FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Shah, VP Younan, NH King, RL AF Shah, Vijay P. Younan, Nicolas H. King, Roger L. TI Joint spectral and spatial quality evaluation of pan-sharpening methods SO JOURNAL OF APPLIED REMOTE SENSING LA English DT Article DE Quality assessment; pan-sharpening; information gain; information divergence; Multispectral image ID IMAGE FUSION; RESOLUTION IMAGES AB This research study presents a novel global index based on harmonic mean theory to jointly evaluate the performance of pan-sharpening algorithms without using a reference image. The harmonic mean of relative spatial information gain and relative spectral information preservation provides a unique global index to compare the performance of different methods. The presented index also facilitates in assigning relevance to either the spectral or spatial quality of an image. The information divergence between the multispectral (MS) bands at lower resolutions and the pan-sharpened image provides a measure of the spectral fidelity and mean-shift. Mutual information between the original pan and the synthetic pan images generated from the MS and pan-sharpened images is used to calculate the relative gain. The relative gain helps to quantify the amount of spatial information injected by the method. A trend comparison of the presented approach with other quality indices using well-known pan-sharpening methods on high resolution and medium resolution datasets reveals that the new index can be used to evaluate the quality of pan-sharpened images at the resolution of the pan image without the availability of a reference image. C1 [Shah, Vijay P.; Younan, Nicolas H.; King, Roger L.] Dept Elect & Comp Engn, Mississippi State, MS 39762 USA. [Shah, Vijay P.; Younan, Nicolas H.; King, Roger L.] Mississippi State Univ, GeoResources Inst, Starkville, MS 39759 USA. RP Shah, VP (reprint author), SAIC Frederick Inc, Natl Canc Inst, Bethesda, MD 20892 USA. EM shahv@mail.nih.gov; younan@ece.msstate.edu; rking@engr.msstate.edu RI Shah, Vijay/D-4083-2014 OI Shah, Vijay/0000-0003-3856-156X NR 24 TC 5 Z9 5 U1 0 U2 8 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1931-3195 J9 J APPL REMOTE SENS JI J. Appl. Remote Sens. PY 2008 VL 2 AR 023531 DI 10.1117/1.2977460 PG 15 WC Environmental Sciences; Remote Sensing; Imaging Science & Photographic Technology SC Environmental Sciences & Ecology; Remote Sensing; Imaging Science & Photographic Technology GA 417AG UT WOS:000264046200036 ER PT J AU Ashwood, P Kwong, C Hansen, R Hertz-Picciotto, I Croen, L Krakowiak, P Walker, W Pessah, IN de Water, JV AF Ashwood, Paul Kwong, Christina Hansen, Robin Hertz-Picciotto, Irva Croen, Lisa Krakowiak, Paula Walker, Wynn Pessah, Isaac N. de Water, Judy Van TI Brief report: Plasma leptin levels are elevated in autism: Association with early onset phenotype? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE inflammation; leptin; autism; regression ID BODY-MASS INDEX; DIAGNOSTIC OBSERVATION SCHEDULE; BLOOD-BRAIN-BARRIER; SPECTRUM DISORDER; AUTOIMMUNE ENCEPHALOMYELITIS; CHILDREN; MICE; ADOLESCENTS; ANTIBODIES; RESPONSES AB There is evidence of both immune dysregulation and autoimmune phenomena in children with autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without autism, and 23 children with developmental disabilities (DD). Children with autism had significantly higher plasma leptin levels compared with TD controls (p < .006). When further sub-classified into regression or early onset autism, children with early onset autism had significantly higher plasma leptin levels compared with children with regressive autism (p < .042), TD controls (p < .0015), and DD controls (p < .004). We demonstrated an increase in leptin levels in autism, a finding driven by the early onset group. C1 [Kwong, Christina; de Water, Judy Van] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med & Microbiol Immunobiol, Davis, CA 95616 USA. [Ashwood, Paul; Hansen, Robin; Hertz-Picciotto, Irva] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Ashwood, Paul; Hansen, Robin; Hertz-Picciotto, Irva; Croen, Lisa; Krakowiak, Paula; Pessah, Isaac N.; de Water, Judy Van] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA. [Hansen, Robin] Univ Calif Davis, Dept Pediat, Davis, CA USA. [Hertz-Picciotto, Irva; Krakowiak, Paula] Univ Calif Davis, Div Epidemiol, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Croen, Lisa] Kaiser Permanente No California, Dept Res, Oakland, CA USA. [Walker, Wynn] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Pessah, Isaac N.] Univ Calif Davis, Dept Vet Mol Biosci, Davis, CA 95616 USA. RP de Water, JV (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510, Davis, CA 95616 USA. EM javandewater@ucdavis.edu FU NIEHS NIH HHS [1 P01 ES11269-01, R01 ES015359] NR 39 TC 29 Z9 30 U1 3 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JAN PY 2008 VL 38 IS 1 BP 169 EP 175 DI 10.1007/s10803-006-0353-1 PG 7 WC Psychology, Developmental SC Psychology GA 248NQ UT WOS:000252160700015 PM 17347881 ER PT J AU Marcobal, AM Sela, DA Wolf, YI Makarova, KS Mills, DA AF Marcobal, Angela M. Sela, David A. Wolf, Yuri I. Makarova, Kira S. Mills, David A. TI Role of hypermutability in the evolution of the genus Oenococcus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA MISMATCH REPAIR; ESCHERICHIA-COLI; LEUCONOSTOC-OENOS; HELICOBACTER-PYLORI; SALMONELLA-TYPHIMURIUM; STAPHYLOCOCCUS-AUREUS; PHYLOGENETIC ANALYSIS; MUTATION FREQUENCIES; RPOB GENE; MUTS AB Oenococcus oeni is an alcohol-tolerant, acidophilic lactic acid bacterium primarily responsible for malolactic fermentation in wine. A recent comparative genomic analysis of O. oeni PSU-1 with other sequenced lactic acid bacteria indicates that PSU-1 lacks the mismatch repair (MMR) genes mutS and mutL. Consistent with the lack of MMR, mutation rates for O. oeni PSU-1 and a second oenococcal species, O. kitaharae, were higher than those observed for neighboring taxa, Pediococcus pentosaceus and Leuconostoc mesenteroides. Sequence analysis of the rpoB mutations in rifampin-resistant strains from both oenococcal species revealed a high percentage of transition mutations, a result indicative of the lack of MMR. An analysis of common alleles in the two sequenced O. oeni strains, PSU-1 and BAA-1163, also revealed a significantly higher level of transition substitutions than were observed in other Lactobacillales species. These results suggest that the genus Oenococcus is hypermutable due to the loss of mutS and mutL, which occurred with the divergence away from the neighboring Leuconostoc branch. The hypermutable status of the genus Oenococcus explains the observed high level of allelic polymorphism among known O. oeni isolates and likely contributed to the unique adaptation of this genus to acidic and alcoholic environments. C1 [Marcobal, Angela M.; Sela, David A.; Mills, David A.] Univ Calif Davis, Dept Viticulture & Enol, Robert Mondavi Inst Wine & Food Sci, Davis, CA 95616 USA. [Wolf, Yuri I.; Makarova, Kira S.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Mills, DA (reprint author), Univ Calif Davis, Dept Viticulture & Enol, Robert Mondavi Inst Wine & Food Sci, 1 Shields Ave, Davis, CA 95616 USA. EM damills@ucdavis.edu RI Mills, David/G-2282-2011 OI Mills, David/0000-0003-1913-9865 NR 60 TC 38 Z9 41 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2008 VL 190 IS 2 BP 564 EP 570 DI 10.1128/JB.01457-07 PG 7 WC Microbiology SC Microbiology GA 251RR UT WOS:000252392100011 PM 17993526 ER PT J AU Yedjou, CG Rogers, C Brown, E Tchounwou, PB AF Yedjou, Clement G. Rogers, Christian Brown, Erika Tchounwou, Paul B. TI Differential effect of ascorbic acid and n-acetyl-L-cysteine on arsenic trioxide-mediated oxidative stress in human leukemia (HL-60) cells SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE arsenic trioxide; HL-60 cells; MDA; ascorbic acid; n-acetyl-L-cysteine ID ACUTE PROMYELOCYTIC LEUKEMIA; INDUCED APOPTOSIS; ALPHA-TOCOPHEROL; VITAMIN-C; IN-VITRO; MULTIPLE-MYELOMA; ACETYLCYSTEINE; INHIBITION; CYTOTOXICITY; MULTICENTER AB Arsenic trioxide (ATO) has been recommended for the treatment of refractory cases of acute promyelocytic leukemia (APL). Recent studies in our laboratory indicated that oxidative stress plays a key role in ATO-induced cytotoxicity in human leukemia (HL-60) cells. In the present investigation, we performed the MTT assay and trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test to determine the levels of malondialdehyde (MDA) production in HL-60 cells coexposed to either ascorbic acid (AA) and ATO or to n-acetyl-L-cysteine (NAC) and ATO. The results of MTT assay indicated that AA exposure potentiates the cytotoxicity of ATO in HL-60 cells, as evidenced by a gradual increase in MDA levels with increasing doses of AA. In contrary, the addition of NAC to ATO-treated HL-60 cells resulted in a dose-dependent decrease of MDA production. From these results, we conclude that the addition of the AA to ATO-treated HL-60 cells enhances the formation of reactive oxygen species (ROS), whereas the addition of NAC under the same experimental condition significantly (p <.05) decreases the level of ROS formation. On the basis of these direct in vitro findings, our studies provide evidence that AA may extend the therapeutic spectrum of ATO. The coadministration of NAC with ATO shows a potential specificity for tumor cells, indicating that it may not enhance the clinical outcome associated with ATO monotherapy in vivo. (c) 2008 Wiley Periodicals, Inc. C1 [Yedjou, Clement G.; Rogers, Christian; Brown, Erika; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH RCMI Ctr Environm Hlth, Cellom & Toxicogenom Res Lab, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH RCMI Ctr Environm Hlth, Cellom & Toxicogenom Res Lab, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [G12 RR013459, 1G12RR13459, G12 RR013459-11] NR 38 TC 15 Z9 16 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2008 VL 22 IS 2 BP 85 EP 92 DI 10.1002/jbt.20223 PG 8 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 299QR UT WOS:000255770600002 PM 18418892 ER PT J AU Wu, CQ Liu, A Yu, KF AF Wu, Chengqing Liu, Aiyi Yu, Kai F. TI An adaptive approach to designing comparative diagnostic accuracy studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE area under a curve; receiver operating characteristic; sample size re-estimation; sensitivity; specificity ID ROC CURVES; SIZE; ROBUSTNESS; MODEL; AREA AB Comparative diagnostic studies usually involve comparison of the area under receiver operating characteristic curves when biomarkers are measured on a continuous or ordinal scales. In designing such studies, specification of a number of nuisance parameters is often required to compute sample sizes. When these parameters are incorrectly specified, statistical power to detect a meaningful difference in area can be substantially adversely affected. We propose an adaptive method to calculate the sample size and show these procedures to be effective in controlling error rates. C1 NICHHD, Biometry & Math Stat Branch, Dept Hlth Human Serv, DESPR, Rockville, MD 20852 USA. RP Liu, A (reprint author), NICHHD, Biometry & Math Stat Branch, Dept Hlth Human Serv, DESPR, 6100 Execut Blvd, Rockville, MD 20852 USA. EM Liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU Intramural NIH HHS NR 16 TC 2 Z9 2 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 1 BP 116 EP 125 DI 10.1080/10543400701668282 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 251DN UT WOS:000252351600008 PM 18161544 ER PT J AU Liu, A Wu, CQ Yu, KF AF Liu, Aiyi Wu, Chengqing Yu, Kai F. TI Point and interval estimation of primary and secondary parameters in a two-stage adaptive clinical trial SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE adaptive design; bias; confidence intervals; effect size; mean squared error; minimal sufficiency; pivot function; sample size reestimation ID SAMPLE-SIZE MODIFICATION; SEQUENTIAL TEST; CONFIDENCE-INTERVALS; UNBIASED ESTIMATION; CONDITIONAL POWER; DESIGNS AB Investigated in this paper is the point estimation and confidence intervals of the treatment efficacy parameter and related secondary parameters in a two-stage adaptive trial. Based on the minimal sufficient statistics, several alternative estimators to the sample averages are proposed to reduce the bias and to improve the precision of estimation. Confidence intervals are constructed using Woodroofe's pivot method. Numerical studies are conducted to evaluate the bias and mean squared error of the estimators and the coverage probability of the confidence intervals. C1 [Liu, Aiyi; Wu, Chengqing; Yu, Kai F.] NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Liu, A (reprint author), NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, Rockville, MD 20852 USA. OI Liu, Aiyi/0000-0002-6618-5082 FU Intramural NIH HHS NR 24 TC 1 Z9 1 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 2 BP 211 EP 226 DI 10.1080/10543400701697125 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 271BD UT WOS:000253763000001 PM 18327717 ER PT J AU Conti, MA Adelstein, RS AF Conti, Mary Anne Adelstein, Robert S. TI Nonmuscle myosin II moves in new directions SO JOURNAL OF CELL SCIENCE LA English DT Article DE cell migration; cell polarity; myosin II ID TUMOR-CELL INVASION; RHO-KINASE; TISSUE MORPHOGENESIS; SIGNALING PATHWAY; ADHESION DYNAMICS; PLANAR POLARITY; DISTINCT ROLES; E-CADHERIN; MIGRATION; PHOSPHORYLATION AB For many years, analyses of the role of the actomyosin cytoskeleton in many basic cellular processes have centered on actin. Increasingly, however, a number of investigators are examining proteins that are proximal to actin; in particular, nonmuscle myosin II (NMII). Recent experiments have increased our understanding of the role of NMII in three related cellular activities: generation of cell polarity, cell migration and cell-cell adhesion. Progress has been particularly promising thanks to the use of new microscopic, genetic and biochemical techniques. In mammalian systems, generation of transgenic mice and the introduction of specific siRNAs have been useful in deciphering the role of the three different isoforms of NMII: NMIIA, NMIIB and NMIIC. Studies in Drosophila and Aplysia, which are informative model systems for investigating the function of NMII, have also shed light on NMII. Recent work examines the contractile and structural roles that NMII plays at cell-cell boundaries, and both its contractile and actin-crosslinking roles in cell migration. In addition, NMII might also function as a scaffold molecule, anchoring signaling molecules, such as kinases and Rho GTPase guanine nucleotide exchange factors. C1 [Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. EM adelster@nhlbi.nih.gov OI Adelstein, Robert/0000-0002-8683-2144 NR 60 TC 193 Z9 200 U1 1 U2 17 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 JAN 1 PY 2008 VL 121 IS 1 BP 11 EP 18 DI 10.1242/jcs.007112 PG 8 WC Cell Biology SC Cell Biology GA 249QH UT WOS:000252243400005 PM 18096687 ER PT J AU Hayward, RM Kirk, MJ Sproull, M Scott, T Smith, S Cooley-Zgela, T Crouse, NS Citrin, DE Camphausen, K AF Hayward, Robert M. Kirk, Melissa J. Sproull, Mary Scott, Tamalee Smith, Sharon Cooley-Zgela, Theresa Crouse, Nancy S. Citrin, Deborah E. Camphausen, Kevin TI Post-collection, pre-measurement variables affecting VEGF levels in urine biospecimens SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE angiogenesis; VEGF; tumour markers; urine; biospecimens ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; INCREASED SERUM-LEVELS; NON-HODGKINS-LYMPHOMA; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; CLINICAL-SIGNIFICANCE; ANGIOGENIC FACTORS; PROSTATE-CANCER; GASTRIC-CANCER AB Angiogenesis, the development and recruitment of new blood vessels, plays an important role in tumour growth and metastasis.Vascular endothelial growth factor (VEGF) is an important stimulator of angiogenesis.Circulating and urinary VEGF levels have been suggested as clinically useful predictors of tumour behaviour, and investigations into these associations are ongoing.Despite recent interest in measuring VEGF levels in patients, little is known about the factors that influence VEGF levels in biospecimens. To begin to address this question, urine samples were collected from patients with solid tumours undergoing radiotherapy and healthy volunteers.Four factors were examined for their effects on VEGF concentrations as measured by chemiluminescent immunoassay: time from sample collection to freezing, number of specimen freeze-thaw cycles, specimen storage tube type and the inclusion or exclusion of urinary sediment. The results of this study indicate that time to freeze up to 4 hrs, number of freeze-thaw cycles between one and five, and different types of polypropylene tubes did not have statistically significant effects on measured urinary VEGF levels. Urinary sediment had higher VEGF levels than supernatant in five of six samples from healthy patients.It is not clear whether there is an active agent in the sediment causing this increase or if the sediment particles themselves are affecting the accuracy of the assay.Therefore, we recommend centrifuging urine, isolating the supernatant, and freezing the sample in polypropylene microcentrifuge tubes or cryogenic vials within 4 hrs of collection.In addition, we recommend the use of samples within five freeze-thaw cycles. C1 [Hayward, Robert M.; Kirk, Melissa J.; Sproull, Mary; Scott, Tamalee; Smith, Sharon; Cooley-Zgela, Theresa; Crouse, Nancy S.; Citrin, Deborah E.; Camphausen, Kevin] NCI, NIH, Ctr Canc Res, Radiat Oncol Branch,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, NIH, Ctr Canc Res, Radiat Oncol Branch,Dept Hlth & Human Serv, Bldg 10,Room B2-3561,10 Ctr Dr, Bethesda, MD 20892 USA. EM Camphauk@mail.nih.gov FU Intramural NIH HHS [Z01 SC010372-06] NR 39 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JAN-FEB PY 2008 VL 12 IS 1 BP 343 EP 350 DI 10.1111/j.1582-4934.2007.00135.x PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 278HJ UT WOS:000254275500026 PM 18366457 ER PT J AU Matarin, M Brown, WM Hardy, JA Rich, SS Singleton, AB Brown, RD Brott, TG Worrall, BB Meschia, JF AF Matarin, Mar Brown, W. Mark Hardy, John A. Rich, Stephen S. Singleton, Andrew B. Brown, Robert D., Jr. Brott, Thomas G. Worrall, Bradford B. Meschia, James F. CA SWISS Study Grp ISGS Study Grp MSGD Study Grp TI Association of integrin alpha 2 gene variants with ischemic stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE atherosclerosis; cerebral infarction; genetics; integrin alpha 2; stroke ID COLLAGEN RECEPTOR POLYMORPHISMS; HARDY-WEINBERG EQUILIBRIUM; GLYCOPROTEIN-IA; ALPHA(2)BETA(1) INTEGRIN; MYOCARDIAL-INFARCTION; YOUNGER PATIENTS; CODING SEQUENCE; RISK; PLATELETS; DISEASE AB Genetic variants in the gene encoding integrin alpha 2 (ITGA2) have been reported to be associated with an increased risk for ischemic stroke. The purpose of this study was to investigate the association between haplotype-tagging single-nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a collection of North American stroke cases and controls. The study included 484 cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and across each tSNP were performed, including haplotype association analysis. Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We observed significant association between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence interval (CI), 1.11 to 2.04; P = 0.009) and disease and a trend toward association at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P= 0.03). These associations remained significant in the haplotype analyses. The associated tSNPs did not distinguish stroke etiology after application of TOAST criteria. Our results suggest that genetic variability within ITGA2 may confer risk for ischemic stroke independent of conventional risk factors. These results provide additional support for a role for platelet receptor genes in the pathogenesis of ischemic stroke of diverse subtypes. C1 [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Matarin, Mar; Hardy, John A.; Singleton, Andrew B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Brown, W. Mark] Wake Forest Univ, Dept Biostat, Winston Salem, NC 27109 USA. [Rich, Stephen S.] Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. RP Meschia, JF (reprint author), Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM meschia.james@mayo.edu RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 FU Medical Research Council [G0701075]; NINDS NIH HHS [R01 NS39987, K08 NS045802, K08 NS045802-04, R01 NS039987, R01 NS042733, R01 NS42733] NR 26 TC 16 Z9 16 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2008 VL 28 IS 1 BP 81 EP 89 DI 10.1038/sj.jcbfm.9600508 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 243TO UT WOS:000251820400009 PM 17534386 ER PT J AU Kraut, MA Beason-Held, LL Elkins, WD Resnick, SM AF Kraut, Michael A. Beason-Held, Lori L. Elkins, Wendy D. Resnick, Susan M. TI The impact of magnetic resonance imaging-detected white matter hyperintensities on longitudinal changes in regional cerebral blood flow SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE aging; human; PET CBF; white matter lesions ID CARDIOVASCULAR HEALTH; OLDER-ADULTS; COGNITIVE PERFORMANCE; HUMAN BRAIN; LESIONS; MRI; DISEASE; ABNORMALITIES; HYPERTENSION; PRESSURE AB White matter hyperintensities are frequently detected on cranial magnetic resonance imaging (MRI) scans of older adults. Given the presumed ischemic contribution to the etiology of these lesions and the posited import of resting brain activity on cognitive function, we hypothesized that longitudinal changes in MRI-detected white matter disease, and its severity at a given time point, would be associated with changes in regional cerebral blood flow (rCBF) over time. We evaluated MRI scans and resting (H2O)-O-15 positron emission tomographic rCBF at baseline and after an average of 7.7-year follow-up in Baltimore Longitudinal Study of Aging participants without dementia. Differences in patterns of rCBF were evident at baseline and at follow-up between the group of subjects showing increased white matter disease over the 8-year interval compared with the group with stable white matter ratings. Furthermore, longitudinal changes over time in rCBF also differed between the two groups. Specifically, the group with progressive white matter abnormalities showed greater increase in the right inferior temporal gyrus/fusiform gyrus, right anterior cingulate, and the rostral aspect of the left superior temporal gyrus. Regions of greater longitudinal decrease in this group were evident in the right inferior parietal lobule and at the right occipital pole. Changes in white matter disease over time and its severity at any given time are associated significantly with both cross-sectional and longitudinal patterns of rCBF. The longitudinal increases may reflect cortical compensation mechanisms for reduced efficacy of interregional neural communications that result from white matter deterioration. C1 [Kraut, Michael A.; Elkins, Wendy D.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Beason-Held, Lori L.; Elkins, Wendy D.; Resnick, Susan M.] NIA, NIH, Lab Personal & Cognit, Intramural Res Program, Baltimore, MD 21224 USA. RP Kraut, MA (reprint author), Johns Hopkins Med Inst, Dept Radiol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM mkraut1@jhmi.edu FU Intramural NIH HHS [Z01 AG000191-12]; NIA NIH HHS [N01-AG-3-2124] NR 30 TC 29 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2008 VL 28 IS 1 BP 190 EP 197 DI 10.1038/sj.jcbfm.9600512 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 243TO UT WOS:000251820400018 PM 17534385 ER PT J AU Klauda, JB Brooks, BR AF Klauda, Jeffery B. Brooks, Bernard R. TI CHARMM force field parameters for nitroalkanes and nitroarenes SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; ISOTROPIC PERIODIC SUM; AB-INITIO; ELECTRON-DIFFRACTION; N-ALKANES; GAS-PHASE; OPLS-AA; NITROBENZENE; EQUILIBRIUM; ENERGY AB New CHARMM force field (FF) parameters are developed for nitro compounds, referred to here as C27rn, for subsequent use in molecular dynamics (MD) simulations. The nonbonded terms are adjusted to best fit densities and hydration energies of nitropropane and nitrobenzene. High-level quantum mechanical calculations are used to obtain accurate conformational energies of nitroalkanes and nitrobenzene and to adjust the torsional potential of the CHARMM FF. For nitroalkanes, the calculated gauche (g) conformer of the C - C - C - N torsion is more stable than trans (t). Consequently, nitropropane MD simulations with C27rn result in 74% population of this g conformer. The C27rn FF is in excellent agreement with experiment for various bulk (density, isothermal compressibility, and heat of vaporization) and interfacial (surface tension) properties of nitropropane, nitrobutane, and nitrobenzene. MD simulations with the OPLS-AA FF for nitropropane and nitrobenzene result in similar property predictions as C27rn, except a reduced stability of the C - C - C - N g conformer. C1 Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Klauda, Jeffery B.; Brooks, Bernard R.] Natl Heart Lung & Blood Inst, Lab Computat Biol, Bethesda, MD 20892 USA. RP Klauda, JB (reprint author), Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. EM jbklauda@umd.edu NR 53 TC 7 Z9 7 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 EI 1549-9626 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD JAN PY 2008 VL 4 IS 1 BP 107 EP 115 DI 10.1021/ct700191v PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 249AG UT WOS:000252198200011 PM 26619984 ER PT J AU Rich, BA Fromm, SJ Berghorst, LH Dickstein, DP Brotman, MA Pine, DS Leibenluft, E AF Rich, Brendan A. Fromm, Stephen J. Berghorst, Lisa H. Dickstein, Daniel P. Brotman, Melissa A. Pine, Daniel S. Leibenluft, Ellen TI Neural connectivity in children with bipolar disorder: impairment in the face emotion processing circuit SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE bipolar disorder; children; face perception; neural connectivity; amygdala ID FUNCTIONAL CONNECTIVITY; FACIAL EXPRESSIONS; PERIRHINAL CORTEX; TEMPORAL-LOBE; RATING-SCALE; YOUNG-ADULTS; ADOLESCENTS; AMYGDALA; RECOGNITION; VOLUMES AB Background: Pediatric bipolar disorder (BD), a highly debilitating illness, is characterized by amygdala. abnormalities, i.e., volume reduction and hyperactivation during face processing. Evidence of perturbed amygdala functional connectivity with other brain regions would implicate a distributed neural circuit in the pathophysiology of BD, and would further elucidate the neural mechanisms associated with BD face emotion misinterpretation. Methods: Thirty-three BD and 24 healthy age, gender, and IQ-matched subjects completed a functional magnetic resonance imaging (fMRI) task of face emotion identification in which attention was directed to emotional (hostility, fearfulness) and nonemotional (nose width) aspects of faces. Voxel-wise analyses examined whole brain functional connectivity with the left amygdala. Results: Compared to healthy subjects, BD subjects had significantly reduced connectivity between the left amygdala and two regions: right posterior cingulate/precuneus and right fusiform gyrus/parahippocampal gyrus. Deficits were evident regardless of mood state and comorbid diagnoses. Conclusions: BD youth exhibit deficient connectivity between the amygdala and temporal association cortical regions previously implicated in processing facial expressions and social stimuli. In conjunction with previously documented volumetric and functional perturbations in these brain regions, dysfunction in this distributed neural circuit may begin to clarify the pathophysiology of the face emotion misperceptions and social deficits seen in BD youth. C1 [Rich, Brendan A.; Fromm, Stephen J.; Berghorst, Lisa H.; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen] NIH, NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Rich, BA (reprint author), NIH, NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, 9000 Rockville Pike,MSC Bldg 15K,Rm 204, Bethesda, MD 20892 USA. EM brendanrich@mail.nih.gov RI Brotman, Melissa/H-7409-2013; Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 FU Intramural NIH HHS; NIMH NIH HHS [K22 MH078044-01A1] NR 62 TC 81 Z9 81 U1 4 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JAN PY 2008 VL 49 IS 1 BP 88 EP 96 DI 10.1111/j.1469-7610.2007.01819.x PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 270KW UT WOS:000253720700009 PM 18181882 ER PT J AU Park, JY Chong, AY Cochran, EK Kleiner, DE Haller, MJ Schatz, DA Gorden, P AF Park, Jean Y. Chong, Angeline Y. Cochran, Elaine K. Kleiner, David E. Haller, Michael J. Schatz, Desmond A. Gorden, Phillip TI Type 1 diabetes associated with acquired generalized lipodystrophy and insulin resistance: The effect of long-term leptin therapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-FAT DISTRIBUTION; FAMILIAL PARTIAL LIPODYSTROPHY; OF-THE-LITERATURE; REPLACEMENT THERAPY; CLINICAL-FEATURES; EFFICACY; TROGLITAZONE; ROSIGLITAZONE; DERANGEMENTS; PIOGLITAZONE AB Context: Acquired generalized lipodystrophy (AGL) is marked by severe insulin resistance and hypertriglyceridemia. Rarely, AGL and type 1 diabetes (T1D) coexist. Objective: Our objective was to describe the response to leptin therapy in patients with coexisting AGL and T1D and to document the autoimmune diseases associated with AGL. Design and Setting: We conducted an open-label prospective study at the Clinical Research Center of the National Institutes of Health. Patients: Participants included 50 patients with generalized or partial lipodystrophy (acquired or congenital); two patients had both AGL and T1D. Intervention: Patients were treated with 12 months of recombinant human leptin administration to achieve high-normal serum concentrations. Results: Two patients had both AGL and T1D. The first was diagnosed with T1D at age 8 yr. Beginning at age 11 yr, he developed generalized lipodystrophy, elevated transaminases, and poor glycemic control [hemoglobin A(1c) (HbA(1c)) 10.7%] despite markedly increased insulin requirements (3.3-5 U/kg.d). Further evaluation revealed hypoleptinemia and hypertriglyceridemia. At age 15 yr, leptin therapy was initiated, and after 1 yr, his insulin requirements fell to 1 U/kg.d, his glycemic control improved (HbA(1c) 8.4%), and both his triglycerides and transaminases normalized. The second patient developed concurrent AGL and T1D at age 6 yr. Despite insulin doses of up to 32 U/kg.d, she developed poor glycemic control (HbA(1c) 10.6%), hypertriglyceridemia (2984 mg/dl), elevated transaminases, and nonalcoholic steatohepatitis. At age 13 yr, leptin therapy was started, and after 1 yr, her glycemic control improved (HbA(1c) 7.3%) and her insulin requirements decreased (17 U/kg.d). Her triglycerides remained elevated but were improved (441 mg/dl). Conclusions: Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL. C1 [Park, Jean Y.; Chong, Angeline Y.; Cochran, Elaine K.; Gorden, Phillip] NCI, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, NIH, NIDDK, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. [Haller, Michael J.; Schatz, Desmond A.] Univ Florida, Coll Med, Dept Pediat, Div Pediat Endocrinol, Gainesville, FL 32610 USA. RP Gorden, P (reprint author), NIH, 10 Ctr Dr,CRC Room 6-5940, Bethesda, MD 20892 USA. EM PhillipG@intra.niddk.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 24 TC 32 Z9 33 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2008 VL 93 IS 1 BP 26 EP 31 DI 10.1210/jc.2007-1856 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 251GC UT WOS:000252359400006 PM 17940115 ER PT J AU Groom, H Dieperink, E Nelson, DB Garrard, J Johnson, JR Ewing, SL Stockley, H Durfee, J Jonk, Y Willenbring, ML Ho, SB AF Groom, Holly Dieperink, Eric Nelson, David B. Garrard, Judith Johnson, James R. Ewing, Stephen L. Stockley, Herbert Durfee, Janet Jonk, Yvonne Willenbring, Mark L. Ho, Samuel B. TI Outcomes of a hepatitis c screening program at a large urban VA Medical Center SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE hepatitis C; screening; interferon alpha; quality improvement ID UNITED-STATES VETERANS; VIRUS-INFECTION; US VETERANS; ANTIVIRAL THERAPY; LIVER FIBROSIS; RISK-FACTORS; PREVALENCE; MANAGEMENT; RIBAVIRIN; EPIDEMIOLOGY AB Goals: To determine the outcomes of implementing clinical care guidelines for Hepatitis C screening, evaluation, and treatment in a large urban Veterans Affairs Medical Center. Background: Little information exists regarding the actual outcomes of institutional screening programs for Hepatitis C. Study: Retrospective review of all patients tested for Hepatitis C at the Minneapolis Veterans Affairs Medical Center from January 1, 2000 to December 31, 2001. Logistic regression was used to determine factors related to successful referral and treatment. Results: During this period 36,422 unique patients were screened for Hepatitis C virus (HCV) risk factors, resulting in 12,485 HCV enzyme-linked immunoassay antibody tests. HCV antibodies were positive in 681 (5.4%) patients and 520 (4.2%) were HCV-RNA-positive. Of HCV-RNA-positive patients, 430 (83%) were referred, 382 (73%) attended the Hepatitis clinic, and 232 (44.6%) received liver biopsies. Patients referred had significantly fewer comorbidities, known marital status, and greater prior clinic attendance than those not referred. Overall, 124 patients with established fibrosis received antiviral therapy (32% of patients attending clinic or 24% of viremic cohort). White race, fewer major medical problems, and age less than 60 years predicted antiviral treatment. Sustained virologic response occurred in 46 (37%) of treated patients (9% of the viremic cohort). Patients with a sustained virologic response include 17 patients with stage 3 to 4 fibrosis. Conclusions: This screening and referral program resulted in 73% of HCV-RNA-positive patients attending a specialty Hepatitis C clinic and 24% of those most likely to benefit received antiviral therapy. Measures to increase referral, engagement in care, and antiviral treatment are needed. C1 [Ho, Samuel B.] Univ Calif San Diego, VA San Diego Healthcare Syst, Gastroenterol Sect 111D, La Jolla, CA 92161 USA. [Ho, Samuel B.] Univ Calif San Diego, VA San Diego Healthcare Syst, Dept Med, La Jolla, CA 92161 USA. [Garrard, Judith] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Willenbring, Mark L.] NIAAA, Rockville, MD 20852 USA. RP Ho, SB (reprint author), Univ Calif San Diego, VA San Diego Healthcare Syst, Gastroenterol Sect 111D, 3350 La Jolla Village Dr, La Jolla, CA 92161 USA. EM samuel.ho2@va.gov OI Groom, Holly/0000-0003-2866-9788 NR 40 TC 34 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JAN PY 2008 VL 42 IS 1 BP 97 EP 106 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248NS UT WOS:000252160900019 PM 18097298 ER PT J AU Harvey, JJ Brant, SR Knutson, JR Han, MK AF Harvey, John J. Brant, Steven R. Knutson, Jay R. Han, Myun K. TI SNP analysis using CataCleave probes SO JOURNAL OF CLINICAL LABORATORY ANALYSIS LA English DT Article DE fluorescence; single nucleotide polymorphism; genotype; RNase H; PCR ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HOMOLOGOUS GENE AMELOGENIN; CROHNS-DISEASE; OLIGONUCLEOTIDE ARRAYS; DNA; MUTATIONS; SUSCEPTIBILITY; ASSOCIATION; VARIANTS; REPEAT AB CataCleave" probes are catalytically cleavable fluorescence probes having a chimeric deoxyribonucleic acid (DNA)ribonucleic acid (RNA)-DNA structure that can be used for real-time detection of single nucleotide polymorphisms (SNPs), insertions, and deletions. Fluorescent donor emission is normally quenched by Forster resonance energy transfer (FRET). Upon binding to the target, if the RNA/DNA hybrid is correctly base-paired, ribonuclease (RNase) H will cleave the RNA moiety and the probe fragments will dissociate. FRET is lost and the donor fluorescence signal is recovered. A single-base mismatch within the hybrid region causes probe cleavage to be significantly reduced. We designed CataCleave probes to detect SNPs located in the insulin-like growth factor 2 (IGF-2) gene and at position 702 within the NOD2/CARD15 gene. Probes were also designed to detect a six-basepair deletion in the amelogenin gene and a partially methylated target DNA. Discrimination between wild-type and SNP is demonstrated for both genes in homogeneous reactions under isothermal and temperature cycling conditions. These probes were also able to identify a multibase deletion and methylated DNA. Cleavage rates were proportional to target concentration. Probe length and position of fluorescent labels may also be modified for use in multiplexing high-throughput SNP assays. This represents a novel method for the detection of SNPs. C1 [Harvey, John J.; Han, Myun K.] Excimus Biotech Inc, Savage, MD 20763 USA. [Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21205 USA. [Brant, Steven R.] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Knutson, Jay R.] NHLBI, NIH, Lab Mol Biophys, Opt Spect Sect, Bethesda, MD 20892 USA. RP Harvey, JJ (reprint author), Excimus Biotech Inc, 8510 Corridor Rd, Savage, MD 20763 USA. EM harvey@excimus.com FU Intramural NIH HHS [ZIA HL006067-01] NR 40 TC 7 Z9 7 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-8013 EI 1098-2825 J9 J CLIN LAB ANAL JI J. Clin. Lab. Anal. PY 2008 VL 22 IS 3 BP 192 EP 203 DI 10.1002/jcla.20240 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 312CN UT WOS:000256646800007 PM 18484652 ER PT J AU Castle, PE Gravitt, PE Solomon, D Wheeler, CM Schiffman, M AF Castle, Philip E. Gravitt, Patti E. Solomon, Diane Wheeler, Cosette M. Schiffman, Mark TI Comparison of linear array and line blot assay for detection of human papillomavirus and diagnosis of cervical precancer and cancer in the atypical squamous cell of undetermined significance and low-grade squamous intraepithelial lesion triage study SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; FEMALE UNIVERSITY-STUDENTS; LIQUID-BASED CYTOLOGY; HPV GENOTYPING TEST; HIGH-RISK; COSTA-RICA; ABSOLUTE RISK; YOUNG-WOMEN; FOLLOW-UP; PCR ASSAY AB We evaluated Linear Array (LA), a newly commercialized PGW09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of cervical precancer and cancer in women with equivocal cytology. C1 [Castle, Philip E.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gravitt, Patti E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. [Gravitt, Patti E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. [Wheeler, Cosette M.] Univ New Mexico, Sch Med, Univ New Mexico Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Wheeler, Cosette M.] Univ New Mexico, Sch Med, Univ New Mexico Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Solomon, Diane; Schiffman, Mark] NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5004,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01 CN055155, N01 CN055105, N01 CN055153, N01 CN055154, N01 CN055156, N01 CN055157, N01 CN055158, N01 CN055159] NR 54 TC 70 Z9 71 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2008 VL 46 IS 1 BP 109 EP 117 DI 10.1128/JCM.01667-07 PG 9 WC Microbiology SC Microbiology GA 251RS UT WOS:000252392200013 PM 17989194 ER PT J AU Asmis, TR Ding, K Seymour, L Shepherd, FA Leighl, NB Winton, TL Whitehead, M Spaans, JN Graham, BC Goss, GD AF Asmis, Timothy R. Ding, Keyue Seymour, Lesley Shepherd, Frances A. Leighl, Natasha B. Winton, Tim L. Whitehead, Marlo Spaans, Johanna N. Graham, Barbara C. Goss, Glenwood D. TI Age and comorbidity as independent prognostic factors in the treatment of non-small-cell lung cancer: A review of national cancer institute of Canada clinical trials group trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID ELDERLY-PATIENTS; GERIATRIC ONCOLOGY; RANDOMIZED-TRIAL; PHASE-III; OF-CANADA; CHEMOTHERAPY; CISPLATIN; SURVIVAL; VINORELBINE; OLDER AB Purpose This study analyzed patients enrolled in two large, prospectively randomized trials of systemic chemotherapy (adjuvant/palliative setting) for non-small-cell lung Cancer (NSCLC). The main objective was to determine if age and/or the burden of chronic medical conditions (comorbidity) are independent predictors of survival, treatment delivery, and toxicity. Patients and Methods Baseline comorbid conditions were scored using the Charlson comorbidity index (CCI), a validated measure of patient comorbidity that is weighted according to the influence of comorbidity on overall mortality. The CCI score (CCIS) was correlated with demographic data,(ie, age, sex, race), performance status ( PS), histology, cancer stage, patient weight, hemoglobin, alkaline phosphatase, lactate dehydrogenase, outcomes of chemotherapy delivery ( ie, type, total dose, and dose intensity), survival, and response. Results A total of 1,255 patients were included in this analysis. The median age was 61 years (range, 34 to 89 years); 34% of patients were elderly ( at least 65 years of age); and 31% had comorbid conditions at randomization. Twenty-five percent of patients had a CCIS of 1, whereas 6% had a CCIS of 2 or greater. Elderly patients were more likely to have a CCIS equal to or greater than 1 compared with younger patients (42% v 26%; P < .0001), as were male patients (35% v 21%; P < .0001) and patients with squamous histology (36% v 29%; P = .001). Although age did not influence overall survival, the CCIS appeared prognostic (CCIS 1 v 0; hazard ratio 1.28; 95% CI, 1.09 to 1.5; P = .003). Conclusion In these large, randomized trials, the presence of comorbid conditions (CCIS >= 1), rather than age more than 65 years, was associated with poorer survival. C1 NCI, Canada Clin Trials Grp, Kingston, ON, Canada. RP Goss, GD (reprint author), Univ Ottawa, Ottawa Hosp, Reg Canc Ctr, 503 Smyth Rd, Ottawa, ON K1H 1C4, Canada. EM ggoss@ottawahospital.on.ca NR 34 TC 137 Z9 142 U1 1 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2008 VL 26 IS 1 BP 54 EP 59 DI 10.1200/JCO.2007.12.8322 PG 6 WC Oncology SC Oncology GA 276XK UT WOS:000254176800014 PM 18165640 ER PT J AU Garcia, AA Hirte, H Fleming, G Yang, DY Tsao-Wei, DD Roman, L Groshen, S Swenson, S Markland, F Gandara, D Scudder, S Morgan, R Chen, H Lenz, HJ Oza, AM AF Garcia, Agustin A. Hirte, Hal Fleming, Gini Yang, Dongyun Tsao-Wei, Denice D. Roman, Lynda Groshen, Susan Swenson, Steve Markland, Frank Gandara, David Scudder, Sidney Morgan, Robert Chen, Helen Lenz, Heinz-Josef Oza, Amit M. TI Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: A trial of the California, Chicago, and princess Margaret hospital phase II consortia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID ENDOTHELIAL GROWTH-FACTOR; GYNECOLOGIC-ONCOLOGY-GROUP; PRIMARY PERITONEAL CARCINOMA; METASTATIC BREAST-CANCER; CHI-SQUARE STATISTICS; TUMOR ANGIOGENESIS; TAMOXIFEN THERAPY; FACTOR EXPRESSION; CARBOPLATIN C; PACLITAXEL P AB Purpose Vascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC. Patients and Methods Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially. Results Seventy patients were enrolled. The probability of being alive and progression free at 6 months was 56% (+/- 6% SE). A partial response was achieved in 17 patients (24%). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome. Conclusion The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted. C1 [Garcia, Agustin A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. City Hope Comprehens Canc Ctr, Duarte, CA USA. Univ Chicago, Chicago, IL 60637 USA. NCI, Bethesda, MD 20892 USA. Juravinski Canc Ctr, Hamilton, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Garcia, AA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, 1441 Eastlake Ave,MS 34, Los Angeles, CA 90033 USA. EM aagarcia@usc.edu FU NCI NIH HHS [N01 CM62209, CM-17102, CM17107, CM62203, P30 CA 14089] NR 53 TC 336 Z9 351 U1 1 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2008 VL 26 IS 1 BP 76 EP 82 DI 10.1200/JCO.2007.12.1939 PG 7 WC Oncology SC Oncology GA 276XK UT WOS:000254176800017 PM 18165643 ER PT J AU Pulay, AJ Dawson, DA Hasin, DS Goldstein, RB Ruan, J Pickering, RP Huang, B Chou, P Grant, BF AF Pulay, Attila J. Dawson, Deborah A. Hasin, Deborah S. Goldstein, Ris B. Ruan, June Pickering, Roger P. Huang, Boji Chou, Patricia Grant, Bridget F. TI Violent behavior and DSM-IV psychiatric disorders: Results from the National Epidemiologic Survey on alcohol and related conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; INTIMATE PARTNER VIOLENCE; GENERAL-POPULATION SAMPLE; UNITED-STATES; PERSONALITY-DISORDERS; DRUG MODULES; ANXIETY DISORDERS; SUBSTANCE-ABUSE; MENTAL-ILLNESS; RELIABILITY AB Objective: To present nationally representative data on the lifetime prevalence and population estimates of violent behavior among individuals with DSM-IV psychiatric disorders. Method: The data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions. Prevalences, population estimates, and associations of violent behavior occurring among individuals with pure, comorbid, and specific DSM-IV psychiatric disorders were examined. Results: After controlling for sociodemographic characteristics and other comorbidity, it was found that the odds of violent behavior were significantly increased (p < .05) among individuals with substance use disorders; pathological gambling; major depressive disorder; bipolar disorders; panic disorder without agoraphobia; specific phobia; and paranoid, schizoid, histrionic, and obsessive-compulsive personality disorders. Percentages of violent behavior among individuals with each comorbid disorder were, with few exceptions, significantly greater (p < .05-p < .001) than the corresponding percentages among those presenting with the pure form of each disorder. Alcohol and drug use disorders were the most significant contributors to the public health burden of violent behavior. Conclusion: The majority of individuals with psychiatric disorders do not engage in violent behavior, and public perception associated with stereotypic violence among individuals with psychiatric disorders appears unwarranted. Elevated risks and burden of violent behavior were not equally shared across the spectrum of psychiatric disorders, with particular disorders, especially substance use disorders, contributing disproportionately to the burden. Future research should examine the circumstances under which violence among individuals with psychiatric disorders occurs with a view toward improving clinical prediction and developing more effective prevention strategies. C1 [Pulay, Attila J.; Dawson, Deborah A.; Goldstein, Ris B.; Huang, Boji; Chou, Patricia; Grant, Bridget F.] NIAAA, NIH, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hasin, Deborah S.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, Div Epidemiol,Mailman Sch Publ Hlth, New York, NY USA. [Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, NIH, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry,Dept Hlth & Human Serv, MS 9304,5635 Fishers Lane,Room 3077, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Pulay, Attila/B-6155-2011; OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS [, NIH0012690046]; PHS HHS [NIH0012690046] NR 57 TC 53 Z9 53 U1 0 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2008 VL 69 IS 1 BP 12 EP 22 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 258ZH UT WOS:000252908400002 PM 18312033 ER PT J AU Dimitrov, DS AF Dimitrov, Dimiter S. TI Brainstorming tumors and nanomedicine: The 2nd Annual Cancer Nanobiology Think Tank SO JOURNAL OF COMPUTATIONAL AND THEORETICAL NANOSCIENCE LA English DT Editorial Material DE nanobiology; nanotechnology; cancer; computational nanobiology; structural nanobiology C1 Natl Canc Inst, NIH, Ctr Canc Res Nanobiol Program, Ft Detrick, MD 21702 USA. RP Dimitrov, DS (reprint author), Natl Canc Inst, NIH, Ctr Canc Res Nanobiol Program, POB B, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1546-1955 J9 J COMPUT THEOR NANOS JI J. Comput. Theor. Nanosci. PD JAN PY 2008 VL 5 IS 1 BP 1 EP 6 DI 10.1166/jctn.2008.001 PG 6 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 257PS UT WOS:000252811600001 ER PT J AU Cibull, C Bechert, C Gleason, B Hiatt, K AF Cibull, C. Bechert, C. Gleason, B. Hiatt, K. TI Chemotherapy induced epidermal dysmaturation mimicking squamous cell carcinoma in-situ in patient with mycosis fungoides SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Cibull, C.; Gleason, B.; Hiatt, K.] Univ Arkansas, Little Rock, AR 72204 USA. [Bechert, C.] 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 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2008 VL 35 IS 1 BP 124 EP 124 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 239XQ UT WOS:000251552000148 ER PT J AU Karai, L Karne, N Lee, C Stern, J Turner, M Rosenberg, S Bergfeld, W AF Karai, L. Karne, N. Lee, C. Stern, J. Turner, M. Rosenberg, S. Bergfeld, W. TI Immunotherapy associated cutaneous reaction in patients presenting with metastatic malignant melanoma SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Karai, L.; Bergfeld, W.] Cleveland Clin, Cleveland, OH 44106 USA. [Karne, N.; Turner, M.; Rosenberg, S.] NCI, NIH, Bethesda, MD 20892 USA. [Lee, C.; Stern, J.] Pathol Lab, 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 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2008 VL 35 IS 1 BP 132 EP 132 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 239XQ UT WOS:000251552000180 ER PT J AU Puri, P Wormack, M Henson, D Schwartz, A Grimley, P Anderson, W AF Puri, P. Wormack, M. Henson, D. Schwartz, A. Grimley, P. Anderson, W. TI Diverging patterns for melanoma among subtypes and gender SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Puri, P.; Schwartz, A.] George Washington Univ, Ctr Med, Washington, DC 20052 USA. [Wormack, M.; Henson, D.] George Washington Univ, Inst Canc, Washington, DC 20052 USA. [Grimley, P.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Anderson, W.] Natl Canc Inst, 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 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2008 VL 35 IS 1 BP 141 EP 141 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 239XQ UT WOS:000251552000216 ER PT J AU Puri, P Schwartz, A Henson, D Wormack, M Grimley, P Anderson, W AF Puri, P. Schwartz, A. Henson, D. Wormack, M. Grimley, P. Anderson, W. TI Site distribution differeces in melanoma in racial and gender groups SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Puri, P.; Schwartz, A.] George Washington Univ, Ctr Med, Washington, DC 20052 USA. [Henson, D.; Wormack, M.] George Washington Univ, Inst Canc, Washington, DC 20052 USA. [Grimley, P.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Anderson, W.] Natl Canc Inst, 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 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2008 VL 35 IS 1 BP 142 EP 142 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 239XQ UT WOS:000251552000220 ER PT J AU Bechert, C Stern, J AF Bechert, C. Stern, J. TI Basal cell carcinoma with perineural invasion: Reexcision perineural invasion? SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Bechert, C.; Stern, J.] Natl Inst Hlth, 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 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2008 VL 35 IS 1 BP 143 EP 143 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 239XQ UT WOS:000251552000223 ER PT J AU Lee, C Shamburek, R Turner, M AF Lee, C. Shamburek, R. Turner, M. TI Xanthoma eruptiva annulare: A very rare and unusual presentation of eruptive xanthoma SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Lee, C.; Turner, M.] Natl Inst Hlth, Natl Canc Inst, Bethesda, MD USA. [Shamburek, R.] Natl Inst Hlth, NHLBI, 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 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2008 VL 35 IS 1 BP 152 EP 152 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 239XQ UT WOS:000251552000258 ER PT J AU Bertoni, AG Clark, JM Feeney, P Yanovski, SZ Bantle, J Montgomery, B Safford, MM Herman, WH Haffner, S AF Bertoni, Alain G. Clark, Jeanne M. Feeney, Patricia Yanovski, Susan Z. Bantle, John Montgomery, Brenda Safford, Monika M. Herman, William H. Haffner, Steven CA Look AHEAD Res Grp TI Suboptimal control of glycemia, blood pressure, and LDL cholesterol in overweight adults with diabetes: the Look AHEAD Study SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE hemoglobin A1c; blood pressure; cholesterol; risk factor control ID NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; NATIONAL-HEALTH; US ADULTS; RISK-FACTORS; WEIGHT-LOSS; LIFE-STYLE; CARE; ASSOCIATION; OUTCOMES AB Background: The characteristics associated with meeting goals for glycemia, blood pressure (BP), and low-density lipoprotein (LDL) cholesterol for participants with diabetes were examined. Methods: Baseline information on demographics, medical history, and anthropometry, as well as on hemoglobin Alc, BP, and LDL cholesterol levels, was measured in 5145 participants of Look AHEAD, a multicenter randomized trial performed to determine whether long-term weight loss and increased physical fitness reduce cardiovascular disease (CVD) in overweight and obese individuals with type 2 diabetes. Logistic regression was used to analyze these cross-sectional data to ascertain associations between participant characteristics and attainment of risk factor goals [hemoglobin A1c < 7.0%, BP < 130/80 mmHg, and LDL < 100 mg/dl]. Results: The study population had a mean age of 58.7 years and a mean body mass index of 36.0 kg/m(2). Of the total number of participants, 59.5% were female, 36.8% were of ethnic/racial minority, and 87.3% were on diabetes medications. Upon enrollment, 45.8% had hemoglobin A1c < 7.0%, 51.7% had BP < 130/80 mmHg, and 37.2% had LDL < 100 mg/dl. All three goals were met by only 10.1%. We found consistent evidence for differences in risk factor control by age, gender, race/ethnicity, degree of obesity, education, income, CVD, source of medical care, and medication use. In multivariable analysis, African-American race, increasing degree of obesity, insulin use, and nonutilization of a lipid-lowering agent were associated with not meeting all risk factor goals. Conclusion: These data demonstrate that numerous baseline characteristics are associated with suboptimal control of these cardiovascular risk factors among overweight and obese adults with diabetes. (c) 2008 Elsevier Inc. All rights reserved. C1 [Bertoni, Alain G.; Feeney, Patricia] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Bertoni, Alain G.] Wake Forest Univ Hlth Sci, Dept Internal Med, Winston Salem, NC USA. [Clark, Jeanne M.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. [Clark, Jeanne M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Bantle, John] Univ Minnesota, Minneapolis, MN 55455 USA. [Montgomery, Brenda] Univ Washington, Seattle, WA 98195 USA. [Safford, Monika M.] Univ Alabama, Birmingham, AL USA. [Herman, William H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Herman, William H.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Haffner, Steven] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. RP Bertoni, AG (reprint author), Med Ctr Blvd, Winston Salem, NC 27157 USA. EM abertoni@wfubmc.edu FU Intramural NIH HHS; NCRR NIH HHS [M01 RR000056 44, M01 RR00051, M01-RR-01066, M01-RR-02719, M01RR00211-40]; NIDDK NIH HHS [DK 046204, DK56990, DK56992, DK57002, DK57008, DK57078, DK57131, DK57135, DK57136, DK57149, DK57151, DK57154, DK57171, DK57177, DK57178, DK57182, DK57219, P30 DK48520] NR 28 TC 42 Z9 42 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2008 VL 22 IS 1 BP 1 EP 9 DI 10.1016/j.jdiacomp.2006.10.003 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253NV UT WOS:000252525800001 PM 18191071 ER PT J AU Karev, GP AF Karev, Georgy P. TI Inhomogeneous maps and mathematical theory of selection SO JOURNAL OF DIFFERENCE EQUATIONS AND APPLICATIONS LA English DT Article DE inhomogeneous difference equation; dynamics of distribution; population model; fundamental theorem of natural selection; equations of price ID NATURAL ROTIFER POPULATIONS; FISHERS FUNDAMENTAL THEOREM; DYNAMICS; COVARIANCE AB In this paper we develop a theory of general selection systems with discrete time and explore the evolution of selection systems, in particular, inhomogeneous populations. We show that the knowledge of the initial distribution of the selection system allows us to determine explicitly the system distribution at the entire time interval. All statistical characteristics of interest, such as mean values of the fitness or any trait can be predicted effectively for indefinite time and these predictions dramatically depend on the initial distribution. The Fisher Fundamental theorem of natural selection (FTNS) and more general the Price equations are the famous results of the mathematical selection theory. We show that the problem of dynamic insufficiency for the Price equations and for the FTNS can be resolved within the framework of selection systems. Effective formulas for solutions of the Price equations and for the FTNS are derived. Applications of the developed theory to some other problems of mathematical biology (dynamics of inhomogeneous logistic and Ricker model, selection in rotifer populations) are also given. Complex behavior of the total population size, the mean fitness (in contrast to the plain FTNS) and other traits is possible for inhomogeneous populations with density-dependent fitness. The temporary dynamics of these quantities can be investigated with the help of suggested methods. C1 NIH, Lockheed Martin, Bethesda, MD 20894 USA. RP Karev, GP (reprint author), NIH, Lockheed Martin, Bldg 38A,Rm 5N511N,8600 Rockville Pike, Bethesda, MD 20894 USA. EM karev@ncbi.nlm.nih.gov NR 33 TC 5 Z9 5 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1023-6198 J9 J DIFFER EQU APPL JI J. Differ. Equ. Appl. PY 2008 VL 14 IS 1 BP 31 EP 58 DI 10.1080/10236190701470233 PG 28 WC Mathematics, Applied SC Mathematics GA 234EN UT WOS:000251143600003 ER PT J AU Resnik, DB AF Resnik, David B. TI Randomized controlled trials in environmental health research: Ethical issues SO JOURNAL OF ENVIRONMENTAL HEALTH LA English DT Article ID EXPLOITATION; JUSTICE AB Randomized controlled trials (RCTs) are becoming increasingly common in environmental health research. Like all studies involving human subjects, environmental health RCTs raise many ethical challenges, ranging from obtaining informed consent to minimizing risks to protecting privacy and confidentiality. One of the most important issues raised by these studies is whether it is ethical to withhold effective environmental health interventions from research subjects in order to satisfy scientific objectives. Although environmental health investigators usually do not have professional obligations to provide medical care to research subjects, they have ethical obligations to avoid exploiting them. Withholding interventions from research subjects can be ethical, provided that it does not lead to exploitation of individuals or groups. To avoid exploiting individuals or groups, investigators should ensure that research subjects and study populations receive a fair share of the benefits of research. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, POB 12233,Mail Drop NH 06, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 18 TC 4 Z9 4 U1 3 U2 4 PU NATL ENVIRON HEALTH ASSOC PI DENVER PA 720 S COLORADO BLVD SUITE 970, SOUTH TOWER, DENVER, CO 80246 USA SN 0022-0892 J9 J ENVIRON HEALTH JI J. Environ. Health PD JAN-FEB PY 2008 VL 70 IS 6 BP 28 EP 30 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 248OX UT WOS:000252164800004 PM 18236934 ER PT J AU Fu, PP Xia, QS Guo, L Yu, HT Chan, PC AF Fu, Peter P. Xia, Qingsu Guo, Lei Yu, Hongtao Chan, Po-Chuen TI Toxicity of kava kava SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Kava; anti-anxiety herbal beverage; top-selling botanical; hepatotoxicity; metabolism; mechanism ID FULMINANT HEPATIC-FAILURE; HERB-DRUG INTERACTIONS; PERFORMANCE LIQUID-CHROMATOGRAPHY; PIPER-METHYSTICUM; IN-VITRO; NATURAL THERAPY; BEVERAGE KAVA; F344 RATS; KAVALACTONES; EXTRACT AB Kava is a traditional beverage of various Pacific Basin countries. Kava has been introduced into the mainstream U.S. market principally as an anti-anxiety preparation. The effects of the long-term consumption of kava have not been documented adequately. Preliminary studies suggest possible serious organ system effects. The potential carcinogenicity of kava and its principal constituents are unknown. As such, kava extract was nominated for the chronic tumorigenicity bioassay conducted by the National Toxicology Program (NTP). At present toxicological evaluation of kava extract is being conducted by the NTP. The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity. C1 [Fu, Peter P.; Xia, Qingsu; Guo, Lei] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. [Chan, Po-Chuen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov; chanp@niehs.nih.gov RI Guo, Lei/E-9232-2011 NR 91 TC 36 Z9 36 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2008 VL 26 IS 1 BP 89 EP 112 DI 10.1080/10590500801907407 PG 24 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 270QJ UT WOS:000253735000003 PM 18322868 ER PT J AU Atkin, CK Smith, SW McFeters, C Ferguson, V AF Atkin, Charles K. Smith, Sandi W. McFeters, Courtnay Ferguson, Vanessa TI A comprehensive analysis of breast cancer news coverage in leading media outlets focusing on environmental risks and prevention SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SCREENING MAMMOGRAPHY; WOMENS MAGAZINES; POPULAR PRESS; PRINT MEDIA; HEALTH; INFORMATION; NEWSPAPERS; AGENDA; MASS AB Breast cancer has a high profile in the news media, which are a major source of information for cancer patients and the general public. To determine the nature Of breast cancer news coverage available to audiences, particularly on the topics of environmental risks and prevention, this content analysis measured a broad array of dimensions in 231 stories appearing in nine leading newspapers, newsmagazines, and television networks in 2003 and 2004. One fourth of all stories reported on various risks such as hormone replacement therapy (HRT) use. Very few items specifically addressed risks related to controllable lifestyle practices such as prepubertal obesity or chemical contaminants in the environment. About one third of the stories included prevention content, primarily focusing narrowly on use of pharmaceutical products. Little information described risk reduction via other individual preventive behaviors (e.g., diet, exercise, and smoking), parental protective measures, or collective actions to combat contamination sites. The more traditional categories of prevalence, detection, and treatment were featured in one third, one quarter, and two fifths of the news items, respectively. There were twice as many stories featuring personal narratives as statistical figures, and two thirds of all the news items cited expert medical professionals, researchers, or organizations. Implications of these findings and directions for future research are addressed. C1 [Atkin, Charles K.; Smith, Sandi W.] Michigan State Univ, E Lansing, MI USA. [McFeters, Courtnay] Natl Canc Inst, Michigan Dept Community Hlth, E Lansing, MI USA. [Ferguson, Vanessa] Eastern Michigan Univ, Ypsilanti, MI 48197 USA. RP Smith, SW (reprint author), 473 Commun Arts & Sci Bldg, E Lansing, MI 48824 USA. EM smiths@msu.edu RI Smith, Sandi/B-7009-2008 FU NIEHS NIH HHS [U01 ES012800, U01 ES012800-019001] NR 46 TC 36 Z9 36 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD JAN-FEB PY 2008 VL 13 IS 1 BP 3 EP 19 DI 10.1080/10810730701806912 PG 17 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 267YY UT WOS:000253546300002 PM 18307133 ER PT J AU Mcqueen, A Vernon, SW Meissner, HI Rakowski, W AF Mcqueen, Amy Vernon, Sally W. Meissner, Helen I. Rakowski, William TI Risk perceptions and worry about cancer: Does gender make a difference? SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article DE . ID AFRICAN-AMERICAN MEN; BREAST-CANCER; PERCEIVED RISK; COLORECTAL-CANCER; PROSTATE-CANCER; FAMILY-HISTORY; COLON-CANCER; HEALTH INFORMATION; PSYCHOLOGICAL DISTRESS; NATIONAL PROBABILITY AB Risk perceptions and worry are important constructs in many theoretical frameworks used to develop cancer screening interventions. Because most cancers for which we have early detection or prevention strategies are gender specific, few investigations have examined gender differences. We examined gender differences in the magnitude of and associations with, perceived risk and worry by cancer type. Our sample included 939 men and 1,580 women >= 50 years old with no history of relevant cancers from the 2003 Health Information National Trends Survey (HINTS). Dependent variables included absolute and comparative perceived risk and worry for gender-specific (breast/prostate) and colon cancers. We examined demographics, health status, health behaviors, cancer beliefs, and cancer communication variables as correlates. Linear regression analyses and pairwise contrasts were conducted with SUDAAN. Men reported greater comparative perceived risk for developing cancers, whereas women reported more frequent cancer worry. For both genders, perceived risk and worry were lowest for colon cancer. Correlates of perceived risk and worry varied, and several associations were moderated by gender. Different risk messages and intervention strategies may be needed to influence males' and females perceived cancer risk and worry. All effect sizes were small, and future prospective research is needed to confirm our findings. C1 [Mcqueen, Amy; Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX 77030 USA. [Meissner, Helen I.] NCI, Behav Res Program, Bethesda, MD USA. [Rakowski, William] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Mcqueen, A (reprint author), Univ Texas Houston, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, 7000 Fannin,Suite 2568, Houston, TX 77030 USA. EM Amy.McQueen@uth.tmc.edu FU NCI NIH HHS [2R25CA57712-11] NR 93 TC 47 Z9 47 U1 3 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD JAN-FEB PY 2008 VL 13 IS 1 BP 56 EP 79 DI 10.1080/10810730701807076 PG 24 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 267YY UT WOS:000253546300005 PM 18307136 ER PT J AU Shaw, BR Dubenske, LL Han, JY Cofta-Woerpel, L Bush, N GuStafson, DH McTavish, F AF Shaw, Bret R. Dubenske, Lori L. Han, Jeong Yeob Cofta-Woerpel, Ludmila Bush, Nigel GuStafson, David H. McTavish, Fiona TI Antecedent characteristics of online cancer information seeking among rural breast cancer patients: An application of the Cognitive-Social Health Information Processing (C-SHIP) model SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID LOW-INCOME WOMEN; QUALITY-OF-LIFE; COMPUTER SUPPORT; DECISION-MAKING; DIGITAL DIVIDE; INTERNET; NEEDS; PARTICIPATION; EXPERIENCE; BEHAVIOR AB Little research has examined the antecedent characteristics of patients most likely to seek online cancer information. This study employs the Cognitive-Social Health Information Processing (C-SHIP) model as a framework to understand what psychosocial characteristics precede online cancer-related information seeking among rural breast cancer patients who often have fewer health care providers and limited local support services. Examining 144 patients who were provided free computer hardware, Internet access, and training for how to use an interactive cancer communication system, pretest survey scores indicating patients' psychosocial status were correlated with specific online cancer information seeking behaviors. Each of the factors specified by the C-SHIP model had significant relationships with online cancer information seeking behaviors, with the strongest findings emerging for cancer-relevant encodings and self-construals, cancer-relevant beliefs and expectancies, and cancer-relevant self-regulatory competencies and skills. Specifically, patients with more negative appraisals in these domains were more likely to seek out online cancer information. Additionally, antecedent variables associated with the C-SHIP model had more frequent relationships with experiential information as compared with to didactic information. This study supports the applicability of the model to discern why people afflicted with cancer may seek online information to cope with their disease. C1 [Shaw, Bret R.] Univ Wisconsin, Dept Life Sci Commun, Madison, WI 53706 USA. [Shaw, Bret R.] Ctr Excellence Canc Commun Res, Madison, WI USA. [Dubenske, Lori L.; Han, Jeong Yeob] Univ Georgia, Dept Telecommun, Grady Coll Journalism & Mass Commun, Athens, GA 30602 USA. [Cofta-Woerpel, Ludmila] Natl Canc Inst Canc Informat Serv S Cent Region, Houston, TX USA. [Cofta-Woerpel, Ludmila] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX USA. [Bush, Nigel] Natl Canc Inst Canc Informat Serv NW Region, Seattle, WA USA. [Bush, Nigel] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [GuStafson, David H.; McTavish, Fiona] Ctr Excellence Canc Commun Res, Madison, WI USA. RP Shaw, BR (reprint author), Univ Wisconsin, Dept Life Sci Commun, Madison, WI 53706 USA. EM brshaw@wisc.edu FU NCI NIH HHS [P50 CA095817] NR 72 TC 24 Z9 24 U1 3 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2008 VL 13 IS 4 BP 389 EP 408 DI 10.1080/10810730802063546 PG 20 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 317XR UT WOS:000257054200007 PM 18569368 ER PT J AU Reynolds, KD Buller, DB Yaroch, AL Maloy, J Geno, CR Cutter, GR AF Reynolds, Kim D. Buller, David B. Yaroch, Amy L. Maloy, Julie Geno, Cristy R. Cutter, Gary R. TI Effects of Program Exposure and Engagement With Tailored Prevention Communication on Sun Protection by Young Adolescents SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SCHOOL SMOKING PREVENTION; MATCHING HEALTH MESSAGES; SKIN-CANCER PREVENTION; LANGUAGE INTENSITY; SOLAR PROTECTION; EDUCATION; CHILDREN; INTERVENTIONS; INFORMATION; BEHAVIORS AB Few family-based interventions to increase sun safe behavior among adolescents have been evaluated. The present study tested an intervention that included tailored and nontailored print communications delivered by mail to adolescents (age 11 to 15) and their parents who were also participating in an evaluation of an in-school intervention. The use of sunscreen, protective clothing, and avoidance of the sun were promoted, and family communication and environmental change strategies were fostered. Adolescents and their parents were pretested in May of 2002 and posttested from August to October. Adolescents (N=599) were stratified on experimental condition in the in-school study (in-school intervention vs control) and randomly were assigned from within strata to receive (N=288) or not receive (N=311) the summer intervention materials. No statistically significant effects were found for adolescents between the randomized experimental conditions. Parents' had increased knowledge (F=5.52, p.05) and propensity to have their child wear sunglasses (F=4.07, p.05). Greater program exposure/engagement led to enhanced sun protection behavior (e.g., fewer sunburns) and psychosocial factors among adolescents and parents. Greater exposure/engagement led to improvements in family interaction and home environment (e.g., shade audit completed). Future research is needed on exposure/engagement with family-based health messaging and on family-based sun safety programs for adolescents. C1 [Reynolds, Kim D.] Claremont Grad Univ, Claremont, CA USA. [Buller, David B.; Maloy, Julie] Klein Buendel Inc, Golden, CO USA. [Yaroch, Amy L.] NCI, Bethesda, MD 20892 USA. [Geno, Cristy R.] Kaiser Permanente Colorado, Colorado Springs, CO USA. [Cutter, Gary R.] Univ Alabama, Birmingham, AL USA. RP Reynolds, KD (reprint author), 1000 S Fremont Ave,Unit 8, Alhambra, CA 91803 USA. EM kdreynol@usc.edu FU NCI NIH HHS [CA79701, R01 CA079701] NR 46 TC 5 Z9 5 U1 2 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2008 VL 13 IS 7 BP 619 EP 636 DI 10.1080/10810730802412149 PG 18 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 366CW UT WOS:000260459200002 PM 18958776 ER PT J AU Evans, WD Blitstein, J Hersey, J Renaud, J Yaroch, A AF Evans, W. Douglas Blitstein, Jonathan Hersey, James C. Renaud, Jeanette Yaroch, Amy L. TI Systematic Review of Public Health Branding SO JOURNAL OF HEALTH COMMUNICATION LA English DT Review ID COMMUNICATION CAMPAIGNS; BEHAVIOR; PREVENTION; EDUCATION; IMPACT AB Brands build relationships between consumers and products, services, or lifestyles by providing beneficial exchanges and adding value to their objects. Brands can be measured through associations that consumers hold for products and services. Public health brands are the associations that individuals hold for health behaviors, or lifestyles that embody multiple health behaviors. We systematically reviewed the literature on public health brands; developed a methodology for describing branded health messages and campaigns; and examined specific branding strategies across a range of topic areas, campaigns, and global settings. We searched the literature for published studies on public health branding available through all relevant, major online publication databases. Public health branding was operationalized as any manuscripts in the health, social science, and business literature on branding or brands in health promotion marketing. We developed formalized decision rules and applied them in identifying articles for review. We initially identified 154 articles and reviewed a final set of 37, 10 from Africa, Australia, and Europe. Branded health campaigns spanned most of the major domains of public health and numerous communication strategies and evaluation methodologies. Most studies provided clear information on planning, development, and evaluation of the branding effort, while some provided minimal information. Branded health messages typically are theory based, and there is a body of evidence on their behavior change effectiveness, especially in nutrition, tobacco control, and HIV/AIDS. More rigorous research is needed, however, on how branded health messages impact specific populations and behaviors. C1 [Evans, W. Douglas; Blitstein, Jonathan; Hersey, James C.; Renaud, Jeanette] RTI Int, Washington, DC USA. [Yaroch, Amy L.] NCI, Rockville, MD USA. RP Evans, WD (reprint author), George Washington Sch Publ Hlth Serv, 2175 K St NW,Suite 700, Washington, DC 20037 USA. EM wdevans@gwu.edu OI Blitstein, Jonathan L./0000-0001-5202-4934 NR 31 TC 19 Z9 19 U1 1 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2008 VL 13 IS 8 BP 721 EP 741 AR PII 906256103 DI 10.1080/10810730802487364 PG 21 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 378QK UT WOS:000261338800002 PM 19051110 ER PT J AU Viswanath, K Blake, K Meissner, H Saiontz, NG Mull, C Freeman, C Hesse, B Croyle, R AF Viswanath, K. Blake, Kelly D. Meissner, Helen I. Saiontz, Nicole Gottlieb Mull, Corey Freeman, Carol S. Hesse, Bradford Croyle, Robert T. TI Occupational Practices and the Making of Health News: A National Survey of US Health and Medical Science Journalists SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER CONTROL; BREAST-CANCER; MASS-MEDIA; PROFESSIONALS; INFORMATION; COVERAGE; PRESS; WOMEN AB News media coverage of health topics can frame and heighten the salience of health-related issues, thus influencing the public's beliefs, attitudes, and behaviors. Through their routine coverage of scientific developments, news media are a critical intermediary in translating research for the public, patients, practitioners, and policymakers. Until now, little was known about how health and medical science reporters and editors initiate, prioritize, and develop news stories related to health and medicine. We surveyed 468 reporters and editors representing 463 local and national broadcast and print media outlets to characterize individual characteristics and occupational practices leading to the development of health and medical science news. Our survey revealed that 70% of respondents had bachelor's degrees; 8% were life sciences majors in college. Minorities are underrepresented in health journalism; 97% of respondents were non-Hispanic and 93% were White. Overall, initial ideas for stories come from a news source followed by press conferences or press releases. Regarding newsworthiness criteria, the potential for public impact and new information or development are the major criteria cited, followed by ability to provide a human angle and ability to provide a local angle. Significant differences were seen between responses from reporters vs. editors and print vs. broadcast outlets. C1 [Viswanath, K.; Blake, Kelly D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Saiontz, Nicole Gottlieb; Hesse, Bradford; Croyle, Robert T.] NCI, Bethesda, MD 20892 USA. [Mull, Corey; Freeman, Carol S.] ORC Macro Int Inc, Calverton, MD USA. RP Viswanath, K (reprint author), 44 Binney St,LW703, Boston, MA 02115 USA. EM vish_viswanath@dfci.harvard.edu OI Hesse, Bradford/0000-0003-1142-1161 NR 41 TC 42 Z9 43 U1 6 U2 31 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2008 VL 13 IS 8 BP 759 EP 777 AR PII 906253738 DI 10.1080/10810730802487430 PG 19 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 378QK UT WOS:000261338800004 PM 19051112 ER PT J AU Henderson, WA Gill, JM Kim, KH Skanderson, M Butt, AA AF Henderson, W. A. Gill, J. M. Kim, K. H. Skanderson, M. Butt, A. A. TI Relationship of hepatitis C virus to hepatocellular carcinoma in dialysis patients SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Henderson, W. A.; Gill, J. M.] NINR, NIH, Dept Hlth & Human Services, Bethesda, MD 20892 USA. [Kim, K. H.] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA. [Skanderson, M.; Butt, A. A.] Univ Pittsburgh, Dept Med Infect Dis, Pittsburgh, PA USA. EM hendersw@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 737 BP S275 EP S275 DI 10.1016/S0168-8278(08)60739-4 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683201228 ER PT J AU Lok, AS Seeff, LB Morgan, TR DiBisceglie, AM Sterling, RK Curto, TM AF Lok, A. S. Seeff, L. B. Morgan, T. R. DiBisceglie, A. M. Sterling, R. K. Curto, T. M. TI Incidence rates and risk factors associated with hepatocellular carcinoma (HCC) in patients with advanced liver disease due to hepatitis C: Results of the halt-C trial SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Lok, A. S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Seeff, L. B.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. [Morgan, T. R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, T. R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [DiBisceglie, A. M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Sterling, R. K.] Virginia Commonwealth Univ, Hepatol Sect, Richmond, VA USA. [Curto, T. M.] New England Res Inst, Watertown, MA 02172 USA. EM aslok@med.umich.edu RI Lok, Anna /B-8292-2009 NR 0 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 101 BP S45 EP S45 DI 10.1016/S0168-8278(08)60103-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683200102 ER PT J AU Oliviero, B Varchetta, S Cerino, A Paudice, E Michelone, G Zaramella, M Mavilio, D Mondelli, MU AF Oliviero, B. Varchetta, S. Cerino, A. Paudice, E. Michelone, G. Zaramella, M. Mavilio, D. Mondelli, M. U. TI Enhanced NK cell cytolytic activity in chronic HCV infection SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Oliviero, B.; Varchetta, S.; Cerino, A.; Paudice, E.; Michelone, G.; Zaramella, M.; Mondelli, M. U.] Univ Pavia, I-27100 Pavia, Italy. [Oliviero, B.; Varchetta, S.; Cerino, A.; Paudice, E.; Michelone, G.; Zaramella, M.; Mondelli, M. U.] IRCCS Fdn Policlin San Matteo, Dept Infect Dis, Pavia, Italy. [Varchetta, S.; Mavilio, D.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM mario.mondelli@unipv.it NR 0 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 115 BP S51 EP S51 DI 10.1016/S0168-8278(08)60117-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683200116 ER PT J AU Salama, HM Zekry, AN Ahmed, NH Bahnasy, AA Al Shabrawy, MA AF Salama, H. M. Zekry, A. N. Ahmed, N. H. Bahnasy, A. A. Al Shabrawy, M. A. TI Autologous adult haematopoietic stem cell transplantation SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Salama, H. M.] Cairo Univ, Fac Med, Cairo, Egypt. [Zekry, A. N.; Bahnasy, A. A.] Cairo Univ, Natl Canc Inst, Cairo, Egypt. [Ahmed, N. H.; Al Shabrawy, M. A.] Cairo Univ, Dept Pediat, Cairo, Egypt. Natl Canc Inst, Bethesda, MD USA. EM hsalama@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 527 BP S198 EP S198 DI 10.1016/S0168-8278(08)60529-2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683201018 ER PT J AU Shiffman, ML Morishima, C Lindsay, KL Hoefs, JC Dienstag, JL Szabo, G Lee, WM Wright, EC AF Shiffman, M. L. Morishima, C. Lindsay, K. L. Hoefs, J. C. Dienstag, J. L. Szabo, G. Lee, W. M. Wright, E. C. CA HALT-C Trial Grp TI Suppression of serum HCV RNA levels during maintenance peginterferon (PEGIFN) alfa-2a therapy and clinical outcomes in the HALT-C trial SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Shiffman, M. L.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Morishima, C.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Lindsay, K. L.] Univ So Calif, Div Gastroenterol & Liver Dis, Los Angeles, CA USA. [Hoefs, J. C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Dienstag, J. L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. [Szabo, G.] Univ Massachusetts, Sch Med, Ctr Liver, Worcester, MA 01605 USA. [Lee, W. M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Wright, E. C.] NIDDK, Dept Hlth & Human Serv, Bethesda, MD USA. EM mshiffma@vcu.edu NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 144 BP S62 EP S62 DI 10.1016/S0168-8278(08)60146-4 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683200145 ER PT J AU Teufel, A Strand, S Maass, T Zhao, Y Kanzler, S Westphal, H Galle, PR AF Teufel, A. Strand, S. Maass, T. Zhao, Y. Kanzler, S. Westphal, H. Galle, P. R. TI Liver specific LDB1 deletion results in enhanced liver cancer development SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Teufel, A.; Strand, S.; Maass, T.; Kanzler, S.; Galle, P. R.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Zhao, Y.; Westphal, H.] NICHD, Lab Mammalian Genes & Dev, Natl Inst Hlth, Bethesda, MD USA. EM teufel@uni-mainz.de NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 351 BP S138 EP S138 DI 10.1016/S0168-8278(08)60353-0 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683200350 ER PT J AU Union, A Buyse, MA Verheyden, G De Brabandere, V Van Put, H Vandenneucker, C Jacobs, D Devos, A Defruyt, M Schryvers, N Dauwe, M Purcell, RH Maertens, G Allosery, K AF Union, A. Buyse, M. A. Verheyden, G. De Brabandere, V. Van Put, H. Vandenneucker, C. Jacobs, D. Devos, A. Defruyt, M. Schryvers, N. Dauwe, M. Purcell, R. H. Maertens, G. Allosery, K. TI Generation of recombinant human anti-E1 monoclonal antibodies that effectively neutralize HCV in vitro SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Union, A.; Buyse, M. A.; Verheyden, G.; De Brabandere, V.; Van Put, H.; Vandenneucker, C.; Jacobs, D.; Devos, A.; Defruyt, M.; Schryvers, N.; Dauwe, M.; Maertens, G.; Allosery, K.] GENimmune NV, Ghent, Belgium. [Purcell, R. H.] NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA. EM ann.union@genimmune.be NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 118 BP S52 EP S52 DI 10.1016/S0168-8278(08)60120-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683200119 ER PT J AU Varchetta, S Oliviero, B Donato, F Agnelli, E Rossi, G Rigamonti, C Colombo, M Paudice, E Mavilio, D Mondelli, MU AF Varchetta, S. Oliviero, B. Donato, F. Agnelli, E. Rossi, G. Rigamonti, C. Colombo, M. Paudice, E. Mavilio, D. Mondelli, M. U. TI Prospective study of NK cell phenotype in recurrent HCV infection after liver transplant SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 23-27, 2008 CL Milan, ITALY SP European Assoc Study Liver C1 [Varchetta, S.; Oliviero, B.; Paudice, E.; Mondelli, M. U.] IRCCS Fdn San Matteo, Pavia, Italy. [Varchetta, S.; Oliviero, B.; Paudice, E.; Mondelli, M. U.] Univ Pavia, I-27100 Pavia, Italy. [Donato, F.; Agnelli, E.; Rossi, G.; Rigamonti, C.; Colombo, M.] IRCCS Fdn Policlin Mangiagalli Regina Elena, Gastroenterol & Liver Transplantat Unit, Milan, Italy. [Varchetta, S.; Mavilio, D.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM mario.mondelli@unipv.it NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2008 VL 48 SU 2 MA 117 BP S51 EP S52 DI 10.1016/S0168-8278(08)60119-1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PL UT WOS:000256683200118 ER PT J AU Marker, LL Wilkerson, AJP Sarno, RJ Martenson, J Breitenmoser-Wuersten, C O'Brien, SJ Johnson, WE AF Marker, Laurie L. Wilkerson, Alison J. Pearks Sarno, Ronald J. Martenson, Janice Breitenmoser-Wuersten, Christian O'Brien, Stephen J. Johnson, Warren E. TI Molecular genetic insights on cheetah (Acinonyx jubatus) ecology and conservation in Namibia SO JOURNAL OF HEREDITY LA English DT Article ID POPULATION-STRUCTURE; CAPTIVE CHEETAHS; AFRICAN CHEETAH; DOMESTIC CAT; DIVERSITY; DNA; MICROSATELLITES; INFERENCE; AMERICAN; WILD AB The extent and geographic patterns of molecular genetic diversity of the largest remaining free-ranging cheetah population were described in a survey of 313 individuals from throughout Namibia. Levels of relatedness, including paternity/maternity (parentage), were assessed across all individuals using 19 polymorphic microsatellite loci, and unrelated cheetahs (n = 89) from 7 regions were genotyped at 38 loci to document broad geographical patterns. There was limited differentiation among regions, evidence that this is a generally panmictic population. Measures of genetic variation were similar among all regions and were comparable with Eastern African cheetah populations. Parentage analyses confirmed several observations based on field studies, including 21 of 23 previously hypothesized family groups, 40 probable parent/offspring pairs, and 8 sibling groups. These results also verified the successful integration and reproduction of several cheetahs following natural dispersal or translocation. Animals within social groups (family groups, male coalitions, or sibling groups) were generally related. Within the main study area, radio-collared female cheetahs were more closely interrelated than similarly compared males, a pattern consistent with greater male dispersal. The long-term maintenance of current patterns of genetic variation in Namibia depends on retaining habitat characteristics that promote natural dispersal and gene flow of cheetahs. C1 [Sarno, Ronald J.; Martenson, Janice; O'Brien, Stephen J.; Johnson, Warren E.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Marker, Laurie L.; Wilkerson, Alison J. Pearks] Cheetah Conservat Fund, Otjiwarongo, Namibia. [Marker, Laurie L.] Univ Oxford, Dept Zool, Wildlife Conservat Res Unit, Oxford OX1 3PS, England. [Breitenmoser-Wuersten, Christian] KORA, CH-3074 Bern, Switzerland. RP Johnson, WE (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM johnsonw@ncifcrf.gov RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 58 TC 11 Z9 11 U1 7 U2 73 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD JAN-FEB PY 2008 VL 99 IS 1 BP 2 EP 13 DI 10.1093/jhered/esm081 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 267DY UT WOS:000253490900002 PM 17982159 ER PT J AU Mariotti, J Foley, J Jung, U Borenstein, T Kantardzic, N Han, S Hanson, JT Wong, E Buxhoeveden, N Trepel, JB Fojo, AT Telford, W Fowler, DH AF Mariotti, Jacopo Foley, Jason Jung, Unsu Borenstein, Todd Kantardzic, Nermina Han, Soo Hanson, Joshua T. Wong, Elaine Buxhoeveden, Nicole Trepel, Jane B. Fojo, Antonio Tito Telford, William Fowler, Daniel H. TI Ex vivo rapamycin generates apoptosis-resistant donor Th2 cells that persist in vivo and prevent hemopoietic stem cell graft rejection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; MAMMALIAN TARGET; PROGENITOR CELLS; BCL-2 FAMILY; VETO CTLS; ENGRAFTMENT; INDUCTION; TOLERANCE AB Because ex vivo rapamycin generates murine Th2 cells that prevent Graft-versus-host disease more potently than control Th2 cells, we hypothesized that rapamycin would generate Th2/Tc2 cells (Th2/Tc2.R cells) that abrogate fully MHC-disparate hemopoietic stem cell rejection more effectively than control Th2/Tc2 cells. In a B6-into-BALB/c graft rejection model, donor Th2/Tc2.R cells were indeed enriched in their capacity to prevent rejection; importantly, highly purified CD4(+) Th2.R cells were also highly efficacious for preventing rejection. Rapamycin-gene rated Th2/Tc2 cells were less likely to die after adoptive transfer, accumulated in vivo at advanced proliferative cycles, and were present in 10-fold higher numbers than control Th2/Tc2 cells. Th2.R cells had a multifaceted, apoptosis-resistant phenotype, including: 1) reduced apoptosis after staurosporine addition, serum starvation, or CD3/CD28 costimulation; 2) reduced activation of caspases 3 and 9; and 3) increased anti-apoptotic Bcl-x(L) expression and reduced proapoptotic Bim and Bid expression. Using host-versus-graft reactivity as an immune correlate of graft rejection, we found that the in vivo efficacy of Th2/Tc2.R cells 1) did not require Th2/Tc2.R cell expression of IL-4, IL-10, perforin, or Fas ligand; 2) could not be reversed by IL-2, IL-7, or IL-15 posttransplant therapy; and 3) was intact after therapy with Th2.R cells relatively devoid of Foxp3 expression. We conclude that ex vivo rapamycin generates Th2 cells that are resistant to apoptosis, persist in vivo, and effectively prevent rejection by a mechanism that may be distinct from previously described graft-facilitating T cells. C1 [Mariotti, Jacopo; Foley, Jason; Jung, Unsu; Borenstein, Todd; Kantardzic, Nermina; Han, Soo; Hanson, Joshua T.; Wong, Elaine; Buxhoeveden, Nicole; Telford, William; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr,East Labs 3, Bethesda, MD 20892 USA. [Trepel, Jane B.; Fojo, Antonio Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Mariotti, J (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr,East Labs 3, 3-3330, Bethesda, MD 20892 USA. EM marriottj@mail.nih.gov FU Intramural NIH HHS NR 63 TC 24 Z9 25 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 JAN 1 PY 2008 VL 180 IS 1 BP 89 EP 105 PG 17 WC Immunology SC Immunology GA 248OF UT WOS:000252162700014 PM 18097008 ER PT J AU Hallett, WHD Ames, E Motarjemi, M Barao, I Shanker, A Tamang, DL Sayers, TJ Hudig, D Murphy, WJ AF Hallett, William H. D. Ames, Erik Motarjemi, Milad Barao, Isabel Shanker, Anil Tamang, David L. Sayers, Thomas J. Hudig, Dorothy Murphy, William J. TI Sensitization of tumor cells to NK cell-mediated killing by proteasome inhibition SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; APOPTOSIS-INDUCING LIGAND; MULTIPLE-MYELOMA; CANCER-THERAPY; CYTOTOXICITY; BORTEZOMIB; PS-341; GROWTH; LYSIS; ACTIVATION AB Bortezomib is a proteasome inhibitor that has direct antitumor effects. We and others have previously demonstrated that bortezomib could also sensitize tumor cells to killing via the death ligand, TRAIL. NK cells represent a potent antitumor effector cell. Therefore, we investigated whether bortezomib could sensitize tumor cells to NK cell-mediated killing. Preincubation of tumor cells with bortezomib had no effect on short-term NK cell killing or purified granule killing assays. Using a 24-h lysis assay, increases in tumor killing was only observed using perforin-deficient NK cells, and this increased killing was found to be dependent on both TRAIL and FasL, correlating with an increase in tumor Fas and DR5 expression. Long-term tumor outgrowth assays allowed for the detection of this increased tumor killing by activated NK cells following bortezomib treatment of the tumor. In a tumor purging assay, in which tumor:bone marrow cell mixtures were placed into lethally irradiated mice, only treatment of these mixtures with a combination of NK cells with bortezomib resulted in significant tumor-free survival of the recipients. These results demonstrate that bortezomib treatment can sensitize tumor cells to cellular effector pathways. These results suggest that the combination of proteasome inhibition with immune therapy may result in increased antitumor efficacy. C1 [Hallett, William H. D.; Ames, Erik; Motarjemi, Milad; Barao, Isabel; Tamang, David L.; Hudig, Dorothy; Murphy, William J.] Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. [Shanker, Anil; Sayers, Thomas J.] NCI, Sci Applicat Int Corp, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. EM wmurphy@medicine.nevada.edu RI Sayers, Thomas/G-4859-2015; OI Shanker, Anil/0000-0001-6372-3669 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, R01 CA093527, R01 CA093527-05, R01 CA102282, R01 CA102282-05, R01CA102282-01A1, R01CA95327-02] NR 28 TC 93 Z9 95 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 JAN 1 PY 2008 VL 180 IS 1 BP 163 EP 170 PG 8 WC Immunology SC Immunology GA 248OF UT WOS:000252162700022 PM 18097016 ER PT J AU Singh, SP Zhang, HH Foley, JF Hedrick, MN Farber, JM AF Singh, Satya P. Zhang, Hongwei H. Foley, John F. Hedrick, Michael N. Farber, Joshua M. TI Human T cells that are able to produce EL-17 express the chemokine receptor CCR6 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; HUMAN TH17 CELLS; AUTOIMMUNE INFLAMMATION; CUTTING EDGE; HELPER-CELLS; DIFFERENTIAL EXPRESSION; LYMPHOCYTES; RESPONSES; CYTOKINE; IL-17 AB Some pathways of T cell differentiation are associated with characteristic patterns of chemokine receptor expression. A new lineage of effector/memory CD4(+) T cells has been identified whose signature products are IL-17 cytokines and whose differentiation requires the nuclear receptor, ROR gamma t. These Th17 cells are critical effectors in mouse models of autoimmune disease. We have analyzed the association between chemokine receptor expression and IL-17 production for human T cells. Activating cord blood (naive) CD4(+) T cells under conditions driving Th17 differentiation led to preferential induction of CCR6, CCR9, and CXCR6. Despite these data, we found no strong correlation between the production of IL-17 and expression of CCR9 or CXCR6. By contrast, our analyses revealed that virtually all IL-17-producing CD4(+) T cells, either made in our in vitro cultures or found in peripheral blood, expressed CCR6, a receptor found on similar to 50% of CD4(+) memory PBL. Compared with CD4(+)CD45RO(+)CCR6(-)cells, CD4(+)CD45RO(+)CCR6(+) cells contained at least 100-fold more IL-17A mRNA and secreted 100-fold more IL-17 protein. The CCR6(+) cells showed a similar enrichment in mRNA for ROR gamma t. CCR6 was likewise expressed on all IL-17-producing CD8(+) PBL. CCR6 has been associated with the trafficking of T, B, and dendritic cells to epithelial sites, but has not been linked to a specific T cell phenotype. Our data reveal a fundamental feature of IL-17-producing human T cells and a novel role for CCR6, suggesting both new directions for investigating IL-17-related immune responses and possible targets for preventing inflammatory injury. C1 [Singh, Satya P.; Zhang, Hongwei H.; Foley, John F.; Hedrick, Michael N.; Farber, Joshua M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N-111,10 Ctr Dr, Bethesda, MD 20892 USA. EM jfarber@niaid.nih.gov FU Intramural NIH HHS NR 59 TC 185 Z9 198 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 JAN 1 PY 2008 VL 180 IS 1 BP 214 EP 221 PG 8 WC Immunology SC Immunology GA 248OF UT WOS:000252162700028 PM 18097022 ER PT J AU Price, DA Bitmansour, AD Edgar, JB Walker, JM Axthelm, MK Douek, DC Picker, LJ AF Price, David A. Bitmansour, Arlene D. Edgar, John B. Walker, Joshua M. Axthelm, Michael K. Douek, Daniel C. Picker, Louis J. TI Induction and evolution of cytomegalovirus-specific CD4(+) T cell clonotypes in rhesus macaques SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; SIMIAN IMMUNODEFICIENCY VIRUS; PERSISTENT VIRUS; VIRAL PERSISTENCE; CHANGING PATTERNS; CLONAL SELECTION; IMMUNE ESCAPE; BONE-MARROW; INFECTION; RESPONSES AB CMV infection induces robust CD4(+) T cell responses in immunocompetent hosts that orchestrate immune control of viral replication, dissemination, and disease. In this study, we characterized the clonotypic composition of CD4(+) T cell populations specific for rhesus CMV (RhCMV) in chronically infected adult rhesus macaques (RM) and in juvenile RM undergoing primary RhCMV infection and subsequent secondary challenge with RhCMV. In adult RM with established chronic infection, RhCMV-specific CD4(+) T cell populations exhibited stable, pauciclonal structures with skewed hierarchies dominated by two or three clonotypes. During primary infection, in contrast, the initial RhCMV-specific CD4(+) T cell populations were highly polyclonal and progressive evolution to the chronic pattern manifest in adults occurred over the ensuing 2-3 years. Clear patterns of clonal succession were observed during this maturation process, such that clonotypes present in the acute phase were largely replaced over time. However, rechallenge with RhCMV expanded virus-specific CD4(+) T cell clonotypes identified solely during acute infection. These findings indicate that, during persistent viral infection, substantial selection pressures and ongoing clonotype recruitment shape the specific CD4(+) T cell repertoire and that rapidly exhausted or superseded clonotypes often remain within the memory T cell pool. C1 [Price, David A.; Douek, Daniel C.] NIAID, Vaccine Res Ctr, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. [Price, David A.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. [Bitmansour, Arlene D.; Edgar, John B.; Walker, Joshua M.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. [Bitmansour, Arlene D.; Edgar, John B.; Walker, Joshua M.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA. [Bitmansour, Arlene D.; Edgar, John B.; Walker, Joshua M.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregan Natl Primate Res Ctr, Beaverton, OR 97006 USA. RP Price, DA (reprint author), NIAID, Vaccine Res Ctr, Human Immunol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dpricel@mail.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G0501963]; NCRR NIH HHS [P51-RR00163, U24-RR018107, U42-RR016025]; NIA NIH HHS [P01-AG023644]; NIAID NIH HHS [R01-AI060392] NR 56 TC 22 Z9 22 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2008 VL 180 IS 1 BP 269 EP 280 PG 12 WC Immunology SC Immunology GA 248OF UT WOS:000252162700034 PM 18097028 ER PT J AU Mueller, YM Do, DH Altork, SR Artlett, CM Gracely, EJ Katsetos, CD Legido, A Villinger, F Altman, JD Brown, CR Lewis, MG Katsikis, PD AF Mueller, Yvonne M. Do, Duc H. Altork, Susan R. Artlett, Carol M. Gracely, Edward J. Katsetos, Christos D. Legido, Agustin Villinger, Francois Altman, John D. Brown, Charles R. Lewis, Mark G. Katsikis, Peter D. TI IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-Specific CD8(+) T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID I MOLECULE MAMU-A-ASTERISK-01; BLOOD MONONUCLEAR-CELLS; NATURAL-KILLER-CELL; RHESUS MACAQUES; CD95/FAS-INDUCED APOPTOSIS; INTERLEUKIN-15 IL-15; NONHUMAN-PRIMATES; IMMUNE-RESPONSES; TYPE-1 INFECTION; DENDRITIC CELLS AB In this study, we examined the effect of in vivo treatment of acutely SIV-infected Mamu-A*0(+) rhesus macaques with IL-15. IL-15 treatment during acute infection increased viral set point by 3 logs and accelerated the development of simian AIDS in two of six animals with one developing early minimal lesion SIV meningoencephalitis. Although IL-15 induced a 2- to 3-fold increase in SIV-specific CD8(+) T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells, this had no impact on peak viremia and did not lower viral set point. At viral set point, however, activated SIV-specific CD8(+) T cells and NK cells were reduced in the blood of IL-15-treated animals and LN SIV-infected cells were increased. Week 30 LN from IL-15-treated animals had significantly increased Gag-specific CD8(+) T cell numbers, whereas total cell, lymphocyte, and CD4(+) T cell numbers were reduced. IL-15 treatment significantly reduced anti-SIV Ab concentrations at week 3 and viral set point. IL-15 increased Ki-67(+)CD4(+) T cells at week I of treatment and reduced blood CCR5(+) and CD45(-)RA(-)CD62L(-) CD4(+) T cells. The frequency of day 7 Ki-67(+)CD4(+) T cells strongly correlated with viral set point. These findings suggest that CD4(+) T cell activation during acute infection determines subsequent viral set point and IL-15 treatment by increasing such activation elevates viral set point. Finally, IL-15-treated acutely SIV-infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection. C1 [Mueller, Yvonne M.; Do, Duc H.; Altork, Susan R.; Artlett, Carol M.; Katsikis, Peter D.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19129 USA. [Katsikis, Peter D.] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Philadelphia, PA 19129 USA. [Mueller, Yvonne M.; Do, Duc H.; Altork, Susan R.; Artlett, Carol M.; Katsikis, Peter D.] Drexel Univ, Coll Med, Ctr Immunol & Vaccine Sci, Philadelphia, PA 19129 USA. [Gracely, Edward J.] Drexel Univ, Coll Med, Dept Family Community & Prevent Med, Philadelphia, PA 19129 USA. [Katsetos, Christos D.; Legido, Agustin] Drexel Univ, Coll Med, Dept Pediat, Philadelphia, PA 19129 USA. [Katsetos, Christos D.] Drexel Univ, Coll Med, Dept Pathol, Philadelphia, PA 19129 USA. [Katsetos, Christos D.] Drexel Univ, Coll Med, Lab Med, Philadelphia, PA 19129 USA. [Legido, Agustin] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19129 USA. [Villinger, Francois] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30329 USA. [Villinger, Francois] Emory Univ, Sch Med, Lab Med, Atlanta, GA 30329 USA. [Altman, John D.] Emory Univ, Sch Med, Emory Vaccine Res Ctr, Atlanta, GA 30329 USA. [Brown, Charles R.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Lewis, Mark G.] Bioqual, Rockville, MD 20850 USA. RP Katsikis, PD (reprint author), Drexel Univ, Coll Med, Dept Microbiol & Immunol, 2900 Queen Lane, Philadelphia, PA 19129 USA. EM Peter.Katsikis@DrexelMed.edu FU NIAID NIH HHS [AI62437, R01 AI052005, R01 AI046719, R01 AI046719-09, R01 AI46719, R01 AI062437-03, AI52005, R01 AI062437] NR 69 TC 62 Z9 62 U1 1 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 JAN 1 PY 2008 VL 180 IS 1 BP 350 EP 360 PG 11 WC Immunology SC Immunology GA 248OF UT WOS:000252162700042 PM 18097036 ER PT J AU Marusina, AI Burgess, SJ Pathmanathan, I Borrego, F Coligan, JE AF Marusina, Alina I. Burgess, Steven J. Pathmanathan, Ishani Borrego, Francisco Coligan, John E. TI Regulation of human DAP10 gene expression in NK and T cells by Ap-1 transcription factors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATING NKG2D RECEPTOR; DOWN-REGULATION; CUTTING EDGE; TUMOR-CELLS; IN-VIVO; HUMAN CYTOMEGALOVIRUS; SIGNAL-TRANSDUCTION; INTERLEUKIN-2 GENE; PROMOTER ACTIVITY; GAMMA PROMOTER AB Human NKG2D/DAP10 is an activation receptor expressed by NK and subsets of T cells, whose ligands include MHC class I chain-related (MIC) protein A and protein B and UL16-binding proteins that are often up-regulated by stress or pathological conditions. DAP10 is required for NKG2D/DAP10 cell surface expression and signaling capacity. Little is known about the mechanisms that regulate DAP10 gene expression. We describe the existence of multiple transcriptional start sites upstream of DAP10 exon 1 and identify the location of the basic promoter upstream of these starting sites. The promoter is active in NK and CD8(+) T cells, but not in CD4(+) T cells. We demonstrate TCR-mediated up-regulation of DAP10 transcription and found that a 40 bp region within the DAP10 promoter, containing an Ap-1 binding site, is largely responsible for this increased transcription. Using pull-down and chromatin immunoprecipitation assays, we show that the DAP10 promoter interacts with Ap-1 transcription factors in primary CD8(+) T and NK cells in vitro and in vivo. Overexpression of c-jun or c-Fos in NK and T cells led to enhanced DAP10 promoter activity and DAP10 protein expression. Taken together, our data indicate that Ap-1 is an important transcription factor for regulating DAP10 gene expression in human NK and T cells, and that Ap-1 plays a key role in the transactivation of DAP10 promoter following TCR stimulation. C1 [Marusina, Alina I.; Burgess, Steven J.; Pathmanathan, Ishani; Borrego, Francisco; Coligan, John E.] NIAID, Immunogenet Lab, Receptor Cell Biol Sect, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Immunogenet Lab, Receptor Cell Biol Sect, NIH, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov FU Intramural NIH HHS NR 73 TC 16 Z9 18 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 JAN 1 PY 2008 VL 180 IS 1 BP 409 EP 417 PG 9 WC Immunology SC Immunology GA 248OF UT WOS:000252162700048 PM 18097042 ER PT J AU Pesce, JT Liu, ZG Hamed, H Alem, F Whitmire, J Lin, HX Liu, Q Urban, JF Gause, WC AF Pesce, John T. Liu, Zhugong Hamed, Hossein Alem, Farhang Whitmire, Jeanette Lin, Hongxia Liu, Qian Urban, Joseph F., Jr. Gause, William C. TI Neutrophils clear bacteria associated with parasitic nematodes augmenting the development of an effective Th2-type response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; IL-4-PRODUCING T-CELLS; DENDRITIC CELLS; IMMUNE-RESPONSE; IN-VIVO; NIPPOSTRONGYLUS-BRASILIENSIS; TH2 RESPONSE; LYMPH-NODES; INFECTION; MICE AB Infection with the parasitic nematode Nippostrongylus brasiliensis induces a potent Th2 response; however, little is known about early stages of the innate response that may contribute to protective immunity. To examine early events in this response, chemokine expression in the draining lymph node was examined after N. brasiliensis inoculation. Pronounced increases of several chemokines, including CCL2, were observed. Compared with wild-type mice, elevations in a Gr-1(bright) population in the draining lymph node was significantly decreased in CCL2(-/-) mice after N. brasiliensis inoculation. Further flow cytometric and immunofluorescent analysis showed that in wild-type mice, Gr-1(+) cells transiently entered and exited the draining lymph node shortly after N brasiliensis inoculation. The Gr-1(bright) population was comprised of neutrophils expressing TGF-beta and TNF-alpha. Following Gr-1(+) cell depletion, N. brasiliensis infection resulted in transient, but significantly increased levels of IFN-gamma, increased serum IgG2a, reduced Th2 cytokines and serum IgE, greatly increased mortality, and delayed worm expulsion. Furthermore, bacteria were readily detected in vital organs. Infection of Gr-1(+) cell-depleted mice with N. brasiliensis larvae that were pretreated with antibiotics prevented bacterial dissemination, Th1 inflammatory responses, and decreases in host survival. This study indicates that parasitic nematodes can be an important vector of potentially harmful bacteria, which is typically controlled by CCL2-dependent neutrophils that ensure the optimal development of Th2 immune responses and parasite resistance. C1 [Liu, Zhugong; Hamed, Hossein; Alem, Farhang; Lin, Hongxia; Liu, Qian; Gause, William C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07101 USA. [Pesce, John T.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Whitmire, Jeanette] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Urban, Joseph F., Jr.] USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA. RP Gause, WC (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, 185 S Orange Ave, Newark, NJ 07101 USA. EM gausewc@umdnj.edu OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [AI066188, R01 AI031678, R01 AI031678-10, R01 AI031678-11, R01 AI031678-12, AI031678, R01 AI031678-13, R01 AI031678-14, R01 AI066188, R01 AI066188-01A1, R01 AI066188-02] NR 48 TC 23 Z9 23 U1 2 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 JAN 1 PY 2008 VL 180 IS 1 BP 464 EP 474 PG 11 WC Immunology SC Immunology GA 248OF UT WOS:000252162700054 PM 18097048 ER PT J AU Palazzolo-Ballance, AM Reniere, ML Braughton, KR Sturdevant, DE Otto, M Kreiswirth, BN Skaar, EP Deleo, FR AF Palazzolo-Ballance, Amy M. Reniere, Michelle L. Braughton, Kevin R. Sturdevant, Daniel E. Otto, Michael Kreiswirth, Barry N. Skaar, Eric P. DeLeo, Frank R. TI Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID OXIDATIVE STRESS RESISTANCE; PEPTIDE-SENSING SYSTEM; GROUP-A STREPTOCOCCUS; UNITED-STATES; ANTIMICROBIAL PEPTIDES; DLT OPERON; VIRULENCE; IRON; INFECTIONS; BACTERIAL AB In recent years, there has been a dramatic increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. MW2 (pulsed-field type USA400), the prototype CA-MRSA strain, is highly virulent and has enhanced ability to evade killing by neutrophils. Although progress has been made, the molecular basis for enhanced virulence of CA-MRSA remains incompletely defined. To that end, we studied resistance of MW2 to key microbicides of human neutrophils. Hydrogen peroxide (H(2)O(2)), hypochlorous acid, and azurophilic granule proteins had significant bacteriostatic but limited staphylocidal activity toward MW2 under the conditions tested. An MW2-specific microarray revealed common changes in S. aureus gene expression following exposure to each microbicide, such as up-regulation of transcripts involved in gene regulation (e.g., saeRS and kdpDE) and stress response. Azurophilic granule proteins elicited the greatest number of changes in MW2 transcripts, including up-regulation of mRNAs encoding multiple toxins and hemolysins (e.g., hlgA, hlgB, hlgC, hla, lukS-PV, lukF-PV, sec4, and set17-26). Notably, H(2)O(2) triggered up-regulation of transcripts related to heme/iron uptake (e.g., isdA, isdB, and isdCDEFsrtBisdG), and an isogenic isdAB-negative strain of MW2 had increased susceptibility to H(2)O(2) (p < 0.001) and human neutrophils (p < 0.05) compared with the wild-type parental strain. These findings reveal a S. aureus survival response wherein Iron-regulated surface determinant (Isd) proteins are important for resistance to innate host defense. Collectively, the data provide an enhanced view of the mechanisms used by S. aureus to circumvent destruction by the innate immune system. C1 [Palazzolo-Ballance, Amy M.; Braughton, Kevin R.; Otto, Michael; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Reniere, Michelle L.; Skaar, Eric P.] Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. [Sturdevant, Daniel E.] NIAID, Res Technol Sect, Genome Unit, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Kreiswirth, Barry N.] Int Ctr Publ Hlth, TB Ctr, Publ Hlth Res Inst, Newark, NJ 07103 USA. RP Deleo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS; NHLBI NIH HHS [T32 HL07751]; NIAID NIH HHS [AI69233] NR 66 TC 85 Z9 85 U1 3 U2 14 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2008 VL 180 IS 1 BP 500 EP 509 PG 10 WC Immunology SC Immunology GA 248OF UT WOS:000252162700058 PM 18097052 ER PT J AU Ishida, Y Gao, JL Murphy, PM AF Ishida, Yuko Gao, Ji-Liang Murphy, Philip M. TI Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROXIMAL TUBULAR CELLS; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; BONE-MARROW; TGF-BETA; ESSENTIAL INVOLVEMENT; DEPENDENT MANNER; KNOCKOUT MICE; STEM-CELLS; IFN-GAMMA AB Wounds heal through a highly regulated, self-limited inflammatory response, however, precise inflammatory mediators have not been fully delineated. In this study, we report that in a mouse model of excisional skin wound healing the chemokine CX3CL1 and its receptor CX3CR1 were both highly induced at wound sites; CX3CL1 colocalized with macrophages and endothelial cells, whereas CX3CR1 colocalized mainly with macrophages and fibroblasts. Loss of CX3CR1 function delayed wound closure in both CX3CR1 knockout (KO) mice and in wild-type mice infused with anti-CX3CR1-neutralizing Ab. Conversely, transfer of bone marrow from donor wild-type mice, but not from donor CX3CR1 KO mice, restored wound healing to normal in CX3CR1 KO-recipient mice. Direct effects of CX3CR1 disruption at the wound site included marked reduction of macrophages and macrophage products, such as TGF-beta 1 and vascular endothelial growth factor. Consistent with this, we observed reduced a-smooth muscle actin (a marker for myofibroblasts) and collagen deposition in skin from wounded CX3CR1 KO mice, as well as reduced neovascularization. Together, the data support a molecular model of skin wound repair in which CX3CR1 mediates direct recruitment of bone marrow-derived monocytes/macrophages which release profibrotic and angiogenic mediators. C1 [Ishida, Yuko; Gao, Ji-Liang; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov FU Intramural NIH HHS NR 68 TC 127 Z9 132 U1 1 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 JAN 1 PY 2008 VL 180 IS 1 BP 569 EP 579 PG 11 WC Immunology SC Immunology GA 248OF UT WOS:000252162700065 PM 18097059 ER PT J AU Abad, JD Wrzensinski, C Overwijk, W De Witte, MA Jorritsma, A Hsu, C Gattinoni, L Cohen, CJ Paulos, CM Palmer, DC Haanen, JBAG Schumacher, TNM Rosenberg, SA Restifo, NP Morgan, RA AF Abad, John D. Wrzensinski, Claudia Overwijk, Willem De Witte, Moniek A. Jorritsma, Annelies Hsu, Cary Gattinoni, Luca Cohen, Cyrille J. Paulos, Chrystal M. Palmer, Douglas C. Haanen, John B. A. G. Schumacher, Ton N. M. Rosenberg, Steven A. Restifo, Nicholas P. Morgan, Richard A. TI T-cell receptor gene therapy of established tumors in a murine melanoma model SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE murine; gene therapy; T-cell receptor; gp100 tumor antigen ID ENHANCED ANTITUMOR-ACTIVITY; HEMATOPOIETIC STEM-CELLS; HUMAN-LYMPHOCYTES; DIRECTED EVOLUTION; CANCER REGRESSION; PHAGE DISPLAY; TCR; ANTIGEN; EXPRESSION; AUTOIMMUNITY AB Adoptive cell transfer therapy using tumor-infiltrating lymphocytes for patients with metastatic melanoma has demonstrated significant objective response rates. One major limitation of these current therapies is the frequent inability to isolate tumor-reactive lymphocytes for treatment. Genetic engineering of peripheral blood lymphocytes with retroviral vectors encoding tumor an tigen-specific T-cell receptors (TCRs) bypasses this restriction. To evaluate the efficacy of TCR gene therapy, a murine treatment model was developed. A retroviral vector was constructed encoding the pmel-1 TCR genes targeting the B16 melanoma antigen, gp100. Transduction of C57BL/6 lymphocytes resulted in efficient pmel-1 TCR expression. Lymphocytes transduced with this retrovirus specifically recognized gp 100-pulsed target cells as measured by interferon-gamma secretion assays. Upon transfer into B16 tumor-bearing mice, the genetically engineered lymphocytes significantly slowed tumor development. The effectiveness of tumor treatment was directly correlated with the number of TCR-engineered T cells administered. These results demonstrated that TCR gene therapy targeting a native tumor antigen significantly delayed the growth of established tumors. When C57BL/6 lymphocytes were added to antigen-reactive pmel-1 T cells, a reduction in the ability of pmel-1 T cell to treat B16 melanomas was seen, suggesting that untransduced cells may be deleterious to TCR gene therapy. This model may be a powerful tool for evaluating future TCR gene transfer-based strategies. C1 [Abad, John D.; Wrzensinski, Claudia; Hsu, Cary; Gattinoni, Luca; Cohen, Cyrille J.; Paulos, Chrystal M.; Palmer, Douglas C.; Rosenberg, Steven A.; Restifo, Nicholas P.] NIH, NCI, Ctr Canc Res, Surg Branch,CRC, Bethesda, MD 20892 USA. [Overwijk, Willem; De Witte, Moniek A.; Jorritsma, Annelies; Haanen, John B. A. G.; Schumacher, Ton N. M.] Netherlands Canc Inst, Amsterdam, Netherlands. RP Morgan, RA (reprint author), NIH, NCI, Ctr Canc Res, Surg Branch,CRC, Rm 3W-3-3864,10 Ctr Dr, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov RI Gattinoni, Luca/A-2281-2008; Wrzesinski, Claudia/A-3077-2008; Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 31 TC 42 Z9 44 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 2008 VL 31 IS 1 BP 1 EP 6 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 245NP UT WOS:000251942400001 PM 18157006 ER PT J AU Sheets, RL Stein, J Bailer, RT Koup, RA Andrews, C Nason, M He, B Koo, E Trotter, H Duffy, C Manetz, TS Gomez, P AF Sheets, Rebecca L. Stein, Judith Bailer, Robert T. Koup, Richard A. Andrews, Charla Nason, Martha He, Bin Koo, Edward Trotter, Holly Duffy, Chris Manetz, T. Scott Gomez, Phillip TI Biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (HIV-1), ebola, or marburg are similar despite differing adenovirus serotype vector, manufacturer's construct, or gene inserts SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Article DE adenovirus vector; adenovirus type 5; adenovirus type 35; HIV-1; Ebola; Marburg; biodistribution; repeated dose toxicology; safety; vaccine ID ACUTE-RESPIRATORY-SYNDROME; DNA PLASMID VACCINES; WEST-NILE-VIRUS; IMMUNOGENICITY EVALUATION; CANDIDATE VACCINE; PHASE-1 SAFETY; IN-VIVO; DEFICIENCY; BACKBONES; INFECTION AB The Vaccine Research Center has developed vaccine candidates for different diseases/infectious agents (including HIV-1, Ebola, and Marburg viruses) built on an adenovirus vector platform, based on adenovirus type 5 or 35. To support clinical development of each vaccine candidate, pre-clinical studies were performed in rabbits to determine where in the body they biodistribute and how rapidly they clear, and to screen for potential toxicities (intrinsic and immunotoxicities). The vaccines biodistribute only to spleen, liver (Ad5 only), and/or iliac lymph node (Ad35 only) and otherwise remain in the site of injection muscle and overlying subcutis. Though similar to 10(11) viral particles were inoculated, already by Day 9, all but 10(3) to 10(5) genome copies per mu g of DNA had cleared from the injection site muscle. By three months, the adenovector was cleared with, at most, a few animals retaining a small number of copies in the injection site, spleen (Ad5), or iliac lymph node (Ad35). This pattern of limited biodistribution and extensive clearance is consistent regardless of differences in adenovector type (Ad5 or 35), manufacturer's construct and production methods, or gene-insert. Repeated dose toxicology studies identified treatment-related toxicities confined primarily to the sites of injection, in certain clinical pathology parameters, and in body temperatures (Ad5 vectors) and food consumption immediately post-inoculation. Systemic reactogenicity and reactogenicity at the sites of injection demonstrated reversibility. These data demonstrate the safety and suitability for investigational human use of Ad5 or Ad35 adenovector-based vaccine candidates at doses of up to 2 x 10(11) given intramuscularly to prevent various infectious diseases. C1 [Sheets, Rebecca L.; Stein, Judith; Bailer, Robert T.; Koup, Richard A.; Andrews, Charla] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Nason, Martha] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. [He, Bin; Koo, Edward] Bridge Labs, Gaithersburg, MD USA. [Trotter, Holly; Duffy, Chris] Althea Technol Inc, San Diego, CA USA. [Manetz, T. Scott] MedImmune Inc, Gaithersburg, MD USA. [Gomez, Phillip] PRTM, Washington, DC USA. RP Sheets, RL (reprint author), NIAID, NIH, US Publ Hlth Serv, Room 5145,6700B Rockledge Dr,MSC-7628, Bethesda, MD 20892 USA. EM rsheets@niaid.nih.gov FU National Institutes of Health; Vaccine Research Center; NIAID FX This research was supported by the Intramural Research Program of the National Institutes of Health, Vaccine Research Center, NIAID. The Authors would like to acknowledge the staff of Bridge Laboratories for the conduct of the biodistribution and toxicology studies and the staff of Althea Technologies, Inc. for the conduct of the biodistribution analyses and providing the clinical grade vaccine candidate tested in one safety study. Further, acknowledgement should be given to the staff of Crucell (Maria Grazia-Pau, Marcel Brink, Isabella Versteege, Jaap Goudsmit) and the staff of GenVec (Bryan Butman, Jason Gall, Douglas Brough, Victoria Haque, Perry Newton, Mike Sowers, and Alena Lizonova) for providing the clinical grade vaccine candidates tested in these safety studies. Finally, we thank Jason Gall, Bryan Butman, and Maria Grazia-Pau for their critical review of the manuscript. NR 20 TC 21 Z9 23 U1 0 U2 4 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PY 2008 VL 5 IS 3 BP 315 EP 335 DI 10.1080/15376510802312464 PG 21 WC Toxicology SC Toxicology GA 355FU UT WOS:000259695600007 PM 18830892 ER PT J AU Petri, WA Kirkpatrick, BD Haque, R Duggal, P AF Petri, William A., Jr. Kirkpatrick, Beth D. Haque, Rashidul Duggal, Priya TI Genes influencing susceptibility to infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; ASCARIS-LUMBRICOIDES; DISEASES; LOCI; PREDISPOSITION; LOCALIZATION; EXPRESSION; LEPROSY C1 [Petri, William A., Jr.] Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. [Kirkpatrick, Beth D.] Univ Vermont, Burlington, VT 05405 USA. [Haque, Rashidul] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Duggal, Priya] NHGRI, Baltimore, MD USA. RP Petri, WA (reprint author), Univ Virginia, Div Infect Dis & Int Hlth, POB 801340, Charlottesville, VA 22908 USA. EM wap3g@virginia.edu FU NIAID NIH HHS [AI 43596, R01 AI043596] NR 23 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2008 VL 197 IS 1 BP 4 EP 6 DI 10.1086/524118 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TV UT WOS:000252399000002 PM 18171277 ER PT J AU Mitre, E Chien, D Nutman, TB AF Mitre, Edward Chien, Daniel Nutman, Thomas B. TI CD4(+) (and not CD25(+)) T cells are the predominant interleukin-10-producing cells in the circulation of filaria-infected patients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; PARASITE-SPECIFIC ANERGY; CYTOKINE PRODUCTION; PERIPHERAL-BLOOD; INTERFERON-GAMMA; IMMUNE-RESPONSES; IN-VIVO; IL-10; HYPORESPONSIVENESS; CLONES AB Background. Interleukin (IL)-10 plays an important role in down-regulating the immune response to filarial parasites. The goal of this study was to characterize the predominant cellular source of IL-10 in human filarial infections. Methods. Multicolor flow cytometry was used to determine the frequencies of IL-10 production from various lymphocyte populations in the circulation of 23 patients with filarial infections and 8 uninfected control subjects. Results. The frequencies of cells spontaneously producing IL-10 was significantly greater in filaria-infected patients than in uninfected control subjects (geometric mean, 93 vs. 18 IL-10-producing cells/100,000 peripheral blood mononuclear cells; P = .03). Most IL-10-producing cells in filaria-infected patients were T cells, with CD4(+) and CD8(+) cells accounting for 48% and 27%, respectively, of all IL-10-producing cells; CD19(+) B cells, CD14(+) monocytes, and CD56(+) NK cells accounted for 10%, 8%, and 7%, respectively. Surprisingly, only 12% of the IL-10-producing CD3(+) CD4(+) cells were CD25(+). Seventy-seven percent of IL-10-producing CD4(+) T cells stained negatively for both IL-4 and interferon (IFN)-gamma, 22% were positive for IL-4, and <1% were positive for IFN-gamma. Conclusions. These experiments demonstrate that the most frequent producers of IL-10 in human filarial infections are CD4(+) T cells, many of which are skewed toward a type 2 phenotype and most of which are not CD25(+). C1 [Mitre, Edward; Chien, Daniel; Nutman, Thomas B.] NIAID, Natl Inst Hlth, Parasit Dis Lab, Bethesda, MD USA. RP Mitre, E (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, B4104,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM emitre@usuhs.mil FU Intramural NIH HHS NR 39 TC 29 Z9 30 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2008 VL 197 IS 1 BP 94 EP 101 DI 10.1086/524301 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TV UT WOS:000252399000016 PM 18171291 ER PT J AU Twigg, HL Weiden, M Valentine, F Schnizlein-Bick, CT Bassett, R Zheng, L Wheat, J Day, RB Rominger, H Collman, RG Fox, L Brizz, B Dragavon, J Coombs, RW Bucy, RP AF Twigg, Homer L., III Weiden, Michael Valentine, Fred Schnizlein-Bick, Carol T. Bassett, Roland Zheng, Lu Wheat, Joseph Day, Richard B. Rominger, Helen Collman, Ronald G. Fox, Lawrence Brizz, Barbara Dragavon, Joan Coombs, Robert W. Bucy, R. Pat CA Aids Clinical Trials Grp Protocol TI Effect of highly active antiretroviral therapy on viral burden in the lungs of HIV-infected subjects SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 101st International Conference of the American-Thoracic-Society CY MAY 20-25, 2005 CL San Diego, CA SP Amer Thorac Soc, Fogarty AIDS Int Training & Res Program ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTIC ALVEOLITIS; IMMUNE RESTORATION; COMBINATION THERAPY; COMPLICATIONS; REPLICATION; SUPPRESSION; STABILITY; EMPHYSEMA AB Background. Human immunodeficiency virus (HIV) is readily detectable in the lungs of infected subjects and leads to an accumulation of CD8(+) lymphocytes in the alveolar space. Although highly active antiretroviral therapy (HAART) is effective in reducing viremia, less is known about its effect on tissue compartments. The AIDS Clinical Trials Group Protocol 723 Team evaluated the effect of HAART on lung viral load and cellular constituents. Methods. Bronchoalveolar lavage (BAL) fluid and blood were collected before initiation of HAART and again at 4 and 24 weeks after initiation of therapy. The BAL cell differential was determined, lymphocyte phenotyping was performed, and acellular BAL fluid, plasma HIV RNA load, and BAL cell and peripheral blood mononuclear cell HIV RNA and DNA loads were measured. Results. HAART induced a rapid decrease in HIV that was detectable in acellular BAL fluid and a slower decrease in the HIV RNA and DNA loads in BAL cells. HAART was associated with a significant decrease in the absolute number and percentage of CD8(+) alveolar lymphocytes. There was a significant correlation between residual BAL cell DNA at 24 weeks and the absolute number of CD4(+) lymphocytes in the alveolar space. Conclusion. HAART is associated with a significant decrease in the pulmonary HIV burden and a return of alveolar cellular constituents to normal. C1 [Twigg, Homer L., III; Schnizlein-Bick, Carol T.; Wheat, Joseph; Day, Richard B.; Rominger, Helen] Indiana Univ, Med Ctr, Richard Roudebush VA Med Ctr, Div Pulm & Crit Care, Indianapolis, IN 46202 USA. [Twigg, Homer L., III; Schnizlein-Bick, Carol T.; Wheat, Joseph; Day, Richard B.; Rominger, Helen] Indiana Univ, Med Ctr, AIDS Clin Trials Unit, Indianapolis, IN 46202 USA. [Weiden, Michael; Valentine, Fred] NYU, Med Ctr, Div Pulm Med, New York, NY 10016 USA. [Weiden, Michael; Valentine, Fred] NYU, Med Ctr, Div Infect Dis, New York, NY 10016 USA. [Bassett, Roland; Zheng, Lu] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Collman, Ronald G.] Univ Penn, Med Ctr, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Fox, Lawrence] NIAID, HIV Res Ctr, Washington, DC USA. [Brizz, Barbara] Social & Sci Syst, Silver Spring, MD USA. [Dragavon, Joan; Coombs, Robert W.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Bucy, R. Pat] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Twigg, HL (reprint author), Indiana Univ, Med Ctr, Richard Roudebush VA Med Ctr, Div Pulm & Crit Care, 1481 W 10th St,VA 111P-IU, Indianapolis, IN 46202 USA. EM htwig@iupui.edu OI Valentine, Fred/0000-0002-6046-5913 FU NCRR NIH HHS [MO1 RR00096, MO1 RR750, P20 RR11126]; NHLBI NIH HHS [R01 HL59834, HL057879]; NIAID NIH HHS [AI 25859, AI 27664, AI 27665, AI 32775, AI 34832, AI 38855, AI 38858] NR 31 TC 17 Z9 18 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2008 VL 197 IS 1 BP 109 EP 116 DI 10.1086/523766 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TV UT WOS:000252399000018 PM 18171293 ER PT J AU Hunt, PW Brenchley, J Sinclair, E McCune, JM Roland, M Page-Shafer, K Hsue, P Emu, B Krone, M Lampiris, H Douek, D Martin, JN Deeks, SG AF Hunt, Peter W. Brenchley, Jason Sinclair, Elizabeth McCune, Joseph M. Roland, Michelle Page-Shafer, Kimberly Hsue, Priscilla Emu, Brinda Krone, Melissa Lampiris, Harry Douek, Daniel Martin, Jeffrey N. Deeks, Steven G. TI Relationship between T cell activation and CD4(+) T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Keystone Symposium on HIV Pathogenesis CY MAR 25-30, 2007 CL Whistler, CANADA ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL LOAD; IMMUNE ACTIVATION; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; GASTROINTESTINAL-TRACT; LYMPHOCYTE ACTIVATION; INFECTED PATIENTS; PREDICTIVE-VALUE; DENDRITIC CELLS AB Background. Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency. Methods. We compared percentages of activated (CD38(+) HLA-DR+) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels. Results. Although the median CD4(+) cell count in controllers was 727 cells/mm(3), 3 (10%) had CD4(+) cell counts < 350 cells/mm(3) and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4(+) and CD8(+) cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8(+) cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4(+) and CD8(+) T cell activation was associated with lower CD4(+) cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P = .001), and in controllers higher LPS level was associated with higher CD8(+) T cell activation (P = .039). Conclusion. HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia. C1 [Hunt, Peter W.; McCune, Joseph M.; Roland, Michelle; Emu, Brinda; Deeks, Steven G.] San Francisco Gen Hosp, Positive Hlth Program, San Francisco, CA 94110 USA. [Hsue, Priscilla] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Sinclair, Elizabeth; McCune, Joseph M.] Univ Calif San Francisco, Div Expt Med, Dept Med, San Francisco, CA 94143 USA. [Krone, Melissa; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Lampiris, Harry] Univ Calif San Francisco, Med Ctr, San Francisco Vet Adm, San Francisco, CA 94143 USA. [Brenchley, Jason; Douek, Daniel] NIAID, Natl Inst Hlth, Vaccine Res Ctr, Human Immunol Sect, Bethesda, MD 20892 USA. RP Hunt, PW (reprint author), San Francisco Gen Hosp, Positive Hlth Program, Bldg 80,Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA. EM phunt@php.ucsf.edu OI Page, Kimberly/0000-0002-7120-1673 FU NCRR NIH HHS [5-MO1-RR00083-37, M01 RR000083]; NIAID NIH HHS [K23 AI065244, K23 AI65244, P30 AI027763, P30 AI27763, R01 AI 52745, R01 AI052745, R37 AI040312, R37 AI40312]; NIH HHS [DP1 OD000329, DPI OD00329]; NIMH NIH HHS [P30 MH062246, P30 MH59037, P30 MH62246]; NINDS NIH HHS [NS 37660, R01 NS037660] NR 49 TC 366 Z9 371 U1 1 U2 11 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 JAN 1 PY 2008 VL 197 IS 1 BP 126 EP 133 DI 10.1086/524143 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TV UT WOS:000252399000020 PM 18171295 ER PT J AU Hope, WW Mickiene, D Petraitis, V Petraitiene, R Kelaher, AM Hughes, JE Cotton, MP Bacher, J Keirns, JJ Buell, D Heresi, G Benjamin, DK Groll, AH Drusano, GL Walsh, TJ AF Hope, William W. Mickiene, Diana Petraitis, Vidmantas Petraitiene, Ruta Kelaher, Amy M. Hughes, Joanna E. Cotton, Margaret P. Bacher, John Keirns, James J. Buell, Donald Heresi, Gloria Benjamin, Daniel K., Jr. Groll, Andreas H. Drusano, George L. Walsh, Thomas J. TI The pharmacokinetics and pharmacodynamics of micafungin in experimental hematogenous Candida meningoencephalitis: Implications for echinocandin therapy in neonates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 46th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 27-30, 2006 CL San Francisco, CA ID CENTRAL-NERVOUS-SYSTEM; BIRTH-WEIGHT INFANTS; AMPHOTERICIN-B; CEREBROSPINAL-FLUID; ALBICANS INFECTION; CASPOFUNGIN; RABBITS; PENETRATION; MENINGITIS; ASPERGILLOSIS AB Background. Hematogenous Candida meningoencephalitis (HCME) is a relatively frequent manifestation of disseminated candidiasis in neonates and is associated with significant mortality and neurodevelopmental abnormalities. The outcome after antifungal therapy is often suboptimal, with few therapeutic options. Limited clinical data suggest that echinocandins may have role to play in the treatment of HCME. Methods. We studied the pharmacokinetics and pharmacodynamics of micafungin in a rabbit model of neonatal HCME and bridged the results to neonates by use of population pharmacokinetics and Monte Carlo simulation. Results. Micafungin exhibited linear plasma pharmacokinetics in the range of 0.25-16 mg/kg. Micafungin penetrated most compartments of the central nervous system (CNS), but only with doses > 2 mg/kg. Micafungin was not reliably found in cerebrospinal fluid. With few exceptions, drug penetration into the various CNS subcompartments was not statistically different between infected and noninfected rabbits. A dose-microbiological response relationship was apparent in the brain, and near-maximal effect was apparent with doses of similar to 8 mg/kg. Monte Carlo simulations revealed that near-maximal antifungal effect was attained at human neonatal doses of 12-15 mg/kg. Conclusions. These results provide a foundation for clinical trials of micafungin in neonates with HCME and a model for antimicrobial bridging studies from bench to bedside in pediatric patients. C1 [Hope, William W.; Mickiene, Diana; Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M.; Hughes, Joanna E.; Cotton, Margaret P.; Groll, Andreas H.; Walsh, Thomas J.] NCI, Natl Inst Hlth, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Bacher, John] NIH, Vet Resources Program, Off Res Serv, Bethesda, MD USA. [Mickiene, Diana; Petraitis, Vidmantas; Petraitiene, Ruta] Sci Applicat Int Corp Frederick Inc, Frederick, MD USA. [Hope, William W.; Drusano, George L.] Ordway Res Inst, Emerging Infect Dis Unit, Albany, NY USA. [Keirns, James J.; Buell, Donald] Astellas Pharma US Inc, Deerfield, IL USA. [Heresi, Gloria] Univ Texas, Sch Med, Houston, TX USA. [Benjamin, Daniel K., Jr.] Duke Univ, Dept Pediat, Duke Clin Res Inst, Durham, NC 27706 USA. [Groll, Andreas H.] Childrens Univ Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. [Groll, Andreas H.] Childrens Univ Hosp, Dept Pediat Hematol Oncol, Munster, Germany. RP Walsh, TJ (reprint author), NCI, Natl Inst Hlth, Immunocompromised Host Sect, Pediat Oncol Branch, CRC,Rm 1-5750, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov OI Hope, William/0000-0001-6187-878X FU Intramural NIH HHS; NICHD NIH HHS [5U10 HD045962-04, HD044799-02, K23 HD044799, K23 HD044799-02, U10 HD045962] NR 30 TC 91 Z9 92 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2008 VL 197 IS 1 BP 163 EP 171 DI 10.1086/524063 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TV UT WOS:000252399000025 PM 18171300 ER PT J AU Childers, ML Cho, JH Regino, CAS Brechbiel, MW DiPasquale, AG Rheingold, AL Torti, SV Torti, FM Planalp, RP AF Childers, Matt L. Cho, Joonhyung Regino, Celeste A. S. Brechbiel, Martin W. DiPasquale, Antonio G. Rheingold, Arnold L. Torti, Suzy V. Torti, Frank M. Planalp, Roy P. TI Influence of ligand structure on Fe(II) spin-state and redox rate in cytotoxic tripodal chelators SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE redox reaction; antitumor agent; ligand design; tripodal chelator; Fe(II) ID OXIDATIVE DEHYDROGENATION; IRON(II) COMPLEXES; METAL CHELATOR; ALPHA-CARBON; CU-II; FE-II; RUTHENIUM; AMINES; AGENTS; TACHPYRIDINE AB The Fe coordination chemistry of several tripodal aminopyridyl hexadentate chelators is reported along with cytotoxicity toward cultured Hela cells. The chelators are based on cis, cis- 1,3,5-triaminocyclohexane (tach) with three pendant -CH2-2-pyridyl groups where 2-pyridyl is R-substituted thus are named tach-x-Rpyr where x = 3, R = Me; x = 3, R = MeO; x = 6; R = Me. The structures of [Fe(tach-3-Mepyr)]Cl-2 and [Fe(tach-3-MeOpyr)](FeCl4) are reported and their metric parameters indicate strongly bound, low-spin Fe(II). The structure of [Fe(tach-6-Mepyr)](ClO4)(2) implies steric effects of 6-Me groups push donor N-py's away so one Fe-N-py bond is substantially longer at 2.380(3) angstrom vs. 2.228(3) A for the others, and Fe(II) in the high-spin-state. Accordingly, anions X- = Cl or SCN afford [Fe(tach-6-Mepyr)(X)](+) from [Fe(tach-6-Mepyr)](2+) (UV-viS spectroscopy). Consistent with a biological cytotoxicity involving Fe chelation, chelators of low-spin Fe(II) have greater toxicity in the order [IC50(72 h) is in parentheses then the spin-state SS = H (high) or L (low)]: tachpyr = tach-3-Mepyr (6 mu M, SS = L) greater than or similar to tach-3-MeOpyr (12 mu M, SS = L) >> tach-6-Mepyr (> 200 mu M, SS = H). Iron-mediated oxidative dehydrogenation with 02 oxidant removes hydrogens from coordinated nitrogen and the adjacent CH2, converting aqueous [Fe(tach-3-Rpyr)](2+) (R = H, Me and MeO) into a mix of low-spin imino- and aminopyridyl-armed complexes, but [Fe(tach-6-Mepyr)]2+ does not react (NMR and EST-MS spectroscopies). The difference Of IC50 for chelators at different time points (Delta IC50 = [IC50(24 h) - IC50(72 h)]) is used to compare rate of cytotoxic action to qualitative rate of oxidation in the Fe-bound chelator, giving the order, from rapid to slow oxidation and cell killing of: [Fe(tach-3-Mepyr)](2+) (Delta IC50 = 5 mu M) > [Fe(tachpyr)](2+) (Delta IC50 = 16 mu M) > [Fe(tach-3-MeOpyr)](2+) (Delta IC50 = 118 mu M). Thus, those chelators whose Fe(II) complexes undergo rapid oxidation kill cells faster, and those that bind Fe(II) as low-spin are far more cytotoxic. (c) 2007 Elsevier Inc. All rights reserved. C1 [Childers, Matt L.; Cho, Joonhyung; Planalp, Roy P.] Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. [Regino, Celeste A. S.; Brechbiel, Martin W.] NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. [DiPasquale, Antonio G.; Rheingold, Arnold L.] Univ Calif San Diego, Dept Chem, La Jolla, CA 92093 USA. [Torti, Suzy V.; Torti, Frank M.] Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 USA. [Torti, Suzy V.; Torti, Frank M.] Wake Forest Univ Hlth Sci, Dept Canc Biol, Winston Salem, NC 27157 USA. [Torti, Suzy V.; Torti, Frank M.] Wake Forest Univ Hlth Sci, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. RP Planalp, RP (reprint author), Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. EM Roy.planalp@unh.edu FU Intramural NIH HHS; NIDDK NIH HHS [DK-57781-R01, R01 DK057781-04, R01 DK057781] NR 34 TC 4 Z9 4 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD JAN PY 2008 VL 102 IS 1 BP 150 EP 156 DI 10.1016/j.jinorgbio.2007.07.039 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 253MV UT WOS:000252523200016 PM 17900698 ER PT J AU Ludlow, LE Purton, LE Klarmann, K Gough, DJ Hii, LL Trapani, JA Keller, JR Clarke, CJP Johnstone, RW AF Ludlow, Louise E. Purton, Louise E. Klarmann, Kim Gough, Daniel J. Hii, Linda L. Trapani, Joseph A. Keller, Jonathan R. Clarke, Christopher J. P. Johnstone, Ricky W. TI The role of p202 in regulating hematopoietic cell proliferation and differentiation SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID INTERFERON-INDUCIBLE GENE; BONE-MARROW-CELLS; MYOBLAST DIFFERENTIATION; MONOCYTE PROGENITORS; 200 CLUSTER; EXPRESSION; PROTEIN; FAMILY; MEMBER; MYOD AB HIN-200 proteins are interferon (IFN)-inducible proteins that can regulate cell proliferation and differentiation in vitro. Characterization of the lineage and cell type-dependent expression of Ifi202 revealed little or no expression of Ifi202 in the Lin(-)/c-Kit(+) fraction enriched for immature hematopoietic progenitor cells (HPCs) but higher levels in more differentiated Lin(-)/c-Kit(-) and Lin(+) populations. The highest levels of Ifi202 expression were observed in CD11b(+)/Gr-1(dim) immature granulocytes in the bone marrow. In the peripheral blood, Ifi202 was expressed only in the myeloid lineage, with the highest level of expression seen in CD11b(+)/Gr-1(dim) immature granulocytes. Constitutive expression of p202 in primary HPCs delayed proliferation of these cells in vitro, caused a reduction in the number and size of myeloid colonies growing on methylcellulose, and affected the ability of the cells to reconstitute irradiated mice but did not significantly affect cell differentiation. Thus, p202 plays a role in regulating the proliferative capacity of hematopoietic cells. C1 [Ludlow, Louise E.; Gough, Daniel J.; Hii, Linda L.; Trapani, Joseph A.; Clarke, Christopher J. P.; Johnstone, Ricky W.] Peter MacCallum Canc Ctr, Gene Regulat Lab, Melbourne, Vic 3002, Australia. [Ludlow, Louise E.; Gough, Daniel J.; Hii, Linda L.; Trapani, Joseph A.; Clarke, Christopher J. P.; Johnstone, Ricky W.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Ludlow, Louise E.] Evanston NW Hlthcare, Dept Med, Evanston, IL 60208 USA. [Purton, Louise E.] Peter MacCallum Canc Ctr, Stem Cell Lab, Melbourne, Vic 3002, Australia. [Klarmann, Kim; Keller, Jonathan R.] NCI, Ctr Canc Res, SAIC Inc, Basic Res Program, Frederick, MD 21702 USA. RP Johnstone, RW (reprint author), Peter MacCallum Canc Ctr, Gene Regulat Lab, Melbourne, Vic 3002, Australia. EM ricky.johnstone@petermac.org OI Gough, Daniel/0000-0001-6479-1735 FU NCI NIH HHS [N01-CO-12400] NR 29 TC 7 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 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JAN PY 2008 VL 28 IS 1 BP 5 EP 11 DI 10.1089/jir.2007.0070 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 258KD UT WOS:000252865900002 PM 18370867 ER PT J AU Singh, UP Singh, S Singh, R Cong, YZ Taub, DD Lillard, JW AF Singh, Udai P. Singh, Shailesh Singh, Rajesh Cong, Yingzi Taub, Dennis D. Lillard, James W., Jr. TI CXCL10-producing mucosal CD4(+) T cells, NK cells, and NKT cells are associated with chronic colitis in IL-10(-/-) mice, which can be abrogated by anti-CXCL10 antibody inhibition SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; LYMPHOCYTE-ACTIVATION GENE-3; DENDRITIC CELLS; IMMUNE-RESPONSES; EPITHELIAL-CELLS; INTERLEUKIN-10-DEFICIENT MICE; CHEMOKINE RECEPTORS; ADAPTIVE IMMUNITY; CXC CHEMOKINES; EXPRESSION AB We have shown previously that there is a temporal increase in the levels of CXCL10 and CXCR3 mRNA during spontaneous murine colitis. We now show that CXCL10 is significantly expressed by mucosal CD4(+) T cells, natural killer (NK) cells, and NKT cells, but not by dendritic cells (DCs), during chronic murine colitis. CXCL10 blockade alleviated chronic colitis and attenuated the associated increase in serum amyloid A (SAA), interleukin-12 (IL-12) p40, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1 alpha, and IL-1 beta levels as well as in the number of CD4(+) T, NKT, and NK cells that express CXCL10 and CXCR3, compared with groups treated with control antibody (Ab). After CXCL10 blockade, the number of CXCR3(+) DCs in the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) were increased to levels found before the onset of colitis. In contrast, the numbers of splenic and intestinal lamina propria (LP) CXCR3+ DCs were reduced after anti-CXCL10 Ab treatment, compared with controls. Ex vivo antigen and CXCL10 stimulation of mucosal cells caused an increase in MHC class II, CD40, and CD86 as well as a decrease in CD30 ligand (CD30L) expression by DCs. This study provides insights into CXCL10 expression during inflammatory bowel disease (IBD) and the cellular and molecular mechanisms of CXCL10-mediated colitis. Our data also support the premise that CXCL10 blockade can attenuate chronic colitis by preventing the activation and recruitment of CXCR3(+) leukocytes during IBD. C1 [Singh, Shailesh; Singh, Rajesh; Lillard, James W., Jr.] Univ Louisville, James Graham Brown Canc Ctr, Dept Microbiol & Immunol, Louisville, KY 40202 USA. [Singh, Udai P.; Lillard, James W., Jr.] Morehouse Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30310 USA. [Cong, Yingzi] Univ Alabama, Dept Med, Div Gastroenterol, Birmingham, AL 35294 USA. [Taub, Dennis D.] NIA, Immunol Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. RP Lillard, JW (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Dept Microbiol & Immunol, 580 S Preston St,Bauxter 2, Room 304C, Louisville, KY 40202 USA. EM james.lillard@louisville.edu FU Intramural NIH HHS [Z01 AG000758-10]; NCRR NIH HHS [G12 RR003034, RR03034]; NIAID NIH HHS [AI57808, R01 AI057808]; NIGMS NIH HHS [S06 GM008248, GM08248]; NIMHD NIH HHS [MD000525, P60 MD000525] NR 37 TC 30 Z9 30 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JAN PY 2008 VL 28 IS 1 BP 31 EP 43 DI 10.1089/jir.2007.0059 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 258KD UT WOS:000252865900005 PM 18370870 ER PT J AU Watabe, H Valencia, JC Le Pape, E Yamaguchi, Y Nakamura, M Rouzaud, F Hoashi, T Kawa, Y Mizoguchi, M Hearing, VJ AF Watabe, Hidenori Valencia, Julio C. Le Pape, Elodie Yamaguchi, Yuji Nakamura, Masayuki Rouzaud, Francois Hoashi, Toshihiko Kawa, Yoko Mizoguchi, Masako Hearing, Vincent J. TI Involvement of dynein and spectrin with early melanosome transport and melanosomal protein trafficking SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID AGOUTI SIGNALING PROTEIN; OCULOCUTANEOUS ALBINISM TYPE-1; NORMAL HUMAN MELANOCYTES; ENDOPLASMIC-RETICULUM; MOLECULAR MOTORS; IN-VITRO; MAMMALIAN TYROSINASE; CYTOPLASMIC DYNEIN; MELANIN FORMATION; ACTIN-FILAMENTS AB Melanosomes are unique membrane-bound organelles specialized for the synthesis and distribution of melanin. Mechanisms involved in the trafficking of proteins to melanosomes and in the transport of mature pigmented melanosomes to the dendrites of melanocytic cells are being characterized, but details about those processes during early stages of melanosome maturation are not well understood. Early melanosomes must remain in the perinuclear area until critical components are assembled. In this study, we characterized the processing of two distinct melanosomal proteins, tyrosinase (TYR) and Pmel17, to elucidate protein processing in early or late steps of the secretory pathway, respectively, and to determine mechanisms underlying the subcellular localization and transport of early melanosomes. We used immunological, biochemical, and molecular approaches to demonstrate that the movement of early melanosomes in the perinuclear area depends primarily on microtubules but not on actin filaments. In contrast, the trafficking of TYR and Pmel17 depends on cytoplasmic dynein and its interaction with the spectrin/ankyrin system, which is involved with the sorting of cargo from the plasma membrane. These results provide important clues toward understanding the processes involved with early events in melanosome formation and transport. C1 [Watabe, Hidenori; Valencia, Julio C.; Le Pape, Elodie; Yamaguchi, Yuji; Rouzaud, Francois; Hoashi, Toshihiko; Hearing, Vincent J.] Natl Canc Inst, NIH, Cell Biol Lab, Bethesda, MD USA. [Watabe, Hidenori; Nakamura, Masayuki; Kawa, Yoko; Mizoguchi, Masako] St Marianna Univ, Sch Med, Dept Dermatol, Kawasaki, Kanagawa, Japan. RP Hearing, VJ (reprint author), NIH, Cell Biol Lab, Bldg 37,Rm 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 FU Intramural NIH HHS [Z01 BC009100-21] NR 62 TC 24 Z9 25 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2008 VL 128 IS 1 BP 162 EP 174 DI 10.1038/sj.jid.5701019 PG 13 WC Dermatology SC Dermatology GA 240UL UT WOS:000251613600021 PM 17687388 ER PT J AU Zhao, JL Oberst, M Kelly, K AF Zhao, J. L. Oberst, M. Kelly, K. TI Role of Ral GTPases in Ras-mediated cancer metatstasis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 30-FEB 02, 2008 CL Carmel, CA SP Amer Federat Med Res C1 Univ Calif Los Angeles, Los Angeles, CA USA. [Zhao, J. L.; Oberst, M.; Kelly, K.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2008 VL 56 IS 1 MA 15 BP 107 EP 108 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 257IV UT WOS:000252793300025 ER PT J AU Mahabadi, V Wang, C Amory, J Page, S Christensen, PD Sitruk-Ware, R Kumar, N Tsong, YY Blithe, D Bremner, WJ Swerdloff, RS AF Mahabadi, V. Wang, C. Amory, J. Page, S. Christensen, P. D. Sitruk-Ware, R. Kumar, N. Tsong, Y. Y. Blithe, D. Bremner, W. J. Swerdloff, R. S. TI Combined transdermal nestorone and testosterone gels suppress gonadotropins in healthy men SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 30-FEB 02, 2008 CL Carmel, CA SP Amer Federat Med Res C1 [Mahabadi, V.; Wang, C.; Christensen, P. D.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Amory, J.; Page, S.; Bremner, W. J.] Univ Washington, Seattle, WA 98195 USA. [Sitruk-Ware, R.; Kumar, N.; Tsong, Y. Y.] Populat Council, New York, NY 10021 USA. [Blithe, D.; Swerdloff, R. S.] NIH, NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2008 VL 56 IS 1 MA 51 BP 120 EP 120 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 257IV UT WOS:000252793300061 ER PT J AU Zhao, JL Oberst, M Kelly, K AF Zhao, J. L. Oberst, M. Kelly, K. TI Role of Ral GTPases in Ras-mediated cancer metatstasis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 30-FEB 02, 2008 CL Carmel, CA SP Amer Federat Med Res C1 [Zhao, J. L.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Zhao, J. L.; Oberst, M.; Kelly, K.] NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2008 VL 56 IS 1 MA 78 BP 129 EP 129 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 257IV UT WOS:000252793300088 ER PT J AU Woods, SM Melvill, J Gavin, A Guo, Y Cesaitis, A Katon, W AF Woods, S. Madden Melvill, J. Gavin, A. Guo, Y. Cesaitis, A. Katon, W. TI Psychosocial stress during pregnancy SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 30-FEB 02, 2008 CL Carmel, CA SP Amer Federat Med Res C1 [Woods, S. Madden; Melvill, J.; Gavin, A.; Guo, Y.; Cesaitis, A.; Katon, W.] Univ Washington, Seattle, WA 98195 USA. [Woods, S. Madden; Gavin, A.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2008 VL 56 IS 1 MA 434 BP 248 EP 248 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 257IV UT WOS:000252793301094 ER PT J AU Wilder, L Merkel, J Kirin, J Costello, R AF Wilder, L. Merkel, J. Kirin, J. Costello, R. TI A clinically-oriented bibliographic database of dietary supplement research and evidence-based recommendations SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2008 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Wilder, L.; Costello, R.] NIH, Bethesda, MD USA. [Merkel, J.; Kirin, J.] USDA, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2008 VL 56 IS 1 MA 140 BP 389 EP 389 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 257IV UT WOS:000252793301290 ER PT J AU Li, Z Lang, LX Ma, Y Kiesewetter, DO AF Li, Zheng Lang, Lixin Ma, Ying Kiesewetter, Dale O. TI [(18)F]Fluoropropylsulfonyl chloride: a new reagent for radiolabeling primary and secondary amines for PET imaging SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE fluorine-18; radiolabeling agent; [(18)F]fluoropropylsulfonyl chloride ID POSITRON-EMISSION-TOMOGRAPHY; EFFICIENT SYNTHESIS; HUMAN-BRAIN; F-18; FLUOROALKYLATION; HYDROLYSIS; MECHANISMS; ANALOGS; DESIGN AB In vivo molecular imaging with positron emission tomography (PET) requires the preparation of an appropriate positron-emitting radiotracer. New methods for the introduction of F-18 into biologically interesting molecules could increase the availability of specific PET radiotracers and increase the application of PET to the study of human diseases. In this work, [(18)F]fluoropropylsulfonyl chloride was synthesized from 3-toluenesulfonyloxypropyl thiocyanate in two steps and was successfully incorporated into molecules containing a reactive amino group. Both a primary amine, L-phenylaianine ethyl ester hydrochloride, and a secondary amine, 1-(2-methoxyphenyl)-piperazine, were successfully radiolabeled by this method. The entire radiochemical synthesis required 90 min. The products were obtained in 25.7 +/- 2.3% (n=3) and 22.8 +/- 9.1 % (n = 6) (EOB). This method provides a useful and easy way to make new F-18 labeled radiopharmaceuticals for PET imaging. C1 [Li, Zheng; Lang, Lixin; Ma, Ying; Kiesewetter, Dale O.] Natl Inst Biomed Imaging & Bioengn, PET Radiochem Grp, NIH, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), Natl Inst Biomed Imaging & Bioengn, PET Radiochem Grp, NIH, Bethesda, MD 20892 USA. EM dkiesewetter@mail.nih.gov NR 18 TC 5 Z9 5 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JAN-FEB PY 2008 VL 51 IS 1-2 BP 23 EP 27 DI 10.1002/jlcr.1466 PG 5 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 282SA UT WOS:000254586300005 ER PT J AU Leeds, HS Richards, EP AF Leeds, Hilary S. Richards, Edward P. TI Legal issues in accommodating the Americans with Disabilities Act to the diabetic worker SO JOURNAL OF LEGAL MEDICINE LA English DT Article C1 [Leeds, Hilary S.; Richards, Edward P.] Louisiana State Univ, Paul M Hebert Law Ctr, Baton Rouge, LA 70803 USA. [Leeds, Hilary S.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70803 USA. [Leeds, Hilary S.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Leeds, HS (reprint author), Louisiana State Univ, Paul M Hebert Law Ctr, Baton Rouge, LA 70803 USA. EM hilaryleeds@hotmail.com; Richards@lsu.edu NR 4 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0194-7648 J9 J LEGAL MED JI J. Legal Med. PY 2008 VL 29 IS 3 BP 271 EP 283 DI 10.1080/01947640802297546 PG 13 WC Law; Social Sciences, Biomedical SC Government & Law; Biomedical Social Sciences GA 341BI UT WOS:000258688800001 PM 18726756 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI All that glitters may be HMGB1: an interview with Dr. Ulf Andersson SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material C1 [Rosenberg, Helene F.] NIH, NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIH, NIAID, Lab Allerg Dis, Bldg 10, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2008 VL 83 IS 1 BP 39 EP 40 DI 10.1189/jlb.1307323 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 243YV UT WOS:000251834100004 ER PT J AU Lee, HJ Rao, JS Chang, L Rapoport, SI Bazinet, RP AF Lee, Ho-Joo Rao, Jagadeesh S. Chang, Lisa Rapoport, Stanley I. Bazinet, Richard P. TI Chronic N-methyl-D-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat SO JOURNAL OF LIPID RESEARCH LA English DT Article DE bipolar disorder; signaling; neuroreceptor ID DNA-BINDING ACTIVITY; NMDA RECEPTOR TRAFFICKING; BIPOLAR DISORDER; DOCOSAHEXAENOIC ACID; FRONTAL-CORTEX; FATTY-ACID; CHRONIC LITHIUM; MESSENGER-RNA; ADJUNCTIVE TOPIRAMATE; SIGNAL TRANSDUCTION AB Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive N-methyl-D-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain arachidonic acid turnover, rats were daily administered NMDA (25 mg/kg, ip) or vehicle for 21 days. In un-anesthetized rats, on day 21, [1-(14)C] arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was euthanized at 5 min and its microwaved brain was subjected to chemical and radio-tracer analysis. Using equations from our in vivo fatty acid model, we found that compared with controls, chronic NMDA increased the net rate of incorporation of plasma unesterified arachidonic acid into brain phospholipids (25-34%) as well as the turnover of arachidonic acid within brain phospholipids (35-58%). These changes were absent at 3 h after a single NMDA injection. C1 [Lee, Ho-Joo; Rao, Jagadeesh S.; Chang, Lisa; Rapoport, Stanley I.; Bazinet, Richard P.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Bazinet, Richard P.] Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON, Canada. RP Bazinet, RP (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM richard.bazinet@utoronto.ca RI Rao, Jagadeesh/C-1250-2009 FU Intramural NIH HHS NR 80 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2008 VL 49 IS 1 BP 162 EP 168 DI 10.1194/jlr.M700406-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243YS UT WOS:000251833800018 PM 17957090 ER PT J AU Puri, A Kramer-Marek, G Campbell-Massa, R Yavlovich, A Tele, SC Lee, SB Clogston, JD Patri, AK Blumenthal, R Capala, J AF Puri, Anu Kramer-Marek, Gabriela Campbell-Massa, Ryan Yavlovich, Amichai Tele, Shrikant C. Lee, Sang-Bong Clogston, Jeffrey D. Patri, Anil K. Blumenthal, Robert Capala, Jacek TI HER2-Specific Affibody-Conjugated Thermosensitive Liposomes (Affisomes) for Improved Delivery of Anticancer Agents SO JOURNAL OF LIPOSOME RESEARCH LA English DT Article DE Affisomes; thermosensitive liposomes; affibody; breast tumor targeting; triggered release; drug delivery ID DRUG-DELIVERY; PRECLINICAL MANUFACTURE; SOLID TUMORS; HYPERTHERMIA; DOXORUBICIN; THERAPY AB Thermosensitive liposomes are attractive vehicles for the delivery and release of drugs to tumors. To improve the targeting efficacy for breast cancer treatment, an 8.3-kDa HER2-specific Affibody molecule (Z(HER2:342)-Cys) was conjugated to the surface of liposomes. The effects of this modification on physical characteristics and stability of the resulting nanoparticles denoted as "Affisomes" were investigated. Thermosensitive small unilamellar vesicle (SUV) liposomes of (80-100 nm) a diameter consisting of dipalmitoyl phosphatidylcholine (DPPC, Tm 41 degrees C) as the matrix lipid and a maleimide-conjugated pegylated phospholipid (DSPE-MaL-PEG2000) were prepared by probe sonication. Fluorescent probes were incorporated into liposomes for biophysical and/or biochemical analysis and/or triggered-release assays. Affibody was conjugated to these liposomes via its C-terminal cysteine by incubation in the presence of a reducing agent (e.g., tributylphosphine) for 16-20 hours under air argon atmosphere. Lipid-conjugated affibody molecule was visible as an 11.3-kDa band on a 4-12% Bis/Tris gel under reducing conditions. Affibody conjugation yields were similar to 70% at a protein-lipid ratio of 20 mu g/mg, with an average number of 200 affibody molecules per Affisome. Affibody conjugation to thermosensitive liposomes did not have any significant effect on the hydrodynamic size distribution of the liposomes. Thermosensitivity of Affisoines was determined by monitoring the release of entrapped calcein (a water-soluble fluorescent probe, lambda ex/em 490/515 nm) as a function of temperature. Calcein was released from Affisomes (thermosensitive liposomes with affibody-Targeted SUV) as well as nomargeted SUV (thermosensitive liposomes without affibody) in a temperature-dependent manner, with optimal leakage (90-100%) at 41 degrees C In contrast, liposomes prepared from Egg phosphatidyl choline (Egg PC, Tm similar to 0 degrees C) under similar conditions released only 5-10% calcein at 41 degrees C. Affisomes, when stored at room temperature, retained > 90% entrapped calcein up to 7 days. Moreover, incubation of liposomes in phosphate-buffered saline, supplemented with 10% heat-inactivated serum (fetal bovine serum) did not result in a destabilization of liposomes. Therefore, Affisomes present promising, novel drug-delivery candidates for breast cancer targeting. C1 [Puri, Anu; Campbell-Massa, Ryan; Yavlovich, Amichai; Tele, Shrikant C.; Blumenthal, Robert] NCI Frederick, CCR Nanobiol Program, Natl Inst Hlth, Bethesda, MD USA. [Kramer-Marek, Gabriela; Lee, Sang-Bong; Capala, Jacek] NCI, Radiat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Clogston, Jeffrey D.; Patri, Anil K.] NCI Frederick, Nanotechnol Characterizat Lab, SAIC Frederick Inc, Natl Inst Hlth, Bethesda, MD USA. RP Puri, A (reprint author), NCI, CCR Nanobiol Program, Natl Inst Hlth, Bldg 469 Rm 216A,POB B,Miller Dr, Frederick, MD 21702 USA. EM apuri@helix.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NIH; National Cancer Institute; Center for Cancer Research; Breast Cancer Research Stamp; National Institutes of Health [N01-CO-12400] FX This research was supported, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was supported by the Center for Cancer Research, an Intramural Research Program of the National Cancer Institute, and by Breast Cancer Research Stamp proceeds awarded through competitive peer review. This project has been funded, in whole or in part, with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 21 TC 49 Z9 52 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0898-2104 J9 J LIPOSOME RES JI J. Liposome Res. PY 2008 VL 18 IS 4 BP 293 EP 307 DI 10.1080/08982100802457377 PG 15 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 400DR UT WOS:000262848700003 PM 18937120 ER PT J AU Kipre, BG Coffi, AA Adima, AA Gokou, T Ito, Y Gosse, BK AF Kipre, Bertin G. Coffi, Antoine A. Adima, Augustin A. Gokou, Tea Ito, Yoichiro Gosse, Benjamin K. TI Total chemical analysis of the seed of Tieghemella heckelii by diverse chromatography techniques SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Tieghemella heckelii; saponins; fatty acids; steroid alcohols ID SAPONINS AB Arganines A, C, D, tieghemelin, fatty acids, and steroid alcohols were isolated and purified in a total study of the seeds of Tieghemella heckelii by diverse chromatography methods. The hexane extracts yielded nine fatty acids and sixteen steroid alcohols resolved by gas chromatography, whilst the water extract gave three relatively homogenous compounds using TLC analysis, and further studies with NMR revealed the arganines previously cited. The optimization of saponins was achieved by the HSCCC method. Aside from this, conversion of Tieghemelin to Arganine C has been fulfilled to seek for the increment of the yield of the most active compound and avoidance of separation of both saponins. Here, we report the isolation and the chemical analysis of the named constituents of the seeds. C1 [Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. [Kipre, Bertin G.; Adima, Augustin A.; Gosse, Benjamin K.] Inst Natl Polytech, Dept Chim, Lab Subst Nat Bioact, Yamoussoukro, Cote Ivoire. [Coffi, Antoine A.; Gokou, Tea] Univ Abidjan, Dept Chim, Chim Organ Struct Lab, Abidjan, Cote Ivoire. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, Natl Inst Hlth, Bldg 50,Rm 3334,50 S Dr,MSC 8014, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov OI Guede, Bertin/0000-0002-5910-3536 NR 8 TC 3 Z9 3 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 2 BP 250 EP 262 DI 10.1080/10826070701739041 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 251CI UT WOS:000252347800011 ER PT J AU Wei, Y Xie, QQ Ito, YC AF Wei, Yun Xie, Qianqian Ito, Yoichiro TI Preparative isolation of kaempferol pyranosides from a traditional Chinese herb using high speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE high speed countercurrent chromatography; kaempferol-3-O-beta-D-glucopyranoside; kaempferol-3-O-a-L-rhamnopyranoside; kaempferol-3-O-beta-D-glucopyranosyl (2-1)-a-L-rhamnopyranoside; Lysimachia christinae Hance ID FLAVONOIDS; OXIDATION; ALBUMIN AB Preparative countercurrent chromatography has been used successfully for the isolation and purification of kaempferol pyranosides including kaempferol-3-O-beta-D-glucopyranosyl (2-1)-a-L-rhamnopyranoside, kaempferol-3-O-beta-D-glucopyranoside, and kaempferol-3-O-a-L-rhamnopyranoside from the traditional Chinese herb "Jin qian cao"-Lysimachia christinae Hance with a two-phase solvent system composed of ethyl acetate-methanol-water with a volume ratio of 50:1:50, v/v. The composition of the phase system was optimized using analytical high speed countercurrent chromatography (HSCCC). The crude extract in the amount of 924mg was separated, yielding 69.8mg of kaempferol-3-O-beta-D-glucopyranosyl (2-1)-a-L-rhamnopyranoside, 45.3mg of kaempferol-3-O-beta-D-glucopyranoside, both at a high purity of over 97% and 8.9mg of kaempferol-3-O-a-L-rhamnopyranoside with the purity of 92%. C1 [Wei, Yun; Xie, Qianqian] Beijing Inst Chem Technol, Dept Appl Chem, Fac Sci, Beijing 100029, Peoples R China. [Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Wei, Y (reprint author), Beijing Inst Chem Technol, Dept Appl Chem, Fac Sci, 15 Beisanhuan E Rd,Chaoyang Dist, Beijing 100029, Peoples R China. EM weiyun@mail.buct.edu.cn NR 15 TC 1 Z9 2 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 3 BP 443 EP 451 DI 10.1080/10826070701780854 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 251CJ UT WOS:000252348000010 ER PT J AU Knight, M Ito, Y Finn, TM AF Knight, Martha Ito, Yoichiro Finn, Thomas M. TI Separation of peptides by spiral countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE spiral disk separation coil; countercurrent chromatography; preparative purification; peptide separation; coil planet centrifuge; partition coefficient ID STATIONARY-PHASE RETENTION; PURIFICATION AB Spiral countercurrent chromatography (CCC) utilizes a new separation rotor composed of 8 high density polyethylene plates with spiral flow channels, mounted in the type-J coil planet centrifuge (CPC). Synthetic peptides were evaluated for partition coefficients in various solvent systems. Approximately 30mg amounts were chromatographed and the fractions analyzed for peptide content and purity. The solvent systems which contained sec-butanol or n-butanol and the mobile phase selected produced good purification. The stationary phase was highly retained over 60%, thus the spiral separation coil is able to retain these more viscous, low interfacial tension solvents that have not been able to be used well in the multi-layer coil for high speed CCC. C1 [Knight, Martha; Finn, Thomas M.] CC Biotech LLC, Rockville, MD 20850 USA. [Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Knight, M (reprint author), CC Biotech LLC, 9700 Great Seneca Highway, Rockville, MD 20850 USA. EM marthaknight@starpower.net OI Knight, Martha/0000-0003-4863-8858 NR 9 TC 6 Z9 6 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 4 BP 471 EP 481 DI 10.1080/10826070701812699 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 251CL UT WOS:000252348200001 ER PT J AU Yu, H Lin, Q Ito, Y AF Yu, Henry Lin, Qi Ito, Yoichiro TI New design in centrifugal precipitation chromatography for the preparative separation of proteins SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE centrifugal precipitation chromatography; ammonium sulfate; protein fractionation; protein separation; preparative separation AB Centrifugal Precipitation Chromatography (CPC) utilizes a moving solvent gradient to separate proteins and macromolecules by repetitive steps of precipitation and dissolution in a column. Proteins fractionate at locations that depend on their solubility in differing ammonium sulfate concentrations. Prior to the current study, construction of a CPC instrument has been difficult due to the complicated design of the separation column and its connections. The current manuscript introduces an innovation that replaces the custom designed column with a commercial one. This change still results in efficient separations of human albumin and -globulin in a mixture, as well as in human serum. C1 [Yu, Henry; Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. [Lin, Qi] OPS, CDER, FDA, Off New Drug Qual Assessment, Silver Spring, MD USA. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 4 BP 517 EP 525 DI 10.1080/10826070701812756 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 251CL UT WOS:000252348200005 ER PT J AU Ito, Y Clary, R Powell, J Knight, M Finn, TM AF Ito, Y. Clary, R. Powell, J. Knight, M. Finn, T. M. TI Spiral tube support for high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE spiral tube support; high speed countercurrent chromatography; peptide separation AB A novel spiral tube support is introduced which allows accommodating a multlilayer spiral column made of a long piece of fluorinated plastic tubing. Two spiral columns tested in this study consist of 1.6mm ID and 0.85mm ID FEP (fluorinated ethylenepropylene) and PTFE (polytetrafluoroethylene) tubing with the total capacity of 100mL and 40mL, respectively. Performance of these spiral columns was examined with a two phase solvent system composed of 1-butanol/acetic acid/water at a volume ratio of 4:1:5 using tryptophyl-tyrosine (try-tyr) and valyl-tyrosine (val-tyr) as test samples under various revolution speeds and flow rates. Among 4 different elution modes tested, L-I-T (lower phase pumped from the internal head end of the spiral column) and U-O-H (upper phase pumped from the external tail of the spiral column) at a low flow rate produced the best results especially for both columns. The highest peak resolution (Rs) of over 3.5 was obtained from U-O-H at a flow rate of 1mL/min with 74% stationary phase retention. At a flow rate of 5mL/min, the highest revolution speed at 1,200rpm improved the peak resolution in both elution modes. The present system may be useful for purification of various polar compounds in biomedical researches. C1 [Ito, Y.] NHLBI, NIH, Bioseparat Technol Biochem & Biophys Ctr, Bethesda, MD 20892 USA. [Clary, R.; Powell, J.] Natl Inst Hlth, Bethesda, MD USA. [Knight, M.; Finn, T. M.] CC Biotech LLC, Rockville, MD USA. RP Ito, Y (reprint author), NHLBI, NIH, Bioseparat Technol Biochem & Biophys Ctr, 10 Ctr Dr,Bldg 10,Room 8N230,MSC 1762, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov OI Knight, Martha/0000-0003-4863-8858 FU Intramural NIH HHS [Z99 HL999999] NR 12 TC 24 Z9 24 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 9 BP 1346 EP 1357 DI 10.1080/10826070802019913 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 284IP UT WOS:000254700400009 PM 19343107 ER PT J AU Yang, Y Wu, T Yang, WX Aisa, HA Zhang, TY Ito, Y AF Yang, Yi Wu, Tao Yang, Wu Xing Aisa, Haji Akber Zhang, Tian You Ito, Yoichiro TI Preparative isolation and purification of four flavonoids from Flos Gossypii by high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE high-speed countercurrent chromatography; Flos Gossypii; flavonoids ID SEPARATION; CONSTITUENTS; EXTRACT AB Following an initial cleanup step on the AB-8 macroporous resin, high-speed countercurrent chromatography (HSCCC) was successfully applied for the first time to the isolation and purification of four flavonoids from Flos Gossypii. HSCCC was performed with a two-phase solvent system composed of chloroform-methanol-isopropanol-water (5:5:1:3, v/v) adding 0.4% phosphoric acid in the aqueous stationary phase. The separation yielded quercetin (5.6mg), quercetin-3'-O-D-glucoside (7.2mg), quercetin-3-O-beta-D-glucoside (16mg), quercetin-7-O-beta-D-glucoside (8.3mg), from 100mg of the crude extract in a one step separation. The structure identification was made by (1)H NMR, (13)C NMR. C1 [Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Yang, Yi; Wu, Tao; Yang, Wu Xing; Aisa, Haji Akber; Zhang, Tian You] Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Urumqi, Peoples R China. [Yang, Yi; Wu, Tao] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China. [Zhang, Tian You] Beijing Inst New Technol Applicat, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 10 TC 11 Z9 11 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 10 BP 1523 EP 1531 DI 10.1080/10826070802039663 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 292NH UT WOS:000255272900011 ER PT J AU Yang, Y Gu, D Wu, H Aisa, HA Zhang, TY Ito, Y AF Yang, Yi Gu, Dongyu Wu, Hankui Aisa, Haji Akber Zhang, Tianyou Ito, Yoichiro TI Application of preparative high-speed countercurrent chromatography for separation of elatine from Delphinium shawurense SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Delphinium shawurense; elatine; high speed countercurrent chromatography (HSCCC) ID PURIFICATION; ALKALOIDS; ACID AB Preparative separation of elatine in Delphinium shawurense was achieved for the first time using high speed countercurrent chromatography (HSCCC). The separation was performed with a solvent system composed of ethyl acetate-chloroform-methanol-water (3:0.1:2:3, v/v) using the lower organic phase as a mobile phase under a revolution speed of 800rpm. This yielded 72mg of elatine at over 97% purity with an approximately 95% recovery. The chemical structure was identified by MS and NMR. C1 [Yang, Yi; Gu, Dongyu; Wu, Hankui; Aisa, Haji Akber; Zhang, Tianyou] Chinese Acad Sci, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Xinjiang Tech Inst Phys & Chem, Urumqi, Peoples R China. [Yang, Yi; Gu, Dongyu; Wu, Hankui] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China. [Zhang, Tianyou] Beijing Inst New Technol, Beijing, Peoples R China. [Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Aisa, HA (reprint author), Chinese Acad Sci, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Xinjiang Tech Inst Phys & Chem, Urumqi, Peoples R China. EM haji@ms.xjb.ac.cn FU Key Project of Knowledge Innovation Program of Chinese Academy of Sciences [KGC X2-SW-213-08]; program for development and research of high technologies in Xinjiang [200515123] FX This work was financially supported by grant (code: KGC X2-SW-213-08) from Key Project of Knowledge Innovation Program of Chinese Academy of Sciences and grant (code: 200515123) from the program for development and research of high technologies in Xinjiang. NR 10 TC 25 Z9 26 U1 2 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 19 BP 3012 EP 3019 DI 10.1080/10826070802424956 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 355FR UT WOS:000259695300009 PM 20351801 ER PT J AU Fitzgerald, PJ AF Fitzgerald, Paul J. TI Adjust your brain: A practical theory for maximizing mental health SO JOURNAL OF LOSS & TRAUMA LA English DT Article C1 [Fitzgerald, Paul J.] Johns Hopkins Univ, Krieger Mind Brain Inst, Dept Neurosci, Baltimore, MD USA. RP Fitzgerald, PJ (reprint author), NIAAA, 5625 Fishers Lane,Room TS20, Bethesda, MD 20852 USA. EM pfitz@mbi.mb.jhu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1532-5024 J9 J LOSS TRAUMA JI J. Loss Trauma PY 2008 VL 13 IS 5 BP 466 EP 470 DI 10.1080/15325020802171425 PG 5 WC Psychology, Social SC Psychology GA 346TT UT WOS:000259092900006 ER PT J AU Castle, PE Sideri, M Jeronimo, J Solomon, D Schiffman, M AF Castle, Philip E. Sideri, Mario Jeronimo, Jose Solomon, Diane Schiffman, Mark TI Risk Assessment to Guide the Prevention of Cervical Cancer SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE human papillomavirus; cervical cancer; cervical cytology; cervical precancer; risk AB Advances in screening and diagnosis make it increasingly possible to prevent cervical cancer. However, if misused or poorly understood, these new tools will only increase costs and potentially harm patients without benefit. As a framework for standardized care that maximizes patient safety and well-being, we propose that a risk model be adopted to guide clinical management now and in the future. The model would use thresholds of increasing risk for cervical precancer and treatable cancer to guide clinical decision making for screening intensity, diagnostic evaluation, or treatment. Experts would decide on these risk thresholds and stratum based on the patient risk to benefit, independent of current (e.g., cytology, carcinogenic human papillomavirus testing, and colposcopy) and future methods of measuring risk. A risk management model for cervical cancer prevention, based on appropriate clinical actions that correspond to risk stratum, can result in better allocation of resources to and increased safety for women at the greatest risk and increased well-being for women at the lowest risk. C1 [Castle, Philip E.; Jeronimo, Jose; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Solomon, Diane] NCI, Canc Prevent Div, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Sideri, Mario] European Inst Oncol, Prevent Gynecol Unit, Milan, Italy. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, 6120 Executive Blvd,Room 5004,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU National Institutes of Health; National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. None of the authors has a conflict of interest to report. The financial activities of P.E.C., J.J., D.S., and M.S. are monitored by the National Cancer Institute Ethics Office. NR 30 TC 31 Z9 32 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD JAN PY 2008 VL 12 IS 1 BP 1 EP 7 DI 10.1097/lgt.0b013e31815ea58b PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA V10YT UT WOS:000207500000001 PM 18162804 ER PT J AU Gage, JC Safaeian, M Jeronimo, J Schiffman, M AF Gage, Julia C. Safaeian, Mahboobeh Jeronimo, Jose Schiffman, Mark TI Spectroscopic Imaging as Triage Test for Cervical Disease SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Letter C1 [Gage, Julia C.; Safaeian, Mahboobeh; Jeronimo, Jose; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, Rockville, MD USA. RP Gage, JC (reprint author), NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, Rockville, MD USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD JAN PY 2008 VL 12 IS 1 BP 52 EP 53 DI 10.1097/lgt.0b013e318149e232 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA V10YT UT WOS:000207500000011 PM 18162814 ER PT J AU Hyodo, F Murugesan, R Matsumoto, K Hyodo, E Subramanian, S Mitchell, JB Krishna, MC AF Hyodo, Fummori Murugesan, Ramachandran Matsumoto, Ken-ichiro Hyodo, Emi Subramanian, Sankaran Mitchell, James B. Krishna, Murali C. TI Monitoring redox-sensitive paramagnetic contrast agent by EPRI, OMRI and MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE redox sensitive contrast agent; EPRI; MRI; OMRI; nitroxide ID MAGNETIC-RESONANCE; ENHANCED MRI; TUMOR; NITROXIDES; TISSUES; OXYGENATION; RESOLUTION; RADICALS; HYPOXIA; IMAGES AB A comparative study of tissue redox-status imaging using commonly used redox sensitive nitroxides has been carried out using electron paramagnetic resonance imaging (EPRI), Overhauser magnetic resonance imaging (OMRI) and conventional T-1-weighted magnetic resonance imaging, MRI. Imaging studies using phantoms of different nitroxides at different concentration levels showed that EPRI and OMRI sensitivities were found to be linearly dependent on line width of nitroxides up to 2 mM, and the enhancement in MRI intensity was linear up to 5 mM. The sensitivity and resolution of EPRI and OMRI images depended significantly on the line width of the nitroxides whereas the MRI images were almost independent of EPR line width. Reduction of the paramagnetic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3CP) by ascorbic acid (AsA) to the diamagnetic by hydroxylamine was monitored from a sequence of temporal images, acquired using the three imaging modalities. The decay rates determined by all the three modalities were found to be similar. However the results suggest that T-1-weighted MRI can monitor the redox status, in addition to providing detailed anatomical structure in a short time. Therefore, a combination of MRI with nitroxides as metabolically responsive contrast agents can be a useful technique for the in vivo imaging probing tissue redox status. Published by Elsevier Inc. C1 [Hyodo, Fummori; Murugesan, Ramachandran; Matsumoto, Ken-ichiro; Hyodo, Emi; Subramanian, Sankaran; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Matsumoto, Ken-ichiro] Natl Inst Radiol Sci, Heavy Ion Radiobiol Res Grp, Chiba 260, Japan. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov FU Intramural NIH HHS [Z01 BC010478-04, Z01 BC010477-04, Z01 BC010476-04] NR 31 TC 42 Z9 42 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2008 VL 190 IS 1 BP 105 EP 112 DI 10.1016/j.jmr.2007.10.013 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 255TN UT WOS:000252680400011 PM 18006345 ER PT J AU Romero, R Nien, JK Espinoza, J Todem, D Fu, W Chung, H Kusanovic, JP Gotsch, F Erez, O Mazaki-Tovi, S Gomez, R Edwin, S Chaiworapongsa, T Levine, RJ Karumanchi, SA AF Romero, Roberto Nien, Jyh Kae Espinoza, Jimmy Todem, David Fu, Wenjiang Chung, Hwan Kusanovic, Juan Pedro Gotsch, Francesca Erez, Offer Mazaki-Tovi, Shali Gomez, Ricardo Edwin, Sam Chaiworapongsa, Tinnakorn Levine, Richard J. Karumanchi, S. Ananth TI A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE intrauterine growth restriction; placental disease; SGA; IUGR; preterm birth; soluble Flt-1; longitudinal; growth curve model; pregnancy ID UTERINE ARTERY DOPPLER; CIRCULATING ANTIANGIOGENIC FACTORS; UTEROPLACENTAL BLOOD-FLOW; HUMAN BONE-MARROW; TYROSINE KINASE-1; MIRROR-SYNDROME; SERUM-LEVELS; FACTOR-BETA; CELLULAR-RESPONSES; OXIDATIVE STRESS AB Introduction. Accumulating evidence suggests that an imbalance between pro-angiogenic (i.e., vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)) and anti-angiogenic factors (i.e., soluble VEGF receptor-1 (sVEGFR-1, also referred to as sFlt1)) is involved in the pathophysiology of preeclampsia (PE). Endoglin is a protein that regulates the pro-angiogenic effects of transforming growth factor , and its soluble form has recently been implicated in the pathophysiology of PE. The objective of this study was to determine if changes in maternal plasma concentration of these angiogenic and anti-angiogenic factors differ prior to development of disease among patients with normal pregnancies and those destined to develop PE (preterm and term) or to deliver a small for gestational age (SGA) neonate. Methods. This longitudinal nested case-control study included 144 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered appropriate for gestational age (AGA) neonates (n=46); (2) patients who delivered an SGA neonate but did not develop PE (n=56); and (3) patients who developed PE (n=42). Longitudinal samples were collected at each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. Plasma concentrations of soluble endoglin (s-Eng), sVEGFR-1, and PlGF were determined by specific and sensitive ELISA. Results. (1) Patients destined to deliver an SGA neonate had higher plasma concentrations of s-Eng throughout gestation than those with normal pregnancies; (2) patients destined to develop preterm PE and term PE had significantly higher concentrations of s-Eng than those with normal pregnancies at 23 and 30 weeks, respectively (for preterm PE: p0.036 and for term PE: p=0.002); (3) patients destined to develop PE (term or preterm) and those who delivered an SGA neonate had lower plasma concentrations of PlGF than those with a normal pregnancy throughout gestation, and the maternal plasma concentration of this analyte became detectable later among patients with pregnancy complications, compared to normal pregnant women; (4) there were no significant differences in the plasma concentrations of sVEGFR-1 between patients destined to deliver an SGA neonate and those with normal pregnancies; (5) patients destined to develop preterm and term PE had a significantly higher plasma concentration of sVEGFR-1 at 26 and 29 weeks of gestation than controls (p=0.009 and p=0.0199, respectively); and (6) there was no significant difference in the increment of sVEGFR-1 between control patients and those who delivered an SGA neonate (p=0.147 at 25 weeks and p=0.8285 at 40 weeks). Conclusions. (1) Changes in the maternal plasma concentration of s-Eng, sVEGFR-1, and PlGF precede the clinical presentation of PE, but only changes in s-Eng and PlGF precede the delivery of an SGA neonate; and (2) differences in the profile of angiogenic and anti-angiogenic response to intrauterine insults may determine whether a patient will deliver an SGA neonate, develop PE, or both. C1 [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Espinoza, Jimmy; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Todem, David; Fu, Wenjiang; Chung, Hwan] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Dr Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Levine, Richard J.] NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Romero, Roberto; Nien, Jyh Kae; Espinoza, Jimmy; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Edwin, Sam] NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Romero, Roberto; Nien, Jyh Kae; Espinoza, Jimmy; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Edwin, Sam] NICHHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R, Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002401-15] NR 86 TC 306 Z9 329 U1 3 U2 17 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 1 BP 9 EP U3 DI 10.1080/14767050701830480 PG 18 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 251AM UT WOS:000252342700003 PM 18175241 ER PT J AU Chaiworapongsa, T Espinoza, J Gotsch, F Kim, YM Kim, GJ Goncalves, LF Edwin, S Kusanovic, JP Erez, O Than, NG Hassan, SS Romero, R AF Chaiworapongsa, Tinnakorn Espinoza, Jimmy Gotsch, Francesca Kim, Yeon Mee Kim, Gi Jin Goncalves, Luis F. Edwin, Samuel Kusanovic, Juan Pedro Erez, Offer Than, Nandor Gabor Hassan, Sonia S. Romero, Roberto TI The maternal plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated in SGA and the magnitude of the increase relates to Doppler abnormalities in the maternal and fetal circulation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE small for gestational age; preeclampsia; soluble VEGFR-1; angiogenesis; uterine artery Doppler; umbilical artery Doppler ID UTERINE ARTERY DOPPLER; FOR-GESTATIONAL-AGE; UTEROPLACENTAL BLOOD-FLOW; VELOCITY WAVE-FORMS; HIGH-RISK PREGNANCIES; LINKED GAMMA-CAMERA; BED SPIRAL ARTERIES; TYROSINE KINASE-1; UMBILICAL ARTERY; PLACENTAL BED AB Objectives. The soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1), an antagonist to vascular endothelial growth factor and placental growth factor, has been implicated in the pathophysiology of preeclampsia. Preeclampsia and pregnancy complicated with small for gestational age (SGA) fetuses share some pathophysiologic derangements, such as failure of physiologic transformation of the spiral arteries, endothelial cell dysfunction, and leukocyte activation. The objectives of this study were to: (1) determine whether plasma concentrations of sVEGFR-1 in mothers with SGA fetuses without preeclampsia at the time of diagnosis are different from those in patients with preeclampsia or normal pregnant women, and (2) examine the relationship between plasma concentrations of sVEGFR-1 and Doppler velocimetry in uterine and umbilical arteries in patients with preeclampsia and those with SGA. Study design. A cross-sectional study was conducted to determine the concentrations of the soluble form of VEGFR-1 in plasma obtained from normal pregnant women (n=135), women with SGA fetuses (n=53), and patients with preeclampsia (n=112). Patients with SGA fetuses and those with preeclampsia were sub-classified according to the results of uterine and umbilical artery Doppler velocimetry examinations. Plasma concentrations of sVEGFR-1 were determined by an ELISA. Since these concentrations change with gestational age, differences among various subgroups were statistically estimated with the delta value, defined as the difference between the observed and expected plasma sVEGFR-1 concentration. The expected values were derived from regression analysis of plasma sVEGFR-1 concentrations in normal pregnancy. Regression analysis and univariate and multivariate analysis were employed. Results. (1) Mothers with SGA fetuses had a mean plasma concentration of sVEGFR-1 higher than normal pregnant women (p0.001), but lower than patients with preeclampsia (p0.001). (2) Among patients with SGA fetuses, only those with abnormal uterine artery Doppler velocimetry had a mean plasma sVEGFR-1 concentration significantly higher than normal pregnant women (p0.001). (3) Among mothers with SGA fetuses in whom Doppler velocimetry was performed (n=41), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta of sVEGFR-1 plasma concentration (meanstandard deviation (SD): 0.690.29). Conversely, patients who had normal Doppler velocimetry in both uterine and umbilical arteries had the lowest mean delta (meanSD: 0.090.29) of sVEGFR-1 plasma concentrations (ANOVA; p0.001). (4) Among patients with preeclampsia in whom Doppler velocimetry was performed (n=69), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta sVEGFR-1 plasma concentration (meanSD: 1.010.22) among all groups classified (ANOVA; p0.001). (5) Among patients with SGA and those with preeclampsia, there was a relationship (Chi-square for trend p0.001 for both) between the severity of Doppler velocimetry abnormalities and the proportion of patients who had high delta sVEGFR-1 plasma concentrations (defined as a concentration two standard deviations (2SD) above the mean delta of normal pregnant women). (6) Multiple regression analysis suggested that the diagnostic category (e.g., SGA or preeclampsia), Doppler abnormalities, and gestational age at blood sampling were associated with an increase in plasma sVEGFR-1 concentrations (p0.001). Conclusions. These observations provide support for the participation of the soluble receptor of vascular endothelial growth factor in the pathophysiology of SGA with abnormal uterine artery Doppler velocimetry and preeclampsia. An excess of sVEGFR-1 is released into the maternal circulation of patients with preeclampsia and those with SGA fetuses, as abnormalities of impedance to blood flow involve uterine and umbilical circulation. C1 [Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Gotsch, Francesca; Kim, Yeon Mee; Kim, Gi Jin; Goncalves, Luis F.; Edwin, Samuel; Kusanovic, Juan Pedro; Erez, Offer; Than, Nandor Gabor; Hassan, Sonia S.; Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Goncalves, Luis F.; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Kim, Yeon Mee] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI USA. [Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Gotsch, Francesca; Kim, Yeon Mee; Kim, Gi Jin; Goncalves, Luis F.; Edwin, Samuel; Kusanovic, Juan Pedro; Erez, Offer; Than, Nandor Gabor; Hassan, Sonia S.; Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, NICHD,Dept OB GYN, 4 Brush 3990 John R St, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu NR 127 TC 70 Z9 71 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 1 BP 25 EP 40 DI 10.1080/14767050701832833 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 251AM UT WOS:000252342700004 PM 18175242 ER PT J AU Chaiworapongsa, T Romero, R Gotsch, F Espinoza, J Nien, JK Goncalves, L Edwin, S Kim, YM Erez, O Kusanovic, JP Pineles, BL Papp, Z Hassan, S AF Chaiworapongsa, Tinnakorn Romero, Roberto Gotsch, Francesca Espinoza, Jimmy Nien, Jyh Kae Goncalves, Luis Edwin, Samuel Kim, Yeon Mee Erez, Offer Kusanovic, Juan Pedro Pineles, Beth L. Papp, Zoltan Hassan, Sonia TI Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE small for gestational age; intrauterine growth restriction; preeclampsia; sVEGFR-2; KDR; pregnancy ID CIRCULATING ANGIOGENIC FACTORS; INTRAUTERINE GROWTH; OXIDATIVE STRESS; FETAL-GROWTH; TYROSINE KINASE-1; INSULIN-RESISTANCE; PROGENITOR CELLS; NORMAL-PREGNANCY; UP-REGULATION; BIRTH-WEIGHT AB Objectives. Preeclampsia is considered an anti-angiogenic state. A role for the anti-angiogenic factors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin in preeclampsia has been proposed. Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) has been detected in human plasma, and the recombinant form of this protein has anti-angiogenic activity. There is a paucity of information about maternal plasma sVEGFR-2 concentrations in patients with preeclampsia and those without preeclampsia with small for gestational age (SGA) fetuses. This study was conducted to determine whether: (1) plasma sVEGFR-2 concentration changes throughout pregnancy; and (2) preeclampsia and SGA are associated with abnormalities in the maternal plasma concentration of sVEGFR-2. Study design. This cross-sectional study included non-pregnant women (n=40), women with normal pregnancies (n=135), women with an SGA fetus (n=53), and women with preeclampsia (n=112). SGA was defined as an ultrasound-estimated fetal weight below the 10th percentile for gestational age that was confirmed by neonatal birth weight. Plasma concentrations of sVEGFR-2 were determined by ELISA. Results. (1) There was no significant difference in the mean plasma concentration of sVEGFR-2 between non-pregnant women and those with normal pregnancies (p=0.8); (2) patients with preeclampsia and those without preeclampsia with SGA fetuses had a lower mean plasma concentration of sVEGFR-2 than that of women with normal pregnancies (p0.001 for both); and (3) there was no significant difference in the mean plasma concentration of sVEGFR-2 between patients with preeclampsia and those without preeclampsia with SGA (p=0.9). Conclusions. Preeclampsia and SGA are associated with low plasma concentrations of sVEGFR-2. One interpretation of the findings is that plasma sVEGFR-2 concentration could reflect endothelial cell function. C1 [Chaiworapongsa, Tinnakorn; Romero, Roberto; Gotsch, Francesca; Espinoza, Jimmy; Nien, Jyh Kae; Goncalves, Luis; Edwin, Samuel; Kim, Yeon Mee; Erez, Offer; Kusanovic, Juan Pedro; Pineles, Beth L.; Hassan, Sonia] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Romero, Roberto; Gotsch, Francesca; Espinoza, Jimmy; Nien, Jyh Kae; Goncalves, Luis; Edwin, Samuel; Kim, Yeon Mee; Erez, Offer; Kusanovic, Juan Pedro; Pineles, Beth L.; Hassan, Sonia] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Goncalves, Luis; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Kim, Yeon Mee] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, H-1085 Budapest, Hungary. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,4 Brush, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu NR 136 TC 51 Z9 55 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 1 BP 41 EP 52 DI 10.1080/14767050701831397 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 251AM UT WOS:000252342700005 PM 18175243 ER PT J AU Nanovskaya, TN Patrikeeva, S Hemauer, S Fokina, V Mattison, D Hankins, GD Ahmed, MS AF Nanovskaya, Tatiana N. Patrikeeva, Svetlana Hemauer, Sarah Fokina, Valentina Mattison, Donald Hankins, Gary D. Ahmed, Mahmoud S. CA OPRU Network TI Effect of albumin on transplacental transfer and distribution of rosiglitazone and glyburide SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the Diabetes-in-Pregnancy-Study-Group-of-North-America CY MAY, 2007 CL New York, NY SP Diabet Pregnancy Study Grp N Amer DE rosiglitazone; glyburide; transplacental transfer; gestational diabetes ID POLYCYSTIC-OVARY-SYNDROME; ORAL HYPOGLYCEMIC AGENTS; INSULIN-RESISTANCE; PLACENTAL-TRANSFER; HUMAN PLASMA; PREGNANCY; EXPOSURE; WOMEN; TRANSPORT; METFORMIN AB Objective.The aims of this investigation were (i) to determine the rate and extent of rosiglitazone transfer across term human placenta, and (ii) to determine the effect of human serum albumin (HSA) on rosiglitazone and glyburide transfer and distribution. Methods.These aims were achieved by utilizing the technique of dual perfusion of placental lobule (DPPL). Each hypoglycemic drug was coperfused with the marker compound antipyrine (AP). In each experiment, the [H-3]-isotope of the hypoglycemic drug and the [C-14]-isotope of AP were added to enhance the detection limits of each drug. Human serum albumin (HSA) was added to both the maternal and fetal circuits in the experiments in which it was investigated. Results.Transplacental transfer of rosiglitazone and glyburide from the maternal to fetal circuits in media devoid of HSA was similar. However, the addition of HSA to the maternal and fetal circuits had different effects on the transfer and distribution of the two drugs, though their binding to HSA (99.8%) was almost identical. HSA increased the maternal (M) to fetal (F) transfer of rosiglitazone, as revealed by an increase in its F/M concentration ratio from 0.17 +/- 0.01 (in the absence of albumin) to 0.33 +/- 0.07 (p < 0.001). Moreover, the addition of albumin decreased the amount of rosiglitazone retained by placental tissue from 539 +/- 148 to 60 +/- 8 ng/g (p < 0.001). Conversely, the addition of HSA to the perfusion media resulted in a decrease in glyburide transfer, as revealed by the change of its F/M concentration ratio from 0.09 +/- 0.02 (in the absence of albumin) to 0.03 +/- 0.01 (p < 0.01). However, similar to rosiglitazone, glyburide retention by the tissue decreased from 103 +/- 26 to 19 +/- 6 ng/g (p < 0.001). Conclusions.These data indicate that the binding of the two drugs to albumin, though similar, is only one of the factors that could affect their placental transfer and distribution. C1 [Nanovskaya, Tatiana N.; Patrikeeva, Svetlana; Hemauer, Sarah; Fokina, Valentina; Hankins, Gary D.; Ahmed, Mahmoud S.] Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Mattison, Donald] NICHD, Ctr Res Mothers & Children, Obstet Fetal Pharmacol Res Units Network, Bethesda, MD USA. RP Ahmed, MS (reprint author), Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, 301 Univ Texas Med Branch, Galveston, TX 77555 USA. EM maahmed@utmb.edu RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU NICHD NIH HHS [U10HD047891] NR 23 TC 18 Z9 24 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 3 BP 197 EP 207 DI 10.1080/14767050801929901 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 267NB UT WOS:000253514600009 PM 18297575 ER PT J AU Toft, JH Lian, IA Tarca, AL Erez, O Espinoza, J Eide, IP Bjorge, L Chen, S Draghici, S Romero, R Austgulen, R AF Toft, Johanne Holm Lian, Ingrid Alsos Tarca, Adi Laurentiu Erez, Offer Espinoza, Jimmy Eide, Irina Poliakova Bjorge, Line Chen, Sun Draghici, Sorin Romero, Roberto Austgulen, Rigmor TI Whole-genome microarray and targeted analysis of angiogenesis-regulating gene expression (ENG, FLT1, VEGF, PlGF) in placentas from pre-eclamptic and small-for-gestational-age pregnancies SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE pre-eclampsia; small-for-gestational-age; placenta; genome-wide gene expression; ENG; FLT1; angiogenesis ID INTRAUTERINE GROWTH RESTRICTION; FETAL-GROWTH; ONSET PREECLAMPSIA; MOLECULAR EVIDENCE; TYROSINE KINASE-1; HYPOXIA; PATHOGENESIS; RETARDATION AB Objective. To compare the placental pathology associated with pre-eclampsia (PE) and/or fetal growth restriction, the transcriptomes of placental tissues from PE and small-for-gestational-age (SGA) pregnancies were explored. In addition, a targeted analysis of angiogenesis-regulating gene expression was performed. Methods. Whole-genome microarray analysis was performed on placental tissue from gestational age-matched PE (n=10), SGA (n=8) and PE+SGA (n=10) pregnancies. The expression of genes regulating angiogenesis (endoglin (ENG), fms-related tyrosine kinase 1 (FLT1), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)) was analyzed by quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR). Results. Microarray analysis did not reveal any significant differences between groups. However, an increased expression of ENG and FLT1 was detected by qRT-PCR in the PE+SGA group. Conclusions. The placental transcriptome did not differ between groups, although an increased anti-angiogenic gene expression in PE+SGA was observed with qRT-PCR analysis. Based on this, we conclude that although microarray technology may represent a powerful tool in generating new hypothesis in complex fields, it may not be sensitive enough to detect subtle changes in gene expression. C1 [Austgulen, Rigmor] Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Med Tekn Senter, N-7489 Trondheim, Norway. [Tarca, Adi Laurentiu; Erez, Offer; Espinoza, Jimmy; Romero, Roberto] NICHHD, Div Intramural Res, Perinatol Res Branch, Detroit, MI USA. [Bjorge, Line; Chen, Sun] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. [Draghici, Sorin] Wayne State Univ, Detroit, MI USA. RP Austgulen, R (reprint author), Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Med Tekn Senter, N-7489 Trondheim, Norway. EM rigmor.austgulen@ntnu.no RI Draghici, Sorin/B-3074-2013; Bjorge, Line/C-1307-2017 OI Draghici, Sorin/0000-0002-0786-8377; Bjorge, Line/0000-0002-0240-2770 NR 30 TC 31 Z9 31 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 4 BP 267 EP 273 DI 10.1080/14767050801924118 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298LK UT WOS:000255689000009 PM 18330824 ER PT J AU Erez, O Romero, R Espinoza, J Fu, WJ Todem, D Kusanovic, JP Gotsch, F Edwin, S Nien, JK Chaiworapongsa, T Mittal, P Mazaki-Tovi, S Than, NG Gomez, R Hassan, SS AF Erez, Offer Romero, Roberto Espinoza, Jimmy Fu, Wenjiang Todem, David Kusanovic, Juan Pedro Gotsch, Francesca Edwin, Samuel Nien, Jyh Kae Chaiworapongsa, Tinnakorn Mittal, Pooja Mazaki-Tovi, Shali Than, Nandor Gabor Gomez, Ricardo Hassan, Sonia S. TI The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE SGA; longitudinal; PlGF; endoglin; sVEGFR-1 ID ENDOTHELIAL GROWTH-FACTOR; BODY-MASS INDEX; UTERINE ARTERY DOPPLER; FACTOR RECEPTOR-1 CONCENTRATION; TYROSINE KINASE-1; SOLUBLE ENDOGLIN; NORMAL-PREGNANCY; ANTIANGIOGENIC FACTORS; 2ND TRIMESTER; SERUM-LEVELS AB Introduction. An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate. Methods. This longitudinal case-control study included 402 singleton pregnancies in the following groups: (1) normal pregnancies with appropriate for gestational age (AGA) neonates (n=201); (2) patients who delivered an SGA neonate (n=145); and (3) patients who developed PE (n=56). Maternal plasma samples were obtained at the time of each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. In this study, we included two samples per patient: (1) first sample obtained between 6 and 15 weeks of gestation ('first trimester' sample), and (2) second sample obtained between 20 and 25 weeks of gestation ('second trimester' sample). Plasma concentrations of s-Eng, sVEGFR-1, and PlGF were determined by specific and sensitive immunoassays. Changes in the maternal plasma concentrations of these angiogenesis-related factors were compared among normal patients and those destined to develop PE or deliver an SGA neonate while adjusting for maternal age, nulliparity, and body mass index. General linear models and polytomous logistic regression models were used to relate the analyte concentrations, ratios, and product to the subsequent development of PE and SGA. Results. (1) An increase in the maternal plasma concentration of s-Eng between the first and second trimesters conferred risk for the development of preterm PE and SGA (OR 14.9, 95% CI 4.9-45.0 and OR 2.9, 95% CI 1.5-5.6, respectively). (2) An increase in the maternal plasma concentration of sVEGFR-1 between the first and second trimester conferred risk for the development of preterm PE (OR 3.9, 95% CI 1.2-12.6). (3) A subnormal increase in maternal plasma PlGF concentration between the first and the second trimester was a risk factor for the subsequent development of preterm and term PE (OR 4.3, 95% CI 1.2-15.5 and OR 2.7, 95% CI 1.2-5.9, respectively). (4) In addition, the combination of the three analytes into a pro-angiogenic versus anti-angiogenic ratio (PlGF/(s-EngVEGFR-1)) conferred risk for the subsequent development of preterm PE (OR 3.7, 95% CI 1.1-12.1). (5) Importantly, patients with a high change in the s-EngsVEGFR-1 product had an OR of 10.4 (95% CI 3.2-33.8) for the development of preterm PE and 1.6 (95% CI 1.0-2.6) for the development of SGA. Conclusions. Changes in the maternal plasma concentrations of s-Eng, sVEGFR-1, PlGF or their ratios between the first and second trimesters of pregnancy confer an increased risk to deliver an SGA neonate and/or develop PE. C1 [Erez, Offer; Romero, Roberto; Espinoza, Jimmy; Kusanovic, Juan Pedro; Gotsch, Francesca; Edwin, Samuel; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Mazaki-Tovi, Shali; Than, Nandor Gabor; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Espinoza, Jimmy; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Fu, Wenjiang; Todem, David] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Nien, Jyh Kae; Gomez, Ricardo] Catholic Univ Chile, Hosp Dr Sotero Del Rio, CEDIP, Punte Alto, Chile. RP Erez, O (reprint author), Wayne State Univ, Hutzel Womens Hosp, DHHS, NIH,NICHD,Perinatol Res Branch, 3990 John R,Box, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-16] NR 57 TC 155 Z9 162 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 5 BP 279 EP 287 DI 10.1080/14767050802034545 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 294VX UT WOS:000255435500001 PM 18446652 ER PT J AU Erez, O Romero, R Kim, SS Kim, JS Kim, YM Wildman, DE Than, NG Mazaki-Tovi, S Gotsch, F Pineles, B Kusanovic, JP Espinoza, J Mittal, P Mazor, M Hassan, SS Kim, CJ AF Erez, Offer Romero, Roberto Kim, Sung-Su Kim, Jung-Sun Kim, Yeon Mee Wildman, Derek E. Than, Nandor Gabor Mazaki-Tovi, Shali Gotsch, Francesca Pineles, Beth Kusanovic, Juan Pedro Espinoza, Jimmy Mittal, Pooja Mazor, Moshe Hassan, Sonia S. Kim, Chong Jai TI Over-expression of the thrombin receptor (PAR-1) in the placenta in preeclampsia: A mechanism for the intersection of coagulation and inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE PAR-1; immunohistochemistry; preterm; trophoblast; tethered ligand; villous infarct ID PROTEASE-ACTIVATED RECEPTORS; CIRCULATING ANGIOGENIC FACTORS; ANTITHROMBIN-III COMPLEX; NECROSIS-FACTOR-ALPHA; INTRAUTERINE GROWTH-RETARDATION; COLONY-STIMULATING FACTOR; NORMAL-PREGNANCY; ENDOTHELIAL-CELLS; BLOOD-COAGULATION; PRETERM LABOR AB Objective. Preeclampsia (PE) is characterized by excessive thrombin generation, which has been implicated in the multiple organ damage associated with the disease. The biological effects of thrombin on coagulation and inflammation are mediated by protease-activated receptor-1 (PAR-1), a G protein-coupled receptor. The aim of this study was to determine whether preterm PE is associated with changes in placental expression of PAR-1. Study design. This cross-sectional study included two groups matched for gestational age at delivery: (1) patients with preterm PE (<37 weeks of gestation; n = 26) and (2) a control group of patients with preterm labor without intra-amniotic infection (n 26). Placental tissue microarrays were immunostained for PAR-1. Immunoreactivity of PAR-1 in the villous trophoblasts was graded as negative, weak-positive, or strong-positive. Results. (1) The proportion of cases with strong PAR-1 immunoreactivity was significantly higher in placentas of patients with PE than in placentas from the control group (37.5% (9/24) vs. 8.7% (2/23); p = 0.036, respectively). (2) PAR-1 immunoreactivity was found in the cellular compartments of the placental villous tree, mainly in villous trophoblasts and stromal endothelial cells. (3) PAR-1 was detected in 92.3% (24/26) of the placentas of women with PE and in 88.5% (23/26) of the placentas from the control group (p = 1). Conclusion. Placentas from pregnancies complicated by preterm PE had a significantly higher frequency of strong PAR-1 expression than placentas from women with spontaneous preterm labor. This observation is consistent with a role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in PE. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of PAR-1, the major receptor for this enzyme. C1 [Erez, Offer; Romero, Roberto; Kim, Sung-Su; Kim, Jung-Sun; Kim, Yeon Mee; Wildman, Derek E.; Than, Nandor Gabor; Mazaki-Tovi, Shali; Gotsch, Francesca; Pineles, Beth; Kusanovic, Juan Pedro; Espinoza, Jimmy; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Dept Pathol, Detroit, MI 48201 USA. [Kim, Jung-Sun; Wildman, Derek E.; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Espinoza, Jimmy; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Obstet & Gynecol, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. RP Erez, O (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS [Z01 HD002400-16] NR 143 TC 23 Z9 23 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 6 BP 345 EP 355 DI 10.1080/14767050802034859 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 315LI UT WOS:000256881100001 PM 18570113 ER PT J AU Romero, R Espinoza, J Rogers, WT Moser, A Nien, JK Kusanovic, JP Gotsch, F Erez, O Gomez, R Edwin, S Hassan, SS AF Romero, Roberto Espinoza, Jimmy Rogers, Wade T. Moser, Allan Nien, Jyh Kae Kusanovic, Juan Pedro Gotsch, Francesca Erez, Offer Gomez, Ricardo Edwin, Sam Hassan, Sonia S. TI Proteomic analysis of amniotic fluid to identify women with preterm labor and intra-amniotic inflammation/infection: The use of a novel computational method to analyze mass spectrometric profiling SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE proteomics; preterm birth; intra-amniotic inflammation/infection; SELDI-TOF; mass spectrometry ID POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION SIGNATURE; NECROSIS-FACTOR-ALPHA; BLOOD-CELL COUNT; PREMATURE RUPTURE; MATRIX METALLOPROTEINASE-8; UREAPLASMA-UREALYTICUM; CLINICAL-SIGNIFICANCE; FUNCTIONAL GENOMICS; INTACT MEMBRANES AB Objective. Examination of the amniotic fluid proteome has been used to identify biomarkers for intra-amniotic inflammation as well as those that may be useful in predicting the outcome of preterm labor. The purpose of this study was to combine a novel computational method of pattern discovery with mass spectrometric proteomic profiling of amniotic fluid to discover biomarkers of intra-amniotic infection/inflammation (IAI). Methods. This cross-sectional study included patients with spontaneous preterm labor and intact membranes who delivered at term (n = 59) and those who delivered preterm with IAI (n 60). Proteomic profiling was performed using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry. A proteomic profile was acquired through multiple simultaneous SELDI conditions, which were combined in a single proteomic 'fingerprint' using a novel computational approach. Classification of patients based on their associated surface-enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectra as belonging to either the class of individuals with preterm delivery with IAI or term delivery was accomplished by constructing an empirical model. The first phase in the construction of this empirical model involved the selection of adjustable parameters utilizing a training/testing subset of data. The second phase tested the generalization of the model by utilizing a blinded validation set of patients who were not employed in parameter selection. Results. Gestational age at amniocentesis was not significantly different between the groups. Thirty-nine unique mass spectrometric peaks discriminated patients with preterm labor/delivery with IAI from those with preterm labor and term delivery. In the testing/training dataset, the classification accuracies (averaged over 100 random draws) were: 91.4% (40.2/44) for patients with preterm delivery with IAI, and 91.2% (40.1/44) for term delivery. The overall accuracy of the classification of patients in the validation dataset was 90.3% (28/31). Conclusions. Proteomic analysis of amniotic fluid allowed the identification of mass spectrometry features, which can distinguish patients with preterm labor with IAI from those with preterm labor without inflammation or infection who subsequently delivered at term. C1 [Romero, Roberto; Espinoza, Jimmy; Nien, Jyh Kae; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Edwin, Sam; Hassan, Sonia S.] Wayne State Univ, Perinatol Res Branch, NICHD,NIH,DHHS, Hutzel Womens Hosp, Detroit, MI 48201 USA. [Romero, Roberto; Espinoza, Jimmy; Nien, Jyh Kae; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Edwin, Sam; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Espinoza, Jimmy; Kusanovic, Juan Pedro; Erez, Offer; Hassan, Sonia S.] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Rogers, Wade T.; Moser, Allan] Cira Discovery Sci Inc, Cira Discovery Sci, Philadelphia, PA USA. [Gomez, Ricardo] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP, Puente Alto, Chile. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD,NIH,DHHS, Hutzel Womens Hosp, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-16] NR 101 TC 31 Z9 32 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 6 BP 367 EP 388 DI 10.1080/14767050802045848 PG 22 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 315LI UT WOS:000256881100004 PM 18570116 ER PT J AU Gotsch, F Romero, R Kusanovic, JP Chaiworapongsa, T Dombrowski, M Erez, O Than, NG Mazaki-Tovi, S Mittal, P Espinoza, J Hassan, SS AF Gotsch, Francesca Romero, Roberto Kusanovic, Juan Pedro Chaiworapongsa, Tinnakorn Dombrowski, Michael Erez, Offer Than, Nandor Gabor Mazaki-Tovi, Shali Mittal, Pooja Espinoza, Jimmy Hassan, Sonia S. TI Preeclampsia and small-for-gestational age are associated with decreased concentrations of a factor involved in angiogenesis: Soluble Tie-2 SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE SGA; intrauterine growth restriction; Tie-2; pregnancy; angiogenesis; angiopoietin ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; BED SPIRAL ARTERIES; BLOOD-VESSEL FORMATION; PLACENTAL BED; TUMOR ANGIOGENESIS; FETAL-GROWTH; IN-VITRO; NORMAL-PREGNANCY; CELL-SURVIVAL AB Objective. An anti-angiogenic state has been described in patients with preeclampsia, small-for-gestational age (SGA) fetuses and fetal death, and changes in the concentration of circulating angiogenic and anti-angiogenic factors can precede the clinical recognition of preeclampsia and SGA by several weeks. Gene deletion studies demonstrate that a selective group of endothelial growth factors are required for vascular development, including members of the vascular endothelial growth factor (VEGF) family, as well as angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), both ligands for the tyrosine kinase endothelial cell receptor Tie-2. These angiogenic factors have been proposed to promote angiogenesis in a coordinated and complementary fashion. Soluble Tie-2 (sTie-2) is the soluble form of the Tie-2 receptor, which is detectable in biological fluids. The purpose of this study was to determine whether patients with preeclampsia and mothers who deliver a SGA neonate have changes in the plasma concentrations of sTie-2. Study design. This cross-sectional study included patients in the following groups: (1) non-pregnant women (n = 40), (2) women with normal pregnancies (n 135), (3) patients with preeclampsia (n = 112), and (4) patients who delivered an SGA neonate (n 53). Maternal plasma concentrations of sTie-2 were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results. (1) The median maternal plasma concentration of sTie-2 was lower in normal pregnant women than in nonpregnant women [median 16.0 ng/mL (range 5.0-71.6) vs. median 20.7 ng/mL (range 10.8-52.4), respectively; p = 0.01)). (2) Plasma sTie-2 concentrations in normal pregnancy changed significantly as a function of gestational age. (3) Patients with preeclampsia and those who delivered SGA neonates had a lower median maternal plasma concentration of sTie-2 than those with a normal pregnancy [preeclampsia: median 14.9 ng/mL (range 4.9-67.3); SGA: median 10.9 ng/mL (range 5.1-29.1); normal pregnancy: median 16.0 ng/mL (range 5.0-71.6); p = 0.048 and p < 0.001, respectively]. (4) Patients with SGA neonates had a lower median plasma concentration of sTie-2 than that of those with preeclampsia [median 10.9 ng/mL (range 5.1-29.1) vs. median 14.9 ng/mL (range 4.9-67.3), respectively; p < 0.001]. (5) Patients with early-onset preeclampsia (<= 34 weeks) had lower concentrations of sTie-2 than women with late-onset preeclampsia (434 weeks) median of delta values: -0.13 ng/mL (range -0.47-0.58) vs. median of delta values: -0.09 ng/mL (range: -0.60-0.58), respectively; p = 0.043]. In contrast, there were no significant differences in the maternal plasma sTie-2 concentration between women with severe and mild preeclampsia (p = 0.6). Conclusion. Patients with preeclampsia and those with SGA fetuses have lower median plasma concentrations of soluble Tie-2 than women with normal pregnancies. C1 [Gotsch, Francesca; Romero, Roberto; Kusanovic, Juan Pedro; Dombrowski, Michael; Erez, Offer; Than, Nandor Gabor; Mazaki-Tovi, Shali; Mittal, Pooja; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Perinatol Res Branch, NICHD,NIH,DHHS, Hutzel Womens Hosp, Detroit, MI 48201 USA. [Gotsch, Francesca; Romero, Roberto; Kusanovic, Juan Pedro; Dombrowski, Michael; Erez, Offer; Than, Nandor Gabor; Mazaki-Tovi, Shali; Mittal, Pooja; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Erez, Offer; Mazaki-Tovi, Shali; Mittal, Pooja; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI 48201 USA. RP Gotsch, F (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD,NIH,DHHS, Hutzel Womens Hosp, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-16] NR 155 TC 36 Z9 38 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 6 BP 389 EP 402 DI 10.1080/14767050802046069 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 315LI UT WOS:000256881100005 PM 18570117 ER PT J AU Facchinetti, F Reddy, U Stray-Pedersen, B Baronciani, D Requejo, JH AF Facchinetti, F. Reddy, U. Stray-Pedersen, B. Baronciani, D. Requejo, J. Harris CA Stillbirth Int Grp TI International issues in stillbirth SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE stillbirth; diagnostic work-up; audit process; parents counselling; research AB The phenomenon of stillbirth has been poorly addressed in terms of reported statistics and as a clinical issue. A Study Group of the European Association of Perinatal Medicine reviewed the topic and highlighted specific issues. Such proposal were discussed in an open workshop held in Modena, Italy last year and this paper reports the final recommendations. Briefly, at least 22 completed weeks of gestation was endorsed as definition for including SB in statistics and for clinical studies. A minimum diagnostic work-up was suggested together with the emphasis toward a local, multidisciplinary audit process, in order to comprehend causality. Attention for parents emotional support and appropriate counselling was believed as essential part of the clinical process. Finally, the need for funding comprehensive research programs in SB through international, multidisciplinary involvement was believed mandatory for developing effective preventative strategies to avert the devastating occurrence of stillbirth. C1 [Facchinetti, F.] Univ Modena & Reggio Emilia, Unit Obstet & Gynecol, Mother Infant Dept, Modena, Italy. [Reddy, U.] NICHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Stray-Pedersen, B.] Univ Oslo, Dept Obstet & Gynecol, Rikshosp HF, Oslo, Norway. [Baronciani, D.] NHS Ctr Evaluat Effectiveness Hlth Care, CeVEAS, Modena, Italy. [Requejo, J. Harris] Univ Texas Austin, Populat Res Ctr, Austin, TX 78712 USA. RP Facchinetti, F (reprint author), Univ Modena, Azienda Osped, Mother Infant Dept, Via Pozzo 71, I-41100 Modena, Italy. EM Facchi@unimore.it RI Facchinetti, Fabio/K-9929-2014 OI Facchinetti, Fabio/0000-0003-4694-9564 NR 0 TC 8 Z9 8 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 6 BP 425 EP 428 DI 10.1080/14767050802040849 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 315LI UT WOS:000256881100010 PM 18570122 ER PT J AU Than, NG Erez, O Wildman, DE Tarca, AL Edwin, SS Abbas, A Hotra, J Kusanovic, JP Gotsch, F Hassan, SS Espinoza, J Papp, Z Romero, R AF Than, Nandor Gabor Erez, Offer Wildman, Derek E. Tarca, Adi L. Edwin, Samuel S. Abbas, Asad Hotra, John Kusanovic, Juan Pedro Gotsch, Francesca Hassan, Sonia S. Espinoza, Jimmy Papp, Zoltan Romero, Roberto TI Severe preeclampsia is characterized by increased placental expression of galectin-1 SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) DE glycocode; inflammation; lectin; pregnancy; semi-allograft; tolerance; trophoblast ID ENDOTHELIAL GROWTH-FACTOR; GALACTOSIDE-BINDING LECTIN; FOR-GESTATIONAL-AGE; FACTOR RECEPTOR-1 CONCENTRATION; HUMAN CHORIONIC-GONADOTROPIN; FRIEDENREICH TF ANTIGEN; TUMOR-IMMUNE PRIVILEGE; UTERINE ARTERY DOPPLER; AMINO-ACID-SEQUENCE; BED SPIRAL ARTERIES AB Objective. Galectin-1 is a major anti-inflammatory protein expressed by the placenta and immune cells that can bias the character of inflammatory responses toward the Th2 type. Galectin-1 is expressed in immune privileged sites, it can facilitate immune tolerance and tumor immune escape, and it has been successfully used for the suppression of experimental autoimmune diseases as well as graft-versus-host disease in murine models. We propose that an abnormal immune response in some pregnancy complications may be associated with changes in placental expression of galectin-1. To test this hypothesis, we studied placental galectin-1 mRNA and protein expression and localization in women with preeclampsia (PE) and in those who delivered a small-for-gestational age (SGA) neonate. Study design. This cross-sectional study included pregnant women matched for gestational age at delivery in the following groups: (1) severe PE (n = 10), (2) severe PE complicated with SGA (n = 10), (3) SGA without PE (n = 10), and (4) controls (n = 10). Galectin-1 mRNA and protein were localized in placentas by in situ hybridization and immunofluorescence microscopy. Galectin-1 mRNA expression was determined by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and galectin-1 protein content by Western blot. Non-parametric statistics were used for analysis. Results. (1) In normal term placentas, galectin-1 mRNA or immunofluorescence signals were detected in the trophoblasts, villous stromal cells, Hofbauer cells, endothelial cells of the villous blood vessels, and the villous stroma. (2) Placental galectin-1 mRNA expression was significantly higher in severe PE (with or without SGA) than in controls (1.47-fold, p = 0.004; 1.44-fold, p = 0.003, respectively) and in SGA (1.68-fold, p = 0.001; 1.64-fold, p = 0.001, respectively). (3) Trophoblasts in placentas of patients with severe PE had the most intense galectin-1 immunostaining. Conclusions. (1) We report for the first time the placental expression and localization of galectin-1 mRNA and demonstrate that the protein is abundantly present in third trimester human placentas. (2) Placental galectin-1 expression is higher in severe PE than in normal pregnancy regardless of the presence of SGA. (3) However, it is not altered in SGA without PE. We propose that the increased placental expression of galectin-1 in patients with severe PE may represent a fetal response to an exaggerated systemic maternal inflammation; thus, galectin-1 may be implicated in maternal-fetal immune tolerance in humans. C1 [Than, Nandor Gabor; Erez, Offer; Wildman, Derek E.; Tarca, Adi L.; Edwin, Samuel S.; Abbas, Asad; Hotra, John; Kusanovic, Juan Pedro; Gotsch, Francesca; Hassan, Sonia S.; Espinoza, Jimmy; Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS, Detroit, MI 48201 USA. [Erez, Offer; Wildman, Derek E.; Kusanovic, Juan Pedro; Hassan, Sonia S.; Espinoza, Jimmy] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA. [Wildman, Derek E.; Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Sch Med, Detroit, MI 48201 USA. [Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, H-1085 Budapest, Hungary. RP Than, NG (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM nthan@med.wayne.edu; prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-16] NR 146 TC 31 Z9 32 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 7 BP 429 EP 442 DI 10.1080/14767050802041961 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 315LJ UT WOS:000256881200001 PM 18570123 ER PT J AU Chaiworapongsa, T Erez, O Kusanovic, JP Vaisbuch, E Mazaki-Tovi, S Gotsch, F Than, NG Mittal, P Kim, YM Camacho, N Edwin, S Gomez, R Hassan, SS Romero, R AF Chaiworapongsa, Tinnakorn Erez, Offer Kusanovic, Juan Pedro Vaisbuch, Edi Mazaki-Tovi, Shali Gotsch, Francesca Than, Nandor Gabor Mittal, Pooja Kim, Yeon Mee Camacho, Natalia Edwin, Samuel Gomez, Ricardo Hassan, Sonia S. Romero, Roberto TI Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE HSP70; intra-amniotic infection; preterm labor; preterm prelabor rupture of membranes; histologic chorioamnionitis; parturition ID HEAT-SHOCK PROTEINS; ENDOGENOUS EXTRACELLULAR HEAT-SHOCK-PROTEIN-72; FETAL INFLAMMATORY RESPONSE; MESSENGER-RIBONUCLEIC-ACID; NECROSIS-FACTOR-ALPHA; IMMUNE-RESPONSE; MOLECULAR CHAPERONES; STRESS-PROTEINS; MYCOBACTERIUM-TUBERCULOSIS; INTRAAMNIOTIC INFECTION AB Objective. Heat shock protein (HSP) 70, a conserved member of the stress protein family, is produced in almost all cell types in response to a wide range of stressful stimuli, and its production has a survival value. Evidence suggests that extracellular HSP70 is involved in the activation of the innate and adaptive immune response. Furthermore, increased mRNA expression of HSP70 has been observed in human fetal membranes following endotoxin stimulation. This study was conducted to determine the changes in amniotic fluid HSP70 concentrations during pregnancy, term and preterm parturition, intra-amniotic infection (IAI), and histologic chorioamnionitis. Study design. A cross-sectional study was conducted in 376 pregnant women in the following groups: (1) women with a normal pregnancy who were classified into the following categories: (a) women in the mid-trimester (14-18 weeks) who underwent amniocentesis for genetic indications and delivered normal infants at term (n = 72); (b) women at term not in labor (n = 23); and (c) those at term in labor (n = 48). (2) Women with spontaneous preterm labor and intact membranes who were subdivided into the following categories: (a) preterm labor who delivered at term without IAI (n = 42); (b) preterm labor who delivered preterm without IAI (n = 57); and (c) preterm labor and delivery with IAI (n = 30). (3) Women with preterm prelabor rupture of membranes (PROM) with (n = 50) and without (n = 54) IAI. Among patients with preterm labor with intact membranes and preterm PROM who delivered within 72 hours of amniocentesis, placenta, umbilical cord, and chorioamniotic membranes were collected and assessed for the presence or absence of acute inflammatory lesions in the extraplacental membranes (histologic chorioamnionitis) and/or umbilical cords (funisitis). HSP70 concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered statistically significant. Results. Immunoreactive HSP70 was detected in 88% (332/376) of amniotic fluid samples. The median amniotic fluid HSP70 concentration was significantly higher in women at term without labor than in those in the mid-trimester (term no labor: median 34.9 ng/mL, range 0-78.1 ng/mL vs. mid-trimester; median 6.6 ng/mL, range 0-20.8 ng/mL; p < 0.001). Among patients with spontaneous preterm labor and preterm PROM, those with IAI had a significantly higher median amniotic fluid HSP70 concentration than those without IAI (preterm labor with IAI: median 82.9 ng/mL, range 0 - 500 ng/mL vs. preterm labor without IAI: median 41.7 ng/mL, range 0-244 ng/mL; p = 0.001; preterm PROM with IAI: median 86.5 ng/mL, range 0-428 ng/ mL vs. preterm PROM without IAI: median 55.9 ng/mL, range 14.9-299.9 ng/ mL; p = 0.007). There was no significant difference in the median amniotic fluid HSP70 concentration between patients with preterm labor who delivered preterm without IAI and those who delivered at term (p = 0.6). However, among patients with preterm labor without IAI, there was an inverse relationship between amniotic fluid concentration of HSP70 and the amniocentesis-to-spontaneous delivery interval (Spearman's Rho = -70.26; p = 0.02). Patients with histologic chorioamnionitis/funisitis had a significantly higher median amniotic fluid HSP70 concentration than those without inflammation (inflammation: median 108.7 ng/mL, range 0-500 ng/mL vs. without inflammation: median 67.9 ng/mL, range 7.1-299.9 ng/mL; p = 0.02). Women at term in labor had a median amniotic fluid concentration of HSP70 significantly higher than those not in labor (term in labor: median 60.7 ng/mL, range 0-359.9 ng/mL vs. term not in labor: median 34.9 ng/mL, range 0-78.1 ng/mL; p = 0.02). Conclusions. Intra-amniotic infection, histologic chorioamnionitis, and term parturition are associated with elevated amniotic fluid HSP70 concentrations. HSP70 plays a role in the host defense mechanism by activating the innate arm of the immune response in women with intrauterine infection. The mechanisms of preterm and term parturition in humans may involve extracellular HSP70. C1 [Chaiworapongsa, Tinnakorn; Erez, Offer; Kusanovic, Juan Pedro; Vaisbuch, Edi; Mazaki-Tovi, Shali; Gotsch, Francesca; Than, Nandor Gabor; Mittal, Pooja; Kim, Yeon Mee; Camacho, Natalia; Edwin, Samuel; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Erez, Offer; Kusanovic, Juan Pedro; Vaisbuch, Edi; Mazaki-Tovi, Shali; Gotsch, Francesca; Than, Nandor Gabor; Mittal, Pooja; Kim, Yeon Mee; Camacho, Natalia; Edwin, Samuel; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Chaiworapongsa, Tinnakorn; Erez, Offer; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Mittal, Pooja; Camacho, Natalia; Hassan, Sonia S.] Wayne State Univ, Dept Gynecol & Obstet, Sch Med, Detroit, MI 48201 USA. [Kim, Yeon Mee] Wayne State Univ, Dept Pathol, Sch Med, Detroit, MI 48201 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Ctr Perinatal Diag & Res CEDIP, Sotero Rio Hosp, Puente Alto, Chile. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural NIH HHS [Z01 HD002400-16] NR 148 TC 50 Z9 50 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 7 BP 449 EP 461 DI 10.1080/14767050802054550 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 315LJ UT WOS:000256881200003 PM 18570125 ER PT J AU Gotsch, F Romero, R Kusanovic, JP Erez, O Espinoza, J Kim, CJ Vaisbuch, E Than, NG Mazaki-Tovi, S Chaiworapongsa, T Mazor, M Yoon, BH Edwin, S Gomez, R Mittal, P Hassan, SS Sharma, S AF Gotsch, Francesca Romero, Roberto Kusanovic, Juan Pedro Erez, Offer Espinoza, Jimmy Kim, Chong Jai Vaisbuch, Edi Than, Nandor Gabor Mazaki-Tovi, Shali Chaiworapongsa, Tinnakorn Mazor, Moshe Yoon, Bo Hyun Edwin, Samuel Gomez, Ricardo Mittal, Pooja Hassan, Sonia S. Sharma, Surendra TI The anti-inflammatory limb of the immune response in preterm labor, intra-amniotic infection/inflammation, and spontaneous parturition at term: A role for interleukin-10 SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE pregnancy; inflammation; anti-inflammation; IL-10; cytokine; amniotic fluid; mid-trimester ID TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; AMNIOTIC-FLUID INTERLEUKIN-6; TRANSFORMING-GROWTH-FACTOR; HUMAN MYOMETRIAL CELLS; PROSTAGLANDIN E-2 PRODUCTION; SYNTHESIS INHIBITORY FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; RECOMBINANT HUMAN INTERLEUKIN-10 AB Objective. The anti-inflammatory limb of the immune response is crucial for dampening inflammation. Spontaneous parturition at term and preterm labor (PTL) are mediated by inflammation in the cervix, membranes, and myometrium. This study focuses on the changes in the amniotic fluid concentrations of the anti-inflammatory cytokine interleukin (IL)-10. The objectives of this study were to determine whether there is a relationship between amniotic fluid concentrations of IL-10 and gestational age, parturition (at term and preterm), and intra-amniotic infection/inflammation (IAI). Study design. A cross-sectional study was conducted including 301 pregnant women in the following groups: (1) mid-trimester of pregnancy who delivered at term (n=112); (2) mid-trimester who delivered preterm neonates (n=30); (3) term not in labor without IAI (n=40); (4) term in labor without IAI (n=24); (5) term in labor with IAI (n=20); (6) PTL without IAI who delivered at term (n=31); (7) PTL without IAI who delivered preterm (n=30); (8) PTL with IAI who delivered preterm (n=14). IL-10 concentrations in amniotic fluid were determined by a specific and sensitive immunoassay. Non-parametric statistics were used for analysis. Results. (1) IL-10 was detectable in amniotic fluid and its median concentration did not change with gestational age from mid-trimester to term. (2) Patients in labor at term had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term not in labor (p=0.04). (3) Women at term in labor with IAI had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term in labor without IAI (p=0.02). (4) Women with PTL and IAI who delivered preterm had a significantly higher median amniotic fluid concentration of IL-10 than those without IAI who delivered preterm and than those who delivered at term (p=0.009 and p < 0.001, respectively). (5) Among patients with preterm labor without IAI, those who delivered preterm had a significantly higher median amniotic fluid IL-10 concentration than those who delivered at term (p=0.03). Conclusions. The anti-inflammatory cytokine IL-10 is detectable in the amniotic fluid of normal pregnant women. Spontaneous parturition at term and in preterm gestation is associated with increased amniotic fluid concentrations of IL-10. IAI (preterm and at term) is also associated with increased amniotic fluid concentrations of IL-10. We propose that IL-10 has a role in the regulation of the immune response invivo by initiating actions that dampen inflammation. C1 [Gotsch, Francesca; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Kim, Chong Jai; Vaisbuch, Edi; Than, Nandor Gabor; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Edwin, Samuel; Mittal, Pooja; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Gomez, Ricardo] Catholic Univ Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Sharma, Surendra] Brown Univ, Dept Pediat & Pathol, Providence, RI 02912 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 219 TC 73 Z9 75 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 8 BP 529 EP 547 DI 10.1080/14767050802127349 PG 19 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 339PX UT WOS:000258590600004 PM 18609361 ER PT J AU Goudar, SS Chakraborty, H Edlavitch, SA Naik, VA Bellad, MB Patted, SS Patel, A Moore, J Mcclure, EM Hartwell, T Moss, N Derman, RJ Kodkany, BS Geller, SE AF Goudar, Shivaprasad S. Chakraborty, Hrishikesh Edlavitch, Stanley A. Naik, Vijaya A. Bellad, M. B. Patted, Shobhana S. Patel, Ashlesha Moore, Janet Mcclure, Elizabeth M. Hartwell, Tyler Moss, Nancy Derman, Richard J. Kodkany, Bhalchandra S. Geller, Stacie E. TI Variation in the postpartum hemorrhage rate in a clinical trial of oral misoprostol SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE postpartum hemorrhage; PPH; misoprostol; provider skills; training monitoring ID RISK-FACTORS AB Objective. The main objective of this study was to identify factors associated with variation in the rate of acute postpartum hemorrhage (PPH), defined as blood loss 500mL within 2 hours of delivery, observed in a randomized clinical trial of misoprostol for the prevention of PPH, conducted in rural India. Although the women in the misoprostol group had a significantly lower probability of having a PPH, we also noted a reduction in the rate of PPH in the placebo group over the course of the study. We hypothesized that this was due to the changing skills of the auxiliary nurse midwives (ANMs) over the course of the study. Methods. We conducted a post-hoc analysis examining variation in PPH rates over the duration of the trial among the women randomized to the placebo arm (n=808). Descriptive, correlation analysis and generalized estimating equations (GEE) were used to predict PPH rates. With no direct measure of ANM skills, we used proxy measures, including: (1) the ANM's point of entry into the study (original ANMs at the initiation of the trial were less skilled than replacement ANMs); (2) the study duration, representing exposure of the ANM to ongoing training and monitoring; and (3) duration of the second stage of labor as a measure of improved delivery practices. Results. As the study duration increased, the duration of the second stage of labor decreased (-0.12, p=0.001) and as the duration of the second stage of labor decreased, the rate of PPH decreased (0.0282; 95% CI 0.0201-0.0363). For each 10-minute increase in the duration of second stage labor increased PPH odds by 7.1% and each 30-day duration of the trial decreased PPH odds by 3.4%. Additionally, a patient delivered by an original ANM was 3.14 times more likely to have a PPH compared to a patient delivered by a replacement ANM. Conclusions. Declining PPH rates were associated with improved skills and delivery practices that decreased duration of the second stage of labor. These improvements appeared to be consistent with the introduction of the more skilled replacement ANMs as well as ongoing training and monitoring for all ANMs over the duration of the trial. C1 [Goudar, Shivaprasad S.] Jawaharlal Nehru Med Coll, Dept Med Educ, Belgaum 590010, Karnataka, India. [Chakraborty, Hrishikesh; Moore, Janet; Mcclure, Elizabeth M.; Hartwell, Tyler] RTI Int, Res Triangle Pk, NC USA. [Edlavitch, Stanley A.; Derman, Richard J.] Univ Missouri, Kansas City Sch Med, Kansas City, MO 64108 USA. [Patel, Ashlesha] John H Stroger Jr Hosp Cook Cty, Chicago, IL USA. [Moss, Nancy] NICHHD, Chicago, IL USA. [Geller, Stacie E.] Univ Illinois, Chicago Coll Med, Chicago, IL USA. RP Goudar, SS (reprint author), Jawaharlal Nehru Med Coll, Dept Med Educ, Belgaum 590010, Karnataka, India. EM sgoudar@jnmc.edu OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053 FU NICHD NIH HHS [1 U01 HD42372-01] NR 14 TC 10 Z9 10 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 8 BP 559 EP 564 DI 10.1080/14767050802132158 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 339PX UT WOS:000258590600007 PM 18609354 ER PT J AU Gotsch, F Romero, R Chaiworapongsa, T Erez, O Vaisbuch, E Espinoza, J Kusanovic, JP Mittal, P Mazaki-Tovi, S Kim, CJ Kim, JS Edwin, S Nhan-Chang, CL Hamill, N Friel, L Than, NG Mazor, M Yoon, BH Hassan, SS AF Gotsch, Francesca Romero, Roberto Chaiworapongsa, Tinnakorn Erez, Offer Vaisbuch, Edi Espinoza, Jimmy Kusanovic, Juan Pedro Mittal, Pooja Mazaki-Tovi, Shali Kim, Chong Jai Kim, Jung Sun Edwin, Samuels Nhan-Chang, Chia-Ling Hamill, Neil Friel, Laraa Than, Nandor Gabor Mazor, Moshe Yoon, Bo Hyun Hassan, Sonia S. TI Evidence of the involvement of caspase-1 under physiologic and pathologic cellular stress during human pregnancy: A link between the inflammasome and parturition SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE interleukin-1 converting enzyme; labor; delivery; intra-amniotic infection; intra-amniotic inflammation; chorioamnionitis; preterm birth; inflammasome ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; TUMOR-NECROSIS-FACTOR; GAMMA-INDUCING FACTOR; HUMAN GESTATIONAL TISSUES; HUMAN MYOMETRIAL CELLS; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; MONOCYTE CHEMOTACTIC PROTEIN-1; AMNIOTIC-FLUID INTERLEUKIN-6; CYTOPLASMIC GROUND SUBSTANCE; NATURAL-KILLER-CELLS AB Objective. Caspase-1 is a component of the NALP3 inflammasome, a cytosolic multiprotein complex that mediates the processing of pro-inflammatory caspases and cytokines. The inflammasome represents the first line of defense against cellular stress and is a crucial component of innate immunity. Caspase-1 is the enzyme responsible for the cleavage and activation of interleukin (IL)-1, which is a potent pro-inflammatory cytokine, and plays a central role in the mechanisms leading to labor (preterm and term) particularly in the context of intrauterine infection/inflammation. In addition, caspase-1 cleaves IL-18 and IL-33. The objectives of this study were to determine whether there is a relationship between amniotic fluid concentrations of caspase-1 and gestational age, parturition (term and preterm), and intra-amniotic infection/inflammation (IAI). Study design. A cross-sectional study was conducted including 143 pregnant women in the following groups: (1) mid-trimester of pregnancy (n=18); (2) term not in labor (n=25); (3) term in labor (n=28); (4) preterm labor (PTL) who delivered at term (n=23); (5) PTL without IAI who delivered preterm (n=32); (6) PTL with IAI who delivered preterm neonates (n=17). Caspase-1 concentrations in amniotic fluid were determined by a specific and sensitive immunoassay. Non-parametric statistics were used for analysis. Results. (1) Caspase-1 was detected in amniotic fluid of women at term, but in none of the mid-trimester samples. (2) Patients in labor at term had a significantly higher median amniotic fluid concentration of caspase-1 than women at term not in labor (term in labor: 10.5pg/mL, range 0.0-666.0 vs. term not in labor: 5.99pg/mL, range 0.0-237.4; p0.05). (3) Among patients with spontaneous PTL, those with IAI (median 41.4pg/mL, range 0.0-515.0) had a significantly higher median amniotic fluid caspase-1 concentration than those without IAI who delivered preterm (median 0.0pg/mL, range 0.0-78.4) and than those who delivered at term (median 0.0pg/mL, range 0.0-199.5); p0.001 for both comparisons. Conclusions. (1) The presence and concentration of caspase-1 in the amniotic fluid varies as a function of gestational age. (2) Women with spontaneous labor at term had a higher median caspase-1 amniotic fluid concentration than women at term without labor. This suggests that the inflammasome may be activated in spontaneous parturition at term. Since most women with labor do not have intra-amniotic infection, we propose that cellular stress during labor accounts for activation of the inflammasome. (3) Preterm labor associated with infection/inflammation was also associated with a high concentration of caspase-1, suggesting that infection may induce caspase-1 production and activation of the inflammasome. (4) The sequential activation of the inflammasome and caspase-1, leading to interleukin-1 processing and secretion, is a candidate pathway leading to the activation of the common pathway of parturition. C1 [Gotsch, Francesca; Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Vaisbuch, Edi; Espinoza, Jimmy; Kusanovic, Juan Pedro; Mittal, Pooja; Mazaki-Tovi, Shali; Kim, Chong Jai; Kim, Jung Sun; Edwin, Samuels; Nhan-Chang, Chia-Ling; Hamill, Neil; Friel, Laraa; Than, Nandor Gabor; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Gotsch, Francesca; Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Vaisbuch, Edi; Espinoza, Jimmy; Kusanovic, Juan Pedro; Mittal, Pooja; Mazaki-Tovi, Shali; Kim, Chong Jai; Kim, Jung Sun; Edwin, Samuels; Nhan-Chang, Chia-Ling; Hamill, Neil; Friel, Laraa; Than, Nandor Gabor; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Erez, Offer; Espinoza, Jimmy; Kusanovic, Juan Pedro; Mittal, Pooja; Mazaki-Tovi, Shali; Nhan-Chang, Chia-Ling; Hamill, Neil; Friel, Laraa; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI 48201 USA. [Kim, Chong Jai; Kim, Jung Sun] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD NIH DHHS, Hutzel Womens Hosp, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Developmente; NIH; DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 152 TC 45 Z9 46 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 9 BP 605 EP 616 DI 10.1080/14767050802212109 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 355FX UT WOS:000259695900003 PM 18828051 ER PT J AU Nien, JK Romero, R Hoppensteadt, D Erez, O Espinoza, J Soto, E Kusanovic, JP Gotsch, F Kim, CJ Mittal, P Fareed, J Santolaya, J Chaiworapongsa, T Edwin, S Pineles, B Hassan, S AF Nien, Jyh Kae Romero, Roberto Hoppensteadt, Debra Erez, Offer Espinoza, Jimmy Soto, Eleazar Kusanovic, Juan Pedro Gotsch, Francesca Kim, Chong Jai Mittal, Pooja Fareed, Jawed Santolaya, Joaquin Chaiworapongsa, Tinnakorn Edwin, Samuel Pineles, Beth Hassan, Sonia TI Pyelonephritis during pregnancy: A cause for an acquired deficiency of protein Z SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE bacteremia; inflammation; pregnancy; factor X; coagulation ID TUMOR-NECROSIS-FACTOR; TISSUE FACTOR PATHWAY; Z PLASMA-LEVELS; ACTIVATED RECEPTORS; ENDOTHELIAL-CELLS; BLOOD-COAGULATION; FACTOR VIIA; FACTOR-XA; FACTOR-ALPHA; PROTHROMBOTIC PHENOTYPE AB Objective. Pyelonephritis has a more severe course during pregnancy than in the non-pregnant state. This has been attributed to the increased susceptibility of pregnant women to microbial products. An acquired protein Z deficiency has been reported when there is excessive thrombin activity. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma protein Z concentrations. Study design. A cross-sectional study was conducted to compare plasma protein Z concentrations between normal pregnant women (N=71) and pregnant women with pyelonephritis (N=42). Protein Z concentrations were measured by enzyme-linked immunosorbent assay. Parametric and non-parametric statistics were used for analysis. Results. Patients with pyelonephritis had a significantly lower median plasma concentration of protein Z than did patients with normal pregnancies (median 2.14g/mL (0.4-3.4) vs. median 2.36g/mL (1.09-3.36); p=0.03). There was no difference in the median plasma concentration of anti-protein Z antibodies between patients with pyelonephritis and those with normal pregnancies. Conclusion. The median maternal plasma protein Z concentration was significantly lower in patients with pyelonephritis during pregnancy than in patients with normal pregnancies. C1 [Nien, Jyh Kae; Romero, Roberto; Erez, Offer; Espinoza, Jimmy; Soto, Eleazar; Kusanovic, Juan Pedro; Gotsch, Francesca; Kim, Chong Jai; Mittal, Pooja; Santolaya, Joaquin; Chaiworapongsa, Tinnakorn; Edwin, Samuel; Pineles, Beth; Hassan, Sonia] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Nien, Jyh Kae; Romero, Roberto; Erez, Offer; Espinoza, Jimmy; Soto, Eleazar; Kusanovic, Juan Pedro; Gotsch, Francesca; Kim, Chong Jai; Mittal, Pooja; Santolaya, Joaquin; Chaiworapongsa, Tinnakorn; Edwin, Samuel; Pineles, Beth; Hassan, Sonia] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Hoppensteadt, Debra; Fareed, Jawed] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Erez, Offer; Espinoza, Jimmy; Kusanovic, Juan Pedro; Mittal, Pooja; Santolaya, Joaquin; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-17] NR 112 TC 9 Z9 9 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 9 BP 629 EP 637 DI 10.1080/14767050802214659 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 355FX UT WOS:000259695900006 PM 18828054 ER PT J AU Chaiworapongsa, T Hong, JS Hull, WM Kim, CJ Gomez, R Mazor, M Romero, R Whitsett, JA AF Chaiworapongsa, Tinnakorn Hong, Joon-Seok Hull, William M. Kim, Chong Jai Gomez, Ricardo Mazor, Moshe Romero, Roberto Whitsett, Jeffrey A. TI The concentration of surfactant protein - A in amniotic fluid decreases in spontaneous human parturition at term SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE surfactant protein; SP-A; SP-B; amniotic fluid; term; labor; parturition ID A-DEFICIENT MICE; PULMONARY SURFACTANT; II CELLS; PRETERM PARTURITION; MICROBIAL INVASION; SPONTANEOUS LABOR; FETAL MEMBRANES; MESSENGER-RNA; LUNG MATURITY; SP-B AB Objective. The fetus is thought to play a central role in the onset of labor. Pulmonary surfactant protein (SP)-A, secreted by the maturing fetal lung, has been implicated in the mechanisms initiating parturition in mice. The present study was conducted to determine whether amniotic fluid concentrations of SP-A and SP-B change during human parturition. Study design. Amniotic fluid SP-A and SP-B concentrations were measured with a sensitive and specific ELISA in the following groups of pregnant women: (1) mid-trimester of pregnancy, between 15 and 18 weeks of gestation (n=29), (2) term pregnancy not in labor (n=28), and (3) term pregnancy in spontaneous labor (n=26). Non-parametric statistics were used for analysis. Results. SP-A was detected in all amniotic fluid samples. SP-B was detected in 24.1% (7/29) of mid-trimester samples and in all samples at term. The median amniotic fluid concentrations of SP-A and SP-B were significantly higher in women at term than in women in the mid-trimester (SP-A term no labor: median 5.6g/mL, range 2.2-15.2g/mL vs. mid-trimester: median 1.64g/mL, range 0.1-4.7g/mL, and SP-B term no labor: median 0.54g/mL, range 0.17-1.99g/mL vs. mid-trimester: median 0g/mL, range 0-0.35g/mL; both p0.001). The median amniotic fluid SP-A concentration in women at term in labor was significantly lower than that in women at term not in labor (term in labor: median 2.7g/mL, range 1.2-10.1g/mL vs. term no labor: median 5.6g/mL, range 2.2-15.2g/mL; p0.001). There was no significant difference in the median amniotic fluid SP-B concentrations between women in labor and those not in labor (term in labor: median 0.47g/mL, range 0.04-1.32g/mL vs. term no labor: median 0.54g/mL, range 0.17-1.99g/mL; p=0.2). Conclusion. The amniotic fluid concentration of SP-A decreases in spontaneous human parturition at term. C1 [Chaiworapongsa, Tinnakorn; Hong, Joon-Seok; Kim, Chong Jai; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Chaiworapongsa, Tinnakorn; Hong, Joon-Seok; Kim, Chong Jai; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Hull, William M.; Whitsett, Jeffrey A.] Univ Cincinnati, Coll Med, Div Pulm Biol, Cincinnati Childrens Hosp Med Ctr,Dept Pediat, Cincinnati, OH USA. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Sotero Rio Hosp, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Mazor, Moshe] Ben Gurion Univ Negev, Dept Obstet & Gynecol, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 54 TC 9 Z9 9 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 9 BP 652 EP 659 DI 10.1080/14767050802215193 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 355FX UT WOS:000259695900010 PM 18828058 ER PT J AU Chaiworapongsa, T Hong, JS Hull, WM Romero, R Whitsett, JA AF Chaiworapongsa, Tinnakorn Hong, Joon-Seok Hull, William M. Romero, Roberto Whitsett, Jeffrey A. TI Amniotic fluid concentration of surfactant proteins in intra-amniotic infection SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE surfactant protein; SP-A; SP-B; SP-D; intra-amniotic infection; amniotic fluid; preterm labor; preterm parturition ID TUMOR-NECROSIS-FACTOR; PULMONARY SURFACTANT; BRONCHOPULMONARY DYSPLASIA; LUNG MATURATION; CEREBRAL-PALSY; FACTOR-ALPHA; FETAL SHEEP; SP-B; CYTOKINES INTERLEUKIN-6; INTRAUTERINE INFECTION AB Objective. Pulmonary surfactant is a complex molecule of lipids and proteins synthesized and secreted by type II alveolar cells into the alveolar epithelial lining. Both lipid and protein components are essential for lung function in postnatal life. Infection is a well-established cause of preterm delivery, and several inflammatory cytokines play a role in the mechanisms of preterm parturition. An increased concentration of inflammatory cytokines in amniotic fluid or fetal plasma has been linked to the onset of preterm parturition and fetal/neonatal injury, including cerebral palsy and chronic lung disease. Experimental evidence indicates that inflammatory mediators also regulate surfactant protein synthesis, and histologic chorioamnionitis is associated with a decreased incidence of hyaline membrane disease in neonates. This study was conducted to determine if amniotic fluid concentrations of surfactant protein (SP)-A, SP-B, and SP-D change in patients with and without intra-amniotic infection (IAI). Materials and methods. A case-control study was conducted to determine amniotic fluid concentrations of SP-A, SP-B, SP-D, and total protein in patients who had an amniocentesis performed between 18 and 34 weeks of gestation for the detection of IAI in patients with spontaneous preterm labor with intact membranes (n=42) and cervical insufficiency prior to the application of cerclage (n=6). Amniotic fluid samples were selected from a bank of biological specimens and included patients with (n=16) and without (n=32) IAI matched for gestational age at amniocentesis. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Each group was further subdivided according to a history of corticosteroid administration within 7 days prior to amniocentesis into the following subgroups: (1) patients without IAI who had received antenatal corticosteroids (n=21), (2) patients with IAI who had received antenatal corticosteroids (n=9), (3) patients without IAI who had not received antenatal corticosteroids (n=11), and (4) patients with IAI who had not received antenatal corticosteroids (n=7). Amniotic fluid was obtained by transabdominal amniocentesis. SP-A, SP-B, and SP-D concentrations in amniotic fluid were determined by enzyme-linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis. Results. Women with IAI had a higher median amniotic fluid concentration of SP-B and of SP-B/total protein, but not other SPs, than those without IAI (both p=0.03). Among patients who had received antenatal corticosteroids, the median amniotic fluid concentration of SP-B and of SP-B/total protein was significantly higher in patients with IAI than in those without IAI (SP-B, IAI: median 148ng/mL, range 37.3-809ng/mL vs. without IAI: median 7.2ng/mL, range 0-1035ng/mL; p=0.005 and SP-B/total protein, IAI: median 14.1ng/mg, range 4.3-237.5ng/mg vs. without IAI: median 1.45ng/mg, range 0-79.5ng/mg; p=0.003). Among women who had not received antenatal corticosteroids, the median amniotic fluid concentrations of SP-B and of SP-B/total protein were not significantly different between patients with and without IAI (SP-B, IAI: median 4ng/mL, range 0-31.4ng/mL vs. without IAI: median 3.4ng/mL, range 0-37ng/mL; p=0.8 and SP-B/total protein, IAI: median 0.55ng/mg, range 0-6.96ng/mg vs. without IAI: median 0.59ng/mg, range 0-3.28ng/mg; p=0.9). The median amniotic fluid concentrations of SP-A, SP-A/total protein, SP-D, and SP-D/total protein were not significantly different between patients with and without IAI whether theyreceived antenatal corticosteroids or not (all p0.05). Conclusions. IAI was associated with an increased amniotic fluid concentration of SP-B in patients who received antenatal corticosteroids within 7 days prior to amniocentesis. C1 [Chaiworapongsa, Tinnakorn; Hong, Joon-Seok; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Chaiworapongsa, Tinnakorn; Hong, Joon-Seok; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Hull, William M.; Whitsett, Jeffrey A.] Univ Cincinnati, Coll Med, Dept Pediat, Div Pulm Biol,Cincinnati Childrens Hosp,Med Ctr, Cincinnati, OH USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 50 TC 17 Z9 18 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 9 BP 663 EP 670 DI 10.1080/14767050802215664 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 355FX UT WOS:000259695900012 PM 18828060 ER PT J AU Bujold, E Romero, R Kusanovic, JP Erez, O Gotsch, F Chaiworapongsa, T Gomez, R Espinoza, J Vaisbuch, E Kim, YM Edwin, S Pisano, M Allen, B Podust, VN Dalmasso, EA Rutherford, J Rogers, W Moser, A Yoon, BH Barder, T AF Bujold, Emmanuel Romero, Roberto Kusanovic, Juan Pedro Erez, Offer Gotsch, Francesca Chaiworapongsa, Tinnakorn Gomez, Ricardo Espinoza, Jimmy Vaisbuch, Edi Kim, Yeon Mee Edwin, Samuel Pisano, Mike Allen, Beth Podust, Vladimir N. Dalmasso, Enrique A. Rutherford, Jennifer Rogers, Wade Moser, Allan Yoon, Bo Hyun Barder, Tim TI Proteomic profiling of amniotic fluid in preterm labor using two-dimensional liquid separation and mass spectrometry SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Preterm birth; intra-amniotic infection; inflammation; chorioamnionitis; IGFBP-1; MALDI-TOF; LC-MS; MS; SELDI-TOF MS; two-dimensional chromatography ID FACTOR-BINDING PROTEIN-1; CERVICAL-VAGINAL FLUID; RNA-POLYMERASE-II; FACTOR (IGF)-BINDING PROTEIN-1; HIGH-DIMENSIONAL BIOLOGY; DOWN-SYNDROME; INTRAAMNIOTIC INFECTION; GEL-ELECTROPHORESIS; GESTATIONAL-AGE; TRANSCRIPTION ELONGATION AB Objective. Simultaneous analysis of the protein composition of biological fluids is now possible. Such an approach can be used to identify biological markers of disease and to understand the pathophysiology of disorders that have eluded classification, diagnosis, and treatment. The purpose of this study was to analyze the differences in protein composition of the amniotic fluid of patients in preterm labor. Study design. Amniotic fluid was obtained by amniocentesis from three groups of women with preterm labor and intact membranes: (1) women without intra-amniotic infection/inflammation (IAI) who delivered at term, (2) women without IAI who delivered a preterm neonate, and (3) women with IAI. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin (IL)-6 (2.3ng/mL). Two-dimensional (2D) chromatography was used for analysis. The first dimension separated proteins by isoelectric point, while the second, by the degree of hydrophobicity. 2D protein maps were generated using different experimental conditions (reducing agents as well as protein concentration). The maps were used to discern subsets of isoelectric point/hydrophobicity containing differentially expressed proteins. Protein identification of differentially expressed fractions was conducted with mass spectrometry. Enzyme-linked immunosorbent assays (ELISA) as well as surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS)-based on-chip antibody capture immunoassays were also used for confirmation of a specific protein that was differentially expressed. Results. (1) Amniotic fluid protein composition can be analyzed using a combination of 2D liquid chromatography and mass spectrometry for the identification of proteins differentially expressed in patients in preterm labor. (2) While total insulin-like growth factor-binding protein-1 (IGFBP-1) concentration did not change, IGFBP-1 fragments at about 13.5kDa were present in patients with IAI. (3) Proteins that were over-expressed in group 1 included von Ebner gland protein precursor, IL-7 precursor, apolipoprotein A1, tropomyosin sk1 (TPMsk1) fragment, ribosomal protein S6 kinase alpha-3, and alpha-1-microglobulin/bikunin precursor (AMBP). (4) Proteins that were over-expressed in group 3 included fibrinopeptide B, transferrin, major histocompatibility complex (MHC) class 1 chain-related A antigen fragment, transcription elongation factor A, sex-determining region Y (SRY) box 5 protein, Down syndrome critical region 2 protein (DSCR2), and human peptide 8 (HP8). (5) One protein, retinol-binding protein, was over-expressed in women who delivered preterm, regardless of the presence of IAI. Conclusions. A combination of techniques involving 2D chromatography, mass spectrometry, and immunoassays allows identification of proteins that are differentially regulated in the amniotic fluid of patients with preterm labor. Specifically, the amount of the IGFBP-1 fragments at approximately 13.5kDa was found to be increased in patients with IAI, while the amount of the intact form of IGFBP-1 was decreased. C1 [Bujold, Emmanuel; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Gomez, Ricardo; Espinoza, Jimmy; Vaisbuch, Edi; Edwin, Samuel] NICHD, Perinatol Res Branch, NIH, DHSS, Bethesda, MD USA. [Bujold, Emmanuel; Kusanovic, Juan Pedro; Erez, Offer; Vaisbuch, Edi] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Bujold, Emmanuel] Univ Laval, Fac Med, Dept Obstet & Gynecol, Quebec City, PQ G1K 7P4, Canada. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP, Puente Alto, Chile. [Kim, Yeon Mee] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Pisano, Mike; Allen, Beth] Proteom Res Serv Inc, Ann Arbor, MI USA. [Podust, Vladimir N.; Dalmasso, Enrique A.] Ciphergen Biosyst Inc, Fremont, CA USA. [Rogers, Wade; Moser, Allan] Cira Discovery Sci Inc, Philadelphia, PA USA. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. [Barder, Tim] Eprogen, Darien, IL USA. RP Bujold, E (reprint author), Univ Laval, Ctr Hosp Univ Quebec, Dept Obstet & Gynecol, 2705 Laurier Blvd, Quebec City, PQ G1V 4G2, Canada. EM emmanuel.bujold@crchul.ulaval.ca RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 90 TC 35 Z9 36 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 10 BP 697 EP 713 AR PII 905550889 DI 10.1080/14767050802053289 PG 17 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 372TS UT WOS:000260925500003 PM 19012186 ER PT J AU Erez, O Espinoza, J Chaiworapongsa, T Gotsch, F Kusanovic, JP Than, NG Mazaki-Tovi, S Vaisbuch, E Papp, Z Yoon, BH Han, YM Hoppensteadt, D Fareed, J Hassan, SS Romero, R AF Erez, Offer Espinoza, Jimmy Chaiworapongsa, Tinnakorn Gotsch, Francesca Kusanovic, Juan Pedro Than, Nandor Gabor Mazaki-Tovi, Shali Vaisbuch, Edi Papp, Zoltan Yoon, Bo Hyun Han, Yu Mi Hoppensteadt, Debra Fareed, Jawed Hassan, Sonia S. Romero, Roberto TI A link between a hemostatic disorder and preterm PROM: a role for tissue factor and tissue factor pathway inhibitor SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Coagulation; inflammation; pregnancy; preterm delivery; thrombin; thrombosis; prematurity; prelabor rupture of membranes ID MOLECULAR-WEIGHT HEPARIN; PLACENTAL PROTEIN-5 PP5; SERINE-PROTEASE INHIBITORS; INDUCED PREMATURE RUPTURE; EX-VIVO THROMBI; FACTOR-XA; COAGULATION INHIBITOR; ENDOMETRIAL HEMOSTASIS; NORMAL-PREGNANCY; FETAL MEMBRANES AB Objective. Vaginal bleeding is a risk factor for preterm PROM (PPROM). A disorder of decidual hemostasis has been implicated in the genesis of PROM. Indeed, excessive thrombin generation has been demonstrated in PPROM both before and at the time of diagnosis. Decidua is a potent source of tissue factor (TF), the most powerful natural pro-coagulant. A decidual hemostatic disorder may link vaginal bleeding, PPROM and placental abruption. This study was conducted to determine the behaviour of maternal TF and its natural inhibitor, the tissue factor pathway inhibitor (TFPI) in PPROM. Methods. This cross-sectional study included women with PPROM (n=123) and women with normal pregnancies (n=86). Plasma concentrations of TF and TFPI were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results. (1) The median maternal plasma TF concentration was significantly higher in patients with PPROM than in women with normal pregnancies (median: 369.5pg/mL; range: 3.27-2551pg/mL vs. median: 291.5pg/mL; range: 6.3-2662.2pg/mL respectively, p=0.001); (2) the median maternal TFPI plasma concentration was significantly lower in patients with PPROM than in women with normal pregnancies (median: 58.7ng/mL; range: 26.3-116ng/mL vs. median: 66.1ng/mL; range: 14.3-86.5ng/mL respectively, p=0.019); (3) there was no correlation between the plasma concentration of TF and TFPI and the gestational age at sample collection; and (4) among patients with PPROM there was no association between the presence of intra-amniotic infection or inflammation and median plasma concentrations of TF and TFPI. Conclusions. (1) Patients with PPROM have a higher median plasma concentration of TF and a lower median plasma concentration of TFPI than women with normal pregnancies. (2) These findings suggest that PPROM is associated with specific changes in the hemostatic/coagulation system. C1 [Erez, Offer] Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, Detroit, MI 48201 USA. [Erez, Offer; Espinoza, Jimmy; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Vaisbuch, Edi; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, H-1085 Budapest, Hungary. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Hoppensteadt, Debra; Fareed, Jawed] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Erez, O (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM oerez@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Programme of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 119 TC 23 Z9 24 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 10 BP 732 EP 744 AR PII 905566813 DI 10.1080/14767050802361807 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 372TS UT WOS:000260925500007 PM 19012190 ER PT J AU Nhan-Chang, CL Romero, R Kusanovic, JP Gotsch, F Edwin, SS Erez, O Mittal, P Kim, CJ Kim, MJ Espinoza, J Friel, LA Vaisbuch, E Than, NG Mazaki-Tovi, S Hassan, SS AF Nhan-Chang, Chia-Ling Romero, Roberto Kusanovic, Juan Pedro Gotsch, Francesca Edwin, Samuel S. Erez, Offer Mittal, Pooja Kim, Chong Jai Kim, Mi Jeong Espinoza, Jimmy Friel, Lara A. Vaisbuch, Edi Than, Nandor Gabor Mazaki-Tovi, Shali Hassan, Sonia S. TI A role for CXCL13 (BCA-1) in pregnancy and intra-amniotic infection/inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Amniotic fluid; BLC; chorioamnionitis; preterm delivery; preterm labor; CXCL13; BCA-1 ID CELL-ATTRACTING CHEMOKINE-1; ECTOPIC GERMINAL CENTER; REGULATORY T-CELLS; HIGH ENDOTHELIAL VENULES; UMBILICAL-CORD PLASMA; WHITE-MATTER LESIONS; CERVICAL-MUCUS PLUG; AMNIOTIC-FLUID; PRETERM LABOR; MICROBIAL INVASION AB Objectives. CXCL13 is a potent chemokine, produced by mature and recently recruited macrophages to sites of inflammation, which has antimicrobial and anti-angiogenic properties. The purpose of this study was to: (1) determine whether CXCL13 is present in maternal serum, umbilical cord blood, and amniotic fluid (AF); (2) to determine if AF concentration changes with intra-amniotic infection/inflammation (IAI); and (3) to localize the production of CXCL13 in chorioamniotic membranes and umbilical cord. Study design. A cross-sectional study on maternal serum was performed including patients in the following groups: (1) non-pregnant women (n=20), (2) normal pregnant women (n=49), (3) patients at term not in labor (n=30), and (4) patients in spontaneous labor at term (n=29). Umbilical cord blood was collected from term neonates with (n=30) and without labor (n=28). Amniotic fluid was obtained from patients in the following groups: (1) midtrimester (n=65); (2) term not in labor (n=22); (3) term in labor (n=47); (4) preterm labor (PTL) with intact membranes leading to term delivery (n=70); and (5) PTL leading to preterm delivery with IAI (n=79) and without IAI (n=60). CXCL13 concentrations were determined by enzyme-linked immunosorbent assay. Chorioamniotic membranes and umbilical cords were examined with immunohistochemistry. Non-parametric statistics were used for analysis. Results. (1) CXCL13 was present in 100% of serum and cord blood samples, and 99% of AF samples (339/343). (2) Serum CXCL13 concentration was significantly higher in pregnant women when compared to non-pregnant women (median 313.3 pg/mL (interquartile range (IQR) 197.2-646.9) vs. 40.5 pg/mL (IQR 29.5-93.5), respectively; p0.001). (3) Serum CXCL13 concentration decreased with advancing gestational age (Spearman's Rho=-0.424; p0.001). (4) There were no significant differences in the median serum CXCL13 concentration between women at term with and without labor (371.6 pg/mL (IQR 194.3-614.3) vs. 235.1 pg/mL (IQR 182.8-354.7), respectively; p=0.6). (5) The concentration of CXCL13 in AF did not change with gestational age (p=0.1). (6) Patients with PTL and delivery with IAI had a significantly higher median concentration of CXCL13 than those without IAI (median 513.2 pg/mL (IQR 199.7-2505.5) vs. 137.3 pg/mL (IQR 96.7-209.6), respectively; p0.001) and those who delivered at term (133.7 pg/mL (IQR 97.8-174.8); p0.001). (7) Spontaneous labor did not result in a change in the median AF concentration of CXCL13 (labor: 86.9 pg/mL (IQR 55.6-152.0) vs. no labor: 77.8 pg/mL (IQR 68.0-98.0); p=0.8). (8) CXCL13 was immunolocalized to macrophages in fetal membranes and umbilical vein. Conclusions. (1) We report for the first time the presence of CXCL13 in AF. (2) AF CXCL13 concentrations are dramatically increased in IAI. (3) Unlike other chemokines, AF and serum CXCL13 concentrations did not change with spontaneous parturition. C1 [Nhan-Chang, Chia-Ling; Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Edwin, Samuel S.; Mittal, Pooja; Kim, Chong Jai; Kim, Mi Jeong; Espinoza, Jimmy; Friel, Lara A.; Vaisbuch, Edi; Than, Nandor Gabor; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Perinatol Res Branch,Intramural Div, NICHD,Eunice Kennedy Shriver Natl Inst Child Hlth, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Nhan-Chang, Chia-Ling; Erez, Offer; Mittal, Pooja; Espinoza, Jimmy; Friel, Lara A.; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto; Edwin, Samuel S.; Kim, Mi Jeong] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. RP Nhan-Chang, CL (reprint author), Wayne State Univ, Perinatol Res Branch,Intramural Div, NICHD,Eunice Kennedy Shriver Natl Inst Child Hlth, NIH,DHHS,Hutzel Womens Hosp, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development,; NIH; DHHS FX This research was supported in part by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 104 TC 34 Z9 35 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 11 BP 763 EP 775 AR PII 905853029 DI 10.1080/14767050802244946 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 376GU UT WOS:000261172900002 PM 19031272 ER PT J AU Mazaki-Tovi, S Romero, R Kusanovic, JP Erez, O Vaisbuch, E Gotsch, F Mittal, P Than, GN Nhan-Chang, C Chaiworapongsa, T Edwin, S Camacho, N Nien, JK Hassan, SS AF Mazaki-Tovi, S. Romero, R. Kusanovic, J. P. Erez, O. Vaisbuch, E. Gotsch, F. Mittal, P. Than, G. N. Nhan-Chang, C. Chaiworapongsa, T. Edwin, S. Camacho, N. Nien, J. K. Hassan, S. S. TI Adiponectin multimers in maternal plasma SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Adiponectin; adipokines; pregnancy; high molecular weight (HMW) adiponectin; medium molecular weight (MMW) adiponectin; low molecular weight (LMW) adiponectin; BMI ID HIGH-MOLECULAR-WEIGHT; GESTATIONAL DIABETES-MELLITUS; ACTIVATED PROTEIN-KINASE; CORONARY-ARTERY-DISEASE; NECROSIS-FACTOR-ALPHA; IMPAIRED GLUCOSE-TOLERANCE; COMPLEMENT-RELATED PROTEIN; IMPROVED INSULIN SENSITIVITY; LINKED-IMMUNOSORBENT-ASSAY; ENDOTHELIAL-CELL APOPTOSIS AB Objective. Adiponectin is an anti-diabetic, anti-atherogenic, anti-inflammatory, and angiogenic adipokine that circulates in oligomeric complexes including: low molecular weight (LMW) trimers, medium molecular weight (MMW) hexamers, and high molecular weight (HMW) isoforms. The aim of this study was to determine whether there are changes in adiponectin multimers in pregnancy and as a function of maternal weight. Study design. In this cross-sectional study, plasma concentrations of total, HMW, MMW, and LMW adiponectin were determined in women included in three groups: (1) normal pregnant women of normal body mass index (BMI) (n=466), (2) overweight pregnant women (BMI 25; n=257), and (3) non-pregnant women of normal weight (n=40). Blood samples were collected once from each woman between 11 and 42 weeks of gestation. Plasma adiponectin multimer concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis. Results. (1) The median HMW adiponectin concentration and the median HMW/total adiponectin ratio were significantly higher, and the median LMW adiponectin concentration was significantly lower in pregnant women than in non-pregnant women. (2) Among pregnant women, the median plasma concentration of total, HMW, and MMW adiponectin was significantly higher in normal weight women than in overweight patients. (3) Maternal HMW was the most prevalent adiponectin multimer regardless of gestational age or BMI status. (4) There were no significant differences in the median concentration of total, MMW, and LMW adiponectin and their relative distribution with advancing gestation. Conclusion. Human pregnancy is characterized by quantitative and qualitative changes in adiponectin multimers, especially the most active isoform, HMW adiponectin. C1 [Mazaki-Tovi, S.; Romero, R.; Kusanovic, J. P.; Erez, O.; Vaisbuch, E.; Gotsch, F.; Mittal, P.; Than, G. N.; Nhan-Chang, C.; Chaiworapongsa, T.; Edwin, S.; Camacho, N.; Hassan, S. S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Mazaki-Tovi, S.; Romero, R.; Kusanovic, J. P.; Erez, O.; Vaisbuch, E.; Gotsch, F.; Mittal, P.; Than, G. N.; Nhan-Chang, C.; Chaiworapongsa, T.; Edwin, S.; Camacho, N.; Hassan, S. S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA. [Mazaki-Tovi, S.; Mittal, P.; Nhan-Chang, C.; Chaiworapongsa, T.; Camacho, N.; Hassan, S. S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Nien, J. K.] Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 268 TC 31 Z9 35 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 11 BP 796 EP 815 AR PII 905942073 DI 10.1080/14767050802266881 PG 20 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 376GU UT WOS:000261172900006 PM 19031276 ER PT J AU Erez, O Romero, R Hoppensteadt, D Than, NG Fareed, J Mazaki-Tovi, S Espinoza, J Chaiworapongsa, T Kim, SS Yoon, BH Hassan, SS Gotsch, F Friel, L Vaisbuch, E Kusanovic, JP AF Erez, Offer Romero, Roberto Hoppensteadt, Debra Than, Nandor Gabor Fareed, Jawed Mazaki-Tovi, Shali Espinoza, Jimmy Chaiworapongsa, Tinnakorn Kim, Sung-Su Yoon, Bo Hyun Hassan, Sonia S. Gotsch, Francesca Friel, Lara Vaisbuch, Edi Kusanovic, Juan Pedro TI Tissue factor and its natural inhibitor in pre-eclampsia and SGA SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Inflammation; coagulation; TFPI-1; TFPI-2; placenta; microparticles ID FACTOR-PATHWAY INHIBITOR; INTRAUTERINE GROWTH RESTRICTION; CIRCULATING ANGIOGENIC FACTORS; MOLECULAR-WEIGHT HEPARIN; PLACENTAL PROTEIN-5 PP5; DISSEMINATED INTRAVASCULAR COAGULATION; MATERNAL INFLAMMATORY RESPONSE; BLOOD MONONUCLEAR-CELLS; EX-VIVO THROMBI; FETAL-GROWTH AB Objective. Tissue factor (TF), the major activator of the extrinsic pathway of coagulation, is abundant in the placenta and decidua. The aim of this study was to determine the maternal plasma concentrations of TF and its primary inhibitor, tissue factor pathway inhibitor (TFPI), in women who delivered small for gestational age (SGA) neonates, and in pre-eclampsia. Study design. A cross-sectional study included the following groups: 1) women with normal pregnancies (n = 86); 2) patients who delivered SGA neonates (n = 61) and 3) women with pre-eclampsia (n = 133). Maternal plasma concentrations of TF and TFPI were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results. 1) Women with pre-eclampsia had a significantly higher median plasma concentration of TF than patients with a normal pregnancy (median: 1187 pg/mL; range: 69-11675 vs. median: 291.5 pg/mL; range: 6.3-2662.2; p < 0.0001, respectively); 2) Similarly, TFPI concentrations were higher in pre-eclampsia than in normal pregnancy (median: 87.5ng/mL; range 25.4-165.1 vs. median: 66.1 ng/mL; range: 14.3-86.5; p < 0.0001, respectively); 3) Surprisingly, mothers with SGA neonates had a lower median maternal plasma concentration of TF (median: 112.2 pg/mL; range: 25.6-1225.3) than women with a normal pregnancy (p < 0.0001). Conclusion. 1) Maternal plasma concentrations of TF in patients with pre-eclampsia, but not in those who delivered an SGA neonate, were higher than in women with normal pregnancies; 2) Although the role of immunoreactive plasma TF in coagulation remains controversial, our observations suggest that changes are present in the context of complications of pregnancy. C1 [Erez, Offer; Romero, Roberto; Than, Nandor Gabor; Mazaki-Tovi, Shali; Espinoza, Jimmy; Chaiworapongsa, Tinnakorn; Kim, Sung-Su; Hassan, Sonia S.; Gotsch, Francesca; Friel, Lara; Vaisbuch, Edi; Kusanovic, Juan Pedro] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Erez, Offer; Mazaki-Tovi, Shali; Espinoza, Jimmy; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Friel, Lara; Vaisbuch, Edi; Kusanovic, Juan Pedro] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Hoppensteadt, Debra; Fareed, Jawed] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD,NIH, DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM oerez@med.wayne.edu; prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 202 TC 31 Z9 31 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 12 BP 855 EP 869 DI 10.1080/14767050802361872 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 397ES UT WOS:000262645800001 PM 19065458 ER PT J AU Kusanovic, JP Romero, R Mazaki-Tovi, S Chaiworapongsa, T Mittal, P Gotsch, F Erez, O Vaisbuch, E Edwin, SS Than, NG Camacho, N Pacora, P Rogers, W Hassan, SS AF Kusanovic, Juan Pedro Romero, Roberto Mazaki-Tovi, Shali Chaiworapongsa, Tinnakorn Mittal, Pooja Gotsch, Francesca Erez, Offer Vaisbuch, Edi Edwin, Samuel S. Than, Nandor Gabor Camacho, Natalia Pacora, Percy Rogers, Wade Hassan, Sonia S. TI Resistin in amniotic fluid and its association with intra-amniotic infection and inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Preterm labour; preterm delivery; preterm prelabour rupture of membranes; PPROM; pregnancy; amniocentesis; microbial invasion of the amniotic cavity; MIAC; adipokines; cytokines; chorioamnionitis ID TUMOR-NECROSIS-FACTOR; GESTATIONAL DIABETES-MELLITUS; INDUCED PRETERM LABOR; BLOOD-CELL COUNT; INSULIN-RESISTANCE; ADIPOSE-TISSUE; SERUM RESISTIN; BIRTH-WEIGHT; INTRAUTERINE INFECTION; MICROBIAL INVASION AB Objective. Intra-amniotic infection/inflammation (IAI) is one of the most important mechanisms of disease in preterm birth. Resistin is an adipocytokine that has been linked to insulin resistance, diabetes, obesity and inflammation. The objective of this study was to determine if resistin is present in amniotic fluid (AF) and if its concentration changes with gestational age, in the presence of labour, and in IAI in patients with spontaneous preterm labour (PTL) and intact membranes, preterm prelabour rupture of membranes (PPROM) and clinical chorioamnionitis. Study design. This cross-sectional study included 648 patients in the following groups: (1) women in the mid-trimester of pregnancy (14-18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n = 61); (2) normal pregnant women at term with (n = 49) and without (n = 50) spontaneous labour; (3) patients with an episode of PTL and intact membranes who were classified into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm (537 weeks gestation) without IAI (n = 108); and (c) PTL with IAI (n 84); (4) women with PPROM with (n = 47) and without (n 44) IAI; and (5) patients with clinical chorioamnionitis at term with (n = 22) and without (n = 30) microbial invasion of the amniotic cavity. Resistin concentration in AF was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results. (1) Resistin was detected in all AF samples; (2) the median AF resistin concentration at term was significantly higher than in the mid-trimester (23.6 ng/mL vs. 10 ng/mL; p<0.001); (3) among patients with PTL, the median AF resistin concentration was significantly higher in patients with IAI than in those without IAI (144.9 ng/mL vs. 18.7 ng/mL; p<0.001) and those with PTL and intact membranes who delivered at term (144.9 ng/mL vs. 16.3 ng/mL; p<0.001); (4) patients with PPROM with IAI had a significantly higher median AF resistin concentration than those without IAI (132.6 ng/mL vs. 13 ng/mL; p<0.001); (5) no significant differences were observed in the median AF resistin concentration between patients with spontaneous labour at term and those at term not in labour (28.7 ng/mL vs. 23.6 ng/mL; p = 0.07); and (6) AF resistin concentration >= 37 ng/mL (derived from a receiver-operating characteristic curve) had a sensitivity of 85.4% and a specificity of 94.3% for the diagnosis of intra-amniotic inflammation. Conclusions. Resistin is a physiologic constituent of the AF, and its concentrations in AF: (1) are significantly elevated in the presence of IAI; (2) increase with advancing gestation; and (3) do not change in the presence of spontaneous labour at term. We propose that resistin may play a role in the innate immune response against intra-amniotic infection. C1 [Kusanovic, Juan Pedro; Romero, Roberto; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Gotsch, Francesca; Erez, Offer; Vaisbuch, Edi; Edwin, Samuel S.; Than, Nandor Gabor; Camacho, Natalia; Pacora, Percy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Kusanovic, Juan Pedro; Romero, Roberto; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Gotsch, Francesca; Erez, Offer; Vaisbuch, Edi; Edwin, Samuel S.; Than, Nandor Gabor; Camacho, Natalia; Pacora, Percy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Erez, Offer; Vaisbuch, Edi; Camacho, Natalia; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynaecol, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Rogers, Wade] Cira Discovery Sci Inc, Philadelphia, PA USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, DHHS,NIH, NICHD,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM jkusanov@med.wayne.edu; prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 101 TC 45 Z9 45 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2008 VL 21 IS 12 BP 902 EP 916 DI 10.1080/14767050802320357 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 397ES UT WOS:000262645800009 PM 19065463 ER PT J AU Bock, BC Graham, AL Whiteley, JA Stoddard, JL AF Bock, Beth C. Graham, Amanda L. Whiteley, Jessica A. Stoddard, Jacqueline L. TI A Review of Web-Assisted Tobacco Interventions (WATIs) SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Smoking cessation; Internet interventions; tobacco dependence ID SMOKING-CESSATION PROGRAM; RANDOMIZED CLINICAL-TRIAL; WORLD-WIDE-WEB; HEALTH INFORMATION; INTERNET; QUALITY; USABILITY; CONSUMERS; THERAPY; SMOKERS AB Background: The Internet has great potential to provide assistance to millions of smokers who seek help with quitting smoking. Objective: The goals of this study were to assess the content and the quality of smoking cessation treatments most likely to be encountered by smokers seeking treatment on the Internet and to examine differences in quality between current websites and those reviewed in 2004. Methods: Internet searches for smoking cessation were designed to mimic the search patterns of most Internet users. PhD-level specialists in tobacco cessation treatments used standardized procedures to review the content of each website, assess the degree to which each site covered key components of evidence-based treatment as described in US national guidelines, determine the accuracy of information presented, and evaluate the use of website interactivity. Results of the current study were compared to results obtained in a prior review. Results: Most websites retrieved in the search met exclusion criteria and were not included in the final analyses in both the current (74%, 65/88) and the prior study (77%, 156/202). In both studies, the majority of websites were excluded because they sold cessation-related products but did not provide treatment recommended by the Public Health Service guidelines. Of the 23 websites included in the current study, 26% (n = 6) provided only minimal coverage (brief mention) of key components of tobacco treatment. However, compared to the earlier study, websites included in the present study scored significantly higher in quality ratings in four areas: providing advice to quit (P =.05), practical counseling (P =.02), and enhancing motivation to quit smoking through personal relevance (P=.05) and risks (P < .001). Most Web-assisted tobacco intervention (WATT) sites (69%, 16/23) contained no inaccurate information. When observed, inaccuracies primarily occurred in content related to pharmacotherapy. The percentage of sites offering at least one interactive feature increased from 39% (18/46) in 2004 to 56% (13/23) in the present study. Despite this improvement, there was a notable underutilization of the interactive capabilities of the Internet to personalize treatment, to connect users with a virtual support system, and to provide follow-up treatment contacts. Conclusions: While the quality of treatment offered in WATIs has improved since our previous review in 2004, there is substantial room for further improvement to ensure that smokers are offered high-quality, evidence-based treatments. It is not clear what degree of informational detail and interactivity is optimal for Web-based smoking cessation treatments. Additional research is needed to understand how to maximize the interactive capabilities of the Internet to produce and sustain population-based health behavior change. C1 [Bock, Beth C.; Whiteley, Jessica A.] Brown Univ, Warren Alpert Sch Med, Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI 02903 USA. [Graham, Amanda L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Stoddard, Jacqueline L.] Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Prevent Sci, Natl Canc Inst, Rockville, MD USA. RP Bock, BC (reprint author), Brown Univ, Warren Alpert Sch Med, Miriam Hosp, Ctr Behav & Prevent Med, Coro W,5th Floor 1 Hoppin St, Providence, RI 02903 USA. EM Beth_Bock@Brown.edu OI Graham, Amanda/0000-0003-3036-9653 NR 24 TC 52 Z9 52 U1 0 U2 4 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2008 VL 10 IS 5 AR e39 DI 10.2196/jmir.989 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 405HW UT WOS:000263214800007 PM 19000979 ER PT J AU Stoddard, JL Augustson, EM Moser, RP AF Stoddard, Jacqueline L. Augustson, Erik M. Moser, Richard P. TI Effect of Adding a Virtual Community (Bulletin Board) to Smokefree.gov: Randomized Controlled Trial SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Smoking cessation; Internet; World Wide Web; randomized trial; self-help ID SMOKING-CESSATION PROGRAM; HEALTH INTERVIEW SURVEY; INTERNET; SMOKERS; HELP; INTERVENTIONS; INFORMATION; SUPPORT; MANAGEMENT; IMPACT AB Background: Demand for online information and help exceeds most other forms of self-help. Web-assisted tobacco interventions (WATIs) offer a potentially low-cost way to reach millions of smokers who wish to quit smoking and to test various forms of online assistance for use/utilization and user satisfaction. Objectives: Our primary aim was to determine the utilization of and satisfaction with 2 versions of a smoking cessation website (smokefree.gov), one of which included an asynchronous bulletin board (BB condition). A secondary goal was to measure changes in smoking behavior 3 months after enrollment in the study. Methods: All participants were adult federal employees or contractors to the federal government who responded to an email and indicated a willingness to quit smoking in 30 days. We randomly assigned participants to either the BB condition or the publicly available version-usual care (UC)-and then assessed the number of minutes of website use and satisfaction with each condition as well as changes in smoking behavior. Results: Among the 1375 participants, 684 were randomized to the BB intervention, and 691 to the control UC condition. A total of 39.7% returned a follow-up questionnaire after 3 months, with similar rates across the two groups (UC: n=279, 40.3%; BB: n=267, 39.0%). Among those respondents assigned to the BB condition, only 81 participants (11.8%) elected to view the bulletin board or post a message, limiting our ability to analyze the impact of bulletin board use on cessation. Satisfaction with the website was high and did not differ significantly between conditions (UC: 90.2%, BB: 84.9%, P=.08). Utilization, or minutes spent on the website, was significantly longer for the BB than the UC condition (18.0 vs 11.1, P = .01) and was nearly double for those who remained in the study (21.2) than for those lost to follow-up (9.6, P< .001). Similar differences were observed between those who made a serious quit attempt versus those who did not (22.4 vs 10.4, P= .02) and between those with a quit date on or a few days prior to the enrollment date versus those with a later quit date (29.4 vs 12.5, P = .001). There were no statistically significant differences in quit rates between the BB and UC group, both in intent-to-treat analysis (ITT) and in analyzing the adherence subgroup (respondents) only. Combined across the UC and BB groups, 7-day abstinence was 6.8% with ITT and 17.6% using only participants in the follow-up (adherence). For participants who attempted to quit within a few days of study entry (vs 30 days), quit rates were 29.6% (ITT) and 44.4% (adherence). Conclusions: Quit rates for participants were similar to other WATIs, with the most favorable outcomes demonstrated by smokers ready to quit at the time of enrolling in the trial and smokers using pharmacotherapy. Utilization of the asynchronous bulletin board was lower than expected, and did not have an impact on outcomes (quit rates). Given the demand for credible online resources for smoking cessation, future studies should continue to evaluate use of and satisfaction with Web features and to clarify results in terms of time since last cigarette as well as use of pharmacotherapy. C1 [Augustson, Erik M.] NCI, DCCPS, BRP, Tobacco Control Res Branch, Rockville, MD 21702 USA. [Stoddard, Jacqueline L.; Augustson, Erik M.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Stoddard, JL (reprint author), NCI, DCCPS, BRP, Tobacco Control Res Branch, 6130 Executive Blvd,EPN 4038, Rockville, MD 21702 USA. EM stoddaja@mail.nih.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400]; PHS HHS [HHS-P23320045016X] NR 28 TC 36 Z9 36 U1 0 U2 5 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2008 VL 10 IS 5 AR e53 DI 10.2196/jmir.1124 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 405HW UT WOS:000263214800014 PM 19097974 ER PT J AU Wood, FB Siegel, ER Feldman, S Love, CB Rodrigues, D Malamud, M Lagana, M Crafts, J AF Wood, Fred B. Siegel, Elliot R. Feldman, Sue Love, Cynthia B. Rodrigues, Dennis Malamud, Mark Lagana, Marie Crafts, Jennifer TI Web evaluation at the US National Institutes of Health: Use of the American customer satisfaction index online customer survey SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE surveys; evaluation studies; satisfaction; Internet; World Wide Web; consumer health information ID INFORMATION; SERVICE AB Background: The National Institutes of Health (NIH), US Department of Health and Human Services (HHS), realized the need to better understand its Web users in order to help assure that websites are user friendly and well designed for effective information dissemination. A trans-NIH group proposed a trans-NIH project to implement an online customer survey, known as the American Customer Satisfaction Index (ACSI) survey, on a large number of NIH websites-the first "enterprise-wide" ACSI application, and probably the largest enterprise Web evaluation of any kind, in the US government. The proposal was funded by the NIH Evaluation Set-Aside Program for two years at a cost of US $1.5 million (US $1.275 million for survey licenses for 60 websites at US S 18,000 per website; US $225,000 for a project evaluation contractor). Objective: The overall project objectives were to assess the value added to the participating NIH websites of using the ACSI online survey, identify any NIH-wide benefits (and limitations) of the ACSI, ascertain any new understanding about the NIH Web presence based on ACSI survey results, and evaluate the effectiveness of a trans-NIH approach to Web evaluation. This was not an experimental study and was not intended to evaluate the ACSI survey methodology, per se, or the impacts of its use on customer satisfaction with NIH websites. Methods: The evaluation methodology included baseline pre-project websites profiles; before and after email surveys of participating website teams; interviews with a representative cross-section of website staff; observations of debriefing meetings with website learns; observations at quarterly traps-NIH Web staff meetings and biweekly traps-NIH leadership team meetings; and review and analysis of secondary data. Results: Of the original 60 NIH websites signed up, 55 implemented the ACSI survey, 42 generated sufficient data for formal reporting of survey results for their sites, and 5 l completed the final project survey. A broad cross-section of websites participated, and a majority reported significant benefits and new knowledge gained from the ACSI survey results. NIH websites as a group scored consistently higher on overall customer satisfaction relative to US government-wide and private sector benchmarks. Conclusions: Overall, the enterprise-wide experiment was successful. On the level of individual websites, the project confirmed the value of online customer surveys as a Web evaluation method. The evaluation results indicated that successful use of the ACSI, whether site-by-site or enterprise-wide, depends in large part on strong staff and management support and adequate funding and time for the use of such evaluative methods. In the age of Web-based e-government, a broad commitment to Web evaluation tray well be needed. This commitment would help assure that the potential of the Web and other information technologies to improve customer and citizen satisfaction is fully realized. C1 [Wood, Fred B.; Siegel, Elliot R.; Love, Cynthia B.] Natl Inst Hlth, Natl Lib Med, US Dept HHS, Bethesda, MD USA. [Feldman, Sue] Natl Inst Hlth, Natl Canc Inst, US Dept HHS, Bethesda, MD USA. [Rodrigues, Dennis] Natl Inst Hlth, Off Commun & Publ Liaison, Off Director, US Dept HHS, Bethesda, MD USA. [Malamud, Mark] NHLBI, Natl Inst Hlth, US Dept HHS, Bethesda, MD USA. [Lagana, Marie] Natl Inst Hlth, Ctr Informat Technol, US Dept HHS, Bethesda, MD USA. [Crafts, Jennifer] Westat Corp, Rockville, MD USA. RP Wood, FB (reprint author), US Natl Inst Hlth, US Dept Hlth & Human Serv, Off Hlth Informat Programs Dev, US Natl Lib Med, 8600 Rockville Pike,Bldg 38,Room 2S-14, Bethesda, MD 20894 USA. EM fredwood@mail.nih.gov NR 50 TC 3 Z9 3 U1 4 U2 18 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JAN-MAR PY 2008 VL 10 IS 1 DI 10.2196/jmir.944 PG 20 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 339OZ UT WOS:000258588200005 ER PT J AU Baker, SG Kramer, BS AF Baker, Stuart G. Kramer, Barnett S. TI Estimating the cumulative risk of a false-positive under a regimen involving various types of cancer screening tests SO JOURNAL OF MEDICAL SCREENING LA English DT Article AB Objectives When evaluating screening for the early detection of cancer, it is important to estimate both harms and benefits. One common harm is a false-positive (FP), which is a positive screening result, perhaps followed by an invasive test, with no cancer detected on the diagnostic work-up or within a specified time period. An important goal is to estimate the risk of at least one FP, which we call the cumulative risk of an FP, if persons took a regimen of various screening tests, as is commonly recommended. The estimation is complicated because the data come from a study in which subjects are offered various screening tests in rounds with some missing tests in most subjects. Previous methods for estimating cumulative risk of FPs with a single type of test are not directly applicable, so a new approach was developed. Methods The tests were ordered by appearance, where the lost test was either the first FP (analogous to a failure time) or the last test taken with no FPs having occurred on that test or previously (analogous to a censoring time). We applied a Kaplan-Meier approach for survival analysis with the innovation that the hazard for a first FP for a given test depends on the type of test and number of previous tests of that type which were taken. Results The method is illustrated with data from the screening arm of the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. With an FP defined as a diagnostic work-up in the absence of cancer (or advanced adenoma) within three years, the probability of at least one FP among 14 tests in men was 60.5% with 95% confidence interval of (59.3%, 61.6%). Conclusion A simple estimate is proposed for the probability of at least one FP if persons took a regimen of multiple screening tests of different types. The methodology is useful for summarizing the burden of multiphasic screening programmes. C1 [Baker, Stuart G.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Canc Prevent Div, EPN 3131,6130 Execut Blvd MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 7 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2008 VL 15 IS 1 BP 18 EP 22 DI 10.1258/jms.2008.007076 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 305HA UT WOS:000256167700005 PM 18416950 ER PT J AU Baker, SG Kramer, BS Prorok, PC AF Baker, Stuart G. Kramer, Barnett S. Prorok, Philip C. TI Early reporting for cancer screening trials SO JOURNAL OF MEDICAL SCREENING LA English DT Article AB Objective Many cancer screening trials involve a screening programme of one or more screenings with follow-up after the last screening. Usually a maximum follow-up time is selected in advance. However, during the follow-up period there is an opportunity to report the results of the trial sooner than planned. Early reporting of results from a randomized screening trial is important because obtaining a valid result sooner translates into health benefits reaching the general population sooner. The health benefits are reduction in cancer deaths if screening is found to be beneficial and more screening is recommended, or avoidance of unnecessary biopsies, work-ups and morbidity if screening is not found to be beneficial and the rate of screening drops. Methods Our proposed method for deciding if results from a cancer screening trial should be reported earlier in the follow-up period is based on considerations involving postscreening noise. Postscreening noise (sometimes called dilution) refers to cancer deaths in the follow-up period that could not have been prevented by screening: (1) cancer deaths in the screened group that occurred after the lost screening in subjects whose cancers were not detected during the screening program and (2) cancer deaths in the control group that occurred after the time of the last screening and whose cancers would not have been detected during the screening programme had they been randomized to screening (the number of which is unobserved). Because postscreening noise increases with follow-up after the last screening, we propose early reporting at the time during the follow-up period when postscreening noise first starts to overwhelm the estimated effect of screening as measured by a z-statistic. This leads to a confidence interval, adjusted for postscreening noise, that would not change substantially with additional follow-up. Details of the early reporting rule were refined by simulation, which also accounts for multiple looks. Results For the re-analysis of the Health Insurance Plan trial for breast cancer screening and the Mayo Lung Project for lung cancer screening, estimates and confidence intervals for the effect of screening on cancer mortality were similar on early reporting and later. Conclusion The proposed early reporting rule for a cancer screening trial with post-screening follow-up is a promising method for making results from the trial available sooner, which translates into health benefits (reduction in cancer deaths or avoidance of unnecessary morbidity) reaching the population sooner. C1 [Baker, Stuart G.; Prorok, Philip C.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Canc Prevent Div, EPN 3131,6130 Execut Blvd MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 11 TC 8 Z9 8 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2008 VL 15 IS 3 BP 122 EP 129 DI 10.1258/jms.2008.007058 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 373ZE UT WOS:000261011200004 PM 18927094 ER PT J AU de Gonzalez, AB Kim, KP Berg, CD AF de Gonzalez, Amy Berrington Kim, Kwang Pyo Berg, Christine D. TI Low-dose lung computed tomography screening before age 55: estimates of the mortality reduction required to outweigh the radiation-induced cancer risk SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID ATOMIC-BOMB SURVIVORS; BREAST-CANCER; CIGARETTE-SMOKING; HODGKINS-DISEASE; SMOKERS; CT; RADIOTHERAPY; PREDICTION; PROGRAM; COHORT AB Objectives To estimate the risk of radiation-induced lung cancer mortality from three annual low-dose lung computed tomography (CT) screens before age 55 years (starting at age 30, 40 or 50) and the mortality reduction from screening (i.e. the efficacy) needed to outweigh these risks for never and current-smokers. The risk of radiation-induced breast cancer was also estimated for women. Methods The Biological Effectiveness of Ionizing Radiation VII committee's risk models were used to estimate radiation risk. Lung cancer mortality rates (based on the Bach model for current and the Cancer Prevention Study for never-smokers) were used to estimate the mortality reduction needed to outweigh this risk. Results For never-smokers, the estimated excess lifetime risk of radiation-induced lung cancer mortality from annual screening aged 40-42 was 1/ 10,000 (90% credibility interval: 0.4-3) for men and 3/10,000 (2-6) for women. For current-smokers, the estimated risks were approximately two-fold higher, with wider credibility intervals. Risks from screening age 30-32 or 50-52 years were of similar magnitude. The mortality reduction required to outweigh these risks was, for female never-smokers: 125% (40-300%) age 30-32 years, 70% (30-190%) age 40-42 years and 25% (10-70%) age 50-52 years, and for male current-smokers: 70% (20-120%) age 30-32 years, 10% (3-20%) age 40-42 years and 2% (1-4%) age 50-52 years. These figures were two to three times higher for females because of the higher radiation risks. The risk of radiation-induced breast cancer was in the range of three to six cases/10,000 females screened. Conclusion Before age 50, the mortality reduction from lung CT screening that is required to outweigh the radiation risk may be substantial, and in some cases unattainable (i.e. >100%). C1 [de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Biostat, Bethesda, MD 20892 USA. [Berg, Christine D.] NCI, Early Detect Res Grp, Bethesda, MD 20892 USA. RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Biostat, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM berringtona@mail.nih.gov NR 36 TC 38 Z9 38 U1 0 U2 4 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2008 VL 15 IS 3 BP 153 EP 158 DI 10.1258/jms.2008.008052 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 373ZE UT WOS:000261011200009 ER PT J AU Engle, RE Russell, RS Purcell, RH Bukh, J AF Engle, Ronald E. Russell, Rodney S. Purcell, Robert H. Bukh, Jens TI Development of a TaqMan assay for the six major genotypes of hepatitis C virus: Comparison with commercial assays SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HCV; viral load; infectious pools; TaqMan; genotypes ID HCV RNA QUANTITATION; NON-B-HEPATITIS; PERFORMANCE-CHARACTERISTICS; CLINICAL MANAGEMENT; VIRAL LOAD; IN-VITRO; NON-A; INFECTION; CHIMPANZEES; PCR AB A quantitative real-time PCR assay was developed that detects genomic RNA from reference strains representing the six major genotypes of hepatitis C virus (HCV) with equal sensitivity and accurately measured HCV RNA in JFH1 HCV-infected Huh7.5 cells. The method is indirectly calibrated to the first international (WHO 96/790) HCV standard preparation and has a linear dynamic range of 10(2.6)-10(6.5) lU/Ml. In addition, the inter- and intra-assay precision were similar to 3% CV and < 2% CV, respectively. Comparison with results obtained by commercially available HCV RNA Nucleic Acid Technology kits (Versant HCV RNA 3.0 b-DNA and Amplicor HCV Monitor), that also employ the WHO standard, allowed validation of the TaqMan assay against all major HCV genotypes. Both commercial methods detected HCV RNA over a wide dynamic range, but showed a consistent difference of about 0.3 log(10) when evaluating samples of different HCV genotypes. The genome titers obtained with the three methods correlated with the infectivity titers previously determined for the HCV reference strains. TaqMan assays have become an essential tool to follow viral load in clinical samples and cell culture-based experiments and this technology offers significant advantages in linear dynamic range, sensitivity and customization. C1 NIAID, NIH, LID, Rockville, MD 20852 USA. NIH, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD USA. Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. Univ Copenhagen, Panum Inst, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. RP Engle, RE (reprint author), NIAID, NIH, LID, 5640 Fishers Lane,Twinbrook 1,Rm 1505, Rockville, MD 20852 USA. EM rengle@niaid.nih.gov FU Intramural NIH HHS NR 31 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JAN PY 2008 VL 80 IS 1 BP 72 EP 79 DI 10.1002/jmv.21043 PG 8 WC Virology SC Virology GA 236XE UT WOS:000251335900010 PM 18041021 ER PT J AU Bukh, J Engle, RE Govindarajan, S Purcell, RH AF Bukh, Jens Engle, Ronald E. Govindarajan, Sugantha Purcell, Robert H. TI Immunity against the GBV-B hepatitis virus in Tamarins can prevent productive infection following rechallenge and is long-lived SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE hepatitis C virus; surrogate model; protective immunity ID NEW-WORLD MONKEYS; C VIRUS; SURROGATE MODEL; IN-VIVO; CHIMPANZEES; AGENT; CLONE; NEUTRALIZATION; FLAVIVIRIDAE; GENERATION AB GB virus-B (GBV-B) is the virus most closely related to hepatitis C virus (HCV). Thus, we have used GBV-B infection of tamarins, which develop acute hepatitis following experimental infection, as a surrogate model to study protective immunity. As challenge virus, we first produced a GBV-B pool from an infected tamarin, which was not infected with the related GBV-A viruses. Its infectivity titer was 10(6.6) tamarin 50% infectious doses per ml. Next, two tamarins that were convalescent from recombinant GBV-B infection were re-challenged. In the original infection viremia persisted for 8 and 12 weeks, respectively, and both animals developed moderately severe hepatitis. Each tamarin was re-challenged four times with 10(4.3) tamarin 50% infectious doses of the GBV-B challenge virus. In one animal, each re-challenge produced 1-2 weeks of viremia; hepatitis was observed following the first re-challenge. In the other animal, however, only the first re-challenge produced viremia, lasting 1 week. During the primary infection, peak GBV-B titers were about 108 genome equivalents/ml in both animals; following re-challenges, peak titers ranged from 10(3) to 10(6) genome equivalents/ml. Analysis of the polyprotein sequence of viruses recovered from both animals following the first re-challenge demonstrated that these did not represent immune escape variants since mutations were not detected. Neutralization studies suggested that the immunity was not humoral in nature. We also demonstrated that the immunity was long-lived: 1 year after the fourth challenge, the animal with sterilizing immunity had low titer viremia for only 1 week following an additional challenge. C1 NIH, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA USA. RP Bukh, J (reprint author), NIH, Infect Dis Lab, Hepatitis Viruses Sect, Bldg 50,Rm 6531,50 S Dr, Bethesda, MD 20892 USA. EM jbukh@niaid.nih.gov FU Intramural NIH HHS NR 25 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JAN PY 2008 VL 80 IS 1 BP 87 EP 94 DI 10.1002/jmv.21013 PG 8 WC Virology SC Virology GA 236XE UT WOS:000251335900012 PM 18041000 ER PT J AU Shah, JP AF Shah, Jay P. TI Uncovering the biochemical milieu of myofascial trigger points using in vivo microdialysis SO JOURNAL OF MUSCULOSKELETAL PAIN LA English DT Article; Proceedings Paper CT International Congress of the International-MYOPAIN-Society CY AUG 20-23, 2007 CL Washington, DC SP Int Myopain Soc DE microdialysis; myofascial pain; rehabilitation; trigger points ID IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS AB Objectives: To 1. confirm our previous findings demonstrating the unique biochemical milieu of substances associated with pain and inflammation in an active myofascial trigger point [TrP] in the upper trapezius muscle, and 2. determine whether these findings are unique to the upper trapezius when compared with a remote uninvolved site in the upper medial gastrocnemius muscle. Methods: We developed and successfully utilized a novel microanalytical system, employing a minimally invasive 32-gauge needle, capable of the in vivo collection of small volumes [similar to 0.5 mu l] and subnanogram, levels [< 75 kDa] of solutes from muscle tissue. The needle also serves as a surrogate acupuncture needle during routine treatment of TrPs. This system provides us the unprecedented ability to safely explore and measure the local biochemical milieu of TrPs before, during, and after a local twitch response [LTR]. We previously found elevated levels of inflammatory mediators, neuropeptides, catecholamines, and cytokines at a standardized location in the upper trapezius muscle of subjects with active TrPs compared with those with latent TrPs and those without TrPs. Furthermore, the local biochemical milieu does appear to change after a LTR. There were nine healthy subjects, all of whom had no calf pain or calf TrPs and were divided into three groups based on the following findings in the trapezius: Active [painful TrP present, three subjects], Latent [nonpainful TrP present, three subjects], and Normal [no pain, no TrP present, three subjects]. Samples were obtained continuously with the microdialysis needle at regular intervals at two standardized anatomical locations: first in the upper trapezius [at acupuncture point GB-21, which is equivalent to region TP1] and then in the upper medial gastrocnemius at acupuncture point LV-7. The main outcome measures were levels of protons, bradykinin, substance P, calcitonin gene-related peptide [CGRP], serotonin, norepinephrine, tumor necrosis factor-alpha, interleukin-1 beta [IL-1 beta], IL-6, and IL-8. Results: At needle insertion in the Active group, levels of all measured analytes were higher in the trapezius than the gastrocnemius [P < 0.05]. This difference was also found in the Latent group for levels of tumor necrosis factor-alpha, substance P and calcitonin gene-related peptide [P < 0.005], and in the Normal group for levels of bradykinin only [P < 0.05]. In the gastrocnemius, all analytes except bradykinin were higher in the Active group than either the Latent and Normal groups [P < 0.01]. Conclusions: Significant differences in analyte levels were demonstrated between the trapezius [at GB-21] and gastrocnemius [at LV-7] in the Active group, suggesting that the vicinity of the active TrP exhibits a unique biochemical milieu of substances associated with pain and inflammation. Gastrocnemius analyte levels were higher in the Active group than either the Latent or Normal groups. This suggests that analyte abnormalities may not be limited to local areas of active TrPs. The application of this microanalytical system to nonarticular musculoskeletal disorders may help elucidate the pathogenesis, persistence, and amplification of myofascial pain syndrome and create a model for chronic soft tissue pain syndromes. Improved treatment strategies and techniques may evolve from understanding the local pathophysiology and the underlying cellular and molecular mechanisms of myofascial pain. C1 NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. RP Shah, JP (reprint author), NIH, Dept Rehabil Med, Clin Res Ctr, 10 Ctr Dr, Bethesda, MD 20892 USA. EM jshah@mail.cc.nih.gov NR 6 TC 8 Z9 9 U1 1 U2 7 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1058-2452 J9 J MUSCULOSKELET PAIN JI J. Musculoskelet. Pain PY 2008 VL 16 IS 1-2 BP 17 EP 20 DI 10.1080/10582450801960099 PG 4 WC Rehabilitation; Rheumatology SC Rehabilitation; Rheumatology GA 307OA UT WOS:000256327000005 ER PT J AU Wang, CKL Colgrave, ML Gustafson, KR Ireland, DC Goransson, U Craik, DJ AF Wang, Conan K. L. Colgrave, Michelle L. Gustafson, Kirk R. Ireland, David C. Goransson, Ulf Craik, David J. TI Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CYCLIC CYSTINE KNOT; KALATA B1; MACROCYCLIC PEPTIDES; CIRCULAR PROTEINS; STRUCTURAL MOTIF; CHASSALIA-PARVIFOLIA; OLDENLANDIA-AFFINIS; GLOBULAR-PROTEINS; PLANT CYCLOTIDES; POLYPEPTIDES AB Cyclotides are macrocyclic plant peptides characterized by a knotted arrangement of three disulfide bonds. They display a range of interesting bioactivities, including anti-HIV and insecticidal activities. More than 100 different cyclotides have been isolated from two phylogenetically distant plant families, the Rubiaceae and Violaceae. In this study we have characterized the cyclotides from Viola yedoensis, an important Chinese herb from the Violaceae family that has been reported to contain potential anti-HIV agents. From V. yedoensis five new and three known cyclotides were identified and shown to have anti-HIV activity. The most active of these is cycloviolacin Y5, which is one of the most potent of all cyclotides tested so far using in vitro XTT-based anti-HIV assays. Cycloviolacin Y5 is the most hydrophobic of the cyclotides from V. yedoensis. We show that there is a positive correlation between the hydrophobicity and the anti-HIV activity of the new cyclotides and that this trend tracks with their ability to disrupt membranes, as judged from hemolytic assays on human erythrocytes. C1 [Wang, Conan K. L.; Colgrave, Michelle L.; Ireland, David C.; Craik, David J.] Univ Queensland, Inst Mol Biosci, Australian Res Council, Special Res Ctr Funct & Appl Genom, Brisbane, Qld 4072, Australia. [Gustafson, Kirk R.] NCI, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21702 USA. [Goransson, Ulf] Uppsala Univ, Biomed Ctr, Dept Med Chem, Div Pharmacognosy, S-75123 Uppsala, Sweden. RP Craik, DJ (reprint author), Univ Queensland, Inst Mol Biosci, Australian Res Council, Special Res Ctr Funct & Appl Genom, Brisbane, Qld 4072, Australia. EM d.craik@imb.uq.edu.au RI Wang, Conan/D-1481-2010; Colgrave, Michelle/A-5710-2012; Craik, David/B-1695-2010; OI Wang, Conan/0000-0002-7973-7632; Colgrave, Michelle/0000-0001-8463-805X; Craik, David/0000-0003-0007-6796; Goransson, Ulf/0000-0002-5005-9612 NR 47 TC 72 Z9 76 U1 1 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 2008 VL 71 IS 1 BP 47 EP 52 DI 10.1021/np070393g PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 255AP UT WOS:000252629400011 PM 18081258 ER PT J AU Pettit, GR Mukku, VJRV Cragg, G Herald, DL Knight, JC Herald, CL Chapuis, JC AF Pettit, George R. Mukku, Venugopal J. R. V. Cragg, Gordon Herald, Delbert L. Knight, John C. Herald, Cherry L. Chapuis, Jean-Charles TI Antineoplastic agents. 558. Ampelocissus sp cancer cell growth inhibitory constituents SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID MITOCHONDRIAL COMPLEX I; ANNONACEOUS ACETOGENINS; CYTOTOXIC WITHANOLIDES; FRUITS AB An investigation of the Phillippine Ampelocissus sp. roots for cancer cell growth inhibitory components led to the isolation of a new acetogenin characterized as 22-epicalamistrin (1) employing primarily 2D NMR and high-resolution mass spectral analysis. Two other antineoplastic constituents proved to be the known acetogenin uvaribonin (2) and chalcone 3. Constituents 1-3 were all found to show significant cancer cell growth inhibitory activity against a panel of human cancer cell lines. C1 [Pettit, George R.; Mukku, Venugopal J. R. V.; Herald, Delbert L.; Knight, John C.; Herald, Cherry L.; Chapuis, Jean-Charles] Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. [Pettit, George R.; Mukku, Venugopal J. R. V.; Herald, Delbert L.; Knight, John C.; Herald, Cherry L.; Chapuis, Jean-Charles] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. [Cragg, Gordon] NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Nat Prod Branch, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. EM bpettit@asu.edu RI Mukku, Venugopal/I-5577-2016 OI Mukku, Venugopal/0000-0002-0292-6064 FU NCI NIH HHS [R01 CA-90441-01-05] NR 34 TC 16 Z9 17 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 2008 VL 71 IS 1 BP 130 EP 133 DI 10.1021/np068050q PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 255AP UT WOS:000252629400028 PM 18177007 ER PT J AU Yao, XH Ping, YF Chen, JH Chen, DL Xu, CP Zheng, J Wang, JM Bian, XW AF Yao, Xiao-Hong Ping, Yi-Fang Chen, Jian-Hong Chen, Dai-Lun Xu, Cheng-Ping Zheng, Jiang Wang, Ji Ming Bian, Xiu-Wu TI Production of angiogenic factors by human glioblastoma cells following activation of the G-protein coupled formylpeptide receptor FPR SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE angiogenesis; formylpeptide receptor; glioma; interleukin 8 (IL-8); vascular endothelial growth factor (VEGF) ID DEPENDENT INTERLEUKIN-8 EXPRESSION; HIGH-GRADE GLIOMA; GROWTH-FACTOR; KAPPA-B; MALIGNANT-MELANOMA; INVOLVEMENT; IL-8; SECRETION; CYTOKINES; DENSITY AB Activation of the formylpeptide receptor (FPR), a G-protein-coupled receptor, by its chemotactic peptide ligand N-formylmethionyl-leucyl-phenylalanine (fMLF) promotes the directional migration and survival of human glioblastoma cells. fMLF also stimulates glioblastoma cells to produce biologically active VEGF, an important angiogenic factor involved in tumor progression. In this study, we examined the capacity of FPR to regulate the production of another angiogenic factor, the chemokine IL-8 (CXCL8), in addition to its demonstrated ability to induce VEGF secretion by malignant glioma cells. We showed that the human glioblastoma cell line U87 secreted considerable levels of IL-8 (CXCL8) upon stimulation by the FPR agonist peptide fMLF. Tumor cells transfected with small interference (si)RNA targeting FPR failed to produce IL-8 as well as VEGF in response to fMLF. Glioblastoma cells bearing FPR siRNA exhibited reduced rate of tumorigenicity in nude mice and tumors formed by such tumor cells showed less active angiogenesis and lower level expression of both IL-8 and VEGF. These results suggest that FPR plays an important role in the angiogenesis of human malignant gliomas through increasing the production of angiogenic factors by FPR positive tumor cells. C1 Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China. Third Mil Med Univ, Med Res Ctr, Southwest Hosp, Chongqing 400038, Peoples R China. NCI, Mol Immunoregulat Lab, Cancer & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Bian, XW (reprint author), Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 28 TC 31 Z9 31 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2008 VL 86 IS 1 BP 47 EP 53 DI 10.1007/s11060-007-9443-y PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 238ZS UT WOS:000251487800006 PM 17611713 ER PT J AU Chefer, SI Pavlova, OA Zhang, Y Vaupel, DB Kimes, AS Horti, AG Stein, E Mukhin, AG AF Chefer, Svetlana I. Pavlova, Olga A. Zhang, Yi Vaupel, D. Bruce Kimes, Alane S. Horti, Andrew G. Stein, Elliot Mukhin, Alexey G. TI NIDA522131, a new radioligand for imaging extrathalamic nicotinic acetylcholine receptors: in vitro and in vivo evaluation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE nicotinic acetylcholine receptors; positron emission tomography; receptor binding ID POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; RADIATION-DOSIMETRY; GRAPHICAL ANALYSIS; BINDING-SITES; LEWY BODIES; PET; BRAIN; DEMENTIA AB A novel radioligand, 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-fluoropyridin-4-yl)pyridine (NIDA522131), for imaging extrathalamic nicotinic acetylcholine receptors (nAChRs) was characterized in vitro and in vivo using positron emission tomography. The K-d and T-1/2 of dissociation of NIDA522131 binding measured at 37 degrees C in vitro were 4.9 +/- 0.4 pmol/L and 81 +/- 5 min, respectively. The patterns of radioactivity distribution in monkey brain in vivo was similar to that of 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2FA), a radioligand that has been successfully used in humans, and matched the alpha(4)beta(2)* nAChRs distribution. Comparison between [F-18]NIDA522131 and 2FA demonstrated better in vivo binding properties of the new radioligand and substantially greater radioactivity accumulation in brain. Consistent with [F-18]NIDA522131 elevated affinity for nAChRs and its increased lipophilicity, both, the total and non-displaceable distribution volumes were substantially higher than those of 2FA. Estimated binding potential values in different brain regions, characterizing the specificity of receptor binding, were 3-4 fold higher for [F-18]NIDA522131 than those of 2FA. Pharmacological evaluation in mice demonstrated a toxicity that was comparable to 2FA and is in agreement with a 2300 fold higher affinity at alpha(4)beta(2)* versus alpha(3)beta(4)* nAChRs. These results suggest that [F-18]NIDA522131 is a promising positron emission tomography radioligand for studying extrathalamic nAChR in humans. C1 [Mukhin, Alexey G.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Ctr Nicotine & Smoking Cessat Res, Durham, NC 27705 USA. [Chefer, Svetlana I.; Pavlova, Olga A.; Zhang, Yi; Vaupel, D. Bruce; Kimes, Alane S.; Horti, Andrew G.; Stein, Elliot; Mukhin, Alexey G.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Mukhin, AG (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Ctr Nicotine & Smoking Cessat Res, 2424 Erwin Rd,Suite 201, Durham, NC 27705 USA. EM a.mukhin@duke.edu FU Intramural NIH HHS NR 32 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2008 VL 104 IS 2 BP 306 EP 315 DI 10.1111/j.1471-4159.2007.05009.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 242ZX UT WOS:000251765800003 PM 17986233 ER PT J AU Lee, JM Tiong, J Maddox, DM Condie, BG Wray, S AF Lee, J. M. Tiong, J. Maddox, D. M. Condie, B. G. Wray, S. TI Temporal migration of gonadotrophin-releasing hormone-1 neurones is modified in GAD67 knockout mice SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE GnRH; GABA; neuronal migration ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; EMBRYONIC OLFACTORY PLACODE; PRIMARY-CELL CULTURE; LHRH NEURONS; CORTICAL-NEURONS; MOUSE STRAINS; CLEFT-PALATE; GABA; RECEPTORS AB Gonadotrophin-releasing hormone (GnRH-1) neurones reside in the forebrain and regulate gonadal function via the hypothalamic-pituitary-gonadal axis. Disruption of this axis results in reproductive dysfunction. During embryonic development, GnRH-1 neurones migrate from the nasal pit through the nasal/forebrain junction (NFJ) into the developing brain. Prenatally gamma-aminobutyric acid (GABA) is excitatory and has been shown to play a role in nervous system development. Both in vivo and in vitro experiments suggest that GABA inhibits migration of GnRH-1 neurones. The present study examines the migration of GnRH-1 neurones in GAD67 knockout (KO) mice to further elucidate the role of GABA on GnRH-1 neuronal development. Three stages were examined, embryonic day (E)12.5, E14.5 and E17.5. GnRH-1 cell number and location were analysed by immunocytochemistry and in situ hybridisation histochemistry. The total number of GnRH-1 immunopositive cells was similar between wild-type (WT) and KO mice. However, significant differences were found in the overall distribution of GnRH-1 immunopositive cells in GAD67 KO compared to WT mice at all stages. Subsequent analysis by area revealed differences occurred at the NFJ with an increase in GnRH-1 cells in GAD67 KO at E14.5 and a decrease in GnRH-1 cells in GAD67 KO at E17.5. Comparable counts for cells expressing GnRH-1 transcript and protein were obtained. These data indicate that attenuated levels of GABA accelerate GnRH-1 cell migration in nasal areas as well as movement of GnRH-1 cells into the central nervous system at the NFJ. C1 [Lee, J. M.; Tiong, J.; Wray, S.] NINDS, NIH, Cellular Dev & Neurobiol Sect, Bethesda, MD 20892 USA. [Maddox, D. M.] Jackson Lab, Bar Harbor, ME 04609 USA. [Maddox, D. M.; Condie, B. G.] Univ Georgia, Dept Genet, Athens, GA 30602 USA. RP Wray, S (reprint author), NINDS, NIH, Cellular Dev & Neurobiol Sect, Bldg 35,Room 3A-1012, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 FU NIMH NIH HHS [R01MH064794] NR 41 TC 21 Z9 21 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JAN PY 2008 VL 20 IS 1 BP 93 EP 103 DI 10.1111/j.1365-2826.2007.01623.x PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 239YJ UT WOS:000251553900005 PM 18081557 ER PT J AU Detrick, B Lee, MT Chin, MS Hooper, LC Chan, CC Hooks, JJ AF Detrick, Barbara Lee, Maria Teresa Chin, Marian S. Hooper, Laura C. Chan, Chi-Chao Hooks, John J. TI Experimental coronavirus retinopathy (ECOR): Retinal degeneration susceptible mice have an augmented interferon and chemokine (CXCL9, CXCL10) response early after virus infection SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE coronavirus; retinal degeneration; chemokines; interferon; autoimmunity ID ACUTE RESPIRATORY SYNDROME; CENTRAL-NERVOUS-SYSTEM; IFN-GAMMA; EPITHELIAL-CELLS; IMMUNE-RESPONSE; VIRAL-INFECTION; INNATE IMMUNITY; EXPRESSION; DISEASE; IP-10 AB Mouse hepatitis virus induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop the late phase. What host factors contribute to the distinct responses to the virus are unknown. Herein, we show that IFN-alpha, IFN-beta and IFN-gamma act in concert as part of the innate immune response to the retinal infection. At day 2, high serum levels of IFN-gamma, CXCL9 and CXCL10, were detected in BALB/c mice. Moreover, elevated levels of CXCL9 and CXCL 10 gene expression were detected in retinal tissue. Although IFN-gamma and the chemokines were detected in CD-1 mice, they were at significantly lower levels compared to BALB/c mice. These augmented innate responses observed correlated with the development of autoimmune reactivity and retinal degeneration and thus may contribute to the pathogenic processes. (C) 2007 Elsevier B.V. All rights reserved. C1 [Detrick, Barbara] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Detrick, B (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 600 N Wolfe St,Meyer B125A, Baltimore, MD 21287 USA. EM bdetrick@jhmi.edu FU Intramural NIH HHS [Z01 EY000222-22] NR 44 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2008 VL 193 IS 1-2 BP 28 EP 37 DI 10.1016/j.jneuroim.2007.09.032 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 263LA UT WOS:000253217400004 PM 18037505 ER PT J AU Ilyas, AA Gu, Y Dalakas, MC Quarles, RH Bhatt, S AF Ilyas, A. A. Gu, Y. Dalakas, M. C. Quarles, R. H. Bhatt, S. TI Induction of experimental ataxic sensory neuronopathy in cats by immunization with purified SGPG SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE antibodies; cat; IgM gammopathy; neuropathy; sensory neuronopathy; MAG; SGPG ID MYELIN-ASSOCIATED GLYCOPROTEIN; IGM MONOCLONAL GAMMOPATHY; SULFATED GLUCURONYL GLYCOLIPIDS; BLOOD-NERVE BARRIER; ANTI-MAG; PERIPHERAL NEUROPATHY; LEWIS RATS; INTRANEURAL INJECTION; SPECIES DISTRIBUTION; DORSAL-ROOT AB IgM paraproteins in about 50% of the patients with neuropathy associated with IgM gammopathy react with carbohydrate moieties in myelin-associated glycoprotein (MAG) and in sulfated glucuronic glycolipids (SGGLs) in human peripheral nerves. However, the role of anti-MAG/SGGL antibodies in the pathogenesis of neuropathy remains unclear. In order to induce an animal model of neuropathy associated with anti-MAG/SGGL antibodies, cats were immunized with sulfoglucuronyl paragloboside (SGPG). All four cats immunized with SGPG developed clinical signs of sensory neuronopathy within 11 months after initial immunization, characterized by unsteadiness, falling, hind limb weakness and ataxia. In two cats the ataxia and hind limb paralysis were so severe that the animals had to be euthanized. Pathological examination revealed sensory ganglionitis with inflammatory infiltrates in the dorsal root ganglia. No overt signs of pathology were noted in the examined roots or nerves. High titer anti-SGPG/MAG antibodies were detected in all 4 cats immunized with SGPG but not in 3 control cats. Our data demonstrate that immunization of cats with SGPG induced anti-SGPG antibodies and sensory neuronopathy clinically resembling the sensory ataxia of patients with monoclonal IgM anti-MAG/SGPG antibodies. This study suggests that these anti-MAG/SGPG antibodies play a role in the pathogenesis of this neuropathy. (C) 2007 Elsevier B.V. All rights reserved. C1 [Ilyas, A. A.; Gu, Y.; Bhatt, S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA. [Dalakas, M. C.; Quarles, R. H.] NINDS, NIH, Bethesda, MD 20892 USA. RP Ilyas, AA (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, 185 S Orange Ave, Newark, NJ 07103 USA. EM ilyasaa@umdnj.edu FU NINDS NIH HHS [R21NS050300, R21 NS050300, R21 NS050300-01A2] NR 43 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2008 VL 193 IS 1-2 BP 87 EP 93 DI 10.1016/j.jneuroim.2007.10.025 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 263LA UT WOS:000253217400010 PM 18037501 ER PT J AU Logroscino, G Traynor, BJ Hardiman, O Chio', A Couratier, P Mitchell, JD Swingler, RJ Beghi, E AF Logroscino, G. Traynor, B. J. Hardiman, O. Chio', A. Couratier, P. Mitchell, J. D. Swingler, R. J. Beghi, E. CA EURALS TI Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review ID MOTOR-NEURON DISEASE; POPULATION-BASED REGISTRY; FRONTOTEMPORAL DEMENTIA; FAMILIAL AGGREGATION; CIGARETTE-SMOKING; EL-ESCORIAL; ENVIRONMENTAL EXPOSURE; COGNITIVE IMPAIRMENT; DIAGNOSTIC-CRITERIA; PARKINSONS-DISEASE AB Amyotrophic lateral sclerosis (ALS) is a relatively rare disease with a reported population incidence of between 1.5 and 2.5 per 100 000 per year. Over the past 10 years, the design of ALS epidemiological studies has evolved to focus on a prospective, population based methodology, employing the El Escorial criteria and multiple sources of data to ensure complete case ascertainment. Five such studies, based in Europe and North America, have been published and show remarkably consistent incidence figures among their respective Caucasian populations. Population based studies have been useful in defining clinical characteristics and prognostic indicators in ALS. However, many epidemiological questions remain that cannot be resolved by any of the existing population based datasets. The working hypotheses is that ALS, like other chronic diseases, is a complex genetic condition, and the relative contributions of individual environmental and genetic factors are likely to be relatively small. Larger studies are required to characterise risks and identify subpopulations that might be suitable for further study. This current paper outlines the contribution of the various population based registers, identifies the limitations of the existing datasets and proposes a mechanism to improve the future design and output of descriptive epidemiological studies. C1 [Logroscino, G.] Harvard Univ, Dept Epidemiol HSPH, Boston, MA 02115 USA. [Traynor, B. J.] NIH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. [Traynor, B. J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Hardiman, O.] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [Hardiman, O.] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Chio', A.] Univ Turin, Dipartimento Neurosci, Turin, Italy. [Couratier, P.] CHU Limoges, Neurol Serv, Limoges, France. [Mitchell, J. D.] Royal Preston Hosp, ALS Care & Res Ctr, Preston, Lancs, England. [Swingler, R. J.] Ninewells Hosp, Dept Neurol, Dundee DD1 9SY, Scotland. [Beghi, E.] Univ Milan, Ist Ric Farmacol Mario Negri, Monza, Italy. RP Logroscino, G (reprint author), Harvard Univ, Dept Epidemiol HSPH 3 819, 677 Huntington Ave, Boston, MA 02115 USA. EM glogrosc@hsph.harvard.edu RI Traynor, Bryan/G-5690-2010; LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chio, Adriano/0000-0001-9579-5341; Hardiman, Orla/0000-0003-2610-1291 NR 83 TC 196 Z9 201 U1 4 U2 18 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN PY 2008 VL 79 IS 1 BP 6 EP 11 DI 10.1136/jnnp.2006.104828 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 240ZD UT WOS:000251625800005 PM 18079297 ER PT J AU O'Toole, O Traynor, BJ Brennan, P Sheehan, C Frost, E Corr, B Hardiman, O AF O'Toole, O. Traynor, B. J. Brennan, P. Sheehan, C. Frost, E. Corr, B. Hardiman, O. TI Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004 SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID NEURON DISEASE; ALS; GASTROSTOMY; MORTALITY; SURVIVAL AB Background: We conducted a prospective, population based study to examine trends in incidence and prevalence of amyotrophic lateral sclerosis (ALS) in Ireland from 1995 to 2004. Methods: The Irish ALS Register was used to identify Irish residents diagnosed with ALS between the 3 year period from 1 January 1995 to 31 December 1997 and the 3 year period from 1 January 2002 to 31 December 2004. Results: 465 Irish residents were diagnosed with ALS during the study periods. The annual incidence rate of ALS in Ireland remained stable over this time (2.0 cases per 100 000 person-years; 95% CI 1.9, 2.2). Median survival of Irish ALS patients was 16.4 months and did not change during the study period. Demographics and clinical features of the incident and prevalent Irish ALS cohorts were markedly different. C1 [O'Toole, O.; Brennan, P.; Sheehan, C.; Corr, B.; Hardiman, O.] Univ Dublin Trinity Coll, Dept Neurol, Beaumont Hosp, Dublin 9, Ireland. [O'Toole, O.; Brennan, P.; Sheehan, C.; Corr, B.; Hardiman, O.] RCSI, Dublin, Ireland. [Traynor, B. J.] NIMH, SDGE, NIH, Bethesda, MD 20892 USA. [Frost, E.] Irish Motor Neurone Dis Assoc, Dublin, Ireland. [Hardiman, O.] Univ Dublin Trinity Coll, Trinity Coll Inst Neurosci, Dublin 2, Ireland. RP Hardiman, O (reprint author), Univ Dublin Trinity Coll, Dept Neurol, Beaumont Hosp, Dublin 9, Ireland. EM ohard@iol.ie RI Traynor, Bryan/G-5690-2010; OI Hardiman, Orla/0000-0003-2610-1291 FU Intramural NIH HHS NR 14 TC 108 Z9 108 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN PY 2008 VL 79 IS 1 BP 30 EP 32 DI 10.1136/jnnp.2007.117788 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 240ZD UT WOS:000251625800010 PM 17634215 ER PT J AU Kim, CH Lee, J Lee, JY Roche, KW AF Kim, Chul Hoon Lee, Jinu Lee, Jae-Youn Roche, Katherine W. TI Metabotropic glutamate receptors: Phosphorylation and receptor signaling SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE mGluR; phosphorylation; protein kinase; protein phosphatase; desensitization; endocytosis; synaptic plasticity ID PROTEIN-KINASE-C; LONG-TERM DEPRESSION; REGULATED KINASE; CALMODULIN-BINDING; GROUP-II; GLUTAMATE-RECEPTOR-1 INTERNALIZATION; PHARMACOLOGICAL CHARACTERIZATION; MOLECULAR CHARACTERIZATION; TYROSINE PHOSPHORYLATION; SELECTIVE REGULATION AB Metabotropic glutamate receptors (mGluRs) play important roles in neurotransmission, neuronal development, synaptic plasticity, and neurological disorders. Recent studies have revealed a sophisticated interplay between mGluRs and protein kinases: activation of mGluRs regulates the activity of a number of kinases, and direct phosphorylation of mGluRs affects receptor signaling, trafficking, and desensitization. Here we review the emerging literature on mGluR phosphorylation, signaling, and synaptic function. (c) 2007Wiley-Liss, Inc. C1 [Kim, Chul Hoon; Lee, Jae-Youn] Yonsei Univ, Coll Med, Dept Pharmacol, Brain Res Inst,Brain Korea Project Med Sci 21, Seoul 120752, South Korea. [Lee, Jinu] Pochon CHA Univ, Coll Med, Dept Pharmacol, Songnam, South Korea. [Roche, Katherine W.] NINDS, NIH, Bethesda, MD 20892 USA. RP Kim, CH (reprint author), Yonsei Univ, Coll Med, Dept Pharmacol, Brain Res Inst,Brain Korea Project Med Sci 21, 134 Shinchon Dong, Seoul 120752, South Korea. EM kimhoon@yuhs.ac OI Roche, Katherine/0000-0001-7282-6539 FU Intramural NIH HHS NR 87 TC 60 Z9 64 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN PY 2008 VL 86 IS 1 BP 1 EP 10 DI 10.1002/jnr.21437 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 253LZ UT WOS:000252521000001 PM 17663464 ER PT J AU Robertson, K Kopnisky, K Hakim, J Merry, C Nakasujja, N Hall, C Traore, M Sacktor, N Clifford, D Newton, C Van Rie, A Holding, P Clements, J Zink, C Mielke, J Hosseinipour, M Lalloo, U Amod, F Marra, C Evans, S Liner, J AF Robertson, Kevin Kopnisky, Kathy Hakim, James Merry, Concepta Nakasujja, Noeline Hall, Colin Traore, Moussa Sacktor, Ned Clifford, David Newton, Charles Van Rie, Annelies Holding, Penny Clements, Janice Zink, Christine Mielke, Jens Hosseinipour, Mina Lalloo, Umesh Amod, Farida Marra, Christina Evans, Scott Liner, Jeff CA NeuroAIDS TI Second assessment of NeuroAIDS in Africa SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE HIV; neurological disease; neuropsychological assessment; resource-limited settings ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CENTRAL-NERVOUS-SYSTEM; HIV-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE INHIBITORS; DISTAL SENSORY POLYNEUROPATHY; SUB-SAHARAN AFRICA; PLASMA VIRAL LOAD; RISK-FACTORS; LACTIC-ACIDOSIS AB In July of 2006, the National Institute of Mental Health (NIMH) Center for Mental Health Research on AIDS (CMHRA) sponsored the second conference on the Assessment of NeuroAIDS in Africa, which was held in Arusha, Tanzania. The conference mission was to address the regional variations in epidemiology of HIV-related neurological disorders as well as the assessment and diagnosis of these disorders. Participants discussed and presented data regarding the relevance and translation of neuroAIDS assessment measures developed in resource intensive settings and the challenges of neuro-assessment in Africa, including the applicability of current tools, higher prevalence of confounding diseases, and the complexity of diverse cultural settings. The conference presentations summarized here highlight the need for further research on neuroAIDS in Africa and methods for assessing HIV-related neurological disorders. C1 [Robertson, Kevin; Hall, Colin; Liner, Jeff] Univ N Carolina, Chapel Hill Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. [Kopnisky, Kathy] NIMH, NIH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. [Hakim, James] Univ Zimbabwe, Sch Med, Dept Med, Harare, Zimbabwe. [Merry, Concepta] Univ Dublin Trinity Coll, Trinity Ctr SJH, Dublin 2, Ireland. [Nakasujja, Noeline] Makerere Univ, Sch Med, Dept Psychiat, Kampala, Uganda. [Traore, Moussa] Univ Bamako, Sch Med, Dept Neurol, Point G Hosp, Bamako, Mali. [Sacktor, Ned] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. [Clifford, David; Marra, Christina] Washington Univ, Dept Neurol & Med, St Louis, MO USA. [Newton, Charles] Kenya Govt Med Res Ctr, Kilifi, Kenya. [Newton, Charles] Inst Child Hlth, Dept Neurosci, London, England. [Van Rie, Annelies] Univ N Carolina, Dept Epidemiol, Chapel Hill Sch Med, Chapel Hill, NC USA. [Holding, Penny] Ctr Geog Med Res, Kemri, Kenya. [Holding, Penny] Univ Oxford, Oxford OX1 2JD, England. [Clements, Janice; Zink, Christine] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. [Mielke, Jens] Univ Zimbabwe, Coll Hlth Sci, Dept Med, Harare, Zimbabwe. [Hosseinipour, Mina] Univ N Carolina, Div Infect Dis, Dept Med, Chapel Hill, NC USA. [Hosseinipour, Mina] Univ N Carolina Project, Lilongwe, Malawi. [Lalloo, Umesh] Univ KwaZulu Natal, Durban, South Africa. [Amod, Farida] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa. [Evans, Scott] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Robertson, K (reprint author), Univ N Carolina, Chapel Hill Sch Med, Dept Neurol, 3114 Bioinformat Bldg,CB7025, Chapel Hill, NC 27599 USA. EM kevinr@neurology.unc.edu RI Van Rie, Annelies/C-2082-2017; OI Van Rie, Annelies/0000-0001-7666-3263; Newton, Charles/0000-0002-6999-5507 NR 73 TC 6 Z9 6 U1 4 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2008 VL 14 IS 2 BP 89 EP 101 DI 10.1080/13550280701829793 PG 13 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 293ZC UT WOS:000255372900001 ER PT J AU McCall, S Vilensky, JA Gilman, S Taubenberger, JK AF McCall, Sherman Vilensky, Joel A. Gilman, Sid Taubenberger, Jeffery K. TI The relationship between encephalitis lethargica and influenza: A critical analysis SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE bird flu; epidemic encephalitis; sleepy sickness; von Economo's disease ID ACUTE NECROTIZING ENCEPHALOPATHY; A VIRUS-INFECTION; POSTENCEPHALITIC PARKINSONISM; EPIDEMIC ENCEPHALITIS; CLINICAL-DIAGNOSIS; PANDEMIC VIRUS; VIRAL CULTURE; BRAIN-TISSUE; GENE; RNA AB Since encephalitis lethargica's (EL) prevalence in the 1920s, epidemiologic and clinical debate has persisted over whether EL was caused by, potentiated by, or merely coincident with the Spanish influenza pandemic. Epidemiologic analyses generally suggest that the disorders were coincidental. Beginning in the 1970s, modern experiments on archival brain samples mainly failed to confirm a direct relationship between influenza and EL. These experimental studies have technical limitations, e. g., the appropriateness of antibodies, polymerase chain reaction (PCR) primers and controls, and the extreme paucity and age of available material. These factors render the case against influenza less decisive than currently perceived. Nevertheless, there is little direct evidence supporting influenza in the etiology of EL. Almost 100 years after the EL epidemic, its etiology remains enigmatic, raising the possibility of a recurrence of EL in a future influenza pandemic. C1 [Vilensky, Joel A.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Ft Wayne, IN 46805 USA. [McCall, Sherman] USA, Med Res Inst Infect Dis, Dept Clin Pathol, Ft Detrick, MD 21702 USA. [Gilman, Sid] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA. [Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Vilensky, JA (reprint author), Indiana Univ, Sch Med, Dept Anat & Cell Biol, 2101 E Coliseum Blvd, Ft Wayne, IN 46805 USA. EM vilensk@ipfw.edu FU Intramural NIH HHS [ZIA AI000995-03] NR 88 TC 17 Z9 17 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2008 VL 14 IS 3 BP 177 EP 185 DI 10.1080/13550280801995445 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 316VS UT WOS:000256978400001 PM 18569452 ER PT J AU McCloskey, DJ AF McCloskey, Donna Jo TI Nurses' perceptions of research utilization in a corporate health care system SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE evidence-based practice; research utilization ID BARRIERS; FACILITATORS AB Purpose: To explore selected characteristics of nurses based upon educational level (masters, baccalaureate, associate degree/diploma), years of experience, and hospital position (management, advanced practice, staff nurse) that might affect perceived availability of research resources, attitude towards research, support, and research use in practice. Design: A descriptive nonexperimental mailed survey design was used for this study. Methods: Nurses in five hospitals within a corporate hospital system were surveyed using the Research Utilization Questionnaire (RUQ). The RUQ was used to measure nurses' perceptions of research utilization in the four dimensions of perceived use of research, attitude toward research, availability of research resources, and perceived support for research activities. Findings: ANOVA was used to analyze the data. Statistically significant differences (p <.001) were found in the perceived use of research, attitude toward research, availability of research resources, and perceived support for research activities based on educational level and organizational position. No significant differences were found in the perception of nurses based on years of experience. Conclusions: The results of this study have implications for staff nurses, administrators, advanced practice nurses, and educators working in hospital systems. The different perceptions based upon educational level and hospital position can be integrated and used at all levels of nursing practice to promote research utilization and evidence-based practice initiatives within the organizational structure. Clinical Implications: The results of this study have nursing implications within administration and for nursing practice. The different perceptions that were found based upon educational level and hospital position can be positively integrated and used by administrators and by nurses all levels of nursing practice to promote research utilization and evidence based practice initiatives within the organizational structure. C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP McCloskey, DJ (reprint author), NIH, Natl Ctr Res Resources, Democracy 1,room 921, Bethesda, MD 20892 USA. EM mccloskd@mail.ih.gov NR 27 TC 25 Z9 25 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2008 VL 40 IS 1 BP 39 EP 45 DI 10.1111/j.1547-5069.2007.00204.x PG 7 WC Nursing SC Nursing GA 267AG UT WOS:000253479600009 PM 18302590 ER PT J AU SanGiovanni, JP Chew, EY Vora, A Ajudua, S Clemons, TE Henning, AK Elashoff, M AF SanGiovanni, J. P. Chew, E. Y. Vora, A. Ajudua, S. Clemons, T. E. Henning, A. K. Elashoff, M. TI Variants in Genes of Metabolic and Signaling Pathways Impacted by Lipid-Based Molecules and Their Association with Age-Related Macular Degeneration SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [SanGiovanni, J. P.; Chew, E. Y.] NEI, NIH, Bethesda, MD 20892 USA. [Vora, A.] UMDNJ, Camden, NJ USA. [Ajudua, S.] Brown Univ, Providence, RI 02912 USA. [Clemons, T. E.; Henning, A. K.; Elashoff, M.] EMMES Corp, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2008 VL 1 IS 1-2 BP 64 EP 65 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 493OD UT WOS:000269745900020 ER PT J AU Milner, J AF Milner, J. TI Frontiers in Nutrigenetics and Nutrigenomics at the National Cancer Institute (NCI) SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Milner, J.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2008 VL 1 IS 1-2 BP 68 EP 68 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 493OD UT WOS:000269745900029 ER PT J AU Sanderson, SC Wardle, J Humphries, SE AF Sanderson, Saskia C. Wardle, Jane Humphries, Steve E. TI Public Health Genomics and Genetic Test Evaluation: The Challenge of Conducting Behavioural Research on the Utility of Lifestyle-Genetic Tests SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Article DE Genetic testing; Lifestyle; Health behaviours; Clinical utility; Public health genomics ID SMOKING-CESSATION TREATMENT; AFRICAN-AMERICAN SMOKERS; HEART-DISEASE; LUNG-CANCER; INSULIN SENSITIVITY; RISK; SUSCEPTIBILITY; PERSPECTIVE; FRAMEWORK; FEEDBACK AB Human genetics research is increasingly concerned with multifactorial conditions such as diabetes and heart disease, which are influenced not only by genetic but also lifestyle factors such as diet and smoking. Although the results of 'lifestyle-genetic' tests using this information could conceivably motivate lifestyle changes in the future, companies are already selling such tests and related lifestyle advice commercially. Some academics and lobby groups have condemned the companies for selling these tests in advance of scientific support. Others are concerned that the tests may not motivate lifestyle improvements, instead causing distress in people receiving adverse test results and complacency in those receiving reassuring results. There is currently no regulatory oversight of genetic test utility, despite consensus in the Public Health Genomics community that clinical utility (including psychological and behavioural impact) of all emerging genetic tests should be evaluated before being introduced for individual use. Clearly, empirical data in this area is much needed, to inform understanding of the potential utility of these tests, and of whether stricter regulation of commercial exploitation is needed. In this article, we review the current situation regarding lifestyle-genetic tests, and discuss the challenges inherent in conducting this kind of behavioural research in the genomics era. Copyright (C) 2008 S. Karger AG, Basel C1 [Sanderson, Saskia C.; Humphries, Steve E.] UCL, Dept Med, Ctr Cardiovasc Genet, London WC1E 6JJ, England. [Sanderson, Saskia C.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Sanderson, Saskia C.; Wardle, Jane] UCL, Dept Epidemiol & Publ Hlth, Hlth Behav Res Ctr, London WC1E 6JJ, England. RP Humphries, SE (reprint author), UCL, Dept Med, Ctr Cardiovasc Genet, Rayne Bldg,5 Univ St, London WC1E 6JJ, England. EM rmhaseh@ucl.ac.uk OI Humphries, Stephen E/0000-0002-8221-6547 NR 56 TC 5 Z9 5 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2008 VL 1 IS 5 BP 224 EP 231 DI 10.1159/000149826 PG 8 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 494FF UT WOS:000269794900002 PM 19776630 ER PT J AU Miller, J AF Miller, J. TI Challenges in Nutrigenetics/Nutrigenomics and Cancer Prevention SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Miller, J.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2008 VL 1 IS 6 BP 281 EP 281 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 494FG UT WOS:000269795000033 ER PT J AU Percival, SS Bukowski, JE Milners, J AF Percival, Susan S. Bukowski, Jack E. Milners, John TI Bioactive food components that enhance gamma delta T cell function may play a role in cancer prevention SO JOURNAL OF NUTRITION LA English DT Article ID PRENYL PYROPHOSPHATE ANTIGENS; MISTLETOE VISCUM-ALBUM; GREEN TEA; NONPEPTIDE ANTIGENS; TUMOR-CELLS; IN-VITRO; EX-VIVO; LYMPHOCYTES; EXTRACT; RECOGNITION AB gamma delta Tcells are found largely within the epithelium and recognize antigens differently than their alpha beta T cell counterparts. TCR delta(-/-) knock out mice exhibit a rapid tumor onset, along with increased tumor incidence. Although limited, research demonstrates that nutrients and bioactive food components can influence gamma delta T cell cytotoxicity, cytokine secretion, and proliferative capacity, and the results are nonetheless intriguing. Among other functions, gamma delta T cells play a role in immunosurveillance against malignant cells, as shown by the T cell receptor (TCR)delta(-/-) knock out mice that exhibit a rapid tumor onset and increased tumor incidence. Some common dietary modifiers of gamma delta T cell numbers or activity are apple condensed tannins, dietary nucleotides, fatty acids, and dietary alkylamines. A recent clinical study demonstrated that ingesting a fruit and vegetable juice concentrate increased the number of circulating gamma delta T cells. Clinical studies also document that the oral consumption of a tea component, L-theanine, enhances gamma delta T cell proliferation and interferon-gamma secretion. The significance of these studies awaits additional examination of the influence of exposures and duration on these and other food components. Adoptive transfer and TCR delta(-/-) knockout mice models should be used more extensively to determine the physiological impact of the number and activity of these cells as a function of dietary component exposures. While clarifying the diet and gamma delta T interrelationship may not be simple, the societal implications are enormous. C1 [Percival, Susan S.] Univ Florida, Gainesville, FL 32611 USA. [Bukowski, Jack E.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02115 USA. [Bukowski, Jack E.] Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02115 USA. [Bukowski, Jack E.] Nutr Sci Res Inst, Boston, MA 02115 USA. [Milners, John] Natl Canc Inst, NIH, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Percival, SS (reprint author), Univ Florida, Gainesville, FL 32611 USA. EM percival@ufl.edu NR 49 TC 17 Z9 18 U1 0 U2 9 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 1 EP 4 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200001 PM 18156395 ER PT J AU Rogers, CJ Berrigan, D Zaharoff, DA Hance, KW Patel, AC Perkins, SN Schlom, J Greiner, JW Hursting, SD AF Rogers, Connie J. Berrigan, David Zaharoff, David A. Hance, Kenneth W. Patel, Arti C. Perkins, Susan N. Schlom, Jeffrey Greiner, John W. Hursting, Stephen D. TI Energy restriction and exercise differentially enhance components of systemic and mucosal immunity in mice SO JOURNAL OF NUTRITION LA English DT Article ID NATURAL-KILLER-CELLS; CALORIE RESTRICTION; PHYSICAL-ACTIVITY; MODERATE EXERCISE; CANCER PREVENTION; IN-VIVO; DIETARY RESTRICTION; TREADMILL EXERCISE; COLORECTAL-CANCER; BODY-COMPOSITION AB The prevalence of obesity, an established risk factor for several chronic diseases, including cancer, has risen dramatically over the past 4 decades. Dietary change and/or increased physical activity are the most commonly recommended lifestyle-based strategies for preventing or reversing obesity. One of several physiological systems that may be enhanced by dietary change and exercise is the immune system. In this study, we examined the effects of energy restriction (ER; 30% reduction relative to control energy intake) and/or exercise (EX; voluntary wheel running) on systemic and mucosal immune function. Female C57BL/6 mice were randomized into 4 treatment conditions: 1) controls consumed ad libitum (AL); 2) AL with access to running wheels (AL + EX); 3) 30% ER; and 4) 30% ER with access to running wheels (ER + EX). Both ER and EX reduced spleen weight and the number of splenic T and B lymphocytes (P < 0.05). ER enhanced natural killer (NK) cell function, but reduced concanavalin A (Con A)-induced T-cell proliferation (P < 0.05). In contrast, EX enhanced Con A-induced proliferation and cytokine production from Peyer's patch cells (P < 0.05). These data suggest that ER and EX enhance some, but not all, components of the immune system and are likely working via different biological mechanisms to regulate NK and T-cell function. C1 [Rogers, Connie J.; Zaharoff, David A.; Hance, Kenneth W.; Patel, Arti C.; Schlom, Jeffrey; Greiner, John W.] NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. [Rogers, Connie J.; Hance, Kenneth W.; Patel, Arti C.] NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. [Perkins, Susan N.; Hursting, Stephen D.] Univ Texas Austin, Dept Human Ecol, Div Nutr Sci, Austin, TX 78712 USA. [Berrigan, David] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hursting, Stephen D.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78712 USA. RP Rogers, CJ (reprint author), NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. EM rogersco@mail.nih.gov FU Intramural NIH HHS [Z01 BC010598-04]; NIEHS NIH HHS [P30 ES007784] NR 70 TC 26 Z9 26 U1 0 U2 3 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 115 EP 122 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200019 PM 18156413 ER PT J AU Nebeling, L AF Nebeling, Linda TI The examination of two short dietary assessment methods, within the contest of multiple behavioral change interventions in adult populations - Preface SO JOURNAL OF NUTRITION LA English DT Editorial Material C1 NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. RP Nebeling, L (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. EM nebelinl@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 181S EP 182S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200028 ER PT J AU Yaroch, AL Nebeling, L Thompson, FE Hurley, TG Hebert, JR Toobert, DJ Resnicow, K Greene, GW Williams, GC Elliot, DL Slier, TG Stacewicz-Sapuntzakis, M Salkeld, J Rossi, S Domas, A Mcgregor, H Defrancesco, C Mccarty, F Costello, RB Peterson, KE AF Yaroch, Amy L. Nebeling, Linda Thompson, Frances E. Hurley, Thomas G. Hebert, James R. Toobert, Deborah J. Resnicow, Ken Greene, Geoffrey W. Williams, Geoffrey C. Elliot, Diane L. Slier, Tamara Goldman Stacewicz-Sapuntzakis, Maria Salkeld, Judith Rossi, Susan Domas, Andrea Mcgregor, Holly Defrancesco, Carol Mccarty, Frances Costello, Rebecca B. Peterson, Karen E. TI Baseline design elements and sample characteristics for seven sites participating in the Nutrition Working Group of the Behavior Change Consortium SO JOURNAL OF NUTRITION LA English DT Article ID FACTOR SURVEILLANCE SYSTEM; VEGETABLE CONSUMPTION; FRUIT; CAROTENOIDS; PROGRAM; ADULTS; QUESTIONNAIRE; INSTRUMENTS; PERFORMANCE; WORKSITE AB The purpose of this article is to describe the baseline design elements and sample characteristics of the Behavior Change Consortium (BCC) Dietary Measurement studies for each of the 7 sites that comprised the BCC Nutrition Working Group (NWG). This article summarizes the project designs, including descriptions of diverse study populations, primary assessment methods, and study outcomes. Common measures used across sites included the National Cancer Institute (NCI) Fruit and Vegetable Screener, NCI Percentage Energy from Fat Screener, 24-h dietary recalls, and a single- or 2-item fruit and vegetable measure. Data on sociodemographic characteristics, body weight and height, smoking status, and serum carotenoids were also collected. Study design information such as assessment time points, as well as baseline sample characteristics, is also described. This paper provides the overall framework and descriptive information and serves as the reference for the BCC NWG special supplement. C1 [Yaroch, Amy L.; Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. [Thompson, Frances E.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Canc Prevent & Control Program, Columbia, SC 29208 USA. [Toobert, Deborah J.] Oregon Res Inst, Eugene, OR 97403 USA. [Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Greene, Geoffrey W.] Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. [Williams, Geoffrey C.; Mcgregor, Holly] Univ Rochester, Dept Med, Rochester, NY 14642 USA. [Williams, Geoffrey C.; Mcgregor, Holly] Univ Rochester, Dept Clin & Social Sci Psychol, Rochester, NY 14642 USA. [Williams, Geoffrey C.; Mcgregor, Holly] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Elliot, Diane L.; Defrancesco, Carol] Oregon Hlth & Sci Univ, Div Hlth Promot & Sports Med, Portland, OR 97239 USA. [Slier, Tamara Goldman] IIT, Inst Psychol, Chicago, IL 60616 USA. [Stacewicz-Sapuntzakis, Maria] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL 60612 USA. [Salkeld, Judith] Brown Univ, Div Biol & Med, Providence, RI 02912 USA. [Rossi, Susan] Univ Rhode Isl, Sch Nursing, Kingston, RI 02881 USA. [Domas, Andrea] Rush Univ, Med Ctr, Dept Nutr & Food Sci, Chicago, IL 60612 USA. [Mccarty, Frances] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Costello, Rebecca B.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Yaroch, AL (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. EM yarocha@mail.nih.gov FU NHLBI NIH HHS [R01HL62156, R01HL62158, R01HL64959]; NIA NIH HHS [R01AG16588]; NIAMS NIH HHS [R01AR45901]; NICHD NIH HHS [R01HD37368]; NIH HHS [RFA OD-93-002]; NIMH NIH HHS [R01MH59594] NR 31 TC 14 Z9 14 U1 2 U2 2 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 185S EP 192S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200030 PM 18156423 ER PT J AU Thompson, FE Midthune, D Williarns, GC Yaroch, AL Hurley, TG Resnicow, K Hebert, JR Toobert, DJ Greene, GW Peterson, K Nebeling, L AF Thompson, Frances E. Midthune, Douglas Williarns, Geoffrey C. Yaroch, Amy L. Hurley, Thomas G. Resnicow, Ken Hebert, James R. Toobert, Deborah J. Greene, Geoffrey W. Peterson, Karen Nebeling, Linda TI Evaluation of a short dietary assessment instrument for percentage energy from fat in an intervention study SO JOURNAL OF NUTRITION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; DOUBLY LABELED WATER; MODIFICATION TRIAL; BREAST-CANCER; BODY-WEIGHT; VALIDATION; WOMEN; PATTERN; RECALL; RISK AB The need for an inexpensive measure of dietary intake in intervention studies led to evaluation of the National Cancer Institute (NCI) Percentage Energy from Fat short instrument (PFat) in a subgroup of the Behavioral Change Consortium (BCC) intervention sites. The PFat's performance was evaluated using multiple nonconsecutive 24-h dietary recalls (24HR) as a reference instrument among participants at baseline in 4 demographically diverse intervention sites of the BCC. Mean estimates of percentage energy from fat for 24HR and PFat were within 2.1 percentage points of each other in all but 2 site/gender comparisons. 24HR and PFat estimates were not significantly different (P < 0.05) among men for 2 of 3 sites, and among women for 2 of 4 sites. Deattenuated Pearson correlation coefficients for the PFat and true intake (as estimated from the 24HR using a measurement error model) were significantly different from 0 (P < 0.05) for men and women in all sites, ranging from 0.52 to 0.77 among men and 0.36 to 0.59 among women. Besides gender and site, no other factors examined (age, education, smoking status, and BMI) consistently moderated validity estimates. If accurate assessment of diet at baseline (and presumably at follow-up) is essential, a more detailed instrument such as multiple 24HR may be warranted. The question of whether the PFat adequately measures change in diet is addressed in another article in this supplement. C1 [Thompson, Frances E.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Midthune, Douglas] NCI, Biometry Program, Div Canc Prevent, Bethesda, MD 20892 USA. [Williarns, Geoffrey C.] Univ Rochester, Dept Med, Rochester, NY 14642 USA. [Williarns, Geoffrey C.] Univ Rochester, Dept Clin & Social Sci Psychol, Rochester, NY 14642 USA. [Williarns, Geoffrey C.] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Yaroch, Amy L.; Nebeling, Linda] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Dept Epidemiol & Biostat, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Canc Prevent & Control Program, Columbia, SC 29208 USA. [Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Toobert, Deborah J.] Oregon Res Inst, Eugene, OR 97403 USA. [Greene, Geoffrey W.] Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. [Peterson, Karen] Harvard Univ, Sch Med, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen] Harvard Univ, Sch Med, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Thompson, FE (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM thompsof@mail.nih.gov FU NHLBI NIH HHS [R01HL62156, R01HL62158, R01HL64959]; NIA NIH HHS [R01AG16588]; NIAMS NIH HHS [R01AR45901]; NICHD NIH HHS [R01HD37368]; NIH HHS [RFA OD-93-002]; NIMH NIH HHS [R01MH59594] NR 41 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 193S EP 199S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200031 PM 18156424 ER PT J AU Greene, GW Resnicow, K Thompson, FE Peterson, KE Hurley, TG Hebert, JR Toobert, DJ Williams, GC Elliot, DL Sher, TG Domas, A Midthune, D Stacewicz-Sapuntzakis, M Yaroch, AL Nebeling, L AF Greene, Geoffrey W. Resnicow, Ken Thompson, Frances E. Peterson, Karen E. Hurley, Thomas G. Hebert, James R. Toobert, Deborah J. Williams, Geoffrey C. Elliot, Diane L. Sher, Tamara Goldman Domas, Andrea Midthune, Douglas Stacewicz-Sapuntzakis, Maria Yaroch, Amy L. Nebeling, Linda TI Correspondence of the NCI Fruit and Vegetable Screener to repeat 24-h recalls and serum Carotenoids in behavioral intervention trials SO JOURNAL OF NUTRITION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; PERFORMANCE; INSTRUMENTS; SERVINGS AB Five sites participating in the NCI Behavior Change Consortium administered the NCI Fruit and Vegetable Screener (FVS) and multiple, nonconsecutive 24-h dietary recall interviews (24HR) to 590 participants. Three sites also obtained serum carotenoids (n = 295). Participants were primarily female, ethnically diverse, and varied by age and education. Correlations between 24HR and FVS by site ranged from 0.31 (P = 0.07) to 0.47 (P < 0.01) in men and from 0.43 to 0.63 (P < 0.01) in women. Compared with 24HR, FVS significantly (P < 0.05) overestimated intake at 2 of 4 sites for men and all 4 sites for women. Differences in estimated total servings of fruits and vegetables/d ranged from 0.16 to 3.06 servings. On average, the FVS overestimated intake by 1.76 servings in men and 2.11 servings in women. Alternative FVS scoring procedures and a 1-item screener lowered correlations with 24HR as well as serum carotenoids but alternate scoring procedures generally improved estimations of servings. C1 [Greene, Geoffrey W.] Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. [Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Thompson, Frances E.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Canc Prevent & Control Program, Columbia, SC 29208 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Toobert, Deborah J.] Oregon Res Inst, Eugene, OR 97403 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Med, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Clin & Social Sci Psychol, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Elliot, Diane L.] Oregon Hlth & Sci Univ, Div Hlth Promot & Sports Med, Portland, OR 97239 USA. [Sher, Tamara Goldman] IIT, Inst Psychol, Chicago, IL 60616 USA. [Domas, Andrea] Rush Univ, Med Ctr, Dept Food & Nutr Serv, Chicago, IL 60612 USA. [Midthune, Douglas] NCI, Div Canc Prevent, Biometry Program, Bethesda, MD 20892 USA. [Stacewicz-Sapuntzakis, Maria] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL 60612 USA. [Yaroch, Amy L.; Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. RP Greene, GW (reprint author), Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. EM gwg@uri.edu FU NHLBI NIH HHS [R01HL62156, R01HL62158, R01HL64959]; NIA NIH HHS [R01AG16588]; NIAMS NIH HHS [R01AR45901]; NICHD NIH HHS [R01HD37368]; NIH HHS [RFA OD-93-002]; NIMH NIH HHS [R01MH59594] NR 26 TC 31 Z9 31 U1 0 U2 5 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 200S EP 204S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200032 PM 18156425 ER PT J AU Davis, RE Resnicow, K Atienza, AA Peterson, KE Domas, A Hunt, A Hurley, TG Yaroch, AL Greene, GW Sher, TG Williams, GC Hebert, JR Nebeling, L Thompson, FE Toobert, DJ Elliot, DL DeFrancesco, C Costello, RB AF Davis, Rachel E. Resnicow, Ken Atienza, Audie A. Peterson, Karen E. Domas, Andrea Hunt, Anne Hurley, Thomas G. Yaroch, Amy L. Greene, Geoffrey W. Sher, Tamara Goldman Williams, Geoffrey C. Hebert, James R. Nebeling, Linda Thompson, Frances E. Toobert, Deborah J. Elliot, Diane L. DeFrancesco, Carol Costello, Rebecca B. TI Use of signal detection methodology to identify subgroups of dietary supplement use in diverse populations SO JOURNAL OF NUTRITION LA English DT Article ID HEALTH INTERVIEW SURVEY; SMOKING-CESSATION; NATIONAL-HEALTH; LOGISTIC-REGRESSION; UNITED-STATES; LIFE-STYLE; ADULTS; VITAMIN; DISEASE; RISK AB Despite widespread use of dietary supplements, little is known about correlates and determinants of their use. Using a diverse sample from 7 interventions participating in the Behavior Change Consortium (n = 2539), signal detection methodology (SDM) demonstrated a method for identifying subgroups with varying supplement use. An SDM model was explored with an exploratory half of the entire sample (n = 1268) and used 5 variables to predict dietary supplement use: cigarette smoking, fruit and vegetable intake, dietary fat consumption, BMI, and stage of change for physical activity. A comparison of rates of supplement use between the exploratory model groups and comparably identified groups in the reserved, confirmatory sample (n = 1271) indicates that these analyses may be generalizable. Significant indicators of any supplement use included smoking status, percentage of energy from fat, and fruit and vegetable consumption. Although higher supplement use was associated with healthy behaviors overall, many of the identified groups exhibited mixed combinations of healthy and unhealthy behaviors. The results of this study suggest that patterns of dietary supplement use are complex and support the use of SDM to identify possible population characteristics for targeted and tailored health communication interventions. C1 [Davis, Rachel E.; Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Atienza, Audie A.; Yaroch, Amy L.; Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Program Publ Hlth Nutr, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Domas, Andrea] Rush Univ, Med Ctr, Dept Clin Nutr, Chicago, IL 60612 USA. [Hunt, Anne] Harvard Univ, Sch Publ Hlth, Program Publ Hlth Nutr, Hunt Consulting Associates, Lyme, NH 03768 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Canc Prevent & Control Program, Columbia, SC 29208 USA. [Greene, Geoffrey W.] Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. [Sher, Tamara Goldman] IIT, Inst Psychol, Chicago, IL 60616 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Med, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Ciln & Social Sci Psychol, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Thompson, Frances E.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Toobert, Deborah J.] Oregon Res Inst, Eugene, OR 97403 USA. [Elliot, Diane L.; DeFrancesco, Carol] Oregon Hlth & Sci Univ, Div Hlth Promot & Sports Med, Portland, OR 97239 USA. [Costello, Rebecca B.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Davis, RE (reprint author), Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. EM reda@umich.edu FU NHLBI NIH HHS [R01HL64959, R01HL62156, R01HL62158]; NIA NIH HHS [R01AG16588]; NIAMS NIH HHS [R01AR45901]; NICHD NIH HHS [R01HD37368]; NIH HHS [RFA OD-93-002]; NIMH NIH HHS [R01MH59594] NR 34 TC 5 Z9 6 U1 1 U2 3 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 205S EP 211S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200033 PM 18156426 ER PT J AU Williams, GC Hurley, TG Thompson, FE Midthune, D Yaroch, AL Resnicow, K Toobert, DJ Greene, GW Peterson, K Nebeling, L Patrick, H Hardin, JW Hebert, JR AF Williams, Geoffrey C. Hurley, Thomas G. Thompson, Frances E. Midthune, Douglas Yaroch, Amv L. Resnicow, Ken Toobert, Deborah J. Greene, Geoffrey W. Peterson, Karen Nebeling, Linda Patrick, Heather Hardin, James W. Hebert, James R. TI Performance of a short percentage energy from fat tool in measuring change in dietary intervention studies SO JOURNAL OF NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MODIFICATION TRIAL; BREAST-CANCER; ASSESSMENT INSTRUMENTS; LIFE-STYLE; RISK; PATTERN; PREVENTION; REDUCTION; NUTRITION AB Measurement of percentage energy from fat is important in surveillance of populations and in epidemiologic studies examining relationships between diet and disease as well as for behavioral intervention studies seeking to change dietary behavior. The NCI percentage energy from fat screener (PFat) has adequately predicted percentage of energy from fat compared with 24-h recalls (24HR) in cross-sectional analyses. However, the instrument has not been evaluated for its ability to assess change of percentage energy from fat over time or in response to interventions to change dietary intake of fat. The objective of this analysis is to evaluate the performance of the PFat in assessing change in percentage energy intake from fat in a behavioral intervention setting. Four individual sites participating in the Behavior Change Consortium Nutrition Working Group administered both the PF at and multiple 24HR at baseline and follow-up to 278 participants. A measurement error model was used to assess agreement between the PFat and 24HR at baseline and follow-up. The PFat was consistent with 24HR in finding there was no significant change in percentage energy from fat as a result of the intervention. Both male and female participants in the intervention group demonstrated a significant increase in the correlation between PFat and 24HR from baseline to follow-up. Percentage energy from fat measured by PFat may be useful to provide estimates of change in mean intake of populations over time in longitudinal studies. Further methodologic research is called for in interventions producing significant changes and in diverse populations with adequate sample size. C1 [Williams, Geoffrey C.; Patrick, Heather] Univ Rochester, Dept Med, Rochester, NY 14642 USA. [Williams, Geoffrey C.; Patrick, Heather] Univ Rochester, Dept Clin & Social Sci Psychol, Rochester, NY 14642 USA. [Williams, Geoffrey C.; Patrick, Heather] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Hurley, Thomas G.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Canc Prevent & Control Program, Columbia, SC 29208 USA. [Thompson, Frances E.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Midthune, Douglas] NCI, Biometry Program, Div Canc Prevent, Bethesda, MD 20892 USA. [Yaroch, Amv L.; Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. [Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Toobert, Deborah J.] Oregon Res Inst, Eugene, OR 97403 USA. [Greene, Geoffrey W.] Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. [Peterson, Karen] Harvard Univ, Sch Publ Hlth, Dept Food & Nutr, Boston, MA 02115 USA. [Hardin, James W.] Univ S Carolina, Dept Epidemiol & Biostat, Ctr Hlth Serv & Policy Res, Columbia, SC 29208 USA. RP Williams, GC (reprint author), Univ Rochester, Dept Med, Rochester, NY 14642 USA. EM geoffrey_williams@urmc.rochester.edu RI Hardin, James/Q-7617-2016 OI Hardin, James/0000-0003-0506-5500 FU NHLBI NIH HHS [R01HL62158, R01HL64959, R01HL62156]; NIA NIH HHS [R01AG16588]; NIAMS NIH HHS [R01AR45901]; NICHD NIH HHS [R01HD37368]; NIH HHS [RFA OD-93-002]; NIMH NIH HHS [R01MH59594] NR 37 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 212S EP 217S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200034 PM 18156427 ER PT J AU Peterson, KE Hebert, JR Hurley, TG Resnicow, K Thompson, FE Greene, GW Shaikh, AR Yaroch, AL Williams, GC Salkeld, J Toobert, DJ Domas, A Elliot, DL Hardin, J Nebeling, L AF Peterson, Karen E. Hebert, James R. Hurley, Thomas G. Resnicow, Ken Thompson, Frances E. Greene, Geoffrev W. Shaikh, Abdul R. Yaroch, Amy L. Williams, Geoffrey C. Salkeld, Judith Toobert, Deborah J. Domas, Andrea Elliot, Diane L. Hardin, James Nebeling, Linda TI Accuracy and precision of two short screeners to assess change in fruit and vegetable consumption among diverse populations participating in health promotion intervention trials SO JOURNAL OF NUTRITION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; 24-HOUR DIETARY RECALL; CANCER PREVENTION; BETA-CAROTENE; LUNG-CANCER; SOCIAL DESIRABILITY; ENERGY-INTAKE; SELF-REPORT; RISK; VALIDITY AB Two short frequency questionnaires, the NCI 19-item Fruit and Vegetable Screener (FVS) and a single question on overall fruit and vegetable consumption (1-item), were evaluated for their ability to assess change in fruit and vegetable (FV) consumption over time and in response to intervention among participants in 5 health promotion trials in the Behavior Change Consortium. Cross-sectional differences and correlations of FV estimates at baseline and at follow-up were compared for the FVS (n = 315) and the 1-item (n = 227), relative to multiple 24-h recall interviews (24HR). The FVS significantly overestimated daily intake by 1.27 servings at baseline among men and by 1.42 and 1.59 servings at baseline and follow-up, respectively, in women, whereas the 1-item measure significantly underestimated intake at both time points in men (0.98 serving at baseline, 0.75 serving at follow-up) and women (0.61 and 0.41 serving). Cross-sectional deattenuated correlations with 24HR at follow-up were 0.48 (FVS) and 0.50 (1-item). To evaluate the capacity of the 2 screeners to assess FV change, we compared mean posttest effects with 24HR by treatment group overall and by gender. Treatment group differences were not significant for either 24HR or 1-item. Among 315 subjects, the FVS treatment group differences were significant both overall and within gender but not when repeated in the sample of 227. Findings suggest multiple 24HR at multiple time points in adequate sample sizes remain the gold standard for FV reports. Biases in FVS estimates may reflect participants' lifestyles and sociodemographic characteristics and require further examination in longitudinal samples representative of diverse populations. C1 [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Program Publ Hlth Nutr, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Hebert, James R.; Hurley, Thomas G.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, S Carolina Statewide Canc Prevent & Control Progr, Columbia, SC 29208 USA. [Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Thompson, Frances E.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Greene, Geoffrev W.] Univ Rhode Isl, Coll Environm & Life Sci, Dept Nutr & Food Sci, Kingston, RI 02881 USA. [Shaikh, Abdul R.; Yaroch, Amy L.; Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Promot Res Branch, Bethesda, MD 20892 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Med, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Clin & Social Sci Psychol, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Salkeld, Judith] Brown Univ, Div Biol & Med, Providence, RI 02912 USA. [Toobert, Deborah J.] Oregon Res Inst, Eugene, OR 97403 USA. [Domas, Andrea] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Domas, Andrea] Rush Univ, Coll Hlth Sci, Rush Med Ctr, Chicago, IL 60612 USA. [Elliot, Diane L.] Oregon Hlth & Sci Univ, Div Hlth Promot & Sports Med, Portland, OR 97239 USA. RP Peterson, KE (reprint author), Harvard Univ, Sch Publ Hlth, Program Publ Hlth Nutr, Dept Nutr, Boston, MA 02115 USA. EM kpeterso@hsph.harvard.edu RI Hardin, James/Q-7617-2016 OI Hardin, James/0000-0003-0506-5500 FU NHLBI NIH HHS [R01HL62156, R01HL62158, R01HL64959]; NIA NIH HHS [R01AG16588]; NIAMS NIH HHS [R01AR45901]; NICHD NIH HHS [R01HD37368]; NIH HHS [RFA OD-93-002]; NIMH NIH HHS [R01MH59594] NR 65 TC 33 Z9 33 U1 1 U2 6 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 218S EP 225S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200035 PM 18156428 ER PT J AU Hebert, JR Hurley, TG Peterson, KE Resnicow, K Thompson, FE Yaroch, AL Ehlers, M Midthune, D Williams, GC Greene, GW Nebeling, L AF Hebert, James R. Hurley, Thomas G. Peterson, Karen E. Resnicow, Ken Thompson, Frances E. Yaroch, Amy L. Ehlers, Margaret Midthune, Doug Williams, Geoffrey C. Greene, Geoffrey W. Nebeling, Linda TI Social desirability trait influences on self-reported dietary measures among diverse participants in a multicenter multiple risk factor trial SO JOURNAL OF NUTRITION LA English DT Review ID FOOD-FREQUENCY QUESTIONNAIRE; DOUBLY LABELED WATER; ENERGY-INTAKE; VEGETABLE CONSUMPTION; PERCENTAGE ENERGY; CANCER-RISK; NUTRIENT INTAKE; OBESE SUBJECTS; CALORIC-INTAKE; FRUIT AB Data collected at 4 Behavioral Change Consortium sites were used to assess social desirability bias in self-reports derived from a dietary fat screener (PFat), a dietary fruit and vegetable screener (FVS), and a 1-item question on fruit and vegetable intake. Comparisons were made with mean intakes derived from up to 3 24-h recall interviews at baseline and follow-up (at 12 mo in 3 sites, 6 mo in the fourth). A social-desirability-related underestimate in fat intake on the PFat relative to the 24HR (percentage energy as fat) was evident in women]baseline b = -0.56 (P = 0.005); follow-up b = -0.62 (P < 0.001)]. There was an overestimate in FVS-derived fruit and vegetable consumption (servings/week) in men enrolled in any intervention at follow-up (b = 0.39, P = 0.05) vs. baseline (b = 0.04, P = 0.75). The 1-item fruit and vegetable question was associated with an overestimate at baseline in men according to SD score (b = 0.14, P = 0.02), especially men with less than college education (b = 0.23, P = 0.01). Women with less than college education expressed a similar bias at follow-up (b = 0.13, P = 0.02). Differences in the magnitude of bias according to gender, type of instrument used, and randomization condition are comparable to what has been seen for other instruments and have important implications for both measuring change in studies of diet and health outcomes and for developing methods to control for such biases. C1 [Hebert, James R.; Hurley, Thomas G.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, S Carolina Statewide Canc Prevent & Control Progr, Columbia, SC 29208 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Thompson, Frances E.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Yaroch, Amy L.; Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. [Midthune, Doug] S Carolina Dept Hlth & Environm Control, Columbia, SC 29204 USA. [Ehlers, Margaret] NCI, Div Canc Control & Populat Sci, Biometry Res Program, Bethesda, MD 20892 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Med, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Ciln & Social Sci Psychol, Rochester, NY 14642 USA. [Williams, Geoffrey C.] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Greene, Geoffrey W.] Univ Rhode Isl, Coll Environm & Life Sci, Dept Nutr & Food Sci, Kingston, RI 02881 USA. RP Hebert, JR (reprint author), Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, S Carolina Statewide Canc Prevent & Control Progr, Columbia, SC 29208 USA. EM jhebert@sc.edu FU NHLBI NIH HHS [R01HL62156, R01HL62158, R01HL64959]; NIA NIH HHS [R01AG16588]; NIAMS NIH HHS [R01AR45901]; NICHD NIH HHS [R01HD37368]; NIH HHS [RFA OD-93-002]; NIMH NIH HHS [R01MH59594] NR 110 TC 62 Z9 62 U1 2 U2 12 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JAN PY 2008 VL 138 IS 1 BP 226S EP 234S PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249LP UT WOS:000252230200036 PM 18156429 ER PT J AU Williamson, JD Vellas, B Furberg, C Nahin, R Dekosky, ST AF Williamson, J. D. Vellas, B. Furberg, C. Nahin, R. Dekosky, S. T. TI Comparison of the design differences between the Ginkgo evaluation of memory study and the GuidAge study SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article; Proceedings Paper CT 3rd Ipsen European Symposium on Alzheimer's Disease Prevention CY JUN 01, 2007 CL Lisbon, PORTUGAL ID BILOBA EXTRACT EGB-761; ISCHEMIC/REPERFUSED RAT HEARTS; EGB 761; TERPENOID CONSTITUENTS; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; RANDOMIZED-TRIAL; DEMENTIA; PREVENTION AB The epidemic of late life dementia, prominence of use of alternative medications and supplements, and initiation of efforts to determine how to prevent dementia have led to efforts to conduct studies aimed at prevention of dementia. The GEM (Ginkgo Evaluation of Memory) and GuidAge studies are ongoing randomized double-blind, placebo-controlled trials of Ginkgo biloba, administered in a dose of 120 mg twice per day as EGb761, to test whether Ginkgo biloba is effective in the prevention of dementia (and especially Alzheimer's disease) in normal elderly or those early cognitive impairment. Both GEM and GuidAge will also add substantial knowledge to the growing need for expertise in designing and implementing clinical trials to test the efficacy of putative disease-modifying agents for the dementias. While there are many similarities between GEM and Guidage, there are also significant differences. We present here the first comparative design and baseline data from GEM and Guidage, two of the largest dementia primary prevention trials to date. C1 [Williamson, J. D.; Furberg, C.] Wake Forest Univ Hlth Sci, Sticht Ctr Aging, Roena Kulynych Ctr Memory & Cognit Res, Sect Gerontol & Geriatr Med, Winston Salem, NC 27151 USA. [Williamson, J. D.; Furberg, C.] Wake Forest Univ Hlth Sci, Dept Med, Winston Salem, NC USA. [Williamson, J. D.; Furberg, C.] Wake Forest Univ Hlth Sci, Dept Publ Hlth Sci, Winston Salem, NC USA. [Vellas, B.] CHU Tuolouse, Purpan Univ Hosp, Dept Geriatr, F-31059 Toulouse 3, France. [Nahin, R.] Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. [Dekosky, S. T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Williamson, JD (reprint author), Wake Forest Univ Hlth Sci, Sticht Ctr Aging, Roena Kulynych Ctr Memory & Cognit Res, Sect Gerontol & Geriatr Med, Med Ctr Blvd, Winston Salem, NC 27151 USA. EM jwilliam@wfubmc.edu FU NCCIH NIH HHS [5 U01 AT000162] NR 46 TC 3 Z9 3 U1 0 U2 2 PU SERDI EDITION PI PARIS PA 320 RUE SAINT-HONORE, PARIS, 75001, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD JAN PY 2008 VL 12 IS 1 BP 73S EP 79S DI 10.1007/BF02982591 PG 7 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 255SY UT WOS:000252678900013 PM 18165850 ER PT J AU Hein, MJ Waters, MA van Wijngaarden, E Deddens, JA Stewart, PA AF Hein, Misty J. Waters, Martha A. van Wijngaarden, Edwin Deddens, James A. Stewart, Patricia A. TI Issues when modeling benzene, toluene, and xylene exposures using a literature database SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE case control studies; exposure assessment; exposure determinants; occupational exposure ID OCCUPATIONAL-EXPOSURE; RETROSPECTIVE EXPOSURE; MATRIX; INFORMATION; VALIDATION; PESTICIDES; HISTORIES AB A database of benzene, toluene, and xylene measurements was compiled from an extensive literature review that contained information on several exposure determinants, including job type, operation, mechanism of release, process type, ventilation, temperature, distance from the source, quantity, and location. The database was used to develop statistical models for benzene, toluene, and xylene exposure as a function of operation and other workplace determinants. These models can be used to predict exposure levels for subjects enrolled in community-based case-control studies. This article presents the derived parameter estimates for specific operations and additional workplace exposure determinants and describes a number of statistical and data limitation issues that are inherent in determinants modeling of historical published data. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource(s): a PDF file of QQ plots and a Word file with references used in the benzene/toluene/xylene exposure database.] C1 [Hein, Misty J.; Waters, Martha A.; Deddens, James A.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [van Wijngaarden, Edwin] Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. [Deddens, James A.] Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA. [Stewart, Patricia A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hein, MJ (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Ctr Dis Control & Prevent, 4676 Columbia Pkwy,Mailstop R-13, Cincinnati, OH 45226 USA. EM MHein@cdc.gov RI Waters, Martha/B-7441-2011 FU Intramural NIH HHS NR 40 TC 24 Z9 24 U1 2 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PY 2008 VL 5 IS 1 BP 36 EP 47 DI 10.1080/15459620701763947 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 250ZS UT WOS:000252340600010 PM 18041643 ER PT J AU Dixon, S Wilson, J Kawecki, C Green, R Phoenix, J Galke, W Clark, S Breysse, J AF Dixon, Sherry Wilson, Jonathan Kawecki, Carol Green, Rodney Phoenix, Janet Galke, Warren Clark, Scott Breysse, Jill TI Selecting a lead hazard control strategy based on dust lead loading and housing condition: I. Methods and results SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE housing condition; interim control; intervention; lead abatement; lead hazard control ID CONTROL GRANT PROGRAM; PAINT; ABATEMENT AB A methodology was developed to classify housing conditions and interior dust lead loadings, using them to predict the relative effectiveness of different lead-based paint hazard control interventions. A companion article in this issue describes how the methodology can be applied. Data from the National Evaluation of the HUD Lead Hazard Control Grant Program, which covered more than 2800 homes in 11 U.S. states, were used. Half these homes (1417) met the study's inclusion criteria. Interior interventions ranged from professional cleaning with spot painting to lead abatement on windows, and enclosure, encapsulation, or removal of other leaded building components. Modeling was used to develop a visual Housing Assessment Tool (HAT), which was then used to predict relative intervention effectiveness for a range of intervention intensities and baseline floor and windowsill dust lead loadings in occupied dwellings. More than 117,000 potential HATs were considered. To be deemed successful, potential HATs were required to meet these criteria: (1) the effect of interior strategy had to differ for HAT ratings of good vs. poor building condition and/or baseline dust lead loadings; (2) the HAT rating had to be a predictor of one year post-intervention loadings; (3) interior intervention strategy had to be a predictor of one-year loadings; (4) higher baseline loadings could not be associated with lower one-year loadings; and (5) neither exterior work nor site/soil work could result in higher predicted one-year loadings for either HAT rating. Of the 1299 HATs that met these criteria, one was selected because it had the most significant differences between strategy intensities when floors and sills were considered together. For the selected HAT, site/soil work was a predictor of one-year loadings for floors (p = 0.009) but not for sills (p = 0.424). Hazard control work on the building exterior was a predictor of both sill and floor one-year loadings (p = 0.004 and p < 0.001, respectively). Regardless of the type of interior intervention strategy, interior work was a predictor of both floor and sill one-year loadings (each p <= 0.001). C1 [Dixon, Sherry; Wilson, Jonathan; Kawecki, Carol; Breysse, Jill] Natl Ctr Healthy Housing, Columbia, MD USA. [Green, Rodney; Phoenix, Janet] Howard Univ, Ctr Urban Progress, Washington, DC 20059 USA. [Galke, Warren] NIH, Bethesda, MD 20892 USA. [Clark, Scott] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. RP Dixon, S (reprint author), Natl Ctr Healthy Housing, Columbia, MD USA. NR 12 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PY 2008 VL 5 IS 8 BP 530 EP 539 DI 10.1080/15459620802219799 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 317ID UT WOS:000257012400009 PM 18569520 ER PT J AU Breysse, J Dixon, S Wilson, J Kawecki, C Green, R Phoenix, J Galke, W Clark, S AF Breysse, Jill Dixon, Sherry Wilson, Jonathan Kawecki, Carol Green, Rodney Phoenix, Janet Galke, Warren Clark, Scott TI Selecting a lead hazard control strategy based on dust lead loading and housing condition: II. Application of Housing Assessment Tool (HAT) modeling results SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE dust lead loading; housing condition; intervention strategy; lead hazard control; risk assessment AB In Part I in this issue, modeling was used to identify a Housing Assessment Tool (HAT) that can be used to predict relative intervention effectiveness for a range of intervention intensities and baseline dust lead loadings in occupied dwellings. The HAT predicts one year post-intervention floor and windowsill loadings and the probability that these loadings will exceed current federal lead hazard standards. This article illustrates the field application of the HAT, helping practitioners determine the minimum intervention intensity needed to reach "acceptable" one year post-intervention levels, with acceptability defined based on specific project needs, local needs, regulations, and resource constraints. The HAT is used to classify a dwelling's baseline condition as good or poor. If the average number of interior non-intact painted surfaces per room is >= 2, then the dwelling is rated as poor. If exterior windows/doors are deteriorated and the average number of exterior non-intact painted surfaces per building side is >= 5, then the dwelling is rated as poor. If neither of these conditions is true, then the dwelling's HAT rating is good. The HAT rating is then combined with baseline average floor loading to help select the treatment intensity. For example, if the baseline floor loading is 100 mu g/ft(2) (1,075 mu g/m(2)) and the HAT rating is poor, the probability that the one-year floor loading exceeds the federal standard of 40 mu g/ft(2) (430 mu g/m(2)) is 27% for a high-intensity strategy (i.e., window lead abatement with other treatments) but is 54% for a lower-intensity strategy (i.e., cleaning and spot painting). If the HAT rating is good, the probability that the one-year floor loading exceeds 40 mu g/ft(2) is approximately the same for low- and high-intensity strategies (18% for window lead abatement with other treatments compared with 16% for cleaning and spot painting). Lead hazard control practitioners can use this information to make empirically based judgments about the treatment intensity needed to ensure that one year post-intervention loadings remain below federal standards. C1 [Breysse, Jill; Dixon, Sherry; Wilson, Jonathan; Kawecki, Carol] Natl Ctr Healthy Housing, Columbia, MD USA. [Green, Rodney; Phoenix, Janet] Howard Univ, Ctr Urban Progress, Washington, DC 20059 USA. [Galke, Warren] NIH, Bethesda, MD 20892 USA. [Clark, Scott] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. RP Breysse, J (reprint author), Natl Ctr Healthy Housing, Columbia, MD USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PY 2008 VL 5 IS 8 BP 540 EP 545 DI 10.1080/15459620802222587 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 317ID UT WOS:000257012400010 PM 18569521 ER PT J AU Krstev, S Ji, BT Shu, XO Gao, YT Blair, A Lubin, J Vermeulen, R Dosemeci, M Zheng, W Rothman, N Chow, WH AF Krstev, Srmena Ji, Bu-Tian Shu, Xiao-Ou Gao, Yu-Tang Blair, Aaron Lubin, Jay Vermeulen, Roel Dosemeci, Mustafa Zheng, Wei Rothman, Nathaniel Chow, Wong-Ho TI Occupation and chronic bronchitis among Chinese women SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; COTTON TEXTILE WORKERS; RESPIRATORY SYMPTOMS; FOLLOW-UP; LANCASHIRE COTTON; MILL OPERATIVES; DUST EXPOSURE; LUNG-FUNCTION; NEW-ZEALAND; HEALTH AB Objective: To examine the association between occupation and chronic bronchitis among a cross section of Chinese women who participated in the Shanghai Women's Health Study. Methods: Cases were 4873 women who self-reported a physician-diagnosed bronchitis during adulthood. Controls were 9746 women randomly selected from Shanghai Women's Health Study participants and matched with the cases by year of birth and age at diagnosis. Lifetime occupational histories were obtained. Logistic regressions were used to evaluate the association between chronic bronchitis and occupation, adjusting for smoking, education, family income, and concurrent asthma. Results: We observed excess Prevalence of bronchitis for textile occupation (odds ratio, OR = 1.09; 95% CI = 1.00-1.18) and industry (OR = 1.11; 95% CI = 1.03-1.19), welders (OR = 1.40; 95% CI = 1.01-1.92), packing and baling workers (OR = 1.39; 95% CI = 1.15-1.68), and warehousing industry (OR = 1.58; 95% CI = 1.08-2.30) We also identified several new associations that may wan-ant further exploration and confirmation, including employment in some metal fabrication industries, postal and telecommunication industry, and a few white-collar occupations and industries. Conclusions: Our study indicates that the risk of chronic bronchitis among women may be increased in some occupations and industries. C1 [Krstev, Srmena; Ji, Bu-Tian; Blair, Aaron; Vermeulen, Roel; Dosemeci, Mustafa; Rothman, Nathaniel; Chow, Wong-Ho] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Krstev, Srmena] Clin Ctr Serbia, Inst Occupat Hlth, Belgrade, Serbia. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Lubin, Jay] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TC Utrecht, Netherlands. RP Ji, BT (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 8104, Bethesda, MD 20892 USA. EM jib@exchange.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS [Z01 CP010123-12]; NCI NIH HHS [CA 70867, R01 CA070867] NR 43 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2008 VL 50 IS 1 BP 64 EP 71 DI 10.1097/JOM.0b013e31815c6cdf PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 250UI UT WOS:000252326100013 PM 18188083 ER PT J AU Ivanova, AV Vortmeyer, A Ivanov, SV Nickerson, ML Maher, ER Lerman, MI AF Ivanova, A. V. Vortmeyer, A. Ivanov, S. V. Nickerson, M. L. Maher, E. R. Lerman, M. I. TI Loss of PL6 protein expression in renal clear cell carcinomas and other VHL-deficient tumours SO JOURNAL OF PATHOLOGY LA English DT Article DE PL6; tumour suppressor; VHL; CC-RCC; Golgi ID VON-HIPPEL-LINDAU; HYPOXIA-INDUCIBLE-FACTOR; HUMAN-CHROMOSOME 3P21.3; SUPPRESSOR GENE; MESSENGER-RNA; EPIDIDYMAL CYSTADENOMAS; INDEPENDENT TARGET; E-CADHERIN; DISEASE; IDENTIFICATION AB Mutations in the von Hippel - Lindau tumour suppressor gene (VHL) cause the VHL hereditary cancer syndrome and occur in most sporadic clear cell renal cell cancers (CC- RCCs). The mechanisms by which VHL loss of function promotes tumour development in the kidney are not fully elucidated. Here, we analyse expression of PL6, one of the potential tumour suppressor genes from the critical 3p21.3 region involved in multiple common cancers. We classify PL6 as a Golgi-resident protein based on its perinuclear cot localization with GPP130 in all cells and tissues analysed. We show that PL6 RNA and protein expression is completely or partially lost in all analysed CC-RCCs and other VHL-views deficient tumours studied, including the early precancerous lesions in VHL disease. The restoration of VHL function in vitro in the VHL-deficient CC-RCC cell lines was found to reinstate PL6 expression, thus establishing a direct link between VHL and PL6. Insensitivity of PL6 to hypoxia suggested that PL6 is regulated by VHL via a HIF-1-independent pathway. We ruled out mutations and promoter methylation as possible causes of PL6 down-regulation in CC-RCC. We hypothesize that loss of a putative PL6 secretory function due to VHL deficiency is an early and important event that may promote tumour initiation and growth. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Ivanova, A. V.; Ivanov, S. V.; Nickerson, M. L.; Lerman, M. I.] NCI, Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Vortmeyer, A.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Nickerson, M. L.] Transgenomic Inc, Gaithersburg, MD USA. [Maher, E. R.] Univ Birmingham, Dept Pediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. [Maher, E. R.] Univ Birmingham, Canc Res UK Renal Mol Concol Res Grp, Sch Med, Birmingham B15 2TT, W Midlands, England. RP Ivanova, AV (reprint author), NYU, Sch Med, Dept Cardiothorac Surg, Lab Thorac Oncol, New York, NY 10016 USA. EM allo.ivonovo@med.nyu.edu OI Ivanov, Sergey/0000-0001-9770-7237 FU Intramural NIH HHS NR 39 TC 3 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2008 VL 214 IS 1 BP 46 EP 57 DI 10.1002/path.2252 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 247TP UT WOS:000252103900007 PM 17973242 ER PT J AU Wynn, TA AF Wynn, T. A. TI Cellular and molecular mechanisms of fibrosis SO JOURNAL OF PATHOLOGY LA English DT Review DE fibrosis; myofibroblast; collagen; wound healing; liver; lung ID INDUCED PULMONARY-FIBROSIS; HEPATIC STELLATE CELLS; GROWTH-FACTOR-BETA; INDUCED LUNG INJURY; GENE-EXPRESSION PROFILES; ALLERGIC AIRWAY DISEASE; MICE LACKING SMAD3; LIVER FIBROSIS; TGF-BETA; IN-VIVO AB Fibrosis is defined by the overgrowth, hardening, and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen-producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial/endothelial-mesenchymaI (EMT/EndMT) transition, as well as from circulating fibroblast-like cells called fibrocytes that are derived from bone-marrow stem cells. Myolibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen-associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL-13, IL-21, TGF-beta 1), chemokines (MCP-1, MIP-1 beta), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator-activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin-angiotensin-aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis. Published in 2007 by John Wiley & Sons, Ltd. C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 50 S Dr,Room 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 FU Intramural NIH HHS [Z01 AI000829-10, Z01 AI001019-01] NR 174 TC 1424 Z9 1534 U1 117 U2 767 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2008 VL 214 IS 2 BP 199 EP 210 DI 10.1002/path.2277 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 254OX UT WOS:000252597000008 PM 18161745 ER PT J AU Kelsall, BL AF Kelsall, B. L. TI Innate and adaptive mechanisms to control of pathological intestinal inflammation SO JOURNAL OF PATHOLOGY LA English DT Review DE intestine; inflammation; Crohn's disease; ulcerative colitis; dendritic cells; epithelium; bacteria ID REGULATORY T-CELLS; ACTIVE CROHNS-DISEASE; EPITHELIAL BARRIER FUNCTION; GROWTH-FACTOR-BETA; BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN; ANTIINTERFERON-GAMMA ANTIBODY; CHRONIC GRANULOMATOUS-DISEASE; PROPRIA DENDRITIC CELLS; BOWEL-DISEASE; RETINOIC-ACID AB The intestine is the home of a tremendous number of commensal organisms that have a primary role in host metabolism. As a consquence, the gut mucosa has evolved multiple layers of protection. This review highlights both innate and adaptive mechanisms that prevent bacterial invasion and abnormal intestinal inflamamation, bow a failure of these mechanisms may be involved in the pathogenesis of inflammatory bowel diseases, and discusses new findings implicating dendritic cells as central to the induction of active mucosal tolerance to commensal bacteria. Copyright (C) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Kelsall, B. L.] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Kelsall, BL (reprint author), 10-11N111,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kelsall@nih.gov FU Intramural NIH HHS NR 216 TC 39 Z9 41 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2008 VL 214 IS 2 BP 242 EP 259 DI 10.1002/path.2286 PG 18 WC Oncology; Pathology SC Oncology; Pathology GA 254OX UT WOS:000252597000012 PM 18161750 ER PT J AU Kim, SY Tsokos, M Helman, LJ AF Kim, Su Young Tsokos, Maria Helman, Lee J. TI Dilemmas associated with congenital Ewing sarcoma family tumors SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Editorial Material ID PRIMITIVE NEUROECTODERMAL TUMOR; TRANSLOCATION; FUSION; NEUROEPITHELIOMA; INFANCY; GENE; HAND; EWS; FEV C1 [Kim, Su Young; Helman, Lee J.] NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Tsokos, Maria] NIH, Dept Pathol, Bethesda, MD 20892 USA. RP Kim, SY (reprint author), NIH, Pediat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. EM kimsuyou@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 18 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JAN PY 2008 VL 30 IS 1 BP 4 EP 7 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 252ZO UT WOS:000252486900002 PM 18176172 ER PT J AU Vistica, DT Krosky, PM Kenney, S Raffeld, M Shoemaker, RH AF Vistica, David T. Krosky, Paula M. Kenney, Susan Raffeld, Mark Shoemaker, Robert H. TI Immunohistochemical discrimination between the ASPL-TFE3 fusion proteins of alveolar soft part sarcoma SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE alveolar soft part sarcoma (ASPS); ASPL-TFE3 type 1 and 2 antibodies; gene fusion epitope detection ID RENAL-CELL CARCINOMAS; TFE3 GENE; LEUKEMIA; 17Q25 AB Alveolar soft part sarcoma (ASPS), a rare soft tissue sarcoma, is characterized by a chromosomal translocation der(17)t(X;17)(p11;q25) resulting in the production of 2 fusion proteins encoded by regions of the genes for alveolar soft part locus (ASPL) and the transcription factor E3 (TFE3). In this study, polyclonal antibodies were generated to 25 mer peptides encompassing the junctional regions of ASPL-TFE3 type 1 and ASPL-TFE3 type 2. The specificity of the affinity purified antibodies for the synthetic peptides and recombinant expressed ASPL-TFE3 type 1 and ASPL-TFE3 type 2 proteins was evaluated by enzyme-linked immunosorbent assay and was highly fusion type specific. Immunohistochemical staining of formalin-fixed, paraffin-embedded ASPS tumors with the fusion-specific antibodies resulted in intense nuclear staining and differentiation between tumors that express the type 1 protein and tumors that express the type 2 protein. These antibodies will be useful for the differential diagnosis of type 1 and type 2 ASPS and also in the detection of the fusion proteins in biochemical and cell biologic investigations. C1 [Vistica, David T.] NCI, Dev Therapeut Program, Screening Technol Branch, Ft Detrick, MD 21702 USA. [Krosky, Paula M.] NCI, SAIC Frederick Inc, Appl Dev Directorate, Frederick, MD 21701 USA. [Raffeld, Mark] NIH, Natl Canc Inst, Pathol Lab, Bethesda, MD 20892 USA. RP Vistica, DT (reprint author), NCI, Dev Therapeut Program, Screening Technol Branch, Bldg 322 Room 104, Ft Detrick, MD 21702 USA. EM Davidvistica@dtpax2.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 18 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JAN PY 2008 VL 30 IS 1 BP 46 EP 52 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 252ZO UT WOS:000252486900010 PM 18176180 ER PT J AU Varma, S Wendler, D AF Varma, Sumeeta Wendler, David TI Research involving wards of the state: Protecting particularly vulnerable children SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID PEDIATRIC RESEARCH C1 [Varma, Sumeeta; Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 14 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD JAN PY 2008 VL 152 IS 1 BP 9 EP 14 DI 10.1016/j.jpeds.2007.07.039 PG 6 WC Pediatrics SC Pediatrics GA 247LG UT WOS:000252080100005 PM 18154889 ER PT J AU Lebiedowska, MK Alter, KE Stanhope, SJ AF Lebiedowska, Maria K. Alter, Katharine E. Stanhope, Steven J. TI Human body shape index based on an experimentally derived model of human growth SO JOURNAL OF PEDIATRICS LA English DT Article ID WEIGHT-FOR-HEIGHT; MASS INDEX; CHILDREN; ADIPOSITY; OBESITY; CHILDHOOD; AGE; ADOLESCENTS; OVERWEIGHT; CURVES AB Objectives To test the assumption of geometrically similar growth by developing experimentally derived models of human body growth during the age interval of 5 to IS years; to use these derived growth models to establish a new human body shape index (HBSI) based on natural age-related changes in human body shape (HBS); and to compare various metrics of relative body weight (body mass index [BMI], ponderal index [PI], and HBSI) in a sample of 5- to 18-year-old children. Study design Nondisabled Polish children (n = 847) participated in this descriptive study. To model growth, the best fit between body height (H) and body mass (M) was calculated for each sex using the allometric equation M = m(i)H(x). HBSI was calculated separately for girls and boys, using sex-specific values for X and a general HBSI from combined data. The customary BMI and PI were calculated and compared with HBSI values. Results The models of growth were M = 13.11H(2.84) (R-2 = 0.90) for girls and M = 13.64H(2.68) (R-2 = 0.91) for boys. HBSI values contained less inherent variability and were less influenced by growth (age and height) compared with BMI and PI. Conclusions Age-related growth during childhood is sex-specific and not geometrically similar. Therefore, indices of HBS formulated from experimentally derived models of human growth are superior to customary geometric similarity-based indices for characterizing HBS in children during the formative growth years. C1 [Lebiedowska, Maria K.; Alter, Katharine E.; Stanhope, Steven J.] Natl Inst Hlth, Phys Disabilities Branch, Bethesda, MD USA. RP Lebiedowska, MK (reprint author), Dept Rehabil Med, Bldg 10 CRC,Rm 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM lebiedowskam@cc.nih.gov FU Intramural NIH HHS [NIH0011951440]; PHS HHS [NIH0011951440] NR 27 TC 5 Z9 6 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD JAN PY 2008 VL 152 IS 1 BP 45 EP 49 DI 10.1016/j.jpeds.2007.05.046 PG 5 WC Pediatrics SC Pediatrics GA 247LG UT WOS:000252080100013 PM 18154897 ER PT J AU Krull, KR Brouwers, P Jain, N Zhang, L Bomgaars, L Dreyer, Z Mahoney, D Bottomley, S Okcu, MF AF Krull, Kevin R. Brouwers, Pim Jain, Neelam Zhang, Linna Bomgaars, Lisa Dreyer, ZoAnn Mahoney, Donald Bottomley, Sarah Okcu, M. Fatih TI Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors SO JOURNAL OF PEDIATRICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CRANIAL IRRADIATION; CHILDREN; CHEMOTHERAPY; PHARMACOGENETICS; REDUCTASE; CANCER; CONSEQUENCES; METHOTREXATE; SEQUELAE AB Objective To test the hypothesis that 5,10-methylenetetrahydroreductase (MTHFR) polymorphisms can partially explain the individual variation in developing attention-deficit/hyperactivity disorder (ADHD) after acute lymphoblastic leukemia (ALL) therapy. Study design Parents of 48 survivors of childhood ALL completed a clinical diagnostic process to identify subtypes of ADHD. Genotyping was performed with peripheral blood DNA for MTHFR (C677T and A1298C) polymorphisms. Results Eleven of the 48 patients (22.9%) had scores consistent with the inattentive symptoms of ADHD. Patients with genotypes related to lower folate levels (11 out of 39; 39.2%) were more likely to have ADHD. The A1298C genotype appeared to be the predominant linkage to the inattentive symptoms, leading to a 7.4-fold increase in diagnosis, compared with a 1.3-fold increase for the C677T genotype. Age at diagnosis and sex were not associated with inattentiveness. Conclusions Preliminary data imply a strong relationship between MTHFR polymorphisms and the inattentive symptoms of ADHD in survivors of childhood ALL. C1 [Krull, Kevin R.; Jain, Neelam] Texas Childrens Hosp, Learn Support Ctr Child Psychol, Houston, TX 77030 USA. [Krull, Kevin R.; Brouwers, Pim; Jain, Neelam; Zhang, Linna; Bomgaars, Lisa; Dreyer, ZoAnn; Mahoney, Donald; Okcu, M. Fatih] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Brouwers, Pim; Zhang, Linna; Bomgaars, Lisa; Dreyer, ZoAnn; Mahoney, Donald; Bottomley, Sarah; Okcu, M. Fatih] Texas Childrens Canc Ctr, Houston, TX USA. [Brouwers, Pim] NIMH, Div AIDS & Hlth Behav Res, Rockville, MD 20857 USA. [Okcu, M. Fatih] Childhood Canc Epidemiol & Prevent Ctr, Houston, TX USA. RP Krull, KR (reprint author), St Jude Childrens Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St,MS 735, Memphis, TN 38105 USA. EM kevir.krull@st.jude.org NR 34 TC 45 Z9 47 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD JAN PY 2008 VL 152 IS 1 BP 101 EP 105 DI 10.1016/j.jpeds.2007.05.047 PG 5 WC Pediatrics SC Pediatrics GA 247LG UT WOS:000252080100025 PM 18154909 ER PT J AU Hamill, N Romero, R Gotsch, F Kusanovic, JP Edwin, S Erez, O Than, NG Mittal, P Espinoza, J Friel, LA Vaisbuch, E Mazaki-Tovi, S Hassan, SS AF Hamill, Neil Romero, Roberto Gotsch, Francesca Kusanovic, Juan Pedro Edwin, Sam Erez, Offer Than, Nandor Gabor Mittal, Pooja Espinoza, Jimmy Friel, Lara A. Vaisbuch, Edi Mazaki-Tovi, Shali Hassan, Sonia S. TI Exodus-1 (CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE amniotic fluid; cytokine; inflammation; LARC; macrophage inflammatory protein 3 alpha; parturition; pregnancy ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; MACROPHAGE INFLAMMATORY PROTEIN-3-ALPHA/CCL20; MONOCYTE CHEMOTACTIC PROTEIN-1; AMNIOTIC-FLUID CONCENTRATIONS; INTESTINAL EPITHELIAL-CELLS; HUMAN GESTATIONAL TISSUES; CD83(+) DENDRITIC CELLS; HUMAN FETAL MEMBRANES; CERVICAL-MUCUS PLUG AB Aim: CCL20, also known as MIP-3 alpha, is a chemokine that participates in chemotaxis of immature dendritic cells, effector/memory T-cells, and B-lymphocytes. The objectives of this study were to determine whether CCL20 can be detected in amniotic fluid (AF) and if AF concentration of this chemokine changes with advancing gestational age, parturition (term and preterm), and intraamniotic infection/inflammation (IAI). Methods: A cross-sectional study was conducted including the following groups: (1) mid-trimester of pregnancy (n=65); (2) term not in labor (TNL; n=22); (3) term in labor (TI L; n = 47); (4) spontaneous preterm labor (PTL) who delivered at term (n = 57); (5) spontaneous PTL without IAI who delivered preterm (n=71); and (6) spontaneous PTL with IAI (n=38). AF CCL20 concentrations were determined using ELISA. Results: (1) The median AF CCL20 concentration in TNL was higher than that of mid-trimester patients; (2) Women in spontaneous labor at term had a higher median AF concentration of CCL20 than patients at term not in labor; (3) Patients with spontaneous PTL and IAI had a significantly higher median AF concentration of CCL20 than those without IAl who delivered preterm and those who delivered at term. Moreover, women with spontaneous PTL without IAl who delivered preterm had a significantly higher median AF concentration than those with PTL who subsequently delivered at term. Conclusions: (1) CCL20 is a physiologic constituent of AF and its concentration increases as term approaches; (2) spontaneous labor (term and preterm) in the absonce of IAl is associated with increased bioavailability of AF CCL20 suggesting that an increase in CCL20 is part of the common pathway of human parturition; (3) patients with IAl had dramatic elevations in the AF CCL20 concentrations suggesting that this chemokine participates in the host response to infection or other stimuli associated with intra-amniotic infection. C1 [Hamill, Neil; Romero, Roberto; Gotsch, Francesca; Kusanovic, Juan Pedro; Edwin, Sam; Erez, Offer; Than, Nandor Gabor; Mittal, Pooja; Espinoza, Jimmy; Friel, Lara A.; Vaisbuch, Edi; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS, Detroit, MI 48201 USA. [Hamill, Neil; Romero, Roberto; Gotsch, Francesca; Kusanovic, Juan Pedro; Edwin, Sam; Erez, Offer; Than, Nandor Gabor; Mittal, Pooja; Espinoza, Jimmy; Friel, Lara A.; Vaisbuch, Edi; Mazaki-Tovi, Shali; Hassan, Sonia S.] DHHS, NIH, NICHD, Perinatol Res Branch, Bethesda, MD USA. [Hamill, Neil; Kusanovic, Juan Pedro; Mittal, Pooja; Espinoza, Jimmy; Friel, Lara A.; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchie-fstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural NIH HHS NR 138 TC 42 Z9 42 U1 0 U2 2 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2008 VL 36 IS 3 BP 217 EP 227 DI 10.1515/JPM.2008.034 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 325JK UT WOS:000257585000006 PM 18576931 ER PT J AU Erez, O Romero, R Hoppensteadt, D Fareed, J Chaiworapongsa, T Kusanovic, JP Mazaki-Tovi, S Gotsch, F Than, NG Vaisbuch, E Kim, CJ Espinoza, J Mittal, P Hamill, N Nhan-Chang, CL Mazor, M Hassan, S AF Erez, Offer Romero, Roberto Hoppensteadt, Debra Fareed, Jawed Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Mazaki-Tovi, Shali Gotsch, Francesca Than, Nandor Gabor Vaisbuch, Edi Kim, Chong Jai Espinoza, Jimmy Mittal, Pooja Hamill, Neil Nhan-Chang, Chia-Ling Mazor, Moshe Hassan, Sonia TI Premature labor: a state of platelet activation? SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Coagulation; inflammation; labor; prematurity; platelet; thrombin; sCD40L ID SOLUBLE CD40 LIGAND; FLOW-CYTOMETRIC DETECTION; HYPER-IGM SYNDROME; PROSTAGLANDIN E-2 PRODUCTION; INFLAMMATORY-BOWEL-DISEASE; X-LINKED IMMUNODEFICIENCY; TISSUE FACTOR EXPRESSION; C-REACTIVE PROTEIN; ENDOTHELIAL-CELLS; CD40-CD40 LIGAND AB Objective: This study was undertaken to determine whether premature labor is associated with changes in the maternal plasma concentration of soluble CD40 ligand (sCD40L), a marker of platelet activation. Methods: A cross-sectional study included patients in the following groups: 1) non-pregnant (n=21); 2) normal pregnancy (n=71); 3) normal pregnancy at term with (n=67) and without labor (n=88); 4) preterm labor (PTL) with intact membranes (n=136) that was divided into the following sub-groups: 4a) PTL who delivered at term (n=49); 4b) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered preterm (n=54); and 4c) PTL with IAI who delivered preterm (n=33). sCD40L concentrations were measured by ELISA. Results: The median maternal plasma sCD40L concentration was higher in pregnant than non-pregnant women (P=0.017). Patients with PTL had a higher median maternal plasma sCD40L concentration than women with normal pregnancies, regardless of the presence or absence of IAI and gestational age at delivery (P<0.001 for all comparisons). IAI was not associated with a higher median maternal plasma concentration of sCD40L. Conclusions: Normal pregnancy is a state in which there is a physiologic increase of sCD40L. PTL was associated with an increased median maternal plasma sCD40L concentration that could not be accounted for by IAI. Thus, our findings suggest that platelet activation occurs during an episode of preterm labor. C1 [Erez, Offer; Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Than, Nandor Gabor; Vaisbuch, Edi; Kim, Chong Jai; Espinoza, Jimmy] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Erez, Offer; Romero, Roberto; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Espinoza, Jimmy; Mittal, Pooja; Hamill, Neil; Nhan-Chang, Chia-Ling; Hassan, Sonia] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Hoppensteadt, Debra; Fareed, Jawed] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 141 TC 9 Z9 9 U1 1 U2 1 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 EI 1619-3997 J9 J PERINAT MED JI J. Perinat. Med. PY 2008 VL 36 IS 5 BP 377 EP 387 DI 10.1515/JPM.2008.082 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 357SC UT WOS:000259865600001 PM 18958919 ER PT J AU Romero, R Espinoza, J Hassan, S Gotsch, F Kusanovic, JP Avila, C Erez, O Edwin, S Schmidt, AM AF Romero, Roberto Espinoza, Jimmy Hassan, Sonia Gotsch, Francesca Kusanovic, Juan Pedro Avila, Cecilia Erez, Offer Edwin, Sam Schmidt, Ann Marie TI Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Amniotic fluid; chorioamnionitis; intra-amniotic infection/inflammation; MIAC; microbial invasion of the amniotic cavity; preterm labor; preterm PROM; preterm delivery ID PRETERM PREMATURE RUPTURE; TUMOR-NECROSIS-FACTOR; BLOOD-CELL COUNT; MONOCYTE CHEMOTACTIC PROTEIN-1; INTRAAMNIOTIC INFECTION; MICROBIAL INVASION; INTRAUTERINE INFECTION; FETAL MEMBRANES; UREAPLASMA-UREALYTICUM; CLINICAL-SIGNIFICANCE AB Objective: The receptor for advanced glycation end products (RAGE) has been proposed to participate in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines, as well as neutrophil chemotaxis in a manner that may be suppressed or stimulated by soluble, truncated forms of RAGE including the soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objective of this study was to determine whether intra-amniotic infection/ inflammation (IAI) is associated with changes in the amniotic fluid concentration of sRAGE and esRAGE. Study design: Amniotic fluid (AF) was retrieved from patients in the following groups: 1) mid-trimester (14-18 weeks of gestation; n=68); 2) term not in labor (n=24); 3) term in labor (n=51); 4) preterm labor and intact membranes (n=124); and 5) preterm PROM (n=80). Intra-amniotic infection and inflammation were defined as the presence of a positive amniotic fluid culture for microorganisms and an AF interleukin-6 concentration >= 2.6 ng/mL, respectively. The AF concentration of sRAGE and esRAGE were determined using specific and sensitive ELISAs which measured total immunoreactive sRAGE and esRAGE, respectively. Patients were matched for gestational age at amniocentesis to compare the AF concentration of sRAGE and esRAGE in patients with and without IAI. Non-parametric statistics were used for analysis and a P<0.05 was considered significant. Results: 1) Patients at term not in labor had higher median AF concentrations of sRAGE and esRAGE than those in the mid-trimester (P<0.001 for both comparisons) and those at term in labor (P=0.03 and P=0.04, respectively); 2) patients with preterm labor and intact membranes with intra-amniotic infection/inflammation (IAI) had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.02 and P=0.005, respectively); 3) similarly, patients with preterm PROM with IAI had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.03 and P=0.02, respectively). Conclusion: Intra-amniotic infection/inflammation is associated with increased amniotic fluid concentrations of sRAGE and esRAGE. Changes in the amniotic fluid concentration of sRAGE and esRAGE may represent part of the immune response to intra-amniotic infection/inflammation. C1 [Romero, Roberto; Espinoza, Jimmy; Hassan, Sonia; Gotsch, Francesca; Kusanovic, Juan Pedro; Erez, Offer; Edwin, Sam] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto; Espinoza, Jimmy; Hassan, Sonia; Gotsch, Francesca; Kusanovic, Juan Pedro; Erez, Offer; Edwin, Sam] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Espinoza, Jimmy; Hassan, Sonia] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Avila, Cecilia] Stony Brook Univ Hosp, Dept Obstet & Gynecol, Stony Brook, NY USA. [Schmidt, Ann Marie] Columbia Univ, Coll Phys & Surg, Dept Surg, Div Surg Sci, New York, NY USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 107 TC 38 Z9 40 U1 0 U2 4 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2008 VL 36 IS 5 BP 388 EP 398 DI 10.1515/JPM.2008.076 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 357SC UT WOS:000259865600002 PM 18593373 ER PT J AU Tsujibe, S Ueyama, T Shirai, Y Thomas, L Saito, N AF Tsujibe, Satoshi Ueyama, Takehiko Shirai, Yasuhito Thomas, Leto Saito, Naoaki TI Differential regulation of Dual oxidase 1 by Duox activator 1 splicing variants SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Tsujibe, Satoshi; Ueyama, Takehiko; Shirai, Yasuhito; Saito, Naoaki] Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 657, Japan. [Thomas, Leto] NIAID, LHD, NIH, Mol Defenses Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 53P EP 53P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265900172 ER PT J AU Zhu, Y Ohno, K Takamatsu, Y Ashina, S Hondo, M Ira, P Kazuto, K Ikeda, K Sakurai, T AF Zhu, Yun Ohno, Kousaku Takamatsu, Yukio Ashina, Syuntarou Hondo, Mari Ira, Pastan Kazuto, Kobayashi Ikeda, Kazutaka Sakurai, Takeshi TI Differential distribution of orexin producing neurons in the hypothalamus SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Zhu, Yun; Ohno, Kousaku; Ashina, Syuntarou; Hondo, Mari; Sakurai, Takeshi] Univ Tsukuba, Dept Pharmacol, Tsukuba, Ibaraki 3058575, Japan. [Takamatsu, Yukio; Ikeda, Kazutaka] Tokyo Inst Psychiat, Setagaya Ku, Tokyo 1568585, Japan. [Ira, Pastan] NCI, NIH, Div Basic Sci, Mol Biol Lab, Bethesda, MD 20892 USA. [Kazuto, Kobayashi] Inst Biomed Sci, Dept Mol Genet, Fukushima, Fukusima 9601295, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 79P EP 79P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265900269 ER PT J AU Onoda, S Chiba, Y Sakai, H Hattori, Y Maitani, Y Kimura, S Misawa, M AF Onoda, Satoshi Chiba, Yoshihiko Sakai, Hiroyasu Hattori, Yoshiyuki Maitani, Yoshie Kimura, Shioko Misawa, Miwa TI Pharmacological studies on the respiratory tract (Rept. 310): Increased expression of a disintegrin and metalloproteinase 8 in mice with allergic bronchial asthma SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Onoda, Satoshi; Chiba, Yoshihiko; Sakai, Hiroyasu; Misawa, Miwa] Hoshi Univ, Sch Pharm, Dept Pharmacol, Shinagawa Ku, Tokyo 1428501, Japan. [Hattori, Yoshiyuki; Maitani, Yoshie] Hoshi Univ, Sch Pharm, Inst Med Chem, Shinagawa Ku, Tokyo 1428501, Japan. [Kimura, Shioko] NCI, Endocrinol Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 85P EP 85P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265900291 ER PT J AU Tanabe, M Chiba, Y Kimura, S Misawa, M AF Tanabe, Miki Chiba, Yoshihiko Kimura, Shioko Misawa, Miwa TI Pharmacological studies on the respiratory tract (Rept. 302): RACK1 as a binding partner for CPl-17 in bronchial smooth muscle SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Tanabe, Miki; Chiba, Yoshihiko; Misawa, Miwa] Hoshi Univ, Sch Pha, Dept Pharmacol, Shinagawa Ku, Tokyo 1428501, Japan. [Kimura, Shioko] NCI, Endocrinol Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 100P EP 100P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265900350 ER PT J AU Ueyama, T Kusakabe, T Karasawa, S Kawasaki, T Shimizu, A Son, J Thomas, L Miyawaki, A Saito, N AF Ueyama, Takehiko Kusakabe, Tomoko Karasawa, Satoshi Kawasaki, Takumi Shimizu, Aya Son, Jeong-hyun Thomas, Leto Miyawaki, Atsushi Saito, Naoaki TI Sequential targeting of cytosolic phox proteins to phagosomes through regulated adaptor proteins during Fc gamma R-mediated phagocytosis SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Ueyama, Takehiko; Kusakabe, Tomoko; Kawasaki, Takumi; Shimizu, Aya; Son, Jeong-hyun; Saito, Naoaki] Kobe Univ, Biosignal Res Ctr, Mol Pharmacol Lab, Nada Ku, Kobe, Hyogo 6578501, Japan. [Karasawa, Satoshi; Miyawaki, Atsushi] RIKEN, Brain Sci Inst, Lab Cell Funct & Dynam, Wako, Saitama 3510198, Japan. [Thomas, Leto] NIAID, Mol Def Sect, LHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 102P EP 102P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265900358 ER PT J AU Kitazawa, T Hirama, R Masunaga, K Nakamura, T Asakawa, K Cao, JS Teraoka, H Unno, T Komori, S Yamada, M Wess, J Taneike, T AF Kitazawa, Takio Hirama, Ryuichi Masunaga, Kozue Nakamura, Tatsuro Asakawa, Koichi Cao, Jinshan Teraoka, Hiroki Unno, Toshihiro Komori, Sei-ichi Yamada, Masahisa Wess, Jurgen Taneike, Tetsurci TI M3 muscarinic receptor mediates carbachol-induced contraction of mouse uterine smooth muscle SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Kitazawa, Takio; Hirama, Ryuichi; Masunaga, Kozue; Nakamura, Tatsuro; Asakawa, Koichi; Cao, Jinshan; Taneike, Tetsurci] Rakuno Gakuen Univ, Sch Vet Med, Dept Pharmacol, Ebetsu, Hokkaido 0698501, Japan. [Teraoka, Hiroki] Rakuno Gakuen Univ, Sch Vet Med, Dept Toxicol, Ebetsu, Hokkaido 0698501, Japan. [Wess, Jurgen] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. [Yamada, Masahisa] RIKEN, Brain Sci inst, Yamada Res Unit, Saitama 3510198, Japan. [Unno, Toshihiro; Komori, Sei-ichi] Gifu Univ, Fac Appl Biol Sci, Pharmacol Lab, Gifu 5011193, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 108P EP 108P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265900385 ER PT J AU Kato, K Kiyonaka, S Nishida, M Ishii, M Mori, E Numaga, T Yoshida, T Miki, T Kobayashi, T Morii, T Harnachi, I Wakamori, M Mori, Y AF Kato, Kenta Kiyonaka, Shigeki Nishida, Motohiro Ishii, Masakazu Mori, Emiko Numaga, Takuro Yoshida, Takashi Miki, Takafumi Kobayashi, Tsutomu Morii, Takashi Harnachi, Itaru Wakamori, Minoru Mori, Yasuo TI A pyrazole compound selectively inhibits receptor activated TRPC3 channel SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Kato, Kenta; Kiyonaka, Shigeki; Mori, Emiko; Miki, Takafumi; Harnachi, Itaru; Mori, Yasuo] Kyoto Univ, Dept Synth Chem & Biol Chem, Grad Sch, Nishikyo Ku, Kyoto 6158510, Japan. [Nishida, Motohiro] Kyushu Univ, Dept Pharmaceut Sci, Fukuoka 8128582, Japan. [Ishii, Masakazu] Showa Univ, Dept Pharmaceut Sci, Tokyo 1428555, Japan. [Numaga, Takuro] NIEHS, Res Triangle Pk, NC 27709 USA. [Morii, Takashi] Kyoto Univ, Inst Adv Energy, Kyoto 6110011, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 210P EP 210P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265901294 ER PT J AU Nezu, A Turner, RJ AF Nezu, Akihiro Turner, R. James TI Identification of an amino acid motif involved in trafficking and expression of the secretory Na-K-2Cl cotransporter SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Nezu, Akihiro] Hlth Sci Univ Hokkaido, Dept Pharmacol, Sch Dent, Ishikari, Hokkaido 0610293, Japan. [Nezu, Akihiro; Turner, R. James] NIH, GTTB, NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 211P EP 211P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265901300 ER PT J AU Araya, R Kitamura, N Kudo, M Kimura, T Wess, J Yamada, M AF Araya, Runa Kitamura, Naohito Kudo, Moeko Kimura, Tetsuya Wess, Jurgen Yamada, Masahisa TI Estrogen restores short-term memory through the improvement of the cerebral circulation in M5 muscarinic acetylcholine receptor knockout mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Araya, Runa; Kitamura, Naohito; Kudo, Moeko; Yamada, Masahisa] RIKEN, Yamada Unit, BSI, Wako, Saitama 3510198, Japan. [Kimura, Tetsuya] RIKEN, Lab Alzheimer, BSI, Wako, Saitama 3510198, Japan. [Wess, Jurgen] NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 239P EP 239P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265901410 ER PT J AU Sakamoto, T Unno, T Matsuyama, H Kitazawa, T Taneike, T Yamada, M Wess, J Komori, S AF Sakamoto, Takashi Unno, Toshihiro Matsuyama, Hayato Kitazawa, Takio Taneike, Tetsuro Yamada, Masahisa Wess, Jurgen Komori, Seiichi TI Activation of cationic channels by diacylglycerol in mouse ileal smooth muscle cells SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 81st Annual Meeting of the Japanese-Pharmacological-Society CY MAR 17-19, 2008 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Sakamoto, Takashi] Gifu Univ, United Grad Sch Vet Sci, Dept Patho Vet Sci, Gifu 5011193, Japan. [Unno, Toshihiro; Matsuyama, Hayato; Komori, Seiichi] Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu 5011193, Japan. [Kitazawa, Takio; Taneike, Tetsuro] Gakuen Univ, Dept Pharmacol Rakuno, Ebetsu, Hokkaido 0698501, Japan. [Yamada, Masahisa] RIKEN, Yamada Res Unit, Wako, Saitama 3510198, Japan. [Wess, Jurgen] NIDDKD, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2008 VL 106 SU 1 BP 270P EP 270P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278ED UT WOS:000254265901533 ER PT J AU Jensen, BM Beaven, MA Iwaki, S Metcalfe, DD Gilfillan, AM AF Jensen, Bettina M. Beaven, Michael A. Iwaki, Shoko Metcalfe, Dean D. Gilfillan, Alasdair M. TI Concurrent inhibition of kit- and Fc epsilon RI-mediated signaling: Coordinated suppression of mast cell activation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TYROSINE KINASE INHIBITOR; C-KIT; WILD-TYPE; IN-VITRO; DASATINIB BMS-354825; ALLERGIC RESPONSE; DOWN-REGULATION; FACTOR-RECEPTOR; IMATINIB; PATHWAYS AB Although primarily required for the growth, differentiation, and survival of mast cells, Kit ligand ( stem cell factor) is also required for optimal antigen-mediated mast cell activation. Therefore, concurrent inhibition of Kit- and Fc epsilon RI-mediated signaling would be an attractive approach for targeting mast cell-driven allergic reactions. To explore this concept, we examined the effects of hypothemycin, a molecule that we identified as having such properties, in human and mouse mast cells. Hypothemycin blocked Kit activation and Kit- mediated mast cell adhesion in a similar manner to the well characterized Kit inhibitor imatinib mesylate ( imatinib). In contrast to imatinib, however, hypothemycin also effectively inhibited Fc epsilon RI-mediated degranulation and cytokine production in addition to the potentiation of these responses via Kit. The effect of hypothemycin on Kit- mediated responses could be explained by its inhibition of Kit kinase activity, whereas the inhibitory effects on Fc epsilon RI-dependent signaling were at the level of Btk activation. Because hypothemycin also significantly reduced the mouse passive cutaneous anaphylaxis response in vivo, these data provide proof of principle for a coordinated approach for the suppression of mast cell activation and provide a rationale for the development of compounds with a similar therapeutic profile. C1 [Jensen, Bettina M.; Iwaki, Shoko; Metcalfe, Dean D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Beaven, Michael A.] NHLBI, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Jensen, BM (reprint author), NIAID, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 AI000967-02] NR 50 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2008 VL 324 IS 1 BP 128 EP 138 DI 10.1124/jpet.107.125237 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 245GM UT WOS:000251923100016 PM 17925481 ER PT J AU Beguin, C Potter, DN DiNieri, JA Munro, TA Richards, MR Paine, TA Berry, L Zhao, Z Roth, BL Xu, W Liu-Chen, LY Carlezon, WA Cohen, BM AF Beguin, Cecile Potter, David N. DiNieri, Jennifer A. Munro, Thomas A. Richards, Michele R. Paine, Tracie A. Berry, Loren Zhao, Zhiyang Roth, Bryan L. Xu, Wei Liu-Chen, Lee-Yuan Carlezon, William A., Jr. Cohen, Bruce M. TI N-methylacetamide analog of salvinorin A: A highly potent and selective kappa-opioid receptor agonist with oral efficacy SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PLANT-DERIVED HALLUCINOGEN; SALVIA-DIVINORUM; IN-VITRO; PHARMACOLOGICAL-ACTIVITIES; NEOCLERODANE DITERPENOIDS; RATS; BINDING; MICE; STIMULATION; INVOLVEMENT AB Several preclinical studies indicate that selective kappa-opioid receptor (KOR) antagonists have antidepressant-like effects, whereas KOR agonists have opposite effects, suggesting that each might be useful in the treatment of mood abnormalities. Salvinorin A (salvA) is a valuable KOR agonist for further study due to its high potency and receptor selectivity. However, it has short lasting effects in vivo and limited oral bioavailability, probably due to acetate metabolism. We compared the in vitro receptor binding selectivity of salvA and four analogs containing an ethyl ether (EE), isopropylamine (IPA), N-methylacetamide (NMA), or N-methylpropionamide (NMP) at C-2. All compounds showed high binding affinity for the KOR (K-i = 0.11-6.3 nM), although only salvA, EE, and NMA exhibited KOR selectivity. In a liver microsomal assay, salvA was least stable, whereas NMA and IPA displayed slower metabolic transformations. Intraperitoneal (i.p.) administration of salvA, NMA, and NMP dose-dependently elevated brain reward thresholds in the intracranial self-administration (ICSS) test, consistent with prodepressive-like KOR agonist effects. NMA and NMP were equipotent to salvA but displayed longer lasting effects (6- and 10-fold, respectively). A dose of salvA with prominent effects in the ICSS test after i.p. administration (2.0 mg/kg) was inactive after oral administration, whereas the same oral dose of NMA elevated ICSS thresholds. These studies suggest that, although salvA and NMA are similar in potency and selectivity as KOR agonists in vitro, NMA has improved stability and longer lasting actions that might make it more useful for studies of KOR agonist effects in animals and humans. C1 [Beguin, Cecile; Potter, David N.; Munro, Thomas A.; Richards, Michele R.; Cohen, Bruce M.] McLean Hosp, Harvard Med Sch, Dept Psychiat, Mol Pharmacol Lab, Belmont, MA 02178 USA. [DiNieri, Jennifer A.; Paine, Tracie A.; Carlezon, William A., Jr.] McLean Hosp, Harvard Med Sch, Dept Psychiat, Behav Genet Lab, Belmont, MA 02178 USA. McLean Hosp, Harvard Med Sch, Dept Psychiat, Belmont, MA 02178 USA. [Berry, Loren; Zhao, Zhiyang] Amgen Inc, Cambridge, MA USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. [Xu, Wei; Liu-Chen, Lee-Yuan] Temple Univ, Sch Med, Dept Pharmacol, Natl Inst Mental Hlth Psychoact Drug Screening P, Philadelphia, PA USA. RP Beguin, C (reprint author), McLean Hosp, Harvard Med Sch, Dept Psychiat, Mol Pharmacol Lab, 115 Mill St, Belmont, MA 02178 USA. RI Munro, Thomas/B-2712-2009; Roth, Bryan/F-3928-2010; Richards, Mickey/E-8140-2011 OI Munro, Thomas/0000-0002-3366-7149; Richards, Mickey/0000-0002-1973-5678 FU NIDA NIH HHS [R01DA016264, DA13429]; NIMH NIH HHS [MH063266]; PHS HHS [N0IMH32004] NR 39 TC 25 Z9 25 U1 1 U2 12 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2008 VL 324 IS 1 BP 188 EP 195 DI 10.1124/jpet.107.129023 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 245GM UT WOS:000251923100022 PM 17951511 ER PT J AU Guo, JA Williams, DJ Puhl, HL Ikeda, SR AF Guo, Juan Williams, Damian J. Puhl, Henry L., III Ikeda, Stephen R. TI Inhibition of N-type calcium channels by activation of GPR35, an orphan receptor, heterologously expressed in rat sympathetic neurons SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DEPENDENT PROTEIN-KINASE; LONG-TERM POTENTIATION; KYNURENIC ACID; COUPLED RECEPTOR; DRUG DISCOVERY; CA2+ CHANNELS; CANNABINOID RECEPTOR; MAMMALIAN NEURONS; INVERSE AGONISM; MODULATION AB GPR35 is a G protein-coupled receptor recently "de-orphanized" using high-throughput intracellular calcium measurements in clonal cell lines expressing a chimeric G-protein alpha-subunit. From these screens, kynurenic acid, an endogenous metabolite of tryptophan, and zaprinast, a synthetic inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase, emerged as potential agonists for GPR35. To investigate the coupling of GPR35 to natively expressed neuronal signaling pathways and effectors, we heterologously expressed GPR35 in rat sympathetic neurons and examined the modulation of N-type (Ca(v)2.2) calcium channels. In neurons expressing GPR35, calcium channels were inhibited in the absence of overt agonists, indicating a tonic receptor activity. Application of kynurenic acid or zaprinast resulted in robust voltage-dependent calcium current inhibition characteristic of G beta gamma-mediated modulation. Both agonist-independent and -dependent effects of GPR35 were blocked by Bordetella pertussis toxin pretreatment indicating the involvement of G(i/o) proteins. In neurons expressing GPR35a, a short splice variant of GPR35, zaprinast was more potent (EC(50) = 1 mu M) than kynurenic acid (58 mu M) but had a similar efficacy (approximately 60% maximal calcium current inhibition). Expression of GPR35b, which has an additional 31 residues at the N terminus, produced similar results but with much greater variability. Both GPR35a and GPR35b appeared to have similar expression patterns when fused to fluorescent proteins. These results suggest a potential role for GPR35 in regulating neuronal excitability and synaptic release. C1 [Guo, Juan; Williams, Damian J.; Puhl, Henry L., III; Ikeda, Stephen R.] NIH, NIAAA, Lab Mol Physiol, Sect Transmitter Signaling, Rockville, MD 20892 USA. RP Ikeda, SR (reprint author), NIH, NIAAA, Lab Mol Physiol, Sect Transmitter Signaling, 5625 Fishers Lane,MSC 9411, Rockville, MD 20892 USA. EM sikeda@mail.nih.gov OI Puhl, Henry/0000-0003-3095-7201; Ikeda, Stephen/0000-0002-4088-9508 FU Intramural NIH HHS NR 37 TC 27 Z9 28 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2008 VL 324 IS 1 BP 342 EP 351 DI 10.1124/jpet.107.127266 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 245GM UT WOS:000251923100040 PM 17940199 ER PT J AU Sarang, SS Lukyanova, SM Brown, DD Cummings, BS Gullans, SR Schnellmann, RG AF Sarang, Satinder S. Lukyanova, Svetlana M. Brown, Daniel D. Cummings, Brian S. Gullans, Steven R. Schnellmann, Rick G. TI Identification, coassembly, and activity of gamma-aminobutyric acid receptor subunits in renal proximal tubular cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ADULT-RAT BRAIN; GABA(A) RECEPTORS; EXPRESSION; SUBTYPES; RABBIT; POPULATIONS AB Although the properties and functions of GABA A receptors in the mammalian central nervous system have been well studied, the presence and significance of GABA A receptors in non-neural tissues are less clear. The goal of this study was to examine the expression of GABA A receptor alpha(1), alpha(2), alpha(4), alpha(5), beta(1), gamma(1), gamma(2), and delta subunits in the kidney and to determine whether these subunits coassemble to form an active renal epithelial cell GABA A receptor. Using reverse transcriptase products from RNA isolated from rat and rabbit kidney cortex and brain or cerebellum through polymerase chain reaction (PCR) and sequencing of the PCR products, we revealed that rat kidney cortex contained the alpha(1), alpha(5), beta(1), gamma(1), and gamma(2) subunits and that they were similar to the neuronal subunits. Sequencing of the PCR products revealed that the rabbit kidney cortex contained the alpha(1) and alpha(2) subunits and that they were similar to their neuronal counterparts. Immunoprecipitation and immunoblot studies using GABA(A) receptor subunit-specific antibodies and detergent-solubilized rat kidney cortex membranes identified a GABA(A) receptor complex containing alpha(5), beta(1), and gamma(1). Isolated rat renal proximal tubular cells exhibited GABA-mediated, picrotoxin-sensitive Cl-36(-) uptake. These studies demonstrate the presence of numerous GABA A receptor subunits in the kidneys of two species, the assembly of the subunits into at least one novel receptor complex, and an active GABA A receptor in renal proximal tubular cells. C1 [Lukyanova, Svetlana M.; Cummings, Brian S.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. [Sarang, Satinder S.; Gullans, Steven R.] Brigham & Womens Hosp, Harvard Ctr Neurol Dis, Cambridge, MA USA. [Brown, Daniel D.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut Sci, 280 Calhoun St,POB 250140, Charleston, SC 29425 USA. EM schnell@musc.edu FU NIDDK NIH HHS [DK-10079, DK-52946] NR 26 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2008 VL 324 IS 1 BP 376 EP 382 DI 10.1124/jpet.107.129957 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 245GM UT WOS:000251923100044 PM 17959749 ER PT J AU Price, SM McDivitt, J Weber, D Wolff, LS Massett, HA Fulton, JE AF Price, Simani M. McDivitt, Judith Weber, Deanne Wolff, Lisa S. Massett, Holly A. Fulton, Janet E. TI Correlates of Weight-Bearing Physical Activity Among Adolescent Girls: Results From a National Survey of Girls and Their Parents SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE physical activity attitudes; physical activity beliefs AB Background: Despite the potential benefits of reducing the risk of osteoporosis in later life, research on adolescent girls' weight-bearing physical activity (WBPA) is limited. This study explores correlates for WBPA in this population. Methods: A nationally representative telephone survey sponsored by the National Bone Health Campaign was conducted with 1000 girls age 9 to 12 years and a parent. Girls' physical activities were coded as weight bearing or not and correlated with cognitive, social, and environmental variables. Results: Regression analysis revealed that WBPA was significantly associated with self-reported parents' education, parental self-efficacy, girls' normative beliefs about time spent in physical activity, being physically active with a parent, having physically active friends, and perceived availability of after-school physical activities. Conclusions: Interventions encouraging parents to participate in WBPA with their daughters and increasing parents' positive attitudes and self-efficacy in getting their daughters to be physically active should be tested. C1 [Price, Simani M.] WESTAT Corp, Rockville, MD 20850 USA. [McDivitt, Judith; Fulton, Janet E.] Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. [Weber, Deanne] Porter Novelli, Gainesville, FL 32605 USA. [Wolff, Lisa S.] Harvard Univ, Cambridge, MA 02139 USA. [Massett, Holly A.] NCI, Rockville, MD 20852 USA. RP Price, SM (reprint author), WESTAT Corp, Rockville, MD 20850 USA. NR 33 TC 8 Z9 8 U1 1 U2 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2008 VL 5 IS 1 BP 132 EP 145 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V18OW UT WOS:000208015100011 PM 18209259 ER PT J AU Nielsen, JB Cohen, LG AF Nielsen, Jens Bo Cohen, Leonardo G. TI The olympic brain. Does corticospinal plasticity play a role in acquisition of skills required for high-performance sports? SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; USE-DEPENDENT PLASTICITY; STROKE PATIENTS; HAND FUNCTION; INTERHEMISPHERIC INHIBITION; CORTICAL REPRESENTATION; UNAFFECTED HEMISPHERE; VOLUNTARY MOVEMENT; PREMOTOR CORTEX AB Non-invasive electrophysiological and imaging techniques have recently made investigation of the intact behaving human brain possible. One of the most intriguing new research areas that have developed through these new technical advances is an improved understanding of the plastic adaptive changes in neuronal circuitries underlying improved performance in relation to skill training. Expansion of the cortical representation or modulation of corticomotor excitability of specific muscles engaged in task performance is required for the aquisition of the skill. These changes at cortical level appear to be paralleled by changes in transmission in spinal neuronal circuitries, which regulate the contribution of sensory feedback mechanisms to the execution of the task. Such adaptive changes also appear to be essential for the consolidation of a memory of performance of motor tasks and thus for the lasting ability of performing highly skilled movements such as those required for Olympic sports. C1 [Nielsen, Jens Bo] Univ Copenhagen, Panum Inst, Dept Neurobiol & Pharmacol, DK-2200 Copenhagen, Denmark. [Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, Bethesda, MD 20892 USA. [Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Clin, Bethesda, MD 20892 USA. RP Nielsen, JB (reprint author), Univ Copenhagen, Panum Inst, Dept Neurobiol & Pharmacol, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM j.b.nielsen@mfi.ku.dk OI Nielsen, Jens Bo/0000-0001-5568-2916 NR 58 TC 34 Z9 36 U1 0 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2008 VL 586 IS 1 BP 65 EP 70 DI 10.1113/jphysiol.2007.142661 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 255SW UT WOS:000252678700011 PM 17717010 ER PT J AU Simmons, WK Hamann, SB Harenski, CL Hu, XP Barsalou, LW AF Simmons, W. Kyle Hamann, Stephan B. Harenski, Carla L. Hu, Xiaoping P. Barsalou, Lawrence W. TI fMRI evidence for word association and situated simulation in conceptual processing SO JOURNAL OF PHYSIOLOGY-PARIS LA English DT Article DE Language and Situated Simulation (LASS); conceptual processing; word recognition; language; action ID PERCEPTUAL SYMBOL SYSTEMS; SEMANTIC MEMORY; LEXICAL DECISION; EPISODIC MEMORY; PROPERTY VERIFICATION; PREFRONTAL CORTEX; MENTAL-IMAGERY; BRAIN; LANGUAGE; RECOGNITION AB The LASS theory proposes that Language and Situated Simulation both play central roles in conceptual processing. Depending on stimuli and task conditions, different mixtures of language and simulation occur. When a word is processed in a conceptual task, it first activates other linguistic forms, such as word associates. More slowly, the word activates a situated simulation to represent its meaning in neural systems for perception, action, and mental states. An fMRI experiment tested the LASS account. In a first scanning session, participants performed the property generation task to provide a measure of conceptual processing. In a second scanning session a week later, participants performed two localizer tasks measuring word association and situated simulation. Conjunction analyses supported predictions of the LASS theory. Activations early in conceptual processing overlapped with activations for word association. Activations late in conceptual processing overlapped with activations for situation generation. These results, along with others in the literature, indicate that conceptual processing uses multiple representations, not one. Furthermore, researchers must be careful drawing conclusions about conceptual processing, given that different paradigms are likely to produce different mixtures of language and simulation. Whereas some paradigms produce high levels of linguistic processing and low levels of simulation, other paradigms produce the opposite pattern. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Hamann, Stephan B.; Hu, Xiaoping P.; Barsalou, Lawrence W.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Simmons, W. Kyle] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Harenski, Carla L.] MIND Inst, Albuquerque, NM 87131 USA. RP Barsalou, LW (reprint author), Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. EM simmonswkyle@mail.nih.gov; barsalou@emory.edu RI Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 FU NIMH NIH HHS [1F31MH070152-01] NR 79 TC 77 Z9 81 U1 4 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0928-4257 J9 J PHYSIOLOGY-PARIS JI J. Physiol.-Paris PD JAN-MAY PY 2008 VL 102 IS 1-3 BP 106 EP 119 DI 10.1016/j.jphysparis.2008.03.014 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 331KZ UT WOS:000258012400013 PM 18468869 ER PT J AU Sigal, JJ Ouimet, MC Margolese, R Panarello, L Stibernik, V Bescec, S AF Sigal, John J. Ouimet, Marie Claude Margolese, Richard Panarello, Laura Stibernik, Vida Bescec, Susan TI How patients with less-advanced and more-advanced cancer deal with three death-related fears: An exploratory study SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE cancer stage; death anxieties; psychological distress; coping styles; optimism; religiosity/spirituality ID STAGE BREAST-CANCER; QUALITY-OF-LIFE; PSYCHOLOGICAL ADJUSTMENT; SPIRITUAL BELIEFS; MALIGNANT-MELANOMA; COPING STYLES; WOMEN; ANXIETY; STRESS; MODEL AB The means used by cancer patients to cope with each of three death anxieties (i.e., fear of pain and suffering, loneliness, and the unknown) that contribute to their psychological distress have rarely been examined. Differences between cancer patients with Stage I or II disease (Group 1) and Stage III or IV disease (Group 2) were explored. T-tests revealed no difference between the groups. Age-controlled Pearson correlations were used to determine the relationship between all three death anxieties, and some recognized coping devices used by cancer patients, namely, coping styles, optimism, and religiosity/spirituality. Results showed that, for Group 1, avoidant coping correlated positively with fear of the unknown, and social diversion correlated positively with fear of pain and suffering. As for similarities between groups, with the exception of fear of pain and suffering for Group 2, emotion-focused coping correlated positively with all three death anxieties, and optimism correlated negatively with fear of the unknown. The advantage for researchers and clinicians of including measures or evaluation of the death anxieties in their considerations of the psychological distress of cancer patients is discussed. C1 [Sigal, John J.; Ouimet, Marie Claude] Sir Mortimer B Davis Jewish Hosp, Dept Psychiat, ICFP, Montreal, PQ H3T 1E2, Canada. [Ouimet, Marie Claude] NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Margolese, Richard] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Panarello, Laura; Stibernik, Vida; Bescec, Susan] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Clin Res Unit, Montreal, PQ H3T 1E2, Canada. RP Sigal, JJ (reprint author), Sir Mortimer B Davis Jewish Hosp, Dept Psychiat, ICFP, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM john.sigal@mcgill.ca NR 41 TC 2 Z9 3 U1 2 U2 4 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2008 VL 26 IS 1 BP 53 EP 68 DI 10.1300/J077v26n01_04 PG 16 WC Psychology, Social SC Psychology GA 242IJ UT WOS:000251718500004 PM 18077262 ER PT J AU O'Neill, SC Kaufman, E DeMarco, T Peshkin, BN McKenna, K Shelby, R Valdimarsdottir, H Rispoli, J Schwartz, MD AF O'Neill, Suzanne C. Kaufman, Elizabeth DeMarco, Tiffani Peshkin, Beth N. McKenna, Kristine Shelby, Rebecca Valdimarsdottir, Heiddis Rispoli, Jessica Schwartz, Marc D. TI Changes in diet and physical activity following BRCA1/2 testing SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE BRCA1/2; diet; physical activity ID BREAST-CANCER RISK; BILATERAL PROPHYLACTIC MASTECTOMY; SMOKING-CESSATION INTERVENTION; PROSE-STUDY-GROUP; MUTATION CARRIERS; OVARIAN-CANCER; GENETIC SUSCEPTIBILITY; GERMLINE MUTATIONS; RANDOMIZED-TRIAL; HEALTH BEHAVIORS AB The present study prospectively examined change in diet and physical activity behaviors in 115 women undergoing BRCA1/2 gene testing (46 mutation positive, 46 uninformative and 23 definitive negative). Participants completed measures of diet and physical activity at three time points: prior to genetic testing and 1- and 6-months after receipt of genetic test results. Repeated measures analyses examined between- and within-group differences among participants who received BRCA1/2 positive, uninformative, or definitive negative results. There were no within-group differences across time points or between-group differences at any time point for diet or physical activity. Most participants, overall and within each group, did not meet recommended guidelines for fruit and vegetable and dietary fat consumption. These findings suggest that women do not make spontaneous changes in diet and physical activity following the genetic testing and counseling process. A brief intervention may be necessary for patients who are interested in making changes in modifiable risk factors to complement more definitive risk-reduction strategies. C1 [O'Neill, Suzanne C.] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Kaufman, Elizabeth; DeMarco, Tiffani; Peshkin, Beth N.; McKenna, Kristine; Shelby, Rebecca; Schwartz, Marc D.] Lombardi Comprehens Canc Ctr, Washington, DC USA. [Valdimarsdottir, Heiddis] Mt Sinai Sch Med, New York, NY USA. [Shelby, Rebecca] Duke Comprehens Canc Ctr, Durham, NC 27710 USA. [McKenna, Kristine] Childrens Hosp, Columbus, OH 43205 USA. RP O'Neill, SC (reprint author), NIH, Social & Behav Res Branch, NHGRI, Bldg 31,Room B1B36B, Bethesda, MD 20892 USA. EM oneills@mail.nih.gov FU NCI NIH HHS [R01 CA82346, 2R25 CA57726] NR 57 TC 7 Z9 7 U1 1 U2 3 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2008 VL 26 IS 3 BP 63 EP 80 DI 10.1080/07347330802116051 PG 18 WC Psychology, Social SC Psychology GA 331VK UT WOS:000258040500004 PM 19042265 ER PT J AU Gautam, D Jeon, J Li, JH Han, SJ Hamdan, FF Cui, YH Lu, HY Deng, CX Gavrilova, O Wess, J AF Gautam, Dinesh Jeon, Jongrye Li, Jian Hua Han, Sung-Jun Hamdan, Fadi F. Cui, Yinghong Lu, Huiyan Deng, Chuxia Gavrilova, Oksana Wess, Juergen TI Metabolic roles of the M-3 muscarinic acetylcholine receptor studied with M-3 receptor mutant mice: A review SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article; Proceedings Paper CT Annual Meeting of the Great Lakes GPCR Retreat CY SEP 27-29, 2007 CL London, CANADA DE glucose homeostasis; insulin; knockout mice; muscarinic receptor; transgenic mice ID FATTY-ACID OXIDATION; KNOCKOUT MICE; UNCOUPLING PROTEINS; GLUCOSE-HOMEOSTASIS; SKELETAL-MUSCLE; ADIPOSE-TISSUE; DEFICIENT MICE; STIMULATION; SUBTYPES; THERMOGENESIS AB The M-3 muscarinic acetylcholine (ACh) receptor (M-3 mAChR) is expressed in many central and peripheral tissues. It is a prototypic member of the superfamily of G protein-coupled receptors and preferentially activates G proteins of the G, family. Recent studies involving the use of newly generated mAChR mutant mice have revealed that the M-3 mAChR plays a key role in regulating many important metabolic functions. Phenotypic analyses of mutant mice that either selectively lacked or overexpressed M-3 receptors in pancreatic beta-cells indicated that beta-cell M-3 mAChRs are essential for maintaining proper insulin release and glucose homeostasis. The experimental data also suggested that strategies aimed at enhancing signaling through beta-cell M-3 mAChRs might be beneficial for the treatment of type 2 diabetes. Recent studies with whole body M-3 mAChR knockout mice showed that the absence of M-3 receptors protected mice against various forms of experimentally or genetically induced obesity and obesity-associated metabolic deficits. Under all experimental conditions tested, M-3 receptor-deficient mice showed greatly ameliorated impairments in glucose homeostasis and insulin sensitivity, reduced food intake, and a significant elevation in basal and total energy expenditure, most likely due to increased central sympathetic outflow and increased rate of fatty acid oxidation. These findings are of potential interest for the development of novel therapeutic approaches for the treatment of obesity and associated metabolic disorders. C1 [Gautam, Dinesh; Jeon, Jongrye; Li, Jian Hua; Han, Sung-Jun; Hamdan, Fadi F.; Cui, Yinghong; Wess, Juergen] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. [Lu, Huiyan] NIDDKD, Mouse Transgen Core Facil, Bethesda, MD 20892 USA. [Deng, Chuxia] NIDDKD, Mammalian Genet Sect, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDKD, Mouse Metab Core Lab, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, Bldg 8A,Room B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Li, Jianhua/B-7671-2011; Han, Sung-Jun/B-9547-2012; deng, chuxia/N-6713-2016 OI Li, Jianhua/0000-0002-5744-3182; NR 46 TC 23 Z9 24 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PY 2008 VL 28 IS 1-2 BP 93 EP 108 DI 10.1080/10799890801942002 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299JR UT WOS:000255752400009 PM 18437633 ER PT J AU Francesco, AL Diego, G Susanna, G Giuseppina, L Amina, WS Sergi, F Rafael, F Kjell, F AF Francesco, Agnati Luigi Diego, Guidolin Susanna, Genedani Giuseppina, Leo Amina, Woods S. Sergi, Ferre Rafael, Franco Kjell, Fuxe TI Integrative Action of Receptor Mosaics: Relevance of Receptor Topology and Allosteric Modulators SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article DE Receptor mosaics; Receptor topology; Allosteric modulators; Homocysteine ID PROTEIN-COUPLED-RECEPTORS; CENTRAL-NERVOUS-SYSTEM; BIOLUMINESCENCE ENERGY-TRANSFER; LIPID RAFTS; PLASMA-MEMBRANE; NEUROPEPTIDE-Y; ELECTROSTATIC INTERACTION; QUANTITATIVE ASSESSMENT; DOPAMINE-D-2 RECEPTORS; THEORETICAL ASPECTS AB After a definition of the receptor mosaic (RM, high order heteromer or homomer) concept, this study analyzes some relevant theoretical aspects related to receptor-receptor interactions (RRIs). In particular, the possible influence of the plasma membrane microdomain on RM integrative functions are discussed. Furthermore, a possible mathematical approach may identify the RM topologies [i.e., the spatial arrangements the receptors (tesserae of the mosaic) can assume within the RM assembly]. Finally, data are presented on homocysteine possible biasing action on the well characterized heterodimer/receptor mosaic formed by adenosine A2A and dopamine D2 receptors. We discuss how these findings can lead to a new possible approach for developing drugs for the treatment of certain neuropsychiatric disorders. C1 [Francesco, Agnati Luigi; Susanna, Genedani; Giuseppina, Leo] Univ Modena & Reggio Emilia, Dept Biomed Sci, Venice, Italy. [Francesco, Agnati Luigi; Susanna, Genedani; Giuseppina, Leo] IRCCS Lido, Venice, Italy. [Diego, Guidolin] Univ Padua, Dept Anat & Physiol, I-35100 Padua, Italy. [Amina, Woods S.; Sergi, Ferre] Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. [Rafael, Franco] Univ Barcelona, Mol Neurobiol Unit, Dept Biochem & Mol Biol, IDIBAPS, Barcelona, Spain. [Kjell, Fuxe] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Francesco, AL (reprint author), Dept Biomed Sci, Physiol Sect, Via Campi 287, I-41100 Modena, Italy. EM agnatiluigi@tin.it RI Genedani, Susanna/K-4370-2016; OI Genedani, Susanna/0000-0003-1526-153X; Guidolin, Diego/0000-0003-2133-3552 FU Khymeia srl (Padova); IRCCS San Camillo (Lido, Venezia); PRIN2006 (MUR, Roma); NIDA IRP FX This study was supported by grants from Khymeia srl (Padova); IRCCS San Camillo (Lido, Venezia); PRIN2006 (MUR, Roma). S. Ferre work was supported by NIDA IRP. NR 77 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PY 2008 VL 28 IS 6 BP 543 EP 565 DI 10.1080/10799890802590420 PG 23 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 386IC UT WOS:000261874900003 PM 19096975 ER PT J AU Macko, RF Benvenuti, F Stanhope, S Macellari, V Taviani, A Nesi, B Weinrich, M Stuart, M AF Macko, Richard F. Benvenuti, Francesco Stanhope, Steven Macellari, Velio Taviani, Antonia Nesi, Barbara Weinrich, Michael Stuart, Mary TI Adaptive physical activity improves mobility function and quality of life in chronic hemiparesis SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE activities of daily living; adaptive physical activity; exercise; group exercise; hemiplegia; home exercise regimen; mobility; quality of life; rehabilitation; stroke ID RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY FUNCTION; BERG BALANCE SCALE; CHRONIC STROKE; CARDIOVASCULAR FITNESS; PERFORMANCE BATTERY; SUBACUTE STROKE; EXERCISE; REHABILITATION; TREADMILL AB This study investigated the effects of an adaptive physical activity (APA) program on mobility function and quality of life (QOL) in chronic stroke patients. Twenty subjects with chronic hemiparesis completed a 2-month, combined group, class-home exercise regimen that emphasized mobility training. APA improved Berg Balance Scale scores (35 2 vs 45 +/- 2, p = 0.00 1), 6-minute walk distances (114 +/- 15 vs 142 +/- 7 m, p < 0.001), and Short Physical Performance Battery scores (3.2 +/- 0.4 vs 5.2 +/- 0.6, p < 0.001). Barthel Index scores increased (75 +/- 4 vs 84 +/- 4, p < 0.001), but Lawton scores were unchanged. Geriatric Depression Scale (p < 0.01) and Stroke Impact Scale (SIS), Mobility, Participation, and Recovery improved with APA (p < 0.03). APA has the potential to improve gait, balance, and basic but not instrumental activities of daily living profiles in individuals with chronic stroke. Improved depression and SIS scores suggest APA improves stroke-specific outcomes related to QOL. C1 [Benvenuti, Francesco; Taviani, Antonia; Nesi, Barbara] Dipartimento Riabilitaz, I-56028 Pisa, Italy. [Macko, Richard F.; Stuart, Mary] VAMC, Dept Vet Affairs Maryland Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. [Macko, Richard F.] VAMC, VA Rehabil Res & Dev Exercise, Baltimore, MD USA. [Macko, Richard F.] VAMC, Robot Ctr Excellence, Baltimore, MD USA. [Macko, Richard F.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Macko, Richard F.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Macko, Richard F.] Univ Maryland, Sch Med, Div Gerontol, Baltimore, MD 21201 USA. [Stanhope, Steven] NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. [Macellari, Velio] Ist Super Sanita, Dipartimento Tecnol & Salute, I-00161 Rome, Italy. [Weinrich, Michael] NICHHD, NIH, Bethesda, MD 20892 USA. [Stuart, Mary] Univ Maryland Baltimore Cty, Dept Sociol, Baltimore, MD 21228 USA. [Stuart, Mary] Univ Maryland Baltimore Cty, Dept Anthropol, Baltimore, MD 21228 USA. RP Benvenuti, F (reprint author), Dipartimento Riabilitaz, AUSL 11,Reg Toscana,Piazza 20,Settembre 13, I-56028 Pisa, Italy. EM f.benvenuti@usl11.tos.it NR 36 TC 29 Z9 30 U1 3 U2 7 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2008 VL 45 IS 2 BP 323 EP 328 DI 10.1682/JRRD.2007.02.0025 PG 6 WC Rehabilitation SC Rehabilitation GA 296LD UT WOS:000255543900012 PM 18566949 ER PT J AU Kim, HJ Yu, B Feuer, EJ AF Kim, Hyune-Ju Yu, Binbing Feuer, Eric J. TI Inference in segmented line regression: a simulation study SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE Joinpoint regression; Grid search; Continuous fitting; Change-points ID CHANGE-POINT MODELS; 2-PHASE REGRESSION; JOIN POINTS AB A segmented line regression model has been used to describe changes in cancer incidence and mortality trends [Kim, H.-J., Fay, M.P., Feuer, E.J. and Midthune, D.N., 2000, Permutation tests for joinpoint regression with applications to cancer rates. Statistics in Medicine, 19, 335-351. Kim, H.-J., Fay, M.P., Yu, B., Barrett., M.J. and Feuer, E.J., 2004, Comparability of segmented line regression models. Biometrics, 60, 1005-1014.]. The least squares fit can be obtained by using either the grid search method proposed by Lerman [Lerman, P.M., 1980, Fitting segmented regression models by grid search. Applied Statistics, 29, 77-84.] which is implemented in Joinpoint 3.0 available at http://srab.cancer.gov/joinpoint/index.html, or by using the continuous fitting algorithm proposed by Hudson [Hudson, D.J., 1966, Fitting segmented curves whose join points have to be estimated. Journal of the American Statistical Association, 61, 1097-1129.] which will be implemented in the next version of Joinpoint software. Following the least squares fitting of the model, inference on the parameters can be pursued by using the asymptotic results of Hinkley [Hinkley, D.V., 1971, Inference in two-phase regression. Journal of the American Statistical Association, 66, 736-743.] and Feder [Feder, P.I., 1975a, On asymptotic distribution theory in segmented regression Problems-Identified Case. The Annals of Statistics, 3, 49-83.] Feder [Feder, P.I., 1975b, The log likelihood ratio in segmented regression. The Annals of Statistics, 3, 84-97.] Via simulations, this paper empirically examines small sample behavior of these asymptotic results, studies how the two fitting methods, the grid search and the Hudson's algorithm affect these inferential procedures, and also assesses the robustness of the asymptotic inferential procedures. C1 [Kim, Hyune-Ju] Syracuse Univ, Dept Math, Syracuse, NY 13244 USA. [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Feuer, Eric J.] NCI, Stat Res & Applicat Branch, Bethesda, MD 20892 USA. RP Kim, HJ (reprint author), Syracuse Univ, Dept Math, 215 Carnegie Bldg, Syracuse, NY 13244 USA. EM hjkim@syr.edu NR 18 TC 5 Z9 5 U1 1 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 EI 1563-5163 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PY 2008 VL 78 IS 11 BP 1087 EP 1103 DI 10.1080/00949650701528461 PG 17 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 364GT UT WOS:000260324900011 ER PT J AU Sacks, S Chandler, R Gonzales, J AF Sacks, Stanley Chandler, Redonna Gonzales, Junius TI Responding to the challenge of co-occurring disorders: Suggestions for future research SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE co-occurring disorders; research findings; research synthesis; severity of mental disorder; research agenda ID BORDERLINE PERSONALITY-DISORDER; DIALECTICAL BEHAVIOR-THERAPY; DRUG-ABUSE TREATMENT; FOLLOW-UP; WOMEN; PREVENTION; OUTCOMES; RELAPSE; TRIAL AB This special issue consolidates some recent research findings and scientific thought on co-occurring disorders from both the substance abuse and mental health fields. This summary article recaps and synthesizes the main findings and themes, then considers additional issues in the field today to arrive at an agenda for future co-occurring disorders research. Plans must: (1) encourage and assist further development of treatment programs that respond to an array of types and severities of co-occurring disorders while taking into account the limited resources typically available; (2) continue the development and testing of continuing care models by exploring strategies that will sustain the recovery of treated individuals who remain vulnerable to relapse; and (3) contribute to our understanding of the mechanisms and processes that enable new interventions and practices to be adopted, implemented, and sustained. '' Co-occurring disorders '' is a relatively new area of research; this special issue illustrates the productivity of work to date and indicates the:potential for advances to come. (c) 2008 Elsevier Inc. All rights reserved. C1 [Sacks, Stanley] Natl Dev & Res Inst, Ctr Integrat Res & Pract, New York, NY 10010 USA. [Chandler, Redonna] Natl Inst Drug Abuse, Serv Res Branch, Bethesda, MD 20892 USA. [Gonzales, Junius] ABT Associates Inc, Hlth Care & Clin Res Div, Bethesda, MD 20814 USA. RP Sacks, S (reprint author), Natl Dev & Res Inst, Ctr Integrat Res & Pract, New York, NY 10010 USA. EM stansacks@mac.com; rehandle@nida.nih.gov; junius-gonzales@abtassoc.com FU NIDA NIH HHS [R01 DA019982-03] NR 32 TC 18 Z9 18 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JAN PY 2008 VL 34 IS 1 BP 139 EP 146 DI 10.1016/j.jsat.2007.03.008 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 246JI UT WOS:000252002900014 PM 17574790 ER PT J AU Rapoport, JL Shaw, P AF Rapoport, Judith L. Shaw, Philip TI Defining the contribution of genetic risk to structural and functional anomalies in ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; MAGNETIC-RESONANCE; METHYLPHENIDATE; CHILDREN C1 [Rapoport, Judith L.; Shaw, Philip] NIMH, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rapoporj@mail.nih.gov NR 12 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2008 VL 47 IS 1 BP 2 EP 3 DI 10.1097/chi.0b013e31815aac83 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 243WF UT WOS:000251827300002 PM 18174819 ER PT J AU Lau, JYF Lissek, S Nelson, EE Lee, Y Roberson-Nay, R Poeth, K Jenness, J Ernst, M Grillon, C Pine, DS AF Lau, Jennifer Y. F. Lissek, Shmuel Nelson, Eric E. Lee, Yoon Roberson-Nay, Roxann Poeth, Kaitlin Jenness, Jessica Ernst, Monique Grillon, Christian Pine, Daniel S. TI Fear conditioning in adolescents with anxiety disorders: Results from a novel experimental paradigm SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE pediatric anxiety disorders; fear conditioning; extinction ID PANIC DISORDER; EXTINCTION; CHILDREN; STARTLE; PARENTS AB Objective: Considerable research examines fear conditioning in adult anxiety disorders but few studies examine youths. Adult data suggest that anxiety disorders involve elevated fear but intact differential conditioning. We used a novel paradigm to assess fear conditioning in pediatric anxiety patients. Method: Sixteen individuals with anxiety disorders and 38 healthy comparisons viewed two photographs of actresses displaying neutral expressions. One picture served as the conditioned stimulus (CS), paired with a fearful expression and a shrieking scream (CS+), whereas the other picture served as a CS unpaired with the aversive outcome (CS-). Conditioning was indexed by self-reported fear. Subjects participated in two visits involving conditioning and extinction trials. Results: Both groups developed greater fear of the CS+ relative to CS-. Higher fear levels collapsed across each CS characterized anxious relative to healthy subjects, but no significant interaction between group and stimulus type emerged. Fear levels at visit 1 predicted avoidance of visit 2. Fear levels to both CS types showed stability even after extinction. Conclusions: Consistent with adult data, pediatric anxiety involves higher fear levels following conditioning but not greater differential conditioning. Extending these methods to neuroimaging studies may elucidate neural correlates of fear conditioning. Implications for exposure therapies are discussed. C1 [Lau, Jennifer Y. F.; Nelson, Eric E.; Poeth, Kaitlin; Jenness, Jessica; Ernst, Monique; Grillon, Christian; Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lee, Yoon] Univ Chicago, Dept Comparat Human Dev, Chicago, IL 60637 USA. [Roberson-Nay, Roxann] Virginia Commonwealth Univ, Sch Med, Virginia Treatment Ctr Children, Commonwealth Inst Child & Family Studies, Richmond, VA 23284 USA. RP Lau, JYF (reprint author), NIMH, Mood & Anxiety Disorders Program, Natl Inst Hlth, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM lauj@mail.nih.gov RI Lissek, Shmuel/B-6577-2008; Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU Intramural NIH HHS [ZIA MH002798-08] NR 29 TC 67 Z9 68 U1 9 U2 32 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2008 VL 47 IS 1 BP 94 EP 102 DI 10.1097/chi.0b01e31815a5f01 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 243WF UT WOS:000251827300013 PM 18174830 ER PT J AU Tuan, RS Lee, FYI Konttinen, YT Wilkinson, JM Smith, RL AF Tuan, Rocky S. Lee, Francis Young-In Konttinen, Yrjoe T. Wilkinson, J. Mark Smith, Robert Lane CA Implant Wear Symposium 2007 Biolog TI What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles? SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article; Proceedings Paper CT AAOS/NIH Osteolysis and Implant Wear: Biological, Biomedical Engineering, and Surgical Principles CY SEP 09-11, 2007 CL Austin, TX SP Amer Adad Orthopaed Surg, Nat Inst Hlth ID TOTAL HIP-REPLACEMENT; MESENCHYMAL STEM-CELLS; ORTHOPEDIC BIOMATERIAL PARTICLES; WEIGHT POLYETHYLENE PARTICLES; SYNOVIAL-LIKE MEMBRANE; HUMAN TRABECULAR BONE; TITANIUM PARTICLES; IN-VITRO; PERIPROSTHETIC OSTEOLYSIS; FACTOR-ALPHA AB New clinical and basic science data on the cellular and molecular mechanisms by which wear particles stimulate the host inflammatory response have provided deeper insight into the pathophysiology of periprosthetic bone loss. Interactions among wear particles, macrophages, osteoblasts, bone marrow-derived mesenchymal stem cells, fibroblasts, endothelial cells, and T cells contribute to the production of pro-inflammatory and proosteoclastogenic cytokines such as TNF-alpha, RANKL, M-SCF, PGE(2), IL-1, IL-6, and IL-8. These cytokines not only promote osteoclastogenesis but interfere with osteogenesis led by osteoprogenitor cells. Recent studies indicate that genetic variations in TNF-alpha, IL-1, and FRZB can result in subtle changes in gene function, giving rise to altered susceptibility or severity for periprosthetic inflammation and bone loss. Continuing research on the biologic effects and mechanisms of action of wear particles will provide a rational basis for the development of novel and effective ways of diagnosis, prevention, and treatment of periprosthetic inflammatory bone loss. C1 [Tuan, Rocky S.] NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA. [Lee, Francis Young-In] Columbia Univ, Dept Orthopaed Surg, New York, NY USA. [Konttinen, Yrjoe T.] Univ Helsinki, Inst Clin Med, Helsinki, Finland. [Wilkinson, J. Mark] Univ Sheffield, No Gen Hosp, Acad Unit Bone Metab, Sheffield S10 2TN, S Yorkshire, England. [Smith, Robert Lane] Stanford Univ, Med Ctr, Dept Orthopaed Surg, Stanford, CA 94305 USA. RP Tuan, RS (reprint author), NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 AR041131-06] NR 56 TC 53 Z9 54 U1 0 U2 8 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PY 2008 VL 16 SU 1 BP S42 EP S48 PG 7 WC Orthopedics SC Orthopedics GA 323UT UT WOS:000257474600010 PM 18612013 ER PT J AU Kastenmayer, RJ Perdue, KA Elkins, WR AF Kastenmayer, Robin J. Perdue, Kathy A. Elkins, William R. TI Eradication of murine norovirus from a mouse barrier facility SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID MURINE-NOROVIRUS-1 INFECTION; INTERFERON; INITIATION; MICE AB Murine norovirus (MNV) is a common viral infection of mice in many research facilities. MNV infects hematopoietic cells and alters their cellular morphology. Because of MNV's probable effects on the systemic immune response of infected mice the decision was made to eradicate the virus from 2 rooms containing infected animals in our vivarium. Two different eradication methods were selected. One room, in which most of the indirectly exposed sentinels had antibodies to MNV, was depopulated and thoroughly cleaned prior to repopulation. In the other room, in which only 13% of the sentinels had positive MNV titers, selective testing was used, and MNV-positive animals were removed. Data from surveillance of the sentinel mice exposed to dirty bedding indicate that the test-and-removal method was ineffective in eliminating MNV from the room, whereas sentinel mice in the room that underwent depopulation and cleaning prior to repopulation have not shown any evidence of MNV since December 2006. C1 [Kastenmayer, Robin J.; Perdue, Kathy A.; Elkins, William R.] NIAID, NIH, Bethesda, MD 20892 USA. RP Kastenmayer, RJ (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rkastenmayer@niaid.nih.gov FU Intramural NIH HHS NR 16 TC 10 Z9 10 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JAN PY 2008 VL 47 IS 1 BP 26 EP 30 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 260YB UT WOS:000253045200005 PM 18210995 ER PT J AU Clarke, CL Eckhaus, MA Zerfas, PM Elkins, WR AF Clarke, Carol L. Eckhaus, Michael A. Zerfas, Patricia M. Elkins, William R. TI Peripheral edema with hypoalbuminemia in a nonhuman primate infected with simian-human immunodeficiency virus: A case report SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID MACAQUE MACACA-NEMESTRINA; BLOOD MONONUCLEAR-CELLS; RHESUS-MONKEYS; HYDROXYETHYL STARCH; RENAL-DISEASE; AIDS; NEPHROPATHY; GLOMERULONEPHRITIS; PREVENTION; HIV AB A rhesus macaque (Macaca mulatta) infected with simian-human immunodeficiency virus (SHIV) while undergoing AIDS research, required a comprehensive physical examination when it presented with slight peripheral edema, hypoalbuminemia, and proteinuria. Many of the clinical findings were consistent with nephrotic syndrome, which is an indication of glomerular disease, but the possibility of concurrent disease needed to be considered because lentiviral induced immune deficiency disease manifests multiple clinical syndromes. The animal was euthanized when its condition deteriorated despite supportive care that included colloidal fluid therapy. Histopathology confirmed membranoproliferative glomerulonephritis, the result of immune complex deposition most likely due to chronic SHIV infection. Clinical symptoms associated with this histopathology in SHIV infected macaques have not previously been described. Here we offer suggestions for the medical management of this condition, which entails inhibition of the renin-angiotensin-aldosterone system and diet modifications. C1 [Clarke, Carol L.; Elkins, William R.] NIAID, Comparat Med Branch, Bethesda, MD 20892 USA. [Eckhaus, Michael A.; Zerfas, Patricia M.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Clarke, CL (reprint author), NIAID, Comparat Med Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM cclarke@mail.nih.gov NR 57 TC 1 Z9 1 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JAN PY 2008 VL 47 IS 1 BP 42 EP 48 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 260YB UT WOS:000253045200008 PM 18210998 ER PT J AU Menzie, CM Yanoff, LB Denkinger, BI McHugh, T Sebring, NG Calis, KA Yanovski, JA AF Menzie, Carolyn M. Yanoff, Lisa B. Denkinger, Blakeley I. McHugh, Teresa Sebring, Nancy G. Calis, Karim A. Yanovski, Jack A. TI Obesity-related hypoferremia is not explained by differences in reported intake of heme and nonheme, iron or intake of dietary factors that can affect iron absorption SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the North-American-Association-for-the-Study-of-Obesity CY OCT 20-24, 2006 CL Boston, MA SP N Amer Assoc Study Obes ID ASCORBIC-ACID; LIFE-STYLE; DEFICIENCY; WOMEN; ADOLESCENTS; COOKING; INDEXES; HUMANS; MEAT AB Hypoferremia is more prevalent in obese than nonobese adults, but the reason for this phenomenon is unknown. To elucidate the role dietary factors play in obesity-related hypoferremia, the intake of heme and nonheme iron and the intake of other dietary factors known to affect iron absorption were compared cross-sectionally from April 2002 to December 2003 in a convenience sample of 207 obese and 177 nonobese adults. Subjects completed 7-day food records, underwent phlebotomy for serum iron measurement, and had body composition assessed by dual-energy x-ray absorptiometry, during a 21-month period. Data were analyzed by analysis of covariance and multiple linear regression. Serum iron (mean +/- standard deviation) was significantly lower in obese than nonobese individuals (72.0 +/- 61.7 vs 85.3 +/- 58.1 mu g/dL [12.888 +/- 11.0443 vs 15.2687 +/- 10.3999 mu mol/L]; P<0.001). The obese cohort reported consuming more animal protein (63.6 +/- 34.5 vs 55.7 +/- 32.5 g/day; P<0.001) and more heme iron (3.6 +/- 2.8 vs 2.7 +/- 2.6 mg/day; P<0.001). Groups did not differ, however, in total daily iron consumption, including supplements. Obese subjects reported consuming less vitamin C (77.2 +/- 94.9 vs 91.8 +/- 89.5 mg/day; P = 0.01), which may increase absorption of nonheme iron, and less calcium (766.2 +/- 665.0 vs 849.0 +/- 627.2 mg/day; P = 0.038), which may decrease nonheme iron absorption, than nonobese subjects. Groups did not significantly differ in intake of other dietary factors that can impact absorption of iron, including phytic acid, oxalic acid, eggs, coffee, tea, zinc, vegetable protein, or copper. After accounting for demographic covariates and dietary factors expected to affect iron absorption, fat mass (P = 0.007) remained a statistically significant negative predictor of serum iron. This cross-sectional, exploratory study suggests that obesity-related hypoferremia is not associated with differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption. C1 [Menzie, Carolyn M.; Yanoff, Lisa B.; Yanovski, Jack A.] NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Denkinger, Blakeley I.; McHugh, Teresa; Sebring, Nancy G.; Calis, Karim A.] NIH, Drug Informat Serv, Clin Ctr Pharm Dept, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Hatfield Clin Res Ctr, 10 Ctr Dr,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [HD000641, Z01 HD000641]; NIH HHS [Y2 OD2067] NR 23 TC 74 Z9 77 U1 0 U2 6 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2008 VL 108 IS 1 BP 145 EP 148 DI 10.1016/j.jada.2007.10.034 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 246IY UT WOS:000252001900029 PM 18156002 ER PT J AU Hartwig, S Bridgewater, D Di Giovanni, V Cain, J Mishina, Y Rosenblum, ND AF Hartwig, Sunny Bridgewater, Darren Di Giovanni, Valeria Cain, Jason Mishina, Yuji Rosenblum, Norman D. TI BMP receptor ALK3 controls collecting system development SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RENAL BRANCHING MORPHOGENESIS; URETERAL BUD; MOUSE EMBRYOGENESIS; METANEPHRIC KIDNEY; MICE LACKING; PROTEINS; DEFECTS; HYPOPLASIA; COOPERATE; REGULATOR AB The molecular signals that regulate growth and branching of the ureteric bud during formation of the renal collecting system are largely undefined. Members of the bone morphogenetic protein (BMP) family signal through the type I BMP receptor ALK3 to inhibit ureteric bud and collecting duct cell morphogenesis in vitro. We investigated the function of the BMP signaling pathway in vivo by generating a murine model of ALK3 deficiency restricted to the ureteric bud lineage (Alk3(UB-/-) mice). At the onset of branching morphogenesis, Alk(UB-/-) kidneys are characterized by an abnormal primary (1 degrees) ureteric bud branch pattern and an increased number of ureteric bud branches. However, during later stages of renal development, Alk3(UB-/-) kidneys have fewer ureteric bud branches and collecting ducts than wild-type kidneys. Postnatal Alk3(UB-/-) mice exhibit a dysplastic renal phenotype characterized by hypoplasia of the renal medulla, a decreased number of medullary collecting ducts, and abnormal expression of beta-catenin and c-MYC in medullary tubules. In summary, normal kidney development requires ALK3-dependent BMP signaling, which controls ureteric bud branching. C1 [Rosenblum, Norman D.] Hosp Sick Children, Div Nephrol, Toronto, ON M5G 1X8, Canada. [Hartwig, Sunny; Bridgewater, Darren; Di Giovanni, Valeria; Cain, Jason; Rosenblum, Norman D.] Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada. [Hartwig, Sunny; Rosenblum, Norman D.] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Di Giovanni, Valeria; Rosenblum, Norman D.] Univ Toronto, Lab Med Pathobiol, Toronto, ON, Canada. [Rosenblum, Norman D.] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Mishina, Yuji] NIH, Reprod & Dev Toxicol Lab, Mol Dev Biol Sect, Bethesda, MD 20892 USA. RP Rosenblum, ND (reprint author), Hosp Sick Children, Div Nephrol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM norman.rosenblum@sickkids.ca NR 28 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2008 VL 19 IS 1 BP 117 EP 124 DI 10.1681/ASN.2007010080 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 250IL UT WOS:000252293100017 PM 18178801 ER PT J AU Kim, BS Aum, JA Kim, HS Kim, SJ Kim, MB Oh, CK Kwon, YW Kwon, KS AF Kim, B. S. Aum, J. A. Kim, H. S. Kim, S. J. Kim, M. B. Oh, C. K. Kwon, Y. W. Kwon, K. S. TI Coexistence of classic lichen planus and lichen planus pigmentosus-inversus: resistant to both tacrolimus and clobetasol propionate ointments SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Letter ID TOPICAL TACROLIMUS C1 [Kim, H. S.; Kim, S. J.; Kim, M. B.; Oh, C. K.; Kwon, K. S.] Pusan Natl Univ, Sch Med, Dept Dermatol, Pusan, South Korea. [Kim, B. S.] Kyungpook Natl Univ, Sch Med, Dept Dermatol, Taegu, South Korea. [Kwon, Y. W.] NIAID, Natl Inst Hlth, Immunopathol Lab, Bethesda, MD 20892 USA. RP Kwon, KS (reprint author), Pusan Natl Univ, Sch Med, Dept Dermatol, Pusan, South Korea. EM kwonks@pusan.ac.kr NR 6 TC 11 Z9 11 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0926-9959 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD JAN PY 2008 VL 22 IS 1 BP 106 EP 107 DI 10.1111/j.1468-3083.2007.02257.x PG 2 WC Dermatology SC Dermatology GA 243PY UT WOS:000251811000020 PM 18181983 ER PT J AU Grafman, J AF Grafman, Jordan TI Paging equals functionality - Introduction SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Editorial Material C1 NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, NIH, Cognit Neurosci Sect, Bld 10,Room 7D43, 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov FU Intramural NIH HHS NR 2 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2008 VL 14 IS 1 BP 152 EP 153 DI 10.1017/S1355617708080211 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 338VI UT WOS:000258537100016 PM 18078542 ER PT J AU Kotzin, S Lyon, B AF Kotzin, Sheldon Lyon, Becky TI Leading into the future: Library Operations at the National Library of Medicine SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Editorial Material C1 [Kotzin, Sheldon; Lyon, Becky] Natl Lib Med, Bethesda, MD 20894 USA. RP Kotzin, S (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM kotzins@mail.nlm.nih.gov; lyonb@mail.nlm.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 4 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2008 VL 96 IS 1 BP 1 EP 2 DI 10.3163/1536-5050.96.1.1 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 251RJ UT WOS:000252391200001 PM 18219374 ER PT J AU Copas, A Seaman, S Raab, G Jewell, CP Presanis, A Sweeting, M Bird, SM Calleja, N Farrington, CP Greenland, S Kalogeropoulos, K Papaspiliopoulos, O Katki, HA Raftery, AE Alkema, L AF Copas, Andrew Seaman, Shaun Raab, Gillian Jewell, Chris P. Presanis, Anne Sweeting, Michael Bird, Sheila M. Calleja, Neville Farrington, C. P. Greenland, Sander Kalogeropoulos, Konstantinos Papaspiliopoulos, Omiros Katki, Hormuzd A. Raftery, Adrian E. Alkema, Leontine TI Discussion on the paper by Goubar, Ades, De Angelis, McGarrigle, Mercer, Tookey, Fenton and Gill SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Editorial Material ID HOMOSEXUAL-MEN; HIV PREVALENCE; MODELS; INFERENCE; UNCERTAINTY; SIMULATION; EPIDEMIC; BEHAVIOR C1 [Copas, Andrew] Med Res Council Clin Trials Unit, London, England. [Seaman, Shaun] UCL, London WC1E 6BT, England. [Raab, Gillian] Napier Univ, Edinburgh EH14 1DJ, Midlothian, Scotland. [Jewell, Chris P.] Univ Lancaster, Lancaster LA1 4YW, England. [Presanis, Anne; Sweeting, Michael; Bird, Sheila M.] Med Res Council Biostat Unit, Cambridge, England. [Calleja, Neville; Farrington, C. P.] Open Univ, Milton Keynes MK7 6AA, Bucks, England. [Greenland, Sander] Univ Calif Los Angeles, Los Angeles, CA USA. [Kalogeropoulos, Konstantinos] Univ Cambridge, Cambridge CB2 1TN, England. [Papaspiliopoulos, Omiros] Univ Pompeu Fabra, Barcelona, Spain. [Katki, Hormuzd A.] NCI, Rockville, MD USA. [Raftery, Adrian E.; Alkema, Leontine] Univ Washington, Seattle, WA 98195 USA. RP Copas, A (reprint author), Med Res Council Clin Trials Unit, London, England. RI Sweeting, Michael/E-7649-2010; Alkema, Leontine/K-1585-2013; Katki, Hormuzd/B-4003-2015 OI Alkema, Leontine/0000-0001-8806-5957; NR 34 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0964-1998 J9 J R STAT SOC A STAT JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2008 VL 171 BP 568 EP 580 PN 3 PG 13 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 300OY UT WOS:000255836300004 ER PT J AU Qin, J Zhang, BA AF Qin, Jing Zhang, Biao TI Empirical-likelihood-based difference-in-differences estimators SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE auxiliary information; biased sampling; bootstrap; observational studies; propensity score; survey sampling ID TRAINING-PROGRAMS; AUXILIARY INFORMATION; MODELS; BIAS AB Recently there has been a surge in econometric and epidemiologic works focusing on estimating average treatment effects under various sets of assumptions. Estimation of average treatment effects in observational studies often requires adjustment for differences in pretreatment variables. Rosenbaum and Rubin have proposed the propensity score method for estimating the average treatment effect by adjusting pretreatment variables. In this paper, the empirical likelihood method is used to estimate average treatment effects on the treated under the difference-in-differences framework. The advantage of this approach is that the common marginal covariate information can be incorporated naturally to enhance the estimation of average treatment effects. Compared with other approaches in the literature, the method proposed can provide more efficient estimation. A simulation study and a real economic data analysis are presented. C1 [Zhang, Biao] Univ Toledo, Dept Math, Toledo, OH 43606 USA. [Qin, Jing] NIAID, Bethesda, MD 20892 USA. RP Zhang, BA (reprint author), Univ Toledo, Dept Math, Toledo, OH 43606 USA. EM bzhang@utnet.utoledo.edu NR 22 TC 6 Z9 6 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2008 VL 70 BP 329 EP 349 DI 10.1111/j.1467-9868.2007.00638.x PN 2 PG 21 WC Statistics & Probability SC Mathematics GA 259TP UT WOS:000252964100003 ER PT J AU Chen, SX Leung, DHY Qin, J AF Chen, Song Xi Leung, Denis H. Y. Qin, Jing TI Improving semiparametric estimation by using surrogate data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE empirical likelihood; estimating equations; missing values; surrogate outcome ID END-POINTS; REGRESSION-MODELS; MISSING DATA; EMPIRICAL LIKELIHOOD; IMPUTATION; EFFICIENCY; SELECTION; TRIALS; SAMPLE AB The paper considers estimating a parameter beta that defines an estimating function U(y, x, beta) for an outcome variable y and its covariate x when the outcome is missing in some of the observations. We assume that, in addition to the outcome and the covariate, a surrogate outcome is available in every observation. The efficiency of existing estimators for beta depends critically on correctly specifying the conditional expectation of U given the surrogate and the covariate. When the conditional expectation is not correctly specified, which is the most likely scenario in practice, the efficiency of estimation can be severely compromised even if the propensity function (of missingness) is correctly specified. We propose an estimator that is robust against the choice of the conditional expectation via an empirical likelihood. We demonstrate that the estimator proposed achieves a gain in efficiency whether the conditional score is correctly specified or not. When the conditional score is correctly specified, the estimator reaches the semiparametric variance bound within the class of estimating functions that are generated by U. The practical performance of the estimator is evaluated by using simulation and a data set that is based on the 1996 US presidential election. C1 [Chen, Song Xi] Iowa State Univ, Dept Stat, Ames, IA 50011 USA. [Chen, Song Xi] Peking Univ, Beijing 100871, Peoples R China. [Leung, Denis H. Y.] Singapore Management Univ, Singapore, Singapore. [Qin, Jing] NIH, Bethesda, MD 20892 USA. RP Chen, SX (reprint author), Iowa State Univ, Dept Stat, Ames, IA 50011 USA. EM songchen@iastate.edu RI LEUNG, Denis Heng Yan/D-1439-2009; OI Chen, Song Xi/0000-0002-2338-0873 NR 35 TC 17 Z9 17 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1369-7412 J9 J R STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2008 VL 70 BP 803 EP 823 DI 10.1111/j.1467-9868.2008.00662.x PN 4 PG 21 WC Statistics & Probability SC Mathematics GA 326QT UT WOS:000257674700009 ER PT J AU Hu, ZH Qin, J Follmann, D AF Hu, Zonghui Qin, Jing Follmann, Dean TI Semiparametric two-sample changepoint model with application to human immunodeficiency virus studies SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE changepoint; empirical distribution; likelihood ratio; maximum empirical likelihood estimation; profile likelihood ID RECOMBINANT GLYCOPROTEIN-120 VACCINE; PLASMA PREPARATION TUBES; CHANGE-POINT; VIRAL LOAD; RANDOM-VARIABLES; CONSTANT HAZARD; HIV-1 INFECTION; LIKELIHOOD; TYPE-1; TESTS AB A two-sample changepoint model is proposed to investigate the difference between two treatments or devices. Under our semiparametric approach, no assumptions are made about the underlying distributions of the measurements from the two treatments or devices, but a parametric link is assumed between the two. The parametric link contains the possible changepoint where the two distributions start to differ. We apply the maximum empirical likelihood for model estimation and show the consistency of the changepoint estimator. An extended changepoint model is studied to handle data censored because of detection limits in viral load assays of human immunodeficiency virus (HIV). Permutation and bootstrap procedures are proposed to test the existence of a changepoint and the goodness of fit of the model. The performance of the semiparametric changepoint model is compared with that of parametric models in a simulation study. We provide two applications in HIV studies: one is a randomized placebo-controlled study to evaluate the effects of a recombinant glycoprotein 120 vaccine on HIV viral load; the other is a study to compare two types of tubes in handling plasma samples for viral load determination. C1 [Hu, Zonghui; Qin, Jing; Follmann, Dean] NIAID, Bethesda, MD 20892 USA. RP Hu, ZH (reprint author), 6700A Rockledge Dr, Bethesda, MD 20892 USA. EM huzo@niaid.nih.gov NR 29 TC 1 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2008 VL 57 BP 589 EP 607 DI 10.1111/j.1467-9876.2008.00632.x PN 5 PG 19 WC Statistics & Probability SC Mathematics GA 349VH UT WOS:000259310900006 ER PT J AU Liang, H Park, S Gallas, BD Myers, KJ Badano, A AF Liang, Hongye Park, Subok Gallas, Brandon D. Myers, Kyle J. Badano, Aldo TI Assessment of display temporal response using a computational observer SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Article; Proceedings Paper CT International Symposium of the Society-for-Information-Display CY MAY 20-25, 2007 CL Long Beach, CA SP Soc Informat Display DE model observer; display quality; contrast sensitivity; temporal response AB Temporal response is one of the major concerns for liquid-crystal-display (LCD) performance. Fast response time is preferred for high-fidelity image rendering. Several methods have been proposed to improve the LCD temporal performance. A method to assess the impact of temporal responses based on measured or modeled device temporal characteristics with a contrast-sensitive computational observer that is intended to predict human performance is reported. A method to compare different devices and temporal blur reduction approaches has been applied. It was found that slow temporal response of the display device greatly affects signal contrast and observer performance. This methodology, after validation with human observers, could be used to compare different displays with different inter-gray-level transition time profiles. C1 [Liang, Hongye; Park, Subok; Gallas, Brandon D.; Myers, Kyle J.; Badano, Aldo] US FDA, CDRH,NIBIB Lab Assessment Med Imaging Syst, Div Imaging & Appl Math,Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Liang, H (reprint author), US FDA, CDRH,NIBIB Lab Assessment Med Imaging Syst, Div Imaging & Appl Math,Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 3116, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 10 TC 2 Z9 2 U1 0 U2 2 PU SOC INFORMATION DISPLAY PI SAN JOSE PA 610 S SECOND STREET, SAN JOSE, CA 95112 USA SN 1071-0922 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD JAN PY 2008 VL 16 IS 1 BP 21 EP 25 DI 10.1889/1.2835030 PG 5 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA 251US UT WOS:000252401400004 ER PT J AU Lee, DS Larson, MG Lunetta, KL Dupuis, J Rong, J Keaney, JF Lipinska, I Baldwin, CT Vasan, RS Benjamin, EJ AF Lee, D. S. Larson, M. G. Lunetta, K. L. Dupuis, J. Rong, J. Keaney, J. F. ., Jr. Lipinska, I. Baldwin, C. T. Vasan, R. S. Benjamin, E. J. TI Clinical and genetic correlates of soluble P-selectin in the community SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE epidemiology; genetics; inflammation; polymorphism single nucleotide; P-selectin; risk factors ID CORONARY-ARTERY-DISEASE; INTERCELLULAR-ADHESION MOLECULE-1; CARDIAC OUTCOMES TRIAL; MYOCARDIAL-INFARCTION; PLATELET ACTIVATION; LINKAGE ANALYSIS; DEFICIENT MICE; HEART-DISEASE; HYPERTENSIVE PATIENTS; ASSOCIATION ANALYSIS AB Background: P-selectin is a cell adhesion molecule that is involved in atherogenesis, and soluble concentrations of this biomarker reflect cardiovascular risk. However, the clinical correlates and genetic characterization of soluble P-selectin have not been clearly elucidated. Objectives: To describe clinical and genetic correlates of circulating P-selectin in the community. Methods: In Framingham Heart Study Offspring (European descent) and Omni (ethnic/racial minority) participants, we examined the association of cardiovascular risk factors with soluble P-selectin concentrations. In Offspring participants, we evaluated heritability, linkage and association of 29 SELP single-nucleotide polymorphisms (SNPs) with adjusted P-selectin concentrations. Results: In multivariable analysis of 3690 participants (54% women, mean age 60 +/- 10 years), higher log-transformed P-selectin concentrations were inversely associated with female sex and hormone replacement therapy, and positively associated with age, ethnic/racial minority status, cigarette smoking, waist circumference, systolic blood pressure, fasting glucose, and total/high-density lipoprotein cholesterol and triglyceride concentrations. Clinical factors explained 10.4% of the interindividual variability in P-selectin concentrations. In 571 extended pedigrees (n = 1841) with >= 2 phenotyped members per family, multivariable-adjusted heritability was 45.4 +/- 5.8%. Among the SELP SNPs examined, a non-synonymous SNP (rs6136) encoding a threonine-to-proline substitution at position 715 was highly significantly associated with decreased P-selectin concentrations (P = 5.2 x 10(-39)), explaining 9.7% of variation after adjustment for clinical factors. Conclusions: Multiple clinical factors and an SNP in the SELP gene were significantly associated with circulating P-selectin concentrations. One SNP in SELP explained significant variation in circulating P-selectin concentrations, even after accounting for known clinical correlates. C1 [Lee, D. S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Lee, D. S.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Lee, D. S.; Larson, M. G.; Rong, J.; Vasan, R. S.; Benjamin, E. J.] NIH, NHLBI, Framingham Heart Study, Boston, MA USA. [Larson, M. G.; Lunetta, K. L.; Dupuis, J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Keaney, J. F. ., Jr.; Lipinska, I.; Vasan, R. S.; Benjamin, E. J.] Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA. [Keaney, J. F. ., Jr.; Lipinska, I.; Vasan, R. S.; Benjamin, E. J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Baldwin, C. T.] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. [Benjamin, E. J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Dept Med, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu RI Lee, Douglas/J-4315-2014; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL076784, HL64753, 2K24HL4334, N01-HC-25195]; PHS HHS [AGO28321] NR 70 TC 19 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2008 VL 6 IS 1 BP 20 EP 31 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 243QV UT WOS:000251813300004 PM 17944986 ER PT J AU Lee, CJ Lin, P Chandrasekaran, V Duke, RE Everse, SJ Perera, L Pedersen, LG AF Lee, C. J. Lin, P. Chandrasekaran, V. Duke, R. E. Everse, S. J. Perera, L. Pedersen, L. G. TI Proposed structural models of human factor Va and prothrombinase SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE factor Va; factor Xa; molecular dynamics simulation; protein-protein docking; prothrombinase ID ACTIVATED PROTEIN-C; COAGULATION FACTOR-XA; 3-DIMENSIONAL MODEL; CRYSTAL-STRUCTURE; HEAVY-CHAIN; COMPLEX; ZYMOGEN; SENSITIVITY; SUBSTRATE; SEQUENCES AB Background: The prothrombinase complex consists of factor Xa, FVa, calcium ions, and phospholipid membrane. The prothrombinase complex plays a key role in the blood coagulation process. Objective: To derive solvent-equilibrated models of human FVa and the prothrombinase complex. Methods: Several modeling techniques have been employed, including homology modeling, protein-protein docking, and molecular dynamics simulation methods, to build the structural models. Results and conclusions: We found, upon simulation, a possibly significant shift towards planarity of the five FVa domains. To estimate a prothrombinase structure, we docked an FXa model to the equilibrated FVa model using experimental data as docking filters. We found that simulation of the docked complex led to some changes in the protein-protein contacts, but not buried surface area, as compared to the initial docking model. Possible locations of prothrombin binding to prothrombinase are indicated. C1 [Lee, C. J.; Lin, P.; Chandrasekaran, V.; Duke, R. E.; Pedersen, L. G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27515 USA. [Duke, R. E.; Perera, L.; Pedersen, L. G.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Everse, S. J.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27515 USA. EM lee_pedersen@unc.edu RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013; Lin, Ping/C-7115-2008 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861; Lin, Ping/0000-0003-1200-4423 FU NHLBI NIH HHS [HL-06350] NR 29 TC 20 Z9 22 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2008 VL 6 IS 1 BP 83 EP 89 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 243QV UT WOS:000251813300012 PM 17973648 ER PT J AU Karami, S Brennan, P Hung, RJ Boffetta, P Toro, J Wilson, RT Zaridze, D Navratilova, M Chatterjee, N Mates, D Janout, V Kollarova, H Bencko, V Szeszenia-Dabrowska, N Holcatova, I Moukeria, A Welch, R Chanock, S Rothman, N Chow, WH Moore, LE AF Karami, S. Brennan, P. Hung, R. J. Boffetta, P. Toro, J. Wilson, R. T. Zaridze, D. Navratilova, M. Chatterjee, N. Mates, D. Janout, V. Kollarova, H. Bencko, V. Szeszenia-Dabrowska, N. Holcatova, I. Moukeria, A. Welch, R. Chanock, S. Rothman, N. Chow, W. -H. Moore, L. E. TI Vitamin D receptor polymorphisms and renal cancer risk in Central and Eastern Europe SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID KIDNEY CANCER; GENE POLYMORPHISM; BREAST-CANCER; FAMILY-HISTORY; CELL CARCINOMA; CALCIUM; ASSOCIATION; JAPANESE; WOMEN; DAIRY AB Previous studies investigated the role of vitamin D intake and cancer risk. The kidney is a major organ for vitamin D metabolism, activity, and calcium homeostasis; therefore, it was hypothesized that dietary vitamin D intake and polymorphisms in the vitamin D receptor (VDR) gene may modify renal cell carcinoma (RCC) risk. Three common VDR gene polymorphisms (BsmI, FokI, TaqI) were evaluated among 925 RCC cases and 1192 controls enrolled in a hospital-based case-control study conducted in Central and Eastern Europe. Overall associations with RCC risk were not observed; however, subgroup analyses revealed associations after stratification by median age of diagnosis and family history of cancer. Among subjects over 60 yr, reduced risks were observed among carriers of the f alleles in the FokI single-nuceotide polymorphism (SNP) (odds ratio [OR] = 0.61 for Ff and OR = 0.74 for ff genotypes) compared to subjects with the FF genotype (P trend = 0.04; P interaction = 0.004). Subjects with the BB BsmI genotype and a positive family history of cancer had lower risk compared to subjects with the bb allele (OR = 0.60; 95% CI: 0.33-1.1; P trend = 0.05). Genotype associations with these subgroups were not modified when dietary sources of vitamin D or calcium were considered. Additional studies of genetic variation in the VDR gene are warranted. C1 [Karami, S.; Toro, J.; Wilson, R. T.; Chatterjee, N.; Rothman, N.; Chow, W. -H.; Moore, L. E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Brennan, P.; Hung, R. J.; Boffetta, P.] Int Agcy Res Canc, F-69372 Lyon, France. [Hung, R. J.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Zaridze, D.; Moukeria, A.] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Janout, V.; Kollarova, H.] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Bencko, V.; Holcatova, I.] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Navratilova, M.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Szeszenia-Dabrowska, N.] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Mates, D.] Inst Publ Hlth, Bucharest, Romania. [Welch, R.; Chanock, S.] NCI, Core Genotyping Facil Adv Technol Ctr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Karami, S (reprint author), 6120 Execut Blvd EPS 8121, Rockville, MD 20852 USA. EM karamis@mail.nih.gov RI Hung, Rayjean/A-7439-2013; Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI mates, dana/0000-0002-6219-9807 FU Intramural NIH HHS [Z99 CA999999, ZIA CP010120-14] NR 28 TC 20 Z9 22 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2008 VL 71 IS 6 BP 367 EP 372 DI 10.1080/15287390701798685 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 262NA UT WOS:000253154000003 PM 18246496 ER PT J AU Willson, PJ Khozani, TT Juurlink, BHJ Senthilselvan, A Rennie, DC Gerdts, V Gawaziuk, J Schneberger, D Burch, LH Dosman, JA AF Willson, P. J. Khozani, T. Talaei Juurlink, B. H. J. Senthilselvan, A. Rennie, D. C. Gerdts, V. Gawaziuk, J. Schneberger, D. Burch, Lauranell H. Dosman, J. A. TI In vitro production of tumor necrosis factor-alpha by human monocytes stimulated with lipopolysaccharide is positively correlated with increased blood monocytes after exposure to a swine barn SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID EPITHELIAL-CELLS; LUNG-FUNCTION; ORGANIC DUST; ENDOTOXIN; BACTERIAL; TLR4; VOLUNTEERS; ASTHMA; TNF AB Recently there has been interest in the air quality in and around intensive livestock production facilities, such as modern swine production barns, where agricultural workers and surrounding residents may be exposed to elevated levels of organic dusts. The health effects of these exposures are not completely understood. The study that is reported here is a component of a larger investigation of the relationships among the acute effects of high-concentration endotoxin exposure (swine barn dust), polymorphisms in the TLR4 gene, and respiratory outcomes following exposure to swine confinement buildings. The relationships among a mediator of acute lung inflammation, tumor necrosis factor alpha (TNF-alpha), and clinical responses to acute swine barn exposure were characterized. Analysis of the results showed that in vitro stimulation of human monocytes with as little as 1 ng/ml of lipopolysaccharide (LPS) produced a significant increase in the monocytes that produced TNF-alpha. Although the proportion of TNF-alpha-positive monocytes after in vitro stimulation with 1 ng/ml of LPS was not associated with gender or TLR4 genotype, it was positively associated with the concentration of monocytes in blood after barn exposure. Thus, these two responses to different forms of LPS exposure are significantly correlated, and more responsive monocytes in vitro indicate a forthcoming relative monocytosis, post barn exposure, which may initiate a cascade of chronic inflammation. C1 [Willson, P. J.; Rennie, D. C.; Schneberger, D.; Dosman, J. A.] Univ Saskatchewan, Coll Med, Canadian Ctr Hlth & Safety Agr, Saskatoon, SK S7N 0W8, Canada. [Willson, P. J.; Gawaziuk, J.] Univ Saskatchewan, Toxicol Ctr, Saskatoon, SK S7N 0W8, Canada. [Khozani, T. Talaei] Shiraz Univ Med Sci, Sch Med, Dept Anat, Shiraz, Iran. [Senthilselvan, A.] Univ Alberta, Sch Publ Hlth, Dept Publ Hlth Sci, Edmonton, AB, Canada. [Gerdts, V.; Gawaziuk, J.] Univ Saskatchewan, Vaccine & Infect Dis Org, Saskatoon, SK S7N 0W8, Canada. [Burch, Lauranell H.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Dosman, JA (reprint author), Univ Saskatchewan, Coll Med, Canadian Ctr Hlth & Safety Agr, Saskatoon, SK S7N 0W8, Canada. EM james.dosman@usask.ca OI Gawaziuk, Justin/0000-0002-0987-5909; talaei-khozani, tahereh/0000-0002-8425-8871 FU Canadian Institutes of Health Research [MOP-57907, STP-53906]; National Institutes of Health; U.S. Department of Health and Human Services FX The authors gratefully acknowledge the technical support provided by Natasha Thiessen and Connie Wong for assistance with the immunocytochemistry. This study was supported by a grant from the Canadian Institutes of Health Research (grant MOP-57907) and the intramural research program at the National Institutes of Health, U.S. Department of Health and Human Services. J. Gawaziuk was supported by a graduate training fellowship from "Public Health and the Agricultural Rural Ecosystem (PHARE)" supported by the Canadian Institutes of Health Research (grant STP-53906). NR 25 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2008 VL 71 IS 21 BP 1401 EP 1406 DI 10.1080/15287390802241015 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 349WP UT WOS:000259314300001 PM 18800289 ER PT J AU Greiffenstein, P Molina, PE AF Greiffenstein, Patrick Molina, Patricia E. TI Alcohol-induced alterations on host defense after traumatic injury SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Review DE trauma; hemorrhage; burn; alcohol; injury; inflammation ID ACUTE ETHANOL INTOXICATION; TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; MULTIPLE ORGAN FAILURE; FACTOR-KAPPA-B; INFLAMMATORY RESPONSE SYNDROME; BURN INJURY; THERMAL-INJURY; HEMORRHAGIC-SHOCK; INTRAPULMONARY ENDOTOXIN C1 [Greiffenstein, Patrick; Molina, Patricia E.] Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA. [Greiffenstein, Patrick; Molina, Patricia E.] Louisiana State Univ, Hlth Sci Ctr, NIAAA, Sponsored Alcohol Res Ctr, New Orleans, LA 70112 USA. RP Molina, PE (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, 1901 Perdido St, New Orleans, LA 70112 USA. EM pmolin@lsuhsc.edu FU NIAAA NIH HHS [AA11290]; NIDA NIH HHS [DA020419-01A1]; PHS HHS [NIAAA-07577] NR 128 TC 21 Z9 21 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JAN PY 2008 VL 64 IS 1 BP 230 EP 240 DI 10.1097/TA.0b013e318158a4ad PG 11 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 250UE UT WOS:000252325700050 PM 18188126 ER PT J AU Bratslavsky, G Liu, JJ Johnson, AD Sudarshan, S Choyke, PL Linehan, WM Pinto, PA AF Bratslavsky, Gennady Liu, Jack J. Johnson, Aaron D. Sudarshan, Sunil Choyke, Peter L. Linehan, W. Marston Pinto, Peter A. TI Salvage partial nephrectomy for hereditary renal cancer: Feasibility and outcomes SO JOURNAL OF UROLOGY LA English DT Article DE kidney; nephrectomy; dialysis; Hippel-Lindau disease; complications ID VONHIPPEL-LINDAU DISEASE; NEPHRON SPARING SURGERY; CELL-CARCINOMA; TUMOR SIZE; EXPERIENCE; HEMODIALYSIS; MULTICENTER; FEATURES; KIDNEY AB Purpose: Patients with von Hippel-Lindau disease may require repeat partial nephrectomies to avoid the need for renal replacement therapy. We evaluated outcomes in patients who underwent third or fourth partial nephrectomies on the same kidney, which we call salvage partial nephrectomy. Materials and Methods: We retrospectively reviewed the charts of patients who underwent surgery at the National Cancer Institute from 1999 to 2006. We identified 11 of 13 patients in whom salvage partial nephrectomy was performed. Surgical outcomes were assessed by renal preservation as well as intraoperative and postoperative complications. Functional outcomes were assessed by comparing serum creatinine, 24-hour urine creatinine clearance, and nuclear renal scan before and after salvage partial nephrectomy. Results: All patients were alive and had no radiographic evidence of metastatic disease at a median followup of 25 months (range 3 to 83). Major perioperative complications occurred in 6 of 13 patients (46%) and loss of a renal unit occurred in 3 (23%). None of the patients in whom renal units were preserved required dialysis, although there was an upward trend in serum creatinine and a downward trend in creatinine clearance at postoperative followup (p = 0.07 and 0.08, respectively). Conclusions: Although salvage partial nephrectomy is technically demanding and it has a high complication rate, it allows many patients to avoid dialysis. We believe that this experience can be used as a reference for surgeons and patients when considering the risks and benefits of salvage partial nephrectomy. C1 [Bratslavsky, Gennady; Liu, Jack J.; Johnson, Aaron D.; Sudarshan, Sunil; Choyke, Peter L.; Linehan, W. Marston; Pinto, Peter A.] Natl Canc Inst, Ctr Canc Res, Natl Inst Hlth, Dept Hlth & Human Serv,Urol Oncol Branch & Mol, Bethesda, MD USA. RP Bratslavsky, G (reprint author), Natl Canc Inst, Urol Oncol Branch, Bldg 10 Room 1-5940, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU Intramural NIH HHS NR 20 TC 33 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2008 VL 179 IS 1 BP 67 EP 70 DI 10.1016/j.juro.2007.08.150 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 241IN UT WOS:000251650200016 PM 17997447 ER PT J AU Kapadia, MR Chow, LW Tsihlis, ND Ahanchi, SS Hrabie, JA Murar, J Martinez, J Popowich, DA Jiang, Q Hrabie, JA Saavedra, JE Keefer, LK HUlvat, JF Stupp, SI Kibbe, MP AF Kapadia, Muneera R. Chow, Lesley W. Tsihlis, Nick D. Ahanchi, Sadaf S. Hrabie, Jason W. Murar, Jozef Martinez, Janet Popowich, Daniel A. Jiang, Qun Hrabie, Joseph A. Saavedra, Joseph E. Keefer, Larry K. HUlvat, James F. Stupp, Samuel I. Kibbe, Melina P. TI Nitric oxide and nanotechnology: A novel approach to inhibit neointimal hyperplasia SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Society-for-Vascular-Surgery CY JUN 06-10, 2007 CL Baltimore, MD SP Soc Vasc Surg ID SMOOTH-MUSCLE-CELL; SYNTHASE GENE-TRANSFER; INTIMAL HYPERPLASIA; L-ARGININE; ARTERIAL INJURY; VEIN GRAFTS; GUANOSINE-MONOPHOSPHATE; PERIVASCULAR DELIVERY; VASCULAR INJURY; BALLOON INJURY AB Objective: Nitric oxide (NO) has been shown to inhibit neointimal hyperplasia after arterial interventions in several animal models. To date, however, NO-based therapies have not been used in the clinical arena. Our objective was to combine nanofiber delivery vehicles with NO chemistry to create a novel, more potent NO-releasing therapy that can be used clinically. Thus, the aim of this study was to evaluate the perivascular application of spontaneously self-assembling NO-releasing nanofiber gels. Our hypothesis was that this application would prevent neointimal hyperplasia. Methods. Gels consisted of a peptide amphiphile, heparin, and a diazeniumdiolate NO donor (1-[N-(3-Aminopropy1)-N-(3-ammoniopropyl)]diazen-1-ium-1,2-diolate [DPTA/NO] or disoditim 1-[(2-Carboxylato)pyrrolidin-1-y1]diazen-1-ium-1,2-diolate [PROLI/NO]). Nitric oxide release from the gels was evaluated by the Griess reaction, and scanning electron microscopy confirmed nanofiber formation. Vascular smooth muscle cell (VSMC) proliferation and cell death were assessed in vitro by (3)H-thymidine incorporation and Personal Cell Analysis (PCA) system (Guava Technologies, Hayward, Calif). For the in vivo work, gels were modified by reducing the free-water content. Neointimal hyperplasia after periadventitial gel application was evaluated using the rat carotid artery injury model at 14 days (n = 6 per group). Inflammation and proliferation were examined in vivo with immunofluorescent staining against CD45, ED1, and Ki67 at 3 days (n = 2 per group), and graded by blinded observers. Endothelialization was assessed by Evans blue injection at 7 days (n = 3 per group). Results. Both DPTA/NO and PROLI/NO, combined with the peptide amphiphile and heparin, formed nanofiber gels and released NO for 4 days. In vitro, DPTA/NO inhibited VSMC proliferation and induced cell death to a greater extent than PROLI/NO. However, the DPTA/NO nanofiber gel only reduced neointimal hyperplasia by 45% (intima/media [I/M] area ratio, 0.45 +/- 0.07), whereas the PROLI/NO nanofiber gel reduced neointimal hyperplasia by 77% (I/M area ratio, 0.19 +/- 0.03, P <.05) vs control (injury alone I/M area ratio, 0.83 0.07; P <.05). Both DPTA/NO and PROLI/NO nanoliber gels significantly inhibited proliferation in vivo (1.06 +/- 0.30 and 0.19 +/- 0.11 vs injury alone, 2.02 +/- 0.20, P <.05), yet had minimal effect on apoptosis. Only the PROLI/NO nanofiber gel inhibited inflammation (monocytes and leukocytes). Both NO-releasing nanofiber gels stimulated re-endothelialization. Conclusions. Perivascular application of NO-releasing self-assembling nanofiber gels is an effective and simple therapy to prevent neointimal hyperplasia after arterial injury. Our study demonstrates that the PROLI/NO nanofiber gel most effectively prevented neointimal hyperplasia and resulted in less inflammation than the DPTA/NO nanofiber gel. This therapy has great clinical potential to prevent neointimal hyperplasia after open vascular interventions inpatients. C1 [Kapadia, Muneera R.; Tsihlis, Nick D.; Ahanchi, Sadaf S.; Hrabie, Jason W.; Murar, Jozef; Martinez, Janet; Popowich, Daniel A.; Jiang, Qun; Kibbe, Melina P.] Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA. [Kapadia, Muneera R.; Chow, Lesley W.; Tsihlis, Nick D.; Ahanchi, Sadaf S.; Hrabie, Jason W.; Murar, Jozef; Martinez, Janet; Popowich, Daniel A.; Jiang, Qun; HUlvat, James F.; Stupp, Samuel I.; Kibbe, Melina P.] Northwestern Univ, Inst BioNanotechnol Med, Chicago, IL 60611 USA. [Chow, Lesley W.; Keefer, Larry K.; HUlvat, James F.; Stupp, Samuel I.] Northwestern Univ, Dept Mat Sci & Engn, Chicago, IL 60611 USA. [Hrabie, Joseph A.; Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. [Chow, Lesley W.; Keefer, Larry K.; HUlvat, James F.; Stupp, Samuel I.] Natl Canc Inst, Canc Res Ctr, Comparat Carcinogenesis Lab, Frederick, MD USA. RP Kibbe, MP (reprint author), Northwestern Univ, Div Vasc Surg, 201 E Huron St,Galter 10-105, Chicago, IL 60611 USA. EM mkibbe@ninh.org RI Stupp, Samuel/B-6737-2009; Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Tsihlis, Nick/0000-0002-0410-0143; Eng, Jason/0000-0002-8219-2290 FU Intramural NIH HHS; NCI NIH HHS [N01 CO012400, N01CO12400]; NHLBI NIH HHS [1K08 HL 084203, K08 HL084203, K08 HL084203-02]; NIBIB NIH HHS [R01 EB003806-02, 5R01 EB 003806-02, R01 EB003806] NR 50 TC 73 Z9 74 U1 1 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2008 VL 47 IS 1 BP 173 EP 182 DI 10.1016/j.jvs.2007.09.005 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 248AQ UT WOS:000252124100031 PM 18178471 ER PT J AU Dasgupta, A Jung, KJ Jeong, SJ Brady, JN AF Dasgupta, Arindam Jung, Kyung-Jin Jeong, Soo-Jin Brady, John N. TI Inhibition of methyltransferases results in induction of G(2)/M checkpoint and programmed cell death in human T-lymphotropic virus type 1-transformed cells SO JOURNAL OF VIROLOGY LA English DT Article ID KAPPA-B KINASE; S-ADENOSYLHOMOCYSTEINE HYDROLASE; MOUSE L929 CELLS; ARGININE METHYLATION; TAX PROTEIN; GENE-EXPRESSION; HTLV-I; TRANSCRIPTIONAL ACTIVITY; FUNCTIONAL IMPAIRMENT; BINDING PROTEINS AB Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia. The HTLV-1-encoded protein Tax transactivates the viral long terminal repeat and plays a critical role in virus replication and transformation. Previous work from our laboratory demonstrated that coactivator-associated arginine methytransferase 1, a protein arginine methytransferase, was important for Tax-mediated transactivation. To further investigate the role of methyltransferases in viral transcription, we utilized adenosine-2,3-dialdehyde (AdOx), an adenosine analog and S-adenosylmethionine-dependent methyltransferase inhibitor. The addition of AdOx decreased Tax transactivation in C81, Hut102, and MT-2 cells. Unexpectedly, we found that AdOx potently inhibited the growth of HTLV-1-transformed cells. Further investigation revealed that AdOx inhibited the Tax-activated NF-kappa B pathway, resulting in reactivation of p53 and induction of p53 target genes. Analysis of the NF-kappa B pathway demonstrated that AdOx treatment resulted in degradation of the I kappa B kinase complex and inhibition of NF-kappa B through stabilization of the NF-kappa B inhibitor I kappa B alpha. Our data further demonstrated that AdOx induced G(2)/M cell cycle arrest and cell death in HTLV-1-transformed but not control lymphocytes. These studies demonstrate that protein methylation plays an important role in NF-kappa B activation and survival of HTLV-1-transformed cells. C1 [Dasgupta, Arindam; Jung, Kyung-Jin; Jeong, Soo-Jin; Brady, John N.] Ctr Canc Res, NIH, Cellular Oncol Lab, Virus Tumor Biol Sect, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), Ctr Canc Res, NIH, Cellular Oncol Lab, Virus Tumor Biol Sect, 41 Medlars Dr,Bldg 41, Bethesda, MD 20892 USA. EM bradyj@mail.nih.gov FU Intramural NIH HHS NR 53 TC 11 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 1 BP 49 EP 59 DI 10.1128/JVI.01497-07 PG 11 WC Virology SC Virology GA 244AO UT WOS:000251838600004 PM 17942556 ER PT J AU DeGottardi, MQ Lew, SK Piatak, M Jia, B Feng, Y Lee, SJ Brenchley, JM Douek, DC Kodama, T Lifson, JD Evans, DT AF DeGottardi, M. Quinn Lew, Sharon K. Piatak, Michael, Jr. Jia, Bin Feng, Yang Lee, Sandra J. Brenchley, Jason M. Douek, Daniel C. Kodama, Toshiaki Lifson, Jeffrey D. Evans, David T. TI Comparison of plasma viremia and antibody responses in Macaques inoculated with envelope variants of single-cycle simian immunodeficiency virus differing in infectivity and cellular tropism SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; MACROPHAGE TROPISM; LATENT RESERVOIR; RHESUS MACAQUES; CHEMOKINE RECEPTORS; TYPE-1 INFECTION; IN-VITRO; HIV-1; REPLICATION AB Molecular differences in the envelope glycoproteins of human immunodeficiency virus type I and simian immunodeficiency virus (SIV) determine virus infectivity and cellular tropism. To examine how these properties contribute to productive infection in vivo, rhesus macaques were inoculated with strains of single-cycle SIN (scSfV) engineered to express three different envelope glycoproteins with full-length (TMopen.) or truncated (TMstop) cytoplasmic tails. The 239 envelope uses CCR5 for infection of memory CD4(+) T cells, the 316 envelope also uses CCR5 but has enhanced infectivity for primary macrophages, and the 155T3 envelope uses CXCR4 for infection of both naive and memory CD4(+) T cells. Separate groups of six rhesus macaques were inoculated intravenously with mixtures of TMopen and TMstop scSIV(mac) 239, scSIV(mac) 316, and scSIV(mac) 155T3. A multiplex real-time PCR assay specific for unique sequence tags engineered into each virus was then used to measure viral loads for each strain independently. Viral loads in plasma peaked on day 4 for each strain and were resolved below the threshold. of detection within 4 to 10 weeks. Truncation of the envelope cytoplasmic tail significantly increased the peak of viremia for all three envelope variants and the titer of SIV-specific antibody responses. Although peak viremias were similar for both R5- and X4-tropic viruses, clearance of scSIV(mac) 155T3 TMstop was significantly delayed relative to the other strains, possibly reflecting the infection of a CXCR4(+) cell population that is less susceptible to the cytopathic effects of virus infection. These studies reveal differences in the peaks and durations of a single round of productive infection that reflect envelope-specific differences in infectivity, chemokine receptor specificity, and cellular tropism. C1 [DeGottardi, M. Quinn; Lew, Sharon K.; Jia, Bin; Evans, David T.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] Natl Canc Inst, SAIC Frederick, AIDS Vaccine Program, Ft Detrick, MD 21702 USA. [Feng, Yang; Lee, Sandra J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brenchley, Jason M.; Douek, Daniel C.] NIH, NIAID, Vaccine Res Ctr, Human Immunol Sect, Bethesda, MD 20892 USA. [Kodama, Toshiaki] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15238 USA. RP Evans, DT (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM devans@hms.harvard.edu FU NIAID NIH HHS [AI63993, AI52751, K22 AI052751, R01 AI063993] NR 56 TC 6 Z9 6 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 1 BP 321 EP 334 DI 10.1128/JVI.01094-07 PG 14 WC Virology SC Virology GA 244AO UT WOS:000251838600030 PM 17942538 ER PT J AU Robertson, SJ Ammann, CG Messer, RJ Carmody, AB Myers, L Dittmer, U Nair, S Gerlach, N Evans, LH Cafruny, WA Hasenkrug, KJ AF Robertson, Shelly J. Ammann, Christoph G. Messer, Ronald J. Carmody, Aaron B. Myers, Lara Dittmer, Ulf Nair, Savita Gerlach, Nicole Evans, Leonard H. Cafruny, William A. Hasenkrug, Kim J. TI Suppression of acute anti-friend virus CD8(+) T-cell responses by coinfection with lactate dehydrogenase-elevating virus SO JOURNAL OF VIROLOGY LA English DT Article ID FOCUS-FORMING VIRUS; ACUTE RESPIRATORY SYNDROME; MURINE LEUKEMIA-VIRUS; RETROVIRUS-INDUCED IMMUNOSUPPRESSION; INFECTED MICE; MONOCLONAL-ANTIBODIES; IN-VIVO; INDUCED ERYTHROLEUKEMIA; MOLECULAR-CLONING; IMMUNE-RESPONSES AB Friend virus (FV) and lactate dehydrogenase-elevating virus (LDV) are endemic mouse viruses that can cause long-term chronic infections in mice. We found that numerous mouse-passaged FV isolates also contained LDV and that coinfection with LDV delayed FV-specific CD8(+) T-cell responses during acute infection. While LDV did not alter the type of acute pathology induced by FV, which was severe splenomegaly caused by erythroproliferation, the immunosuppression mediated by LDV increased both the severity and the duration of FV infection. Compared to mice infected with FV alone, those coinfected with both FV and LDV had delayed CD8(+) T-cell responses, as measured by FV-specific tetramers. This delayed response accounted for the prolonged and exacerbated acute phase of FV infection. Suppression of FV-specific CD8(+) T-cell responses occurred not only in mice infected concomitantly with LDV but also in mice chronically infected with LDV 8 weeks prior to infection with FV. The LDV-induced suppression was not mediated by T regulatory cells, and no inhibition of the CD4(+) T-cell or antibody responses was observed. Considering that most human adults are carriers of chronically infectious viruses at the time of new virus insults and that coinfections with viruses such as human immunodeficiency virus and hepatitis C virus are currently epidemic, it is of great interest to determine how infection with one virus may impact host responses to a second infection. Coinfection of mice with LDV and FV provides a well-defined, natural host model for such studies. C1 [Robertson, Shelly J.; Ammann, Christoph G.; Messer, Ronald J.; Carmody, Aaron B.; Myers, Lara; Evans, Leonard H.; Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. [Dittmer, Ulf; Nair, Savita; Gerlach, Nicole] Univ Duisburg Essen, Inst Virol, D-45122 Essen, Germany. [Cafruny, William A.] Univ S Dakota, Stanford Sch Med, Vermillion, SD 57069 USA. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov OI Ammann, Christoph/0000-0002-6267-1286 FU Intramural NIH HHS NR 66 TC 49 Z9 49 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 1 BP 408 EP 418 DI 10.1128/JVI.01413-07 PG 11 WC Virology SC Virology GA 244AO UT WOS:000251838600037 PM 17959678 ER PT J AU Jelacic, TM Thompson, D Hanson, C Cmarik, JL Nishigaki, K Ruscetti, S AF Jelacic, Tanya M. Thompson, Delores Hanson, Charlotte Cmarik, Joan L. Nishigaki, Kazuo Ruscetti, Sandra TI The tyrosine kinase sf-Stk and its downstream signals are required for maintenance of friend spleen focus-forming virus-induced fibroblast transformation SO JOURNAL OF VIROLOGY LA English DT Article ID N-TERMINAL KINASE; TRUNCATED FORM; PROTEIN-KINASE; CONSTITUTIVE ACTIVATION; ERYTHROPOIETIN RECEPTOR; ERYTHROLEUKEMIA-CELLS; ENVELOPE GLYCOPROTEIN; PUTATIVE ONCOGENE; MOLECULAR-CLONING; DNA-BINDING AB Infection of erythroid progenitor cells by Friend spleen focus-forming virus (SFFV) leads to acute erythroid hyperplasia and eventually to erythroleukemia in susceptible strains of mice. The viral envelope protein, SFFV gp55, forms a complex with the erythropoietin receptor (EpoR) and a short form of the receptor tyrosine kinase Stk (sf-Stk), activating both and inducing Epo-independent proliferation. Recently, we discovered that coexpression of SFFV gp55 and sf-Stk is sufficient to transform NIH 3T3 and primary fibroblasts. In the current study, we demonstrate that sf-Stk and its downstream effectors are critical to this transformation. Unlike SFFV-derived erythroleukemia cells, which depend on PU.1 expression for maintenance of the transformed phenotype, SFFV gp55-sf-Stk-transformed fibroblasts are negative for PU.1. Underscoring the importance of sf-Stk to fibroblast transformation, knockdown of sf-Stk abolished the ability of these cells to form anchorage-independent colonies. Like SFFV-infected erythroid cells, SFFV gp55-sf-Stk-transformed fibroblasts express high levels of phosphorylated MEK, ERK, phosphatidylinositol 3-kinase (PI3K), Gab1/2, Akt, Jun kinase (JNK), and STAT3, but unlike virus-infected erythroid cells they fail to express phosphorylated STATs 1 and 5, which may require involvement of the EpoR. In addition, the p38 mitogen-activated protein kinase (MAPK) stress response is suppressed in the transformed fibroblasts. Inhibition of either JNK or the PI3K pathway decreases both monolayer proliferation and anchorage-independent growth of the transformed fibroblasts as does the putative kinase inhibitor luteolin, but inhibition of p38 MAPK has no effect. Our results indicate that sf-Stk is a molecular endpoint of transformation that could be targeted directly or with agents against its downstream effectors. C1 [Jelacic, Tanya M.; Thompson, Delores; Hanson, Charlotte; Cmarik, Joan L.; Nishigaki, Kazuo; Ruscetti, Sandra] Natl Canc Inst, Lab Canc Prevent, Ft Detrick, MD 21702 USA. RP Ruscetti, S (reprint author), Natl Canc Inst, Lab Canc Prevent, Bldg 469,Rm 205, Ft Detrick, MD 21702 USA. EM ruscetti@ncifcrf.gov FU Intramural NIH HHS NR 35 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 1 BP 419 EP 427 DI 10.1128/JVI.01349-07 PG 9 WC Virology SC Virology GA 244AO UT WOS:000251838600038 PM 17959667 ER PT J AU Oh, J Chang, KW Wierzchoslawski, R Alvord, WG Hughes, SH AF Oh, Jangsuk Chang, Kevin W. Wierzchoslawski, Rafal Alvord, W. Gregory Hughes, Stephen H. TI Rous sarcoma virus (RSV) integration in vivo: a CA dinucleotide is not required in U3, and RSV linear DNA does not autointegrate SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RNASE-H CLEAVAGE; TYPE-1 INTEGRASE; PRODUCTIVE INFECTION; RETROVIRAL DNA; CELL-LINE; SEQUENCE; PROTEIN; REPLICATION; MUTATIONS AB The sequences required for integration of retroviral DNA have been analyzed in vitro. However, the in vitro experiments do not agree on which sequences are required for integration: for example, whether or not the conserved CA dinucleotide in the 3' end of the viral DNA is required for normal integration. At least a portion of the problem is due to differences in the experimental conditions used in the in vitro assays. To avoid the issue of what experimental conditions to use, we took an in vivo approach. We made mutations in the 5' end of the U3 sequence of the Rous sarcoma virus (RSV)-derived vector RSVP(A)Z. We present evidence that, in RSV, the CA dinucleotide in the 5' end of U3 is not essential for appropriate integration. This result differs from the results seen with mutations in the U5 end, where the CA appears to be essential for proper integration in vivo. In addition, based on the structure of circular viral DNAs smaller than the full-length viral genome, our results suggest that there is little, if any, integrase-mediated autointegration of RSV linear DNA in vivo. C1 [Oh, Jangsuk; Chang, Kevin W.; Wierzchoslawski, Rafal; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Alvord, W. Gregory] Natl Canc Inst, Data Management Serv, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, PO Box B, Bldg 539, Rm 130A, Frederick, MD 21702 USA. EM Hughes@ncifcrf.gov FU Intramural NIH HHS NR 33 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 1 BP 503 EP 512 DI 10.1128/JVI.01441-07 PG 10 WC Virology SC Virology GA 244AO UT WOS:000251838600046 PM 17959663 ER PT J AU Bao, YM Bolotov, P Dernovoy, D Kiryutin, B Zaslavsky, L Tatusova, T Ostell, J Lipman, D AF Bao, Yiming Bolotov, Pavel Dernovoy, Dmitry Kiryutin, Boris Zaslavsky, Leonid Tatusova, Tatiana Ostell, Jim Lipman, David TI The influenza virus resource at the national center for biotechnology information SO JOURNAL OF VIROLOGY LA English DT Editorial Material ID EVOLUTION C1 [Bao, Yiming; Bolotov, Pavel; Dernovoy, Dmitry; Kiryutin, Boris; Zaslavsky, Leonid; Tatusova, Tatiana; Ostell, Jim; Lipman, David] Natl Lib Med, NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Bao, YM (reprint author), Natl Lib Med, NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM bao@ncbi.nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 17 TC 525 Z9 545 U1 2 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 2 BP 596 EP 601 DI 10.1128/JVI.02005-07 PG 6 WC Virology SC Virology GA 249LF UT WOS:000252229100001 PM 17942553 ER PT J AU Davies, DH Wyatt, LS Newman, FK Earl, PL Chun, S Hernandez, JE Molina, DM Hirst, S Moss, B Frey, SE Felgner, PL AF Davies, D. Huw Wyatt, Linda S. Newman, Frances K. Earl, Patricia L. Chun, Sookhee Hernandez, Jenny E. Molina, Douglas M. Hirst, Siddiqua Moss, Bernard Frey, Sharon E. Felgner, Philip L. TI Antibody profiling by proteome microarray reveals the immunogenicity of the attenuated smallpox vaccine modified vaccinia virus Ankara is comparable to that of Dryvax SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODY; COMPARATIVE EFFICACY; RECOMBINANT VECTOR; MATURE VIRION; PROTECTS MICE; MVA STRAIN; HOST-RANGE; CHALLENGE; IDENTIFICATION; SAFETY AB Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that is under consideration as an alternative to the conventional smallpox vaccine Dryvax. MVA was attenuated by extensive passage of vaccinia virus Ankara in chicken embryo fibroblasts. Several immunomodulatory genes and genes that influence host range are deleted or mutated, and replication is aborted in the late stage of infection in most nonavian cells. The effect of these mutations on immunogenicity is not well understood. Since the structural genes appear to be intact in MVA, it is hypothesized that critical targets for antibody neutralization have been retained. To test this, we probed microarrays of the Western Reserve (WR) proteome with sera from humans and macaques after MVA and Dryvax vaccination. As most protein sequences of MVA are 97 to 99% identical to those of other vaccinia virus strains, extensive binding cross-reactivity is expected, except for those deleted or truncated. Despite different hosts and immunization regimens, the MVA and Dryvax antibody profiles were broadly similar, with antibodies against membrane and core proteins being the best conserved. The responses to nonstructural proteins were less well conserved, although these are not expected to influence virus neutralization. The broadest antibody response was obtained for hyperimmune rabbits with WR, which is pathogenic in rabbits. These data indicate that, despite the mutations and deletions in MVA, its overall immunogenicity is broadly comparable to that of Dryvax, particularly at the level of antibodies to membrane proteins. The work supports other information suggesting that MVA may be a useful alternative to Dryvax. C1 [Davies, D. Huw; Chun, Sookhee; Hernandez, Jenny E.; Hirst, Siddiqua; Felgner, Philip L.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92697 USA. [Wyatt, Linda S.; Earl, Patricia L.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Newman, Frances K.; Frey, Sharon E.] St Louis Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. [Molina, Douglas M.] ImmPORT Therapeut Inc, Irvine, CA 92618 USA. RP Davies, DH (reprint author), Univ Calif Irvine, Dept Med, Div Infect Dis, 3501 Hewitt Hall, Irvine, CA 92697 USA. EM ddavies@uci.edu FU Intramural NIH HHS; NIAID NIH HHS [N01-AI-25464, 1U01AI061363, N01AI25464, R41 AI058365, HHSN266200400036C, AI058365, R44 AI058365, U01 AI056464, U01 AI061363, U01AI056464] NR 39 TC 76 Z9 80 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 2 BP 652 EP 663 DI 10.1128/JVI.01706-07 PG 12 WC Virology SC Virology GA 249LF UT WOS:000252229100007 PM 17977963 ER PT J AU Oh, J McWilliams, MJ Julias, JG Hughes, SH AF Oh, Jangsuk McWilliams, Mary Jane Julias, John G. Hughes, Stephen H. TI Mutations in the U5 region adjacent to the primer binding site affect tRNA cleavage by human immunodeficiency virus type 1 reverse transcriptase in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID STRAND DNA-SYNTHESIS; RIBONUCLEASE-H; POLYPURINE TRACT; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; CIRCLE JUNCTION; HIV-1 RT; SEQUENCE; INTEGRATION; REPLICATION AB In retroviruses, the first nucleotide added to the tRNA primer defines the end of the U5 region in the right long terminal repeat, and the subsequent removal of this tRNA primer by RNase H exactly defines the U5 end of the linear double-stranded DNA. In most retroviruses, the entire tRNA is removed by RNase H cleavage at the RNA/DNA junction. However, the RNase H domain of human immunodeficiency virus type I (HIV-1) reverse transcriptase cleaves the tRNA I nucleotide from the RNA/DNA junction at the U5/primer binding site (PBS) junction, which leaves an rA residue at the U5 terminus. We made sequence changes at the end of the U5 region adjacent to the PBS in HIV-1 to determine whether such changes affect the specificity of tRNA primer cleavage by RNase H. In some of the mutants, RNase H usually removed the entire tRNA, showing that the cleavage specificity was shifted by 1 nucleotide. This result suggests that the tRNA cleavage specificity of the HIV-1 RNase domain H depends on sequences in U5. C1 [Oh, Jangsuk; McWilliams, Mary Jane; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Julias, John G.] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Rm 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov FU Intramural NIH HHS NR 37 TC 11 Z9 11 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 2 BP 719 EP 727 DI 10.1128/JVI.02611-06 PG 9 WC Virology SC Virology GA 249LF UT WOS:000252229100014 PM 17989171 ER PT J AU Giraldo-Vela, JP Rudersdorf, R Chung, CW Qi, Y Wallace, LT Bimber, B Borchardt, GJ Fisk, DL Glidden, CE Loffredo, JT Piaskowski, SM Furlott, JR Morales-Martinez, JP Wilson, NA Rehrauer, WM Lifson, JD Carrington, M Watkins, DI AF Giraldo-Vela, Juan P. Rudersdorf, Richard Chung, Chungwon Qi, Ying Wallace, Lyle T. Bimber, Benjamin Borchardt, Gretta J. Fisk, Debra L. Glidden, Chrystal E. Loffredo, John T. Piaskowski, Shari M. Furlott, Jessica R. Morales-Martinez, Juan P. Wilson, Nancy A. Rehrauer, William M. Lifson, Jeffrey D. Carrington, Mary Watkins, David I. TI The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infecte rhesus macaque elite controllers SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; GASTROINTESTINAL-TRACT; SIV INFECTION; LYMPHOCYTE RESPONSES; DISEASE PROGRESSION; EPITOPE HOTSPOTS; HIV-1 INFECTION; HELPER-CELLS; IN-VIVO; REPLICATION AB The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4' T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-11 allelles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of < 0.0001). The study of MHC-II allelles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design. C1 [Giraldo-Vela, Juan P.; Piaskowski, Shari M.; Rehrauer, William M.; Watkins, David I.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53711 USA. [Rudersdorf, Richard; Chung, Chungwon; Wallace, Lyle T.; Bimber, Benjamin; Borchardt, Gretta J.; Fisk, Debra L.; Glidden, Chrystal E.; Loffredo, John T.; Furlott, Jessica R.; Morales-Martinez, Juan P.; Wilson, Nancy A.; Watkins, David I.] NCI, SAIC Frederick Inc, Lab Geonom Divers, Frederick, MD 21702 USA. [Qi, Ying; Carrington, Mary] NCI, SAIC Frederick Inc, AIDS Vaccine Program, Basic Res Program, Frederick, MD 21702 USA. RP Watkins, DI (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, 555 Sci Dr, Madison, WI 53711 USA. EM watkins@primate.wisc.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [R24-RR015371, C06 RR015459, P51-RR000167, R24 RR015371, R24-RR016038, C06 RR020141, P51 RR000167, R24 RR016038, RR020141-01, RR15459-01]; NIAID NIH HHS [R01-AI049120, R01-AI052056, R01 AI049120, R01 AI052056] NR 60 TC 53 Z9 55 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 2 BP 859 EP 870 DI 10.1128/JVI.01816-07 PG 12 WC Virology SC Virology GA 249LF UT WOS:000252229100027 PM 17989178 ER PT J AU Duffy, S Holmes, EC AF Duffy, Siobain Holmes, Edward C. TI Phylogenetic evidence for rapid rates of molecular evolution in the single-stranded DNA begomovirus Tomato yellow leaf curl virus SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; STREAK-MOSAIC-VIRUS; RNA VIRUSES; SPONTANEOUS MUTATION; INFECTIOUS CLONE; CHINA-VIRUS; INTERSPECIFIC-RECOMBINATION; NATURAL RECOMBINATION; GENOME ORGANIZATION; MEDITERRANEAN BASIN AB Geminiviruses are devastating viruses of plants that possess single-stranded DNA (ssDNA) DNA genomes. Despite the importance of this class of phytopathogen, there have been no estimates of the rate of nucleotide substitution in the geminiviruses. We report here the evolutionary rate of the tomato yellow leaf curl disease-causing viruses, an intensively studied group of monopartite begomoviruses. Sequences from GenBank, isolated from diseased plants between 1988 and 2006, were analyzed using Bayesian coalescent methods. The mean genomic substitution rate was estimated to be 2.88 X 10(-4) nucleotide substitutions per site per year (subs/site/year), although this rate could be confounded by frequent recombination within Tomato yellow leaf curl virus genomes. A recombinant-free data set comprising the coat protein (V1) gene in isolation yielded a similar mean rate (4.63 X 10(-4) subs/site/year), validating the order of magnitude of genomic substitution rate for protein-coding regions. The intergenic region, which is known to be more variable, was found to evolve even more rapidly, with a mean substitution rate of similar to 1.56 X 10(-3) subs/site/year. Notably, these substitution rates, the first reported for a plant DNA virus, are in line with those estimated previously for mammalian ssDNA viruses and RNA viruses. Our results therefore suggest that the high evolutionary rate of the geminiviruses is not primarily due to frequent recombination and may explain their ability to emerge in novel hosts. C1 [Duffy, Siobain; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Duffy, S (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, Univ Park, University Pk, PA 16802 USA. EM smdl6@psu.edu RI Duffy, Siobain/A-9104-2009; OI Duffy, Siobain/0000-0003-0753-223X; Holmes, Edward/0000-0001-9596-3552 NR 95 TC 122 Z9 128 U1 2 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 2 BP 957 EP 965 DI 10.1128/JVI.01929-07 PG 9 WC Virology SC Virology GA 249LF UT WOS:000252229100036 PM 17977971 ER PT J AU Meunier, JC Russell, RS Goossens, V Priem, S Walter, H Depla, E Union, A Faulk, KN Bukh, J Emerson, SU Purcell, RH AF Meunier, Jean-Christophe Russell, Rodney S. Goossens, Vera Priem, Sofie Walter, Hugo Depla, Erik Union, Ann Faulk, Kristina N. Bukh, Jens Emerson, Suzanne U. Purcell, Robert H. TI Isolation and characterization of broadly neutralizing human monoclonal antibodies to the E1 glycoprotein of hepatitis C virus SO JOURNAL OF VIROLOGY LA English DT Article ID HYPERVARIABLE REGION 1; SINGLE-SOURCE OUTBREAK; IN-VITRO; HYPERIMMUNE SERUM; IMMUNE-RESPONSES; CELL ENTRY; INFECTION; PROTEIN; ENVELOPE; SEQUENCE AB The relative importance of Immoral and cellular immunity in the prevention or clearance of hepatitis C virus (HCV) infection is poorly understood. However, there is considerable evidence that neutralizing antibodies are involved in disease control. Here we describe the detailed analysis of human monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes la, 1b, 4a, 5a, and 6a and less strongly neutralize HCVpp bearing the envelope glycoproteins of genotype 2a. Genotype 3a was not neutralized. The epitopes for both MAbs were mapped to the region encompassing amino acids 313 to 327. In addition, robust neutralization was also observed against cell culture-adapted viruses of genotypes 1a and 2a. Results from this study suggest that these MAbs may have the potential to prevent HCV infection. C1 [Meunier, Jean-Christophe; Russell, Rodney S.; Faulk, Kristina N.; Bukh, Jens; Emerson, Suzanne U.; Purcell, Robert H.] NIAID, NIH, Infect Dis Lab, Hepatitis Viruses & Mol Hepatitis Sect,LID, Bethesda, MD 20892 USA. [Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. [Goossens, Vera; Priem, Sofie; Walter, Hugo; Depla, Erik; Union, Ann] GENimmune, Ghent, Belgium. [Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. RP Emerson, SU (reprint author), NIAID, NIH, Infect Dis Lab, Hepatitis Viruses & Mol Hepatitis Sect,LID, Bldg 50 Rm 6537,50 South Dr,MSC 8009, Bethesda, MD 20892 USA. EM semerson@niaid.nih.gov FU Intramural NIH HHS NR 42 TC 87 Z9 93 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2008 VL 82 IS 2 BP 966 EP 973 DI 10.1128/JVI.01872-07 PG 8 WC Virology SC Virology GA 249LF UT WOS:000252229100037 PM 17977972 ER PT J AU Wisely, SM Howard, J Williams, SA Bain, O Santymire, RM Bardsley, KD Williams, ES AF Wisely, Samantha M. Howard, JoGayle Williams, Steven A. Bain, Odile Santymire, Rachel M. Bardsley, Katherine D. Williams, Elizabeth S. TI An unidentified filarial species and its impact on fitness in wild populations of the black-footed ferret (Mustela nigripes) SO JOURNAL OF WILDLIFE DISEASES LA English DT Article DE black-footed ferret; cross-reactivity; Dirofilaria immitis; heartworm antigen; microfilaria; molecular characterization; Mustela nigripes; seroprevalence ID HEARTWORM DIROFILARIA-IMMITIS; SP-N; DISEASES; RACCOON; ONCHOCERCIDAE; SQUIRREL; COYOTES; HEALTH; ISLAND AB Disease can threaten the restoration of endangered species directly by substantially decreasing host survival or indirectly via incremental decreases in survival and reproduction. During a biomedical survey of reintroduced populations of the highly endangered black-footed ferret from 2002 to 2005, microfilariae discovered in the blood were putatively identified as Dirofilaria immitis, and widespread screening was initiated using a commercially available antigen-based ELISA test. A subset of animals (n = 16) was screened for D. immitis using a highly sensitive PCR-based assay. Microfilariae were also molecularly and morphologically characterized. Of 198 animals at six reintroduction sites, 12% bad positive results using the ELISA test. No antigen-positive animals which were screened via PCR (n=11) had positive PCR results, and all antigen-positive animals (n=24) were asymptomatic. No significant differences were found in body mass of antigen-positive (male: 1223 +/- 82 g [mean +/- SD], female: 726 +/- 75 g) vs. antigen-negative (male: 1,198 +/- 19 g, female: 710 +/- 53 g) individuals (P=0.4). Antigen prevalence was lower in juveniles (3%) than adults (12%; P=0.03), and higher in in situ, captive-reared individuals (33%) than wild-born individuals (10%; P=0.005). Morphologic analysis of microfilariae revealed they were neither D. immitis nor any other previously characterized North American species. PC R amplification of die 5S spacer region of rDNA revealed that the filarial sequence shared only 76% identity with D. immitis. This previously unidentified filarial sequence was present in all antigen positive animals (11 of 11 tested). It appears that black-footed ferrets were infected with a previously undescribed species of filaria whose antigen cross-reacted with the ELISA assay, although further analysis is needed to make a conclusive statement. Nonetheless, this previously undescribed filaria does not appear to threaten recovery for this highly endangered mammal. C1 [Wisely, Samantha M.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. [Howard, JoGayle; Santymire, Rachel M.] Smithsonian Inst, Natl Zool Pk, Dept Reprod Sci, Washington, DC 20008 USA. [Williams, Steven A.] Smith Coll, NIH, NIAID, Filarial Res Resource Repository Ctr,Clark Sci Ct, Northampton, MA 01063 USA. [Williams, Steven A.] Smith Coll, Clark Sci Ctr, Dept Biol Sci, Northampton, MA 01063 USA. [Bain, Odile] Museum Natl Hist Nat, USM Parasitol Comparee & Modeles Expt 307, F-75231 Paris, France. [Santymire, Rachel M.] Davee Ctr Epidemiol & Endocrinol, Chicago, IL 60614 USA. [Bardsley, Katherine D.; Williams, Elizabeth S.] Univ Wyoming, Wyoming State Vet Lab, Laramie, WY 82071 USA. RP Wisely, SM (reprint author), Kansas State Univ, Div Biol, Ackert Hall, Manhattan, KS 66506 USA. EM wisely@ksu.edu NR 41 TC 7 Z9 7 U1 0 U2 14 PU WILDLIFE DISEASE ASSOC, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD JAN PY 2008 VL 44 IS 1 BP 53 EP 64 PG 12 WC Veterinary Sciences SC Veterinary Sciences GA 262VW UT WOS:000253177100006 PM 18263821 ER PT J AU Attipoe, S Park, JY Fenty, N Phares, D Brown, M AF Attipoe, Selasi Park, Joon-Young Fenty, Nicola Phares, Dana Brown, Michael TI Oxidative stress levels are reduced in postmenopausal women with exercise training regardless of hormone replacement therapy status SO JOURNAL OF WOMEN & AGING LA English DT Article DE oxidative stress; postmenopause; hormone replacement therapy; exercise ID ESTROGEN REPLACEMENT; HEART-DISEASE; MEN; PROGRAM; TRIAL AB This study investigated whether postmenopausal women on HRT Would experience a greater reduction in oxidative stress after 24 weeks of aerobic exercise training compared to postmenopausal women not on HRT. Plasma thiobarbituric acid reactive substances (TBARS), an indicator of oxidative stress, was measured. in 48 previously sedentary postmenopausal women on HRT (n = 21) and not on HRT (n = 27) before and after 24 weeks of aerobic exercise training. Baseline levels of TBARS differed significantly between groups after controlling for age, BMI, and fasting blood glucose (P = 0.03). There was a significant reduction in TBARS after 24 weeks of training in the overall group. When analyzed separately, both postmenopausal women on HRT and those not on HRT had a significant reduction in TBARS; however, there wash no significant difference between groups (-0.71 +/- 0.14 nmol/ml in nonHRT users vs. -0.50 +/- 0.16 nmol/ml in HRT users; P = 0.33) even after controlling for age, BMI, and baseline levels of TBARS. Our results showed that aerobic exercise training significantly decreased oxidative stress in postmenopausal women; however, both HRT users and non-HRT users benefited equally. C1 [Attipoe, Selasi; Fenty, Nicola] Univ Maryland, Dept Kinesiol, Coll Hlth & Human Performance, College Pk, MD 20742 USA. [Park, Joon-Young] NHLBI, NIH, Div Intramural Res, Cardiol Branch, Bethesda, MD 20892 USA. [Phares, Dana] Human Performance Syst Inc, Beltsville, MD USA. [Brown, Michael] Temple Univ, Dept Kinesiol, Coll Hlth Profess, Philadelphia, PA 19122 USA. RP Attipoe, S (reprint author), Univ Maryland, Dept Kinesiol, Coll Hlth & Human Performance, College Pk, MD 20742 USA. EM sattipoe@umd.edu; parkjy@nhibl.nih.gov; nfenty@umd.edu; daphares@humanperfsys.com; brownmd@temple.edu RI Attipoe, Selasi/G-1938-2015 OI Attipoe, Selasi/0000-0001-9212-8412 NR 27 TC 10 Z9 10 U1 0 U2 6 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0895-2841 J9 J WOMEN AGING JI J. Women Aging PY 2008 VL 20 IS 1-2 BP 31 EP 45 DI 10.1300/J074v20n01_04 PG 15 WC Gerontology; Women's Studies SC Geriatrics & Gerontology; Women's Studies GA 277JF UT WOS:000254207800004 PM 18581699 ER PT J AU Sheaffer, AT Lange, E Bondy, CA AF Sheaffer, Alexis T. Lange, Eileen Bondy, Carolyn A. TI Sexual function in women with turner syndrome SO JOURNAL OF WOMENS HEALTH LA English DT Article ID PREMATURE OVARIAN FAILURE; COGNITIVE FUNCTION; YOUNG-WOMEN; SELF-ESTEEM; ADULT WOMEN; CHROMOSOME; TRANSITION; HORMONES; SHYNESS; ANXIETY AB Background: Turner syndrome (TS) (45,X) is associated with premature ovarian failure, usually occurring during childhood. Estrogen treatment is required for the development of secondary sexual characteristics and to maintain feminization. The present study aimed to determine the level of sexual activity in adult women with TS participating as volunteers in the NIH natural history study. Methods: The Derogatis Interview for Sexual Functioning was administered to 98 women, average age 37 +/- 10 years (range 18-59) with karyotype-proven TS. Results were compared to gender-based norms, expressed as standardized area T-scores. Results: The average total score was 32 +/- 12, approximately at the 10th centile, based on nonpatient community respondents. The survey included independent sections on fantasy, arousal, experience, orgasm, and relationship. Scores on sexual fantasy were in the normal range and were significantly greater than scores on all the other sections (p < 0.001). Approximately 30% of the study group were involved in a partner relationship, and this group scored within the average range on all sections. We examined factors that might influence sexual function, including age; parental origin of the single normal X chromosome; physical stigmata, such as neck webbing; estrogen use; testosterone levels; age of puberty; and hearing loss, but none of these appeared to contribute. Of all factors investigated, only height and years of education were positively correlated with partnership status and sexual function. In summary, women with TS in a partner relationship report relatively normal overall sexual function, but the majority of unpartnered women reported very low level sexual functioning. Conclusions: Further study is needed to elucidate the nature of psychosocial impediments affecting establishment of partner relations and sexual functioning in women with TS. C1 [Sheaffer, Alexis T.; Lange, Eileen; Bondy, Carolyn A.] NIH, CRC 1 3330, NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NIH, CRC 1 3330, NICHHD, Dev Endocrinol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS NR 30 TC 12 Z9 12 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JAN-FEB PY 2008 VL 17 IS 1 BP 27 EP 33 DI 10.1089/jwh.2007.0488 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 268JE UT WOS:000253575300004 PM 18240979 ER PT J AU Braitstein, P Boulle, A Nash, D Brinkhof, MWG Dabis, F Laurent, C Schechter, M Tuboi, SH Sprinz, E Miotti, P Hosseinipour, M May, M Egger, M Bangsberg, DR Low, N AF Braitstein, Paula Boulle, Andrew Nash, Denis Brinkhof, Martin W. G. Dabis, Francois Laurent, Christian Schechter, Mauro Tuboi, Suely H. Sprinz, Eduardo Miotti, Paolo Hosseinipour, Mina May, Margaret Egger, Matthias Bangsberg, David R. Low, Nicola CA Antiretroviral Therapy Lower Grp TI Gender and the use of antiretroviral treatment in resource-constrained settings: Findings from a multicenter collaboration SO JOURNAL OF WOMENS HEALTH LA English DT Article ID REPRODUCTIVE HEALTH; INCOME COUNTRIES; PUBLIC-HEALTH; HIV; THERAPY; ANEMIA; WOMEN; MORTALITY; CONTEXT; ISSUES AB Aims: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. Methods: The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. Results: Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. Conclusions: Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART. C1 [Brinkhof, Martin W. G.; Low, Nicola] Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland. [Braitstein, Paula] Indiana Univ, Dept Med, Indianapolis, IN 46204 USA. [Braitstein, Paula] Moi Univ, Sch Med, Eldoret, Kenya. [Boulle, Andrew] Univ Cape Town, Sch Publ Hlth & Family Med, ZA-7925 Cape Town, South Africa. [Nash, Denis] Columbia Univ, Int Ctr AIDS Care & Treatment Programs, New York, NY USA. [Dabis, Francois] Univ Victor Segalen Bordeaux, Inst Sante Publ Epidemiol & Dev, INSERM U593, Bordeaux, France. [Laurent, Christian] Inst Rech Pour Dev, UMR 145, Montpellier, France. [Schechter, Mauro] Univ Fed Rio de Janeiro, Hosp Univ Clemintino Fraga Filho, Rio De Janeiro, Brazil. [Tuboi, Suely H.] Univ Fed Rio Grande do Sul, Hosp Escola S Francisco Assis, Rio De Janeiro, Brazil. [Sprinz, Eduardo] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, BR-90046900 Porto Alegre, RS, Brazil. [Miotti, Paolo] NIH, Bethesda, MD 20892 USA. [Hosseinipour, Mina] Univ N Carolina Project, Lilongwe, Malawi. [May, Margaret; Egger, Matthias] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Bangsberg, David R.] Univ Calif San Francisco, Epidemiol Prevent & Intervent Ctr, San Francisco, CA 94143 USA. RP Low, N (reprint author), Univ Bern, Inst Social & Prevent Med, Finkenhubelweg 11, CH-3012 Bern, Switzerland. EM low@ispm.unibe.ch RI May, Margaret/E-8099-2013; OI May, Margaret/0000-0002-9733-1003; Low, Nicola/0000-0003-4817-8986; Weigel, Ralf/0000-0001-9034-2634; Hankins, Catherine/0000-0002-1642-8592; Brinkhof, Martin/0000-0002-9319-665X FU Medical Research Council [G0700820]; NIAID NIH HHS [U01 AI069924]; NIMH NIH HHS [R01 MH054907] NR 29 TC 126 Z9 127 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JAN-FEB PY 2008 VL 17 IS 1 BP 47 EP 55 DI 10.1089/jwh.2007.0353 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 268JE UT WOS:000253575300006 PM 18240981 ER PT J AU Zhu, H Stybayeva, G Macal, M Ramanculov, E George, MD Dandekar, S Revzin, A AF Zhu, He Stybayeva, Gulnaz Macal, Monica Ramanculov, Erlan George, Michael D. Dandekar, Satya Revzin, Alexander TI A microdevice for multiplexed detection of T-cell-secreted cytokines SO LAB ON A CHIP LA English DT Article ID DETECTION PROTEIN ARRAYS; FLOW-CYTOMETRY; MICROFLUIDIC CHAMBERS; FUNCTIONAL SUBSETS; MICROARRAY; INFECTION; ELISPOT; BLOOD; DIFFERENTIATION; IDENTIFICATION AB Cytokines are produced by immune cells in response to viral or bacterial pathogens and therefore have significant diagnostic value. The goal of the present study was to develop a miniature device for detection of interleukin (IL)-2 and interferon (IFN)-gamma cytokines secreted by a small population of CD4 and CD8 T-cells. Microarrays of T-cell-and cytokine-specific Ab spots were printed onto poly(ethylene glycol) (PEG) hydrogel-coated glass slides and enclosed inside a microfluidic device, creating a miniature (similar to 3 mu L) immunoreaction chamber. Introduction of the red blood cell (RBC) depleted whole human blood into the microfluidic device followed by washing at a pre-defined shear stress resulted in isolation of pure CD4 and CD8 T-cells on their respective Ab spots. Importantly, the cells became localized next to anti-IL-2 and -IFN-gamma Ab spots. Mitogenic activation of the captured T-cells was followed by immunofluorescent staining (all steps carried out inside a microfluidic device), revealing concentration gradients of surface-bound cytokine molecules. A microarray scanner was then used to quantify the concentration of IFN-gamma and IL-2 near CD4 and CD8 T-cells. This study represents one of the first demonstrations of a microdevice for capturing desired T-cell subsets from a small blood volume and determining, on-chip, cytokine profiles of the isolated cells. Such a microdevice is envisioned as an immunology tool for multi-parametric analysis of T-cell function with direct applications in diagnosis/monitoring of HIV and other infectious diseases. C1 [Zhu, He; Stybayeva, Gulnaz; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Stybayeva, Gulnaz; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 E Hlth Sci St 2619, Davis, CA 95616 USA. EM arevzin@ucdavis.edu FU California Research Center for the Biology of HIV in Minorities; California HIV/AIDS Research Program [CH05-D-606]; NIH [DK61297, EB003827]; National Center for Biotechnology, Republic of Kazakhstan FX We thank Prof. Louie's lab in the Department of Biomedical Engineering at UC Davis for providing assistance with confocal microscopy. Scanning of the microarrays was performed at Expression Analysis Facility at UC Davis. Financial support for this work was provided in part by the California Research Center for the Biology of HIV in Minorities, California HIV/AIDS Research Program # CH05-D-606. Additional financial support was provided in part by an NIH grant DK61297 awarded to SD. HZ was supported through an NIH Training Grant (EB003827). GS was supported through a Biotechnology Fellowship from National Center for Biotechnology, Republic of Kazakhstan. NR 34 TC 60 Z9 60 U1 3 U2 34 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2008 VL 8 IS 12 BP 2197 EP 2205 DI 10.1039/b810244a PG 9 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 383PT UT WOS:000261686200029 PM 19023487 ER PT J AU Cardiff, RD Ward, JM Barthold, SW AF Cardiff, Robert D. Ward, Jerrold M. Barthold, Stephen W. TI 'One medicine-one pathology': are veterinary and human pathology prepared? SO LABORATORY INVESTIGATION LA English DT Article DE comparative pathology; one medicine; genomic biology; genomic pathology; education ID GENETICALLY-ENGINEERED MICE; MOUSE MODELS; CONSENSUS REPORT; COLON-CANCER; INTRAEPITHELIAL NEOPLASIA; BIOMEDICAL-RESEARCH; BETHESDA PROPOSALS; DEFICIENT MICE; ANIMAL-MODELS; MUTANT MICE AB The American Medical Association and the American Veterinary Medical Association have recently approved resolutions supporting 'One Medicine' or 'One Health' that bridge the two professions. The concept is far from novel. Rudolf Virchow, the Father of Modern Pathology, and Sir William Osler, the Father of Modern Medicine, were outspoken advocates of the concept. The concept in its modern iteration was re-articulated in the 1984 edition of Calvin Schwabe's 'Veterinary Medicine and Human Health.' The veterinary and medical pathology professions are steeped in a rich history of 'One Medicine,' but they have paradoxically parted ways, leaving the discipline of pathology poorly positioned to contribute to contemporary science. The time has come for not only scientists but also all pathologists to recognize the value in comparative pathology, the consequences of ignoring the opportunity and, most importantly, the necessity of preparing future generations to meet the challenge inherent in the renewed momentum for 'One Medicine.' The impending glut of new genetically engineered mice creates an urgent need for prepared investigators and pathologists. C1 [Cardiff, Robert D.; Barthold, Stephen W.] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. [Cardiff, Robert D.; Barthold, Stephen W.] Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Davis, CA 95616 USA. [Ward, Jerrold M.] NIAID, NIH, Comparat Med Branch, Bethesda, MD USA. [Barthold, Stephen W.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. RP Cardiff, RD (reprint author), Univ Calif Davis, Ctr Comparat Med, County Rd 98 & Hutchison Dr, Davis, CA 95616 USA. EM rdcardiff@ucdavis.edu FU Intramural NIH HHS; NCRR NIH HHS [U42 RR14905] NR 81 TC 65 Z9 67 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 IS 1 BP 18 EP 26 DI 10.1038/labinvest.3700695 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 243TQ UT WOS:000251820600002 PM 18040269 ER PT J AU Henson, DE Schwartz, AM Nsouli, H Grimly, PM Anderson, WF AF Henson, D. E. Schwartz, A. M. Nsouli, H. Grimly, P. M. Anderson, W. F. TI In situ and invasive carcinoma of the female breast pre- and post-mammography SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 George Washington Univ, Washington, DC USA. USUHS, Bethesda, MD USA. NIH, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 159 BP 37A EP 38A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181100159 ER PT J AU Walter, BA Valera, VA Tresserra, F Merino, MJ AF Walter, B. A. Valera, V. A. Tresserra, F. Merino, M. J. TI Loss of heterozygosity of PTEN in pregnancy-associated breast cancer and its correlation with BRCA1/2, p53, NM23, Her-2 and hormonal status SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Natl Canc Inst, Bethesda, MD USA. Inst Univ Dexcus, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 262 BP 59A EP 59A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181100262 ER PT J AU Bechert, CJ Ackerman, B AF Bechert, C. J. Ackerman, B. TI Risks associated with permanent synthetic dermal fillers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD USA. Ackerman Acad Dermatopathol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 405 BP 91A EP 91A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181100405 ER PT J AU Cheung, WL Krizman, DB Alvarez, H Hood, BL Darfler, MM Veenstra, TD Mollenhauer, J Habbe, N Feldman, G Maita, A AF Cheung, W. L. Krizman, D. B. Alvarez, H. Hood, B. L. Darfler, M. M. Veenstra, T. D. Mollenhauer, J. Habbe, N. Feldman, G. Maita, A. TI Application of a global proteomic approach to archival precursor lesions: Upregulation of DMBT-1 and TG2 in pancreatic cancer precursors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Express Path Inc, Gaithersburg, MD USA. NCI, Frederick, MD 21701 USA. Deutschen Krebsforschungszentrum, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 524 BP 115A EP 116A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181100524 ER PT J AU Merino, MJ Linehan, WM AF Merino, M. J. Linehan, W. M. TI Premalignant lesions of the kidney SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Merino, M. J.; Linehan, W. M.] NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 777 BP 170A EP 170A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181100777 ER PT J AU Navas, R Linehan, WM Merino, MJ AF Navas, R. Linehan, W. M. Merino, M. J. TI Oncocytic tumors of undetermine malignant potential SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Navas, R.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 790 BP 173A EP 173A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181100790 ER PT J AU Valera, VA Roberts, D Linehan, WM Merino, MJ AF Valera, V. A. Roberts, D. Linehan, W. M. Merino, M. J. TI Proteomic analysis identifies key metabolic and stress proteins differentially expressed in renal cell carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Valera, V. A.; Roberts, D.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 853 BP 186A EP 187A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181100853 ER PT J AU Elishuey, E Guido, R Dabbs, D Chatterjee, N Lacey, J Mueller, C Sherman, ME AF Elishuey, E. Guido, R. Dabbs, D. Chatterjee, N. Lacey, J., Jr. Mueller, C. Sherman, M. E. TI Frequency of PTEN loss in benign endometria of premenopausal women: A preliminary analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Sch Med, Magee Womens Hosp, Pittsburgh, PA USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 923 BP 202A EP 202A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101052 ER PT J AU Mani, H Merino, MJ AF Mani, H. Merino, M. J. TI Malignant mesothelioma presenting as, and mimicking, ovarian cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Mani, H.; Merino, M. J.] NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 973 BP 212A EP 213A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101102 ER PT J AU Sanz, J Teller, L Vockes, C Lineham, WM Sanz-Esponera, J Merino, MJ AF Sanz, J. Teller, L. Vockes, C. Lineham, W. M. Sanz-Esponera, J. Merino, M. J. TI Genetic alterations of uterine fibroids in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Hosp Clin San Carlos, Madrid, Spain. NCI, Bethesda, MD 20892 USA. RI Sanz, Julian/G-5276-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1021 BP 223A EP 223A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101150 ER PT J AU Choi, WWL Weisenburger, DD Greiner, TC Piris, MA Banham, AH Jaye, DL Wade, PA Iqbal, J Hans, CP Fu, K Gascoyne, RD Delabie, J Rosenwald, A Rimsza, L Campo, E Jaffe, ES Staudt, LM Chan, WC AF Choi, W. W. L. Weisenburger, D. D. Greiner, T. C. Piris, M. A. Banham, A. H. Jaye, D. L. Wade, P. A. Iqbal, J. Hans, C. P. Fu, K. Gascoyne, R. D. Delabie, J. Rosenwald, A. Rimsza, L. Campo, E. Jaffe, E. S. Staudt, L. M. Chan, W. C. TI A new immunostain algorithm improves the classification of diffuse large B-cell lymphoma into prognostically significant subgroups SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Nebraska Med Ctr, Omaha, NE USA. Spanish Natl Canc Ctr, Madrid, Spain. Univ Oxford, Oxford, England. Emory Univ, Atlanta, GA 30322 USA. BCCA, Vancouver, BC, Canada. Norwegian Radium Hosp, Oslo, Norway. Univ Wurzburg, Wurzburg, Germany. Univ Arizona, Tucson, AZ USA. Univ Barcelona, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. RI Banham, Alison/B-2966-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1144 BP 250A EP 250A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101273 ER PT J AU Gradowski, JF Jaffe, ES Warnke, R Pittaluga, S Surti, U Gole, L Swerdlow, SH AF Gradowski, J. F. Jaffe, E. S. Warnke, R. Pittaluga, S. Surti, U. Gole, L. Swerdlow, S. H. TI Do follicular lymphomas (FL) with Plasmacytic differentiation (PCD) have characteristic features? An lmmunoFISH study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Pittsburgh, PA USA. Natl Canc Inst, Bethesda, MD USA. Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1168 BP 255A EP 255A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101297 ER PT J AU Jiang, L Yuan, C Janik, J Stetler-Stevenson, M AF Jiang, L. Yuan, C. Janik, J. Stetler-Stevenson, M. TI Heterogeneous expression of CD52 evaluated by flow cytometry analysis among neoplasms of mature T lymphocytes and NK cells SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Jiang, L.; Yuan, C.; Janik, J.; Stetler-Stevenson, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1184 BP 258A EP 259A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101312 ER PT J AU Maric, I Fu, W Stoddard, J Wilson, TM Metcalfe, DD Robyn, J Noel, P AF Maric, I. Fu, W. Stoddard, J. Wilson, T. M. Metcalfe, D. D. Robyn, J. Noel, P. TI Occurrence of JAK2 V617F mutation in patients with systemic mastocytosis and thrombocytosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NIH, CC, Bethesda, MD 20892 USA. NIH, NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1209 BP 264A EP 265A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101337 ER PT J AU Rahemtullah, A Jaffe, ES Harris, NL Hasserjian, RP AF Rahemtullah, A. Jaffe, E. S. Harris, N. L. Hasserjian, R. P. TI Nodular lymphocyte predominant Hodgkin lymphoma with an interfollicular growth pattern and atypical T cells: A distinct disease variant? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1235 BP 270A EP 270A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101363 ER PT J AU Rizzo, KA Streubel, B Chott, A Pittaluga, S Raffeld, M Jaffe, ES AF Rizzo, K. A. Streubel, B. Chott, A. Pittaluga, S. Raffeld, M. Jaffe, E. S. TI Pediatric marginal zone B-cell lymphomas; Analysis of histopathology, immunophenotype and genetic aberrations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Vienna Gen Hosp, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1240 BP 271A EP 272A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101368 ER PT J AU Felipe-Silva, A Quezado, M Garfield, S Wincovitch, S Alves, V AF Felipe-Silva, A. Quezado, M. Garfield, S. Wincovitch, S. Alves, V. TI Analysis of nucleic acid index in hepatocellular carcinoma, dysplastic nodules, regenerative macronodules and cirrhotic liver SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Natl Inst Hlth, Bethesda, MD USA. Univ Sao Paulo, Sao Paulo, Brazil. RI FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1385 BP 304A EP 304A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101513 ER PT J AU Mani, H Kleiner, DE AF Mani, H. Kleiner, D. E. TI Validation of a feature recording system for hepatic graft-versushost disease SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Mani, H.; Kleiner, D. E.] NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1417 BP 311A EP 311A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101545 ER PT J AU Galli, S Li, G Tsokos, M AF Galli, S. Li, G. Tsokos, M. TI Expression of insulin-like growth factor type 1 receptor (IGF-1R) in ewing sarcoma family tumors (ESFT) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Galli, S.; Li, G.; Tsokos, M.] NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1518 BP 332A EP 332A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101646 ER PT J AU Galli, S Tsokos, M Przygodzki, R Ahmed, A AF Galli, S. Tsokos, M. Przygodzki, R. Ahmed, A. TI Expression of caspase 8, bcl-2, survivin and XIAP in Wilms' tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NIH, NCI, Bethesda, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1517 BP 332A EP 332A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101645 ER PT J AU Fowler, CB Cunningham, RE Waybright, TJ Blonder, J Veenstra, TD Mason, JT O'Leary, TJ AF Fowler, C. B. Cunningham, R. E. Waybright, T. J. Blonder, J. Veenstra, T. D. Mason, J. T. O'Leary, T. J. TI Elevated hydrostatic pressure promotes protein recovery from formalin-fixed, paraffin-embedded tissue surrogates SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Armed Forces Inst Pathol, Rockville, MD USA. Vet Hlth Adm, Washington, DC USA. Natl Canc Inst, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1661 BP 365A EP 365A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101789 ER PT J AU Rodriguez-Canales, J Majumdar, ZK Ory, EC Hanson, JC Pohida, TJ Tangrea, MA Chuaqui, RF Bonner, RF Emmer-Buck, MR AF Rodriguez-Canales, J. Majumdar, Z. K. Ory, E. C. Hanson, J. C. Pohida, T. J. Tangrea, M. A. Chuaqui, R. F. Bonner, R. F. Emmer-Buck, M. R. TI Expression microdissection: A new immuno-based dissection technology for cellular and nuclear procurement SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD USA. NICHD, Bethesda, MD USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1687 BP 371A EP 371A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101815 ER PT J AU Valera, VA Walter, BA Merino, MJ AF Valera, V. A. Walter, B. A. Merino, M. J. TI Optimal protein extraction from formalin-fixed paraffin-embedded tissues for expression profiling of tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Valera, V. A.; Walter, B. A.; Merino, M. J.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2008 VL 88 SU 1 MA 1696 BP 373A EP 373A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 248UG UT WOS:000252181101824 ER PT J AU Modlin, IM Oberg, K Chung, DC Jensen, RT de Herder, WW Thakker, RV Caplin, M Delle Fave, G Kaltsas, GA Krenning, EP Moss, SF Nilsson, O Rindi, G Salazar, R Ruszniewski, P Sundin, A AF Modlin, Irvin M. Oberg, Kjell Chung, Daniel C. Jensen, Robert T. de Herder, Wouter W. Thakker, Rajesh V. Caplin, Martyn Delle Fave, Gianfranco Kaltsas, Greg A. Krenning, Eric P. Moss, Steven F. Nilsson, Ola Rindi, Guido Salazar, Ramon Ruszniewski, Philippe Sundin, Anders TI Gastroenteropancreatic neuroendocrine tumours SO LANCET ONCOLOGY LA English DT Review ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; MULTIPLE ENDOCRINE NEOPLASIA; ZOLLINGER-ELLISON-SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; MIDGUT CARCINOID-TUMORS; LIVER METASTASES; SURGICAL-TREATMENT; CELL TUMORS; SURVIVAL; CHEMOEMBOLIZATION AB Gastroenteropancreatic (GEP) neuroendocrine tumours (NETS) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETS have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETS, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics. C1 [Modlin, Irvin M.] Yale Univ, Dept Surg Gastroenterol, New Haven, CT 06520 USA. [Oberg, Kjell] Univ Uppsala Hosp, Dept Internal Med, Endocrine Oncol Unit, S-75185 Uppsala, Sweden. [Chung, Daniel C.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jensen, Robert T.] NIDDK, Natl Inst Hlth, Dis Branch, Bethesda, MD USA. [de Herder, Wouter W.] Univ Rotterdam Hosp, Erasmus Med Ctr, Dept Internal Med 3, Rotterdam, Netherlands. [de Herder, Wouter W.] Univ Oxford, Nuffield Dept Clin Med, Acad Endocrine Unit, Oxford, England. [Caplin, Martyn] Royal Free Hosp, Ctr Gastroenterol, Neuroendocrine Tumour Unit, London NW3 2QG, England. [Delle Fave, Gianfranco] Univ Roma La Sapienza, Dept Digest & Liver Dis, Rome, Italy. [Kaltsas, Greg A.] George Genimatas Hosp, Dept Endocrinol, Athens, Greece. [Krenning, Eric P.] Erasmus MC, Dept Nucl Med, Rotterdam, Netherlands. [Moss, Steven F.] Brown Univ, Rhode Isl Hosp, Dept Med, Div Gastroenterol, Providence, RI 02903 USA. [Nilsson, Ola] Sahlgrens Univ Hosp, Lundberg Lab Cancer Res, Dept Pathol, S-41345 Gothenburg, Sweden. [Rindi, Guido] Univ Parma, Dept Pathol, I-43100 Parma, Italy. [Rindi, Guido] Univ Parma, Lab Med, I-43100 Parma, Italy. [Salazar, Ramon] Catalan Inst Oncol, Dept Med Oncol, Barcelona, Spain. [Ruszniewski, Philippe] Beaujon Hosp, Dept Gastroenterol, Clichy, France. [Sundin, Anders] Uppsala Univ, Dept Radiol, Ctr Med Imaging, Uppsala, Sweden. RP Modlin, IM (reprint author), Yale Univ, Dept Surg Gastroenterol, New Haven, CT 06520 USA. EM imodlin@optonline.net OI RINDI, Guido/0000-0003-2996-4404; Thakker, Rajesh/0000-0002-1438-3220 FU Medical Research Council [G9825289] NR 78 TC 641 Z9 674 U1 4 U2 45 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2008 VL 9 IS 1 BP 61 EP 72 DI 10.1016/S1470-2045(07)70410-2 PG 12 WC Oncology SC Oncology GA 252RN UT WOS:000252464400027 PM 18177818 ER PT J AU Habermann, JK Bader, FG Franke, C Zimmermann, K Gemoll, T Fritzsche, B Ried, T Auer, G Bruch, HP Roblick, UJ AF Habermann, Jens K. Bader, Franz G. Franke, Christian Zimmermann, Kaja Gemoll, Timo Fritzsche, Britta Ried, Thomas Auer, Gert Bruch, Hans-Peter Roblick, Uwe J. TI From the genome to the proteome-biomarkers in colorectal cancer SO LANGENBECKS ARCHIVES OF SURGERY LA English DT Article DE colorectal cancer; biomarkers; genomics; transcriptomics; proteomics ID PREOPERATIVE CARCINOEMBRYONIC ANTIGEN; DIFFERENCE GEL-ELECTROPHORESIS; FECAL OCCULT BLOOD; COLON-CANCER; PROSTATE-CANCER; MOLECULAR MARKERS; MASS-SPECTROMETRY; SERUM BIOMARKERS; GENE-EXPRESSION; BREAST-CANCER AB Background and aims Colorectal cancer is the second leading cause of cancer-related death. Current clinical practice in colorectal cancer screening (fecal occult blood test, FOBT; colonoscopy) has contributed to a reduction of mortality. However, despite these screening programs, about 70% of carcinomas are detected at advanced tumor stages (UICC III/IV) presenting poor patient prognosis. Thus, innovative tools and methodologies for early cancer detection can directly result in improving patient survival rates. Patients/methods Biomedical research has advanced rapidly in recent years with the availability of technologies such as global gene and protein expression profiling. Comprehensive tumor profiling has become a field of intensive research aiming at identifying biomarkers relevant for improved diagnostics and therapeutics. Results In this paper, we report a comprehensive review of genomic, transcriptomic, and proteomic approaches for biomarker identification in tissue and blood with a main emphasis on two-dimensional gel-electrophoresis (2-DE) and mass spectrometry analyses. Conclusion Proteomics-based technologies enable to distinguish the healthy patient from the tumor patient with high sensitivity and specificity and could greatly improve common classification systems and diagnostics. However, this progress has not yet been transferred from bench to bedside but could open the door to a more accurate and target specific personalized medicine with improved patient survival. C1 Univ Schleswig, Dept Surg, D-23538 Lubeck, Germany. Karolinska Biom Ctr, Karolinska Inst, S-17176 Stockholm, Sweden. NIH, Natl Canc Inst, Genet Branch, Bethesda, MD 20892 USA. RP Roblick, UJ (reprint author), Univ Schleswig, Dept Surg, Holstein Campus Lubeck,Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM Jens.Habermann@gmail.com; DrDr.UJRoblick@t-online.de RI Bruch, Hans-Peter/E-7731-2010; Habermann, Jens/E-2968-2010 NR 81 TC 21 Z9 25 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PD JAN PY 2008 VL 393 IS 1 BP 93 EP 104 DI 10.1007/s00423-007-0230-1 PG 12 WC Surgery SC Surgery GA 235MG UT WOS:000251237700014 PM 17938952 ER PT J AU Tong, YX Francis, AL Gandour, JT AF Tong, Yunxia Francis, Alexander L. Gandour, Jackson T. TI Processing dependencies between segmental and suprasegmental features in Mandarin Chinese SO LANGUAGE AND COGNITIVE PROCESSES LA English DT Article ID DRIVEN ATTENTIONAL CAPTURE; SPEECH-PERCEPTION; STIMULUS DIMENSIONS; INFORMATION; DISCRIMINATION; VOWELS; SPOKEN; PITCH; TONE; RECOGNITION AB The aim of this study was to examine processing interactions between segmental (consonant, vowel) and suprasegmental (tone) dimensions of Mandarin Chinese. Using a speeded classification paradigm, processing interactions were examined between each pair of dimensions. Listeners were asked to attend to one dimension while ignoring the variation along another. Asymmetric interference effects were observed between segmental and suprasegmental dimensions, with segmental dimensions interfering more with tone classification than the reverse. Among the three dimensions, vowels exerted greater interference on consonants and tones than vice versa. Comparisons between each pair of dimensions revealed greater integrality between tone and vowel than between tone and consonant. Findings suggest that the direction and degree of interference between segmental and suprasegmental dimensions in spoken word recognition reflect differences in acoustic properties as well as other factors of an informational nature. C1 [Tong, Yunxia; Francis, Alexander L.; Gandour, Jackson T.] Purdue Univ, Dept Speech Language Hearing Sci, W Lafayette, IN 47907 USA. [Tong, Yunxia] NIMH, NIH, Bethesda, MD 20892 USA. RP Gandour, JT (reprint author), Purdue Univ, Dept Speech Language Hearing Sci, 1353 Heavilon Hall,500 Oval Dr, W Lafayette, IN 47907 USA. EM gandour@purdue.edu RI Tong, Yunxia/C-1276-2010 NR 51 TC 29 Z9 30 U1 0 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0169-0965 J9 LANG COGNITIVE PROC JI Lang. Cogn. Process. PY 2008 VL 23 IS 5 BP 689 EP 708 DI 10.1080/01690960701728261 PG 20 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 318IF UT WOS:000257084100003 ER PT J AU Humbert, LA Poletto, CJ Saxon, KG Kearney, PR Ludlow, CL AF Humbert, Lanessa A. Poletto, Christopher J. Saxon, Keith G. Kearney, Pamela R. Ludlow, Christy L. TI The Effect of Surface Electrical Stimulation on Vocal Fold Position SO LARYNGOSCOPE LA English DT Article DE Dysphagia; true vocal fold paralysis; swallowing; aspiration; therapy ID THYROARYTENOID MUSCLE; PHARYNGEAL DYSPHAGIA; ASPIRATION; LARYNGEAL; CLOSURE; REST; IMMOBILITY AB Objectives/Hypothesis: Closure of the true and false vocal folds is a normal part of airway protection during swallowing. Individuals with reduced or delayed true vocal fold closure can be at risk for aspiration and may benefit from intervention to ameliorate the problem. Surface electrical stimulation is currently used during therapy for dysphagia, despite limited knowledge of its physiological effects. Design: Prospective single effects study. Methods: The immediate physiological effect of surface stimulation on true vocal fold angle was examined at rest in 27 healthy adults using 10 different electrode placements on the submental and neck regions. Fiberoptic nasolaryngoscopic recordings during passive inspiration were used to measure change in true vocal fold angle with stimulation. Results: Vocal fold angles changed only to a small extent during two electrode placements (P <= .05). When two sets of electrodes were placed vertically on the neck, the mean true vocal fold abduction was 2.4 degrees; while horizontal placements of electrodes in the submental region produced a mean adduction of 2.8 degrees (P = .03). Conclusions: Surface electrical stimulation to the submental and neck regions does not produce immediate true vocal fold adduction adequate for airway protection during swallowing, and one position may produce a slight increase in true vocal fold opening. C1 [Humbert, Lanessa A.] Univ Madison Wisconsin, Wm S Middleton Vet Hosp, Geriatr Res Educ & Clin Ctr, Dept Med, Madison, WI USA. [Humbert, Lanessa A.] Univ Madison Wisconsin, Wm S Middleton Vet Hosp, Geriatr Res Educ & Clin Ctr, Dept Radiol, Madison, WI USA. [Poletto, Christopher J.] Medtronic Inc, Minneapolis, MN USA. [Saxon, Keith G.] Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. [Kearney, Pamela R.; Ludlow, Christy L.] NINDS, Speech Sect, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), 10 Ctr Dr MSC 1416,Bldg 10 Rm 5D38, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU National Institutes of Health; National Institute of Neurological Disorders and Stroke FX This work was financially supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. NR 24 TC 6 Z9 6 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2008 VL 118 IS 1 BP 14 EP 19 DI 10.1097/MLG.0b013e318155a47d PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 386CR UT WOS:000261860400004 PM 18043496 ER PT J AU Garcia-Teague, L AF Garcia-Teague, Lorraine BE McNeill, BW Cervantes, JM TI An Appreciation of Dr. Michael W. Smith (1960-2006) SO LATINA/O HEALING PRACTICES: MESTIZO AND INDIGENOUS PERSPECTIVES LA English DT Biographical-Item; Book Chapter C1 [Garcia-Teague, Lorraine] Univ Calif Los Angeles, HIV Educ Adherence Program, Los Angeles, CA 90024 USA. RP Garcia-Teague, L (reprint author), Harbor UCLA Res Ctr Psychobiol Ethn, NIMH, Torrance, CA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-89327-2 PY 2008 BP IX EP X PG 2 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BUP17 UT WOS:000289952300001 ER PT J AU Ascani, G Smith, MW AF Ascani, German Smith, Michael W. BE McNeill, BW Cervantes, JM TI The Use of Psychotropic Herbal and Natural Medicines in Latina/o and Mestiza/o Populations SO LATINA/O HEALING PRACTICES: MESTIZO AND INDIGENOUS PERSPECTIVES LA English DT Article; Book Chapter ID ST JOHNS WORT; GINKGO-BILOBA EXTRACT; SEVILLE ORANGE JUICE; ANTICARCINOGENIC ENZYME INDUCERS; VALERIAN ROOT EXTRACT; HOPS HUMULUS-LUPULUS; CASIMIROA-EDULIS; ALTERNATIVE MEDICINE; GRAPEFRUIT JUICE; PRENYLATED FLAVONOIDS C1 [Smith, Michael W.] Harbor UCLA Med Ctr, Alliance Mentally Ill A Better Life Endeavor Inte, Torrance, CA 90509 USA. [Smith, Michael W.] Harbor UCLA Res Ctr Psychobiol Ethn, NIMH, Torrance, CA USA. [Smith, Michael W.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Smith, Michael W.] Los Angeles Cty Dept Hlth Serv, Expert Comm Psychiat Medicat, Los Angeles, CA USA. RP Ascani, G (reprint author), San Francisco Mission Mental Hlth Clin, San Francisco, CA USA. NR 121 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-89327-2 PY 2008 BP 83 EP 137 PG 55 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BUP17 UT WOS:000289952300006 ER PT J AU Buske, C Gisselbrecht, C Gribben, J Letai, T McLaughlin, P Wilson, W AF Buske, Christian Gisselbrecht, Christian Gribben, John Letai, Tony McLaughlin, Peter Wilson, Wyndham TI Refining the treatment of follicular lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 6th International Workshop on Non-Hodgkin Lymphoma CY NOV 16-17, 2007 CL Boston, MA DE follicular lymphoma; rituximab; FLIPI; biological factors; novel treatments ID LARGE-CELL LYMPHOMA; INTERNATIONAL PROGNOSTIC INDEX; NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP; STUDY-GROUP EXPERIENCE; REGULATORY T-CELLS; STAGE-I; LOW-GRADE; PROLONGS SURVIVAL; FRONT-LINE AB Many effective treatments are currently available for patients with follicular lymphoma (FL). However, given the heterogeneity of this disease, identifying the most beneficial treatment for an individual patient remains a challenge, although clinical, genetic and biological features can all potentially be used to refine therapies in individual cases. The Follicular Lymphoma international prognostic index (FLIPI) algorithm is a valuable prognostic tool for risk categorisation. Despite its current limitations, further investigation will help to develop the role of FLIPI in treatment decision-making, and will increase its value in identifying the optimal therapy for individuals. Biological factors such as bulky disease, over-expression of Bcl-2, or histological grade can help to identify patients at high risk of relapse, and distinguish between the benefits of early intervention vs. a watch-and-wait policy in early-stage FL. The tumor microenvironment plays an important role in the development of FL, and identification of biological and genetic markers could help clinicians determine the prognosis of individual patients. Although much work remains to be done, a greater understanding of the biology of FL will lead to the development of novel therapeutic targets and therapies, bringing individualised treatment a step closer. C1 [Buske, Christian] Univ Munich, Klinikum Grosshadern, Dept Internal Med 3, D-8000 Munich, Germany. [Gisselbrecht, Christian] Hop St Louis, Inst Hematol, Paris, France. [Gribben, John] Barts & Royal London Sch Med, Inst Canc, London, England. [Letai, Tony] Dana Farber Canc Inst, Boston, MA 02115 USA. [McLaughlin, Peter] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Wilson, Wyndham] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Buske, C (reprint author), Univ Munich, Klinikum Grosshadern, Dept Internal Med 3, D-8000 Munich, Germany. EM christian.buske@med.uni-muenchen.de NR 58 TC 7 Z9 8 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 SU 1 BP 18 EP 26 DI 10.1080/10428190802311409 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 354NI UT WOS:000259645900004 PM 18821429 ER PT J AU Cohen, JI Bollard, CM Khanna, R Pittaluga, S AF Cohen, Jeffrey I. Bollard, Catherine M. Khanna, Rajiv Pittaluga, Stefania TI Current understanding of the role of Epstein-Barr virus in lymphomagenesis and therapeutic approaches to EBV-associated lymphomas SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 6th International Workshop on Non-Hodgkin Lymphoma CY NOV 16-17, 2007 CL Boston, MA DE Epstein-Barr virus; lymphomagenesis; EBV-associated lymphomas; immunodeficiency; immunocompetency; therapeutic approaches ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; MEMBRANE-PROTEIN 1; CYTOTOXIC T-CELLS; MONOCLONAL-ANTIBODY RITUXIMAB; SOLID-ORGAN-TRANSPLANTATION; ADOPTIVE TRANSFER; ARGININE BUTYRATE; HODGKINS-LYMPHOMA; LYMPHOCYTES; RECIPIENTS AB A heterogeneous group of malignancies are associated with Epstein-Barr virus (EBV) infection. These malignancies arise in both immunosuppressed and immunocompetent individuals and can be divided into three patterns of latency depending on the viral genes that are expressed. In Type III latency malignancies, such as post-transplant lymphoproliferative disorder (PTLD), EBV has a direct role and the activated B-cell phenotype is characterised by high-level expression of all the immunodominant EBV latency proteins. Thus, EBV-infected B cells are good targets for EBV-specific cytotoxic T lymphocytes (CTLs). New immune-based treatments for PTLD include transfer of ex vivo generated autologous EBV-specific CTLs or, in the case of bone marrow transplant recipients, donor-derived EBV-specific T cells. This strategy could, perhaps, also work in Type II latency malignancies, where EBV acts like a cofactor rather than having a direct role. In initial studies, T cells specific for the weakly immunogenic latent membrane protein 2 have been expanded ex vivo and have promoted tumor regression in a subset of patients. Another potential therapeutic strategy could be to try to induce lytic EBV infection in the tumor cells. This could be done by targeting genes that switch the EBV-infected B cells from the latent to the lytic cycle. C1 [Cohen, Jeffrey I.] NIAID, Natl Inst Hlth, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Bollard, Catherine M.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Khanna, Rajiv] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Pittaluga, Stefania] Natl Inst Hlth, Hemopathol Sect, Pathol Lab, Bethesda, MD USA. RP Cohen, JI (reprint author), NIAID, Natl Inst Hlth, Med Virol Sect, Lab Clin Infect Dis, Bldg 10,Rm 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov RI Khanna, Rajiv/A-7691-2008 OI Khanna, Rajiv/0000-0003-2241-0353 FU Intramural NIH HHS [ZIA AI000913-08] NR 47 TC 48 Z9 53 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 SU 1 BP 27 EP 34 DI 10.1080/10428190802311417 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 354NI UT WOS:000259645900005 PM 18821430 ER PT J AU Landgren, O Tilly, H AF Landgren, Ola Tilly, Herve TI Epidemiology, pathology and treatment of non-follicular indolent lymphomas SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 6th International Workshop on Non-Hodgkin Lymphoma CY NOV 16-17, 2007 CL Boston, MA DE non-Hodgkin lymphoma; non-follicular lymphoma; indolent lymphoma ID MARGINAL-ZONE LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOMA; HEPATITIS-C-VIRUS; NON-HODGKINS-LYMPHOMA; HELICOBACTER-PYLORI ERADICATION; V-H GENES; VILLOUS LYMPHOCYTES; LOW-GRADE; FAMILIAL AGGREGATION AB Non-follicular indolent subtypes of non-Hodgkin lymphoma (NHL), which include chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL) and marginal zone lymphomas (MZL), are a diverse group of disorders with different presenting features, behaviour patterns and treatment outcomes. Current knowledge of these subtypes is largely based on retrospective analyses. A precise diagnosis can be difficult to achieve, and specific diagnostic criteria are needed to more precisely define some of the rarer indolent tumors, such as nodal and splenic MZLs. Although some subtypes of NHL have a prolonged indolent course, with a good prognosis (e.g. SLL), others (e.g. nodal and splenic MZLs) can rapidly evolve into more aggressive subtypes. In asymptomatic patients, treatment may be deferred until the disease progresses and the patient becomes symptomatic. Universally accepted therapeutic guidelines do not exist, however, and carefully designed, prospective clinical studies are needed to further assess optimal therapeutic approaches for these indolent NHLs. C1 [Landgren, Ola] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Tilly, Herve] Ctr Henri Becquerel, Dept Hematol, F-76038 Rouen, France. RP Landgren, O (reprint author), NCI, Natl Inst Hlth, 6120 Executive Blvd,Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov FU Intramural NIH HHS NR 64 TC 7 Z9 8 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 SU 1 BP 35 EP 42 DI 10.1080/10428190802311425 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 354NI UT WOS:000259645900006 PM 18821431 ER PT J AU Rubenstein, J Ferreri, AJM Pittaluga, S AF Rubenstein, James Ferreri, Andres J. M. Pittaluga, Stefania TI Primary lymphoma of the central nervous system: epidemiology, pathology and current approaches to diagnosis, prognosis and treatment SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 6th International Workshop on Non-Hodgkin Lymphoma CY NOV 16-17, 2007 CL Boston, MA DE primary CNS lymphoma; PCNSL; epidemiology; biomarkers ID PRIMARY CNS LYMPHOMA; B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; INTRAOCULAR LYMPHOMA; EXPRESSION; AIDS; RADIOTHERAPY; SURVIVAL; THERAPY; DNA AB An overview of the current approaches to the management of patients with primary central nervous system lymphoma (PCNSL) is provided. Although accumulating evidence demonstrates that PCNSL is a curable type of brain tumor, in many cases establishing the diagnosis and overcoming chemotherapeutic resistance remain significant obstacles. The issue of treatment-related neurotoxicity is also a central consideration in treatment planning. The introduction of highly active antiretroviral therapy has had a major impact on this disease in that the incidence of AIDS-related central nervous system lymphoma, once highly prevalent in the 1980s and 1990s, has now virtually disappeared. However, the problem of diagnostic delays secondary to steroid effects, radiation-induced neurotoxicity and methotrexate resistance represent unique and important problems in this disease. The use of anti-CD20 antibody in this disease represents the first application of biologically based targeted therapies for PCNSL; however, the overall impact of this modality in brain lymphoma awaits further evaluation in ongoing studies The application of proteomic as well as gene expression technologies is yielding insights into PCNSL pathogenesis, in particular specific oncogenic pathways, which may be exploited to develop new therapies. C1 [Rubenstein, James] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ferreri, Andres J. M.] Ist Sci San Raffaele, Med Oncol Unit, Milan, Italy. [Pittaluga, Stefania] Natl Inst Hlth, Bethesda, MD USA. RP Rubenstein, J (reprint author), Univ Calif San Francisco, Box 1270,ACC 5th Floor, San Francisco, CA 94143 USA. EM jamesr@medicine.ucsf.edu RI Ferreri, Andres Jose Maria/A-6662-2013 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124 FU NCI NIH HHS [K23 CA100291] NR 51 TC 39 Z9 46 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 SU 1 BP 43 EP 51 DI 10.1080/10428190802311441 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 354NI UT WOS:000259645900007 PM 18821432 ER PT J AU O'Mahony, D Debnath, I Janik, J Aisner, D Jaffe, E Waldmann, T Morris, J AF O'Mahony, Deirdre Debnath, Indranil Janik, John Aisner, Dara Jaffe, Elaine Waldmann, Thomas Morris, John TI Cardiac involvement with human T-cell lymphotrophic virus type-1-associated adult T-cell leukemia/lymphoma: The NIH experience SO LEUKEMIA & LYMPHOMA LA English DT Article DE adult T cell leukemia/lymphoma; HTLV-1; cardiac neoplasm ID LEUKEMIA-LYMPHOMA; MALIGNANT-LYMPHOMA; MYCOSIS-FUNGOIDES; EXPRESSION; HEART; CHEMOKINE; RETROVIRUS; CCR4; PROGRESSION; MANAGEMENT AB Malignant cardiac involvement is rare in patients with human T cell lymphotrophic virus type-1-associated adult T cell leukemia/lymphoma (ATLL). We report a single institution experience of eight patients with pathologically documented cardiac involvement with ATLL. Pericardial effusion and tamponade, cardiac valvular infiltration, valve leaflet tumor nodules and endocardial and myocardial tumors were observed. Cardiac involvement with ATLL was most often identified post-mortem; however, three cases were diagnosed clinically. All but one of the patients had the acute or lymphomatous subtypes of ATLL and had progressed through at least one prior systemic therapy. Patients with ATLL-related cardiac disease were also found to have pulmonary involvement suggesting that this may be a sign of increased risk of cardiac involvement. One patient with the chronic form of ATLL remains alive 10 years after undergoing cardiac valve replacement. C1 [O'Mahony, Deirdre; Debnath, Indranil; Janik, John; Waldmann, Thomas; Morris, John] NCI, Ctr Canc Res, Metab Branch, Mark O Hatfield Clin Res Ctr,Natl Inst Hlth, Bethesda, MD 20892 USA. [Aisner, Dara; Jaffe, Elaine] NCI, Ctr Canc Res, Hematopathol Sect, Pathol Lab,Natl Inst Hlth, Bethesda, MD 20892 USA. RP Morris, J (reprint author), NCI, Ctr Canc Res, Metab Branch, Mark O Hatfield Clin Res Ctr,Natl Inst Hlth, Room 4-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM jmorris@mail.nih.gov FU Intramural NIH HHS NR 48 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 IS 3 BP 439 EP 446 DI 10.1080/10428190701809164 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 267MO UT WOS:000253513300010 PM 18297519 ER PT J AU Thieblemont, C Rolland, D Baseggio, L Felman, P Gazzo, S Callet-Bauchu, E Traverse-Glehen, A Houlgatte, R Fu, K Weisenburger, D De Jong, D Jaffe, ES Rosenwald, A Ott, G Coiffier, B Berger, F AF Thieblemont, Catherine Rolland, Delphine Baseggio, Lucile Felman, Pascale Gazzo, Sophie Callet-Bauchu, Evelyne Traverse-Glehen, Alexandra Houlgatte, Remi Fu, Kai Weisenburger, Dennis De Jong, Daphne Jaffe, Elaine S. Rosenwald, Andreas Ott, German Coiffier, Bertrand Berger, Francoise TI Comprehensive analysis of GST-pi expression in B-cell lymphomas: Correlation with histological subtypes and survival SO LEUKEMIA & LYMPHOMA LA English DT Letter ID NON-HODGKINS-LYMPHOMAS; LYMPHOCYTIC LYMPHOMA; CENTROCYTIC LYMPHOMA; TRANSLOCATION C1 [Thieblemont, Catherine] Univ Paris 07, Hop St Louis, Serv Hematooncol, F-75010 Paris, France. [Rolland, Delphine; Baseggio, Lucile; Felman, Pascale; Gazzo, Sophie; Callet-Bauchu, Evelyne] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Serv Hematol Biol, F-69495 Pierre Benite, France. [Traverse-Glehen, Alexandra; Berger, Francoise] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Serv Anat Pathol, F-69495 Pierre Benite, France. [Traverse-Glehen, Alexandra; Berger, Francoise] Univ Lyon 1, Equipe Accueil 3737, Fac Lyon Sud, F-69495 Lyon, France. [Houlgatte, Remi] CHU Nantes, Inst Thorax, F-44000 Nantes, France. [Houlgatte, Remi] INSERM, U915, F-44000 Nantes, France. [Houlgatte, Remi] Univ Nantes, Fac Med, Inst Thorax, F-44000 Nantes, France. [Fu, Kai; Weisenburger, Dennis] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [De Jong, Daphne] Antoni Von Leevenhoek Hosp, Dept Pathol, Netherlands Canc Inst, Amsterdam, Netherlands. [Jaffe, Elaine S.] Natl Canc Inst Hlth, Ctr Canc Res, Metab Branch, Bethesda, MD USA. [Jaffe, Elaine S.] Natl Canc Inst Hlth, Ctr Canc Res, Hematopathol Sect, Bethesda, MD USA. [Jaffe, Elaine S.] Natl Canc Inst Hlth, Ctr Canc Res, Sect Lymphoma Clin Res, Bethesda, MD USA. [Rosenwald, Andreas; Ott, German] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. [Coiffier, Bertrand] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Serv Hematol Clin, F-69495 Pierre Benite, France. RP Thieblemont, C (reprint author), Univ Paris 07, Hop St Louis, Serv Hematooncol, F-75010 Paris, France. EM catherine.thieblemont@sls.aphp.fr RI Rolland, Delphine/C-3101-2011 FU Intramural NIH HHS [Z01 SC000550-27] NR 13 TC 8 Z9 9 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 IS 7 BP 1403 EP 1406 DI 10.1080/10428190802094245 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 322AS UT WOS:000257348200028 PM 18604726 ER PT J AU Kreisl, TN Panageas, KS Elkin, EB Deangelis, LM Abrey, LE AF Kreisl, Teri N. Panageas, Katherine S. Elkin, Elena B. Deangelis, Lisa M. Abrey, Lauren E. TI Treatment patterns and prognosis in patients with human immunodeficiency virus and primary central system lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE HIV; central nervous system lymphoma; prognosis; treatment ID ACTIVE ANTIRETROVIRAL THERAPY; NON-HODGKINS-LYMPHOMA; PRIMARY CNS LYMPHOMA; UNITED-STATES; AIDS; SURVIVAL; RADIOTHERAPY; ERA; CHEMOTHERAPY; METHOTREXATE AB The incidence of human immunodeficiency virus (HIV)-associated primary central nervous system lymphoma (PCNSL) has decreased in the era of highly active anti-retroviral therapy, but PCNSL continues to be a prominent AIDS-defining illness. Using surveillance epidemiology and end results, cancer registry data linked with Medicare, we identified PCNSL cases diagnosed from 1994 to 2002. The effects of comorbidity, year of diagnosis, and sociodemographic characteristics on the odds of receiving treatment were assessed. One hundred and eighty-four patients with both HIV and PCNSL were identified. Forty-six per cent were treated with radiation therapy (RT) alone, 10% received RT and chemotherapy, 4% received chemotherapy alone, and 40% received no treatment. No time trends in treatment patterns were observed, and no sociodemographic factors were associated with receipt of treatment. Median survival was 2 months. Age did not impact survival. Survival was improved for patients diagnosed with PCNSL after 1996 (p=0.028). Despite improved treatment for both diseases over the past decade, survival remains dismal in this cohort of Medicare/Medicaid beneficiaries with HIV-related PCNSL. These results may not apply to the general HIV population. C1 [Kreisl, Teri N.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Panageas, Katherine S.; Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Deangelis, Lisa M.; Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. RP Kreisl, TN (reprint author), NCI, Neurooncol Branch, NIH, 9030 Old Georgetown Rd,Rm 243, Bethesda, MD 20892 USA. EM kreislt@mail.nih.gov FU MSKCC Cancer and Aging Programme, Seaver Fund FX This study was supported by MSKCC Cancer and Aging Programme, Seaver Fund. NR 25 TC 10 Z9 10 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 IS 9 BP 1710 EP 1716 DI 10.1080/10428190802238560 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 348WJ UT WOS:000259240500012 PM 18661394 ER PT J AU Davis, RE AF Davis, R. Eric TI In vitro chemosensitivity testing in the genomic era SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID B-CELL LYMPHOMA; EXPRESSION; CHEMOTHERAPY; SURVIVAL; PREDICT; SUBGROUPS; OVERCOMES C1 NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. RP Davis, RE (reprint author), NCI, Ctr Canc Res, Metab Branch, Bldg 10,Room 6B-05,10 Ctr Dr, Bethesda, MD 20892 USA. EM redavis@mail.nih.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2008 VL 49 IS 11 BP 2040 EP 2041 DI 10.1080/10428190802541823 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 374IK UT WOS:000261036800006 PM 19021046 ER PT J AU Karp, JE Giles, FJ Gojo, L Morris, L Greer, J Johnson, B Thein, M Sznol, M Low, J AF Karp, Judith E. Giles, Francis J. Gojo, Lvana Morris, Lawrence Greer, Jacqueline Johnson, Bonny Thein, Mya Sznol, Mario Low, Jennifer TI A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine((R))) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders SO LEUKEMIA RESEARCH LA English DT Article DE refractory acute leukemia; myeloproliferative disorders; rbonucleotide reductase; Triapine; fludarabine ID CHRONIC MYELOGENOUS LEUKEMIA; INTERNATIONAL WORKING GROUP; NERVOUS-SYSTEM TOXICITY; MYELODYSPLASTIC SYNDROMES; INDUCTION THERAPY; RESPONSE CRITERIA; ARA-C; HYDROXYUREA; CELLS; METABOLISM AB Triapine((R)) is a potent ribonucleotide reductase (RR) inhibitor that depletes intracellular deoxyribonculeotide pools, especially dATP. We designed a Phase I trial of Triapine followed by the adenosine analog fludarabine in adults with refractory acute leukemias and aggressive myeloproliferative disorders (MPD). Two schedules were examined: (A) Triapine 105 mg/m(2)/day over 24 h followed by fludarabine daily x 5 (24 patients, fludarabine 15-30 mg/m(2)/dose); (B) Triapine 200mg/m(2) over 24 h followed by 5 days of fludarabine 30 mg/m(2) /day (9 patients). Complete and partial responses (CR, PR) Occurred in Schedule A (5/24, 21 %), with CR occurring at the 2 highest fludarabine doses (2/12, 17%). In contrast, no CR or PR Occurred in Schedule B. Four of the 5 responses occurred in patients with underlying MPD (4/14, 29%). Drug-related toxicities included fever and metabolic acidosis. Triapine 105 mg/m(2) followed by fludarabine 30 mg/m2 daily x 5 is active in refractory myeloid malignancies and warrants continuing study for patients with aggressive MPD. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Karp, Judith E.; Greer, Jacqueline] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Hematol Malignancies, Leukemia Program, Baltimore, MD 21231 USA. [Giles, Francis J.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Gojo, Lvana] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Morris, Lawrence] Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA. [Johnson, Bonny; Sznol, Mario] Vion Pharmaceut, New Haven, CT USA. [Low, Jennifer] Natl Canc Inst, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD USA. RP Karp, JE (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Hematol Malignancies, Leukemia Program, Baltimore, MD 21231 USA. EM jkarp2@jhmi.edu FU NCI NIH HHS [U01 CA70095, U01 CA070095, U01 CA070095-14]; NCRR NIH HHS [M01 RR000052, M01-RR0052] NR 36 TC 53 Z9 54 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2008 VL 32 IS 1 BP 71 EP 77 DI 10.1016/j.leukres.2007.05.003 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 244VE UT WOS:000251892600012 PM 17640728 ER PT S AU Hristovski, D Friedman, C Rindflesch, TC Peterlin, B AF Hristovski, D. Friedman, C. Rindflesch, T. C. Peterlin, B. BE Bruza, P Weeber, M TI Literature-Based Knowledge Discovery using Natural Language Processing SO LITERATURE-BASED DISCOVERY SE Information Science and Knowledge Management LA English DT Article; Book Chapter ID BIOMEDICAL TEXT; FISH-OIL; DISEASE; LEVODOPA; ONTOLOGY; RAYNAUDS; SYSTEM AB Literature-based discovery (LBD) is an emerging methodology for uncovering nonovert relationships in the online research literature. Making such relationships explicit supports hypothesis generation and discovery. Currently LBD systems depend exclusively on co-occurrence of words or concepts in target documents, regardless of whether relations actually exist between the words or concepts. We describe a method to enhance LBD through capture of semantic relations from the literature via use of natural language processing (NLP). This paper reports on an application of LBD that combines two NLP systems: BioMedLEE and SemRep, which are coupled with an LBD system called BITOLA. The two NLP systems complement each other to increase the types of information utilized by BITOLA. We also discuss issues associated with combining heterogeneous systems. Initial experiments suggest this approach can uncover new associations that were not possible using previous methods. C1 [Hristovski, D.] Univ Ljubljana, Fac Med, Inst Biomed Informat, Ljubljana 1104, Slovenia. [Friedman, C.] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. [Rindflesch, T. C.] Natl Lib Med, Bethesda, MD USA. [Peterlin, B.] UMC, Div Med Genet, Ljubljana, Slovenia. RP Hristovski, D (reprint author), Univ Ljubljana, Fac Med, Inst Biomed Informat, Vrazov Trg 2-2, Ljubljana 1104, Slovenia. EM dimitar.hristovski@mf.uni-lj.si NR 33 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1568-1300 BN 978-3-540-68685-9 J9 INFORM SCI KNOWL MAN PY 2008 VL 15 BP 133 EP 152 D2 10.1007/978-3-540-68690-3 PG 20 WC Information Science & Library Science SC Information Science & Library Science GA BJW67 UT WOS:000267322000009 ER PT S AU Woolfe, A Elgar, G AF Woolfe, Adam Elgar, Greg BE VanHeyningen, V Hill, RE TI Organization of Conserved Elements Near Key Developmental Regulators in Vertebrate Genomes SO LONG-RANGE CONTROL OF GENE EXPRESSION SE Advances in Genetics LA English DT Review; Book Chapter ID NON-GENIC SEQUENCES; NONCODING SEQUENCES; FUGU-RUBRIPES; MOUSE GENOME; COMPUTATIONAL IDENTIFICATION; MULTIPLE ALIGNMENT; MAMMALIAN GENOMES; DISTAL ENHANCER; TELEOST FISH; MODEL GENOME AB Sequence conservation has traditionally been used as a means to target functional regions of complex genomes. In addition to its use in identifying coding regions of genes, the recent availability of whole genome data for a number of vertebrates has permitted high-resolution analyses of the noncoding "dark matter" of the genome. This has resulted in the identification of a large number of highly conserved sequence elements that appear to be preserved in all bony vertebrates. Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation. This chapter describes the identification and characterization of these elements, with particular reference to their composition and organization. (C) 2008, Elsevier Inc. C1 [Woolfe, Adam; Elgar, Greg] Univ London, Sch Biol & Chem Sci, London E1 4NS, England. RP Woolfe, A (reprint author), NHGRI, Genome Technol Branch, NIH, Rockville, MD 20870 USA. OI Elgar, Greg/0000-0001-7323-1596 FU Medical Research Council [G0401138] NR 92 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 BN 978-0-12-373881-3 J9 ADV GENET JI Adv. Genet. PY 2008 VL 61 BP 307 EP 338 DI 10.1016/S0065-2660(07)00012-0 PG 32 WC Genetics & Heredity SC Genetics & Heredity GA BQB47 UT WOS:000280569600013 PM 18282512 ER PT J AU Parks, CG Cooper, GS Dooley, MA Park, MM Treadwell, EL Gilkeson, GS AF Parks, C. G. Cooper, G. S. Dooley, M. A. Park, M. M. Treadwell, E. L. Gilkeson, G. S. TI Childhood agricultural and adult occupational exposures to organic dusts in a population-based case-control study of systemic lupus erythematosus SO LUPUS LA English DT Article DE systemic lupus erythematosus; endotoxins; hygiene hypothesis; occupational exposure; livestock; epidemiology ID SOUTHEASTERN UNITED-STATES; AUTOIMMUNE-DISEASES; CRYSTALLINE SILICA; RISK-FACTORS; EARLY-LIFE; ASTHMA; MICE; WORKERS; LIPOPOLYSACCHARIDE; INFECTIONS AB Organic dust exposure can influence the development and symptoms of immune-related diseases such as atopy and asthma, but has rarely been examined in relation to systemic autoimmunity. The present analyses explore the association of lifetime farm and occupational organic dust exposures with systemic lupus erythematosus (SLE) in recently diagnosed patients (n = 265) compared with controls (n = 355) frequency matched by age, sex and state. Questionnaire data included childhood farm residence, childhood and adult experience with specific crops, and adult work in textiles, hog or poultry processing and paper or furniture manufacture. Adjusted odds ratios (OR) and 95% confidence intervals (0) were estimated by logistic regression models including age, sex, state, race, education and silica exposure. Overall childhood or adult farm contact and childhood farm residence were not associated with SLE. Farm contact with livestock was inversely associated with SLE (OR = 0.55, 95% CI 0.35, 0.88). This effect was most pronounced among those with childhood farm residence and both childhood and adult livestock exposure (OR = 0.19; 95% CI 0.06, 0.63), but was difficult to separate from adult exposure to grains or corn. Other adult occupational exposures were not associated with SLE risk overall, regardless of childhood farm residence or livestock exposure, although an inverse association was seen among non-smokers (OR = 0.59; 95% CI 0.33, 1.1), particularly for textile work (OR = 0.34; 95% CI 0.19, 0.64). These exploratory findings support the development of studies to specifically investigate the effects of organic dust exposure on SLE risk, with particular attention to exposure assessment and characterization of demographics, smoking and other occupational exposures. C1 [Parks, C. G.] NIEHS, Epidemiol Branch, Durham, NC 27709 USA. [Parks, C. G.] NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Morgantown, WV USA. [Cooper, G. S.] US EPA, Washington, DC 20460 USA. [Dooley, M. A.; Park, M. M.] Univ N Carolina, Div Rheumatol, Chapel Hill, NC USA. [Treadwell, E. L.] E Carolina Univ, Sch Med, Dept Med, Greenville, NC USA. [Gilkeson, G. S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, POB 12233, Durham, NC 27709 USA. EM parks1@mail.nih.gov OI Parks, Christine/0000-0002-5734-3456 NR 33 TC 9 Z9 9 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2008 VL 17 IS 8 BP 711 EP 719 DI 10.1177/0961203308089436 PG 9 WC Rheumatology SC Rheumatology GA 337MT UT WOS:000258440900003 PM 18625648 ER PT J AU El-Chemaly, S Levine, SJ Moss, J AF El-Chemaly, Souheil Levine, Stewart J. Moss, Joel TI Lymphatics in lung disease SO LYMPHATIC CONTINUUM REVISITED SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE lymphangiogenesis; metastasis; lymphangiectasis; lymphangioleiomyomatosis; VEGF-D; VEGF-C ID ENDOTHELIAL GROWTH-FACTOR; BRONCHIOLITIS OBLITERANS SYNDROME; PULMONARY LYMPHANGIECTASIA; AIRWAY VASCULATURE; NODE METASTASIS; FACTOR-C; TUMOR LYMPHANGIOGENESIS; VESSEL DEVELOPMENT; NONIMMUNE HYDROPS; FACTOR RECEPTOR-3 AB The lymphatic circulation appears to be a vital component in lung biology in health and in disease. Animal models have established the role of the lymphatic circulation in neoplastic and inflammatory diseases of the lung, such as asthma and cancer, and allowed for the understanding of the molecular controls of lymphangiogenesis in normal lung development. Understanding the role of lymphatics in human lung disease appears likely to contribute to the understanding of the pathogenesis of disease and the development of novel therapeutic targets. C1 [El-Chemaly, Souheil; Levine, Stewart J.; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Rrn 6D03,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL002541-12] NR 80 TC 25 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1131 BP 195 EP 202 DI 10.1196/annals.1413.017 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHV94 UT WOS:000256902600018 PM 18519971 ER PT J AU Glasgow, CG Taveira-DaSilva, AM Darling, TN Moss, J AF Glasgow, Connie G. Taveira-DaSilva, Angelo M. Darling, Thomas N. Moss, Joel TI Lymphatic involvement in lymphangioleiomyomatosis SO LYMPHATIC CONTINUUM REVISITED SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE lymphangiogenesis; metastasis; lymphangioleiomyomatosis; VEGF-D; VEGF-C ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY-FUNCTION TESTS; SMOOTH-MUSCLE-CELLS; MATRIX METALLOPROTEINASES; PROGESTERONE-RECEPTORS; RENAL ANGIOMYOLIPOMAS; LUNG TRANSPLANTATION; PROGNOSTIC-FACTORS; DIURNAL-VARIATION; TISSUE INHIBITOR AB Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease affecting primarily premenopausal women. The disease is characterized by cystic lung disease, at times leading to respiratory compromise, abdominal tumors (in particular, renal angiomyolipomas), and involvement of the axial lymphatics (e.g., adenopathy, lymphangioleiomyomas). Disease results from the proliferation of neoplastic cells (LAM cells), which, in many cases, have a smooth muscle cell phenotype, express melanoma antigens, and have mutations in one of the tuberous sclerosis complex genes (TSC1 or TSC2). In the lung, LAM cells found in the vicinity of cysts are, at times, localized in nodules and may be responsible for cyst formation through the production of proteases. Lymphatic channels, expressing characteristic lymphatic endothelial cell markers, are found within the LAM lung nodules. LAM cells may also be localized within the walls of the axial lymphatics, and, in some cases, penetrate the wall and proliferate in the surrounding adipose tissue. Consistent with extensive lymphatic involvement in LAM, the serum concentration of VEGF-D, a lymphangiogenic factor, is higher in LAM patients than in healthy volunteers. C1 [Glasgow, Connie G.; Taveira-DaSilva, Angelo M.; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. RP Moss, J (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Rm 6D03,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov OI Darling, Thomas/0000-0002-5161-1974 FU Intramural NIH HHS [ZIA HL002541-16] NR 74 TC 14 Z9 15 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1131 BP 206 EP 214 DI 10.1196/annals.1413.018 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHV94 UT WOS:000256902600020 PM 18519973 ER PT J AU Pholphirul, P Vichyanond, P AF Pholphirul, Piriya Vichyanond, Pakorn BE Fanelli, JM TI Thailand SO MACROECONOMIC VOLATILITY, INSTITUTIONS AND FINANCIAL ARCHITECTURES: THE DEVELOPING WORLD EXPERIENCE LA English DT Article; Book Chapter C1 [Pholphirul, Piriya] NIDA, Sch Dev Econ, Bethesda, MD USA. [Pholphirul, Piriya] Chulalongkorn Univ, Bangkok 10330, Thailand. [Pholphirul, Piriya] Siam Cement Grp, Bangkok, Thailand. [Vichyanond, Pakorn] World Bank, Res Team, Washington, DC USA. RP Pholphirul, P (reprint author), NIDA, Sch Dev Econ, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PALGRAVE PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND BN 978-0-230-59018-2 PY 2008 BP 157 EP 189 D2 10.1057/9780230590182 PG 33 WC Business, Finance; Economics SC Business & Economics GA BRM98 UT WOS:000283134100007 ER PT J AU Ledesma-Carbayo, MJ Derbyshire, JA Sampath, S Santos, A Desco, M McVeigh, ER AF Ledesma-Carbayo, Maria J. Derbyshire, J. Andrew Sampath, Smita Santos, Andres Desco, Manuel McVeigh, Elliot R. TI Unsupervised estimation of myocardial displacement from tagged MR sequences using nonrigid registration SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; heart; myocardial motion; tagged MRI; motion tracking; nonrigid registration ID MAGNETIC-RESONANCE; SPATIAL MODULATION; IMAGE REGISTRATION; MOTION ESTIMATION; DEFORMATION; TRACKING; VALIDATION; RECOVERY; ECHOES; HEART AB We propose a fully automatic cardiac motion estimation technique that uses nonrigid registration between temporally adjacent images to compute the myocardial displacement field from tagged MR sequences using as inputs (sources) both horizontally and vertically tagged images. We present a new multi-source nonrigid registration algorithm employing a semilocal deformation model that provides controlled smoothness. The method requires no segmentation. We apply a multiresolution optimization strategy for better speed and robustness. The accuracy of the algorithm is assessed on experimental data (animal model) and healthy volunteer data by calculating the root mean square (RMS) difference in position between the estimated tag trajectories and manual tracings outlined by an expert. For the similar to 20000 tag lines analyzed (45 slices over 20-40 time frames), the RMS difference between the automatic tag trajectories and the manually segmented tag trajectories was 0.51 pixels (0.25 mm) for the animal data and 0.49 pixels (0.49 mm) for the human volunteer data. The RMS difference in the separation between adjacent tag lines (RMS_TS) was also assessed, resulting in an RMS_TS of 0.40 pixels (0.19 mm) in the experimental data and 0.52 pixels (0.56 mm) in the volunteer data. These results confirm the subpixel accuracy achieved using the proposed methodology. Magn Reson Med 59: 181-189, 2008. (C) 2007 Wiley-Liss, Inc. C1 [Ledesma-Carbayo, Maria J.; Derbyshire, J. Andrew; Sampath, Smita; McVeigh, Elliot R.] NHLBI, NIH, Cardiac Energet Lab, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ledesma-Carbayo, Maria J.; Santos, Andres] Univ Politecn Madrid, ETSI Telecomun, E-28040 Madrid, Spain. [Desco, Manuel] Univ Gregorio Maranon, Gen Hosp, Madrid, Spain. RP McVeigh, ER (reprint author), NHLBI, NIH, Cardiac Energet Lab, Dept Hlth & Human Serv, 10 Ctr Dr,MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM emcveigh@nih.gov RI Santos, Andres/C-4012-2009; Ledesma-Carbayo, Maria /D-5529-2009; Desco, Manuel/D-2822-2009 OI Santos, Andres/0000-0001-7423-9135; Ledesma-Carbayo, Maria /0000-0001-6846-3923; Desco, Manuel/0000-0003-0989-3231 FU NHLBI NIH HHS [Z01HL004609] NR 40 TC 24 Z9 25 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2008 VL 59 IS 1 BP 181 EP 189 DI 10.1002/mrm.21444 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 246AJ UT WOS:000251979600023 PM 18058938 ER PT S AU Basser, PJ AF Basser, Peter J. BE Hurlimann, MD Song, YQ Fantazzini, P Bortolotti, V TI Neural Tissue as Porous Media SO Magnetic Resonance in Porous Media SE AIP Conference Proceedings LA English DT Proceedings Paper CT 9th International Bologna Conference on Magnetic Resonance in Porous Media CY JUL 13-17, 2008 CL Cambridge, MA SP Schlumberger, Chevron, Bruker, Magritek, Tecmag, T2 Biosystems, ABQMR, Westview Press, Springer, Alma Mater Studiorum, Univ Bologna, Varian, ACT NMR Solut, Spinlock, Nova Med, JS Res, Spectra Phys, Oxford Univ Press, Wiley VCH, Newport DE diffusion; MRI; porous media; neuroradiology; q-space ID MOLECULAR SELF-DIFFUSION; CENTRAL-NERVOUS-SYSTEM; HUMAN BRAIN; FIELD GRADIENT; SPIN-ECHO; TENSOR; NMR; MRI; SPACE; SPECTROSCOPY AB The fields of MR in Porous Media and Neuroradiology have largely developed separately during the past two decades with little appreciation of the problems. challenges and methodologies of the other. However, this trend is clearly changing and possibilities for significant cross-fertilization and synergies are now being realized. C1 NIH, Bethesda, MD 20892 USA. RP Basser, PJ (reprint author), NIH, 13 South Dr,MSC 5772,Bldg 13,Rm 3W16, Bethesda, MD 20892 USA. EM pjbasser@helix.nih.gov NR 39 TC 1 Z9 1 U1 1 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0612-4 J9 AIP CONF PROC PY 2008 VL 1081 BP 26 EP 28 PG 3 WC Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Physics; Radiology, Nuclear Medicine & Medical Imaging GA BIS75 UT WOS:000262472000007 ER PT J AU Liu, Y Bohr, VA Lansdorp, P AF Liu, Yie Bohr, Vilhelm A. Lansdorp, Peter TI Telomere, telomerase and aging SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material C1 [Liu, Yie; Bohr, Vilhelm A.] NIA, NIH, Lab Mol Gerontol, GRC, Baltimore, MD 21224 USA. [Lansdorp, Peter] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Lansdorp, Peter] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Bohr, VA (reprint author), NIA, NIH, Lab Mol Gerontol, GRC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 0 TC 7 Z9 8 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN-FEB PY 2008 VL 129 IS 1-2 BP 1 EP 2 DI 10.1016/j.mad.2007.12.001 PG 2 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 282MD UT WOS:000254571000001 PM 18215415 ER PT J AU Savage, SA Alter, BP AF Savage, Sharon A. Alter, Blanche P. TI The role of telomere biology in bone marrow failure and other disorders SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE telomere; bone marrow failure; dyskeratosis congenita; pulmonary fibrosis; aplastic anemia ID STEM-CELL TRANSPLANTATION; DIAMOND-BLACKFAN-ANEMIA; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; CHRONIC MYELOID-LEUKEMIA; REVERSE-TRANSCRIPTASE COMPONENT; LINKED DYSKERATOSIS-CONGENITA; ACQUIRED APLASTIC-ANEMIA; HIGH-DOSE CHEMOTHERAPY; MYELODYSPLASTIC SYNDROMES; FANCONI-ANEMIA AB Telomeres, consisting of nucleotide repeats and a protein complex at chromosome ends, are essential in maintaining chromosomal integrity. Dyskeratosis congenita (DC) is the inherited bone marrow failure syndrome (IBMFS) that epitomizes the effects of abnormal telomere biology. Patients with DC have extremely short telomere lengths (< 1 st percentile) and many have mutations in telomere biology genes. Interpretation of telomere length in other IBMFSs is less straightforward. Abnormal telomere shortening has been reported in patients with apparently acquired hematologic disorders, including aplastic anemia, myeolodysplasia, paroxysmal nocturnal hemoglobinuria, and leukemia. In these disorders, the shortest-lived cells have the shortest telomeres, suggestive of increased hematopoietic stress. Telomeres are also markers of replicative and/or oxidative stress in other complex disease pathways, such as inflammation, stress, and carcinogenesis. The spectrum of related disorders caused by mutations in telomere biology genes extends beyond classical DC to include marrow failure that does not respond to immunosuppression, idiopathic pulmonary fibrosis, and possibly other syndromes. We suggest that such patients be categorized as having an inherited disorder of telomere biology. Longitudinal studies of patients with very short telomeres but without classical DC are necessary to further understand the long-term sequelae, such as malignancy, osteonecrosis/osteoporosis, and pulmonary and liver disease. Published by Elsevier Ireland Ltd. C1 [Savage, Sharon A.; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 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 [Z99 CA999999] NR 150 TC 42 Z9 48 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN-FEB PY 2008 VL 129 IS 1-2 BP 35 EP 47 DI 10.1016/j.mad.2007.11.002 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 282MD UT WOS:000254571000006 PM 18160098 ER PT J AU Weng, NP AF Weng, Nan-ping TI Telomere and adaptive immunity SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE human; telomere; telomerase; aging; T cells; B cells ID CD8(+) T-CELLS; DOMINANT DYSKERATOSIS-CONGENITA; REPLICATIVE SENESCENCE; B-LYMPHOCYTES; REVERSE-TRANSCRIPTASE; LIFE-SPAN; FUNCTIONAL-CHARACTERIZATION; SHORTENED TELOMERES; LENGTH; MEMORY AB The adaptive immune response relies on the ability of lymphocytes to undergo periodic massive expansion. It is an enigma how lymphocytes are able to undergo this seemingly unlimited number of cell divisions. Telomeres and telomerase play a critical role in regulation of the replicative lifespan of cells, providing a potential mechanism which lymphocytes may employ. Here I will review the recent progress of the role of telomeres and telomerase in lymphocyte differentiation, function, and aging. Published by Elsevier Ireland Ltd. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wengn@mail.nih.gov FU Intramural NIH HHS [Z01 AG000756-10] NR 60 TC 38 Z9 41 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN-FEB PY 2008 VL 129 IS 1-2 BP 60 EP 66 DI 10.1016/j.mad.2007.11.005 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 282MD UT WOS:000254571000008 PM 18199471 ER PT J AU Olson, MT Epstein, JA Yergey, AL AF Olson, Matthew T. Epstein, Jonathan A. Yergey, Alfred L. BE Vekey, K Telekes, A Vertes, A TI De novo sequencing of peptides SO MEDICAL APPLICATIONS OF MASS SPECTROMETRY LA English DT Article; Book Chapter ID TANDEM MASS-SPECTROMETRY; COMPUTER-PROGRAM; ALGORITHM; IDENTIFICATION; DATABASES; SPECTRA C1 [Olson, Matthew T.; Epstein, Jonathan A.; Yergey, Alfred L.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Yergey, AL (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM aly@helix.nih.gov NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-055465-5 PY 2008 BP 195 EP 201 DI 10.1016/B978-044451980-1.50011-2 PG 7 WC Engineering, Biomedical SC Engineering GA BEN59 UT WOS:000317479200010 ER PT J AU Kannel, WB Benjamin, EJ AF Kannel, William B. Benjamin, Emelia J. TI Status of the epidemiology of atrial fibrillation SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; RISK-FACTORS; DIASTOLIC DYSFUNCTION; STROKE PREVENTION; UNITED-STATES; ALCOHOL-CONSUMPTION AB Atrial fibrillation (AF), an increasingly common dysrhythmia, is responsible for substantial morbidity and mortality. Currently in the United States, approximately 2.3 million people are diagnosed with AF and, based on the census, this number may rise to 5.6 million by 2050. Risk factors for AF include advancing age and cardiovascular disease and its risk factors. The chief hazard of AF is embolic stroke, which is increased four- to fivefold, assuming great importance in advanced age when it becomes a dominant factor. AF is associated with about a doubling of mortality. C1 [Kannel, William B.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA. [Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Kannel, William B.; Benjamin, Emelia J.] Boston Univ, Sch Med, Med Ctr, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Med Ctr, Boston, MA 02118 USA. RP Kannel, WB (reprint author), Boston Univ, Framingham Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM billkannel@yahoo.com OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01 HC025195, N01-HC 25195, N01HC25195, R01 HL076784]; NIA NIH HHS [1R01 AG028321, R01 AG028321]; NINDS NIH HHS [6R01-NS 17950, R01 NS017950] NR 95 TC 151 Z9 155 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2008 VL 92 IS 1 BP 17 EP + DI 10.1016/j.mcna.2007.09.002 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA 246YU UT WOS:000252045100003 PM 18060995 ER PT S AU Chen, J Yao, JH Thornasson, D AF Chen, Jeremy Yao, Jianhua Thornasson, David BE Metaxas, D Axel, L Fichtinger, G Szekely, G TI Automatic Determination of Arterial Input Function for Dynamic Contrast Enhanced MRI in Tumor Assessment SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2008, PT I, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 11th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2008) CY SEP 06-10, 2008 CL New York, NY SP Rutgers Univ, New York Univ, Robarts Res Inst, NE Digital Inc, Medtron Inc, Siemens Corp Res, Philips, GE DE DCE-MRI; AIF; tumor imaging AB Dynamic Contrast Enhanced MRI (DCE-MRI) is today one of the most Popular methods for tumor assessment. Several pharmacokinctic models have been proposed to analyze DCE-MRI. Most of them depend on an accurate arterial input function (AIF). We propose an automatic and versatile method to determine the AIF. The method has two stages, detection and se-mentation. incorporating, knowledge about artery structure, fluid kinetics, and the dynamic temporal property of DCE-MRI. We have applied Our method in DCE-MRIs of four different body parts: breast, brain, liver and prostate. The results show that we achieve average 89.5% success rate for 40 cases. The pharmacokinetic parameters computed from the automatic AIF are highly agreeable with those from a manually derived AIF (R(2)=0.89. P(T double left arrow t)=0.19) and a semiautomatic AIF (R(2)=0.98. P(T double left arrow t)=0.01). C1 [Chen, Jeremy; Yao, Jianhua; Thornasson, David] Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Chen, J (reprint author), Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 8 TC 8 Z9 8 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-85987-1 J9 LECT NOTES COMPUT SC PY 2008 VL 5241 BP 594 EP 601 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BIO76 UT WOS:000261373700071 ER PT S AU Saybasili, H Kellman, P Derbyshire, JA McVeigh, ER Guttman, MA AF Saybasili, Haris Kellman, Peter Derbyshire, J. Andrew McVeigh, Elliot R. Guttman, Michael A. BE Metaxas, D Axel, L Fichtinger, G Szekely, G TI Parallelized Hybrid TGRAPPA Reconstruction for Real-Time Interactive MRI SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2008, PT II, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 11th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2008) CY SEP 06-10, 2008 CL New York, NY SP Rutgers Univ, New York Univ, Robarts Res Inst, NE Digital Inc, Medtron Inc, Siemens Corp Res, Philips, GE ID TSENSE AB Real-time parallel MRI reconstruction was demonstrated using a hybrid implementation of the TGRAPPA algorithm. The GRAPPA coefficients were calculated in k-space and applied in the image domain after appropriate transformation, thereby achieving improved speed and excellent image quality. Adaptive B1-weighted combining of the per coil images permitted use of pre-calculated composite image domain weights providing significant, decrease in computation. The weight calculation was decoupled from the real-time image reconstruction as a Parallel processing thread which was updated in an adaptive manner to speed convergence in the event of interactive change in scan plane. The computation was parallelized and implemented on a general purpose multicore architecture. Reconstruction speeds of 65-70 frames per second were achieved with a matrix of 192x144 with 15 coils. C1 [Saybasili, Haris; Kellman, Peter; Derbyshire, J. Andrew; Guttman, Michael A.] NHLBI, NIH, DHHS, Bldg 10, Bethesda, MD 20892 USA. [Saybasili, Haris] Bogazici Univ, Biomed Engn Inst, Istanbul, Turkey. [McVeigh, Elliot R.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. RP Saybasili, H (reprint author), NHLBI, NIH, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM saybasilih@mail.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-85989-5 J9 LECT NOTES COMPUT SC PY 2008 VL 5242 BP 163 EP 170 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BIO77 UT WOS:000261373800020 ER PT S AU Wu, M Chang, LC Walker, L Lemaitre, H Barnett, AS Marenco, S Pierpaoli, C AF Wu, M. Chang, L. -C. Walker, L. Lemaitre, H. Barnett, A. S. Marenco, S. Pierpaoli, C. BE Metaxas, D Axel, L Fichtinger, G Szekely, G TI Comparison of EPI Distortion Correction Methods in Diffusion Tensor MRI Using a Novel Framework SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2008, PT II, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 11th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2008) CY SEP 06-10, 2008 CL New York, NY SP Rutgers Univ, New York Univ, Robarts Res Inst, NE Digital Inc, Medtron Inc, Siemens Corp Res, Philips, GE DE DTI; EPI distortion correction; B-0 field mapping; B-spline image registration ID IMAGES; ECHO; MODEL AB Diffusion weighted images (DWIs) are commonly acquired with Echo-planar imaging (EPI). B0 inhomogeneities affect EPI by producing spatially nonlinear image distortions. Several strategies have been proposed to correct EPI distortions including B-0 field mapping (B0M) and image registration. In this study. an experimental framework is proposed to evaluation the performance of different EPI distortion correction methods in improving DT-derived quantities. A deformable registration based method with mutual information metric and cubic B-spline modeled constrained deformation field (BSP) is proposed as an alternative when B-0 mapping data are not available. BSP method is qualitatively and quantitatively compared to B0M method using the framework. Both methods can successful reduce EPI distortions and significantly improve the quality of DT-derived quantities. Overall, B0M was clearly superior in infratentorial regions including brainstem and cerebellum, as well as in the ventral areas of the temporal lobes while BSP was better in all rostral brain regions. C1 [Wu, M.; Walker, L.; Pierpaoli, C.] NICHHD, NIH, Bethesda, MD 20892 USA. [Wu, M.] Univ Pittsburgh, Dept Elect & Comp Engn, Pittsburgh, PA USA. [Chang, L. -C.] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC USA. [Lemaitre, H.; Barnett, A. S.; Marenco, S.] NIMH, NIH, Bethesda, MD 20892 USA. RP Wu, M (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM cpla@nih.gov NR 13 TC 30 Z9 30 U1 1 U2 7 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-85989-5 J9 LECT NOTES COMPUT SC PY 2008 VL 5242 BP 321 EP 329 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BIO77 UT WOS:000261373800039 ER PT S AU Li, M Mazilu, D Horvath, KA AF Li, Ming Mazilu, Dumitru Horvath, Keith A. BE Metaxas, D Axel, L Fichtinger, G Szekely, G TI Robotic System for Transapical Aortic Valve Replacement with MRI Guidance SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2008, PT II, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 11th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2008) CY SEP 06-10, 2008 CL New York, NY SP Rutgers Univ, New York Univ, Robarts Res Inst, NE Digital Inc, Medtron Inc, Siemens Corp Res, Philips, GE ID PROSTATE INTERVENTIONS; CLOSED MRI; BIOPSY AB This paper reports our work oil developing a robotic surgical system for transapical beating heart aortic valve replacement (AVR) under interactive real-time magnetic resonance imaging (rtMRI) guidance. Our system integrates a real-time MRI system, a compound MRI robot, as well as an interface for the surgeon to plan the procedure and manipulate the robot. The compound robot consists of a positioning module and a valve delivery module. A 5-DOF Innomotion positioning arm provides and maintains direct access to the native aortic valve. A newly developed 3-DOF robotic valve delivery module allows the surgeon to remotely control bioprosthetic valve delivery with MRI guidance. Preliminary evaluation of the parameters of the robotic system demonstrates it can provide sufficient capability to successfully assist the surgeon. C1 [Li, Ming; Mazilu, Dumitru; Horvath, Keith A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RP Li, M (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA. EM lim2@mail.nih.gov; mazilud@mail.nih.gov; horvathka@mail.nih.gov NR 12 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-85989-5 J9 LECT NOTES COMPUT SC PY 2008 VL 5242 BP 476 EP 484 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BIO77 UT WOS:000261373800057 ER PT S AU Irfanoglu, MO Machiraju, R Sammet, S Pierpaoli, C Knopp, MV AF Irfanoglu, M. O. Machiraju, R. Sammet, S. Pierpaoli, C. Knopp, M. V. BE Metaxas, D Axel, L Fichtinger, G Szekely, G TI Automatic Deformable Diffusion Tensor Registration for Fiber Population Analysis SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2008, PT II, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 11th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2008) CY SEP 06-10, 2008 CL New York, NY SP Rutgers Univ, New York Univ, Robarts Res Inst, NE Digital Inc, Medtron Inc, Siemens Corp Res, Philips, GE ID MAGNETIC-RESONANCE IMAGES; MRI AB In this work, we propose a novel method for deformable tensor-to-tensor registration of Diffusion Tenser Images. Our registration method models the distances in between the tensors with Geode-sic-Loxodromes and employs a version of Multi-Dimensional Scaling (MDS) algorithm to unfold the manifold described with this metric. Defining the same shape properties as tensors, the vector images obtained through MDS are fed into a multi-step vector-image registration scheme and the resulting deformation fields are used to reorient the tenser fields. Results on brain DTI indicate that the proposed method is very suitable for deformable fiber-to-fiber correspondence and DTI-atlas construction. C1 [Irfanoglu, M. O.; Machiraju, R.] Ohio State Univ, Dept Comp Sci & Engn, Columbus, OH 43210 USA. [Sammet, S.; Knopp, M. V.] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. [Pierpaoli, C.] NIH, NICHHD, Bethesda, MD 20892 USA. RP Irfanoglu, MO (reprint author), Ohio State Univ, Dept Comp Sci & Engn, Columbus, OH 43210 USA. EM irfanoglu.1@osu.edu RI Sammet, Steffen/E-4009-2011 OI Sammet, Steffen/0000-0001-6564-9132 NR 11 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-85989-5 J9 LECT NOTES COMPUT SC PY 2008 VL 5242 BP 1014 EP 1022 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BIO77 UT WOS:000261373800122 ER PT S AU Wang, SJ Yao, JH Summers, RM AF Wang, Shijun Yao, Jianhua Summers, Ronald M. BE Giger, ML Karssemeijer, N TI DMLLE: A large-scale dimensionality reduction method for detection of polyps in CT colonography - art. no. 69150C SO MEDICAL IMAGING 2008: COMPUTER-AIDED DIAGNOSIS, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE computed tomographic colonography; dimensionality reduction; Diffusion Map; Locally Linear Embedding; DMLLE; SVM AB Computer-aided diagnosis systems have been shown to be feasible for polyp detection on computed tomography (CT) scans. After 3-D image segmentation and feature extraction, the dataset of colonic polyp candidates has large-scale and high dimension characteristics. In this paper, we propose a large-scale dimensionality reduction method based on Diffusion Map and Locally Linear Embedding for detection of polyps in CT colonography. By selecting partial data as landmarks, we first map the landmarks into a low dimensional embedding space using Diffusion Map. Then by using Locally Linear Embedding algorithm, non-landmark samples are embedded into the same low dimensional space according to their nearest landmark samples. The local geometry of samples is preserved in both the original space and the embedding space. We applied the proposed method called DMLLE to a colonic polyp dataset which contains 58336 candidates (including 85 6-9mm true polyps) with 155 features. Visual inspection shows that true polyps with similar shapes are mapped to close vicinity in the low dimensional space. FROC analysis shows that SVM with DMLLE achieves higher sensitivity with lower false positives per patient than that of SVM using all features. At the false positives of 8 per patient, SVM with DMLLE improves the average sensitivity from 64% to 75% for polyps whose sizes are in the range from 6 mm to 9 mm (p < 0.05). This higher sensitivity is comparable to unaided readings by trained radiologists. C1 [Wang, Shijun; Yao, Jianhua; Summers, Ronald M.] NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20895 USA. RP Wang, SJ (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20895 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7099-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6915 BP C9150 EP C9150 DI 10.1117/12.769844 PG 4 WC Biophysics; Engineering, Biomedical; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Engineering; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging GA BHU04 UT WOS:000256380300011 ER PT S AU Kinnard, LT Gavrielides, MA Myers, KJ Zeng, R Peregoy, J Pritchard, W Karanian, JW Petrick, N AF Kinnard, Lisa T. Gavrielides, Marlos A. Myers, Kyle J. Zeng, Rongping Peregoy, Jennifer Pritchard, William Karanian, John W. Petrick, Nicholas BE Giger, ML Karssemeijer, N TI Volume error analysis for lung nodules attached to pulmonary vessels in an anthropomorphic thoracic phantom - art. no. 69152Q SO MEDICAL IMAGING 2008: COMPUTER-AIDED DIAGNOSIS, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE volume estimation; lung nodule; lung tumor measures; phantom studies; CT imaging; bias and variance ID COMPUTED-TOMOGRAPHY; CT; SEGMENTATION; THICKNESS; ACCURACY; TUMORS; RISKS AB High-resolution CT, three-dimensional (3D) methods for nodule volumetry have been introduced, with the hope that such methods will be more accurate and consistent than currently used planar measures of size. However, the error associated with volume estimation methods still needs to be quantified. Volume estimation error is multi-faceted in the sense that it is impacted by characteristics of the patient, the software tool and the CT system. The overall goal of this research is to quantify the various sources of measurement error and, when possible, minimize their effects. In the current study, we estimated nodule volume from ten repeat scans of an anthropomorphic phantom containing two synthetic spherical lung nodules (diameters: 5 and 10 mm; density: -630 HU), using a 16-slice Philips CT with 20, 50, 100 and 200 mAs exposures and 0.8 and 3.0 mm slice thicknesses. True volume was estimated from an average of diameter measurements, made using digital calipers. We report variance and bias results for volume measurements as a function of slice thickness, nodule diameter, and X-ray exposure. C1 NIBIB, CDRH,Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst,US FDA, Div Imaging & Math,Off Sci & Engn Labs, Rockville, MD 20857 USA. US FDA, Lab Cardiovasc & Intervent Therapeut, Div Biol, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kinnard, LT (reprint author), NIBIB, CDRH,Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst,US FDA, Div Imaging & Math,Off Sci & Engn Labs, Rockville, MD 20857 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7099-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6915 BP Q9152 EP Q9152 DI 10.1117/12.773039 PG 9 WC Biophysics; Engineering, Biomedical; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Engineering; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging GA BHU04 UT WOS:000256380300094 ER PT S AU Wang, SJ Van Uitert, RL Summers, RM AF Wang, Shijun Van Uitert, Robert L. Summers, Ronald M. BE Giger, ML Karssemeijer, N TI Automated matching of supine and prone colonic polyps based on PCA and SVMs SO MEDICAL IMAGING 2008: COMPUTER-AIDED DIAGNOSIS, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE computed tomographic colonography; computer aided detection; supine and prone polyp matching; principal component analysis; Support Vector Machines ID CT COLONOGRAPHY AB Computed tomographic colonography (CTC) is a feasible and minimally invasive method for the detection of colorectal polyps and cancer screening. In current practice, a patient will be scanned twice during the CTC examination - once supine and once prone. In order to assist the radiologists in evaluating colon polyp candidates in both scans, we expect the computer aided detection (CAD) system can provide not only the locations of suspicious polyps, but also the possible matched pairs of polyps in two scans. In this paper, we propose a new automated matching method based on the extracted features of polyps by using principal component analysis (PCA) and Support Vector Machines (SVMs). Our dataset comes from the 104 CT scans of 52 patients with supine and prone positions collected from three medical centers. From it we constructed two groups of matched polyp candidates according to the size of true polyps: group A contains 12 true polyp pairs (> 9 mm) and 454 false pairs; group B contains 24 true polyp pairs (6-9 mm) and 514 false pairs. By using PCA, we reduced the dimensions of original data (with 157 attributes) to 30 dimensions. We did leave-one-patient-out test on the two groups of data. ROC analysis shows that it is easier to match bigger polyps than that of smaller polyps. On group A data, when false alarm probability is 0.20, the sensitivity of SVM achieves 0.83 which shows that automated matching of polyp candidates is practicable for clinical applications. C1 [Wang, Shijun; Van Uitert, Robert L.; Summers, Ronald M.] NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20895 USA. RP Wang, SJ (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20895 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7099-7 J9 PROC SPIE PY 2008 VL 6915 AR 69150B DI 10.1117/12.769583 PG 5 WC Biophysics; Engineering, Biomedical; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Engineering; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging GA BHU04 UT WOS:000256380300010 ER PT S AU Park, S Clarkson, E AF Park, Subok Clarkson, Eric BE Sahiner, B Manning, DJ TI Markov-chain Monte Carlo for the performance of a channelized-ideal observer in detection tasks with non-Gaussian lumpy backgrounds - art. no. 69170T SO MEDICAL IMAGING 2008: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE Bayesian ideal observer; channelized-ideal observer; Markov-chain Monte Carlo; efficient channels; non-Gaussian lumpy backgrounds AB The Bayesian ideal observer is optimal among all observers and sets an upper bound for observer performance in binary detection tasks.(1) This observer provides a quantitative measure of diagnostic performance of an imaging system, summarized by the area under the receiver operating characteristic curve (AUC),(1) and thus should be used for image quality assessment whenever possible. However, computation of ideal-observer performance is difficult because this observer requires the full description of the statistical properties of the signal-absent and signal-present data, which are often unknown in tasks involving complex backgrounds. Furthermore, the dimension of the integrals that need to be calculated for the observer is huge. To estimate ideal-observer performance in detection tasks with non-Gaussian lumpy backgrounds, Kupinski et al.(2) developed a Markov-chain Monte Carlo (MCMC) method, but this method has a disadvantage of long computation times. In an attempt to reduce the computation load and still approximate ideal-observer performance, Park et al.(3,4) investigated a channelized-ideal observer (CIO) in similar tasks and found that the CIO with singular vectors of the imaging system approximated the performance of the ideal observer. But, in that work, an extension of the Kupinski MCMC was used for calculating the performance of the CIO and it did not reduce the computational burden. In the current work, we propose a new MCMC method, which we call a CIO-MCMC, to speed up the computation of the CIO. We use singular vectors of the imaging system as efficient channels for the ideal observer. Our results show that the CIO-MCMC has the potential to speed up the computation of ideal observer performance with a large number of channels. C1 [Park, Subok] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Park, S (reprint author), 10903 New Hampshire Ave,Bldg 62,Room 3111, Silver Spring, MD 20993 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7101-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6917 BP T9170 EP T9170 DI 10.1117/12.771704 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHT13 UT WOS:000256058800026 ER PT S AU Paquerault, S Samuelson, FW Petrick, N Myers, KJ AF Paquerault, Sophie Samuelson, Frank W. Petrick, Nicholas Myers, Kyle J. BE Sahiner, B Manning, DJ TI Comparing signal-based,and case-based methodologies for CAD assessment in a detection task SO MEDICAL IMAGING 2008: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE computer-aided detection; multiple reader multiple case (MRMC) analysis; free-response receiver operating characteristics; receiver operating characteristics ID COMPUTER-AIDED DETECTION; SCREENING MAMMOGRAPHY; SENSITIVITY AB We are investigating the potential for differences in study conclusions when assessing the estimated impact of a computer-aided detection (CAD) system on readers' performance using a signal-based performance analysis derived from Free-response Receiver Operating Characteristics (FROC) versus a case-based performance analysis derived from Receiver Operating Characteristics (ROC) analysis. To consider this question, we utilized reader data from a CAD assessment study based on 100 mammographic background images to which fixed-size and fixed-intensity Gaussian signals were added, generating a low- and high-intensity set. The study thus allowed CAD assessment in two situations: when CAD sensitivity was 1) superior or 2) equivalent or lower than the average reader. Seven readers were asked to review each set using CAD in both second-reader and concurrent modes. Signal-based detection results were analyzed using the area under the FROC curve below 0.5 false positives per image. Case-based decision results were analyzed using the area under the parametric ROC curve. The results were consistent between the signal-based and case-based analyses for the low-intensity set, suggesting that CAD in both reading modes can increase reader signal-based detection and case-based decision accuracies. For the high-intensity set, the signal-based and case-based analysis suggested different conclusions regarding the utility of CAD, although neither analysis resulted in statistical significance. C1 [Paquerault, Sophie; Samuelson, Frank W.; Petrick, Nicholas; Myers, Kyle J.] US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. RP Paquerault, S (reprint author), US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7101-7 J9 PROC SPIE PY 2008 VL 6917 AR 691708 DI 10.1117/12.771498 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHT13 UT WOS:000256058800006 ER PT S AU Tan, S Yao, JH Yao, L Summers, RM Ward, MM AF Tan, Sovira Yao, Jianhua Yao, Lawrence Summers, Ronald M. Ward, Michael M. BE Reinhardt, JM Pluim, JPW TI Vertebral surface registration using ridgelines/crestlines - art. no. 69140H SO MEDICAL IMAGING 2008: IMAGE PROCESSING, PTS 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE surface registration; ICP; ridgelines/crestlines; level set; triangular mesh AB The Iterative Closest Point (ICP) algorithm is an efficient and popular technique for surface registration. It however suffers from the well-known problem of local minima that make the algorithm stop before it reaches the desired global solution. ICP can be improved by the use of landmarks or features. We recently developed a level set capable of evolving on the surface of an object represented by a triangular mesh. This level set permits the segmentation of portions of a surface based on curvature features. The boundary of a segmented portion forms a ridgeline/crestline. We show that the ridgelines/crestlines and corresponding enclosed surfaces extracted by the algorithm can substantially improve ICP registration. We compared the performance of an ICP algorithm in three setups: 1) ICP without landmarks. 2) ICP using ridgelines. 3) ICP using ridgelines and corresponding enclosed surfaces. Our material consists of vertebral body surfaces extracted for a study about the progression of Ankylosing Spondylitis. Same vertebrae scanned at intervals of one or two years were rigidly registered. Vertebral body rims and the end plate surfaces they enclose were used as landmarks. The performance measure was the mean error distance between the registered surfaces. From the one hundred registrations that we performed the average mean error was respectively 0.503mm, 0.335mm and 0.254mm for the three setups. Setup 3 almost halved the average error of setup 1. Moreover the error range is dramatically reduced from [0.0985, 2.19]mm to just [0.0865, 0.532]mm, making the algorithm very robust. C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIAMSD, NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7098-0 J9 P SOC PHOTO-OPT INS PY 2008 VL 6914 BP H9140 EP H9140 DI 10.1117/12.769472 PN 1-3 PG 8 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BHT12 UT WOS:000256058600015 ER PT S AU Tan, S Ward, MM AF Tan, Sovira Ward, Michael M. BE Reinhardt, JM Pluim, JPW TI Semi-synthetic digital phantoms incorporating natural structured noise and boundary inhomogeneities - art. no. 69144W SO MEDICAL IMAGING 2008: IMAGE PROCESSING, PTS 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE validation; segmentation; digital phantom; parameter optimization; natural structured noise ID ACTIVE CONTOURS AB Validating segmentation algorithms remains a difficult problem. Manual segmentation taken as gold standard is time-consuming and can still be contentious especially in the case of complex 3D objects and in the presence of important partial volume effect (PVE). In contrast digital phantoms have well-defined built-in boundaries even when PVE is simulated. However their degree of realism is questionable. In particular the rich natural structures inside an object that constitute one of the most difficult obstacles to segmentation are to this day too complex to model. A new method for constructing semi-synthetic digital phantoms was recently proposed that incorporates natural structured noise and boundary inhomogeneities. However only one phantom was presented and validation was lacking. In the present work we constructed 5 phantoms of vertebral bodies. Validation of phantoms should test their ability to predict how an algorithm will perform when confronted to real data. Our phantoms were used to compare the performance of two level set based segmentation algorithms and find the parameters that optimize their performances. We validated the phantoms by correlating the results obtained on them with those obtained on 50 real vertebrae. We show that: 1) the phantoms accurately predict which segmentation algorithm will perform better with real clinical data. 2) by combining the results obtained by the 5 different phantoms we can extract useful predictions about the performance of different sets of parameters on real data. Because the phantoms possess the high variability of real data predictions based on only one phantom would fail. C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIAMSD, NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7098-0 J9 P SOC PHOTO-OPT INS PY 2008 VL 6914 BP W9144 EP W9144 DI 10.1117/12.770465 PN 1-3 PG 8 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BHT12 UT WOS:000256058600168 ER PT S AU Sonkova, P Evangelou, IE Gallo, A Cantor, FK Ohayon, J McFarland, HF Bagnato, F AF Sonkova, Pavlina Evangelou, Iordanis E. Gallo, Antonio Cantor, Fredric K. Ohayon, Joan McFarland, Henry F. Bagnato, Francesca BE Reinhardt, JM Pluim, JPW TI Semi-automatic segmentation and modeling of the cervical spinal cord for volume quantification in multiple sclerosis patients from Magnetic Resonance Images SO MEDICAL IMAGING 2008: IMAGE PROCESSING, PTS 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE segmentation; level sets; MRI; spinal cord; atrophy; multiple sclerosis ID EDGE-DETECTION; MRI; DISABILITY; ATROPHY; DIFFUSION; SPACE; SHAPE; AREA AB Spinal cord (SC) tissue loss is known to occur in some patients with multiple sclerosis (MS), resulting in SC atrophy. Currently, no measurement tools exist to determine the magnitude of SC atrophy from Magnetic Resonance Images (MRI). We have developed and implemented a novel semi-automatic method for quantifying the cervical SC volume (CSCV) from Magnetic Resonance Images (MRI) based on level sets. The image dataset consisted of SC MRI exams obtained at 1.5 Tesla from 12 MS patients (10 relapsing-remitting and 2 secondary progressive) and 12 age- and gender-matched healthy volunteers (HVs). 3D high resolution image data were acquired using an IR-FSPGR sequence acquired in the sagittal plane. The mid-sagittal slice (MSS) was automatically located based on the entropy calculation for each of the consecutive sagittal slices. The image data were then pre-processed by 3D anisotropic diffusion filtering for noise reduction and edge enhancement before segmentation with a level set formulation which did not require re-initialization. The developed method was tested against manual segmentation (considered ground truth) and intra-observer and inter-observer variability were evaluated. C1 [Sonkova, Pavlina; Evangelou, Iordanis E.; Gallo, Antonio; Cantor, Fredric K.; Ohayon, Joan; McFarland, Henry F.; Bagnato, Francesca] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Evangelou, IE (reprint author), NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. EM evangeloui@ninds.nih.gov NR 21 TC 1 Z9 1 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7098-0 J9 PROC SPIE PY 2008 VL 6914 AR 69144I DI 10.1117/12.773055 PN 1-3 PG 10 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BHT12 UT WOS:000256058600155 ER PT S AU Xue, ZY Long, LR Antani, S Jeronimo, J Thoma, GR AF Xue, Zhiyun Long, L. Rodney Antani, Sameer Jeronimo, Jose Thoma, George R. BE Andriole, KP Siddiqui, KM TI A web-accessible content-based cervicographic image retrieval system SO MEDICAL IMAGING 2008: PACS AND IMAGING INFORMATICS SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE content-based image retrieval; Web-based medical image system; uterine cervix cancer AB Content-based image retrieval (CBIR) is the process of retrieving images by directly using image visual characteristics. In this paper, we present a prototype system implemented for CBIR for a uterine cervix image (cervigram) database. This cervigram database is a part of data collected in a multi-year longitudinal effort by the National Cancer Institute (NCI), and archived by the National Library of Medicine (NLM), for the study of the origins of, and factors related to, cervical precancer/cancer. Users may access the system with any Web browser. The system is built with a distributed architecture which is modular and expandable; the user interface is decoupled from the core indexing and retrieving algorithms, and uses open communication standards and open source software. The system tries to bridge the gap between a user's semantic understanding and image feature representation, by incorporating the user's knowledge. Given a user-specified query region, the system returns the most similar regions from the database, with respect to attributes of color, texture, and size. Experimental evaluation of the retrieval performance of the system on "ground-truth" test data illustrates its feasibility to serve as a possible research tool to aid the study of the visual characteristics of cervical neoplasia. C1 [Xue, Zhiyun; Long, L. Rodney; Antani, Sameer; Thoma, George R.] Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Xue, ZY (reprint author), Natl Lib Med, NIH, Bethesda, MD 20894 USA. EM xuez@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 NR 17 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7103-1 J9 PROC SPIE PY 2008 VL 6919 AR 691907 DI 10.1117/12.769440 PG 9 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BHU33 UT WOS:000256422200006 ER PT S AU Linguraru, MG Mukherjee, N Van Uitert, RL Summers, RM Gladwin, MT Machado, RF Wood, BJ AF Linguraru, Marius George Mukherjee, Nisha Van Uitert, Robert L. Summers, Ronald M. Gladwin, Mark T. Machado, Roberto F. Wood, Bradford J. BE Hu, XP Clough, AV TI Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension - art. no. 691612 SO MEDICAL IMAGING 2008: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE pulmonary hypertension; sickle cell disease; pulmonary artery; segmentation; skeletonization; quantification ID RISK-FACTOR; DISEASE; DEATH; CT AB Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed,to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance. C1 [Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Wood, Bradford J.] Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NR 18 TC 2 Z9 2 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7100-0 J9 P SOC PHOTO-OPT INS PY 2008 VL 6916 BP 91612 EP 91612 DI 10.1117/12.770485 PG 8 WC Engineering, Biomedical; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BHT07 UT WOS:000256051300035 ER PT S AU Yao, JH Frentz, S Li, J Summers, R AF Yao, Jianhua Frentz, Suzanne Li, Jiang Summers, Ronald BE Hu, XP Clough, AV TI Polyp height and width measurement using topographic height map - art. no. 69160B SO MEDICAL IMAGING 2008: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE CT colonography; polyp measurement; topographic height map ID CT COLONOGRAPHY AB The height and width of colonic polyps are important characteristics to evaluate the status and malignancy of polyps. We borrow the idea from geographic information systems to employ topographic height maps to compute the polyp height and width. The height map is generated using a ray-casting algorithm through an orthogonal projection. A concentric index is devised to gauge the quality of the height map and is maximized in a multi-scale spiral spherical search for the optimal projection. We then locate the polyp tip and neck using directional height profiles, and derive height and width measurement based on geometrical analysis. We manually measured the height and width of 58 polyps and performed paired t-tests between manual measurement and height map measurement. The test shows that Pearson correlation is 0.742 and P(T<=t) is 0.01 for height measurement; and Pearson correlation is 0.663 and P(T<=t) is 0.002 for width measurement. C1 [Yao, Jianhua; Frentz, Suzanne; Li, Jiang; Summers, Ronald] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7100-0 J9 P SOC PHOTO-OPT INS PY 2008 VL 6916 BP B9160 EP B9160 DI 10.1117/12.769463 PG 10 WC Engineering, Biomedical; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BHT07 UT WOS:000256051300009 ER PT S AU Roney, CA Xie, JW Xu, BY Jabour, P Griffiths, G Summers, RM AF Roney, Celeste A. Xie, Jianwu Xu, Biying Jabour, Paul Griffiths, Gary Summers, Ronald M. BE Hu, XP Clough, AV TI Glycoprotein expression by adenomatous polyps of the colon SO MEDICAL IMAGING 2008: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE colon cancer; UEA-1; drug targeting; computed tomography; polymerized liposomes ID ULEX-EUROPAEUS AGGLUTININ-1; COLORECTAL-CANCER; BINDING-SITES; CT COLONOGRAPHY; NORMAL MUCOSA; STOOL; DNA; BIOSYNTHESIS; NONPOLYPOSIS; POPULATIONS AB Colon cancer is the second leading cause of cancer related deaths in the United States. Specificity in diagnostic imaging for detecting colorectal adenomas, which have a propensity towards malignancy, is desired. Adenomatous polyp specimens of the colon were obtained from the mouse model of colorectal cancer called adenomatous polyposis coli-multiple intestinal neoplasia (APC(Min))., Histological evaluation, by the legume protein Ulex europaeus agglutinin I (UEA-1), determined expression of the glycoprotein a-L-fucose. FITC-labelled UEA-1 confirmed overexpression of the glycoprotein by the polyps on fluorescence microscopy in 17/17 cases, of which 13/17 included paraffin-fixed mouse polyp specimens. In addition, FITC-UEA-1 ex vivo multispectral optical imaging of 4/17 colonic specimens displayed over-expression of the glycoprotein by the polyps, as compared to non-neoplastic mucosa. Here, we report the surface expression of (x-L-fucosyl terminal residues by neoplastic mucosal cells of APC specimens of the mouse. Glycoprotein expression was validated by the carbohydrate binding protein UEA-1. Future applications of this method are the development of agents used to diagnose cancers by biomedical imaging modalities, including computed tomographic colonography (CTC). UEA-1 targeting to colonic adenomas may provide a new avenue for the diagnosis of colorectal carcinoma by CT imaging. C1 [Roney, Celeste A.; Xie, Jianwu; Jabour, Paul; Summers, Ronald M.] Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Roney, CA (reprint author), Ctr Clin, Dept Diagnost Radiol, Bldg 10,Room 1C368X,MSC 1182, Bethesda, MD 20892 USA. NR 44 TC 3 Z9 3 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7100-0 J9 PROC SPIE PY 2008 VL 6916 AR 69161O DI 10.1117/12.769224 PG 10 WC Engineering, Biomedical; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BHT07 UT WOS:000256051300055 ER PT S AU Cheng, R Bokinsky, A Hemler, P McCreedy, E McAuliffe, M AF Cheng, Ruida Bokinsky, Alexandra Hemler, Paul McCreedy, Evan McAuliffe, Matthew BE Miga, MI Cleary, KR TI Java based volume rendering frameworks - art. no. 691804 SO MEDICAL IMAGING 2008: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND MODELING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE visualization; rendering; model; CPU; Jog1; Java3D; medical imaging AB In recent years, the number and utility of 3-D rendering frameworks has grown substantially. A quantitative and qualitative evaluation of the capabilities of a subset of these systems is important to determine the applicability of these methods to typical medical visualization tasks. The libraries evaluated in this paper include the Java3D Application Programming Interface (API), Java OpenGL(C) (Jog1) API, a multi-histogram software-based rendering method, and the WildMagic API. Volume renderer implementations using each of these frameworks were developed using the platform-independent Java programming language. Quantitative performance measurements (frames per second, memory usage) were used to evaluate the strengths and weaknesses of each implementation. C1 [Cheng, Ruida; McCreedy, Evan; McAuliffe, Matthew] NIH, Bethesda, MD 20892 USA. RP Cheng, R (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7102-4 J9 P SOC PHOTO-OPT INS PY 2008 VL 6918 BP 91804 EP 91804 DI 10.1117/12.770529 PN 1-2 PG 15 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BHT14 UT WOS:000256059000003 ER PT S AU Tan, S Yao, J Yao, L Summers, RM Ward, MM AF Tan, Sovira Yao, Jianhua Yao, Lawrence Summers, Ronald M. Ward, Michael M. BE Miga, MI Cleary, KR TI Acetabular rim and surface segmentation for hip surgery planning and dysplasia evaluation SO MEDICAL IMAGING 2008: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND MODELING, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE pelvic procedures; hip surgery; acetabular rim; dysplasia; level set; triangular mesh; ridgeline/crestline ID ACTIVE CONTOURS AB Knowledge of the acetabular rim and surface can be invaluable for hip surgery planning and dysplasia evaluation. The acetabular rim can also be used as a landmark for registration purposes. At the present time acetabular features are mostly extracted manually at great cost of time and human labor. Using a recent level set algorithm that can evolve on the surface of a 3D object represented by a triangular mesh we automatically extracted rims and surfaces of acetabulae. The level set is guided by curvature features on the mesh. It can segment portions of a surface that are bounded by a line of extremal curvature (ridgeline or crestline). The rim of the acetabulum is such an extremal curvature line. Our material consists of eight hemi-pelvis surfaces. The algorithm is initiated by putting a small circle (level set seed) at the center of the acetabular surface. Because this surface distinctively has the form of a cup we were able to use the Shape Index feature to automatically extract an approximate center. The circle then expands and deforms so as to take the shape of the acetabular rim. The results were visually inspected. Only minor errors were detected. The algorithm also proved to be robust. Seed placement was satisfactory for the eight hemi-pelvis surfaces without changing any parameters. For the level set evolution we were able to use a single set of parameters for seven out of eight surfaces. C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIAMSD, Ctr Clin, NIH, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7102-4 J9 PROC SPIE PY 2008 VL 6918 AR 69181N DI 10.1117/12.769550 PN 1-2 PG 10 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BHT14 UT WOS:000256059000056 ER PT J AU Stergiopoulou, T De Lucca, AJ Meletiadis, J Sein, T Boue, SM Schaufele, R Roilides, E Ghannoum, M Walsh, TJ AF Stergiopoulou, Theodouli De Lucca, Anthony J. Meletiadis, Joseph Sein, Tin Boue, Stephen M. Schaufele, Robert Roilides, Emmanuel Ghannoum, Mahmoud Walsh, Thomas J. TI In vitro activity of CAY-1, a saponin from Capsicum frutescens, against Microsporum and Trichophyton species SO MEDICAL MYCOLOGY LA English DT Article DE dermatophytes; Capsicum frutenses; saponin ID FUNGAL-INFECTIONS; PLANT-EXTRACTS; DERMATOPHYTES AB Dermatomycoses are among the world's most common diseases and their incidence has increased over recent years, particularly in immunosuppressed patients. In previous studies, the saponin CAY-1 from cayenne pepper (Capsicum frutescens), has shown antifungal activities against Candida albicans and Aspergillus spp. We therefore studied the in vitro antifungal activity of CAY-1 against non-germinating conidia and hyphae of clinical isolates of the dermatophytes Trichophyton mentagrophytes, T. rubrum, T. tonsurans and Microsporum canis. We used a microdilution method to assess the growth inhibitory activities of CAY-1 against conidia (CLSI document M38-A) and a colorimetric procedure (XTT method) to investigate the metabolic inhibitory activity of CAY-1 against hyphae. The minimal inhibitory concentrations (complete visual growth inhibition) of CAY-1 against non-germinating conidia ranged from 10-20 g/ml for all dermatophyte isolates included in this investigation. In addition, we found 90% inhibition of hyphal metabolic activity of these same isolates with 10-20 g/ml of CAY-1. Results indicate that CAY-1 merits further investigation as a potential agent for the treatment of dermatomycoses. C1 [Stergiopoulou, Theodouli; Meletiadis, Joseph; Sein, Tin; Schaufele, Robert; Roilides, Emmanuel; Walsh, Thomas J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [De Lucca, Anthony J.; Boue, Stephen M.] USDA, So Reg Res Lab, Los Angeles, CA USA. [Meletiadis, Joseph] Univ Gen Hosp Attikon, Sch Med, Lab Clin Microbiol, Athens, Greece. [Sein, Tin] SAIC Frederick Inc, Frederick, MD USA. [Stergiopoulou, Theodouli; Roilides, Emmanuel] Aristotle Univ Thessaloniki, Hippokration Hosp, Pediat Dept 3, GR-54006 Thessaloniki, Greece. [Ghannoum, Mahmoud] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 1-5888, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 19 TC 5 Z9 5 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2008 VL 46 IS 8 BP 805 EP 810 AR PII 792965086 DI 10.1080/13693780802089831 PG 6 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 369FV UT WOS:000260680700005 PM 18608885 ER PT J AU Troiano, RP Berrigan, D Dodd, KW Masse, LC Tilert, T Mcdowell, M AF Troiano, Richard P. Berrigan, David Dodd, Kevin W. Masse, Louise C. Tilert, Timothy Mcdowell, Margaret TI Physical activity in the United States measured by accelerometer SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the ACSM CY MAY 25-31, 2008 CL Indianapolis, IN SP Amer Coll Sports Med DE NHANES; moderate; vigorous; bouts; youth; adults ID ENERGY-EXPENDITURE; PUBLIC-HEALTH; OBESITY; MONITOR; WALKING AB Purpose: To describe physical activity levels of children (6-11 yr), adolescents (12-19 yr), and adults (20+ yr), using objective data obtained with accelerometers from a representative sample of the U.S. population. Methods: These results were obtained from the 2003-2004 National Health and Nutritional Examination Survey (NHANES), a cross-sectional study of a complex, multistage probability sample of the civilian, noninstitutionalized U.S. population in the United States. Data are described from 6329 participants who provided at least 1 d of accelerometer data and from 4867 participants who provided four or more days of accelerometer data. Results: Males are more physically active than females. Physical activity declines dramatically across age groups between childhood and adolescence and continues to decline with age. For example, 42% of children ages 6-11 yr obtain the recommended 60 min.d(-1) of physical activity, whereas only 8% of adolescents achieve this goal. Among adults, adherence to the recommendation to obtain 30 min.d(-1) of physical activity is less than 5%. Conclusions: Objective and subjective measures of physical activity give qualitatively similar results regarding gender and age patterns of activity. However, adherence to physical activity recommendations according to accelerometer-measured activity is substantially lower than according to self-report. Great care must be taken when interpreting self-reported physical activity in clinical practice, public health program design and evaluation, and epidemiological research. C1 [Troiano, Richard P.] NCI, Bethesda, MD 20892 USA. [Troiano, Richard P.; Berrigan, David; Dodd, Kevin W.; Masse, Louise C.] NIH, Natl Canc Inst, Bethesda, MD USA. [Tilert, Timothy; Mcdowell, Margaret] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD USA. RP Troiano, RP (reprint author), NCI, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM troianor@mail.nih.gov RI Loureiro, Nuno/I-6400-2012; OI Loureiro, Nuno/0000-0002-1166-3219; Troiano, Richard/0000-0002-6807-989X NR 35 TC 2477 Z9 2506 U1 38 U2 303 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JAN PY 2008 VL 40 IS 1 BP 181 EP 188 DI 10.1249/mss.0b013e31815a51b3 PG 8 WC Sport Sciences SC Sport Sciences GA 244MV UT WOS:000251870900025 PM 18091006 ER PT S AU Popat, VB Prodanov, T Calis, KA Nelson, LM AF Popat, Vaishali B. Prodanov, Tamara Calis, Karim A. Nelson, Lawrence M. BE Gordon, CM Welt, C Rebar, RW Hillard, PJA Matzuk, MM Nelson, LM TI The menstrual cycle - A biological marker of general health in adolescents SO MENSTRUAL CYCLE AND ADOLESCENT HEALTH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Meeting on the Menstrual Cycle and Adolescent Health CY OCT 17-19, 2007 CL Potomac, MD DE menstrual cycle; amenorrhea; primary amenorrhea; secondary amenorrhea; hypothalamic-pituitary-ovarian axis; bone health; delay in diagnosis; hormone replacement therapy; estrogen deficiency ID PREMATURE OVARIAN FAILURE; YOUNG-WOMEN; HORMONE-THERAPY; MENOPAUSE; GIRLS AB Menstruation is the cyclic, orderly sloughing of the uterine lining on account of the interactions of hormones produced by the hypothalamus, pituitary, and ovaries. There is a tendency among parents and clinicians to view oligo-amenorrhea as a normal variant in the teen years. In fact, the 95th percentile for the time interval between cycles is 90 days. Thus, it is abnormal for an adolescent to be amenorrheic for greater than 3 months, even in the early gynecologic years. Identification of abnormal menstrual patterns throughout adolescence may permit early identification of potential health concerns for adulthood. Few problems in gynecologic endocrinology are as complex or challenging to the clinician as amenorrhea. However, thorough evaluation of menstrual cycle disorders in adolescence provides a window of opportunity for early diagnosis and treatment of conditions affecting the hypothalamic-pituitary-ovarian (HPO) axis. Here we discuss a systematic approach to the evaluation and treatment of amenorrhea in adolescents who do not have androgen excess. There is strong evidence that estrogen deficiency is a risk factor for later development of osteoporosis and hip fracture. Delay in the evaluation and treatment of disordered menses in some cases may contribute to reduced bone density. Both patients and clinicians need to view the ovary as an important endocrine organ that helps maintain health, especially bone health. C1 NICHHD, NIH, CRC,Integrat Reprod Med Unit, Intramural Res Program Repord & Adult Endocrinol, Bethesda, MD 20892 USA. [Calis, Karim A.] NIH, Dept Pharm, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, NIH, CRC,Integrat Reprod Med Unit, Intramural Res Program Repord & Adult Endocrinol, Room 1-330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM Lawrence_Nelson@nih.gov; Lawrence_Nelson@nih.gov FU Intramural NIH HHS [Z01 HD000633-17] NR 19 TC 23 Z9 25 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-715-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1135 BP 43 EP 51 DI 10.1196/annals.1429.040 PG 9 WC Multidisciplinary Sciences; Obstetrics & Gynecology SC Science & Technology - Other Topics; Obstetrics & Gynecology GA BHY42 UT WOS:000257452900006 PM 18574207 ER PT S AU Covington, SN Martinez, PE Popat, V Nandagopal, R Ryand, M Nelson, LM AF Covington, Sharon N. Martinez, Pedro E. Popat, Vaishali Nandagopal, Radha Ryand, Mary Nelson, Lawrence M. BE Gordon, CM Welt, C Rebar, RW Hillard, PJA Matzuk, MM Nelson, LM TI The psychology of antecedents to adult reproductive disorders in adolescent girls SO MENSTRUAL CYCLE AND ADOLESCENT HEALTH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Meeting on the Menstrual Cycle and Adolescent Health CY OCT 17-19, 2007 CL Potomac, MD DE adolescence; impaired fertility; reproductive disorders; family systems; emotional communication; infertility; psychology ID INFORMED-CONSENT; CANCER-PATIENTS; TRUTH; PATIENT; PHYSICIANS; DISCLOSURE; ATTITUDES AB The normal developmental tasks and roles of adolescence are altered by a diagnosis of a reproductive disorder. The crisis of impaired fertility affects both parent and child, stressing the family system. For the adolescent girl, a reproductive disorder has an impact on her developing sense of self, body-image, and sexuality, which, in turn, can affect her self-esteem and relationships with others. Because of the sexual nature of a reproductive disorder, feelings of embarrassment or protectiveness are often engendered that can make it difficult for families to discuss. Nonetheless, families do best with openness and honesty regarding the condition and should be discouraged from keeping the diagnosis a secret. Adolescence encompasses a broad spectrum of emotional maturity, which needs to be considered by parents and clinicians when communicating information. Understanding that the family is an emotional unit, a family systems approach to deal with health issues is most appropriate. In this context, parents need to first deal with their own feelings about the diagnosis, before they can help their child. Secondly, parents must be provided with tools to build an ongoing conversation with their child that will avoid stigmatizing her condition and handicapping her growth into healthy adulthood. The goal for parent and clinician is to help the adolescent girl formulate positive self-esteem and body image, despite impaired fertility. C1 [Covington, Sharon N.; Popat, Vaishali; Nelson, Lawrence M.] NICHHD, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA. [Martinez, Pedro E.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Nandagopal, Radha] NICHHD, Inter Inst Pediat Endocrinol Training Program, Dev Endocrinol Branch, Bethesda, MD 20892 USA. [Ryand, Mary] Natl Inst Hlth Lib, Natl Inst Hlth, Bethesda, MD USA. RP Covington, SN (reprint author), 15001 Shady Grove Rd,Suite 220, Rockville, MD 20850 USA. EM sharon.covington@integramed.com FU Intramural NIH HHS [Z01 HD000633-17] NR 21 TC 6 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-715-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1135 BP 155 EP 162 DI 10.1196/annals.1429.016 PG 8 WC Multidisciplinary Sciences; Obstetrics & Gynecology SC Science & Technology - Other Topics; Obstetrics & Gynecology GA BHY42 UT WOS:000257452900020 PM 18574221 ER PT S AU Gordon, CM Loriaux, DL Grumbach, MM Rogol, AD Nelson, LM AF Gordon, Catherine M. Loriaux, D. Lynn Grumbach, Melvin M. Rogol, Alan D. Nelson, Lawrence M. BE Gordon, CM Welt, C Rebar, RW Hillard, PJA Matzuk, MM Nelson, LM TI Reflections on future research in adolescent reproductive health SO MENSTRUAL CYCLE AND ADOLESCENT HEALTH SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on the Menstrual Cycle and Adolescent Health CY OCT 17-19, 2007 CL Potomac, MD DE research; adolescents; reproductive health; menstrual cycle ID POLYCYSTIC-OVARY-SYNDROME; LIFE-HISTORY; GROWTH; FEMALE; AGE; PUBERTY; GIRLS; SIGN AB A group of basic scientists, clinicians, clinical investigators, psychologists, patient advocacy groups, and representatives from professional societies and governmental agencies met at the National Institutes of Health in October, 2007 with the long-term goal of having the menstrual cycle accepted and understood as a marker of general health in adolescent girls. An equally important goal was to develop a research agenda for this area of investigation. This chapter comprises the highlights of discussions throughout that meeting, with an emphasis on ideas generated during a final session led by an internationally renowned physician-scientist, in which reports from four breakout groups were presented. The specific goal assigned to each group was to develop an agenda that would set the stage for how research should be conducted over the next 100 years, and to identify the pressing research questions that should be addressed related to the menstrual cycle and adolescent health. The four research areas represented in discussion groups included: emotional health; genetics; metabolism and reproduction; and the promotion of conduct of clinical research. Insights are also provided by five clinical investigators, including two outside experts, on topics of priority for a research agenda in the area of adolescent reproductive health, as well as how the research itself should be conducted. C1 [Gordon, Catherine M.] Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. [Gordon, Catherine M.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Loriaux, D. Lynn] Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97201 USA. [Grumbach, Melvin M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Rogol, Alan D.] Univ Virginia, Charlottesville, VA USA. [Rogol, Alan D.] Indiana Univ, Sch Med, Riley Hosp, Indianapolis, IN USA. [Nelson, Lawrence M.] NICHHD, Integrat Reprod Med Unit, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Gordon, CM (reprint author), Childrens Hosp, Div Adolescent Med, 300 Longwood Ave, Boston, MA 02115 USA. EM catherine.gordon@childrens.harvard.edu; catherine.gordon@childrens.harvard.edu FU Intramural NIH HHS; NICHD NIH HHS [R01 HD043869-06, R01 HD043869, R01 HD43869] NR 24 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-715-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1135 BP 296 EP 305 DI 10.1196/annals.1429.036 PG 10 WC Multidisciplinary Sciences; Obstetrics & Gynecology SC Science & Technology - Other Topics; Obstetrics & Gynecology GA BHY42 UT WOS:000257452900035 PM 18574236 ER PT S AU Gordon, CM Hijane, K Heyman, C Bell, ML Busby, MB Nelson, LM AF Gordon, Catherine M. Hijane, Karima Heyman, Carly Bell, Maureen Lindenhofen Busby, Mary Beth Nelson, Lawrence M. BE Gordon, CM Welt, C Rebar, RW Hillard, PJA Matzuk, MM Nelson, LM TI Passion for participatory research on the menstrual cycle SO MENSTRUAL CYCLE AND ADOLESCENT HEALTH SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on the Menstrual Cycle and Adolescent Health CY OCT 17-19, 2007 CL Potomac, MD DE adolescents; menstrual cycle; research models ID GIRLS AB A two-day symposium entitled "The Menstrual Cycle and Adolescent Health" was held in Potomac, Maryland in mid October 2007. Groups sponsoring the meeting included the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), the National Institute of Child Health and Human Development, the American Society for Reproductive Medicine, the NIH Office of Research on Women's Health, the NIH Office of Rare Diseases, the U.S. Food and Drug Administration Office of Women's Health, the DHHS Office of Women's Health, and Rachel's Well, Inc. Attendees included patients, patient advocates, and experts from a variety of fields and disciplines. The effort identified areas in which there are only sparse data from which to create evidence-based recommendations for management of menstrual problems in young adolescents. In a final session of the meeting, participants worked together to develop a manifesto regarding research on the menstrual cycle in adolescents, which is the subject of this report. The group reached two major conclusions. First, there is need for a new research model that integrates grass roots community passion for participatory research with research planning and regulatory oversight. Second, there is a need for a coordinated research effort on the menstrual cycle and its disorders in adolescents. This could initially take the form of a Study of Puberty across the Nation (SPAN), similar to the Study of Women across the Nation (SWAN) that addresses the normal menopausal process. C1 [Gordon, Catherine M.] Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. [Gordon, Catherine M.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Hijane, Karima] Rachels Well Inc, Burke, VA USA. [Heyman, Carly] Fragile X Assoc Georgia, Atlanta, GA USA. [Bell, Maureen Lindenhofen] Parents Galactosem Children Inc, Mandeville, LA USA. [Busby, Mary Beth] Fragile X Res Fdn FRAXA, Newburyport, MA USA. [Nelson, Lawrence M.] NIH, Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. RP Gordon, CM (reprint author), Childrens Hosp, Div Adolescent Med, 300 Longwood Ave, Boston, MA 02115 USA. EM catherine.gordon@childrens.harvard.edu; catherine.gordon@childrens.harvard.edu FU Intramural NIH HHS; NICHD NIH HHS [R01 HD43869, R01 HD043869-06, R01 HD043869] NR 8 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-715-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1135 BP 306 EP 308 DI 10.1196/annals.1429.037 PG 3 WC Multidisciplinary Sciences; Obstetrics & Gynecology SC Science & Technology - Other Topics; Obstetrics & Gynecology GA BHY42 UT WOS:000257452900036 PM 18574237 ER PT B AU Mather, KJ Baron, A Quon, MJ AF Mather, Kieren J. Baron, Alain Quon, Michael J. BE Hansen, BC Bray, GA TI Insulin Action and Endothelial Function SO METABOLIC SYNDROME: EPIDEMIOLOGY, CLINICAL TREATMENT, AND UNDERLYING MECHANISMS SE Contemporary Endocrinology LA English DT Article; Book Chapter ID NITRIC-OXIDE SYNTHASE; TYPE-2 DIABETES-MELLITUS; TUMOR-NECROSIS-FACTOR; MUSCLE GLUCOSE-UPTAKE; HUMAN SKELETAL-MUSCLE; SPONTANEOUSLY HYPERTENSIVE-RATS; CELL-ADHESION MOLECULES; LOW-DENSITY-LIPOPROTEIN; UPTAKE IN-VIVO; BLOOD-FLOW C1 [Mather, Kieren J.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Baron, Alain] Amylin Pharmaceut, San Diego, CA USA. [Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Mather, KJ (reprint author), Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. NR 175 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-738-9 J9 CONTEMP ENDOCRINOL S PY 2008 BP 107 EP 135 DI 10.1007/978-1-60327-116-5_7 D2 10.1007/978-1-60327-116-5 PG 29 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO56 UT WOS:000266907200008 ER PT S AU Walker, AM Stevens, JJ Tchounwou, PB AF Walker, Alice M. Stevens, Jacqueline J. Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Arsenic trioxide-mediated apoptosis in breast (MCF-7) and lung (A549) carcinoma cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID MECHANISMS; CANCER; INDUCTION; GROWTH; ARREST; CYCLE AB Arsenic has been reported to induce cytotoxicity via a variety of mechanisms influencing numerous signal transduction pathways resulting in cellular effects such as growth inhibition and angiogenesis inhibition., cell cycle modulation, and/or apoptosis. In a recent study, we demonstrated that oxidative stress plays a key role in arsenic-induced toxicity in vitro. The present research aimed at studying its potential to induce programmed cell death in breast and lung carcinoma cell lines. To accomplish this objective, breast cancer (MCF-7) and lung cancer (A549) cells were cultured and exposed to various doses (0, 2, 4, 6, 8, and 10 mu g/ml) of arsenic trioxide for 48 h, and DNA laddering assay using agarose gel, was subsequently performed following standard test protocols. Experimental data indicated that arsenic trioxide exposure significantly induced apoptosis in both cell lines, as characterized by substantial DNA fragmentation in arsenic-treated cells compared to control cells. C1 [Walker, Alice M.; Stevens, Jacqueline J.; Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, Mol & Cellular Biol Res Lab, NIH Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Walker, AM (reprint author), Jackson State Univ, Mol Toxicol Res Lab, Mol & Cellular Biol Res Lab, NIH Ctr Environm Hlth,Coll Sci Engn & Technol, 1400 JR Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@isums.edu NR 22 TC 1 Z9 1 U1 0 U2 6 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 135 EP 139 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900022 ER PT S AU Tchounwou, PB Newsome, C Williams, J Glass, K AF Tchounwou, Paul B. Newsome, Cecilia Williams, Joyce Glass, Konsuela BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Copper-induced cytotoxicity and transcriptional activation of stress genes in human liver carcinoma (HepG(2)) cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID EXPRESSION; CADMIUM; ASSAY; LEAD AB Copper is a naturally occurring element found as a component of many minerals. It is an essential nutrient that is normally present in a wide variety of tissues. In humans, ingestion of large quantities of copper salts may cause gastrointestinal, hepatic, and renal effects with symptoms such as severe abdominal pain, vomiting, diarrhea, hemolysis, hepatic necrosis, hematuria, proteinuria, hypotension, tachycardia, convulsions, coma, and death. The chronic toxicity of copper has been characterized in patients with Wilson's disease, a genetic disorder causing copper accumulation in tissues. Although the clinical manifestations of Wilson's disease (cirrhosis of the liver, hemolytic anemia, neurologic abnormalities, and corneal opacities) are known, the cellular and molecular events associated with copper toxicity are poorly understood. In the present study, we used human liver carcinoma (HepG(2)) cells as a model to study the cytotoxicity, and the potential mechanisms of copper-induced toxicity and carcinogenesis. We hypothesized that copper-induction of stress genes may play a role in the cellular and molecular events leading to toxicity and tumor formation in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, the CAT-Tox(L) assay for gene induction, to assess the transcriptional activation of stress genes. Data obtained from the MTT assay indicated a strong dose-response relationship with respect to copper toxicity. Upon 48 h of exposure, the chemical dose required to cause 50% reduction in cell viability (LD(50)) was Computed to be 220.5 +/- 23.8 mu g/mL copper sulfate. The CAT-Tox (L) assay showed statistically significant inductions (p < 0.05) of a significant number of stress genes including c-fos, HMTIIA, HSP70, GRP78, RARE, GADD153, and RARE. These data support previous research indicating that copper overload is hepatotoxic. The CAT-Tox data on the other hand indicate that copper overload induces proteotoxic effects (HMTIIA, HSP70, GRP78), inflammatory reactions/ oxidative stress (c-fos), and growth arrest and DNA damage (p53, GADD153). The induction of RARE points to its potential involvement in growth and development. C1 [Tchounwou, Paul B.; Newsome, Cecilia; Williams, Joyce; Glass, Konsuela] Jackson State Univ, Coll Sci Engn & Technol, NIH RCMI Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH RCMI Ctr Environm Hlth, Mol Toxicol Res Lab, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [G12 RR013459, G12 RR013459-11] NR 14 TC 9 Z9 9 U1 1 U2 2 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 285 EP 290 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900047 PM 21423838 ER PT S AU Patlolla, A Armstrong, N Tchounwou, PB AF Patlolla, Anita Armstrong, Najealicka Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Cytogenetic evaluation of potassium clichromate toxicity in bone marrow cells of Sprague-Dawley rats SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID CHROMIUM; INVIVO; CARCINOGENICITY; ABERRATIONS; MECHANISMS; CHROMATE AB Hexavalent chromium is a well-known mutagen and carcinogen. Chromium is widely used in numerous industrial processes and as a result, it is a contaminant of many environmental systems. As there are very few reports on the acute in vivo genotoxic effect of potassium dichromate [K(2)Cr(2)O(7)], the present study was undertaken to obtain an insight into the effect of intraperitoneal administration of potassium dichromate in Sprague-Dawley rats. The aim of this study was to assess the in vivo genotoxic effect of potassium dichromate using mitotic index (MI) and Structural chromosomal aberrations (SCA) as the toxicological endpoints in the bone-marrow cells of Sprague-Dawley rats. Four groups of five male rats each, weighing approximately 60 +/- 2g, were injected intraperitoneally, once a day for five days with doses of 2.5, 5, 7.5, and 10 mg/kg bodyweight of potassium dichromate (K(2)Cr(2)O(7)) dissolved in distilled water. Control groups were also made of 5 animals injected with distilled water (negative), or mytomicin C (positive). All the animals were sacrificed at the end of the treatment period. Chromosome and micronuclei preparation were obtained from bone marrow cells following standard protocols. Potassium dichromate exposure significantly increased the mitotic index (MI); the number of structural chromosomal aberrations (CA) and frequency of micronuclei induction in treated group when compared to the control group. The increase in MI and CA was found to be dose-dependent indicating a gradual increase in CA and MI with increasing doses of potassium dichromate. However, the increase in micronuclei formation was found to be non-significant in the treated group compared to control. Our results demonstrate that potassium dichromate has a clastogenic/genotoxic potential as measured by the bone marrow CA assays in Sprague-Dawley rats. Chromosome aberration [CA] assay is promising techniques to assess the clastogenic potential of chromium and its compounds. C1 [Patlolla, Anita; Armstrong, Najealicka; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Patlolla, A (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. EM paul.b.tchounvvou@jsums.edu NR 19 TC 0 Z9 0 U1 2 U2 3 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 353 EP 358 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900058 ER PT S AU Yedjou, CG Brown, E Rogers, C Tchounwou, PB AF Yedjou, Clement G. Brown, Erika Rogers, Christian Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Ascorbic acid - modulation of arsenic trioxide toxicity: implication for the clinical treatment of acute promyelocytic leukemia SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID MULTIPLE-MYELOMA; VITAMIN-C; CELLS; MULTICENTER; ACTIVATION; APOPTOSIS; STRESS; GROWTH AB Acute Promyelocytic Leukemia (APL) is a subtype of acute leukemia which can affect people of any age. It strikes about 1,500 patients in the United States each year. Recent in vitro and in Vivo Studies have shown that arsenic trioxide (ATO) can induce clinical remission in de-novo and APL patients that have relapsed from conventional treatment. Ascorbic acid (AA) is an anti-oxidant and free radical scavenger effective against peroxyl- and hydroxyl-radicals, Superoxide, singlet oxygen and peroxynitrite. Although research has shown that AA can prevent cancer by deactivating free radicals before they can damage DNA and initiate tumor growth, there are also published reports indicating that it may act as a pro-oxidant that helps the body's own free radical defense mechanism destroy tumors in their early stages. The aim of this research was to study the modulatory effect of AA on ATO-induced oxidative stress in leukemia cells. To achieve this aim, we performed the MTT assay and trypan blue exclusion test for cell viability, and the thiobarbituric acid test to determine the levels of malondialdehyde (NIDA) production in HL-60 cells co-exposed to ascorbic acid (AA) and ATO. The results of MTT assay indicated that AA exposure potentiates the cytotoxicity of ATO in HL-60 cells, as evidenced by a gradual increase in cell death and MDA levels with increasing doses of AA. From these results, it is evident that the addition of ascorbic acid to ATO-treated HL-60 cells enhances the formation of reactive oxygen species (ROS), resulting in increased lipid peroxidation. Based on these direct in vitro findings, our study provides evidence that AA may extend the therapeutic spectrum of ATO, and improve the clinical Outcome associated with ATO monotherapy in vivo. C1 [Yedjou, Clement G.; Brown, Erika; Rogers, Christian; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Cellom & Toxicogenom Res Lab, Jackson, MS 39217 USA. RP Yedjou, CG (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Cellom & Toxicogenom Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [G12 RR013459, G12 RR013459-010007] NR 15 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 413 EP 418 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900068 PM 26549974 ER PT S AU Yedjou, CG Waters, D Tchounwou, PB AF Yedjou, Clement G. Waters, Daren Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI N-acetyl-cysteine protection against lead-induced oxidative stress and genotoxicity in human liver carcinoma (HepG(2)) cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID MAMMALIAN-CELLS AB The human liver carcinoma (HepG2) cells as well as other cell lines are particularly Susceptible to oxidative damage, and it is therefore important to find agents that protect against this process. N-acetyl-cysteine (NAC) is the acetylated form of L-cysteine. It has an impressive list of protective effects including: antioxidant activity, decrease of the biologically effective dose of carcinogens, anti-inflammatory activity, immunological effects, inhibition of progression to malignancy and metastasis, and protection from the adverse effects of chemopreventive and chemotherapeutic agents. Previous studies in our laboratory have shown that lead nitrate induces cytotoxicity and oxidative stress to HepG(2) cells in a dose-dependent manner. In this research, we hypothesized that the antioxidant, n-acetyl-l-cysteine attenuates oxidative stress and genotoxicity, and thereby provides cellular protection against lead toxicity. To this hypothesis, we performed the thiobarbituric acid test for lipid peroxidation and the microgel electrophoresis (comet) assay for genotoxicity. The results generated from the thiobarbituric acid test showed a significant reduction of lipid peroxidation by-product (malondialdehyde) in HepG(2) cells co-exposed to NAC and lead nitrate compared to lead nitrate alone. Incubation of HepG(2) cells with increasing concentrations of NAC decreased the amount of MDA formation progressively in lead nitrate-treated HepG(2) cells. Data obtained from the cornet assay indicated a strong dose-response relationship with regard to lead nitrate-induced genotoxic damage in HepG(2) cells. However, the addition of NAC ill vitro showed a significant reduction (p < 0.05) in the comet tail length, percentage of DNA cleavage, comet tail moment, as well as cornet tail arm respectively in cells co-treated with NAC and lead nitrate. Findings from these Studies demonstrated that NAC inhibits malondialdehyde (NIDA) production and genotoxicity in lead nitrate-treated HepG(2) cells in a dose-dependent manner. Under this ill vitro condition, NAC was found to be effective in reducing NIDA formation, Cellular injury, and genotoxic damage in HepG(2) cells exposed to lead nitrate. C1 [Yedjou, Clement G.; Waters, Daren; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Cellom & Toxicogenom Res Lab, Jackson, MS 39217 USA. RP Yedjou, CG (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Cellom & Toxicogenom Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [G12 RR013459, G12 RR013459-010007, G12 RR013459-10]; NIMH NIH HHS [R25 MH057113] NR 15 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 419 EP 424 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900069 PM 26549975 ER PT S AU Stevens, JJ Graham-Evans, B Walker, AM Armstead, B Tchounwou, PB AF Stevens, Jacqueline J. Graham-Evans, Barbara Walker, Alice M. Armstead, Brinda Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Cytotoxic effect of arsenic trioxide in adenocarcinorna colorectal cancer (HT-29) cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID HUMAN LEUKEMIA HL-60; MOLECULAR-MECHANISMS; OXIDATIVE STRESS; IN-VITRO; T-CELLS; PROLIFERATION; TOXICITY; ASSAYS; LINES AB Arsenic is a heavy metal that exhibits a high degree of toxicity to various organ systems. In humans, this compound is associated with an increase risk of skin cancer, and may cause cancers of the lung, liver, bladder, kidney, and colon. The mechanism of arsenic-related carcinogenicity remains to be elucidated. Hence, the aim of the present study was to investigate the cytotoxic effects of arsenic trioxide (As(2)O(3)) on adenocarcinoma colorectal cancer (HT-29) cells using the MTT [3-(4,5 dimethylthiazoyl-2-yl)-2,5- diphenyltetrazolium bromide] assay for cell viability. To achieve this objective, HT-29 cells were cultured and exposed to various doses (0, 2, 4, 6, 8, 10, 12, and 14 mu g/ml) of arsenic trioxide for 24 h, 48 h, and 72 11 respectively, and subsequently assessed for viability following a standard MTT test protocol. Experimental data indicated that arsenic trioxide is cytotoxic to colon cancer cells showing LD(50) values of 9.8, 9.4 and 9.0 mu g/ml upon 24, 48 and 72 h of exposure, respectively. There was a dose-dependent response with regard to As(2)O(3) toxicity in HT-29 cells. Although there was a reduction in LD(50) value with increasing exposure time, this decrease was not statistically significant. C1 [Stevens, Jacqueline J.] Jackson State Univ, Mol & Cellular Biol Res Lab, NIH, Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Stevens, JJ (reprint author), Jackson State Univ, Mol & Cellular Biol Res Lab, NIH, Ctr Environm Hlth,Coll Sci Engn & Technol, 1400 JR Lynch St,Box 18540, Jackson, MS 39217 USA. EM jacqueline.j.stevens@jsums.eclu FU NCRR NIH HHS [G12 RR013459-115530, G12 RR013459]; NIGMS NIH HHS [R25 GM067122] NR 20 TC 3 Z9 3 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 458 EP 462 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900075 PM 21603592 ER PT S AU Yedjou, C Haynes, L Dorsey, W McMurray, R Tchounwou, PB AF Yedjou, Clement Haynes, Linden Dorsey, Waneene McMurray, Robert Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Lead-induced cytotoxicity and oxidative stress in human leukemia (HL-60) cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID TRANSCRIPTIONAL ACTIVATION; ANTIOXIDANT ENZYMES; EXPRESSION; CADMIUM; GENES; HEPG2 AB Lead poisoning has been extensively studied over the years. Many adverse physiological and behavioral impacts on the human body have been reported due to the entry of this heavy metal. It especially causes the hematological effects to people of all ages. However, its molecular mechanisms of action remain largely unknown. Hence, the aim of the present Study was to evaluate the cytotoxicity and oxidative stress induced by lead nitrate in a human leukemia cell line using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide], and lipid hydroperoxide assays, respectively. HL-60 cells were treated with different doses of lead nitrate for 24 h prior to cytotoxicity oxidative stress assessment. The results obtained from the MTT assay indicated that lead nitrate significantly decreases the viability of HL-60 cells in a dose-dependent manner. Similar result was obtained with the trypan blue exclusion test. Data generated from lipid hydroperoxide assay resulted in a significant increase (p < 0.05) in the production of hydroperoxides (degradation products of lipid peroxidation) with increasing doses of lead nitrate. Upon 24 h of exposure, the hydroperoxide concentrations in the sample [mu M] (mean +/- SE, n = 3) compared to untreated control were 6.7 +/- 21, 7.1 +/- 1, 14.7 +/- 2, 15.7 +/- 1, 16.2 +/- 1, and 15.2 +/- 1 in 0, 10, 20, 30, 40, and 50. mu g/mL of lead nitrate, respectively. In summary, findings from this study demonstrated that lead nitrate is cytotoxic to HL-60 cells. This cytotoxicity is found to be associated with oxidative stress. C1 [Yedjou, Clement; Haynes, Linden; Dorsey, Waneene; McMurray, Robert; Tchounwou, Paul B.] Jackson State Univ, Cellom & Toxicogenom Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Yedjou, C (reprint author), Jackson State Univ, Cellom & Toxicogenom Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,POB 18340, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu NR 16 TC 2 Z9 2 U1 0 U2 2 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 489 EP 494 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900081 ER PT S AU Yedjou, C Sutton, L Tchounwou, PB AF Yedjou, Clement Sutton, La'Mont Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Genotoxic mechanisms of arsenic trioxide effect in human Jurkat T-lymphoma cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID HUMAN LEUKEMIA HL-60; IN-VITRO; APOPTOSIS; EXPRESSION; PROTEINS; STRESS AB Arsenic trioxide (As(2)O(3)) has cytotoxic effects on several cancer cell lines. However, the molecular mechanisms of action are not completely elucidated. Hence, the aim of the present Study was to evaluate the cytotoxicity and genotoxicity induced by As(2)O(3) in a human Jurkat T-lymphoma cell line using the trypan blue exclusion test and alkaline single cell gel electrophoresis (Comet) assays, respectively. Jurkat T-cells were treated with different doses of As(2)O(3) for 24 h and 48 h prior to cytogenetic assessment. Data obtained from the trypan blue exclusion test indicated that As(2)O(3) significantly (p < 0.05) reduced the viability of Jurkat T-cells in a dose- and time-dependent manner. Data generated from the comet assay also indicated a significant dose and time-dependent increase in DNA damage in Jurkat T-cells associated with As(2)O(3) exposure. We observed a significant increase) < 0.05) in comet tail-length, tail arm and tail moment, as well as in percentage of DNA cleavage at all doses tested, showing an evidence of As(2)O(3) -induced genotoxic damage in Jurkat T-cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by heavy metals such as arsenic. Taken together, our findings suggest that As(2)O(3) exposure significantly (p < 0.05) reduces cellular viability and induces DNA damage in human Jurkat T-lymphoma cells. C1 [Yedjou, Clement; Sutton, La'Mont; Tchounwou, Paul B.] Jackson State Univ, Cellom & Toxicogenom Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Yedjou, C (reprint author), Jackson State Univ, Cellom & Toxicogenom Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [G12 RR013459, G12 RR013459-10] NR 10 TC 1 Z9 1 U1 1 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 495 EP 499 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900082 PM 21796259 ER PT S AU Brown, E Yedjou, CG Tchounwou, PB AF Brown, Erika Yedjou, Clement G. Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Cytotoxicity and oxidative stress in human liver carcinoma cells exposed to arsenic trioxide (HepG(2)) SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID DNA-DAMAGE; CARCINOGENESIS; ACTIVATION; TOXICITY AB Arsenic is a trace element that occurs naturally in the earth's crust. It has been found to be a major contaminant in groundwater supply in several countries of the world. Whether ingested or inhaled, arsenic induces both systemic (skin disorders, cardiovascular diseases, anemia, peripheral neuropathy, liver and kidney damage) and carcinogenic (skin, lung, bladder and liver neoplasms) effects. However, its molecular mechanisms of toxicity are not completely understood. In this research, we used HepG(2) cells as a model to study the cytotoxicity and oxidative stress associated with exposure to arsenic trioxide. We hypothesized that oxidative stress plays a role in arsenic trioxide induced cytotoxicity. To test this hypothesis, we performed both MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay and trypan blue exclusion test for cell viability and the thiobarbituric acid test for lipid peroxidation. Data obtained from the MTT assay indicated that arsenic trioxide significantly reduced the viability of HepG(2) cells, showing a LD(50) value of about 23 mu g/mL upon 24 h of exposure, indicating a dose-dependent response. Similar trend was obtained with the trypan blue exclusion test. Data generated from the thiobarbituric acid test showed a significant increase (p <= 0.05) in MDA levels in arsenic trioxide-treated HepG(2) cells compared to control cells. Arsenic trioxide treatment significantly increased cellular content of reactive oxygen species (ROS), as evidenced by the increase in lipid peroxidation by-products. Taken together, these results indicate that arsenic trioxide is cytotoxic to HepG(2) cells. This cytotoxicity is mediated by oxidative stress, a biomarker of cellular injury. C1 [Brown, Erika; Yedjou, Clement G.; Tchounwou, Paul B.] Jackson State Univ, Cellom & Toxicogenom Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Brown, E (reprint author), Jackson State Univ, Cellom & Toxicogenom Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [G12 RR013459-11, G12 RR013459] NR 14 TC 8 Z9 8 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 583 EP 587 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900098 PM 20657712 ER PT S AU Armstrong, NN Patlolla, AK Tchounwou, PB AF Armstrong, Najealicka N. Patlolla, Anita K. Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Protective effect of ascorbic acid against chromium-induced hepatic and renal toxicity in Sprague-Dawley rats SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard ID OXIDATIVE STRESS; DICHROMATE; CARCINOGENICITY; NEPHROTOXICITY; CR(VI) AB Cellular exposure to exogenously or endogenously generated oxidants causes macromolecular damage, including protein oxidation, lipid peroxidation, and nucleic acid instability, and mutation. Chromium (VI) compounds have been reported to be more toxic and carcinogenic than chromium (III), because the former can pass through cell membranes more easily than the latter. However, once inside cells, chromium (VI) is believed to be subsequently reduced through intermediates to chromium (III) by cellular reductants, including ascorbic acid. It has been found that ascorbic acid is a more potent reductant of chromium (VI) than any other biological reductant. However, the contribution of ascorbic acid against chromium-induced damage is not clear. The aim of this study was to determine the effect of pretreatment with ascorbic acid (Vitamin C) on dichromate-induced hepatic and renal damage using alkaline (ALP) and acid phosphatase (ACP) activities as the endpoints in Sprague-Dawley rats. Four groups of 5 male rats each weighing an average of 60 +/- 2 g were used in this study. Potassium dichromate was intraperitoneally administered to the rats at the doses of 2.5, 5, 7.5 and 10 mg/kg bodyweight (BW), and one dose per 24 hours given for 5 days. A control group was also made of 5 animals injected with distilled water without chemical. A,group of 5 rats were pretreated with 25 mg/kg (BW) ascorbic acid for 48 hours prior to exposure to potassium dichromate. Following anesthesia, blood specimens were immediately collected using heparinized syringes, alkaline and acid phosphatases (ALP & ACP) were detected and quantified in serum samples by spectrophotometry. Pretreatment with ascorbic acid prior to exposure resulted in a significant decrease in the activities of both alkaline and acid phosphatases in the serum samples of Sprague-Dawley rats. Phosphatase activities of 0.198 +/- 0.032; 0.259 +/- 0.018; 0.282 +/- 0.013; 0.281 +/- 0.014; 0.472 +/- 0.027; 0.141 +/- 0.031 (ALP) and 0.227 +/- 0.040; 0.222 +/- 0.055; 0.271 +/- 0.039; 0.343 +/- 0.036; 0.396 +/- 0.049; 0.218 +/- 0.027 (ACP) were recorded for 0, 2.5, 5.0, 7.5, 10 mg/kg potassium dichromate and 25 mg/kg ascorbic acid respectively; indicating a gradual increase in phosphatase activity with increasing doses of chromium, and a significant decrease in activity with ascorbic acid administration. These findings indicate that ascorbic acid is protective against chromium induced hepatic and renal injuries in Sprague-Dawley rats. C1 [Armstrong, Najealicka N.; Patlolla, Anita K.; Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Armstrong, NN (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu NR 19 TC 0 Z9 0 U1 1 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 636 EP 641 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900106 ER PT S AU Velma, V Tchounwou, PB AF Velma, Venkatramreddy Tchounwou, Paul B. BE Collery, P Maymard, I Theophanides, T Khassanova, L Collery, T TI Acute toxicity of sodium dichromate to goldfish, Carassium auratus SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 10 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 10th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 2008 CL Bastia, FRANCE SP Polyclin Maymard DE sodium dichromate; acute toxicity; goldfish ID MINNOWS PIMEPHALES-PROMELAS; TROUT SALMO-GAIRDNERI; FRESH-WATER TELEOST; HEXAVALENT CHROMIUM; PROLONGED EXPOSURE AB Chromium is a common contaminant in ground water and surface water. It also enters into the environment as effluent from several industrial operations such as tanneries, ceramic, mining, dying, electroplating, metal finishing, printing and pharmaceutical industries. Chromium exists in the environment in divalent, trivalent and hexavalent forms, but the hexavalent form is more toxic than the other forms. Release of chromium containing effluents from the industries into the aquatic environment poses a major threat to the growth and survival of icthyofauna. In this study we evaluated the dose-response and time-response relationships of chromium (sodium dichromate) toxicity to goldfish. The study was conducted using 96-hour static renewal bioassay, according to the U.S. EPA protocol. Study results indicated that the mortality rate of gold fish increased with increasing concentrations of chromium and exposure time periods. LC50 values of 187.99 +/- 5.42 mg/L, 124.7 +/- 5.68 mg/L, 107.04 +/- 4.32 mg/L and 85.7 +/- 4.89 mg/L were computed for 24 h, 48 h, 72 h and 96 h of exposure respectively. In summary, these data indicate that the toxicity of sodium dichromate to Carassius auratus fish is both concentration- and time-dependent. C1 [Velma, Venkatramreddy; Tchounwou, Paul B.] Jackson State Univ, Environm Toxicol Res Lab, NIH, RCMI,Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Environm Toxicol Res Lab, NIH, RCMI,Ctr Environm Hlth,Coll Sci Engn & Technol, 1400 Lynch St, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu NR 22 TC 2 Z9 3 U1 2 U2 2 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 978-2-7420-0714-1 J9 METAL IONS BIOL MED JI Met. Ions Biol. Med. PY 2008 VL 10 BP 642 EP 646 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA BIC67 UT WOS:000258426900107 ER PT J AU Bianco, C Strizzi, L De Luca, A Normanno, N Salomon, DS AF Bianco, Caterina Strizzi, Luigi De Luca, Antonella Normanno, Nicola Salomon, David S. BE Hayat, MA TI Breast and Colon Carcinomas: Detection with Plasma CRIPTO-1 SO METHODS OF CANCER DIAGNOSIS, THERAPY AND PROGNOSIS, VOL 1: BREAST CARCINOMA SE Methods of Cancer Diagnosis Therapy and Prognosis LA English DT Article; Book Chapter ID DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION; MAMMARY EPITHELIAL-CELLS; FACTOR-RELATED PROTEINS; CANCER CELLS; GROWTH-INHIBITION; TRANSGENIC MICE; ANTISENSE OLIGONUCLEOTIDES; MESENCHYMAL TRANSITION; COLORECTAL TUMORS; CFC DOMAIN C1 [Bianco, Caterina; Strizzi, Luigi; Normanno, Nicola; Salomon, David S.] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [De Luca, Antonella] ITN Fdn Pascale, Cell Biol & Preclin Models Unit, Naples, Italy. RP Bianco, C (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bldg 37,Room 1112, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov NR 49 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4020-8369-3 J9 METHODS CANCER DIAGN PY 2008 VL 1 BP 189 EP 202 DI 10.1007/978-1-4020-8369-3_15 D2 10.1007/978-1-4020-8369-3 PG 14 WC Oncology; Medicine, General & Internal SC Oncology; General & Internal Medicine GA BNO99 UT WOS:000275163000016 ER PT J AU Ball, MJ Silva, JS Bierstock, S Douglas, JV Norcio, AF Chakraborty, J Srini, J AF Ball, M. J. Silva, J. S. Bierstock, S. Douglas, J. V. Norcio, A. F. Chakraborty, J. Srini, J. TI Failure to provide clinicians useful IT systems: Opportunities to leapfrog current technologies SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material DE clinical workstations; health professional workstations AB Objective: To discuss why clinical information systems are failing. Method. Subjectively analyzing the development of clinical IT systems during the last decades. Results and Conclusions: The challenge is to anticipate what information clinicians need and then deliver it in a way that is tailored for their unique views. Clinicians need workstations that offer the highest level possible of user-determined flexibility and customization. We envision and outline a so-called point of care work station, automatically scaling to the display, hardware capacity, operating system, applications (local or distributed) the user needs and across diverse health IT systems. C1 [Ball, M. J.; Douglas, J. V.] Johns Hopkins Univ, Sch Nursing, Ctr Healthcare Management, IBM Res, Baltimore, MD 21210 USA. [Silva, J. S.] NCI, Ctr Bioinformat, Eldersburg, MD USA. [Bierstock, S.] Champions Healthcare, Delray Beach, FL USA. [Norcio, A. F.; Chakraborty, J.] Univ Maryland Baltimore Cty, Dept Informat Syst, Baltimore, MD 21228 USA. [Srini, J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Ball, MJ (reprint author), Johns Hopkins Univ, Sch Nursing, Ctr Healthcare Management, IBM Res, Baltimore, MD 21210 USA. EM marionboll@us.ibm.com NR 26 TC 15 Z9 15 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2008 VL 47 IS 1 BP 4 EP 7 PG 4 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 256EP UT WOS:000252710800002 PM 18213422 ER PT J AU Cheung, GYC Dickinson, P Sing, G Craigon, M Ghazal, P Parton, R Coote, JG AF Cheung, Gordon Y. C. Dickinson, Paul Sing, Garwin Craigon, Marie Ghazal, Peter Parton, Roger Coote, John G. TI Transcriptional responses of murine macrophages to the adenylate cyclase toxin of Bordetella pertussis SO MICROBIAL PATHOGENESIS LA English DT Article DE Bordetella pertussis; Adenylate cyclase toxin; CyaA; Macrophage; Microarray; Transcriptional responses ID PROTEIN-KINASE-A; DENDRITIC CELLS; NITRIC-OXIDE; ARGININE TRANSPORT; APOPTOTIC CELLS; NO PRODUCTION; ARGINASE-II; T-CELLS; CAMP; EXPRESSION AB Three different recombinant forms of CyaA were used to investigate transcriptional responses of murine bone marrow-derived macrophages (BMMs) using Affymetrix Mouse Genome GeneChips (R). These forms were enzymically active, invasive CyaA, non-enzymically active, invasive CyaA (CyaA*) and non-enzymically active, non-invasive CyaA (proCyaA*). BMMs, treated with 20 ng/ml of CyaA for 24 h, showed over 1000 significant changes in gene transcription compared with control cells. CyaA caused an increase in transcription of many inflammatory genes and genes associated with various signalling cascades such as those involved in cyclic AMP-dependent protein kinase A signalling. Most strikingly, CyaA caused down-regulation of numerous genes involved in cell proliferation. CyaA* at 20 ng/ml significantly up-regulated the transcription of only twelve genes after 24 It whereas proCyaA* at this concentration significantly increased the transcription of only two genes. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Cheung, Gordon Y. C.; Parton, Roger; Coote, John G.] Univ Glasgow, Div Infect & Immun, Inst Biomed & Life Sci, Glasgow Biomed Res Ctr, Glasgow G12 8TA, Lanark, Scotland. [Cheung, Gordon Y. C.; Dickinson, Paul; Sing, Garwin; Craigon, Marie; Ghazal, Peter] Univ Edinburgh, Scottish Ctr Gen Technol & Informat, Edinburgh EH16 4SB, Midlothian, Scotland. RP Cheung, GYC (reprint author), NIAID, NIH, LBD, 33 North Dr,Bldg 33,Room 1W20, Bethesda, MD 20892 USA. EM cheunggo@niaid.nih.gov RI Cheung, Yiu Chong /K-3565-2012; Dickinson, Paul/B-7598-2014 NR 44 TC 14 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JAN PY 2008 VL 44 IS 1 BP 61 EP 70 DI 10.1016/j.micpath.2007.08.007 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA 396KN UT WOS:000262590700008 PM 17890046 ER PT J AU Santoyo, G Strathern, JN AF Santoyo, Gustavo Strathern, Jeffrey N. TI Non-homologous end joining is important for repair of Cr(VI)-induced DNA damage in Saccharomyces cerevisiae SO MICROBIOLOGICAL RESEARCH LA English DT Article DE chromium; non-homologous end joining; homologous recombination; yeast ID STRAND-BREAK REPAIR; HOMOLOGOUS RECOMBINATION; CELL-CYCLE; CHROMIUM; YEAST AB Hexavalent chromium is known to be a potent carcinogen that leads to many different DNA lesions, including DNA - protein crosslinks, and single- and doubte-strand breaks. In Saccharomyces cerevisiae, DNA double-strand breaks are mainly repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ) repair pathways. Here, we show that mutants deficient in NHEJ (yku70 Delta, rad50 Delta, dnl4 Delta, mre11 Delta, xrs2 Delta) of S. cerevisiae are more sensitive to Cr(VI) toxic effects than wild-type cells. Also, a deletion mutant of SAE2 showed a similar sensitivity to Cr(VI), even though it has no apparent direct role in NHEJ. We also found that double mutants in HR and NHEJ (yku70 Delta/rad52 Delta, rad50 Delta/rad52 Delta, dnl4 Delta/rad52 Delta, mre11 Delta/rad52 Delta, xrs2 Delta/rad52 Delta) are synergistically more sensitive to Cr(VI) exposure than any of the single mutants, indicating that both repair pathways are involved in the repair of Cr(Vl)-induced lesions. Finally, when the NHEJ mutants were exposed to Cr(VI) under anaerobic growth conditions, Cr(VI) toxicity was suppressed. (c) 2007 Elsevier GmbH. All rights reserved. C1 [Santoyo, Gustavo; Strathern, Jeffrey N.] NCI, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. RP Santoyo, G (reprint author), Univ Michoacana, Inst Invest Quim Biol, Lab Recombinac & Diversidad Genom, Edificio B-5,Ciudad Univ, Morelia 58060, Michoacan, Mexico. EM gustavo_santoyo@yahoo.com OI Santoyo, Gustavo/0000-0002-0374-9661 FU Intramural NIH HHS NR 27 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-5013 J9 MICROBIOL RES JI Microbiol. Res. PY 2008 VL 163 IS 1 BP 113 EP 119 DI 10.1016/j.micres.2007.09.001 PG 7 WC Microbiology SC Microbiology GA 257MM UT WOS:000252803200013 PM 17923397 ER PT J AU Macura, T Goldberg, I AF Macura, Tomasz Goldberg, Ilya BA Wu, Q Merchant, FA Castleman, KR BF Wu, Q Merchant, FA Castleman, KR TI Image Data and Workflow Management SO MICROSCOPE IMAGE PROCESSING LA English DT Article; Book Chapter ID QUANTITATIVE-ANALYSIS; GENE ONTOLOGY; INFORMATICS; ENVIRONMENT; MICROSCOPY; TOOL C1 [Macura, Tomasz; Goldberg, Ilya] NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH,IRP, Baltimore, MD 21224 USA. RP Macura, T (reprint author), NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH,IRP, Baltimore, MD 21224 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055854-7 PY 2008 BP 499 EP 530 DI 10.1016/B978-0-12-372578-3.00018-0 PG 32 WC Microscopy; Imaging Science & Photographic Technology SC Microscopy; Imaging Science & Photographic Technology GA BGG50 UT WOS:000322840500020 ER PT J AU Heinrich, KM Jitnarin, N Suminski, RR Berkel, L Hunter, CM Alvarez, L Brundige, AR Peterson, AL Foreyt, JP Haddock, CK Poston, WSC AF Heinrich, Katie M. Jitnarin, Nattinee Suminski, Richard R. Berkel, LaVerne Hunter, Christine M. Alvarez, Lisa Brundige, Antionette R. Peterson, Alan L. Foreyt, John P. Haddock, C. Keith Poston, Walker S. C. TI Obesity classification in military personnel: A comparison of body fat, waist circumference, and body mass index measurements SO MILITARY MEDICINE LA English DT Article ID 4-COMPARTMENT MODEL; PREVALENCE; PERCENTAGE; CHINESE; WEIGHT AB Objective: The purpose of this study was to evaluate obesity classifications from body fat percentage (BF%), body mass index (BMI), and waist circumference (WC). Methods: A total of 451 overweight/obese active duty military personnel completed all three assessments. Results: Most were obese (men, 81%; women, 98%) using National Institutes of Health (NIH) BF% standards (men, >25%; women, >30%). Using the higher World Health Organization (WHO) BF >35% standard, 86% of women were obese. BMI (55.5% and 51.4%) and WC (21.4% and 31.9%) obesity rates were substantially lower for men and women, respectively (p < 0.05). BMI/WC were accurate discriminators for BF% obesity (0 for all comparisons >0.75, p < 0.001). Optimal cutoff points were lower than NIH/WHO standards; WC = 100 cm and BMI = 29 maximized sensitivity and specificity for men, and WC = 79 cm and BMI = 25.5 (NIH) or WC = 83 cm and BMI = 26 (WHO) maximized sensitivity and specificity for women. Conclusions: Both WC and BMI measures had high rates of false negatives compared to BF%. However, at a population level, WC/BMI are useful obesity measures, demonstrating fair-to-high discriminatory power. C1 [Heinrich, Katie M.] Univ Hawaii Manoa, Dept Publ Hlth Sci, Honolulu, HI 96822 USA. [Jitnarin, Nattinee; Berkel, LaVerne; Haddock, C. Keith; Poston, Walker S. C.] Univ Missouri, Dept Informat Med & Personalized Hlth, Sch Med, Western Missouri Mental Hlth Ctr, Kansas City, MO 64108 USA. [Suminski, Richard R.] Kansas City Univ Med & Biosci, Dept Physiol, Kansas City, MO 64106 USA. [Hunter, Christine M.] NIDDK, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA. [Alvarez, Lisa; Foreyt, John P.] Baylor Coll Med, Dept Med, Behav Med Res Ctr, Houston, TX 77030 USA. [Brundige, Antionette R.; Peterson, Alan L.] Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Heinrich, KM (reprint author), Univ Hawaii Manoa, Dept Publ Hlth Sci, 1960 East West Rd,Biomed D104B, Honolulu, HI 96822 USA. RI Heinrich, Katie/B-4782-2013 OI Heinrich, Katie/0000-0002-6837-408X NR 27 TC 18 Z9 18 U1 0 U2 4 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JAN PY 2008 VL 173 IS 1 BP 67 EP 73 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 251KT UT WOS:000252373000010 PM 18251334 ER PT S AU Neutzner, A Benard, G Youle, RJ Karbowski, M AF Neutzner, Albert Benard, Giovanni Youle, Richard J. Karbowski, Mariusz BE Gibson, GE Ratan, RR Beal, MF TI Role of the Ubiquitin Conjugation System in the Maintenance of Mitochondrial Homeostasis SO MITOCHONDRIA AND OXIDATIVE STRESS IN NEURODEGENERATIVE DISORDERS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Mitochondria and Oxisative Stress in Neurodegenerative Disorders CY SEP 26-29, 2007 CL New York Acad Sci, New York, NY SP Weill Med Coll, Cornell Univ, Grad Sch Med Sci, Ellison Med Fdn, Burke Med Res Inst HO New York Acad Sci DE ubiquitin; mitochondria; fusion; fission; quality control ID CELL-DEATH; SACCHAROMYCES-CEREVISIAE; DEPENDENT DEGRADATION; SPERM MITOCHONDRIA; QUALITY-CONTROL; APOPTOSIS; PROTEINS; DISEASE; PROTEASOME; LIGASE AB Mitochondria are essential for a variety of cellular functions, including ATP production, lipid biosynthesis, and calcium homeostasis. Moreover, a number of major cell signaling pathways, including apoptosis, require mitochondria. Consistent with a major role of mitochondria in the control of cell function, defects of these organelles are thought to induce a variety of pathologies ranging from diabetic neuropathies to Parkinson's and Alzheimer's diseases. Here we discuss the role of ubiquitin (Ub) conjugation in the maintenance of mitochondrial function. We found that at least four putative RING finger E3 Ub ligases, the main determinants of substrate specificity in the ubiquitination system, localize to mitochondria. Our data also demonstrate that mitochondria, membrane dynamics is under the regulatory control of the Ub-conjugation system. These and data recently published by others indicate that the Ub-conjugation system and proteasomal degradation of mitochondrial proteins might be vital for the maintenance of mitochondrial homeostasis and lead to cell demise when dysfunctional. C1 [Benard, Giovanni; Karbowski, Mariusz] Univ Maryland, Inst Biotechnol, MBC, Baltimore, MD 21201 USA. [Neutzner, Albert; Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. RP Karbowski, M (reprint author), Univ Maryland, Inst Biotechnol, MBC, 725 W Lombard St, Baltimore, MD 21201 USA. EM karbowsk@umbi.umd.edu RI Benard, Giovanni/M-3485-2014; OI Neutzner, Albert/0000-0001-9254-5558 NR 64 TC 52 Z9 52 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-713-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1147 BP 242 EP 253 DI 10.1196/annals.1427.012 PG 12 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Physiology SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIR99 UT WOS:000262397800022 PM 19076446 ER PT S AU Liu, D Pitta, M Mattson, MP AF Liu, Dong Pitta, Michael Mattson, Mark P. BE Gibson, GE Ratan, RR Beal, MF TI Preventing NAD(+) Depletion Protects Neurons against Excitotoxicity Bioenergetic Effects of Mild Mitochondrial Uncoupling and Caloric Restriction SO MITOCHONDRIA AND OXIDATIVE STRESS IN NEURODEGENERATIVE DISORDERS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Mitochondria and Oxisative Stress in Neurodegenerative Disorders CY SEP 26-29, 2007 CL New York Acad Sci, New York, NY SP Weill Med Coll, Cornell Univ, Grad Sch Med Sci, Ellison Med Fdn, Burke Med Res Inst HO New York Acad Sci DE excitotoxicity; bioenergetics; mitochondrial uncoupling; caloric restriction; NAD(+)/NADH; SIRT1; GLUT1; nicotinamide ID NEURODEGENERATIVE DISORDERS; OXIDATIVE STRESS; BRAIN; DEATH; METABOLISM; GLUTAMATE; PROTEIN-2; MECHANISMS; ISCHEMIA; STROKE AB Neurons are excitable cells that require large amounts of energy to support their survival and functions and are therefore prone to excitotoxicity, which involves energy depletion. By examining bioenergetic changes induced by glutamate, we found that: the cellular nicotinamide adenine dinucleotide (NAD(+)) level is a critical determinant of neuronal survival. The bioenergetic effects of mitochondrial uncoupling and caloric restriction were also examined in cultured neurons and rodent brain. 2, 4-dinitrophenol (DNP) is a chemical mitochondrial uncoupler that stimulates glucose uptake and oxygen consumption on cultured neurons, which accelerates oxidation of NAD(P)H to NAD(+) in mitochondria. The NAD(+)-dependent histone deacetylase sirtulin 1 (SIRT1) and glucose transporter 1 (GLUT1) mRNA are upregulated mouse brain under caloric restriction. To examine whether NAD(+) mediates neuroprotective effects, nicotinamide, a precursor of NAD(+) and inhibitor of SIRT1 and poly (ADP-ribose) polymerase 1 (PARP1) (two NAD(+)-dependent enzymes), was employed. Nicotinamide attenuated excitotoxic death and preserved cellular NAD(+) levels to support SIRT1 and PARP I activities. Our findings suggest that mild mitochondrial uncoupling and caloric restriction exert hormetic effects by stimulating bioenergetics in neurons thereby increasing tolerance of neurons to metabolic stress. C1 [Liu, Dong; Pitta, Michael; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Liu, D (reprint author), NIA, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM liudo@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000315-07] NR 26 TC 55 Z9 58 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-713-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1147 BP 275 EP 282 DI 10.1196/annals.1427.028 PG 8 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Physiology SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIR99 UT WOS:000262397800025 PM 19076449 ER PT J AU Henson, DE Schwartz, AM Nsouli, H Grimley, PM Anderson, WF AF Henson, D. E. Schwartz, A. M. Nsouli, H. Grimley, P. M. Anderson, W. F. TI In situ and invasive carcinoma of the female breast pre- and post-mammography SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 George Washington Univ, Washington, DC USA. USUHS, Bethesda, MD USA. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 159 BP 37A EP 38A PG 2 WC Pathology SC Pathology GA 248UA UT WOS:000252180200159 ER PT J AU Walter, BA Valera, VA Tresserra, F Merino, MJ AF Walter, B. A. Valera, V. A. Tresserra, F. Merino, M. J. TI Loss of heterozygosity of PTEN in pregnancy-associated breast cancer and its correlation with BRCA 1/2, p53, NM23, HER-2 and hormonal status SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Inst Univ Dexeus, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 262 BP 59A EP 59A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180200262 ER PT J AU Bechert, CJ Ackerman, B AF Bechert, C. J. Ackerman, B. TI Risks associated with permanent synthetic dermal fillers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. [Bechert, C. J.; Ackerman, B.] Ackerman Acad Dermatopathol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 405 BP 91A EP 91A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180200405 ER PT J AU Cheung, WL Krizman, DB Alvarez, H Hood, BL Darfer, MM Veensira, TD Mollenhauer, J Habbe, N Feldman, G Maitra, A AF Cheung, W. L. Krizman, D. B. Alvarez, H. Hood, B. L. Darfer, M. M. Veensira, T. D. Mollenhauer, J. Habbe, N. Feldman, G. Maitra, A. TI Application of a global proteomic approach to archival precursor lesions: Upregulation of DMBT-1 and TG2 in pancreatic cancer precursors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Express Path Inc, Gaithersburg, MD USA. NCI, Frederick, MD USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 524 BP 115A EP 116A PG 2 WC Pathology SC Pathology GA 248UA UT WOS:000252180200524 ER PT J AU Merino, MJ Linehan, WM AF Merino, M. J. Linehan, W. M. TI Premalignant lesions of the kidney SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Merino, M. J.; Linehan, W. M.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 777 BP 170A EP 170A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180200776 ER PT J AU Navas, R Linehan, WM Merino, MJ AF Navas, R. Linehan, W. M. Merino, M. J. TI Oncocytic tumors of undetermine malignant potential SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Navas, R.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 790 BP 173A EP 173A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180200789 ER PT J AU Valera, VA Roberts, D Linehan, WM Merino, HJ AF Valera, V. A. Roberts, D. Linehan, W. M. Merino, H. J. TI Proteomic analysis identifies key metabolic and stress proteins differentially expressed in renal cell carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Valera, V. A.; Roberts, D.; Linehan, W. M.; Merino, H. J.] NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 853 BP 186A EP 187A PG 2 WC Pathology SC Pathology GA 248UA UT WOS:000252180200852 ER PT J AU Elishaev, E Guido, R Dabbs, D Chatterjee, N Lacey, J Muller, C Sherman, ME AF Elishaev, E. Guido, R. Dabbs, D. Chatterjee, N. Lacey, J., Jr. Muller, C. Sherman, M. E. TI Frequency of PTEN loss in benign endometria of premenopausal women: A preliminary analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Magee Womens Hosp, Sch Med, Pittsburgh, PA 15260 USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 923 BP 202A EP 202A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201052 ER PT J AU Mani, H Merino, MJ AF Mani, H. Merino, M. J. TI Malignant mesothelioma presenting as, and mimicking, ovarian cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Mani, H.; Merino, M. J.] NIH, Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 973 BP 212A EP 213A PG 2 WC Pathology SC Pathology GA 248UA UT WOS:000252180201102 ER PT J AU Sanz, J Teller, L Vockes, C Linehan, WM Sanz-Esponera, J Merino, MJ AF Sanz, J. Teller, L. Vockes, C. Linehan, W. M. Sanz-Esponera, J. Merino, M. J. TI Genetic alterations of uterine fibroids in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Hosp Clin San Carlos, Madrid, Spain. NCI, Bethesda, MD USA. RI Sanz, Julian/G-5276-2013 NR 0 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1021 BP 223A EP 223A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201150 ER PT J AU Choi, WWL Weisenburger, DD Greiner, TC Piris, MA Banham, AH Jaye, DL Wade, PA Iqbal, J Hans, CP Fu, K Gascoyne, RD Delabie, J Rosenwald, A Rimsza, L Campo, E Jaffe, ES Staudt, LM Chan, WC AF Choi, W. W. L. Weisenburger, D. D. Greiner, T. C. Piris, M. A. Banham, A. H. Jaye, D. L. Wade, P. A. Iqbal, J. Hans, C. P. Fu, K. Gascoyne, R. D. Delabie, J. Rosenwald, A. Rimsza, L. Campo, E. Jaffe, E. S. Staudt, L. M. Chan, W. C. TI A new immunostain algorithm improves the classification of diffuse large B-cell lymphoma into prognostically significant subgroups SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Univ Nebraska Med Ctr, Omaha, NE USA. Spanish Natl Canc Ctr, Madrid, Spain. Univ Oxford, Oxford OX1 2JD, England. Emory Univ, Atlanta, GA 30322 USA. British Columbia Canc Agcy, Vancouver, BC, Canada. Norwegian Radium Hosp, Oslo, Norway. Univ Wurzburg, D-97070 Wurzburg, Germany. Univ Arizona, Tucson, AZ 85721 USA. Univ Barcelona, E-08007 Barcelona, Spain. NCI, Bethesda, MD USA. RI Banham, Alison/B-2966-2009 NR 0 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1144 BP 250A EP 250A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201273 ER PT J AU Gradowski, JF Joffe, E Warnke, R Pittaluga, S Surti, U Gole, L Swerdlow, SH AF Gradowski, J. F. Joffe, E. S. Warnke, R. Pittaluga, S. Surti, U. Gole, L. Swerdlow, S. H. TI Do follicular lymphomas (FL) with plasmacytic differentiation (PCD) have characteristic features? An immunoFISH study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. NCI, Bethesda, MD 20892 USA. Stanford Univ, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1168 BP 255A EP 255A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201297 ER PT J AU Jiang, L Yuan, C Janik, J Stetler-Stevenson, M AF Jiang, L. Yuan, C. Janik, J. Stetler-Stevenson, M. TI Heterogeneous expression of CD52 evaluated by flow Cytometry analysis among neoplasms of mature T lymphocytes and NK cells SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Jiang, L.; Yuan, C.; Janik, J.; Stetler-Stevenson, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1184 BP 258A EP 259A PG 2 WC Pathology SC Pathology GA 248UA UT WOS:000252180201313 ER PT J AU Marie, I Fu, W Stoddard, J Wilson, TM Metcalfe, DD Robyn, J Noel, P AF Marie, I. Fu, W. Stoddard, J. Wilson, T. M. Metcalfe, D. D. Robyn, J. Noel, P. TI Occurrence of JAK2 V617F mutation in patients with systemic mastocytosis and thrombocytosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 CC NIH, Bethesda, MD USA. NIH, NIAID, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1209 BP 264A EP 265A PG 2 WC Pathology SC Pathology GA 248UA UT WOS:000252180201338 ER PT J AU Rahemtullah, A Jaffe, ES Harris, NL Hassejian, RP AF Rahemtullah, A. Jaffe, E. S. Harris, N. L. Hassejian, R. P. TI Nodular lymphocyte predominant Hodgkin lymphoma with an interfollicular growth pattern and atypical T cells: A distinct disease variant? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1235 BP 270A EP 270A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201364 ER PT J AU Rizzo, KA Streubel, B Chott, A Pittaluga, S Raffeld, M Raffeld, ES Jaffe, ES AF Rizzo, K. A. Streubel, B. Chott, A. Pittaluga, S. Raffeld, M. Raffeld, E. S. Jaffe, E. S. TI Pediatric marginal zone B-cell lymphomas; Analysis of histopathology, immunophenotype and genetic aberrations SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Natl Inst Hlth, Bethesda, MD USA. Vienna Gen Hosp, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1240 BP 271A EP 272A PG 2 WC Pathology SC Pathology GA 248UA UT WOS:000252180201369 ER PT J AU Felipe-Silva, A Quezado, M Gatfield, S Wincovitch, S Alves, F AF Felipe-Silva, A. Quezado, M. Gatfield, S. Wincovitch, S. Alves, F. TI Analysis of nucleic acid index in hepatocellular carcinoma, dysplastic nodules, regenerative macronodules and cirrhotic liver SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD USA. Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. RI FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1385 BP 304A EP 304A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201514 ER PT J AU Mani, H Kleiner, DE AF Mani, H. Kleiner, D. E. TI Validation of a feature recording system for hepatic graft-versus-host disease SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Mani, H.; Kleiner, D. E.] NIH, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1417 BP 311A EP 311A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201546 ER PT J AU Galli, S Li, G Tsokos, M AF Galli, S. Li, G. Tsokos, M. TI Expression of insulin-like growth factor type 1 receptor (IGF-1R) in ewing sarcoma family tumors (ESFT) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Galli, S.; Li, G.; Tsokos, M.] NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1518 BP 332A EP 332A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201646 ER PT J AU Galli, S Tsokos, M Prygodzki, R Ahmed, A AF Galli, S. Tsokos, M. Prygodzki, R. Ahmed, A. TI Expression of caspase 8, bcl-2, survivin and XIAP in Wilms' tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Washington, DC 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1517 BP 332A EP 332A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201645 ER PT J AU Fowler, CB Cunningham, RE Waybright, TJ Blonder, J Veenstra, TD Mason, JT O'Leary, TJ AF Fowler, C. B. Cunningham, R. E. Waybright, T. J. Blonder, J. Veenstra, T. D. Mason, J. T. O'Leary, T. J. TI Elevated hydrostatic pressure promotes protein recovery from formalin-fixed, paraffin-embedded tissue surrogates SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 Armed Forces Inst Pathol, Rockville, MD USA. Vet Hlth Adm, Washington, DC USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1661 BP 365A EP 365A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201789 ER PT J AU Rodriguez-Canales, J Majumdar, ZK Ory, EC Hanson, JC Pohida, TJ Tangrea, MA Chuaqui, RF Bonner, RF Emmert-Buck, MR AF Rodriguez-Canales, J. Majumdar, Z. K. Ory, E. C. Hanson, J. C. Pohida, T. J. Tangrea, M. A. Chuaqui, R. F. Bonner, R. F. Emmert-Buck, M. R. TI Expression microdissection: A new immuno-based dissection technology for cellular and nuclear procurement SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NICHD, Bethesda, MD USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1687 BP 371A EP 371A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201815 ER PT J AU Valera, VA Walter, BA Merino, MJ AF Valera, V. A. Walter, B. A. Merino, M. J. TI Optimal protein extraction from formalin-fixed paraffin-embedded tissues for expression profiling of tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol C1 [Valera, V. A.; Walter, B. A.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2008 VL 21 SU 1 MA 1696 BP 373A EP 373A PG 1 WC Pathology SC Pathology GA 248UA UT WOS:000252180201824 ER PT J AU Aoyagi, S Archer, TK AF Aoyagi, Sayura Archer, Trevor K. TI Nicotinamide uncouples hormone-dependent chromatin remodeling from transcription complex assembly SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BREAST-CANCER CELLS; MAMMALIAN MEDIATOR COMPLEX; ESTROGEN-RECEPTOR-ALPHA; NUCLEAR RECEPTORS; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; IN-VIVO; COACTIVATOR COMPLEXES; PROTEIN DEACETYLASES; HISTONE DEACETYLASE AB Sirtuins, homologs of the yeast SIR2 family, are protein deacetylases that require nicotinamide adenosine dinucleotide as cofactor. To determine whether the sirtuin family of deacetylases is involved in progesterone receptor (PR)-mediated transcription, the effect of sirtuin inhibitor, nicotinamide (NAM), was monitored in T47D breast cancer cells. NAM suppressed hormone-dependent activation of PR-regulated genes in a dose-dependent manner. Surprisingly, NAM-mediated inhibition of PR-mediated transcription occurs independently of SIRT1 and PARP1. Chromatin immunoprecipitation experiments did not show that PR binding nor that of the coactivators CBP and SRC3 was compromised. Consistent with the recruitment of the BRG1 chromatin remodeling complex, promoter chromatin remodeling still occurs despite NAM inhibition of PR transactivation. Rather, we show that this inhibition of transcription is due to dramatic loss of recruitment of the basal transcriptional machinery to the promoter. These results show that NAM uncouples promoter chromatin remodeling from transcription preinitiation complex assembly and suggest the existence of vital NAM-regulated steps required for promoter chromatin remodeling and basal transcription complex communication. C1 [Aoyagi, Sayura; Archer, Trevor K.] NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, 111 Alexander Dr,POB 12233,MD D4-01, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov FU Intramural NIH HHS NR 66 TC 20 Z9 20 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2008 VL 28 IS 1 BP 30 EP 39 DI 10.1128/MCB.01158-07 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245HI UT WOS:000251925300002 PM 17954562 ER PT J AU Galban, S Kuwano, Y Pullmann, R Martindale, JL Kim, HH Lal, A Abdelmohsen, K Yang, XL Dang, YJ Liu, JO Lewis, SM Holcik, M Gorospe, M AF Galban, Stefanie Kuwano, Yuki Pullmann, Rudolf, Jr. Martindale, Jennifer L. Kim, Hyeon Ho Lal, Ashish Abdelmohsen, Kotb Yang, Xiaoling Dang, Youngjun Liu, Jun O. Lewis, Stephen M. Holcik, Martin Gorospe, Myriam TI RNA-Binding proteins HuR and PTB promote the translation of hypoxia-inducible factor 1 alpha SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; INTERNAL-RIBOSOME-ENTRY; LUNG EPITHELIAL-CELLS; MESSENGER-RNA; MEDIATED TRANSLATION; KINASE PATHWAY; FACTOR 1-ALPHA; HIF-1-ALPHA; EXPRESSION; CANCER AB The levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) are tightly controlled. Here, we investigated the post-transcriptional regulation of HIF-1 alpha expression in human cervical carcinoma HeLa cells responding to the hypoxia mimetic CoCl2. Undetectable in untreated cells, HIF-1 alpha levels increased dramatically in CoCl2-treated cells, while HIF-1 alpha mRNA levels were unchanged. HIF-1 alpha translation was potently elevated by CoCl, treatment, as determined by de novo translation analysis and by monitoring the polysomal association of HIF-1 alpha mRNA. An internal ribosome entry site in the HIF-1 alpha 5' untranslated region (UTR) was found to enhance translation constitutively, but it did not further induce translation in response to CoCl, treatment. Instead, we postulated that RNA-binding proteins HuR and PTB, previously shown to bind HIF-1 alpha mRNA, participated in its translational upregulation after CoCl2 treatment. Indeed, both RNA-binding proteins were found to bind HIF-1 alpha mRNA in a CoCl2-inducible manner as assessed by immunoprecipitation of endogenous ribonucleoprotein complexes. Using a chimeric reporter, polypyrimidine tract-binding protein (PTB) was found to bind the HIF-1 alpha 3'UTR, while HuR associated principally with the 5'UTR. Lowering PTB expression or HuR expression using RNA interference reduced HIF-1 alpha translation and expression levels but not HIF-1 alpha mRNA abundance. Conversely, HIF-1 alpha expression and translation in response to CoCl2 were markedly elevated after HuR overexpression. We propose that HuR and PTB jointly upregulate HIF-1 alpha translation in response to CoCl2. C1 [Galban, Stefanie; Kuwano, Yuki; Pullmann, Rudolf, Jr.; Martindale, Jennifer L.; Kim, Hyeon Ho; Lal, Ashish; Abdelmohsen, Kotb; Yang, Xiaoling; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Aging Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Dang, Youngjun; Liu, Jun O.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Lewis, Stephen M.; Holcik, Martin] Childrens Hosp Eastern Ontario, Res Inst, Apoptosis Res Ctr, Ottawa, ON K1H 8L1, Canada. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Aging Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov RI Holcik, Martin/A-9768-2008; Lewis, Stephen/E-5533-2010; dang, yongjun/A-8095-2011; Holcik, Martin/E-5372-2011; dang, yongjun/M-6531-2016 OI Lewis, Stephen/0000-0001-9537-5822; dang, yongjun/0000-0001-7237-1132 FU Intramural NIH HHS NR 67 TC 150 Z9 154 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2008 VL 28 IS 1 BP 93 EP 107 DI 10.1128/MCB.00973-07 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245HI UT WOS:000251925300008 PM 17967866 ER PT J AU Sinha, D Klise, A Sergeev, Y Hose, S Bhutto, IA Hackler, L Malpic-Ilanos, T Samtuni, S Grebe, R Goldberg, MF Hejtmancik, JF Nath, A Zack, DJ Fariss, RN McLeod, DS Sundin, O Broman, KW Lutty, GA Zigler, JS AF Sinha, Debasish Klise, Andrew Sergeev, Yuri Hose, Stacey Bhutto, Imran A. Hackler, Laszlo, Jr. Malpic-Ilanos, Tanya Samtuni, Sonia Grebe, Rhonda Goldberg, Morton F. Hejtmancik, J. Fielding Nath, Avindra Zack, Donald J. Fariss, Robert N. McLeod, D. Scott Sundin, Olof Broman, Karl W. Lutty, Gerard A. Zigler, J. Samuel, Jr. TI beta A3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE beta A3/A1-crystallin; astrocytes; retinal vasculature; remodeling; intermediate filaments; rat spontaneous mutation ID CONGENITAL NUCLEAR CATARACT; RAT OPTIC-NERVE; SPONTANEOUS MUTATION; DOMINANT CATARACT; BETA-CRYSTALLIN; ASTROCYTES; EYE; MIGRATION; PROTEIN; DIFFERENTIATION AB Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague-Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nucl allele results from mutation of the beta A3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nucl astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nucl retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate beta A3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina. (C) 2007 Elsevier Inc. All rights reserved. C1 [Sinha, Debasish; Klise, Andrew; Hose, Stacey; Bhutto, Imran A.; Hackler, Laszlo, Jr.; Grebe, Rhonda; Goldberg, Morton F.; Zack, Donald J.; McLeod, D. Scott; Sundin, Olof; Lutty, Gerard A.; Zigler, J. Samuel, Jr.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21231 USA. [Malpic-Ilanos, Tanya; Nath, Avindra] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Sergeev, Yuri; Samtuni, Sonia; Hejtmancik, J. Fielding; Fariss, Robert N.] NEI, NIH, Bethesda, MD 20892 USA. [Broman, Karl W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Stat, Baltimore, MD USA. RP Sinha, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Bunting Blaustein Canc Res Bldg 2,1550 Orleans St, Baltimore, MD 21231 USA. EM Debasish@jhmi.edu OI Zack, Don/0000-0002-7966-1973 FU Intramural NIH HHS; NEI NIH HHS [R01 EY009357-16, EY009357, EY009769, R01 EY009357, R01 EY009769]; NIGMS NIH HHS [GM074244, R01 GM074244]; NIMH NIH HHS [P01 MH070056, P01 MH070306, P01MH070306, P01MH70056] NR 39 TC 34 Z9 34 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2008 VL 37 IS 1 BP 85 EP 95 DI 10.1016/j.men.2007.08.016 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 255UM UT WOS:000252683100008 PM 17931883 ER PT J AU Pramatarova, A Chen, K Howell, BW AF Pramatarova, Albena Chen, Kelian Howell, Brian W. TI A genetic interaction between the APP and Dab1 genes influences brain development SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Dab1; reelin; APP; brain development; cerebellum; cortical lamination ID AMYLOID PRECURSOR PROTEIN; REELER-LIKE PHENOTYPE; PHOSPHOTYROSINE-BINDING DOMAIN; CAJAL-RETZIUS NEURONS; EMBRYONIC STEM-CELLS; ALZHEIMERS-DISEASE; MOUSE DISABLED-1; LAMINAR ORGANIZATION; TRANSGENIC MICE; FE65 AB The Dahl docking protein is required for the proper organization of brain laminae and for a signal transduction pathway initiated by Reelin binding to the ApoER2 and VLDLR receptors on the cell surface of neurons. Dahl physically interacts with APP; however, it is not known whether the APP gene influences Dab1 function. Here we demonstrate a genetic interaction between Dab1 and APP. Dab1-hypomorphic animals have neuronal ectopias in the neocortex and reduced cerebellar volume, possibly a consequence of Purkinje cell misplacement. These phenotypes are exacerbated in transgenic animals overexpressing a mutant form of APP, APP(swe), which is characterized by increased processing at the beta-secretase site. The Dah1-hypomorphic phenotype is improved in the cerebellum of animals that are deficient for APP. Together this suggests that APP expression constrains the consequences of Dab1 activity during brain development. Published by Elsevier Inc. C1 [Pramatarova, Albena; Chen, Kelian; Howell, Brian W.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Howell, BW (reprint author), NINDS, Neurogenet Branch, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM howellb@ninds.nih.gov OI Howell, Brian/0000-0002-0204-0773 FU Intramural NIH HHS [Z01 NS002987-08] NR 53 TC 25 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2008 VL 37 IS 1 BP 178 EP 186 DI 10.1016/j.mcn.2007.09.008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 255UM UT WOS:000252683100016 PM 18029196 ER PT J AU Basu, MK Rogozin, IB Deusch, O Dagan, T Martin, W Koonin, EV AF Basu, Malay Kumar Rogozin, Igor B. Deusch, Oliver Dagan, Tal Martin, William Koonin, Eugene V. TI Evolutionary dynamics of introns in plastid-derived genes in plants: Saturation nearly reached but slow intron gain continues SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE intron gain; intron loss; plant evolution; plastid-derived genes ID MULTIPLE SEQUENCE ALIGNMENT; MONOCOT-DICOT DIVERGENCE; HIGHLY EXPRESSED GENES; GROUP-II INTRONS; SPLICEOSOMAL INTRONS; EUKARYOTIC EVOLUTION; CHLOROPLAST GENOMES; MAXIMUM-LIKELIHOOD; EXON THEORY; POSITIONS AB Some of the principal transitions in the evolution of eukaryotes are characterized by engulfment of prokaryotes by primitive eukaryotic cells. In particular, similar to 1.6 billion years ago, engulfment of a cyanobacterium that became the ancestor of chloroplasts and other plastids gave rise to Plantae, the major branch of eukaryotes comprised of glaucophytes, red algae, green algae, and green plants. After endosymbiosis, there was large-scale migration of genes from the endosymbiont to the nuclear genome of the host such that similar to 18% of the nuclear genes in Arabidopsis appear to be of chloroplast origin. To gain insights into the process of evolution of gene structure in these, originally, intronless genes, we compared the properties and the evolutionary dynamics of introns in genes of plastid origin and ancestral eukaryotic genes in Arabidopsis, poplar, and rice genomes. We found that intron densities in plastid-derived genes were slightly but significantly lower than those in ancestral eukaryotic genes. Although most of the introns in both categories of genes were conserved between monocots (rice) and dicots (Arabidopsis and poplar), lineage-specific intron gain was more pronounced in plastid-derived genes than in ancestral genes, whereas there was no significant difference in the intron loss rates between the 2 classes of genes. Thus, after the transfer to the nuclear genome, the plastid-derived genes have undergone a massive intron invasion that, by the time of the divergence of dicots and monocots (150-200 MYA), yielded intron densities only slightly lower than those in ancestral genes. Nevertheless, the accumulation of introns in plastid-derived genes appears not to have reached saturation and continues to this time, albeit at a low rate. The overall pattern of intron gain and loss in the plastid-derived genes is shaped by this continuing gain and the more general tendency for loss that is characteristic of the recent evolution of plant genes. C1 [Basu, Malay Kumar; Rogozin, Igor B.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Deusch, Oliver; Dagan, Tal; Martin, William] Univ Dusseldorf, Inst Bot 3, Dusseldorf, Germany. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nim.nih.gov RI Martin, William /O-5446-2015; Martin, William/C-5680-2008 OI Martin, William /0000-0003-1478-6449; FU Intramural NIH HHS NR 72 TC 22 Z9 22 U1 4 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JAN PY 2008 VL 25 IS 1 BP 111 EP 119 DI 10.1093/molbev/msm234 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 265QL UT WOS:000253375900012 PM 17974547 ER PT J AU Kohn, KW Aladjem, MI Weinstein, JN Pommier, Y AF Kohn, Kurt W. Aladjem, Mirit I. Weinstein, John N. Pommier, Yves TI Chromatin challenges during DNA replication: A systems representation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HISTONE DEACETYLASE ACTIVITY; CELL NUCLEAR ANTIGEN; FUNCTIONAL COOPERATION; ASSEMBLY FACTOR-1; STRUCTURAL BASIS; HUMAN ASF1; H3; HETEROCHROMATIN; METHYLATION; COMPLEX AB In a recent review, A. Groth and coworkers presented a comprehensive account of nucleosome disassembly in front of a DNA replication fork, assembly behind the replication fork, and the copying of epigenetic information onto the replicated chromatin. Understanding those processes however would be enhanced by a comprehensive graphical depiction analogous to a circuit diagram. Accordingly, we have constructed a molecular interaction map (MIM) that preserves in essentially complete detail the processes described by Groth et al. The MIM organizes and elucidates the information presented by Groth et al. on the complexities of chromatin replication, thereby providing a tool for system-level comprehension of the effects of genetic mutations, altered gene expression, and pharmacologic intervention. C1 [Kohn, Kurt W.; Aladjem, Mirit I.; Weinstein, John N.; Pommier, Yves] Natl Canc Inst, Mol Pharmacol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), Natl Canc Inst, Mol Pharmacol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. EM kohnk@dc37a.nci.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 NR 44 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2008 VL 19 IS 1 BP 1 EP 7 DI 10.1091/mbc.E07-06-0528 PG 7 WC Cell Biology SC Cell Biology GA 343IT UT WOS:000258847500001 PM 17959828 ER PT J AU Satyanarayana, A Hilton, MB Kaldis, P AF Satyanarayana, Ande Hilton, Mary Beth Kaldis, Philipp TI p21 inhibits Cdk1 in the absence of Cdk2 to maintain the G1/S phase DNA damage checkpoint SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; LIVER-REGENERATION; RETINOBLASTOMA PROTEIN; SIGNALING PATHWAYS; GENOTOXIC STRESS; GENE-EXPRESSION; CDC2 KINASE; PHOSPHORYLATION; ARREST AB Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2(-/-) mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial hepatectomy (PH) in Cdk2(-/-) mice, arrest promptly at the G1/S checkpoint in response to gamma-irradiation due to activation of p53 and p21 inhibiting Cdk1. Furthermore re-entry into S phase after irradiation was delayed in Cdk2(-/-) cells due to prolonged and impaired DNA repair activity. In addition, Cdk2(-/-) mice were more sensitive to lethal irradiation compared to wild-type and displayed delayed resumption of DNA replication in regenerating liver cells. Our results suggest that the G1/S DNA damage checkpoint is intact in the absence of Cdk2, but Cdk2 is important for proper repair of the damaged DNA. C1 [Satyanarayana, Ande; Hilton, Mary Beth; Kaldis, Philipp] Natl Canc Inst, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Kaldis, P (reprint author), Inst Mol & Cell Biol, Cell Div & Canc Lab, Singapore 138673, Singapore. EM kaldis@imcb.a-star.edu.sg RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX We thank Matt McCollum and Angie Smith for animal care; Rodney Wiles for helping with the irradiation; and Donna Butcher, Roberta Smith, and the Pathology/ Histotechnology Laboratory for tissue sectioning and staining. We thank Prabhakar Gudla for helping with confocal microscopy. We appreciated the help of the Kaldis lab members for discussions and support. We are thankful to Weimin Li and Kasim Diril for comments on the manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 65 TC 77 Z9 80 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2008 VL 19 IS 1 BP 65 EP 77 DI 10.1091/mbc.E07-06-0525 PG 13 WC Cell Biology SC Cell Biology GA 343IT UT WOS:000258847500007 PM 17942597 ER PT J AU Page, EL Chan, DA Giaccia, AJ Levine, M Richard, DE AF Page, Elisabeth L. Chan, Denise A. Giaccia, Amato J. Levine, Mark Richard, Darren E. TI Hypoxia-inducible factor-1 alpha stabilization in nonhypoxic conditions: Role of oxidation and intracellular ascorbate depletion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SMOOTH-MUSCLE-CELLS; TUMOR-SUPPRESSOR PROTEIN; FACTOR 1-ALPHA HIF-1-ALPHA; MITOCHONDRIAL COMPLEX-III; HUMAN ERYTHROPOIETIN GENE; FACTOR-I; ANGIOTENSIN-II; HIF-ALPHA; PROLYL HYDROXYLATION; TRANSCRIPTIONAL ACTIVATION AB Hypoxia-inducible factor-1 (HIF-1) is a decisive element for the transcriptional regulation of many genes induced under low oxygen conditions. Under normal oxygen conditions, HIF-1 alpha, the active subunit of HIF-1, is hydroxylated on proline residues by specific HIF prolyl-hydroxylases, leading to ubiquitination and degradation by the proteasome. In hypoxia, hydroxylation and ubiquitination are blocked and HIF-1 alpha accumulates in cells. Recent studies have shown that in normal oxygen conditions G-protein-coupled receptor agonists, including angiotensin (Ang) II and thrombin, potently induce and activate HIF-1 in vascular smooth muscle cells. The current study identifies HIF-1 alpha protein stabilization as a key mechanism for HIF-1 induction by Ang II. We show that hydroxylation on proline 402 is altered by Ang II, decreasing pVHL binding to HIF-1 alpha and allowing HIF-1 alpha protein to escape subsequent ubiquitination and degradation mechanisms. We show that HIF-1 alpha stability is mediated through the Ang II-mediated generation of hydrogen peroxide and a subsequent decrease in ascorbate levels, leading to decreased HIF prolyl-hydroxylase activity and HIF-1 alpha stabilization. These findings identify novel and intricate signaling mechanisms involved in HIF-1 complex activation and will lead to the elucidation of the importance of HIF-1 in different Ang II-related cell responses. C1 [Page, Elisabeth L.; Richard, Darren E.] Univ Laval, Dept Med, Ctr Rech Hotel Dieu Quebec, Quebec City, PQ G1R 2J6, Canada. [Chan, Denise A.; Giaccia, Amato J.] Stanford Univ, Dept Radiat Oncol, Ctr Clin Sci Res, Stanford, CA 94305 USA. [Levine, Mark] NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Richard, DE (reprint author), Univ Laval, Dept Med, Ctr Rech Hotel Dieu Quebec, Quebec City, PQ G1R 2J6, Canada. EM darren.richard@crhdq.ulaval.ca OI Richard, Darren/0000-0003-2690-0480 FU Canadian Institutes of Health Research (CIHR) [MOP-49609]; Heart and Stroke Foundations of Quebec and Canada FX We are grateful to Guylaine Soucy and Genevieve Robitaille for their excellent technical assistance. We also thank Dr. Christopher Pugh, Dr. Edurne Berra, and Amandine Ginouves for help with plasmid constructs. This work was supported by grants from the Canadian Institutes of Health Research (CIHR, MOP-49609) and the Heart and Stroke Foundations of Quebec and Canada. D. E. R. is the recipient of a CIHR New Investigator Award. E. L. P. holds a Canada Graduate Scholarship from the CIHR. NR 62 TC 95 Z9 98 U1 2 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2008 VL 19 IS 1 BP 86 EP 94 DI 10.1091/mbc.E07-06-0612 PG 9 WC Cell Biology SC Cell Biology GA 343IT UT WOS:000258847500009 PM 17942596 ER PT J AU Hsu, KL Gildersleeve, JC Mahal, LK AF Hsu, Ku-Lung Gildersleeve, Jeffrey C. Mahal, Lara K. TI A simple strategy for the creation of a recombinant lectin microarray SO MOLECULAR BIOSYSTEMS LA English DT Article ID PSEUDOMONAS-AERUGINOSA LECTIN; UROPATHOGENIC ESCHERICHIA-COLI; CYSTIC-FIBROSIS PATIENTS; PA-IIL; STRUCTURAL BASIS; SALMONELLA-TYPHIMURIUM; MASS-SPECTROMETRY; EPITHELIAL-CELLS; TYPE-1 FIMBRIAE; RAPID ANALYSIS AB Glycomics, i.e. the high-throughput analysis of carbohydrates, has yet to reach the level of ease and import of its counterparts, genomics and proteomics, due to the difficulties inherent in carbohydrate analysis. The advent of lectin microarray technology addresses many of these problems, providing a straightforward approach for glycomic analysis. However, current microarrays are limited to the available lectin set, which consists mainly of plant lectins isolated from natural sources. These lectins have inherent problems including inconsistent activity and availability. Also, many plant lectins are glycosylated, complicating glycomic evaluation of complex samples, which may contain carbohydrate-binding proteins. The creation of a recombinant, well-defined lectin set would resolve many of these issues. Herein, we describe an efficient strategy for the systematic creation of recombinant lectins for use in microarray technology. We present a small panel of simple-to-purify bacterially-derived lectins that show reliable activity and de. ne their binding specificities by both carbohydrate microarray and ELISA. We utilize this panel to create a recombinant lectin microarray that is able to distinguish glycopatterns for both proteins and cell samples. This work opens the door to the establishment of a vast set of defined lectins via high-throughout approaches, advancing lectin microarray technology for glycomic analysis. C1 [Mahal, Lara K.] Univ Texas Austin, Dept Chem & Biochem, Ctr Syst & Synthet Biol, Austin, TX 78712 USA. [Gildersleeve, Jeffrey C.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Mahal, LK (reprint author), Univ Texas Austin, Dept Chem & Biochem, Ctr Syst & Synthet Biol, 1 Univ Stn,A5300, Austin, TX 78712 USA. EM lmahal@cm.utexas.edu RI Hsu, Ku-Lung/J-2885-2014; Gildersleeve, Jeffrey/N-3392-2014 OI Hsu, Ku-Lung/0000-0001-5620-3972; FU Intramural NIH HHS NR 70 TC 55 Z9 57 U1 1 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2008 VL 4 IS 6 BP 654 EP 662 DI 10.1039/b800725j PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304JW UT WOS:000256106800025 PM 18493664 ER PT J AU Clore, GM AF Clore, G. Marius TI Visualizing lowly-populated regions of the free energy landscape of macromolecular complexes by paramagnetic relaxation enhancement SO MOLECULAR BIOSYSTEMS LA English DT Review ID PROTEIN-PROTEIN ASSOCIATION; SITE-DIRECTED SPIN; TRANSIENT ENCOUNTER COMPLEXES; MALTOSE-BINDING PROTEIN; N-TERMINAL DOMAIN; PANCREATIC TRYPSIN-INHIBITOR; DISPERSION NMR-SPECTROSCOPY; GLOBAL FOLD DETERMINATION; HOMEODOMAIN-DNA COMPLEX; OVERHAUSER EFFECT DATA AB Many biological macromolecular interactions proceed via lowly-populated, highly transient species that arise from rare excursions between the minimum free energy configuration and other local minima of the free energy landscape. Little is known about the structural properties of such lowly-occupied states since they are difficult to trap and hence inaccessible to conventional structural and biophysical techniques. Yet these states play a crucial role in a variety of dynamical processes including molecular recognition and binding, allostery, induced-fit and self-assembly. Here we highlight recent progress in paramagnetic nuclear magnetic resonance to detect, visualize and characterize lowly-populated transient species at equilibrium. The underlying principle involves the application of paramagnetic relaxation enhancement (PRE) in the fast exchange regime. Under these conditions the footprint of the minor species can be observed in the PRE profiles measured for the major species, providing distances between the paramagnetic label and protons of interest are shorter in the minor species than the major one. Ensemble simulated annealing refinement directly against the PRE data permits one to obtain structural data on the minor species. We have used the PRE (a) to detect and characterize the stochastic target search process whereby a sequence-specific transcription factor (the Hox-D9 homeodomain) binds to non-cognate DNA sites as a means of enhancing the rate of specific association via intramolecular sliding and intermolecular translocation; (b) to directly visualize the distribution of non-specific transient encounter complexes involved in the formation of stereospecific protein-protein complexes; (c) to detect and visualize ultra-weak self-association of a protein, a process that is relevant to early nucleation events involved in the formation of higher order structures; and (d) to determine the structure of a minor species for a multidomain protein (maltose binding protein) where large interdomain motions are associated with ligand binding, thereby shedding direct light on the fundamental question of allostery versus induced fit in this system. The PRE offers unique opportunities to directly probe and explore in structural terms lowly-populated regions of the free energy landscape and promises to yield fundamental new insights into biophysical processes. C1 [Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM mariusc@mail.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX This work was supported by the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. I thank Attila Szabo for useful discussions. NR 101 TC 50 Z9 51 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2008 VL 4 IS 11 BP 1058 EP 1069 DI 10.1039/b810232e PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 384KL UT WOS:000261743600003 PM 18931781 ER PT J AU Li, AG Walling, J Kotliarov, Y Center, A Steed, ME Ahn, SJ Rosenblum, M Mikkelsen, T Zenklusen, JC Fine, HA AF Li, Aiguo Walling, Jennifer Kotliarov, Yuri Center, Angela Steed, Mary Ellen Ahn, Susie J. Rosenblum, Mark Mikkelsen, Tom Zenklusen, Jean Claude Fine, Howard A. TI Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas SO MOLECULAR CANCER RESEARCH LA English DT Article ID HUMAN ASTROCYTIC TUMORS; OLIGONUCLEOTIDE ARRAYS; HYBRIDIZATION; TISSUE; SNPS; CGH AB Genetic aberrations, such as gene amplification, deletions, and loss of heterozygosity, are hallmarks of cancer and are thought to be major contributors to the neoplastic process. Established cancer cell lines have been the primary in vitro and in vivo models for cancer for more than 2 decades; however, few such cell lines have been extensively characterized at the genomic level. Here, we present a high-resolution genome-wide chromosomal alteration and gene expression analyses of five of the most commonly used glioma cell lines and compare the findings with those observed in 83 primary human gliomas. Although genomic alterations known to occur in primary tumors were identified in the cell lines, we also observed several novel recurrent aberrations in the glioma cell lines that are not frequently represented in primary tumors. Additionally, a global gene expression cluster distinct from primary tumors was identified in the glioma cell lines. Our results indicate that established cell lines are generally a poor representation of primary tumor biology, presenting a host of genomic and gene expression changes not observed in primary tissues, although some discrete features of glioma biology were conserved in the established cell lines. Refined maps of genetic alterations and transcriptional divergence from the original tumor type, such as the one presented here, may help serve as a guideline for a more biologically rational and clinically relevant selection of the most appropriate glioma model for a given experiment. C1 [Li, Aiguo; Walling, Jennifer; Kotliarov, Yuri; Center, Angela; Steed, Mary Ellen; Ahn, Susie J.; Zenklusen, Jean Claude; Fine, Howard A.] NINDS, NIH, Neuro Oncol Branch, NCI, Bethesda, MD 20892 USA. [Rosenblum, Mark; Mikkelsen, Tom] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Neurol & Neurosurg, Detroit, MI 48202 USA. RP Fine, HA (reprint author), NINDS, NIH, Neuro Oncol Branch, NCI, 9030 Old Georgetown Dr,MSC8200,Bldg 82,Room 225, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Kotliarov, Yuri/B-6938-2017 FU Intramural NIH HHS NR 21 TC 111 Z9 111 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2008 VL 6 IS 1 BP 21 EP 30 DI 10.1158/1541-7786.MCR-07-0280 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 260YJ UT WOS:000253046000003 PM 18184972 ER PT J AU Wang, Y Zhang, ZQ Lu, Y Yao, RS Jia, DM Wen, W LaRegina, M Crist, K Lubet, R You, M AF Wang, Yian Zhang, Zhongqiu Lu, Yan Yao, Ruisheng Jia, Dongmei Wen, Weidong LaRegina, Marie Crist, Keith Lubet, Ronald You, Ming TI Enhanced susceptibility to chemical induction of ovarian tumors in mice with a germ line p53 mutation SO MOLECULAR CANCER RESEARCH LA English DT Article ID SUPPRESSOR GENE; MISMATCH REPAIR; STRAND BIASES; FEMALE MICE; CANCER; GROWTH; EXPRESSION; DYNEIN; CELLS; MOUSE AB Mice with a germ line p53 mutation (p53(Ala135Val/wt)) display increased susceptibility to lung, skin, and colon carcinogenesis. Here, we show that p53Ala135Val/wt mice developed ovarian tumors significantly more rapidly than their wild-type littermates after 7,12-dimethylbenz(a)anthracene (DMBA) treatment. Approximately 50% of the ovarian tumors in P53(wt/wt) mice and 23% in p53(Ala135Vat/wt) mice are adenocarcinomas and the remaining tumors were adenocarcinoma mixed with sarcoma or ovarian sarcomas. All of the p53(Ala135Val/wt) mice had died of ovarian tumors 25 weeks after the initial DMBA treatment, whereas > 50% of p53(wt/wt) mice were still alive. These mice not only have a shortened tumor latency but also closely resemble a subset of human ovarian tumors containing the p53 mutation. Microarray and GenMAPP analyses revealed that the mutant p53 (Ala135Val) affected several cellular processes, including the cell cycle, apoptosis, and Wnt pathways. These findings indicate that a germ line p53 mutation significantly enhanced DMBA-induced ovarian tumor development and progression. C1 [Wang, Yian; Zhang, Zhongqiu; Yao, Ruisheng; Jia, Dongmei; Wen, Weidong; You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [LaRegina, Marie] Washington Univ, Sch Med, Div Comparat Med, St Louis, MO 63110 USA. [Crist, Keith] Med Coll Ohio, Toledo, OH 43699 USA. [Lubet, Ronald] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu FU NCI NIH HHS [R01 CA 113793] NR 40 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2008 VL 6 IS 1 BP 99 EP 109 DI 10.1158/1541-7786.MCR-07-0216 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 260YJ UT WOS:000253046000010 PM 18234966 ER PT J AU To, KKW Polgar, O Huff, LM Morisaki, K Bates, SE AF To, Kenneth K. W. Polgar, Orsolya Huff, Lyn M. Morisaki, Kuniaki Bates, Susan E. TI Histone modifications at the ABCG2 promoter following treatment with histone deacetylase inhibitor mirror those in multidrug-resistant cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; ACTIVE GENES; TRANSCRIPTIONAL CONTROL; DEPSIPEPTIDE FR901228; CHROMATIN-STRUCTURE; H3 ACETYLATION; LEUKEMIA-CELLS; COLON-CANCER; METHYLATION; PROTEIN AB ABCG2 is a ubiquitous ATP-binding cassette transmembrane protein that is important in pharmacology and may play a role in stem cell biology and clinical drug resistance. To study the mechanism(s) regulating ABCG2 expression, we used ChIP to investigate the levels of acetylated histone H3, histone deacetylases (HDAC), histone acetyltransferases, and other transcription regulatory proteins associated with the ABCG2 promoter. Following selection for drug resistance and the subsequent overexpression of ABCG2, an increase in acetylated histone H3 but a decrease in class I HDACs associated with the ABCG2 promoter was observed. Permissive histone modifications, including an increase in histone H3 lysine 4 trimethylation (Me-3-K4 H3) and histone H3 serine 10 phosphorylation (P-S10 H3), were observed accompanying development of the resistance phenotype. These changes mirrored those in some cell lines treated with a HDAC inhibitor, romidepsin. A repressive histone mark, trimethylated histone H3 lysine 9 (Me-3-K9 H3), was found in untreated parental cells;and cells that did not respond to HDAC inhibition with ABCG2 up-regulation. Interestingly, although all five studied cell lines showed global histone acetylation and MDR1 up-regulation upon HDAC inhibition, only those cells with removal of the repressive mark, and recruitment of RNA polymerase 11 and a chromatin remodeling factor Brg-1 from the ABCG2 promoter, showed increased ABCG2 expression. In the remaining cell lines, HDAC1 binding in association with the repressive Me3-K9 H3 mark apparently constrains the effect of HDAC inhibition on ABCG2 expression. These studies begin to address the differential effect of HDAC inhibitors widely observed in gene expression studies. C1 [To, Kenneth K. W.; Polgar, Orsolya; Huff, Lyn M.; Morisaki, Kuniaki; Bates, Susan E.] NCI, Ctr Canc Res, Med Oncol Branch, Mol Therapeut Sect,NIH, Bethesda, MD 20892 USA. RP To, KKW (reprint author), NCI, Ctr Canc Res, Med Oncol Branch, Mol Therapeut Sect,NIH, Bldg 10,Room 13N220,10 Ctr Dr, Bethesda, MD 20892 USA. EM tok@mail.nih.gov RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU Intramural NIH HHS [Z01 BC010622-04] NR 63 TC 66 Z9 69 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2008 VL 6 IS 1 BP 151 EP 164 DI 10.1158/1541-7786.MCR-07-0175 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 260YJ UT WOS:000253046000015 PM 18234970 ER PT J AU Blower, PE Chung, JH Verducci, JS Lin, SL Park, JK Dai, ZY Liu, CG Schmittgen, TD Reinhold, WC Croce, CM Weinstein, JN Sadee, W AF Blower, Paul E. Chung, Ji-Hyun Verducci, Joseph S. Lin, Shili Park, Jong-Kook Dai, Zunyan Liu, Chang-Gong Schmittgen, Thomas D. Reinhold, William C. Croce, Carlo M. Weinstein, John N. Sadee, Wolfgang TI MicroRNAs modulate the chemosensitivity of tumor cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID EXPRESSION PROFILES; CANCER CHEMOSENSITIVITY; GENE-EXPRESSION; BREAST-CANCER; GROWTH; CHEMORESISTANCE; APOPTOSIS; TARGETS; MIRNAS; CHEMOTHERAPY AB MicroRNAs are strongly implicated in such processes as development, carcinogenesis, cell survival, and apoptosis. It is likely, therefore, that they can also modulate sensitivity and resistance to anticancer drugs in substantial ways. To test this hypothesis, we studied the pharmacologic roles of three microRNAs previously implicated in cancer biology (let-7i, mir-16, and mir-21) and also used in silico methods to test pharmacologic microRNA effects more broadly. In the experimental system, we increased the expression of individual microRNAs by transfecting their precursors (which are active) or suppressed the expression by transfection of antisense oligomers. In three NCI-60 human cancer cell lines, a panel of 60 lines used for anticancer drug discovery, we assessed the growth-inhibitory potencies of 14 structurally diverse compounds with known anticancer activities. Changing the cellular levels of let-7i, mir-16, and mir-21 affected the potencies of a number of the anticancer agents by up to 4-fold. The effect was most prominent with mir-21, with 10 of 28 cell-compound pairs showing significant shifts in growth-inhibitory activity. Varying mir-21 levels changed potencies in opposite directions depending on compound class; indicating that different mechanisms determine toxic and protective effects. In silico comparison of drug potencies with microRNA expression profiles across the entire NCI-60 panel revealed that similar to 30 microRNAs, including mir-21, show highly significant correlations with numerous anticancer agents. Ten of those microRNAs have already been implicated in cancer biology. Our results support a substantial role for microRNAs in anticancer drug response, suggesting novel potential approaches to the improvement of chemotherapy. C1 [Blower, Paul E.; Chung, Ji-Hyun; Dai, Zunyan; Sadee, Wolfgang] Ohio State Univ, Program Pharmocogenom, Dept Pharmacol, Columbus, OH 43210 USA. [Blower, Paul E.; Chung, Ji-Hyun; Dai, Zunyan; Sadee, Wolfgang] Ohio State Univ, Ctr Comprehens Canc, Coll Med, Columbus, OH 43210 USA. [Verducci, Joseph S.; Lin, Shili] Ohio State Univ, Ctr Comprehens Canc, Dept Stat, Columbus, OH 43210 USA. [Verducci, Joseph S.; Lin, Shili] Ohio State Univ, Ctr Comprehens Canc, Math Biosci Inst, Columbus, OH 43210 USA. [Park, Jong-Kook; Schmittgen, Thomas D.] Ohio State Univ, Ctr Comprehens Canc, Coll Pharm, Columbus, OH 43210 USA. [Liu, Chang-Gong; Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Reinhold, William C.; Weinstein, John N.] NCI, Ctr Canc Res, Mol Pharmacol Lab, Genom & Bioinformat Grp, Bethesda, MD 20892 USA. RP Blower, PE (reprint author), Ohio State Univ, Program Pharmocogenom, Dept Pharmacol, 333 W Tenth St, Columbus, OH 43210 USA. EM blower.7@osu.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM61390] NR 40 TC 221 Z9 241 U1 4 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2008 VL 7 IS 1 BP 1 EP 9 DI 10.1158/1535-7163.MCT-07-0573 PG 9 WC Oncology SC Oncology GA 254IS UT WOS:000252580900001 PM 18187804 ER PT J AU Stevens, EV Nishizuka, S Antony, S Reimers, M Varma, S Young, L Munson, PJ Weinstein, JN Kohn, EC Pommier, Y AF Stevens, Ellen V. Nishizuka, Satoshi Antony, Smitha Reimers, Mark Varma, Sudhir Young, Lynn Munson, Peter J. Weinstein, John N. Kohn, Elise C. Pommier, Yves TI Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; TUMOR-CELL-LINES; SOFT-TISSUE SARCOMAS; DNA MISMATCH REPAIR; ECTEINASCIDIN-743 ET-743; MOLECULAR PHARMACOLOGY; MINOR-GROOVE; EXPRESSION; RESISTANCE; ERCC1 AB Molecular profiling of markers involved in the activity of chemotherapeutic agents can shed light on the successes and failures of treatment in patients and can also provide a basis for individualization of therapy. Toward those ends, we have used reverse-phase protein lysate microarrays to evaluate expression of protein components of the nucleotide excision repair (NER) pathways. Those pathways strongly influence the anticancer activities of numerous drugs, including those that are the focus here, cisplatin and ecteinascidin 743 (Et-743; Yondelis, Trabectedin). Cisplatin is generally more active in cell types deficient in NER, whereas Et-743 tends to be less active in those cells. We measured protein expression and sensitivity to those drugs in 17 human ovarian and colon cancer cell lines (13 of them from the NCI-60 panel) and five xeroderma pigmentosum (XP) patient cell types, each containing a different NER defect. Of the NER proteins giving reliable signals, XPF and XPG showed the highest correlations of protein expression with drug activity across all three tissue-of-origin groups. When we compared protein expression data with mRNA expression data from Affymetrix U133A chips, we found no consistent correlation between the two across the cell lines studied, which reinforces the conclusion that protein measurements can give more interpretable mechanistic information than can transcript measurements. The work reported here provides motivation for larger proteomic studies with more cell types focused on potential biomarkers in additional pharmacologically pertinent pathways. C1 [Stevens, Ellen V.; Nishizuka, Satoshi; Antony, Smitha; Reimers, Mark; Varma, Sudhir; Weinstein, John N.; Pommier, Yves] NCI, Ctr Informat Technol, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Kohn, Elise C.] NCI, Ctr Informat Technol, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Young, Lynn; Munson, Peter J.] NCI, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD USA. RP Pommier, Y (reprint author), NCI, Ctr Informat Technol, Mol Pharmacol Lab, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Varma, Sudhir/N-8763-2014 OI Varma, Sudhir/0000-0002-4096-4782 FU Intramural NIH HHS NR 42 TC 45 Z9 48 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2008 VL 7 IS 1 BP 10 EP 18 DI 10.1158/1535-7163.MCT-07-0192 PG 9 WC Oncology SC Oncology GA 254IS UT WOS:000252580900002 PM 18187810 ER PT J AU Sissung, TM Danesi, R Price, DK Steinberg, SM de Wit, R Zahid, M Gaikwad, N Cavalieri, E Dahut, WL Sackett, DL Figg, WD Sparreboom, A AF Sissung, Tristan M. Danesi, Romano Price, Douglas K. Steinberg, Seth M. de Wit, Ronald Zahid, Muhammad Gaikwad, Nilesh Cavalieri, Ercole Dahut, William L. Sackett, Dan L. Figg, William D. Sparreboom, Alex TI Association of the CYP1B1*3 allele with survival in patients with prostate cancer receiving docetaxel SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PHASE-II TRIAL; TUBULIN POLYMERIZATION; HUMAN CYP1B1; CYTOCHROME P450CYP1B1; COLCHICINE SITE; BREAST-CANCER; THALIDOMIDE; METABOLISM; EXPRESSION; SURAMIN AB Using a single nucleotide polymorphism association study in 52 men with prostate cancer receiving docetaxel, we found that individuals carrying two copies of the CYP1B1*3 polymorphic variant had a poor prognosis after docetaxel-based therapies compared with individuals carrying at least one copy of the CYP1B1*1 allele (30.6 versus 12.8 months; P = 0.0004). The association between CYP1B1*3 and response to therapy was not observed in similar subjects receiving non-taxane-based therapy (P = 0.18). The systemic clearance of docetaxel was also unrelated to CYP1B1 genotype status (P = 0.39), indicating that the association of CYP1B1*3 with clinical response is not due to docetaxel metabolism. To explain these results, we hypothesized that an indirect gene-drug interaction was interfering with the primary mechanism of action of docetaxel, tubulin polymerization. We therefore conducted tubulin polymerization experiments with taxanes in the presence or absence of certain CYP1B1 estrogen metabolites, which are known to bind to nucleophilic sites in proteins and DNA, that revealed the primary estrogen metabolite of CYP1B1, 4-hydroxyestradiol (4-OHE2), when oxidized to estradiol-3,4-quinone strongly inhibits tubulin polymerization. The 4-OHE2 is also formed more readily by the protein encoded by the CYP1B1*3 allele, validating further our data in patients. Furthermore, estradiol-3,4-quinone reacted in vitro with docetaxel to form the 4-OHE2-docetaxel adduct. This pilot study provides evidence that CYP1B1*3 may be an important marker for estimating docetaxel efficacy in patients with prostate cancer. This link is likely associated with CYP1B1*3 genotype-dependent estrogen metabolism. C1 [Sissung, Tristan M.; Figg, William D.; Sparreboom, Alex] NCI, Ctr Canc Res, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Price, Douglas K.; Dahut, William L.; Figg, William D.] NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. [Danesi, Romano] Univ Pisa, Dept Oncol Transplants & Adv Technol Med, Pisa, Italy. [de Wit, Ronald] Erasmus MC Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. [Zahid, Muhammad; Gaikwad, Nilesh; Cavalieri, Ercole] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA. RP Figg, WD (reprint author), NCI, Med Oncol Clin Res Unit, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 31 TC 45 Z9 47 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2008 VL 7 IS 1 BP 19 EP 26 DI 10.1158/1535-7163.MCT-07-0557 PG 8 WC Oncology SC Oncology GA 254IS UT WOS:000252580900003 PM 18187806 ER PT J AU Janakiram, NB Cooma, I Mohammed, A Steele, VE Rao, CV AF Janakiram, Naveena B. Cooma, Indranie Mohammed, Altaf Steele, Vernon E. Rao, Chinthalapally V. TI beta-ionone inhibits colonic aberrant crypt foci formation in rats, suppresses cell growth, and induces retinoid X receptor-alpha in human colon cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PROTEIN-KINASE; VITAMIN-E; IN-VITRO; CAROTENE; VEGETABLES; ACID; CHEMOPREVENTION; CARCINOGENESIS; PROLIFERATION; EXPRESSION AB beta-ionone, an end-ring analogue of beta-carotenoid, which is a constituent of vegetables and fruits, has been analyzed for colon cancer chemoprevention and treatment. beta-Ionone induced cell growth inhibition and apoptosis in human colon cancer HCT116 cell line. We tested the in vivo chemopreventive efficacy in rat colon carcinogenesis model using aberrant crypt foci (ACF) as endpoint marker. HCT116 cells treated with subtoxic concentrations of beta-ionone resulted dose-dependent cell growth suppression with G(1)-S-phase growth arrest and significant induction of apoptosis. beta-ionone up-regulated expression of retinoid X receptor-alpha mRNA dose-dependently in HCT116 cells. To evaluate inhibitory properties of beta-ionone on colonic ACF, 7-week-old male F344 rats were fed experimental diets containing 0%, 0.1%, or 0.2% beta-ionone. After 1 week, rats received s.c. injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Rats were continued on respective experimental diets and sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated histopathologically for ACF. Administration of dietary 0.1% and 0.2% beta-ionone significantly suppressed total colonic ACF formation up to 34% to 38% [P < 0.0002 to P < 0.0009), respectively, when compared with control group. Importantly, rats fed 0-ionone showed > 55% inhibition (P < 0.0001) of foci containing four or more aberrant crypts. Results from in vitro and in vivo bioassay clearly suggest that beta-ionone could be further developed for prevention and treatment of colon cancer. C1 [Janakiram, Naveena B.; Cooma, Indranie; Mohammed, Altaf; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Henonc Sect,OU Canc Inst, Oklahoma City, OK 73104 USA. [Steele, Vernon E.] NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD USA. RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, Henonc Sect,OU Canc Inst, 975 NE 10th St,BRC Bldg,Room 1203, Oklahoma City, OK 73104 USA. EM cv-rao@ouhsc.edu RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CN-6500, N01CN-53300, R01CA-94962] NR 49 TC 32 Z9 32 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2008 VL 7 IS 1 BP 181 EP 190 DI 10.1158/1535-7163.MCT-07-0529 PG 10 WC Oncology SC Oncology GA 254IS UT WOS:000252580900019 PM 18202021 ER PT J AU Fenton, JI Lavigne, JA Perkins, SN Liu, H Chandramouli, GVR Shih, JH Hord, NG Hursting, SD AF Fenton, Jenifer I. Lavigne, Jackie A. Perkins, Susan N. Liu, Huaitian Chandramouli, Gadisetti V. R. Shih, Joanna H. Hord, Norman G. Hursting, Stephen D. TI Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype-dependent fashion SO MOLECULAR CARCINOGENESIS LA English DT Article DE leptin; IGF; IGFBP; microarray; IMCE; YAMC; colon cancer ID GROWTH-FACTOR-I; COLORECTAL-CANCER RISK; PROSTATE-CANCER; EXPRESSION; ADIPONECTIN; RECEPTORS; MIGRATION; MUTATION; PROTEIN; LINES AB The imbalance in systemic mediators of inflammation, such as leptin, is thought to be involved in obesity-associated cancers. in addition, systemic endocrine signals can influence the local autocrine/paracrine factors produced within this microenvironment to influence epithelial cell fate. We previously demonstrated that leptin preferentially promotes the survival and proliferation of colon epithelial cells possessing an Apc mutation (IMCE) but not model normal cells (YAMC). Therefore, the purpose of this study was to identify leptin-induced functional gene family changes which characterize the response of colon epithelial cells possessing an Apc mutation but not normal cells. Consistent with our knowledge of colon carcinogenesis, genes regulating the Wnt/beta-catenin-mediated pathway including Mdm2, Pik3r1, and Rb1 were upregulated by leptin. Importantly, leptin induced IGF-mediated pathway gene expression changes and their protein products in IMCE cells. In the IMCE cells IGFBP-6, IGF-1, and Crim1 expression was upregulated, while IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and Nov expression was downregulated by leptin treatment. These data establish a biologically plausible mechanistic link between the elevated levels of growth factors and the increased risk of colon cancer associated with obesity. (c) 2007 Wiley-Liss, Inc. C1 [Fenton, Jenifer I.; Hord, Norman G.] Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. [Lavigne, Jackie A.] NCI, Div Canc Program, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Liu, Huaitian] NCI, Ctr Bioinformat, Sci Applicat Int Corp, Rockville, MD USA. [Chandramouli, Gadisetti V. R.] NCI, Lab Biosyst & Carcinogenesis, Bethesda, MD 20892 USA. [Liu, Huaitian; Shih, Joanna H.] NCI, Biometr Res Branch, Rockville, MD USA. [Perkins, Susan N.; Hursting, Stephen D.] Univ Texas Austin, Div Nutr Sci, Austin, TX 78712 USA. RP Fenton, JI (reprint author), Michigan State Univ, Dept Food Sci & Human Nutr, 210 GM Trout Bldg, E Lansing, MI 48824 USA. OI Fenton, Jenifer/0000-0002-8875-3239 NR 47 TC 19 Z9 20 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2008 VL 47 IS 1 BP 9 EP 21 DI 10.1002/mc.20357 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 253ES UT WOS:000252502100002 PM 17620308 ER PT J AU Lekman, M Paddock, S McMahon, FJ AF Lekman, Magnus Paddock, Silvia McMahon, Francis J. TI Pharmacogenetics of Major Depression Insights from Level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Trial SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Review ID SEROTONIN TRANSPORTER GENE; NATIONAL-COMORBIDITY-SURVEY; GENOME-WIDE ASSOCIATION; GLUCOCORTICOID-RECEPTOR GENE; ANTIDEPRESSANT TREATMENT; SUICIDAL-BEHAVIOR; PROMOTER POLYMORPHISM; REUPTAKE INHIBITORS; PSYCHIATRIC-DISORDERS; CITALOPRAM TREATMENT AB Major depression is a serious mental illness frequently associated with devastating consequences for those affected. Suicide rates are significantly elevated, creating a sense of urgency to identify effective yet safe treatment options. A plethora of antidepressants are available on the market today, designed to act on different neurotransmitter systems in the brain, providing the clinician with several treatment strategies. There is, however, very little guidance as to which antidepressant may be most successful in a certain individual. Biomarkers that can predict treatment outcome would thus be of great value, shortening the time until remission and reducing costs for the healthcare system by reducing unsuccessful treatment attempts. The proven contribution of heredity to major depression risk suggests that genetic markers may be good biomarkers for treatment outcome. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and a large ancillary pharmacogenetic study in 1953 STAR*D participants constitute the largest effort to date to identify genetic predictors of antidepressant treatment outcome. In this review, the results of candidate gene studies carried out so far are summarized and discussed, and some future directions are proposed. C1 [Lekman, Magnus; Paddock, Silvia] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. [Paddock, Silvia; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Mood & Anxie, DHHS, NIH, Bethesda, MD 20892 USA. RP Lekman, M (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8,B2 Plan 4, S-17177 Stockholm, Sweden. EM magnus.lekman@ki.se OI McMahon, Francis/0000-0002-9469-305X FU Swedish Research Council; Swedish Foundation for Strategic Research; Karolinska Institute Foundations; Center for Gender Medicine at the Karolinska Institute; National Alliance for Research in Schizophrenia and Depression (Francis McMahon and Silvia Paddock); US National Institute of Mental Health Intramural Research Program (Francis McMahon) FX This work was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, Karolinska Institute Foundations, the Center for Gender Medicine at the Karolinska Institute, the National Alliance for Research in Schizophrenia and Depression (Francis McMahon and Silvia Paddock), and the US National Institute of Mental Health Intramural Research Program (Francis McMahon). NR 120 TC 14 Z9 15 U1 2 U2 4 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2008 VL 12 IS 5 BP 321 EP 330 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 357ZT UT WOS:000259886600006 PM 18803430 ER PT J AU Napolitano, C Bennett, M Johnson, WE O'Brien, SJ Marquet, PA Barria, I Poulin, E Iriarte, A AF Napolitano, Constanza Bennett, Magdalena Johnson, Warren E. O'Brien, Stephen J. Marquet, Pablo A. Barria, Ivan Poulin, Elie Iriarte, Agustin TI Ecological and biogeographical inferences on two sympatric and enigmatic Andean cat species using genetic identification of faecal samples SO MOLECULAR ECOLOGY LA English DT Article DE Andean mountain cat; food habits; genetic variation; mountain viscacha; pampas cat ID MOUNTAIN CAT; OREAILURUS-JACOBITA; NORTHERN CHILE; DNA; ALTIPLANO; ECOSYSTEMS; CARNIVORES; ARGENTINA; TRACKING; FELIDAE AB The carnivore community of the altiplano ecosystem of the high Andes, including the Andean mountain cat (Leopardus jacobita) and pampas cat (Leopardus colocolo), is one of the least studied in the world. We determined the origin of 186 carnivore samples (184 faeces and two skulls) collected above 3000 m above sea level in northern Chile, including 33 from the Andean mountain cat and 75 from the pampas cat using diagnostic molecular genetic sequence variation. We determined for the first time food habits, habitat and physiographic associations, and general patterns of molecular genetic variation of the Andean mountain cat and the pampas cat in Chile. Both species had narrow dietary niches dominated by small rodents and there was a wide overlap in diet composition (0.82), suggesting low levels of prey partitioning between species. The mountain viscacha (Lagidium viscacia) made up a large proportion of the biomass of the diet of both species, especially for the Andean mountain cat (93.9% vs. 74.8% for the pampas cat), underscoring the importance of further research and conservation focus on this vanishing prey species. Although the probability of finding Andean mountain cat scats increased with altitude and slope, there was substantial geographical overlap in distribution between species, revealing that the pampas cat distribution includes high-altitude grassland habitats. The Andean mountain cat had relatively low levels of mitochondrial DNA (mtDNA) genetic variation (two mtDNA haplotypes) compared with the pampas cat (17 mtDNA haplotypes), suggestive of a distinct evolutionary history and relatively smaller historic populations. These insights will facilitate and provide tools and hypotheses for much-needed research and conservation efforts on these species and this ecosystem. C1 [Napolitano, Constanza; Poulin, Elie] Univ Chile, Fac Ciencias, Dept Ciencias Ecol, Lab Ecol Mol, Santiago, Chile. [Napolitano, Constanza; Marquet, Pablo A.; Poulin, Elie] Univ Chile, Fac Ciencias, Dept Ciencias Ecol, Inst Ecol & Biodivers, Santiago, Chile. [Bennett, Magdalena; Marquet, Pablo A.; Barria, Ivan; Iriarte, Agustin] Pontificia Univ Catolica Chile, Ctr Adv Studies Ecol & Biodivers, Dept Ecol, Santiago, Chile. [Johnson, Warren E.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Iriarte, Agustin] Fdn Biodivers, Santiago, Chile. RP Johnson, WE (reprint author), Univ Chile, Fac Ciencias, Dept Ciencias Ecol, Lab Ecol Mol, Casilla 653, Santiago, Chile. EM johnsonw@ncifcrf.gov RI Marquet, Pablo /B-7732-2009; Poulin, Elie/C-2654-2012; Johnson, Warren/D-4149-2016 OI Marquet, Pablo /0000-0001-6369-9339; Poulin, Elie/0000-0001-7736-0969; Johnson, Warren/0000-0002-5954-186X NR 59 TC 18 Z9 26 U1 5 U2 42 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1083 J9 MOL ECOL JI Mol. Ecol. PD JAN PY 2008 VL 17 IS 2 BP 678 EP 690 DI 10.1111/j.1365-294X.2007.03606.x PG 13 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 251TO UT WOS:000252398300016 PM 18205675 ER PT J AU Tohno, M Ueda, W Azuma, Y Shimazu, T Katoh, S Wang, JM Aso, H Takada, H Kawai, Y Saito, T Kitazawa, H AF Tohno, Masanori Ueda, Wataru Azuma, Yuko Shimazu, Tomoyuki Katoh, Shinichiro Wang, Ji Ming Aso, Hisashi Takada, Haruhiko Kawai, Yasushi Saito, Tadao Kitazawa, Haruki TI Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-2 (NOD2) SO MOLECULAR IMMUNOLOGY LA English DT Article DE NOD2; cDNA cloning; swine; GALT; immunobiotics ID INTESTINAL EPITHELIAL-CELLS; PATTERN-RECOGNITION RECEPTORS; LACTIC-ACID BACTERIA; KAPPA-B ACTIVATION; MURAMYL DIPEPTIDE; SWINE; PEPTIDOGLYCAN; TRANSFECTANT; EXPRESSION; INDUCTION AB The nucleotide-oligomerization domain (NOD) 2 is an important molecule involved in host defense. In this study, we report the cloning and characterization of porcine NOD2 (poNOD2) cDNA. The open reading frame of poNOD2 contains 3042 bp which encode 1013 amino acid residues. The putative poNOD2 protein shares higher level of homology with human counterpart (81.6% amino acid identity) than the mouse protein (76.6% amino acid identity). In order to determine the function of poNOD2, we established human embryonic kidney (HEK) 293 cells transfected to express poNOD2 cDNA. We found that poNOD2 was expressed not only in the cytoplasm but also in the inner side of the plasma membrane of HEK293 cells. HEK293 cells expressing poNOD2 responded to muramyl dipeptide (MDP) by activation of the nuclear factor kappa B (NF-kappa B). Quantitative real-time PCR revealed that poNOD2 mRNA was expressed by a number of tissues isolated from adult and newborn swine such as esophagus. duodenum, jejunum, ileum, ileal Peyer's patches (Pps), colon, spleen, and mesenteric lymph nodes (MLNs). In the newborn swine, the expression of poNOD2 mRNA was detected at higher levels in MLNs and spleen as compared to other tissues. In the adult swine, the highest expression was observed in ileal Pps. Furthermore, Toll-like receptor (TLR) and NOD2 ligands as well as immunobiotic lactic acid bacteria (LAB) enhanced the expression of NOD2 in gut-associated lymphoid tissues (GALT) in adult and newborn swine. Our results implicate NOD2 as an important immunoregulator in the swine intestinal immunity. (C) 2007 Elsevier Ltd. All rights reserved. C1 Tohoku Univ, Grad Sch Agr Sci, Lab Anim Prod Chem, Sendai, Miyagi 9818555, Japan. NCI, Ctr Canc Res, Frederick, MD 21702 USA. Tohoku Univ, Grad Sch Agr Sci, Lab Funct Morphol, Sendai, Miyagi 9818555, Japan. Tohoku Univ, Grad Sch Dent, Dept Microbiol & Immunol, Aoba Ku, Sendai, Miyagi 9808575, Japan. RP Kitazawa, H (reprint author), Tohoku Univ, Grad Sch Agr Sci, Lab Anim Prod Chem, Sendai, Miyagi 9818555, Japan. EM haruki@bios.tohoku.ac.jp RI Kitazawa, Haruki/C-1256-2011 NR 36 TC 44 Z9 44 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2008 VL 45 IS 1 BP 194 EP 203 DI 10.1016/j.molimm.2007.04.019 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 218KE UT WOS:000250013600022 PM 17559936 ER PT J AU Elloumi, HZ Holland, SM AF Elloumi, Houda Zghal Holland, Steven M. TI Complex regulation of human cathelicidin gene expression: Novel splice variants and 5'UTR negative regulatory element SO MOLECULAR IMMUNOLOGY LA English DT Article DE antimicrobial peptide; promoter; regulatory elemenm; gene regulation; splice variants; innate immunity ID HUMAN ANTIBACTERIAL CATHELICIDIN; ANTIMICROBIAL PEPTIDE LL-37; OPEN READING FRAME; MESSENGER-RNA; HUMAN KERATINOCYTES; CELL-LINES; HCAP-18; FAMILY; PR-39; SITE AB Cationic antimicrobial peptides play important roles in host defense, linking innate and adaptive immunity. hCAP18, the only human antimicrobial cathelicidin, consists of a conserved N-terminal cathelin-like domain and a C-terminal peptide, LL-37. Expression is regulated during myeloid differentiation, and tightly controlled during infection and inflammation, suggesting active regulation. Using 5' RACE (rapid amplification of cDNA ends), multiple transcription initiation sites were identified, as well as new splice variants leading to novel augmentations of hCAP18 amino acid composition in bone marrow but not peripheral blood neutrophils. Having expressed hCAP18 promoter constructs in cell lines, we found that full-length (-1739) and truncated (-978) promoter constructs had lower luciferase activities than 5'UTR deletion constructs. Transient transfection of progressively deleted constructs in the non-permissive K562 cell line led us to identify a negative regulatory element within the 53 bp immediately upstream of the ATG of hCAP18. Additionally, transient transfection of 5' deletion constructs identified a positive regulatory element within the 101 bases 5' of promoter sequence containing two GT-boxes. Negative and positive regulatory elements within the hCAP18 Gene promoter provide new insights into the possible molecular basis of myeloid gene expression. Published by Elsevier Ltd. C1 NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU Intramural NIH HHS [Z01 AI000647-16] NR 39 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2008 VL 45 IS 1 BP 204 EP 217 DI 10.1016/j.molimm.2007.04.023 PG 14 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 218KE UT WOS:000250013600023 PM 17709140 ER PT J AU Alvarez, Y Tang, X Coligan, JE Borrego, F AF Alvarez, Yelina Tang, Xiaobin Coligan, John E. Borrego, Francisco TI The CD300a (IRp60) inhibitory receptor is rapidly up-regulated on human neutrophils in response to inflammatory stimuli and modulates CD32a (Fc gamma IIa) mediated signaling SO MOLECULAR IMMUNOLOGY LA English DT Article DE neutrophils; CD300a; inhibitory receptor; inflammation; reactive oxygen species; ITAM; ITIM ID IG-LIKE RECEPTOR-1; IMMUNOGLOBULIN SUPERFAMILY; GM-CSF; CELLS; DIFFERENTIATION; ACTIVATION; EXPRESSION; INDUCTION; ADHESION; CLECSF6 AB To achieve an adequate response, cells of the immune system must be tightly regulated to avoid hypo or hyper responsiveness. One of the mechanisms used by the immune system to avoid excessive inflammation is the modulation of the response through inhibitory receptors containing immunoreceptor tyrosine based inhibitory motifs (ITIM). Here, we show that human neutrophils from peripheral blood express the ITIM containing CD300a (also known as lRp60 and CMRF-35H) receptor. By using the HL-60 differentiation model, we show that the expression of CD300a receptor is developmentally regulated. Stimulation of human neutrophils with LPS and GM-CSF increased the cell surface expression of CD300a as a result of the rapid translocation of an intracellular pool of the receptor to the cell surface. Co-figation of CD300a with the immunoreceptor tyrosine based activating motif (ITAM) containing CD32a (Fc gamma RIIa) activation receptor inhibited CD32a mediated signalling; whereas, it did not inhibit toll-like receptor (TLR)-4 mediated reactive oxygen species (ROS) production. Therefore, at least for human neutrophils, the inhibitory signals mediated by the CD300a receptor may be selective in their action. (C) Published by Elsevier Ltd. C1 NIH, NIAID, Immunogenet Lab, Receptor Cell Biol Sect, Rockville, MD 20852 USA. RP Borrego, F (reprint author), NIH, NIAID, Immunogenet Lab, Receptor Cell Biol Sect, Rockville, MD 20852 USA. EM Fborrego@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000964-02, Z99 OD999999] NR 28 TC 41 Z9 42 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2008 VL 45 IS 1 BP 253 EP 258 DI 10.1016/j.molimm.2007.05.006 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 218KE UT WOS:000250013600028 PM 17588661 ER PT J AU Richl, P Stem, U Lipsky, PE Girschick, HJ AF Richl, P. Stem, U. Lipsky, P. E. Girschick, H. J. TI The lambda gene immunoglobulin repertoire of human neonatal B cells SO MOLECULAR IMMUNOLOGY LA English DT Article DE human neonatal B lymphocytes; V lambda repertoire; terminal desoxynucleotidyl transferase ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MOLECULAR-MECHANISMS; EXPRESSION; CD5; SELECTION; RECOMBINATION; ARTHRITIS; ANTIBODY AB The dynamics of immunoglobulin rearrangements and selection, which depend on age, antigen exposure and tolerance functions, are only partly understood. Thus, we analyzed and compared the lambda chain immunoglobulin repertoire of individual IgD+ human neonatal B cells with the adult peripheral B cell V lambda J lambda repertoire. Some V lambda genes, 4C, 2A2, 2132, 5A, 1G and 4B, were overexpressed in the non-productive neonatal repertoire, whereas other V lambda genes (2E, 2A2, 3H, 2B2, 1C and 1G) were overexpressed in the productive repertoire. The adult B cell repertoire revealed nearly the same predominance of genes in the non-productive and productive repertoire. A comparison of the non-productive and productive repertoire indicated that the genes 3H and 1C were positively selected, whereas the genes 4C, 2A 1, 3I, 5A, 9A, 4A and 4B were negatively selected. All four functional J lambda genes were used in both repertoires. J lambda 2/3 was used mainly. Insertions of non-templated nucleotides at the V lambda J lambda-junction by the enzyme TdT were less frequent as compared to the adult, but the CDR3 length was the same. Comparison of CD5+IgD+ and CD5-IgD+ B cells revealed no differences between neonatal productive rearrangements. However, the genes IC and IG were used more often in the non-productive repertoire of CD5+ B cells, whereas gene 4B was used significantly more frequent in CD5- B cells. These data provide evidence that the primary usage and subsequent selection of V lambda genes in the neonate are surprisingly comparable with the adult. This suggests that selection into the productive V lambda repertoire in principal might be driven mainly by autoantigens in the newborn, as well as in adulthood, since newborns have not been exposed to exogenous antigens. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Wurzburg, Childrens Hosp, Wurzburg, Germany. Univ Texas, SW Med Ctr, Harold C Simmons Arthritis res Ctr, Dept Internal Med, Dallas, TX 75235 USA. NIH, NIAMS, Bethesda, MD USA. RP Richl, P (reprint author), Childrens Hosp, Josef-Schneider-Str 2, D-97080 Wurzburg, Germany. EM Petra.Richl@uni-wuerzburg.de NR 27 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2008 VL 45 IS 2 BP 320 EP 327 DI 10.1016/j.molimm.2007.06.155 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 221TE UT WOS:000250249400002 PM 17675156 ER PT J AU Rawat, SS Zimmerman, C Johnson, BT Cho, E Lockett, SJ Blumenthal, R Puri, A AF Rawat, Satinder S. Zimmerman, Christina Johnson, Benitra T. Cho, Edward Lockett, Stephen J. Blumenthal, Robert Puri, Anu TI Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion SO MOLECULAR MEMBRANE BIOLOGY LA English DT Article DE CD4 receptor localization in the plasma membrane; receptor mobility restriction and HIV-1 fusion ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIPID RAFTS; T-CELLS; CHEMOKINE RECEPTORS; VIRAL FUSION; LIVING CELLS; TYPE-1 HIV-1; ENTRY; MICRODOMAINS; CCR5 AB We investigated the effect of receptor mobility on HIV-1 envelope glycoprotein (Env)-triggered fusion using B16 mouse melanoma cells that are engineered to express CD4 and CXCR4 or CCR5. These engineered cells are resistant to fusion mediated CD4-dependent HIV-1 envelope glycoprotein. Receptor mobility was measured by fluorescence recovery after photobleaching (FRAP) using either fluorescently-labeled antibodies or transient expression of GFP-tagged receptors in the cells. No significant differences between B16 and NIH3T3 (fusion-permissive) cells were seen in lateral mobility of CCR5 or lipid probes. By contrast CD4 mobility in B16 cells was about seven-fold reduced compared to its mobility in fusion-permissive NIH3T3 cells. However, a CD4 mutant (RA5) that localizes to non-raft membrane microdomains exhibited a three-fold increased mobility in B16 cells as compared with WT-CD4. Interestingly, the B16 cells expressing the RA5 mutant (but not the wild type CD4) and coreceptors supported HIV-1 Env-mediated fusion. Our data demonstrate that the lateral mobility of CD4 is an important determinant of HIV-1 fusion/entry. C1 [Rawat, Satinder S.; Zimmerman, Christina; Johnson, Benitra T.; Blumenthal, Robert; Puri, Anu] NCI, CCRNP, NIH, Frederick, MD 21702 USA. [Cho, Edward; Lockett, Stephen J.] Frederick Inc, SAIC, Image Anal Lab, Adv Technol Program, Frederick, MD USA. RP Puri, A (reprint author), NCI, CCRNP, NIH, POB B,Bldg 469,Rm 216A Miller Dr, Frederick, MD 21702 USA. EM apuri@helix.nih.gov RI Cho, Edward/B-3727-2012 OI Cho, Edward/0000-0002-0278-334X FU Intramural NIH HHS [Z01 BC008303-36]; NCI NIH HHS [N01-CO-12400] NR 38 TC 16 Z9 17 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PY 2008 VL 25 IS 1 BP 83 EP 94 DI 10.1080/09687680701613713 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251DY UT WOS:000252352700008 PM 18097956 ER PT J AU BoseDasgupta, S Ganguly, A Das, BB Roy, A Khalkho, NVM Majumder, HK AF BoseDasgupta, Somdeb Ganguly, Agneyo Das, Benu Brata Roy, Amit Khalkho, Neeta V. M. Majumder, Hemanta K. TI The large subunit of Leishmania topoisomerase I functions as the 'molecular steer' in type IB topoisomerase SO MOLECULAR MICROBIOLOGY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; UNIVERSAL MINICIRCLE SEQUENCE; DNA TOPOISOMERASE; RNA INTERFERENCE; KINETOPLAST DNA; DONOVANI; REPLICATION; FUSION; ENZYME; RECONSTITUTION AB Kinetoplastid topoisomerase IB is an unusual bisubunit enzyme where reconstitution of the large (LdTOPIL or L) and small (LdTOPIS or S) subunits shows functional activity. It is yet to be deciphered whether one subunit or both navigate the heterodimer to its cellular DNA targets. Tethering a specific DNA-binding protein to topoisomerase I alters its site specificity. The chimeric constructs UMSBP-LdTOPIL/S or U-L/S (fusion of UMSBP to the N-terminus of L and reconstituted with S) and LdTOPIL/UMSBP-LdTOPIS or L/U-S (fusion of UMSBP to the N-terminus of S and reconstituted with L) exhibit relaxation activity. Only U-L/S shows altered site specificity and enhanced DNA-binding affinity for the universal minicircle sequence (UMS) containing substrate. This proves that L alone serves as the 'molecular steer' for this heterodimer. Reconstituted U-L/S also induces cleavage close to UMS and causes minicircle linearization. The differential properties of the reconstituted chimeras U-L/S and L/U-S reveal the structural and functional asymmetry between the heterodimer. Therefore this study helps in a better understanding of the mechanistic details underlying topoisomerization by this bi-subunit enzyme. C1 Indian Inst Chem Biol, Dept Mol Parasitol, Kolkata 700032, W Bengal, India. Ctr Canc Res, Natl Canc Inst, Mol Pharmacol Lab, Bethesda, MD USA. RP Majumder, HK (reprint author), Indian Inst Chem Biol, Dept Mol Parasitol, 4 Raja SC Mullick Rd, Kolkata 700032, W Bengal, India. EM hkmajumder@iicb.res.in NR 31 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2008 VL 67 IS 1 BP 31 EP 46 DI 10.1111/j.1365-2958.2007.06002.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 238GF UT WOS:000251434700003 PM 18036140 ER PT J AU Gan, J Shaw, G Tropea, JE Waugh, DS Court, DL Ji, X AF Gan, Jianhua Shaw, Gary Tropea, Joseph E. Waugh, David S. Court, Donald L. Ji, Xinhua TI A stepwise model for double-stranded RNA processing by ribonuclease III SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; STRUCTURAL BASIS; SUBSTRATE RECOGNITION; BACTERIOPHAGE-LAMBDA; GENE-EXPRESSION; NUCLEASE DOMAIN; MECHANISM; CLEAVAGE; CATALYSIS; COMPLEX AB RNA interference is mediated by small interfering RNAs produced by members of the ribonuclease III (RNase III) family represented by bacterial RNase III and eukaryotic Rnt1p, Drosha and Dicer. For mechanistic studies, bacterial RNase III has been a valuable model system for the family. Previously, we have shown that RNase III uses two catalytic sites to create the 2-nucleotide (nt) 3' overhangs in its products. Here, we present three crystal structures of RNase III in complex with double-stranded RNA, demonstrating how Mg2+ is essential for the formation of a catalytically competent protein-RNA complex, how the use of two Mg2+ ions can drive the hydrolysis of each phosphodiester bond, and how conformational changes in both the substrate and the protein are critical elements for assembling the catalytic complex. Moreover, we have modelled a protein-substrate complex and a protein-reaction intermediate (transition state) complex on the basis of the crystal structures. Together, the crystal structures and the models suggest a stepwise mechanism for RNase III to execute the phosphoryl transfer reaction. C1 Ctr Canc Res, Natl Canc Inst, NIH, Frederick, MD 21702 USA. RP Ji, X (reprint author), Ctr Canc Res, Natl Canc Inst, NIH, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU Intramural NIH HHS NR 55 TC 66 Z9 67 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2008 VL 67 IS 1 BP 143 EP 154 DI 10.1111/j.1365-2958.2007.06032.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 238GF UT WOS:000251434700011 PM 18047582 ER PT J AU Ieva, R Skillman, KM Bernstein, HD AF Ieva, Raffaele Skillman, Kristen M. Bernstein, Harris D. TI Incorporation of a polypeptide segment into the beta-domain pore during the assembly of a bacterial autotransporter SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI K-12; TRANSLOCATOR DOMAIN; TERTIARY STRUCTURE; IGA PROTEASE; SECRETION; BIOGENESIS; MECHANISM; TRANSPORT; COMPLEX AB Bacterial autotransporters consist of an N-terminal 'passenger domain' that is transported into the extracellular space by an unknown mechanism and a C-terminal 'beta-domain' that forms a beta-barrel in the outer membrane. Recent studies have revealed that fully assembled autotransporters have an unusual architecture in which a small passenger domain segment traverses the pore formed by the beta-domain. It is unclear, however, whether this configuration forms prior to passenger domain translocation or results from the translocation of the passenger domain through the beta-domain pore. By examining the accessibility of tobacco etch virus protease sites and single-cysteine residues in the passenger domain of the Escherichia coli O157:H7 autotransporter EspP at different stages of protein biogenesis, we identified a novel pre-translocation intermediate whose topology resembles that of the fully assembled protein. This intermediate was isolated in the periplasm in cell fractionation experiments. The data strongly suggest that the EspP beta-domain and an embedded polypeptide segment are integrated into the outer membrane as a single pre-formed unit. The data also provide indirect evidence that at least some outer membrane proteins acquire considerable tertiary structure prior to their membrane integration. C1 Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. NIDDK, NIH, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. EM harris_bernstein@nih.gov RI Ieva, Raffaele/J-9207-2014 OI Ieva, Raffaele/0000-0002-3405-0650 FU Intramural NIH HHS NR 36 TC 56 Z9 57 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2008 VL 67 IS 1 BP 188 EP 201 DI 10.1111/j.1365-2958.2007.06048.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 238GF UT WOS:000251434700014 PM 18047580 ER PT J AU Hayton, K Templeton, TJ AF Hayton, Karen Templeton, Thomas J. TI Osmiophilic bodies and the odd organelles of alveolates SO MOLECULAR MICROBIOLOGY LA English DT Editorial Material ID PLASMODIUM-FALCIPARUM; TOXOPLASMA-GONDII; FINE STRUCTURE; PROTEIN; GAMETOCYTES; ATTACK; CELL; GAMETOGENESIS; EXTRUSOMES; PARASITES AB The apicomplexa are parasitic protozoa that are responsible for important human and animal diseases, including malaria, toxoplasmosis, cryptosporidiosis, coccidiosis and babesiosis. Like other members of the superphylum Alveolata, apicomplexans have regulated exocytosis of specialized secretory organelles, such as the apicomplexan-specific rhoptries and micronemes that are required for host cell invasion. The secretions of another class of organelles, the dense granules and osmiophilic bodies, are proposed to be required for maintenance of the parasitophorous vacuole and host cell egress. Little is known about the osmiophilic bodies and to date only one protein, P377, has been localized to this organelle. In this issue, de Koning-Ward et al. describe the disruption of pfg377 in the virulent human malaria parasite, Plasmodium falciparum, which results in reduced osmiophilic body formation, a marked decrease in female fitness, and dramatically impaired infectivity to mosquitoes. These findings suggest that targeting PFG377 may be a strategy to block parasite transmission. C1 [Hayton, Karen] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Templeton, Thomas J.] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. RP Hayton, K (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. EM KHayton@niaid.nih.gov; tjt2001@med.cornell.edu NR 29 TC 4 Z9 4 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2008 VL 67 IS 2 BP 236 EP 240 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 242ZY UT WOS:000251765900003 PM 18086183 ER PT J AU Pattarozzi, A Gatti, M Barbieri, F Wurth, R Porcile, C Lunardi, G Ratto, A Favoni, R Bajetto, A Ferrari, A Florio, T AF Pattarozzi, Alessandra Gatti, Monica Barbieri, Federica Wuerth, Roberto Porcile, Carola Lunardi, Gianluigi Ratto, Alessandra Favoni, Roberto Bajetto, Adriana Ferrari, Angelo Florio, Tullio TI 17 beta-estradiol promotes breast cancer cell proliferation-inducing stromal cell-derived factor-1-mediated epidermal growth factor receptor transactivation: reversal by gefitinib pretreatment SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; ESTROGEN-RECEPTOR; EXTRACELLULAR SIGNAL; ENDOCRINE THERAPY; ZD-1839 IRESSA; OVARIAN-CANCER; BETA-ARRESTIN; EGF RECEPTOR; TUMOR-GROWTH; IN-VITRO AB The coordinated activity of estrogens and epidermal growth factor receptor ( EGFR) family agonists represents the main determinant of breast cancer cell proliferation. Stromal cell-derived factor-1 (SDF-1) enhances extracellular signal-regulated kinases 1 and 2 ( ERK1/2) activity via the transactivation of EGFR and 17 beta-estradiol (E2) induces SDF-1 production to exert autocrine proliferative effects. On this basis, we evaluated whether the inhibition of the tyrosine kinase (TK) activity of EGFR may control different mitogenic stimuli in breast tumors using the EGFR-TK inhibitor gefitinib to antagonize the proliferation induced by E2 in T47D human breast cancer cells. EGF, E2, and SDF-1 induced a dose-dependent T47D cell proliferation, that being nonadditive suggested the activation of common intracellular pathways. Gefitinib treatment inhibited not only the EGF-dependent proliferation and ERK1/2 activation but also the effects of SDF-1 and E2, suggesting that these activities were mediated by EGFR transactivation. Indeed, both SDF-1 and E2 caused EGFR tyrosine phosphorylation. The molecular link between E2 and SDF-1 proliferative effects was identified because 1,1'-(1,4- phenylenebis(methylene))bis- 1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD3100), a CXCR4 antagonist, inhibited SDF-1- and E2-dependent proliferation and EGFR and ERK1/2 phosphorylation. EGFR transactivation was dependent on c-Src activation. E2 treatment caused a powerful SDF-1 release from T47D cells. Finally, in SKBR3, E2-resistant cells, EGFR was constitutively activated, and AMD3100 reduced EGFR phosphorylation and cell proliferation, whereas HER2-neu was transactivated by SDF-1 in SKBR3 but not in T47D cells. In conclusion, we show that activation of CXCR4 transduces proliferative signals from the E2 receptor to EGFR, whose inhibition is able to revert breast cancer cell proliferation induced by multiple receptor activation. C1 [Pattarozzi, Alessandra; Gatti, Monica; Barbieri, Federica; Wuerth, Roberto; Porcile, Carola; Bajetto, Adriana; Florio, Tullio] Univ Genoa, Dept Oncol Biol & Genet, Pharmacol Sect, Genoa, Italy. [Lunardi, Gianluigi; Favoni, Roberto] Natl Canc Inst, Genoa, Italy. [Ratto, Alessandra; Ferrari, Angelo] Natl Reference Ctr Vet & Comparat Oncol, Ist Zooprofilatt Speriment Piemonte, Liguria Valle DAosta, Genoa, Italy. RP Florio, T (reprint author), Univ Genoa, Dipartimento Oncol Biol & Genet, Sez Farmacol, Viale Benedetto XV,2, I-16132 Genoa, Italy. EM tullio.florio@unige.it RI Florio, Tullio/A-2211-2012; Barbieri, Federica/L-8753-2015; OI Florio, Tullio/0000-0002-2394-996X; Barbieri, Federica/0000-0001-8988-6896; Monica, Gatti/0000-0002-2016-0285; Ratto, Alessandra/0000-0003-0445-2306 FU Associazione Italiana per la Ricerca sul Cancro NR 42 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2008 VL 73 IS 1 BP 191 EP 202 DI 10.1124/mol.107.039974 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 243JP UT WOS:000251792900020 PM 17959712 ER PT J AU Mendoza, FN Lopez-Rendon, R Lopez-Lemus, J Cruz, J Alejandre, J AF Noe Mendoza, Francisco Lopez-Rendon, Roberto Lopez-Lemus, Jorge Cruz, Julian Alejandre, Jose TI Surface tension of hydrocarbon chains at the liquid-vapour interface SO MOLECULAR PHYSICS LA English DT Article DE surface tension; hydrocarbon chains; Ewald sums; liquid-vapour ID MOLECULAR-DYNAMICS SIMULATIONS; MONTE-CARLO SIMULATIONS; N-ALKANES; PHASE-EQUILIBRIA; LATTICE SUMS; OLIGOMERS; ENSEMBLE; HEXANE; FLUIDS AB Molecular dynamics simulations were performed at constant temperature to obtain the surface tension of hydrocarbon chains at the liquid-vapour interface. The Ewald sum was used to calculate the dispersion forces of the Lennard-Jones potential to take into account the full interaction. The NERD and TraPPE_UA flexible force field models were used to simulate molecules from ethane to hexadecane along the coexistence curve. The simulation results for the TraPPE_UA model are in good agreement with experimental data, whereas the NERD model predicts slightly higher values. C1 [Noe Mendoza, Francisco; Lopez-Rendon, Roberto; Alejandre, Jose] Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Mexico City 09340, DF, Mexico. [Noe Mendoza, Francisco] NIEHS, Res Triangle Pk, NC 27709 USA. [Lopez-Lemus, Jorge] Univ Autonoma Estado Mexico, Fac Ciencias, Toluca 50000, Mexico. [Cruz, Julian] Univ Autonoma Estado Hidalgo, Ctr Invest Quim, Unidad Univ, Pachuca Hidalgo 42184, Mexico. RP Alejandre, J (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Mexico City 09340, DF, Mexico. EM jra@xanum.uam.mx RI Alejandre, Jose/B-3191-2015; Lopez, Jorge/A-3328-2016; OI Alejandre, Jose/0000-0003-3158-6027; Lopez, Jorge/0000-0002-9486-6942; Lopez-Rendon, Roberto/0000-0002-9374-0977 NR 36 TC 14 Z9 14 U1 2 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0026-8976 J9 MOL PHYS JI Mol. Phys. PY 2008 VL 106 IS 8 BP 1055 EP 1059 DI 10.1080/00268970802119694 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 329VX UT WOS:000257899800011 ER PT S AU Kobayashi, H Koyama, Y Barrett, T Hama, Y Choyke, PL AF Kobayashi, Hisataka Koyama, Yoshinori Barrett, Tristan Hama, Yukihiro Choyke, Peter L. BE Achilefu, S Bornhop, DJ Raghavachari, R TI Multi-excitation near infrared (NIR) spectral fluorescence imaging using organic fluorophores SO MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS II SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Molecular Probes for Biomedical Applications II CY JAN 21-22, 2008 CL San Jose, CA SP SPIE DE fluorescent probe; cancer; multiple color imaging; spectral fluorescence imaging; fluorescent protein; multiexcitation; molecular imaging; molecular targeting ID QUANTUM DOTS AB The ability to obtain multi-color fluorescent imaging in vivo simultaneously using multi-targeted imaging probes could be of potential benefit from both a research and a clinical perspective. However, the simultaneous acquisition of more than 2 separate organic fluorophores usually requires more than one excitation source, since a single excitation source may not optimally excite all the fluorophores. In this study, we employed a multi-excitation approach in order to acquire optimized images with multiple near infrared (NIR) organic fluorophores at the same time. Using 3 sets of excitation filters (595 +/- 20nm, 640 +/- 25nm, 688 +/- 17nm) to acquire 3 distinct spectra and spectral unmixing software (CRi, Woburn, MA), it was possible to resolve the emission spectra of each of the NIR fluorophores using commercial software (Nuance, CRi, Woburn, MA) To demonstrate the utility of this approach 2 mouse models were investigated; In one model, mice bearing four implanted malignancies were injected with a cocktail of 3 fluorescently labeled monoclonal antibodies, each with its own distinct NIR fluorophore. In the second model five different lymph node drainage basins were imaged with 5-color dendrimer-based lymphatic imaging agents tagged with 5 different NIR fluorophores. We successfully detected each of the targeted tumors in the first model and all of the lymph nodes by their distinct color in the second model; neither of which would have been possible using the single excitation method. In conclusion, multi-excitation NIR spectral fluorescence imaging is feasible in a reasonable time frame and opens. the possibility for in vivo immunohistochemical imaging (IHCi). C1 [Kobayashi, Hisataka; Koyama, Yoshinori; Barrett, Tristan; Hama, Yukihiro; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 1 U2 9 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7042-3 J9 PROC SPIE PY 2008 VL 6867 AR 686703 DI 10.1117/12.762380 PG 8 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Optics SC Engineering; Science & Technology - Other Topics; Optics GA BHS97 UT WOS:000256021200001 ER PT J AU Hallett, M AF Hallett, Mark TI The intrinsic and extrinsic aspects of freezing of gait SO MOVEMENT DISORDERS LA English DT Review DE Parkinson disease; freezing of gait; automaticity; self-initiated; externally triggered; attention; dual-task ID POSITRON-EMISSION-TOMOGRAPHY; EXTERNALLY TRIGGERED MOVEMENTS; PARKINSONS-DISEASE; AREAS AB Freezing of gait appears to result from a number of fundamental problems in patients with Parkinson disease. Antomaticity is impaired, putting more stress on voluntary mechanisms. Internal drivers of movement are impaired, likely because of deficient basal ganglia function. Deficiency of internal forces to initiate movement is a major factor in freezing. This deficiency gives a greater influence to external or sensory factors. The sensory factors can both help or hinder freezing Analogous to the problem with set-shifting, there is also some difficulty in regulation of internal versus external factors and in regulation of different external factors. (c) 2008 Movement Disorder Society. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS [ZIA NS003031-09] NR 15 TC 42 Z9 43 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PY 2008 VL 23 SU 2 BP S439 EP S443 DI 10.1002/mds.21836 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 337GE UT WOS:000258422700004 PM 18668625 ER PT J AU Brenchley, JM Douek, DC AF Brenchley, J. M. Douek, D. C. TI HIV infection and the gastrointestinal immune system SO MUCOSAL IMMUNOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL DEPLETION; ACTIVE ANTIRETROVIRAL THERAPY; LYMPHATIC TISSUE FIBROSIS; SMALL-INTESTINAL PERMEABILITY; INFLAMMATORY-BOWEL-DISEASE; DEFICIENCY SYNDROME AIDS; HUMAN EPITHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; MONONUCLEAR-CELLS AB There has recently been a resurgence of interest in the gastrointestinal pathology observed in patients infected with HIV. The gastrointestinal tract is a major site of HIV replication, which results in massive depletion of lamina propria CD4 T cells during acute infection. Highly active antiretroviral therapy leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of gastrointestinal CD4 T cells. The gastrointestinal pathology associated with HIV infection comprises significant enteropathy with increased levels of inflammation and decreased levels of mucosal repair and regeneration. Assessment of gut mucosal immune system has provided novel directions for therapeutic interventions that modify the consequences of acute HIV infection. C1 [Brenchley, J. M.; Douek, D. C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov FU Intramural NIH HHS [Z99 AI999999, ZIA AI001029-02, Z01 AI001029-01] NR 103 TC 202 Z9 210 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2008 VL 1 IS 1 BP 23 EP 30 DI 10.1038/mi.2007.1 PG 8 WC Immunology SC Immunology GA 365LP UT WOS:000260408400005 PM 19079157 ER PT J AU Brenchley, JM Knox, KS Asher, AI Price, DA Kohli, LM Gostick, E Hill, BJ Hage, CA Brahmi, Z Khoruts, A Twigg, HL Schacker, TW Douek, DC AF Brenchley, J. M. Knox, K. S. Asher, A. I. Price, D. A. Kohli, L. M. Gostick, E. Hill, B. J. Hage, C. A. Brahmi, Z. Khoruts, A. Twigg, H. L., III Schacker, T. W. Douek, D. C. TI High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage SO MUCOSAL IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR IMMUNE-RESPONSES; GASTROINTESTINAL-TRACT; CHRONIC INFECTION; TYPE-1 INFECTION; LYMPHOCYTIC ALVEOLITIS; VIRAL SUPPRESSION; LYMPHOID-TISSUE; SIV INFECTION; REPLICATION AB The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to illuminate the pathogenesis of HIV-associated disease. Here, we studied depletion and HIV infection frequencies of CD4 T cells from the gastrointestinal tract, bronchoalveolar lavage (BAL), and blood with the frequencies and functional profiles of HIV-specific T cells in these anatomically distinct sites in HIV-infected individuals. The major findings to emerge were as follows: (i) depletion of gastrointestinal CD4 T cells is associated with high frequencies of infected CD4 T cells; (ii) HIV-specific T cells are present at low frequencies in the gastrointestinal tract compared to blood; (iii) BAL CD4 T cells are not massively depleted during the chronic phase; (iv) infection frequencies of BAL CD4 T cells are similar to those in blood; (v) significantly higher frequencies and increased functionality of HIV-specific T cells were observed in BAL compared to blood. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might circumvent global depletion of mucosal CD4 T cells. C1 [Brenchley, J. M.; Asher, A. I.; Price, D. A.; Hill, B. J.; Douek, D. C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Knox, K. S.; Kohli, L. M.; Hage, C. A.; Twigg, H. L., III] Indiana Univ, Div Pulm & Crit Care Med, Indianapolis, IN 46204 USA. [Knox, K. S.; Hage, C. A.] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Price, D. A.; Gostick, E.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England. [Brahmi, Z.] Indiana Univ, Med Ctr, Dept Med, Indianapolis, IN USA. [Khoruts, A.; Schacker, T. W.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. RP Brenchley, JM (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council (UK); NIH [K08HL04545-05, R01 HL083468, R01HL59834, R01 AI54232, K24 AI056986, R01 DE-12934]; NIAID FX We thank Drs Rhame, Lifson, Kline, Simpson, Baker, Gupta, and Goldman for patient referral and the Indiana University GCRC for patient care. DAP is a Medical Research Council (UK) Senior Clinical Fellow. KSK is supported by NIH Grants K08HL04545-05 and R01 HL083468. HLT is supported by NIH Grant R01HL59834. TWS is supported by NIH Grants R01 AI54232, K24 AI056986, and R01 DE-12934. This work was supported, in part, by intramural funding from NIAID, NIH. NR 48 TC 48 Z9 48 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2008 VL 1 IS 1 BP 49 EP 58 DI 10.1038/mi.2007.5 PG 10 WC Immunology SC Immunology GA 365LP UT WOS:000260408400008 PM 19079160 ER PT S AU Masedunskas, A Weigert, R AF Masedunskas, Andrius Weigert, Roberto BE Periasamy, A So, PTC TI Internalization of fluorescent dextrans in the submandibular salivary glands of live animals: a study combining intravital two-photon microscopy and second harmonic generation SO MULTIPHOTON MICROSCOPY IN THE BIOMEDICAL SCIENCES VIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Multiphoton Microscopy in the Biomedical Sciences VIII CY JAN 20-22, 2008 CL San Jose, CA SP SPIE, Becker & Hickl, Boston Elect, Carl Zeiss Inc, Coherent Inc, HighQ Laser, Newport Spectra Phys, Chroma Technol Corp, Omega Opt DE intravital two-photon microscopy; second harmonic generation; endocytosis; salivary glands; live animals ID EXCITATION MICROSCOPY; CELLS; SECRETION; TISSUES; KIDNEY; RAT AB Here we show that a combination of two-photon microscopy and second harmonic generation can be successfully used to study endocytosis in the submandibular salivary glands of live animals. First, we have characterized the three-dimensional structure of the acini and the ducts forming the parenchyma of the excised glands by exciting various endogenous molecules, which highlight the shape of the cells and various components of the extracellular matrix. Next, by time-lapse imaging we show the dynamic distribution of fluorescent probes injected systemically. This was achieved by using a custom-made holder aimed to reduce the motion artifacts associated with the heartbeat and the respiration in the live animals. Finally, we show that fluorescent dextrans are internalized primarily by the supporting cells in the salivary glands, a characteristic shared by other secretory organs such as the pancreas. C1 [Masedunskas, Andrius; Weigert, Roberto] NIDCR, Intracellular Membrane Trafficking Unit, OPCB, NIH, Bethesda, MD 20892 USA. RP Weigert, R (reprint author), NIDCR, Intracellular Membrane Trafficking Unit, OPCB, NIH, 30 Convent Dr 303A, Bethesda, MD 20892 USA. EM weigertr@mail.nih.gov OI Masedunskas, Andrius/0000-0002-4533-5467 NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7035-5 J9 PROC SPIE PY 2008 VL 6860 AR 68601V DI 10.1117/12.768051 PG 12 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BHS92 UT WOS:000256019000038 ER PT J AU Shukla, V Vaissiere, T Herceg, Z AF Shukla, Vivek Vaissiere, Thomas Herceg, Zdenko TI Histone acetylation and chromatin signature in stem cell identity and cancer SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE epigenetic mechanisms; chromatin modifications; histone acetylation; histone acetyltransferases; stem and progenitor cells; cancer ID LOCUS-CONTROL REGION; BETA-GLOBIN LOCUS; ACETYLTRANSFERASE COMPLEX; SELF-RENEWAL; DNA-REPAIR; C-MYC; DEPSIPEPTIDE FR901228; DEACETYLASE INHIBITOR; MAMMALIAN-CELLS; GENES AB Cancers are traditionally viewed as a primarily genetic disorder, however this view has recently been modified by compelling evidence arguing that epigenetic events play important roles in most human cancers. Deregulation of epigenetic information (encoded in DNA methylation and histone modification patterns) in cells with pluripotent potential may alter defining properties of stem cells, self-renewal and differentiation potential, leading to cancer initiation and progression. The level of compaction of chromatin dictates accessibility to genomic DNA and therefore has a key role in establishing and maintaining distinct gene expression patterns and consequently pluripotent state and differentiation fates of stem cells. Unique properties of stem cells defined as "stemness" may be determined by acetylation and methylation of histones near gene promoters that regulate gene transcription, however these histone modifications elsewhere in the genome may also be important. In this review, we discuss new insights into possible mechanisms by which histone acetyltransferases (HATs) and histone acetylation in concert with other chromatin modifications may regulate pluripotency, and speculate how deregulation of histone marking may lead to tumourigenesis. (c) 2007 Elsevier B.V. All rights reserved. C1 [Shukla, Vivek; Vaissiere, Thomas; Herceg, Zdenko] Int Agcy Res Canc, Epigenet Grp, F-69008 Lyon, France. [Shukla, Vivek] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Herceg, Z (reprint author), Int Agcy Res Canc, Epigenet Grp, 150 Cours Albert Thomas, F-69008 Lyon, France. EM herceg@iarc.fr RI Vaissiere, Thomas/E-1121-2011 NR 108 TC 45 Z9 47 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JAN 1 PY 2008 VL 637 IS 1-2 BP 1 EP 15 DI 10.1016/j.mrfmmm.2007.07.012 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 256RR UT WOS:000252747800001 PM 17850830 ER PT S AU Newsom-Davis, J Cutter, G Wolfe, GI Kaminski, HJ Jaretzki, A Minisman, G Aban, I Conwit, R AF Newsom-Davis, John Cutter, Gary Wolfe, Gil I. Kaminski, Henry J. Jaretzki, Alfred, III Minisman, Greg Aban, Inmaculada Conwit, Robin BE Kaminski, HJ Barohn, RJ TI Status of the thymectomy trial for nonthymomatous myasthenia gravis patients receiving prednisone SO MYASTHENIA GRAVIS AND RELATED DISORDERS: 11TH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 11th International Conference on Myasthenia Gravis and Related Disorder CY MAY, 2007 CL Chicago, IL DE myasthenia gravis; thymectomy; prednisone ID STANDARDS; NEUROLOGY AB The primary study [MGTX] aims to answer three questions: does extended transsternal thymectomy combined with the prednisone protocol, when compared with the prednisone protocol alone: (1) result in a greater improvement in myasthenic weakness, (2) result in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, (3) enhance the quality of life by reducing adverse events and symptoms associated with the therapies? Inclusion criteria are MGFA Class 2, 3, or 4; acetylcholine receptor antibody positive; age at least 18.0 years and <60.0 years; MG history of <3 years. Patients can be prednisone naive or not. The National Institute for Neurological Disorders and Stroke awarded funding for MGTX in September 2005, and NIH awarded funding for the ancillary Biomarkers study (BioMG) in February 2006. Diverse regulatory obstacles have been encountered in this international study, but we now have a total of over 70 centers in 22 countries (North America, South America, Europe, Australasia, South Africa) either actively recruiting or at various levels of readiness. C1 [Kaminski, Henry J.] St Louis Univ, Sch Med, Dept Neurol & Psychiat, St Louis, MO 63104 USA. [Newsom-Davis, John] Univ Oxford, Oxford, England. [Cutter, Gary; Minisman, Greg; Aban, Inmaculada] Univ Alabama, Birmingham, AL USA. [Wolfe, Gil I.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Jaretzki, Alfred, III] Columbia Univ, Med Ctr, New York, NY USA. [Conwit, Robin] NINDS, Bethesda, MD 20892 USA. RP Kaminski, HJ (reprint author), St Louis Univ, Sch Med, Dept Neurol & Psychiat, 1438 S Grand Blvd, St Louis, MO 63104 USA. EM Henry.Kaminski@tenethcalth.com; Henry.Kaminski@tenethcalth.com NR 4 TC 32 Z9 35 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-687-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1132 BP 344 EP 347 DI 10.1196/annals.1405.014 PG 4 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BHX10 UT WOS:000257139900042 PM 18567886 ER PT J AU Tyagi, AK Singh, R Gupta, V AF Tyagi, Anil K. Singh, Ramandeep Gupta, Vibha BE Daffe, M Reyrat, JM TI The Role of Mycobacterial Kinases and Phosphatases in Growth, Pathogenesis, and Cell Wall Metabolism SO MYCOBACTERIAL CELL ENVELOPE LA English DT Article; Book Chapter ID PROTEIN-TYROSINE-PHOSPHATASE; 2-COMPONENT SIGNAL-TRANSDUCTION; ORALLY BIOAVAILABLE INHIBITOR; SERINE/THREONINE KINASE; RESPONSE REGULATOR; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; SER/THR KINASE; IN-VIVO; ACID-PHOSPHATASE C1 [Tyagi, Anil K.; Gupta, Vibha] Univ Delhi, Dept Biochem, New Delhi 110021, India. [Singh, Ramandeep] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Tyagi, AK (reprint author), Univ Delhi, Dept Biochem, South Campus,Benito Juarez Rd, New Delhi 110021, India. NR 180 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-578-3 PY 2008 BP 323 EP 343 PG 21 WC Biotechnology & Applied Microbiology; Cell Biology; Microbiology SC Biotechnology & Applied Microbiology; Cell Biology; Microbiology GA BOX93 UT WOS:000277989500021 ER PT S AU Kobayashi, H AF Kobayashi, Hisataka BE Bulte, JWM Modo, MMJ TI MR Lymphangiography Using Nano-Sized Paramagnetic Contrast Agents with Dendrimer Cores SO NANOPARTICLES IN BIOMEDICAL IMAGING: EMERGING TECHNOLOGIES AND APPLICATIONS SE Fundamental Biomedical Technologies LA English DT Article; Book Chapter ID SENTINEL LYMPH-NODE; MAGNETIC RESONANCE LYMPHANGIOGRAPHY; EARLY BREAST-CANCER; GAMMA-DETECTING PROBE; POLYAMIDOAMINE DENDRIMER; PHARMACOKINETIC PROPERTIES; HIGH-GENERATION; MICE; LYMPHOSCINTIGRAPHY; LYMPHOGRAPHY AB Imaging of the lymphatic system is difficult because its channels and lymph nodes are small and not directly accessible. Currently, two clinical methods, the direct lymphangiography and the lymphoscintigraphy, are used to visualize parts of the human lymphatic system, but have significant limitations. Nano-sized contrast agents have recently been evaluated to be advantageous for Visualization of the lymphatic system because of their appropriate physical sizes and the potential of signal amplification. In this review, the magnetic resonance lymphangiography using a series of nano-sized paramagnetic contrast agents, gadolinium labeled dendrimers, is discussed focusing on the synthetic method, their pharmacokinetic characteristics for selection Of appropriate agents, and applications for Visualization of various lymphatic disorders in mouse models. C1 NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov NR 40 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1559-7083 BN 978-0-387-72026-5 J9 FUND BIOMED TECHNOL JI Fundam. Biomed. Technol. PY 2008 BP 9 EP 23 D2 10.1007/978-0-387-72027-2 PG 15 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BKH69 UT WOS:000268131300002 ER PT S AU Shapiro, EM Koretsky, AP AF Shapiro, Erik M. Koretsky, Alan P. BE Bulte, JWM Modo, MMJ TI Micron-Sized Iron Oxide Particles (MPIOs) for Cellular Imaging: More Bang for the Buck SO NANOPARTICLES IN BIOMEDICAL IMAGING: EMERGING TECHNOLOGIES AND APPLICATIONS SE Fundamental Biomedical Technologies LA English DT Article; Book Chapter DE MRI; stem cell; iron oxide; particle; contrast agent; transplant ID MESENCHYMAL STEM-CELLS; SINGLE MAMMALIAN-CELLS; MR CONTRAST AGENT; TRANSFECTION AGENTS; FERRITE PARTICLES; PROGENITOR; RELAXATION; BRAIN; NANOPARTICLES; MIGRATION AB Iron oxide particles have been used for molecular and cellular magnetic resonance imaging since the 1980s. Interestingly, early research in these fields used particles in the micron size range. After a long disappearance, the utility of micron-sized iron oxide particles, or MPIOs, has been rediscovered, largely due to their improved construction and stability. Due to the very high iron content of single MPIOs, their use as a cell-tracking agent has enabled the detection of single particles in single cells, the detection of single cells in vivo, and the ability to label cells directly in vivo. This chapter begins by discussing the physical and magnetic properties of MPIOs and compares them to the more commonly used iron oxide particles, USPIOs and SPIOs. Next, the unique properties of MPIOs as an MRI agent are illustrated, with examples of MRI experiments on the particles themselves, and on cells labeled with MPIOs. The chapter then reviews work on various applications of cell therapy, using cells labeled with MPIOs, with a section on the detection of single cells in vivo. Lastly, there is a presentation of work using MPIOs to directly label cells in vivo. C1 [Shapiro, Erik M.] Yale Univ, Sch Med, Dept Diagnost Radiol, Mol & Cellular Imaging Lab, New Haven, CT 06510 USA. [Koretsky, Alan P.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Shapiro, EM (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, Mol & Cellular Imaging Lab, New Haven, CT 06510 USA. EM erik.shapiro@yale.edu RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 NR 48 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1559-7083 BN 978-0-387-72026-5 J9 FUND BIOMED TECHNOL JI Fundam. Biomed. Technol. PY 2008 BP 141 EP 161 D2 10.1007/978-0-387-72027-2 PG 21 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BKH69 UT WOS:000268131300007 ER PT B AU Westem, KA AF Westem, Karl A. BE Georgiev, VS Western, KA McGowan, JJ TI National Institute of Allergy and Infectious Diseases (NIAID): An Overview SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth C1 NIAID, Off Global Res, NIH, Bethesda, MD 20892 USA. RP Westem, KA (reprint author), NIAID, Off Global Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 3 EP 8 DI 10.1007/978-1-59745-569-5_1 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500001 ER PT B AU Simonsen, L Bernabe, G Lacourciere, K Taylor, RJ Giovanni, MY AF Simonsen, Lone Bernabe, Gayle Lacourciere, Karen Taylor, Robert J. Giovanni, Maria Y. BE Georgiev, VS Western, KA McGowan, JJ TI The NIAID Influenza Genome Sequencing Project SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease-Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth ID UNITED-STATES; ADAMANTANE RESISTANCE; MORTALITY; VIRUSES; EVOLUTION; GENESIS C1 [Simonsen, Lone; Bernabe, Gayle] NIAID, Off Global Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Lacourciere, Karen; Giovanni, Maria Y.] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. [Taylor, Robert J.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA. RP Simonsen, L (reprint author), NIAID, Off Global Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIAID FX The authors thank their colleagues David Spiro for providing Figure 12.1 , and Eddie Holmes, Elodie Ghedin, and Jessica Bernstein for helpful comments on the manuscript. This research was supported by NIAID. NR 11 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFECT DIS-SER PY 2008 BP 109 EP + DI 10.1007/978-1-59745-569-5_13 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500013 ER PT B AU Herz, KT AF Herz, Katherine T. BE Georgiev, VS Western, KA McGowan, JJ TI Research in Emerging and Re-emerging Diseases in Central Asia and the Caucasus: Contributions by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth ID GEORGIA; STRAINS C1 NIAID, Off Global Res, Bethesda, MD 20892 USA. RP Herz, KT (reprint author), NIAID, Off Global Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 251 EP 252 DI 10.1007/978-1-59745-569-5_27 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500027 ER PT B AU Berger, EA AF Berger, Edward A. BE Georgiev, VS Western, KA McGowan, JJ TI Virus Receptor Wars: Entry Molecules Used for and Against Viruses Associated with AIDS SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth ID CORECEPTOR BINDING-SITE; KAPOSIS-SARCOMA; CHEMOKINE RECEPTORS; HIV-1 INFECTION; CELL-FUSION; GLYCOPROTEIN; NEUTRALIZATION; GP120; TRANSMISSION; DISEASE C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 271 EP 277 DI 10.1007/978-1-59745-569-5_31 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500031 ER PT B AU Dimitrov, DS AF Dimitrov, Dimiter S. BE Georgiev, VS Western, KA McGowan, JJ TI Human Monoclonal Antibodies Against HIV and Emerging Viruses SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth ID ACUTE RESPIRATORY SYNDROME; HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR-BINDING DOMAIN; POTENT NEUTRALIZING ANTIBODIES; EMERGENT DEADLY PARAMYXOVIRUS; SARS-ASSOCIATED CORONAVIRUS; RED-CELL APLASIA; INTRAVENOUS IMMUNOGLOBULIN; NIPAH VIRUS; PASSIVE-IMMUNIZATION C1 NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21701 USA. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21701 USA. NR 97 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 299 EP 308 DI 10.1007/978-1-59745-569-5_34 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500034 ER PT B AU Bums, DN Black, R AF Bums, David N. Black, Roberta BE Georgiev, VS Western, KA McGowan, JJ TI NIAID HIV/AIDS Prevention Research SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth ID HIV PREVENTION; MALE CIRCUMCISION; PERSONS AWARE; EPIDEMIC; IMPACT; RISK; TRANSMISSION; BEHAVIOR; UNAWARE; AFRICA C1 [Bums, David N.; Black, Roberta] NIAID, Prevent Sci Branch, Div Aids, NIH, Bethesda, MD 20892 USA. RP Bums, DN (reprint author), NIAID, Prevent Sci Branch, Div Aids, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 319 EP 325 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500036 ER PT B AU Davidson, WF Mukhopadhyay, P Williams, MS Naghashfar, Z Zhou, JX Morse, HC AF Davidson, Wendy F. Mukhopadhyay, Partha Williams, Mark S. Naghashfar, Zohreh Zhou, Jeff X. Morse, Herbert C., III BE Georgiev, VS Western, KA McGowan, JJ TI A Model System for Studying Mechanisms of B-cell Transformation in Systemic Autoimmunity SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease-Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth ID HEPATITIS-C VIRUS; PRIMARY SJOGRENS-SYNDROME; LUPUS-ERYTHEMATOSUS SLE; NON-HODGKIN LYMPHOMAS; LYMPHOPROLIFERATIVE SYNDROME; RHEUMATOID-ARTHRITIS; MALIGNANT-LYMPHOMA; MIXED CRYOGLOBULINEMIA; ANTIGEN RECEPTOR; CLONAL EVOLUTION C1 [Davidson, Wendy F.; Mukhopadhyay, Partha] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Dept Microbiol Immunol, Ctr Vascular & Inflammatory Dis, BioPk Bldg I, Baltimore, MD 21228 USA. [Mukhopadhyay, Partha] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Ctr Vascular & Inflammatory Dis, Baltimore, MD 21228 USA. [Williams, Mark S.] Univ Maryland, Dept Microbiol Immunol, Sch Med, Ctr Vascular & Inflammatory Dis, Baltimore, MD 21228 USA. [Naghashfar, Zohreh; Zhou, Jeff X.; Morse, Herbert C., III] NIH, NIAID, Immunopathol Lab, Rockville, MD USA. RP Davidson, WF (reprint author), Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Dept Microbiol Immunol, Ctr Vascular & Inflammatory Dis, BioPk Bldg I, Baltimore, MD 21228 USA. NR 91 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFECT DIS-SER PY 2008 BP 385 EP + DI 10.1007/978-1-59745-569-5_43 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500043 ER PT B AU Hornbeak, H Jackson, PR AF Hornbeak, Hortencia Jackson, Peter R. BE Georgiev, VS Western, KA McGowan, JJ TI Strategies for a Competitive Research Career SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth C1 [Hornbeak, Hortencia; Jackson, Peter R.] NIAID, NIH, Bethesda, MD 20892 USA. RP Hornbeak, H (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 483 EP 485 DI 10.1007/978-1-59745-569-5_51 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500051 ER PT B AU Mehrotra, P Hornbeak, H Jackson, PR Baizman, E AF Mehrotra, Priti Hornbeak, Hortencia Jackson, Peter R. Baizman, Eugene BE Georgiev, VS Western, KA McGowan, JJ TI Selecting the Appropriate Funding Mechanism SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth C1 [Mehrotra, Priti; Hornbeak, Hortencia; Jackson, Peter R.; Baizman, Eugene] NIAID, NIH, Bethesda, MD 20892 USA. RP Mehrotra, P (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 487 EP 495 DI 10.1007/978-1-59745-569-5_52 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500052 ER PT B AU Jackson, PR Hornbeak, H AF Jackson, Peter R. Hornbeak, Hortencia BE Georgiev, VS Western, KA McGowan, JJ TI Preparing and Submitting a Competitive Grant Application SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth C1 [Jackson, Peter R.; Hornbeak, Hortencia] NIAID, NIH, Bethesda, MD 20892 USA. RP Jackson, PR (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 497 EP 505 DI 10.1007/978-1-59745-569-5_53 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500053 ER PT B AU Baizman, E Hornbeak, H Jackson, PR Mehrotra, P AF Baizman, Eugene Hornbeak, Hortencia Jackson, Peter R. Mehrotra, Priti BE Georgiev, VS Western, KA McGowan, JJ TI Identifying Research Resources and Funding Opportunities SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 1: FRONTIERS IN RESEARCH SE Infectious Disease Series LA English DT Proceedings Paper CT Reseach Conference of the National-Institute-of-Allergy-and-Infectious-Diseases CY JUN 24-30, 2006 CL Opatija, CROATIA SP Natl Inst Hlth C1 [Baizman, Eugene; Hornbeak, Hortencia; Jackson, Peter R.; Mehrotra, Priti] NIAID, NIH, Bethesda, MD 20892 USA. RP Baizman, E (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-77-0 J9 INFEC DIS S PY 2008 BP 507 EP 517 DI 10.1007/978-1-59745-569-5_54 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BIP70 UT WOS:000261705500054 ER PT J AU Bewley, CA AF Bewley, Carole A. TI Illuminating the switch in influenza viruses SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID RECEPTOR-BINDING; A VIRUSES; HEMAGGLUTININS; SPECIFICITY AB Integrating data from glycan microarrays and X-ray structures sheds light on human adaptation of influenza viruses. C1 [Bewley, Carole A.] NIDDK, Natl Inst Hlth, Bioorgan Chem Lab, Bethesda, MD 20817 USA. RP Bewley, CA (reprint author), NIDDK, Natl Inst Hlth, Bioorgan Chem Lab, Bethesda, MD 20817 USA. EM caroleb@mail.nih.gov NR 12 TC 14 Z9 15 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2008 VL 26 IS 1 BP 60 EP 62 DI 10.1038/nbt0108-60 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 249IW UT WOS:000252222500021 PM 18183018 ER PT J AU Shirey, JK Xiang, ZX Orton, D Brady, AE Johnson, KA Williams, R Ayalai, JE Rodriguez, AL Wess, J Weaver, D Niswender, CM Conn, PJ AF Shirey, Jana K. Xiang, Zixiu Orton, Darren Brady, Ashley E. Johnson, Kari A. Williams, Richard Ayalai, Jennifer E. Rodriguez, Alice L. Wess, Juergen Weaver, David Niswender, Colleen M. Conn, P. Jeffrey TI An allosteric potentiator of M-4 mAChR modulates hippocampal synaptic transmission SO NATURE CHEMICAL BIOLOGY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; ALZHEIMERS-DISEASE; PYRAMIDAL CELLS; DOUBLE-BLIND; CHOLINERGIC MECHANISMS; PRESYNAPTIC INHIBITION; PARKINSONS-DISEASE; ANTIPSYCHOTIC-LIKE; RAT HIPPOCAMPUS; DEMENTIA AB Muscarinic acetylcholine receptors (mAChRs) provide viable targets for the treatment of multiple central nervous system disorders. We have used cheminformatics and medicinal chemistry to develop new, highly selective M-4 allosteric potentiators. VU10010, the lead compound, potentiates the M-4 response to acetylcholine 47-fold while having no activity at other mAChR subtypes. This compound binds to an allosteric site on the receptor and increases affinity for acetylcholine and coupling to G proteins. Whole-cell patch clamp recordings revealed that selective potentiation of M-4 with VU10010 increases carbachol-induced depression of transmission at excitatory but not inhibitory synapses in the hippocampus. The effect was not mimicked by an inactive analog of VU 10010 and was absent in M-4 knockout mice. Selective regulation of excitatory transmission by M4 suggests that targeting of individual mAChR subtypes could be used to differentially regulate specific aspects of mAChR modulation of function in this important forebrain structure. C1 [Shirey, Jana K.; Xiang, Zixiu; Brady, Ashley E.; Johnson, Kari A.; Ayalai, Jennifer E.; Rodriguez, Alice L.; Weaver, David; Niswender, Colleen M.; Conn, P. Jeffrey] Vanderbilt Program Drug Discovery, Dept Pharmacol, Nashville, TN 37232 USA. [Orton, Darren; Williams, Richard; Rodriguez, Alice L.; Weaver, David; Niswender, Colleen M.; Conn, P. Jeffrey] Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA. [Orton, Darren; Williams, Richard] Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA. [Wess, Juergen] NIDDK, NIH, Bethesda, MD 20892 USA. RP Conn, PJ (reprint author), Vanderbilt Program Drug Discovery, Dept Pharmacol, 23rd Ave S Pierce, Nashville, TN 37232 USA. EM jeff.conn@vanderbilt.edu RI Conn, Peter/D-7848-2012; OI Xiang, Zixiu/0000-0002-1678-209X NR 46 TC 91 Z9 94 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JAN PY 2008 VL 4 IS 1 BP 42 EP 50 DI 10.1038/nchembio.2007.55 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246EJ UT WOS:000251990000012 PM 18059262 ER PT J AU van Es, MA van Vught, PW Blauw, HM Franke, L Saris, CG Van Den Bosch, L de Jong, SW de Jong, V Baas, F van't Slot, R Lemmens, R Schelhaas, HJ Birve, A Sleegers, K Van Broeckhoven, C Schymick, JC Traynor, BJ Wokke, JH Wijmenga, C Robberecht, W Andersen, PM Veldink, JH Ophoff, RA van den Berg, LH AF van Es, Michael A. van Vught, Paul Wj Blauw, Hylke M. Franke, Lude Saris, Christiaan G. J. Van Den Bosch, Ludo de Jong, Sonja W. de Jong, Vianney Baas, Frank van't Slot, Ruben Lemmens, Robin Schelhaas, Helenius J. Birve, Anna Sleegers, Kristel Van Broeckhoven, Christine Schymick, Jennifer C. Traynor, Bryan J. Wokke, John H. J. Wijmenga, Cisca Robberecht, Wim Andersen, Peter M. Veldink, Jan H. Ophoff, Roel A. van den Berg, Leonard H. TI Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis SO NATURE GENETICS LA English DT Article ID SPORADIC ALS; MUTATIONS AB We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04x10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18 - 1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies. C1 [van Es, Michael A.; van Vught, Paul Wj; Blauw, Hylke M.; Saris, Christiaan G. J.; de Jong, Sonja W.; Wokke, John H. J.; Veldink, Jan H.; van den Berg, Leonard H.] Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands. [Franke, Lude; van't Slot, Ruben; Wijmenga, Cisca] Univ Med Utrecht, Dept Biomed Genet, Complex Genet Sect, NL-3584 CX Utrecht, Netherlands. [Van Den Bosch, Ludo; Robberecht, Wim] Univ Hosp Gasthuisberg, Dept Neurol, B-3000 Louvain, Belgium. [de Jong, Vianney] Univ Amsterdam, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Baas, Frank] Univ Amsterdam, Dept Neurogenet, NL-1105 AZ Amsterdam, Netherlands. [Schelhaas, Helenius J.] Univ Nijmegen, Med Ctr, Dept Neurol, NL-6525 GA Nijmegen, Netherlands. [Birve, Anna] Umea Univ Hosp, Inst Clin Neurosci, SE-90185 Umea, Sweden. [Baas, Frank; Sleegers, Kristel] VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, B-2610 Antwerp, Belgium. [Sleegers, Kristel; Van Broeckhoven, Christine] Univ Antwerp VIB, B-2610 Antwerp, Belgium. [Schymick, Jennifer C.] NIA, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Traynor, Bryan J.] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands. [Wijmenga, Cisca] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands. [Ophoff, Roel A.] Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90095 USA. RP van den Berg, LH (reprint author), Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands. EM Ophoff@ucla.edu; L.H.vandenBerg@umcutrecht.nl RI Schelhaas, Helenius Jurgen/E-2815-2010; Van Den Bosch, Ludo/B-7258-2012; Traynor, Bryan/G-5690-2010; Wijmenga, Cisca/D-2173-2009; Baas, Frank/F-9574-2010; Saris, C.G.J./L-4623-2015; Franke, Lude/P-7036-2016; OI Baas, Frank/0000-0003-3912-5428; Franke, Lude/0000-0002-5159-8802; Wijmenga, Cisca/0000-0002-5635-1614 FU NIGMS NIH HHS [GM68875]; NIMH NIH HHS [MH078075] NR 14 TC 136 Z9 137 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2008 VL 40 IS 1 BP 29 EP 31 DI 10.1038/ng.2007.52 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 247YN UT WOS:000252118600014 PM 18084291 ER PT J AU Pasqualucci, L Bhagat, G Jankovic, M Compagno, M Smith, P Muramatsu, M Honjo, T Morse, HC Nussenzweig, MC Dalla-Favera, R AF Pasqualucci, Laura Bhagat, Govind Jankovic, Mila Compagno, Mara Smith, Paula Muramatsu, Masamichi Honjo, Tasuku Morse, Herbert C., III Nussenzweig, Michel C. Dalla-Favera, Riccardo TI AID is required for germinal center-derived lymphomagenesis SO NATURE GENETICS LA English DT Article ID CYTIDINE DEAMINASE AID; CLASS SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; CENTER B-CELLS; ANTIBODY DIVERSIFICATION; SOMATIC HYPERMUTATION; EXPRESSION; TRANSLOCATIONS; PHENOTYPE; REGION AB Most human B cell non-Hodgkin's lymphomas (B-NHLs) derive from germinal centers (GCs), the structure in which B cells undergo somatic hypermutation (SHM) and class switch recombination (CSR) before being selected for high-affinity antibody production(1). The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant SHM, which arise from mistakes occurring during CSR and SHM2-4. A direct link between these DNA remodeling events and GC lymphoma development, however, has not been demonstrated. Here we have crossed three mouse models of B cell lymphoma driven by oncogenes (Myc, Bcl6 and Myc/Bcl6; refs. 5,6) with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both CSR and SHM7,8. We show that AID deficiency prevents Bcl6-dependent, GC-derived B-NHL, but has no impact on Myc-driven, pre-GC lymphomas. Accordingly, abrogation of AID is associated with the disappearance of CSR- and SHM-mediated structural alterations. These results show that AID is required for GC-derived lymphomagenesis, supporting the notion that errors in AID-mediated antigen-receptor gene modification processes are principal contributors to the pathogenesis of human B-NHL. C1 [Pasqualucci, Laura; Bhagat, Govind; Compagno, Mara; Smith, Paula; Dalla-Favera, Riccardo] Columbia Univ, Inst Canc Genet, Dept Pathol, New York, NY 10032 USA. [Pasqualucci, Laura; Bhagat, Govind; Compagno, Mara; Smith, Paula; Dalla-Favera, Riccardo] Columbia Univ, Inst Canc Genet, Dept Genet & Dev, New York, NY 10032 USA. [Pasqualucci, Laura; Bhagat, Govind; Compagno, Mara; Smith, Paula; Dalla-Favera, Riccardo] Columbia Univ, Inst Canc Genet, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Jankovic, Mila; Muramatsu, Masamichi] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. [Muramatsu, Masamichi] Kanazawa Univ, Grad Sch Med Sci, Dept Mol Genet, Kanazawa, Ishikawa 9208640, Japan. [Honjo, Tasuku] Kyoto Univ, Grad Sch Med, Dept Immunol & Genom Med, Kyoto 6068501, Japan. [Morse, Herbert C., III] NIAID, NIH, Immunopathol Lab, Bethesda, MD 20892 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Pasqualucci, L (reprint author), Columbia Univ, Inst Canc Genet, Dept Pathol, New York, NY 10032 USA. EM lp171@columbia.edu; rd10@columbia.edu RI Muramatsu, Masamichi/C-4339-2015; Honjo, Tasuku/N-4470-2016; OI Muramatsu, Masamichi/0000-0002-0153-3533; Morse, Herbert/0000-0002-9331-3705; Bhagat, Govind/0000-0001-6250-048X FU Intramural NIH HHS NR 30 TC 199 Z9 200 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2008 VL 40 IS 1 BP 108 EP 112 DI 10.1038/ng.2007.35 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 247YN UT WOS:000252118600026 PM 18066064 ER PT J AU Ramalingam, TR Pescel, JT Sheikh, F Cheever, AW Mentink-Kane, MM Wilson, MS Stevens, S Valenzuela, DM Murphy, AJ Yancopoulos, GD Urban, JF Donnelly, RP Wynn, TA AF Ramalingam, Thirumalai R. Pescel, John T. Sheikh, Faruk Cheever, Allen W. Mentink-Kane, Margaret M. Wilson, Mark S. Stevens, Sean Valenzuela, David M. Murphy, Andrew J. Yancopoulos, George D. Urban, Joseph F., Jr. Donnelly, Raymond P. Wynn, Thomas A. TI Unique functions of the type 11 interleukin 4 receptor identified in mice lacking the interleukin 13 receptor alpha 1 chain SO NATURE IMMUNOLOGY LA English DT Article ID ALTERNATIVELY ACTIVATED MACROPHAGES; IL-13 INDUCES PROLIFERATION; HUMAN B-CELLS; NIPPOSTRONGYLUS-BRASILIENSIS; GRANULOMATOUS PATHOLOGY; NEMATODE PARASITES; IMMUNE-RESPONSE; GENE-EXPRESSION; TH2 CYTOKINES; TNF-ALPHA AB The interleukin 4 receptor (IL-4R) is a central mediator of T helper type 2 (T(H)2)-mediated disease and associates with either the common gamma-chain to form the type I IL-4R or with the IL-13R alpha 1 chain (IL-13R alpha 1) to form the type II IL-4R. Here we used II13ral(-/-) mice to characterize the distinct functions of type I and type II IL-4 receptors in vivo. In contrast to II4ra(-/-) mice, which have weak T(H)2 responses, II13ra1(-/-) mice had exacerbated T(H)2 responses. II13ra1(-/-) mice showed much less mortality after infection with Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis. IL-13R alpha 1 was essential for allergen-induced airway hyperreactivity and mucus hypersecretion but not for fibroblast or alternative macrophage activation. Thus, type I and II IL-4 receptors exert distinct effects on immune responses. C1 [Ramalingam, Thirumalai R.; Pescel, John T.; Mentink-Kane, Margaret M.; Wilson, Mark S.; Wynn, Thomas A.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. [Cheever, Allen W.] Inst Biomed Res, Rockville, MD 20892 USA. [Stevens, Sean; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Urban, Joseph F., Jr.] USDA, BHNRC, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA. RP Wynn, TA (reprint author), NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; OI Murphy, Andrew/0000-0003-4152-4081 FU Intramural NIH HHS [Z01 AI001019-01, Z01 AI000829-10] NR 49 TC 104 Z9 106 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2008 VL 9 IS 1 BP 25 EP 33 DI 10.1038/ni1544 PG 9 WC Immunology SC Immunology GA 243TS UT WOS:000251820800008 PM 18066066 ER PT J AU Ledgerwood, LG Lal, G Zhang, N Garin, A Esses, SJ Ginhoux, F Merad, M Peche, H Lira, SA Ding, YZ Yang, Y He, XX Schuchman, EH Allende, ML Ochando, JC Bromberg, JS AF Ledgerwood, Levi G. Lal, Girdhari Zhang, Nan Garin, Alexandre Esses, Steven J. Ginhoux, Florent Merad, Miriam Peche, Helene Lira, Sergio A. Ding, Yaozhong Yang, Yu He, Xingxuan Schuchman, Edward H. Allende, Maria L. Ochando, Jordi C. Bromberg, Jonathan S. TI The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics SO NATURE IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELL LINE; TRANSENDOTHELIAL MIGRATION; TRANSCELLULAR MIGRATION; LYMPHOID ORGANS; L-SELECTIN; IN-VIVO; EXPRESSION; TRAFFICKING; SPHINGOSINE-1-PHOSPHATE; ADHESION AB Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an experimental model to recapitulate this process in vitro. Agonism of sphingosine 1-phosphate receptor I inhibited the entry of tissue T cells into afferent lymphatics in homeostatic and inflammatory conditions and caused the arrest, mediated at least partially by interactions of the integrin LFA-1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at the basal surface of lymphatic but not blood vessel endothelium. Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress. C1 [Ledgerwood, Levi G.; Lal, Girdhari; Zhang, Nan; Garin, Alexandre; Esses, Steven J.; Ginhoux, Florent; Merad, Miriam; Peche, Helene; Lira, Sergio A.; Ding, Yaozhong; Yang, Yu; Ochando, Jordi C.; Bromberg, Jonathan S.] Mt Sinai Sch Med, Ctr Immunol, Dept Gene & Cell Med, New York, NY 10029 USA. [Yang, Yu] Mt Sinai Sch Med, Dept Surg, New York, NY 10029 USA. [Ding, Yaozhong; Yang, Yu; Bromberg, Jonathan S.] Mt Sinai Sch Med, Recanati Miller Transplant Inst, New York, NY 10029 USA. [He, Xingxuan; Schuchman, Edward H.] Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. [Allende, Maria L.] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Bromberg, JS (reprint author), Mt Sinai Sch Med, Ctr Immunol, Dept Gene & Cell Med, New York, NY 10029 USA. EM Jon.Bromberg@mountsinai.org RI Ochando, Jordi/B-6219-2008; OI Lal, Girdhari/0000-0002-3799-3603 FU NIAID NIH HHS [AI41428, AI62765]; NIDDK NIH HHS [DK67381] NR 50 TC 134 Z9 135 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2008 VL 9 IS 1 BP 42 EP 53 DI 10.1038/ni1534 PG 12 WC Immunology SC Immunology GA 243TS UT WOS:000251820800010 PM 18037890 ER PT J AU Bansal, G Xie, Z Ra, S Nocka, KH Druey, KM AF Bansal, Geetanjali Xie, Zhihui Ra, Sudhir Nocka, Karl H. Druey, Kirk M. TI Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13 SO NATURE IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; MAST-CELL ACTIVATION; PHOSPHATIDYLINOSITOL 3-KINASE; GENE-EXPRESSION; RGS PROTEINS; CYTOKINE PRODUCTION; B-LYMPHOCYTES; RECEPTOR; DEGRANULATION; KINASE AB Mast cells elicit allergic responses through degranulation and release of proinflammatory mediators after antigen crosslinking of the immunoglobulin E receptor Fc epsilon RI. Proteins of the 'regulator of G protein signaling' MISS) family negatively control signaling mediated by G protein-coupled receptors through GTPase-accelerating protein activity. Here we show that RGS13 inhibited allergic responses by physically interacting with the regulatory p85 alpha subunit of phosphatidylinositol-3-OH kinase in mast cells and disrupting its association with an Fc epsilon RI-activated scaffolding complex. Rgs13(-/-) mice had enhanced immunoglobulin E-mediated mast cell degranulation and anaphylaxis. Thus, RGS13 inhibits the assembly of immune receptor-induced signalosomes in mast cells. Abnormal RGS13 expression or function may contribute to disorders of amplified mast cell activity, such as idiopathic anaphylaxis. C1 [Bansal, Geetanjali; Xie, Zhihui; Druey, Kirk M.] NIH, NIAID, Lab Allerg Dis, Mol Signal Transduct Sect, Bethesda, MD 20892 USA. [Ra, Sudhir; Nocka, Karl H.] UCB Pharma, Cambridge, MA 02139 USA. RP Druey, KM (reprint author), NIH, NIAID, Lab Allerg Dis, Mol Signal Transduct Sect, Bldg 10, Bethesda, MD 20892 USA. EM kdruey@niaid.nih.gov RI Bansal, Geetanjali/C-3854-2009 FU Intramural NIH HHS [Z01 AI000746-10] NR 49 TC 37 Z9 37 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2008 VL 9 IS 1 BP 73 EP 80 DI 10.1038/ni1533 PG 8 WC Immunology SC Immunology GA 243TS UT WOS:000251820800013 PM 18026105 ER PT J AU Vig, M DeHaven, WI Bird, GS Billingsley, JM Wang, H Rao, PE Hutchings, AB Jouvin, MH Putney, JW Kinet, JP AF Vig, Monika DeHaven, Wayne I. Bird, Gary S. Billingsley, James M. Wang, Huiyun Rao, Patricia E. Hutchings, Amy B. Jouvin, Marie-Helene Putney, James W. Kinet, Jean-Pierre TI Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels SO NATURE IMMUNOLOGY LA English DT Article ID CAPACITATIVE CA2+ ENTRY; FC-EPSILON-RI; LEUKOTRIENE C-4 SECRETION; AFFINITY IGE RECEPTOR; INTRACELLULAR CALCIUM; TRANSCRIPTION FACTORS; ADENYLYL CYCLASES; PLASMA-MEMBRANE; T-CELLS; PROTEINS AB CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium release-activated calcium channels. A point mutation in the gene encoding CRACM1 is associated with severe combined immunodeficiency disease in humans. Here we generated CRACM1-deficient mice in which P-galactosidase activity 'reported' CRACM1 expression. CRACM1-deficient mice were smaller in size. Mast cells derived from CRACM1-deficient mice showed grossly defective degranulation and cytokine secretion, and the allergic reactions elicited in vivo were inhibited in CRACM1-deficient mice. We detected robust CRACM1 expression in skeletal muscles and some regions of the brain, heart and kidney but not in the lymphoid regions of thymus and spleen. In contrast, we found CRACM2 expression to be much higher in mouse T cells. In agreement with those findings, the store-operated calcium influx and development and proliferation of CRACM1-deficient T cells was unaffected. Thus, CRACM1 is crucial in mouse mast cell effector function, but mouse T cell calcium release-activated calcium channels are functional in the absence of CRACM1. C1 [Vig, Monika; Billingsley, James M.; Wang, Huiyun; Jouvin, Marie-Helene; Kinet, Jean-Pierre] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [DeHaven, Wayne I.; Putney, James W.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Rao, Patricia E.; Hutchings, Amy B.] Synta Pharmaceut, Lexington, MA 02421 USA. RP Vig, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. EM mvig@bidmc.harvard.edu FU Intramural NIH HHS [Z01 ES090087-11, Z99 ES999999]; NIGMS NIH HHS [GM 053950, R01 GM053950, R37 GM053950] NR 40 TC 244 Z9 249 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2008 VL 9 IS 1 BP 89 EP 96 DI 10.1038/ni1550 PG 8 WC Immunology SC Immunology GA 243TS UT WOS:000251820800015 PM 18059270 ER PT J AU Knepper, MA Star, RA AF Knepper, Mark A. Star, Robert A. TI Vasopressin: friend or foe? SO NATURE MEDICINE LA English DT Editorial Material ID ALPHA-MSH; RATS; KIDNEY; AQUAPORINS; ISCHEMIA; DISEASE; WATER AB Vasopressin plays a vital part in homeostasis by regulating water excretion in the kidney. But it seems that vasopressin also dampens the inflammatory response to uropathogenic Escherichia coli-a finding that adds to a growing list of adverse actions of the 'antidiuretic hormone'. C1 [Knepper, Mark A.] NHLBI, Natl Inst Hlth, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. [Star, Robert A.] NIDDKD, Natl Inst Hlth, Renal Diag & Therapeut Unit, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Natl Inst Hlth, Kidney & Electrolyte Metab Lab, Bldg 10, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 12 TC 8 Z9 8 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JAN PY 2008 VL 14 IS 1 BP 14 EP 16 DI 10.1038/nm0108-14 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 249IV UT WOS:000252222400008 PM 18180711 ER PT J AU Wirth, A Benyo, Z Lukasova, M Leutgeb, B Wettschureck, N Gorbey, S Orsy, P Horvath, B Maser-Gluth, C Greiner, E Lemmer, B Schuetz, N Gutkind, S Offermanns, S AF Wirth, Angela Benyo, Zoltan Lukasova, Martina Leutgeb, Barbara Wettschureck, Nina Gorbey, Stefan Orsy, Petra Horvath, Bela Maser-Gluth, Christiane Greiner, Erich Lemmer, Bjoern Schuetz, Nther Gutkind, Silvio Offermanns, Stefan TI G(12)-G(13)-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension SO NATURE MEDICINE LA English DT Article ID BLOOD-PRESSURE; MYOSIN PHOSPHATASE; DIETARY SALT; G-PROTEINS; RHO; ACTIVATION; DISEASES; KINASE; REORGANIZATION; CONTRACTION AB The tone of vascular smooth muscle cells is a primary determinant of the total peripheral vascular resistance and hence the arterial blood pressure. Most forms of hypertension ultimately result from an increased vascular tone that leads to an elevated total peripheral resistance(1-3). Regulation of vascular resistance under normotensive and hypertensive conditions involves multiple mediators, many of which act through G protein-coupled receptors on vascular smooth muscle cells(4). Receptors that mediate vasoconstriction couple with the G-proteins G(q)-G(11) and G(12)-G(13) to stimulate phosphorylation of myosin light chain (MLC) via the Ca2+/MLC kinase- and Rho/Rho kinase-mediated signaling pathways, respectively(4-6). Using genetically altered mouse models that allow for the acute abrogation of both signaling pathways by inducible Cre/loxP-mediated mutagenesis in smooth muscle cells, we show that G(q)-G(11)-mediated signaling in smooth muscle cells is required for maintenance of basal blood pressure and for the development of salt-induced hypertension. In contrast, lack of G(12)-G(13), as well as of their major effector, the leukemiaassociated Rho guanine nucleotide exchange factor (LARG), did not alter normal blood pressure regulation but did block the development of salt-induced hypertension. This identifies the G(12)-G(13)-LARG-mediated signaling pathway as a new target for antihypertensive therapies that would be expected to leave normal blood pressure regulation unaffected. C1 [Wirth, Angela; Benyo, Zoltan; Lukasova, Martina; Leutgeb, Barbara; Wettschureck, Nina; Orsy, Petra; Horvath, Bela; Maser-Gluth, Christiane; Offermanns, Stefan] Univ Heidelberg, Inst Pharmacol, D-69120 Heidelberg, Germany. [Benyo, Zoltan] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, H-1082 Budapest, Hungary. [Gorbey, Stefan; Lemmer, Bjoern] Univ Heidelberg, Med Fac Mannheim, Inst Pharmacol, D-68169 Mannheim, Germany. [Greiner, Erich; Schuetz, Nther] German Canc Res Ctr, Div Mol Biol Cell 1, D-69120 Heidelberg, Germany. [Gutkind, Silvio] Natl Inst Dent & Craniofacial Res, Natl Inst Hlth, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. [Leutgeb, Barbara; Greiner, Erich] EvotecOAI AG, D-22525 Hamburg, Germany. RP Offermanns, S (reprint author), Univ Heidelberg, Inst Pharmacol, Neuenheimer Feld 366, D-69120 Heidelberg, Germany. EM Stefan.Offermanns@pharma.uni-heidelberg.de RI Gutkind, J. Silvio/A-1053-2009; Horvath, Bela/A-7368-2009; Benyo, Zoltan/C-9184-2009; Gorbey, Stefan/P-3874-2015; OI Gorbey, Stefan/0000-0002-6852-1756; Benyo, Zoltan/0000-0001-6015-0359 NR 30 TC 230 Z9 234 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2008 VL 14 IS 1 BP 64 EP 68 DI 10.1038/nm1666 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 249IV UT WOS:000252222400023 PM 18084302 ER PT J AU Bekar, L Libionka, W Tian, GF Xu, QW Torres, A Wang, XH Lovatt, D Williams, E Takano, TH Schnermann, J Bakos, R Nedergaard, M AF Bekar, Lane Libionka, Witold Tian, Guo-Feng Xu, Qiwu Torres, Arnulfo Wang, Xiaohai Lovatt, Ditte Williams, Erika Takano, Takahiro Schnermann, Jurgen Bakos, Robert Nedergaard, Maiken TI Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor SO NATURE MEDICINE LA English DT Article ID HARMALINE-INDUCED TREMOR; ATP RELEASE; RAT; INHIBITION; DISORDERS; SYNAPSES; MICE AB Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders(1-3). In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested(4-6). Despite the rapid increase in the number of individuals with surgically implanted stimulation electrodes, the cellular pathways involved in mediating the effects of DBS remain unknown(1). Here we show that DBS is associated with a marked increase in the release of ATP, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses excitatory transmission in the thalamus and reduces both tremor-and DBS-induced side effects. Intrathalamic infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null mice show involuntary movements and seizure at stimulation intensities below the therapeutic level. Furthermore, our data indicate that endogenous adenosine mechanisms are active in tremor, thus supporting the clinical notion that caffeine, a nonselective adenosine receptor antagonist, can trigger or exacerbate essential tremor(7). Our findings suggest that nonsynaptic mechanisms involving the activation of A1 receptors suppress tremor activity and limit stimulation-induced side effects, thereby providing a new pharmacological target to replace or improve the efficacy of DBS. C1 [Bekar, Lane; Libionka, Witold; Tian, Guo-Feng; Xu, Qiwu; Torres, Arnulfo; Wang, Xiaohai; Lovatt, Ditte; Williams, Erika; Takano, Takahiro; Bakos, Robert; Nedergaard, Maiken] Univ Rochester, Dept Neurosurg, Div Glial Dis & Therapeut, Rochester, NY 14642 USA. [Schnermann, Jurgen] NIDDKD, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Bekar, L (reprint author), Univ Rochester, Dept Neurosurg, Div Glial Dis & Therapeut, 601 Elmwood Ave, Rochester, NY 14642 USA. EM lane_bekar@urmc.rochester.edu; nedergaard@urmc.rochester.edu OI Wang, Xiaohai/0000-0001-5814-4072 FU NINDS NIH HHS [NS050315, NS30007, NS39559] NR 30 TC 111 Z9 113 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2008 VL 14 IS 1 BP 75 EP 80 DI 10.1038/nm1693 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 249IV UT WOS:000252222400025 PM 18157140 ER PT J AU Bauer, TR Allen, JM Hai, M Tuschong, LM Khan, IF Olson, EM Adler, RL Burkholder, TH Gu, YC Russell, DW Hickstein, DD AF Bauer, Thomas R., Jr. Allen, James M. Hai, Mehreen Tuschong, Laura M. Khan, Iram F. Olson, Erik M. Adler, Rima L. Burkholder, Tanya H. Gu, Yu-chen Russell, David W. Hickstein, Dennis D. TI Successful treatment of canine leukocyte adhesion deficiency by foamy virus vectors SO NATURE MEDICINE LA English DT Article ID GENE-THERAPY; DISEASE PHENOTYPE; COMBINED IMMUNODEFICIENCY; REPOPULATING CELLS; HUMAN GENOME; TRANSDUCTION; TRANSCRIPTION; REPLICATION; INTEGRATION; REVERSE AB Recent successes in treating genetic immunodeficiencies have demonstrated the therapeutic potential of stem cell gene therapy(1-4). However, the use of gammaretroviral vectors in these trials led to insertional activation of nearby oncogenes and leukemias in some study subjects, prompting studies of modified or alternative vector systems(5). Here we describe the use of foamy virus vectors to treat canine leukocyte adhesion deficiency ( CLAD). Four of five dogs with CLAD that received nonmyeloablative conditioning and infusion of autologous, CD34(+) hematopoietic stem cells transduced by a foamy virus vector expressing canine CD18 had complete reversal of the CLAD phenotype, which was sustained more than 2 years after infusion. In vitro assays showed correction of the lymphocyte proliferation and neutrophil adhesion defects that characterize CLAD. There were no genotoxic complications, and integration site analysis showed polyclonality of transduced cells and a decreased risk of integration near oncogenes as compared to gammaretroviral vectors. These results represent the first successful use of a foamy virus vector to treat a genetic disease, to our knowledge, and suggest that foamy virus vectors will be effective in treating human hematopoietic diseases. C1 [Allen, James M.; Khan, Iram F.; Olson, Erik M.; Russell, David W.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Bauer, Thomas R., Jr.; Hai, Mehreen; Tuschong, Laura M.; Adler, Rima L.; Gu, Yu-chen; Hickstein, Dennis D.] NCI, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Burkholder, Tanya H.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA. [Russell, David W.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RP Russell, DW (reprint author), Univ Washington, Dept Med, Div Hematol, 1959 NE Pacific St,Box 357720, Seattle, WA 98195 USA. EM drussell@u.washington.edu; hicksted@mail.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL53750, P01 HL053750, R01 HL085107] NR 30 TC 86 Z9 87 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2008 VL 14 IS 1 BP 93 EP 97 DI 10.1038/nm1695 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 249IV UT WOS:000252222400028 PM 18157138 ER PT J AU Hu, WG Ferris, SP Tweten, RK Wu, GX Radaeva, S Gao, B Bronson, RT Halperin, JA Qin, XB AF Hu, Weiguo Ferris, Sean P. Tweten, Rodney K. Wu, Gongxiong Radaeva, Svetlana Gao, Bin Bronson, Roderick T. Halperin, Jose A. Qin, Xuebin TI Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin SO NATURE MEDICINE LA English DT Article ID STREPTOCOCCUS-INTERMEDIUS; PLATELET ACTIVATION; NITRIC-OXIDE; IN-VIVO; RECEPTOR; DISEASE; ENDOTHELIUM; HEMOGLOBIN; THROMBOSIS; HEMOLYSIS AB Conditional targeted cell ablation is a powerful approach for investigating the pathogenesis of human diseases and in vivo cellular functions. Intermedilysin (ILY) is a cytolytic poreforming toxin secreted by Streptococcus intermedius that lyses human cells exclusively, owing to its receptor specificity for human CD59. We generated two transgenic mouse strains that express human CD59 either on erythrocytes (strain ThCD59(RBC)) or on endothelia (strain ThCD59(END)). Intravenous injection of ILY in ThCD59(RBC) mice induced acute intravascular hemolysis, leading to reduced nitric oxide bioavailability, increased platelet activation and rapid death. In ThCD59(END) mice, ILY induced rapid endothelial damage, leading to acute death and disseminated intravascular coagulation. Additionally, we show that human serum contains ILY-specific neutralizing antibodies not found in any other animal species. Together, these results suggest that this new rapid conditional targeted ILY-mediated cell ablation technique can be used in combination with any available transgenic expression system to study the physiologic role of specific cell populations. C1 [Hu, Weiguo; Halperin, Jose A.; Qin, Xuebin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hu, Weiguo; Ferris, Sean P.; Wu, Gongxiong; Halperin, Jose A.; Qin, Xuebin] Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA. [Tweten, Rodney K.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Radaeva, Svetlana] NIAAA, Natl Inst Hlth, Lab Physiol Studies, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. [Gao, Bin] NIAAA, Natl Inst Hlth, Sect Liver Biol, Lab Physiol Studies, Bethesda, MD 20892 USA. [Bronson, Roderick T.] Harvard Univ, Ctr Canc, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. RP Qin, XB (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM xuebin_qin@hms.harvard.edu FU NIAID NIH HHS [R01 AI061174, R01 AI063444]; NIDDK NIH HHS [R01 DK060979] NR 29 TC 20 Z9 21 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2008 VL 14 IS 1 BP 98 EP 103 DI 10.1038/nm1674 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 249IV UT WOS:000252222400029 PM 18157141 ER PT J AU Xu, JH McNeil, B Wu, W Nees, D Bai, L Wu, LG AF Xu, Jianhua McNeil, Benjamin wu, Wei Nees, David Bai, Li Wu, Ling-Gang TI GTP-independent rapid and slow endocytosis at a central synapse SO NATURE NEUROSCIENCE LA English DT Article ID RETINAL BIPOLAR CELLS; SHORT-TERM DEPRESSION; VESICLE ENDOCYTOSIS; MEMBRANE RETRIEVAL; CHROMAFFIN CELLS; MEDIAL NUCLEUS; TRAPEZOID BODY; 2 MODES; DYNAMIN; CALYX AB Vesicle endocytosis is essential for maintaining synaptic transmission. Its key step, membrane scission, is thought to be mediated by the GTPase dynamin in all forms of endocytosis at synapses. Our findings indicate that GTP-independent and probably dynamin-independent endocytosis co-exist with GTP- and dynamin-dependent endocytosis at the same synaptic nerve terminal, the calyx of Held, in rats. This previously undescribed form of endocytosis could be slow (tens of seconds) and/or rapid (a few seconds), similar to GTP- and dynamin-dependent endocytosis. It was activated during intense stimulation, whereas GTP- and dynamin-dependent endocytosis dominated during mild stimulation. These results establish a new model, in which vesicles are divided into two pools depending on their requirement for GTP and dynamin for retrieval. The GTP- and dynamin-dependent pool has higher priority for release and retrieval, but limited capacity, saturation of which leads to release and thus retrieval of GTP- and dynamin-independent vesicles. C1 [Xu, Jianhua; McNeil, Benjamin; wu, Wei; Nees, David; Bai, Li; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, 35 Convent Dr,Bldg 35,Rm 2B-1012, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov OI Xu, Jianhua/0000-0003-0084-8856; McNeil, Benjamin/0000-0001-7545-3598 FU Intramural NIH HHS NR 48 TC 49 Z9 50 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2008 VL 11 IS 1 BP 45 EP 53 DI 10.1038/nn2021 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 247YG UT WOS:000252117900011 PM 18066059 ER PT J AU Kalueff, AV Keisala, T Minasyan, A Kumar, SR LaPorte, JL Murphy, DL Tuohimaa, P AF Kalueff, Allan V. Keisala, Tiina Minasyan, Anna Kumar, Senthil R. LaPorte, Justin L. Murphy, Dennis L. Tuohimaa, Pentti TI The regular and light-dark Suok tests of anxiety and sensorimotor integration: utility for behavioral characterization in laboratory rodents SO NATURE PROTOCOLS LA English DT Article ID ELEVATED PLUS-MAZE; PURKINJE-CELL DEGENERATION; VIDEO TRACKING SYSTEM; SHIRPA PRIMARY SCREEN; MOTOR COORDINATION; TRANSGENIC MICE; BALANCE CONTROL; MOUSE BEHAVIOR; MUTANT MICE; EXPLORATORY BEHAVIOR AB Animal behavioral models are crucial for neurobiological research, allowing for the thorough investigation of brain pathogenesis to be performed. In both animals and humans, anxiety has long been linked to vestibular disorders. However, although there are many tests of anxiety and vestibular deficits, there are few protocols that address the interplay between these two domains. The Suok test and its light-dark modification presented here appear to be suitable for testing this pathogenetic link in laboratory rodents. This protocol adds a new dimension to previously used tests by assessing animal anxiety and balancing simultaneously, resulting in efficient, high-throughput screens for testing psychotropic drugs, phenotyping genetically modified animals, and modeling clusters of human disorders related to stress/anxiety and balancing. C1 [Kalueff, Allan V.; Keisala, Tiina; Minasyan, Anna; Tuohimaa, Pentti] Univ Tampere, Sch Med, Dept Anat, Tampere 33014, Finland. [Kalueff, Allan V.; LaPorte, Justin L.; Murphy, Dennis L.] NIH, Clin Sci Lab, NIMH, Bethesda, MD 20892 USA. [Kumar, Senthil R.] St Mathews Univ, Sch Med, Dept Pharmacol & Therapeut, Grand Cayman, Cayman Islands, Jamaica. RP Kalueff, AV (reprint author), Univ Tampere, Sch Med, Dept Anat, Tampere 33014, Finland. EM avkalueff@inbox.ru FU Intramural NIH HHS NR 71 TC 13 Z9 14 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2008 VL 3 IS 1 BP 129 EP 136 DI 10.1038/nprot.2007.516 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HU UT WOS:000253140400014 PM 18193029 ER PT J AU Kouprina, N Larionov, V AF Kouprina, Natalay Larionov, Vladimir TI Selective isolation of genomic loci from complex genomes by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae SO NATURE PROTOCOLS LA English DT Article ID PROSTATE-CANCER; GENE; EVOLUTION; SEQUENCE; HUMAN-CHROMOSOME-19; SYSTEM; REGION AB Here, we describe a protocol for the selective isolation of any genomic fragment or gene of interest up to 250 kb in size from complex genomes as a circular yeast artificial chromosome (YAC). The method is based on transformation-associated recombination (TAR) in the yeast Saccharomyces cerevisiae between genomic DNA and a linearized TAR cloning vector containing targeting sequences homologous to a region of interest. Recombination between the vector and homologous sequences in the co-transformed mammalian DNA results in the establishment of a YAC that is able to propagate, segregate and be selected for in yeast. Yield of gene-positive clones varies from 1% to 5%. The entire procedure takes 2 weeks to complete once the TAR vector is constructed and genomic DNA is prepared. The TAR cloning method has a broad application in functional and comparative genomics, long-range haplotyping and characterization of chromosomal rearrangements, including copy number variations. C1 [Kouprina, Natalay; Larionov, Vladimir] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Kouprina, N (reprint author), NCI, Mol Pharmacol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kouprinn@mail.nih.gov NR 21 TC 68 Z9 69 U1 4 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2008 VL 3 IS 3 BP 371 EP 377 DI 10.1038/nprot.2008.5 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 276JM UT WOS:000254137100005 PM 18323808 ER PT J AU Lichti, U Anders, J Yuspa, SH AF Lichti, Ulrike Anders, Joanna Yuspa, Stuart H. TI Isolation and short-term culture of primary keratinocytes, hair follicle populations and dermal cells from newborn mice and keratinocytes from adult mice for in vitro analysis and for grafting to immunodeficient mice SO NATURE PROTOCOLS LA English DT Article ID MOUSE EPIDERMAL-CELLS; DIFFERENTIATION; GROWTH; RESISTANCE; TISSUE; TUMORS; LINES; SKIN AB Protocols for preparing and culturing primary keratinocytes from newborn and adult mouse epidermis have evolved over the past 35 years. This protocol is now routinely applied to mice of various genetic backgrounds for in vitro studies of signaling pathways in differentiation and cell transformation, and for assessing the in vivo phenotype of altered keratinocytes in grafts of cells on immunodeficient mice. Crucial in the development and application of the procedure was the observation that keratinocytes proliferate in media of low calcium concentration, but rapidly commit to differentiation at calcium concentrations > 0.07 mM after the initial attachment period. Preparing primary keratinocytes from ten newborn mice requires 2-3 h of hands-on time. Related procedures are also provided: preparing immature hair follicle buds, developing dermal hair follicles and fibroblasts from newborn mice, preparing primary keratinocytes from adult mice and grafting cell mixtures on athymic nude mice. C1 [Lichti, Ulrike; Anders, Joanna; Yuspa, Stuart H.] NCI, NIH, CCR, Lab Canc Biol & Genet,In Vitro Pathognesis Sect, Bethesda, MD 20892 USA. RP Lichti, U (reprint author), NCI, NIH, CCR, Lab Canc Biol & Genet,In Vitro Pathognesis Sect, 37 Convent Dr,Bldg 37-4068, Bethesda, MD 20892 USA. EM lichtiu@mail.nih.gov NR 22 TC 175 Z9 182 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2008 VL 3 IS 5 BP 799 EP 810 DI 10.1038/nprot.2008.50 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 337GN UT WOS:000258423600005 PM 18451788 ER PT J AU Malnati, MS Scarlatti, G Gatto, F Salvatori, F Cassina, G Rutigliano, T Volpi, R Lusso, P AF Malnati, Mauro S. Scarlatti, Gabriella Gatto, Francesca Salvatori, Francesca Cassina, Giulia Rutigliano, Teresa Volpi, Rosy Lusso, Paolo TI A universal real-time PCR assay for the quantification of group-M HIV-1 proviral load SO NATURE PROTOCOLS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; POLYMERASE-CHAIN-REACTION; C-VIRUS HCV; DNA LOAD; DISEASE PROGRESSION; BLOOD-DONORS; RNA LOAD; INFECTION; RESERVOIR AB Quantification of human immunodeficiency virus type-1 (HIV-1) proviral DNA is increasingly used to measure the HIV-1 cellular reservoirs, a helpful marker to evaluate the efficacy of antiretroviral therapeutic regimens in HIV-1-infected individuals. Furthermore, the proviral DNA load represents a specific marker for the early diagnosis of perinatal HIV-1 infection and might be predictive of HIV-1 disease progression independently of plasma HIV-1 RNA levels and CD4(+) T-cell counts. The high degree of genetic variability of HIV-1 poses a serious challenge for the design of a universal quantitative assay capable of detecting all the genetic subtypes within the main (M) HIV-1 group with similar efficiency. Here, we describe a highly sensitive real-time PCR protocol that allows for the correct quantification of virtually all group-M HIV-1 strains with a higher degree of accuracy compared with other methods. The protocol involves three stages, namely DNA extraction/lysis, cellular DNA quantification and HIV-1 proviral load assessment. Owing to the robustness of the PCR design, this assay can be performed on crude cellular extracts, and therefore it may be suitable for the routine analysis of clinical samples even in developing countries. An accurate quantification of the HIV-1 proviral load can be achieved within 1 d from blood withdrawal. C1 [Scarlatti, Gabriella; Salvatori, Francesca; Volpi, Rosy] Ist Sci San Raffaele, Unit Viral Evolut & Transmiss, Dept Biol & Technol Res DIBIT, I-20132 Milan, Italy. [Malnati, Mauro S.; Gatto, Francesca; Cassina, Giulia; Rutigliano, Teresa; Lusso, Paolo] Ist Sci San Raffaele, Unit Human Virol, I-20132 Milan, Italy. RP Lusso, P (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mauro.malnati@hsr.it; paolo.lusso@hsr.it FU WHO-UNAIDS Network for HIV Isolation and Characterization; Centre for AIDS reagents (CFAR); National Institute for Biological Standard and Control (NIBSC), South Mimms, UK; VI National AIDS Project; Istituto Superiore di Sanita, Rome, Italy FX This work was supported by the WHO-UNAIDS Network for HIV Isolation and Characterization, which provided primary HIV-1 isolates through the WHO Repository at the Centre for AIDS reagents (CFAR), National Institute for Biological Standard and Control (NIBSC), South Mimms, UK, and by grants from the VI National AIDS Project, Istituto Superiore di Sanita, Rome, Italy. NR 37 TC 44 Z9 44 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2008 VL 3 IS 7 BP 1240 EP 1248 DI 10.1038/nprot.2008.108 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 337GP UT WOS:000258423800014 PM 18600229 ER PT J AU Pacher, P Nagayama, T Mukhopadhyay, P Batkai, S Kass, DA AF Pacher, Pal Nagayama, Takahiro Mukhopadhyay, Partha Batkai, Sandor Kass, David A. TI Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats SO NATURE PROTOCOLS LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; IN-VIVO; HEART-FAILURE; DYSFUNCTION; PROTECTS; STRESS AB Ventricular pressure-volume relationships have become well established as the most rigorous and comprehensive ways to assess intact heart function. Thanks to advances in miniature sensor technology, this approach has been successfully translated to small rodents, allowing for detailed characterization of cardiovascular function in genetically engineered mice, testing effects of pharmacotherapies and studying disease conditions. This method is unique for providing measures of left ventricular (LV) performance that are more specific to the heart and less affected by vascular loading conditions. Here we present descriptions and movies for procedures employing this method (anesthesia, intubation and surgical techniques, calibrations). We also provide examples of hemodynamics measurements obtained from normal mice/rats, and from animals with cardiac hypertrophy/heart failure, and describe values for various useful load-dependent and load-independent indexes of LV function obtained using different types of anesthesia. The completion of the protocol takes 1-4 h ( depending on the experimental design/end points). C1 [Pacher, Pal; Mukhopadhyay, Partha; Batkai, Sandor] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Nagayama, Takahiro; Kass, David A.] Johns Hopkins Univ Hosp, Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov; dkass@jhmi.edu RI MUKHOPADHYAY, PARTHA/G-3890-2010; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; FU NIH/NIAAA; NIH-NHLBI [HL-077180, HL-59408] FX This research was supported by the Intramural Research Program of NIH/NIAAA (to P.P.). NIH-NHLBI HL-077180; HL-59408. We are indebted to Huntly Millar and Tim Daugherty for reading the protocol and valuable suggestions and acknowledge Millar Instruments for the permission to use animations in the movies and for providing background information on the use of Millar PV systems. P. P. dedicates this protocol to his beloved mother Iren Bolfert and grandmother Ilona Kerenyi. NR 25 TC 300 Z9 306 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2008 VL 3 IS 9 BP 1422 EP 1434 DI 10.1038/nprot.2008.138 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 337GS UT WOS:000258424100006 PM 18772869 ER PT J AU Dexheimer, TS Pommier, Y AF Dexheimer, Thomas S. Pommier, Yves TI DNA cleavage assay for the identification of topoisomerase I inhibitors SO NATURE PROTOCOLS LA English DT Article ID DIOL EPOXIDE ADDUCTS; ANTITUMOR-ACTIVITY; ANTICANCER DRUGS; NITRATED INDENOISOQUINOLINES; CAMPTOTHECIN DERIVATIVES; MJ-III-65 NSC-706744; COMPLEX-FORMATION; COVALENT COMPLEX; OXYGEN RADICALS; STRAND BREAKS AB The inhibition of DNA topoisomerase I (Top1) has proven to be a successful approach in the design of anticancer agents. However, despite the clinical successes of the camptothecin derivatives, a significant need for less toxic and more chemically stable Top1 inhibitors still persists. Here, we describe one of the most frequently used protocols to identify novel Top1 inhibitors. These methods use uniquely 3'-radiolabeled DNA substrates and denaturing polyacrylamide gel electrophoresis to provide evidence for the Top1-mediated DNA cleaving activity of potential Top1 inhibitors. These assays allow comparison of the effectiveness of different drugs in stabilizing the Top1-DNA intermediate or cleavage (cleavable) complex. A variation on these assays is also presented, which provides a suitable system for determining whether the inhibitor blocks the forward cleavage or religation reactions by measuring the reversibility of the drug-induced Top1-DNA cleavage complexes. This entire protocol can be completed in similar to 2 d. C1 [Dexheimer, Thomas S.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Center for Cancer Research, NCI, NIH FX Our studies are supported by the Intramural Program of the Center for Cancer Research, NCI, NIH. We thank all members of the Laboratory of Molecular Pharmacology, past and present, for their contributions. Special thanks to Dr Kurt W. Kohn who pioneered studies on DNA topoisomerases and first proposed the trapping of topoisomerases by anticancer drugs (Ross, W. E., Glaubiger, D. & Kohn, K. W. Qualitative and quantitative aspects of intercalator-induced DNA strand breaks. Biochim. Biophys. Acta 562, 41-50 (1979)). NR 98 TC 59 Z9 59 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2008 VL 3 IS 11 BP 1736 EP 1750 DI 10.1038/nprot.2008.174 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PQ UT WOS:000265781600007 PM 18927559 ER PT J AU Spurrier, B Ramalingam, S Nishizuka, S AF Spurrier, Brett Ramalingam, Sundhar Nishizuka, Satoshi TI Reverse-phase protein lysate microarrays for cell signaling analysis SO NATURE PROTOCOLS LA English DT Article ID STEM-CELLS; CANCER; VALIDATION; ARRAY; TECHNOLOGY; ACTIVATION; SPECIMENS; PATHWAYS AB 'Reverse-phase' protein lysate microarray (RPA) assays use micro-scale, cell lysate dot blots that are printed to a substrate, followed by quantitative immunochemical protein detection, known to be particularly effective across many samples. Large-scale sample collection is a labor-intensive and time-consuming process; the information yielded from RPA assays, however, provides unique opportunities to experimentally interpret theoretical protein networks quantitatively. When specific antibodies are used, RPA can generate 1,000 times more data points using 10,000 times less sample volume than an ordinary western blot, enabling researchers to monitor quantitative proteomic responses for various time-scale and input-dose gradients simultaneously. Hence, the RPA system can be an excellent method for experimental validation of theoretical protein network models. Besides the initial screening of primary antibodies, collection of several hundreds of sample lysates from 1- to 8-h periods can be completed in similar to 10 d; subsequent RPA printing and signal detection steps require an additional 2-3 d. C1 [Spurrier, Brett; Nishizuka, Satoshi] NCI, Mol Translat Technol Sect, Mol Therapeut Program, NIH, Bethesda, MD 20892 USA. [Spurrier, Brett] Aushon BioSyst, Billerica, MA 01821 USA. [Ramalingam, Sundhar] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Nishizuka, Satoshi] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. [Nishizuka, Satoshi] Iwate Med Univ, Dept Surg, Mol Therapeut Lab, Morioka, Iwate 0208505, Japan. RP Nishizuka, S (reprint author), NCI, Mol Translat Technol Sect, Mol Therapeut Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM snishizu@iwate-med.ac.jp NR 24 TC 92 Z9 92 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2008 VL 3 IS 11 BP 1796 EP 1808 DI 10.1038/nprot.2008.179 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PQ UT WOS:000265781600012 PM 18974738 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI An audience with - Anthony Fauci SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JAN PY 2008 VL 7 IS 1 BP 12 EP 12 DI 10.1038/nrd2491 PG 1 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 247QO UT WOS:000252094600004 ER PT J AU Youle, RJ Strasser, A AF Youle, Richard J. Strasser, Andreas TI The BCL-2 protein family: opposing activities that mediate cell death SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID CYTOCHROME-C RELEASE; MITOCHONDRIAL OUTER-MEMBRANE; STRESS-INDUCED APOPTOSIS; CHANNEL-FORMING ACTIVITY; BH3-ONLY PROTEINS; DEFICIENT MICE; MEMBER BIM; X-L; PROSURVIVAL BCL-2; ENDOPLASMIC-RETICULUM AB BCL-2 family proteins, which have either pro- or anti-apoptotic activities, have been studied intensively for the past decade owing to their importance in the regulation of apoptosis, tumorigenesis and cellular responses to anti- cancer therapy. They control the point of no return for clonogenic cell survival and thereby affect tumorigenesis and host pathogen interactions and regulate animal development. Recent structural, phylogenetic and biological analyses, however, suggest the need for some reconsideration of the accepted organizational principles of the family and how the family members interact with one another during programmed cell death. Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying hypothesis for the mechanisms they use to activate caspases remains elusive. C1 [Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, NIH, Bethesda, MD 20892 USA. [Strasser, Andreas] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RP Youle, RJ (reprint author), Natl Inst Neurol Disorders & Stroke, Biochem Sect, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov; strasser@wehi.edu.au RI Strasser, Andreas/C-7581-2013; OI Strasser, Andreas/0000-0002-5020-4891 NR 166 TC 2164 Z9 2252 U1 34 U2 310 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JAN PY 2008 VL 9 IS 1 BP 47 EP 59 DI 10.1038/nrm2308 PG 13 WC Cell Biology SC Cell Biology GA 249MA UT WOS:000252231300012 PM 18097445 ER PT J AU Smith, LEH Connor, KM SonGiovanni, JP Lofqvist, C Hellstrom, A AF Smith, L. E. H. Connor, K. M. SonGiovanni, J. P. Lofqvist, C. Hellstrom, A. TI Increased dietary intake of omega-3-polyunsaturated fatty acids reduces retinopathy SO NEONATOLOGY LA English DT Meeting Abstract ID DOCOSAHEXAENOIC ACID; ISCHEMIC RETINOPATHY; ANGIOGENESIS; INFLAMMATION; RECEPTOR; RETINA; NEOVASCULARIZATION; PROLIFERATION; DOCOSATRIENES; BRAIN C1 [Smith, L. E. H.; Connor, K. M.] Harvard Univ, Sch Med, Dept Ophthalmol, Childrens Hosp Boston, Boston, MA 02115 USA. [SonGiovanni, J. P.] NEI, Bethesda, MD 20892 USA. [Lofqvist, C.; Hellstrom, A.] Gothenburg Univ, Dept Pediat, S-41124 Gothenburg, Sweden. NR 21 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-7800 J9 NEONATOLOGY JI Neonatology PY 2008 VL 94 IS 3 MA 6 BP 218 EP 219 PG 2 WC Pediatrics SC Pediatrics GA 353CD UT WOS:000259542800018 ER PT J AU Vondruskova, E Malik, R Sevcik, J Kleiblova, P Kleibl, Z AF Vondruskova, E. Malik, R. Sevcik, J. Kleiblova, P. Kleibl, Z. TI Long-term BRCA1 down-regulation by small hairpin RNAs targeting the 3 ' untranslated region SO NEOPLASMA LA English DT Article DE BRCA1; retroviral infection; RNAi; shRNA; UTR ID SHORT INTERFERING RNAS; MAMMALIAN-CELLS; TUMOR SUPPRESSION; SIRNA; EXPRESSION; SPECIFICITY; CANCER; SYSTEM; CONTRIBUTE; SELECTION AB Mutations in the BRAC1 gene are responsible for the majority of hereditary breast/ovarian cancers. The functional significance of many mutations/splicing variants identified during the screening of high-risk individuals is difficult to predict due to the lack of in vitro functional tests correlating sequence variants with a risk of cancer development. RNA interference is a promising tool in analyzing functional properties of BRCA1 mutations. Here we designed and functionally analyzed shRNAs directed to 3'-UTR of BRCA1 mRNA that may be used to knock-down expression of endogenous BRCA1. Using retroviral infection, we achieved long-term down-regulation of BRCA1 in a cell-type specific manner. We propose that 3'-UTR-directed shRNAs, coupled with up-regulation of exogenous mutated BRCA1 variants, may constitute a versatile system for the functional analysis of BRCA1 gene alterations. C1 [Vondruskova, E.; Sevcik, J.; Kleiblova, P.; Kleibl, Z.] Charles Univ Prague, Inst Biochem & Ecpt Oncol, Prague, Czech Republic. [Malik, R.] Charles Univ Prague, Dept Gynaecol & Obstet, Fac Med 1, Prague, Czech Republic. [Kleiblova, P.] Natl Canc Inst, Eukaryotic Transcript Regulat Sect, Lab Prot Dynam & Signaling, Frederick, MD USA. RP Vondruskova, E (reprint author), Charles Univ Prague, Inst Biochem & Ecpt Oncol, Prague, Czech Republic. EM escho@lfl.cuni.cz RI Malik, Radek/G-3578-2014; Kleibl, Zdenek/A-2009-2008 OI Kleibl, Zdenek/0000-0003-2050-9667 NR 48 TC 2 Z9 2 U1 0 U2 3 PU VEDA, SLOVAK ACAD SCIENCES PI BRASTISLAVA PA DUBRAVSKA CESTA 9, 842 34 BRASTISLAVA, SLOVAKIA SN 0028-2685 J9 NEOPLASMA JI Neoplasma PY 2008 VL 55 IS 2 BP 130 EP 137 PG 8 WC Oncology SC Oncology GA 263PN UT WOS:000253229100009 PM 18237251 ER PT J AU Iguchi, M Kakinuma, Y Kurabayashi, A Sato, T Shuin, T Hong, SB Schmidt, LS Furihata, M AF Iguchi, Mitsuko Kakinuma, Yoshihiko Kurabayashi, Atsushi Sato, Takayuki Shuin, Taro Hong, Seung-Beom Schmidt, Laura S. Furihata, Mutsuo TI Acute Inactivation of the VHL Gene Contributes to Protective Effects of Ischemic Preconditioning in the Mouse Kidney SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE Ischemia-reperfusion injury; Von Hippel-Lindau gene; Hypoxia-inducible factor; Ischemic preconditioning ID HYPOXIA-INDUCIBLE FACTORS; ISCHEMIA/REPERFUSION INJURY; REPERFUSION INJURY; GROWTH-FACTOR; TARGET GENES; FACTOR-I; EXPRESSION; INDUCTION; PROTEIN; CELLS AB Background/Aims: The von Hippel-Lindau (VHL) protein functions as an E3 ubiquitin ligase, controlling the stability of hypoxia-inducible factor (HIF). Preinduction of HIF-1 alpha before pathological insult activates a self-defense mechanism and suppresses further aggravation of organ or cellular injury by ischemia. We investigated whether acute inactivation of the VHL gene might play a role in the response of mice to ischemic renal injury. Methods: We generated tamoxifen-inducible conditional VHL knockout (VHL-KO) mice to inactivate the VHL gene in an acute manner during renal ischemia-reperfusion injury (IRI) induced by bilateral clamping of kidney arteries. Renal IRI is characterized by renal dysfunction and tubular damage. Results: After the procedure of IRI, blood urea nitrogen (BUN) and creatinine (CRN) levels in control mice were significantly higher (BUN, 138.10 +/- 13.03 mg/dl; CRN, 0.72 +/- 0.16 mg/dl) than in VHL-KO mice (BUN, 52.12 +/- 6.61 mg/dl; CRN, 0.24 +/- 0.04 mg/dl; BUN: p < 0.05; CRN: p < 0.05). Histologically, tubular injury scores were higher in control mice than in VHL-KO mice (p < 0.05). Conclusion: We suggest that the acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in renal tubules of the mouse. Copyright (C) 2008 S. Karger AG, Basel C1 [Kakinuma, Yoshihiko; Sato, Takayuki] Kochi Med Sch, Dept Cardiovasc Control, Nankoku, Kochi 7838505, Japan. [Iguchi, Mitsuko; Kurabayashi, Atsushi; Furihata, Mutsuo] Kochi Med Sch, Dept Pathol, Nankoku, Kochi 7838505, Japan. [Shuin, Taro] Kochi Med Sch, Dept Urol, Nankoku, Kochi 7838505, Japan. [Hong, Seung-Beom; Schmidt, Laura S.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Schmidt, Laura S.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Kakinuma, Y (reprint author), Kochi Med Sch, Dept Cardiovasc Control, Nankoku, Kochi 7838505, Japan. EM kakinuma@kochi-u.ac.jp FU Japan Society for the Promotion of Science [19590251]; Intramural Research Program of the National Institutes of Health (NIH); National Cancer Institute; Center for Cancer Research; NIH [N01-C012400] FX This research was supported by Grants-in-Aid from the Japan Society for the Promotion of Science (19590251), and also in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. This project has been funded in part with federal funds from the National Cancer Institute, NIH, under contract N01-C012400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 31 TC 12 Z9 12 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PY 2008 VL 110 IS 3 BP E82 EP E90 DI 10.1159/000166994 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 366PI UT WOS:000260494500002 PM 18957870 ER PT S AU Eiden, LE Samal, B Gerdin, MJ Mustafa, T Vaudry, D Stroth, N AF Eiden, Lee E. Samal, Babru Gerdin, Matthew J. Mustafa, Tomris Vaudry, David Stroth, Nikolas BE Goetzl, EJ TI Discovery of Pituitary Adenylate Cyclase-Activating Polypeptide-Regulated Genes through Microarray Analyses in Cell Culture and In Vivo SO Neural Signaling: Opportunities for Novel Diagnostic Approaches and Therapies SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Neural Signaling - Opportunities for Novel Diagnostic Approaches and Therapies CY FEB 16-20, 2008 CL Pacific Grove, CA DE bioinformatics; gene discovery; microarray; neuropeptide; neuroprotection; PACAP; PC12; pituitary adenylate cyclase-activating polypeptide; signal transduction; stress response ID INDEPENDENT SIGNALING PATHWAY; LONG-TERM POTENTIATION; PROTEIN-KINASE-A; PC12 CELLS; NEURITE OUTGROWTH; CHROMAFFIN CELLS; MUTANT MICE; PACAP ACTS; TRANSCRIPTION; EXPRESSION AB Pituitary adenylate cyclase-activating polypeptide (PACAP) is an evolutionarily well conserved neuropeptide with multiple functions in the nervous, endocrine, and immune systems. PACAP provides neuroprotection from ischemia and toxin exposure, is anti-inflammatory in gastric inflammatory disease and sepsis, controls proliferative signaling pathways involved in neural cell transformation, and modulates gluco-homeostasis. PACAP-based, disease-targeted therapeutics might thus be both effective and benign, enhancing homeostatic responses to behavioral, metabolic, oncogenic, and inflammatory stressors. PACAP signal transduction employs synergistic regulation of calcium and cyclic adenosine monophosphate (cAMP), and noncanonical activation of both calcium- and cAMP-dependent processes. Pharmacological activation of PACAP signaling should consequently have highly specific effects even in vivo. Here, a combined cellular biochemical, pharmacologic, transcriptomic, and bioinformatic approach to understanding PACAP signal transduction by identifying PACAP target genes with oligonucleotide- and cDNA-based microarray is described. Calcium- and cAMP-dependent PACAP signaling pathways for regulation of genes encoding proteins required for neuritogenesis, changes in cell morphology, and cell survival have been traced in PC 12 cells. Pharmacological experiments have linked gene expression to cell physiological responses in this system, in which gene silencing can also be employed to confirm the functional significance of induction of specific transcripts. Differential transcriptional responses to metabolic, ischemic, and other stressors in wild type compared to PACAP-deficient mice establish in principle which PACAP-responsive transcripts in culture are PACAP-dependent in vivo. Bioinformatic approaches aid in creating a pipeline for identifying neuropeptide-regulated genes, validating their cellular functions, and defining their expression in the context of neuropeptide signaling physiology, required for discovery of new targets for drug action. C1 [Eiden, Lee E.; Samal, Babru; Gerdin, Matthew J.; Mustafa, Tomris; Stroth, Nikolas] NIMH IRP, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. [Vaudry, David] Univ Rouen, INSERM, Lab Cellular & Mol Neuroendocrinol, European Inst Peptide Res,U413, Rouen, France. RP Eiden, LE (reprint author), NIMH IRP, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Eiden, Lee/0000-0001-7524-944X; Vaudry, David/0000-0003-3567-7452 FU Intramural NIH HHS [Z01 MH002386-22, ZIA MH002386-23] NR 62 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-704-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1144 BP 6 EP 20 DI 10.1196/annals.1418.019 PG 15 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BIT17 UT WOS:000262481000003 PM 19076358 ER PT S AU Mattson, MP AF Mattson, Mark P. BE Goetzl, EJ TI Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease SO Neural Signaling: Opportunities for Novel Diagnostic Approaches and Therapies SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Neural Signaling - Opportunities for Novel Diagnostic Approaches and Therapies CY FEB 16-20, 2008 CL Pacific Grove, CA DE Alzheimer's disease; AMPA receptors; BDNF; calcium homeostasis; GDNF; Huntington's disease; NMDA; Parkinson's disease ID FIBROBLAST-GROWTH-FACTOR; LONG-TERM POTENTIATION; AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN-INJURY; BDNF MESSENGER-RNA; METHYL-D-ASPARTATE; METABOLIC EXCITOTOXIC INSULTS; AMYLOID PRECURSOR PROTEIN; MAJOR DEPRESSIVE DISORDER; STRESS-INDUCED IMPAIRMENT AB Glutamate's role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis, and neuron survival in the developing and adult mammalian nervous system. Cell-surface glutamate receptors are coupled to Ca(2+). influx and release from endoplasmic reticulum stores, which causes rapid (kinase- and protease-mediated) and delayed (transcription-dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain-derived neurotrophic factor (BDNF), which, in turn, modifies neuronal glutamate sensitivity, Ca(2+) homeostasis, and plasticity. Neurotrophic factors may modify glutamate signaling directly, by changing the expression of glutamate receptor subunits and Ca(2+)-regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy-regulating proteins, and antiapoptotic Bcl-2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer's disease to psychiatric disorders. By enhancing neurotrophic factor signaling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signaling and protect against neurological disorders. C1 NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21221 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21221 USA. RI Mattson, Mark/F-6038-2012 FU National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging of the National Institutes of Health. I thank K.C. Alexander for preparing the figures, and the many postdocs and students who contributed to the original research from my laboratory, described in this article. NR 173 TC 256 Z9 270 U1 5 U2 40 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-704-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1144 BP 97 EP 112 DI 10.1196/annals.1418.005 PG 16 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BIT17 UT WOS:000262481000014 PM 19076369 ER PT J AU Yaffe, K Kanaya, AM Lindquist, K Hsueh, WC Cummings, SR Beamer, B Newman, A Rosano, C Li, R Harrisi, T AF Yaffe, K. Kanaya, A. M. Lindquist, K. Hsueh, W. C. Cummings, S. R. Beamer, B. Newman, A. Rosano, C. Li, R. Harrisi, T. TI PPAR-gamma Pro12Ala genotype and risk of cognitive decline in elders SO NEUROBIOLOGY OF AGING LA English DT Article DE cognitive function; PPAR-gamma; cognitive impairment; dementia; metabolism ID BODY-MASS INDEX; ACTIVATED RECEPTOR-GAMMA-2 GENE; AFRICAN-AMERICANS; ALZHEIMER-DISEASE; OLDER WOMEN; PEROXISOME; PPAR-GAMMA-2; POLYMORPHISM; DEMENTIA; INSULIN AB Background: The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been associated with decreased risk of diabetes and obesity, both disorders linked to cognitive impairment. We tested whether this polymorphism is associated with cognition. Methods: Two thousand nine hundred sixty-one participants (mean age, 74.1; 41% Black; 52% women) were administered the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and 4 year follow-up. Test scores were adjusted for age, sex, education, cerebrovascular disease, depression and APOE genotype and additionally for race. We determined the association between Ala allele and development of cognitive decline (3MS decline of >= 5 points). Results: At baseline, unadjusted scores on both cognitive tests were higher for Ala carriers compared to non-carriers (3MS, 94.2 versus 92.5, p<0.001; DSST, 40.2 versus 34.5, p<0.001). Similarly, follow-up scores were higher for Ala carriers. Multivariable adjustment led to similar results; additional adjustment for race attenuated the baseline 3MS results. After 4 years, 17.5% of Ala carriers developed cognitive decline compared to 25% among non-carriers (unadjusted OR = 0.61; 95%CI, 0.46-0.82; adjusted OR = 0.75; 95%CI, 0.55-1.02). Further adjustment for metabolic variables including fasting blood glucose and lipid level did not change the results. Conclusions: The PPAR-gamma Ala12 allele carriers may have less risk of developing cognitive decline. (C) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Psychiat & Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. Calif Pacific Med Ctr, San Francisco, CA USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Tennessee, Ctr Hlth Sci, Ctr Genom & Bioinformat, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat & Neurol, POB 181,4150 Clement St, San Francisco, CA 94121 USA. EM Kristine.yaffe@ucsf.edu RI Newman, Anne B./C-6408-2013; OI Newman, Anne B./0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01 AG021918, R01 AG021918-03]; NIDDK NIH HHS [DK070713, R21 DK070713, R21 DK070713-01] NR 29 TC 20 Z9 21 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2008 VL 29 IS 1 BP 78 EP 83 DI 10.1016/j.neurobiolaging.2006.09.010 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 239SD UT WOS:000251537100008 PM 17052804 ER PT J AU Selmeczy, Z Vizi, ES Csoka, B Pacher, P Hasko, G AF Selmeczy, Zsolt Vizi, E. Sylvester Csoka, Balazs Pacher, Pal Hasko, Gyoergy TI Role of nonsynaptic communication in regulating the immune response SO NEUROCHEMISTRY INTERNATIONAL LA English DT Review DE nonsynaptic communication; immune cells; microglia; adenosine receptors; adrenergic receptors ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE PRODUCTION; CULTURED MICROGLIAL CELLS; BETA-ADRENERGIC AGONISTS; CENTRAL-NERVOUS-SYSTEM; TNF-ALPHA PRODUCTION; ADENOSINE RECEPTOR AGONISTS; RAT MICROGLIA; INTERLEUKIN-10 PRODUCTION; SYMPATHETIC INNERVATION AB The discovery of nonsynaptic communication in the 1960s and 1970s was an important milestone in investigating the function of the nervous system, and it revolutionized our view about information transmission between neurons. In addition, nonsynaptic communication has a practical importance not only within the nervous system, but in the communication between the peripheral nervous system and other organ systems. Nonsynaptic communication takes place in different immune organs, which are innervated by sympathetic nerve terminals. In addition, the function of microglia, one of the immunocompetent cell types of the brain, can also be affected by neurotransmitters released from axon varicosities. The various functions of immune cells are modulated by released neurotransmitters without any direct synaptic contact between nerve endings and targeted immune cells requiring only functional neurotransmitter receptors on immune cells. Here, we briefly overview the role of the various receptor subtypes mediating nonsynaptic modulation of the function of immunocompetent cells both in the periphery and in the central nervous system. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Selmeczy, Zsolt; Vizi, E. Sylvester; Hasko, Gyoergy] Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1450 Budapest, Hungary. [Pacher, Pal] Natl Inst Hlth, NIAAA, Lab Physiol Studies, Sect Oxidat Stress Tisue Injury, Bethesda, MD 20892 USA. [Csoka, Balazs; Hasko, Gyoergy] Univ Med & Dent New Jersey, Sch Med, Dept Surg, Newark, NJ 07103 USA. RP Selmeczy, Z (reprint author), Inst Expt Med, Szigony Utca 43, H-1083 Budapest, Hungary. EM selmeczy@koki.hu RI Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130 FU Intramural NIH HHS [Z01 AA000375-02]; NIGMS NIH HHS [R01 GM066189, R01 GM066189-01, R01 GM066189-02, R01 GM66189] NR 126 TC 10 Z9 10 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JAN PY 2008 VL 52 IS 1-2 BP 52 EP 59 DI 10.1016/j.neuint.2007.06.001 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 253FN UT WOS:000252504200008 PM 17640770 ER PT J AU Webster, JA Myers, A Pearson, JV Craig, DW Diane, HL Coon, KD Zismann, VL Beach, T Leunge, D Bryden, L Halperin, RF Marlowe, L Kaleem, M Huentelman, MJ Joshipura, K Walker, D Heward, CB Ravidi, R Rogers, J Papassotiropoulos, A Hardy, J Reiman, EM Stephan, DA AF Webster, Jennifer A. Myers, AmandaJ. Pearson, John V. Craig, David W. Diane, Hu-Lincea Coon, Keith D. Zismann, Victoria L. Beach, Thomas Leunge, Doris Bryden, Leslie Halperin, Rebecca F. Marlowe, Lauren Kaleem, Mona Huentelman, Matthew J. Joshipura, Keta Walker, Douglas Heward, Christopher B. Ravidi, Rivka Rogers, Joseph Papassotiropoulos, Andreas Hardy, John Reiman, Eric M. Stephan, Dietrich A. TI Sorl1 as an Alzheimer's disease predisposition gene? SO NEURODEGENERATIVE DISEASES LA English DT Article DE Sorl1; Alzheimer's disease; predisposition gene; APOE gene; sortilin-related receptor ID ASSOCIATION; POPULATION; GENOTYPE AB Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively disabling impairments in memory, cognition, and non-cognitive behavioural symptoms. Sporadic AD is multifactorial and genetically complex. While several monogenic mutations cause early-onset AD and gene alleles have been suggested as AD susceptibility factors, the only extensively validated susceptibility gene for late-onset AD is the apolipoprotein E (APOE) epsilon 4 allele. Alleles of the APOE gene do not account for all of the genetic load calculated to be responsible for AD predisposition. Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts. Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval. Copyright (C) 2007 S. Karger AG, Basel. C1 [Webster, Jennifer A.; Pearson, John V.; Craig, David W.; Diane, Hu-Lincea; Coon, Keith D.; Zismann, Victoria L.; Halperin, Rebecca F.; Huentelman, Matthew J.; Joshipura, Keta; Papassotiropoulos, Andreas; Reiman, Eric M.; Stephan, Dietrich A.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA. [Myers, AmandaJ.; Hardy, John] Univ Maine, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. [Beach, Thomas; Walker, Douglas; Rogers, Joseph] Sun Hlth Res Inst, Sun City, AZ USA. [Beach, Thomas; Walker, Douglas; Rogers, Joseph; Reiman, Eric M.; Stephan, Dietrich A.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Leunge, Doris; Bryden, Leslie; Marlowe, Lauren; Kaleem, Mona] NIA, Neurogenet Lab, NIH, Bethesda, MD USA. [Heward, Christopher B.] Kronos Sci Labs, Phoenix, AZ USA. [Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Ravidi, Rivka] Royal Dutch Acad Sci, Amsterdam, Netherlands. [Papassotiropoulos, Andreas] Univ Zurich, Dept Psychiat Res, Zurich, Switzerland. RP Stephan, DA (reprint author), Translat Genom Res Inst, Neurogenom Div, 445 N 5th St, Phoenix, AZ 85004 USA. EM dstephan@tgen.org RI Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009; Pearson, John/F-2249-2011; Leung, Doris/R-5447-2016 OI Myers, Amanda/0000-0002-3100-9396; Pearson, John/0000-0003-0904-4598; Leung, Doris/0000-0002-2558-7798 FU Intramural NIH HHS; Medical Research Council [G0701075]; NHLBI NIH HHS [U01HL084744]; NIA NIH HHS [AG05128, P30 AG19610, P30-AG13846, P50 AG16570, P50-AG08671, U01 AG016976]; NIMH NIH HHS [MH60451]; NINDS NIH HHS [NS39764, U24NS051872] NR 9 TC 49 Z9 50 U1 5 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2008 VL 5 IS 2 BP 60 EP 64 DI 10.1159/000110789 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 255FV UT WOS:000252644000002 PM 17975299 ER PT J AU Ghetti, B Spina, S Murrella, JR Huey, ED Pietrini, P Sweeney, B Wassermann, EM Keohane, C Farlow, MR Grafman, J AF Ghetti, Bernardino Spina, Salvatore Murrella, Jili R. Huey, Edward D. Pietrini, Pietro Sweeney, Brian Wassermann, Eric M. Keohane, Catherine Farlow, Martin R. Grafman, Jordan TI In vivo and postmortem clinicoanatomical correlations in frontotemporal dementia and parkinsionism linked to chromosome 17 SO NEURODEGENERATIVE DISEASES LA English DT Article; Proceedings Paper CT 8th International Conference on Alzheimers and Parkinsons Diseases CY MAR 14-18, 2007 CL Salzburg, AUSTRIA DE frontotemporal dementia and parkinsonism linked; to chromosome 17; tau; ubiquitin; TDP-43; neuropathology ID CORTICOBASAL SYNDROME; GENE-MUTATIONS; TAU; TAUOPATHY; CONSENSUS; APHASIA AB Background: Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is associated with mutations in the Microtubule-Associated Protein Tau (MAPT) gene or the Progranulin (PGRN) gene. MAPT mutations lead to widespread deposition of hyperphosphorylated tau protein (FTDP-17T). PGRN mutations are associated with ubiquitin- and TDP-43-positive inclusions in the frontotemporal cortex, striatum and hippocampus (FTDP-17U). Despite the differences, FTDP-17T and FTDP-17U sharea largely overlapping clinical phenotype. Objective:To determine whether neuroimaging studies may allow an in vivo early differentiation between FTDP-17T and FTDP-17U. Methods: We studied 25 individuals affected with FTDP-17T associated with either the exon 10+3 (24 subjects) or the G335S (I subject) MAPT mutation, as well as 3 FTDP-17U individuals, who were carriers of the A9D, IVS6-2A > G or R493X PGRN mutation. Neuroimaging studies, obtained along the course of the disease, were compared to the neuropathologic findings. Results: FTDP-17T cases were associated with symmetric frontotemporal atrophy. Behavioral changes constituted the predominant clinical presentation. Conversely, an asymmetric degenerative process was seen in all 3 PGRN cases, who presented with either corticobasal syndrome (A9D) or frontotemporal dementia and language deterioration (IVS62A > G and R493X). Conclusion: Neuroimaging data, in the early disease stage of FTDP-17, may offer the possibility of an early differentiation of FTDP-17T and FTDP-17U phenotypes, independent of the genetic analysis. Copyright (c) 2008 S. Karger AG, Basel. C1 [Ghetti, Bernardino; Spina, Salvatore; Murrella, Jili R.; Farlow, Martin R.] Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Spina, Salvatore] Univ Siena, Dept Neurol & Behav Sci, I-53100 Siena, Italy. [Huey, Edward D.; Wassermann, Eric M.; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. [Pietrini, Pietro] Univ Pisa, Lab Clin Biochem & Mol Biol, Pisa, Italy. [Sweeney, Brian; Keohane, Catherine] Cork Univ Hosp, Div Neurosci, Cork, Ireland. RP Ghetti, B (reprint author), Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indiana Alzheimer Dis Ctr, Med Sci Bldg A138,635 Branhill Dr, Indianapolis, IN 46202 USA. EM bghetti@iupui.edu RI Sweeney, Brian/D-2569-2013 FU Intramural NIH HHS; NIA NIH HHS [AG10133, P30 AG010133] NR 15 TC 15 Z9 16 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2008 VL 5 IS 3-4 BP 215 EP 217 DI 10.1159/000113706 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 275ZA UT WOS:000254109700030 PM 18322394 ER PT J AU Cai, HB Shim, H Lai, C Xie, CS Lin, X Yang, WJ Chandran, J AF Cai, Huaibin Shim, Hoon Lai, Chen Xie, Chengsong Lin, Xian Yang, Wan Jou Chandran, Jayanth TI ALS2/alsin knockout mice and motor neuron diseases SO NEURODEGENERATIVE DISEASES LA English DT Article DE amyotrophic lateral sclerosis; ALS2; alsin; knockout mice; mouse model; guanine nucleotide exchange factor; primary lateral sclerosis; hereditary spastic paraplegia ID AMYOTROPHIC-LATERAL-SCLEROSIS; NUCLEOTIDE EXCHANGE FACTOR; HEREDITARY SPASTIC PARALYSIS; SMALL GTPASE RAB5; ALS2 GENE; ENDOSOME TRAFFICKING; ALS2-DEFICIENT MICE; MISSENSE MUTATION; SPINAL-CORD; DEGENERATION AB Autosomal recessive mutations in the ALS2 gene have been linked to juvenile-onset amyotrophic lateral sclerosis (ALS2), primary lateral sclerosis and juvenile-onset ascending hereditary spastic paraplegia. Except for two recently identified missense mutations, all other mutations in the ALS2 gene lead to a premature stop codon and likely abrogate all the potential functions of alsin, the protein encoded by the ALS2 gene. To study the pathologic mechanisms of ALS2 deficiency, four different lines of ALS2 knockout (ALS2(-/-)) mice have been generated by independent groups. The loss of ALS2/alsin does not have a drastic effect on the survival or function of motor neurons in mice. However, subtle deficits observed in the behavior and pathology of these mice have aided in our understanding of the relationship between alsin and motor neuron dysfunction. In this review, we summarize and reconcile major findings of ALS2(-/-) mice and attempt to place these results within the larger context of modeling recessive movement disorders in mice. Copyright (C) 2008 S. Karger AG, Basel. C1 [Cai, Huaibin] NIA, Unit Transgenesis, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cai, HB (reprint author), NIA, Unit Transgenesis, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Intramural NIH HHS [Z01 AG000959-04, Z99 AG999999] NR 39 TC 18 Z9 19 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2008 VL 5 IS 6 BP 359 EP 366 DI 10.1159/000151295 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 347ZK UT WOS:000259180200005 PM 18714162 ER PT S AU Nielsen, L Phillips, JWR AF Nielsen, Lisbeth Phillips, John W. R. BE Houser, D McCabe, K TI HEALTH ECONOMIC CHOICES IN OLD AGE: INTERDISCIPLINARY PERSPECTIVES ON ECONOMIC DECISIONS AND THE AGING MIND SO NEUROECONOMICS SE Advances in Health Economics and Health Services Research LA English DT Article; Book Chapter ID ADULT LIFE-SPAN; TERM-CARE INSURANCE; EVENT-RELATED FMRI; RISK-TAKING; PREFRONTAL CORTEX; NEURAL BASIS; NEGATIVE AFFECT; WORKING-MEMORY; SOCIOEMOTIONAL SELECTIVITY; MEDICATION NONADHERENCE AB Purpose - This chapter offers an integrative review of psychological and neurobiological differences between younger and older adults that might impact economic behavior. Focusing on key health economic challenges facing the elderly, it offers perspectives on how these psychological and neurobiological factors may influence decision-making over the life course and considers future interdisciplinary research directions. Methodology/approach - We review relevant literature from three domains that are essential for developing a comprehensive science of decision-making and economic behavior in aging (psychology, neuroscience, and economics), consider implications for prescription drug coverage and long-term care (LTC) insurance, and highlight future research directions. Findings - Older adults face many complex economic decisions that directly affect their health and well-being, including LTC insurance, prescription drug plans, and end of life care. Economic research suggests that many older Americans are not making cost-effective and economically rational decisions. While economic models provide insight into some of the financial incentives associated with these decisions, they typically do not consider the roles of cognition and affect in decision-making. Research has established that older age is associated with predictable declines in many cognitive functions and evidence is accumulating that distinct social motives and affect-processing profiles emerge in older age. It is unknown how these age differences impact the economic behaviors of older people and implies opportunities for path-breaking interdisciplinary research. Originality/value of the chapter - Our chapter looks to develop interdisciplinary research to better understand the causes and consequences of age-related changes in economic decision-making and guide interventions to improve public programs and overall social welfare. C1 [Nielsen, Lisbeth; Phillips, John W. R.] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA. RP Nielsen, L (reprint author), NIA, Div Behav & Social Res, Bethesda, MD 20892 USA. NR 194 TC 2 Z9 2 U1 5 U2 12 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY, W YORKSHIRE BD16 1WA, ENGLAND SN 0731-2199 BN 978-1-84855-304-0 J9 ADV HEALTH ECON HEAL PY 2008 VL 20 BP 227 EP 270 DI 10.1016/S0731-2199(08)20010-5 PG 44 WC Psychology, Biological; Behavioral Sciences; Economics; Neurosciences; Psychology, Experimental SC Psychology; Behavioral Sciences; Business & Economics; Neurosciences & Neurology GA BLR52 UT WOS:000270876300011 PM 19552311 ER PT J AU Macova, M Armando, I Zhou, J Baiardi, G Tyurmin, D Larrayoz-Roldan, IM Saavedra, JM AF Macova, Miroslava Armando, Ines Zhou, Jin Baiardi, Gustavo Tyurmin, Dmitri Larrayoz-Roldan, Ignacio M. Saavedra, Juan M. TI Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT(2) Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats SO NEUROENDOCRINOLOGY LA English DT Article DE Renin-angiotensin system; Angiotensin II AT(1) receptors; Adrenal medulla; Adrenal cortex; Reproductive hormones; Transcription factors; Fra-2; Tyrosine hydroxylase; Aldosterone ID SPONTANEOUSLY HYPERTENSIVE-RATS; GENE-DISRUPTED MICE; BOVINE ADRENOCORTICAL-CELLS; ENDOTHELIAL NITRIC-OXIDE; TYPE-2 RECEPTOR; MESSENGER-RNA; TYROSINE-HYDROXYLASE; BLOOD-PRESSURE; IN-VIVO; QUANTITATIVE AUTORADIOGRAPHY AB We studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT(1) and AT(2) receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT 1 receptor expression in the adrenal zona glomerulosa and medulla, and decreased adrenomedullary catecholamine content and Fra-2 expression when compared to intact female rats. In the zona glomerulosa, estrogen replacement normalized AT(1) receptor expression, decreased AT(1B) receptor mRNA, and increased AT(2) receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were: normalized AT(1) receptor expression, increased AT(2) receptor expression, AT(2) receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT(1) receptors, catecholamine synthesis and Fra-2 expression are partially under the control of reproductive hormones. Our results suggest that estrogen treatment decreases aldosterone production through AT(1) receptor downregulation and AT(2) receptor upregulation. AT(2) receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT(2) receptor upregulation and the decrease in AT(1) receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy. Copyright (C) 2008 S. Karger AG, Basel C1 [Macova, Miroslava; Armando, Ines; Zhou, Jin; Baiardi, Gustavo; Tyurmin, Dmitri; Larrayoz-Roldan, Ignacio M.; Saavedra, Juan M.] NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1514,Bldg 10,Rm 2D-57, Bethesda, MD 20892 USA. EM Saavedrj@mail.nih.gov RI Larrayoz, Ignacio/I-5613-2012 OI Larrayoz, Ignacio/0000-0003-1629-152X FU Intramural NIH HHS [Z01 MH002762-11, Z99 MH999999] NR 75 TC 18 Z9 19 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2008 VL 88 IS 4 BP 276 EP 286 DI 10.1159/000150977 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 377UW UT WOS:000261277400005 PM 18679017 ER PT J AU Ahlman, H Nilsson, O McNicol, AM Ruszniewski, P Niederle, B Ricke, J Jensen, R Kos-Kudla, B Oberg, K O'Connor, JM Pavel, ME Vullierme, MP AF Ahlman, Hakan Nilsson, Ola McNicol, Anne M. Ruszniewski, Philippe Niederle, Bruno Ricke, Jens Jensen, Robert Kos-Kudla, Beata Oberg, Kjell O'Connor, Juan M. Pavel, Marianne E. Vullierme, Marie-Pierre TI Poorly-differentiated endocrine carcinomas of midgut and hindgut origin SO NEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Conference on ENETS Guidelines for the Diagnosis and Treatment of Neuroendocrine Gastrointestinal Tumor CY NOV 01-04, 2006 CL Frascati, ITALY ID SMALL-CELL CARCINOMAS; NEUROENDOCRINE CARCINOMAS; GENETIC ALTERATIONS; GASTROINTESTINAL-TRACT; COLON; TUMORS; RECTUM; EXPRESSION; ESOPHAGUS; THERAPY C1 [Ahlman, Hakan] Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden. [McNicol, Anne M.] Royal Infirm Hosp, Dept Pathol & Oncol, Glasgow, Lanark, Scotland. [Ruszniewski, Philippe] Beaujon Hosp, Dept Gastroenterol, Clichy, France. [Niederle, Bruno] Med Univ Vienna, Dept Surg, Div Gen Surg, Vienna, Austria. [Ricke, Jens] Univ Magdeburg, Dept Radiol & Nucl Med, D-39106 Magdeburg, Germany. [Jensen, Robert] Natl Inst Hlth, Cell Biol Sect, Bethesda, MD USA. [Kos-Kudla, Beata] Klin Endokrynol, Slaska Akad Medyczna, Zabrze, Poland. [Oberg, Kjell] Univ Uppsala Hosp, Dept Internal Med, Endocrine Unit, S-75185 Uppsala, Sweden. [O'Connor, Juan M.] Inst Alexander Fleming, Buenos Aires, DF, Argentina. [Pavel, Marianne E.] Charite Univ Med Berlin, Dept Internal Med, Div Gastroenterol & Hepatol, Berlin, Germany. [Vullierme, Marie-Pierre] Hop Beaujon, Serv Gastroenterol, Clichy, France. RP Ahlman, H (reprint author), Inst Surg Sci, Dept Surg, SE-41345 Gothenburg, Sweden. EM hakan.ahlman@surgery.gu.se RI Lopes, Jose Manuel/J-7428-2013; scarpa, aldo/K-6832-2016; OI Lopes, Jose Manuel/0000-0001-8597-3474; scarpa, aldo/0000-0003-1678-739X; Falconi, Massimo/0000-0001-9654-7243; RINDI, Guido/0000-0003-2996-4404; OConnor, Juan Manuel/0000-0002-6975-5466; Niederle, Bruno/0000-0001-8107-4068; Perren, Aurel/0000-0002-6819-6092 NR 31 TC 39 Z9 40 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2008 VL 87 IS 1 BP 40 EP 46 DI 10.1159/000109976 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 241MX UT WOS:000251661600005 PM 17940332 ER PT J AU Xiong, CJ Tang, YX van Belle, G Miller, JP Launer, LJ Morris, JC AF Xiong, Chengjie Tang, Yuxiao van Belle, Gerald Miller, J. Philip Launer, Lenore J. Morris, John C. TI Evaluating the quality of longitudinal statistical applications in original publications on Alzheimer's disease SO NEUROEPIDEMIOLOGY LA English DT Article DE Alzheimer's disease, longitudinal studies; neurodegenerative disease; cognition; reliability coefficient ID RANDOMIZED CONTROLLED TRIALS; COGNITIVE IMPAIRMENT; CLINICAL-TRIALS; STANDARDS; DIAGNOSIS; DECLINE; MODEL; DRUG AB Background/Aims: To evaluate the quality of longitudinal statistical applications in published studies on Alzheimer's disease (AD). Methods: A 21-item instrument, the Quality of Longitudinal AD Studies (QLADS), was developed by the research team (4 biostatisticians, 1 neuroepidemiologist, and 1 neurologist). All items were extensively discussed within the team for content validity. After pilot testing on 5 publications, the instrument was revised and tested for reliability with a sample of 40 published longitudinal AD studies randomly sampled from MEDLINE. Results: Item-specific test-retest reliability coefficients for QLADS ranged from 0.53 to 1.00 with the associated standard error (SE) ranging from 0.02 to 0.13. The test-retest reliability for the overall score over the 21 items was high (intraclass correlation coefficient (ICC) = 0.94, 95% CI 0.90, 0.97). Item-specific inter-rater reliability coefficients for QLADS ranged from 0.46 to 1.00 with the associated SE ranging from 0.07 to 0.18. The inter-rater reliability for the overall score was also high (ICC = 0.87, 95% CI 0.77, 0.93). Conclusions: This study indicates that the quality of longitudinal statistical applications in AD publications can be reliably assessed. Copyright (C) 2008 S. Karger AG, Basel. C1 [Xiong, Chengjie; Miller, J. Philip] Washington Univ, Div Biostat, St Louis, MO 63110 USA. [Xiong, Chengjie; Morris, John C.] Washington Univ, Alzheimers Dis Res Ctr, St Louis, MO 63110 USA. [Tang, Yuxiao] Univ Washington, Program Appropriate Technol Hlth, Seattle, WA 98195 USA. [van Belle, Gerald] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. [Morris, John C.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA. [Morris, John C.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Xiong, CJ (reprint author), Washington Univ, Div Biostat, Campus Box 8067, St Louis, MO 63110 USA. EM chengjie@wubios.wustl.edu RI Morris, John/A-1686-2012 FU NIA NIH HHS [AG 03991, AG 05681, K25 AG025189, P01 AG003991, P01 AG026276, P50 AG005681] NR 38 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2008 VL 30 IS 2 BP 112 EP 119 DI 10.1159/000120024 PG 8 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 280HV UT WOS:000254417700007 PM 18334827 ER PT J AU Schmidt, S Allen, KD Loiacono, VT Norman, B Stanwyck, CL Nord, KM Williams, CD Kasarskis, EJ Kamel, F McGuire, V Nelson, LM Oddone, EZ AF Schmidt, Silke Allen, Kelli D. Loiacono, Valerie T. Norman, Barbara Stanwyck, Catherine L. Nord, Kristina M. Williams, Christina D. Kasarskis, Edward J. Kamel, Freya McGuire, Valerie Nelson, Lorene M. Oddone, Eugene Z. CA VA ALS Registry Grp TI Genes and environmental exposures in veterans with amyotrophic lateral sclerosis: The GENEVA study SO NEUROEPIDEMIOLOGY LA English DT Article DE amyotrophic lateral sclerosis, case-control study; GENEVA study recruitment methods; gene-environment interaction ID MOTOR-NEURON-DISEASE; GULF-WAR VETERANS; OCCUPATIONAL CASE-CONTROL; WESTERN WASHINGTON-STATE; SPORADIC ALS; APOLIPOPROTEIN-E; CIGARETTE-SMOKING; MILITARY SERVICE; ANTECEDENT EVENTS; MILLENNIUM COHORT AB Recent reports of a potentially increased risk of amyotrophic lateral sclerosis (ALS) for veterans deployed to the 1990-1991 Persian Gulf War prompted the Department of Veterans Affairs to establish a National Registry of Veterans with ALS, charged with the goal of enrolling all US veterans with a neurologist-confirmed diagnosis of ALS. The Genes and Environmental Exposures in Veterans with ALS study (GENEVA) is a case-control study presently enrolling cases from the Department of Veterans Affairs registry and a representative sample of veteran controls to evaluate the joint contributions of genetic susceptibility and environmental exposures to the risk of sporadic ALS. The GENEVA study design, recruitment strategies, methods of collecting DNA samples and environmental risk factor information are described here, along with a summary of demographic characteristics of the participants (537 cases, 292 controls) enrolled to date. Copyright (c) 2008 S. Karger AG, Basel. C1 [Schmidt, Silke; Loiacono, Valerie T.; Stanwyck, Catherine L.; Nord, Kristina M.; Williams, Christina D.] Duke Univ, Med Ctr, Dept Med, Ctr Human Genet, Durham, NC 27710 USA. [Schmidt, Silke; Allen, Kelli D.; Loiacono, Valerie T.; Norman, Barbara; Stanwyck, Catherine L.; Nord, Kristina M.; Williams, Christina D.; Oddone, Eugene Z.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Kamel, Freya] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Kasarskis, Edward J.] Univ Kentucky, Med Ctr, Lexington, KY USA. [McGuire, Valerie; Nelson, Lorene M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Schmidt, S (reprint author), Duke Univ, Med Ctr, Dept Med, Ctr Human Genet, Box 3445, Durham, NC 27710 USA. EM silke.schmidt@duke.edu RI Nelson, Lorene/D-1305-2011 FU NIEHS NIH HHS [R01 ES013244-02, ES013244, R01 ES013244, R01 ES013244-01, R01 ES013244-03, R01 ES013244-04, R01 ES013244-05] NR 94 TC 20 Z9 20 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2008 VL 30 IS 3 BP 191 EP 204 DI 10.1159/000126911 PG 14 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 289XL UT WOS:000255087100010 PM 18421219 ER PT J AU Abe, K Zoghbi, SS Inoue, O Itoh, T Hong, J Pike, VW Innis, RB Fujita, M AF Abe, Kohji Zoghbi, S. S. Inoue, O. Itoh, T. Hong, J. Pike, V. W. Innis, R. B. Fujita, M. TI In vivo density and affinity of [C-11](R)-rolipram binding to phosphodiesterase 4 in rat measured with and without anesthesia SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst ID BRAIN C1 [Abe, Kohji; Zoghbi, S. S.; Itoh, T.; Hong, J.; Pike, V. W.; Innis, R. B.; Fujita, M.] NIMH, Mol Imaging Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Abe, Kohji; Inoue, O.] Osaka Univ, Grad Sch Med, Div Hlth Sci, Osaka, Japan. [Abe, Kohji] Shionogi & Co Ltd, Res & Dev Labs, Osaka, Japan. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T48 EP T48 DI 10.1016/j.neuroimage.2008.04.222 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800035 ER PT J AU Brown, AK Simeon, F Liow, JS Zoghbi, S Kimara, Y Fujita, M MoZley, PD Pike, V Innis, RB AF Brown, Amira K. Simeon, F. Liow, J. S. Zoghbi, S. Kimara, Y. Fujita, M. MoZley, P. D. Pike, V. Innis, R. B. TI Radiation dosimetry and human brain imaging of [F-18]SP203: A PET radioligand for the metabotropic glutamate mG1uR5 receptor SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Brown, Amira K.; Simeon, F.; Liow, J. S.; Zoghbi, S.; Kimara, Y.; Fujita, M.; Pike, V.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [MoZley, P. D.] Merck Res Labs, West Point, PA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T178 EP T178 DI 10.1016/j.neuroimage.2008.04.145 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800160 ER PT J AU Carlson, PJ Bain, E Tinsley, R Nugent, A Carson, R Luckenbaugh, D Kling, M Gold, P Remaley, A Drevets, WC AF Carlson, Paul J. Bain, E. Tinsley, R. Nugent, A. Carson, R. Luckenbaugh, D. Kling, M. Gold, P. Remaley, A. Drevets, W. C. TI Relationship between serotonin-1A binding and HPA axis in subjects with major depression and healthy controls SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Carlson, Paul J.; Bain, E.; Tinsley, R.; Nugent, A.; Carson, R.; Luckenbaugh, D.; Kling, M.; Gold, P.; Remaley, A.; Drevets, W. C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 0 TC 2 Z9 2 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T146 EP T146 DI 10.1016/j.neuroimage.2008.04.114 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800130 ER PT J AU Chefer, SI Spinelli, S Carson, RE Jagoda, EM Suomi, SJ Stein, EA AF Chefer, Svetlana I. Spinelli, S. Carson, R. E. Jagoda, E. M. Suomi, S. J. Stein, E. A. TI Gender differences in 5HT(1A) receptor density and affinity measured by [(18)F]FPWAY and PET in juvenile rhesus monkeys SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathWorks Matlab, MERCK, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Chefer, Svetlana I.; Stein, E. A.] NIDA, NIH, DHHS, Neuroimaging Res Branch, Baltimore, MD USA. [Spinelli, S.] NIAAA, NIH, DHHS, Bethesda, MD USA. [Carson, R. E.] Yale Univ, Sch Med, Yale PET Ctr, New Haven, CT USA. [Jagoda, E. M.] NIBIB, NIH, DHHS, Bethesda, MD USA. [Suomi, S. J.] NICHD, NIH, DHHS, Bethesda, MD USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T147 EP T147 DI 10.1016/j.neuroimage.2008.04.115 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800131 ER PT J AU Donohue, SR Finnema, SJ Truong, P Andersson, J Gulyas, B Pike, VW Halldin, C AF Donohue, Sean R. Finnema, S. J. Truong, P. Andersson, J. Gulyas, B. Pike, V. W. Halldin, C. TI Discovery and labeling of a homochiral high affinity 3,4-diarylpyrazoline as a candidate radioligand for in vivo imaging of cannabinoid type-1 receptors SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Donohue, Sean R.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Donohue, Sean R.; Finnema, S. J.; Truong, P.; Andersson, J.; Gulyas, B.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T90 EP T90 DI 10.1016/j.neuroimage.2008.04.059 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800075 ER PT J AU Fujimura, Y Yasuno, F Farris, A Liow, JS Geraci, M Drevets, W Pine, D Lerner, A Hargreaves, R Burns, D Morse, C Pike, VW Innis, RB AF Fujimura, Yota Yasuno, F. Farris, A. Liow, J. -S. Geraci, M. Drevets, W. Pine, D. Lerner, A. Hargreaves, R. Burns, D. Morse, C. Pike, V. W. Innis, R. B. TI Decreased neurokinin-1 (Substance P) receptor binding in patients with panic disorder: Positron emission tomography study with [(18)F]SPA-RQ SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathWorks Matlab, MERCK, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Fujimura, Yota; Yasuno, F.; Farris, A.; Liow, J. -S.; Lerner, A.; Morse, C.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Geraci, M.; Drevets, W.; Pine, D.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Hargreaves, R.; Burns, D.] Merck Res Labs, West Point, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T184 EP T184 DI 10.1016/j.neuroimage.2008.04.151 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800166 ER PT J AU Fujimura, Y Kreisl, WC Zoghbi, SS Hong, J Gladding, RL Pike, VW Innis, RB Fujita, M AF Fujimura, Yota Kreisl, W. C. Zoghbi, S. S. Hong, J. Gladding, R. L. Pike, V. W. Innis, R. B. Fujita, M. TI Quantification of specific binding in brain and radiation dosimetry of [C-11](R)-PK 11195 in rhesus monkey SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst ID BENZODIAZEPINE-RECEPTOR PBR; LIGANDS C1 [Fujimura, Yota; Kreisl, W. C.; Zoghbi, S. S.; Hong, J.; Gladding, R. L.; Pike, V. W.; Innis, R. B.; Fujita, M.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T112 EP T112 DI 10.1016/j.neuroimage.2008.04.081 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800097 ER PT J AU Fujimura, Y Zoghbi, SS Gladding, R Simeon, FG Taku, A Pike, VW Innis, RB Fujita, M AF Fujimura, Yota Zoghbi, S. S. Gladding, R. Simeon, F. G. Taku, A. Pike, V. W. Innis, R. B. Fujita, M. TI Kinetic analysis in healthy humans and radiation dosimetry in monkeys of a novel positron emission tomography radioligand, [F-18]PBR06, to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Fujimura, Yota; Zoghbi, S. S.; Gladding, R.; Simeon, F. G.; Taku, A.; Pike, V. W.; Innis, R. B.; Fujita, M.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T111 EP T111 DI 10.1016/j.neuroimage.2008.04.080 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800096 ER PT J AU Fujita, M Zoghbi, SS Irnaizurni, M Hong, J Gladding, RL Pike, VW Innis, RB AF Fujita, Masahiro Zoghbi, S. S. Irnaizurni, M. Hong, J. Gladding, R. L. Pike, V. W. Innis, R. B. TI Species differences in brain phosphodiesterase levels measured with [C-11](R)-Rolipram PET SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Fujita, Masahiro; Zoghbi, S. S.; Irnaizurni, M.; Hong, J.; Gladding, R. L.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T185 EP T185 DI 10.1016/j.neuroimage.2008.04.152 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800167 ER PT J AU Fujita, M Imaizumi, M Zoghbi, SS Fujimura, Y Farris, AG Suhara, T Hong, J Pike, VW Innis, RB AF Fujita, Masahiro Imaizumi, M. Zoghbi, S. S. Fujimura, Y. Farris, A. G. Suhara, T. Hong, J. Pike, V. W. Innis, R. B. TI Kinetic analysis in healthy humans of [C-11]PBR28, a new positron emission tomography radioligand to image the peripheral benzodiazepine receptor SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst ID LIGANDS; BRAIN C1 [Fujita, Masahiro; Imaizumi, M.; Zoghbi, S. S.; Fujimura, Y.; Farris, A. G.; Hong, J.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Suhara, T.] Natl Inst Radiol Sci, Mol Imaging Ctr, Mol Neuroimaging Grp, Chiba 260, Japan. NR 3 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T34 EP T34 DI 10.1016/j.neuroimage.2008.04.208 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800021 ER PT J AU Hammond, DA Endres, CJ Uzuner, O Hammond, ER Kaplin, AI Nath, A Pomper, MG AF Hammond, Dima A. Endres, C. J. Uzuner, O. Hammond, E. R. Kaplin, A. I. Nath, A. Pomper, M. G. TI Imaging of the serotonin transporter in depressed HIV-positive patients using [C-11]DASB-PET SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Hammond, Dima A.] NIH, Bethesda, MD 20892 USA. [Endres, C. J.; Uzuner, O.; Pomper, M. G.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Hammond, E. R.; Kaplin, A. I.; Nath, A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T43 EP T43 DI 10.1016/j.neuroimage.2008.04.217 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800030 ER PT J AU Le Foll, B Chefer, SI Kimes, AS Shumway, D Stein, EA Mukhin, AG Goldberg, SR AF Le Foll, Bernard Chefer, S. I. Kimes, A. S. Shumway, D. Stein, E. A. Mukhin, A. G. Goldberg, S. R. TI Inverse relationship between basal expression of alpha 4 beta 2*nicotinic acetylcholine receptors and motivation to self-administer nicotine in non-human primates SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Le Foll, Bernard; Chefer, S. I.; Kimes, A. S.; Shumway, D.; Stein, E. A.; Mukhin, A. G.] NIDA, NIH, DHHS, Neuroimaging Res Branch, Baltimore, MD USA. [Le Foll, Bernard; Goldberg, S. R.] NIDA, NIH, DHHS, Behav Neurosci Res Branch, Baltimore, MD USA. [Le Foll, Bernard] CAMH, Toronto, ON, Canada. [Mukhin, A. G.] Duke Univ, Med Ctr, Durham, NC USA. RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T189 EP T189 DI 10.1016/j.neuroimage.2008.04.156 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800171 ER PT J AU Liow, JS Kreisl, W Zoghbi, SS Lazarova, N Seneca, N Gladding, R Tuan, E Taku, A Herscovitch, P Pike, VW Innis, RB AF Liow, Jeih-San Kreisl, W. Zoghbi, S. S. Lazarova, N. Seneca, N. Gladding, R. Tuan, E. Taku, A. Herscovitch, P. Pike, V. W. Innis, R. B. TI P-glycoprotein function imaged with [C-11]N-desmethly-operamide in monkey SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Liow, Jeih-San; Kreisl, W.; Zoghbi, S. S.; Lazarova, N.; Seneca, N.; Gladding, R.; Tuan, E.; Taku, A.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD USA. [Herscovitch, P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T27 EP T27 DI 10.1016/j.neuroimage.2008.04.201 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800015 ER PT J AU Lu, SY Liow, JS Zoghbi, SS Gladding, RL Innis, RB Pike, VW AF Lu, Shuiyu Liow, J. S. Zoghbi, S. S. Gladding, R. L. Innis, R. B. Pike, V. W. TI Evaluation of [F-18]SL702 as a prospective agonist PET radioligand for brain 5-HT1A receptors in mice and monkey SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Lu, Shuiyu; Liow, J. S.; Zoghbi, S. S.; Gladding, R. L.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T157 EP T158 DI 10.1016/j.neuroimage.2008.04.125 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800140 ER PT J AU Martin-Soelch, C Szczepanik, J Barhaghi, K Rollis, D Cannon, D Nugent, A Herscovitch, P Carson, RE Drevets, WC AF Martin-Soelch, Chantal Szczepanik, J. Barhaghi, K. Rollis, D. Cannon, D. Nugent, A. Herscovitch, P. Carson, R. E. Drevets, W. C. TI Lack of dopamine release in response to monetary reward in depressed patients: A [C-11]raclopride PET study SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Martin-Soelch, Chantal; Szczepanik, J.; Barhaghi, K.; Rollis, D.; Nugent, A.; Drevets, W. C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Martin-Soelch, Chantal] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. [Cannon, D.] Natl Univ Ireland, Galway Co, Dept Psychiat, Galway, Ireland. [Herscovitch, P.] NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. [Carson, R. E.] Yale Univ, Dept Diagnost Radiol, PET Ctr, New Haven, CT 06510 USA. RI Cannon, Dara/C-1323-2009; Carson, Richard/H-3250-2011 OI Cannon, Dara/0000-0001-7378-3411; Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T56 EP T56 DI 10.1016/j.neuroimage.2008.04.230 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800043 ER PT J AU Mukhin, AG Chefer, SI LeFoll, B Matochik, JA Contoreggi, CS Kimes, AS AF Mukhin, Alexey G. Chefer, S. I. LeFoll, B. Matochik, J. A. Contoreggi, C. S. Kimes, A. S. TI 2-[F-18]fluoro-A-85380 BPND in brains of smokers and non-smokers: Validation of extracerebral reference region approach SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst ID ACETYLCHOLINE-RECEPTORS; QUANTIFICATION C1 [Mukhin, Alexey G.; Chefer, S. I.; LeFoll, B.; Matochik, J. A.; Contoreggi, C. S.; Kimes, A. S.] NIDA, NIH, DHHS, Neuroimaging Res Branch, Baltimore, MD USA. [Mukhin, Alexey G.] Duke Univ, Med Ctr, Durham, NC USA. [LeFoll, B.] NIDA, NIH, DHHS, Behav Neurosci Res Branch, Baltimore, MD USA. [LeFoll, B.] CAMH, Toronto, ON, Canada. [Matochik, J. A.] NIAAA, NIH, DHHS, Div Neurosci & Behav, Rockville, MD 20852 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T191 EP T191 DI 10.1016/j.neuroimage.2008.04.158 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800173 ER PT J AU Seneca, N Zoghbi, SS Skinbjerg, M Liow, JS Hong, J Sibley, DR Pike, VW Halldin, C Innis, RB AF Seneca, Nicholas Zoghbi, S. S. Skinbjerg, M. Liow, J. S. Hong, J. Sibley, D. R. Pike, V. W. Halldin, C. Innis, R. B. TI Occupancy of dopamine D-2/D-3 receptors in rat brain by endogenous dopamine measured with the agonist positron emission tomography radioligand [C-11]MNPA SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Seneca, Nicholas; Zoghbi, S. S.; Skinbjerg, M.; Liow, J. S.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Seneca, Nicholas; Skinbjerg, M.; Hong, J.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. [Skinbjerg, M.; Sibley, D. R.] NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T138 EP T138 DI 10.1016/j.neuroimage.2008.04.106 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800122 ER PT J AU Seneca, N Skinbjerg, M Zoghbi, SS Liow, JS Gladding, RL Hong, J Kannan, P Tuan, E Sibley, DR Halldin, C Pike, VW Innis, RB AF Seneca, Nicholas Skinbjerg, M. Zoghbi, S. S. Liow, J. S. Gladding, R. L. Hong, J. Kannan, P. Tuan, E. Sibley, D. R. Halldin, C. Pike, V. W. Innis, R. B. TI Kinetic brain analysis and whole-body imaging in monkey of [C-11]MNPA, a dopamine agonist radioligand SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Seneca, Nicholas; Skinbjerg, M.; Zoghbi, S. S.; Liow, J. S.; Gladding, R. L.; Hong, J.; Kannan, P.; Tuan, E.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Seneca, Nicholas; Skinbjerg, M.] Karolinska Inst, Dept Clin Neurosci, Sect Psychiat, Stockholm, Sweden. [Skinbjerg, M.; Sibley, D. R.] NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T139 EP T139 DI 10.1016/j.neuroimage.2008.04.107 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800123 ER PT J AU Seneca, N Zoghbi, SS Tuan, E Kannan, P Innis, RB Pike, VW AF Seneca, Nicholas Zoghbi, S. S. Tuan, E. Kannan, P. Innis, R. B. Pike, V. W. TI Inhibition of metabolism of [C-11]Loperamide in mouse by the potent CYP3A4 inhibitor, ketoconazole SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Seneca, Nicholas; Zoghbi, S. S.; Tuan, E.; Kannan, P.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T100 EP T100 DI 10.1016/j.neuroimage.2008.04.069 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800085 ER PT J AU Skinbjerg, M Narnkung, Y Halldin, C Innis, RB Sibley, DR AF Skinbjerg, Mette Narnkung, Y. Halldin, C. Innis, R. B. Sibley, D. R. TI Pharmacological characterization of the interactions of 2-methoxy-N-propylnorapomorphine (MNPA) with D-2 and D-3 dopamine receptors SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Skinbjerg, Mette; Narnkung, Y.; Sibley, D. R.] NINDS, NIH, Mol Neuropharmacol Sect, Bethesda, MD USA. [Skinbjerg, Mette; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Skinbjerg, Mette; Innis, R. B.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T140 EP T140 DI 10.1016/j.neuroimage.2008.04.108 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800124 ER PT J AU Terry, GE Liow, JS Chernet, E Zoghbi, SS Phebus, L Lerner, A Felder, CC Tauscher, J Schaus, JM Pike, VW Halldin, C Innis, RB AF Terry, Garth E. Liow, J. -S. Chernet, E. Zoghbi, S. S. Phebus, L. Lerner, A. Felder, C. C. Tauscher, J. Schaus, J. M. Pike, V. W. Halldin, C. Innis, R. B. TI Evaluation of an inverse agonist with high affinity for the CB1 receptor, [C-11]MePPEP, in rodents and humans SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Terry, Garth E.; Liow, J. -S.; Zoghbi, S. S.; Lerner, A.; Pike, V. W.; Innis, R. B.] NIMH, Bethesda, MD 20892 USA. [Chernet, E.; Phebus, L.; Felder, C. C.; Tauscher, J.; Schaus, J. M.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Terry, Garth E.; Halldin, C.] Karolinska Inst, Stockholm, Sweden. NR 1 TC 2 Z9 2 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T197 EP T197 DI 10.1016/j.neuroimage.2008.04.164 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800179 ER PT J AU Tomasi, G Bertoldo, A Schmidt, K Turkheimer, FE Smith, CB Cobelli, C AF Tomasi, Giampaolo Bertoldo, A. Schmidt, K. Turkheimer, F. E. Smith, C. B. Cobelli, C. TI Residual-based comparison of different weighting schemes for pixel-wise kinetic analysis at the pixel level in PET SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Tomasi, Giampaolo] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Tomasi, Giampaolo; Bertoldo, A.; Cobelli, C.] Univ Padua, Dept Informat Engn, Padua, Italy. [Schmidt, K.; Smith, C. B.] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA. [Turkheimer, F. E.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London, England. [Turkheimer, F. E.] Hammersmith Hosp, Div Neurosci, London, England. NR 0 TC 2 Z9 2 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T84 EP T84 DI 10.1016/j.neuroimage.2008.04.053 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800069 ER PT J AU Vaupel, DB Chefer, SI Stein, EA Mukhin, AG AF Vaupel, D. Bruce Chefer, S. I. Stein, E. A. Mukhin, A. G. TI Brain and muscle accumulation of 2-[F-18]F-A-85380 radioactive metabolites: Implication for quantitative studies of nicotinic receptors with PET SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Vaupel, D. Bruce; Chefer, S. I.; Stein, E. A.; Mukhin, A. G.] DHHS, NIH, NIDA IRP, Neuroimaging Res Branch, Baltimore, MD USA. [Mukhin, A. G.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T199 EP T199 DI 10.1016/j.neuroimage.2008.04.269 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800181 ER PT J AU Zhou, Y Ye, W Resnick, SM Brasic, JR Crabb, AH Wong, DF AF Zhou, Yun Ye, W. Resnick, S. M. Brasic, J. R. Crabb, A. H. Wong, D. F. TI Analysis of the noise-induced underestimation in the DV and DVR images generated by graphical analysis and an SRTM model with linear regression SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst ID PET C1 [Zhou, Yun; Ye, W.; Brasic, J. R.; Crabb, A. H.; Wong, D. F.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Resnick, S. M.] NIA, IRP, NIH, Baltimore, MD 21224 USA. RI Brasic, James/B-3503-2008 OI Brasic, James/0000-0002-3948-4853 NR 5 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T87 EP T87 DI 10.1016/j.neuroimage.2008.04.056 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800072 ER PT J AU Zoghbi, SS Liow, JS Lazarova, N Hong, J Tuan, E Gladding, RL Innis, RB Pike, VW AF Zoghbi, Sami S. Liow, J. -S. Lazarova, N. Hong, J. Tuan, E. Gladding, R. L. Innis, R. B. Pike, V. W. TI [C-11]N-Desmethyl-Loperamide is an improved radiotracer for studying brain P-gp function SO NEUROIMAGE LA English DT Meeting Abstract CT 7th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 17-19, 2008 CL Pittsburgh, PA SP Natl Inst Ment Hlth, Amgen, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, MathworksMatlab, Merek & Co Inc, Pfizer, PMOD Technol, Raytest, GmBH, Siemens Med Syst C1 [Zoghbi, Sami S.; Liow, J. -S.; Lazarova, N.; Hong, J.; Tuan, E.; Gladding, R. L.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2008 VL 41 SU 2 BP T106 EP T106 DI 10.1016/j.neuroimage.2008.04.075 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 326QK UT WOS:000257673800091 ER PT J AU Silverman, MN Sternberg, EM AF Silverman, Marni N. Sternberg, Esther M. TI Neuroendocrine-immune interactions in rheumatoid arthritis: Mechanisms of glucocorticoid resistance SO NEUROIMMUNOMODULATION LA English DT Review DE glucocorticoids; glucocorticoid resistance; corticosteroid binding globulin; multidrug resistance transporter; 11 beta-hydroxysteroid dehydrogenase; glucocorticoid receptor; cytokines; inflammation; autoimmune disease ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; CORTICOSTEROID-BINDING GLOBULIN; I MDR-I; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MIGRATION INHIBITORY FACTOR; BLOOD MONONUCLEAR-CELLS; P-GLYCOPROTEIN ACTIVITY; RECEPTOR BETA-ISOFORM; NECROSIS-FACTOR-ALPHA; N-TERMINAL KINASE AB Rheumatoid arthritis ( RA) is characterized by chronic inflammation of the synovial membrane, leading to joint destruction. Many autoimmune diseases and disease states of chronic inflammation are accompanied by alterations in the complex interactions between the endocrine, nervous and immune systems. Glucocorticoids, an end product of the hypothalamic-pituitary-adrenal axis, are a mainstay treatment for many autoimmune diseases, including RA, because of their potent anti-inflammatory action. However, about 30% of patients with RA fail to respond to steroid therapy. There are various mechanisms that may contribute to the development of glucocorticoid resistance in inflammatory disorders, which will be the subject of this review. In addition, glucocorticoid resistance may be a contributing factor in the development of inflammatory/autoimmune diseases themselves. Therefore, further elucidation of these mechanisms will reveal new targets for therapeutic intervention in the treatment of RA. Copyright (C) 2008 S. Karger AG, Basel. C1 [Silverman, Marni N.] Natl Inst Mental Hlth, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, Rockville, MD 20852 USA. RP Silverman, MN (reprint author), Natl Inst Mental Hlth, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, 5625 Fishers Lane MSC-9041, Rockville, MD 20852 USA. EM sternbee@mail.nih.gov FU Intramural NIH HHS [Z01 MH002585-17, ZIA MH002585-19] NR 103 TC 29 Z9 30 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2008 VL 15 IS 1 BP 19 EP 28 DI 10.1159/000135620 PG 10 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 334ME UT WOS:000258225100003 PM 18667796 ER PT J AU Wang, Y Chandran, JS Cai, HB Mattson, MP AF Wang, Yue Chandran, Jayanth S. Cai, Huaibin Mattson, Mark P. TI DJ-1 is essential for long-term depression at hippocampal CA1 synapses SO NEUROMOLECULAR MEDICINE LA English DT Article DE DJ-1; LTD; LTP; Parkinson's disease; dopamine receptor; hippocampal CA1 ID PARKINSONS-DISEASE; SYNAPTIC PLASTICITY; DOPAMINE-RECEPTORS; ALPHA-SYNUCLEIN; POTENTIATION; DYSFUNCTION; MUTATIONS; INDUCTION; DEFICITS; REGION AB Mutations in DJ-1 cause inherited Parkinson's disease (PD) in several families. The normal function of DJ-1 is unknown, but mice lacking DJ-1 exhibit a deficit in dopaminergic signaling in the striatum. Since the hippocampus contains relatively high levels of DJ-1, and PD patients are often cognitively impaired, we evaluated the effects of DJ-1 deficiency on the plasticity of hippocampal CA1 synapses. LTP was slightly impaired and LTD was abolished in DJ-1-/- mice, whereas DJ-1+/- mice exhibited no alterations in synaptic plasticity. The dopamine receptor D2/3 agonist quinpirole rescued LTD in DJ-1-/- mice, suggesting a role for impaired dopaminergic signaling in the hippocampal LTD deficit. C1 [Wang, Yue] NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. [Wang, Yue; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Chandran, Jayanth S.; Cai, Huaibin] NIA, Neurogenet Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Wang, Y (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wangyu@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Intramural NIH HHS NR 31 TC 12 Z9 13 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2008 VL 10 IS 1 BP 40 EP 45 DI 10.1007/s12017-008-8023-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 271OL UT WOS:000253797700005 PM 18246449 ER PT J AU Stranahan, AM Mattson, MP AF Stranahan, Alexis M. Mattson, Mark P. TI Impact of Energy Intake and Expenditure on Neuronal Plasticity SO NEUROMOLECULAR MEDICINE LA English DT Review DE Diet; Hippocampus; Caloric restriction; Exercise ID LONG-TERM POTENTIATION; ADULT DENTATE GYRUS; HIPPOCAMPAL SYNAPTIC PLASTICITY; GENERATED GRANULE CELLS; TRANSGENIC MOUSE MODEL; MEDIAL TEMPORAL-LOBE; HIGH-FAT DIET; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; DENDRITIC SPINES AB The Roman poet Horace was among the first to recognize that when "clogged with yesterday's excess, the body drags the mind down with it." Although considerable attention has been paid in neuroscience to the enhancement of neuronal function by wheel running and caloric restriction. far less is known about the other side of this issue. What are the consequences of unhealthy habits to central nervous system function? Prolonged exposure to excessive caloric intake impairs neuronal function and also contributes to obesity and other risk factors for diabetes. Diabetes, a disease characterized by reduced sensitivity to Glucose and insulin, is also associated with deficits in brain structure and function. In contrast, enhancement of somatic metabolism by wheel running or caloric restriction improves central neuroplasticity. Generalizing across Studies reveals a relationship between global metabolic efficiency and neuroplasticity in the hippocampus, a brain region that is essential for learning and memory. The specific principles upheld by these findings are suggestive of a continuum, with global metabolic alterations fluctuating in concert with neuroplasticity in the hippocampus. C1 [Stranahan, Alexis M.; Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU NRSA predoctoral fellowship; National Institute on Aging Intramural Research Program FX This work was Supported by a NRSA predoctoral fellowship to A. S. and by the National Institute on Aging Intramural Research Program. NR 108 TC 38 Z9 39 U1 3 U2 18 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2008 VL 10 IS 4 BP 209 EP 218 DI 10.1007/s12017-008-8043-0 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 400HL UT WOS:000262858500001 PM 18543119 ER PT J AU Son, TG Camandola, S Mattson, MP AF Son, Tae Gen Camandola, Simonetta Mattson, Mark P. TI Hormetic Dietary Phytochemicals SO NEUROMOLECULAR MEDICINE LA English DT Review DE Nrf2; Antioxidant response element; Hormesis; Sirtuin; Stress; Sulforaphane; Resveratrol ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTOR NRF2; MEDIATED GENE-EXPRESSION; SKIN TUMOR PROMOTION; E-DEFICIENT MICE; OXIDATIVE STRESS; HEME OXYGENASE-1; FERULIC ACID; GREEN TEA AB Compelling evidence from epidemiological studies suggests beneficial roles of dietary phytochemicals in protecting against chronic disorders such as cancer, and inflammatory and cardiovascular diseases. Emerging findings suggest that several dietary phytochemicals also benefit the nervous system and, when consumed regularly, may reduce the risk of disorders such as Alzheimer's and Parkinson's diseases. The evidence supporting health benefits of vegetables and fruits provide a rationale for identification of the specific phytochemicals responsible, and for investigation of their molecular and cellular mechanisms of action. One general mechanism of action of phytochemicals that is emerging from recent studies is that they activate adaptive cellular stress response pathways. From an evolutionary perspective, the noxious properties of such phytochemicals play an important role in dissuading insects and other pests from eating the plants. However at the subtoxic doses ingested by humans that consume the plants, the phytochemicals induce mild cellular stress responses. This phenomenon has been widely observed in biology and medicine, and has been described as 'preconditioning' or 'hormesis.' Hormetic pathways activated by phytochemicals may involve kinases and transcription factors that induce the expression of genes that encode antioxidant enzymes, protein chaperones, phase-2 enzymes, neurotrophic factors, and other cytoprotective proteins. Specific examples of such pathways include the sirtuin-FOXO pathway, the NF-kappa B pathway, and the Nrf-2/ARE pathway. In this article, we describe the hormesis hypothesis of phytochemical actions with a focus on the Nrf2/ARE signaling pathway as a prototypical example of a neuroprotective mechanism of action of specific dietary phytochemicals. C1 [Son, Tae Gen; Camandola, Simonetta; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Camandola, S (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM camandolasi@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000315-07] NR 122 TC 123 Z9 126 U1 4 U2 25 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2008 VL 10 IS 4 BP 236 EP 246 DI 10.1007/s12017-008-8037-y PG 11 WC Neurosciences SC Neurosciences & Neurology GA 400HL UT WOS:000262858500003 PM 18543123 ER PT J AU Cohen, JE Fields, RD AF Cohen, Jonathan E. Fields, R. Douglas TI Activity-dependent neuron-glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development SO NEURON GLIA BIOLOGY LA English DT Article DE Activity dependent; cytokine; glial differentiation; neuron-glia signaling; synaptic plasticity ID FIBRILLARY ACIDIC PROTEIN; TERM SYNAPTIC POTENTIATION; FIBROBLAST-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; GFAP-EXPRESSING CELLS; FACTOR MESSENGER-RNA; VISUAL-CORTEX; IMMUNOREACTIVE ASTROCYTES; FACTOR-RECEPTOR; RAT-BRAIN AB Activity-dependent signaling between neurons and astrocytes contributes to experience-dependent plasticity and development of the nervous system. However, mechanisms responsible for neuron-glial interactions and the releasable factors that underlie these processes are not well understood. The pro-inflammatory cytokine, leukemia-inhibitory factor (LIF), is transiently expressed postnatally by glial cells in the hippocampus and rapidly up-regulated by enhanced neural activity following seizures. To test the hypothesis that spontaneous neural activity regulates glial development in hippocampus via LIF signaling, we blocked spontaneous activity with the sodium channel blocker tetrodotoxin (TTX) in mixed hippocampal cell cultures in combination with blockers of LIF and purinergic signaling. TTX decreased the number of GFAP-expressing astrocytes in hippocampal cell culture. Furthermore, blocking purinergic signaling by P(2)Y receptors contributed to reduced numbers of astrocytes. Blocking activity or purinergic signaling in the presence of function-blocking antibodies to LIF did not further decrease the number of astrocytes. Moreover, hippocampal cell cultures prepared from LIF -/- mice had reduced numbers of astrocytes and activity-dependent neuron-glial signaling promoting differentiation of astrocytes was absent. The results show that endogenous LIF is required for normal development of hippocampal astrocytes, and this process is regulated by spontaneous neural impulse activity through the release of ATP. C1 [Cohen, Jonathan E.; Fields, R. Douglas] NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov RI Moyal, Elizabeth/A-9802-2015 OI Moyal, Elizabeth/0000-0002-6593-9276 FU Intramural NIH HHS [Z01 HD000713-13] NR 52 TC 17 Z9 18 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2008 VL 4 BP 43 EP 55 DI 10.1017/S1740925X09000076 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 426GW UT WOS:000264697000007 PM 19267953 ER PT J AU Dityatev, A Bukalo, O Schachner, M AF Dityatev, Alexander Bukalo, Olena Schachner, Melitta TI Modulation of synaptic transmission and plasticity by cell adhesion and repulsion molecules SO NEURON GLIA BIOLOGY LA English DT Review DE LTP; LTD; spine; cell adhesion; synaptic plasticity ID LONG-TERM POTENTIATION; ACTIVATED PROTEIN-KINASE; SEMAPHORIN GENE-EXPRESSION; GROWTH CONE COLLAPSE; RECEPTOR-TYPE-Z; POLYSIALIC ACID; CLOSE HOMOLOG; MICE DEFICIENT; HIPPOCAMPAL-NEURONS; AXON GUIDANCE AB Adhesive and repellent molecular cues guide migrating cells and growing neurites during development. They also contribute to synaptic function, learning and memory in adulthood. Here, we review the roles of cell adhesion molecules of the immunoglobulin superfamily (Ig-CAMs) and semaphorins (some of which also contain Ig-like domains) in regulation of synaptic transmission and plasticity. Interestingly, among the seven studied Ig-CAMs, the neuronal cell adhesion molecule proved to be important for all tested forms of hippocampal plasticity, while its associated unusual glycan polysialic acid is necessary and sufficient part for synaptic plasticity only at CA3-CA1 synapses. In contrast, Thy-1 and L1 specifically regulate long-term potentiation (LTP) at synapses formed by entorhinal axons in the dentate gyrus and cornu ammonis, respectively. Contactin-1 is important for long-term depression but not for LTP at CA3-CA1 synapses. Analysis of CHL1-deficient mice illustrates that at intermediate stages of development a deficit in a cell adhesion molecule is compensated but appears as impaired LTP during early and late postnatal development. The emerging mechanisms by which adhesive Ig-CAMs contribute to synaptic plasticity involve regulation Of activities of NMDA receptors and L-type Ca(2+) channels, signaling via mitogen-activated protein kinase p38, changes in GABAergic inhibition and motility of synaptic elements. Regarding repellent molecules, available data for semaphorins demonstrate their activity-dependent regulation in normal and pathological conditions, synaptic localization of their receptors and their potential to elevate or inhibit synaptic transmission either directly or indirectly. C1 [Dityatev, Alexander] Italian Inst Technol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy. [Bukalo, Olena] NICHHD, NIH, Bethesda, MD 20892 USA. [Schachner, Melitta] Zentrum Mol Neurobiol Hamburg, Hamburg, Germany. [Schachner, Melitta] Rutgers State Univ, Keck Ctr Collaborat Neurosci, Piscataway, NJ USA. [Schachner, Melitta] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. [Schachner, Melitta] Shantou Univ, Coll Med, Ctr Neurosci, Shantou, Peoples R China. RP Dityatev, A (reprint author), Italian Inst Technol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy. EM alexander.dityatev@iit.it RI Dityatev, Alexander/A-4034-2008; OI Dityatev, Alexander/0000-0002-0472-0553 NR 127 TC 41 Z9 41 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2008 VL 4 BP 197 EP 209 DI 10.1017/S1740925X09990111 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 512LW UT WOS:000271251900005 PM 19674506 ER PT J AU Liu, J Wang, L Harvey-White, J Huang, BX Kim, HY Luquet, S Palmiter, RD Krystal, G Rai, R Mahadevan, A Razdan, RK Kunos, G AF Liu, Jie Wang, Lei Harvey-White, Judith Huang, Bill X. Kim, Hee-Yong Luquet, Serge Palmiter, Richard D. Krystal, Gerald Rai, Ravi Mahadevan, Anu Razdan, Raj K. Kunos, George TI Multiple pathways involved in the biosynthesis of anandamide SO NEUROPHARMACOLOGY LA English DT Article DE anandamide; biosynthesis; N-arachidonoyl phosphatidylethanolamine; glycerophosphoarachidonoyl ethanolamide; phosphoanandamide ID N-ACYLETHANOLAMINE PHOSPHOLIPIDS; ENDOCANNABINOID SYSTEM; CANNABINOID-RECEPTOR; INACTIVATION; PHOSPHODIESTERASE; ETHANOLAMINE; METABOLISM; ACTIVATION; OBESITY; FAMILY AB Endocannabinoids, including anandamide (arachidonoyl ethanolamide) have been implicated in the regulation of a growing number of physiological and pathological processes. Anandamide can be generated from its membrane phospholipid precursor N-arachidonoyl phosphatidylethanolamine (NAPE) through hydrolysis by a phospholipase D (NAPE-PLD). Recent evidence indicates, however, the existence of two additional, parallel pathways. One involves the sequential deacylation of NAPE by alpha,beta-hydrolase 4 (Abhd4) and the subsequent cleavage of glycerophosphate to yield anandamide, and the other one proceeds through phospholipase C-mediated hydrolysis of NAPE to yield phosphoanandamide, which is then dephosphorylated by phosphatases, including the tyrosine phosphatase PTPN22 and the mositol 5' phosphatase SHIP1. Conversion of synthetic NAPE to AEA by brain homogenates from wild-type and NAPE-PLD-/- mice can proceed through both the PLC/phosphatase and Abdh4 pathways, with the former being dominant at shorter (< 10 min) and the latter at longer (60 min) incubations. In macrophages, the endotoxin-induced synthesis of anandamide proceeds uniquely through the phospholipase C/phosphatase pathway. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Liu, Jie; Wang, Lei; Harvey-White, Judith; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Huang, Bill X.; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA. [Luquet, Serge; Palmiter, Richard D.] Univ Washington, Dept Biochem, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Krystal, Gerald] British Columbia Canc Agcy, Terry Fox Labs, Vancouver, BC V5Z 4E6, Canada. [Rai, Ravi; Mahadevan, Anu; Razdan, Raj K.] Organix Inc, Woburn, MA 01801 USA. RP Liu, J (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,MS 9413, Bethesda, MD 20892 USA. EM jiel@mail.nih.gov OI luquet, serge/0000-0001-8668-6645 FU Intramural NIH HHS [Z99 AA999999] NR 26 TC 126 Z9 129 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2008 VL 54 IS 1 BP 1 EP 7 DI 10.1016/j.neuropharm.2007.05.020 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 254BC UT WOS:000252560300001 PM 17631919 ER PT J AU Yin, HH Adermark, L Lovinger, DA AF Yin, Henry H. Adermark, Louise Lovinger, David A. TI Neurotensin reduces glutamatergic transmission in the dorsolateral striatum via retrograde endocannabinoid signaling SO NEUROPHARMACOLOGY LA English DT Article DE neurotensin; synaptic plasticity; neuropeptides; dopamine; glutamate; basal ganglia; striatum; endocannabinoid; CB1 ID LONG-TERM DEPRESSION; DOPAMINE D2 RECEPTORS; NUCLEUS-ACCUMBENS; METABOTROPIC GLUTAMATE; NEOSTRIATAL NEURONS; DORSAL STRIATUM; HABIT FORMATION; RAT STRIATUM; RELEASE; ACTIVATION AB Neurotensin is a peptide that has been suggested to mimic the actions of antipsychotics, but little is known about how it affects synaptic transmission in the striatum, the major input nucleus of the basal ganglia. In this study we measured the effects of neurotensin on EPSCs from medium spiny projection neurons in the sensorimotor striatum, a region implicated in habit formation and control of motor sequences. We found that bath-applied neurotensin reduced glutamate release from presynaptic terminals, and that this effect required retrograde endocannabinoid signaling, as it was prevented by the CB I cannabinoid receptor antagonist AM251. Neurotensin-mediated inhibition of striatal EPSCs was also blocked by antagonists of D2-like dopamine receptors and group I metabotropic glutamate receptors, as well as by intracellular calcium chelation and phospholipase C inhibition. These results suggest that neurotensin can indirectly engage an endocannabinoid-mediated negative feedback signal to control glutamatergic input to the basal ganglia. Published by Elsevier Ltd. C1 [Yin, Henry H.; Adermark, Louise; Lovinger, David A.] NIAAA, Sect Synpat Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Lovinger, DA (reprint author), NIAAA, Sect Synpat Pharmacol, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,TS-13, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov RI Adermark, Louise/D-2297-2014 OI Adermark, Louise/0000-0002-7165-9908 FU Intramural NIH HHS [Z01 AA000407-06] NR 44 TC 13 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2008 VL 54 IS 1 BP 79 EP 86 DI 10.1016/j.neuropharm.2007.06.004 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 254BC UT WOS:000252560300011 PM 17675102 ER PT J AU Scherma, M Medalie, J Fratta, W Vadivel, SK Makriyannis, A Piomelli, D Mikics, E Haller, J Yasar, S Tanda, G Goldberg, SR AF Scherma, Maria Medalie, Julie Fratta, Walter Vadivel, Subramanian K. Makriyannis, Alexandros Piomelli, Daniele Mikics, Eva Haller, Jozsef Yasar, Sevil Tanda, Gianluigi Goldberg, Steven R. TI The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition SO NEUROPHARMACOLOGY LA English DT Article DE endogenous cannabinoids; anandamide; FAAH; URB597; WIN 55,212-2; conditioned place preferences; anxiety; locomotor activity; rats ID CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS SHELL; SPRAGUE-DAWLEY RATS; SQUIRREL-MONKEYS; CB1 RECEPTORS; MICE; DELTA(9)-TETRAHYDROCANNABINOL; DELTA-9-TETRAHYDROCANNABINOL; TRANSMISSION; TRANSPORT AB Converging evidence suggests that the endocannabinoid. system is an important constituent of neuronal substrates involved in brain reward processes and emotional responses to stress. Here, we evaluated motivational effects of intravenously administered anandamide, an endogenous ligand for cannabinoid CB1-receptors, in Sprague-Dawley rats, using a place-conditioning procedure in which drugs abused by humans generally produce conditioned place preferences (reward). Anandamide (0.03-3 mg/kg intravenous) produced neither conditioned place preferences nor aversions. However, when rats were pre-treated with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester; 0.3 mg/kg intraperitoneal), which blocks anandamide's metabolic degradation, anandamide produced dose-related conditioned place aversions. In contrast, URB597 alone showed no motivational effects. Like URB597 plus anandamide, the synthetic CB1-receptor ligand WIN 55,212-2 (50-300 mu g/kg, intravenous) produced dose-related conditioned place aversions. When anxiety-related effects of anandamide and URB597 were evaluated in a light/dark box, both a low anandamide dose (0.3 mg/kg) and URB597 (0.1 and 0.3 mg/kg) produced anxiolytic effects when given alone, but produced anxiogenic effects when combined. A higher dose of anandamide (3 mg/kg) produced anxiogenic effects and depressed locomotor activity when given alone and these effects were potentiated after URB597 treatment. Finally, anxiogenic effects of anandamide plus URB597 and development of place aversions with URB597 plus anandamide were prevented by the CBI-receptor antagonist AM251 (3 mg/kg intraperitoneal). Thus, additive interactions between the effects of anandamide on brain reward processes and on anxiety may account for its aversive effects when intravenously administered during FAAH inhibition with URB597. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Scherma, Maria; Medalie, Julie; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD USA. [Scherma, Maria; Fratta, Walter] Univ Cagliari, Bb Brodie Dept Neurosci, I-09124 Cagliari, Italy. [Vadivel, Subramanian K.; Makriyannis, Alexandros] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. [Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA. [Mikics, Eva; Haller, Jozsef] Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. [Tanda, Gianluigi] Natl Inst Drug Abuse, Psychobiol Sect, Med Discovery Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD USA. EM sgoldber@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; OI Tanda, Gianluigi/0000-0001-9526-9878; Haller, Jozsef/0000-0002-1953-3726 FU Intramural NIH HHS [Z01 DA000001-23, Z01 DA000003-22]; NIDA NIH HHS [R01 DA007215, DA09158, DA12413, DA12447, DA7215, P01 DA009158, R01 DA012413, R01 DA012447] NR 47 TC 88 Z9 91 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2008 VL 54 IS 1 BP 129 EP 140 DI 10.1016/j.neuropharm.2007.08.011 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 254BC UT WOS:000252560300016 PM 17904589 ER PT J AU Martinowich, K Lu, B AF Martinowich, Keri Lu, Bai TI Interaction between BDNF and serotonin: Role in mood disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE depression; anxiety; p75(NTR); TrkB; 5-HTT; SSRI ID NEUROTROPHIC FACTOR BDNF; ELEMENT-BINDING PROTEIN; CHRONIC ANTIDEPRESSANT TREATMENT; GENE CONFERS SUSCEPTIBILITY; FAMILY-BASED ASSOCIATION; FACTOR KNOCKOUT MICE; TRKB MESSENGER-RNA; ADULT-RAT BRAIN; HIPPOCAMPAL NEUROGENESIS; IN-VIVO AB Brain-derived neurotrophic factor ( BDNF) and serotonin ( 5-hydroxytryptamine, 5-HT) are two seemingly distinct signaling systems that play regulatory roles in many neuronal functions including survival, neurogenesis, and synaptic plasticity. A common feature of the two systems is their ability to regulate the development and plasticity of neural circuits involved in mood disorders such as depression and anxiety. BDNF promotes the survival and differentiation of 5-HT neurons. Conversely, administration of antidepressant selective serotonin reuptake inhibitors ( SSRIs) enhances BDNF gene expression. There is also evidence for synergism between the two systems in affective behaviors and genetic epitasis between BDNF and the serotonin transporter genes. C1 Natl Inst Hlth, NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Natl Inst Hlth, NICHD, Sect Neural Dev & Plascticity, Bethesda, MD USA. RP Lu, B (reprint author), Bldg 35,Rm 1C1004,35 Convent Dr,MSC 3714, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI Lu, Bai/A-4018-2012; Martinowich, Keri/F-9841-2012; OI Martinowich, Keri/0000-0002-5237-0789 NR 130 TC 249 Z9 258 U1 11 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 1 BP 73 EP 83 DI 10.1038/sj.npp.1301571 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235XH UT WOS:000251267100007 PM 17882234 ER PT J AU Schloesser, RJ Huang, J Klein, PS Manji, HK AF Schloesser, Robert J. Huang, Jian Klein, Peter S. Manji, Husseini K. TI Cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE bipolar disorder; neuroplasticity; intracellular signaling cascades; lithium; valproic acid; mood stabilizer ID GLYCOGEN-SYNTHASE KINASE-3; MAGNETIC-RESONANCE-SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; WHITE-MATTER HYPERINTENSITIES; ANTERIOR CINGULATE CORTEX; INOSITOL-POLYPHOSPHATE 1-PHOSPHATASE; REDUCES TAU-PHOSPHORYLATION; MICE OVEREXPRESSING BCL-2; GROWTH-ASSOCIATED PROTEIN AB Bipolar disorder ( BPD) is characterized by recurrent episodes of disturbed affect including mania and depression as well as changes in psychovegetative function, cognitive performance, and general health. A growing body of data suggests that BPD arises from abnormalities in synaptic and neuronal plasticity cascades, leading to aberrant information processing in critical synapses and circuits. Thus, these illnesses can best be conceptualized as genetically influenced disorders of synapses and circuits rather than simply as deficits or excesses in individual neurotransmitters. In addition, commonly used mood-stabilizing drugs that are effective in treating BPD have been shown to target intracellular signaling pathways that control synaptic plasticity and cellular resilience. In this article we draw on clinical, preclinical, neuroimaging, and post-mortem data to discuss the neurobiology of BPD within a conceptual framework while highlighting the role of neuroplasticity in the pathophysiology and treatment of this disorder. C1 NIMH, NIH, Lab Mol Pathophysiol Mood Anxiety & Disorders Pro, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Med Hematol Oncol, Philadelphia, PA USA. RP Manji, HK (reprint author), NIMH, Porter Neurosci Res Ctr, Lab Mol Pathophysiol Mood & Anxiety Disorders Pro, Bldg 35,Rm 1C-917,35 Convent Dr, Bethesda, MD 20892 USA. EM manjih@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [R01 MH058324, R01 MH058324-10] NR 244 TC 128 Z9 131 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 1 BP 110 EP 133 DI 10.1038/sj.npp.1301575 PG 24 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235XH UT WOS:000251267100010 PM 17912251 ER PT J AU Rapoport, JL Gogtay, N AF Rapoport, Judith L. Gogtay, Nitin TI Brain neuroplasticity in healthy, hyperactive and psychotic children: Insights from neuroimaging SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE brain; neuroplasticity; neuroimaging; healthy development; childhood schizophrenia; ADHD ID CHILDHOOD-ONSET SCHIZOPHRENIA; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; LONG-TERM POTENTIATION; RESONANCE-IMAGING MORPHOMETRY; ANTERIOR CINGULATE CORTEX; MESSENGER-RNA EXPRESSION; PRIMARY VISUAL-CORTEX; CEREBRAL BLOOD-FLOW; GRAY-MATTER LOSS; CORTICAL THICKNESS AB Noninvasive brain imaging permits longitudinal studies of anatomic brain development in healthy and psychiatrically ill children. The time course for gray matter maturation varies by region and parallels earlier histological studies, indicating dynamic patterns of overproduction and regression. Developmental trajectories vary in relation to gender, intelligence, and overall functioning. Twin studies show high heritability for brain volumes, which varies with region and with age. Diagnostically specific, illness-related changes as well as outcome-associated plastic response are observed as illustrated for two pediatric populations, childhood-onset schizophrenia and attention-deficit/hyperactivity disorder, conditions which may be, in part, disorders of brain plasticity. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Rm 3N202,MSC-1600, Bethesda, MD 20892 USA. EM gogtayn@mail.nih.gov RI Gogtay, Nitin/A-3035-2008 NR 178 TC 60 Z9 61 U1 10 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 1 BP 181 EP 197 DI 10.1038/sj.npp.1301553 PG 17 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235XH UT WOS:000251267100014 PM 17851542 ER PT J AU Goldman, D AF Goldman, David TI Whole-genome association for complex psychiatric disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material C1 NIAAA, Neurogenet Lab, Rockville, MD USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, Rockville, MD USA. EM davidgoldman@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 1 BP 201 EP 201 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235XH UT WOS:000251267100019 ER PT J AU Lipska, BK AF Lipska, Barbara K. TI Genes and modeling of schizophrenia: the curse of plentitude? SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID BRAIN C1 NIMH, IRP, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), NIMH, IRP, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov NR 7 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 1 BP 202 EP 203 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235XH UT WOS:000251267100021 ER PT J AU Zarate, CA Manji, HK AF Zarate, Carlos A., Jr. Manji, Husseini K. TI Raising the bar in drug development for depression: antidepressant response in hours instead of weeks SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID KETAMINE C1 NIMH, Mood & Anxiety Disorders Program, Lab Mol Pathophysiol & Expt Therapeut, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Mood & Anxiety Disorders Program, Lab Mol Pathophysiol & Expt Therapeut, Bethesda, MD 20892 USA. EM manjih@mail.nih.gov NR 4 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 1 BP 208 EP 208 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235XH UT WOS:000251267100027 ER PT J AU Dowling, GJ Weiss, SRB Condon, TP AF Dowling, Gayathri J. Weiss, Susan R. B. Condon, Timothy P. TI Drugs of abuse and the aging brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE brain; aging; neurotoxicity; neuroprotection; neurotransmitters; addiction ID AGE-RELATED DECLINE; POSITRON-EMISSION-TOMOGRAPHY; LIVING HUMAN BRAIN; CENTRAL SEROTONIN TRANSPORTER; RECEPTOR-BINDING SITES; ALCOHOL-USE DISORDERS; MANAGED CARE PROGRAM; DOPAMINE TRANSPORTERS; SUBSTANCE-ABUSE; OLDER-ADULTS AB Substance abuse among older adults has received little attention in the past, presumably because this population has traditionally accounted for only a small percentage of the drug abuse problem in the United States. The aging of the baby boomer generation (born 1946-1964), however, will soon swell the ranks of older adults and dramatically alter the demography of American society. Several observations suggest that this expansion will likely be accompanied by a precipitous increase in the abuse of drugs, including prescription medications and illicit substances, among older adults. While it is now evident that the brain changes continuously across life, how drugs of abuse interact with these age-related changes remains unclear. The dynamic nature of brain function, however, suggests that substance abuse during older age may augment the risks and require unique considerations for diagnosis and treatment. In addition to describing current and projected prevalence estimates of substance abuse among older adults, the present review discusses how aging affects brain systems involved in drug abuse, and explores the potential impact of drug abuse on the aging brain. Future directions for substance abuse research among older adults will also be considered. C1 Natl Inst Drug Abuse, Off Sci Policy & Commun, NIH, DHHS, Bethesda, MD 20892 USA. RP Dowling, GJ (reprint author), Natl Inst Drug Abuse, Off Sci Policy & Commun, NIH, DHHS, 6001 Execut Blvd,Room 5235,MSC 9591, Bethesda, MD 20892 USA. EM dowlingg@mail.nih.gov NR 155 TC 52 Z9 52 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 2 BP 209 EP 218 DI 10.1038/sj.npp.1301412 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 239SN UT WOS:000251538100001 PM 17406645 ER PT J AU Yasuno, F Brown, AK Zoghbi, SS Krushinski, JH Chernet, E Tauscher, J Schaus, JM Phebus, LA Chesterfield, AK Felder, CC Gladding, RL Hong, J Halldin, C Pike, VW Innis, RB AF Yasuno, Fumihiko Brown, Amira K. Zoghbi, Sami S. Krushinski, Joseph H. Chernet, Eyassu Tauscher, Johannes Schaus, John M. Phebus, Lee A. Chesterfield, Amy K. Felder, Christian C. Gladding, Robert L. Hong, Jinsoo Halldin, Christer Pike, Victor W. Innis, Robert B. TI The PET radioligand [C-11]MePPEP binds reversibly and with high specific signal to cannabinoid CB1 receptors in nonhuman primate brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cannabinoid; CB1 receptors; [C-11]MePPEP; kinetic analysis; PET ID P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; IN-VIVO; RAT; BIODISTRIBUTION; QUANTIFICATION; INHIBITION; ANTAGONIST; IOMAZENIL; BARRIER AB The cannabinoid CB1 receptor is one of the most abundant G protein-coupled receptors in the brain and is a promising target of therapeutic drug development. Success of drug development for neuropsychiatric indications is significantly enhanced with the ability to directly measure spatial and temporal binding of compounds to receptors in central compartments. We assessed the utility of a new positron emission tomography ( PET) radioligand to image CB1 receptors in monkey brain. [C-11]MePPEP ((3R,5R)-5-(3-methoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one) has high CB1 affinity (K-b = 0.574 +/- 0.207 nM) but also moderately high lipophilicity ( measured LogD(7.4) = 4.8). After intravenous injection of [C-11] MePPEP, brain activity reached high levels of almost 600% standardized uptake value (SUV) within 10-20 min. The regional uptake was consistent with the distribution of CB1 receptors, with high radioactivity in striatum and cerebellum and low in thalamus and pons. Injection of pharmacological doses of CB1-selective agents confirmed that the tracer doses of [ 11 C] MePPEP reversibly labeled CB1 receptors. Preblockade or displacement with two CB1 selective agents (ISPB; (4-(3-cyclopentyl-indole-1-sulfonyl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamide) and rimonabant) showed that the majority (> 89%) of brain uptake in regions with high receptor densities was specific and reversibly bound to CB1 receptors in the high binding regions. [C-11] MePPEP was rapidly removed from arterial plasma. Regional brain uptake could be quantified as distribution volume relative to the concentration of parent radiotracer in plasma. The P-glycoprotein (P-gp) inhibitor DCPQ (( R)4-[(1a,6,10b)-1,1-dichloro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]-[(5-quinolinyloxy) methyl]-1- piperazineethanol) did not significantly increase brain uptake of [C-11] MePPEP, suggesting it is not a substrate for this efflux transporter at the blood - brain barrier. [C-11] MePPEP is a radioligand with high brain uptake, high specific signal to CB1 receptors, and adequately fast washout from brain that allows quantification with (11C) (half-life = 20 min). These promising results in monkey justify studying this radioligand in human subjects. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, Stockholm, Sweden. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, Bldg 31,Room B2B37,31 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Tauscher, Johannes/M-5976-2016 FU Intramural NIH HHS; NIMH NIH HHS [Z01-MH-002795-04] NR 39 TC 46 Z9 46 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 2 BP 259 EP 269 DI 10.1038/sj.npp.1301402 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 239SN UT WOS:000251538100006 PM 17392732 ER PT J AU Chefer, SI Kimes, AS Matochik, JA Horti, AG Kurian, V Shumway, D Domino, EF London, ED Mukhin, AG AF Chefer, Svetlana I. Kimes, Alane S. Matochik, John A. Horti, Andrew G. Kurian, Varughese Shumway, Dean Domino, Edward F. London, Edythe D. Mukhin, Alexey G. TI Estimation of d2-like receptor occupancy by dopamine in the putamen of hemiparkinsonian monkeys SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE PET; [C-11]raclopride; MPTP model of PD; striatum ID POSITRON-EMISSION-TOMOGRAPHY; MPTP-INDUCED PARKINSONISM; NICOTINIC ACETYLCHOLINE-RECEPTORS; C-11 RACLOPRIDE BINDING; D2 RECEPTORS; IN-VIVO; HIGH-AFFINITY; SYNAPTIC DOPAMINE; SUBSTANTIA-NIGRA; RHESUS-MONKEYS AB To advance understanding of the neurochemical changes in Parkinson's disease (PD), we compared D2-like dopamine receptor occupancy by dopamine in the control and lesioned putamen of four pig-tailed macaques treated unilaterally with MPTP. PET and in vitro binding techniques were used to measure binding potential (BP*) and density of D2-like dopamine receptors (B-max), respectively. As would be expected in PD, relatively higher values of BP* and Bmax and less amphetamine-induced decrease in [C-11]raclopride binding were observed in the lesioned compared with the contralateral putamen in each animal. The percent differences between lesioned and contralateral sides were similar whether the measurements were of [C-11]raclopride BP* or Bmax values, measured in vivo and in vitro, respectively. As [C-11] raclopride BP* is a measure of the density of D2-like dopamine receptors available for radioligand binding (i.e., not occupied by dopamine), these findings suggest that the fractional occupancy of receptors by endogenous dopamine in the lesioned putamen is nearly equal to that in the contralateral putamen. Therefore, the absolute number of receptors occupied by dopamine, which is a product of receptor density and fractional occupancy by dopamine, is greater in the lesioned than in the contralateral putamen. One possible explanation for the lack of differences in fractional occupancy of D2 receptors by dopamine (despite a loss in available dopamine) is a lesion-induced increase in a portion of low-affinity D2 receptors to a state of high affinity for dopamine. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Ctr Nicotine & Smoking Cessat Res, Durham, NC 27705 USA. Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. NIAAA, Div Neurosci & Behav, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. Johns Hopkins Med Inst, Dept Radiol, Div Nucl Med, Baltimore, MD 21205 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Mukhin, AG (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Ctr Nicotine & Smoking Cessat Res, 2424 Erwin Rd,Suite 201, Durham, NC 27705 USA. EM a.mukhin@duke.edu FU Intramural NIH HHS NR 47 TC 11 Z9 11 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 2 BP 270 EP 278 DI 10.1038/sj.npp.1301404 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 239SN UT WOS:000251538100007 PM 17429408 ER PT J AU Sjoberg, RL Ducci, F Barr, CS Newman, TK Dell'Osso, L Virkkunen, M Goldman, D AF Sjoberg, Rickard L. Ducci, Francesca Barr, Christina S. Newman, Timothy K. Dell'Osso, Liliana Virkkunen, Matti Goldman, David TI A non-additive interaction of a functional MAO-A VNTR and testosterone predicts antisocial behavior SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE antisocial personality disorder; antisocial behavior; MAO-A gene; testosterone; gene by hormone interaction; MHPG ID MONOAMINE-OXIDASE-A; GENE PROMOTER; CEREBROSPINAL-FLUID; GLUCOSE-METABOLISM; SEX-DIFFERENCES; AGGRESSION; GENOTYPE; POLYMORPHISM; METAANALYSIS; CHILDHOOD AB A functional VNTR polymorphism in the promoter of the monoamine oxidase A gene (MAOA-LPR) has previously been shown to be an important predictor of antisocial behavior in men. Testosterone analogues are known to interact with the MAOA promoter in vitro to influence gene transcription as well as in vivo to influence CSF levels of the MAO metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in human males. We examined the possible joint effects of testosterone (measured in CSF) and MAOA-LPR genotype on antisocial personality disorder and scores on the Brown-Goodwin Aggression scale in 95 unrelated male criminal alcoholics and 45 controls. The results confirm that MAOA genotype and CSF testosterone interact to predict antisocial behaviors. The MAOA/testosterone interaction also predicted low levels of CSF MHPG, which tentatively suggests the possibility that the interaction may be mediated by a direct effect on gene transcription. If replicated these findings offer plausible explanations for previous inconsistencies in studies of the relationship between testosterone and male human aggression, as well as for how MAOA genotype may influence aggressive behavior in human males. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Uppsala Univ, Clin Res Ctr, Cent Hosp, Vasteras, Sweden. NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD USA. Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. Univ Pisa, Dept Psychiat, Pisa, Italy. Univ Helsinki, Dept Psychiat, Sch Med, SF-00180 Helsinki, Finland. RP Sjoberg, RL (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA. EM sjobergr@mail.nih.gov RI Sjoberg, Rickard/B-9337-2008; Sjoberg, Rickard/M-4690-2014; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS [Z01 AA000306-02] NR 34 TC 60 Z9 63 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2008 VL 33 IS 2 BP 425 EP 430 DI 10.1038/sj.npp.1301417 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 239SN UT WOS:000251538100023 PM 17429405 ER PT J AU Mazzocchio, R Meunier, S Ferrante, S Molteni, F Cohen, LG AF Mazzocchio, Riccardo Meunier, Sabine Ferrante, Simona Molteni, Franco Cohen, Leonardo G. TI Cycling, a tool for locomotor recovery after motor lesions? SO NEUROREHABILITATION LA English DT Review ID SPINAL-CORD-INJURY; SOLEUS H-REFLEX; POSITIVE FORCE FEEDBACK; SINUSOIDAL HIP MOVEMENTS; LOW-FREQUENCY DEPRESSION; ADULT SQUIRREL-MONKEYS; ELECTRICAL-STIMULATION; PARAPLEGIC PATIENTS; PATTERN GENERATORS; LOWER-EXTREMITY C1 [Mazzocchio, Riccardo] Univ Siena, Sez Neurofisiol Clin, Dipartimento Sci Neurol & Comportamento, Policlin Le Scotte, I-53100 Siena, Italy. [Meunier, Sabine] INSERM, UMRS 731, Paris, France. [Meunier, Sabine] Univ Paris 06, UMRS 731, Paris, France. [Ferrante, Simona] Politecn Milan, Dept Bioengn, NITLAB, I-20133 Milan, Italy. [Molteni, Franco] Osped Valduce, Ctr Riabilitaz Villa Beretta, Lecce, Italy. [Cohen, Leonardo G.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD USA. [Cohen, Leonardo G.] Natl Inst Neurol Disorders & Stroke, Stroke Neurorehabil Clin, NIH, Bethesda, MD USA. RP Mazzocchio, R (reprint author), Univ Siena, Sez Neurofisiol Clin, Dipartimento Sci Neurol & Comportamento, Policlin Le Scotte, Viale Bracci, I-53100 Siena, Italy. EM mazzocchio@unisi.it RI meunier, sabine/G-7622-2014; Mazzocchio, Riccardo/H-4223-2012; Ferrante, Simona/K-4122-2016 OI meunier, sabine/0000-0002-6167-4602; Mazzocchio, Riccardo/0000-0002-0628-2868; Ferrante, Simona/0000-0002-7835-1965 FU Intramural NIH HHS NR 136 TC 11 Z9 11 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 EI 1878-6448 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2008 VL 23 IS 1 BP 67 EP 80 PG 14 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 284XE UT WOS:000254739800007 PM 18356590 ER PT J AU Marsh, AA Blair, RJR AF Marsh, Abigail A. Blair, R. J. R. TI Deficits in facial affect recognition among antisocial populations: A meta-analysis SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE facial affect; fearful expression; antisocial; amygdala; psychopathy; emotion; meta-analysis ID COGNITIVE NEUROSCIENCE PERSPECTIVE; BORDERLINE PERSONALITY-DISORDER; BILATERAL AMYGDALA DAMAGE; EMOTION RECOGNITION; EXPRESSION RECOGNITION; NEURAL RESPONSES; FEAR-RECOGNITION; PSYCHOPATHIC TENDENCIES; MENTAL-RETARDATION; CHILDREN AB Individuals with disorders marked by antisocial behavior frequently show deficits in recognizing displays of facial affect. Antisociality may be associated with specific deficits in identifying fearful expressions, which would implicate dysfunction in neural structures that subserve fearful expression processing. A meta-analysis of 20 studies was conducted to assess: (a) if antisocial populations show any consistent deficits in recognizing six emotional expressions; (b) beyond any generalized impairment, whether specific fear recognition deficits are apparent; and (c) if deficits in fear recognition are a function of task difficulty. Results show a robust link between antisocial behavior and specific deficits in recognizing fearful expressions. This impairment cannot be attributed solely to task difficulty. These results suggest dysfunction among antisocial individuals in specified neural substrates, namely the amygdala, involved in processing fearful facial affect. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Marsh, Abigail A.; Blair, R. J. R.] NIH, NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Marsh, AA (reprint author), NIH, NIMH, Mood & Anxiety Program, Bldg 10,15k N Dr,MSC 2670, Bethesda, MD 20892 USA. EM marsha@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 97 TC 250 Z9 255 U1 10 U2 69 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2008 VL 32 IS 3 BP 454 EP 465 DI 10.1016/j.neubiorev.2007.08.003 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 265ZM UT WOS:000253400600011 PM 17915324 ER PT J AU Kobayashi, T Kai, N Kobayashi, K Fujiwara, T Akagawa, K Onda, M Pastan, I Kobayashi, K AF Kobayashi, Tomoko Kai, Nobuyuki Kobayashi, Kenta Fujiwara, Tomonori Akagawa, Kimio Onda, Masanori Pastan, Ira Kobayashi, Kazuto TI Functional analysis of the striatopallidal neural pathway by conditional transmission silencing SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Kobayashi, Tomoko; Kai, Nobuyuki; Kobayashi, Kenta; Kobayashi, Kazuto] Fukushima Med Univ, Dept Mol Geret, Fukushima, Japan. [Kobayashi, Tomoko; Kobayashi, Kazuto] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama, Japan. [Fujiwara, Tomonori; Akagawa, Kimio] Kyorin Univ, Dept Cell Physiol, Mitaka, Tokyo, Japan. [Onda, Masanori; Pastan, Ira] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2008 VL 61 BP S240 EP S240 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 381PJ UT WOS:000261548101571 ER PT J AU Maier, A Wilke, M Aura, C Zhu, C Ye, FQ Leopold, DA AF Maier, Alexander Wilke, Melanie Aura, Christopher Zhu, Charles Ye, Frank Q. Leopold, David A. TI What happens in primary visual cortex when a stimulus becomes visible? Insights from fMRI and layer-specific neurophysiology in non-human primates SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Maier, Alexander; Wilke, Melanie; Aura, Christopher; Leopold, David A.] NIMH, LICNI, LN, NIH, Bethesda, MD 20892 USA. [Zhu, Charles; Ye, Frank Q.; Leopold, David A.] NIMH, NIF, LN, NIH, Bethesda, MD 20892 USA. RI Maier, Alexander/B-7489-2009 OI Maier, Alexander/0000-0002-7250-502X 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 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2008 VL 61 BP S32 EP S32 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 381PJ UT WOS:000261548100188 ER PT J AU Minamimoto, T Saunders, RC Richmond, BJ AF Minamimoto, Takafumi Saunders, Richard C. Richmond, Barry J. TI Rapid learning of visual categories without lateral prefrontal cortex in monkeys SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Minamimoto, Takafumi; Saunders, Richard C.; Richmond, Barry J.] Natl Inst Radiol Sci, Chiba 260, Japan. [Minamimoto, Takafumi; Saunders, Richard C.; Richmond, Barry J.] NIMH, NIH, Bethesda, MD 20892 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 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2008 VL 61 BP S119 EP S119 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 381PJ UT WOS:000261548100709 ER PT J AU Nagai, N Li, XR Matsuo, O AF Nagai, Nobuo Li, Xuri Matsuo, Osamu TI VEGF-B is an anti-apoptotic factor on neuronal cells SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Nagai, Nobuo; Matsuo, Osamu] Kinki Univ, Higashiosaka, Osaka 577, Japan. [Li, Xuri] NEI, Unit Vasc Retinal Neurobiol Res, NIH, Porter Neurosci Res Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2008 VL 61 BP S237 EP S237 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 381PJ UT WOS:000261548101555 ER PT J AU Tanaka, S Honda, M Hanakawa, T Cohen, LG AF Tanaka, Satoshi Honda, Manabu Hanakawa, Takashi Cohen, Leonardo G. TI Practice schedule and motor consolidation SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Tanaka, Satoshi; Cohen, Leonardo G.] NINDS, NIH, Bethesda, MD 20892 USA. [Honda, Manabu; Hanakawa, Takashi] NCNP, NINS, Dept Cort Funct Disorder, Kodaira, Tokyo, Japan. 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 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2008 VL 61 BP S113 EP S113 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 381PJ UT WOS:000261548100675 ER PT J AU Tanji, K Leopold, D Ye, F Zhu, C Malloy, M Saunders, R Mishkin, M AF Tanji, Kazuyo Leopold, David Ye, Frank Zhu, Charles Malloy, Megan Saunders, Richard Mishkin, Mortimer TI Sound-level dependent activation in the macaque auditory cortex: An fMRI study SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Tanji, Kazuyo; Leopold, David; Ye, Frank; Zhu, Charles; Malloy, Megan; Saunders, Richard; Mishkin, Mortimer] NIMH, Bethesda, MD 20892 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 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2008 VL 61 BP S64 EP S64 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 381PJ UT WOS:000261548100381 ER PT J AU Toda, K Sugase-Miyamoto, Y Mizuhiki, T Richmond, BJ Shidara, M AF Toda, Koji Sugase-Miyamoto, Yasuko Mizuhiki, Takashi Richmond, Barry J. Shidara, Munetaka TI Interaction between reward size and trial number on performance of reward schedules of the monkey SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Toda, Koji; Mizuhiki, Takashi; Shidara, Munetaka] Univ Tsukuba, Tsukuba, Ibaraki, Japan. [Toda, Koji; Sugase-Miyamoto, Yasuko; Shidara, Munetaka] AIST, Tsukuba, Ibaraki, Japan. [Richmond, Barry J.] NIMH, Neurophysiol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2008 VL 61 BP S115 EP S115 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 381PJ UT WOS:000261548100683 ER PT J AU Smith, LM LaGasse, LL Derauf, C Grant, P Shah, R Arria, A Huestis, M Haning, W Strauss, A Della Grotta, S Fallone, M Liu, J Lester, BM AF Smith, Lynne M. LaGasse, Linda L. Derauf, Chris Grant, Penny Shah, Rizwan Arria, Amelia Huestis, Marilyn Haning, William Strauss, Arthur Della Grotta, Sheri Fallone, Melissa Liu, Jing Lester, Barry M. TI Prenatal methamphetamine use and neonatal neurobehavioral outcome SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE prenatal exposure; neurodevelopment; drug; meconium ID MATERNAL LIFE-STYLE; COCAINE EXPOSURE; SUBSTANCE EXPOSURE; IN-UTERO; PREGNANCY; CHILDREN; AMPHETAMINE; ALCOHOL; INFANTS; SMOKING AB Background: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How prenatal MA exposure affects neonatal neurobehavior is unknown. Objective: To examine the neurobehavioral effects of prenatal MA exposure. Design: The Infant Development, Environment and Lifestyle (IDEAL) study screened 13,808 subjects and 1632 were eligible and consented. 166 (n = 74 exposed) were enrolled in a longitudinal follow-up. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life. Analyses conducted on NNNS summary scores included exposure group effects, heavy MA use effects, association with frequency of use by trimester, and dose-response relationships with amphetamine metabolites. Results: After adjusting for covariates, exposure to MA was associated with increased physiological stress. Heavy MA use was related to lower arousal, more lethargy, and increased physiological stress. First trimester MA use was related to elevated stress abstinence. Third trimester use was related to poorer quality of movement. Higher level of amphetamine metabolites in meconium was associated with increased CNS stress. Conclusions: Prenatal MA exposure was associated with neurobehavioral patterns of decreased arousal, increased stress, and poor quality of movement. The dose-response relationships may represent neurotoxic effects from MA. (c) 2007 Elsevier Inc. All rights reserved. C1 [Smith, Lynne M.] Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Los Angeles Biomed Inst, Torrance, CA 90502 USA. [Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Torrance, CA USA. [LaGasse, Linda L.; Della Grotta, Sheri; Fallone, Melissa; Liu, Jing; Lester, Barry M.] Brown Med Sch, Providence, RI 02912 USA. [LaGasse, Linda L.; Della Grotta, Sheri; Fallone, Melissa; Liu, Jing; Lester, Barry M.] Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA. [Derauf, Chris; Haning, William] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Grant, Penny] Univ Oklahoma, Norman, OK 73019 USA. [Shah, Rizwan] Iowa Hlth Des Moines, Blank Childerns Hosp, Iowa City, IA 52242 USA. [Arria, Amelia] Univ Maryland, College Pk, MD 20742 USA. [Huestis, Marilyn] Natl Inst Drug Abuse, Sect Chem & Drug Metab, Bethesda, MD 20892 USA. [Strauss, Arthur] Long Beach Mem Med Ctr, Long Beach, CA 90806 USA. RP Smith, LM (reprint author), Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Los Angeles Biomed Inst, 1124 W Carson St,Box 446, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU NCRR NIH HHS [P20 RR11091, P20 RR011091, M01 RR000425-36, M01 RR000425, 3 M01 RR00425]; NIDA NIH HHS [1R01DA014918, R01 DA014948-06, R01 DA014948] NR 49 TC 95 Z9 95 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2008 VL 30 IS 1 BP 20 EP 28 DI 10.1016/j.ntt.2007.09.005 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 265NG UT WOS:000253365700002 PM 18031987 ER PT J AU Mueller, E Wei, J Nygaard, I Brubaker, L Varner, E Visco, A Cundiff, GW Weber, AM Ghetti, C Kreder, K AF Mueller, Elizabeth Wei, John Nygaard, Ingrid Brubaker, Linda Varner, Ed Visco, Anthony Cundiff, Geoffrey W. Weber, Anne M. Ghetti, Chiara Kreder, Karl TI The correlation of voiding variables between non-instrumented uroflowmetery and pressure-flow studies in women with pelvic organ prolapse SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE non-instrumented uroflow study; obstruction; pelvic organ prolapse; pressure-flow study; urodynamics; voiding ID BLADDER OUTLET OBSTRUCTION; URINARY-INCONTINENCE; PREVALENCE; PARAMETERS AB Aims: To (1) correlate peak and maximum flow rates from non-instrumented flow (NIF) and pressure-flow studies (PFS) in women with pelvic organ prolapse (POP); (2) measure the impact of voided volume and degree of prolapse on correlations. Methods: We compared four groups of women with stages II-IV POP. Groups 1 and 2 were symptomatically stress continent women participating in the colpopexy and urinary reduction efforts (CARE) trial; during prolapse reduction before sacrocolpopexy, Group 1 (n = 67) did not have and Group 2 (n = 84) had urodynamic stress incontinence (USI). Group 3 (n 74) and Group 4 participants (n = 73), recruited specifically for this study, had stress urinary incontinence (SUI) symptoms. Group 3 planned sacrocolpopexy. Group 4 planned a different treatment option. Participants completed standardized uroflowmetry and pressure voiding studies. Results: Subjects' median age was 61 years; median parity 3% and 80% had stage III or IV POP. Based on the Blaivas-Groutz nomogram, 49% of all women were obstructed. NIF and PFS peak and average flow rates had low correlations with one another (0.31, P < 0.001 and 0.35, P < 0.001, respectively). When NIF and PFS voided volumes were within 25% of each other, the peak and average flow rate correlations improved (0.52, P < 0.001 and 0.57, P < 0.001, respectively). As vaginal prolapse increased, correlations between NIF and PFS peak and average flow rates decreased. Conclusion: Peak and average flow rates are highly dependent on voided volume in women with prolapse. As the prolapse stage increases, correlations between NIF and PFS variables decrease. C1 [Mueller, Elizabeth; Brubaker, Linda] Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA. [Mueller, Elizabeth; Brubaker, Linda] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. [Wei, John] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Nygaard, Ingrid] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Varner, Ed] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Visco, Anthony] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Cundiff, Geoffrey W.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. [Weber, Anne M.] NICHHD, NIH, Bethesda, MD 20892 USA. [Ghetti, Chiara] Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Kreder, Karl] Univ Iowa, Dept Urol, Carver Coll Med, Iowa City, IA 52242 USA. RP Mueller, E (reprint author), Loyola Univ, Med Ctr, Dept Urol, 2160 S 1st Ave,Bldg 103,Room 1004, Maywood, IL 60153 USA. EM emuelle@lumc.edu OI Mueller, Elizabeth R./0000-0003-3069-4069 FU NICHD NIH HHS [U10 HD41269, U10 HD41248, U10HD41261, U10 HD41268, U01 HD41249, U10 HD041261, U10 HD41267, U10 HD41263, U10 HD41250] NR 24 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2008 VL 27 IS 6 BP 515 EP 521 DI 10.1002/nau.20568 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 335GJ UT WOS:000258278500012 PM 18551567 ER PT J AU Fitzgerald, MP Anderson, RU Payne, CK Peters, KM Clemens, JQ Potts, J Cen, L Chuai, S Kusek, JW Nyberg, LM AF Fitzgerald, M. P. Anderson, R. U. Payne, C. K. Peters, K. M. Clemens, J. Q. Potts, J. Cen, L. Chuai, S. Kusek, J. W. Nyberg, L. M. CA Urologic Pelvic Pain Collaborative TI Randomized multicenter pilot trial shows benefit of manual physical therapies in treatment of urologic chronic pelvic pain SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 38th Annual Meeting of the International-Continence-Society CY OCT 20-24, 2008 CL Cairo, EGYPT SP Int Continence Soc C1 [Fitzgerald, M. P.] Loyola Univ Med Ctr, Sch Med, Maywood, IL 60153 USA. [Anderson, R. U.; Payne, C. K.] Stanford Univ, Stanford, CA 94305 USA. [Peters, K. M.] Beaumont Hosp, Feinberg Sch Med, Deroit, MI USA. [Clemens, J. Q.] Northwestern Univ, Evanston, IL 60208 USA. [Potts, J.] Cleveland Clin, Cleveland, OH 44106 USA. [Cen, L.; Chuai, S.] Univ Penn, Philadelphia, PA 19104 USA. [Kusek, J. W.; Nyberg, L. M.] NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2008 VL 27 IS 7 MA 96 BP 684 EP 684 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 347BU UT WOS:000259114800097 ER PT J AU Abroms, LC Windsor, R Simons-Morton, B AF Abroms, Lorien C. Windsor, Richard Simons-Morton, Bruce TI Getting young adults to quit smoking: A formative evaluation of the X-Pack Program SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID YOUTH TOBACCO CESSATION; COLLEGE-STUDENTS; INTERVENTION; INTERNET; SMOKERS; INFORMATION; ADOLESCENT; MESSAGES; TRIAL; TOOL AB The lack of promising smoking cessation interventions targeting young adults is a recognized public health problem. This study was designed to determine the feasibility of a young-adult-oriented program, the X-Pack Program, when administered to college student smokers, and to estimate its effect on smoking cessation. Participants (N=83) were randomized after enrollment to receive either a moderately intensive, E-mail-based, young-adult intervention (the X-Pack group) or a less-intensive program aimed at a general adult audience (the Clearing the Air group). Participants were assessed at baseline and at 3 and 6 months after enrollment. Participants in the X-Pack group rated their treatment more favorably overall, were more engaged in program activities, and quit for more consecutive days at the 3- and 6-month follow-ups, compared with the Clearing the Air group. Differences in quit rates favored the X-Pack group at the two follow-ups, but the differences were not significant. These findings offer some support for the X-Pack Program when administered to college smokers. C1 [Abroms, Lorien C.; Windsor, Richard] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA. [Simons-Morton, Bruce] Natl Inst Hlth, Bethesda, MD USA. RP Abroms, LC (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, 2175 K St,NW 7th Floor, Washington, DC 20037 USA. EM lorien@gwu.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z01 HD002110-16]; NIMHD NIH HHS [263-MD-501757] NR 35 TC 18 Z9 18 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 1 BP 27 EP 33 DI 10.1080/14622200701767852 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 251AN UT WOS:000252342800003 PM 18188742 ER PT J AU Chriqui, JF Ribisl, KM Wallace, RM Williams, RS O'Connor, JC el Arculli, R AF Chriqui, Jamie F. Ribisl, Kurt M. Wallace, Raedell M. Williams, Rebecca S. O'Connor, Jean C. el Arculli, Regina TI A comprehensive review of state laws governing Internet and other delivery sales of cigarettes in the United States SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID WESTERN NEW-YORK; TOBACCO CONTROL; RATING SYSTEM; YOUTH-ACCESS; STUDENTS; WEB; USA AB All U.S. states regulate face-to-face tobacco sales at retail outlets. However, the recent growth of delivery sales of tobacco products by Internet and mail-order vendors has prompted new state regulations focused on preventing youth access and tax evasion. To date, there are no comprehensive and systematic analyses of these laws. The objectives of this study were to: (a) document the historical enactment of the laws; (b) assess the nature and extent of the laws; and (c) examine the relationship between the presence of laws and state tobacco control policy and other contextual variables. Between 1992 and 2006, 34 states (67%) enacted a relevant law, with 27 states' laws (45%) effective between 2003 and 2006. Five states banned direct-to-consumer shipment of cigarettes. The remaining 29 states' laws included a combination of requirements addressing minimum age/ID, payment issues, shipping, vendor licensure and related issues, tax collection/remittance, and penalties/enforcement. States with delivery sales laws have stronger youth tobacco access policies and state tobacco control environments, as well as higher state cigarette excise tax rates and revenue, past-month cigarette use rates, and perceptions of risk of use by adolescents. This paper provides the policy context for understanding Internet and other cigarette delivery sales laws in the U.S. It also provides a systematic framework for ongoing policy surveillance and will contribute to future analyses of the impact of these laws on successfully reducing youth access to cigarettes and preventing tax evasion. C1 [Chriqui, Jamie F.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60608 USA. [Chriqui, Jamie F.] MayaTech Corp, Silver Spring, MD USA. [Ribisl, Kurt M.] Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. [Ribisl, Kurt M.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA. [Williams, Rebecca S.] Univ N Carolina, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC USA. [O'Connor, Jean C.] Emory Univ, Atlanta, GA 30322 USA. [el Arculli, Regina] NCI, NIH, Bethesda, MD USA. RP Chriqui, JF (reprint author), Univ Illinois, Inst Hlth Res & Policy, 1747 W Roosevelt Rd,M-C 275,Room 558, Chicago, IL 60608 USA. EM jchriqui@uic.edu RI Ribisl, Kurt/C-4867-2015 OI Ribisl, Kurt/0000-0003-3318-8524 FU NCI NIH HHS [N02-CO-21017, N02CO21017] NR 40 TC 12 Z9 12 U1 2 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 2 BP 253 EP 265 DI 10.1080/14622200701838232 PG 13 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 259IJ UT WOS:000252932700002 PM 18236290 ER PT J AU Kaufman, DJ Roman, MJ Devereux, RB Fabsitz, RR MacCluer, JW Dyke, B Ebbesson, SOE Wenger, CR Romanesko, T Comuzzie, AG Howard, BV AF Kaufman, David J. Roman, Mary J. Devereux, Richard B. Fabsitz, Richard R. MacCluer, Jean W. Dyke, Bennett Ebbesson, Sven O. E. Wenger, Charlotte R. Romanesko, Terry Comuzzie, Anthony G. Howard, Barbara V. TI Prevalence of smoking and its relationship with carotid atherosclerosis in Alaskan Eskimos of the Norton Sound region: The GOCADAN Study SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID BERING STRAITS REGION; SIBERIA PROJECT; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; RISK-FACTORS; WEIGHT-GAIN; OBESITY; HYPERTENSION; ASSOCIATION; CESSATION AB Since 2000, the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study has been collecting information on cardiovascular disease (CVD) and its risk factors from 1,214 Alaska Natives of the Norton Sound region, a population with increasing rates of heart disease and stroke. Because smoking was reported in a large proportion of the participants, this analysis was undertaken to evaluate smoking patterns and their relation to other risk factors and to CVD. The relationships among smoking habits and demographic factors, body mass index, plasma fibrinogen, prevalent hypertension, and carotid plaque were evaluated. Eighty percent of participants had smoked 100+ cigarettes in their lifetime. Fifty-seven percent of women and 63% of men (p=.12) were current smokers: one in four smokers had quit. Current smokers (OR=2.1; 95% CI=1.1-3.8) and those who had quit <5 years ago (OR=1.6; 95% CI=1.1-2.2) were more likely than non-smokers to have carotid plaque. Pack-years smoked also were correlated with carotid plaque. The high prevalence of smoking and low rates of cessation in this population demonstrate an urgent need for smoking prevention and cessation programs among Alaskan Eskimos of the Norton Sound region and other Alaska Native groups. C1 [Kaufman, David J.] Johns Hopkins Univ, Washington, DC USA. [Devereux, Richard B.] Cornell Univ, Weill Med Coll, New York, NY USA. [Fabsitz, Richard R.] NHLBI, Rockville, MD USA. [Dyke, Bennett; Wenger, Charlotte R.; Comuzzie, Anthony G.] Southwest Fdn Biomed Res, San Antonio, TX USA. [Ebbesson, Sven O. E.; Romanesko, Terry] Norton Sound Hlth Corp, Nome, AK USA. [Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD 20783 USA. RP Howard, BV (reprint author), MedStar Res Inst, 6495 New Hampshire Ave,Suite 201, Hyattsville, MD 20783 USA. EM Barbara.V.Howard@MedStar.net FU NHLBI NIH HHS [U01 HL064244-05, U01 HL041642, U01 HL064244] NR 32 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 3 BP 483 EP 491 DI 10.1080/14622200801901955 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 271BH UT WOS:000253763400012 PM 18324567 ER PT J AU Willis, G Lawrence, D Hartman, A Kudela, MS Levin, K Forsyth, B AF Willis, Gordon Lawrence, Deirdre Hartman, Anne Kudela, Martha Stapleton Levin, Kerry Forsyth, Barbara TI Translation of a tobacco survey into Spanish and Asian languages: The Tobacco Use Supplement to the Current Population Survey SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID DIVERSE POPULATIONS; UNITED-STATES; QUALITY; ENGLISH; ACCULTURATION; QUESTIONNAIRE; ISSUES AB Because of the vital need to attain cross-cultural comparability of estimates of tobacco use across subgroups of the U.S. population that differ in primary language use, the National Cancer Institute (NCI) Tobacco Use Special Cessation Supplement to the Current Population Survey (TUSCS-CPS) was translated into Spanish, Chinese (Mandarin and Cantonese), Korean, Vietnamese, and Khmer (Cambodian). The questionnaire translations were extensively tested using an eight-step process that focused on both translation procedures and empirical pretesting. The resulting translations are available on the Internet at http://riskfactor.cancer.gov/studies/tus-cps/translation/questionnaires.html for tobacco researchers to use in their own surveys, either in full, or as material to be selected as appropriate. This manuscript provides information to guide researchers in accessing and using the translations, and describes the empirical procedures used to develop and pretest them (cognitive interviewing and behavior coding). We also provide recommendations concerning the further development of questionnaire translations. C1 [Willis, Gordon] NCI, ARP, DCCPS, NIH, Bethesda, MD 20892 USA. RP Willis, G (reprint author), NCI, ARP, DCCPS, NIH, 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. EM willisg@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N02-PC-54407, N02PC54407] NR 50 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 6 BP 1075 EP 1084 DI 10.1080/14622200802087572 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 319EH UT WOS:000257146400015 PM 18584471 ER PT J AU Kaufman, AR Augustson, EM AF Kaufman, Annette R. Augustson, Erik M. TI Predictors of regular cigarette smoking among adolescent females: Does body image matter? SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID WEIGHT CONTROL BEHAVIORS; SELF-ESTEEM; CONTROL STRATEGY; YOUNG-WOMEN; MASS INDEX; GIRLS; INITIATION; GENDER; OBESITY; ADULTS AB This study examined how factors associated with body image predict regular smoking in adolescent females. Data were from the National Longitudinal Study of Adolescent Health (Add Health), a study of health-related behaviors in a nationally representative sample of adolescents in grades 7 through 12. Females in Waves I and II (n=6,956) were used for this study. Using SUDAAN to adjust for the sampling frame, univariate and multivariate analyses were performed to investigate if baseline body image factors, including perceived weight, perceived physical development, trying to lose weight, and self-esteem, were predictive of regular smoking status 1 year later. In univariate analyses, perceived weight (p <.01), perceived physical development (p.0001), trying to lose weight (p <.05), and self-esteem (p <.0001) significantly predicted regular smoking 1 year later. In the logistic regression model, perceived physical development (p <.05), and self-esteem (p <.001) significantly predicted regular smoking. The more developed a female reported being in comparison to other females her age, the more likely she was to be a regular smoker. Lower self-esteem was predictive of regular smoking. Perceived weight and trying to lose weight failed to reach statistical significance in the multivariate model. This current study highlights the importance of perceived physical development and self-esteem when predicting regular smoking in adolescent females. Efforts to promote positive self-esteem in young females may be an important strategy when creating interventions to reduce regular cigarette smoking. C1 [Kaufman, Annette R.; Augustson, Erik M.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kaufman, Annette R.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. RP Kaufman, AR (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Executive Blvd,Ste 4039 MSC 7337, Bethesda, MD 20892 USA. EM kaufmana@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01 CO 12400, N01CO12400]; NICHD NIH HHS [P01 HD 31921, P01 HD031921] NR 48 TC 18 Z9 18 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 8 BP 1301 EP 1309 DI 10.1080/14622200802238985 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 335BL UT WOS:000258265700005 PM 18686177 ER PT J AU Green, KJ Hunter, CM Bray, RM Pemberton, M Williams, J AF Green, Kathy J. Hunter, Christine M. Bray, Robert M. Pemberton, Michael Williams, Jason TI Peer and role model influences for cigarette smoking in a young adult military population SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID RISK-FACTORS; NATURAL-HISTORY; UNITED-STATES; ALCOHOL-USE; CESSATION; TOBACCO; ADOLESCENT; PREVALENCE; PREDICTORS; INITIATION AB Previous research has shown that 8% to 10% of nonsmokers initiated smoking during their first year of military service despite a period of forced abstinence during boot camp. To our knowledge, no studies have looked at the influence of peers and role models on the initiation of smoking among U.S. Air Force personnel who recently completed boot camp. This cross-sectional study examined the role of perceived peer norms, roommate influence, role model influence, perceived norms of all active duty personnel, and depressive symptoms in the initiation and reinitiation of smoking among 2,962 Air Force technical training students. Previous nonsmokers were more likely to initiate smoking if they perceived that the majority of their classmates smoked (OR=1.67, 95% CI[1.05-2.67]) and if they reported that their military training leader or classroom instructor used tobacco products (OR=1.69, 95% CI[1.12-2.56]). Additionally, previous nonsmokers were more likely to initiate smoking if their roommate smoked (OR=1.67, 95% CI[1.09-2.56]). Similar results were seen with previous smokers who perceived that the majority of their classmates smoked (OR=1.63, 95% CI[1.03-2.58]) and if they reported that their military training leader or classroom instructor used tobacco products (OR=1.95, 95% CI[1.29-2.94]). Our study suggests that military role models who use tobacco, peer smoking behavior, and perceived smoking norms increase the likelihood of smoking initiation among newly enlisted military personnel who have recently undergone a period of forced abstinence. C1 [Green, Kathy J.] USAF, Med Operat Agcy, Off Surg Gen, Washington, DC 20032 USA. [Hunter, Christine M.] NIDDK, Div Diabet Endocrinol & Metab Dis, Bethesda, MD USA. [Bray, Robert M.; Pemberton, Michael; Williams, Jason] RTI Int, Res Triangle Pk, NC USA. RP Green, KJ (reprint author), USAF, Med Operat Agcy, Off Surg Gen, 110 Luke Ave,Room 405, Washington, DC 20032 USA. EM kathy.green@pentagon.af.mil OI Williams, Jason/0000-0002-3804-2594 FU USAMARMC Fort Detrick Peer Reviewed Medical Research Program [DAMD17-00-1-0581.]; Uniformed Services University of the Health Sciences FX Data collection was performed by RTI International (a trade name of Research Triangle Institute). Analysis and write-up were performed at RTI, Uniformed Services University of the Health Sciences, and Bolling AFB, DC. The views, opinions, and findings contained in this report are those of the authors and should not be construed as an official position, policy or decision of the Department of Army, Department of the Air Force, Department of Defense, or the US Government unless so designated by other official documentation. This study was supported by USAMARMC Fort Detrick Peer Reviewed Medical Research Program grant number DAMD17-00-1-0581.; The authors thank Dr. Dana Bradshaw, Uniformed Services University of the Health Sciences, who provided valuable support with the concept and design of this project. The authors report no competing interests. NR 43 TC 16 Z9 16 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 10 BP 1533 EP 1541 DI 10.1080/14622200802398763 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 363IA UT WOS:000260259800002 PM 18946772 ER PT J AU Rutten, LJF Augustson, EM Moser, RP Beckjord, EB Hesse, BW AF Rutten, Lila J. Finney Augustson, Erik M. Moser, Richard P. Beckjord, Ellen Burke Hesse, Bradford W. TI Smoking knowledge and behavior in the United States: Sociodemographic, smoking status, and geographic patterns SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID UNREALISTIC OPTIMISM; CIGARETTE SMOKERS; RISK; FUTURE; CANCER AB Smoking is the leading cause of preventable death in the United States and has been linked to several dire health consequences including cancer and cardiovascular disease. However, knowledge of the associated risks of tobacco use may not be evenly distributed within the population. We analyzed data from the National Cancer Institute's Health Information National Trends Survey (HINTS, 2003) to characterize current knowledge of cancer prevention and smoking risk in the adult U.S. population and to identify associated sociodemographic, smoking status, and geographic factors. To account for the complex survey design of HINTS, SUDAAN was used to calculate population estimates and confidence intervals. Geographic Information System (GIS) isopleth maps were generated to examine smoking behavior and knowledge. Females, non-Hispanic Whites, those with higher incomes, and former smokers (compared with current smokers) were more likely to reject smoking myths. More accurate smoking risk beliefs were reported by respondents with some college (OR=1.76) and college degrees (OR=2.13) compared with those with less than a high school education. Former smokers (OR=2.53) and never-smokers (OR=3.26) reported more accurate risk beliefs than current smokers. Knowledge of lung cancer mortality was lower among females (OR=0.38), older adults (OR age 65-79=0.69; OR age 80+=0.48), and non-Hispanic Blacks (OR=0.64). GIS analyses revealed lower knowledge of smoking risk and higher tobacco use in the regions with higher tobacco production and higher tobacco-related mortality. Disparities in tobacco-related knowledge, morbidity, and mortality underscore the need for continued development and delivery of effective prevention and treatment interventions to reduce the population burden of tobacco-related disease. C1 [Rutten, Lila J. Finney; Augustson, Erik M.; Moser, Richard P.; Hesse, Bradford W.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Commun & Informat Res Branch,NIH, Bethesda, MD 20892 USA. [Beckjord, Ellen Burke] RAND Corp, Pittsburgh, PA USA. RP Rutten, LJF (reprint author), 6130 Execut Blvd,Suite 4078,MSC 7365, Bethesda, MD 20892 USA. EM finneyl@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 FU NIH [NO2-PC-35023] FX This research was funded, in part, by NIH Contract NO2-PC-35023. The authors do not have any conflict of interest to report. NR 27 TC 38 Z9 38 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 10 BP 1559 EP 1570 DI 10.1080/14622200802325873 PG 12 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 363IA UT WOS:000260259800005 PM 18946775 ER PT J AU Ziedonis, D Hitsman, B Beckham, J Zvolensky, M Adler, L Audrain-McGovern, J Breslau, N Brown, R George, T Williams, J Calhoun, P Riley, W AF Ziedonis, Douglas Hitsman, Brian Beckham, Jean C. Zvolensky, Michael Adler, Lawrence E. Audrain-McGovern, Janet Breslau, Naomi Brown, Richard A. George, Tony P. Williams, Jill Calhoun, Patrick S. Riley, William T. TI Tobacco use and cessation in psychiatric disorders: National Institute of Mental Health report SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; PLACEBO-CONTROLLED TRIAL; DEFICIT HYPERACTIVITY DISORDER; ADOLESCENT SMOKING PROGRESSION; NICOTINIC RECEPTOR MECHANISMS; BUPROPION SUSTAINED-RELEASE; SELF-MEDICATION HYPOTHESIS; INCREASES ABSTINENCE RATES AB The National Institute of Mental Health (NIMH) convened a meeting in September 2005 to review tobacco use and dependence and smoking cessation among those with mental disorders, especially individuals with anxiety disorders, depression, or schizophrenia. Smoking rates are exceptionally high among these individuals and contribute to the high rates of medical morbidity and mortality in these individuals. Numerous biological, psychological, and social factors may explain these high smoking rates, including the lack of smoking cessation treatment in mental health settings. Historically, self-medication and individual rights have been concerns used to rationalize allowing ongoing tobacco use and limited smoking cessation efforts in many mental health treatment settings. Although research has shown that tobacco use can reduce or ameliorate certain psychiatric symptoms, overreliance on the self-medication hypothesis to explain the high rates of tobacco use in psychiatric populations may result in inadequate attention to other potential explanations for this addictive behavior among those with mental disorders. A more complete understanding of nicotine and tobacco use in psychiatric patients also can lead to new psychiatric treatments and a better understanding of mental illness. Greater collaboration between mental health researchers and nicotine and tobacco researchers is needed to better understand and develop new treatments for cooccurring nicotine dependence and mental illness. Despite an accumulating literature for some specific psychiatric disorders and tobacco use and cessation, many unstudied research questions remain and are a focus and an emphasis of this review. C1 [Ziedonis, Douglas] UMass Mem Hlth Care, Worcester, MA USA. [Hitsman, Brian] Northwestern Univ, Dept Prevent Med, Evanston, IL USA. [Hitsman, Brian] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. [Beckham, Jean C.] Duke Univ, Durham VA Med Ctr, Durham, NC USA. [Zvolensky, Michael] Univ Vermont, Burlington, VT USA. [Adler, Lawrence E.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Audrain-McGovern, Janet] Univ Penn, Philadelphia, PA 19104 USA. [Breslau, Naomi] Michigan State Univ, E Lansing, MI 48824 USA. [Brown, Richard A.] Butler Hosp, Brown Med Sch, Providence, RI 02906 USA. [George, Tony P.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Williams, Jill] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Riley, William T.] NIMH, Bethesda, MD 20892 USA. [Ziedonis, Douglas] Univ Massachusetts, Dept Psychiat, Sch Med, UMass Mem Med Ctr, Worcester, MA 01655 USA. RP Ziedonis, D (reprint author), Univ Massachusetts, Dept Psychiat, Sch Med, UMass Mem Med Ctr, 55 Lake Ave N, Worcester, MA 01655 USA. EM ziedonid@ummhc.org RI Breslau , Naomi/I-3196-2012 FU National Institutes of Health [DA020705, DA015537]; Massachusetts Department of Mental Health; New Jersey Department of Health and Senior Services; NIDA [DA017145]; Office of Research and Development Clinical Science, Department of Veterans Affairs [DA016388, CA081595, DA019704, MH07662901, DA018734-01A1, DA16307-01]; Department of Veterans Affairs [VISN 19 MIRECC, MH050787-11, DAMD17-01-1-0760, CA109250, CA096836, DA023190, DA016738, DA017947, AA015950]; National Alliance for Research on Schizophrenia and Depression [DA13672, DA14039, DA16611]; Canadian Institutes for Health Research; University of Toronto; National Institute on Drug Abuse [MH076672-01A1]; New Jersey Division of Mental Health Services; Pfizer FX The NIMH Tobacco Use and Cessation in Psychiatric Disorders Workgroup meeting was supported by NIMH, including additional support to Douglas Ziedonis, Brian Hitsman, and Jean C. Beckman for the writing of the manuscript. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the funding agencies. This work also was supported by National Institutes of Health grants (DA020705 and DA015537), Massachusetts Department of Mental Health support for the UMass/DMH Research Center of Excellence for Systemic and Psychosocial Research, and the New Jersey Department of Health and Senior Services grants through funds from New Jersey's Comprehensive Tobacco Control Program for the UMDNJ Tobacco Dependence Program to Douglas Ziedonis; a NIDA Mentored Clinical Scientist Development Award (DA017145) to Brian Hitsman; Office of Research and Development Clinical Science, Department of Veterans Affairs, grants DA016388, CA081595, and DA019704 to Jean C. Beckham; grants MH07662901, DA018734-01A1, and DA16307-01 to Michael Zvolensky; Department of Veterans Affairs grant VISN 19 MIRECC and grants MH050787-11 and DAMD17-01-1-0760 to Lawrence E. Adler; grants CA109250 and CA096836 to Janet Audrain-McGovern; grants DA023190, DA016738, DA017947, and AA015950 to Richard A. Brown; grants DA13672, DA14039, and DA16611, an Independent Investigator Award from the National Alliance for Research on Schizophrenia and Depression, the Canadian Institutes for Health Research, the Endowed Chair in Addiction Psychiatry from the University of Toronto to Tony P. George; grant MH076672-01A1, grants from the National Institute on Drug Abuse, and grants from the New Jersey Division of Mental Health Services and the New Jersey Department of Health and Senior Services, through funds from New Jersey's Comprehensive Tobacco Control Program to Jill Williams. Also, since the time of the NIMH workgroup meeting (September 2005), the authors acknowledge the following competing interest sources of support: Douglas Ziedonis has consulted for Pfizer, Bristol-Myers Squibb, Janssen, Eli Lilly, and Alkermes/Cephalon and has received research grant support from Bristol-Myers Squibb, Janssen, and Eli Lilly. Jill Williams is on the Speakers Bureau for Pfizer, Inc. Research grants have been awarded from Targacept Inc. and Pfizer to Tony P. George. Tony P. George has served as consultant for Pfizer, Janssen-Ortho International, Lilly and Evotec. The authors thank Nicki Fox for editorial support. NR 285 TC 324 Z9 332 U1 19 U2 65 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2008 VL 10 IS 12 BP 1691 EP 1715 AR PII 905756217 DI 10.1080/14622200802443569 PG 25 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 376OZ UT WOS:000261194200003 PM 19023823 ER PT J AU Cokic, VP Beleslin-Cokic, BB Noguchi, CT Schechter, AN AF Cokic, Vladan P. Beleslin-Cokic, Bojana B. Noguchi, Constance T. Schechter, Alan N. TI Globin gene stimulation by nitric oxide produced by the hematopoietic microenvironment SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Noguchi, Constance T.; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S65 EP S66 DI 10.1016/j.niox.2008.06.194 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500189 ER PT J AU Malik, MO Niedelman, W Lee, J Yuspa, SH AF Malik, Mariam O. Niedelman, Wendy Lee, Jessica Yuspa, Stuart H. TI Nitric oxide directly regulates nuclear translocation of chloride intracellar channel CLIC4 SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Malik, Mariam O.; Niedelman, Wendy; Lee, Jessica; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S21 EP S21 DI 10.1016/j.niox.2008.06.007 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500007 ER EF