 2006 VL 14 IS 17 BP 5981 EP 5988 DI 10.1016/j.bmc.2006.05.031 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 076HL UT WOS:000239947500018 PM 16735122 ER PT J AU Nguyen, TL Gussio, R Smith, JA Lannigan, DA Hecht, SM Scudiero, DA Shoemaker, RH Zaharevitz, DW AF Nguyen, Tam Luong Gussio, Rick Smith, Jeffrey A. Lannigan, Deborah A. Hecht, Sidney M. Scudiero, Dominic A. Shoemaker, Robert H. Zaharevitz, Daniel W. TI Homology model of RSK2 N-terminal kinase domain, structure-based identification of novel RSK2 inhibitors, and preliminary common pharmacophore SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE ribosomal S6 kinase 2; homology model; ATP-binding site; virtual screening; ligand docking; pharmacophore ID COFFIN-LOWRY-SYNDROME; RIBOSOMAL S6 KINASE; CANCER-CELL-PROLIFERATION; DEPENDENT PROTEIN-KINASE; MUTATIONS; BINDING; ACTIVATION; DOCKING; POTENT; GENE AB Ribosomal S6 kinase 2 (RSK2) is a serine/threonine kinase that plays a role in human cancer and Coffin-Lowry syndrome and is comprised of two nonidentical kinase domains, each domain with its own ATP-binding site. RSK2 can be inactivated by different types of small organic molecules. Potent RSK2 inhibitors include the two classic bisindole maleimide PKC inhibitors, Ro31-8220 and GF109203X, and the natural product SL0101 that was shown to bind specifically to the ATP pocket of the N-terminal domain (NTD). In this paper, we present an atomic model of the RSK2 NTD (residues 68-323), which was built to simultaneously bind the distinctive molecular scaffolds of SL0101, Ro31-8220, and GF109203X. The RSK2 NTD model was used to identify two novel RSK2 inhibitors from the National Cancer Institute open chemical repository and to develop a preliminary structure-based pharmacophore model. Published by Elsevier Ltd. C1 SAIC Frederick Inc, NCI Frederick, Target Structure Based Drug Discovery Grp, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Informat Technol Branch, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA. Univ Virginia, Dept Pathol, Ctr Cell Signaling, Charlottesville, VA 22908 USA. Univ Virginia, Dept Microbiol, Ctr Cell Signaling, Charlottesville, VA 22908 USA. SAIC Frederick Inc, NCI Frederick, Screening Technol Branch, Charlottesville, VA 22901 USA. NCI, Dev Therapeut Program, Screening Technol Branch, Frederick, MD 21702 USA. RP Nguyen, TL (reprint author), SAIC Frederick Inc, NCI Frederick, Target Structure Based Drug Discovery Grp, Frederick, MD 21702 USA. EM nguyent@mail.ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 24 TC 30 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP 1 PY 2006 VL 14 IS 17 BP 6097 EP 6105 DI 10.1016/j.bmc.2006.05.001 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 076HL UT WOS:000239947500032 PM 16723234 ER PT J AU Nunemaker, CS Bertram, R Sherman, A Tsaneva-Atanasova, K Daniel, CR Satin, LS AF Nunemaker, Craig S. Bertram, Richard Sherman, Arthur Tsaneva-Atanasova, Krasimira Daniel, Camille R. Satin, Leslie S. TI Glucose modulates [Ca2+](i) oscillations in pancreatic islets via ionic and glycolytic mechanisms SO BIOPHYSICAL JOURNAL LA English DT Article ID PULSATILE INSULIN-SECRETION; INDUCED ELECTRICAL-ACTIVITY; SINGLE-MOUSE ISLETS; CYTOPLASMIC CA2+ CONCENTRATION; BETA-CELLS; IN-VIVO; OXYGEN-CONSUMPTION; B-CELLS; ACTION-POTENTIALS; K+ CHANNELS AB Pancreatic islets of Langerhans display complex intracellular calcium changes in response to glucose that include fast (seconds), slow (similar to 5 min), and mixed fast/slow oscillations; the slow and mixed oscillations are likely responsible for the pulses of plasma insulin observed in vivo. To better understand the mechanisms underlying these diverse patterns, we systematically analyzed the effects of glucose on period, amplitude, and plateau fraction ( the fraction of time spent in the active phase) of the various regimes of calcium oscillations. We found that in both fast and slow islets, increasing glucose had limited effects on amplitude and period, but increased plateau fraction. In some islets, however, glucose caused a major shift in the amplitude and period of oscillations, which we attribute to a conversion between ionic and glycolytic modes (i.e., regime change). Raising glucose increased the plateau fraction equally in fast, slow, and regime-changing islets. A mathematical model of the pancreatic islet consisting of an ionic subsystem interacting with a slower metabolic oscillatory subsystem can account for these complex islet calcium oscillations by modifying the relative contributions of oscillatory metabolism and oscillatory ionic mechanisms to electrical activity, with coupling occurring via KATP channels. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA. NIH, Lab Biol Modeling, Bethesda, MD USA. Virginia Tech, Dept Math, Blacksburg, VA 24061 USA. RP Satin, LS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA. EM lsatin@hsc.vcu.edu RI Tsaneva-Atanasova, Krasimira/A-7153-2011; OI Tsaneva-Atanasova, Krasimira/0000-0002-6294-7051 FU Intramural NIH HHS; NIDDK NIH HHS [F32 DK 065462, F32 DK065462, R01 DK 46409, R01 DK046409] NR 68 TC 48 Z9 48 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2006 VL 91 IS 6 BP 2082 EP 2096 DI 10.1529/biophysj.106.087296 PG 15 WC Biophysics SC Biophysics GA 078US UT WOS:000240130500014 PM 16815907 ER PT J AU Chen, H Puhl, HL Koushik, SV Vogel, SS Ikeda, SR AF Chen, Huanmian Puhl, Henry L., III Koushik, Srinagesh V. Vogel, Steven S. Ikeda, Stephen R. TI Measurement of FRET efficiency and ratio of donor to acceptor concentration in living cells SO BIOPHYSICAL JOURNAL LA English DT Article ID RESONANCE ENERGY-TRANSFER; FLUORESCENT PROTEIN; MICROSCOPY; VARIANT AB Measurement of fluorescence resonance energy transfer ( FRET) efficiency and the relative concentration of donor and acceptor fluorophores in living cells using the three-filter cube approach requires the determination of two constants: 1), the ratio of sensitized acceptor emission to donor fluorescence quenching ( G factor) and 2), the ratio of donor/acceptor fluorescence intensity for equimolar concentrations in the absence of FRET (k factor). We have developed a method to determine G and k that utilizes two donor-acceptor fusion proteins with differing FRET efficiencies - the value of which need not be known. We validated the method by measuring the FRET efficiency and concentration ratio of the fluorescent proteins Cerulean and Venus in mammalian cells expressing a series of fusion proteins with varying stoichiometries. The method greatly simplifies quantitative FRET measurement in living cells as it does not require cell fixation, acceptor photobleaching, protein purification, or specialized equipment for determining fluorescence spectra or lifetime. C1 NIAAA, Lab Mol Physiol, Sect Transmitter Signaling, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Mol Physiol, Sect Cellular Biophoton, NIH, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Lab Mol Physiol, Sect Transmitter Signaling, NIH, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov RI Vogel, Steven/A-3585-2012; OI Ikeda, Stephen/0000-0002-4088-9508; Puhl, Henry/0000-0003-3095-7201; Vogel, Steven/0000-0002-3005-2667 FU Intramural NIH HHS NR 13 TC 105 Z9 106 U1 4 U2 26 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2006 VL 91 IS 5 BP L39 EP L41 DI 10.1529/biophysj.106.088773 PG 3 WC Biophysics SC Biophysics GA 074CP UT WOS:000239790400001 PM 16815904 ER PT J AU Tefferi, A Barosi, G Mesa, RA Cervantes, F Deeg, HJ Reilly, JT Verstovsek, S Dupriez, B Silver, RT Odenike, O Cortes, J Wadleigh, M Solberg, LA Camoriano, JK Gisslinger, H Noel, P Thiele, J Vardiman, JW Hoffman, R Cross, NCP Gilliland, DG Kantarjian, H AF Tefferi, Ayalew Barosi, Giovanni Mesa, Ruben A. Cervantes, Francisco Deeg, H. Joachim Reilly, John T. Verstovsek, Srdan Dupriez, Brigitte Silver, Richard T. Odenike, Olatoyosi Cortes, Jorge Wadleigh, Martha Solberg, Lawrence A., Jr. Camoriano, John K. Gisslinger, Heinz Noel, Pierre Thiele, Juergen Vardiman, James W. Hoffman, Ronald Cross, Nicholas C. P. Gilliland, D. Gary Kantarjian, Hagop TI International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT) SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; LOW-DOSE THALIDOMIDE; LEUKEMIA GROUP-B; MYELODYSPLASTIC SYNDROMES; IDIOPATHIC MYELOFIBROSIS; INTERFERON-ALPHA; CYTOGENETIC ABNORMALITIES; MARROW-TRANSPLANTATION; LENALIDOMIDE CC-5013; CIRCULATING CD34(+) AB Myelofibrosis with myeloid metaplasia (MMM) is a clinicopathologic entity characterized by stem cell-derived clonal myeloproliferation, ineffective erythropoiesis, extramedullary hematopoiesis, and bone marrow fibrosis and osteosclerosis. Patients with MMM have shortened survival and their quality of life is compromised by progressive anemia, marked hepatosplenomegaly, and severe constitutional symptoms including cachexia. After decades of frustration with ineffective therapy, patients are now being served by promising treatment approaches that include allogeneic hematopoietic stem cell transplantation and immunomodulatory drugs. Recent information regarding disease pathogenesis, including a contribution to the myeloproliferative disorder phenotype by a gain-of-function JAK2 mutation (JAK2(V617F)), has revived the prospect of targeted therapeutics as well as molecular monitoring of treatment response. Such progress calls for standardization of response criteria to accurately assess the value of new treatment modalities, to allow accurate comparison between studies, and to ensure that the definition of response reflects meaningful health outcome. Accordingly, an international panel of experts recently convened and delineated 3 response categories: complete remission (CR), partial remission (PR), and clinical improvement (CI). Bone marrow histologic and hematologic remissions characterize CR and CR/PR, respectively. The panel agreed that the CI response category is applicable only to patients with moderate to severe cytopenia or splenomegaly. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Policlin San Matteo, Ist Ric & Curo Carattere Sci, I-27100 Pavia, Italy. Hosp Clin Barcelona, Inst Invest Biomed August Pi I Sunyer, E-08036 Barcelona, Spain. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cornell Univ, Med Ctr, New York, NY 10021 USA. Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. Univ Vienna, Dept Hematol & Blood Coagulat, Vienna, Austria. NIH, Bethesda, MD 20892 USA. Univ Cologne, Inst Pathol, D-5000 Cologne, Germany. Univ Illinois, Chicago, IL USA. Wessex Reg Genet Lab, Salisbury, Wilts, England. RP Tefferi, A (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu RI Cross, Nicholas/B-4817-2009; Solberg, Lawrence/A-3824-2014 OI Cross, Nicholas/0000-0001-5481-2555; Solberg, Lawrence/0000-0001-9550-5180 NR 53 TC 196 Z9 210 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 SEP 1 PY 2006 VL 108 IS 5 BP 1497 EP 1503 DI 10.1182/blood-2006-03-009746 PG 7 WC Hematology SC Hematology GA 080TO UT WOS:000240271500018 PM 16675707 ER PT J AU Rudelius, M Pittaluga, S Nishizuka, S Pham, THT Fend, F Jaffe, ES Quintanilla-Martinez, L Raffeld, M AF Rudelius, Martina Pittaluga, Stefania Nishizuka, Satoshi Pham, Trinh H. -T Fend, Falko Jaffe, Elaine S. Quintanilla-Martinez, Leticia Raffeld, Mark TI Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma SO BLOOD LA English DT Article ID NF-KAPPA-B; NON-HODGKINS-LYMPHOMAS; PHOSPHOINOSITIDE 3-KINASE PATHWAY; PROTEIN-KINASE-B; CYCLIN D1; MAMMALIAN TARGET; HUMAN CANCER; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; AGGRESSIVE VARIANTS; MUTATIONAL ANALYSIS AB To determine whether the PI3K/Akt signaling pathway is involved in the pathogenesis of mantle cell lymphoma (MCL), we investigated the phosphorylation status of Akt and multiple downstream targets in primary MCL cases and cell lines. Akt was phosphorylated in 12 of 12 aggressive blastold MCL variants and in 4 of 4 MCL cell lines. In contrast, phosphorylated Akt was present in only 5 of 16 typical MCL, 3 at comparable levels to the blastoid cases, and 2 at low levels. The presence of p-Akt was accompanied by the phosphorylation of p27(kip1), FRKHL-1, MDM2, Bad, mTOR, and p70S6K. Inhibition of the PI3K/Akt pathway in the MCL cell lines abrogated or reduced the phosphorylation of Akt, p27(kip1), FRKHL-1, MDM2, Bad, mTOR, GSK-3 beta, I kappa B, and led to cell-cycle arrest and apoptosis. Six MCL cases (5 with activated Akt and 1 with inactive Akt) and 3 of 4 cell lines showed loss of PTEN expression. PIK3CA mutations were not detected. We conclude that constitutive activation of the PI3K/Akt pathway contributes to the pathogenesis of MCL and preferentially occurs in blastoid variants. One possible mechanism of activation is loss of PTEN expression. These data suggest that PI3K/Akt inhibitors may be effective in the treatment of Akt-activated MCL. C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Mol Therapeut Program, NIH, Bethesda, MD 20892 USA. SAIC, Lab Proteom & Analyt Technol, Frederick, MD USA. Tech Univ Munich, Inst Pathol, D-8000 Munich, Germany. Natl Res Ctr Hlth & Environm, GSF, Neuherberg, Germany. RP Raffeld, M (reprint author), NCI, Pathol Lab, Hematopathol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mraff@mail.nih.gov FU Intramural NIH HHS NR 84 TC 144 Z9 155 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2006 VL 108 IS 5 BP 1668 EP 1676 DI 10.1182/blood-2006-04-015586 PG 9 WC Hematology SC Hematology GA 080TO UT WOS:000240271500041 PM 16645163 ER PT J AU Burkholder, TH Colenda, L Tuschong, LM Starost, MF Bauer, TR Hickstein, DD AF Burkholder, Tanya H. Colenda, Lyn Tuschong, Laura M. Starost, Matthew F. Bauer, Thomas R., Jr. Hickstein, Dennis D. TI Reproductive capability in dogs with canine leukocyte adhesion deficiency treated with nonmyeloablative conditioning prior to allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; GONADAL-FUNCTION; DISEASE PHENOTYPE; CHILDHOOD; CYCLOPHOSPHAMIDE; LEUKEMIA AB Nonmyeloablative conditioning regimens are increasingly replacing myeolablative conditioning prior to allogeneic hematopoietic stem cell transplantation (SCT). The recent advent of these conditioning regimens has limited the assessment of the long-term effects of this treatment, including analysis of reproductive function. To address the question of reproductive function after nonmyeloablative transplantation, we analyzed a cohort of young dogs with the genetic disease canine leukocyte adhesion deficiency that were treated with a nonmyeloablative dose of 200 cGy total body irradiation followed by matched-littermate SCT Five males and 5 females entered puberty; all 5 males and 4 females subsequently sired or delivered litters following transplantation. We demonstrate that fertility is intact and dogs have uncomplicated parturitions following nonmyeloablative conditioning for SCT These results are encouraging for children and adults of childbearing age who receive similar conditioning regimens prior to allogeneic transplantation. C1 NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Burkholder, TH (reprint author), NIH, Div Vet Resources, Off Res Serv, 9000 Rockville Pike,Bldg 28,Rm 104, Bethesda, MD 20892 USA. EM burkholt@mail.nih.gov FU Intramural NIH HHS [NIH0011280553]; PHS HHS [NIH0011280553] NR 17 TC 12 Z9 12 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 SEP 1 PY 2006 VL 108 IS 5 BP 1767 EP 1769 DI 10.1182/blood-2006-02-005645 PG 3 WC Hematology SC Hematology GA 080TO UT WOS:000240271500053 PM 16645166 ER PT J AU Savage, SA Stewart, BJ Weksler, BB Baerlocher, GM Lansdorp, PM Chanock, SJ Alter, BP AF Savage, Sharon A. Stewart, Brian J. Weksler, Babette B. Baerlocher, Gabriela M. Lansdorp, Peter M. Chanock, Stephen J. Alter, Blanche P. TI Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Letter ID GENETIC-VARIATION; PROCESSIVITY C1 NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Weill Med Coll, Dept Med, New York, NY 10021 USA. Univ British Columbia, Terry Fox Lab, British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. Univ Bern, Dept Hematol, Bern, Switzerland. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-7018, Rockville, MD 20892 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural NIH HHS; NIAID NIH HHS [AI29524] NR 12 TC 18 Z9 18 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2006 VL 37 IS 2 BP 134 EP 136 DI 10.1016/j.bcmd.2006.07.001 PG 3 WC Hematology SC Hematology GA 091KH UT WOS:000241025700011 PM 16934504 ER PT J AU Sigurdsson, G Aspelund, T Chang, ML Jonsdottir, B Sigurdsson, S Eiriksdottir, G Gudmundsson, A Harris, TB Gudnason, V Lang, TF AF Sigurdsson, Gunnar Aspelund, Thor Chang, Milan Jonsdottir, Birma Sigurdsson, Sigurdur Eiriksdottir, Gudny Gudmundsson, Adalsteinn Harris, Tamara B. Gudnason, Vilmundur Lang, Thomas F. TI Increasing sex difference in bone strength in old age: The Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK) SO BONE LA English DT Article DE aging; bone geometry; bone QCT; osteoporosis; strength indices ID UNRECOGNIZED MYOCARDIAL-INFARCTION; QUANTITATIVE COMPUTED-TOMOGRAPHY; GENDER-DIFFERENCES; FEMORAL-NECK; HIP; DENSITY; SIZE; EPIDEMIOLOGY; OSTEOPOROSIS; POPULATION AB Introduction: It is important to identify possible pathological mechanisms that underlie the known sexual dimorphism in bone fragility in old age. In this cross-sectional population-based study, we use data from three different skeletal sites to examine sex differences in volumetric bone density, geometry and strength indices and determine whether sex differences in these bone strength measures continue to increase into very old age. Materials and methods: A total of 1715 elderly individuals (807 men and 908 women) age 67-93 years, participants in a population-based study, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK) and not taking medications affecting bone metabolism, were studied. Quantitative computed tomography (QCT) was performed in the lumbar spine, hip and mid-femoral shaft to estimate volumetric trabecular, cortical and integral BMD, bone geometry and bone strength indices. Regression models were used to assess the effects of age and gender-adjustment for standing midlife height and current weight. Results: At age 67-69 years, men had 24.9-31.7% larger cross-sectional bone size at measured sites than women. At all bone sites, women had two- to fivefold diminution in net bone mass with age compared to men but had comparable increments in bone size (1.8-6.0% per 10 years). This was reflected in significantly worse (more than twofold) bone strength measures with age in women, including compressive strength indices at the spine, femoral neck and trochanter and bending strength indices at the femoral neck. Conclusion: With the limitations of a cross-sectional study, our data support the hypothesis that sex differences in bone strength continue into old age. These sex differences appear to be due to greater net bone loss in women rather than due to greater bone gain in men. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Iceland, Dept Med, Div Endocrinol & Metab, Landspitali, IS-108 Reykjavik, Iceland. NIA, Intramural Res Program, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Iceland Heart Assoc, Kopavogur, Iceland. RP Sigurdsson, G (reprint author), Univ Iceland, Dept Med, Div Endocrinol & Metab, Landspitali, IS-108 Reykjavik, Iceland. EM gunnars@landspitali.is RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Lang, Thomas/B-2685-2012; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Lang, Thomas/0000-0002-3720-8038; Gudnason, Vilmundur/0000-0001-5696-0084 FU NIA NIH HHS [N01-AG-1-2100] NR 21 TC 75 Z9 76 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD SEP PY 2006 VL 39 IS 3 BP 644 EP 651 DI 10.1016/j.bone.2006.03.020 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 078OU UT WOS:000240113900026 PM 16790372 ER PT J AU Shatunov, A Sambuughin, N Jankovic, J Elble, R Lee, HS Singleton, AB Dagvadorj, A Ji, J Zhang, YP Kimonis, VE Hardy, J Hallett, M Goldfarb, LG AF Shatunov, Alexey Sambuughin, Nyamkhishig Jankovic, Joseph Elble, Rodger Lee, Hee Suk Singleton, Andrew B. Dagvadorj, Ayush Ji, Jay Zhang, Yiping Kimonis, Virginia E. Hardy, John Hallett, Mark Goldfarb, Lev G. TI Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23 SO BRAIN LA English DT Article DE essential tremor; focal dystonia; linkage mapping; chromosome 6p ID SHARING STATISTICS; PARKINSON-DISEASE; HS1-BP3 GENE; DISORDER; VARIANT; RECOMBINATION; EPIDEMIOLOGY; ASSOCIATION; PREVALENCE; DIAGNOSIS AB Essential tremor (ET) is the most prevalent adult-onset movement disorder showing evidence of non-random accumulation in some families. ET has previously been mapped to genetic loci on chromosomes 2p and 3q, but no causative genes identified. We conducted genomewide linkage screening with subsequent fine mapping in seven large North American families comprising a total of 325 genotyped individuals that included 65 patients diagnosed as definite ET. Linkage analysis was based on methodology implemented in SimWalk2 and LINKAGE programs. A multigenerational family revealed suggestive linkage to a locus on chromosome 6p23 with maximal nonparametric linkage (NPL) multipoint score 3.281 (P = 0.0005) and parametric multipoint log of the odds (LOD) score 2.983. A second family showed positive linkage to the same 6p23 region with a maximal NPL score 2.125 (P = 0.0075) and LOD score 1.265. Haplotype analysis led to the identification of a 600 kb interval shared by both families. Sequencing of coding regions of 15 genes located in the linked region detected numerous sequence variants, some of them predicting a change of the encoded amino acid, but each was also found in controls. Our findings provide evidence for linkage to a novel susceptibility locus on chromosome 6p23. Analysis of additional ET-affected families is needed to confirm linkage and identify the underlying gene. C1 NINDS, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. Biotech Res Labs Inc, Gaithersburg, MD USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. So Illinois Univ, Sch Med, Springfield, IL USA. Univ Cincinnati, Coll Med, Ctr Genome Informat, Cincinnati, OH USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. RP Goldfarb, LG (reprint author), NINDS, NIH, 5625 Fishers Lane,Room 4S06, Bethesda, MD 20892 USA. EM GoldfarbL@ninds.nih.gov RI Singleton, Andrew/C-3010-2009; Shatunov, Aleksey/E-6946-2011; Hardy, John/C-2451-2009 FU Intramural NIH HHS; Medical Research Council [G0701075] NR 61 TC 65 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2006 VL 129 BP 2318 EP 2331 DI 10.1093/brain/awl120 PN 9 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 086NG UT WOS:000240679700008 PM 16702189 ER PT J AU Begnami, M Rushing, EJ Santi, M Quezado, M AF Begnami, Maria Rushing, Elisabeth J. Santi, Mariarita Quezado, Martha TI Evaluation of NF2 gene deletion in pediatric meningiomas by chromogenic in situ hybridization (CISH) and immunohistochemistry SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 NCI, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 219 BP S100 EP S100 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600220 ER PT J AU McKeever, PE Mobley, BC Shah, GV Roulston, D Bijwaard, KE AF McKeever, Paul E. Mobley, Bret C. Shah, Gaurang V. Roulston, Diane Bijwaard, Karen E. TI Peripheral pNET/Ewing sarcoma of the craniospinal vault: Two case reports and review of similar cases SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 224 BP S102 EP S102 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600225 ER PT J AU Troncoso, JC Resnick, SM O'Brien, R Zonderman, AB Martin, L Rudow, GL Pletnikova, O Riudavets, MA AF Troncoso, Juan C. Resnick, Susan M. O'Brien, Richard Zonderman, Alan B. Martin, Lee Rudow, Gay L. Pletnikova, Olga Riudavets, Miguel A. TI Nuclear hypertrophy in anterior cingulate and hippocampal neurons in asymptomatic subjects with Alzheimer's pathology SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 NIA, Lab Personal & Cognit, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. FLENI, Dept Neuropathol, Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 285 BP S128 EP S128 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600286 ER PT J AU Gaudet, MM Bensen, JT Schroeder, J Olshan, AF Terry, MB Eng, SM Teitelbaum, SL Britton, JA Lehman, TA Neugut, AI Ambrosone, CB Santella, RM Gammon, MD AF Gaudet, Mia M. Bensen, Jeannette T. Schroeder, Jane Olshan, Andrew F. Terry, Mary Beth Eng, Sybil M. Teitelbaum, Susan L. Britton, Julie A. Lehman, Teresa A. Neugut, Alfred I. Ambrosone, Christine B. Santella, Regina M. Gammon, Marilie D. TI Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article ID GENE POLYMORPHISM; LINKAGE PHASE; COMT GENOTYPE; RISK; ASSOCIATION; SCHIZOPHRENIA; SUSCEPTIBILITY; VARIANT; TRAITS; TESTS AB The gene encoding catechol-O-methyltransferase (COMT), critical to the inactivation of reactive catechol estrogens, has several single nucleotide polymorphisms (SNPs) that influence enzyme activity. A 3-SNP haplotype (IVS1+255 C > T; Ex4-12 G > A; 3'UTR-521 A > G), which has been shown to reduce COMT expression in the human brain, has been identified. To evaluate the influence of genetic variation of COMT on breast cancer risk, these 3-SNPs were genotyped in 1052 cases and 1098 controls. We estimated the associations between breast cancer and individual SNPs, as well as, multilocus haplotypes. We also examined surrogates of hormone exposure as potential modifiers of the putatively functional Ex4-12 SNP-breast cancer association. Odds ratios (OR) and 95% confidence intervals (CI) were based on age-adjusted unconditional logistic regression models. We found no association between the individual SNPs alone and breast cancer. When examining the association between breast cancer and the 3-SNP haplotypes, we observed a 19% increase in risk associated with each copy of the TGG haplotype (OR=1.19, 95% CI 0.96-1.49), relative to the common TAA haplotype, which was statistically significant when assuming a dominant model (OR=1.32, 95% CI 1.05-1.67, p-value=0.02). In this report of COMT haplotypes and breast cancer, we found some evidence that additional genetic variability beyond the Ex4-12 G > A SNP contributes to risk of breast cancer among a small subgroup of women; however, these results need to be replicated in additional studies. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14222 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27516 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. Pfizer Inc, Worldwide Safety & Risk Management, Global Epidemiol, New York, NY 10017 USA. CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. Bioserve Biotechnol Ltd, Laurel, MD 20707 USA. RP Gaudet, MM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-7055, Rockville, MD 20852 USA. EM gaudetm@mail.nih.gov FU NCI NIH HHS [P50CA55283, P50CA58223, U01CA/ES66572, U01CA66572]; NIEHS NIH HHS [P30 ES009089, P30ES09089, P30ES10126] NR 32 TC 17 Z9 17 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 SEP PY 2006 VL 99 IS 2 BP 235 EP 240 DI 10.1007/s10549-006-9205-0 PG 6 WC Oncology SC Oncology GA 077GI UT WOS:000240016500014 PM 16596327 ER PT J AU Bodenreider, O Stevens, R AF Bodenreider, Olivier Stevens, Robert TI Bio-ontologies: current trends and future directions SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE bio-ontology; medical ontology; annotation; knowledge; knowledge representation; history ID BIOMEDICAL ONTOLOGIES; MEDICAL ONTOLOGIES; FOUNDATIONAL MODEL; PUBLIC-HEALTH; BIOINFORMATICS; CARE; TERMINOLOGIES; INFORMATICS; INTEGRATION; DESIDERATA AB In recent years, as a knowledge-based discipline, bioinformatics has been made more computationally amenable. After its beginnings as a technology advocated by computer scientists to overcome problems of heterogeneity, ontology has been taken up by biologists themselves as a means to consistently annotate features from genotype to phenotype. In medical informatics, artifacts called ontologies have been used for a longer period of time to produce controlled lexicons for coding schemes. In this article, we review the current position in ontologies and how they have become institutionalized within biomedicine. As the field has matured, the much older philosophical aspects of ontology have come into play. With this and the institutionalization of ontology has come greater formality. We review this trend and what benefits it might bring to ontologies and their use within biomedicine. C1 Natl Lib Med, Cognit Sci Branch, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. RP Bodenreider, O (reprint author), Natl Lib Med, Cognit Sci Branch, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike,MS 3841, Bethesda, MD 20894 USA. EM olivier@nlm.nih.gov RI Smith, Barry/A-9525-2011 OI Smith, Barry/0000-0003-1384-116X FU Intramural NIH HHS [Z99 LM999999] NR 75 TC 155 Z9 160 U1 3 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD SEP PY 2006 VL 7 IS 3 BP 256 EP 274 DI 10.1093/bib/bbl027 PG 19 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 090PZ UT WOS:000240964500005 PM 16899495 ER PT J AU Chesney, MA Neilands, TB Chambers, DB Taylor, JM Folkman, S AF Chesney, Margaret A. Neilands, Torsten B. Chambers, Donald B. Taylor, Jonelle M. Folkman, Susan TI A validity and reliability study of the coping self-efficacy scale SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article ID MEN; HIV; STRESS; FIT; OPTIMISM; OUTCOMES; EMOTION; HEALTH; RISK; AIDS AB Objectives. Investigate the psychometric characteristics of the coping self-efficacy (CSE) scale, a 26-item measure of one's confidence in performing coping behaviors when faced with life challenges. Design. Data came from two randomized clinical trials (NI = 149, N2 = 199) evaluating a theory-based Coping Effectiveness Training (CET) intervention in reducing psychological distress and increasing positive mood in persons coping with chronic illness. Methods. The 348 participants were HIV-seropositive men with depressed mood who have sex with men. Participants were randomly assigned to intervention and comparison conditions and assessed pre- and post-intervention. Outcome variables included the CSE scale, ways of coping, and measures of social support and psychological distress and well-being. Results. Exploratory (EFA) and confirmatory factor analyses (CFA) revealed a 13-item reduced form of the CSE scale with three factors: Use problem-focused coping (6 items, alpha =.91), stop unpleasant emotions and. thoughts (4 items, alpha =.9 1), and get support from friends and family (3 items, alpha =.80). Internal consistency and test-retest reliability are strong for all three factors. Concurrent validity analyses showed these factors assess self-efficacy for different types of coping. Predictive validity analyses showed that residualized change scores in using problem- and emotion-focused coping skills were predictive of reduced psychological distress and increased psychological well-being over time. Conclusions. The CSE scale provides a measure of a person's perceived ability to cope effectively with life challenges, as well as a way to assess changes in CSE over time in intervention research. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. RP Chesney, MA (reprint author), NIH, Natl Ctr Complementary & Alternat Med, 31 Ctr Dr,Room 2B11,MSC2182, Bethesda, MD 20892 USA. EM chesneym@mail.nih.gov FU NIMH NIH HHS [R01 MH057233, R01-MH46805, R01-MH57233] NR 45 TC 130 Z9 134 U1 0 U2 43 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 1359-107X J9 BRIT J HEALTH PSYCH JI Br. J. Health Psychol. PD SEP PY 2006 VL 11 BP 421 EP 437 DI 10.1348/135910705X53155 PN 3 PG 17 WC Psychology, Clinical SC Psychology GA 077JC UT WOS:000240024100005 PM 16870053 ER PT J AU Kazerouni, N Greene, MH Lacey, JV Mink, PJ Schairer, C AF Kazerouni, Neely Greene, Mark H. Lacey, James V., Jr. Mink, Pamela J. Schairer, Catherine TI Family history of breast cancer as a risk factor for ovarian cancer in a prospective study SO CANCER LA English DT Article DE breast cancer; family history; ovarian cancer ID WOMEN; SUSCEPTIBILITY; ASSOCIATION; RELATIVES; MORTALITY; IMPACT AB BACKGROUND. A family history of breast cancer has been associated with increased ovarian cancer risk. However, few studies have assessed risk according to characteristics that suggest an inherited cancer susceptibility disorder, such as earlier-than-usual age at cancer diagnosis, family members with double primary cancers of different types, multiple relatives with cancer, and cancer in both members of paired organs. METHODS. ovarian cancer risk was assessed according to a detailed breast cancer family history among 49,975 participants in the Breast Cancer Detection Demonstration Project Breast Cancer Defection Demenstration Project (BCDDP) Followup Study (1979-1998). In all, 362 incident ovarian cancers were identified during follow-up and rate ratios (RRs) were calculated by Poisson regression. RESULTS. Breast cancer in a first- or second-degree relative was associated with increased risk of ovarian cancer (RR = 1.4; 95% confidence interval [CI] = 1.11.7). Having 2 or more affected first-degree relatives was associated with increased risk (RR = 1.8; 95% Cl 1.1-2.8), especially for women diagnosed with ovarian cancer before age 60 (RR 4.2; 95% Cl = 1.9-9.2) or with a personal history of breast cancer (RR = 3.7; 95% Cl 1.8-7.7). Risk was also particularly high for women with 2 or more first-degree relatives with breast cancer and at least I affected relative diagnosed before age 50 (RR = 2.6; 95% Cl = 1.4-4.8) or with bilateral breast cancer (RR = 4.2; 95% Cl = 1.7-10). CONCLUSIONS. A detailed breast cancer family history as well as an individual's age and personal history of breast cancer are useful for identifying women at elevated genetic risk of ovarian cancer. C1 NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, Hormone & Reprod Epidemiol Branch, NIH, Rockville, MD USA. Exponent Hlth Grp, Washington, DC USA. NCI, Div Canc Epidemiol Biostat Branch, NIH, Rockville, MD USA. RP Schairer, C (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, 6120 Execut Blvd EPS,Room 8030-MSC 7234, Rockville, MD 20852 USA. EM schairec@exchange.nih.gov FU Intramural NIH HHS NR 27 TC 11 Z9 11 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2006 VL 107 IS 5 BP 1075 EP 1083 DI 10.1002/cncr.22082 PG 9 WC Oncology SC Oncology GA 077TV UT WOS:000240054200023 PM 16881078 ER PT J AU Stewart, SL Wike, JM Kato, I Lewis, DR Michaud, F AF Stewart, Sherri L. Wike, Jennifer M. Kato, Ikuko Lewis, Denise R. Michaud, Frances TI A population-based study of colorectal cancer histology in the United States, 1998-2001 SO CANCER LA English DT Review DE colorectal; cancer; histology; adenocarcinoma; signet ring; sarcoma; mucin; epidemiology; surveillance ID RING CELL-CARCINOMA; 40 YEARS OLD; TUMORS; COLON; RECTUM; ADENOCARCINOMAS; SURVIVAL; EPIDEMIOLOGY; EXPERIENCE; POLYPS AB BACKGROUND. Histology is an important factor in the etiology, treatment, and prognosis of cancer. The purpose of this study was to descriptively characterize colorectal cancer (CRC) histology in the United States population. METHODS. Data from cancer registries in the National Program of Cancer Registries (NPCR) or Surveillance, Epidemiology and End Results (SEER) program, representing 88% of the U.S. population, were used in the study. The analysis included 522,630 microscopically confirmed CRC cases diagnosed from 1998-2001. RESULTS. About 96% of CRCs were adenocarcinomas, approximately 2% were other specified carcinomas (including carcinoid tumors), about 0.4% were epidermoid carcinomas, and about 0.08% were sarcomas. The proportion of epidermoid carcinomas, mucin-producing carcinomas, and carcinoid tumors was greater among females. Several histologic patterns with regard to race and ethnicity existed, including a higher percentage of carcinoid tumors among most non-white populations. With respect to age, higher percentages of sarcomas, mucin-producing adenocarcinomas, signet ring cell tumors, and carcinoid tumors were found in individuals under age 40. Overall, adenocarcinomas were more likely to be diagnosed at regional stages with moderate differentiation. Compared with other adenocarcinomas, signet ring cell tumors were more often poorly differentiated and were at distant stage at diagnosis. Carcinoid tumors and sarcomas were mainly poorly differentiated and were at localized stage at diagnosis. Small cell carcinomas were more likely undifferentiated and were at distant stage at diagnosis. CONCLUSIONS. To date, this is the largest population-based study to analyze CRC histology in the United States. Distinct demographic and clinical patterns associated with different histologies may be helpful for future epidermiologic, laboratory, and clinical studies. C1 Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. CDC, NPCR Contractor, Northrop Grumman, Atlanta, GA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. NCI, NIH, Bethesda, MD USA. RP Stewart, SL (reprint author), CDC, 4770 Buford Highway,K-53, Atlanta, GA 30341 USA. EM sstewart2@cdc.gov NR 44 TC 26 Z9 29 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 SEP 1 PY 2006 VL 107 IS 5 SU S BP 1128 EP 1141 DI 10.1002/cncr.22010 PG 14 WC Oncology SC Oncology GA 079BT UT WOS:000240151200005 PM 16802325 ER PT J AU Fairley, TL Cardinez, CJ Martin, J Alley, L Friedman, C Edwards, B Jamison, P AF Fairley, Temeika L. Cardinez, Cheryll J. Martin, Jim Alley, Linda Friedman, Carol Edwards, Brenda Jamison, Patricia TI Colorectal cancer in US adults younger than 50 years of age, 1998-2001 SO CANCER LA English DT Review DE young adults; colorectal; cancer; incidence; colon; rectal; screening ID PATIENTS LESS; UNITED-STATES; COLON-CANCER; CARCINOMA; POPULATION; SUBSITE; RATES; STAGE; RISK; RACE AB BACKGROUND. Colorectal cancer (CRC) incidence rates are increasing among persons younger than 50 years of age, a population routinely not screened unless an individual has a high risk of CRC. This population-based study focuses primarily on describing the CRC burden for persons in this age group. METHODS. The data used for this study were derived from the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) surveillance systems. Age-adjusted incidence rates, rate ratios, and their corresponding 95% confidence intervals were calculated. RESULTS. CRC is ranked among the top 10 cancers occurring in males and females aged 20-49 years regardless of race. Persons younger than 50 years were more likely to present with less localized and more distant disease than do older adults. Among younger adults, age-adjusted incidence rates for poorly differentiated cancers were twice as high as rates for well-differentiated cancers. Incidence rates for poorly differentiated cancers were 60% higher than that for well-differentiated cancers diagnosed in older adults. Rates were significantly higher for blacks and significantly lower for Asians/Pacific Islanders when compared with that for whites for the most demographic and tumor characteristics examined. CONCLUSIONS. This study confirms the findings of previous population-based studies suggesting that younger patients present with more advanced disease than do older patients. This study also identifies racial and ethnic disparities in CRC incidence in this population. These findings suggest the need for additional studies to understand the behavior and etiology of CRC in blacks. C1 Ctr Dis Control & Prevent, Div Canc Prevent & Control, Comprehens Canc Control Branch, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. Virginia Canc Registry, Virginia Dept Hlth, Richmond, VA USA. NCI, Canc Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Fairley, TL (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Comprehens Canc Control Branch, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy,NE K-57, Atlanta, GA 30341 USA. EM tfairley@cdc.gov NR 41 TC 74 Z9 74 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 SEP 1 PY 2006 VL 107 IS 5 SU S BP 1153 EP 1161 DI 10.1002/cncr.22012 PG 9 WC Oncology SC Oncology GA 079BT UT WOS:000240151200007 PM 16862554 ER PT J AU Ahmed, F Goodman, MT Kosary, C Ruiz, B Wu, XC Chen, VW Correa, CN AF Ahmed, Faruque Goodman, Marc T. Kosary, Carol Ruiz, Bernardo Wu, Xiao-Cheng Chen, Vivien W. Correa, Catherine N. TI Excess risk of subsequent primary cancers among colorectal carcinoma survivors, 1975-2001 SO CANCER LA English DT Review DE colorectal neoplasms; second primary neoplasms; uterine neoplasms; ovarian neoplasms; stomach neoplasms; gastrointestinal neoplasms; pancreatic neoplasms; prostatic neoplasms; kidney neoplasms; breast neoplasms ID 2ND PRIMARY CANCERS; PROSTATE-CANCER; BRAIN-TUMORS; ASSOCIATION; COLON; RECTUM; SITES; NEOPLASMS AB BACKGROUND. Studies of persons with colorectal cancer have reported increased risk of subsequent primary cancers. Results have not been consistent, however, and there is little information about such risk in specific races and ethnic populations. METHODS. Using 1975-2001 data from the Surveillance, Epidemiology, and End Results (SEER) Program, we assembled 262,600 index cases of colorectal carcinoma to assess the occurrence of subsequent primary cancers in 13 noncolonic sites. Observed (0) subsequent cancers were compared with those expected (E) based on age-/sex-/race-/year-/site-specific rates in the SEER population. The standardized incidence ratio (SIR) and the absolute excess risk (AER) represent 'O divided by E' and 'O - E,' respectively. RESULTS. Colorectal carcinoma patients had significantly elevated SIRs for small gut, stomach (males), kidney, and corpus uteri cancers, ranging from 1.13 for stomach cancer in males to 3.45 for small gut cancer in females. Elevated SIRs for additional sites were seen in certain population subgroups: pancreas and ovary in persons aged < 50 years, and prostate in black males. The excess burden, as assessed by AER, was notable for prostate cancer in black males and for corpus uteri cancer in females aged < 50 years (26.5 and 9.5 cancers per 10,000 person-years, respectively), and it persisted beyond 5 years of follow-up. CONCLUSIONS. Although significantly elevated SIRs were found for several cancers, the excess burden was notable only for cancer of the prostate in black males and of the corpus uteri in females under age 50. C1 Ctr Dis Control & Prevent, Div Canc Prevent & Control, Canc Surveillance Branch, Atlanta, GA 30341 USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. NCI, Canc Stat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. Louisiana State Univ, Hlth Sci Ctr, Louisiana Tumor Registry, Epidemiol Program,Sch Publ Hlth, New Orleans, LA USA. RP Ahmed, F (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Canc Surveillance Branch, 4770 Buford Hwy NE,MS K-53, Atlanta, GA 30341 USA. EM fahmed@cdc.gov NR 38 TC 21 Z9 22 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2006 VL 107 IS 5 SU S BP 1162 EP 1171 DI 10.1002/cncr.22013 PG 10 WC Oncology SC Oncology GA 079BT UT WOS:000240151200008 PM 16838312 ER PT J AU Coughlin, SS Richards, TB Thompson, T Miller, BA VanEenwyk, J Goodman, MT Sherman, RL AF Coughlin, Steven S. Richards, Thomas B. Thompson, Trevor Miller, Barry A. VanEenwyk, Juliet Goodman, Marc T. Sherman, Recinda L. TI Rural/nonrural differences in colorectal cancer incidence in the United States, 1998-2001 SO CANCER LA English DT Review DE Asians and Pacific Islanders; blacks; colorectal cancer; Hispanics; incidence; poverty ID RATES; WOMEN; MEN AB BACKGROUND. Few studies of colorectal cancer incidence by rural, suburban, and metropolitan residence have been published. METHODS. The authors examined colorectal cancer incidence among men and women in U.S. counties classified as rural, suburban, and metropolitan for the period 1998-2001. They examined rural/suburban/metropolitan differences in incidence by age, race, Hispanic ethnicity, stage at diagnosis, histology, and percentage of the total county population below the poverty level, using data from the CDC's National Program of Cancer Registries, the NCI's Surveillance, Epidemiology, and End Results Program, and the 2000 U.S. Census. RESULTS. A total of 495,770 newly diagnosed or incident cases of colorectal cancer were included in this analysis (249,919 among men and 245,851 among women). Over the period 1998-2001, the colorectal cancer incidence rates among men tended to be lower among those who resided in rural areas, for each of the subgroups examined, with the exception of Asians and Pacific Islanders and those living in more affluent counties. Among women aged 75 years and older, the colorectal cancer incidence rates tended to be lower among rural than metropolitan or suburban residents, though the differences were slight. In multivariate analysis, the incidence of colorectal cancer was higher in metropolitan, suburban, and rural areas for blacks than that for whites (incidence rate ratios [RR] 1.12, 1.07, and 1.06, respectively, all P < 0.015). CONCLUSIONS. This study suggests that black men who reside in metropolitan areas have a higher risk of colorectal cancer than black men who reside in rural areas. This finding suggests the need for diverse approaches for reducing colorectal cancer when targeting rural compared with metropolitan areas. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, Atlanta, GA 30341 USA. NCI, Canc State Branch, Div Control & Populat Sci, Bethesda, MD USA. Washington State Dept Hlth, Olympia, WA USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. Oregon State Canc Registry, Portland, OR USA. RP Coughlin, SS (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, 4770 Buford Hwy,NE K-55, Atlanta, GA 30341 USA. EM sic9@cdc.gov NR 21 TC 23 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2006 VL 107 IS 5 SU S BP 1181 EP 1188 DI 10.1002/cncr.22015 PG 8 WC Oncology SC Oncology GA 079BT UT WOS:000240151200010 PM 16802323 ER PT J AU Jakowlew, SB AF Jakowlew, Sonia B. TI Transforming growth factor-beta in cancer and metastasis SO CANCER AND METASTASIS REVIEWS LA English DT Review DE TGF-beta; tumor suppressor; pro-oncogene; proliferation; invasion ID HUMAN BREAST-CANCER; SQUAMOUS-CELL CARCINOMA; PROSTATIC STROMAL CELLS; RECEPTOR-TYPE-II; P38 MAP KINASE; SIGNAL-TRANSDUCTION PATHWAYS; MOUSE LUNG CARCINOGENESIS; BIGLYCAN GENE-EXPRESSION; HUMAN GASTRIC-CANCER; MAMMARY-TUMOR CELLS AB Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory polypeptide that is the prototypical member of a large family of cytokines that controls many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. The actions of TGF-beta are dependent on several factors including cell type, growth conditions, and the presence of other polypeptide growth factors. One of the biological effects of TGF-beta is the inhibition of proliferation of most normal epithelial cells using an autocrine mechanism of action, and this suggests a tumor suppressor role for TGF-beta. Loss of autocrine TGF-beta activity and/or responsiveness to exogenous TGF-beta appears to provide some epithelial cells with a growth advantage leading to malignant progression. This suggests a pro-oncogenic role for TGF-beta in addition to its tumor suppressor role. During the early phase of epithelial tumorigenesis, TGF-beta inhibits primary tumor development and growth by inducing cell cycle arrest and apoptosis. In late stages of tumor progression when tumor cells become resistant to growth inhibition by TGF-beta due to inactivation of the TGF-beta signaling pathway or aberrant regulation of the cell cycle, the role of TGF-beta becomes one of tumor promotion. Resistance to TGF-beta-mediated inhibition of proliferation is frequently observed in multiple human cancers, as are various alterations in the complex TGF-beta signaling and cell cycle pathways. TGF-beta can exert effects on tumor and stromal cells as well as alter the responsiveness of tumor cells to TGF-beta to stimulate invasion, angiogenesis, and metastasis, and to inhibit immune surveillance. Because of the dual role of TGF-beta as a tumor suppressor and pro-oncogenic factor, members of the TGF-beta signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis, as well as molecular targets for prevention and treatment of cancer and metastasis. C1 NCI, Cell & Canc Biol Branch, Rockville, MD 20850 USA. RP Jakowlew, SB (reprint author), NCI, Cell & Canc Biol Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM jakowles@mail.nih.gov FU Intramural NIH HHS NR 211 TC 272 Z9 279 U1 0 U2 12 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD SEP PY 2006 VL 25 IS 3 BP 435 EP 457 DI 10.1007/s10555-006-9006-2 PG 23 WC Oncology SC Oncology GA 114HK UT WOS:000242657100012 PM 16951986 ER PT J AU Dancey, JE AF Dancey, Janet E. TI Therapeutic targets - MTOR and related pathways SO CANCER BIOLOGY & THERAPY LA English DT Review DE mammalian target of rapamycin; sirolimus; temsirolimus; everolimus; AP34573 ID PHASE-II TRIAL; TUBEROUS SCLEROSIS COMPLEX; HUMAN PROSTATE-CANCER; LYMPHOPROLIFERATIVE-DISEASE TREATMENT; RECURRENT GLIOBLASTOMA-MULTIFORME; EARLY CYCLOSPORINE WITHDRAWAL; INDUCIBLE FACTOR 1-ALPHA; CELL-CYCLE INHIBITOR; INDUCED G(1) ARREST; TEMSIROLIMUS CCI-779 AB The mammalian target of rapamycin (mTOR), a protein kinase of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, has a central role in controlling malignant cellular growth. As a result, mTOR is viewed as an important target for anticancer drug development. Inhibitors of mTOR currently under evaluation in cancer clinical trials are rapamycin (also known as sirolimus, Wyeth) and derivatives temsirolimus (CCI-779, Wyeth), everolimus, (RAD001, Novartis Pharma AG), and AP23573 (Ariad Pharmaceuticals). Preclinical studies suggest that sensitivity to mTOR inhibitors may correlate with activation of the PI3K pathway and/or with aberrant expression of cell cycle regulatory or anti-apoptotic proteins. Clinical trial results show that mTOR inhibitors are well tolerated and may induce prolonged stable disease and tumor regressions in cancer patients. Future research should evaluate optimal, schedule, patient selection, and combination strategies for this novel class of agents. C1 NCI, Invest Drug Branch, CTEP, DCTD, Rockville, MD 20852 USA. RP Dancey, JE (reprint author), NCI, Invest Drug Branch, CTEP, DCTD, 6130 Execut Blvd,Room 7131, Rockville, MD 20852 USA. EM danceyj@mail.nih.gov NR 99 TC 127 Z9 131 U1 1 U2 10 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 SEP PY 2006 VL 5 IS 9 BP 1065 EP 1073 DI 10.4161/cbt.5.9.3175 PG 9 WC Oncology SC Oncology GA 117CE UT WOS:000242849500012 PM 16969122 ER PT J AU Beverage, JN Figg, WD AF Beverage, Jacob N. Figg, William D. TI The quantification of PSA mRNA copies in pathologically normal pelvic lymph nodes is a viable prognostic indicator SO CANCER BIOLOGY & THERAPY LA English DT Article DE biochemical failure; prostate; metastases; prognostic ID PROSTATE-SPECIFIC ANTIGEN; RADICAL RETROPUBIC PROSTATECTOMY; CANCER; PROGRESSION; RADIATION; THERAPY; MEN AB Localized prostate cancer is a disease associated with significant biochemical recurrence with rising serum prostate-specific antigen (PSA) levels and marked progression. More specific prognostic methods are needed to identify the occult micrometastases that lead to biochemical recurrence. Ferrari et al. report on the technique of quantifying pathologically occult metastases in pelvic lymph nodes via PCR quantification. The group reports statistically significant biochemical failurefree recurrence in the comparison of 100 or greater normalized PSA mRNA copies (PSA-N) versus PSA-N of less than 100 at a median follow up of four years. PSA-N quantification appears to be an important method for predicting biochemical recurrence and characterizing the recurrence risk of localized prostate cancer patients with pathologically normal pelvic lymph nodes. This method warrants further investigation in prospective trials. C1 NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 11 TC 2 Z9 2 U1 0 U2 0 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 SEP PY 2006 VL 5 IS 9 BP 1094 EP 1095 DI 10.4161/cbt.5.9.3287 PG 2 WC Oncology SC Oncology GA 117CE UT WOS:000242849500018 PM 17012834 ER PT J AU Hurt, EM Thomas, SB Peng, B Farrar, WL AF Hurt, Elaine M. Thomas, Suneetha B. Peng, Benjamin Farrar, William L. TI Reversal of p53 epigenetic silencing in multiple myeloma permits apoptosis by a p53 activator SO CANCER BIOLOGY & THERAPY LA English DT Article DE multiple myeloma; p53; methylation; apoptosis; molecular target ID HUMAN CANCER-CELLS; DNA METHYLATION; PROMOTER METHYLATION; GENE-MUTATIONS; WILD-TYPE; PEPTIDE; MDM2; THERAPY; OVEREXPRESSION; PROLIFERATION AB Inactivation of the p53 pathway is a common feature of neoplasia. Dysregulation of the p53 pathway has been shown to involve mutations of p53, increased expression of the p53 inhibitor HDM-2, or epigenetic silencing of the p53 promoter. In multiple myeloma, a neoplasia of terminally differentiated B cells, p53 mutations and deletions are relatively rare and occur in late stage disease. Here, we show that the p53 promoter is hypermethylated in several multiple myeloma cell lines in comparison to normal plasma cells. Two cell lines containing mutant p53, Lp-1 and OPM-2, show a methylation pattern that suggests that they contain one methylated and one unmethylated mutant allele. Two other cell lines, KMS-11 and OPM-2, show hypermethylation of p53 with a lack of expression. In all cell lines tested, treatment with a demethylating agents results in higher expression of p53. Furthermore, following increased expression of p53, treatment of the myeloma cell lines with a p53 activating peptide induces apoptosis. Therefore, combinatorial treatment with demethylating agents followed by delivery of a p53 activating peptide may be an effective therapeutic strategy against multiple myeloma. C1 NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. Univ Melbourne, Sch Dent Sci, Melbourne, Vic 3000, Australia. RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, 1050 Boyles St,Bldg 560,Room 31-68, Frederick, MD 21702 USA. EM farrar@mail.ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 35 TC 18 Z9 19 U1 1 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 SEP PY 2006 VL 5 IS 9 BP 1154 EP 1160 DI 10.4161/cbt.5.9.3001 PG 7 WC Oncology SC Oncology GA 117CE UT WOS:000242849500031 PM 16855375 ER PT J AU Samanic, C Chow, WH Gridley, G Jarvholm, B Fraumeni, JF AF Samanic, Claudine Chow, Wong-Ho Gridley, Gloria Jarvholm, Bengt Fraumeni, Joseph F., Jr. TI Relation of body mass index to cancer risk in 362,552 Swedish men SO CANCER CAUSES & CONTROL LA English DT Article DE obesity; cancer incidence; body mass index; Sweden ID CUTANEOUS MALIGNANT-MELANOMA; ORAL-CONTRACEPTIVE USE; CELL ESOPHAGEAL CANCER; MILLION NORWEGIAN MEN; NON-HODGKINS-LYMPHOMA; LIFE-STYLE FACTORS; PANCREATIC-CANCER; PROSTATE-CANCER; REPRODUCTIVE FACTORS; COLORECTAL-CANCER AB Obesity has been linked with increased risk for cancers of the colon, kidney, breast, endometrium and gallbladder. For other cancer sites, the relationship with obesity is less well quantified, and the effect of weight change on cancer risk is unclear. We examined the health records of 362,552 Swedish men who underwent at least one physical examination from 1971 to 1992, and were followed until death or the end of 1999. Incident cancer cases were identified by linkage to the Swedish cancer registry. Poisson regression models were used to estimate relative risks of cancer for both body-mass index (BMI) at baseline exam and, in a subgroup of 107,815 men, change in BMI after six years of follow-up, adjusting for age and smoking status. Compared to men of normal weight, obese men had a significantly increased risk of all cancers combined (RR = 1.1; 95% CI = 1.0-1.2). The risks were most pronounced for esophageal adenocarcinoma (RR = 2.7; 95% CI = 1.3-5.6), renal cell carcinoma (RR = 1.8; 95% CI = 1.4-2.4), malignant melanoma (RR = 1.4; 95% CI = 1.1-1.7), and cancers of the colon (RR = 1.7; 95% CI = 1.5-2.0), rectum (RR = 1.4; 95% CI = 1.1-1.7), and liver (RR = 3.6; 95% CI = 2.6-5.0). Risk of esophageal squamous cell carcinoma was elevated for underweight men whose BMI was less than 18.5 (RR = 3.1; 95% CI = 1.1-8.3). An excess risk for cancers of the pancreas and connective tissue was observed only among nonsmokers. Compared to men whose weight remained stable, men with more than a 15% increase in BMI after six years of follow-up had an elevated risk of pancreas and renal cell cancers. Obesity and weight gain increase the risk for several forms of cancer in men, and underscore the need for further study into carcinogenic mechanisms and preventive interventions. C1 NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. RP Samanic, C (reprint author), NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 8115, Bethesda, MD 20892 USA. EM samanicc@mail.nih.gov FU Intramural NIH HHS NR 93 TC 205 Z9 216 U1 7 U2 16 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2006 VL 17 IS 7 BP 901 EP 909 DI 10.1007/s10552-006-0023-9 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 063SO UT WOS:000239040100004 PM 16841257 ER PT J AU Warren, K Jakacki, R Widemann, B Aikin, A Libucha, M Packer, R Vezina, G Reaman, G Shaw, D Krailo, M Osborne, C Cehelsky, J Caldwell, D Stanwood, J Steinberg, SM Balis, FM AF Warren, K Jakacki, R Widemann, B Aikin, A Libucha, M Packer, R Vezina, G Reaman, G Shaw, D Krailo, M Osborne, C Cehelsky, J Caldwell, D Stanwood, J Steinberg, SM Balis, FM TI Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children's Oncology Group SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE brain tumors; lobradimil; children; ependymoma; glioma; medulloblastoma; phase II; RMP-7 ID INTRACAROTID INFUSION; BRADYKININ ANALOG; MALIGNANT GLIOMA; RMP-7 AB Backround: Lobradimil is a synthetic bradykinin analog that rapidly and transiently increases the permeability of the blood-brain barrier (BBB). The combination of lobradimil and carboplatin was studied in pediatric patients with primary brain tumors in a phase II trial, the primary endpoints of which were to estimate the response rate and time to disease progression. Patients and methods: Patients were stratified by histology into five cohorts: brainstem glioma, high-grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve a target AUC of 3.5 mg min/ml per day (7 mg center dot min/ml/cycle) intravenously over 15 min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2 consecutive days each 28 day cycle. Results: Forty-one patients, age 2-19 years, were enrolled; 38 patients, including 1 patient ultimately determined to have atypical neurocytoma, were evaluable for response. No objective responses were observed in the brainstem glioma (n=12) and high-grade glioma (n=9) cohorts, although two patients with high-grade glioma had prolonged disease stabilization (> 6 months). The study was closed for commercial reasons prior to achieving the accrual goals for the ependymoma (n=8), medulloblastoma/PNET (n=6) and low-grade glioma (n=2) cohorts, although responses were observed in 1 patient with PNET and 2 patients with ependymoma. Conclusion: The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas. C1 NCI, Neurooncol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Washington, DC USA. Childrens Hosp Pittsburgh, Washington, DC USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Oncol Grp, Cambridge, MA USA. Alkermes Inc, Cambridge, MA USA. NCI, Biostat & Data Management Sect, Washington, DC USA. RP Warren, K (reprint author), NCI, Neurooncol Branch, Bldg 82,Rm 219,9030 Old Georgetown Rd, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov FU Intramural NIH HHS NR 14 TC 50 Z9 50 U1 0 U2 0 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 SEP PY 2006 VL 58 IS 3 BP 343 EP 347 DI 10.1007/s00280-005-0172-7 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 046PO UT WOS:000237823700007 PM 16408203 ER PT J AU Vaught, JB AF Vaught, Jimmie B. TI Biorepository and Biospecimen Science: A new focus for CEBP SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Vaught, JB (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM vaughtj@mail.nih.gov NR 4 TC 20 Z9 21 U1 1 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 SEP PY 2006 VL 15 IS 9 BP 1572 EP 1573 DI 10.1158/1055-9965.EPI-06-0632 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800002 PM 16985012 ER PT J AU Vaught, JB AF Vaught, Jimmie B. TI Blood collection, shipment, processing, and storage SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT Methods Workshop on Sample Collection, Processing and Storage for Large Scale Studies CY APR 01, 2006 CL Washington, DC SP Amer Assoc Canc Res AB As part of the AACR Annual Meeting Methods Workshop "Sample Collection, Processing, and Storage for Large-Scale Studies: Biorepositories to Support Cancer Research," blood specimen collection, processing, storage, and dissemination issues were discussed. Whole blood and blood fractions comprise a major portion of biospecimen collections for population-based studies. Although procedures for collecting, processing, storing, and shipping blood components are generally standardized and well documented, several important factors need to be considered before a new study involving blood collection is initiated. Blood is collected from study participants for a variety of purposes, including as a source of DNA, and for a variety of laboratory analyses that may be done on whole blood or blood fractions, including serum, plasma, and lymphocytes. Blood or blood fractions may be shipped to laboratories and biorepositories either at ambient temperature, cooled or frozen, depending on the intended analyses. Blood processing may include fractionation, cryopreservation to preserve the viability of lymphocytes, or purification of nucleic acids. The proper storage conditions depend on a variety of factors, including the intended analyses and whether the specimens will be used within a short period or need to be stored for longer periods. As for all laboratory and biorepository procedures, blood collection, shipment, processing, and storage should be conducted under a strict quality assurance program, including standard operating procedures and regular quality control reviews. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Vaught, JB (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, EPS 7030,MSC 7242, Bethesda, MD 20892 USA. EM vaughtj@mail.nih.gov NR 13 TC 43 Z9 45 U1 3 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2006 VL 15 IS 9 BP 1582 EP 1584 DI 10.1158/1055-9965.EPI-06-0630 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800006 PM 16985016 ER PT J AU Lou, JR Fatima, N Xiao, Z Stauffer, S Smythers, G Greenwald, P Ali, IU AF Lou, Jianrong Fatima, Naheed Xiao, Zhen Stauffer, Stacy Smythers, Gary Greenwald, Peter Ali, Iqbal Unnisa TI Proteomic profiling identifies cyclooxygenase-2-independent global proteomic changes by celecoxib in colorectal cancer cells SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INHIBITOR CELECOXIB; LUNG-CANCER; ADENOMATOUS POLYPOSIS; GEL-ELECTROPHORESIS; GROWTH-INHIBITION; INDUCE APOPTOSIS; CYCLE REGULATION; MAP KINASE; IN-VITRO; LINES AB Celecoxib, a selective inhibitor of the enzyme cyclooxygenase-2 (COX-2), has been shown to be a promising chemo-prevention agent. The chemopreventive efficacy of celecoxib is believed to be a consequence of its COX-2-dependent and COX-2-independent effects on a variety of cellular processes including proliferation, apoptosis, angiogenesis, and immunosurveillance. In an attempt to identify proteomic markers modulated by celecoxib that are independent of its inhibitory effect on COX-2, the colorectal cancer cell line HCT-116, a nonexpresser of COX-2, was treated with celecoxib. We used the powerful, state-of-the-art two-dimensional difference gel electrophoresis technology coupled with mass spectrometric sequencing to compare global proteomic profiles of HCT-116 cells before and after treatment with celecoxib. Among the differentially expressed proteins identified following celecoxib treatment were proteins involved in diverse cellular functions including glycolysis, protein biosynthesis, DNA synthesis, mRNA processing, protein folding, phosphorylation, redox regulation, and molecular chaperon activities. Our study presents a comprehensive analysis of large-scale celecoxib-modulated proteomic alterations, at least some of which may be mechanistically related to the COX-2-independent chemopreventive effect of celecoxib. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Basic Res Program, Frederick, MD USA. Lab Proteom & Analyt Technol, Frederick, MD USA. Sci Applicat Int Corp, Adv Biomed Comp Ctr, Frederick, MD USA. RP Ali, IU (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM alii@mail.nih.gov RI Ali, Imran/F-7710-2010 OI Ali, Imran/0000-0001-6511-8374 FU PHS HHS [N01-C0-12400] NR 54 TC 27 Z9 30 U1 1 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 SEP PY 2006 VL 15 IS 9 BP 1598 EP 1606 DI 10.1158/1055-9965.EPI-06-0216 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800009 PM 16985019 ER PT J AU Moore, LE Fung, ET McGuire, M Rabkin, CC Molinaro, A Wang, Z Zhang, FJ Wang, J Yip, C Meng, XY Pfeiffer, RM AF Moore, Lee E. Fung, Eric T. McGuire, Marielena Rabkin, Charles C. Molinaro, Annette Wang, Zheng Zhang, Fujun Wang, Jing Yip, Christine Meng, Xiao-Ying Pfeiffer, Ruth M. TI Evaluation of apolipoprotein A1 and posttranslationally modified forms of transthyretin as biomarkers for ovarian cancer detection in an independent study population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROTEOMIC PATTERNS; SERUM PROTEOMICS; CLASSIFICATION; PLASMA; HEALTH AB Background: Although overall 5-year survival rates for ovarian cancer are poor (10-30%), stage I/Ila patients have a 95% 5-year survival. New biomarkers that improve the diagnostic performance of existing tumor markers are critically needed. A previous study by Zhang et al. reported identification and validation of three biomarkers using proteomic profiling that together improved early-stage ovarian cancer detection. Methods: To evaluate these markers in an independent study population, postdiagnostic/pretreatment serum samples were collected from women hospitalized at the Mayo Clinic from 1980 to 1989 as part of the National Cancer Institute Immunodiagnostic Serum Bank. Sera from 42 women with ovarian cancer, 65 with benign tumors, and 76 with digestive diseases were included in this study. Levels of various posttranslationally forms of transthyretin and apolipoprotein A1 were measured in addition to CA125. Results: Mean levels of five of the six forms of transthyretin were significantly lower in cases than in controls. The specificity of a model including transthyretin and apolipoprotein A1 alone was high [96.5%; 95% confidence interval (95% CI), 91.9-98.8%] but sensitivity was low (52.4%; 95% CI, 36.4-68.0%). A class prediction algorithm using all seven markers, CA125, and age maintained high specificity (94.3%; 95% CI, 89.1-97.5%) but had higher sensitivity (78.6%; 95% CI, 63.2-89.7%). Conclusions: We were able to replicate the findings reported by Zhang et al. in an independently conducted blinded study. These results provide some evidence that including age of patient and these markers in a model may improve specificity, especially when CA125 levels are >= 35 units/mL. Influences of sample handling, subject characteristics, and other covariates on biomarker levels require further consideration in discovery and replication or validation studies. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. Ciphergen Biosyst Inc, Fremont, CA USA. RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,EPS 8118, Rockville, MD 20852 USA. EM moorele@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 24 TC 54 Z9 56 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 SEP PY 2006 VL 15 IS 9 BP 1641 EP 1646 DI 10.1158/1055-9965.EPI-05-0980 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800015 PM 16985025 ER PT J AU Lim, U Subar, AF Mouw, T Hartge, P Morton, LM Stolzenberg-Solomon, R Campbell, D Hollenbeck, AR Schatzkin, A AF Lim, Unhee Subar, Amy F. Mouw, Traci Hartge, Patricia Morton, Lindsay M. Stolzenberg-Solomon, Rachael Campbell, David Hollenbeck, Albert R. Schatzkin, Arthur TI Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; NONNUTRITIVE SWEETENERS; ARTIFICIAL SWEETENERS; CONSENSUS CONFERENCE; COHORT; RISK; REPRODUCIBILITY; EPIDEMIOLOGY; REGISTRATION; ASSOCIATION AB Background: In a few animal experiments, aspartame has been linked to hematopoietic and brain cancers. Most animal studies have found no increase in the risk of these or other cancers. Data on humans are sparse for either cancer. Concern lingers regarding this widely used artificial sweetener. Objective: We investigated prospectively whether aspartame consumption is associated with the risk of hematopoietic cancers or gliomas (malignant brain cancer). Methods: We examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet and Health Study cohort. Daily aspartame intake was derived from responses to a baseline self-administered food frequency questionnaire that queried consumption of four aspartame-containing beverages (soda, fruit drinks, sweetened iced tea, and aspartame added to hot coffee and tea) during the past year. Histologically confirmed incident cancers were identified from eight state cancer registries. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression that adjusted for age, sex, ethnicity, body mass index, and history of diabetes. Results: During over 5 years of follow-up (1995-2000), 1,888 hematopoietic cancers and 315 malignant gliomas were ascertained. Higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer (RR for > 600 mg/d, 0.98; 95% CI, 0.76-1.27), glioma (RR for >= 400 mg/d, 0.73; 95% CI, 0.46-1.15; P for inverse linear trend = 0.05), or their subtypes in men and women. Conclusions: Our findings do not support the hypothesis that aspartame increases hematopoietic or brain cancer risk. C1 NCI, Div Canc Control & Populat Sci, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. Div Canc Epidemiol & Genet, Rockville, MD USA. Informat Management Serv Inc, Rockville, MD USA. AARP, Washington, DC USA. RP Subar, AF (reprint author), NCI, Div Canc Control & Populat Sci, Dept Hlth & Human Serv, NIH, 6130 Execut Blvd,EPN 4005, Rockville, MD 20852 USA. EM subara@mail.nih.gov RI Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU Intramural NIH HHS NR 45 TC 40 Z9 40 U1 6 U2 84 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 SEP PY 2006 VL 15 IS 9 BP 1654 EP 1659 DI 10.1158/1055-9965.EPI-06-0203 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800017 PM 16985027 ER PT J AU Fortuny, J Kogevinas, M Garcia-Closas, M Real, FX Tardon, A Garcia-Closas, R Serra, C Carrato, A Lloreta, J Rothman, N Villanueva, C Dosemeci, M Malats, N Silverman, D AF Fortuny, Joan Kogevinas, Manolis Garcia-Closas, Montserrat Real, Francisco X. Tardon, Adonina Garcia-Closas, Reina Serra, Consol Carrato, Alfredo Lloreta, Josep Rothman, Nat Villanueva, Cristina Dosemeci, Mustafa Malats, Nuria Silverman, Debra TI Use of analgesics and nonsteroidal anti-inflammatory drugs, genetic predisposition, and bladder cancer risk in Spain SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RENAL-CELL CARCINOMA; MALE F344 RATS; URINARY-BLADDER; ASPIRIN USE; UROTHELIAL CANCER; ACETAMINOPHEN; POPULATION; DIPYRONE; COHORT; TUMOR AB Background: We assessed use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), aspirin, paracetamol (acetaminophen), phenacetin, and metamizol (dipyrone) and risk of bladder cancer and their interaction with polymorphisms in drug-metabolizing genes. Methods: We analyzed personal interview data from 958 incident bladder cancer cases and 1,029 hospital controls from a multicenter case-control study in Spain. A drug matrix was developed to estimate cumulative lifetime dose of active ingredients. Polymorphisms in GSTP1, SULT1A1, CYP2E1, CYP2C9, and NAT2 were examined. Results: A significant reduction in bladder cancer risk [adjusted odds ratio (OR), 0.4; 95% confidence interval (95% CI) 0.2-0.9] was observed for regular users of nonaspirin NSAIDs compared with never users. Regular users of aspirin experienced no reduction in risk (OR, 1.0; 95% CI, 0.7-1.5). Regular users of paracetamol had no overall increased risk of bladder cancer (OR, 0.8; 95% CL 0.4-1.3), but our data suggested a qualitative interaction with the GSTP1 I105V genotype. Subjects with at least one copy of the 359L or 144C variant alleles in the NSAID-metabolizing gene CYP2C9 had a slightly decreased risk of bladder cancer (OR, 0.8; 95% CI, 0.7-1.0; P = 0.037); however, having at least one copy of the 359L or 144C variant alleles did not significantly modify the protective effect of nonaspirin NSAID use. Conclusion: Regular use of nonaspirin NSAIDs was associated with a reduced risk of bladder cancer, which was not modified by polymorphisms in the NSAID-metabolizing gene CYP2C9. We found no evidence of an overall effect for paracetamol or aspirin use. C1 Municipal Inst Med Res, Ctr Res Environm Epidemiol, Barcelona, Catalonia, Spain. Inst Municipal Invest Med, Unitat Biol Cellular & Mol, E-08003 Barcelona, Catalonia, Spain. Univ Pompeu Fabra, Barcelona, Spain. Univ Autonoma Barcelona, Hosp Mar, IMAS Inst Municipal Invest Med, Dept Pathol, E-08003 Barcelona, Spain. Med Sch Crete, Iraklion, Greece. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Oviedo, Oviedo, Spain. Hosp Univ Canarias, San Cristobal la Laguna, Spain. Consorci Hosp Parc Tali, Catalonia, Spain. Hosp Gen Univ Elx, Elx, Spain. RP Fortuny, J (reprint author), Municipal Inst Med Res, Ctr Res Environm Epidemiol, Barcelona, Catalonia, Spain. EM jfortuny@imim.es RI Serra, C/E-6879-2014; Lloreta, J/I-2112-2014; Garcia-Closas, Montserrat /F-3871-2015; Villanueva, Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015; OI Serra, C/0000-0001-8337-8356; Lloreta, J/0000-0003-1644-9470; Garcia-Closas, Montserrat /0000-0003-1033-2650; Villanueva, Cristina/0000-0002-0783-1259; Real, Francisco X/0000-0001-9501-498X; Malats, Nuria/0000-0003-2538-3784 FU Intramural NIH HHS; NCI NIH HHS [CA34627, N02-CP-11015] NR 56 TC 25 Z9 25 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2006 VL 15 IS 9 BP 1696 EP 1702 DI 10.1158/1055-9965.EPI-06-0038 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800022 PM 16985032 ER PT J AU Ho, M Onda, M Wang, QC Hassan, R Pastan, I Lively, MO AF Ho, Mitchell Onda, Masanori Wang, Qing-cheng Hassan, Raffit Pastan, Ira Lively, Mark O. TI Mesothelin is shed from tumor cells SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter C1 NCI, Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27109 USA. RP Ho, M (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RI Ho, Mitchell/F-5059-2015 NR 5 TC 37 Z9 38 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 SEP PY 2006 VL 15 IS 9 BP 1751 EP 1751 DI 10.1158/1055-9965.EPI-06-0479 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800033 PM 16985043 ER PT J AU Arons, E Sorbara, L Raffeld, M Stetler-Stevenson, M Steinberg, SM Liewehr, DJ Pastan, I Kreitman, RJ AF Arons, E Sorbara, L Raffeld, M Stetler-Stevenson, M Steinberg, SM Liewehr, DJ Pastan, I Kreitman, RJ TI Characterization of T-cell repertoire in hairy cell leukemia patients before and after recombinant immunotoxin BL22 therapy SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE hairy cell leukemia; immunotoxin BL22; T-cell receptor; monoclonal antibody ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TERM-FOLLOW-UP; GRANULAR LYMPHOCYTES; RECEPTOR REPERTOIRE; CLONAL EXPANSION; 2-CHLORODEOXYADENOSINE; CLADRIBINE; RITUXIMAB; DISEASE; ASSOCIATION AB We previously reported that hairy cell leukemia (HCL) patients have high percentages of CD56+/CD57+/CD3+ large granular lymphocytes consistent with cytotoxic T-lymphocytes (CTLs), and other investigators have reported skewing of the T-cell repertoire. In previous studies of up to seven HCL patients, many of the 22 established T-cell receptor (TCR) beta variable region (TRBV) families showed mono- or oligoclonal restriction. To determine whether percentages of CTLs are correlated with TRBV clonal excess, we studied 20 HCL patients with flow cytometry, PCR of TCR gamma and TRBV regions, and fractional gel electrophoresis of PCR-amplified TRBV CDR3 domains (CDR3 spectratyping). Increased percentages of CD3+/CD8+/CD57+ CTLs correlated with more mono/oligoclonal and fewer polyclonal TRBV families (r=0.53; P=0.016). Age correlated with number of mono/oligoclonal TRBV families (r=0.51; P=0.022). Time since last purine analog therapy correlated with number of polyclonal TRBV families (r=0.46; P=0.040), but treatment with the anti-CD22 recombinant immunotoxin BL22 was not related to clonal excess. We conclude that abnormalities in the T-cell repertoire in HCL patients may represent deficient immunity, and may be exacerbated by purine analogs. Increased CD3+/CD57+ T-cells may be a useful marker of abnormal TRBV repertoire in HCL patients, and might prove useful in deciding whether patients should receive biologic antibody-based treatment rather than repeated courses of purine analog for relapsed disease. C1 NCI, Lab Mol Biol & Pathol, NIH, Bethesda, MD 20892 USA. NCI, Lab Biostat, NIH, Bethesda, MD 20892 USA. NCI, Data Management Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), Mol Biol Lab, Clin Immunotherapy Sect, 9000 Rockville Pike,Bldg 37,Room 512B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU Intramural NIH HHS NR 47 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 2006 VL 55 IS 9 BP 1100 EP 1110 DI 10.1007/s00262-005-0099-1 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 046PS UT WOS:000237824100008 PM 16311729 ER PT J AU Williams, CM AF Williams, Cynthia M. TI Dyspnea SO CANCER JOURNAL LA English DT Article ID QUALITY-OF-LIFE; OBSTRUCTIVE PULMONARY-DISEASE; PLACEBO-CONTROLLED CROSSOVER; RANDOMIZED CONTROLLED-TRIAL; ADVANCED CANCER-PATIENTS; VISUAL ANALOG SCALE; NEBULIZED MORPHINE; LUNG-CANCER; FUNCTIONAL-CAPACITY; CARDIORESPIRATORY DISEASES AB Dyspnea, defined as uncomfortable or labored breathing, is a common and often devastating cause of distress for patients and their caregivers with advanced cancer and other life-threatening illnesses. The mechanism by which dyspnea develops is not fully understood, but it involves integration of the central respiratory complex with the sensory (perceptual) cortex. The gold standard of diagnosis is patient self-report. Careful assessment should be undertaken to identify reversible existing causes. Systemic opioids are the first-line therapy for symptomatic management, along with other general comfort measures (positioning, cool air, calming environment). Medical or surgical management can be directed toward underlying causes. Advanced care planning should include discussions concerning the burdens and benefits of medical/surgical management of underlying causes of dyspnea to more effectively direct goals of care. This article reviews current literature on dyspnea, with a focus on items published since 2000. C1 NIH, Bethesda, MD 20892 USA. RP Williams, CM (reprint author), 9233 Singleton Dr, Bethesda, MD 20817 USA. NR 71 TC 12 Z9 14 U1 1 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2006 VL 12 IS 5 BP 365 EP 373 DI 10.1097/00130404-200609000-00006 PG 9 WC Oncology SC Oncology GA 098FD UT WOS:000241505500006 PM 17034673 ER PT J AU Mansky, PJ Wallerstedt, DB AF Mansky, Patrick J. Wallerstedt, Dawn B. TI Complementary medicine in palliative care and cancer symptom management SO CANCER JOURNAL LA English DT Article DE cancer; palliative care; symptom management; complementary medicine ID CONTROLLED CLINICAL-TRIAL; STRESS REDUCTION PROGRAM; PROCEDURE-RELATED PAIN; MINDFULNESS MEDITATION; BREAST-CANCER; ALTERNATIVE MEDICINE; PHASE-II; HYPNOSIS; ACUPUNCTURE; THERAPY AB Complementary and alternative medicine (CAM) use among cancer patients varies according to geographical area, gender, and disease diagnosis. The prevalence of CAM use among cancer patients in the United States has been estimated to be between 7% and 54%. Most cancer patients use CAM with the hope of boosting the immune system, relieving pain, and controlling side effects related to disease or treatment. Only a minority of patients include CAM in the treatment plan with curative intent. This review article ocuses on practices belonging to the CAM domains of mind-body medicine, CAM botanicals, manipulative practices, and energy medicine, because they are widely used a's complementary approaches to palliative cancer care and cancer symptom management. In the area of cancer symptom management, auricular acupuncture, therapeutic touch, and hypnosis may help to manage cancer pain. Music therapy, massage, and hypnosis may have an effect on anxiety, and both acupuncture and massage may have a therapeutic role in cancer fatigue. Acupuncture and selected botanicals may reduce chemotherapy-induced nausea and emesis,and hypnosis and guided imagery may be beneficial in anticipatory nausea and vomiting. Transcendental meditation and the mindfulness-based stress reduction can play a role in the management of depressed mood and anxiety. Black cohosh and phytoestrogen-rich foods may reduce vasomotor symptoms in postmenopausal women. Most CAM approaches to the treatment of cancer are safe when used by a CAM practitioner experienced in the treatment of cancer patients. The potential for many commonly used botanical to interact with prescription drugs continues to be a concern. Botanicals should be used with caution by cancer patients and only under the guidance of an oncologist knowledgeable in their use. C1 NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS, Bethesda, MD 20892 USA. RP Mansky, PJ (reprint author), NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS, 10 Ctr Dr,Bldg 10,CRC,Room 4-1730,MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov NR 50 TC 68 Z9 69 U1 4 U2 37 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2006 VL 12 IS 5 BP 425 EP 431 DI 10.1097/00130404-200609000-00011 PG 7 WC Oncology SC Oncology GA 098FD UT WOS:000241505500011 PM 17034678 ER PT J AU Alfano, CM Rowland, JH AF Alfano, Catherine M. Rowland, Julia H. TI Recovery issues in cancer survivorship: A new challenge for supportive care SO CANCER JOURNAL LA English DT Review DE cancer; survivors; psychosocial factors; review ID QUALITY-OF-LIFE; STAGE BREAST-CANCER; POSTTRAUMATIC-STRESS-DISORDER; PROBLEM-SOLVING INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; LOCALIZED PROSTATE-CANCER; LONG-TERM; PHYSICAL-ACTIVITY; PSYCHOSOCIAL INTERVENTIONS; PSYCHOLOGICAL INTERVENTIONS AB The growing population of cancer survivors represents a clear challenge to clinicians and researchers to look beyond the search for a cure and to address the multifaceted needs of those living with and beyond a cancer diagnosis. Common sequelae that disrupt the psychosocial aspects of life for adult cancer survivors after primary treatment include: fatigue; cognitive changes; body image; sexual health and functioning; infertility; fear of recurrence; PTSD and stress syndromes; family/caregiver distress; socioeconomic issues; and distress, anxiety, and depression. Psychosocial interventions, particularly group-based interventions and physical activity programs, have shown great promise in improving these outcomes. Future research will identify even better targeted, more efficacious, and more cost effective programs and disseminate them into cancer care settings. Healthcare providers must realize that they serve as vital gatekeepers to services that will help optimize cancer survivors' psychosocial as well as physical outcomes. Addressing these issues in the post-treatment period represents the new challenge to supportive care. C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Sch Publ Hlth, Columbus, OH 43210 USA. NCI, NIH, DHHS, Div Canc Control & Populat Sci,Office Canc Surviv, Bethesda, MD 20892 USA. RP Alfano, CM (reprint author), Ohio State Univ, Ctr Comprehens Canc, A343 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM Catherine.Alfano@osumc.edu NR 173 TC 108 Z9 110 U1 5 U2 19 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2006 VL 12 IS 5 BP 432 EP 443 DI 10.1097/00130404-200609000-00012 PG 12 WC Oncology SC Oncology GA 098FD UT WOS:000241505500012 PM 17034679 ER PT J AU Sunde, JS Donninger, H Wu, KM Johnson, NE Pestell, RG Rose, GS Mok, SC Brady, J Bonome, T Birrer, MJ AF Sunde, Jan S. Donninger, Howard Wu, Kongming Johnson, Nhchael E. Pestell, Richard G. Rose, G. Scott Mok, Samuel C. Brady, John Bonome, Tomas Birrer, Michael J. TI Expression profiling identifies altered expression of genes that contribute to the inhibition of transforming growth factor-beta signaling in ovarian cancer SO CANCER RESEARCH LA English DT Article ID RECEPTOR-TYPE-II; TGF-BETA; MUTATION ANALYSIS; PROBABLE TARGET; CELL CARCINOMAS; SMAD PROTEINS; EVI-1; ONCOPROTEIN; MECHANISMS; BINDING AB Ovarian cancer is resistant to the antiproliferative effects of transforming growth factor-beta (TGF-beta); however, the mechanism of this resistance remains unclear. We used oligonucleotide arrays to profile 37 undissected, 68 microdissected advanced-stage, and 14 microdissected early-stage papillary serous cancers to identify signaling pathways involved in ovarian cancer. A total of seven genes involved in TGF-beta signaling were identified that had altered expression > 1.5-fold (P < 0.001) in the ovarian cancer specimens compared with normal ovarian surface epithelium. The expression of these genes was coordinately altered: genes that inhibit TGF-beta signaling (DACH1, BMP7, and EVI1) were up-regulated in advanced-stage ovarian cancers and, conversely, genes that enhance TGF-beta signaling (PCAF, TFE3, TGFBRII, and SMAD4) were down-regulated compared with the normal samples. The microarray data for DACH1 and EVI1 were validated using quantitative real-time PCR on 22 microdissected ovarian cancer specimens. The EVI1 gene locus was amplified in 43% of the tumors, and there was a significant correlation (P = 0.029) between gene copy number and EVI1 gene expression. No amplification at the DACH1 locus was found in any of the samples. DACH1 and EVI1 inhibited TGF-beta signaling in immortalized normal ovarian epithelial cells, and a dominant-negative DACH1, DACH1-Delta DS, partially restored signaling in an ovarian cancer cell line resistant to TGF-beta. These results suggest that altered expression of these genes is responsible for disrupted TGF-beta signaling in ovarian cancer and they may be useful as new and novel therapeutic targets for ovarian cancer. C1 NCI, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Virus Tumor Biol Sect, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Gynecol Oncol, Boston, MA 02115 USA. RP Birrer, MJ (reprint author), NCI, Dept Cell & Canc Biol, 37 Convent Dr,Room 1130, Bethesda, MD 20892 USA. EM birrerm@bprb.nci.nih.gov FU Intramural NIH HHS NR 50 TC 65 Z9 67 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8404 EP 8412 DI 10.1158/0008-5472.CAN-06-0683 PG 9 WC Oncology SC Oncology GA 081PL UT WOS:000240329400015 PM 16951150 ER PT J AU Synowitz, M Glass, R Farber, K Markovic, D Kronenberg, G Herrmann, K Schnermann, J Nolte, C van Rooijen, N Kiwit, J Kettenmann, H AF Synowitz, Mchael Glass, Rainer Faerber, Katrin Markovic, Darko Kronenberg, Golo Herrmann, Ken Schnermann, Juergen Nolte, Christiane van Rooijen, Nico Kiwit, Juergen Kettenmann, Helmut TI A(1) adenosine receptors in microglia control glioblastoma-host interaction SO CANCER RESEARCH LA English DT Article ID RAT MICROGLIA; MICE LACKING; MULTIPLE-SCLEROSIS; TNF-ALPHA; EXPRESSION; CELLS; A(2A)-RECEPTORS; MACROPHAGES; ACTIVATION; MECHANISM AB We report that experimental glioblastoma grow more vigorously in A(1) adenosine receptor (A(1)AR)-deficient mice associated with a strong accumulation of microglial cells at and around the tumors. A(1)ARs were prominently expressed in microglia associated with tumor cells as revealed with immunocytochemistry but low in microglia in the unaffected brain tissue. The A(1)AR could also be detected on microglia from human glioblastoma resections. To study functional interactions between tumor and host cells, we studied glioblastoma growth in organotypical brain slice cultures. A(1)AR agonists suppressed tumor growth. When, however, microglial cells were depleted from the slices, the agonists even stimulated tumor growth. Thus, adenosine attenuates glioblastoma growth acting via A(1)AR in microglia. C1 Max Delbruck Ctr Mol Med, Cell Neurosci Grp, D-13092 Berlin, Germany. Free Univ Berlin, Dept Psychiat, D-1000 Berlin, Germany. Helios Hosp Berlin, Dept Neurosurg, Berlin, Germany. NIDDK, NIH, Bethesda, MD USA. Fac Med, Dept Mol Cell Biol, Amsterdam, Netherlands. RP Kettenmann, H (reprint author), Max Delbruck Ctr Mol Med, Cell Neurosci Grp, Robert Rossle Str 10, D-13092 Berlin, Germany. EM kettenmann@mde-berlin.de RI Herrmann, Ken/E-8956-2015; Kronenberg, Golo/F-8772-2010 NR 42 TC 37 Z9 38 U1 0 U2 3 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 SEP 1 PY 2006 VL 66 IS 17 BP 8550 EP 8557 DI 10.1158/0008-5472.CAN-06-0365 PG 8 WC Oncology SC Oncology GA 081PL UT WOS:000240329400032 PM 16951167 ER PT J AU Mani, A Oh, AS Bowden, ET Lahusen, T Lorick, KL Weissman, AM Schlegel, R Wellstein, A Riegel, AT AF Mani, Aparna Oh, Annabell S. Bowden, Emma T. Lahusen, Tyler Lorick, Kevin L. Weissman, Allan M. Schlegel, Richard Wellstein, Anton Riegel, Anna T. TI E6AP mediates regulated proteasomal degradation of the nuclear receptor coactivator amplified in breast cancer 1 in immortalized cells SO CANCER RESEARCH LA English DT Article ID UBIQUITIN-PROTEIN LIGASE; BREAST-CANCER CELLS; ESTROGEN-RECEPTOR; STEROID-RECEPTOR; TRANSCRIPTIONAL COACTIVATOR; E6-ASSOCIATED PROTEIN; TRANSGENIC MICE; TYPE-16 E6; AIB1; EXPRESSION AB The steroid receptor coactivator oncogene, amplified in breast cancer 1 (AIB1; also known as ACTR/RAC-3/TRAM-1/SRC-3/p/CIP), is amplified and overexpressed in a variety of epithelial tumors. AIB1 has been reported to have roles in both steroid-dependent and steroid-independent transcription during tumor progression. In this report, we describe that the cellular levels of AM are controlled through regulated proteasomal degradation. We found that serum withdrawal or growth in high cell density caused rapid degradation of AIB1 protein, but not mRNA, in immortalized cell lines. Proteasome inhibitors prevented this process, and high molecular weight ubiquitylated species of AIB1 were detected. Nuclear export was required for proteasomal degradation of AM and involved the ubiquitin ligase, E6AP. AIB1/E6AP complexes were detected in cellular extracts, and reduction of cellular E6AP levels with E6AP short interfering RNA prevented proteasomal degradation of AIB1. Conversely, overexpression of E6AP promoted AIB1 degradation. The COOH terminus of AIB1 interacted with E6AP in vitro and deletion of this region in AIB1 rendered it resistant to degradation in cells. From our results, we propose a model whereby signals promoted by changes in the cellular milieu initiate E6AP-mediated proteasomal degradation of AIB1 and thus contribute to the control of steady-state levels of this protein. C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Pathol, Washington, DC 20007 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Riegel, AT (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. EM ariege01@georgetown.edu OI Oh, Annabell S./0000-0002-0676-1164; Wellstein, Anton/0000-0002-0570-4950 FU Intramural NIH HHS; NCI NIH HHS [CA108441, CA113677] NR 51 TC 43 Z9 44 U1 0 U2 3 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 SEP 1 PY 2006 VL 66 IS 17 BP 8680 EP 8686 DI 10.1158/0008-5472.CAN-06-0557 PG 7 WC Oncology SC Oncology GA 081PL UT WOS:000240329400048 PM 16951183 ER PT J AU Campbell, MJ Esserman, LJ Zhou, Y Shoemaker, M Lobo, M Borman, E Baehner, F Kumar, AS Adduci, K Marx, C Petricoin, EF Liotta, LA Winters, M Benz, S Benz, CC AF Campbell, Michael J. Esserman, Laura J. Zhou, Yamei Shoemaker, Mark Lobo, Margaret Borman, Elizabeth Baehner, Frederick Kumar, Anjali S. Adduci, Kelly Marx, Corina Petricoin, Emanuel F. Liotta, Lance A. Winters, Mary Benz, Stephen Benz, Christopher C. TI Breast cancer growth prevention by statins SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; HMG-COA REDUCTASE; RISK; ACTIVATION; INHIBITORS; ISOPRENOIDS; PRAVASTATIN; SIMVASTATIN; EXPRESSION; MUTATIONS AB Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation reactions and reduction of signals driving cell proliferation and survival responses. The objectives of this study were to examine the effects of statins on breast cancer cells, both in vitro and in vivo, and to begin to determine their mechanism of action. We evaluated the effects of statins on breast cancer cell growth, phosphoprotein signaling intermediates, survival/apoptosis regulators, cell cycle regulators, and activated transcription factors. We also examined the in vivo effect of statin administration in a mouse ErbB(2+) breast cancer model. Only lipophilic statins had direct anticancer activity in vitro. Breast cancer cells with activated Ras or ErbB2 pathways seemed to be more sensitive than those overexpressing estrogen receptor, and this correlated with endogenous levels of activated nuclear factor kappa B (NF-kappa B). Key intermediates regulating cell survival by NF-kappa B activation, as well as cell proliferation by the mitogen activated protein kinase cascade, were among the earliest phosphoproteins influenced by statin treatment. These early effects were followed by declines in activator protein-1 and NF-kappa B activation and concordant changes in other mediators of proliferation and apoptosis. In vivo results showed that oral dosing of statins significantly inhibited the growth of a mouse mammary carcinoma. Lipophilic statins can exert direct anticancer activity in vitro by reducing proliferation and survival signals in susceptible breast cancer phenotypes. Tumor growth inhibition in vivo using a clinically relevant statin dose also seems to be associated with reduced tumor cell proliferation and survival. These findings provide supporting rationale for future statin trials in breast cancer patients. C1 Univ Calif San Francisco, Dept Surg, Mt Zion Med Ctr, Ctr Comprehens Canc, San Francisco, CA 94115 USA. US FDA, Clin Proteom Program, NCI, Bethesda, MD 20014 USA. Buck Inst Age Res, Novato, CA USA. Wheaton Coll, Norton, MA 02766 USA. RP Campbell, MJ (reprint author), Univ Calif San Francisco, Dept Surg, Mt Zion Med Ctr, Ctr Comprehens Canc, Room C342,1600 Divisadero, San Francisco, CA 94115 USA. EM campbellm@surgery.ucsf.edu OI Benz, Stephen/0000-0002-4067-0602 FU NCI NIH HHS [P50-CA58207, R01-CA36773, R01-CA71468]; NIA NIH HHS [R01-AG020521] NR 46 TC 162 Z9 169 U1 2 U2 13 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 SEP 1 PY 2006 VL 66 IS 17 BP 8707 EP 8714 DI 10.1158/0008-5472.CAN-05-4061 PG 8 WC Oncology SC Oncology GA 081PL UT WOS:000240329400051 PM 16951186 ER PT J AU Cohen, CJ Zhao, YB Zheng, ZL Rosenberg, SA Morgan, RA AF Cohen, Cyrille J. Zhao, Yangbing Zheng, Zhili Rosenberg, Steven A. Morgan, Richard A. TI Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability SO CANCER RESEARCH LA English DT Article ID TUMOR-ANTIGEN; HIGH-AFFINITY; SINGLE-CHAIN; CONSTANT-REGION; GENES; CD4(+); EFFICIENCY; COMPLEX; SPECIFICITY; RECOGNITION AB Little is known about the biology of murine T-cell receptors (TCR) expressed in human cells. We recently observed that a murine anti-human p53 TCR is highly functional when expressed in human lymphocytes. Herein, we compare human and mouse TCR function and expression to delineate the molecular basis for the apparent superior biological activity of murine receptors in human T lymphocytes. To this end, we created hybrid TCRs where we swapped the original constant regions with either human or mouse ones, respectively. We showed that murine or "murinized" receptors were overexpressed on the surface of human lymphocytes compared with their human/humanized counterparts and were able to mediate higher levels of cytokine secretion when cocultured with peptide-pulsed antigen-presenting cells. Preferential pairing of marine constant regions and improved CD3 stability seemed to be responsible for these observations. These enhanced biological properties translated into significantly greater antitumor response mediated by TCR with mouse constant regions. Furthermore, we were able to circumvent the natural low avidity of class I MHC TCR in CD4(+) cells by introducing the murinized TCR into CD4(+) lymphocytes, giving them the ability to recognize melanoma tumors. These findings have implications for human TCR gene transfer therapy and may provide new insights into the biology of the TCR/CD3 complex. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1201,Bldg 10,Room 3W5940, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 49 TC 182 Z9 188 U1 1 U2 3 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 SEP 1 PY 2006 VL 66 IS 17 BP 8878 EP 8886 DI 10.1158/0008-5472.CAN-06-1450 PG 9 WC Oncology SC Oncology GA 081PL UT WOS:000240329400070 PM 16951205 ER PT J AU Ablamunits, V Cohen, Y Brazee, IB Gaetz, HP Vinson, C Klebanov, S AF Ablamunits, Vitaly Cohen, Yehuda Brazee, Irina B. Gaetz, Harold P. Vinson, Charles Klebanov, Simon TI Susceptibility to induced and spontaneous carcinogenesis is increased in fatless A-ZIP/F-1 but not in obese ob/ob mice SO CANCER RESEARCH LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; SKIN TUMOR PROMOTION; GROWTH-FACTOR-I; HIGH-FAT DIET; CALORIE RESTRICTION; INSULIN-RESISTANCE; TRANSGENIC MICE; ADIPOSE-TISSUE; CONSTITUTIVE EXPRESSION; MAMMARY TUMORIGENESIS AB Obesity is typically associated with increased tumor susceptibility, whereas caloric restriction, a regimen resulting in leanness, inhibits carcinogenesis. The link between adiposity and malignancies suggests that adipose tissue may influence carcinogenesis. An adipose tissue hormone, leptin, could be procarcinogenic because it stimulates proliferation in various tissues and tumor cell lines. Leptin may contribute to the correlation between adiposity and malignancies as its levels are usually increased in obese subjects and reduced by caloric, restriction. We hypothesized that leptin deficiency, despite obesity, would inhibit carcinogenesis in leptin-null ob/ob mice and tested this hypothesis in two models: (a) two-stage skin carcinogenesis initiated by 7,12-dimethylbenz(a)anthracene and promoted by phorbol 12-myristate 13-acetate (PMA) and (b) p53 deficiency. Contrary to a typical association between obesity and enhanced carcinogenesis, obese ob/ob mice developed induced skin papillomas and spontaneous p53-deficient malignancies, mostly lymphomas, similarly to their lean littermates. Surprisingly, lipodystrophic (ZIP) mice that had very little both adipose tissue and leptin were highly susceptible to carcinogenesis. Hyperphagia, hyperinsulinemia, and hyperglycemia are unlikely to have contributed significantly to the enhancement of carcinogenesis in ZIP mice because similarly hyperphagic, hyperinsulinemic, and hyperglycemic ob/ob mice had normal susceptibility to carcinogenesis. Our data suggest that, in contrast to a well-known correlation between obesity and cancer, the direct effect of adipose tissue may rather be protective. C1 St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10025 USA. St Lukes Roosevelt Hosp, Anat Pathol Corp, New York, NY 10025 USA. SUNY Stony Brook, Hlth Sci Ctr, Sch Med, Stony Brook, NY 11794 USA. Univ Calif San Diego, Revelle Coll, La Jolla, CA 92093 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Klebanov, S (reprint author), St Lukes Roosevelt Hosp, Obes Res Ctr, 1111 Amsterdam Ave,WH1020, New York, NY 10025 USA. EM sk2525@columbia.edu FU NIA NIH HHS [AG 19894] NR 64 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8897 EP 8902 DI 10.1158/0008-5472.CAN-05-4679 PG 6 WC Oncology SC Oncology GA 081PL UT WOS:000240329400072 PM 16951207 ER PT J AU Wang, SS Davis, S Cerhan, JR Hartge, P Severson, RK Cozen, W Lan, Q Welch, R Chanock, SJ Rothman, N AF Wang, Sophia S. Davis, Scott Cerhan, James R. Hartge, Patricia Severson, Richard K. Cozen, Wendy Lan, Qing Welch, Robert Chanock, Stephen J. Rothman, Nathaniel TI Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma SO CARCINOGENESIS LA English DT Article ID MANGANESE-SUPEROXIDE-DISMUTASE; LUNG-CANCER RISK; ACTIVATED RECEPTOR-GAMMA; BREAST-CANCER; NITRIC-OXIDE; MNSOD POLYMORPHISM; MALIGNANT-LYMPHOMA; ANTIOXIDANT STATUS; PROSTATE-CANCER; MESSENGER-RNA AB Evidence supporting the contribution of oxidative stress to key pathways in cancer, such as inflammation and DNA damage, continues to mount. We investigated variations within genes mediating oxidative stress to determine whether they alter risk for non-Hodgkin lymphoma (NHL). Thirteen single nucleotide polymorphisms (SNPs) from 10 oxidative stress genes (AKR1A1, AKR1C1, CYBA, GPX, MPO, NOS2A, NOS3, OGG1, PPARG and SOD2) were genotyped in 1172 NHL cases and 982 population-based controls from a USA multicenter case-control study. For NHL and five subtypes (diffuse large B-cell, follicular, marginal zone, small lymphocytic and T-cell), SNP associations were calculated. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for sex, age (< 45, 45-64, 65+ years), race (white, black, other) and study site. Overall, the oxidative stress pathway was associated significantly with the B-cell NHL subtype, diffuse large B-cell lymphoma (DLBCL) (global P-value = 0.003). Specifically, for nitric oxide synthase (NOS2A Ser608Leu, rs2297518) Leu/Leu homozygotes, there was a 2-fold risk increase for NHL (OR = 2.2, 95% CI = 1.1-4.4) (referent = Ser/Ser and Ser/Leu). This risk increase was consistent by cell lineage (B- and T-cell NHL) and pronounced for the two most common subtypes, diffuse large B-cell (OR = 3.4, 95% CI = 1.5-7.8) and follicular lymphoma (OR = 2.6, 95% CI = 1.0-6.8). In an analysis of manganese superoxide dismutase (SOD2 Val16Ala, rs1799725) Ala/Ala homozygotes, we observed moderately increased risks for B-cell lymphomas (OR = 1.3, 95% CI = 1.0-1.6; referent = Val/Val and Val/Ala) that was consistent across the B-cell subtypes. Genetic variations that result in an increased generation of reactive oxygen species appear to increase risk for NHL and its major subtypes, particularly DLBCL. Independent replication of our findings are warranted and further evaluation of oxidative stress in the context of inflammation, DNA repair and the induction of the NF-kappa B pathway may further reveal important clues for lymphomagenesis. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ Iowa, Iowa City, IA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Univ So Calif, Los Angeles, CA USA. Natl Canc Inst, Adv Technol Corp, Gaithersburg, MD USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. EM wangso@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS NR 49 TC 64 Z9 67 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2006 VL 27 IS 9 BP 1828 EP 1834 DI 10.1093/carcin/bgl013 PG 7 WC Oncology SC Oncology GA 075QT UT WOS:000239901000011 PM 16543247 ER PT J AU Ahn, JY Gammon, MD Santella, RM Gaudet, MM Britton, JA Teitelbaum, SL Terry, MB Neugut, AI Eng, SM Zhang, YS Garza, C Ambrosone, CB AF Ahn, Jiyoung Gammon, Marilie D. Santella, Regina M. Gaudet, Mia M. Britton, Julie A. Teitelbaum, Susan L. Terry, Mary Beth Neugut, Alfred I. Eng, Sybil M. Zhang, Yuesheng Garza, Cutberto Ambrosone, Christine B. TI Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers on breast cancer risk SO CARCINOGENESIS LA English DT Article ID DNA-ADDUCTS; LONG-ISLAND; EXPRESSION; ISOTHIOCYANATES; POLYMORPHISMS; VEGETABLES; GSTM1; CELLS; CONSUMPTION; PROMOTER AB Glutathione S-transferases (GSTs) are phase II enzymes that are involved in the detoxification of a wide range of carcinogens. The novel GSTA1*A and GSTA1*B genetic polymorphism results in differential expression, with lower transcriptional activation of GSTA1*B (variant) than that of GSTA1*A (common) allele. Considering that cruciferous vegetables induce GSTs, which metabolize tobacco smoke carcinogens, we hypothesized that the variant GSTA1*B genotype may predispose women to breast cancer, particularly among low cruciferous vegetable consumers and among smokers. Thus, we evaluated potential relationships between GSTA1 polymorphisms and breast cancer risk, in relation to vegetable consumption and smoking status in the Long Island Breast Cancer Study Project (1996-1997), a population-based case-control study. Genotyping (1036 cases and 1089 controls) was performed, and putative breast cancer risk factors and usual dietary intakes were assessed. Having GSTA1*A/*B or *B/*B genotypes was not associated with increased breast cancer risk, compared to having the common *A/*A genotype. However, among women in the lowest two tertiles of cruciferous vegetable consumption, *B/*B genotypes were associated with increased risk (OR (95% CI) = 1.73 (1.10-2.72) for 0-1 servings/week), compared to women with *A/*A genotypes. Among women with *B/*B genotypes, a significant inverse trend between cruciferous vegetable consumption and breast cancer risk was observed (P for trend = 0.05), and higher consumption (4+ servings/week) ameliorated the increased risk associated with the genotype. Current smokers with *B/*B genotypes had a 1.89-fold increase in risk (OR (95% CI) = 1.89 (1.09-3.25)), compared with never smokers with *A/*A genotypes. These data indicate that GSTA1 genotypes related to reduced GSTA1 expression are associated with increased breast cancer primarily among women with lower consumption of cruciferous vegetables and among current smokers. C1 Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Chemoprevent, Buffalo, NY 14263 USA. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Columbia Univ, Dept Environm Hlth Sci, New York, NY 10032 USA. Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY 10032 USA. CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. Pfizer Inc, Global Epidemiol Safety & Risk Management, New York, NY USA. RP Ahn, JY (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,Room 3029, Bethesda, MD 20892 USA. EM ahnj@mail.nih.gov FU NCI NIH HHS [CA/ES66572, CA58233]; NIEHS NIH HHS [P30ES10126, P30 ES009089, P30ES09089] NR 39 TC 30 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2006 VL 27 IS 9 BP 1876 EP 1882 DI 10.1093/carcin/bgl038 PG 7 WC Oncology SC Oncology GA 075QT UT WOS:000239901000017 PM 16624829 ER PT J AU Goldstein, DS AF Goldstein, David S. TI L-dihydroxyphenylserine (L-DOPS): A norepinephrine prodrug SO CARDIOVASCULAR DRUG REVIEWS LA English DT Review DE Autonomic Failure; DHPG; dihydroxyphenylglycol; dihydroxyphenylserine; droxydopa; L-DOPS; norepinephrine; orthostatic hypotension ID NEUROGENIC ORTHOSTATIC HYPOTENSION; DOPAMINE-BETA-HYDROXYLASE; L-THREO-DOPS; L-THREO-3,4-DIHYDROXYPHENYLSERINE L-DOPS; SHY-DRAGER SYNDROME; NORADRENALINE PRECURSOR L-THREO-3,4-DIHYDROXYPHENYLSERINE; FAMILIAL AMYLOIDOTIC POLYNEUROPATHY; PROGRESSIVE SUPRANUCLEAR PALSY; SYMPATHETIC-NERVE ACTIVITY; MULTIPLE SYSTEM ATROPHY AB L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10 Room 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov NR 112 TC 47 Z9 48 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0897-5957 J9 CARDIOVASC DRUG REV JI Cardiovasc. Drug Rev. PD FAL-WIN PY 2006 VL 24 IS 3-4 BP 189 EP 203 DI 10.1111/j.1527-3466.2006.00189.x PG 15 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 119OW UT WOS:000243022600001 PM 17214596 ER PT J AU Isenberg, JS Wink, DA Roberts, DD AF Isenberg, Jeff S. Wink, David A. Roberts, David D. TI Thrombospondin-1 antagonizes nitric oxide-stimulated vascular smooth muscle cell responses SO CARDIOVASCULAR RESEARCH LA English DT Article DE smooth muscle; signal transduction; nitric oxide; extracellular matrix ID HEPARIN-BINDING PEPTIDES; GROWTH-FACTOR; ENDOTHELIAL-CELLS; GUANYLYL CYCLASE; I REPEATS; PROLIFERATION; CHEMOTAXIS; INTEGRIN; ADHESION; PATHWAY AB Objective: Endothelial-derived nitric oxide (NO), by increasing cGMP, is a major physiological regulator of vascular tone and of vascular smooth muscle cell (VSMC) adhesion, chemotaxis, and proliferation. Thrombospondin-1 is a potent antagonist of NO/cGMP signaling in endothelial cells. Because endothelial and VSMC typically exhibit opposing responses to thrombospondin-1, we examined thrombospondin-1 effects on NO signaling in VSMC. Methods: Effects of exogenous thrombospondin-1 on human VSMC adhesion, chemotaxis, proliferation, and cGMP signaling were examined. Endogenous thrornbospondin-1 function was characterized by comparing NO signaling in VSMC from wild type and thrombospondin-1 null mice. Results: Picomolar concentrations of exogenous thrombospondin-1 prevented adhesive, chemotactic, and proliferative responses of human aortic VSMC stimulated by low dose NO. A recombinant CD36-binding domain of thrombospondin-1 or antibody ligation of CD36 similarly inhibited NO-stimulated VSMC responses. Thrombospondin-1 and CD36 ligation inhibited NO responses in VSMC by preventing cGMP accumulation. Thrombospondin-1 null VSMC responses to NO and cGMP signaling were enhanced relative to wild type murine VSMC. Conclusions: In the presence of NO, thrombospondin-1 is converted from a weak stimulator to a potent inhibitor of VSMC responses. Both exogenous and endogenous thrombospondin-1 inhibit NO signaling in VSMC. This activity is mediated by the type I repeats and utilizes the same CD36-dependent cGMP signaling pathway in endothelial and VSMC. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS NR 50 TC 67 Z9 69 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP 1 PY 2006 VL 71 IS 4 BP 785 EP 793 DI 10.1016/j.cardiores.2006.05.024 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 080SP UT WOS:000240268800021 PM 16820142 ER PT J AU Jones, NJ Bates, ER Chetcuti, SJ Lederman, RJ Grossman, PM AF Jones, Noah J. Bates, Eric R. Chetcuti, Stanley J. Lederman, Robert J. Grossman, P. Michael TI Usefulness of translesional pressure gradient and pharmacological provocation for the assessment of intermediate renal artery disease SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE pressure gradient; acetylcholine; renal artery disease ID FRACTIONAL FLOW RESERVE; BLOOD-FLOW; GUIDE-WIRE; STENOSIS; HYPERTENSION; ANGIOPLASTY; SEVERITY; ACETYLCHOLINE; ANGIOGRAPHY; VALIDATION AB Objective: We sought to determine the hemodynamic significance of intermediate RAS by measuring translesional systolic pressure gradients (TSPG), using a pressure-sensing guidewire at baseline and after acetylcholine (ACh) induced hyperemia, following selective renal artery angiography. Background: Renal artery stenosis (RAS) is a cause of reversible hypertension and nephropathy. Stenting effectively relieves RAS, however improvement in blood pressure control or renal function is variable and unpredictable. Hemodynamic significance is usually present with RAS when diameter stenosis is >75%, but is less predictable in intermediate (30%-75%) RAS. Methods: Twenty-two patients (26 renal arteries) with uncontrolled hypertension underwent invasive hemodynamic assessment because of intermediate RAS, defined as radiocontrast angiographic diameter stenosis (DS) between 30% and 75% (quantitative DS was measured prospectively). Translesional pressure gradients were measured using a 0.014" pressure-sensing wire. Hyperemia was induced by administration of intrarenal ACh. Results: Visual and measured angiographic lesion severity did not correlate with TSPG either at baseline (visual DS, R-2 = 0.091, P = 0.13; measured DS, R-2 = 0.124, P = 0.07) or with hyperemia (visual DS, R-2 = 0.057, P = 0.24; measured DS, R-2 = 0.101, P = 0.12). Baseline and maximal hyperemic gradient did correlate (R-2 = 0.567; P < 0.05). Pharmacological provocation produced a significant increase in TSPG (mean; baseline, 18 : 21 vs. hyperemia, 34 +/- 41 mm Hg; P < 0.05). A hemodynamically significant lesion (TSPG > 20 mm Hg) was found in 14/26 (54%) arteries (13 patients); 13 (60%) patients subsequently underwent renal artery stenting for hemodynamically significant RAS. At follow-up (at least 30 days), there was a significant decrease in systolic blood pressure (mean; 167 +/- 24 vs. 134 +/- 19 mm Hg; P < 0.001). Conclusions: Intrarenal administration of ACh induces hyperemia and can be used to unmask resistive renal artery lesions. Gradient measurement and induced hyperemia may be warranted in the invasive assessment of intermediate renal artery stenoses, rather than relying on stenosis severity alone. Further study is needed to determine whether translesional pressure gradients and pharmacological provocation predict clinical benefit after renal artery stenting. (C) 2006 Wiley-Liss, Inc. C1 Univ Michigan, Div Cardiovasc Med, Med Ctr, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Grossman, PM (reprint author), Univ Michigan, Div Cardiovasc Med, Med Ctr, Ctr Cardiovasc, 1500 E Med Ctr Dr,TC B1 226, Ann Arbor, MI 48109 USA. EM pagross@umich.edu OI lederman, robert/0000-0003-1202-6673 NR 30 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP PY 2006 VL 68 IS 3 BP 429 EP 434 DI 10.1002/ccd.20697 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 081FH UT WOS:000240302100017 PM 16892443 ER PT J AU Kruhlak, MJ Celeste, A Nussenzweig, A AF Kruhlak, Michael J. Celeste, Arkady Nussenzweig, Andre TI Spatio-temporal dynamics of chromatin containing DNA breaks SO CELL CYCLE LA English DT Article DE chromatin; histones; DNA repair; doublestrand breaks; ATP; GFP; PAGFP; electron microscopy; H2AX ID DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS; DAMAGE; REPAIR; SITES; SENSITIVITY; IRRADIATION; PROTEINS; DOMAINS; COMPLEX AB The cellular response to DNA breaks consists of a complex signaling network that coordinates the initial recognition of the lesion with the induction of cell cycle checkpoints and DNA repair. With DNA wrapped around histone proteins and packaged into higher order levels of chromatin structure, the detection of a single DNA break (DSB) in the genome is the molecular equivalent of finding a needle in a haystack. A recent study from our laboratory used high-resolution electron microscropy and live cell imaging to demonstrate that chromatin undergoes a marked reorganization in response to a DSB. In an energy dependent manner, chromatin rapidly decondenses to a more open configuration in the regions surrounding the lesion. We propose that this ATP dependent chromatin-remodeling event facilitates the subsequent recognition and processing of damaged DNA. While the chromatin surrounding the lesion remodels to a more open configuration, the DNA break itself remains relatively immobile over time, consistent with the idea that DNA damage response proteins migrate to positionally stable sites of damaged DNA.(1) The lack of significant movement of chromatin regions containing DSBs has implications for the process by which chromosomal translocations form. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 4B04, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov NR 22 TC 31 Z9 33 U1 0 U2 6 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 1 PY 2006 VL 5 IS 17 BP 1910 EP 1912 DI 10.4161/cc.5.17.3169 PG 3 WC Cell Biology SC Cell Biology GA 089EA UT WOS:000240861900002 PM 16929171 ER PT J AU Malet, G Martin, AG Orzaez, M Vicent, MJ Masip, I Sanclimens, G Ferrer-Montiel, A Mingarro, I Messeguer, A O Fearnhead, H Perez-Paya, E AF Malet, G. Martin, A. G. Orzaez, M. Vicent, M. J. Masip, I. Sanclimens, G. Ferrer-Montiel, A. Mingarro, I. Messeguer, A. O Fearnhead, H. Perez-Paya, E. TI Small molecule inhibitors of Apaf-1-related caspase-3/-9 activation that control mitochondrial-dependent apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; apoptosome; Apaf-1; caspasa-3; caspasa-9; combinatorial libraries; inhibitor; molecular recognition; peptoid; protein-protein interactions; small molecule ID CYTOCHROME-C; DRUG DISCOVERY; CELL-DEATH; APAF-1; COMPLEX; PROCASPASE-9; IDENTIFICATION; PEPTIDES; PROTEINS; PEPTOIDS AB Apoptosis is a biological process relevant to human disease states that is strongly regulated through protein-protein complex formation. These complexes represent interesting points of chemical intervention for the development of molecules that could modulate cellular apoptosis. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated Apaf-1 (apoptotic protease-activating factor), dATP and procaspase- 9 that link mitochondria disfunction with activation of the effector caspases and in turn is of interest for the development of apoptotic modulators. In the present study we describe the identification of compounds that inhibit the apoptosome-mediated activation of procaspase-9 from the screening of a diversity-oriented chemical library. The active compounds rescued from the library were chemically optimised to obtain molecules that bind to both recombinant and human endogenous Apaf-1 in a cytochrome c-noncompetitive mechanism that inhibits the recruitment of procaspase- 9 by the apoptosome. These newly identified Apaf-1 ligands decrease the apoptotic phenotype in mitochondrial-mediated models of cellular apoptosis. C1 Ctr Invest Principe Felipe, Dept Med Chem, E-46013 Valencia, Spain. Univ Valencia, Dept Biochem & Mol Biol, E-46100 Burjassot, Valencia, Spain. NCI, NIH, Apoptosis Sect, Regulat Cell Growth Lab, Frederick, MD 21702 USA. IIQAB, CSIC, Dept Biol Organ Chem, E-08034 Barcelona, Spain. Univ Miguel Hernandez, Inst Biol Mol & Celular, Elx Alacant 03202, Spain. CSIC, E-46013 Valencia, Spain. RP Perez-Paya, E (reprint author), Ctr Invest Principe Felipe, Dept Med Chem, Avda Autopista Saler,16, E-46013 Valencia, Spain. EM eperez@ochoa.fib.es RI Fearnhead, Howard/D-4826-2012; Mingarro, Ismael/B-4745-2014; Vicent, Maria J./A-9690-2014; Orzaez, Mar/B-4992-2014; Ferrer-Montiel, Antonio/C-3072-2015; OI Mingarro, Ismael/0000-0002-1910-1229; Fearnhead, Howard/0000-0002-8054-9794; Vicent, Maria J./0000-0001-7771-3373; Orzaez, Mar/0000-0003-3231-5835; Ferrer-Montiel, Antonio/0000-0002-2973-6607; Garcia Martin, Angel/0000-0002-3831-2769 NR 42 TC 51 Z9 51 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 2006 VL 13 IS 9 BP 1523 EP 1532 DI 10.1038/sj.cdd.4401828 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 075XL UT WOS:000239920600011 PM 16341125 ER PT J AU Ronningen, KS Paltiel, L Meltzer, HM Nordhagen, R Lie, KK Hovengen, R Haugen, M Nystad, W Magnus, P Hoppin, JA AF Ronningen, K. S. Paltiel, L. Meltzer, H. M. Nordhagen, R. Lie, K. K. Hovengen, R. Haugen, M. Nystad, W. Magnus, P. Hoppin, J. A. TI The biobank of the Norwegian Mother and Child Cohort Study SO CELL PRESERVATION TECHNOLOGY LA English DT Meeting Abstract C1 Norwegian Inst Publ Hlth, Oslo, Norway. NIEHS, NIH, DHHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PD FAL PY 2006 VL 4 IS 3 MA 1 BP 211 EP 211 PG 1 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 106OE UT WOS:000242109500009 ER PT J AU Ayers, LW McGrath, MS Silver, S Orenstein, J Bhatia, K AF Ayers, L. W. McGrath, M. S. Silver, S. Orenstein, J. Bhatia, K. TI RNA, DNA and molecular targets in archived paraffin-embedded tissue samples, 1980-2005 SO CELL PRESERVATION TECHNOLOGY LA English DT Meeting Abstract C1 Ohio State Univ, ACSR, Columbus, OH 43210 USA. Univ Calif San Francisco, ACSR, San Francisco, CA 94143 USA. George Washington Univ, ACSR, Washington, DC USA. NCI, ACSR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PD FAL PY 2006 VL 4 IS 3 MA 31 BP 225 EP 226 PG 2 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 106OE UT WOS:000242109500039 ER PT J AU Paltiel, L Meltzer, HM Hoppin, JA Skjerden, T Baker, SV Magnus, P Ronningen, KS AF Paltiel, L. Meltzer, H. M. Hoppin, J. A. Skjerden, T. Baker, S. V. Magnus, P. Ronningen, K. S. TI Quality assurance/quality control in the biobank of the Norwegian Mother and Child Cohort Study SO CELL PRESERVATION TECHNOLOGY LA English DT Meeting Abstract C1 Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. Norwegian Inst Publ Hlth, Div Environm Chem, Oslo, Norway. NIEHS, Epidemiol Branch, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PD FAL PY 2006 VL 4 IS 3 MA 34 BP 227 EP 227 PG 1 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 106OE UT WOS:000242109500042 ER PT J AU Campa, F Machuy, N Klein, A Rudel, T AF Campa, Fanny Machuy, Nikolaus Klein, Alexander Rudel, Thomas TI A new interaction between Abi-1 and beta PIX involved in PDGF-activated actin cytoskeleton reorganisation SO CELL RESEARCH LA English DT Article DE beta PIX; Abi-1; PDGF; membrane dorsal ruffling; cytoskeleton ID PLECKSTRIN HOMOLOGY DOMAINS; NUCLEOTIDE EXCHANGE FACTORS; EPIDERMAL-GROWTH-FACTOR; ABL TYROSINE KINASE; BINDING-PROTEIN; STRESS FIBERS; RHO-GTPASES; C-ABL; RAC; FAMILY AB Members of the Rho family of GTPases are key regulators of the actin cytoskeleton. In particular, activated Rac1 stimulates membrane dorsal ruffle formation in response to platelet-derived growth factor (PDGF). Abl-interactor (Abi)-1 and beta RIX, a guanine nucleotide exchange factor for Rac1, localise at these Rac1-induced actin structures and play important roles in the induction of membrane dorsal ruffling in response to PDGF in fibroblasts. Here, we demonstrate a novel interaction between Abi-1 and beta PIX using the yeast two-hybrid system, in vitro pull-down assays, and in vivo co-immunoprecipitation experiments. In vitro, the C-terminal fragment of beta PIX interacted with Abi-1, while in vivo the N-terminal fragment of beta PIX interacted with Abi-1. The biological function of this interaction was investigated in mouse fibroblasts in response to PDGF stimulation. Abi-1 and beta PIX co-localised in the cytoplasm and to membrane dorsal ruffles after PDGF treatment. We show that the co-expression of Abi-1 and truncated forms of beta PIX in mouse fibroblasts blocked PDGF-induced membrane dorsal ruffles. Together, these results show that the interaction between Abi-1 and beta RIX is involved in the formation of growth factor-induced membrane dorsal ruffles. C1 Max Planck Inst Infect Biol, Dept Biol Mol, D-10117 Berlin, Germany. NCI, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Rudel, T (reprint author), Max Planck Inst Infect Biol, Dept Biol Mol, Campus Charite Mitte,Charitepl 1, D-10117 Berlin, Germany. EM rudel@mpiib-berlin.mpg.de NR 39 TC 6 Z9 9 U1 0 U2 0 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD SEP PY 2006 VL 16 IS 9 BP 759 EP 770 DI 10.1038/sj.cr.7310091 PG 12 WC Cell Biology SC Cell Biology GA 097ZT UT WOS:000241489800004 PM 16940963 ER PT J AU Czifra, G Toth, IB Marincsak, R Juhasz, I Kovacs, I Acs, P Kovacs, L Blumberg, PA Biro, T AF Czifra, Gabriella Toth, Istvan Balazs Marincsak, Rita Juhasz, Istvan Kovacs, Ilona Acs, Peter Kovacs, Laszlo Blumberg, Peter A. Biro, Tamas TI Insulin-like growth factor-I-coupled mitogenic signaling in primary cultured human skeletal muscle cells and in C2C12 myoblasts. A central role of protein kinase C delta SO CELLULAR SIGNALLING LA English DT Article DE human skeletal muscle; C2C12 cells; insulin-like growth factor-I (IGF-I); protein kinase C (PKC); PKC delta; mitogen-activated protein kinase (MAPK); proliferation ID MYOTONIC-DYSTROPHY; REGULATED KINASE; SATELLITE CELLS; IGF-I; DIFFERENTIATION; PROLIFERATION; KERATINOCYTES; RECEPTOR; EXPRESSION; PHOSPHORYLATION AB In this study, we have investigated the effects of insulin-like growth factor-I (IGF-I) on cellular responses of primary human skeletal muscle cells and mouse C2C12 myoblasts. In human muscle, IGF-I stimulated proliferation and fusion of the cells and the expression of the differentiation marker desmin. These effects were completely inhibited by Rottlerin, the inhibitor of the protein kinase C (PKC)6, but were not affected by the inhibition of the mitogen-activated protein kinase (MAPK) or the phosphatidylinositide 3-kinase (PI-3K) pathways. Furthermore, IGF-I initiated the selective translocation of PKC delta to the nucleus. In C2C12 myoblasts, the growth-promoting effects of lGF-I were abrogated by inhibition of PKC delta, but not by the inhibition of the PI-3K system. However, in contrast to the human data, the MAPK inhibitor PD098059 partially (yet significantly) also inhibited the action of IGF-I and, furthermore, IGF-I induced phosphorylation of the MAPK Erk-1/2. In addition, overexpression of constitutively active form of PKC6 in C2C12 cells fully mimicked, whereas overexpression of kinase inactive mutant of the isoform prevented the action of IGF-I. Finally, the inhibition of PKC6 suspended the IGF-I-induced phosphorylation of Erk-1/2 and, moreover, the inhibition of the MAPK pathway partially (yet significantly) inhibited the accelerated growth of C2C12 cells overexpressing PKC delta. Taken together, these results demonstrate a novel, central and exclusive involvement of PKC6 in mediating the action of IGF-I on human skeletal muscle cells, with an additional yet PKC delta-dependent contribution of the MAPK pathway on C2C12 myoblasts. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Debrecen, Dept Physiol, Med & Hlth Sci Ctr, Res Ctr Mol Med, H-4012 Debrecen, Hungary. Univ Debrecen, Cell Physiol Res Grp, Hungarian Acad Sci, Med & Hlth Sci Ctr,Res Ctr Mol Med, H-4012 Debrecen, Hungary. Univ Debrecen, Res Ctr Mol Med, Dept Dermatol, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. Kenezy Cty Hosp, Dept Pathol, Debrecen, Hungary. NCI, Mol Mech Tumor Promot Sect, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD USA. RP Biro, T (reprint author), Univ Debrecen, Dept Physiol, Med & Hlth Sci Ctr, Res Ctr Mol Med, Nagyerdei Krt 98,POB 22, H-4012 Debrecen, Hungary. EM biro@phys.dote.hu NR 47 TC 24 Z9 25 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD SEP PY 2006 VL 18 IS 9 BP 1461 EP 1472 DI 10.1016/j.cellsig.2005.11.007 PG 12 WC Cell Biology SC Cell Biology GA 061JO UT WOS:000238868200013 PM 16403461 ER PT J AU Kim, UK Wooding, S Riaz, N Jorde, LB Drayna, D AF Kim, Un-kyung Wooding, Stephen Riaz, Naveeda Jorde, Lynn B. Drayna, Dennis TI Variation in the human TAS1R taste receptor genes SO CHEMICAL SENSES LA English DT Article DE evolution; human TAS1R genes; SNP; sweet taste; umami taste ID SINGLE-NUCLEOTIDE POLYMORPHISMS; SWEET-TASTE; HUMAN GENOME; HAPLOTYPE RECONSTRUCTION; SACCHARIN PREFERENCE; STATISTICAL-METHOD; SEQUENCE VARIATION; NATURAL-SELECTION; MAMMALIAN SWEET; UMAMI TASTE AB We have performed a comprehensive evaluation of single-nucleotide polymorphisms (SNPs) and haplotypes in the human TAS1R gene family, which encodes receptors for sweet and umami tastes. Complete DNA sequences of TAS1R1-, TAS1R2-, and TAS1R3-coding regions, obtained from 88 individuals of African, Asian, European, and Native American origin, revealed substantial coding and noncoding diversity: polymorphisms are common in these genes, and polymorphic sites and SNP frequencies vary widely in human populations. The genes TAS1R1 and TAS1R3, which encode proteins that act as a dimer to form the umami (glutamate) taste receptor, showed less variation than the TAS1R2 gene, which acts as a dimer with TAS1R3 to form the sweet taste receptor. The TAS1R3 gene, which encodes a subunit common to both the sweet and umami receptors, was the most conserved. Evolutionary genetic analysis indicates that these variants have come to their current frequencies under natural selection during population growth and support the view that the coding sequence variants affect receptor function. We propose that human populations likely vary little with respect to umami perception, which is controlled by one major form of the receptor that is optimized for detecting glutamate but may vary much more with respect to sweet perception. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Kyungpook Natl Univ, Dept Biol, Taegu 702701, South Korea. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [ES 12125]; NIGMS NIH HHS [GM59290]; PHS HHS [Z01-000046-05] NR 45 TC 52 Z9 56 U1 4 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD SEP PY 2006 VL 31 IS 7 BP 599 EP 611 DI 10.1093/chemse/bjj065 PG 13 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 086NK UT WOS:000240680100001 PM 16801379 ER PT J AU Kim, HY AF Kim, H. Y. TI Lipidomics of the brain: application of mass spectrometry in membrane-related signaling research SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Meeting Abstract CT 47th International Conference on Bioscience of Lipids CY SEP 05-10, 2006 CL Pecs, HUNGARY SP Hungarian Biochem Soc, Hungarian Acad Sci, Biol Res Ctr, Straub Heritage Fdn, European Lipidom Initiat, Int Lecithin & Phospholipid Soc C1 NIAAA, Sect Mass Spectrometry, LMBB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD SEP PY 2006 VL 143 IS 1-2 BP 41 EP 41 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 075JL UT WOS:000239880900008 ER PT J AU Kim, HY AF Kim, H. Y. TI Phosphatidylserine in neuronal signaling SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Meeting Abstract CT 47th International Conference on Bioscience of Lipids CY SEP 05-10, 2006 CL Pecs, HUNGARY SP Hungarian Biochem Soc, Hungarian Acad Sci, Biol Res Ctr, Straub Heritage Fdn, European Lipidom Initiat, Int Lecithin & Phospholipid Soc C1 NIAAA, Sect Mass Spectrometry, LMBB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD SEP PY 2006 VL 143 IS 1-2 BP 55 EP 55 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 075JL UT WOS:000239880900045 ER PT J AU Pinsky, PF Freedman, M Kvale, P Oken, M Caporaso, N Gohagan, J AF Pinsky, Paul F. Freedman, Matthew Kvale, Paul Oken, Martin Caporaso, Neal Gohagan, John TI Abnormalities on chest radiograph reported in subjects in a cancer screening trial SO CHEST LA English DT Article DE chest radiograph; COPD; lung cancer; mortality; pulmonary fibrosis; screening ID LUNG-CANCER; SPIRAL CT; RADIOLOGISTS; VARIABILITY; DISEASE AB Background: Chest radiographs (CXRs) are commonly performed for diagnostic and other purposes. There is little literature either on the prevalence in the general population of various abnormalities seen on CXRs or on the risks associated with these abnormalities. Methods: We followed up > 70,000 men and women who were enrolled in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Subjects received four annual posteroanterior CXRs for the early detection of lung cancer. Radiologists noted the presence of non-cancer-related abnormalities as well as nodules/masses that were suspicious for lung cancer. Subjects were followed up for mortality and cancer incidence. Results: Abnormalities that were not suspicious for lung cancer were observed on 35% of examinations, compared to 8% of examinations with findings that were suspicious for cancer. The most commonly reported noncancer abnormalities were granuloma (10.7% of examinations), scarring/pulmonary fibrosis (8.2% of examinations), bone/soft tissue lesions (5.5% of examinations), cardiac abnormalities (4.4% of examinations), pleural fibrosis (3.6% of examinations), and COPD/emphysema (2.5% of examinations). Most noncancer abnormalities were more prevalent in men, older subjects, and smokers. Controlling for age, smoking, and other factors, scarring/pulmonary fibrosis was significantly associated with an increased risk of lung cancer with a hazard ratio (HR) of 2.0, while cardiac abnormalities (HR, 2.1), scarxing/pulmonary fibrosis (HR, 1.4), COPD (HR, 1.7), and pleural fluid (HR, 2.3) were significantly associated with increased overall (i.e, non-lung cancer) mortality. Conclusion: Abnormalities that are not suspicious for lung cancer are common in a population undergoing screening. Some of these abnormalities are associated with an increased risk for lung cancer incidence and/or overall mortality. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Henry Ford Hlth Syst, Josephine Ford Canc Ctr, Detroit, MI USA. N Mem Hosp, Hubert Humphrey Canc Ctr, Minneapolis, MN USA. RP Pinsky, PF (reprint author), 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 15 TC 7 Z9 7 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2006 VL 130 IS 3 BP 688 EP 693 DI 10.1378/chest.130.3.688 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 085EG UT WOS:000240585600015 PM 16963664 ER PT J AU Bianco, C Strizzi, L Mancino, M Rehman, A Hamada, S Watanabe, K De Luca, A Jones, B Balogh, G Russo, J Mailo, D Palaia, R D'Aiuto, G Botti, G Perrone, F Salomon, DS Normanno, N AF Bianco, Caterina Strizzi, Luigi Mancino, Mario Rehman, Aasia Hamada, Shin Watanabe, Kazuhide De Luca, Antonella Jones, Brenda Balogh, Gabriela Russo, Jose Mailo, Daniel Palaia, Raffaele D'Aiuto, Giuseppe Botti, Gerardo Perrone, Francesco Salomon, David S. Normanno, Nicola TI Identification of Cripto-1 as a novel serologic marker for breast and colon cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; EMBRYONIC STEM-CELLS; GROWTH-FACTOR-ALPHA; EGF-CFC FAMILY; MAMMARY-GLAND; TYROSINE PHOSPHORYLATION; THERAPEUTIC INTERVENTION; TRANSGENIC MICE; SERUM-LEVELS; GENE FAMILY AB Purpose: Human Cripto-1 (CR-1), a cell membrane glycosylphosphatidylinositol-anchored glycoprotein that can also be cleaved from the membrane, is expressed at high levels in several different types of human tumors. We evaluated whether CR-1 is present in the plasma of patients with breast and colon cancer, and if it can represent a new biomarker for these malignancies. Experimental Design: We determined CR-1 plasma levels using a sandwich-type ELISA in 21 healthy volunteers, 54 patients with breast cancer, 33 patients with colon carcinoma, and 21 patients with benign breast lesions, Immunohistochemical analysis was also used to assess CR-1 expression in cancerous tissues. Results: Very low levels of CR-1 (mean +/- SD) were detected in the plasma of healthy volunteers (0.32 +/- 0.19 ng/mL). A statistically significant increase in the levels of plasma CR-1 was found in patients with colon carcinoma (4.68 +/- 3.5 ng/mL) and in patients with breast carcinoma (2.97 +/- 1.48 ng/mL; P < 0.001). Although moderate levels of plasma CR-1 were found in women with benign lesions of the breast (1.7 +/- 0.99 ng/mL), these levels were significantly lower than in patients with breast cancer (P < 0.001). Finally, immunohistochemical analysis and real-time reverse transcription-PCR confirmed strong positivity for CR-1 in colon and/or breast tumor tissues. Conclusion: This study suggests that plasma CR-1 might represent a novel biomarker for the detection of breast and colon carcinomas. C1 NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Mol & Cellular Biol, Ann Arbor, MI USA. ITN Fdn Pascale, Cell Biol & Preclin Models Unit, Naples, Italy. ITN Fdn Pascale, Clin Trials Unit, Naples, Italy. ITN Fdn Pascale, Surg Oncol Unit C, Naples, Italy. ITN Fdn Pascale, Surg Oncol Unit A, Naples, Italy. ITN Fdn Pascale, Pathol Unit, Naples, Italy. Fox Chase Canc Ctr, Breast Canc Res Lab, Philadelphia, PA 19111 USA. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Canc Res Ctr,NIH, Bldg 37,Room 1108B, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov; nicnorm@yahoo.com RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Balogh, Gabriela/0000-0001-8836-3284; Normanno, Nicola/0000-0002-7158-2605 FU Intramural NIH HHS NR 41 TC 44 Z9 47 U1 0 U2 3 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 SEP 1 PY 2006 VL 12 IS 17 BP 5158 EP 5164 DI 10.1158/1078-0432.CCR-06-0274 PG 7 WC Oncology SC Oncology GA 082MX UT WOS:000240392000024 PM 16951234 ER PT J AU Barker, PE Wagner, PD Stein, SE Bunk, DM Srivastava, S Omenn, GS AF Barker, Peter E. Wagner, Paul D. Stein, Stephen E. Bunk, David M. Srivastava, Sudhir Omenn, Gilbert S. TI Standards for plasma and serum proteomics in early cancer detection: A needs assessment report from the National Institute of Standards and Technology-National Cancer Institute Standards, Methods, Assays, Reagents and Technologies Workshop, August 18-19, 2005 SO CLINICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY DATA; REFERENCE SPECIMENS; PROTEIN IDENTIFICATION; PILOT PHASE; PROJECT; PEPTIDE; COLLECTION; SPECTRA AB NIST and the National Cancer Institute cosponsored a workshop on August 18-19, 2005, to examine needs for reference materials for early cancer detection. This meeting focused on standards, methods, assays, reagents, and technologies. Needs for plasma and serum proteomics, DNA methylation, and specimen reference collections were discussed, and recommendations from participants were solicited. This report summarizes the discussion and recommendations for proteomics reference materials. (c) 2006 American Association for Clinical Chemistry C1 NIST, NCI, Canc Biomarker Reference Lab, Gaithersburg, MD 20899 USA. NIST, Mass Spectrometry Data Ctr, Gaithersburg, MD 20899 USA. NIST, Analyt Chem Div, Gaithersburg, MD 20899 USA. NCI, Canc Biomarkers Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Michigan, Ctr Biomed Proteom, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA. RP Barker, PE (reprint author), NIST, NCI, Canc Biomarker Reference Lab, Gaithersburg, MD 20899 USA. EM peter.barker@nist.gov FU NIDA NIH HHS [U54DA021519] NR 30 TC 27 Z9 30 U1 1 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2006 VL 52 IS 9 BP 1669 EP 1674 DI 10.1373/clinchem.200.067249 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 080XV UT WOS:000240282700009 PM 16840585 ER PT J AU Pirnay, SO Abraham, TT Huestis, MA AF Pirnay, Stephane O. Abraham, Tsadik T. Huestis, Marilyn A. TI Sensitive gas chromatography-mass spectrometry method for simultaneous measurement of MDEA, MDMA, and metabolites HMA, MDA, and HMMA in human urine SO CLINICAL CHEMISTRY LA English DT Article ID SOLID-PHASE EXTRACTION; LIQUID-CHROMATOGRAPHY; DESIGNER DRUGS; GC-MS; FLUORESCENCE DETECTION; SELF-REPORTS; WHOLE-BLOOD; AMPHETAMINE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; METHAMPHETAMINE AB Background: A sensitive gas chromatography-mass spectrometry method was developed and validated for the simultaneous measurement of MDEA, MDMA, and its metabolites, 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy), and its metabolites, 4-hydroxy-3methoxyamphetamine (HMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMMA) in human urine. Methods: We hydrolyzed 1 mL urine, fortified with MDMA-d(5), MDA-d(5), and MDEA-d(6), with 100 mu L of concentrated hydrochloric acid at 120 degrees C for 40 min, then added 100 mu L 10 N sodium hydroxide and 3 mL phosphate buffer 0.1 N (pH 6.0) were added to hydrolyzed urine specimens before solid-phase extraction. After elution and evaporation, we derivatized extracts with heptafluorobutyric acid anhydride and analyzed with gas chromatography-mass spectrometry operated in EI-selected ion-monitoring mode. Results: Limits of quantification were 25 mu g/L for MDEA, MDMA, and its metabolites. Calibration curves were linear to 5000 mu g/L for MDEA, MDMA, HMA, MDA, and HMMA, with a minimum r(2) > 0.99. At 3 concentrations spanning the linear dynamic range of the assay, mean overall extraction efficiencies from urine were > 85.5% for all compounds of interest. Intra- and interassay imprecisions, produced as CV, were < 15% for all drugs at 30, 300, and 3000 mu g/L. Conclusions: This gas chromatography-mass spectrometry assay provides adequate sensitivity and performance characteristics for the simultaneous quantification of MDEA, MDMA, and its metabolites HMMA, MDA, and HMA in human urine. The method meets and exceeds the requirements of the proposed Substance Abuse and Mental Health Services Administration's guidelines for federal workplace drug testing of MDEA and MDMA in urine. (c) 2006 American Association for Clinical Chemistry C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 30 TC 21 Z9 21 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2006 VL 52 IS 9 BP 1728 EP 1734 DI 10.1373/clinchem.2006.069054 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 080XV UT WOS:000240282700017 PM 16858076 ER PT J AU Austin, JC Peay, HL AF Austin, J. C. Peay, H. L. TI Applications and limitations of empiric data in provision of recurrence risks for schizophrenia: a practical review for healthcare professionals providing clinical psychiatric genetics consultations SO CLINICAL GENETICS LA English DT Review DE empiric risk assessment; family history; genetic counseling; mental illness; relatives ID EPIDEMIOLOGICALLY-BASED FAMILY; X ENVIRONMENT INTERACTION; CANNABIS USE; MORBID RISK; PSYCHOTIC DISORDERS; SPECTRUM DISORDERS; ROSCOMMON FAMILY; HEAD-INJURY; FOLLOW-UP; ONSET AB Schizophrenia is a common disorder that may frequently be encountered when taking family histories in the genetics clinic, whether or not the referral is for a psychiatric indication. Like in other common disorders, the provision of recurrence risks for schizophrenia is a complex clinical issue because empiric recurrence risks (while reasonably well established) can rarely be used without individual tailoring. This review seeks to identify and detail some pertinent issues surrounding the clinical utility of empiric recurrence risks for schizophrenia, and to provide an overview of important factors to consider when tailoring empiric risks for individual patients. C1 Univ British Columbia, Vancouver Gen Hosp, Ctr Complex Disorders, Vancouver, BC V5Z 1L8, Canada. Univ British Columbia, Vancouver Gen Hosp, Dept Psychiat, Vancouver, BC V5Z 1L8, Canada. Peace Arch Hosp, Early Psychosis Intervent Program, White Rock, BC, Canada. Natl Human Genome Res Inst, Social & Beahav Res Branch, Bethesda, MD USA. RP Austin, JC (reprint author), Univ British Columbia, Vancouver Gen Hosp, Ctr Complex Disorders, Res Pavil 211-828, Vancouver, BC V5Z 1L8, Canada. EM jcaustin@interchange.ubc.ca FU Intramural NIH HHS NR 84 TC 18 Z9 18 U1 3 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD SEP PY 2006 VL 70 IS 3 BP 177 EP 187 DI 10.1111/j.1399-0004.2006.00658.x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 072FO UT WOS:000239659500001 PM 16922717 ER PT J AU Sartor, O Alchalabi, T Figg, WD AF Sartor, Oliver Alchalabi, Tania Douglas Figg, William TI Assessing progress against prostate cancer SO CLINICAL GENITOURINARY CANCER LA English DT Editorial Material C1 Harvard Univ, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RP Sartor, O (reprint author), Harvard Univ, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RI Figg Sr, William/M-2411-2016 NR 4 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2006 VL 5 IS 2 BP 102 EP 103 DI 10.3816/CGC.2006.n.025 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 113TC UT WOS:000242619300001 PM 17026796 ER PT J AU Rakowski, DA Caillard, S Agodoa, LY Abbott, KC AF Rakowski, Daniel A. Caillard, Sophie Agodoa, Lawrence Y. Abbott, Kevin C. TI Dementia as a predictor of mortality in dialysis patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; CARDIOVASCULAR HEALTH; UNITED-STATES; THERAPY; DEATH; RISK; WITHDRAWAL; INITIATION; DECISIONS; SURVIVAL AB The life expectancy of patients who have dementia and are initiated on dialysis in the United States has not been described in the medical literature. A retrospective cohort study was conducted of 272,024 Medicare/Medicaid primary patients in the US Renal Data System who were started on ESRD therapy between April 1, 1995, and December 31, 1999, and followed through December 31, 2001. Cox regression was used to calculate adjusted hazard ratios for risk for death after initiation of dialysis for patients whose dementia was diagnosed before the initiation of dialysis as shown by Medicare claims. The average time to death for patients with dementia was 1.09 versus 2.7 yr (P < 0.001) with an adjusted hazard ratio of 1.87 (95% confidence interval 1.77 to 1.98). The 2-yr survival for patients with dementia was 24 versus 66% for patients without dementia (P < 0.001 via log rank test). Dementia that is diagnosed before initiation on dialysis is an independent risk factor for subsequent death. Such patients should be considered for time-limited trials of dialysis and careful discussion in choosing whether to pursue initiation of dialysis or palliative care. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 20 TC 49 Z9 50 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2006 VL 1 IS 5 BP 1000 EP 1005 DI 10.2215/CJN.00470705 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 107LL UT WOS:000242173000017 PM 17699319 ER PT J AU Furth, SL Cole, SR Moxey-Mims, M Kaskel, F Mak, R Schwartz, G Wong, C Munoz, A Warady, BA AF Furth, Susan L. Cole, Stephen R. Moxey-Mims, Marva Kaskel, Frederick Mak, Robert Schwartz, George Wong, Craig Munoz, Alvaro Warady, Bradley A. TI Design and methods of the chronic kidney disease in children (CKiD) prospective cohort study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC-RENAL-FAILURE; COGNITIVE FUNCTION; DIALYSIS PATIENTS; LONGITUDINAL DATA; SERUM CREATININE; BLOOD-PRESSURE; LINEAR-MODELS; UNITED-STATES; PROGRESSION AB An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m(2) was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior, and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured annually for 2 yr, then every other year using iohexol, HPLC creatinine, and cystatin C. Using age, gender, and serial measurements of Tanner stage, height, and creatinine, compared with iohexol GFR, a formula to estimate GFR that will improve on traditional pediatric GFR estimating equations when applied longitudinally is expected to be developed. Every other year, echocardiography and ambulatory BP monitoring will assess risk for cardiovascular disease. The primary outcome is the rate of decline of GFR. The CKiD study will be the largest North American multicenter study of pediatric CKD. C1 Johns Hopkins Childrens Ctr, Dept Pediat, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. Johns Hopkins Med Inst, Dept Pediat, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NIDDK, Bethesda, MD USA. Univ Rochester, Rochester, NY USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Furth, SL (reprint author), Johns Hopkins Med Inst, Dept Pediat, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St, Baltimore, MD 21287 USA. EM sfurth@jhmi.edu FU NCRR NIH HHS [M01 RR000997]; NIDDK NIH HHS [K24 DK078737, U01 DK066116, U01 DK066143, U01 DK066174, U01-DK-66116, U01-DK-66143, U01-DK-66174] NR 56 TC 143 Z9 156 U1 0 U2 3 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2006 VL 1 IS 5 BP 1006 EP 1015 DI 10.2215/CJN.01941205 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 107LL UT WOS:000242173000018 PM 17699320 ER PT J AU Eldadah, BA Pechnik, SL Holmes, CS Moak, JP Saleem, AM Goldstein, DS AF Eldadah, Basil A. Pechnik, Sandra L. Holmes, Courtney S. Moak, Jeffrey P. Saleem, Ahmed M. Goldstein, David S. TI Failure of propranolol to prevent tilt-evoked systemic vasodilatation, adrenaline release and neurocardiogenic syncope SO CLINICAL SCIENCE LA English DT Article DE adrenaline; beta-blocker; neurally mediated hypotension; tilt testing; vasovagal syncope ID HEAD-UP TILT; NEURALLY-MEDIATED SYNCOPE; VASOVAGAL SYNCOPE; IMPEDANCE CARDIOGRAPHY; BETA-BLOCKADE; HEALTHY-MEN; EPINEPHRINE; MECHANISMS; HUMANS; NOREPINEPHRINE AB In patients with neurocardiogenic syncope, head-up tilt often evokes acute loss of consciousness accompanied by vasodilatation, increased plasma adrenaline and systemic hypotension. Since hypotension increases adrenaline levels and adrenaline can produce skeletal muscle vasodilatation by activating,beta(2) receptors, adrenaline might induce a positive feedback loop precipitating circulatory collapse. We hypothesized that propranolol, a non-selective beta-blocker, would prevent adrenaline-induced vasodilatation and thereby prevent syncope. Eight subjects with recurrent neurocardiogenic syncope and previously documented tilt-induced syncope with elevated plasma adrenaline levels participated in the present study. Subjects underwent tilt table testing after receiving oral propranolol or placebo in a double-blind randomized crossover fashion. Haemodynamic and neurochemical variables were measured using intra-arterial monitoring, impedance cardiography, arterial blood sampling and tracer kinetics of simultaneously infused [H-3]noradrenaline and [H-3]adrenaline. The occurrence of tilt-induced neurally mediated hypotension and syncope, duration of tilt tolerance, extent of the decrease in SVRI (systemic vascular resistance index) and magnitude of plasma adrenaline increases did not differ between the propranolol and placebo treatment phases. SVRI was inversely associated with fractional increase in plasma adrenaline during both phases. One subject did not faint when on propranolol; this subject's response is discussed in the context of central effects of propranolol. In this small, but tightly controlled, study, propranolol did not prevent tilt-induced vasodilatation, syncope or elevated plasma adrenaline. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. RP Eldadah, BA (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM eldadahb@ninds.nih.gov FU Intramural NIH HHS NR 49 TC 11 Z9 12 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0143-5221 EI 1470-8736 J9 CLIN SCI JI Clin. Sci. PD SEP PY 2006 VL 111 IS 3 BP 209 EP 216 DI 10.1042/CS20060017 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 080SC UT WOS:000240267300006 PM 16634720 ER PT J AU Giacoia, GR Mattison, DR AF Giacoia, George R. Mattison, Donald R. TI Selected proceedings of the NICHD/FDA newborn drug development initiative: Part II SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Newborn Drug Development Initiative Workshop CY MAR 29-30, 2004 CL Baltimore, MD SP NICHD, FDA DE neonate; National Institute of Child Health and Human Development; US Food and Drug Administration; Newborn Drug Development Initiative ID INTENSIVE-CARE-UNIT; PATTERNS; PRETERM AB Background: In February 2003, the National Institute of Child Health and Human Development (NICHD) and the US Food and Drug Administration (FDA) created the Newborn Drug Development Initiative (NDDI), an ongoing program to determine gaps in knowledge in neonatal therapeutics and to explore clinical study designs for use in the newborn population. Working groups were established in 3 therapeutic areas: the central nervous, pulmonary, and cardiovascular systems. Three additional groups discussed pain control, drug prioritization, and ethics in neonatal clinical trials. Objective: The purpose of this article was to provide an overview of the 5 articles written by members of the Neurology, Cardiology, Drug Prioritization, and Ethics Groups. Methods: Information for the current article, as well as the 5 articles presented in this supplemental section, was gathered from the proceedings of a workshop cosponsored by the NICHD and the FDA. This workshop took place March 29 and 30, 2004, in Baltimore, Maryland. Results: The Neurology Group addressed the treatment of 2 common and interrelated conditions in the newborn population: neonatal seizures and hypoxic-ischemic encephalopathy. The unsubstantiated clinical preference for using phenobarbital to treat neonatal seizures, coupled with the development of several newer antiepileptic drugs with application in children, dictates the need for rigorous clinical trials of these drugs in the neonatal population. A number of pharmacologic agents currently undergoing extensive investigations in experimental animals and adult humans may have application in the newborn population. The Cardiology Group reviewed controversial approaches to the diagnosis and treatment of cardiovascular instability of preterm infants and identified gaps in knowledge. The group discussed issues of study design and developed 2 study proposals: (1) a placebo-controlled trial with a rescue arm for symptomatic infants; and (2) a targeted blood pressure (BP) trial. The Drug Prioritization Group focused on the fact that the uniqueness of the newborn population is due to distinctive and changing physiologic characteristics, conditions, and diseases that are different from those affecting older children, as well as the large differences in developmental patterns between 23 weeks of gestation and term. All of these factors help explain the lack of adequate trials and the sparseness of evidence regarding efficacy and toxicity risks of most drugs used in the newborn population. Unfortunately, the frequency of drug use and polypharmacy is highest in very-low-birth-weight infants. The large number of drugs requiring study and the uniqueness of the indications for those drugs preclude the use of the prioritization process used in older children. The focus of the Drug Prioritization Group was the determination of factors that identify which drugs are most important for study. The Ethics Group was unique in that its members were integrated into the therapeutic groups. This approach allowed for the identification of similarities and dissimilarities in the proposed clinical trial design framework. The summary report included here identifies common themes voiced in the various NDDI reports and deliberations. Conclusions: The 5 articles included in this issue address different issues but share common themes: the need to develop innovative trial designs and biomarkers of efficacy, consideration of ethical concerns, and selection of appropriate drugs for study. (Clin Ther. 2006;28: 1337-1341) Copyright (c) 2006 Excerpta Medica, Inc. C1 NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20847 USA. RP Giacoia, GR (reprint author), NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20847 USA. EM giacoiag@exchange.nih.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 15 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP PY 2006 VL 28 IS 9 BP 1337 EP 1341 DI 10.1016/j.clinthera.2006.09.003 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100RF UT WOS:000241685600009 PM 17062307 ER PT J AU Ward, RM Benitz, WE Benjamin, DK Blackmon, L Giacoia, GP Hudak, M Lasky, T Rodriguez, W Selen, A AF Ward, Robert M. Benitz, William E. Benjamin, Daniel K., Jr. Blackmon, Lillian Giacoia, George P. Hudak, Mark Lasky, Tamar Rodriguez, William Selen, Arzu TI Criteria supporting the study of drugs in the newborn SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Newborn Drug Development Initiative Workshop CY MAR 29-30, 2004 CL Baltimore, MD SP NICHD, FDA DE newborns; drugs prioritization; neonatal therapeutics; pediatric study ID RESPIRATORY-DISTRESS-SYNDROME; BIRTH-WEIGHT INFANTS; HYPERTROPHIC PYLORIC-STENOSIS; NUTRITION-ASSOCIATED CHOLESTASIS; MECONIUM ASPIRATION SYNDROME; PREMATURE-INFANTS; RANDOMIZED-TRIAL; NEONATAL HYPERBILIRUBINEMIA; SYNTHETIC SURFACTANT; PORACTANT ALPHA AB Background: Profound changes in the development and the maturation of neonates' organs and organ systems over variable periods of time potentially place neonates at increased risk and/or at different risks compared with adults or older children on exposure to pharmaceutical agents. Most studies of drugs in neonates focus on pharmacokinetic and pharmacodynamic end points and include insufficient numbers of patients to permit evaluation of safety. Only one fourth to one third of approved drugs have received adequate pediatric study to permit labeling for treatment of all appropriate pediatric populations. Objective: The initial goal of the Newborn Drug Prioritization Group was to develop a reproducible, objective process for evaluating drugs most in need of study in the neonatal population based on a universally acceptable priority ranking. The criteria would be applicable across therapeutic classes and would identify those drugs for which immediate study was most needed. Methods: Because the therapeutic requirements of the neonate are unique in comparison to older infants and children, the National Institute of Child Health and Human Development and the US Food and Drug Administration (FDA) developed the Newborn Drug Development Initiative to address the limited study of off-patent drugs in newborns. In March 2003, they convened a meeting of pediatric pharmacologists and pediatric specialists from the FDA, the American Academy of Pediatrics, the National Institutes of Health, and academic institutions to discuss how to increase the study of drugs for the newborn. One of the working groups was charged to develop generic criteria for overall prioritization of drugs for study in newborns. Because resources are limited, and not all drugs identified by the 4 clinically focused working groups can receive study at the same time, a process for priority ranking is necessary. Results: The panel identified 4 general categories containing different numbers of criteria as important for ranking drugs for priority investigation: (1) the disease and indication, including elements such as the potential for adverse outcomes, frequency in newborns, and level of evidence for treatment of newborns; (2) drug characteristics, including elements such as duration of dosing, lack of age-appropriate formulation, clinically relevant drug-drug and drug-disease interactions, and drug disposition in newborns; (3) feasibility and methodology for newborn studies, including both analytical considerations and clinical end points; and (4) the ethical basis for study, including elements to address benefit or harm due to exposure to the study drug, study methodology, and benefit of the new treatment relative to established standard therapy. Based on these categories, a list of criteria to warrant study of a drug in newborns was developed. Conclusion: A process for judicious use of limited resources to rectify these deficiencies remains an urgent public health need. (Clin Ther. 2006;28:13851398) Copyright (c) 2006 Excerpta Medica, Inc. C1 Univ Utah, Pediat Pharmacol Program, Salt Lake City, UT 84108 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. Lucile Packard Childrens Hosp, Palo Alto, CA USA. Duke Univ, Dept Pediat, Durham, NC 27706 USA. Duke Clin Res Inst, Durham, NC 27706 USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. NICHHD, Pediat Pharmacol Res Unit Network, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Pediat, Jacksonville, FL USA. NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Ward, RM (reprint author), Univ Utah, Pediat Pharmacol Program, 417 Wakara Way,Suite 3510, Salt Lake City, UT 84108 USA. EM robert.ward@hsc.utah.edu FU NCRR NIH HHS [5 M01 RR000070-43]; NICHD NIH HHS [1U10-HD45962-02, 1 U10 HD45986-01, HD-044799-01, 5 U10 HD027880-15] NR 75 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP PY 2006 VL 28 IS 9 BP 1385 EP 1398 DI 10.1016/j.clinthera.2006.09.007 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100RF UT WOS:000241685600013 PM 17062311 ER PT J AU Glazer, WM Conley, RR Citrome, L AF Glazer, William M. Conley, Robert R. Citrome, Leslie TI Are we treating schizophrenia effectively? Understanding the primary outcomes of The CATIE study SO CNS SPECTRUMS LA English DT Article ID INTERVENTION EFFECTIVENESS CATIE; CLINICAL ANTIPSYCHOTIC TRIALS AB The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study for schizophrenia was designed to independently evaluate the effectiveness of antipsychotic treatment in "real-world" patients. To assess the effectiveness of the conventional antipsychotics compared to the atypicals as well as the differences among the atypicals, patients were randomized to one of four atypical antipsychotics (olanzapine, quetiapine, risperidone, ziprasidone) or a representative conventional antipsychotic (perphenazine). Effectiveness was defined by time to discontinuation and duration of successful treatment. Time to "all-cause" discontinuation reflects both efficacy (ability of a drug to reduce symptoms) and safety/tolerability. Phase I revealed discontinuation rates ranging from 64% for olanzapine to 82% for quetiapine. Differences among the medications may be important in the selection of a drug for a particular patient. Physicians should involve the patient in choosing their medication by inquiring about the patient's past experience with medications and side effects, educating the patient on the risk-benefit ratio, and considering the patient's preference. To demonstrate how results of the CATIE study can contribute to the knowledge of practicing clinicians, this monograph presents a representative clinical case patient and illustrates how the CATIE safety and efficacy data has important implications for the patient. C1 Glazer Med Solut, Menemsha, MA 02552 USA. Univ Maryland, Baltimore, MD 21201 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. NIDA, Inst Review Board, Lexington, KY USA. NYU, Sch Med, New York, NY USA. Nathan S Kline Inst Psychiat Res, Clin Res & Evaluat Facil, Orangeburg, NY 10962 USA. RP Glazer, WM (reprint author), Glazer Med Solut, Menemsha, MA 02552 USA. RI Citrome, Leslie/G-6428-2012 NR 12 TC 0 Z9 0 U1 2 U2 2 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD SEP PY 2006 VL 11 IS 9 SU 10 BP 4 EP 11 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 090NJ UT WOS:000240957700001 ER PT J AU Blair, RJR AF Blair, R. J. R. TI The emergence of psychopathy: Implications for the neuropsychological approach to developmental disorders SO COGNITION LA English DT Review DE psychopathy; reward and punishment; development; amygdala ID ORBITOFRONTAL CORTEX DYSFUNCTION; PRESCHOOL CHILDRENS CONCEPTIONS; VENTROMEDIAL PREFRONTAL CORTEX; FRONTAL-LOBE DAMAGE; FACIAL EXPRESSIONS; RESPONSE REVERSAL; DECISION-MAKING; HUMAN AMYGDALA; ANTISOCIAL PERSONALITY; SOCIAL INFORMATION AB In this paper, I am going to examine the disorder of psychopathy and consider how genetic anomalies could give rise to the relatively specific neuro-cognitive impairments seen in individuals with this disorder. I will argue that genetic anomalies in psychopathy reduce the salience of punishment information (perhaps as a function of noradrenergic disturbance). I will argue that the ability of the amygdala to form the stimulus-punishment associations necessary for successful socialization is disrupted and that because of this, individuals with psychopathy do not learn to avoid actions that will harm others. It is noted that this model follows the neuropsychological approach to the study of developmental disorders, an approach that has been recently criticized. I will argue that these criticisms are less applicable to psychopathy. Indeed, animal work on the development of the neural systems necessary for emotion, does not support a constructivist approach with respect to affect. Importantly, such work indicates that while environmental effects can alter the responsiveness of the basic neural architecture mediating emotion, environmental effects do not construct this architecture. However, caveats to the neuropsychological approach with reference to this disorder are noted. Published by Elsevier B.V. C1 NIMH, Mood & Anxiety Disorders Program, US Dept HHS, NIH, Bethesda, MD USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Disorders Program, US Dept HHS, NIH, Bethesda, MD USA. EM blairj@intra.nimh.nih.gov NR 168 TC 88 Z9 90 U1 14 U2 45 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD SEP PY 2006 VL 101 IS 2 BP 414 EP 442 DI 10.1016/j.cognition.2006.04.005 PG 29 WC Psychology, Experimental SC Psychology GA 082VF UT WOS:000240414600006 PM 16904094 ER PT J AU Lotze, M Cohen, LG AF Lotze, Martin Cohen, Leonardo G. TI Volition and imagery in neurorehabilitation SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE motivation; attention; motor imagery; hemiparesis; rehabilitation; forced use; volition; stroke; motor system; motor cortex ID HUMAN MOTOR CORTEX; POSITRON EMISSION TOMOGRAPHY; USE-DEPENDENT PLASTICITY; CORTICAL REORGANIZATION; MENTAL PRACTICE; FINGER MOVEMENTS; HAND MOVEMENTS; STROKE; PERFORMANCE; BRAIN AB New interventional approaches have been proposed in the last few years to treat the motor deficits resulting from brain lesions. Training protocols represent the gold-standard of these approaches. However, the degree of motor recovery experienced by most patients remains incomplete. It would be important to improve our understanding of the mechanisms underlying functional recovery. This chapter examines the role of two possible mechanisms that could operate to improve motor function in this setting: volition and motor imagery. It is argued that both represent possible strategies to enhance training effects. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Lotze, M (reprint author), Univ Tubingen, Inst Med Psychol & Verhaltensneurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM martin.lotze@uni-tuebingen.de NR 68 TC 43 Z9 46 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD SEP PY 2006 VL 19 IS 3 BP 135 EP 140 DI 10.1097/01.wnn.0000209875.56060.06 PG 6 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 089UZ UT WOS:000240908100004 PM 16957491 ER PT J AU Gardiner, JM Brandt, KR Vargha-Khadem, F Baddeley, A Mishkin, M AF Gardiner, John M. Brandt, Karen R. Vargha-Khadem, Faraneh Baddeley, Alan Mishkin, Mortimer TI Effects of level of processing but not of task enactment on recognition memory in a case of developmental amnesia SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID SUBJECT-PERFORMED TASKS; EPISODIC MEMORY; SEMANTIC MEMORY; HIPPOCAMPAL DAMAGE; WORKING-MEMORY; ACTION EVENTS; RECOLLECTION; ORGANIZATION; ACQUISITION; FAMILIARITY AB We report the performance in four recognition memory experiments of Jon, a young adult with early-onset developmental amnesia whose episodic memory is gravely impaired in tests of recall, but seems relatively preserved in tests of recognition, and who has developed normal levels of performance in tests of intelligence and general knowledge. Jon's recognition performance was enhanced by deeper levels of processing in comparing a more meaningful study task with a less meaningful one, but not by task enactment in comparing performance of an action with reading an action phrase. Both of these variables normally enhance episodic remembering, which Jon claimed to experience. But Jon was unable to support that claim by recollecting what it was that he remembered. Taken altogether, the findings strongly imply that Jon's recognition performance entailed little genuine episodic remembering and that the levels-of-processing effects in Jon reflected semantic, not episodic, memory. C1 Univ Sussex, Dept Psychol, Brighton BN1 9QH, E Sussex, England. Univ Keele, Keele ST5 5BG, Staffs, England. UCL, London, England. Great Ormond St Hosp Sick Children, London WC1N 3JH, England. Univ York, York YO10 5DD, N Yorkshire, England. NIMH, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Gardiner, JM (reprint author), Univ Sussex, Dept Psychol, Brighton BN1 9QH, E Sussex, England. EM J.M.Gardiner@sussex.ac.uk RI Vargha-Khadem, Faraneh/C-2558-2008 FU Medical Research Council [G0300117] NR 46 TC 23 Z9 23 U1 0 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD SEP PY 2006 VL 23 IS 6 BP 930 EP 948 DI 10.1080/02643290600588442 PG 19 WC Psychology; Psychology, Experimental SC Psychology GA 088QD UT WOS:000240825300007 PM 21049360 ER PT J AU Josic, D Clifton, JG Wang, A Li, X Hixson, D Dong, H Rosenquist, T AF Josic, D. Clifton, J. G. Wang, A. Li, X. Hixson, D. Dong, H. Rosenquist, T. TI Proteomics of aristolochic acid nephropathy SO COLLEGIUM ANTROPOLOGICUM LA English DT Meeting Abstract C1 SUNY Stony Brook, Sch Med, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. Rhode Isl Hosp, COBRE, Ctr Canc Res Dev, Providence, RI 02903 USA. RI Clifton, James/C-7289-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLLEGIUM ANTROPOLOGICUM PI ZAGREB PA INST ANTHROPOLOGICAL RES, P O BOX 290, ULICA GRADA VUKOVARA 72/IV, 10000 ZAGREB, CROATIA SN 0350-6134 J9 COLLEGIUM ANTROPOL JI Coll. Anthropol. PD SEP PY 2006 VL 30 SU 1 BP 28 EP 28 PG 1 WC Anthropology SC Anthropology GA 111ID UT WOS:000242443700020 ER PT J AU Gupta, R Sharma, S Brosh, RM AF Gupta, Rigu Sharma, Sudha Brosh, Robert M., Jr. TI The emerging importance of DNA helicases to stabilize the replication fork SO CURRENT GENOMICS LA English DT Review DE helicase; replication; chromatin remodeling; genomic instability ID WERNER-SYNDROME PROTEIN; BLOOMS-SYNDROME HELICASE; SUBSTRATE-SPECIFIC INHIBITION; STRAND-ANNEALING ACTIVITIES; ROTHMUND-THOMSON-SYNDROME; S-PHASE ARREST; RECQ HELICASE; FLAP ENDONUCLEASE-1; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE AB DNA helicases have historically been implicated in the initiation or elongation phases of DNA replication; however, elegant studies in prokaryotic systems have suggested more specialized functions of helicases to stabilize the replication fork when DNA replication is impeded. More recently, it has become increasingly evident that eukaryotic DNA helicases function at replication forks to participate in processes that include DNA damage detection and signaling, resolution of alternate DNA structures, fork regression, and replication restart. Genetic and biochemical studies have begun to elucidate the molecular roles of DNA helicases at the replication fork in the coordination of the synthesis and processing of leading and lagging strand, a vital function to preserve genomic integrity. In addition, ATP-dependent chromatin remodeling by helicase-like proteins during replication initiation, elongation, or restart may have important roles as well. These themes will be discussed with an emphasis on the cellular mechanisms of DNA helicases/chromatin remodeling enzymes implicated in human disease and proposed to function with other protein factors during replication. C1 NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, NIH, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 NR 108 TC 1 Z9 1 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD SEP PY 2006 VL 7 IS 6 BP 387 EP 398 DI 10.2174/138920206778948709 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 115RB UT WOS:000242750400005 ER PT J AU Semenova, EA Johnson, AA Marchand, C Pommier, Y AF Semenova, Elena A. Johnson, Allison A. Marchand, Christophe Pommier, Yves TI Integration of human immunodeficiency virus as a target for antiretroviral therapy SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE antiretroviral therapy; clinical trial; HIV; inhibitor; integrase; preintegration complex AB Purpose of review Most of the studies investigating inhibition of human immunodeficiency virus integration have focused on blocking the enzymatic functions of HIV integrase, with the predominant judgment that integration inhibitors need to block at least one of the integrase-catalyzed reactions. Recent studies, however, have highlighted the importance of other proteins and their contacts with integrase in the preintegration complex, and their involvement in chromosomal integration of the viral DNA. Recent findings Promising results of clinical trials for two new integrase inhibitors were announced recently, providing the proof of the concept for using HIV-1 integrase inhibitors as antiretroviral therapy. Two strategies are currently employed for the development of novel inhibitors of HIV integrase: synthesis of hybrid molecules comprising core structures of two or more known inhibitors, and three-dimensional pharmacophore searches based on previously discovered compounds. By highlighting the role of the cellular cofactor LEDGF/p75 in HIV integration, novel approaches are indicated that aim to develop compounds altering contact between HIV integrase and integration cofactors. Summary By the discovery of novel inhibitors and targets for HIV integration, coupled with recent studies in characterizing preintegration complex formation, new insight is provided for the rational design of anti-HIV integration inhibitors. C1 [Semenova, Elena A.; Johnson, Allison A.; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Marchand, Christophe/D-8559-2016 FU NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 72 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD SEP PY 2006 VL 1 IS 5 BP 380 EP 387 DI 10.1097/01.COH.0000239850.14991.f9 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NP UT WOS:000208417400005 PM 19372837 ER PT J AU Ameye, LG Young, MF AF Ameye, Laurent G. Young, Marian F. TI Animal models of osteoarthritis: lessons learned while seeking the 'Holy Grail' SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE animal models; bone; 'gold standard'; osteoarthritis ID SPONTANEOUS KNEE OSTEOARTHRITIS; CRUCIATE LIGAMENT TRANSECTION; OVEREXPRESSING CATHEPSIN-K; SUBCHONDRAL BONE CHANGES; GUINEA-PIG MODEL; CANINE EXPERIMENTAL OSTEOARTHRITIS; SYNOVIAL LINING MACROPHAGES; NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE; COLLAGEN TYPE-II AB Purpose of review Difficulties in studying osteoarthritis in humans that stem from both the low sensitivity of diagnostic tools and the low availability of diseased tissues explain why research on animal models remains highly dynamic. This review will summarize the recent advances in this field. Recent findings With regard to the etiology of osteoarthritis, synovial macrophages mediate osteophyte formation, whereas increased ligament laxity could be responsible for spontaneous osteoarthritis in guinea pigs. The concomitant changes in subchondral bone and cartilage reported in several models, and the structure-modifying effects of some bone inhibitors have confirmed the importance of bone in osteoarthritis. With regard to cartilage pathobiology, ADAMTS-5 is the major aggrecanase responsible for cartilage destruction, whereas inadequate control of oxidative stress and decreased expression of transforming growth factor-beta receptors could predispose to osteoarthritis. New models include a postmenopausal rat model, the groove model and a joint-specific bone morphogenetic receptor-deficient mouse. The iodoacetate model was also validated as the first pain model of osteoarthritis. Summary In view of the multiple animal models available, there is a need to reach a consensus on one or several gold standard animal model(s). New studies indicate that important differences in therapeutic response exist between young and old animals, and between spontaneous and surgical models, suggesting that not all models are adequate models of osteoarthritis. C1 Nestle Res Ctr, Nutr & Hlth Dept, CH-1000 Lausanne, Switzerland. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Ameye, LG (reprint author), Nestle Res Ctr, Nutr & Hlth Dept, CH-1000 Lausanne, Switzerland. EM laurent.ameye@rdls.nestle.com NR 108 TC 77 Z9 78 U1 0 U2 20 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 SEP PY 2006 VL 18 IS 5 BP 537 EP 547 DI 10.1097/01.bor.0000240369.39713.af PG 11 WC Rheumatology SC Rheumatology GA 086DI UT WOS:000240652900018 PM 16896297 ER PT J AU Campbell, RM DiGiovanna, JJ AF Campbell, Ross M. DiGiovanna, John J. TI Skin cancer chemoprevention with systemic retinoids: an adjunct in the management of selected high-risk patients SO DERMATOLOGIC THERAPY LA English DT Article DE carcinoma; chemoprevention; xeroderma pigmentosum; ultraviolet radiation ID RENAL-TRANSPLANT RECIPIENTS; BASAL-CELL CARCINOMA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BREAST-CANCER; POSTMENOPAUSAL WOMEN; XERODERMA-PIGMENTOSUM; RANDOMIZED-TRIAL; TAMOXIFEN THERAPY; ORAL ISOTRETINOIN; PREVENTION AB Systemic retinoids (isotretinoin, etretinate, and acitretin) have been shown to be effective chemotherapeutic agents in studies of patients with xeroderma pigmentosum, the nevoid basal cell carcinoma syndrome, and recipients of organ or bone marrow transplantation. In addition, patients who do not have these disorders but who are actively developing large numbers of new skin cancers may also benefit from this approach. All patients developing large numbers of skin cancers need rigorous UV protection and frequent dermatologic examinations. Although isotretinoin and acitretin share overlapping toxicities, there are differences that may affect drug choice. Because low doses may be effective, there are advantages to beginning treatment at a low dose, and subsequently, increasing dose if necessary, based on patient response. Laboratory monitoring including pregnancy testing should be performed before and during treatment. Long-term toxicity, primarily involving the skeletal system, can be monitored with imaging studies. C1 Brown Med Sch, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02903 USA. Rhode Isl Hosp, Providence, RI 02903 USA. NCI, DNA Repair Sect, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP DiGiovanna, JJ (reprint author), Brown Med Sch, Dept Dermatol, Div Dermatopharmacol, JBS-1,593 Eddy St, Providence, RI 02903 USA. EM jdg@Brown.edu NR 38 TC 29 Z9 30 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD SEP-OCT PY 2006 VL 19 IS 5 BP 306 EP 314 DI 10.1111/j.1529-8019.2006.00088.x PG 9 WC Dermatology SC Dermatology GA 088PU UT WOS:000240824400008 PM 17014486 ER PT J AU Francis, RJB Lo, CW AF Francis, Richard J. B. Lo, Cecilia W. TI Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation SO DEVELOPMENT LA English DT Article DE PGC; Cx43; migration; p53; beta 1 integrin; apoptosis; mouse ID MICE LACKING CONNEXIN43; GAP JUNCTIONAL COMMUNICATION; INTERCELLULAR COMMUNICATION; GRANULOSA-CELLS; SURVIVAL SIGNALS; EXPRESSION; MIGRATION; PROLIFERATION; EMBRYOS; GROWTH AB Connexin 43 knockout (Cx43 alpha 1KO) mice exhibit germ cell deficiency, but the underlying cause for the germ cell defect was unknown. Using an Oct4-GFP reporter transgene, we tracked the distribution and migration of primordial germ cells (PGCs) in the Cx43 alpha 1KO mouse embryo. Analysis with dye injections showed PGCs are gap-junction-communication competent, with dye coupling being markedly reduced in Cx43 alpha 1-deficient PGCs. Time-lapse videomicroscopy and motion analysis showed that the directionality and speed of cell motility were reduced in the Cx43 alpha 1KO PGCs. This was observed both in E8.5 and E11.5 embryos. By contrast, PGC abundance did not differ between wild-type and heterozygous/homozygous Cx43 alpha 1KO embryos until E11.5, when a marked reduction in PGC abundance was detected in the homozygous Cx43 alpha 1KO embryos. This was accompanied by increased PGC apoptosis and increased expression of activated p53. Injection of alpha-pifithrin, a p53 antagonist, inhibited PGC apoptosis and prevented the loss of PGC. Analysis using a cell adhesion assay indicated a reduction in beta 1-integrin function in the Cx43 alpha 1KO PGCs. Together with the abnormal activation of p53, these findings suggest the possibility of anoikis-mediated apoptosis. Overall, these findings show Cx43 alpha 1 is essential for PGC survival, with abnormal p53 activation playing a crucial role in the apoptotic loss of PGCs in the Cx43 alpha 1KO mouse embryos. C1 NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lo, CW (reprint author), NHLBI, Dev Biol Lab, NIH, Bldg 50,Room 4537,9000 Rockville Pike, Bethesda, MD 20892 USA. EM loc@nhlbi.nih.gov RI Francis, Richard/P-2524-2015 FU Intramural NIH HHS NR 52 TC 37 Z9 39 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 1 PY 2006 VL 133 IS 17 BP 3451 EP 3460 DI 10.1242/dev.02506 PG 10 WC Developmental Biology SC Developmental Biology GA 073QW UT WOS:000239758700018 PM 16887824 ER PT J AU Park, C Lavine, K Mishina, Y Deng, CX Ornitz, DM Choi, K AF Park, Changwon Lavine, Kory Mishina, Yuji Deng, Chu-Xia Ornitz, David M. Choi, Kyunghee TI Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation SO DEVELOPMENT LA English DT Article DE hematopoiesis; vasculogenesis; endocardial cushion; FLK1 (KDR); ALK3 (BMPR1A); SMAD4; mouse ID EPITHELIAL-MESENCHYMAL TRANSITION; CONDITIONAL KNOCKOUT MICE; ENDOTHELIAL GROWTH-FACTOR; EMBRYONIC STEM-CELLS; SMOOTH-MUSCLE-CELLS; NEURAL CREST CELLS; IN-VITRO ANALYSIS; OUTFLOW-TRACT; VASCULAR DEVELOPMENT; DEFICIENT MICE AB Bone morphogenetic protein 4 (BMP4) is crucial for the formation of FLK1-expressing (FLK1+) mesodermal cells. To further define the requirement for BMP signaling in the differentiation of blood, endothelial and smooth muscle cells from FLK1+ mesoderm, we inactivated Alk3 (Bmpr1a) in FLK1(+) cells by crossing Alk3(floxed/floxed) and Flk1(+/Cre)Alk3(+/floxed) mice. Alk3 conditional knockout (CKO) mice died between E10.5 and E11.5. Unexpectedly, Alk3 CKO embryos did not show any hematopoietic defects. However, Alk3 CKO embryos displayed multiple abnormalities in vascular development, including vessel remodeling and maturation, which contributed to severe abdominal hemorrhage. Alk3 CKO embryos also displayed defects in atrioventricular canal (AVC) endocardial cushion formation in the heart. Collectively, our studies indicate a crucial role for ALK3 in vessel remodeling, vessel integrity and endocardial cushion formation during the development of the circulation system. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dev Biol Program, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. NIEHS, Mol Dev Biol Grp, Res Triangle Pk, NC 27709 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Choi, K (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid, St Louis, MO 63110 USA. EM kchoi@wustl.edu RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS; NHLBI NIH HHS [HL55337, R01S HL63736] NR 71 TC 66 Z9 67 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 1 PY 2006 VL 133 IS 17 BP 3473 EP 3484 DI 10.1242/dev.02499 PG 12 WC Developmental Biology SC Developmental Biology GA 073QW UT WOS:000239758700020 PM 16887829 ER PT J AU Dickstein, DP Leibenluft, E AF Dickstein, Daniel P. Leibenluft, Ellen TI Emotion regulation in children and adolescents: Boundaries between normalcy and bipolar disorder SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID ANTERIOR CINGULATE CORTEX; FUSIFORM FACE AREA; DEFICIT HYPERACTIVITY DISORDER; SUBGENUAL PREFRONTAL CORTEX; FRONTAL-LOBE CONTRIBUTIONS; VOXEL-BASED MORPHOMETRY; ORBITOFRONTAL CORTEX; FACIAL EXPRESSIONS; ANXIETY DISORDERS; ATTENTION-DEFICIT AB Much controversy has surrounded the diagnosis of bipolar disorder (BD) in children and adolescents. However, recent work from an affective neuroscience perspective has advanced what is known about the boundaries of emotion regulation in BD compared to typically developing youth. In this article, we first briefly review the clinical issues that have contributed to this diagnostic controversy. Second, we discuss our phenotyping system, which can be used to guide neurobiological research designed to address these controversial issues. Third, we review what is known about the fundamentals of emotion regulation in human and nonhuman primate models. Fourth, we present recent data demonstrating how children and adolescents with BD differ from those without psychopathology on measures of emotion regulation. Taken as a whole, this work implicates a neural circuit encompassing the prefrontal cortex, amygdala, and striatum in the pathophysiology of pediatric BD. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Dickstein, DP (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, 9000 Rockville Pike,MSC 2670,Bldg 15K,Room 204, Bethesda, MD 20892 USA. EM dicksted@mail.nih.gov RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 FU Intramural NIH HHS; NIMH NIH HHS [K22-MH 74945] NR 187 TC 33 Z9 34 U1 21 U2 26 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 2006 VL 18 IS 4 BP 1105 EP 1131 DI 10.1017/S0954579406060536 PG 27 WC Psychology, Developmental SC Psychology GA 104CJ UT WOS:000241933300008 PM 17064430 ER PT J AU Post, RM Leverich, GS AF Post, R. M. Leverich, G. S. TI The role of psychosocial stress in the onset and progression of bipolar disorder and its comorbidities: The need for earlier and alternative modes of therapeutic intervention SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID TREATMENT ENHANCEMENT PROGRAM; PITUITARY-ADRENAL AXIS; MAJOR DEPRESSION; LIFE EVENTS; ANXIETY DISORDERS; ANTIDEPRESSANT TREATMENT; GENDER-DIFFERENCES; SUICIDAL-BEHAVIOR; MENTAL-DISORDERS; HOME VISITATION AB Psychosocial stress plays an important role at multiple junctures in the onset and course of bipolar disorder. Childhood adversity may be a risk factor for vulnerability to early onset illness, and an array of stressors may be relevant not only to the onset, recurrence, and progression of affective episodes, but the highly prevalent substance abuse comorbidities as well. A substantial group of controlled studies indicate that various cognitive behavioral psychotherapies and psychoeducational approaches may yield better outcomes in bipolar disorder than treatment as usual. Yet these approaches do not appear to be frequently or systematically employed in clinical practice, and this may contribute to the considerable residual morbidity and mortality associated with conventional treatment. Possible practical approaches to reducing this deficit (in an illness that is already underdiagnosed and undertreated even with routine medications) are offered. Without the mobilization of new clinical and public health approaches to earlier and more effective treatment and supportive interventions, bipolar illness will continue to have grave implications for many patients' long-term well being. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Penn State Univ, Sch Med, University Pk, PA 16802 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3S239,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. EM robert.post@speakeasy.net NR 124 TC 69 Z9 73 U1 10 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 2006 VL 18 IS 4 BP 1181 EP 1211 DI 10.1017/S0954579406060573 PG 31 WC Psychology, Developmental SC Psychology GA 104CJ UT WOS:000241933300012 PM 17064434 ER PT J AU Steingrimsson, E Copeland, NG Jenkins, NA AF Steingrimsson, Eirikur Copeland, Neal G. Jenkins, Nancy A. TI Mouse coat color mutations: From fancy mice to functional genomics SO DEVELOPMENTAL DYNAMICS LA English DT Review DE mouse; coat color; melanocyte; development ID MELANOCYTE STEM-CELL; LYSOSOME-RELATED ORGANELLES; NEURAL CREST DEVELOPMENT; ENDOTHELIN-B RECEPTOR; OCULOCUTANEOUS ALBINISM; DILUTE SUPPRESSOR; MELANOSOME TRANSPORT; ZIPPER TRANSCRIPTION; HAIR PIGMENTATION; DISTINCT ROLES AB Mouse coat color mutations have a long history in biomedical research. The viable and visible phenotype of most coat color mutations has made the pigment cell, the melanocyte, an ideal system for genetic, molecular, and cellular analysis. Molecular cloning and analysis of many of the different coat color mutations have revealed the roles of a diverse range of genes, and today we know more about the pathways and proteins that regulate the development and function of pigment cells than we know about most other cell types in mammalian organisms. Coat color mutations have also provided novel insights into stem cell biology and human diseases, including melanoma. In the future, it will be important to build on this history and knowledge by taking advantage of the extensive repertoire of recently developed genome-wide methodologies, available genomic information, and the powerful methods that have been developed for modifying the mouse genome to systematically dissect the development and function of this important cell type. The usefulness of coat color mutations has just begun to emerge. C1 Univ Iceland, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland. NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD USA. RP Steingrimsson, E (reprint author), Univ Iceland, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland. EM eirikurs@hi.is FU Intramural NIH HHS NR 76 TC 40 Z9 41 U1 0 U2 8 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 SEP PY 2006 VL 235 IS 9 BP 2401 EP 2411 DI 10.1002/dvdy.20840 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 080QG UT WOS:000240262000010 PM 16691561 ER PT J AU Ko, MSH AF Ko, Minoru S. H. TI Expression profiling of the mouse early embryo: Reflections and perspectives SO DEVELOPMENTAL DYNAMICS LA English DT Review DE expression profiling; microarray; stem cells; preimplantation embryos; embryogenomics; large-scale analysis ID SUPPRESSION SUBTRACTIVE HYBRIDIZATION; IN-SITU HYBRIDIZATION; GENE-EXPRESSION; STEM-CELLS; PREIMPLANTATION EMBRYOS; MICROARRAY PLATFORMS; GENOME-WIDE; SIGNALING PATHWAYS; MESSENGER-RNA; CDNA PROJECT AB The laboratory mouse model plays important roles in our understanding of early mammalian development and provides an invaluable model for human early embryos, which are difficult to study for ethical and technical reasons. A comprehensive collection of cDNA clones, their sequences, and complete genome sequence information, which have been accumulated over the past two decades, reveal even further the value of the mouse models. Here, the progress in global gene expression profiling in early mouse embryos and, to some extent, stem cells is reviewed and future directions and challenges are discussed. The discussions include the restatement of global gene expression profiles as a snapshot of cellular status, and subsequent distinction between the differentiation state and physiological state of the cells. The discussions then extend to the biological problems that can be addressed only through global expression profiling, including a bird's-eye view of global gene expression changes, molecular index for developmental potency, cell lineage trajectory, microarray-guided cell manipulation, and the possibility of delineating gene regulatory cascades and networks. C1 NIA, Dev Genomics & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genomics & Aging Sect, Genet Lab, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS [Z01 AG000655-09, Z01 AG000656-09, Z01 AG000662-07] NR 98 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2006 VL 235 IS 9 BP 2437 EP 2448 DI 10.1002/dvdy.20859 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 080QG UT WOS:000240262000013 PM 16739220 ER PT J AU Nakamura, E Nguyen, MT Mackem, S AF Nakamura, Eiichiro Nguyen, Minh-Thanh Mackem, Susan TI Kinetics of tamoxifen-regulated Cre activity in mice using a cartilage-specific CreER(T) to assay temporal activity windows along the proximodistal limb skeleton SO DEVELOPMENTAL DYNAMICS LA English DT Article DE tamoxifen-dependent Cre; Col2a1 transgenic promoter; chondrogenic deleter line; CreER(T) in cartilage ID PRO-ALPHA-1(II) COLLAGEN GENE; TRANSGENIC MICE; CHONDROCYTE DIFFERENTIATION; ENDOCHONDRAL SKELETON; INDUCIBLE FORM; MOUSE; EXPRESSION; RECOMBINASE; IDENTIFICATION; MORPHOGENESIS AB Cartilage differentiation occurs over a broad time range from early embryonic development, when the mesenchymal condensations that give rise to cartilage models for future bone first appear, and continuing through adult life, when there is ongoing maintenance of articular joint surfaces and re-activation of cartilage formation after fracture. The chondrogenic response also figures in the pathogenesis of degenerative and inflammatory joint diseases. We have generated a transgenic line expressing tamoxifen-dependent Cre recombinase that gives efficient recombination in the chondrogenic lineage, both during embryogenesis and postnatally, and provides a valuable tool for analysis of gene function selectively in chondrogenic cells using conditional genetic approaches. Because the cartilage model of the limb skeleton forms progressively in a proximodistal order during discrete, well-defined time periods, evaluation of the spatial extent of tamoxifen-induced recombination along the limb axis during these time windows has also enabled us to examine the pharmacokinetics of single-dose tamoxifen injections during pregnancy. Developmental Dynamics 235:2603-2612, 2006. (c) 2006 Wiley-Liss, Inc. C1 NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mackem, S (reprint author), NCI, Pathol Lab, Canc Res Ctr, NIH, Bldg 10,Rm 2A33, Bethesda, MD 20892 USA. EM smack@helix.nih.gov NR 34 TC 116 Z9 116 U1 0 U2 3 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 SEP PY 2006 VL 235 IS 9 BP 2603 EP 2612 DI 10.1002/dvdy.20892 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 080QG UT WOS:000240262000028 PM 16894608 ER PT J AU Bonnycastle, LL Willer, CJ Conneely, KN Jackson, AU Burrill, CP Watanabe, RM Chines, PS Narisu, N Scott, LJ Enloe, ST Swift, AJ Duren, WL Stringham, HM Erdos, MR Riebow, NL Buchanan, TA Valle, TT Tuomilehto, J Bergman, RN Mohlke, KL Boehnke, M Collins, FS AF Bonnycastle, Lori L. Willer, Cristen J. Conneely, Karen N. Jackson, Anne U. Burrill, Cecily P. Watanabe, Richard M. Chines, Peter S. Narisu, Narisu Scott, Laura J. Enloe, Sareena T. Swift, Amy J. Duren, William L. Stringham, Heather M. Erdos, Michael R. Riebow, Nancy L. Buchanan, Thomas A. Valle, Timo T. Tuomilehto, Jaakko Bergman, Richard N. Mohlke, Karen L. Boehnke, Michael Collins, Francis S. TI Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns SO DIABETES LA English DT Article ID NUCLEAR FACTOR-4-ALPHA GENE; BETA-CELL FUNCTION; CAUCASIAN POPULATION; HNF1-ALPHA GENE; FACTOR 4-ALPHA; ASSOCIATION; PROMOTER; SUSCEPTIBILITY; POLYMORPHISMS; MUTATIONS AB Prior reports have suggested that variants in the genes for maturity-onset diabetes of the young (MODY) may confer susceptibility to type 2 diabetes, but results have been conflicting and coverage of the MODY genes has been incomplete. To complement our previous studies of HNF4A, we examined the other five known MODY genes for association with type 2 diabetes in Finnish individuals. For each of the five genes, we selected 1) nonredundant single nucleotide polymorphisms (SNPs) (r(2)< 0.8 with other SNPs) from the HapMap database or another linkage disequilibrium map, 2) SNPs with previously reported type 2 diabetes association, and 3) nonsynonymous coding SNPs. We tested 128 SNPs for association with type 2 diabetes in 786 index cases from type 2 diabetic families and 619 normal glucose-tolerant control subjects. We followed tip 35 of the most significant SNPs by genotyping them on another 384 case subjects and 366 control subjects from Finland. We also supplemented our previous HNF4A results by genotyping 12 SNPs on additional Finnish samples. After correcting for testing multiple correlated SNPs within a gene, we find evidence of type 2 diabetes association with SNPs in five of the six known MODY genes: GCK, HNF1A, HNF1B, NEUROD1, and HNF4A. Our data suggest that common variants in several MODY genes play a modest role in type 2 diabetes susceptibility. C1 NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90089 USA. Natl Inst Publ Hlth, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. S Ostrobothnia Cent Hosp, Seinajoki, Finland. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. RP Collins, FS (reprint author), NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. EM francisc@mail.nih.gov OI Willer, Cristen/0000-0001-5645-4966 FU Intramural NIH HHS; NHGRI NIH HHS [1Z01HG000024-11]; NIDDK NIH HHS [DK27619, DK29867, DK62370, DK72193, R01 DK029867, R01 DK072193] NR 50 TC 48 Z9 52 U1 0 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 SEP PY 2006 VL 55 IS 9 BP 2534 EP 2540 DI 10.2337/db06-0178 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LC UT WOS:000240456400015 PM 16936201 ER PT J AU Zeggini, E Damcott, CM Hanson, RL Karim, MA Rayner, NW Groves, CJ Baier, LJ Hale, TC Hattersley, AT Hitman, GA Hunt, SE Knowler, WC Mitchell, BD Ng, MCY O'Connell, JR Pollin, TI Vaxillaire, M Walker, M Wang, XQ Whittaker, P Kunsun, X Jia, WP Chan, JCN Froguel, P Deloukas, P Shuldiner, AR Elbein, SC McCarthy, MI AF Zeggini, Eleftheria Damcott, Coleen M. Hanson, Robert L. Karim, Mohammad A. Rayner, N. William Groves, Christopher J. Baier, Leslie J. Hale, Terri C. Hattersley, Andrew T. Hitman, Graham A. Hunt, Sarah E. Knowler, William C. Mitchell, Braxton D. Ng, Maggie C. Y. O'Connell, Jeffrey R. Pollin, Toni I. Vaxillaire, Martine Walker, Mark Wang, Xiaoqin Whittaker, Pamela Kunsun, Xiang Jia, Weiping Chan, Juliana C. N. Froguel, Philippe Deloukas, Panos Shuldiner, Alan R. Elbein, Steven C. McCarthy, Mark I. CA Int Type 2 Diabet 1q Consortium TI Variation within the gene encoding the upstream stimulatory factor 1 does not influence susceptibility to type 2 diabetes in samples from populations with replicated evidence of linkage to chromosome 1q SO DIABETES LA English DT Article ID FAMILIAL COMBINED HYPERLIPIDEMIA; GENOME-WIDE SCAN; COMPLEX HUMAN-DISEASES; HONG-KONG CHINESE; METABOLIC SYNDROME; INDEPENDENT REPLICATION; QUANTITATIVE TRAITS; GLUCOSE; ASSOCIATION; LOCUS AB The gene encoding the transcription factor upstream stimulatory factor (USF)1 influences susceptibility to familial combined hyperlipidemia (FCHL) and triglyceride levels. Phenotypic overlap between FCHL and type 2 diabetes makes USF1 a compelling positional candidate for the widely replicated type 2 diabetes linkage signal on chromosome 1q. We typed 22 variants in the F11R/USF1 region (1 per 3 kb), including those previously implicated in FCHL-susceptibility (or proxies thereof) in 3,726 samples preferentially enriched for 1q linkage. We also examined glucose- and lipid-related continuous traits in an overlapping set of 1,215 subjects of European descent. There was no convincing evidence for association with type 2 diabetes in any of seven case-control comparisons, individually or combined. Family-based association analyses in 832 Pima subjects were similarly negative. At rs3737787 (the variant most strongly associated with FCHL), the combined odds ratio, per copy of the rarer A-allele, was 1.10 (95% CI 0.97-1.24, P = 0.13). In 124 Utah subjects, rs3737787 was significantly associated (P = 0.002) with triglyceride levels, but direction of this association was opposite to previous reports, and there was no corroboration in three other samples. These data exclude USF1 as a major contributor to type 2 diabetes susceptibility and the basis for the chromosome 1q linkage. They reveal only limited evidence for replication of USF1 effects on continuous metabolic traits. C1 Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. NIDDK, Phoenix Epidemiol & Clin Res Sect, Phoenix, AZ USA. Cent Arkansas Vet Healthcare Syst, Med Serv, Endocrinol Sect, Little Rock, AR USA. Univ Arkansas Med Sci, Coll Med, Dept Internal Med, Div Endocrinol & Metab, Little Rock, AR 72205 USA. Peninsula Med Sch, Inst Clin & Biomed Sci, Exeter, Devon, England. Barts & London St Marys Sch Med & Dent, Ctr Diabet & Metab Med, London, England. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China. Inst Biol Lille, Lille, France. Univ Newcastle, Dept Med, Newcastle Upon Tyne, Tyne & Wear, England. Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai 200030, Peoples R China. Univ London Imperial Coll Sci Technol & Med, Fac Life Sci, London SW7 2AZ, England. RP McCarthy, MI (reprint author), Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Old Rd, Oxford OX3 7LJ, England. EM mark.mccarthy@drl.ox.ac.uk RI Deloukas, Panos/B-2922-2013; Hanson, Robert/O-3238-2015; Chan, Juliana /B-7918-2016; OI Deloukas, Panos/0000-0001-9251-070X; Hanson, Robert/0000-0002-4252-7068; Chan, Juliana /0000-0003-1325-1194; Hunt, Sarah/0000-0002-8350-1235; Zeggini, Eleftheria/0000-0003-4238-659X; Mitchell, Braxton/0000-0003-4920-4744 FU Intramural NIH HHS; NCI NIH HHS [K07-CA67960]; NCRR NIH HHS [M01RR14288]; NIA NIH HHS [T32-AG00219]; NIDDK NIH HHS [K24-DK02673, R01-DK39311, R01-DK54261, U01-DK58026] NR 45 TC 26 Z9 26 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2006 VL 55 IS 9 BP 2541 EP 2548 DI 10.2337/db06-0088 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LC UT WOS:000240456400016 PM 16936202 ER PT J AU Scott, LJ Bonnycastle, LL Willer, CJ Sprau, AG Jackson, AU Narisu, N Duren, WL Chines, PS Stringham, HM Erdos, MR Valle, TT Tuomilehto, J Bergman, RN Mohlke, KL Collins, FS Boehnke, M AF Scott, Laura J. Bonnycastle, Lori L. Willer, Cristen J. Sprau, Andrew G. Jackson, Anne U. Narisu, Narisu Duren, William L. Chines, Peter S. Stringham, Heather M. Erdos, Michael R. Valle, Timo T. Tuomilehto, Jaakko Bergman, Richard N. Mohlke, Karen L. Collins, Francis S. Boehnke, Michael TI Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample SO DIABETES LA English DT Article ID RISK; SUSCEPTIBILITY; SUGGESTS; ACCOUNT; KCNJ11; GENES AB Transcription factor 7-like 2 (TCF7L2) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, similar to 1 Mb from TCF7L2, in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele (P value < 0.05) for all five SNPs. Our strongest results were for rs1255372 (odds ratio [OR] 1.36 [95% CI 1.15-1.61], P = 0.00026) and rs7903146 (1.33 [1.14-1.56], P = 0.00042). Based on the CEU HapMap data, we selected and tested 12 additional SNPs to tag SNPs in linkage disequilibrium with rs1255372. None of these SNPs showed stronger evidence of association than rs12255372 or rs7903146 (OR <= 1.26, P >= 0.0054). Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes. C1 Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. S Ostrobothnia Cent Hosp, Seinajoki, Finland. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. RP Scott, LJ (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, 1420 Washington Heights, Ann Arbor, MI 48109 USA. EM ljst@umich.edu OI Willer, Cristen/0000-0001-5645-4966 FU Intramural NIH HHS; NHGRI NIH HHS [1 Z01 HG000024]; NIDA NIH HHS [U54 DA021519]; NIDDK NIH HHS [DK29867, R01 DK072193, R01 DK029867, DK27619, DK62370, DK72193] NR 19 TC 170 Z9 176 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2006 VL 55 IS 9 BP 2649 EP 2653 DI 10.2337/db06-0341 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LC UT WOS:000240456400031 PM 16936217 ER PT J AU Figaro, MK Kritchevsky, SB Resnick, HE Shorr, RI Butler, J Shintani, A Penninx, BW Simonsick, EM Goodpaster, BH Newman, AB Schwartz, AV Harris, TB AF Figaro, M. Kathleen Kritchevsky, Stephen B. Resnick, Helaine E. Shorr, Ronald I. Butler, Javed Shintani, Ayumi Penninx, Brenda W. Simonsick, Eleanor M. Goodpaster, Bret H. Newman, Anne B. Schwartz, Ann V. Harris, Tamara B. CA Health Aging Body Composition Stud TI Diabetes, inflammation, and functional decline in older adults - Findings from the health, aging and body composition (ABC) study SO DIABETES CARE LA English DT Article ID C-REACTIVE PROTEIN; INCIDENT MOBILITY LIMITATION; CARDIOVASCULAR RISK-FACTORS; WOMENS HEALTH; US ADULTS; POSTMENOPAUSAL WOMEN; PHYSICAL PERFORMANCE; INSULIN-RESISTANCE; METABOLIC SYNDROME; DISABILITY AB OBJECTIVE - Age, diabetes, and elevated inflammatory markers independently increase the risk of functional decline. We examined the effect of C-reactive protein (CRP) and interleukin-6 (IL-6) on the incident mobility limitation in older adults with and without diabetes. RESEARCH DESIGN AND METHODS - We analyzed data from a cohort of 2,895 well-functioning adults aged 70-79 years, followed for development of persistent functional limitation over 3.5 years. Participants were assessed for the presence of diabetes according to fasting glucose and/or hypoglycemic medication use and were divided into three equal groups (tertiles) according to level of CRP or IL-6. Persistent functional limitation was defined as difficulty climbing 10 steps or walking one-quarter mile on two consecutive semiannual assessments. RESULTS - At baseline, 702 participants (24%) had diabetes. CRP values were (median SD) 2.8-4.4 versus 3.7-5.4 for those with normal glucose and diabetes, respectively (P < 0.001). The unadjusted incidence of functional limitation associated With increased levels of CRP and IL-6 was greater among participants with diabetes. After adjusting for clinical and demographic covariates, persistent functional limitation for the highest tertile was greater compared with that for the lowest tertile of CRP or IL-6 for those with and without diabetes. CRP hazard ratios (HRs) were 1.7 (95% CI 1.2-2.3) versus 1.4 (1.1-1.6), respectively. IL-6 HRs were 1.8 (1.3-2.5) versus 1.6 (1.4-2.0), respectively. CONCLUSIONS - In initially high-functioning older adults, those with diabetes and higher inflammatory burden had an increased risk of functional decline. interventions at early stages to reduce inflammation may preserve function in these individuals. C1 Vanderbilt Univ, Dept Internal Med, Nashville, TN 37212 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. MedStar, Hyattsville, MD USA. Univ Tennessee, Memphis, TN USA. NIA, Baltimore, MD 21224 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Figaro, MK (reprint author), Vanderbilt Univ, Med Ctr, GRECC, Dept Med, 1310 24th Ave S,Room 4B111, Nashville, TN 37212 USA. EM kathleen.figaro@vanderbilt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01 AG 62101, N01 AG 62103, N01 AG 62106] NR 46 TC 49 Z9 51 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2006 VL 29 IS 9 BP 2039 EP 2045 DI 10.2337/dc06-0245 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LG UT WOS:000240456800008 PM 16936150 ER PT J AU Acton, RT Reboussin, DM Barton, JC McLaren, GD Passmore, LV Harris, EL Adams, PC Bent, TC Speechley, MR Vogt, TM Castro, O Sholinsky, P AF Acton, Ronald T. Reboussin, David M. Barton, James C. McLaren, Gordon D. Passmore, Leah V. Harris, Emily L. Adams, Paul C. Bent, Thomas C. Speechley, Mark R. Vogt, Thomas M. Castro, Oswaldo Sholinsky, Phyliss TI Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the hemochromatosis and iron overload screening (HEIRS) study SO DIABETES CARE LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; GLUCOSE-TOLERANCE; RISK-FACTORS; US ADULTS; STORES; C282Y; MEN; POPULATION; PREVALENCE; HEALTH AB OBJECTIVE - We evaluated the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and Iron Overload Screening (HEIRS) study. RESEARCH DESIGN AND METHODS - Analyses were conducted on 97,470 participants. Participants who reported a previous diagnosis of diabetes and/or hemochromatosis or iron overload were compared with participants who did not report a previous diagnosis. RESULTS - The overall prevalence of diabetes was 13.8%; the highest prevalence was in Pacific Islanders (20.1%). Of all participants with diabetes, 2.0% reported that they also had hemochromatosis or iron overload. The mean serum ferritin concentration was significantly greater in women with diabetes in all racial/ethnic groups and in Native-American men with diabetes than in those without diabetes. The mean serum ferritin concentration was significantly lower in Asian men with diabetes than in those without diabetes. Mean TfSat was lower in participants with diabetes from all racial/ethnic groups except Native-American women than in those without diabetes. There was no significant association of diabetes with HFE genotype. The mean serum ferritin concentration was greater (P < 0.0001) in women with diabetes than in those without diabetes for HFE genotypes except C282Y/C282Y and C282Y/H63D. Log serum ferritin concentration was significantly associated with diabetes in a logistic regression analysis after adjusting for age, sex, racial/ethnic group, HFE genotype, and field center. CONCLUSIONS - Serum ferritin concentration is associated with diabetes, even at levels below those typically associated with hemochromatosis or iron overload. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. So Iron Disorders Ctr, Birmingham, AL USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA. London Hlth Sci Ctr, Dept Med, London, ON, Canada. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. Howard Univ, Dept Med, Washington, DC USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Acton, RT (reprint author), MCLM 265,1530 3rd Ave S, Birmingham, AL 35294 USA. EM acton@uab.edu FU NCRR NIH HHS [M01 RR 10284, M01 RR 00032, M01 RR 00827]; NHLBI NIH HHS [N01 HC 05190, N01 HC 05186, N01 HC 05189, N01 HC 05192, N01 HC 05188, N01 HC 05185, UH1 HL 03679-05, N01 HC 05191] NR 24 TC 53 Z9 54 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2006 VL 29 IS 9 BP 2084 EP 2089 DI 10.2337/dc05-1592 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LG UT WOS:000240456800015 PM 16936157 ER PT J AU Hamman, RF Wing, RR Edelstein, SL Lachin, JM Bray, GA Delahanty, L Hoskin, M Kriska, AM Mayer-Davis, EJ Pi-Sunyer, X Regensteiner, J Venditti, B Wylie-Rosett, J AF Hamman, Richard F. Wing, Rena R. Edelstein, Sharon L. Lachin, John M. Bray, George A. Delahanty, Linda Hoskin, Mary Kriska, Andrea M. Mayer-Davis, Elizabeth J. Pi-Sunyer, Xavier Regensteiner, Judith Venditti, Beth Wylie-Rosett, Judith CA Diabet Prevention Program Res Grp TI Effect of weight loss with lifestyle intervention on risk of diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; PREVENTION-PROGRAM; FAT DISTRIBUTION; BASE-LINE; MELLITUS; EXERCISE; OBESITY; DIET; OVERWEIGHT; REDUCTION AB OBJECTIVE - Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants. RESEARCH DESIGN AND METHODS - For this Study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up. RESULTS - A total of 1,079 participants were aged 25-84 years (mean 50.6 years, BMI 33.9 kg/m(2)). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.5]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of Calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence. CONCLUSIONS - interventions to reduce diabetes risk should primarily target weight reduction. C1 George Washington Univ, Diabet Prevent Program Coodinat Ctr, Ctr Biostat, Rockville, MD 20852 USA. Univ Colorado, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Massachusetts Gen Hosp, Ctr Diabet Res, Boston, MA USA. NIDDK, SW Indian Ctr, Phoenix, AZ USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ S Carolina, Sch Publ Hlth, Columbia, SC 29208 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Hamman, RF (reprint author), George Washington Univ, Diabet Prevent Program Coodinat Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu OI Kriska, Andrea/0000-0002-3522-0869; Lachin, John/0000-0001-9838-2841 FU NIDDK NIH HHS [U01 DK048489] NR 29 TC 392 Z9 401 U1 1 U2 31 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2006 VL 29 IS 9 BP 2102 EP 2107 DI 10.2337/dc06-0560 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LG UT WOS:000240456800018 PM 16936160 ER PT J AU Jimenez-Corona, A Lopez-Ridaura, R Pavkov, ME Gonzalez-Villalpando, C Nelson, RG AF Jimenez-Corona, A. Lopez-Ridaura, R. Pavkov, M. E. Gonzalez-Villalpando, C. Nelson, R. G. TI Incidence of type 2 diabetes in Pima Indian and Mexican populations SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Inst Nacl Salud Publ, Direcc Enfermedades Cron, Cuernavaca, Morelos, Mexico. NIDDK, Epidemiol & Clin Res Branch, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0308 BP 193 EP 193 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200307 ER PT J AU Franks, PW Hanson, RL Infante, AM Knowler, WC Looker, HC AF Franks, P. W. Hanson, R. L. Infante, A. M. Knowler, W. C. Looker, H. C. TI Childhood predictors of young onset type 2 diabetes mellitus SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 NIDDK, NIH, Phoenix, AZ USA. Umea Univ Hosp, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0320 BP 200 EP 201 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200319 ER PT J AU Olafsdottir, E Aspelund, T Sigurdsson, G Thorsson, B Benediktsson, R Harris, TB Launer, LJ Eiriksdottir, G Gudnason, V AF Olafsdottir, E. Aspelund, T. Sigurdsson, G. Thorsson, B. Benediktsson, R. Harris, T. B. Launer, L. J. Eiriksdottir, G. Gudnason, V. TI Gender differences in metabolic features of type 2 diabetes in the AGES-Reykjavik Study SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Iceland Heart Fdn, Heart Prevent Clin, Kopavogur, Iceland. Iceland Heart Fdn, Res Inst, Kopavogur, Iceland. Landspitali Univ Hosp, Fac Med, Reykjavik, Iceland. NIA, NIH, Bethesda, MD 20892 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0380 BP 235 EP 235 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200378 ER PT J AU Harashima, SI Notkins, AL AF Harashima, S. -I. Notkins, A. L. TI Overexpression of IA-2 induces G2/M arrest and apoptosis in beta cells SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 NIDCR, Expt Med Sect, NIH, Bethesda, MD USA. Haradoi Hosp, Dept Clin Res, Fukuoka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0432 BP 264 EP 265 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200429 ER PT J AU Elahi, D Rastellini, C Basadonna, G Uknis, M Meneilly, GS Fung, M Egan, JM Thompson, D Warnock, G Thompson, MJ Andersen, DK AF Elahi, D. Rastellini, C. Basadonna, G. Uknis, M. Meneilly, G. S. Fung, M. Egan, J. M. Thompson, D. Warnock, G. Thompson, M. J. Andersen, D. K. TI Impaired stimulation of insulin secretion by GLP-1 after islet auto- and allo-transplantation in humans SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Johns Hopkins, Dept Surg, Baltimore, MD USA. Univ Massachusetts, Dept Surg, Worcester, MA 01605 USA. Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Surg, Vancouver, BC V5Z 1M9, Canada. NIA, Diabet Sect, Baltimore, MD 21224 USA. Univ Massachusetts, Dept Med, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0438 BP 268 EP 268 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200435 ER PT J AU Holness, MJ Greenwood, GK Samsuddin, S Zeldin, DC Bishop-Bailey, D Sugden, MC AF Holness, M. J. Greenwood, G. K. Samsuddin, S. Zeldin, D. C. Bishop-Bailey, D. Sugden, M. C. TI Over-expression of CYP2J2 specifically augments cardiac pyruvate dehlydrogenase kinase 4 expression SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0532 BP 325 EP 325 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200529 ER PT J AU Maurovich-Horvat, P Massaro, J Fox, CS Moselewski, F O'Donnell, CJ Hoffmann, U AF Maurovich-Horvat, P. Massaro, J. Fox, C. S. Moselewski, F. O'Donnell, C. J. Hoffmann, U. TI Assessment of abdominal subcutaneous and visceral adipose tissue volumes with multi detector-row computed tomography SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Semmelweis Univ, Dept Cardiovasc Surg, H-1085 Budapest, Hungary. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0764 BP 463 EP 463 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626201150 ER PT J AU Todoric, J Loffler, M Huber, J Bilban, M Reimers, M Kadl, A Zeyda, M Waldhausl, W Stulnig, TM AF Todoric, J. Loeffler, M. Huber, J. Bilban, M. Reimers, M. Kadl, A. Zeyda, M. Waldhaeusl, W. Stulnig, T. M. TI Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids SO DIABETOLOGIA LA English DT Article DE adiponectin; adipose tissue; diabetes mellitus; fish oil; inflammation; macrophages; obesity; polyunsaturated fatty acids ID INDUCED INSULIN-RESISTANCE; TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; MONONUCLEAR-CELLS; MACROPHAGES; DISEASE; SENSITIVITY; GAMMA; RISK; MEN AB Aims/hypothesis Inflammatory alterations in white adipose tissue appear to underlie complications of obesity including diabetes mellitus. Polyunsaturated fatty acids (PUFA), particularly those of the n-3 series, modulate immune responses and may ameliorate insulin sensitivity. In this study, we investigated how PUFA affect white adipose tissue inflammation and gene expression in obese diabetic animals. Materials and methods We treated db/db mice as well as lean non-diabetic mice (db/+) with either low-fat standard diet (LF) or high-fat diets rich in (1) saturated/monounsaturated fatty acids (HF/S), (2) n-6 PUFA (HF/6) and (3) the latter including purified marine n-3 PUFA (HF/3). Results Many genes involved in inflammatory alterations were upregulated in db/db mice on HF/S compared with LF in parallel with phosphorylation of c-Jun N-terminal kinase (JNK). In parallel, adipose tissue infiltration with macrophages was markedly enhanced by HF/S. When compared with HF/S, HF/6 showed only marginal effects on adipose tissue inflammation. However, inclusion of n-3 PUFA in the diet (HF/3) completely prevented macrophage infiltration induced by high-fat diet and changes in inflammatory gene expression, also tending to reduce JNK phosphorylation (p < 0.1) in diabetic mice despite unreduced body weight. Moreover, high-fat diets (HF/S, HF/6) downregulated expression and reduced serum concentrations of adiponectin, but this was not the case with n-3 PUFA. Conclusions/interpretaion n-3 PUFA prevent adipose tissue inflammation induced by high-fat diet in obese diabetic mice, thereby dissecting obesity from adipose tissue inflammation. These data suggest that beneficial effects of n-3 PUFA on diabetes development could be mediated by their effect on adipose tissue inflammation. C1 Med Univ Vienna, Dept Internal Med 3, Clin Div Endocrinol & Metab, A-1090 Vienna, Austria. Austrian Acad Sci, Ctr Mol Med, A-1010 Vienna, Austria. Med Univ Vienna, Clin Inst Med & Chem Lab Diagnost, Vienna, Austria. Ludwig Boltzmann Inst Clin & Expt Oncol, Vienna, Austria. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA 22901 USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA 22901 USA. RP Stulnig, TM (reprint author), Med Univ Vienna, Dept Internal Med 3, Clin Div Endocrinol & Metab, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM thomas.stulnig@meduniwien.ac.at RI Loffler, Michael/F-1748-2013; OI Loffler, Michael/0000-0002-6529-9723; Stulnig, Thomas/0000-0003-3300-6161; Zeyda, Maximilian/0000-0001-5000-1974 NR 48 TC 160 Z9 161 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 IS 9 BP 2109 EP 2119 DI 10.1007/s00125-006-0300-x PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 070TY UT WOS:000239548800018 PM 16783472 ER PT J AU Schinstine, M Abati, A Tsokos, M Fox, E Filie, AC AF Schinstine, Malcolm Abati, Andrea Tsokos, Maria Fox, Elizabeth Filie, Armando C. TI Cytological identification of metastatic epithelial nephroblastoma in pleural fluid: Report of a case and review of literature SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE nephroblastoma; Wilms' tumor; pleural effusion; cytology ID WILMS-TUMOR; EXFOLIATIVE CYTOLOGY; ASPIRATION CYTOLOGY; EXPRESSION; DIAGNOSIS; CHILDREN; WT1 AB Nephroblastoma (Wilms' tumor) is the most common childhood renal tumor and usually presents with a histology and cytology consisting of blastemal, epithelial, and stromal cells. Effusions are not uncommon and may suggest an unfavorable prognosis when containing anaplastic tumor cells. In the present case, we report the cytological appearance of a Wilms' tumor metastatic to the pleura. The effusion consisted primarily of tumor cells demonstrating epithelial differentiation. The tumor cells mostly presented as three-dimensional aggregates in an inflammatory background. Many cystic and tubular structures were identified. The tumor cells demonstrated strong CD56 and WT1 immunoreactivity. The histology of a subsequent surgical specimen reflected the features seen in cytology. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Filie, AC (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A19,10 Ctr Dr, Bethesda, MD 20892 USA. EM afilie@mail.nih.gov NR 25 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD SEP PY 2006 VL 34 IS 9 BP 621 EP 625 DI 10.1002/dc.20535 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 080QJ UT WOS:000240262300006 PM 16900470 ER PT J AU Wang, SS Sherman, ME Rader, JS Carreon, J Schiffman, M Baker, CC AF Wang, Sophia S. Sherman, Mark E. Rader, Janet S. Carreon, Joseph Schiffman, Mark Baker, Carl C. TI Cervical tissue collection methods for RNA preservation: Comparison of snap-frozen, ethanol-fixed, and RNAlater-fixation SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE RNA; preservation; tissue; cervix ID PARAFFIN-EMBEDDED TISSUE AB Promising molecular techniques may allow for testing of novel and complex hypotheses such as defining gene expression profiles in specific cells, tumors, or their microenvironments. For most large cancer epiderniologic and population-based studies, however, application of such promising techniques may not be possible owing to constraints of specimen preservation from paraffin-embedded tissues. Alternative methods would ideally preserve tissue morphology and not degrade DNA or RNA. We conducted a comparison of snap-freezing (freezing with liquid nitrogen), ethanol-fixation with low melt polyester wax embedding, and RNAlater-preservation techniques to determine which method was optimal for subsequent assessment of gene expression changes in cervical cancer. From each of 15 women with cancer and 30 without, we procured 3 pieces of cervical tissue and compared snap-freezing, ethanol-fixation, and RNA later-preservation techniques. Despite slight loss in morphologic quality from snap-frozen cervix tissues, RNA quality was equivalent to or better than RNAlater-preserved tissues and significantly exceeded that from ethanol-fixed/polyester wax embedded tissue. In conclusion, despite the moderate logistical constraints in set-up that required either liquid nitrogen or dry ice on-site for snap-freezing tissue, the ease of downstream processing and consistent high quality RNA made it preferable to the other 2 methods. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Washington Univ, Dept Obstet & Gynecol, Sch Med, St Louis, MO 63110 USA. RP Wang, SS (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPSw MSC 7234, Bethesda, MD 20892 USA. EM wangso@mail.nih.gov FU PHS HHS [263-MQ-116176-3] NR 7 TC 24 Z9 26 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 2006 VL 15 IS 3 BP 144 EP 148 DI 10.1097/01.pdm.0000213460.53021.cd PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 084CW UT WOS:000240510500004 PM 16932069 ER PT J AU Yang, XR Charette, LA Garcia-Closas, M Lissowska, J Paal, E Sidawy, M Hewitt, SM Rimm, DL Sherman, ME AF Yang, Xiaohong Rose Charette, Lori A. Garcia-Closas, Montserrat Lissowska, Jolanta Paal, Edina Sidawy, Mary Hewitt, Stephen M. Rimm, David L. Sherman, Mark E. TI Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE tissue microarrays (TMAs); DCIS; TDLUs; breast cancer ID TECHNOLOGY; CANCER AB Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of similar to 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (< 10%, 10% to 50%, >= 50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed. C1 NCI, Genet Epidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20852 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. George Washington Univ, Dept Pathol, Washington, DC USA. NCI, Tissue Array Res Program, Pathol Lab,DHHS, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Yang, XR (reprint author), NCI, Genet Epidemiol Branch, DCEG, NIH,DHHS, 6120 Execut Blvd,Room 7014, Bethesda, MD 20852 USA. EM royang@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Hewitt, Stephen/0000-0001-8283-1788; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 7 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 2006 VL 15 IS 3 BP 157 EP 161 DI 10.1097/01.pdm.0000213453.45398.e0 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 084CW UT WOS:000240510500006 PM 16932071 ER PT J AU Patel, VN Rebustini, IT Hoffman, MP AF Patel, Vaishali N. Rebustini, Ivan T. Hoffman, Matthew P. TI Salivary gland branching morphogenesis SO DIFFERENTIATION LA English DT Review DE salivary gland; submandibular gland; branching morphogenesis; fibroblast growth factors; extracellular matrix; laminin; collagen; fibronectin; FGF10; FGFR2b; EGF ID MOUSE SUBMANDIBULAR-GLAND; FIBROBLAST-GROWTH-FACTOR; HEPARAN-SULFATE PROTEOGLYCANS; LAMININ ALPHA-1 CHAIN; BETA-D-XYLOSIDE; EPITHELIAL MORPHOGENESIS; FACTOR RECEPTOR; BASEMENT-MEMBRANE; MICE LACKING; EXTRACELLULAR-MATRIX AB Salivary gland branching morphogenesis involves coordinated cell growth, proliferation, differentiation, migration, apoptosis, and interaction of epithelial, mesenchymal, endothelial, and neuronal cells. The ex vivo analysis of embryonic mouse submandibular glands, which branch so reproducibly and beautifully in culture, is a powerful tool to investigate the molecular mechanisms regulating epithelium-mesenchyme interactions during development. The more recent analysis of genetically modified mice provides insight into the genetic regulation of branching morphogenesis. The review begins, as did the field historically, focusing on the role of the extracellular matrix (ECM), and its components such as glycosaminoglycans, collagens, and laminins. Following sections describe the modification of the ECM by proteases and the role of cell-matrix and cell-cell receptors. The review then focuses on two major families of growth factors implicated in salivary gland development, the fibroblast growth factors (FGFs) and the epidermal growth factors (EGFs). The salivary gland phenotypes in mice with genetic modification of FGFs and their receptors highlight the central role of FGFs during salivary gland branching morphogenesis. A broader section mentions other molecules implicated from analysis of the phenotypes of genetically modified mice or organ culture experiments. The review concludes with speculation on some future areas of research. C1 Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov FU Intramural NIH HHS NR 184 TC 138 Z9 140 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD SEP PY 2006 VL 74 IS 7 BP 349 EP 364 DI 10.1111/j.1432-0436.2006.00088.x PG 16 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 072WT UT WOS:000239704400003 PM 16916374 ER PT J AU Feld, JJ Meddings, J Heathcote, EJ AF Feld, Jordan J. Meddings, Jonathan Heathcote, E. Jenny TI Abnormal intestinal permeability in primary biliary cirrhosis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE primary biliary cirrhosis; intestinal permeability; molecular mimicry; portal hypertension ID HELICOBACTER-PYLORI INFECTION; PYRUVATE-DEHYDROGENASE COMPLEX; AUTO-ANTIGENS; DIHYDROLIPOAMIDE ACETYLTRANSFERASE; GASTROINTESTINAL PERMEABILITY; LIVER-CIRRHOSIS; AUTOANTIBODIES; REACTIVITY; ACID; DISEASE AB Antimitochondrial antibodies (AMAs) found in patients with primary biliary cirrhosis (PBC) cross-react with bacterial proteins and hence molecular mimicry has been proposed as a mechanism for AMA development. Alterations in gastrointestinal permeability would provide a potential route for increased exposure of gut flora to the immune system. In this study we aimed to compare the measured gastrointestinal permeability in patients with PBC to that in patients with liver disease (hepatitis C) and healthy control populations. Subjects drank a mixture of sucrose, lactulose, and mannitol dissolved in water. Eight-hour urinary excretion of the sugars was measured to assess intestinal permeability. Antiendomysial antibody testing was performed to exclude subclinical celiac disease. Eighty-six patients with PBC were evaluated and compared to 69 hepatitis C patients and 155 healthy controls. The mean urinary excretion of sucrose in the PBC patients (133.89 +/- 72.56 mg) was significantly higher than that in hepatitis C patients (101.07 +/- 63.35) or healthy controls (89.46 +/- 41.76) (P=0.0001), suggesting abnormal gastric or proximal small intestinal permeability. Sucrose excretion was not increased among patients with hepatitis C compared to healthy controls. The ratio of lactulose:mannitol excretion, reflecting small bowel permeability, was also elevated in the PBC group (0.017 +/- 0.012) compared to healthy controls (0.012 +/- 0.007) (P=0.0001) but was equal to that found among patients with hepatitis C (0.016 +/- 0.011) (P=NS). We conclude that the permeability of both the stomach and the small bowel is increased in patients with PBC, however, it is unclear if it is a cause, consequence, or manifestation of the disease. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Toronto, Div Gastroenterol, Toronto, ON, Canada. Univ Calgary, Div Gastroenterol, Calgary, AB, Canada. RP Feld, JJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Room 9B16,MSC 1800, Bethesda, MD 20892 USA. EM feldj@niddk.nih.gov NR 45 TC 29 Z9 30 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2006 VL 51 IS 9 BP 1607 EP 1613 DI 10.1007/s10620-006-9544-z PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 082HO UT WOS:000240377500015 PM 16937077 ER PT J AU Volkow, ND AF Volkow, Nora D. TI Hispanic drug abuse research: Challenges and opportunities SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material ID NATIONAL-COMORBIDITY-SURVEY; MAJOR DEPRESSIVE DISORDER; ALCOHOL-USE DISORDERS; PSYCHIATRIC-DISORDERS; GENDER-DIFFERENCES; RACIAL-DIFFERENCES; RECEPTOR GENE; SAN-FRANCISCO; UNITED-STATES; SUBSTANCE USE C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 48 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP PY 2006 VL 84 SU 1 BP S4 EP S7 DI 10.1016/j.drugalcdep.2006.05.002 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 082RR UT WOS:000240405400002 PM 16793222 ER PT J AU Zhen, YY Slanar, O Krausz, KW Chen, C Slavik, J McPhail, KL Zabriskie, TM Perlik, F Gonzalez, FJ Idle, JR AF Zhen, Yueying Slanar, Ondrej Krausz, Kristopher W. Chen, Chi Slavik, Josef McPhail, Kerry L. Zabriskie, T. Mark Perlik, Frantisek Gonzalez, Frank J. Idle, Jeffrey R. TI 3,4-Dehydrodebrisoquine, a novel debrisoquine metabolite formed from 4-hydroxydebrisoquine that affects the CYP2D6 metabolic ratio SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CYTOCHROME-P450 2D6; GENETIC-POLYMORPHISM; CLINICAL EVALUATION; 4-HYDROXYLATION; HYDROXYLATION; OXIDATION; SULFATE; NORTRIPTYLINE; POPULATION; PHENOTYPES AB Considerable unexplained intersubject variability in the debrisoquine metabolic ratio ( urinary debrisoquine/4-hydroxydebrisoquine) exists within individual CYP2D6 genotypes. We speculated that debrisoquine was converted to as yet undisclosed metabolites. Thirteen healthy young volunteers, nine CYP2D6*1 homozygotes [ extensive metabolizers ( EMs)] and four CYP2D6*4 homozygotes [ poor metabolizers (PMs)] took 12.8 mg of debrisoquine hemisulfate by mouth and collected 0- to 8- and 8- to 24-h urines, which were analyzed by gas chromatography-mass spectrometry (GCMS) before and after treatment with beta-glucuronidase. Authentic 3,4-dehydrodebrisoquine was synthesized and characterized by GCMS, liquid chromatography- tandem mass spectrometry, and H-1 NMR. 3,4- Dehydrodebrisoquine is a novel metabolite of debrisoquine excreted variably in 0- to 24- h urine, both in EMs (3.1-27.6% of dose) and PMs (0-2.1% of dose). This metabolite is produced from 4-hydroxydebrisoquine in vitro by human and rat liver microsomes. A previously unstudied CYP2D6*1 homozygote was administered 10.2 mg of 4-hydroxydebrisoquine orally and also excreted 3,4-dehydrodebrisoquine. EMs excreted 6-hydroxydebrisoquine (0-4.8%) and 8-hydroxydebrisoquine (0-1.3%), but these phenolic metabolites were not detected in PM urine. Debrisoquine and 4-hydroxydebrisoquine glucuronides were excreted in a highly genotype-dependent manner. A microsomal activity that probably does not involve cytochrome P450 participates in the further metabolism of 4-hydroxydebrisoquine, which we speculate may also lead to the formation of 1- and 3-hydroxy-debrisoquine and their ring-opened products. In conclusion, this study suggests that the traditional metabolic ratio is not a true measure of the debrisoquine 4-hydroxylation capacity of an individual and thus may, in part, explain the wide intragenotype variation in metabolic ratio. C1 Charles Univ, Fac Med 1, Inst Pharmacol, Prague 12800 2, Czech Republic. Oregon State Univ, Dept Pharmaceut Sci, Corvallis, OR 97331 USA. Univ Bern, Inst Clin Pharmacol, Bern, Switzerland. NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD USA. RP Idle, JR (reprint author), Charles Univ, Fac Med 1, Inst Pharmacol, Albertov 4, Prague 12800 2, Czech Republic. EM jeff@cyp2d6.com RI Chen, Chi/B-4618-2008; OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005562-18] NR 44 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 2006 VL 34 IS 9 BP 1563 EP 1574 DI 10.1124/dmd.105.008920 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 076DZ UT WOS:000239938500019 PM 16782768 ER PT J AU Scheiner, SM Rosenthal, JP AF Scheiner, Samuel M. Rosenthal, Joshua P. TI Ecology of infectious disease: Forging an alliance SO ECOHEALTH LA English DT Article DE ecology; infectious disease; National Institutes of Health; National Science Foundation ID BELIZE AB The Ecology of Infectious Diseases (EID) program is a joint National Science Foundation-National Institutes of Health initiative to produce predictive understanding of disease dynamics, with a focus on diseases with an environmental component. The interdisciplinary research projects funded by this program take advantage of the wide range of theoretical and methodological advances developed over the past 30 years. The challenge for disease ecology is to unravel these systems, discover how complex they truly are, and to determine if they can be predicted and controlled using targeted environmental, public health, or medical interventions. Between 1999 and 2005, a total of 42 research awards were made under the EID program. EID projects have had affects on policy in two areas: adoption of novel interventions on a local scale and use of models by government agencies for the purpose of allocating public health resources. The past 6 years have been an exciting time for the field of disease ecology; we expect the coming years to be even more exciting and productive. C1 Natl Sci Fdn, Div Environm Biol, Arlington, VA 22230 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Scheiner, SM (reprint author), Natl Sci Fdn, Div Environm Biol, 4201 Wilson Blvd, Arlington, VA 22230 USA. EM sscheine@nsf.gov RI Scheiner, Sam/A-4320-2009 OI Scheiner, Sam/0000-0003-1677-9752 NR 12 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1612-9202 J9 ECOHEALTH JI EcoHealth PD SEP PY 2006 VL 3 IS 3 BP 204 EP 208 DI 10.1007/s10393-006-0035-7 PG 5 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 092WH UT WOS:000241127500012 ER PT J AU Biggar, RJ Ortiz-Conde, BA Bagni, RK Bakaki, PM Wang, CD Engels, EA Mbulaiteye, SM Ndugwa, CM AF Biggar, Robert J. Ortiz-Conde, Betty A. Bagni, Rachel K. Bakaki, Paul M. Wang, Cheng-Dian Engels, Eric A. Mbulaiteye, Sam M. Ndugwa, Christopher M. TI Hepatitis C virus genotype 4 in Ugandan children and their mothers SO EMERGING INFECTIOUS DISEASES LA English DT Article ID INFECTION; EPIDEMIOLOGY; TRANSMISSION; TANZANIA; EGYPT AB In Kampala, Uganda, in 2001, hepatitis C virus antibodies were found in 27 (4%) of 603 children and in 62 (12%) of 525 of their mothers. However, only approximate to 10% of positive results were confirmed by reverse transcription-PCR, which suggests frequent false-positive results or viral clearance All sequenced types were genotype 4. C1 NCI, Rockville, MD 20852 USA. Natl Canc Inst, Frederick, MD USA. Makerere Univ, Sch Med, Kampala, Uganda. Mulago Hosp, Kampala, Uganda. RP Biggar, RJ (reprint author), NCI, 6120 Execut Blvd,EPS 8014, Rockville, MD 20852 USA. EM biggarb@mail.nih.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 15 TC 8 Z9 8 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2006 VL 12 IS 9 BP 1440 EP 1443 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 078DJ UT WOS:000240081400023 PM 17073099 ER PT J AU Tahera, Y Meltser, I Johansson, P Hansson, AC Canlon, B AF Tahera, Yeasmin Meltser, Inna Johansson, Peter Hansson, Anita C. Canlon, Barbara TI Glucocorticoid receptor and nuclear factor-kappa B interactions in restraint stress-mediated protection against acoustic trauma SO ENDOCRINOLOGY LA English DT Article ID AMINOGLYCOSIDE-INDUCED OTOTOXICITY; SENSORINEURAL HEARING-LOSS; MESSENGER-RNA; RAT COCHLEA; HEAT-STRESS; INNER-EAR; EXPRESSION; SENSITIVITY; MECHANISMS; PATHWAY AB The role of glucocorticoid receptors (GRs) in the protective effect of restraint stress (RS) before acoustic trauma was studied in spiral ganglion neurons of CBA mice. RS increased corticosterone and protected against elevated auditory brain stem thresholds caused by acoustic trauma. This protection was inhibited by the pretreatment with a corticosterone synthesis inhibitor, metyrapone (MET), and a GR antagonist (RU486). RS followed by acoustic trauma caused an immediate increase in corticosterone that triggered nuclear translocation of GR, without a change in the expression of GR protein. RU486 + MET before RS and acoustic trauma caused an immediate increase in GR mRNA followed by increased GR protein expression (24 h after trauma). GR signaling was further characterized by analyzing nuclear factor-kappa B (NF kappa B) nuclear translocation and protein expression. NF kappa B nuclear translocation was reduced after acoustic trauma or pretreatment with RU486 + MET before RS and acoustic trauma. On the contrary, RS protected against the trauma-induced NF kappa B reduction of its nuclear translocation in inhibitory-kappa B (I kappa B)dependent manner. RU486 + MET caused a simultaneous decreased I kappa B expression and NF kappa B nuclear translocation, demonstrating an interference with the I kappa B-mediated activation of NF kappa B. In summary, RS protects the cochlea from acoustic trauma by increasing corticosterone and activating GRs. These results emphasis how GR activity modulates hearing sensitivity and its importance for the rationale use of glucocorticoids in inner ear diseases. C1 Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. NIAAA, NIH, Bethesda, MD 20892 USA. RP Canlon, B (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. EM barbara.canlon@ki.se NR 47 TC 33 Z9 33 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2006 VL 147 IS 9 BP 4430 EP 4437 DI 10.1210/en.2006-0260 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 074CM UT WOS:000239790100047 PM 16777974 ER PT J AU Schwartz, DA AF Schwartz, David A. TI A year in review SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM david.schwartz@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 SEP PY 2006 VL 114 IS 9 BP A514 EP A514 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 087PZ UT WOS:000240755700001 ER PT J AU Hartge, P AF Hartge, Patricia TI Estimating the burden of disease and the benefits of prevention SO EPIDEMIOLOGY LA English DT Editorial Material ID CANCER C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hartge, P (reprint author), NCI, Div Canc Epidemiol & Genet, Executive Plaza S,Rm 8093,6120 Execut Blvd, Bethesda, MD 20892 USA. EM hartgep@mail.nih.gov NR 7 TC 1 Z9 1 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 SEP PY 2006 VL 17 IS 5 BP 498 EP 499 DI 10.1097/01.ede.0000231371.40737.ad PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 077KT UT WOS:000240028900005 PM 16906054 ER PT J AU Sallmen, M Sandler, DP Hoppin, JA Blair, A Baird, DD AF Sallmen, Markku Sandler, Dale P. Hoppin, Jane A. Blair, Aaron Baird, Donna Day TI Reduced fertility among overweight and obese men SO EPIDEMIOLOGY LA English DT Article ID BODY-MASS INDEX; OVULATORY INFERTILITY; ERECTILE-DYSFUNCTION; AGRICULTURAL HEALTH; SEMEN QUALITY; RISK-FACTORS; WEIGHT; HYPOGONADISM; HORMONES AB Background: Overweight and obese men. have been reported to have lower sperm counts and hormonal changes, but data are lacking regarding effects on couple fertility. Methods: We examined the relationship between male body mass index(BMI) and infertility in couples enrolled in the Agricultural Health Study in the United States. The analysis sample was limited to couples (wife < 40 years old) with an attempt at pregnancy, in the last 4 years based on pregnancy and fertility data provided by wives Infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred. Self-reported weight and height were used to calculate BMI (kg/m(2)). Adjusted odds ratios (aORs) for infertility associated with increases in male BMI were calculated with logistic regression. Results: Adjusting for potential confounders, a 3-unit increase in male BMI was associated with infertility (aOR = 1.12; 95% confidence interval = 1.01-1.25; n = 1329). There was a dose-response relationship, and the BMI effect was stronger when the data were limited to couples with the highest-quality infertility data. The association between BMI and infertility was similar for older and younger men, suggesting that erectile dysfunction in older men does not explain the association. Conclusions: This report of lower fertility in overweight and obese men needs replication. If the findings are robust, programs to prevent obesity may improve men's reproductive health and save medical costs for infertility treatment. C1 Finnish Inst Occupat Hlth, Ctr Expertise Hlth & Work Abil, FI-00250 Helsinki, Finland. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD USA. RP Sallmen, M (reprint author), Finnish Inst Occupat Hlth, Ctr Expertise Hlth & Work Abil, Topeliuksenkatu 41 aA, FI-00250 Helsinki, Finland. EM Markku.Sallmen@ttl.fi RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 21 TC 116 Z9 127 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2006 VL 17 IS 5 BP 520 EP 523 DI 10.1097/01.ede.0000229953.76862.e5 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 077KT UT WOS:000240028900009 PM 16837825 ER PT J AU Norris, KC Agodoa, LY AF Norris, Keith C. Agodoa, Lawrence Y. TI Expanding the minority biomedical pipeline: The NIDDK National High School Student Summer Research Program SO ETHNICITY & DISEASE LA English DT Editorial Material C1 Charles R Drew Univ, Dept Med, Lynwood, CA 90262 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Norris, KC (reprint author), Charles R Drew Univ, Dept Med, 11705 Deputy Yamamoto Pl,Suite B, Lynwood, CA 90262 USA. EM knorris@ucla.edu NR 6 TC 1 Z9 1 U1 1 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2006 VL 16 IS 4 SU 5 BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 124PM UT WOS:000243381700001 PM 17186588 ER PT J AU Silver, K Williams, M Macario, E AF Silver, Karen Williams, Meredith Macario, Everly TI The National Eye Health Education Program: Increasing awareness of diabetic eye disease among American Indians and Alaska natives SO ETHNICITY & DISEASE LA English DT Article DE American Indians; Alaska natives; cultural appropriateness; diabetic eye disease; focus groups; program development; qualitative research AB With the highest prevalence of diabetes in the United States, American Indians and Alaska Natives are at greatest risk for diabetic eye disease (DED), a leading cause of blindness. The National Eye Institute (NEI) conducted formative research to understand DED-related knowledge, identify approaches to managing this disease, and design a communication plan to increase awareness and reduce DED among these populations. The NEI conducted qualitative research at five locations in Indian country with representatives from national organizations, tribal members, and healthcare providers. While diabetes ranked high on their list of primary community health issues in need of attention, study participants had only a basic level of diabetes-related knowledge, acknowledged the need for DED education, and underscored the importance of the use of interpersonal and culturally appropriate communication strategies. This is the first exploratory qualitative research study to examine the status of diabetic eye disease among American Indians and Alaska Natives whose primary purpose was to inform the design of a national DED communication campaign. C1 IQ Solut, Rockville, MD USA. NEI, NIH, Bethesda, MD 20892 USA. RP Silver, K (reprint author), 8201 Grubb Rd, Silver Spring, MD 20910 USA. EM kr_silver@hotmail.com NR 8 TC 5 Z9 5 U1 1 U2 4 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2006 VL 16 IS 4 BP 920 EP 925 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 094KN UT WOS:000241238400025 PM 17061747 ER PT J AU Mayer, AMS Gustafson, KR AF Mayer, Alejandro M. S. Gustafson, Kirk R. TI Marine pharmacology in 2003-2004: Anti-tumour and cytotoxic compounds SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE marine; anti-tumour; cytotoxic; anti-cancer; anti-neoplastic; agents; preclinical; clinical; pharmacology; review; global ID STARFISH CERTONARDOA-SEMIREGULARIS; DINOFLAGELLATE AMPHIDINIUM SP; BREAST-CANCER CELLS; FUNGUS EMERICELLA-VARIECOLOR; HARE DOLABELLA-AURICULARIA; CYANOBACTERIUM SYMPLOCA-SP; SOFT CORAL; ANTINEOPLASTIC AGENTS; IN-VITRO; A-C AB During 2003 and 2004, marine pharmacology research directed towards the discovery and development of novel anti-tumour agents was published in 163 peer-reviewed articles. The purpose of this review is to present a structured assessment of the anti-tumour and cytotoxic properties of 150 marine natural products, many of which are novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids and peptides. The organisms yielding these bioactive marine compounds include invertebrate animals, algae, fungi and bacteria. Anti-tumour pharmacological studies were conducted with 31 structurally defined marine natural products in a number of experimental and clinical models that further defined their mechanisms of action. Particularly potent in vitro cytotoxicity data generated with murine and human tumour cell lines was reported for 119 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy is the fact that marine anti-cancer research was sustained by a global collaborative effort, involving researchers from Australia, Austria, Canada, China, Egypt, France, Germany, Italy, Japan, Mexico, the Netherlands, New Zealand, Papua New Guinea, the Philippines, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand and the United States of America (USA). Finally, this 2003-2004 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine anti-tumour agents continued at the same pace as during 1998-2002. (c) 2006 Elsevier Ltd. All rights reserved. C1 Midwestern Univ, Dept Pharmacol, Chicago Coll Osteopath Med, Downers Grove, IL 60515 USA. NCI, Mol Targets Dev Program, Canc Res Ctr, Frederick, MD 21702 USA. RP Mayer, AMS (reprint author), Midwestern Univ, Dept Pharmacol, Chicago Coll Osteopath Med, Prabhu Hall 108,555 31st St, Downers Grove, IL 60515 USA. EM amayer@midwestern.edu OI Mayer, Alejandro /0000-0002-8358-4528 FU Intramural NIH HHS; NIEHS NIH HHS [1 R15 ES12654-01] NR 170 TC 69 Z9 75 U1 2 U2 22 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 SEP PY 2006 VL 42 IS 14 BP 2241 EP 2270 DI 10.1016/j.ejca.2006.05.019 PG 30 WC Oncology SC Oncology GA 091GV UT WOS:000241016000015 PM 16901686 ER PT J AU Jin, T Hereld, D AF Jin, Tian Hereld, Dale TI Moving toward understanding eukaryotic chemotaxis SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE Dictyostelium; chemotaxis; signaling network; modeling ID GREEN FLUORESCENT PROTEIN; G-BETA-GAMMA; DIRECTIONAL CELL-MOVEMENT; CYCLIC-AMP PULSES; DICTYOSTELIUM-DISCOIDEUM; LEADING-EDGE; CHEMOATTRACTANT RECEPTOR; ACTIN CYTOSKELETON; SIGNAL-TRANSDUCTION; LIVING CELLS AB The discovery in 1947 of directed cell movement in Dictyostelium discoideum quietly gave a birth to a new line of investigation into the molecular basis of chemotaxis. Some 60 years later, D. discoideum continues to be a key model system for the study of eukaryotic chemotaxis as well as an array of other important biological processes. As one of the most influential scientists, Guenther Gerisch has inspired several generations of researchers with his insightful and rigorous approaches applied to this model system. His studies have greatly contributed to current knowledge of many fundamental processes, such as cell-cell adhesion, phagocytosis, endocytosis, cytokinesis, cell signaling and chemotaxis. In this review, we wish to look back at the journey that has led to our current understanding of chemotaxis of eukaryotic cells. Published by Elsevier GmbH. C1 NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Univ Texas, Sch Med, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. RP Jin, T (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM tjin@niaid.nih.gov FU Intramural NIH HHS NR 66 TC 29 Z9 29 U1 5 U2 7 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 EI 1618-1298 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD SEP PY 2006 VL 85 IS 9-10 BP 905 EP 913 DI 10.1016/j.ejcb.2006.04.008 PG 9 WC Cell Biology SC Cell Biology GA 095YS UT WOS:000241344800006 PM 16735076 ER PT J AU Rosel, D Kimmel, AR AF Rosel, Daniel Kimmel, Alan R. TI The COP9 signalosome regulates cell proliferation of Dictyostelium discoideum SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE CSN proteins; protein-protein interactions; RNAi; proteasome; Cullin; Dictyostelium ID GENE-EXPRESSION; FISSION YEAST; COMPLEX; COP9/SIGNALOSOME; DIFFERENTIATION; DEGRADATION; TRANSDUCTION; PROTEOLYSIS; MECHANISMS; DICTYBASE AB Regulated protein destruction involving SCF (Skp1/Cullin/F-box, E3 ubiquitin ligase) complexes is required for multicellular development of Dielyostelium discoideum. Dynamic modification of cullin by nedd8 is required for the proper action of SCF. The COP9 signalosome (CSN), first identified in a signaling pathway for light response in plants, functions as a large multi-protein complex. that regulates cullin neddylation in eukaryotes. Still, there is extreme sequence divergence of CSN subunits of the yeasts in comparison to the multicellular plants and animals. Using the yeast two-hybrid system, we have identified the CSN5 subunit as a potential interacting partner of a cell surface receptor of Dictyostelium. We further identified and characterized all 8 CSN subunits in Dictyostelium discoideum. Remarkably, despite the ancient origin of Dictyostelium, its CSN proteins cluster very closely with their plant and animal counterparts. We additionally show that the Dictyostelium subunits, like those of other systems are capable of multi-protein interactions within the CSN complex. Our data also indicate that CSN5 (and CSN2) are essential for cell proliferation in Dictyostelium, a phenotype similar to that of multicellular organisms, but distinct from that of the yeasts. Finally, we speculate on a potential role of CSN in cullin function and regulated protein destruction during multicellular development of Diclyostelium. Published by Elsevier GmbH. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Charles Univ Prague, Dept Cell Physiol & Biochem, Prague, Czech Republic. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov FU Intramural NIH HHS NR 42 TC 20 Z9 29 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD SEP PY 2006 VL 85 IS 9-10 BP 1023 EP 1034 DI 10.1016/j.ejcb.2006.04.006 PG 12 WC Cell Biology SC Cell Biology GA 095YS UT WOS:000241344800017 PM 16781008 ER PT J AU Boeckeler, K Adley, K Xu, X Jenkins, A Jin, T Williams, RSB AF Boeckeler, Katrina Adley, Kathryn Xu, ehua Xu Jenkins, Alex Jin, Tian Williams, Robin S. B. TI The neuroprotective agent, valproic acid, regulates the mitogen-activated protein kinase pathway through modulation of protein kinase A signalling in Dictyostelium discoideum SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE cAMP; Dictyostelium; ERK2; GSK3; lithium; MAP kinase; neuroprotection; PKA; signalling; valproic acid ID GLYCOGEN-SYNTHASE KINASE-3; MOOD STABILIZER; IN-VIVO; ERK PATHWAY; LITHIUM; CELLS; CAMP; PHOSPHORYLATION; INHIBITION; NEURONS AB Activation of the mitogen-activated protein kinase (MAPK) cascade gives rise to a neuroprotective effect in a variety of cell types. The bipolar disorder treatment, valproic acid (VPA), increases the activity of this pathway by modulating extracellular signal-regulated kinase 2 (ERK2) phosphorylation through an unknown mechanism. To investigate the molecular basis of this effect, we have used the biomedical model system Dictyostelium discoideurn to dissect this signalling pathway. We find that, similar to mammalian systems, VPA causes a transient increase in the activation of the MAPK signalling pathway, as shown by ERK2 phosphorylation. We show that the MAP kinase and phosphatase, protein kinase A (PKA) and glycogen synthase kinase signalling pathways all function in controlling the levels of phospho-ERK2 (pERK2). We find that VPA induces elevated pERK2 levels through attenuation of the PKA signalling pathway. Interestingly, pERK2 levels are also controlled by another bipolar disorder drug, lithium, providing a common effect of these two drugs. This work therefore suggests a conserved pathway in eukaryotes that is targeted by neuroprotective and bipolar disorder drugs and allows us to propose a model for this neuroprotective effect. (c) 2006 Elsevier GmbH. All rights reserved. C1 UCL, Dept Biol, London WC1E 6BT, England. UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England. NIAID, Immunogenet Lab, Chemotaxis Signal Sect, Rockville, MD 20852 USA. RP Williams, RSB (reprint author), UCL, Dept Biol, Mortimer St, London WC1E 6BT, England. EM robin.williams@ucl.ac.uk RI Williams, Robin/G-6807-2011; OI xu, xuehua/0000-0002-3863-9593 FU Intramural NIH HHS NR 50 TC 25 Z9 28 U1 0 U2 6 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD SEP PY 2006 VL 85 IS 9-10 BP 1047 EP 1057 DI 10.1016/j.ejcb.2006.04.013 PG 11 WC Cell Biology SC Cell Biology GA 095YS UT WOS:000241344800019 PM 16759735 ER PT J AU Frisch, M Pedersen, BV Wohlfahrt, J Hjalgrim, H Biggar, RJ AF Frisch, Morten Pedersen, Bo V. Wohlfahrt, Jan Hjalgrim, Henrik Biggar, Robert J. TI Reproductive patterns and non-Hodgkin lymphoma risk in Danish women and men SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; lymphoma; non-Hodgkin; pregnancy; reproductive factors; subfertility ID CANCER; DISEASE; PREGNANCY; QUALITY; SEMEN; AGE AB Reproductive patterns have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL) in women, and fathering patterns in relation to NHL risk have not been studied. The authors conducted a register-based cohort study of 4.1 million Danes to investigate associations of livebirths with subsequent NHL incidence (85 million person-years, 3819 NHL cases). The impact of induced abortions, ectopic pregnancies, spontaneous abortions, missed abortions, stillbirths, and hydatidiform moles on subsequent NHL incidence was studied in a subcohort of 1.2 million women. Ratios of NHL incidence rates, accompanying trend tests and two-sided p-values were calculated by log-linear Poisson regression analyses. Pregnancies, whether ending in livebirths or not, were unrelated to NHL incidence in women. The only statistically significant finding in women was that, among parous women, age at first child-birth was inversely associated with NHL incidence (p-trend = 0.001). In men, there was no overall difference in NHL incidence between fathers and non-fathers. However, in men with children, NHL risk declined with increasing number of children (p-trend = 0.02) and increased with time since birth of the most recent child (p-trend < 0.001). Pregnancies have limited impact, if any, on subsequent NHL risk in women. Our findings in men need replication, but, if verified, they may reflect lymphomagenesis-associated male subfertility prior to NHL diagnosis. C1 Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Frisch, M (reprint author), Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, 5 Artillerivej, DK-2300 Copenhagen S, Denmark. EM mfr@ssi.dk RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 24 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD SEP PY 2006 VL 21 IS 9 BP 673 EP 679 DI 10.1007/s10654-006-9035-8 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 104HA UT WOS:000241948300005 PM 17048087 ER EF